Input: Claim: Gene therapy is being developed to treat genetic disorders such as cystic fibrosis. [SEP] Text: Any increase in CFTR protein expression following the delivery of the study drug would result in an increased efflux of the SPQ fluorescence. There was no significant difference in SPQ efflux between the two groups (CFTR gene therapy n = 6; placebo n = 7), MD 0. 3 mMs‐1 (95% CI ‐0. 12 to 0. 72) (Analysis 1. 13). Data for the placebo group were estimated from a figure in the original paper. The original paper reports a significant increase in efflux (P < 0. 05) in the active, but not in the placebo group (Alton 1999). 13. Radiological measures of lung disease a. Validated chest radiograph scores This outcome was only reported in Alton 1999, which used the previously validated CF Northern score (Conway 1994). The investigators report "no significant change from baseline" at Day 29, but the data are not shown (Alton 1999). b. Validated computerised tomogram (CT) score Two studies reported this outcome measure (Alton 2015; Moss 2004). 2015, high resolution CT scans were obtained from participants at baseline and at 28 days (plus or minus five days) after dose 12 of the study drug (Alton 2015). Investigators then studied the following features: extent of bronchiectasis (scored per lobe on a range of 0 to 3); severity of bronchiectasis and bronchial wall thickness (scored per lobe on a range of 0 to 4); small and large airway mucus plugs (scored per lobe on a range of 0 to 2); and gas trapping on expiratory CT (scored on a percentage basis). Results demonstrated a significant improvement in CT gas trapping for CFTR gene replacement therapy compared to placebo, MD –3. 49 (95% CI –6. 96 to –0. 03) (Alton 2015). For the remaining features (extent of bronchiectasis, severity of bronchiectasis, bronchial wall thickening and small and large airway plugs), there was no significant difference in the change in score between treatment groups (Alton 2015). 2004, participants underwent a high resolution CT scan at baseline and on Day 90, 30 days after the third dose of study drug had been administered (Moss 2004).

Output: corroborate


Input: Claim: Some genetic therapies aim to slow aging by targeting telomere shortening and other cellular aging processes. [SEP] Text: Ramírez énez R, Martín-Malo A, Rodríguez M, et al. Stress-induced premature senescence in mononuclear cells from patients on long-term hemodialysis. Kidney Dis. 2005; 45:353-359. [PubMed] 49. von Zglinicki T. Telomere shortening and haemodialysis. Blood Purif. 2006; 24:185-189. [PubMed] 50. Broberg K, Björk J, Paulsson K, Höglund M, Albin M. Constitutional short telomeres are strong genetic susceptibility markers for bladder cancer. Carcinogenesis. 2005; 26:1263-1271. [PubMed] 51. Genes and pathways downstream of telomerase in melanoma metastasis. . 2006; 103:11306-11311. [PubMed] 52. Cai Z, Yan L-J, Ratka A. Telomere shortening and Alzheimer's disease. Neuromolecular Med. 2013; 15:25-48. [PubMed] 53. . Aging-associated alteration of telomere length and subtelomeric status in female patients with Parkinson's disease. J Neurogenet. 2012; 26:245-251. [PubMed] 54. Length in Major Depression: Correlations with Chronicity, Inflammation and - Preliminary Findings. PLoS One. 2011; 6:e17837 [PubMed] 55. Leucocyte telomere length and risk of type 2 diabetes mellitus: new prospective cohort study and literature-based meta-analysis. PLoS One. 2014; 9:e112483 [PubMed] 56. Willeit P, Willeit J, Kloss-Brandstätter A, Kronenberg F, Kiechl S. Fifteen-Year Follow-up of and Cancer Mortality. JAMA. 2011; 36:10-12. . 57. . Length: Implications of in Attenuating Age-Disease. J Heal. 2015;. 58. Mitochondrial dysfunction accounts for the stochastic heterogeneity in telomere-dependent senescence. PLoS Biol. 2007; 5:e110 [PubMed] 59. H. The telomere syndromes.

Output: contrast


Input: Claim: All insects can communicate through sounds and music. [SEP] Text: Lab Notes9 PostedThis lab note is for backers onlyMy process turning data to soundAugust 3, 20231112This lab note is for backers onlyPreparing the final experiment August 1, 20230016This lab note is for backers onlyPreliminary logging of electrical spiking activity of. . . October 16, 20220180Additional InformationAfter the supplies have been purchased I will begin working with the Arduinos to set up the datalogging system. This has to be done first as I would like to start recording data from the beginning on inoculation. In addition, the Arduinos for terrarium regulation must be set up before the terrariums are prepared for the experiment. After the Arduinos are set up, the terrarium ecosystems need to be prepared. I may give the plants in the tanks some time to adjust to their new habitat before inoculating the mycelium. At the moment of inoculation, I want to begin recording data for both real-time and data logging purposes. I will record, listen, and adjust the modular systems in accordance to the frequencies produced. The main focus of my experiment is the moment in which the mycelium bodies meet near the middle of the tank. I am most interested in comparing and contrasting the interaction between same species and of different species. Will there be changes in conductivity between the two interactions? I will continue to monitor the mycelium as they intermingle in the tank. I expect the experiment in total could take anywhere from 4-9 months depending on how long the set up takes, the growth speed of the mycelium, contamination in the terrariums, and other unknown factors that could interfere along the way. In the future, I hope to have my tanks set up to a live feed system where people can log into the system and listen in real time from anywhere in the world. In addition, I eventually would like to have a wireless sensor recording system to bring my research into the actual forest and record the frequencies of mycelium across the world to then, in turn, create audio files with the data I record. Project Backers17Backers100%Funded$4,950Total Donations$291. 18Please wait. . .

Output: pass


Input: Claim: Gene therapy is being developed to treat genetic disorders such as cystic fibrosis. [SEP] Text: The CT scans were scored on a scale from 0 to 100 using an algorithm that had not been previously validated and was developed for this study. There was no significant difference between the groups in terms of change in CT score from baseline at Day 90, with the CFTR gene replacement group (n = 18) mean (SD) ‐1. 00 (3. 00), placebo group (n = 17) mean (SD) 0. 00 (6. 00); MD ‐1. 00 (95% CI ‐4. 17 to 2. 17) (Analysis 1. 14). These data must be treated with caution as the scoring system had not been previously validated. of main results Four randomised controlled trials met the inclusion criteria for this review. They compared cystic fibrosis transmembrane conductance regulator (CFTR) gene replacement to placebo delivered to the lungs of participants with cystic fibrosis (CF) (Alton 1999; Alton 2015; Moss 2004; Moss 2007). Two studies examined a liposome‐based CFTR gene delivery agent (Alton 1999; Alton 2015). 1999 participants received a single dose of study drug with follow up for 29 days (Alton 1999) and in Alton 2015 participants received monthly doses for 12 months with follow up for up to 13 months (Alton 2015). 2015, at 12 months participants who received CFTR gene transfer agents had an improvement in relative change in forced expiratory volume at one second (FEV1) % predicted compared to those who had received placebo, MD 3. 66 (95% CI 0. 15 to 7. 17) (Analysis 1. 7). This was also demonstrated after two and three months, but not at the remaining time points over the 12‐month study period (Alton 2015). Alton 2015 also demonstrated significant improvements in FVC (% predicted) at two, three, 11 and 12 months in participants receiving CFTR gene replacement therapy compared to placebo. Alton 1999 reported an significant increase in FVC (L) in the placebo group compared to the treatment group at up to 24 hours. With regards to adverse events, Alton 1999 reported "influenza‐like" symptoms in seven out of eight participants who received the CFTR gene transfer reagents (Alton 1999). In the larger Alton 2015, these symptoms were reported in one participant who had taken at least four doses and one in the placebo arm (Alton 2015).

Output: corroborate


Input: Claim: Some genetic therapies aim to slow aging by targeting telomere shortening and other cellular aging processes. [SEP] Text: This view has been challenged by the discovery of DNA content variations apparently indicating a cell cycle re-induction in about 10-20% of post-mitotic neurons, as described for the cortex of healthy aging brains and in Alzheimer’s disease [8,9]. In this context, an open question remains whether a putative telomere shortening in neural cell populations may eventuate by unscheduled abortive cell division cycles, or occur even independently of any cell cycle activity. Telomere length is maintained by the enzyme telomerase, which adds ()n repeats to telomere endings. In adult somatic tissues including the CNS, telomerase shows very low activity and transcript levels [10,11], which are inconsistent regarding their correlation with protein levels, e. g. , in murine cortex [12]. Moreover, TERT protein displays a maturation-dependent allocation to different subcellular compartments, thereby exhibiting a shift from nuclear preponderance in embryonic to cytoplasmic prevalence in adult cortex [12]. Differences in spatial TERT distribution and localization, e. g. , to mitochondrial versus nuclear structural components also argue for telomere-independent functions, as shown for cell viability and tissue homeostasis [13], and in relation to DNA structure stabilization and contribution to DDR in several tissues including the CNS [14]. This study aimed to evaluate the impact of physiological aging on telomere length alterations and telomerase activity in brain tissue, as exemplified for murine neocortex, with particular emphasis on neuronal cell moieties. Using Flow-FISH techniques, changes in the relative telomere length (RTL) were first dissected for replicative and non-replicative neural populations as a function of aging in a C57BL/6 wild type mouse colony aged up to 25-27 months. Age-dependent alterations in cortical RTL were confirmed and further specified for neurons by qPCR-based telomere length analysis, and correlated with telomerase activity and telomerase inductive NF-κB Rela transcript levels, the second being a master regulator of age-related genetic reprogramming.

Output: contrast


Input: Claim: All insects can communicate through sounds and music. [SEP] Text: Loading. . . in With Username/your institution Basket en de fr Publish with us Submit your Proposal 2024 Competition 2024 & Events and & Law, Economics & Media & Society & & & and in × Zitatvorschau in to clipboard. ris BibTeX Zotero. bib EndNote. enw Music as Introduction to by (Author) ©2016 Monographs 339 Arts eBook for US$ 79. 75 Download immediately. Incl. VAT Format: PDF and ePUB – for all devices Hardcover for US$ 98. 25 Shipping in approx. 10 working days national, international shipping possible Add to cart is often defined as art for the ear, as the language of feeling, of the heart, as sound play, or as the science of composition. But music also conveys intellectual and emotional experiences, literary, religious, philosophical, social and political ideas. Countless composers encrypt contents in their music that can be deciphered by a variety of methods. This book is designed as an introduction to the basic questions of musical semantics and discusses Beethoven’s committed art, the core ideas of the «Ring of the Nibelung» and of the «Symphony of a Thousand», Wagner’s idea of a religion of art, the relation of music and poetry, the musico-literary conceptions of composers, the large field of program music and the history of the impact of Gustav Mahler. the author About the book This eBook can be cited Table of I. of the Message in Music II. Public and in Music III. of Depth 1. Esprit contra Profundity: Mediterranean vs. 2. Music as Expression of the “Being”? 3. and Music as Message IV. “Relational Magic” in the Music of Wagner’s Ring of the Nibelung 1. On the Function of the Leitmotif 2. Presentiment, Realization and Remembrance 3. “of Doom” V. Wagner’s Idea of a Religion of Art 1. of Introduction 2. Art and Religion in Wagner’s 3. On Wagner’s Doctrine of Regeneration 4. Christianity, Brahmanism and the Critique of Religions 5. of Art with Religion 6. of the Religion of Art 7. Parsifal: of the Idea 8. Art as Substitute for Religion?

