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Title:
COVID-19: Epidemiology, Evolution, and Cross-Disciplinary Perspectives
Abstract:
The basic reproductive number (R0) of 2019-nCoV is higher than R0 of severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV).
COVID-19 presents with asymptomatic infections, with potential to propagate and perpetuate this epidemic.
2019-nCoV isolated from patients shows limited sequence diversity, suggesting that the interspecies transmission event was very recent and that the source of the virus was focused, possibly a point-source event.
The amino acid sequence in the ACE2 receptor responsible for 2019-nCoV binding in farm animals and cats has only a few exchanges compared with the human receptor, suggesting that the species barrier for virus transmission is small. | 214,755,547 |
Title:
Coronavirus Disease 2019 in elderly patients: characteristics and prognostic factors based on 4-week follow-up
Abstract:
OBJECTIVE ::: To investigate the characteristics and prognostic factors in the elderly patients with COVID-19. ::: ::: ::: METHODS ::: Consecutive cases over 60 years old with COVID-19 in Renmin Hospital of Wuhan University from Jan 1 to Feb 6, 2020 were included.
The primary outcomes were death and survival till March 5.
Data of demographics, clinical features, comorbidities, laboratory tests and complications were collected and compared for different outcomes.
Cox regression was performed for prognostic factors.
::: ::: ::: RESULTS ::: 339 patients with COVID-19 (aged 71±8 years,173 females (51%)) were enrolled, including 80 (23.6%) critical, 159 severe (46.9%) and 100 moderate (29.5%) cases.
Common comorbidities were hypertension (40.8%), diabetes (16.0%) and cardiovascular disease (15.7%).
Common symptoms included fever (92.0%), cough (53.0%), dyspnea (40.8%) and fatigue (39.9%).
Lymphocytopenia was a common laboratory finding (63.2%).
Common complications included bacterial infection (42.8%), liver enzyme abnormalities (28.7%) and acute respiratory distress syndrome (21.0%).
Till Mar 5, 2020, 91 cases were discharged (26.8%), 183 cases stayed in hospital (54.0%) and 65 cases (19.2%) were dead.
Shorter length of stay was found for the dead compared with the survivors (5 (3-8) vs. 28 (26-29), P < 0.001).
Symptoms of dyspnea (HR 2.35, P = 0.001), comorbidities including cardiovascular disease (HR 1.86, P = 0.031) and chronic obstructive pulmonary disease (HR 2.24, P = 0.023), and acute respiratory distress syndrome (HR 29.33, P < 0.001) were strong predictors of death.
And a high level of lymphocytes was predictive of better outcome (OR = 0.10, P < 0.001). ::: ::: ::: CONCLUSIONS ::: High proportion of severe to critical cases and high fatality rate were observed in the elderly COVID-19 patients.
Rapid disease progress was noted in the dead with a median survival time of 5 days after admission.
Dyspnea, lymphocytopenia, comorbidities including cardiovascular disease and chronic obstructive pulmonary disease, and acute respiratory distress syndrome were predictive of poor outcome.
Close monitoring and timely treatment should be performed for the elderly patients at high risk. | 214,756,358 |
Title:
Using observational data to quantify bias of traveller-derived COVID-19 prevalence estimates in Wuhan, China
Abstract:
BACKGROUND ::: The incidence of coronavirus disease 2019 (COVID-19) in Wuhan, China, has been estimated using imported case counts of international travellers, generally under the assumptions that all cases of the disease in travellers have been ascertained and that infection prevalence in travellers and residents is the same.
However, findings indicate variation among locations in the capacity for detection of imported cases.
Singapore has had very strong epidemiological surveillance and contact tracing capacity during previous infectious disease outbreaks and has consistently shown high sensitivity of case-detection during the COVID-19 outbreak. ::: ::: ::: METHODS ::: We used a Bayesian modelling approach to estimate the relative capacity for detection of imported cases of COVID-19 for 194 locations (excluding China) compared with that for Singapore.
We also built a simple mathematical model of the point prevalence of infection in visitors to an epicentre relative to that in residents. ::: ::: ::: FINDINGS ::: The weighted global ability to detect Wuhan-to-location imported cases of COVID-19 was estimated to be 38% (95% highest posterior density interval [HPDI] 22-64) of Singapore's capacity.
This value is equivalent to 2·8 (95% HPDI 1·5-4·4) times the current number of imported and reported cases that could have been detected if all locations had had the same detection capacity as Singapore.
Using the second component of the Global Health Security index to stratify likely case-detection capacities, the ability to detect imported cases relative to Singapore was 40% (95% HPDI 22-67) among locations with high surveillance capacity, 37% (18-68) among locations with medium surveillance capacity, and 11% (0-42) among locations with low surveillance capacity.
Treating all travellers as if they were residents (rather than accounting for the brief stay of some of these travellers in Wuhan) contributed modestly to underestimation of prevalence. ::: ::: ::: INTERPRETATION ::: Estimates of case counts in Wuhan based on assumptions of 100% detection in travellers could have been underestimated by several fold.
Furthermore, severity estimates will be inflated several fold since they also rely on case count estimates.
Finally, our model supports evidence that underdetected cases of COVID-19 have probably spread in most locations around the world, with greatest risk in locations of low detection capacity and high connectivity to the epicentre of the outbreak. ::: ::: ::: FUNDING ::: US National Institute of General Medical Sciences, and Fellowship Foundation Ramon Areces. | 214,757,463 |
Title:
Experimental Treatment with Favipiravir for COVID-19: An Open-Label Control Study
Abstract:
An outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and its caused coronavirus disease 2019 (COVID-19) has been reported in China since December 2019.
More than 16% of patients developed acute respiratory distress syndrome, and the fatality ratio was about 1%–2%.
No specific treatment has been reported.
Herein, we examine the effects of Favipiravir (FPV) versus Lopinavir (LPV)/ritonavir (RTV) for the treatment of COVID-19.
Patients with laboratory-confirmed COVID-19 who received oral FPV (Day 1: 1600 mg twice daily; Days 2–14: 600 mg twice daily) plus interferon (IFN)-α by aerosol inhalation (5 million U twice daily) were included in the FPV arm of this study, whereas patients who were treated with LPV/RTV (Days 1–14: 400 mg/100 mg twice daily) plus IFN-α by aerosol inhalation (5 million U twice daily) were included in the control arm.
Changes in chest computed tomography (CT), viral clearance, and drug safety were compared between the two groups.
For the 35 patients enrolled in the FPV arm and the 45 patients in the control arm, all baseline characteristics were comparable between the two arms.
A shorter viral clearance time was found for the FPV arm versus the control arm (median (interquartile range, IQR), 4 (2.5–9) d versus 11 (8–13) d, P < 0.001).
The FPV arm also showed significant improvement in chest imaging compared with the control arm, with an improvement rate of 91.43% versus 62.22% (P = 0.004).
After adjustment for potential confounders, the FPV arm also showed a significantly higher improvement rate in chest imaging.
Multivariable Cox regression showed that FPV was independently associated with faster viral clearance.
In addition, fewer adverse reactions were found in the FPV arm than in the control arm.
In this open-label nonrandomized control study, FPV showed significantly better treatment effects on COVID-19 in terms of disease progression and viral clearance; if causal, these results should be important information for establishing standard treatment guidelines to combat the SARS-CoV-2 infection. | 214,758,813 |
Title:
An initial industrial flora: A framework for botanical research in cooperation with industry for biodiversity conservation
Abstract:
Humans have created an accelerating, increasingly connected, globalized economy, resulting in a more globalized, shared flora.
The prevention of new, establishing species is less costly, both economically and ecologically, and is more manageable than eradicating nonnative invasive species once they are widespread and negatively impactful.
We ask if international trade hubs and points-of-entry with high-volume trade, constant disturbance, and propagule rain have a higher number of nonnative species compared to surrounding areas and if they may serve as initial establishment sites and refugia of nonnative, invasive populations.
Therefore, we partnered with various federal, state, and private interests to evaluate the floristic composition at the Garden City Terminal of the Port of Savannah, Georgia, USA.
We conducted the following study to demonstrate the collaborative relationship-building between researchers and industry and to develop a framework for biodiversity conservation.
In our study, we collected all reproductive vascular plants in the secured areas of the Garden City Terminal during four major seasonal time points over two years.
The percent of nonnative species and number of nonnative plant species per hectare at this industrial location exceeded all other comparison floras.
The mean coefficient of conservatism was lowest among the comparison floras, indicating a highly disturbed habitat with nonnative, weedy native, and other native species tolerant of disturbance.
Our study represents one of the first inventories of an Industrialized Flora and indicates that such areas are hot-spots of nonnative plant diversity and possible sources of emergent plant invasions.
We posit that industrial sites and international points-of-entry should be considered laboratories for research on species transport and introduction, adaptability, and taxonomic delineation to better understand the mechanisms and consequences of biotic homogenization due to the volume and frequency of anthropogenic activities. | 214,767,570 |
Title:
Control of brain tumor growth by reactivating myeloid cells with niacin
Abstract:
By rejuvenating the deficient activity of myeloid cells in glioblastoma, niacin improves the treatment of otherwise incurable brain tumors.
An old vitamin’s new tricks Although innate immune cells are typically present inside tumors, they often have an inactive phenotype such that they are ineffective at killing the cancer cells or even promote tumor growth.
Sarkar et al. discovered that it may be possible to reprogram these cells to a more active type using niacin (vitamin B3).
The authors showed that niacin-exposed monocytes can inhibit the growth of brain tumor–initiating cells.
Moreover, niacin treatment of intracranial mouse models of glioblastoma increased monocyte and macrophage infiltration into the tumors, stimulated antitumor immune responses, and extended the animals’ survival, especially when combined with the chemotherapeutic drug temozolomide.
Glioblastomas are generally incurable partly because monocytes, macrophages, and microglia in afflicted patients do not function in an antitumor capacity.
Medications that reactivate these macrophages/microglia, as well as circulating monocytes that become macrophages, could thus be useful to treat glioblastoma.
We have discovered that niacin (vitamin B3) is a potential stimulator of these inefficient myeloid cells.
Niacin-exposed monocytes attenuated the growth of brain tumor–initiating cells (BTICs) derived from glioblastoma patients by producing anti-proliferative interferon-α14.
Niacin treatment of mice bearing intracranial BTICs increased macrophage/microglia representation within the tumor, reduced tumor size, and prolonged survival.
These therapeutic outcomes were negated in mice depleted of circulating monocytes or harboring interferon-α receptor–deleted BTICs.
Combination treatment with temozolomide enhanced niacin-promoted survival.
Monocytes from glioblastoma patients had increased interferon-α14 upon niacin exposure and were reactivated to reduce BTIC growth in culture.
We highlight niacin, a common vitamin that can be quickly translated into clinical application, as an immune stimulator against glioblastomas. | 214,773,001 |
Title:
Surgical Indications for Hepatocellular Carcinoma with Non-hypervascular Hypointense Nodules Detected by Gd-EOB-DTPA-Enhanced MRI
Abstract:
BACKGROUND ::: The surgical indication for non-hypervascular hypointense nodules (NHVN) detected incidentally on gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging (Gd-EOB-MRI) for classical hepatocellular carcinoma (HCC) is unknown.
Our aim is to clarify the long-term outcomes in patients with this finding. ::: ::: ::: METHODS ::: We reviewed the cases of 290 HCC patients, including 66 patients with NHVN, who underwent Gd-EOB-MRI prior to hepatectomy, between October 2008 and December 2017 at our center.
We divided the patients into three groups: a no-NHVN group, a treated NHVN group, and an untreated NHVN group. ::: ::: ::: RESULTS ::: There was no significant difference in (RFS) or overall survival (OS) between the no-NHVN and untreated NHVN groups (p = 0.103 and 0.103, respectively).
There was no significant difference between these two groups after propensity score matching.
Multivariate analyses showed that microscopic intrahepatic metastases and the size of the main classical HCC, the target tumor, were independent prognostic factors of overall survival, but the presence of non-hypervascular hypointense nodules was not.
There was no significant difference in RFS or OS between the treated NHVN and untreated NHVN groups (p = 0.158 and 0.109, respectively). ::: ::: ::: CONCLUSIONS ::: Non-hypervascular hypointense nodules detected incidentally on Gd-EOB-MRI associated with targeted hypervascular HCC did not reflect prognosis of HCC after hepatectomy.
Surgical procedures for classical enhancing HCC may be performed even if non-hypervascular hypointense nodules adjacent to the targeted HCC cannot be removed completely. | 214,783,176 |
Title:
Respiratory virus shedding in exhaled breath and efficacy of face masks
Abstract:
We identified seasonal human coronaviruses, influenza viruses and rhinoviruses in exhaled breath and coughs of children and adults with acute respiratory illness.
Surgical face masks significantly reduced detection of influenza virus RNA in respiratory droplets and coronavirus RNA in aerosols, with a trend toward reduced detection of coronavirus RNA in respiratory droplets.
Our results indicate that surgical face masks could prevent transmission of human coronaviruses and influenza viruses from symptomatic individuals.
A study of 246 individuals with seasonal respiratory virus infections randomized to wear or not wear a surgical face mask showed that masks can significantly reduce detection of coronavirus and influenza virus in exhaled breath and may help interrupt virus transmission. | 214,783,460 |
Title:
Functional brain network reconfiguration during learning in a dynamic environment
Abstract:
When learning about dynamic and uncertain environments, people should update their beliefs most strongly when new evidence is most informative, such as when the environment undergoes a surprising change or existing beliefs are highly uncertain.
Here we show that modulations of surprise and uncertainty are encoded in a particular, temporally dynamic pattern of whole-brain functional connectivity, and this encoding is enhanced in individuals that adapt their learning dynamics more appropriately in response to these factors.
The key feature of this whole-brain pattern of functional connectivity is stronger connectivity, or functional integration, between the fronto-parietal and other functional systems.
Our results provide new insights regarding the association between dynamic adjustments in learning and dynamic, large-scale changes in functional connectivity across the brain. | 214,784,423 |
Title:
Pan-cancer Drivers are Recurrent Transcriptional Regulatory Heterogeneities in Early-stage Luminal Breast Cancer
Abstract:
The heterogeneous composition of solid tumors is known to impact disease progression and response to therapy.
Malignant cells coexist in different regulatory states that can be accessed transcriptomically by single-cell RNA sequencing, but these methods have many caveats related to sensitivity, noise, and sample handling.
We revised a statistical fluctuation analysis called stochastic profiling to combine with 10-cell RNA sequencing, which was designed for laser-capture microdissection (LCM) and extended here for immuno-LCM.
When applied to a cohort of late-onset, early-stage luminal breast cancers, the integrated approach identified thousands of candidate regulatory heterogeneities.
Intersecting the candidates from different tumors yielded a relatively stable set of 710 recurrent heterogeneously expressed genes (RHEGs) that were significantly variable in >50% of patients.
RHEGs were not confounded by dissociation artifacts, cell cycle oscillations, or driving mutations for breast cancer.
Rather, we detected RHEG enrichments for epithelial-to-mesenchymal transition genes and, unexpectedly, the latest pan-cancer assembly of driver genes across cancer types other than breast.
Heterogeneous transcriptional regulation conceivably provides a faster, reversible mechanism for malignant cells to sample the effects of potential oncogenes or tumor suppressors on cancer hallmarks.
Statement of significance Profiling intratumor heterogeneity of luminal breast carcinoma cells identifies a recurrent set of genes suggesting sporadic activation of pathways known to drive other types of cancer. | 214,793,551 |
Title:
Reference Intervals of the Ratio of Urine Iodine to Creatinine in Pregnant Women in an Iodine-Replete Area of China
Abstract:
The assessment method of iodine nutrition for pregnant women lacks strong evidence-based medicine.
The prevalence of iodine deficiency in pregnant women may be overestimated using urinary iodine concentration (UIC).
The reference intervals of UIC-to-urinary creatinine concentration ratio (UIC/UCr) were established using a self-sequential longitudinal study of pregnant women with singleton gestation who were recruited using the criteria of the National Academy of Clinical Biochemistry in Dandong City, which is a long-term iodine-replete area.
Nine thousand one hundred sixty-four pregnant women in the first trimester from Dalian City, Dandong City, and Shenyang City were included to verify our proposed reference intervals.
UIC and concentrations of urinary creatinine, serum iodine, TSH, FT4, TPOAb, and TgAb were measured.
The reference intervals of UIC/UCr were 38.63-489.46 μg/g for the first trimester, 58.48-644.03 μg/g for the second trimester, and 56.27-644.93 μg/g for the third trimester.
The prevalence of iodine deficiency was 49.50% using UIC as the indicator (< 150 μg/L), while the prevalence was 3.28% using UIC/UCr (< 38.63 μg/g).
The prevalence of iodine excess was 3.21% using UIC as the indicator (> 500 μg/L) while the prevalence was 1.45% using UIC/UCr (> 489.46 μg/g).
The highest prevalence of overt hypothyroidism and positive thyroid antibodies was in the group with UIC/UCr < 38.63 μg/g.
In contrast to the place of residence and age, BMI was an influencing factor for UIC/UCr.
The reference intervals of UIC/UCr were established.
UIC/UCr may eliminate the effect of urine volume and reflect the actual prevalence of iodine deficiency in pregnant women. | 214,793,889 |
Title:
Coordinated activities of retrosplenial ensembles during resting-state encode spatial landmarks
Abstract:
The brain likely uses offline periods to consolidate recent memories.
One hypothesis holds that the hippocampal output provides a unique, global linking or 'index' code for each memory, and that this code is stored in the cortex in association with locally encoded attributes of each memory.
Activation of the index code is hypothesized to evoke coordinated memory trace reactivation thus facilitating consolidation.
Retrosplenial cortex (RSC) is a major recipient of hippocampal outflow and we have described populations of neurons there with sparse and orthogonal coding characteristics that resemble hippocampal 'place' cells, and whose expression depends on an intact hippocampus.
