Input: Claim: The majority of age-related illnesses can be prevented by a single genetic alteration. [SEP] Text: recombinant insulin for diabetes; human growth hormone for dwarfism; interferon-beta for multiple sclerosis) and rare, orphan diseases (recombinant human deoxyribonuclease for cystic fibrosis). This periodalso witnessed the fulfilmentof humanised and fully humanmonoclonal antibodies’ promisein the treatment of cancer and other inflammatory diseases such as rheumatoid arthritis. The challenge in chronic disease: Targeting multiple target and pathways The success in conquering human disease has led to longer lives but has come with a price – the emergence of chronic indications associated with aging and longer lifespans. Thus, although there has been significant success in developing novel drugs with the single target paradigm, drug development in chronic diseases has increasingly been challenging. It is becoming clear that chronic diseases involve multiple, dysfunctional pathways thatmay need simultaneous modulation [1,2]. Most of the targets being modulated by current drugs or drugs in development are downstream of the disease pathway and correlate more with symptoms rather than the cause of the disease. Targets such as TNF (tumour necrosis factor)-alpha in inflammation and hyperglycaemia in diabetes are examples of this. Currenttrendsin combination therapy and precision medicinein oncologywith different immunotherapies and chemotherapies represent strategies in simultaneously targeting multiple pathways to manage disease. Recent discoveries on the role of the microbiomehave also led to a better understanding of its interaction with the host and its contribution to chronic diseases. Although it is possible that there are a limited number of control points which would have more broad and effective effects to manage disease, these are currently unknown. A key element in most chronic diseases is inflammation. Notwithstanding, therapeutic targets in inflammation remain vague and elusive due to multiple pathways. Not only is it important to identify which targets to address but it are also imperative to identify where in the pathway to intervene. Inrheumatoid arthritis, the cause of inflammation in different joints was attributed to various pathways[3]. Anotherobservation is cross-talk between rheumatoid arthritis and coronary artery diseasewithin the same inflammationpathway [4]. Thus, modulating a single target or pathway associated with inflammation is probably not sufficient to manage or treat a chronic illness. Furthermore, the more upstream in the pathway the target is the better.

Output: contrast


Input: Claim: All insects can communicate through sounds and music. [SEP] Text: The examples above shed light on ways to navigate uninvited sounds that may be useful to workshop leaders or teachers (ignore, accept as alternative narratives and incorporate into the main musical narrative). In the following examples, disruptive sounds are actively reframed as ways to manage the disruption to music improvisation workshops in care homes. Reframing heckles: the tea trolley and the care home The following accounts are from an interview with Julian West, a musician specialising in co-created, freely improvised music with people with dementia (Zeilig et al. , and WEST2019). In a care home environment, tea trolleys often come into the room during music sessions, interrupting what can be a carefully construed atmosphere: and the team I was working with were quite annoyed by [the tea trolley] every time it came in. [The atmosphere] would be totally obliterated … it’s quite a noisy thing you know when it comes in; there’s crockery, and often the member of staff that brings it in [is] entering the space in quite a performative way (laughs), because they’re here to do something, to give out tea and cake … Eventually, we were able to understand the tea trolley as a heckle – that this was an event that happens in the care home that’s part of the routine. (Interview with the author, 2022) As residents were ready for their tea and cake, it was difficult to ignore the trolley. Its sound was acknowledged as part of the wider project context, ‘a call back to doing something that’s … responding to the needs of the care home’ (Interview, 2022). On the other hand, framing it as a heckle within an improvised music session provided a way to accept the sound as a call from the margins that interrupts, but does not derail, the overall musical trajectory. A second strategy was to reframe the trolley as part of the improvisation: In a later project where I was working with a dancer, this came up again and the dancer knew instinctively what to do; she interacted with the tea trolley – when it came into the room and danced with the trolley, jumped on it and rode it round the room … So, the tea trolley did then become part of the piece that we were making.

Output: pass


Input: Claim: Genetic testing can provide insights into ancestry and potential health risks. [SEP] Text: Based on TUD-PGS, we divided the study sample into quintiles and estimated the odds ratio of TUD for each quintile compared to the bottom quintile. When compared to the quintile with the lowest TUD-PGS, the quintile with the highest TUD-PGS demonstrated an OR = 1. 69 (CI: [1. 51, 1. 88]) in EA and 1. 71 (CI: [1. 36, 2. 14]) in HL ancestry groups. The TUD-PGS offered strong risk stratification for individuals of EA GIA and for the top two risk quintiles in HL. Risk stratification was weaker and inconsistent in the EAA, (OR = 1. 60, CI = [1. 15, 2. 24]) and AA ancestry groups (OR = 1. 02, CI = [0. 71, 1. 47]) (Fig. 1, 2). This TUD-PGS risk stratifies individuals in EA and HL ancestry groups, potentially identifying individuals at a higher risk of tobacco use disorder within these ancestry groups. However, this risk stratification was inconsistent or absent in EAA and AA ancestry groups. Systemic comorbidities in TUD-predisposed individuals identified by TUD-PGS- PheWAS Next, we systematically evaluated associations between a genetic predisposition to TUD with 1847 traits or diseases across the phenome. The TUD-PGS captures the genetic predisposition to TUD and the 1847 traits are captured using phecodes extracted from each individual’s electronic health record. In a PheWAS of the TUD-PGS across 1847 phecodes (Supp Fig. 1a), meta-analyzed across 4 GIAs, we found 17 significant associations at Bonferroni-adjusted P < 0. 05 after adjusting for age, sex, first 5 principal components of the genotype matrix, and health insurance information. The top phecodes associated with the TUD-PGS were ‘morbid obesity’, ‘obstructive chronic bronchitis’, ‘substance addiction and disorders’, and ‘ischemic heart disease’ (P = 1. 38E-09, 2. 73E-09, 4. 45E-08, 1. 61E-07) (Fig. 2a).

Output: corroborate


Input: Claim: Genetic anti-aging interventions are proven to eliminate all signs of aging at the cellular level. [SEP] Text: Download PDF Review | | 3 May 2023 Cardiovascular aging: from cellular and molecular changes to therapeutic interventions English中文DeutschFrançais日本語Русский язык한국어ItalianoEspañolPortuguês No data Views: 1933 | Downloads: 767 | Cited: 3 Angeliki Vakka1 1of Pharmacology and Systems Physiology, University of of Medicine, Cincinnati, OH 45267, USA. 2Center for Vascular and Heart Research, Department of at 24016, USA. 23. 10. 20517/jca. 2023. 09 | © The Author(s) 2023. 19. 1 million deaths globally[1]. According to the Association, the prevalence of CVD (including coronary heart disease, heart failure, stroke, and hypertension) in men and women in the US is ~38% for people 40-59 years old, ~73% for 60-79 years old, and ~80%-85% for 80 years and above[2], indicating a strong association between aging and incidence of CVD. These statistics, in light of the projection that the number of people aged 65 years or older will rise from 10% in 2022 to 16% in 2050[3], signify the importance of deciphering the mechanisms of cardiovascular aging, which will identify potential targets for therapeutic interventions. Aging leads to progressive structural and functional deterioration of the cardiovascular system. Specifically, age-related changes in the heart and vasculature include cardiac hypertrophy, diastolic dysfunction, myocardial fibrosis, arterial stiffness, and endothelial dysfunction[4-8]. Major cellular hallmarks of cardiovascular aging include oxidative stress, mitochondrial dysfunction, reduced autophagy, inflammation, and telomere dysfunction[9-11]. Some of the molecular mechanisms that underlie these processes are involved in causing both myocardial and vascular aging [Figure 1]. To identify these molecular mechanisms and discover potential therapeutic targets, animal models of natural and experimental-induced aging are widely used. Figure 1. Cellular processes and signaling pathways that are common in myocardial and vascular aging.

Output: contrast


Input: Claim: All insects can communicate through sounds and music. [SEP] Text: … [The residents] completely got the joke – so it became something that really added to the session rather than something that detracted from it. (Interview, 2022) In West’s accounts, the workshop leaders embrace the tea trolley appearances as part of the improvisation environment. Irritation is dispelled by an acceptance of the trolley clanking in relation to the more deliberate music and dance features of the session. The acceptance of unpredictable elements within a social context recognises that not every action in this delicate environment can be controlled and that the entries of trolleys were an additional contribution to the session by offering refreshments – another way of meeting residents’ needs in a care home. A/Part, the formulation of several ‘modes of play’ (participation) enabled a new way to read the workshop. Rather than making the off-task sounds and heckles subaltern, the research team began to consider all workshop sounds as meaningful – what were the sounds articulating about a player’s preferred way to participate, enthusiasm, their rhythmic or aural skill, musical p30. They are not a panacea for problems raised by inclusion; any more than improvisation should be a panacea for the challenges surrounding music creation and performance. The appreciation of marginalised sounds, tempered with Roth’s (Reference ROTH2019) and Mullen’s (2008) reminders to steward them responsibly, may offer a constructive outlook to teachers and workshop leaders. There is no ideal ‘freeness or tightness of rein’ when leading an improvisation session. A good area of focus is on accepting and enjoying the dynamic environment, listening keenly to all sounds that emerge and adjusting the reins as needed to maintain an appropriate level of complexity. Inclusive practices can be cultivated through listening to sounds that fall beyond teacher/leader-defined aims, considering all session sounds as informative. Heckles, stims and private noodling can be reframed as modes of play. Heckles and off-task sounds may be routes into participation on the terms of the participants, rather than those of workshop leaders or teachers. For participants, they may be a way of testing the ground, ‘dipping a toe’ before plunging into the improvisation. For LaBelle, sounds are ‘a powerful force from which we learn the entanglement of worldly contact’ (2018, p.

Output: pass


Input: Claim: Genetic testing can provide insights into ancestry and potential health risks. [SEP] Text: Phecode categories with multiple associations were circulatory (n = 5), respiratory (n = 3), neurological (n = 2), and metabolic (n = 2) phenotypes (3). The results of this analysis systematically identify the health risks associated with a genetic predisposition to tobacco use captured by the PGS. However, it must be noted that these associations may reflect the traits and diseases associated with tobacco use behavior, which lies on the TUD-PGS to trait/disease pathway (Supp Fig. 1b). To study the potential pleiotropic effects of germline variants that predispose to TUD, we leveraged the fact that individuals with genetic predisposition to TUD may choose not to engage in tobacco use behaviors. We can remove the effect of tobacco use behavior to identify systemic risks of TUD genetic predisposition by stratifying to individuals with no smoking history recorded in their electronic health records. Accordingly, we repeated the PGS-PheWAS association analysis, restricting to “never-smokers” in individuals of EA ancestry, i. e. individuals who reported to their provider that they have never smoked tobacco (Supp Fig. 1b). In this analysis, the TUD-PGS demonstrated associations with obesity, alcohol-related disorders, cancer of the esophagus, and hypertension (P = 3. 54E-07, 1. 61E-06, 3. 05E-06, 2. 62E-05) (Fig. 2b, 4). In an evaluation of the trends of obesity and alcohol-related disorders across quintiles of the TUD-PGS, we observed higher ORs among never-smokers compared to ever-smokers for obesity and alcohol-related disorders. TUD-PGS offered inconsistent risk stratification for obesity and alcohol-related disorders in ever-smokers, or individuals with a history of smoking (Fig. 3). In contrast, a reverse trend is noted in lung cancer, an established trait associated with smoking behavior, which can thus serve as a negative control, where we observed higher ORs in ever-smokers compared to never-smokers. (Supp Fig. 2) We can conclude from this analysis that, individuals predisposed to TUD show associations with obesity and alcohol-related disorder even in the absence of tobacco use behavior.