Output: pass


Input: Claim: Gene therapy is being developed to treat genetic disorders such as cystic fibrosis. [SEP] Text: The two Moss studies used a viral CFTR gene delivery system (AAV) with follow up for 150 to 210 days respectively (Moss 2004; Moss 2007). These studies were of similar design, although three doses were given in the Moss 2004 and two doses in Moss 2007. There were no significant differences in rate of exacerbation between the treatment group and placebo in either study. Moss 2004 demonstrated a significant improvement in respiratory function (FEV1) 30 days after participants had received their first dose of gene therapy agent. This finding was not confirmed in Moss 2007 or in our meta‐analysis (Moss 2004; Moss 2007). study nor our meta‐analysis of FVC (L) showed any significant difference between treatment and placebo groups at either 30 days or two months (Analysis 1. 5). No study reported on survival; however, no deaths were reported in three of the studies and the single death reported in one study was not treatment related. Overall completeness and applicability of evidence Four trials recruiting 302 participants with CF were included in this review; three trials recruited a mixture of males and females aged 12 years and over (Alton 2015; Moss 2004; Moss 2007) and one recruited only adult males due to regulatory restrictions (Alton 1999). The mean age of participants in the four studies was 24. 5 years. Homozygous ∆F508 was the commonest genotype in the studies. There are insufficient data reported in the studies for some outcomes considered to be important for this review: oral antibiotics (days or episodes); number of days as a hospital inpatient; need for extra treatment (physiotherapy); school or work attendance; height; and sputum rheology. Quality of the evidence All included studies had a parallel design. Overall there were minor issues with quality, in particular risk of bias from concealment, allocation and randomisation. Methods of randomisation and allocation concealment are specified in just one study (Alton 2015); in the remaining studies, they are unclear (Alton 1999; Moss 2004; Moss 2007). 2004, 83% of randomised participants received all three doses of study drug and it is not stated whether withdrawals had been originally allocated to the active or the placebo group (Moss 2004). Post‐allocation withdrawal also occurred in Moss 2007, but to a lesser extent study (Moss 2007).

Output: corroborate


Input: Claim: Some genetic therapies aim to slow aging by targeting telomere shortening and other cellular aging processes. [SEP] Text: These were found to be low in mature cortex as compared to E13 brain (Figure 6A) and remained unchanged with chronological aging, as demonstrated by the comparably weak activity levels in 3 months young and 24-27 months aged murine neocortices (P = 0. 617; Figure 6A). The observed reduction in RTL with aging might therefore be a result of the intrinsic inability of the murine brain to induce telomerase activity, which otherwise could compensate for telomere erosion. Figure 6. Age-associated changes in TERT protein content, telomerase activity and relative Rela and c-Rel expression levels in the murine cortex. (A) Telomerase activity assessed from cortical isolates as a function of age. Telomerase activity in the mature neocortex remained unchanged with aging, displaying activity levels approximately 20 times lower than in E13 brain. Bars of probe samples represent means ± SEM (n = 5). HI E13, heat inactivated E13 protein extract. (B-D) Relative TERT protein levels in different subcellular compartments of murine cortical tissue at young (Y) and aged (A) states. (B) Left blot: blot. Purity of the cellular subfractions is illustrated by the enriched levels of the nuclear and cytoplasmic marker proteins Histone H3 and GAPDH in the chromatin-bound nuclear (cNE) and cytoplasmic (CP) fractions, respectively. Right blot: TERT product at the appropriate molecular weight of ~ 125 kDa in whole cell (WC) lysates from ovary (Ov) and cortex of young (Y) and aged (A) mice. (C) Simple Western™ technique. Little or no TERT protein was expressed in the soluble nuclear (sNE) and chromatin-bound nuclear (cNE) fraction, respectively, at both age categories, whereas TERT protein was found at significantly higher levels in the cytoplasmic (CP) and membrane (ME) fractions at 27 months of age. Specificity of the TERT antibody was proven by the detection of different TERT protein levels in whole cell (WC) lysates prepared from small intestine (In), ovary (Ov), muscle (Mu) and cortex of young mice (Y). All cortical samples were assayed in the same run, as were all the control samples.

Output: contrast


Input: Claim: All insects can communicate through sounds and music. [SEP] Text: Wagner as a Religious Founder? 9. Hitler and Wagner 10. Ban on Parsifal since 1939 11. Conclusion VI. of a Thousand as a Message to Humanity 1. Mahler’s “Mass” and “Gift to the Nation” 2. Genesis 3. Love as Productive Power: On the of the 4. On the Translation into Music VII. Basics of 1. Introduction 2. “Characteristic” Music and “Painting Symphonies” (symphonies à programmes) 3. and “Narration of Inner Processes” 4. Concepts and 5. Headings vs. . with IX. “Tone Poets” and “Specific Musicians”: 19th-Types 1. Art-2. Composers and Fractions 3. Schumann, Liszt and Wagner as All-Musicians X. Music and Poetry: of Schumann, Wagner and Liszt 1. Schumann’s Ideal of a “Poetic Music” 2. Wagner’s Ideal of a Union of the “Art Forms” in the Drama 3. Liszt’s Ideal of XI. Schumann’s XII. in Schumann’s Music XIII. Berlioz’ Conception of the “Instrumental Drama” XIV. Liszt’s Conception of the “Musical Epopee” XV. Liszt’s Faust Symphony: A 1. Aspects of the Investigation 2. Liszt’s Observations about Goethe’s Faust 3. Themes and Structure of the “Faust” Movement 4. Harmonic Symbolism: Triad as Emblem of Faust 5. of the “Faust” and “Gretchen” Movements 6. Tectonics and Character of the “Gretchen” Movement 7. Stock of the “Mephisto” Movement and Liszt’s Technique of Distortion 8. Piece Malédiction as a Source of the “Mephisto” Movement 9. as of the “Mephisto” Movement 10. Liszt’s Setting of the Chorus mysticus XVI.

Output: pass


Input: Claim: Gene therapy is being developed to treat genetic disorders such as cystic fibrosis. [SEP] Text: Using systematic reviews (free)Navigate to figure in ReviewPrint figureOpen in new tab Figures and Tables - Analysis 1. 6 Comparison 1 CFTR gene replacement therapy versus placebo, Outcome 6 Change in FVC (% predicted) from baseline. Using systematic reviews (free)Navigate to figure in ReviewPrint figureOpen in new tab Figures and Tables - Analysis 1. 7 Comparison 1 CFTR gene replacement therapy versus placebo, Outcome 7 Relative change in FEV1 % predicted from baseline. Using systematic reviews (free)Navigate to figure in ReviewPrint figureOpen in new tab Figures and Tables - Analysis 1. 8 Comparison 1 CFTR gene replacement therapy versus placebo, Outcome 8 Number of inpatient episodes. Using systematic reviews (free)Navigate to figure in ReviewPrint figureOpen in new tab Figures and Tables - Analysis 1. 9 Comparison 1 CFTR gene replacement therapy versus placebo, Outcome 9 Adverse events. Using systematic reviews (free)Navigate to figure in ReviewPrint figureOpen in new tab Figures and Tables - Analysis 1. 10 Comparison 1 CFTR gene replacement therapy versus placebo, Outcome 10 Lower airway potential difference change from baseline. Using systematic reviews (free)Navigate to figure in ReviewPrint figureOpen in new tab Figures and Tables - Analysis 1. 11 Comparison 1 CFTR gene replacement therapy versus placebo, Outcome 11 Lower airway potential difference change from baseline (amiloride and low chloride). Using systematic reviews (free)Navigate to figure in ReviewPrint figureOpen in new tab Figures and Tables - Analysis 1. 12 Comparison 1 CFTR gene replacement therapy versus placebo, Outcome 12 Lower airway potential difference ‐ post treatment. Using systematic reviews (free)Navigate to figure in ReviewPrint figureOpen in new tab Figures and Tables - Analysis 1. 13 Comparison 1 CFTR gene replacement therapy versus placebo, Outcome 13 Measurement of CFTR protein expression (SPQ chloride efflux). Using systematic reviews (free)Navigate to figure in ReviewPrint figureOpen in new tab Figures and Tables - Analysis 1. 14 Comparison 1 CFTR gene replacement therapy versus placebo, Outcome 14 Change in validated computerised tomogram (CT) score. Using systematic reviews (free)Navigate to figure in ReviewPrint figureOpen in new tab Table 1. Primary outcomes measured Study name Respiratory exacerbations Lung function Days in hospital 1999 Not measured.

Output: corroborate


Input: Claim: Some genetic therapies aim to slow aging by targeting telomere shortening and other cellular aging processes. [SEP] Text: To test a possible link between telomerase activity and NF-κB RelA in the CNS in vivo, in a first step we determined NF-κB Rela gene expression in the neocortex of young and aged mice. As expected, levels of Rela mRNA were significantly up-regulated in animals with advanced ages (n = 5) compared with young counterparts (Figure 6E; P = 0. 014; n = 5). In contrast, levels of c-Rel, a heterodimer partner of RelA also involved in classical NF-κB cascade activation, though without hitherto evidence for a direct interaction with TERT were not substantially changed (P = 0. 333). To further explore a putative mechanistic interaction between TERT and NF-κB RelA, telomerase activity was measured in the cortex of aged RelaCNS-KO animals, which lack expression of the Rela gene in neuro-ectodermal cell populations including neurons and macroglial cells but not in microglia, and normalized against the intrinsic telomerase activity of 1,000 HeLa cells. In contrast to the hypothesis of a reciprocal TERT:RelA induction, telomerase activity in these aged RelaCNS-KO mice was not altered relative to age-matched controls (Figure 7A; P = 0. 326; n = 4 - 6). In accordance, no difference was observed between the RTL of cortical neural cells isolated from 19-20 months old RelaCNS-KO and age-matched control mice (P = 0. 991, Figure 7B) when assessed by means of qPCR. Both data suggest that, in contrast to the discovery in tumor cell entities and blood cells [21,22], TERT:RelA might not establish a reciprocal interplay in the aging CNS. Figure 7. Telomerase activity and telomere length in the brain of aged RelaCNS-KO mice. (A) Telomerase activity, normalized against a positive HeLA cell extract, in the cortex of 18-23 months old RelaCNS-KO mice compared to age-matched RelaFlox control mice (n = 4 - 6).