Using two-photon Ca2+ imaging, we recorded ensembles of neurons in the RSC during periods of immobility before and after active running on a familiar linear treadmill track.
Synchronous bursting of distinct groups of neurons occurred during rest both prior to and after running.
In the second rest epoch, these patterns were associated with the locations of tactile landmarks and reward.
Complementing established views on the functions of the RSC, our findings indicate that the structure is involved with processing landmark information during rest.
This article is part of the Theo Murphy meeting issue 'Memory reactivation: replaying events past, present and future'. | 214,793,974 |
Title:
Harmonized global maps of above and belowground biomass carbon density in the year 2010
Abstract:
Remotely sensed biomass carbon density maps are widely used for myriad scientific and policy applications, but all remain limited in scope.
They often only represent a single vegetation type and rarely account for carbon stocks in belowground biomass.
To date, no global product integrates these disparate estimates into an all-encompassing map at a scale appropriate for many modelling or decision-making applications.
We developed an approach for harmonizing vegetation-specific maps of both above and belowground biomass into a single, comprehensive representation of each.
We overlaid input maps and allocated their estimates in proportion to the relative spatial extent of each vegetation type using ancillary maps of percent tree cover and landcover, and a rule-based decision schema.
The resulting maps consistently and seamlessly report biomass carbon density estimates across a wide range of vegetation types in 2010 with quantified uncertainty.
They do so for the globe at an unprecedented 300-meter spatial resolution and can be used to more holistically account for diverse vegetation carbon stocks in global analyses and greenhouse gas inventories. | 214,798,904 |
Title:
Gait rehabilitation in persons with spinal cord injury using innovative technologies: an observational study
Abstract:
STUDY DESIGN ::: Prospective, quasi-experimental study, pre- and post-design, single arm study. ::: ::: ::: OBJECTIVES ::: Investigate whether persons affected by SCI can safely experience walking function using Robotic Exoskeletons and Functional Electrical Stimulation (FES). ::: ::: ::: SETTING ::: Inpatient METHODS: 52 persons with SCI were recruited (36 completed the protocol) and assigned to one of two groups based on their Lower Limb Motor Scores (LEMS): Group A: LEMS ≥ 10 and Group B: LEMS < 10.
Participants in Group A (n = 19) underwent 20 sessions of Robot-Assisted Gait Training (RAGT) on a treadmill followed by 20 sessions of FES during Overground Gait (FES-OG).
Participants in Group B (n = 17) received 20 sessions of FES-cycling followed by 20 sessions of overground RAGT.
The main outcome measures were: WISCI-II, 10MWT, 6MWT, TUG and SCIM-II. ::: ::: ::: RESULTS ::: 36 persons completed the study with no complications; only 4 of the 16 dropped out because of mild complications during the RAGT.
Participants in Group A exhibited significant improvements in WISCI-II, 10MWT, 6MWT and TUG (p < 0.05), while those in Group B did not significantly improve their gait function but their walking velocity and resistance with the assistance of the robotic exoskeleton increased.
SCIM-II scores increased followed therapy only in Group A. ::: ::: ::: CONCLUSIONS ::: Persons affected by SCI can safely experience their walking function with RAGT and FES therapy; only few mild complications were observed.
Our data provides initial evidence of the potential value of these technologies, especially in persons with SCI having LEMS > 10. | 214,808,771 |
Title:
Automated Entire Thrombus Density Measurements for Robust and Comprehensive Thrombus Characterization in Patients with Acute Ischemic Stroke
Abstract:
textabstractBackground and Purpose: In acute ischemic stroke (AIS) management, CT-based thrombus density has been associated with treatment success.
However, currently used thrombus measurements are prone to inter-observer variability and oversimplify the heterogeneous thrombus composition.
Our aim was first to introduce an automated method to assess the entire thrombus density and then to compare the measured entire thrombus density with respect to current standard manual measurements.
Materials and Method: In 135 AIS patients, the density distribution of the entire thrombus was determined.
Density distributions were described usingmedians, interquartile ranges (IQR), kurtosis, and skewedness.
Differences between themedian of entire thrombusmeasurements and commonly applied manualmeasurements using 3 regions of interest were determined using linear regression.
Results: Density distributions varied considerably with medians ranging from 20.0 to 62.8 HU and IQRs ranging from 9.3 to 55.8 HU.
The average median of the thrombus density distributions (43.5 ± 10.2 HU) was lower than the manual assessment (49.6 ± 8.0 HU) (p<0.05).
The difference between manual measurements and median density of entire thrombus decreased with increasing density (r = 0.64; p<0.05), revealing relatively higher manual measurements for low density thrombi such that manual density measurement tend overestimates the real thrombus density.
Conclusions: Automatic measurements of the full thrombus expose a wide variety of thrombi density distribution, which is not grasped with currently used manual measurement.
Furthermore, discrimination of low and high density thrombi is improved with the automated method. | 214,818,811 |
Title:
Changes in peripheral immune cell numbers and functions in octogenarian walkers – an acute exercise study
Abstract:
BackgroundAge-related changes of the immune system, termed immunosenescence, may underlie the increased risk of infections and morbidity in the elderly.
Little is known about the effects of acute exercise on peripheral immune parameters in octogenarians.
Therefore, we investigated acute exercise-induced changes in phenotype and function of the immune system in octogenarians participating in the 2013 edition of the Nijmegen Four Days Marches.
Blood sampling was performed at baseline and immediately after 4 days of the walking exercise (30 km/day).
A comprehensive set of adaptive and innate immune traits were enumerated and analyzed by flow-cytometry.
Peripheral blood mononuclear cells, isolated before and after walking were stimulated with LPS and supernatants were analysed for IL-1β, IL-6, IL-8 and TNF-α concentrations by ELISA.
CMV serostatus was determined by ELISA.ResultsThe walking exercise induced a clear leucocytosis with numerical increases of granulocytes, monocytes and lymphocytes.
These exercise-induced changes were most profound in CMV seropositive subjects.
Within lymphocytes, numerical increases of particularly CD4+ T cells were noted.
Further T cell differentiation analysis revealed profound increases of naïve CD4+ T cells, including naïve Treg.
Significant increases were also noted for CD4+ memory T cell subsets.
In contrast, only slight increases in naïve and memory CD8+ T cell subsets were detected.
Exercise did not affect markers of immune exhaustion in memory T cell subsets.
NK cells demonstrated a numerical decline and a change in cellular composition with a selective decrease of the mature CD56dim NK cells.
The latter was seen in CMV seronegative subjects only.
Also, a higher IL-6 and IL-8 production capacity of LPS-stimulated PBMC was seen after walking.
ConclusionIn this exceptional cohort of octogenarian walkers, acute exercise induced changes in immune cell numbers and functions.
A clear response of CD4+ T cells, rather than CD8+ T cells or NK cells was noted.
Remarkably, the response to exercise within the CD4+ T cell compartment was dominated by naïve CD4+ subsets. | 214,843,815 |
Title:
Alternative Pathway Inhibition by Exogenous Factor H Fails to Attenuate Inflammation and Vascular Leakage in Experimental Pneumococcal Sepsis in Mice
Abstract:
Streptococcus pneumoniae is a common cause of sepsis.
Effective complement activation is an important component of host defence against invading pathogens, whilst excessive complement activation has been associated with endothelial dysfunction and organ damage.
The alternative pathway amplification loop is important for the enhancement of complement activation.
Factor H is a key negative regulator of the alternative pathway amplification loop and contributes to tight control of complement activation.
We assessed the effect of inhibition of the alternative pathway on sepsis associated inflammation and disease severity using human factor H treatment in a clinically relevant mice model of pneumococcal sepsis.
Mice were infected intravenously with live Streptococcus pneumoniae.
At the first clinical signs of infection, 17 hours post-infection, mice were treated with ceftriaxone antibiotic.
At the same time purified human factor H or in controls PBS was administered.
Treatment with human factor H did not attenuate disease scores, serum pro-inflammatory cytokines, or vascular permeability and did not significantly affect C3 and C3a production at 26 h post-infection.
Therefore, we conclude that inhibition of the alternative complement pathway by exogenous human factor H fails to attenuate inflammation and vascular leakage at a clinically relevant intervention time point in pneumococcal sepsis in mice. | 214,985,625 |
Title:
Pathogenic T cells and inflammatory monocytes incite inflammatory storm in severe COVID-19 patients
Abstract:
Pathogenic human coronavirus infections, such as severe acute respiratory syndrome CoV (SARS-CoV) and Middle East respiratory syndrome CoV (MERS-CoV), cause high morbidity and mortality1, 2 .
Recently, a severe pneumonia-associated respiratory syndrome caused by a new coronavirus (SARS-CoV-2) was reported at December 2019 in the city Wuhan, Hubei province, China3, 4, 5, which was also named as pneumonia-associated respiratory syndrome (PARS)6 and can cause coronavirus disease 2019 (COVID-19) to seriously endanger human health.
Up to 24th of February 2020, at least 77779 cases have been reported with 2666 fatal cases according to the report from China CDC.
However, the immune mechanism that potential orchestrated acute mortality from COVID-19 patients is still unknown.
Here we show that after the SARS-CoV-2 infection, CD4+ T lymphocytes are rapidly activated to become pathogenic T helper (Th) 1 cells and generate GM-CSF etc.
The cytokines environment induces inflammatory CD14+CD16+ monocytes with high expression of IL-6 and accelerate the inflammation.
Given that large amount of inflammatory cells infiltrations have been observed in lungs from severe COVID-19 patients7, 8, these aberrant pathogenic Th1 cells and inflammatory monocytes may enter the pulmonary circulation in huge numbers and play an immune damaging role to causing lung functional disability and quick mortality.
Our results demonstrate that excessive non-effective host immune responses by pathogenic T cells and inflammatory monocytes may associate with severe lung pathology.
Thus, we suggest that monoclonal antibodies targeting GM-CSF or interleukin 6 may be effective in blocking inflammatory storms and, therefore, be a promising treatment of severe COVID-19 patients | 215,088,050 |
Title:
Differential lexical predictors of reading comprehension in fourth graders
Abstract:
The mental lexicon plays a central role in reading comprehension (Perfetti & Stafura, 2014).
It encompasses the number of lexical entries in spoken and written language (vocabulary breadth), the semantic quality of these entries (vocabulary depth), and the connection strength between lexical representations (semantic relatedness); as such, it serves as an output for the decoding process and as an input for comprehension processes.
Although different aspects of the lexicon can be distinguished, research on the role of the mental lexicon in reading comprehension often does not take these individual aspects of the lexicon into account.
The current study used a multicomponent approach to examine whether measures of spoken and written vocabulary breadth, vocabulary depth, and semantic relatedness were differentially predictive of individual differences in reading comprehension skills in fourth-grade students.
The results indicated that, in addition to nonverbal reasoning, short-term memory, and word decoding, the four measures of lexical quality substantially added (30 %) to the proportion of explained variance of reading comprehension (adding up to a total proportion of 65 %).
Moreover, each individual measure of lexical quality added significantly to the prediction of reading comprehension after all other measures were taken into account, with written lexical breadth and lexical depth showing the greatest increase in explained variance.
It can thus be concluded that multiple components of lexical quality play a role in children’s reading comprehension. | 215,093,278 |
Title:
Maximum-Entropy Models of Sequenced Immune Repertoires Predict Antigen-Antibody Affinity
Abstract:
The immune system has developed a number of distinct complex mechanisms to shape and control the antibody repertoire.
One of these mechanisms, the affinity maturation process, works in an evolutionary-like fashion: after binding to a foreign molecule, the antibody-producing B-cells exhibit a high-frequency mutation rate in the genome region that codes for the antibody active site.
Eventually, cells that produce antibodies with higher affinity for their cognate antigen are selected and clonally expanded.
Here, we propose a new statistical approach based on maximum entropy modeling in which a scoring function related to the binding affinity of antibodies against a specific antigen is inferred from a sample of sequences of the immune repertoire of an individual.
We use our inference strategy to infer a statistical model on a data set obtained by sequencing a fairly large portion of the immune repertoire of an HIV-1 infected patient.
The Pearson correlation coefficient between our scoring function and the IC50 neutralization titer measured on 30 different antibodies of known sequence is as high as 0.77 (p-value 10−6), outperforming other sequence- and structure-based models. | 215,098,674 |
Title:
Developing a Sense of Knowing and Acquiring the Skills to Manage Pain in Children with Profound Cognitive Impairments: Mothers' Perspectives
Abstract:
Children with profound cognitive impairment (PCI) are a heterogenous group who often experience frequent and persistent pain.
Those people closest to the child are key to assessing their pain.
This mixed method study aimed to explore how parents acquire knowledge and skills in assessing and managing their child’s pain.
Eight mothers completed a weekly pain diary and were interviewed at weeks 1 and 8.
Qualitative data were analysed using thematic analysis and the quantitative data using descriptive statistics.
Mothers talked of learning through a system of trial and error (“learning to get on with it”); this was accomplished through “learning to know without a rule book or guide”; “learning to be a convincing advocate”; and “learning to endure and to get things right.
” Experiential and reflective learning was evident in the way the mothers developed a “sense of knowing” their child’s pain.
They drew on embodied knowledge of how their child usually expressed and responded to pain to help make pain-related decisions.
Health professionals need to support mothers/parents to develop their knowledge and skills and to gain confidence in pain assessment and they should recognise and act on the mothers’ concerns. | 215,114,196 |
Title:
Practicing Emotionally Biased Retrieval Affects Mood and Establishes Biased Recall a Week Later
Abstract:
Cognitive Bias Modification (CBM) can yield clinically relevant results.
Only few studies have directly manipulated memory bias, which is prominent in depression.
In a new approach to CBM, we sought to simulate or oppose ruminative processes by training the retrieval of negative or positive words.
Participants studied positive and negative word pairs (Swahili cues with Dutch translations).
In the positive and negative conditions, each of the three study trials was followed by a cued-recall test of training-congruent translations; a no-practice condition merely studied the pairs.
Recall of the translations was tested after the training and after 1 week.
Both recall tests revealed evidence of training-congruent bias and bias was associated with emotional autobiographical memory.
Positive retrieval practice yielded stable positive mood, in contrast to the other conditions.
The results indicate that memory bias can be established through retrieval practice and that the bias transfers to mood and autobiographical memory. | 215,117,544 |
Title:
Longitudinal Analysis of Music Education on Executive Functions in Primary School Children
Abstract:
Background: Research on the effects of music education on cognitive abilities has generated increasing interest across the scientific community.
Nonetheless, longitudinal studies investigating the effects of structured music education on cognitive sub-functions are still rare.
Prime candidates for investigating a relationship between academic achievement and music education appear to be executive functions such as planning, working memory, and inhibition.
Methods: One hundred and forty-seven primary school children, Mage = 6.4 years, SD = 0.65 were followed for 2.5 years.
Participants were randomized into four groups: two music intervention groups, one active visual arts group, and a no arts control group.
Neuropsychological tests assessed verbal intelligence and executive functions.
Additionally, a national pupil monitor provided data on academic performance.
Results: Children in the visual arts group perform better on visuospatial memory tasks as compared to the three other conditions.
However, the test scores on inhibition, planning and verbal intelligence increased significantly in the two music groups over time as compared to the visual art and no arts controls.
Mediation analysis with executive functions and verbal IQ as mediator for academic performance have shown a possible far transfer effect from executive sub-function to academic performance scores.
Discussion: The present results indicate a positive influence of long-term music education on cognitive abilities such as inhibition and planning.
Of note, following a two-and-a-half year long visual arts program significantly improves scores on a visuospatial memory task.
All results combined, this study supports a far transfer effect from music education to academic achievement mediated by executive sub-functions. | 215,164,691 |
Title:
Inter-observer agreement according to three methods of evaluating mammographic density and parenchymal pattern in a case control study: impact on relative risk of breast cancer
Abstract:
BackgroundMammographic breast density and parenchymal patterns are well-established risk factors for breast cancer.
We aimed to report inter-observer agreement on three different subjective ways of assessing mammographic density and parenchymal pattern, and secondarily to examine what potential impact reproducibility has on relative risk estimates of breast cancer.
MethodsThis retrospective case–control study included 122 cases and 262 age- and time matched controls (765 breasts) based on a 2007 screening cohort of 14,736 women with negative screening mammograms from Bispebjerg Hospital, Copenhagen.
Digitised randomized film-based mammograms were classified independently by two readers according to two radiological visual classifications (BI-RADS and Tabár) and a computerized interactive threshold technique measuring area-based percent mammographic density (denoted PMD).
Kappa statistics, Intraclass Correlation Coefficient (ICC) (equivalent to weighted kappa), Pearson’s linear correlation coefficient and limits-of-agreement analysis were used to evaluate inter-observer agreement.
High/low-risk agreement was also determined by defining the following categories as high-risk: BI-RADS’s D3 and D4, Tabár’s PIV and PV and the upper two quartiles (within density range) of PMD.
The relative risk of breast cancer was estimated using logistic regression to calculate odds ratios (ORs) adjusted for age, which were compared between the two readers.
ResultsSubstantial inter-observer agreement was seen for BI-RADS and Tabár (κ=0.68 and 0.64) and agreement was almost perfect when ICC was calculated for the ordinal BI-RADS scale (ICC=0.88) and the continuous PMD measure (ICC=0.93).
The two readers judged 5% (PMD), 10% (Tabár) and 13% (BI-RADS) of the women to different high/low-risk categories, respectively.
Inter-reader variability showed different impact on the relative risk of breast cancer estimated by the two readers on a multiple-category scale, however, not on a high/low-risk scale.
Tabár’s pattern IV demonstrated the highest ORs of all density patterns investigated.
ConclusionsOur study shows the Tabár classification has comparable inter-observer reproducibility with well tested density methods, and confirms the association between Tabár’s PIV and breast cancer.