Output: corroborate


Input: Claim: Genetic anti-aging interventions are proven to eliminate all signs of aging at the cellular level. [SEP] Text: Oxidative stress and mitochondrial dysfunction in the aged cardiovascular system are associated with decreased SIRT1 levels, which increases p66Shc and Arg2 levels, as well as the expression of NOX4, while it decreases Klotho levels, resulting in higher NRF2 proteolysis. Aging decreases AMPK activation in the cardiovascular system, leading to increased mTORC1 activity, increases ROCK1 and ROCK2, and decreases Parkin, resulting in impaired autophagy. Assembly of NLRP3 inflammasome, and elevated expression of TLR4 and NF-κΒ in the aged heart and arteries result in higher production of inflammatory cytokines, while the increased levels of 1 and ROCK2, and the decreased levels of PAR2 are associated with age-related cardiac and arterial fibrosis; image created on biorender. com. In this 0. 7% in people aged 18-44 years old to 13. 3% in people that are 75 years or older in the US has been reported[23]. The most common valvular complication is mitral regurgitation, followed by aortic stenosis, aortic regurgitation, and, lastly, mitral stenosis[23]. Aged heart valves become stiffer due to greater matrix collagen content, collagen cross-linking, fibrosis, and lower glycosaminoglycans content[24,25]. Also, calcification can develop in aging heart valves, resulting in dysfunctional movements and blood flow complications[26,27]. Therefore, LV afterload rise, LV hypertrophy, diastolic dysfunction, atrial fibrillation, valvular calcification, arterial stiffness, and endothelial dysfunction occur frequently in the elderly. stressPro-oxidant pathways in agingThe heart has a higher oxygen uptake rate and produces more reactive oxygen species (ROS) compared with other tissues in the human body[28]. The free radical theory of aging, first described by in 1956, proposes that aging and age-related diseases are caused by the harmful side attacks of free radicals on cellular components[29].

Output: contrast


Input: Claim: All insects can communicate through sounds and music. [SEP] Text: Юрий Каспаров Выпуск № 3 (775) │ 2021 Не все то музыка, что звучит Юрий Каспаров Выпуск № 3 (775) │ 2021 Не все то музыка, что звучит В чем заключается работа композитора? В том, чтобы найти материал и «отработать» его до состояния музыкальной формы. Чем талантливее композитор, тем ярче и необычнее материал, который он находит. И чем композитор профессиональнее, тем больше впечатляет его работа с этим материалом и конечный продукт в целом.

Output: pass


Input: Claim: Genetic testing can provide insights into ancestry and potential health risks. [SEP] Text: A major strength of this study is that we evaluated TUD-PGS in an information-rich biobank across multiple genetically inferred ancestry groups. The rich phenotypic information available in the biobank allowed us to test associations across the phenome in a hypothesis-free manner, allowing for the discovery of disease associations. Another strength of the paper is that we accounted for possible confounding bias introduced by participation/access to healthcare bias, which can arise from using data from a hospital-based biobank, by using an insurance class variable as a proxy marker for participation and access. We conclude with limitations and future considerations of our work. Our study included a multi-ancestry sample of patients, but non-European ancestries are represented at smaller sample sizes for most analyses using the biobank. With continued enrollment, we hope to increase our non-European sample sizes and evaluate differential genetic effects in these ancestries. Next, phecodes are derived from ICD codes which are billing codes and, accordingly, may not always capture the full extent of an individual’s disease history. The interpretations of our analyses are within the limitations of these phenotype definitions. We emphasize that the risk of having a phecode in the electronic health record does not accurately reflect the risk of having the disease. Phecode assignments come with biases, including access to healthcare. We have attempted to address this bias introduced by healthcare access by including an insurance class information variable. Nevertheless, this difference must be considered when applying these results to the general population. The results of our study have implications for public health and clinical approaches to the treatment of tobacco use disorder. Future research should strive to improve the prediction and risk stratification of TUD-PGS in all ancestry groups. With consistent performance across ancestry groups and improved individual-level prediction, TUD-PGS can be useful to identify individuals who can benefit from comprehensive preventive and therapeutic strategies to manage their underlying addictive tendencies. Given the growing evidence on health risks associated with obesity and tobacco use, our results suggest possible shared genetic etiology between these two risk factors, strengthening the argument that public health approaches must consider this shared risk while formulating interventions. Declarations2017. Geneva: Organization, 2017. for Prevention and (US) Office on Smoking and Health. Consequences of Smoking—50 Years of Progress: A Report of the Surgeon General. Centers for and Prevention (US); 2014. 14, 2022. . Social and.

Output: corroborate


Input: Claim: Genetic anti-aging interventions are proven to eliminate all signs of aging at the cellular level. [SEP] Text: Further studies have shown that excessive levels of ROS, including the superoxide radical (O2•-), the hydroxyl radical (•OH), and hydrogen peroxide (H2O2), are associated with a wide range of cardiovascular diseases, such as arterial hypertension, atherosclerosis, heart failure, and atrial fibrillation[30-33]. Although ROS are generated by various cellular compartments, mitochondria constitute their main source during oxidative phosphorylation[34,35]. With age, mitochondria become dysfunctional due to the accumulation of ROS-induced damage, such as mtDNA (mitochondrial DNA) mutations, leading to elevated ROS[36,37]. Evidence for the role of mitochondrial ROS in cardiac aging is provided by experiments with mice overexpressing an antioxidant, catalase targeted to mitochondria (mCAT)[38,39]. Constitutive mCAT expression attenuates murine cardiac aging likely due to lower mitochondrial proteome oxidation, and leads to fewer mtDNA mutations and lack of activation of the calcineurin-NFAT pathway, along with preservation of the sarcoplasmic reticulum Ca2+ ATPase (SERCA) pump content[38]. Also, late-life constitutive mCAT expression by administration of an adeno-associated virus serotype-9 vector expressing mCAT (AAV9-mCAT) improves diastolic function in aged mice[40]. Mitochondrial expression of cardiac NADPH oxidase 4 (NOX4), which catalyzes the first step of ROS formation, increases with age and cardiac stress, thus becoming a main source of mitochondrial oxidative stress[41]. Moreover, NOX4 expression is elevated in the vasculature of old mice[42]. The association of NOX4 with vascular aging was established with experiments using young transgenic mice with high mitochondrial NOX4 expression, which demonstrate aortic stiffening and impaired aortic contractility similar to those observed in aged mice. Aortic vascular smooth muscle cells (VSMCs) of these mice show elevated mitochondrial H2O2 and superoxide production, increased DNA damage and suppressed expression of superoxide dismutase 2 (SOD2), the main scavenger of mitochondrial superoxide[43].

Output: contrast


Input: Claim: All insects can communicate through sounds and music. [SEP] Text: Из этого и следует исходить в процессе обучения студента-композитора. Талант развить, наверное, можно. Но алгоритма его развития не существует.

Output: pass


Input: Claim: Genetic testing can provide insights into ancestry and potential health risks. [SEP] Text: ancestry and health Submit manuscript. . . MOJ eISSN: 2373-4442 0151. DOI: 10. 15406/moji. 2017. 05. 00151 about genetic ancestry has a great value in health studies and other related areas of expertise such as anthropology, forensics and pharmacogenomics. In this review, we highlight several aspects of health that can be significantly improved by better understanding of genetic ancestry. These observations were made possible based on our own medical genetic research in Asia/Pacific populations (i. e. in particular regarding Maori and of respectively). The major objectives of this programme of investigations has been to capture and understand genetic diversity in these populations and subsequently to make recommendations in order to maximise the health benefits of this type of population genetic research. Keywords: genetics, ancestry, health, Polynesians, maori, malays, orang asli, new Zealand, malaysia Abbreviations HPA: Antigen; HNA: Antigen; MICA: Complex class I chain–related gene A; HLA: Antigen; KIR: Killer cell Immunoglobulin–like Receptor; SNP: Genetic methods play a significant role in many research areas including medicine, forensics and ancestry study. In this respect, we highlight the ways in which knowledge about genetic ancestry has become an important element in health and medical treatments. This viewpoint is largely based on our own experience working on various genetic markers in Asia/Pacific populations such as Maori, Polynesians, Malays and in New Zealand, and Malaysia. These diagnostic markers include many loci (e. g. HLA, blood group, HPA, cytokines and HNA) that determine transfusion and transplant success, our immune responses to disease and as causal agents in autoimmunity. Ancestry and health We have completed and reported a comprehensive set of ancestrally informative genetic data across many Asia/Pacific populations. These systems include blood group, cytokine, HNA and HPA. 1–20 These new datasets not only provide special insights into the ancestry of these people, but also is of significant value in health; as recently reviewed by. 21–22 This is because these genes are determinants of transfusion and transplant success or have been directly associated with other immune and important biological functions. For example, matching of HLA markers between patient and donor is important before proceeding with transplant operations.

Output: corroborate


Input: Claim: Genetic anti-aging interventions are proven to eliminate all signs of aging at the cellular level. [SEP] Text: Furthermore, along with NOX4, phosphorylated and oxidative Ca2+/calmodulin-dependent protein kinase II (CaMKII) is increased in the hearts of old rats. NOX4/ROS-activated CaMKII phosphorylates Ryanodine receptor 2 (RYR2), a major Ca2+ channel protein in cardiac muscle, leading to acceleration of Ca2+ release and prolongation of diastolic relaxation[44]. Thus, this study implies a potential causality of the NOX4-CaMKII-RYR2 pathway with cardiac remodeling, mitochondrial oxidative stress, and ventricular tachyarrhythmia in aged mice. The p66Shc protein, which is a member of the Src homologous-collagen homolog (ShcA) adaptor protein family that mediates ROS-induced mitochondrial ROS release (RIRR), has also been related to cardiovascular aging. Upon oxidative stress-induced phosphorylation[45], p66Shc translocates to mitochondria, where it transfers electrons from cytochrome C to molecular oxygen, forming H2O2 and leading to apoptosis[46]. Mitochondria from the hearts of aged rats have increased levels of p66Shc[47], while p66shc-/- mice have higher nitric oxide bioavailability, decreased superoxide levels and are protected from age-dependent endothelial dysfunction[48]. Silent information regulator 1 (SIRT1), a nicotinamide adenine dinucleotide (NAD+)-dependent class III histone deacetylase (HDAC), represses transcription of p66Shc via epigenetic changes and is downregulated during aging[49,50]. Activation of SIRT1 with SRT1720, a specific SIRT1 activator, alleviates vascular endothelial dysfunction in old mice by reducing oxidative stress, nuclear factor-kappa B (NF-κB) activation, and tumor necrosis factor alpha (TNF-α) levels and increasing cyclooxygenase-2 signaling[51]. SIRT1 activation reverses endothelial dysfunction in microvessels isolated from subcutaneous adipose tissue of old patients, which is associated with lower p66Shc and Arginase II (Arg2) levels, and increased expression of mitochondrial enzymes with antioxidant properties, such as SIRT3 and SOD2.