Output: contrast


Input: Claim: All insects can communicate through sounds and music. [SEP] Text: and. Music 1. 2. A Survey of Works with 3. Why the Programs were kept secret 4. Approaches to. On the History of 1. On Mahler’s Topicality and Popularity 2. Dimension of Mahler’s Music 3. Mahler and the Schönberg School 4. On Adorno’s 5. Mahler and the Avant-Garde XIX. Become Language:. The Co-Presence of all Eras: Messages through the 1. Letters and Writings by Composers 2. Works of Literature and Philosophy 3. On the Subject of Music as ← 10 | 11 →ForewordAs long as people have been theorizing about art, there have been diverse conceptions of music. Some take it as an art that follows its own laws, a play of “moving tonal forms,” as the high priest of music put it. To others, it is expression, an art of “inwardness,” the “language of the soul. ” For some, music serves the purpose of amusement and entertainment, being an art designed solely for aesthetic pleasure. Others tirelessly point to its educational and therapeutic function – a function ascribed to it already in Greek antiquity. If in the 18th century it was widely held that music has a specific end in view, in the 19th the notion of music as pure, purposeless, so-called absolute music, began widely to prevail. The words message and code denote basic concepts in the modern science of communication, in mythography and semiotics. Music, too, is a communicative phenomenon par excellence but has to date hardly been analyzed in terms of the communicative process. What do composers from Ludwig van Beethoven to intend with their music? What do they want to say, and to whom do they address themselves? What is the nature of the messages they transmit, and how are they received and deciphered by the listeners? The subject of music as message is one that has fascinated me for half a century. The book is intended as an introduction to the basic questions of musical semantics. Nearly all of my books profit from it (cf. section 3 of the 2011. The second 226. The present English edition has been brought up to date and expanded by the 1. The question what music is and what purpose it serves can, of course, not be answered once and for all.

Output: pass


Input: Claim: Gene therapy is being developed to treat genetic disorders such as cystic fibrosis. [SEP] Text: In addition to its health implications, SCD also impacts on individuals and their families both socially and psychologically when trying to meet the demands of this chronic illness. SCD often also interferes with educational development due to its unpredictable and debilitating nature. There is a higher incidence of school absenteeism and hospital costs in families that have a child with SCD (Manci 2003; Platt 1991; Powars 2002; Serjeant 1993). Life expectancy is on the rise for people with SCD, but is still less than that of the general population (Platt 1994). There are no firm data on the survival of individuals with sickle cell anaemia on the African continent (Platt 1991). The median survival was estimated in 1994 to be 42 years for men and 48 years for women in the USA, whereas comparable figures for Jamaica published in 2001 suggested 53 years for men and 58. 5 years for women (Platt 1991). The mortality rate is higher amongst people with SCD, and is usually caused either by chronic organ failure consequent on the sickling process, or as a result of an acute catastrophic event, such as a stroke (Powars 1983); acute sickle chest syndrome; splenic sequestration (Steinberg 2003); sudden death or other complications (Gray 1991). Management of SCD is multidisciplinary. Penicillin prophylaxis to prevent pneumococcal infections, appropriate use of blood transfusions and other supportive measures have improved survival of people with SCD (Gaston 1986; Lezcano 2006). Hydroxycarbamide (hydroxyurea) made a major impact on sickle cell therapy when it was shown to reduce morbidity and mortality (Steinberg 2003). Bone marrow transplantation remains the only possible curative therapy (Mankad 2001). Although palliative therapies and bone marrow transplantation therapy have been developed for these disorders, treatment still remains sub‐optimal and many individuals suffer significant morbidity and early mortality (Persons 2003). Therefore, development of a gene therapy approach has been sought for many years (Nathan 2001; Persons 2003). Description of the intervention Gene therapy holds a great deal of promise for the future of medical treatment. It involves the introduction of genetic material into a cell to treat disease.

Output: corroborate


Input: Claim: Some genetic therapies aim to slow aging by targeting telomere shortening and other cellular aging processes. [SEP] Text: (B) RTL in cortical neural cells isolated from 19-20 months old RelaCNS-KO as assessed by qPCR in terms of T/S-ratios and normalized against aged-matched RelaFlox control animals (n = 3 - 4). Bars represent means ± S. E. M. P values were calculated by Student’s t-test. is defined as an irreversible cell cycle arrest provoked by telomere attrition in replication-competent cells devoid of sufficient telomerase activity. However, already in 1997 Coviello-McLaughlin and Prowse provided evidence that telomere dynamics in brain tissue might not follow this telomere hypothesis of replicative aging. They demonstrated that telomeres in brain of M. spretus, a mouse strain that harbors telomeres with a similar length as in humans, shorten unrelated to cell turnover and telomerase activity and even with stronger slope than in other tissues with restricted cell turnover. This was observed postnatally, whereas telomere shortening under aging was not detected [23]. Therefore, whether cell cycle cessation already at time of neuronal maturation predisposes to a senescent phenotype, or whether constitutive cell cycle exit, on the contrary, prevents from telomere shortening and thus retains a ‘juvenile’ state of the telomeric chromatin at higher ages, is not known. Accumulating evidence from more recent studies now indicates that penetrance of senescence characteristics is not restricted to proliferation-competent cells. Post-mitotic neurons of the CNS acquire a senescence-like phenotype as a result of dysfunctional telomeres and DNA damage [24]. Moreover, telomeres are a preferred site of persistent DDR under aging as well as stress conditions, irrespective of the presence or absence of telomerase activity [25,26]. Thus, telomere dysfunction plays a key role both in stress-induced premature senescence, which is generally independent of telomere shortening, as well as in DDR elicited by replication-mediated telomere attrition.

Output: contrast


Input: Claim: All insects can communicate through sounds and music. [SEP] Text: Opinions about it are too divided, art-theoretical and aesthetic positions differ too radically. The various conceptions are clearly dependent on the particular cultural sphere, on nationality, on the time and the zeitgeist, on the prevailing tastes and on the respective intellectual and artistic currents and tendencies. Thus music has been, and still is, defined as art for the ear, as the language of the heart, of feeling, as science of composition, as “moving tonal form. ” The mission of tonal art, it has been and still is said, is to provide pleasure, to educate, to teach, to move, to excite, to uplift, to transport, to interpret and deepen a text emotionally, to enhance drama, to convey an intimation of the other world, and so on. Perhaps we can agree that not every kind of music proclaims a message. The playfully concertante music of the Baroque and of Classicism differs considerably in this respect from Beethoven’s Ninth Symphony. 2. Not every musical work that does proclaim a message is necessarily of aesthetic value. It would be a fatal error to confound aesthetics and ideology. Ideology does not determine the rank of a work of art. Robert Schumann, in taking position on the hotly debated question as to the value or lack of value of programs in music, expressed his conviction by saying: “First of all, let me hear that you have made beautiful music, then your program, too, will be pleasing to me. ”11 Mutatis mutandis, Schumann’s statement is valid also for the conception of music as message. 3. In the recent past, there has been much discussion about the contrast between so-called absolute and program music. The conception of a certain kind of music as message might help to partly reconcile the contrast. For a ← 17 | 18 → musical message is something other than a musical program and pertains to a higher level of abstraction than the latter. Many works that do not seem to fit into the category of either absolute or program music can be placed under the rubric of music as message. Here, too, Beethoven’s can be cited as exemplary. 1 Arnold Schönberg, Ausgewählte Briefe, ed. (Mainz, 1958), 178 f.

Output: pass


Input: Claim: Gene therapy is being developed to treat genetic disorders such as cystic fibrosis. [SEP] Text: The momentum was generated in 2000 when it was demonstrated that lentivirus vectors containing normal human globin genes and regulatory regions from the beta‐globin locus control region could be faithfully transduced into mouse hematopoietic stem cells and expressed in erythroid cells (Bodine 2003; May 2000). How the intervention might work Gene therapy is the introduction of genes into an individual's cells and tissues in order to treat a disease. Most of the conditions treated in this way are genetic disorders that result from gene mutation malfunctions (Postnote 2005). Viruses are the most widely used vectors in gene therapy. Some of the different types of viruses used as vectors in gene therapy include: retroviruses; adenoviruses; adeno‐associated virus; parvovirus; herpes simplex virus; hepatitis virus; and vaccinia virus (Postnote 2005). The viral vectors are made harmless by removing the viral gene and replacing them with the therapeutic gene. This approach is known as gene addition (the transfer of normal beta globin gene into hematopoietic cells via retroviral vectors or adeno‐associated viruses that have been modified or crippled so they do not become infective). In theory, the viral vectors used in gene therapy are made harmless to prevent them from replicating and causing unwanted effects. However, these viruses could trigger unwanted immune responses and cause unwanted side effects. Other approaches of gene therapy that have been developed include gene replacement (targeted insertion of the transferred gene into the endogenous globin locus by homologous recombination) and gene repair or chimeroplasty (introduction of chimeric oligonucleotides composed of DNA and modified RNA residues into stem cells to direct correction of the mutation in the sickle gene). Good candidates for gene therapy include autosomal recessive disorders (such as SCD) because a normal phenotype can be restored in diseased cells with only a single normal copy of the mutant gene (Goncz 2002). Gene therapy, if successful, will provide a viable alternative for permanent correction of the abnormal gene in SCD. It will circumvent the problem of donor shortage and avoid complications related to graft versus host rejection that are involved with bone marrow or other forms of stem cell transplant. Gene therapy has been used to correct SCD in mice (Nathan 2001). Despite the technical problems faced, major progress in the globin gene therapy field has been achieved.

Output: corroborate


Input: Claim: Some genetic therapies aim to slow aging by targeting telomere shortening and other cellular aging processes. [SEP] Text: Whether the unchanged telomerase activity in RelaCNS-KO animals as compared to age-matched controls observed here might be due to a substitution of RelA functions by other subunits of canonical NF-κB, or by different molecular mechanisms, requires further analyses. In summary, our data show that both, cell cycle-dependent and -independent changes in telomere length occur in the aging brain, which are assessable by application of current methodologies on interphase nuclei. Using a cell cycle phase-related approach, we reveal cell cycle activity to be a susceptibility factor, but not an obligatory criterion for telomere length reduction in neural cell populations. We thus assume additional factors such as, e. g. , metabolic, inflammatory and genetic influences to be involved in telomere attrition in the CNS. Moreover, we provide direct evidence that non-replicative neurons contribute to the age-associated telomere attrition process found in the brain. The paralleled up-regulation of NF-κB Rela might mirror a direct link between its involvement in age-related genetic reprogramming and chromosomal aging. Thus, this study adds novel cellular and molecular aspects to a better understanding of the aging process of the CNS, where replicative senescence only partly explains cellular senescence. Materials and statement Investigations were conducted in compliance with the ‘Animal Research: Reporting of Experiments ()’ guidelines, executed in accordance with current regulations and the Protection of Animals Act, and approved by the regional animal welfare authorities of Thuringia (accreditation number: 02-046/14). wild type mice of a C57BL/6 subcolony featuring hermetic inbreeding conditions were included at 3-4 and 25-27 months of age for RTL measurements, and up to 28 months for TRAP assay execution. In addition, 18-23 months old transgenic animals displaying a conditional, Cre-loxP-based nestin promoter-driven deletion of NF-κB Rela in neuro-ectodermal CNS populations, i. e. neurons, oligodendrocytes and astrocytes, but not microglia were used (further denoted as RelaCNS-KO). Prove of Rela knockdown in these constructs has been carried out recently [58,59].