In spite of comparable high inter-observer agreement for all three methods, impact on ORs for breast cancer seems to differ according to the density scale used.
Automated computerized techniques are needed to fully overcome the impact of subjectivity. | 215,187,512 |
Title:
Inflammatory and Metabolic Alterations of Kager's Fat Pad in Chronic Achilles Tendinopathy
Abstract:
Background ::: Achilles tendinopathy is a painful inflammatory condition characterized by swelling, stiffness and reduced function of the Achilles tendon.
Kager’s fat pad is an adipose tissue located in the area anterior to the Achilles tendon.
Observations reveal a close physical interplay between Kager’s fat pad and its surrounding structures during movement of the ankle, suggesting that Kager’s fat pad may stabilize and protect the mechanical function of the ankle joint. ::: ::: ::: Aim ::: The aim of this study was to characterize whether Achilles tendinopathy was accompanied by changes in expression of inflammatory markers and metabolic enzymes in Kager’s fat pad. ::: ::: ::: Methods ::: A biopsy was taken from Kager’s fat pad from 31 patients with chronic Achilles tendinopathy and from 13 healthy individuals.
Gene expression was measured by reverse transcription-quantitative PCR.
Focus was on genes related to inflammation and lipid metabolism. ::: ::: ::: Results ::: Expression of the majority of analyzed inflammatory marker genes was increased in patients with Achilles tendinopathy compared to that in healthy controls.
Expression patterns of the patient group were consistent with reduced lipolysis and increased fatty acid β-oxidation.
In the fat pad, the pain-signaling neuropeptide substance P was found to be present in one third of the subjects in the Achilles tendinopathy group but in none of the healthy controls.
::: ::: ::: Conclusion ::: Gene expression changes in Achilles tendinopathy patient samples were consistent with Kager’s fat pad being more inflamed than in the healthy control group.
Additionally, the results indicate an altered lipid metabolism in Kager’s fat pad of Achilles tendinopathy patients. | 215,187,996 |
Title:
EGFR Mutant Structural Database: computationally predicted 3D structures and the corresponding binding free energies with gefitinib and erlotinib
Abstract:
BackgroundEpidermal growth factor receptor (EGFR) mutation-induced drug resistance has caused great difficulties in the treatment of non-small-cell lung cancer (NSCLC).
However, structural information is available for just a few EGFR mutants.
In this study, we created an EGFR Mutant Structural Database (freely available at http://bcc.ee.cityu.edu.hk/data/EGFR.html), including the 3D EGFR mutant structures and their corresponding binding free energies with two commonly used inhibitors (gefitinib and erlotinib).ResultsWe collected the information of 942 NSCLC patients belonging to 112 mutation types.
These mutation types are divided into five groups (insertion, deletion, duplication, modification and substitution), and substitution accounts for 61.61% of the mutation types and 54.14% of all the patients.
Among all the 942 patients, 388 cases experienced a mutation at residue site 858 with leucine replaced by arginine (L858R), making it the most common mutation type.
Moreover, 36 (32.14%) mutation types occur at exon 19, and 419 (44.48%) patients carried a mutation at exon 21.
In this study, we predicted the EGFR mutant structures using Rosetta with the collected mutation types.
In addition, Amber was employed to refine the structures followed by calculating the binding free energies of mutant-drug complexes.
ConclusionsThe EGFR Mutant Structural Database provides resources of 3D structures and the binding affinity with inhibitors, which can be used by other researchers to study NSCLC further and by medical doctors as reference for NSCLC treatment. | 215,220,517 |
Title:
Telemedicine’s Potential to Support Good Dying in Nigeria: A Qualitative Study
Abstract:
OBJECTIVES: This qualitative study explores Nigerian health care professionals' concepts of good dying/a good death and how telemedicine technologies and services would fit the current Nigerian palliative care practice.
MATERIALS AND METHODS: Supported by the Centre for Palliative Care Nigeria (CPCN) and the University College Hospital (UCH) in Ibadan, Nigeria, the authors organized three focus groups with Nigerian health care professionals interested in palliative care, unstructured interviews with key role players for palliative care and representatives of telecom companies, and field visits to primary, secondary and tertiary healthcare clinics that provided palliative care.
Data analysis consisted of open coding, constant comparison, diagramming of categorizations and relations, and extensive member checks.
RESULTS: The focus group participants classified good dying into 2 domains: a feeling of completion of the individual life and dying within the community.
Reported barriers to palliative care provision were socio-economic consequences of being seriously ill, taboos on dying and being ill, restricted access to adequate medical-technical care, equation of religion with medicine, and the faulty implementation of palliative care policy by government.
The addition of telemedicine to Nigeria's palliative care practice appears problematic, due to irregular bandwidth, poor network coverage, and unstable power supply obstructing interactivity and access to information.
However, a tele-education 'lite' scenario seemed viable in Nigeria, wherein low-tech educational networks are central that build on non-synchronous online communication.
DISCUSSION: Nigerian health care professionals' concepts on good dying/a good death and barriers and opportunities for palliative care provision were, for the greater part, similar to prior findings from other studies in Africa.
Information for and education of patient, family, and community are essential to further improve palliative care in Africa.
Telemedicine can only help if low-tech solutions are applied that work around network coverage problems by focusing on non-synchronous online communication. | 215,227,467 |
Title:
Klotho Pathways, Myelination Disorders, Neurodegenerative Diseases, and Epigenetic Drugs
Abstract:
In this review we outline a rationale for identifying neuroprotectants aimed at inducing endogenous Klotho activity and expression, which is epigenetic action, by definition.
Such an approach should promote remyelination and/or stimulate myelin repair by acting on mitochondrial function, thereby heralding a life-saving path forward for patients suffering from neuroinflammatory diseases.
Disorders of myelin in the nervous system damage the transmission of signals, resulting in loss of vision, motion, sensation, and other functions depending on the affected nerves, currently with no effective treatment.
Klotho genes and their single-pass transmembrane Klotho proteins are powerful governors of the threads of life and death, true to the origin of their name, Fates, in Greek mythology.
Among its many important functions, Klotho is an obligatory co-receptor that binds, activates, and/or potentiates critical fibroblast growth factor activity.
Since the discovery of Klotho a little over two decades ago, it has become ever more apparent that when Klotho pathways go awry, oxidative stress and mitochondrial dysfunction take over, and age-related chronic disorders are likely to follow.
The physiological consequences can be wide ranging, potentially wreaking havoc on the brain, eye, kidney, muscle, and more.
Central nervous system disorders, neurodegenerative in nature, and especially those affecting the myelin sheath, represent worthy targets for advancing therapies that act upon Klotho pathways.
Current drugs for these diseases, even therapeutics that are disease modifying rather than treating only the symptoms, leave much room for improvement.
It is thus no wonder that this topic has caught the attention of biomedical researchers around the world. | 215,243,875 |
Title:
Experiential education in the pharmacy undergraduate curricula in Brazil
Abstract:
Objective ::: Considering the curriculum reform process taking place in pharmacy undergraduate programs in Brazil and the importance of practical experience to students throughout their learning process in university, this study aims to provide an overview of pharmacy undergraduate programs in Brazil and their respective internships. ::: ::: ::: Methods ::: An observational, descriptive, cross-sectional study.
A documentary analysis of pharmacy undergraduate programs in the face-to-face modality was carried out, with data obtained from the Political Pedagogical Projects of the programs, the curricula, and course descriptions containing information on internships, all provided by the Brazilian Ministry of Education.
The data collected concerned higher education institutions (HEIs), pharmacy programs and internships. ::: ::: ::: Results ::: Pharmacy undergraduate programs in Brazil have a median duration of 10 semesters, requiring from students a median of 6 internships, from the 6th semester on, totalizing 826 hours.
The programs lack uniformity among their internships, mainly regarding total hours and the semester in which internships start.
The pharmacy internships cover, in greater number, the areas of outpatient and community pharmacy, clinical analysis, and pharmaceutical technology, respectively, being clinical analysis the area with more hours.
Public and private HEIs have different internship proceedings in their curricula, hence no homogeneity among them in the different regions of Brazil. ::: ::: ::: Conclusions ::: This study demonstrates the diversity of pharmacy programs in Brazil in the context of internships, reflecting on the training and the activity of pharmacists in recent decades.
Further studies are needed to deepen the understanding of this theme. | 215,248,905 |
Title:
The spatiotemporal dynamics of binocular rivalry: evidence for increased top-down flow prior to a perceptual switch
Abstract:
According to most theories, perceptual switching during binocular rivalry is caused by competition between the neural representations of the two input images.
It remains unclear whether competition is resolved already at the early stages of visual processing and that information about the dominant percept is then fed forward to more high-level areas or whether competition is first resolved in high-level areas and then fed back to lower levels.
This study aimed to dissociate between these theories by investigating the direction of information flow prior to a perceptual switch, using Granger causality on classifier output originating from occipital, temporal, parietal and frontal regions of interest.
The results point toward increased top-down information flow between temporal and occipital areas before a switch in dominance.
These findings do not support a low-level account of binocular rivalry but are in line with high-level and hybrid explanations. | 215,334,398 |
Title:
Neural representation of form-contingent color filling-in in the early visual cortex
Abstract:
Perceptual filling-in exemplifies the constructive nature of visual processing.
Color, a prominent surface property of visual objects, can appear to spread to neighboring areas that lack any color.
We investigated cortical responses to a color filling-in illusion that effectively dissociates perceived color from the retinal input (van Lier, Vergeer, & Anstis, 2009).
Observers adapted to a star-shaped stimulus with alternating red- and cyan-colored points to elicit a complementary afterimage.
By presenting an achromatic outline that enclosed one of the two afterimage colors, perceptual filling-in of that color was induced in the unadapted central region.
Visual cortical activity was monitored with fMRI, and analyzed using multivariate pattern analysis.
Activity patterns in early visual areas (V1-V4) reliably distinguished between the two color-induced filled-in conditions, but only higher extrastriate visual areas showed the predicted correspondence with color perception.
Activity patterns allowed for reliable generalization between filled-in colors and physical presentations of perceptually matched colors in areas V3 and V4, but not in earlier visual areas.
These findings suggest that the perception of filled-in surface color likely requires more extensive processing by extrastriate visual areas, in order for the neural representation of surface color to become aligned with perceptually matched real colors. | 215,412,775 |
Title:
Evidence for unlimited capacity processing of simple features in visual cortex
Abstract:
Performance in many visual tasks is impaired when observers attempt to divide spatial attention across multiple visual field locations.
Correspondingly, neuronal response magnitudes in visual cortex are often reduced during divided compared with focused spatial attention.
This suggests that early visual cortex is the site of capacity limits, where finite processing resources must be divided among attended stimuli.
However, behavioral research demonstrates that not all visual tasks suffer such capacity limits: The costs of divided attention are minimal when the task and stimulus are simple, such as when searching for a target defined by orientation or contrast.
To date, however, every neuroimaging study of divided attention has used more complex tasks and found large reductions in response magnitude.
We bridged that gap by using functional magnetic resonance imaging to measure responses in the human visual cortex during simple feature detection.
The first experiment used a visual search task: Observers detected a low-contrast Gabor patch within one or four potentially relevant locations.
The second experiment used a dual-task design, in which observers made independent judgments of Gabor presence in patches of dynamic noise at two locations.
In both experiments, blood-oxygen level-dependent (BOLD) signals in the retinotopic cortex were significantly lower for ignored than attended stimuli.
However, when observers divided attention between multiple stimuli, BOLD signals were not reliably reduced and behavioral performance was unimpaired.
These results suggest that processing of simple features in early visual cortex has unlimited capacity. | 215,413,757 |
Title:
Distribution, size, shape, growth potential and extent of abdominal aortic calcified deposits predict mortality in postmenopausal women
Abstract:
BackgroundAortic calcification is a major risk factor for death from cardiovascular disease.
We investigated the relationship between mortality and the composite markers of number, size, morphology and distribution of calcified plaques in the lumbar aorta.
Methods308 postmenopausal women aged 48-76 were followed for 8.3 ± 0.3 years, with deaths related to cardiovascular disease, cancer, or other causes being recorded.
From lumbar X-rays at baseline the number (NCD), size, morphology and distribution of aortic calcification lesions were scored and combined into one Morphological Atherosclerotic Calcification Distribution (MACD) index.
The hazard ratio for mortality was calculated for the MACD and for three other commonly used predictors: the EU SCORE card, the Framingham Coronary Heart Disease Risk Score (Framingham score), and the gold standard Aortic Calcification Severity score (AC24) developed from the Framingham Heart Study cohorts.
ResultsAll four scoring systems showed increasing age, smoking, and raised triglyceride levels were the main predictors of mortality after adjustment for all other metabolic and physical parameters.
The SCORE card and the Framingham score resulted in a mortality hazard ratio increase per standard deviation (HR/SD) of 1.8 (1.51-2.13) and 2.6 (1.87-3.71), respectively.
Of the morphological x-ray based measures, NCD revealed a HR/SD >2 adjusted for SCORE/Framingham.
The MACD index scoring the distribution, size, morphology and number of lesions revealed the best predictive power for identification of patients at risk of mortality, with a hazard ratio of 15.6 (p < 0.001) for the 10% at greatest risk of death.
ConclusionsThis study shows that it is not just the extent of aortic calcification that predicts risk of mortality, but also the distribution, shape and size of calcified lesions.
The MACD index may provide a more sensitive predictor of mortality from aortic calcification than the commonly used AC24 and SCORE/Framingham point card systems. | 215,416,455 |
Title:
Effects of IL-6 on pyruvate dehydrogenase regulation in mouse skeletal muscle
Abstract:
Skeletal muscle regulates substrate choice according to demand and availability and pyruvate dehydrogenase (PDH) is central in this regulation.
Circulating interleukin (IL)-6 increases during exercise and IL-6 has been suggested to increase whole body fat oxidation.
Furthermore, IL-6 has been reported to increase AMP-activated protein kinase (AMPK) phosphorylation and AMPK suggested to regulate PDHa activity.
Together, this suggests that IL-6 may be involved in regulating PDH.
The aim of this study was to investigate the effect of a single injection of IL-6 on PDH regulation in skeletal muscle in fed and fasted mice.
Fed and 16–18 h fasted mice were injected with either 3 ng · g−1 recombinant mouse IL-6 or PBS as control.
Fasting markedly reduced plasma glucose, muscle glycogen, muscle PDHa activity, as well as increased PDK4 mRNA and protein content in skeletal muscle.
IL-6 injection did not affect plasma glucose or muscle glycogen, but increased AMPK and ACC phosphorylation and tended to decrease p38 protein content in skeletal muscle in fasted mice.
In addition IL-6 injection reduced PDHa activity in fed mice and increased PDHa activity in fasted mice without significant changes in PDH-E1α phosphorylation or PDP1 and PDK4 mRNA and protein content.
The present findings suggest that IL-6 contributes to regulating the PDHa activity and hence carbohydrate oxidation, but the metabolic state of the muscle seems to determine the outcome of this regulation.
In addition, AMPK and p38 may contribute to the IL-6-mediated PDH regulation in the fasted state. | 215,416,481 |
Title:
Prepregnancy body mass index and risk of preterm birth: association heterogeneity by preterm subgroups
Abstract:
To evaluate the association between prepregnancy body mass index (BMI) is associated with early vs. late and medically-induced vs. spontaneous preterm birth (PTB) subtypes.
Using data from the Boston Birth Cohort, we examined associations of prepregnancy BMI with 189 early (<34 completed weeks) and 277 late (34–36 completed weeks) medically-induced PTBs and 320 early and 610 late spontaneous PTBs vs. 3281 term births (37–44 weeks) in multinomial regression.
To assess for mediation by important pregnancy complications, we performed sequential models with and without hypertensive disorders of pregnancy, chorioamnionitis, and gestational diabetes.
Prevalence of prepregnancy obesity (BMI ≥ 30.0 kg/m2) was 28% among mothers with medically-induced PTBs, 18% among mothers with spontaneous PTBs, and 18% among mothers with term births (p = <0.001).
After adjustment for demographic and known risk factors for PTB, prepregnancy obesity was associated with higher odds of both early [OR 1.78 (1.19, 2.66)] and late [OR 1.49 (1.09, 2.04)] medically-induced PTB.
These effect estimates were attenuated with inclusion of hypertensive disorders of pregnancy and gestational diabetes.
For spontaneous deliveries, prepregnancy obesity was associated with decreased odds of PTB (0.76 [0.58, 0.98]) and underweight was nearly associated with increased odds of PTB (1.46 [0.99, 2.16]).
Prepregnancy obesity is associated with higher risk of medically-induced, but not spontaneous PTB.
Hypertensive disorders of pregnancy and gestational diabetes appear to partially explain the association between prepregnancy obesity and early and late medically-induced PTB. | 215,478,750 |
Title:
Semidefinite bounds for nonbinary codes based on quadruples
Abstract:
For nonnegative integers q, n, d, let A q ( n , d ) denote the maximum cardinality of a code of length n over an alphabet [q] with q letters and with minimum distance at least d. We consider the following upper bound on A q ( n , d ) .
For any k, let C k be the collection of codes of cardinality at most k. Then A q ( n , d ) is at most the maximum value of ∑ v ∈ [ q ] n x ( { v } ) , where x is a function C 4 → R + such that x ( ∅ ) = 1 and x ( C ) = 0 if C has minimum distance less than d, and such that the C 2 × C 2 matrix ( x ( C ∪ C ' ) ) C , C ' ∈ C 2 is positive semidefinite.