Output: contrast


Input: Claim: All insects can communicate through sounds and music. [SEP] Text: Да, в Московской консерватории мы делаем все возможное: знакомим молодых людей с новой музыкой практически всех существующих направлений; анализируем важные, ключевые партитуры; углубляем знания студентов в области истории музыки, а также гармонии, полифонии, формы… У нас даже есть практические занятия с ансамблем солистов «Студия новой музыки» — лучшим камерным коллективом страны в области современного музыкального искусства, — на которых студенты и аспиранты м

Output: pass


Input: Claim: Genetic testing can provide insights into ancestry and potential health risks. [SEP] Text: Certain HLA types have also been shown to be contributing factors in the pathogenesis of various diseases. 23 In the following sub–sections, we will discuss several aspects of health which can be significantly improved based on our understanding of ancestry and genetic diversity in Maori, Malays, and several Polynesian sub–populations. Allelic variations and disease prevalence: Many diseases have been mapped to particular regions of the human genome and certain allelic types have been associated with high risk of disease In this context, relative risk of autoimmune diseases can be predicted from the prevalence of particular antigen types in a population. For example, medical conditions such as ankylosing spondylitis and rheumatoid arthritis are rare in Maori/Polynesians, but relatively common among Europeans. They are typically associated with the HLA–B*27:05 and HLA–DRB1*04:01 tissue types in Europeans and HLA–B*27:04 and HLA–DRB1*04:05 in Asians/Polynesians, respectively. 24–26 The HLA–B*27:04 and HLA–DRB1*04:05 alleles are quite rare in Polynesians (0–0. 01 and 0. 02–0. 08, respectively) which may explain the unusually low occurrence of ankylosing spondylitis and rheumatoid arthritis in Maori/Polynesians. 5 Candidate genes for disease study: Many genetic markers characterized in various populations across the globe are now available as population datasets and can be readily retrievable from public databases; e. g. 8 for Allele Frequencies. net and. 27 for IPD – Database. These datasets can be used not only as a reference standard for disease association studies (see later), but also provide important resources to search for candidate susceptibility genes in disease studies. A good candidate gene(s) will be one with greatest differences in allele frequency among populations, including between ethnically related populations which show different schedules of disease prevalence. This is one of the main molecular signatures of the highly polymorphic immune system genes, where patterns of allelic variation at population level are shaped by local demographic or selective factors; e. g. see.

Output: corroborate


Input: Claim: Genetic anti-aging interventions are proven to eliminate all signs of aging at the cellular level. [SEP] Text: Also, it upregulates the expression of genes involved in the mitochondrial respiratory chain, such as ATP synthase 6 (ATP6), cytochrome b (Cytb), NADH dehydrogenase 2 (ND2) and NADH dehydrogenase 5 (ND5), thus preventing mitochondrial ROS generation[49]. The association of Arg2 with aging is also demonstrated with increased vascular and cardiac levels. Arg2 catalyzes hydrolysis of mitochondrial arginine to ornithine and urea and has also been associated with atherosclerosis[52,53]. Elevation of Arg2 levels in human senescent VSMCs has been associated with activation of extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and ribosomal S6 kinase 1 (S6K1) by p66Shc[52], while genetic deficiency of Arg2 in mice extends lifespan mainly in females, which is associated with inhibition of p16 inhibitor of CDK4 (p16Ink4a), p66Shc, and S6K1 pathways[54]. Antioxidant mechanisms in agingBesides increasing pro-oxidant proteins, aging lowers the expression of the antioxidant nuclear factor erythroid 2-related factor 2 (NRF2), as it has been shown in aortas of aged rats and in cultured VSMCs of aged rhesus macaques, which contributes to vascular oxidative stress[55]. Besides the vasculature, NRF2 seems to be also important for preventing aging of cardiac muscle, as shown by the aggravation of D-galactose-induced oxidative stress and acceleration of cardiac aging in Nrf2-/- mice. Moreover, protection from cardiac aging has been reported in mice treated with an NRF2 activator, CDDO-imidazolide[56]. The protective role of NRF2 for cardiac aging has also been shown via the beneficial effects of a regulator of NRF2, secreted Klotho. Klotho is named after one of the three greek mythology “Fates” that controlled the thread of life of every person. Klotho incurs its anti-aging effects by upregulating NRF2 and (GR) and preventing cardiac hypertrophy[57].

Output: contrast


Input: Claim: All insects can communicate through sounds and music. [SEP] Text: огут проверить любые, самые сложные и необычные приемы звукоизвлечения, самые фантасмагорические сочетания тембров, а также поэкспериментировать с фактурой и драматургией.

Output: pass


Input: Claim: Genetic testing can provide insights into ancestry and potential health risks. [SEP] Text: Unlike next generation sequencing technology which is fully capable of capturing data from entire coding/non–coding regions, earlier techniques such as sequence based typing (SBT) and sequence specific primer (SSP) recorded only relatively small specifically targeted segments of the human genome. Both, SBT and SSP can reflect serological expression provided that all genetic variants associated with a particular phenotype can be included in the screen. For example, Duffy blood group phenotypes might be falsely identified if clinical analysts only identify the 125G>A SNP (FY*A to FY*B alleles, respectively) on chromosome 1. 29 Two further SNPs (67T>C and 286C>T) in the sequence encoding the FY*B allele should also be scored for erythroid silent. Fy(a–b–) and weak (Fya–bweak) expression of Duffy antigens, respectively. 30–32 The erythroid silent variant is common in Africa, but relatively rare in the other populations. 1–33 Hence, high resolution molecular screening of the erythroid silent variant in donors and patients could significantly reduce false prediction rates for Duffy phenotypes in African populations. Wider applications of population data for ethnically related populations: From a genetic standpoint, any research conducted on individual groups of people might have beneficial values for others, especially for closely related populations. For example, cytokines and HNA have never been genetically characterized in Maori and Polynesians. However, markers frequencies have been reported for both types of loci in some of their Austronesian relatives; namely the Malay subethnic groups. 9–13 In this context, these datasets from Malay subethnic groups can be used as a prospective guide to values for Maori and Polynesians. Nonetheless, any such inferences should be made with caution because each population might have experienced different evolutionary pressures after they split from one another around 5000 years ago. A most obvious example is that provided by our recent work on cytokine gene SNPs in Malays and where significant differences were recorded not only between groups (Semang vs. Senoi. vs. Proto–Malays), but also between their sub–groups; Lanoh vs. Kensiu vs. Bateq of Semang group. 12–13 Conclusion Overall, our understanding of genetic ancestry has a great potential to inform health and other related areas such as in forensic DNA studies and pharmacogenomics.

Output: corroborate


Input: Claim: Genetic anti-aging interventions are proven to eliminate all signs of aging at the cellular level. [SEP] Text: Aging decreases circulating Klotho levels in both mice and humans, and increases Kelch-like ECH-associated protein 1 (KEAP1) levels in isolated cardiomyocytes, which promotes NRF2 proteolysis[57,58]. Accordingly, treatment of aged mice with secreted Klotho reduces cardiac oxidative stress and rescues cardiac aging[57]. Thus, aging alters cardiac and vascular expression of proteins that regulate redox balance, such as NOX4, CaMKII, p66Shc, Arg-1, Nrf2, Klotho, SOD2, 2, resulting in elevated ROS levels and mitochondrial dysfunction in the aged heart and vessels. Impaired autophagyAutophagy is a cellular degradation process through which the cells recycle their own components. Autophagy decreases with age in numerous tissues, including the heart, and leads to accumulation of dysfunctional organelles, misfolded proteins, and lipofuscin granules[59,60]. One of the main regulators of autophagy is the mammalian target of rapamycin (mTOR), a serine/threonine kinase that also regulates cell proliferation, protein synthesis, lifespan, and aging[61]. mTOR is a component of the protein complexes mTORC1 and mTORC2[62]. mTORC1 is a suppressor of autophagy and is sensitive to rapamycin, while mTORC2 is not sensitive to short-term rapamycin treatment. Cardiac and vascular mTOR activity is significantly increased in aged mice[63,64]. Accordingly, in mice that do not express glycogen synthase kinase-3α (GSK3A), which inhibits mTORC1 activity, autophagy is decreased, and cardiac aging appears early and is accompanied by cardiac hypertrophy, systolic dysfunction, and impaired diastolic relaxation[65]. Conversely, chronic cardiomyocyte-specific activation of an activator of mTOR signaling, protein kinase B (Akt), leads to aging-induced cardiac hypertrophy and myocardial contractile dysfunction[63].

Output: contrast


Input: Claim: All insects can communicate through sounds and music. [SEP] Text: Иными словами, максимальное расширение кругозора идет параллельно с получением серьезных знаний во всех необходимых областях. Это мотивирует, создает благоприятную почву для поиска новых идей, концепций, методов, но не гарантирует развития таланта.

Output: pass


Input: Claim: Genetic testing can provide insights into ancestry and potential health risks. [SEP] Text: 22–37 The major challenges ahead are to investigate, describe and understand genetic variability in order to maximise the health benefits of population genetic research. 73. 16th IHIW: Global distribution of extended HLA haplotypes. Immunogenet. 2013;40(1):31–38. ínola H, et al. HLA polymorphism in six Malay sub–ethnic groups in Malaysia. Hum Immunol. 2009;70(7):518–526. Using HLA loci to inform ancestry and health in Polynesian and Maori populations. Tissue Antigens. 2012;80(6):509–522. HLA and MICA polymorphism in Polynesians and Maori: implications for ancestry and health. Hum Immunol. 2013;74(9):1119–1129. Molecular approaches to transfusion medicine in Polynesians and Maori in New Zealand. Immunogenet. 2013;40(6):460–470. Human platelet antigens frequencies in Maori and Polynesian populations. Transfus Med. 2013;23(5):330–337. González– Allele frequency net 2015 update: new features for HLA epitopes, KIR and disease and HLA adverse drug reaction associations. Res. 2015;43(Database issue):D784–D788. in Banjar, Bugis, Champa, Jawa and in Peninsular Malaysia. Blood Transfus. 2015;13(4):1–6. HNA Diversity in of in Peninsular Malaysia. Transfus Med. 2016;26(4):305–307. Nemat– KIR diversity in Māori and Polynesians: populations in which HLA–B is not a significant KIR ligand. Immunogenetics. 2014;66(11):597–611. Distribution of cytokine gene polymorphisms in five Malay subethnic groups in Peninsular Malaysia. Immunogenet. 2015;42(3):200–203. Distribution of cytokine gene polymorphisms in six subgroups in Peninsular Malaysia. Hum Immunol. 2016;77(4):338–339. Sequence polymorphisms of mtDNA HV1, HV2, and HV3 regions in the Malay population of Peninsular Malaysia. Legal Med.