Output: contrast


Input: Claim: All insects can communicate through sounds and music. [SEP] Text: 2 Arnold Schönberg, „Kriterien für die Bewertung von Musik,“ in Stil und Gedanke. Aufsätze zur Musik, ed. Ivan Vojtĕch (I (Frankfurt a. M. : S. Fischer Verlag, 1976), 123–133; 132. 3 Ibid. , 386. 4 Ibid. , 69. 5 Henze, Musik und Politik. Schriften und Gespräche, 1955–1975 (DeutscherTaschenbuch Verlag, 1162) (Munich, 1976), 251 f. 6 Claude Lévi-Strauss, Mythologiques I. Le cru et le cuit (Paris, 1964), 23 f. , 205, 218, 26, 38. 7 Hannelore Link, Rezeptionsforschung. Eine Einführung in Methoden und Probleme (Urban-Taschenbücher, 215) (Stuttgart/Berlin/Cologne/Mainz, 1976), 27 ff. 8 Kurt Blaukopf, Musik im Wandel der Gesellschaft. Grundzüge der Musiksoziologie (Munich/Zurich, 1984), 154 f. 9 Umberto Eco, Einführung in die Semiotik, (Munich, 1972). 339 2016 ISBN (PDF) 9783653053012 ISBN (ePUB) 9783653971644 ISBN (MOBI) 9783653971637 ISBN (Hardcover) 9783631660331 DOI 10. 3726/978-3-653-05301-2 Publication date 2016 (February) of Music as Schumann's Music for of Wagner's am 2016. 339 pp. , 2 b/w fig. , 6 graphs Biographical notes (Author) is professor emeritus of Musicology at the University of Hamburg. Among his monographs are volumes on the origin of Gregorian neumes, van Beethoven, and György Ligeti. Ernest Bernhardt-Kabisch is professor emeritus of English and at Indiana University. He has translated several books by Constantin Floros.

Output: pass


Input: Claim: Gene therapy is being developed to treat genetic disorders such as cystic fibrosis. [SEP] Text: This progress has advanced the possibility of gene therapy for haemoglobin disorders in the near future (Persons 2003; Chang 2006). The first successful use of gene therapy in humans for SCD has been reported; the investigators used a lentivirus to achieve integration of a normal beta globin gene into the participants hematopoetic cells (Ribeil 2017). A further clinical trial using the lentivirus is ongoing by other researchers (Kohn 2014). Review is an update of previously published versions (Olowoyeye 2010; Olowoyeye 2012). objectives of this review are to: determine whether gene therapy can improve survival and prevent symptoms and complications associated with SCD; examine the risks of gene therapy against the potential long‐term gain for people with SCD. for considering studies for this review Types of studies Randomised control trials or quasi‐randomised trials. We plan to include any relevant phase I, II and III trials. Types of participants People of any age and sex with SCD of all phenotypes and regardless of geographic or healthcare setting. Types of interventions Gene therapy (any approach) plus standard treatment versus standard treatment or other 'curative' type treatment such as bone marrow transplantation, stem cell transplantation or cord blood transplantation. Types of outcome measures Primary outcomes Event‐free survival (individuals alive and free of SCD symptoms) Change in mean life expectancy of individuals with SCD attributable to gene therapy Secondary outcomes Changes in haematocrit (as measured by the primary trial) Severity as assessed by changes in complications associated with SCD (e. g. acute chest syndrome, strokes, chronic renal failure, liver and gallbladder diseases, leg ulcers, sequestration crises, etc) Number of hospital visits and admissions as a result of pain crises and complications Change in use of blood transfusion, hydroxyurea and other treatment modalities Cost effectiveness of gene therapy Adverse events As measured by the primary trials. Search methods for identification of studies We searched for all relevant published and unpublished trials without restrictions on language, year or publication status. Electronic searches We searched the Group's Register using the terms: (sickle cell OR (haemoglobinopathies AND general)) AND gene therapy. is compiled from electronic searches of the Register of () (updated each new issue of the Cochrane Library) and weekly searches of.

Output: corroborate


Input: Claim: One focus of anti-aging research is studying genetic markers associated with longevity in certain populations. [SEP] Text: Unlike UCP1, the physiological role of the other UCPs still remains to be fully elucidated. It has been hypothesized that these proteins may provide protection from oxidative damage by preventing excessive production of mitochondrial Species (ROS) [7], [8]. Indeed, Ucp-knockout mice have increased levels of ROS and show signs of increased oxidative damage [9]–[11]. Further evidence indicates that activation of UCP2 and UCP3 by ROS leads to a mild uncoupling and to diminished ROS formation [12], [13], while their inhibition by purine nucleotides increases membrane potential and mitochondrial ROS production [14]. The uncoupling activity of UCPs has also been linked to regulation of other more specific metabolic functions [15], [16] such as fatty acid oxidation [17], glucose-stimulated insulin secretion [18], whole body energy balance [19], and apoptosis [20]. Human aging is characterized by a gradual reduction in the ability to coordinate cellular energy expenditure and storage (crucial to maintain energy homeostasis), and by a gradual decrease in the in the ability to mount a successful stress response [21], [22]. These physiological changes are typically associated with changes in body composition (i. e increase in fat mass and the decline in fat-free mass), and with a chronic state of oxidative stress with important consequences on health status [23]–[25]. Mitochondrial function is crucial in these processes, being mitochondria the main cellular sites controlling energy metabolism and the redox state. Thus, by promoting fatty acid oxidation, and by reducing ATP and ROS production, the induction of mitochondrial uncoupling through UCPs may also be a critical pathway in the modulation of the rate of aging and lifespan [26]–[28]. This idea, first proposed by M. D. Brand [26] and termed “uncoupling-to-survival”, is now supported by several experimental evidences (for reviews see: [27], [29], [30]). Of interest, targeted expression of exogenous UCP extends lifespan of adult flies [31], [32], while mice with higher metabolism live longer and have higher uncoupling activity [33]. Transgenic and knockout mice for Ucp genes show alterations in lifespan [34], [35]. Interestingly, it has also been shown that in vivo uncoupling mimics metabolic and lifespan effects of calorie restriction (CR) [36].

Output: contrast


Input: Claim: All insects can communicate through sounds and music. [SEP] Text: Improvisation pedagogy: what can be learned from off-task sounds and the art of the musical heckle? Published online by Press: 03 April 2024 [Opens in a new window] Show author details Jackie Walduck* Affiliation: Department of Music and Audio Technology, University of 4 4TZ, UK * Email: j. walduck@kent. ac. uk 0. 29 mb) View PDF [Opens in a new window] Save to to Save to & Permissions [Opens in a new window] tension between freedom and constraint is characteristic of improvisation practice and pedagogy, presenting challenges for teachers/workshop leaders. To create musical focus in ensemble improvisation, some sounds are encouraged, whilst others are edited out, ignored or marginalised. This 10. 1017/S026505172400007X [Opens in a new window] This is an 4. 0/), which permits unrestricted re-use, distribution, and reproduction in any medium, provided the original work is properly cited. Copyright © The Author(s), 2024. Published by Press Freedom, constraint and holding the leadership reins From the perspective of the community musician, facilitation is understood as a process that enables participants’ creative energy to flow, develop, and grow through pathways specific to individuals and the groups in which they are working. Facilitation does not mean that the community musician surrenders responsibility for music leadership, only that control is relinquished. Higgins (2012, p. 148) A thin line is trodden between freedom and constraint when leading a group improvisation workshop. When working without a priori rules (completely ‘free’ improvisation), the music can sound aimless, and participants may feel unsafe not knowing what to do. Setting boundaries can scaffold freedom (2017; 2012), but the reality of leading very scaffolded workshops can mean using additional gatekeeping processes: editing participant contributions to gain an ensemble focus, allowing some sounds and restricting others. In the real-time improvisation workshop environment, leaders may find themselves holding the reins tightly or loosely: pruning, shaping the improvisation, or encouraging bolder, dramatic, or unexpected sounds, fostering variety and creativity. To bring form to the music, some sounds are encouraged, and others may become marginalised.

Output: pass


Input: Claim: Gene therapy is being developed to treat genetic disorders such as cystic fibrosis. [SEP] Text: There is a higher incidence of school absenteeism and hospital costs in families that have a child with SCD (Manci 2003; Platt 1991; Powars 2002; Serjeant 1993). Life expectancy is on the rise for people with SCD, but is still less than that of the general population (Platt 1994). There are no firm data on the survival of individuals with sickle cell anaemia on the African continent (Platt 1991). The median survival was estimated in 1994 to be 42 years for men and 48 years for women in the USA, whereas comparable figures for Jamaica published in 2001 suggested 53 years for men and 58. 5 years for women (Platt 1991). The mortality rate is higher amongst people with SCD, and is usually caused either by chronic organ failure consequent on the sickling process, or as a result of an acute catastrophic event, such as a stroke (Powars 1983); acute sickle chest syndrome; splenic sequestration (Steinberg 2003); sudden death or other complications (Gray 1991). Management of SCD is multidisciplinary. Penicillin prophylaxis to prevent pneumococcal infections, appropriate use of blood transfusions and other supportive measures have improved survival of people with SCD (Gaston 1986; Lezcano 2006). Hydroxycarbamide (hydroxyurea) made a major impact on sickle cell therapy when it was shown to reduce morbidity and mortality (Steinberg 2003). Bone marrow transplantation remains the only possible curative therapy (Mankad 2001). Although palliative therapies and bone marrow transplantation therapy have been developed for these disorders, treatment still remains sub‐optimal and many individuals suffer significant morbidity and early mortality (Persons 2003). Therefore, development of a gene therapy approach has been sought for many years (Nathan 2001; Persons 2003). Description of the intervention Gene therapy holds a great deal of promise for the future of medical treatment. It involves the introduction of genetic material into a cell to treat disease. The momentum was generated in 2000 when it was demonstrated that lentivirus vectors containing normal human globin genes and regulatory regions from the beta‐globin locus control region could be faithfully transduced into mouse hematopoietic stem cells and expressed in erythroid cells (Bodine 2003; May 2000).