By the symmetry of the problem, we can apply representation theory to reduce the problem to a semidefinite programming problem with order bounded by a polynomial in n. It yields the new upper bounds A 4 ( 6 , 3 ) ≤ 176 , A 4 ( 7 , 3 ) ≤ 596 , A 4 ( 7 , 4 ) ≤ 155 , A 5 ( 7 , 4 ) ≤ 489 , and A 5 ( 7 , 5 ) ≤ 87 . | 215,496,891 |
Title:
Marennine, Promising Blue Pigments from a Widespread Haslea Diatom Species Complex
Abstract:
In diatoms, the main photosynthetic pigments are chlorophylls a and c, fucoxanthin, diadinoxanthin and diatoxanthin.
The marine pennate diatom Haslea ostrearia has long been known for producing, in addition to these generic pigments, a water-soluble blue pigment, marennine.
This pigment, responsible for the greening of oysters in western France, presents different biological activities: allelopathic, antioxidant, antibacterial, antiviral, and growth-inhibiting.
A method to extract and purify marennine has been developed, but its chemical structure could hitherto not be resolved.
For decades, H. ostrearia was the only organism known to produce marennine, and can be found worldwide.
Our knowledge about H. ostrearia-like diatom biodiversity has recently been extended with the discovery of several new species of blue diatoms, the recently described H. karadagensis, H. silbo sp. inedit. and H. provincialis sp. inedit.
These blue diatoms produce different marennine-like pigments, which belong to the same chemical family and present similar biological activities.
Aside from being a potential source of natural blue pigments, H. ostrearia-like diatoms thus present a commercial potential for aquaculture, cosmetics, food and health industries. | 215,511,490 |
Title:
Drosophila Imp iCLIP identifies an RNA assemblage coordinating F-actin formation
Abstract:
BackgroundPost-transcriptional RNA regulons ensure coordinated expression of monocistronic mRNAs encoding functionally related proteins.
In this study, we employ a combination of RIP-seq and short- and long-wave individual-nucleotide resolution crosslinking and immunoprecipitation (iCLIP) technologies in Drosophila cells to identify transcripts associated with cytoplasmic ribonucleoproteins (RNPs) containing the RNA-binding protein Imp.
ResultsWe find extensive binding of Imp to 3′ UTRs of transcripts that are involved in F-actin formation.
A common denominator of the RNA–protein interface is the presence of multiple motifs with a central UA-rich element flanked by CA-rich elements.
Experiments in single cells and intact flies reveal compromised actin cytoskeletal dynamics associated with low Imp levels.
The former shows reduced F-actin formation and the latter exhibits abnormal neuronal patterning.
This demonstrates a physiological significance of the defined RNA regulon.
ConclusionsOur data imply that Drosophila Imp RNPs may function as cytoplasmic mRNA assemblages that encode proteins which participate in actin cytoskeletal remodeling.
Thus, they may facilitate coordinated protein expression in sub-cytoplasmic locations such as growth cones. | 215,513,592 |
Title:
Algorithm for post-clustering curation of DNA amplicon data yields reliable biodiversity estimates
Abstract:
DNA metabarcoding is promising for cost-effective biodiversity monitoring, but reliable diversity estimates are difficult to achieve and validate.
Here we present and validate a method, called LULU, for removing erroneous molecular operational taxonomic units (OTUs) from community data derived by high-throughput sequencing of amplified marker genes.
LULU identifies errors by combining sequence similarity and co-occurrence patterns.
To validate the LULU method, we use a unique data set of high quality survey data of vascular plants paired with plant ITS2 metabarcoding data of DNA extracted from soil from 130 sites in Denmark spanning major environmental gradients.
OTU tables are produced with several different OTU definition algorithms and subsequently curated with LULU, and validated against field survey data.
LULU curation consistently improves α-diversity estimates and other biodiversity metrics, and does not require a sequence reference database; thus, it represents a promising method for reliable biodiversity estimation.
A central problem in biodiversity estimation from genetic markers is the ability of algorithms to retain ‘true’ species while discarding artefacts.
Here, the authors present a new post-clusturing curation algorithm using OTU co-occurrences to estimate plant biodiversity from soil samples. | 215,513,858 |
Title:
High-precision camera distortion measurements with a"calibration harp"
Abstract:
This paper addresses the high-precision measurement of the distortion of a digital camera from photographs.
Traditionally, this distortion is measured from photographs of a flat pattern that contains aligned elements.
Nevertheless, it is nearly impossible to fabricate a very flat pattern and to validate its flatness.
This fact limits the attainable measurable precisions.
In contrast, it is much easier to obtain physically very precise straight lines by tightly stretching good quality strings on a frame.
Taking literally “plumb-line methods,” we built a “calibration harp” instead of the classic flat patterns to obtain a high-precision measurement tool, demonstrably reaching 2/100 pixel precisions.
The harp is complemented with the algorithms computing automatically from harp photographs two different and complementary lens distortion measurements.
The precision of the method is evaluated on images corrected by state-of-the-art distortion correction algorithms, and by popular software.
Three applications are shown: first an objective and reliable measurement of the result of any distortion correction.
Second, the harp permits us to control state-of-the art global camera calibration algorithms: it permits us to select the right distortion model, thus avoiding internal compensation errors inherent to these methods.
Third, the method replaces manual procedures in other distortion correction methods, makes them fully automatic, and increases their reliability and precision. | 215,514,896 |
Title:
Subjective Memory Ability and Long-Term Forgetting in Patients Referred for Neuropsychological Assessment
Abstract:
It has been suggested that the memory complaints of patients who are not impaired on formal memory tests may reflect accelerated forgetting.
We examined this hypothesis by comparing the 1-week delayed recall and recognition test performance of outpatients who were referred for neuropsychological assessment and who had normal memory performance during standard memory assessment with that of a non-patient control group.
Both groups performed equally in verbal learning and delayed recall.
However, after 1 week, the patients performed worse than controls on both recall and recognition tests.
Although subjective memory ability predicted short-term memory function in patients, it did not predict long-term delayed forgetting rates in either the patients or controls.
Thus, long-term delayed recall and recognition intervals provided no additional value to explain poor subjective memory ability in the absence of objective memory deficits. | 215,514,949 |
Title:
Widening Access to Bayesian Problem Solving
Abstract:
Bayesian reasoning and decision making is widely considered normative because it minimizes prediction error in a coherent way.
However, it is often difficult to apply Bayesian principles to complex real world problems, which typically have many unknowns and interconnected variables.
Bayesian network modeling techniques make it possible to model such problems and obtain precise predictions about the causal impact that changing the value of one variable may have on the values of other variables connected to it.
But Bayesian modeling is itself complex, and has until now remained largely inaccessible to lay people.
In a large scale lab experiment, we provide proof of principle that a Bayesian network modeling tool, adapted to provide basic training and guidance on the modeling process to beginners without requiring knowledge of the mathematical machinery working behind the scenes, significantly helps lay people find normative Bayesian solutions to complex problems, compared to generic training on probabilistic reasoning.
We discuss the implications of this finding for the use of Bayesian network software tools in applied contexts such as security, medical, forensic, economic or environmental decision making. | 215,516,558 |
Title:
The S gene of canine coronavirus, strain UCD-1, is more closely related to the S gene of transmissible gastroenteritis virus than to that of feline infectious peritonitis virus1
Abstract:
To gain insight into the genetic relationships among six canine coronavirus (CCV) strains, the variable region of the spike (S) protein gene was sequenced.
The CCV strains were: two ATCC reference strains, the Insavc-1 vaccine strain, the National Veterinary Services Laboratories (Ames, IA) challenge strain, and two California field isolates (UCD-1 and UCD-2) from the 1970s.
All six strains, downstream of the nucleocapsid (N) protein gene, had sufficient size for an ORF 7b, and thus, none were transmissible gastroenteritis virus (TGEV)-like since TGEV lacks ORF 7b.
By sequence analysis of the variable domain at the 5' end of the S gene, five of the six CCV strains had a high degree of identity with feline infectious peritonitis virus (FIPV).
However, one CCV field isolate (UCD-1) was different and had a high degree of identity with the 5' end of the TGEV S gene.
This suggests that RNA recombination occurred at this site between antigenically related coronaviruses.
The low passage field isolates, UCD-1 and UCD-2, varied in their initial infectivity for swine testicular cells suggesting that sequence differences in the variable domain of the S gene may account for biological variation among CCVs. | 215,516,619 |
Title:
To Each According to its Degree: The Meritocracy and Topocracy of Embedded Markets
Abstract:
Support from the MIT Media Lab Consortia, Fundacion Caja Madrid (Spain), ::: UAM-Santander (Spain) and CONICYT grants: Anillo en Complejidad Social SOC-1101 ::: and Fondecyt 1110351 is gratefully acknowledged | 215,518,989 |
Title:
The New Global Health
Abstract:
Global health reflects the realities of globalization, including worldwide dissemination of infectious and noninfectious public health risks.
Global health architecture is complex and better coordination is needed between multiple organizations.
Three overlapping themes determine global health action and prioritization: development, security, and public health.
These themes play out against a background of demographic change, socioeconomic development, and urbanization.
Infectious diseases remain critical factors, but are no longer the major cause of global illness and death.
Traditional indicators of public health, such as maternal and infant mortality rates no longer describe the health status of whole societies; this change highlights the need for investment in vital registration and disease-specific reporting.
Noncommunicable diseases, injuries, and mental health will require greater attention from the world in the future.
The new global health requires broader engagement by health organizations and all countries for the objectives of health equity, access, and coverage as priorities beyond the Millennium Development Goals are set. | 215,519,472 |
Title:
Laparoscopy to predict the result of primary cytoreductive surgery in advanced ovarian cancer patients (LapOvCa-trial): a multicentre randomized controlled study
Abstract:
BackgroundStandard treatment of advanced ovarian cancer is surgery and chemotherapy.
The goal of surgery is to remove all macroscopic tumour, as the amount of residual tumour is the most important prognostic factor for survival.
When removal off all tumour is considered not feasible, neoadjuvant chemotherapy (NACT) in combination with interval debulking surgery (IDS) is performed.
Current methods of staging are not always accurate in predicting surgical outcome, since approximately 40% of patients will have more than 1 cm residual tumour after primary debulking surgery (PDS).
In this study we aim to assess whether adding laparoscopy to the diagnostic work-up of patients suspected of advanced ovarian carcinoma may prevent unsuccessful primary debulking surgery for ovarian cancer.
MethodsMulticentre randomized controlled trial, including all gynaecologic oncologic centres in the Netherlands and their affiliated hospitals.
Patients are eligible when they are planned for PDS after conventional staging.
Participants are randomized between direct PDS or additional diagnostic laparoscopy.
Depending on the result of laparoscopy patients are treated by PDS within three weeks, followed by six courses of platinum based chemotherapy or with NACT and IDS 3-4 weeks after three courses of chemotherapy, followed by another three courses of chemotherapy.
Primary outcome measure is the proportion of PDS's leaving more than one centimetre tumour residual in each arm.
In total 200 patients will be randomized.
Data will be analysed according to intention to treat.
DiscussionPatients who have disease considered to be resectable to less than one centimetre should undergo PDS to improve prognosis.
However, there is a need for better diagnostic procedures because the current number of debulking surgeries leaving more than one centimetre residual tumour is still high.
Laparoscopy before starting treatment for ovarian cancer can be an additional diagnostic tool to predict the outcome of PDS.
Despite the absence of strong evidence and despite the possible complications, laparoscopy is already implemented in many countries.
We propose a randomized multicentre trial to provide evidence on the effectiveness of laparoscopy before primary surgery for advanced stage ovarian cancer patients.
Trial registrationNetherlands Trial Register number NTR2644 | 215,523,440 |
Title:
A distinctive gene expression fingerprint in mentally retarded male patients reflects disease-causing defects in the histone demethylase KDM5C
Abstract:
BackgroundMental retardation is a genetically heterogeneous disorder, as more than 90 genes for this disorder has been found on the X chromosome alone.
In addition the majority of patients are non-syndromic in that they do not present with clinically recognisable features.
This makes it difficult to determine the molecular cause of this disorder on the basis of the phenotype alone.
Mutations in KDM5C (previously named SMCX or JARID1C), a gene that encodes a transcriptional regulator with histone demethylase activity specific for dimethylated and trimethylated H3K4, are a comparatively frequent cause of non-syndromic X-linked mental retardation (NS-XLMR).
Specific transcriptional targets of KDM5C, however, are still unknown and the effects of KDM5C deficiency on gene expression have not yet been investigated.
ResultsBy whole-mount in situ hybridisation we showed that the mouse homologue of KDM5C is expressed in multiple tissues during mouse development.
We present the results of gene expression profiling performed on lymphoblastoid cell lines as well as blood from patients with mutations in KDM5C.
Using whole genome expression arrays and quantitative reverse transcriptase polymerase chain reaction (QRT-PCR) experiments, we identified several genes, including CMKOR1, KDM5B and KIAA0469 that were consistently deregulated in both tissues.
ConclusionsOur findings shed light on the pathological mechanisms underlying mental retardation and have implications for future diagnostics of this heterogeneous disorder. | 215,524,128 |
Title:
A Hybrid Model for Automatic Emotion Recognition in Suicide Notes
Abstract:
We describe the Open University team's submission to the 2011 i2b2/VA/Cincinnati Medical Natural Language Processing Challenge, Track 2 Shared Task for sentiment analysis in suicide notes.
This Shared Task focused on the development of automatic systems that identify, at the sentence level, affective text of 15 specific emotions from suicide notes.
We propose a hybrid model that incorporates a number of natural language processing techniques, including lexicon-based keyword spotting, CRF-based emotion cue identification, and machine learning-based emotion classification.
The results generated by different techniques are integrated using different vote-based merging strategies.
The automated system performed well against the manually-annotated gold standard, and achieved encouraging results with a micro-averaged F-measure score of 61.39% in textual emotion recognition, which was ranked 1st place out of 24 participant teams in this challenge.
The results demonstrate that effective emotion recognition by an automated system is possible when a large annotated corpus is available. | 215,524,618 |
Title:
GPCRDB: an information system for G protein-coupled receptors
Abstract:
For the past 20 years, the GPCRDB (G protein-coupled receptors database; http://www.gpcr.org/7tm/) has been a 'one-stop shop' for G protein-coupled receptor (GPCR)-related data.
The GPCRDB contains experimental data on sequences, ligand-binding constants, mutations and oligomers, as well as many different types of computationally derived data, such as multiple sequence alignments and homology models.
The GPCRDB also provides visualization and analysis tools, plus a number of query systems.
In the latest GPCRDB release, all multiple sequence alignments, and >65,000 homology models, have been significantly improved, thanks to a recent flurry of GPCR X-ray structure data.
Tools were introduced to browse X-ray structures, compare binding sites, profile similar receptors and generate amino acid conservation statistics.
Snake plots and helix box diagrams can now be custom coloured (e.g. by chemical properties or mutation data) and saved as figures.
A series of sequence alignment visualization tools has been added, and sequence alignments can now be created for subsets of sequences and sequence positions, and alignment statistics can be produced for any of these subsets. | 215,524,780 |
Title:
SigniSite: Identification of residue-level genotype-phenotype correlations in protein multiple sequence alignments
Abstract:
Identifying which mutation(s) within a given genotype is responsible for an observable phenotype is important in many aspects of molecular biology.
Here, we present SigniSite ,a n online application for subgroup-free residue-level genotype–phenotype correlation.
In contrast to similar methods, SigniSite does not require any pre-definition of subgroups or binary classification.
Input is a set of protein sequences where each sequence has an associated real number, quantifying a given phenotype.
SigniSite will then identify which amino acid residues are significantly associated with the data set phenotype.
As output, SigniSite displays a sequence logo, depicting the strength of the phenotype association of each residue and a heat-map identifying ‘hot’ or ‘cold’ regions.
SigniSite was benchmarked against SPEER, a state-of-the-art method for the prediction of specificity determining positions (SDP) using a set of human immunodeficiency virus protease-inhibitor genotype–phenotype data and corresponding resistance mutation scores from the Stanford University HIV Drug Resistance Database, and a data set of protein families with experimentally annotated SDPs.
For both data sets, SigniSite was found to outperform SPEER.
SigniSite is available at: http://www.cbs.dtu.dk/services/SigniSite/. | 215,524,797 |
Title:
Neuropathological background of phenotypical variability in frontotemporal dementia
Abstract:
Frontotemporal lobar degeneration (FTLD) is the umbrella term encompassing a heterogeneous group of pathological disorders.
With recent discoveries, the FTLDs have been show to classify nicely into three main groups based on the major protein deposited in the brain: FTLD-tau, FTLD-TDP and FTLD-FUS.
These pathological groups, and their specific pathologies, underlie a number of well-defined clinical syndromes, including three frontotemporal dementia (FTD) variants [behavioral variant frontotemporal dementia (bvFTD), progressive non-fluent aphasia, and semantic dementia (SD)], progressive supranuclear palsy syndrome (PSPS) and corticobasal syndrome (CBS).
Understanding the neuropathological background of the phenotypic variability in FTD, PSPS and CBS requires large clinicopathological studies.
We review current knowledge on the relationship between the FTLD pathologies and clinical syndromes, and pool data from a number of large clinicopathological studies that collectively provide data on 544 cases.
Strong relationships were identified as follows: FTD with motor neuron disease and FTLD-TDP; SD and FTLD-TDP; PSPS and FTLD-tau; and CBS and FTLD-tau.
However, the relationship between some of these clinical diagnoses and specific pathologies is not so clear cut.
In addition, the clinical diagnosis of bvFTD does not have a strong relationship to any FTLD subtype or specific pathology and therefore remains a diagnostic challenge.
Some evidence suggests improved clinicopathological association of bvFTD by further refining clinical characteristics.
Unlike FTLD-tau and FTLD-TDP, FTLD-FUS has been less well characterized, with only 69 cases reported.
However, there appears to be some associations between clinical phenotypes and FTLD-FUS pathologies.