Output: corroborate


Input: Claim: Genetic anti-aging interventions are proven to eliminate all signs of aging at the cellular level. [SEP] Text: In a similar manner, suppression of the myosin light chain (MLC)/focal adhesion kinase (FAK)/Akt/mTOR signaling axis via deletion of Rho-associated coiled-coil-containing protein kinase (ROCK)1 and ROCK2 promotes autophagy and reduces cardiac fibrosis in aged mice[66]. ROCK 1 and ROCK2, which have a central role in regulating actomyosin cytoskeleton contractility, promote age-related aortic stiffening as well[67]. Interestingly, although mTORC1 seems to promote cardiac aging[68], it was recently found that activation of mTORC2 alone increases autophagy and improves age-related cardiomyopathy in Drosophila[69], indicating additional layers of regulation of mTOR signaling in regards to its involvement in cardiac aging. AMPK, which is a serine/threonine protein kinase that acts as a cellular energy sensor of low intracellular ATP levels, a stimulator of autophagy in cardiomyocytes[70], and an mTOR inhibitor[71], also has low expression in the aged heart and arteries, which corroborates with increased mTOR signaling and reduced autophagy. AMPK deficiency exacerbates age-related cardiomyopathy[72,73]. Aging-induced deactivation of AMPK has been correlated with decreased SIRT1 activity. Consequently, SIRT1 activation in aged hearts activates AMPK and improves their tolerance to ischemic stress[74]. Moreover, combined deletion of both Akt2 (the main cardiac isoform of Akt) and AMPK suppresses autophagy and promotes aging-induced cardiac hypertrophy, interstitial fibrosis, and contractile dysfunction[75]. A certain type of autophagy that targets mitochondria, thus referred to as mitophagy, is induced by PTEN-induced putative kinase protein 1 (PINK1), which accumulates on the damaged mitochondria and phosphorylates the E3 ubiquitin ligase Parkin. Parkin marks proteins on the outer mitochondrial membrane with phosphoubiquitin, leading to lysosome-mediated mitochondrial degradation[76]. Parkin levels are significantly decreased in the hearts of aged mice[77].

Output: contrast


Input: Claim: All insects can communicate through sounds and music. [SEP] Text: Иногда случается так, что молодой композитор подает огромные надежды: он легко и быстро работает, и каждое новое сочинение существенно глубже, интереснее и необычнее предыдущего… Но в какой-то момент его творческий рост неожиданно останавливается, и никакие усилия как с его стороны, так и со стороны педагогов ни к чему не приводят. Мы никогда не знаем, до какого уровня в этом смысле может вырасти тот или иной наш подопечный.

Output: pass


Input: Claim: Genetic testing can provide insights into ancestry and potential health risks. [SEP] Text: AMA Journal of Ethics® Illuminating the Art of navigation 433. doi: 10. 1001/virtualmentor. 2014. 16. 6. ecas2-1406. Citation PDF Altmetric email Case Ms. Stewart was eagerly awaiting her upcoming trip to Boston to celebrate her parents’ fiftieth wedding anniversary. She had grown up in a large Irish family, with two brothers and two sisters, but she rarely got to see them since moving to Oregon for her job. She was especially looking forward to seeing her sister Anna, who was recovering from a mastectomy after receiving a diagnosis of breast cancer several months earlier. As a gift to her parents, Ms. Stewart had decided to create a book tracing the family’s genealogy. Growing up, her mother told her stories about how her great-grandfather had arrived at with hardly anything besides the clothes on his back, and she had always been curious about the family’s roots in Ireland. As she was searching the Internet for genealogy records websites, an advertisement on the side of her screen caught her eye. “Find out where your genes come from! ” Her curiosity piqued, Ms. Stewart clicked on the link to geneheritage. com, an online service for genetic testing of ancestry and ethnicity. She had heard of these online genetic testing services before and even read in a magazine that one of her favorite actresses had gotten one, but she had never before thought of doing it herself. “I could put it in the book,” she thought, as she perused the website. She decided to order a kit and, a few days later, she sent off a cheek swab for the DNA tests. Two weeks later, Ms. Stewart got her eagerly awaited results. To her surprise, the results indicated that she carried several polymorphisms that are known to be more common among than in the general population. According to the test, she had 23 percent ancestry in her genetic panel. Later that week, Ms. Stewart went to see her primary care physician, Dr. Lowe, for her annual physical. During the review of systems when Dr. Lowe asked her whether she had had any lumps or pain in her breasts, Ms. Stewart hesitated a bit. “haven’t had any problems, but I was thinking…I want to get tested for the breast cancer gene.

Output: corroborate


Input: Claim: Genetic anti-aging interventions are proven to eliminate all signs of aging at the cellular level. [SEP] Text: Inhibition of Parkin mitochondrial translocation -via p53- in the hearts of aged mice impairs mitophagy and causes cardiac dysfunction[78]. Conversely, overexpression of Parkin improves mitophagy and cardiac function in aged hearts[77]. Thus, aging-induced alterations in the expression of proteins involved in cell proliferation, cytoskeleton contractility and protein degradation, such as mTORC1, ROCK1, ROCK2, and AMPK, lead to impaired autophagy in aged hearts and vessels. Aging-related alterations in metabolic homeostasisAging is associated with major metabolic events, including insulin resistance[79,80]. Although it is known that insulin-like growth factor-I (IGF-I) facilitates glucose metabolism and inhibits apoptosis of cardiomyocytes[81,82], a study showed that the role of IGF-I receptor (IGF-IR) in cardiac health is age-dependent. Specifically, mice with cardiomyocyte-specific overexpression of IGF-IR show superior cardiac contractility at a young age, but pathological cardiac hypertrophy, increased LV fibrosis and reduced EF at 20 months of age. This pathological phenotype is attributed to reduced autophagy and lower oxidative phosphorylation in the heart[83]. Even in mice of 11 month-old, cardiomyocyte-specific inactivation of IGF-IR suppresses diastolic cardiac function to a greater extent than in their age-matched controls[84]. Moreover, mice with cardiomyocyte-specific expression of a dominant-negative mutant of phosphoinositide 3-kinase (PI3K) (dnPI3K), which is a downstream effector of insulin/IGF-1 signaling, have preserved cardiac function and less fibrosis at 20-24 months of age, decreased levels of oxidative stress and proinflammatory factors, and enhanced autophagy[85]. Thus, inhibition of IGF-IR in late life may prevent age-related cardiac changes. Aging-related mitochondrial dysfunction is also associated with changes in intracellular calcium handling[86]. SERCA activity decreases due to increased oxidation, although its expression is not altered[87,88]. activity increases calcium stagnation in cytoplasm, which prolongs diastolic relaxation[89].

Output: contrast


Input: Claim: All insects can communicate through sounds and music. [SEP] Text: Наша главная задача — растить профессиональных композиторов. Смысл этого в том, чтобы композитор знал, как работать с тем или иным материалом, и умел из найденных «первокирпичей» создать убедительную форму. История помнит немало случаев, когда великие мастера нарочно использовали тусклый, неинтересный и страшно неудобный, негибкий материал для создания своих произведений.

Output: pass


Input: Claim: Genetic testing can provide insights into ancestry and potential health risks. [SEP] Text: ” Somewhat surprised, Dr. Lowe explained that the BRCA is not a routine test and is recommended for women who are at increased risk of breast cancer due to their family history and ancestry. “Well that’s just it,” Ms. Stewart responded. “You know my sister had breast cancer recently, and now I just took this test and it turns out that I’m part Jewish. I think I need the test. ” the case of breast cancer risk, genetic testing can provide important information to help guide the patient through a number of personal and medical choices about her health [1]. Genetic testing is most informative when performed first on the family member at the highest risk of having a mutation. In this case, it would be Ms. Stewart’s sister [2], and her breast cancer is sufficient indication for genetic counseling and possible testing even in absence of ancestry information [3]. Ancestry information can assist in identifying people who may be at increased risk for heritable disease. Most commonly, this information is obtained from discussions with family members, discussions that can be key in identifying and contextualizing an individual’s heritable health risk. While reported family history provides insight into possible risk status, it may be limited since some families are not fully aware of or forthcoming about their family history. Increasingly, patients are turning to ancestry testing to gain this information, using direct-to-consumer (DTC) kits sold by independent manufacturers. These tests use either a single genetic and genomic analytic approach or a combination of methods to analyze an individual’s DNA and draw inferences about ancestry [4]. In the hypothetical case of Ms. Stewart, information from the ancestry test may not significantly alter the course of action regarding referral for genetic counseling and possible testing. However, it is important to recognize the ethical issues associated with DTC genetic testing [5]. One of most relevant issues for this case is the fact that the results may not accurately reflect Ms. Stewart’s ancestral background. This could be due to the genetic markers the test manufacturer elects to use, how it defines reference populations, and the statistical methods and interpretations used to analyze the genetic data, all these in addition to baseline variability in human genetic diversity [6, 7].

Output: corroborate


Input: Claim: Genetic anti-aging interventions are proven to eliminate all signs of aging at the cellular level. [SEP] Text: iron-sulfur domain-containing protein 2 (Cisd2), which is also important for intracellular Ca2+ homeostasis, decreases with aging in the heart[90], leading to mitochondrial Ca2+ overload in cardiomyocytes that accounts for cardiac structural defects and functional decline[91]. The occurrence of oxidative stress and mitochondrial damage in cardiovascular aging affects cellular and systemic metabolic homeostasis in the elderly. The advances in metabolomic methods have availed a powerful tool that allows for screening the numerous metabolites in biofluids and tissue. Leveraging mass spectrometry (MS)-based metabolomics, several studies identified altered metabolites and circulating prognostic biomarkers in the progression of various human diseases, including cancer, heart failure, and Alzheimer’s disease[92-94]. Animal studies have suggested that aging per se leads to alterations in plasma metabolic profile[95,96]. Although MS-based metabolomics study in aging is still limited, the altered plasma levels of amino acids and lipid species have been consistently reported as metabolic signatures of aging in humans and mice[95,97,98]. A recent study on metabolomic analysis of human serum samples from healthy individuals aged 20-70 years old[98] showed that plasma levels of branched-chain amino acids (BCAA, isoleucine; leucine; valine), aspartate, 3-hydroxyisobutyrate are significantly decreased after the age of sixty. On the contrary, the plasma levels of hippuric acid are increased after this age[98], which may be correlated to the enrichment of gut microbiota after the age of sixty, since hippuric acid is a metabolite deriving from the degradation of dietary polyphenols by a range of gut microbe[99]. However, the same study[98] showed that despite the elevated levels of hippuric acid in plasma, variables related to cardiac autonomic modulation and cardiorespiratory fitness decrease with age and present the lowest values in the oldest age group (60-70 years old). Another recent targeted metabolomics study of microbe-derived metabolites demonstrated that the plasma levels of hippuric acid are negatively correlated with peripheral artery disease[100], suggesting the use of plasma hippuric acid as a biomarker that will identify a lower risk of CVD in the elderly.