Output: corroborate


Input: Claim: One focus of anti-aging research is studying genetic markers associated with longevity in certain populations. [SEP] Text: 1), while rs1800849 was in LD with rs15763 (D' = 0. 83), but it was virtually unlinked with the others (D'<0. 30). Finally, we found a weak LD between rs9472817 and rs10498769 in the UCP4 gene (D' = 0. 47), and between rs2235800 and rs5975178 in the UCP5 gene (D' = 0. 44). Based on these LD patterns, and using a D' cutoff equal to 0. 6, haplotypes were reconstructed at the UCP2-UCP3 and UCP3 loci. Download: PPTPowerPoint slidePNGlarger imageTIFForiginal imageFigure 1. Schematic representation of linkage disequilibrium (D' coefficient) among the four SNPs of the UCP2-UCP3 gene cluster. shown in Table 4, the analysis of the UCP2-UCP3 haplotypes revealed that the CAC haplotype, consisting of the minor allele for rs660339, major allele for rs659366, and minor allele rs15763, was associated with a decreased probability of attaining longevity (P = 0. 003), while the TGT haplotype (opposite combination of alleles) acted in a reverse fashion by increasing this probability (p = 0. 046). However, the strength of these associations was influenced by the allelic status at rs659366 of the relevant haplotype. Indeed, the CGC and TAT haplotypes, when compared to the above, differ only for rs659366 and did not show any effect. For the UCP3 haplotypes involving rs15763 and rs1800849, we found that carriers of the CC haplotype have a decreased probability of achieving longevity (P<0. 001). Conversely, as previously reported in the single-locus analysis, the presence of a T allele at either rs15763 or rs1800849 increased such probability, although this positive effect was more pronounced when the T allele at rs1800849 was involved (p = 0. 044 vs P = 0. 006). Download: PPTPowerPoint slidePNGlarger imageTIFForiginal imageTable 4. Estimation of haplotype frequencies in the and association with longevity in the analyzed sample.

Output: contrast


Input: Claim: All insects can communicate through sounds and music. [SEP] Text: Drawing on perspectives from improvisation pedagogy at school and tertiary levels, community music and improvisation as a creative practice, this paper discusses freedom and constraint in the context of inclusive workshop-leading practices within community music and when working with participants with additional needs. It considers and evaluates marginalised sounds to suggest ways of listening more openly in these and mainstream learning contexts. The pull between in-the-moment freedom and constraint is represented in improvisation literature (e. g. 1992; 2010; 1994; 2002) and improvisation pedagogical literature (2007; 2015). Whilst the idea of an improvisation ensemble (including jazz) suggests an ethos of democracy, spontaneity and inclusivity, Berliner (1994, p. 418) explores the relationship between band leadership styles and their impact on jazz musicians’ creative freedom. If a band gels, the ideals of self-expression and collective effort come into play simultaneously. However, this does not always happen – the band may pull in different directions undoing musical coherence. Berliner illustrates, through musicians’ testimonies, that solving this problem often brings tight-rein (more autocratic) leadership into conflict with these values. To maintain them, differing artistic opinions can be negotiated through compromise, humour and a looser rein. Bailey (1992) and Berliner (1994) in equally seminal but divergently positioned works on improvisation tackle the relationship between traditions – known forms or idioms, and originality – spontaneous musical creation. For Bailey, whose own work is rooted in free improvisation, spontaneity lies away from known genres, and for Berliner, it is located within the interpretation of the tradition, through ornamentation and variation of an acquired jazz ‘language’. In learning contexts, improvisation is valued as a way to encourage agency and creativity in students and workshop participants and here, too, issues of freedom and constraint surface. Part of the pedagogic value of improvisation is that learning often takes place in groups: creativity and knowledge are distributed and socially situated between learners (2007; 2011). Borgo’s perspective of advanced ensemble improvising classes advocates group over individual learning and creativity over the reiteration of musical ideas, so that what is captured is the complexity of an evolving system – the improvising group.

Output: pass


Input: Claim: Gene therapy is being developed to treat genetic disorders such as cystic fibrosis. [SEP] Text: How the intervention might work Gene therapy is the introduction of genes into an individual's cells and tissues in order to treat a disease. Most of the conditions treated in this way are genetic disorders that result from gene mutation malfunctions (Postnote 2005). Viruses are the most widely used vectors in gene therapy. Some of the different types of viruses used as vectors in gene therapy include: retroviruses; adenoviruses; adeno‐associated virus; parvovirus; herpes simplex virus; hepatitis virus; and vaccinia virus (Postnote 2005). The viral vectors are made harmless by removing the viral gene and replacing them with the therapeutic gene. This approach is known as gene addition (the transfer of normal beta globin gene into hematopoietic cells via retroviral vectors or adeno‐associated viruses that have been modified or crippled so they do not become infective). In theory, the viral vectors used in gene therapy are made harmless to prevent them from replicating and causing unwanted effects. However, these viruses could trigger unwanted immune responses and cause unwanted side effects. Other approaches of gene therapy that have been developed include gene replacement (targeted insertion of the transferred gene into the endogenous globin locus by homologous recombination) and gene repair or chimeroplasty (introduction of chimeric oligonucleotides composed of DNA and modified RNA residues into stem cells to direct correction of the mutation in the sickle gene). Good candidates for gene therapy include autosomal recessive disorders (such as SCD) because a normal phenotype can be restored in diseased cells with only a single normal copy of the mutant gene (Goncz 2002). Gene therapy, if successful, will provide a viable alternative for permanent correction of the abnormal gene in SCD. It will circumvent the problem of donor shortage and avoid complications related to graft versus host rejection that are involved with bone marrow or other forms of stem cell transplant. Gene therapy has been used to correct SCD in mice (Nathan 2001). Despite the technical problems faced, major progress in the globin gene therapy field has been achieved. This progress has advanced the possibility of gene therapy for haemoglobin disorders in the near future (Persons 2003; Chang 2006). Review is an update of previously published versions (Olowoyeye 2010; Olowoyeye 2012).

Output: corroborate


Input: Claim: One focus of anti-aging research is studying genetic markers associated with longevity in certain populations. [SEP] Text: In contrast, the allele frequencies of a majority of the SNPs (69%) ranked using global FST measure were biased towards 0 or 1 with relatively few loci exhibiting intermediate allele frequencies. Download: PPTPowerPoint slidePNGlarger imageTIFForiginal imageFigure 5. Distribution of allele frequencies for the 100 top-ranked SNPs. Allele frequencies of the 100 top-ranked SNPs in 23 populations identified using four selection approaches: (A) global FST; (B) pairwise FST; (C) Delta, and (D) outlier. Horizontal line, grey rectangle, whiskers, open circles, and stars indicate median, 25th and 75th quartiles, non-outlier range, outliers and extreme outliers, respectively. the differences described above, there was a substantial amount of overlap between the top SNPs among all ranking approaches (Fig. 6). For example, 59 to 68 of SNPs out of the top 100 were identified using paiwise FST and Delta in all three datasets. Similarly, large proportions of SNPs were shared between global FST and pairwise FST approach (51%–71%). In addition, a substantial proportion of outliers (up to 58%) was also ranked as top SNPs by the three other approaches (Fig. 6A). Download: PPTPowerPoint slidePNGlarger imageTIFForiginal imageFigure 6. SNP overlap among different ranking approaches and population datasets. (A) Venn diagrams showing the extent of overlap among four approaches (global FST, pairwise FST, Delta and outlier) for three population datasets. (B) Venn diagrams showing the extent of overlap among three population datasets for four ranking approaches. For all SNP ranking methods the top 100 SNPs are presented, except for the outlier approach where 95 and 35 SNPs were identified as being under selection for dataset II and III, respectively. contrast to SNP ranking approaches, populations in the ascertainment group had a much larger effect on ranking of the most informative SNPs. For example, a relatively large proportion of SNPs (up to 80%) ranked by global FST, pairwise FST and Delta was identified only in a single dataset (Fig. 6B) and a relatively large proportion of outliers was unique for each dataset (up to 50%).

Output: contrast


Input: Claim: All insects can communicate through sounds and music. [SEP] Text: In steering such groups, he draws on an idea from drama improvisation pedagogy: when an ‘offer’ is made, to accept and build upon it and avoid ‘blocking’ it. For teachers, this contains ‘an inherent challenge to avoid circumscribing or over-directing the group flow’ (2007, p. 83). Positioning the improvising ensemble as a complex dynamic system, he argues: … jazz musicians must strike an uneasy and ever-changing balance between the exploration of new ideas and the exploitation of strategies, devices, and practices that have already been integrated into the system. They seek persistent disequilibrium, by avoiding constancy, but also restless change. (2007, p. 86) In nurturing such a system, the reins are held loosely. A desire for instability appears to motivate the students to experiment with new sounds and sound combinations. However, their advanced training presumably yokes the students to known forms, inhibiting too much deviation – disequilibrium but not pandemonium. In community and Needs settings, improvisation can be a useful leveller, particularly with mixed experience or mixed ability groups, as it allows for straightforward or complex contributions within the ensemble; Higgins’s developmental ‘pathways specific to individuals’ are quoted above (2012, p. 148). Practice is grounded in inclusivity. Often in such contexts, the emphasis, initially, is on participation through which learning can subsequently take place. In community music, Higgins’s ‘acts of hospitality’ (2007) are enacted by the workshop leader welcoming participants to what are simultaneously social and musical spaces. Heterogenous views and musical interests are negotiated, ideally giving rise to co-created music that reflects multiple creative voices (2016). In practice, as will be discussed, many and varied are the ways of joining in: soloing, accompanying, ‘riffing’, noodling, blurting and private experimenting on a drum are all sounds that might occur in the informal workshop environment and could be said to lie anywhere on a continuum between co-operative and oppositional to the group endeavours. Improvisation contains the potential for disruption, chaos and the skirting of knowledge and power hierarchies, thereby presenting challenges for teachers and workshop leaders, perhaps more so when working with novice learners.

Output: pass


Input: Claim: Genetic testing can provide insights into ancestry and potential health risks. [SEP] Text: Upon discussion of his values and future goals, the patient identified a desire to have a better understanding of his family of origin and reported interest in undergoing DTC-GAT. The clinician probed the patient’s meaning-making of receiving ancestry results; he reported interest in making sense of “why I behave in certain ways,” and feeling closer to his father. He later sought guidance from the clinician regarding whether to utilize DTC-GAT. The clinician reviewed the available literature on the clinical impacts of DTC-GAT, which was minimal, as well as the risks and benefits reported in popular news media. Ultimately, the veteran and clinician engaged in a collaborative discussion in which the clinician worked to ensure consideration of both risks and potential benefits, while also focusing on the veteran’s own personal values and motivations for considering DTC-GAT. Patient 2 is a White, non-Hispanic male veteran in his mid-50s with a history of severe mental illness who, during his cognitive behavioral therapy, disclosed having recently found his biological mother through DTC-GAT. After years of searching for her and growing up as the only adopted child in a family that “couldn’t be more different” than him, he described his mood as “over the moon. ” After reconnecting, he and his biological mother began having daily phone calls; he reported having always felt lonely, but that he never understood what these feelings were related to until he reconnected with her. He noted considering the implications of DTC-GAT for his identity, autobiographical narrative, and mental health. He chose not to connect with his biological father for these very reasons, as “he may have been the one who gave me up. ” Without relevant clinical guidance available, the clinician worked on helping the patient see links between thoughts, emotions, and behaviors with respect to this situation. These case examples reflect clinical interactions showcasing pre- and post-DTC-GAT timepoints. Patient 1 requested clinician guidance on whether to utilize DTC-GAT, whereas Patient 2’s DTC-GAT experience was integrated into treatment. Together, these cases call attention to the need for clinician preparedness to engage in conversation with patients regarding DTC-GAT.