Clinical diagnosis is therefore promising in predicting molecular pathology. | 215,525,002 |
Title:
Agreement between QuantiFERON®-TB Gold In-Tube and the tuberculin skin test and predictors of positive test results in Warao Amerindian pediatric tuberculosis contacts
Abstract:
Interferon-gamma release assays have emerged as a more specific alternative to the tuberculin skin test (TST) for detection of tuberculosis (TB) infection, especially in Bacille Calmette-Guérin (BCG) vaccinated people.
We determined the prevalence of Mycobacterium tuberculosis infection by TST and QuantiFERON®-TB Gold In-Tube (QFT-GIT) and assessed agreement between the two test methods and factors associated with positivity in either test in Warao Amerindian children in Venezuela.
Furthermore, progression to active TB disease was evaluated for up to 12 months.
163 HIV-negative childhood household contacts under 16 years of age were enrolled for TST, QFT-GIT and chest X-ray (CXR).
Follow-up was performed at six and 12 months.
Factors associated with TST and QFT-GIT positivity were studied using generalized estimation equations logistic regression models.
At baseline, the proportion of TST positive children was similar to the proportion of children with a positive QFT-GIT (47% vs. 42%, p = 0.12).
Overall concordance between QFT-GIT and TST was substantial (kappa 0.76, 95% CI 0.46-1.06).
Previous BCG vaccination was not associated with significantly increased positivity in either test (OR 0.68, 95% CI 0.32-1.5 for TST and OR 0.51, 95% CI 0.14-1.9 for QFT-GIT).
Eleven children were diagnosed with active TB at baseline.
QFT-GIT had a higher sensitivity for active TB (88%, 95% CI 47-98%) than TST (55%, 95% CI 24-83%) while specificities were similar (respectively 58% and 55%).
Five initially asymptomatic childhood contacts progressed to active TB disease during follow-up.
Replacement of TST by the QFT-GIT for detection of M. tuberculosis infection is not recommended in this resource-constrained setting as test results showed substantial concordance and TST positivity was not affected by previous BCG vaccination.
The QFT-GIT had a higher sensitivity than the TST for the detection of TB disease.
However, the value of the QFT-GIT as an adjunct in diagnosing TB disease is limited by a high variability in QFT-GIT results over time. | 215,525,594 |
Title:
Improving ancient DNA read mapping against modern reference genomes
Abstract:
BackgroundNext-Generation Sequencing has revolutionized our approach to ancient DNA (aDNA) research, by providing complete genomic sequences of ancient individuals and extinct species.
However, the recovery of genetic material from long-dead organisms is still complicated by a number of issues, including post-mortem DNA damage and high levels of environmental contamination.
Together with error profiles specific to the type of sequencing platforms used, these specificities could limit our ability to map sequencing reads against modern reference genomes and therefore limit our ability to identify endogenous ancient reads, reducing the efficiency of shotgun sequencing aDNA.ResultsIn this study, we compare different computational methods for improving the accuracy and sensitivity of aDNA sequence identification, based on shotgun sequencing reads recovered from Pleistocene horse extracts using Illumina GAIIx and Helicos Heliscope platforms.
We show that the performance of the Burrows Wheeler Aligner (BWA), that has been developed for mapping of undamaged sequencing reads using platforms with low rates of indel-types of sequencing errors, can be employed at acceptable run-times by modifying default parameters in a platform-specific manner.
We also examine if trimming likely damaged positions at read ends can increase the recovery of genuine aDNA fragments and if accurate identification of human contamination can be achieved using a strategy previously suggested based on best hit filtering.
We show that combining our different mapping and filtering approaches can increase the number of high-quality endogenous hits recovered by up to 33%.ConclusionsWe have shown that Illumina and Helicos sequences recovered from aDNA extracts could not be aligned to modern reference genomes with the same efficiency unless mapping parameters are optimized for the specific types of errors generated by these platforms and by post-mortem DNA damage.
Our findings have important implications for future aDNA research, as we define mapping guidelines that improve our ability to identify genuine aDNA sequences, which in turn could improve the genotyping accuracy of ancient specimens.
Our framework provides a significant improvement to the standard procedures used for characterizing ancient genomes, which is challenged by contamination and often low amounts of DNA material. | 215,526,184 |
Title:
Computational and statistical approaches to analyzing variants identified by exome sequencing
Abstract:
New sequencing technology has enabled the identification of thousands of single nucleotide polymorphisms in the exome, and many computational and statistical approaches to identify disease-association signals have emerged. | 215,526,877 |
Title:
Effects of Aerobic Fitness on Aging-Related Changes of Interhemispheric Inhibition and Motor Performance
Abstract:
Physical Fitness has been long associated with maintenance and improvement of motor performance as we age.
In particular, measures of psychomotor speed and motor dexterity tend to be higher in physically fit aging adults as compared to their sedentary counterparts.
Using functional magnetic resonance imaging and transcranial magnetic stimulation, we explored the patterns of neural activity that may, in part, account for differences between individuals of varying physical fitness levels.
In this study, we enrolled both sedentary and physically fit middle age (40-60) and younger (18-30) adults and measured upper extremity motor performance during behavioral testing.
In a follow-up session, we employed TMS and fMRI to assess levels of interhemispheric communication during unimanual tasks.
Results show that increased physical fitness is associated with better upper extremity motor performance on distal dexterity assessments and increased levels of interhemispheric inhibition in middle-age adults.
Further, the functional correlates of changes of ipsilateral activity appears to be restricted to the aging process as younger adults of varying fitness levels do not differ in hemispheric patterns of activity or motor performance.
We conclude that sedentary aging confers a loss of interhemispheric inhibition that is deleterious to some aspects of motor function, as early as midlife, but these changes can be mediated by chronic engagement in aerobic exercise. | 215,527,492 |
Title:
Student performance of the general physical examination in internal medicine: an observational study
Abstract:
BackgroundMany practicing physicians lack skills in physical examination.
It is not known whether physical examination skills already show deficiencies after an early phase of clinical training.
At the end of the internal medicine clerkship students are expected to be able to perform a general physical examination in every new patient encounter.
In a previous study, the basic physical examination items that should standardly be performed were set by consensus.
The aim of the current observational study was to assess whether medical students were able to correctly perform a general physical examination regarding completeness as well as technique at the end of the clerkship internal medicine.
MethodsOne hundred students who had just finished their clerkship internal medicine were asked to perform a general physical examination on a standardized patient as they had learned during the clerkship.
They were recorded on camera.
Frequency of performance of each component of the physical examination was counted.
Adequacy of performance was determined as either correct or incorrect or not assessable using a checklist of short descriptions of each physical examination component.
A reliability analysis was performed by calculation of the intra class correlation coefficient for total scores of five physical examinations rated by three trained physicians and for their agreement on performance of all items.
ResultsApproximately 40% of the agreed standard physical examination items were not performed by the students.
Students put the most emphasis on examination of general parameters, heart, lungs and abdomen.
Many components of the physical examination were not performed as was taught during precourses.
Intra-class correlation was high for total scores of the physical examinations 0.91 (p <0.001) and for agreement on performance of the five physical examinations (0.79-0.92 p <0.001).ConclusionsIn conclusion, performance of the general physical examination was already below expectation at the end of the internal medicine clerkship.
Possible causes and suggestions for improvement are discussed. | 215,529,814 |
Title:
Superinfection with drug-resistant HIV is rare and does not contribute substantially to therapy failure in a large European cohort
Abstract:
Superinfection with drug resistant HIV strains could potentially contribute to compromised therapy in patients initially infected with drug-sensitive virus and receiving antiretroviral therapy.
To investigate the importance of this potential route to drug resistance, we developed a bioinformatics pipeline to detect superinfection from routinely collected genotyping data, and assessed whether superinfection contributed to increased drug resistance in a large European cohort of viremic, drug treated patients.
We used sequence data from routine genotypic tests spanning the protease and partial reverse transcriptase regions in the Virolab and EuResist databases that collated data from five European countries.
Superinfection was indicated when sequences of a patient failed to cluster together in phylogenetic trees constructed with selected sets of control sequences.
A subset of the indicated cases was validated by re-sequencing pol and env regions from the original samples.
4425 patients had at least two sequences in the database, with a total of 13816 distinct sequence entries (of which 86% belonged to subtype B).
We identified 107 patients with phylogenetic evidence for superinfection.
In 14 of these cases, we analyzed newly amplified sequences from the original samples for validation purposes: only 2 cases were verified as superinfections in the repeated analyses, the other 12 cases turned out to involve sample or sequence misidentification.
Resistance to drugs used at the time of strain replacement did not change in these two patients.
A third case could not be validated by re-sequencing, but was supported as superinfection by an intermediate sequence with high degenerate base pair count within the time frame of strain switching.
Drug resistance increased in this single patient.
Routine genotyping data are informative for the detection of HIV superinfection; however, most cases of non-monophyletic clustering in patient phylogenies arise from sample or sequence mix-up rather than from superinfection, which emphasizes the importance of validation.
Non-transient superinfection was rare in our mainly treatment experienced cohort, and we found a single case of possible transmitted drug resistance by this route.
We therefore conclude that in our large cohort, superinfection with drug resistant HIV did not compromise the efficiency of antiretroviral treatment. | 215,530,461 |
Title:
The integration hypothesis of human language evolution and the nature of contemporary languages
Abstract:
How human language arose is a mystery in the evolution of Homo sapiens.
Miyagawa, Berwick, & Okanoya (Frontiers 2013) put forward a proposal, which we will call the Integration Hypothesis of human language evolution, which holds that human language is composed of two components, E for expressive, and L for lexical.
Each component has an antecedent in nature: E as found, for example, in birdsong, and L in, for example, the alarm calls of monkeys.
E and L integrated uniquely in humans to give rise to language.
A challenge to the Integration Hypothesis is that while these non-human systems are finite-state in nature, human language is known to require characterization by a non-finite state grammar.
Our claim is that E and L, taken separately, are finite-state; when a grammatical process crosses the boundary between E and L, it gives rise to the non-finite state character of human language.
We provide empirical evidence for the Integration Hypothesis by showing that certain processes found in contemporary languages that have been characterized as non-finite state in nature can in fact be shown to be finite-state.
We also speculate on how human language actually arose in evolution through the lens of the Integration Hypothesis. | 215,531,921 |
Title:
Coexistence of nitrifying, anammox and denitrifying bacteria in a sequencing batch reactor
Abstract:
Elevated nitrogen removal efficiencies from ammonium-rich wastewaters have been demonstrated by several applications, that combine nitritation and anammox processes.
Denitrification will occur simultaneously when organic carbon is also present.
In this study, the activity of aerobic ammonia oxidizing, anammox and denitrifying bacteria in a full scale Sequencing Batch Reactor, treating digester supernatants, was studied by means of batch-assays.
AOB and anammox activities were maximum at pH of 8.0 and 7.8-8.0, rispectively.
Short term effect of nitrite on anammox activity was studied, showing nitrite up to 42 mg/L did not result in inhibition.
Both denitrification via nitrate and nitrite were measured.
To reduce nitrite-oxidizing activity, high of NH3 – N (1.9-10 mg N-NH3/L) and low nitrite (3-8 mg TNN/L) are required conditions during the whole SBR cycle.
Molecular analysis showed the nitritation-anammox sludge harbored a high microbial diversity, where each microorganism has a specific role.
Using ammonia monooxygenase α –subunit (amoA) gene as a marker, our analyses suggested different macro- and micro-environments in the reactor strongly affect the AOB community, allowing the development of different AOB species, such as N. europaea/eutropha and N. oligotropha groups, which improve the stability of nitritation process.
A specific PCR primer set, used to target the 16S rRNA gene of anammox bacteria, confirmed the presence of the “Ca.
Brocadia fulgida” type, able to grow in precence of organic matter and to tolerate high nitrite concentrations.
The diversity of denitrifiers was assessed by using dissimilatory nitrite reductase (nirS) gene-based analyses, who showed denitifiers were related to different betaproteobacterial genera, such as Thauera, Pseudomonas, Dechloromonas and Aromatoleum, able to assist in forming microbial aggregates.
Concerning possible secondary processes, no n-damo bacteria were found while NOB from the genus of Nitrobacter was detected. | 215,532,996 |
Title:
Rationale, design, and implementation protocol of the Dutch clinical practice guideline Pain in patients with cancer: a cluster randomised controlled trial with short message service (SMS) and interactive voice response (IVR)
Abstract:
BackgroundOne-half of patients with cancer have pain.
In nearly one out of two cancer patients with pain, this was undertreated.
Inadequate pain control still remains an important problem in this group of patients.
Therefore, in 2008 a national, evidence-based multidisciplinary clinical practice guideline 'pain in patients with cancer' has been developed.
Yet, publishing a guideline is not enough.
Implementation is needed to improve pain management.
An innovative implementation strategy, Short Message Service with Interactive Voice Response (SVS-IVR), has been developed and pilot tested.
This study aims to evaluate on effectiveness of this strategy to improve pain reporting, pain measurement and adequate pain therapy.
In addition, whether the active role of the patient and involvement of caregivers in pain management may change.
Methods/designA cluster randomised controlled trial with two arms will be performed in six oncology outpatient clinics of hospitals in the Southeastern region of the Netherlands, with three hospitals in the intervention and three in the control condition.
Follow-up measurements will be conducted in all hospitals to study the long-term effect of the intervention.
The intervention includes training of professionals (medical oncologists, nurses, and general practitioners) and SMS-IVR to report pain in patients with cancer to improve pain reporting by patients, pain management by medical oncologists, nurses, and general practitioners, and decrease pain intensity.
DiscussionThis innovative implementation strategy with technical tools and the involvement of patients, may enhance the use of the guideline 'pain in patients with cancer' for pain management.
Short Message Service alerts may serve as a tool to support self-management of patients.
Therefore, the SMS-IVR intervention may increase the feeling of having control over one's life.
Trail registrationNetherlands Trial Register (NTR): NTR2739 | 215,533,289 |
Title:
How to promote healthy behaviours in patients? An overview of evidence for behaviour change techniques
Abstract:
To identify the evidence for the effectiveness of behaviour change techniques, when used by health-care professionals, in accomplishing health-promoting behaviours in patients.
Reviews were used to extract data at a study level.
A taxonomy was used to classify behaviour change techniques.
We included 23 systematic reviews: 14 on smoking cessation, 6 on physical exercise, and 2 on healthy diets and 1 on both exercise and diets.
None of the behaviour change techniques demonstrated clear effects in a convincing majority of the studies in which they were evaluated.
Techniques targeting knowledge (n = 210 studies) and facilitation of behaviour (n = 172) were evaluated most frequently.
However, self-monitoring of behaviour (positive effects in 56% of the studies), risk communication (52%) and use of social support (50%) were most often identified as effective.
Insufficient insight into appropriateness of technique choice and quality of technique delivery hinder precise conclusions.
Relatively, however, self-monitoring of behaviour, risk communication and use of social support are most effective.
Health professionals should avoid thinking that providing knowledge, materials and professional support will be sufficient for patients to accomplish change and consider alternative strategies which may be more effective. | 215,533,370 |
Title:
Serotonin receptor 3A polymorphism c.-42C > T is associated with severe dyspepsia
Abstract:
BackgroundThe association between anxiety and depression related traits and dyspepsia may reflect a common genetic predisposition.
Furthermore, genetic factors may contribute to the risk of having increased visceral sensitivity, which has been implicated in dyspeptic symptom generation.
Serotonin (5-HT) modulates visceral sensitivity by its action on 5-HT3 receptors.
Interestingly, a functional polymorphism in HTR3A, encoding the 5-HT3 receptor A subunit, has been reported to be associated with depression and anxiety related traits.
A functional polymorphism in the serotonin transporter (5-HTT), which terminates serotonergic signalling, was also found associated with these psychiatric comorbidities and increased visceral sensitivity in irritable bowel syndrome, which coexistence is associated with higher dyspeptic symptom severity.
We investigated the association between these functional polymorphisms and dyspeptic symptom severity.
MethodsData from 592 unrelated, Caucasian, primary care patients with dyspepsia participating in a randomised clinical trial comparing step-up and step-down antacid drug treatment (The DIAMOND trial) were analysed.
Patients were genotyped for HTR3A c.-42C > T SNP and the 44 bp insertion/deletion polymorphism in the 5-HTT promoter (5-HTTLPR).
Intensity of 8 dyspeptic symptoms at baseline was assessed using a validated questionnaire (0 = none; 6 = very severe).
Sum score ≥20 was defined severe dyspepsia.
ResultsHTR3A c.-42T allele carriers were more prevalent in patients with severe dyspepsia (OR 1.50, 95% CI 1.06-2.20).
This association appeared to be stronger in females (OR 2.05, 95% CI 1.25-3.39) and patients homozygous for the long (L) variant of the 5-HTTLPR genotype (OR 2.00, 95% CI 1.01-3.94).
Females with 5-HTTLPR LL genotype showed the strongest association (OR = 3.50, 95% CI = 1.37-8.90).ConclusionsThe HTR3A c.-42T allele is associated with severe dyspeptic symptoms.
The stronger association among patients carrying the 5-HTTLPR L allele suggests an additive effect of the two polymorphisms.
These results support the hypothesis that diminished 5-HT3 mediated antinociception predisposes to increased visceral sensitivity of the gastrointestinal tract.
Moreover, the HTR3A c.-42C > T and 5-HTTLPR polymorphisms likely represent predisposing genetic variants in common to psychiatric morbidity and dyspepsia. | 215,533,522 |
Title:
Tyrosine-specific MAPK phosphatases and the control of ERK signaling in PC12 cells
Abstract:
Background ::: Spatio-temporal control of extracellular signal-regulated kinase (ERK) activity, a critical determinant of the cell's response to growth factors, requires timely dephosphorylation of its regulatory tyrosine and/or threonine residue by MAPK phosphatases.