Output: contrast


Input: Claim: All insects can communicate through sounds and music. [SEP] Text: Обладая незаурядной композиторской техникой, они выжимали из него максимум возможного, и результат неизменно оказывался достойным всяческого восхищения. Композиторы таким образом бравировали своим мастерством, демонстрировали его в максимально открытом виде: смотрите, я беру неликвид — на него и посмотреть-то страшно, — а какое чудо я из него делаю! Среди многих прочих сегодня мы сталкиваемся с одной очень серьезной проблемой.

Output: pass


Input: Claim: Genetic testing can provide insights into ancestry and potential health risks. [SEP] Text: This includes appropriate pre- and post-test counseling to prepare the patient for personal and medical consequences that can come from learning such information. Genetic counseling can often be reassuring in situations in which a likelihood of heritable cancer risk is low. Genetic counseling may empower both Ms. Stewart and her sister to make educated and informed decisions about genetic testing, cancer screening, and prevention. In absence of pre- and post-test counseling, users may not be ready to confront personal risk information that can alter perspectives and choices about their life and health care or to frame future reproductive decisions based on knowledge of a heritable risk [5]. For example, Ms. Stewart’s sister, who already has the diagnosis of breast cancer, has a 1 in 10 chance of being a BRCA gene mutation carrier if, in fact, the ancestry information is accurate [10]. Furthermore, users may learn information about their families that may be unexpected or even considered undesirable, something that could result in profound personal conflict [6]. This raises larger questions about when and how to disclose what has been learned. Finally, ambiguity surrounds how individual DTC test manufacturers subsequently store and use the genetic sample, so consumers must also be aware of issues related to privacy and confidentiality of their information after the testing process is completed. It is imperative that a patient be referred for genetic counseling if there is concern about a genetic predisposition for disease. When evaluating an individual with breast cancer or who is at high risk for developing breast cancer, it is important to obtain a detailed medical and family history. Information gathering includes ancestry as certain ethnic groups, such as those listed here, are a few of the better known groups with documented genetic mutations. Until further data can be obtained about the accuracy and precision of DTC ancestry tests and their clinical utility, family history remains a primary way of acquiring this information. However, given the growing presence of genetics and genomics, clinicians must educate themselves about the medical and ethical implications of such tests, whether offered in the clinical or DTC context. Without such knowledge, clinicians will be limited in how they guide their patients through the often difficult decisions that must be made in light of this information. Genetics/Genetic counseling Genetics/Genetic testing 40. View 1. 2014). 13, 2014. In some situations, even in the absence of testing or with negative test results, heightened surveillance based on breast or other cancers may be recommended.

Output: corroborate


Input: Claim: Genetic anti-aging interventions are proven to eliminate all signs of aging at the cellular level. [SEP] Text: According to plasma metabolomic analysis of young (3-4 months) and old mice (22 months), the circulating metabolic footprint of aging was found in the altered levels of amino acids (i. e. , phenylalanine, tryptophan, taurine, isoleucine), phospholipids and organic acids (i. e. , gluconic acid, citric acid)[95]. It remains elusive what organ(s) are responsible for releasing those metabolites into circulation in aging, as well as whether they play a role in contributing to myocardial remodeling during aging. In summary, although various metabolic processes are compromised during aging, only recent MS-based metabolomic analyses have identified metabolites that may serve as biomarkers or potential targets of therapeutic interventions. The challenge going forward will be to design studies aiming to discover new biomarkers that can predict risks of pathogenic aging and help elucidate the critical metabolic pathways that account for the onset and progression of aging-related cardiovascular diseases. InflammationDysregulation of the immune system in the elderly leads to chronic sterile low-grade inflammation[101]. This process, called “inflammaging”, is a key factor in the development of frailty and age-related degenerative diseases, including cardiovascular complications[102,103]. A major pathway of cardiovascular inflammaging is the NOD-like receptor protein (NLRP) 3/caspase-1 cascade[104]. NLRP3 is an intracellular detector of endogenous danger signals, microbial motifs and environmental irritants, leading to the formation and activation of the inflammasome. During aging, damaged mitochondria and defective autophagy lead to ROS accumulation and the release of damage-associated molecular patterns (DAMPs) that trigger the NLRP3 inflammasome[105]. Assembly of the NLRP3 inflammasome results in the secretion of caspase-1-dependent proinflammatory cytokines, such as IL-1β and IL-18[106]. In a D-galactose-induced model of cardiomyocyte aging, NLRP3 inflammasome is activated and IL-1β levels are increased, whereas inhibition of NLRP3 inflammasomes by MCC950 or N-acetylcysteine attenuates cardiomyocyte aging[107].

Output: contrast


Input: Claim: All insects can communicate through sounds and music. [SEP] Text: Современным композиторам тесно в условиях звукоряда, причем неважно, какой именно это звукоряд — любой тормозит! Совершенно очевидно, что искусственное вычленение отдельных частот из непрерывного спектра и структурирование дискретного пространства действительно весьма и весьма ограничивают возможности творцов. Сегодня многие пытаются расширить рабочее пространство и перейти от мощности счетного множества к мощности континуума.

Output: pass


Input: Claim: Genetic testing can provide insights into ancestry and potential health risks. [SEP] Text: AbstractThe past hundred years have given birth to arguably the most profound changes in society, medicine, and technology the world has ever witnessed. Genetics is one such field that has enjoyed a meteoric rise during this time. Progressing from Mendelian genetics to the discovery of DNA to the ability to sequence the human genome, perhaps no other discipline holds more promise to affect future change than genetics. Technology currently exists to evaluate some of the genetic information held by developing embryos in the context of an in vitro fertilization (IVF) cycle. This information is then used to determine which embryos are selected for uterine transfer. Many societies have enacted legislation to protect against possible abuses utilizing this technology. However, it is incumbent upon society to continue ensuring that preimplantation genetic diagnosis (PGD)–-and genetic testing in general–-is applied in a way that utilizes its potential in a responsible manner to improve health care. Since the dawn of civilization, mankind has placed great importance on our genetic composition. From the ancient civilizations of Egypt to the royalty of European nations today, the familial pedigree or bloodline of an individual has historically been of paramount importance in determining expectations and opportunity for advancement in society. In contrast, an ideal of many modern societies, often termed meritocracy, has been to move past the concept of inherited potential to allow individuals to achieve based on their merits alone. 1 Indeed, the capitalistic system that grew out of the tends to reward companies for hiring the best person for the job regardless of their background (but, of course, there are exceptions). This environment has become a standard, that is, a new goal for western society. It is frowned upon for individuals to obtain a position in a company or school that is connected to a family donation. Politicians from humble backgrounds use their lack of connections in early life as a centerpiece of their campaigns. While individuals’ family backgrounds certainly still shape their futures, this is far less of a factor today than arguably at any other time in human history. Given this background of a growing social emphasis on allowing individuals to achieve and be judged on their merits, it is understandable that society is cautious about technology that could predict an individual's potential based on the results of genetic analysis. As genetic diagnostic technology continues to advance, our understanding of the genetic origins of disease is taking shape.

Output: corroborate


Input: Claim: Genetic anti-aging interventions are proven to eliminate all signs of aging at the cellular level. [SEP] Text: NLRP3 inflammasome also participates in vascular endothelial cell senescence via a mechanism that involves binding of TXNIP to NLRP3, which is triggered by oxidative stress[108]. Moreover, increased cardiac and aortic expression of Toll-like receptor 4 (TLR4), which is a pattern recognition receptor of the innate immune system, is observed with aging[109] and accounts for higher production of inflammatory cytokines, such as IFN-β, IL-1β, IL-6, and TNF-α. To this end, aged TLR4-/- mice have lower levels of these cytokines and improved cardiac function and vascular relaxation[109]. Transcriptional factor NF-κB, which is involved in TLR4 signaling and is tightly associated with inflammation, also plays an important role in cardiovascular aging[110]. Treatment of endothelial cells with TNF-α activates NF-κB and increases proatherogenic inflammatory mediators, such as iNOS and adhesion molecules, and incurs age-related alterations of the arterial endothelium, such as impaired acetylcholine-induced relaxation[111,112]. Aged hearts also have increased NF-κB signaling that mediates inflammatory response, while NF-κB inhibition alleviates cardiac inflammation, apoptosis, and age-associated LV remodeling[113,114]. Specifically, supplementation with the anti-aging serum soluble Klotho inhibits the TLR4/Myd88/NF-κB pathway, resulting in improved cardiac function in aged mice[110]. Matrix metalloproteinase- (MMP-)9, monocyte chemotactic protein (MCP)-1 levels, and macrophage density increase in the left ventricles of senescent mice[115]. MMP-9 stimulates cardiac macrophage activation and proinflammatory response in aged mice, while MMP-9 deletion results in decreased proinflammatory gene expression and collagen deposition, and attenuates age-related LV diastolic dysfunction[116]. Thus, NLRP3 inflammasome activation, increased TLR4 expression, elevated production of inflammatory cytokines, and increased NF-κB signaling are important processes and factors in inflammaging, which is a major cellular process involved in cardiovascular aging. FibrosisThe development of myocardial fibrosis is another hallmark of cardiovascular aging.

Output: contrast


Input: Claim: All insects can communicate through sounds and music. [SEP] Text: Отсюда огромная популярность сонористики во всем ее фактурном многообразии. Вот здесь-то и возникают новые проблемы! Мы не знаем, как структурировать сонористику — это слишком молодое направление, и накопленный опыт пока недостаточен.