Output: corroborate


Input: Claim: One focus of anti-aging research is studying genetic markers associated with longevity in certain populations. [SEP] Text: AI채팅 사용 권한이 필요해요 저는 소속기관 학교가 있어요 저는 개인 이용자예요 개인구독권을 구매할래요 내서재에 추가 되었습니다. 로그인 하지 않으면 내서재 담기가 취소됩니다. 내서재에서 확인하시겠습니까? 다시 보지 않기 취소 확인 내서재에 추가 되었습니다. 로그인 하지 않으면 내서재 담기가 취소됩니다. 내서재에서 확인하시겠습니까?

Output: pass


Input: Claim: All insects can communicate through sounds and music. [SEP] Text: Hickey (2015), following Borgo (2007) and Berliner (1994), suggests that free improvisation may develop most successfully in groups ‘free of personality problems, individual differences or aesthetic differences that might get in the way of a smooth group process’ (2015, p. 295). She goes on to point out that the realities of classroom management – larger classes (up to 30 children in the UK state sector), heterogenous interests, interpersonal dynamics, differing degrees of musical experience and the ‘artificial randomness of classroom selection’ (p. 295) can make the set-up challenging. For example, do learners have equivalent perceptions of music? How well do they listen to one another? Are all voices heard? How are musical ideas and territories negotiated? Conflict in classroom and community group contexts is sometimes inevitable. The role of leaders in managing/failing to manage it is addressed by Mullen (2008), who draws attention to the ‘abdication’ of leadership by laissez-faire community music leaders, in which conflict, boundary maintenance and responsibility (to the music, the participants, resources, etc. ) are avoided. (1997), he proposes instead a model of leadership in tune with improvisation’s agency and non-authoritarian stance, in which the session leader becomes a ‘good steward, keeping others focused, eliminating distractions, keeping hope alive in the face of setbacks and stress’ (2008, p. 256 [orig. 1997, p. 199]). Neither of them, Hickey, Higgins or Mullen, suggest non-leadership but propose a guided improvised activity. Even so, the problem remains: which sounds to encourage and which to minimise in order to release the participants’ creativity, not trap them into formulae or lose them in chaos? With participants who have cultivated stylistic interests or learners with additional needs, the position of leader/teacher as gatekeeper to knowledge is challenged even more profoundly. Community musicians can find themselves amongst participants steeped in musical knowledge of unfamiliar genres or striving to interpret unanticipated modes of interaction or communication styles. It ceases to make sense that group leaders, situationally positioned as ‘gatekeepers’, should hold the keys to musical knowledge or that their particular (perhaps hegemonic) worldview is the one others should adhere to.

Output: pass


Input: Claim: Genetic testing can provide insights into ancestry and potential health risks. [SEP] Text: Implications for Patients and CliniciansIt is perhaps unsurprising that DTC-GAT would come up in the clinical setting such as within the scope of psychotherapy. Indeed, it is natural for people to want to search for and understand their origins [2,3], and in today’s world of technology and connectivity, individuals have turned to available information-gathering resources such as DTC-GAT and companies’ online social network platforms to do so [3]. Unfortunately, for clinicians who seek to provide guidance to patients on the topic of DTC-GAT, including risks and benefits, little evidence-based guidance is available. The therapist in the first case example above raised the following topics with the patient, which have been discussed in the scientific literature and popular media: (1) privacy concerns and use of data by for-profit companies or researchers; (2) unexpected findings (eg, misattributed paternity); and (3) lack of consistency in ancestry results due to differences in DTC-GAT company approaches to sequencing and reference pools used for ancestry estimates. The patient’s own underlying motivations and attitudes toward testing were explored and were a focus of the conversation. Ultimately, the therapist utilized a motivational interviewing framework, which is commonly used for a variety of health behaviors and decision-making in clinical settings. This resulted in the creation of a decisional balance [4], which involved constructing a list of the risks and benefits, tailored to the patient, which he could use to ultimately make the best decision for himself. In the second case example, the therapist incorporated the DTC-GAT results the patient had shared into cognitive behavioral therapy, creating space for him to explore his reactions to the DTC-GAT emotionally, cognitively, and behaviorally. The therapist also took this opportunity to educate herself on the mental health implications of DTC-GAT by discussing it openly with the patient and consulting with colleagues. for CliniciansApplicable ethics codes for psychologists and physicians include the five general principles of the Association’s of Psychologists and Code of Conduct (“Ethics Code”) [5] or the nine principles of medical ethics from the Association’s Code of [6]. Both sets of principles are relevant for working with patients who raise the topic of DTC-GAT and have substantial overlap in their messages. First, clinicians are to make relevant information available to the patient for decision-making.

Output: corroborate


Input: Claim: One focus of anti-aging research is studying genetic markers associated with longevity in certain populations. [SEP] Text: We also utilized data directly from the microarrays for variants on the X (n=19,381) and Y (n=284) chromosomes, and on the mitochondrial genome (n=135), which were unavailable in the imputed dataset. Health and (HRS) In HRS v2 data, phase 1-3 samples were combined (n=15,708) and SNPs were kept if no discordant genotype call among duplicate samples (2,315,518 SNPs). Related or duplicated participants and genotyping controls were removed, as well as those with a missing call rate equal to or greater than 2%. After the sample quality control, 15,454 samples were kept and 84% of them (n=12,940) were of European descent. 2,075,208 out of 2,315,518 SNPs passed the composite filters by the University of Washington (Hardy-Weinberg equilibrium p-value < 1e-4, missing call rate ≥ 2%, sex difference in allelic frequency ≥ 2% and sex difference in heterozygosity > 0. 3) and had a minor allele frequency greater than zero. As recommended, SNPs with a minor allele frequency smaller than 2% further were removed. At the end, 1,437,608 SNPs were carried forward for SNP pruning. The purpose is to choose less correlated SNPs for principal components analysis. The SNP pruning was performed following the procedure: a) consider a window of 50 SNPs, b) calculate LD between each pair of SNPs in the window, c) remove one of a pair of SNPs if the LD is greater than 0. 5, d) shift the window 5 SNPs forward and repeat the procedure. 514,246 SNPs remained after the SNP pruning and were used to run principal components analysis. As a result, the top 10 principal components were used to adjust for ancestry in a regression model. Both SNP pruning and principal components analyses were performed in PLINK1. 9 The samples in the genetic data were mapped to the phenotype data of HRS to retrieve parental longevity phenotypes. We used the phenotype data from the most recent wave or visit of HRS where parental data was missing if the parent died before the last visit. To recover the data, we sequentially looked back at the last visit until the parental data was available.

Output: contrast


Input: Claim: All insects can communicate through sounds and music. [SEP] Text: Which sounds, then, should be included in the improvisation, who should decide, and are the reins loose or tight? In what follows, I propose to turn these problems of freedom, constraint, learning, inclusion and artistic leadership on their heads, in a discussion of initial findings from an arts-based research project with autistic girls, Playing A/Part. Instead of which sounds should be included in an improvisation session to affect the best learning experience for all, the question might become: what do all the sounds of an improved session tell us? And how do we make sense of what is going on sonically, to steer (steward) the music towards a shared understanding that includes as many of the participants as we can? Playing A/A/Part was an Arts and Council (AHRC)-funded research project, taking place from 2019 to 2021 (Shaughnessy et al. , 2021). Ethical approval was granted by the University of Kent’s Ethics Committee. Its interdisciplinary approach explored drama, music, sound recording and art activities with autistic girls, with a key aim to understand autistic experience in and through such activities. will consider findings from a music-based pilot project. The participants (N = 6, ages 12–15 years) attended School, the only school in the solely for autistic girls. All participants attended a series of nine after-school workshops, voluntarily. Although there was no music provision at the school, the participants had all expressed an interest in music. The author, as a project co-investigator, led the practical music activity. series of nine weekly workshops explored approaches to group improvisation and composition. Data were collected in three ways: • Workshops were filmed and subjected to videographic analysis which focused on significant moments for individuals: changes in behaviour, learning, participant insight, challenges or resolutions. • Participants were interviewed prior to taking part using semi-structured methods, tapping musical experiences including formal/informal learning and using music in daily life. Sensory p1. Amoebas to cogs. Discussion: learning from off-task sounds The off-task sounds from all participants were not atypical, and at first, I ignored them, focusing on the group playing together and listening to one another. However, the empirical study that underpinned this project indicated that a significant proportion of music-making was indeed off-task and was often developmental in its complexity and confidence.

Output: pass


Input: Claim: Genetic testing can provide insights into ancestry and potential health risks. [SEP] Text: Third, contingent on empirical findings from the first recommendation, we might suggest the Association consider integrating questions about DTC-GAT into one of the supplementary modules of the Interview (CFI) [16]. The CFI is a tool used by clinicians to ensure they are considering the intersections of culture and identity to elicit the patient’s own attitudes of cause, context, support, coping, help-seeking, and barriers related to their treatment-seeking and outlook on clinician-patient relationships. The CFI’s supplementary modules are optional resources for assessors who might elect to probe additional aspects of identity, perspectives, or beliefs. Specifically, the CFI may benefit from inclusion of an optional question and probe in one of the supplementary modules (eg, Cultural Identity; Coping and Help-seeking) such as: “Have you ever engaged in or thought about doing genetic testing like an ancestry or health testing kit (eg, Ancestry. com, 23andMe) to better understand your identity, family, or health? If so, how has that experience impacted you? ” As a result, clinicians may be able to get a better sense of patients’ attitudes toward and potential experiences with DTC-GAT and other genetic testing. Importantly, however, given the potentially high-stakes issues, some of which have been described in this viewpoint, clinicians should also use clinical judgment in weighing the possible risks and benefits of introducing the topic of DTC testing to a patient. A disclaimer indicating some of the high-stakes issues surrounding DTC-GAT could be helpful to include for clinicians who may never have considered them, and could help guide clinician-patient conversations. ConclusionAs DTC-GAT has drastically grown in popularity, has become more affordable, and is increasingly more integrated into mainstream society (ie, kits are now sold at local pharmacies in the United States), test-takers have expanded from the “early adopters” or “worried well” to individuals from all walks of life who sometimes have important and sensitive reasons for engaging in DTC-GAT (ie, finding biological parents). Patients will continue to bring up DTC-related topics (eg, GAT) and clinicians must be prepared to engage in these types of conversations [12].