We studied the physiological role of kinase interaction motif (KIM)-containing protein tyrosine phosphatases (PTPs) in the control of EGF- and NGF-induced ERK activity in neuroendocrine PC12 cells. | 215,534,884 |
Title:
White matter correlates of cognitive domains in normal aging with diffusion tensor imaging
Abstract:
The ability to perform complex as well as simple cognitive tasks engages a network of brain regions that is mediated by the white matter fiber bundles connecting them.
Different cognitive tasks employ distinctive white matter fiber bundles.
The temporal lobe and its projections subserve a variety of key functions known to deteriorate during aging.
In a cohort of 52 healthy subjects (ages 25–82 years), we performed voxel-wise regression analysis correlating performance in higher-order cognitive domains (executive function, information processing speed, and memory) with white matter integrity, as measured by diffusion tensor imaging (DTI) fiber tracking in the temporal lobe projections [uncinate fasciculus (UF), fornix, cingulum, inferior longitudinal fasciculus (ILF), and superior longitudinal fasciculus (SLF)].
The fiber tracts were spatially registered and statistical parametric maps were produced to spatially localize the significant correlations.
Results showed that performance in the executive function domain is correlated with DTI parameters in the left SLF and right UF; performance in the information processing speed domain is correlated with fractional anisotropy (FA) in the left cingulum, left fornix, right and left ILF and SLF; and the memory domain shows significant correlations with DTI parameters in the right fornix, right cingulum, left ILF, left SLF and right UF.
These findings suggest that DTI tractography enables anatomical definition of region of interest (ROI) for correlation of behavioral parameters with diffusion indices, and functionality can be correlated with white matter integrity. | 215,537,044 |
Title:
Persistence survey of Toxic Shock Syndrome toxin-1 producing Staphylococcus aureus and serum antibodies to this superantigen in five groups of menstruating women
Abstract:
BackgroundMenstrual Toxic Shock Syndrome (mTSS) is thought to be associated with the vaginal colonization with specific strains of Staphylococcus aureus TSST-1 in women who lack sufficient antibody titers to this toxin.
There are no published studies that examine the seroconversion in women with various colonization patterns of this organism.
Thus, the aim of this study was to evaluate the persistence of Staphylococcus aureus colonization at three body sites (vagina, nares, and anus) and serum antibody to toxic shock syndrome toxin-producing Staphylococcus aureus among a small group of healthy, menstruating women evaluated previously in a larger study.
MethodsOne year after the completion of that study, 311 subjects were recalled into 5 groups.
Four samples were obtained from each participant at several visits over an additional 6-11 month period: 1) an anterior nares swab; 2) an anal swab; 3) a vagina swab; and 4) a blood sample.
Gram stain, a catalase test, and a rapid S. aureus-specific latex agglutination test were performed to phenotypically identify S. aureus from sample swabs.
A competitive ELISA was used to quantify TSST-1 production.
Human TSST-1 IgG antibodies were determined from the blood samples using a sandwich ELISA method.
ResultsWe found only 41% of toxigenic S. aureus and 35.5% of non-toxigenic nasal carriage could be classified as persistent.
None of the toxigenic S. aureus vaginal or anal carriage could be classified as persistent.
Despite the low persistence of S. aureus colonization, subjects colonized with a toxigenic strain were found to display distributions of antibody titers skewed toward higher titers than other subjects.
Seven percent (5/75) of subjects became seropositive during recall, but none experienced toxic shock syndrome-like symptoms.
ConclusionsNasal carriage of S. aureus appears to be persistent and the best predicator of subsequent colonization, whereas vaginal and anal carriage appear to be more transient.
From these findings, it appears that antibody titers in women found to be colonized with toxigenic S. aureus remained skewed toward higher titers whether or not the colonies were found to be persistent or transient in nature.
This suggests that colonization at some point in time is sufficient to elevate antibody titer levels and those levels appear to be persistent.
Results also indicate that women can become seropositive without experiencing signs or symptoms of toxic shock syndrome. | 215,539,492 |
Title:
Target for improvement: a cluster randomised trial of public involvement in quality-indicator prioritisation (intervention development and study protocol)
Abstract:
BackgroundPublic priorities for improvement often differ from those of clinicians and managers.
Public involvement has been proposed as a way to bridge the gap between professional and public clinical care priorities but has not been studied in the context of quality-indicator choice.
Our objective is to assess the feasibility and impact of public involvement on quality-indicator choice and agreement with public priorities.
MethodsWe will conduct a cluster randomised controlled trial comparing quality-indicator prioritisation with and without public involvement.
In preparation for the trial, we developed a 'menu' of quality indicators, based on a systematic review of existing validated indicator sets.
Participants (public representatives, clinicians, and managers) will be recruited from six participating sites.
In intervention sites, public representatives will be involved through direct participation (public representatives, clinicians, and managers will deliberate together to agree on quality-indicator choice and use) and consultation (individual public recommendations for improvement will be collected and presented to decision makers).
In control sites, only clinicians and managers will take part in the prioritisation process.
Data on quality-indicator choice and intended use will be collected.
Our primary outcome will compare quality-indicator choice and agreement with public priorities between intervention and control groups.
A process evaluation based on direct observation, videorecording, and participants' assessment will be conducted to help explain the study's results.
The marginal cost of public involvement will also be assessed.
DiscussionWe identified 801 quality indicators that met our inclusion criteria.
An expert panel agreed on a final set of 37 items containing validated quality indicators relevant for chronic disease prevention and management in primary care.
We pilot tested our public-involvement intervention with 27 participants (11 public representatives and 16 clinicians and managers) and our study instruments with an additional 21 participants, which demonstrated the feasibility of the intervention and generated important insights and adaptations to engage public representatives more effectively.
To our knowledge, this study is the first trial of public involvement in quality-indicator prioritisation, and its results could foster more effective upstream engagement of patients and the public in clinical practice improvement.
Trial registrationNTR2496 (Netherlands National Trial Register, http://www.trialregister.nl). | 215,542,656 |
Title:
Differences in sequencing technologies improve the retrieval of anammox bacterial genome from metagenomes
Abstract:
BackgroundSequencing technologies have different biases, in single-genome sequencing and metagenomic sequencing; these can significantly affect ORFs recovery and the population distribution of a metagenome.
In this paper we investigate how well different technologies represent information related to a considered organism of interest in a metagenome, and whether it is beneficial to combine information obtained using different technologies.
We analyze comparatively three metagenomic datasets acquired from a sample containing the anammox bacterium Candidatus ’Brocadia fulgida’ (B. fulgida).
These datasets were obtained using Roche 454 FLX and Sanger sequencing with two different libraries (shotgun and fosmid).ResultsIn each dataset, the abundance of the reads annotated to B. fulgida was much lower than the abundance expected from available cell count information.
This was due to the overrepresentation of GC-richer organisms, as shown by GC-content distribution of the reads.
Nevertheless, by considering the union of B. fulgida reads over the three datasets, the number of B. fulgida ORFs recovered for at least 80% of their length was twice the amount recovered by the best technology.
Indeed, while taxonomic distributions of reads in the three datasets were similar, the respective sets of B. fulgida ORFs recovered for a large part of their length were highly different, and depth of coverage patterns of 454 and Sanger were dissimilar.
ConclusionsPrecautions should be sought in order to prevent the overrepresentation of GC-rich microbes in the datasets.
This overrepresentation and the consistency of the taxonomic distributions of reads obtained with different sequencing technologies suggests that, in general, abundance biases might be mainly due to other steps of the sequencing protocols.
Results show that biases against organisms of interest could be compensated combining different sequencing technologies, due to the differences of their genome-level sequencing biases even if the species was present in not very different abundances in the metagenomes. | 215,544,293 |
Title:
Characteristics and clustering of human ribosomal protein genes
Abstract:
Background ::: The ribosome is a central player in the translation system, which in mammals consists of four RNA species and 79 ribosomal proteins (RPs).
The control mechanisms of gene expression and the functions of RPs are believed to be identical.
Most RP genes have common promoters and were therefore assumed to have a unified gene expression control mechanism. | 215,544,319 |
Title:
Effectiveness of a multifaceted implementation strategy on physicians’ referral behavior to an evidence-based psychosocial intervention in dementia: a cluster randomized controlled trial
Abstract:
To evaluate the effectiveness of a multifaceted implementation strategy on physicians’ referral rate to and knowledge on the community occupational therapy in dementia program (COTiD program).
A cluster randomized controlled trial with 28 experimental and 17 control clusters was conducted.
Cluster included a minimum of one physician, one manager, and two occupational therapists.
In the control group physicians and managers received no interventions and occupational therapists received a postgraduate course.
In the experimental group physicians and managers had access to a website, received newsletters, and were approached by telephone.
In addition, physicians were offered one outreach visit.
In the experimental group occupational therapists received the postgraduate course, training days, outreach visits, regional meetings, and access to a reporting system.
Main outcome measure was the number of COTiD referrals received by each cluster which was assessed at 6 and 12 months after the start of the intervention.
Referrals were included from both participating physicians (enrolled in the study and received either the control or experimental intervention) and non-participating physicians (not enrolled but of whom referrals were received by participating occupational therapists).
Mixed model analyses were used to analyze the data.
All analyses were based on the principle of intention-to-treat.
At 12 months experimental clusters received significantly more referrals with an average of 5,24 referrals (SD 5,75) to the COTiD program compared to 2,07 referrals in the control group (SD 5,14).
The effect size at 12 months was 0.58.
Although no difference in referral rate was found for the physicians participating in the study, the number of referrals from non-participating physicians (t −2,55 / 43 / 0,02) differed significantly at 12 months.
Passive dissemination strategies are less likely to result in changes in professional behavior.
The amount of physicians exposed to active strategies was limited.
In spite of this we found a significant difference in the number of referrals which was accounted for by more referrals of non-participating physicians in the experimental clusters.
We hypothesize that the increase in referrals was caused by an increase in occupational therapists’ efforts to promote their services within their network.
NCT01117285 | 215,545,498 |
Title:
A prospective longitudinal in vivo 1H MR spectroscopy study of the SIV/macaque model of neuroAIDS
Abstract:
BACKGROUND ::: The neurological complications of HIV infection remain poorly understood.
Clinically, in vivo 1H magnetic resonance spectroscopy (MRS) demonstrates brain injury caused by HIV infection even when the MRI is normal.
Our goal was to undertsand the dynamics of cerebral injury by performing a longitudinal in vivo 1H MRS study of the SIV/macaque model of neuroAIDS. ::: ::: ::: RESULTS ::: Eight rhesus macaques were infected with SIVmac251 and serially imaged with MRI and 1H MRS to terminal AIDS or the endpoint of 2 years.
During acute infection, there were stereotypical brain MRS changes, dominated by a significant elevation of the Cho/Cr ratio in the frontal cortex.
Subsequently, brain metabolic patterns diverged between animals.
There was an elevation of basal ganglia Cho/Cr four weeks post-inoculation in 2 animals that developed SIV encephalitis (p = 0.022).
Metabolite ratios averaged across all 8 animals were not significantly different from baseline at any time point after 2 weeks post inoculation.
However, linear regression analysis on all 8 animals revealed a positive correlation between a change in frontal lobe Cho/Cr and plasma viral load (P < 0.001, R = 0.80), and a negative correlation between NAA/Cr in the basal ganglia and the plasma viral load (P < 0.02, R = -0.73).
No MRI abnormalities were detected at any time. ::: ::: ::: CONCLUSIONS ::: After infection with SIV, macaque brain metabolism changes in a complex manner that is dependent on brain region, host factors and viral load.
An elevation of basal ganglia Cho/Cr 4 weeks after SIV infection may be marker of a propensity to develop SIV encephalitis.
Elevations of Cho/Cr, often observed in CNS inflammation, were associated with increased plasma viral load during acute and chronic infection.
Evidence of neuronal injury in the basal ganglia was associated with increased plasma viral load in the chronic stage of infection.
These observations support the use of drugs capable of controlling the viral replication and trafficking of virus into the CNS, and may help explain the reduction in incidence of HIV-associated dementia in the era of HAART despite the inability of most of those drugs to effectively enter the CNS. | 215,550,536 |
Title:
The influence of population characteristics on variation in general practice based morbidity estimations
Abstract:
BackgroundGeneral practice based registration networks (GPRNs) provide information on morbidity rates in the population.
Morbidity rate estimates from different GPRNs, however, reveal considerable, unexplained differences.
We studied the range and variation in morbidity estimates, as well as the extent to which the differences in morbidity rates between general practices and networks change if socio-demographic characteristics of the listed patient populations are taken into account.
MethodsThe variation in incidence and prevalence rates of thirteen diseases among six Dutch GPRNs and the influence of age, gender, socio economic status (SES), urbanization level, and ethnicity are analyzed using multilevel logistic regression analysis.
Results are expressed in median odds ratios (MOR).ResultsWe observed large differences in morbidity rate estimates both on the level of general practices as on the level of networks.
The differences in SES, urbanization level and ethnicity distribution among the networks' practice populations are substantial.
The variation in morbidity rate estimates among networks did not decrease after adjusting for these socio-demographic characteristics.
ConclusionSocio-demographic characteristics of populations do not explain the differences in morbidity estimations among GPRNs. | 215,550,955 |
Title:
Molecular neuropathology of the synapse in sheep with CLN5 Batten disease
Abstract:
Aims ::: ::: Synapses represent a major pathological target across a broad range of neurodegenerative conditions.
Recent studies addressing molecular mechanisms regulating synaptic vulnerability and degeneration have relied heavily on invertebrate and mouse models.
Whether similar molecular neuropathological changes underpin synaptic breakdown in large animal models and in human patients with neurodegenerative disease remains unclear.
We therefore investigated whether molecular regulators of synaptic pathophysiology, previously identified in Drosophila and mouse models, are similarly present and modified in the brain of sheep with CLN5 Batten disease.
::: ::: ::: ::: Methods ::: ::: Gross neuropathological analysis of CLN5 Batten disease sheep and controls was used alongside postmortem MRI imaging to identify affected brain regions.
Synaptosome preparations were then generated and quantitative fluorescent Western blotting used to determine and compare levels of synaptic proteins.
::: ::: ::: ::: Results ::: ::: The cortex was particularly affected by regional neurodegeneration and synaptic loss in CLN5 sheep, whilst the cerebellum was relatively spared.
Quantitative assessment of the protein content of synaptosome preparations revealed significant changes in levels of seven out of eight synaptic neurodegeneration proteins investigated in the motor cortex, but not cerebellum, of CLN5 sheep (α-synuclein, CSP-α, neurofascin, ROCK2, calretinin, SIRT2, and UBR4). ::: ::: ::: ::: Conclusions ::: ::: Synaptic pathology is a robust correlate of region-specific neurodegeneration in the brain of CLN5 sheep, driven by molecular pathways similar to those reported in Drosophila and rodent models.
Thus, large animal models, such as sheep, represent ideal translational systems to develop and test therapeutics aimed at delaying or halting synaptic pathology for a range of human neurodegenerative conditions. | 215,554,033 |
Title:
Association of a variable number tandem repeat in the NLRP3 gene in women with susceptibility to RVVC
Abstract:
Vaginal infections with Candida spp.
frequently occur in women of childbearing age.
A small proportion of these women experience recurrent vulvovaginal candidosis (RVVC), which is characterized by at least three episodes of infection in one year.
In addition to known risk factors such as antibiotics, diabetes, or pregnancy, host genetic variation and inflammatory pathways such as the IL-1/Th17 axis have been reported to play a substantial role in the pathogenesis of RVVC.
In this study, we assessed a variable number tandem repeat (VNTR) polymorphism in the NLRP3 gene that encodes a component of the inflammasome, processing the proinflammatory cytokines IL-1β and IL-18.
A total of 270 RVVC patients and 583 healthy controls were analyzed, and increased diseases susceptibility was associated with the presence of the 12/9 genotype.
Furthermore, functional studies demonstrate that IL-1β production at the vaginal surface is higher in RVVC patients bearing the 12/9 genotype compared to controls, whereas IL-1Ra levels were decreased and IL-18 levels remained unchanged.
These findings suggest that IL-1β-mediated hyperinflammation conveyed by the NLRP3 gene plays a causal role in the pathogenesis of RVVC and may identify this pathway as a potential therapeutic target in the disease. | 215,556,766 |
Title:
Cost-effectiveness Analysis of Rivaroxaban in the Secondary Prevention of Acute Coronary Syndromes in Sweden
Abstract:
Worldwide, coronary heart disease accounts for 7 million deaths each year.
In Sweden, acute coronary syndrome (ACS) is a leading cause of hospitalization and is responsible for 1 in 4 deaths.
The aim of this analysis was to assess the cost-effectiveness of rivaroxaban 2.5 mg twice daily (BID) in combination with standard antiplatelet therapy (ST-APT) versus ST-APT alone, for the secondary prevention of ACS in adult patients with elevated cardiac biomarkers without a prior history of stroke/transient ischemic attack (TIA), from a Swedish societal perspective, based on clinical data from the global ATLAS ACS 2-TIMI 51 trial, literature-based quality of life data and costs sourced from Swedish national databases.
A Markov model was developed to capture rates of single and multiple myocardial infarction (MI), ischemic and hemorrhagic stroke, thrombolysis in myocardial infarction (TIMI) major, minor, and “requiring medical attention” bleeds, revascularization events, and associated costs and utilities in patients who were stabilized after an initial ACS event.
Efficacy and safety data for the first 2 years came from the ATLAS ACS 2-TIMI 51 trial.
Long-term probabilities were extrapolated using safety and effectiveness of acetylsalicylic acid data, which was estimated from published literature, assuming constant rates in time.
Future cost and effects were discounted at 3.0%.
Univariate and probabilistic sensitivity analyses were conducted.
In the base case, the use of rivaroxaban 2.5 mg BID was associated with improvements in survival and quality-adjusted life years (QALYs), yielding an incremental cost per QALY of 71,246 Swedish Krona (SEK) (€8045).