Output: pass


Input: Claim: Genetic testing can provide insights into ancestry and potential health risks. [SEP] Text: We as a species are just now approaching the point where we can predict, to a limited degree, certain genes that may predispose an individual for a certain disease or condition. This ability to diagnose genetic traits awoke basic fears of future abuse in the scientific community and society at large. An excellent example of these concerns is illustrated by the 1997 science fiction film 2 In the film, essentially all individuals in society are conceived in a laboratory at which time their DNA is sequenced and, based upon their genetic potential, their life (school, career, etc) are planned. In the world, social class and potential are defined almost exclusively by an individual's genetic code, eerily similar to the blood line concept of inherited potential that has been a centerpiece of human history. The film chronicles the struggle of an individual with “nonideal” DNA to achieve greatness through tenacity and drive despite tremendous discrimination. We are now able to identify single nucleotide polymorphisms (SNPs), markers on our genetic code, that if detected in a certain pattern are predictive, to some degree, of the development of such conditions as diabetes. 2–4 Several companies have begun to offer adult testing for predictive genetics. Predictive genetics technology tests for markers correlating with a slight increased chance of being diagnosed with a host of medical disorders ranging from depression to asthma. 5,6 Many of these tests are available without a physician's order and require only a saliva sample or a blood spot collection. 5–7This technology has been looked upon with concern by the medical and public policy communities. Specifically, the ability of the consumer to interpret the test results is questionable, especially in cases where the scientific foundation for the tested mutation, such as those associated with common conditions like depression, is lacking. 5–7 Such results could lead to potentially damaging and inaccurate information. 5–7 Additionally, while there are some regulatory mechanisms in place for such laboratories, some believe that more stringent regulations are warranted. 7,8 These concerns have led to consumer advocates and professional societies discouraging the public from using such testing services. 6,9,10For many disorders, such as Huntington's disease and cystic fibrosis, there are clear genetic mutations that are strongly tied to the development of disease. For the majority of medical disorders, such as type 2 diabetes and hypertension, however, what determines the development of disease appears to be more complex.

Output: corroborate


Input: Claim: Genetic anti-aging interventions are proven to eliminate all signs of aging at the cellular level. [SEP] Text: Fibroblast activation and proliferation, along with hypertrophy of myocytes, compensate for myocyte loss due to apoptosis and necrosis[117-120]. Fibrosis is characterized by excessive deposition of extracellular matrix by cardiac myofibroblasts, which constitute the main cardiac cell type that undergoes senescence[121]. Senescence in cardiac fibroblasts depends on p53/p21 and p16/Rb pathways. However, genetic ablation of p53 and p16(INK4a) (Trp53-/-Cdkn2a-/- mice) eliminates senescence, but it exacerbates fibrosis with pressure overload, resulting in severe cardiac dysfunction[121]. Furthermore, cardiac-specific induction of senescence in the same study lowered perivascular fibrosis, which contradicts findings that correlate fibrosis with cardiac aging. This finding indicates potential protective effects of isolated cellular senescence against fibrosis in a young heart as opposed to an aged heart that cellular senescence is extensive. TGF-β signaling, which is one of the primary regulators of tissue fibrosis, is also activated in cardiac aging. Mice with heterozygous Tgfb1 deletion have decreased age-related myocardial fibrosis and improved LV compliance[122]. Moreover, chronic inhibition of TGF-β receptors prevents ventricular fibrotic remodeling with aging[123]. Surprisingly, the expression of TGF-β receptor I (TβRI) is decreased in aged murine cardiac mesenchymal stem cells (MSCs) and MSC-derived mesenchymal fibroblasts[124]. It remains to be elucidated whether age-related cardiac fibrosis is caused by the elevated activity of TGF-β or defects in the TGF-β signaling[125]. Fibrosis is also modulated by the renin-angiotensin-aldosterone system (RAAS), which is a critical regulator of blood pressure, fluid balance, and systemic vascular resistance.

Output: contrast


Input: Claim: All insects can communicate through sounds and music. [SEP] Text: Мы структурируем ее не «изнутри», а «снаружи», то есть во всех вариантах — будь то некий «сюжет», на который все накручивается-наверчивается, или «сверху спущенная» блок-схема, как в программировании, — мы вначале конструируем форму и лишь затем насыщаем ее сонорным содержанием. Так или иначе, пусть мы знаем мало и умеем не много, но думать о структуре необходимо. Однако среди молодых это делают единицы!

Output: pass


Input: Claim: Genetic testing can provide insights into ancestry and potential health risks. [SEP] Text: At this point in time, an individual's family history and environment along with diet and exercise patterns are vastly more predictive of disease development compared to the currently defined associated disease markers. 2 It is believed that the disease markers currently described represent approximately 10% of total familial risk. 2 Therefore, as we continue to catalog more and more genetic markers associated with disease, our ability to predict disease based on genetics alone will exponentially grow. At some point, it is conceivable that genetic analysis will be the most predictive method by which to assess risk for the development for many medical disorders. Genetic testing is not limited to adults or even children. Preimplantation genetic diagnosis or PGD is a term used to describe the testing of human embryos in a laboratory for genetic disorders. 11,12 PGD is performed in conjunction with in vitro fertilization or IVF. IVF was developed as a modality for helping couples suffering from infertility. The procedure is accomplished by surgically retrieving eggs from human ovaries and fertilizing these with sperm in a laboratory. These fertilized eggs, or embryos, are then grown in the laboratory for 3 to 6 days and then placed in the mother's uterus. More than 20 years ago, some laboratories began taking one or two cells from these developing embryos and conducting genetic tests on these cells. 13,14 In this way, limited amounts of genetic information could be obtained about the embryo, and this guided which embryos were placed into the uterus and which embryos were diagnosed with problems. As technology advanced, more detailed genetic analysis was possible, and specific genetic disorders that were known to exist in parents were able to be avoided in offspring through this process. PGD allows the selection of embryos with certain characteristics for uterine transfer and is, therefore, fundamentally different from purely diagnostic technologies such as fetal evaluation through maternal cell free DNA. However, the early days of PGD were limited to testing for specific known parental genetic mutations and did not offer any insights into traits that could be perceived as otherwise advantageous such as intelligence, strength, and so on. Something that could be evaluated, however, was the sex of the embryo. There is increasing acceptance of the utilization of this technology in certain instances. For example, if there is a medical disorder in a couple's family that is sex-linked, that is, unmasked only in one gender, PGD for sex selection is generally accepted as an appropriate medical test.

Output: corroborate


Input: Claim: Genetic anti-aging interventions are proven to eliminate all signs of aging at the cellular level. [SEP] Text: Sustained RAAS activation, characterized by increased levels of angiotensin-converting enzyme (ACE), angiotensin II (Ang II) and Ang II type 1 receptor (AT1R), leads to NADPH oxidase activation, which activates MMP-2 and increases the expression of pro-fibrotic connective tissue growth factor (CTGF) and TGF-β1. This cascade of events leads to cardiac fibrosis and remodeling in aged rats[126]. In the thoracic aorta of old mice, the prorenin receptor (PRR) -ACE-Ang II-AT1R axis is activated, whereas the ACE2-Mas receptor (MasR) axis is inhibited. This altered expression of RAS components correlates with fibrosis and oxidative stress in the aging aorta[127]. Additionally, similarly to old rats, young adult animals develop cardiomyocyte hypertrophy and vascular remodeling when they are chronically treated with angiotensin II[126]. In contrast, mice with smooth muscle cell mineralocorticoid receptor (MR) deletion are protected from age-related vascular and cardiac stiffening and fibrosis[128]. Moreover, protease-activated receptor (PAR) 2 is a significant regulator of pro-fibrotic PAR1 and TGF-β signaling in the heart[129]. Levels of PAR2 decrease with age in the aortas of rats with metabolic syndrome[130]. Aged PAR2-knockout mice exhibit cardiac fibrosis and diastolic dysfunction with higher transcription of TGF-βR and PAR1 compared to WT mice[129]. Treatment with vorapaxar, a PAR1 antagonist, reduces cardiac collagen deposition by 44%, inflammation, and TGF-β expression in a metabolic disease model of apolipoprotein E-knockout mice, which also demonstrate cardiac fibrosis and with Fraction (HFpEF)[129]. Therefore, PAR2, TGF-β, and RAAS play an important role in aging-related fibrosis of the heart and vessels. Telomere dysfunctionTelomeres are DNA-protein complexes that cap the end of each chromosome arm in order to maintain chromosomal stability and integrity[131]. In proliferating tissues, telomeres become shortened with cell cycle divisions.

Output: contrast


Input: Claim: All insects can communicate through sounds and music. [SEP] Text: Большинство находит какой-нибудь прием и начинает бессмысленно «сидеть» на нем, наслаждаясь звучанием, тем и ограничиваются. Если бы все было так просто, то композитором мог бы стать любой, причем не обязательно человек с музыкальным образованием… И где-то сегодня так нередко и происходит. Не всем можно объяснить, что это пока еще не музыка.

Output: pass


Input: Claim: A single gene determines all aspects of a person's intelligence. [SEP] Text: In the experiments performed to rescue flight duration in Set2RNAi individuals the authors overexpress STIM and attribute the effect to "Excess STIM presumably drives higher SOCE sufficient to rescue flight bout durations caused by deficient Set2 levels. ". This should be experimentally tested as the STIM:Orai stoichiometry has been demonstrated as essential for SOCE. The assumption that STIM overexpression drives higher SOCE is based upon previously published work from Drosophila neurons (Agrawal et al. , 2010; Chakraborty et al, 2016; Deb et al. , 2016) which demonstrates that excess overcomes IP3R deficiencies (RNAi or hypomorphic mutants) to rescue SOCE. We agree that STIM-Orai stoichiometry is essential for SOCE, and propose that the rescue backgrounds possess sufficient WT Orai, which is recruited by the excess STIM to mediate the rescue. We have referenced the earlier work to validate our use of for rescue of SOCE (226-233). Here, we propose that Set2 is part of a positive feedback loop (see Lines 286-307) driving transcription of mAChR and IP3R (Figure 3F). In keeping with this hypothesis, we posit that the phenotypes observed in the Set2RNAi background (Figure 2D) result from decreased itpr and mAChR expression (validated in Figure 3E). This is further validated by the Set2 overexpression mediated rescue of OraiE180A (Figure 2D) and rescue of itpr/mAChR expression in the OraiE180A background (Figure 3B-E; THD’>OraiE180A; Set2OE). The authors show that overexpression of OraiE108A results in Stim downregulation at a mRNA level. What about the protein level? And more important, how does OraiE108A downregulate Stim expression? Does it promote Stim degradation? Does it inhibit Stim expression?