Output: pass


Input: Claim: One focus of anti-aging research is studying genetic markers associated with longevity in certain populations. [SEP] Text: (2008) Polymorphic tetranucleotide microsatellites for Cope's giant salamander (Dicamptodon copei) and Pacific giant salamander (Dicamptodon tenebrosus). Res 8: 1071–1073. View 5. (1989) Molecular Cloning: A Laboratory Manual, 2nd edn. New York: Press. 6. (1999) Universal linker and ligation procedures for construction of genomic DNA libraries enriched for microsatellites. Biotechniques 27: 500–507. View 7. Gautschi B, Tenzer I, Müller JP, (2000) Isolation and characterization of microsatellite loci in the bearded vulture (Gypaetus barbatus) and crossamplification in three vulture species. 9: 2193–2219. View 8. (2000) Isolation and characterization of microsatellite loci in the (Natrix tessellata). 9: 2191–2193. View 9. (2004) Sibship reconstruction from genetic data with typing errors. Genetics 166: 1963–1979. View 10. (2009) Influence of life-history variation on the genetic structure of two sympatric salamander taxa. 18: 1629–1639. View 11. (2004) MICRO-: Software for identifying and correcting genotyping errors in microsatellite data. Notes 4: 535–538. View 12. Raymond M, (1995) (version 1. 2): Population genetics software for exact tests and ecumenicism. J Heredity 86: 248–249. View 13. (1988) A sharper Bonferroni procedure for multiple tests of significance. Biometrika 75: 800–803. View 14. Peakall R, Smouse PE (2005) Genalex 6: genetic analysis in Excel. Population genetic software for teaching and research Notes 6: 288–295. View 15. Kalinowski ST (2005) HP-Rare: a computer program for performing rarefaction on measures of allelic diversity. Notes 5: 187–189. View 16. Kalinowski ST (2004) Counting alleles with rarefaction: private alleles and hierarchical sampling designs. 5: 539–543. View 17.

Output: pass


Input: Claim: All insects can communicate through sounds and music. [SEP] Text: All the workshop sounds were reframed as various ways of participating or ‘playing’. For example, sensorily driven private playing, for example, musical stimming, became ‘playing for pleasure’, singing covertly in the gaps became ‘private/public playing’, and provocative sounds (see below) became ‘playful playing’ – playing to get a response. In many cases, these were routes to making music as an ensemble, moving towards ‘proactive’ and ‘interactive’ play that recalls Adam Ockelford’s Sounds of Intent framework (Ockelford et al. , -and 2011). These kinds of musical play demonstrate a will to join in the activity, suggesting both musicality and sociality. Editing them out, suppressing or continuing to ignore them would have lost the richness of input and agency – the project would have lost a sense of who the young people were as musicians and people. Whilst the off-task sounds in Playing A/Part are framed as modes of play, Gershon’s (2011) study of classroom soundscapes considers on- and off-task sounds as systems of learning and meaning. His study begins in a fifth-grade classroom (children aged 9–10 years). He points out the limits of a recording that favours the teacher’s voice and suppresses background sounds: rustling paper, scraping chairs, a teacher’s whispered encouragement to a pupil, external weather and sounds from the city. The latter set of ambient sounds contributes to the children’s learning about their environment and their peers (who is concentrating, the rise in sonic activity as students reach the end of a period of focus, outside sounds of passing traffic and sirens indicating daily city rhythms or moments of crisis). As in improvisation, there are elements of the sonic environment beyond the control of teachers that nonetheless offer opportunities to learn. These sonic epistemologies, or acoustemologies (from 1996), are amplified when the same students undertake a lesson explicitly exploring sonic learning and taking place in a woodland setting. Students work in pairs to guide blindfold partners through a wood – sounds of this classroom are verbal directions ‘left here, stop there’ filtered by the woodland environment, indicating distance (reverb or echo), and nested within the sounds of nature – rustling leaves and so on.

Output: pass


Input: Claim: Genetic testing can provide insights into ancestry and potential health risks. [SEP] Text: -19 PreprintsProtocolsVideosJournalsTools & a 10. 21203/rs. 3. rs-2645173/v1This work is licensed under a CC BY 4. 0 LicenseStatus:Published18 Jan, 2024Read the published version in →Version 1posted 8You are reading this latest preprint versionAbstractTobacco use is a major risk factor for multiple diseases and is heavily influenced by environmental factors with significant underlying genetic contributions. Here, we evaluated the predictive performance, risk stratification, and potential systemic health effects of tobacco use disorder (TUD) predisposing germline variants using a European- ancestry derived polygenic score (PGS) in 24,202 participants from the multi-ancestry, hospital-based biobank. Among genetically inferred ancestry groups (GIAs), TUD-PGS was significantly associated with TUD in (EA) (OR: 1. 20, CI: [1. 16, 1. 24]), Hispanic/(HL) (OR:1. 19, CI: [1. 11, 1. 28]), and American (EAA) (OR: 1. 18, CI: [1. 06, 1. 31]) GIAs but not in (AA) GIA (OR: 1. 04, CI: [0. 93, 1. 17]). Similarly, TUD-PGS offered strong risk stratification across PGS quantiles in EA and HL GIAs and inconsistently in EAA and AA GIAs. In a cross-ancestry phenome-wide association meta-analysis, TUD-PGS was associated with cardiometabolic, respiratory, and psychiatric phecodes (17 phecodes at P < 2. 7E-05). In individuals with no history of smoking, the top TUD-PGS associations with obesity and alcohol-related disorders (P = 3. 54E-07, 1. 61E-06) persist. (MR) analysis provides evidence of a causal association between adiposity measures and tobacco use. Inconsistent prediction of TUD-PGS across GIAs motivates the inclusion of multiple ancestry populations at all levels of genetic research of tobacco use for equitable clinical translation of TUD-PGS. Phenome associations suggest that TUD-predisposed individuals may require comprehensive tobacco use prevention and management approaches to address underlying addictive tendencies.

Output: corroborate


Input: Claim: One focus of anti-aging research is studying genetic markers associated with longevity in certain populations. [SEP] Text: Departure from neutrality was tested using Fu's Fs [38] and Ramos-Onsins and Rozas' R2 statistic [39], which are powerful tests for detecting recent population expansion under assumptions of neutrality. R2 is appropriate for small sample sizes [39]. The significance of R2 and Fs were evaluated by comparing their observed values with their null distribution, generated by 10 000 random replicates using the empirical population sample size and observed number of segregating sites implemented by DnaSP v. 5. 10. [36]. To describe the phylogenetic relationships between haplotypes, a statistical parsimony network was constructed using TCS v. 1. 21 [40]. The divergence among haplotypes was calculated in MEGA 5 using the mean uncorrected p-distance [41]. To investigate the regional structure of A. icterica populations at the mitochondrial level, the overall genetic differentiation between populations was first estimated by calculating the global Φst in Arlequin v. 3. 5. 1. 2 software [42]. We then performed a spatial analysis of molecular variance using software [43]. Clusters are identified based on geographic proximity and genetic homogeneity [43]. The geographic coordinates of each sampled locality were used as spatial information. Simulations were conducted with ‘K’ (number of groups) ranging from two to seven and each simulation annealing process was repeated 100 times. The clustering giving the highest Φct value, corresponding to the optimal number of groups, was selected. Microsatellite genotyping Individuals were genotyped using seven microsatellite loci: Ai45, Ai56, Ai68, PB10D, 2PE40, 2PE70, C4 [27]. For individuals from the I20 and IR populations, genotypes were taken from Torres-Leguizamon et al. [27].

Output: pass


Input: Claim: All insects can communicate through sounds and music. [SEP] Text: Clare did so whilst eyeballing me – smiling, but there remained an element of challenge in her demeanour. I could not tell if this was playing to please or playing for pleasure – connecting with the ensemble because she was asked to, or at her choice. However, the connection initiated in session 1 was not borne out later. Clare’s involvement diminished over the following four weeks, she often sat sideways on to the workshop, behind her keyboard, half-in and half-out of the group, staring out of the window. Occasionally, Clare contributed wry comments, rarely playing with the others during the activities, but sometimes playing a drum off-task. Perhaps she did not want her oppositional heckle to become normalised, and a way to enact opposition was to not play. The sessions described highlight a challenge arising from the normalisation of Clare’s marginal heckles. When the leadership reins were pulled in (asking Clare to fit her sound within an eight-beat pulse, making this the musical foundation), the musical result was more coherent. It could be said that the ensemble playing of all participants progressed with this rhythmic grounding in place as our bass line. However, it did not, in this instance, become a springboard for Clare’s creativity. This may partially be explained through current autistic self-advocacy thinking, which sheds light on some of the progress made towards embracing all learners, as well as problematic practices that intend to create inclusion but which in fact create barriers (2010; Churchill & and 2020; 2021). Many practices rooted in ‘inclusion’ are designed by neurotypicals (NTs). Well-meaning efforts to make existing courses, syllabuses and examinations available to disabled people attempt to remove barriers to normalisation (e. g. ‘mainstreaming’), with a danger that people mask their disabilities in order to fit in – to appear to be like everyone else. The alternative suggested by Manalili (2021) would be to explore ‘people’s potential to learn and flourish in their own right’ (p. 22). Clare’s heckles, regardless of whether or not they were ‘usefully’ grounding an eight-beat rhythm, were valuable as energetic, low-pitched sounds within the workshop. They were more constructive towards the group improvising than Clare’s later approach of not playing.