The outcomes were robust to changes in inputs.
The probabilistic sensitivity analysis demonstrated rivaroxaban 2.5 mg BID to be cost-effective in >99.9% of cases, assuming a willingness-to-pay threshold of SEK 500,000 (€56,458).
Compared with ST-APT alone, the use of rivaroxaban 2.5 mg BID in combination with ST-APT can be considered a cost-effective treatment option for ACS patients with elevated cardiac biomarkers without a prior history of stroke/TIA in Sweden.
Bayer Pharma AG. | 215,562,420 |
Title:
A computational method for identification of vaccine targets from protein regions of conserved human leukocyte antigen binding
Abstract:
BackgroundComputational methods for T cell-based vaccine target discovery focus on selection of highly conserved peptides identified across pathogen variants, followed by prediction of their binding of human leukocyte antigen molecules.
However, experimental studies have shown that T cells often target diverse regions in highly variable viral pathogens and this diversity may need to be addressed through redefinition of suitable peptide targets.
MethodsWe have developed a method for antigen assessment and target selection for polyvalent vaccines, with which we identified immune epitopes from variable regions, where all variants bind HLA.
These regions, although variable, can thus be considered stable in terms of HLA binding and represent valuable vaccine targets.
ResultsWe applied this method to predict CD8+ T-cell targets in influenza A H7N9 hemagglutinin and significantly increased the number of potential vaccine targets compared to the number of targets discovered using the traditional approach where low-frequency peptides are excluded.
ConclusionsWe developed a webserver with an intuitive visualization scheme for summarizing the T cell-based antigenic potential of any given protein or proteome using human leukocyte antigen binding predictions and made a web-accessible software implementation freely available at http://met-hilab.cbs.dtu.dk/blockcons/. | 215,566,519 |
Title:
Testing the efficacy of web-based cognitive behavioural therapy for adult patients with chronic fatigue syndrome (CBIT): study protocol for a randomized controlled trial
Abstract:
Cognitive behavioural therapy (CBT) is an effective treatment for fatigue and disabilities in patients with chronic fatigue syndrome (CFS).
However, treatment capacity is limited.
Providing web-based CBT and tailoring the amount of contact with the therapist to the individual needs of the patient may increase the efficiency of the intervention.
Web-based CBT for adolescents with CFS has proven to be effective in reducing fatigue and increasing school attendance.
In the proposed study the efficacy of a web-based CBT intervention for adult patients with CFS will be explored.
Two different formats of web-based CBT will be tested.
In the first format named protocol driven feedback, patients report on their progress and receive feedback from a therapist according to a preset schedule.
In the second format named support on demand, feedback and support of the therapist is only given when patients ask for it.
The primary objective of the study is to determine the efficacy of a web-based CBT intervention on fatigue severity.
A randomized clinical trial will be conducted.
Two-hundred-forty adults who have been diagnosed with CFS according to the US Centers for Disease Control and Prevention (CDC) consensus criteria will be recruited and randomized to one of three conditions: web-based CBT with protocol driven feedback, web-based CBT with support on demand, or wait list.
Feedback will be delivered by therapists specialized in CBT for CFS.
Each of the web-based CBT interventions will be compared to a wait list condition with respect to its effect on the primary outcome measure; fatigue severity.
Secondary outcome measures are level of disability, physical functioning, psychological distress, and the proportion of patients with clinical significant improvement in fatigue severity.
Outcomes will be assessed at baseline and six months post randomization.
The web-based CBT formats will be compared with respect to the time therapists need to deliver the intervention.
As far as we know this is the first randomized controlled trial (RCT) that evaluates the efficacy of a web-based CBT intervention for adult patients with CFS.
NTR4013 | 215,589,288 |
Title:
Clinical and laboratory manifestation and outcome of icterohemorrhagic leptospirosis patients in Northern Iran
Abstract:
BACKGROUND ::: Icterohemorrhagic form of leptospirosis has a high mortality rate.
In this study, the clinical manifestations, epidemiologic and laboratory findings and outcome of Weil's disease were investigated.
::: ::: ::: METHODS ::: A descriptive cross- sectional study was conducted on 66 consecutive patients with icterohemorrhagic leptospirosis who were admitted to Razi Hospital (The Therapeutic Center of Infectious Diseases in the North of Iran) in 2013.
The inclusion criteria were as follows: All patients who had clinical and epidemiological data suggestive of leptospirosis and displayed icterohemorrhagic form at the time of admission or during hospitalization.
All patients were visited on admission, one, two and six weeks later.
Demographic data, clinical, laboratory features and complications were evaluated, and statistical analysis was performed using SPSS version 13.0. ::: ::: ::: RESULTS ::: Among 66 patients, 89.4% (n = 59) were male, 60% (n = 40) were farmers and 9.1% (n= 6) had a history of swimming in rivers.
The most common complaints were fever and jaundice, respectively.
The most common clinical symptoms were fever (90.9%), myalgia (75.8%), chills (70.8%) and headache (65.1%).
Hyponatremia and hypernatremia were seen in 7.6% and 72.8% of the participants, respectively.
Also, hypokalemia was observed in two patients (3%).
Approximately, half of the cases had leukocytosis and 90% had thrombocytopenia.
Rise of AST, ALT, ALP and bilirubin were seen in 95.2%, 93.6%, 76.2% and 100% of the patients, respectively.
Of the patients, 42.4% experienced complications of icterohemorrhagic leptospirosis including acute renal failure (30.3%) pneumonia (25.8%), pancreatitis (4.5%), subarachnoid hemorrhage (1.5%) and gastrointestinal bleeding (1.5%).
Three cases (4.5%) died, 42 cases (63.7%) were discharged with residual effects and 52 patients (78.8%) had positive serology. ::: ::: ::: CONCLUSION ::: The most significant biochemical abnormalities were thrombocytopenia, hyperbilirubinemia, hyponatremia and hypernatremia and azotemia and the latter remained stable in 2% of the patients at least until the end of the 6-week period. | 215,627,204 |
Title:
Salmonella Typhimurium undergoes distinct genetic adaption during chronic infections of mice
Abstract:
BackgroundTyphoid fever caused by Salmonella enterica serovar Typhi (S. Typhi) is a severe systemic human disease and endemic in regions of the world with poor drinking water quality and sewage treatment facilities.
A significant number of patients become asymptomatic life-long carriers of S. Typhi and serve as the reservoir for the disease.
The specific mechanisms and adaptive strategies enabling S. Typhi to survive inside the host for extended periods are incompletely understood.
Yet, elucidation of these processes is of major importance for improvement of therapeutic strategies.
In the current study genetic adaptation during experimental chronic S. Typhimurium infections of mice, an established model of chronic typhoid fever, was probed as an approach for studying the molecular mechanisms of host-adaptation during long-term host-association.
ResultsIndividually sequence-tagged wild type strains of S. Typhimurium 4/74 were used to establish chronic infections of 129X1/SvJ mice.
Over the course of infections, S. Typhimurium bacteria were isolated from feces and from livers and spleens upon termination of the experiment.
In all samples dominant clones were identified and select clones were subjected to whole genome sequencing.
Dominant clones isolated from either systemic organs or fecal samples exhibited distinct single nucleotide polymorphisms (SNPs).
One mouse appeared to have distinct adapted clones in the spleen and liver, respectively.
Three mice were colonized in the intestines by the same clone containing the same non-synonymous SNP in a transcriptional regulator, kdgR, of metabolic genes.
This likely indicates transmission of this clone between mice.
The mutation was tracked to have occurred prior to 2 weeks post infection in one of the three mice and had subsequently been transmitted to the other two mice.
Re-infection with this clone confirmed that it is superior to the wild type for intestinal colonization.
ConclusionsDuring 4 to 6 weeks of chronic infections, S. Typhimurium acquired distinct SNPs in known regulators of metabolic and virulence genes.
One SNP, the kdgR-SNP was confirmed to confer selective advantage during chronic infections and constitute a true patho-adaptive mutation.
Together, the results provide evidence for rapid genetic adaptation to the host of S. Typhimurium and validate experimental evolution in the context of host infection as a strategy for elucidating pathogen host interactions at the molecular level. | 215,628,348 |
Title:
Validity of the Montreal Cognitive Assessment and the HIV Dementia Scale in the assessment of cognitive impairment in HIV-1 infected patients
Abstract:
The gold standard for evaluating cognitive impairments in HIV-infected patients is to administer an extensive neuropsychological assessment.
This may, however, be time-consuming and hence not always feasible in the clinic.
Therefore, several brief screening tools have been developed.
This study determined the validity of the Montreal Cognitive Assessment (MoCA) and the HIV Dementia Scale (HDS) in detecting cognitive impairment using both the Frascati and cognitive impairment, no dementia (CIND) criteria to classify cognitive impairment in HIV-1 infected patients.
The MoCA, HDS, and an extensive neuropsychological assessment, covering nine cognitive domains, were administered in a group of 102 HIV-infected patients who were all on cART and virologically suppressed for at least 1 year.
Results show that the areas under the curve (AUCs) for both the MoCA and the HDS were statistically significant, using both the Frascati and the CIND criteria as gold standard.
However, the AUCs for the MoCA and HDS did not differ significantly, regardless of the used classification criteria (Frascati: z = 0.37, p = 0.35; CIND: z = −0.62, p = 0.27).
Sensitivity of both the MoCA and HDS were low for the recommended cutoff scores (Frascati: MoCA (<26) = 0.56, HDS (<11) = 0.26; CIND: MoCA (<26) = 0.55, HDS (<11) = 0.36).
Cutoff scores with good sensitivity and adequate specificity could not be determined for both screening instruments.
Therefore, the HDS and MoCA are not recommended as sole instruments to diagnose HIV-associated cognitive impairment. | 215,655,780 |
Title:
Disentangling longitudinal relations between physical activity, work-related fatigue, and task demands
Abstract:
This longitudinal study examined ‘normal’, ‘reversed’, and ‘reciprocal’ relationships between (1) physical activity and work-related fatigue; and (2) physical activity and task demands.
Furthermore, the effects of across-time change in meaningful physical activity groups on levels of employees’ work-related fatigue and task demands were studied.
These groups were based on employees’ compliance with the international physical activity norm.
Two waves with a one-year time lag of a national representative survey on the quality of work, health, and well-being among Dutch employees were used (N = 2275).
Longitudinal effects were tested using Structural Equation Modelling.
Meaningful physical activity groups were compared using group-by-time analysis of covariance.
Support was found for reciprocal relations between physical activity and work-related fatigue.
It was found that an increase in physical activity is associated with a decrease in work-related fatigue over time and that an increase in work-related fatigue is associated with a decrease in physical activity over time.
No significant longitudinal relations were found between physical activity and task demands.
Employees whose compliance with the physical activity norm changed over time showed fairly stable levels of work-related fatigue and task demands.
The current findings provide evidence for the potential role of physical activity in the prevention and reduction in work-related fatigue.
However, results also indicate that fatigued workers, who would benefit most from physical activity, are less physically active.
Our results further indicate that relying on changes in compliance to the physical activity norm may not be the most suitable way to examine changes in work-related fatigue. | 215,657,067 |
Title:
Assessing species diversity of Coral Triangle artisanal fisheries: A DNA barcode reference library for the shore fishes retailed at Ambon harbor (Indonesia)
Abstract:
The Coral Triangle (CT), a region spanning across Indonesia and Philippines, is home to about 4,350 marine fish species and is among the world's most emblematic regions in terms of conservation.
Threatened by overfishing and oceans warming, the CT fisheries have faced drastic declines over the last decades.
Usually monitored through a biomass-based approach, fisheries trends have rarely been characterized at the species level due to the high number of taxa involved and the difficulty to accurately and routinely identify individuals to the species level.
Biomass, however, is a poor proxy of species richness, and automated methods of species identification are required to move beyond biomass-based approaches.
Recent meta-analyses have demonstrated that species richness peaks at intermediary levels of biomass.
Consequently, preserving biomass is not equal to preserving biodiversity.
We present the results of a survey to estimate the shore fish diversity retailed at the harbor of Ambon Island, an island located at the center of the CT that display exceptionally high biomass despite high levels of threat, while building a DNA barcode reference library of CT shore fishes targeted by artisanal fisheries.
We sampled 1,187 specimens and successfully barcoded 696 of the 760 selected specimens that represent 202 species.
Our results show that DNA barcodes were effective in capturing species boundaries for 96% of the species examined, which opens new perspectives for the routine monitoring of the CT fisheries. | 215,658,068 |
Title:
Piezosurgery in implant dentistry
Abstract:
Piezosurgery, or the use of piezoelectric devices, is being applied increasingly in oral and maxillofacial surgery.
The main advantages of this technique are precise and selective cuttings, the avoidance of thermal damage, and the preservation of soft-tissue structures.
Through the application of piezoelectric surgery, implant-site preparation, bone grafting, sinus-floor elevation, edentulous ridge splitting or the lateralization of the inferior alveolar nerve are very technically feasible.
This clinical overview gives a short summary of the current literature and outlines the advantages and disadvantages of piezoelectric bone surgery in implant dentistry.
Overall, piezoelectric surgery is superior to other methods that utilize mechanical instruments.
Handling of delicate or compromised hard- and soft-tissue conditions can be performed with less risk for the patient.
With respect to current and future innovative surgical concepts, piezoelectric surgery offers a wide range of new possibilities to perform customized and minimally invasive osteotomies. | 215,659,477 |
Title:
Community occupational therapy for people with dementia and family carers (COTiD-UK) versus treatment as usual (Valuing Active Life in Dementia [VALID] programme): study protocol for a randomised controlled trial
Abstract:
A community-based occupational therapy intervention for people with mild to moderate dementia and their family carers (Community Occupational Therapy in Dementia (COTiD)) was found clinically and cost effective in the Netherlands but not in Germany.
This highlights the need to adapt and implement complex interventions to specific national contexts.
The current trial aims to evaluate the United Kingdom-adapted occupational therapy intervention for people with mild to moderate dementia and their family carers living in the community (COTiD-UK) compared with treatment as usual.
This study is a multi-centre, parallel-group, pragmatic randomised trial with internal pilot.
We aim to allocate 480 pairs, with each pair comprising a person with mild to moderate dementia and a family carer, who provides at least 4 hours of practical support per week, at random between COTiD-UK and treatment as usual.
We shall assess participants at baseline, 12 and 26 weeks, and by telephone at 52 and 78 weeks (first 40 % of recruits only) after randomisation.
The primary outcome measure is the Bristol Activities of Daily Living Scale (BADLS) at 26 weeks.
Secondary outcome measures will include quality of life, mood, and resource use.
To assess intervention delivery, and client experience, we shall collect qualitative data via audio recordings of COTiD-UK sessions and conduct semi-structured interviews with pairs and occupational therapists.
COTiD-UK is an evidence-based person-centred intervention that reflects the current priority to enable people with dementia to remain in their own homes by improving their capabilities whilst reducing carer burden.
If COTiD-UK is clinically and cost effective, this has major implications for the future delivery of dementia services across the UK.
Current Controlled Trials ISRCTN10748953 Date of registration: 18 September 2014. | 215,671,791 |
Title:
Liquid biopsies in patients with diffuse glioma
Abstract:
Diffuse gliomas are the most common malignant primary tumors of the central nervous system.
Like other neoplasms, these gliomas release molecular information into the circulation.
Tumor-derived biomarkers include proteins, nucleic acids, and tumor-derived extracellular vesicles that accumulate in plasma, serum, blood platelets, urine and/or cerebrospinal fluid.
Recently, also circulating tumor cells have been identified in the blood of glioma patients.
Circulating molecules, vesicles, platelets, and cells may be useful as easily accessible diagnostic, prognostic and/or predictive biomarkers to guide patient management.
Thereby, this approach may help to circumvent problems related to tumor heterogeneity and sampling error at the time of diagnosis.
Also, liquid biopsies may allow for serial monitoring of treatment responses and of changes in the molecular characteristics of gliomas over time.
In this review, we summarize the literature on blood-based biomarkers and their potential value for improving the management of patients with a diffuse glioma.
Incorporation of the study of circulating molecular biomarkers in clinical trials is essential for further assessment of the potential of liquid biopsies in this context. | 215,675,628 |
Title:
Bartonella quintana lipopolysaccharide (LPS): structure and characteristics of a potent TLR4 antagonist for in-vitro and in-vivo applications
Abstract:
The pattern recognition receptor TLR4 is well known as a crucial receptor during infection and inflammation.
Several TLR4 antagonists have been reported to inhibit the function of TLR4.
Both natural occurring antagonists, lipopolysaccharide (LPS) from Gram-negative bacteria as well as synthetic compounds based on the lipid A structure of LPS have been described as potent inhibitors of TLR4.
Here, we have examined the characteristics of a natural TLR4 antagonist, isolated from Bartonella quintana bacterium by elucidating its chemical primary structure.
We have found that this TLR4 antagonist is actually a lipooligosaccharide (LOS) instead of a LPS, and that it acts very effective, with a high inhibitory activity against triggering by the LPS-TLR4 system in the presence of a potent TLR4 agonist (E. coli LPS).
Furthermore, we demonstrate that B. quintana LPS is not inactivated by polymyxin B, a classical cyclic cationic polypeptide antibiotic that bind the lipid A part of LPS, such as E. coli LPS.
Using a murine LPS/D-galactosamine endotoxaemia model we showed that treatment with B. quintana LPS could improve the survival rate significantly.
Since endogenous TLR4 ligands have been associated with several inflammatory- and immune-diseases, B. quintana LPS might be a novel therapeutic strategy for TLR4-driven pathologies. | 215,675,870 |
Title:
Spinal plasticity in robot-mediated therapy for the lower limbs
Abstract:
Robot-mediated therapy can help improve walking ability in patients following injuries to the central nervous system.