Output: pass


Input: Claim: Genetic anti-aging interventions are proven to eliminate all signs of aging at the cellular level. [SEP] Text: When they reach a critical length, they cannot bind enough proteins on the cap and are sensed as exposed DNA ends, leading to proliferation arrest and senescence-associated secretory phenotype (SASP)[132,133]. Impairments in telomere length maintenance are related to cardiovascular function impairments. Leukocyte telomere shortening is a risk factor for CVD[134]. Telomerase deficient (Terc-/-) mice of generation 3 (G3) develop severe ventricular dysfunction, impaired mitochondrial biogenesis and function[135,136], enhanced apoptosis, cardiomyocyte hypertrophy[137], and vascular endothelial dysfunction similar to aged WT mice[138]. Aged mice with a deficiency in telomeric repressor activator protein 1 (Rap1) (Rap1-/-) show telomere shortening, DNA damage, lower cardiac fatty acid metabolism, and development of aging-associated cardiac structural and functional changes[139]. Nevertheless, it should be noted that there are differences between the length and role of telomeres in senescence between rodents and humans. Specifically, although rodents have longer telomeres and ubiquitous telomerase expression, they have shorter lifespans than humans[133]. Also, in contrast with humans, telomere length does not determine the proliferative capacity of mouse cells[140,141]. However, cardiomyocytes are postmitotic cells, and their ability to proliferate is limited. Thus, telomere dysfunction in cardiomyocytes is less likely due to telomere shortening[142] but due to DNA damage within telomeres[133], which can be caused by oxidative stress[143]. Specifically, length-independent telomere damage occurs in aged cardiomyocytes via the activation of the classical senescence-inducing pathways, cyclin-dependent kinase inhibitor 1 (p21CIP) and p16Ink4a, and leads to a non-canonical SASP, which induces myofibroblast activation and cardiomyocyte hypertrophy[143]. Therefore, telomere dysfunction is an additional cause, beyond oxidative stress, mitochondrial dysfunction, impaired autophagy, inflammation, and fibrosis, that leads to cardiovascular aging. investigate the pathophysiology of cardiovascular aging and identify potential therapeutic targets, various animal models are used [Table 1].

Output: contrast


Input: Claim: All insects can communicate through sounds and music. [SEP] Text: Это то же самое, как если бы вы в лесу нашли пень, напоминающий кого-то, кого все знают, и выдали бы его за свою художественную работу. Я часто привожу такой пример. Допустим, я вхожу в зону действия сильного магнитного поля и широким жестом сеятеля разбрасываю металлический порошок. Под действием магнитного поля он ложится ровными красивыми спиралями. Есть ли логика в получившейся картине? Несомненно, есть! Значит, мы можем говорить о гармонии? Разумеется, можем.

Output: pass


Input: Claim: Cloning humans is already possible and has been secretly performed. [SEP] Text: In 1854, Siemens built the first ozone generator. At that time, it was already known that ozone was unstable, having to be produced and then used. With the construction of the ozone generators, its use was initiated in industrial applications, or even to clean water, promoting its potent microbicidal action. 10 Ozone has been used for the treatment of drinking water in Europe since the beginning of the 20th century, without loss in the organoleptic properties, and in relation to microorganisms, its action is as effective as chlorine. 12 Payr, an Austrian physician, Fisch, a Swiss dentist, and Wolff, a German physician are the pioneers in clinical research involving ozone,1 though their observations were empirical. Currently there are scientific reports that prove the benefits of ozone in the treatment of wounds, dental use, disinfection, treatment of herniated disc and hepatitis C. 13 Ozone therapy: use of ozone in medicine The practice of ozone began in tuberculosis treatment, followed by its use in dental clinics and gangrene treatments. The surgeon Payr was the first one to be use the ozone rectal route. 14 However, the inappropriate use of gas via intravenous by individuals with no practice in ozone therapy or in medicine resulted in death by embolism. In this way, the use of ozone was condemned in some countries. 10 Ozone has the ability to assist in eliminating bacteria, viruses and parasites as well as biofilms. In this context, it was assumed that the intravenous injection of a gas mixture composed of O2 and O3 into bacterial sepsis in patients with HIV would inactivate the pathogens and would cure the disease. In the early 1990’s, technicians migrated to Africa and to to perform such procedure; indeed, it was seen that intravenous administration of O2–O3 caused embolism and patients’ death. The ozone administration by intravenous route has been banned in Europe since 1984. 13 The use of ozone should never be used by inhalation or injection in accordance with the on Ozone Therapy. 15 However, there are publication proving the security of ozone by inhalation route in low concentrations. 16 In countries such as Cuba, Russia and Ukraine this therapy is widely used for several treatments, in form of infusion of ozonated saline solution and rectal ozone insufflations due to the low cost and the applicability in thousands of patients.

Output: pass


Input: Claim: Genetic anti-aging interventions are proven to eliminate all signs of aging at the cellular level. [SEP] Text: Mice at 24 months of age, which are equivalent to 70-year-old humans, have increased left ventricular mass, enhanced fibrosis, aortic stiffness, and decreased cardiac diastolic function[144,145]. Rhesus monkeys (Macaca mulatta), which have a median lifespan of 25 years, are also used in gerontology research of the cardiovascular system due to their 92. 5%-95% genetic homology to humans and their ability to develop cardiac fibrosis and hypertrophy[146]. Although the naturally aging models are most suitable for these studies, models of premature aging, artificially induced aging models, and genetically modified models are also used. Table 1Animal models of cardiovascular agingModelRelevance to agingCardiovascular phenotypeRefs. 1. Natural agingAged C57BL/6J miceCardiac hypertrophy and dysfunction, enhanced fibrosis, aortic stiffness[217,218]344 ratsLV hypertrophy, diastolic dysfunction, abdominal aorta with decreased sodium nitroprusside-mediated relaxation[219,220]344/F1 ratsLV dilatation, mild hypertrophy, fibrosis, LV diastolic and systolic dysfunction[221]macaque (Macaca mulatta)Myocardial fibrosis, cardiac hypertrophy, aortic valve calcification[146]2. Premature agingSenescence-accelerated prone (SAMP) miceSelective inbreeding of AKR/J mice with inherited senescenceCardiac diastolic dysfunction, cardiac fibrosis, vascular dysfunction[148,222]Mus musculus castaneus (CAST)Mice with short telomeres from birthCardiac dysfunction, hypertrophy, fibrosis and senescence[149]3. Chemically induced agingD-galactose-induced aging in mice and ratsD-galactose treatment increases the levels of senescence-associated β-galactosidase (SA-β-gal) Increase in heart weight, cardiac hypertrophy, cardiac fibrosis and LV dysfunction[150]4.

Output: contrast


Input: Claim: All insects can communicate through sounds and music. [SEP] Text: Но является ли это произведением искусства? Нет, конечно, как не является произведением искусства морозный узор на окнах. И картина, нарисованная хвостом непокорного мула, тоже — как бы она ни была любопытна и оригинальна. Для меня пространство, организованное без участия интеллекта творца, никак не может быть произведением музыкального искусства.

Output: pass


Input: Claim: Nanotechnology is used in medicine to deliver drugs more precisely to specific cells. [SEP] Text: Impact factor12. 4 ISSN: 1838-7640Aims and scope Editorial board Author info Submit manuscript Manuscript login issue 2024 2023 2022 2021 2020 534. Full text PDF Nanotheranostics 2024; 8(4): 506-520. Full text of of Journal of reach, higher impact PDF Theranostics 2020; 10(8):3474-3487. doi:10. 7150/thno. 39434 This issue cell-derived exosomes home to their cells of origin and can be used as Trojan horses to deliver cancer drugs Li Qiao1,2,3, Shiqi Hu1,2, Ke Huang1,2, Teng Su1,2, Zhenhua Li1,2, Adam Vandergriff1,2, Jhon Cores1,2, Phuong-Uyen Dinh1,2, Tyler Allen1,2, Deliang Shen1,2,4, Hongxia Liang1,2,5, Yongjun Li3, Ke Cheng1,2, 1. Department of. 2. Department of Biomedical Engineering, University of North Carolina, Chapel Hill, and. 3. Department of Cardiology, Hospital of University, Shijiazhuang, China. 4. Department of and Hepatology, of Zhengzhou University, Zhengzhou, China. 5. Department of Cardiology, of Zhengzhou University, Zhengzhou, China. ✉ Corresponding author: Ke Cheng. Tel: (919)5137371; Email: Ke_Chengedu or Ke_Chengedu Citation:. Tumor cell-derived exosomes home to their cells of origin and can be used as Trojan horses to deliver cancer drugs. Theranostics 2020; 10(8):3474-3487. doi:10. 7150/thno. 39434. styles go to File – Import. Select the file that you have just downloaded and select import option (RIS). Click on Import. File import instruction is the second leading cause of death worldwide and patients are in urgent need of therapies that can effectively target cancer with minimal off-target side effects. Exosomes are extracellular nano-shuttles that facilitate intercellular communication between cells and organs.

Output: corroborate


Input: Claim: Genetic anti-aging interventions are proven to eliminate all signs of aging at the cellular level. [SEP] Text: Progeria modelsLmnaG609G/G609G miceLMNA point mutation (G609G) that activates a cryptic donor splice site and produces progerin, a truncated form of prelamin AHutchinson-Gilford progeria syndrome (HGPS), cardiac fibrosis, electrocardiographic alterations, cardiac diastolic dysfunction, HFpEF[157]LmnaN195K/N195K miceLMNA missense mutation (N195K) in lamins A and CDilated cardiomyopathy with conduction system disease[223]LmnaH222P/H222P miceLMNA missense mutation (H222P) identified in a family with autosomal dominant Emery-Dreifuss muscular dystrophy (EDMD)[224]Hypomorphic BubR1 mutant(BubR1H/H) miceReduced expression of spindle assembly checkpoint kinase BubR1, leading to chromosome number instabilityCardiac arrhythmias, arterial wall stiffening[225,226] 5. Mitochondrial mutationsCardiac-specific termed Y955C Polg mutant micePolg point mutation (Y955C) leading to mtDNA depletionLV hypertrophy, increased ventricular volume[160,227]D257A Polg mutant micePolg mutation (D257A) in the N-terminal "proofreading" exonuclease domain, resulting in a protein without polymerase proofreading function in mitochondriaBiventricular hypertrophy, fibrosis, heart failure, arterial stiffening[161,228]Tafazzin-deficient miceMice lacking tafazzin, a mitochondrial transacylase essential for cardiolipin remodelingBarth syndrome, LV dilation, reduced ejection fraction [229]heart/muscle-specific Mn-SOD-deficient mice (H/M-Sod2-/-)Mice with a specific in the heart and skeletal muscle loss of manganese superoxide dismutase (Mn-SOD) expression, a principal scavenger enzyme in mitochondrial matrixDilated cardiomyopathy, reduced cardiac contractility[230]6.

Output: contrast


Input: Claim: All insects can communicate through sounds and music. [SEP] Text: И применяться интеллект должен прежде всего через художественный образ, который соединяет в себе созерцание, субъективную интерпретацию и авторскую оценку. Все это порой бывает очень трудно объяснить молодому композитору, который, находясь под сильным впечатлением от своих находок, не понимает, почему звучание не самодостаточно и зачем нужно городить огород: применять интеллект, выстраивать систему образов.