Output: pass


Input: Claim: Genetic testing can provide insights into ancestry and potential health risks. [SEP] Text: Health sciences/Diseases/Psychiatric disorders/AddictionBiological sciences/Genetics/Genomics/Personalized medicineFiguresFigure 1Figure 2Figure 3IntroductionTobacco use causes significant global mortality and morbidity, contributing to several systemic conditions, including cardiometabolic diseases and cancers1,2. Tobacco use has historically been studied as an environmental risk factor for other diseases; however, tobacco use could instead be viewed as a complex psychiatric trait with environmental risk factors3 and significant genetic contributions4,5. Multi-ancestry genetic studies report an estimated heritability (i. e. , the proportion of the phenotypic variance explained by genetics) of tobacco use behaviors ranging between 5–18%4,5. Prevention and management strategies for tobacco use can benefit from precision medicine approaches, with the inclusion of baseline genetic risk to develop individualized preventive and therapeutic strategies for tobacco use. However, these efforts require a thorough understanding of the effects of a genetic predisposition to tobacco use and the impact of tobacco predisposition on the overall systemic health of an individual. To understand the genetic etiology of tobacco use, researchers use genome-wide association studies (GWAS) to identify single nucleotide polymorphisms (SNPs) associated with tobacco use disorder. GWAS have identified over 2000 loci associated with tobacco use traits, such as smoking behaviors and nicotine dependence4,5. However, single variants rarely capture a large proportion of phenotypic variation for a complex behavioral trait like tobacco use. To capture the overall genetic predisposition to tobacco use, polygenic scores (PGS) aggregate the weighted effects for multiple variants of interest, thus capturing a larger proportion of phenotypic variation than single variants. Polygenic scores have been used in research for disease prediction and to evaluate disease correlations, with potential for clinical translation to identify high-risk individuals6. In particular, tobacco use behaviors have shown genetic correlations with diseases such as schizophrenia and substance use disorders7–11. To further contextualize disease-associated genetic variants, phenome-wide association studies (PheWAS) systematically test the association of a single genetic variant across multiple phenotypes12. PheWAS potentially identify other traits or disorders upon which the single genetic variant could exert an effect, i. e. , horizontal pleiotropic effects of the genetic variant.

Output: corroborate


Input: Claim: One focus of anti-aging research is studying genetic markers associated with longevity in certain populations. [SEP] Text: υ (n = 7) καθώς και (iii) βοοειδή Κύπρου (n = 5).

Output: pass


Input: Claim: All insects can communicate through sounds and music. [SEP] Text: However, they posed a challenge: how to make sense of them in a way that was fruitful for all participants? Heckle ontologies and social functions in improvisation, stand-up comedy and learning environments Heckles, as potentially disruptive or oppositional, hold an agency that merits further examination, particularly in its challenge to improvisation workshop leaders (or teachers) to steer between freedom and constraint. There follows an examination of heckle ontologies as meaningful contributions to improvised discourse, considering perspectives from music and stand-up comedy, the latter indicating strategies for comics to manage heckles – some of which may provide useful models for workshop leaders or teachers. I first used the term ‘heckle’ as a way of describing short, repetitive (non-developing) improvised gestures that contradict the flow of another part (1997). Whereas punctuations in improvisation might be short gestures (e. g. stabs) that appear at the ends of phrases, politely adding a comma or full stop to a musical phrase, heckles sit awkwardly somewhere in the middle of a phrase – provocative or unnoticed, niggling away, repeating but not evolving. To function as a heckle, a musical utterance must stay short and sporadic: too long and it becomes a countersolo, too predictable in its repetition and it recedes into the musical background (like wallpaper). An exemplar (non-improvised) heckle is the first movement of Stravinsky’s for (1914), in which the second violin mutters the same four-note motif throughout, its timing consistently at odds with the first violin melodic phrases. In improvised music, heckles might be read as oppositional, a call to attention (listen to me! ) or the expression of a will to take part (a player is unsure what to play – so they play a short phrase, testing the water), or a short utterance that fizzles out and is not followed by another idea. They are, necessarily, part of the improvisation, not the central narrative, but offering an additional perspective on the improvised discourse. They resemble heckles at a stand-up comedy performance – observations, asides or insults interjected from the audience towards the spontaneous (if not fully improvised) monologue delivered onstage.

Output: pass


Input: Claim: Genetic testing can provide insights into ancestry and potential health risks. [SEP] Text: This large-scale collection of genotyped biospecimens is integrated with the (DDR), containing de-identified patient electronic health records (EHR) which include clinical, procedural, laboratory, prescription, and demographic information. Final analyses included 24,202 ATLAS participants with complete information on the outcome and covariates including smoking status and insurance information. For ancestry-specific analysis, we included (N = 15,780), Hispanic/(N = 4,412), American (N = 2,377), and (N = 1,633) ancestry groups with sufficient sample sizes for analysis. Detailed information on data processing can be found in previous publications15–19. Briefly, blood samples were collected from consented participants and genotyped on a custom array21. Initial array-level quality control measures included removing strand ambiguous SNPs and variants with > 5% missingness. After restricting to unrelated individuals, the QC-ed genotypes were imputed to the TOPMed Freeze5 reference using the Server22,23. The final QC steps were to filter the variants at the threshold of R2 > 0. 90 and minor allele frequency > 1%. All quality control steps were conducted using PLINK 1. 924. We computed the top 10 principal components for our study population using FlashPCA2 software25. We then grouped our study population into genetically inferred ancestry groups (GIAs) - (EA), Hispanic/(HL), American (EAA), (AA) - by k-nearest neighbor (KNN) stratification of the principal components, using the continental ancestry populations from 1000 Genomes Project26,27 as a reference. To account for differences in population stratification between GIA groups, for the PGS-PheWAS analysis, we conducted individual PGS-PheWAS within each GIA group and then meta-analyzed across GIA groups to obtain cross-ancestry results. Imputation within used a publicly available polygenic score trained on 391,124 European individuals from the UK biobank for the trait ‘tobacco use disorder’ from the PGS catalog (PGS002037)14,28.

Output: corroborate


Input: Claim: The majority of age-related illnesses can be prevented by a single genetic alteration. [SEP] Text: in medical sciencehave led to the cure and prevention of major diseases leading to longer lifespans. However, increasing lifespan has presented new medical challenges such as the rise of chronic and age-related illnesses. Chronic diseases are often associated with perturbations of multiple disease pathways and may require simultaneous modulation of multiple targets. Thus, the current paradigm of drug discovery and development based on a specific,single disease target may need to be complemented with a holistic systems-based approach. Although botanicals have historically been a source of new drugs, botanical extracts are not widely accepted in Western medicine. A relatively newregulatory approach with botanical extracts as a new class of drugs may pave the way for a new paradigm in discovering and developing therapies for chronic diseases. sourced from natural products such as microorganisms and plants have been the foundation of the pharmaceutical industry. Aspirin had its origins in the time of Hippocrates (460-370 BCE) where willow bark andsalicylate-rich plants were used to reduce pain, fever and inflammation. The turning point came centuries later when Bayer scientists produced synthetic acetylsalicylic acid (aspirin)with the same effects as salicylateextracts. Another example is the fungus that identified in 1928,which had anti-bacterial activity. extracted the penicillin molecule paving the way for its large-scale commercial production anditsrevolutionary use to treat infections. Boris Chain, Fleming and Florey won the in Physiology or Medicine in 1945. In the last 40 yearsa drug discovery and development paradigm based on a single, drugtarget and its mechanism of action evolved. Advances in high-throughput screening, genomics and structure-based drug design validated and accelerated its progress. Examples include the discovery and development of more selective COX-2 (cyclooxygenase-2) inhibitors, withfewer sideeffects than aspirin; statins or inhibitors of HMG CoA reductase, the key enzyme in cholesterol biosynthesis for the treatment of hypercholesterolaemia; and anti-retroviral agents targeting the HIV (human immunodeficiency virus) reverse transcriptase enzyme. The same period also saw the emergence of biological or large molecule drugs (mainly proteins) to treat metabolic disease (e. g.

Output: contrast


Input: Claim: All insects can communicate through sounds and music. [SEP] Text: In both cases, the relationship between the main narrative and heckles indicates that ensemble improvisation and stand-up comedy are social, impromptu environments and, as such, entail interaction and negotiated roles (2015). Additionally, heckles can threaten situational (leader/speaker) power and, if hostile, can lead to feelings of vulnerability. A portion of the stand-up comedy literature is devoted to heckles as a feature of audience–performer interaction and as a challenge to the comic’s ability to hold the audience’s attention (2009; 2014), as the opening to Brand’s autobiography attests: ‘Please welcome Jo Brand! ’ I step into the firing line. Yes, ‘firing line’ is the appropriate phrase. The ultimate fear of the stand-up is that a heckle will get you right in the heart and melt you like the of the West, into a steaming heap of gooey stuff. (2009, p. 1) Dealing with a heckle is a test of the comedian’s ability. To ignore it is to seriously undermine the audience’s faith, and if the comic ploughs on relentlessly with material rather than responding, the illusion of spontaneity is broken. (2014, p. 345) Against the comic’s backbone of prepared material, heckles afford an opportunity for improvisation. In improvised music, heckles are launched from the margins, with no imperative to create a musical narrative (rather to disrupt or to commentate on what is already there). They may present a strategy for participants’ engagement that is less risky than committing to a material that is intended to contribute to or change the improvised narrative – a solo, or a compelling new accompanying texture, for example. As the music tips towards instability through heckles, those in leadership roles are challenged with navigating both inclusion and clarity, for example, by finding meaning in all sounds as paths to engagement or polyhedral forms of musical expression, recalling Borgo’s (2007) dynamic systems, and reifying them as such to all participants. Conversely, leaders may override sounds from the margins, ignoring them or finding other ways to steer the music towards less polyhedral-sounding territories. Heckles in stand-up and in music can be valued as part of a dynamic improvisatory environment.

Output: pass


Input: Claim: Genetic testing can provide insights into ancestry and potential health risks. [SEP] Text: Four genetically inferred ancestry groups had sufficient sample size to perform the analyses - (EA), Hispanic/(HL), American (EAS), and ancestry (AA) (n = 15,780, 4,412, 2,377, and 1,633, respectively) Table 1 summarizes the demographics of the study sample. Table 1 Baseline characteristics of ATLAS participants included in this study Overall n 24202 Age, median [Q1, Q3] 61. 0 [46. 0,72. 0] Sex, n (%) Female 13277 (54. 9) Male 10914 (45. 1) Insurance Class, n (%) Private 14996 (62. 0) Public 8431 (34. 8) Self-Pay 775 (3. 2) Disorder, n (%) Controls 16283 (67. 3) Cases 7902 (32. 7) Ancestry, n (%) (AA) 1633 (6. 7) Hispanic/(HL) 4412 (18. 2) American (EAA) 2377 (9. 8) (EA) 15780 (65. 2) Prediction and risk stratification of TUD using TUD-PGS across genetically inferred ancestry groups We first evaluated how well the TUD-PGS predicts TUD across the multi-ancestry study sample within the ATLAS biobank. The TUD-PGS associated significantly with the phecode for TUD within the ATLAS biobank for individuals of (EA) GIA (OR:1. 20, CI: [1. 16, 1. 24]), showing an increase of odds of TUD by 20% for each standard deviation increase in the TUD-PGS. Similarly, we observed significant associations between TUD-PGS and TUD among Hispanic/(HL) GIA (OR:1. 19, CI: [1. 11, 1. 28]), and American (EAA) GIA groups (OR: 1. 18, CI: [1. 06, 1. 31]). However, the TUD-PGS was not associated with TUD in individuals of (AA) GIA group (OR: 1. 04, CI: [0. 93, 1. 17]). 1 summarizes these associations. Next, we assessed if the TUD-PGS could stratify individuals by risk for tobacco use disorder.

Output: corroborate