However, the efficacy of this treatment varies between patients, and evidence for the mechanisms underlying functional improvements in humans is poor, particularly in terms of neural changes in the spinal cord.
Here, we review the recent literature on spinal plasticity induced by robotic-based training in humans and propose recommendations for the measurement of spinal plasticity using robotic devices.
Evidence for spinal plasticity in humans following robotic training is limited to the lower limbs.
Body weight-supported (BWS) robotic-assisted step training of patients with spinal cord injury (SCI) or stroke patients has been shown to lead to changes in the amplitude and phase modulation of spinal reflex pathways elicited by electrical stimulation or joint rotations.
Of particular importance is the finding that, among other changes to the spinal reflex circuitries, BWS robotic-assisted step training in SCI patients resulted in the re-emergence of a physiological phase modulation of the soleus H-reflex during walking.
Stretch reflexes elicited by joint rotations constitute a tool of interest to probe spinal circuitry since the technology necessary to produce these perturbations could be integrated as a natural part of robotic devices.
Presently, ad-hoc devices with an actuator capable of producing perturbations powerful enough to elicit the reflex are available but are not part of robotic devices used for training purposes.
A further development of robotic devices that include the technology to elicit stretch reflexes would allow for the spinal circuitry to be routinely tested as a part of the training and evaluation protocols. | 215,683,025 |
Title:
Rumination-focused cognitive behaviour therapy vs. cognitive behaviour therapy for depression: study protocol for a randomised controlled superiority trial
Abstract:
Cognitive behavioural therapy is an effective treatment for depression.
However, one third of the patients do not respond satisfactorily, and relapse rates of around 30 % within the first post-treatment year were reported in a recent meta-analysis.
In total, 30–50 % of remitted patients present with residual symptoms by the end of treatment.
A common residual symptom is rumination, a process of recurrent negative thinking and dwelling on negative affect.
Rumination has been demonstrated as a major factor in vulnerability to depression, predicting the onset, severity, and duration of future depression.
Rumination-focused cognitive behavioural therapy is a psychotherapeutic treatment targeting rumination.
Because rumination plays a major role in the initiation and maintenance of depression, targeting rumination with rumination-focused cognitive behavioural therapy may be more effective in treating depression and reducing relapse than standard cognitive behavioural therapy.
This study is a two-arm pragmatic randomised controlled superiority trial comparing the effectiveness of group-based rumination-focused cognitive behaviour therapy with the effectiveness of group-based cognitive behavioural therapy for treatment of depression.
One hundred twenty-eight patients with depression will be recruited from and given treatment in an outpatient service at a psychiatric hospital in Denmark.
Our primary outcome will be severity of depressive symptoms (Hamilton Rating Scale for Depression) at completion of treatment.
Secondary outcomes will be level of rumination, worry, anxiety, quality of life, behavioural activation, experimental measures of cognitive flexibility, and emotional attentional bias.
A 6-month follow-up is planned and will include the primary outcome measure and assessment of relapse.
The clinical outcome of this trial may guide clinicians to decide on the merits of including rumination-focused cognitive behavioural therapy in the treatment of depression in outpatient services.
ClinicalTrials.gov Identifier: NCT02278224, registered 28 Oct. 2014. | 215,683,514 |
Title:
Sex differences in risk-taking and associative learning in rats
Abstract:
In many species, males tend to have lower parental investment than females and greater variance in their reproductive success.
Males might therefore be expected to adopt more high-risk, high-return behaviours than females.
Next to risk-taking behaviour itself, sexes might also differ in how they respond to information and learn new associations owing to the fundamental link of these cognitive processes with the risk–reward axis.
Here we investigated sex differences in both risk-taking and learned responses to risk by measuring male and female rats’ (Rattus norvegicus) behaviour across three contexts in an open field test containing cover.
We found that when the environment was novel, males spent more time out of cover than females.
Males also hid less when exposed to the test arena containing predator odour.
By contrast, females explored more than males when the predator odour was removed (associatively learned risk).
These results suggest that males are more risk-prone but behave more in line with previous experiences, while females are more risk-averse and more responsive to changes in their current environment.
Our results suggest that male and female rats differ in how they cope with risk and highlight that a general link may exist between risk-taking behaviour and learning style. | 215,690,875 |
Title:
Dutch and English toddlers' use of linguistic cues in predicting upcoming turn transitions
Abstract:
Adults achieve successful coordination during conversation by using prosodic and lexicosyntactic cues to predict upcoming changes in speakership.
We examined the relative weight of these linguistic cues in the prediction of upcoming turn structure by toddlers learning Dutch (Experiment 1; N = 21) and British English (Experiment 2; N = 20) and adult control participants (Dutch: N = 16; English: N = 20).
We tracked participants' anticipatory eye movements as they watched videos of dyadic puppet conversation.
We controlled the prosodic and lexicosyntactic cues to turn completion for a subset of the utterances in each conversation to create four types of target utterances (fully incomplete, incomplete syntax, incomplete prosody, and fully complete).
All participants (Dutch and English toddlers and adults) used both prosodic and lexicosyntactic cues to anticipate upcoming speaker changes, but weighed lexicosyntactic cues over prosodic ones when the two were pitted against each other.
The results suggest that Dutch and English toddlers are already nearly adult-like in their use of prosodic and lexicosyntactic cues in anticipating upcoming turn transitions. | 215,703,953 |
Title:
Amplification of pico-scale DNA mediated by bacterial carrier DNA for small-cell-number transcription factor ChIP-seq
Abstract:
Background ::: Chromatin-Immunoprecipitation coupled with deep sequencing (ChIP-seq) is used to map transcription factor occupancy and generate epigenetic profiles genome-wide.
The requirement of nano-scale ChIP DNA for generation of sequencing libraries has impeded ChIP-seq on in vivo tissues of low cell numbers. | 215,710,620 |
Title:
Dynamic gaze-position prediction of saccadic eye movements using a Taylor series
Abstract:
Gaze-contingent displays have been widely used in vision research and virtual reality applications.
Due to data transmission, image processing, and display preparation, the time delay between the eye tracker and the monitor update may lead to a misalignment between the eye position and the image manipulation during eye movements.
We propose a method to reduce the misalignment using a Taylor series to predict the saccadic eye movement.
The proposed method was evaluated using two large datasets including 219,335 human saccades (collected with an EyeLink 1000 system, 95% range from 1° to 32°) and 21,844 monkey saccades (collected with a scleral search coil, 95% range from 1° to 9°).
When assuming a 10-ms time delay, the prediction of saccade movements using the proposed method could reduce the misalignment greater than the state-of-the-art methods.
The average error was about 0.93° for human saccades and 0.26° for monkey saccades.
Our results suggest that this proposed saccade prediction method will create more accurate gaze-contingent displays. | 215,712,348 |
Title:
Scalable photonic network architecture based on motional averaging in room temperature gas
Abstract:
Quantum interfaces between photons and ensembles of atoms have emerged as powerful tools for quantum technologies.
A major objective for such interfaces is high fidelity storage and retrieval of a photon in a collective quantum state of many atoms.
This requires long-lived collective superposition states, which is typically achieved with immobilized atoms.
Thermal atomic vapors, which present a simple and scalable resource, have, so far, only been used for continuous variable processing or for discrete variable processing on short time scales where atomic motion is negligible.
We develop a theory based on the concept of motional averaging to enable room temperature discrete variable quantum memories and coherent single photon sources.
We show that by choosing the interaction time so that atoms kept under spin protecting conditions can cross the light beam several times during the interaction combined with suitable spectral filtering, we erase the"which atom"information and obtain an efficient and homogenous coupling between all atoms and the light.
Heralded single excitations can thus be created and stored as collective spinwaves, which can later be read out to produce coherent single photons in a scalable fashion.
We demonstrate the feasibility of this approach to scalable quantum memories with a proof-of-principle experiment with room temperature atoms contained in microcells with spin protecting coating, placed inside an optical cavity.
The experiment is performed at conditions corresponding to a few photons per pulse and clearly demonstrates a long coherence time of the forward scattered photons, which is the essential feature of the motional averaging. | 215,713,250 |
Title:
Machine learning-based CT radiomics model for predicting hospital stay in patients with pneumonia associated with SARS-CoV-2 infection: A multicenter study
Abstract:
Abstract Objectives To develop and test machine learning-based CT radiomics models for predicting hospital stay in patients with pneumonia associated with SARS-CoV-2 infection.
Design Cross-sectional Setting Multicenter Participants A total of 52 patients with laboratory-confirmed SARS-CoV-2 infection and their initial CT images were enrolled from 5 designated hospitals in Ankang, Lishui, Zhenjiang, Lanzhou, and Linxia between January 23, 2020 and February 8, 2020.
As of February 20, patients remained in hospital or with non-findings in CT were excluded.
Therefore, 31 patients with 72 lesion segments were included in the final analysis.
Intervention CT radiomics models based on logistic regression (LR) and random forest (RF) were developed on features extracted from pneumonia lesions in training and inter-validation datasets.
The predictive performance was further evaluated in test dataset on lung lobe- and patients-level.
Main outcomes Short-term hospital stay (≤10 days) and long-term hospital stay (>10 days).
Results The CT radiomics models based on 6 second-order features were effective in discriminating short- and long-term hospital stay in patients with pneumonia associated with SARS-CoV-2 infection, with areas under the curves of 0.97 (95%CI 0.83-1.0) and 0.92 (95%CI 0.67-1.0) by LR and RF, respectively, in the test dataset.
The LR model showed a sensitivity and specificity of 1.0 and 0.89, and the RF model showed similar performance with sensitivity and specificity of 0.75 and 1.0 in test dataset.
Conclusions The machine learning-based CT radiomics models showed feasibility and accuracy for predicting hospital stay in patients with pneumonia associated with SARS-CoV-2 infection. | 215,718,655 |
Title:
Transmission potential of the novel coronavirus (COVID-19) onboard the Diamond Princess Cruises Ship, 2020
Abstract:
An outbreak of COVID-19 developed aboard the Princess Cruises Ship during January-February 2020.
Using mathematical modeling and time-series incidence data describing the trajectory of the outbreak among passengers and crew members, we characterize how the transmission potential varied over the course of the outbreak.
Our estimate of the mean reproduction number in the confined setting reached values as high as ~11, which is higher than mean estimates reported from community-level transmission dynamics in China and Singapore (approximate range: 1.1-7).
Our findings suggest that Rt decreased substantially compared to values during the early phase after the Japanese government implemented an enhanced quarantine control.
Most recent estimates of Rt reached values largely below the epidemic threshold, indicating that a secondary outbreak of the novel coronavirus was unlikely to occur aboard the Diamond Princess Ship. | 215,718,721 |
Title:
Amplicon based MinION sequencing of SARS-CoV-2 and metagenomic characterisation of nasopharyngeal swabs from patients with COVID-19
Abstract:
COVID-19 is a complex disease phenotype where the underlying microbiome could influence morbidity and mortality.
Amplicon and metagenomic MinION based sequencing was used to rapidly (within 8 hours) identify SARS-CoV-2 and assess the microbiome in nasopharyngeal swabs obtained from patients with COVID-19 by the ISARIC 4C consortium. | 215,718,865 |
Title:
Clinical Characteristics of Two Human to Human Transmitted Coronaviruses: Corona Virus Disease 2019 versus Middle East Respiratory Syndrome Coronavirus.
Abstract:
After the outbreak of the middle east respiratory syndrome (MERS) worldwide in 2012.
Currently, a novel human coronavirus has caused a major disease outbreak, and named corona virus disease 2019 (COVID-19).
The emergency of MRES-COV and COVID-19 has caused global panic and threatened health security.
Unfortunately, the similarities and differences between the two coronavirus diseases remain to be unknown.
The aim of this study, therefore, is to perform a systematic review to compare epidemiological, clinical and laboratory features of COVID-19 and MERS-COV population.
We searched PubMed, EMBASE and Cochrane Register of Controlled Trials database to identify potential studies reported COVID-19 or MERS-COV.
Epidemiological, clinical and laboratory outcomes, the admission rate of intensive cure unit (ICU), discharge rate and fatality rate were evaluated using GraphPad Prism software.
Thirty-two studies involving 3770 patients (COVID-19 = 1062, MERS-COV = 2708) were included in this study.
The present study revealed that compared with COVID-19 population, MERS-COV population had a higher rate of ICU admission, discharge and fatality and longer incubation time.
It pointed out that fever, cough and generalised weakness and myalgia were main clinical manifestations of both COVID-19 and MERS-COV, whereas ARDS was main complication.
The most effective drug for MERS-COV is ribavirin and interferon. | 215,718,878 |
Title:
SARS-CoV-2 transmission in cancer patients of a tertiary hospital in Wuhan
Abstract:
In December 2019, an outbreak of atypical pneumonia known as 2019 novel coronavirus disease (COVID-19) occurred in Wuhan, China.
This new type of pneumonia is characterized by rapid human-to-human transmission.
Among the different disease types, cancer patients are often recalled to the hospital for treatment and disease surveillance, and the majority of cancer treatments such as chemotherapy and radiotherapy are immunosuppressive.
This prompts us to consider if cancer patients were at an elevated risk of SARS-CoV-2 infection.
A total of 1,524 cancer patients who were managed at our tertiary cancer institution-Zhongnan hospital of Wuhan University were reviewed during the period of Dec 30, 2019 to Feb 17, 2020.
It was found that cancer patients had an estimated 2-fold increased risk of COVID-19 than the general population.
We identified twelve patients who were infected with SARS-CoV-2, with two recorded deaths (16.7%), albeit one patient passed away from a COVID-19 unrelated cause.
Interestingly, only five of these patients were ongoing treatment at the time of contracting the virus, suggesting that hospital visitation was the likely factor contributing to the elevated incidence in cancer patients.
Moreover, we also observed that the incidence of severe COVID-19 was not higher than in the general population.
Consequently, for cancer patients who require treatment, proper isolation protocols must be in place to mitigate the risk of SARS-CoV-2 infection. | 215,718,880 |
Title:
Role of temperature and humidity in the modulation of the doubling time of COVID-19 cases
Abstract:
COVID-19 is having a great impact on public health, mortality and economy worldwide, in spite of the efforts to prevent its epidemy.
The SARS-CoV-2 genome is different from that of MERS-CoV and SARS-CoV, although also expected to spread differently according to meteorological conditions.
Our main goal is to investigate the role of some meteorological variables on the expansion of this outbreak.
In this study, an exponential model relating the number of accumulated confirmed cases and time was considered.
The rate of COVID-19 spread, using as criterion the doubling time of the number of confirmed cases, was used as dependent variable in a linear model that took four independent meteorological variables: temperature, humidity, precipitation and wind speed.
Only China cases were considered, to control both cultural aspects and containment policies.
Confirmed cases and the 4 meteorological variables were gathered between January 23 and March 1 (39 days) for the 31 provinces of Mainland China.
Several periods of time were sampled for each province, obtaining more than one value for the rate of disease progression.
Two different periods of time were tested, of 12 and 15 days, along with 3 and 5 different starting points in time, randomly chosen.
The median value for each meteorological variable was computed, using the same time period; models with adjusted R square above 0.75 were selected.
The rate of progression and doubling time were computed and used to fit a linear regression model.
Models were evaluated using alpha=0.05.
Results indicate that the doubling time correlates positively with temperature and inversely with humidity, suggesting that a decrease in the rate of progression of COVID-19 with the arrival of spring and summer in the north hemisphere.
A 20oC increase is expected to delay the doubling time in 1.8 days.
Those variables explain 18% of the variation in disease doubling time; the remaining 82% may be related to containment measures, general health policies, population density, transportation or cultural aspects. | 215,718,897 |
Title:
Risk factors related to hepatic injury in patients with corona virus disease 2019
Abstract:
Aims: Corona virus disease 2019 (COVID-19) has rapidly become the most severe public health issue all over the world.
Despite respiratory symptoms, hepatic injury has also been observed in clinical settings.
This study aimed to investigate the risk factors involved with hepatic injury in the patients with COVID-19.
Methods: A total of 85 hospitalized patients who were diagnosed with COVID-19 in Beijing Youan Hospital were retrospectively analyzed.
According to liver function, they were divided into ALT normal group (n=52) and ALT elevation group (n=33).
Clinical features and laboratory data were compared between the two groups.
The independent risk factors for liver injury were analyzed.
Results: There were 33 patients with hepatic injury in our study, accounting for 38.8% (33/85).
The patients in ALT elevation group were older than those in ALT normal group.
The levels of lactic acid, CRP, myoglobin, and neutrophils were significantly higher in ALT elevation group.
The lymphocytes and albumin were significantly lower in ALT elevation group.
The proportion of severe and critical patients in ALT elevation group was significantly higher.
Multivariate logistic regression analysis showed CRP ≥20 mg/L and lymphocyte count< 1.1*10^9/L were independently related to hepatic injury.
Conclusions: Lymphopenia and CRP may serve as the risk factors related to hepatic injury in patients with COVID-19, which might be related to inflammatory cytokine storm in liver injury.
Early detection and timely treatment of hepatic injury in patients with COVID-19 are necessary. | 215,718,960 |
Title:
Spatial Information in Large-Scale Neural Recordings
Abstract:
To record from a given neuron, a recording technology must be able to separate the activity of that neuron from the activity of its neighbors.
Here, we develop a Fisher information based framework to determine the conditions under which this is feasible for a given technology.
This framework combines measurable point spread functions with measurable noise distributions to produce theoretical bounds on the precision with which a recording technology can localize neural activities.
If there is suffi□cient information to uniquely localize neural activities, then a technology will, from an information theoretic perspective, be able to record from these neurons.
We (1) describe this framework, and (2) demonstrate its application in model experiments.
This method generalizes to many recording devices that resolve objects in space and should be useful in the design of next generation scalable neural recording systems. | 215,721,368 |
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