Output: pass


Input: Claim: Nanotechnology is used in medicine to deliver drugs more precisely to specific cells. [SEP] Text: It has been established that tumor-derived exosomes contain a similar protein and lipid composition to that of the cells that secrete them, indicating that exosomes might be uniquely employed as carriers for anti-cancer therapeutics. Methods: We isolated exosomes from two cancer cell lines, then co-cultured each type of cancer cells with these two kinds of exosomes and quantified exosome. HT1080 or Hela exosomes were systemically injected to Nude mice bearing a subcutaneous HT1080 tumor to investigate their cancer-homing behavior. Moreover, cancer cell-derived exosomes were engineered to carry Doxil (a common chemotherapy drug), known as D-exo, were used to detect their target and therapeutic efficacy as anti-cancer drugs. Exosome proteome array analysis were used to reveal the mechanism underly this phenomenon. Results: Exosomes derived from cancer cells fuse preferentially with their parent cancer cells, in vitro. Systemically injected tumor-derived exosomes home to their original tumor tissues. Moreover, compared to Doxil alone, the drug-loaded exosomes showed enhanced therapeutic retention in tumor tissues and eradicated them more effectively in nude mice. Exosome proteome array analysis revealed distinct integrin expression patterns, which might shed light on the underlying mechanisms that explain the exosomal cancer-homing behavior. Conclusion: Here we demonstrate that the exosomes' ability to target the parent cancer is a phenomenon that opens up new ways to devise targeted therapies to deliver anti-tumor drugs. Keywords: exosome, homing, integrin, doxorubicin, cancer therapy is a life-threating public health problem responsible for an estimated 9. 6 million deaths worldwide in 2018 [1]. The most common treatment option available for cancer patients is chemotherapy. While chemotherapeutic drugs can inhibit the progression of cancers and even suppress cancer to the point of remission, they come with many serious side-effects. The systemic infusion of chemotherapy drugs can cause cardiomyopathy, vomiting, asthenia, and alopecia due to their inability to target the cancerous tissue of the body exclusively. Therefore, effective new targeted cancer treatments are urgently needed. Tumor cells produce and secrete more nucleic acids, proteins, and lipids than healthy cells.

Output: corroborate


Input: Claim: Genetic anti-aging interventions are proven to eliminate all signs of aging at the cellular level. [SEP] Text: Other global gene mutationsKlotho-deficient (KL-/-) miceKnock-out of KlothoImpaired cardiac function, increased heart size, increased LV myocardial mass[57]G5 telomerase-deficient (telomerase RNA component, TERC-/-) miceTelomerase-deficient mice after G3 generation have short telomeres, aneuploidy, and end-to-end chromosome fusionsPathological cardiac remodeling, severe ventricular dysfunction[231,232]Pim triple knock-out mice (Pim1-/-, Pim2-/- and Pim3-/-)Mice lacking Pim kinases, which are highly conserved serine/threonine kinases, have altered mitochondrial morphology Cardiac hypertrophy, heart failure, cardiac fibrosis[233]Interleukin-10 knockout IL-10(tm/tm) miceMice lacking IL-10, which is an anti-inflammatory cytokineStiffer vessels, reduced vascular relaxation, asymmetric hypertrophy, systolic and diastolic dysfunction[234]DNA-helicase-regulatory protein (WRN) WRN-K577M mutant miceAmino acid substitution of WRN at position 577 eliminates the ATPase and helicase activityWerner syndrome, diastolic LV dysfunction, cardiac fibrosis and hypertrophy[235]The senescence-accelerated mouse prone (SAMP) 8 is a model of accelerated aging that was developed by selective inbreeding of AKR/J mice with inherited senescence[147]. SAMP8 mice are especially used in studies of cardiovascular aging, since they show accelerated aging, increased cardiac fibrosis, and diastolic dysfunction at 6 months of age[148]. Wild mouse strain Mus musculus castaneus (CAST), which have short telomeres from birth, are also used as a model of cardiac aging, as they develop cardiac diastolic dysfunction by their 1st year of age[149]. Another model of cardiovascular aging is the D-galactose-induced aging model, which uses 2-3-month-old rodents treated with D-galactose injections at doses of 100-500 mg/kg/day for 4-12 weeks[150].

Output: contrast


Input: Claim: All insects can communicate through sounds and music. [SEP] Text: Приходится возвращаться назад к вопросу: а что такое вообще музыка? И порой встречаются такие, кто удивляется, что не все то музыка, что звучит. Студентам-первокурсникам очень важно сразу объяснить, как работают интуитивное и рациональное начала, то есть где следует опираться на ощущение, а где — на расчет.

Output: pass


Input: Claim: Nanotechnology is used in medicine to deliver drugs more precisely to specific cells. [SEP] Text: Some of these molecules are transported in the blood or encapsulated in extracellular microvesicles, such as exosomes, that are released into the extracellular environment. Once released, these exosomes become a part of a communication network used by other tumor cells and organs [2-4]. Tumor-derived exosomes contain an abundant biological content that resembles that of their parent tumor cell. These include transmembrane receptors, growth factors, angiogenic factors, and extracellular matrix (ECM) molecules [2]. In addition, they store intercellular signaling messengers involved in the pathogenesis, development, progression, and metastasis of cancer [3, 4]. Previous studies have proven the concept of delivering exosome-encapsulated molecules, including chemotherapeutics, to tumor sites. et. al. , for example, encapsulated doxorubicin in immature dendritic cell-derived exosomes for targeting αv integrin-positive cancer cells [5]. Herein, we utilize the abundance and ease of acquisition of cancer-derived exosomes to create an even more effective targeted delivery platform. To date, the signaling mechanisms involved in exosome release, transmission, and uptake have not been clearly described. Previous studies, including those from our lab, suggest that exosome can be absorbed by the parent cell line, as well as other cells of various origins [6-9]. However, they seem to most readily interact with cancer cells, compared to normal cells, and it appears that this interaction is driven, at least in part, by lipid mixing [10-12]. Since exosomes are extracellular nano-shuttles that facilitate intercellular communication between cells, the constitution of exosomes, as well as their biological activity, is largely dependent on the demands of their parent cells. Tumor-derived exosomes contain a similar protein and lipid composition to that of the cells that secrete them, indicating that exosomes might be uniquely designed to interact with their parent cell line in comparison to other cells. Thus, we hypothesized that tumor cell-derived exosomes might be especially effective at traveling back to the parent cell line that produced them. If so, their exosomes could be used as Trojan horses that deliver anticancer drugs to the cancer cells.

Output: corroborate


Input: Claim: Genetic anti-aging interventions are proven to eliminate all signs of aging at the cellular level. [SEP] Text: D-galactose administration increases the levels of senescence-associated β-galactosidase (SA-β-gal) in the cardiac tissue[151,152]. D-galactose treatment increases ROS levels and decreases cardiac levels of Nrf2, SIRT1 and phosphorylated AMPK, leading to oxidative stress and decreased autophagy[153], and activates NF-κB inflammatory signaling pathway[154]. In this way, D-galactose-induced aging models demonstrate LV wall thickening, cardiac fibrosis, and reduced cardiac function[150]. Mutations in the LMNA gene cause laminopathies, a number of disorders with a wide range of phenotypes, including premature aging and cardiomyopathy[155]. LMNA gene encodes the intermediate filament proteins, lamins A and C, which are major structural components of the nuclear lamina. Homozygous LmnaG609G/G609G mice express lamin A, lamin C, and progerin (a truncated form of prelamin A) with the same protein expression pattern of patients with Hutchinson-Gilford progeria syndrome (HGPS), and exhibit metabolic abnormalities, cardiac electrical alterations and HFpEF, similar to the normally aged mice[156,157]. Moreover, mice with mutations in the Polg gene, which encodes the mitochondrial DNA polymerase responsible for replication and repair of mtDNA, are also used as models of cardiovascular aging. Specifically, mice with a homozygous mutation in the exonuclease encoding domain of mitochondrial DNA polymerase gamma (Polg) (Polgm/m) develop an age-dependent accumulation of mtDNA mutations and display accelerated aging starting at 7-9 months of age. Also, they exhibit age-dependent cardiomyopathy, which is more severe than the usual phenotype of cardiac aging[39,158,159], and specifically demonstrate cardiac hypertrophy, dilatation, fibrosis and dysfunction by 13-14 months of age[153]. Transgenic mice for a cardiac-specific mutant of Polg (termed Y955C) develop LV hypertrophy at 94 days of age[160], while mice with a homozygous mutation in the encoding domain (D257A) of a proofreading deficient version of Polg develop biventricular hypertrophy at 10-12 months of age[161].

Output: contrast


Input: Claim: All insects can communicate through sounds and music. [SEP] Text: И очень важно, чтобы студент действительно осознавал, что такое фундаментальные понятия в музыке — не как-то интуитивно, а чтобы мог четко изложить, что такое гармония и форма… Парадоксально, но многие даже опытные музыканты, уже в возрасте, не понимают элементарных вещей. Именно поэтому периодически вспыхивают острые и оживленные дискуссии, например, о том, умерла мелодия или еще жива.

Output: pass


Input: Claim: Nanotechnology is used in medicine to deliver drugs more precisely to specific cells. [SEP] Text: To test this idea, we investigated the biodistribution of tumor-derived exosomes, and profiled the proteome of exosomes from mouse tumor models. We found that exosomal integrins might direct the tumor-specific colonization of cancer exosomes. Remarkably, we found that the tropism exhibited by tumor-secreted exosomes can be utilized to shuttle Doxil, a cancer therapeutic with no specific targeting capacity, to tumor sites. exosomes home to their parent cells in vitro and in vivoTo detect whether tumor exosomes home to their parent cells in vitro, we isolated exosomes from HT1080 (a fibrosarcoma cell line) and HeLa (a cervical cancer cell line) cell lines. Flow cytometry was used to detect common exosome markers: CD81, CD63 and CD9 (Figure S1). We then co-cultured HT1080 cells with DiI-labeled-HT1080 exosomes or Dil-labeled-HeLa exos for 12 hours and quantified exosome uptake in HT1080 cells using fluorescence microscopy, the labeling efficiency is higher than 90% (Figure S2). We observed twice as much uptake of HT1080 exosomes versus HeLa exosomes in HT1080 cells (Figures 1 A-C). To make sure this finding was not an HT1080-specific phenomenon, we tested whether exosomes from HeLa cells would also exhibit parental cell tropism. We co-cultured HeLa cells with red (DiI) fluorescently labeled HeLa exosomes and green (DiO) fluorescently labeled HT1080 exosomes. Although both types of exosomes were internalized in HeLa cells, there was significantly more HeLa exosome uptake than HT1080 exosome uptake. Interestingly, HT1080 cells absorbed HT1080 exosomes about twice as efficiently as HeLa cells absorbed HeLa exosomes (Figures 1 D-E; Figures S3A-B). Then, the dye labeling for the exosomes were reversed to ensure that the uptake differences are not due to differences in labeling (Figures S3C-D). Subsequently, we designed another in vitro test, using a quantitative fluorometer to validate these findings. HeLa and HT1080 cells were seeded in different wells and treated with exosomes derived from the same cell type or the other.

Output: corroborate