Miracle-dz/UniFAR-FTUs huggingface dataset:
Physical properties of the chromosomes and implications for development

Remarkable progress has been made in understanding chromosome structures inside the cell nucleus. Recent advances in Hi‐C technologies enable the detection of genome‐wide chromatin interactions, providing insight into three‐dimensional (3D) genome organization. Advancements in the spatial and temporal resolutions of imaging as well as in molecular biological techniques allow the tracking of specific chromosomal loci, improving our understanding of chromosome movements. From these data, we are beginning to understand how the intra‐nuclear locations of chromatin loci and the 3D genome structure change during development and differentiation. This emerging field of genome structure and dynamics research requires an interdisciplinary approach including efficient collaborations between experimental biologists and physicists, informaticians, or engineers. Quantitative and mathematical analyses based on polymer physics are becoming increasingly important for processing and interpreting experimental data on 3D chromosome structures and dynamics. In this review, we aim to provide an overview of recent research on the physical aspects of chromosome structure and dynamics oriented for biologists. These studies have mainly focused on chromosomes at the cellular level, using unicellular organisms and cultured cells. However, physical parameters that change during development, such as nuclear size, may impact genome structure and dynamics. Here, we discuss how chromatin dynamics and genome structures in early embryos change during development, which we expect will be a hot topic in the field of chromatin dynamics in the near future. We hope this review helps developmental biologists to quantitatively investigate the physical natures of chromosomes in developmental biology research.
Cellular force assay detects altered contractility caused by a nephritis‐associated mutation in nonmuscle myosin IIA

Recent progress in understanding the essential roles of mechanical forces in regulating various cellular processes expands the field of biology to one where interdisciplinary approaches with engineering techniques become indispensable. Contractile forces or contractility—inherently present in proliferative cells due to the activity of ubiquitous nonmuscle myosin II (NMII)—are one of such mechano‐regulators, but because NMII works downstream of diverse signaling pathways, it is often difficult to predict how the inherent cellular forces change upon perturbations to particular molecules. Here, we determine whether the contractility of individual cells is upregulated or downregulated based on an assay analyzing specific deformations of silicone gel substrates. We focus on the effect of mutations in the human MYH9 gene that encodes NMIIA, which have been implicated in the pathogenesis of various diseases including nephritis. Our assay equipped with a high‐throughput data analysis capability reveals that a point mutation of E1841K but not I1816V significantly reduces the magnitude of the endogenous forces of human embryonic kidney (HEK293) cells. Given the increasingly recognized roles of the endogenous forces as a critical mechano‐regulator as well as that no apparent morphological changes were induced to cells even by introducing the mutations, our findings suggest a possibility that the detected reduction in the force magnitude at the individual cellular level may underlie the pathogenesis of the kidney disease.
Live-Birth Rate Associated With Repeat In Vitro Fertilization Treatment Cycles.

IMPORTANCE The likelihood of achieving a live birth with repeat in vitro fertilization (IVF) is unclear, yet treatment is commonly limited to 3 or 4 embryo transfers. OBJECTIVE To determine the live-birth rate per initiated ovarian stimulation IVF cycle and with repeated cycles. DESIGN, SETTING, AND PARTICIPANTS Prospective study of 156,947 UK women who received 257,398 IVF ovarian stimulation cycles between 2003 and 2010 and were followed up until June 2012. EXPOSURES In vitro fertilization, with a cycle defined as an episode of ovarian stimulation and all subsequent separate fresh and frozen embryo transfers. MAIN OUTCOMES AND MEASURES Live-birth rate per IVF cycle and the cumulative live-birth rates across all cycles in all women and by age and treatment type. Optimal, prognosis-adjusted, and conservative cumulative live-birth rates were estimated, reflecting 0%, 30%, and 100%, respectively, of women who discontinued due to poor prognosis and having a live-birth rate of 0 had they continued. RESULTS Among the 156,947 women, the median age at start of treatment was 35 years (interquartile range, 32-38; range, 18-55), and the median duration of infertility for all 257,398 cycles was 4 years (interquartile range, 2-6; range, <1-29). In all women, the live-birth rate for the first cycle was 29.5% (95% CI, 29.3%-29.7%). This remained above 20% up to and including the fourth cycle. The cumulative prognosis-adjusted live-birth rate across all cycles continued to increase up to the ninth cycle, with 65.3% (95% CI, 64.8%-65.8%) of women achieving a live birth by the sixth cycle. In women younger than 40 years using their own oocytes, the live-birth rate for the first cycle was 32.3% (95% CI, 32.0%-32.5%) and remained above 20% up to and including the fourth cycle. Six cycles achieved a cumulative prognosis-adjusted live-birth rate of 68.4% (95% CI, 67.8%-68.9%). For women aged 40 to 42 years, the live-birth rate for the first cycle was 12.3% (95% CI, 11.8%-12.8%), with 6 cycles achieving a cumulative prognosis-adjusted live-birth rate of 31.5% (95% CI, 29.7%-33.3%). For women older than 42 years, all rates within each cycle were less than 4%. No age differential was observed among women using donor oocytes. Rates were lower for women with untreated male partner-related infertility compared with those with any other cause, but treatment with either intracytoplasmic sperm injection or sperm donation removed this difference. CONCLUSIONS AND RELEVANCE Among women in the United Kingdom undergoing IVF, the cumulative prognosis-adjusted live-birth rate after 6 cycles was 65.3%, with variations by age and treatment type. These findings support the efficacy of extending the number of IVF cycles beyond 3 or 4.
Efficient Texture Parameterization Driven by Perceptual‐Loss‐on‐Screen

Texture mapping is a ubiquitous technique to enrich the visual effect of a mesh, which represents the desired signal (e.g. diffuse color) on the mesh to a texture image discretized by pixels through a bijective parameterization. To achieve high visual quality, large number of pixels are generally required, which brings big burden in storage, memory and transmission. We propose to use a perceptual model and a rendering procedure to measure the loss coming from the discretization, then optimize a parameterization to improve the efficiency, i.e. using fewer pixels under a comparable perceptual loss. The general perceptual model and rendering procedure can be very complicated, and non‐isotropic property rooted in the square shape of pixels make the problem more difficult to solve. We adopt a two‐stage strategy and use the Bayesian optimization in the triangle‐wise stage. With our carefully designed weighting scheme, the mesh‐wise optimization can take the triangle‐wise perceptual loss into consideration under a global conforming requirement. Comparing with many parameterizations manually designed, driven by interpolation error, or driven by isotropic energy, ours can use significantly fewer pixels with comparable perception loss or vise vesa.
Prevalence of impaired glucose regulation in Europe: a meta-analysis.

BACKGROUND Impaired glucose regulation represents an opportunity to prevent Type 2 diabetes mellitus. It is important to have a clear understanding of the prevalence of this condition in order to be able to plan interventions and health care provision. This paper presents a meta-analysis of literature assessing the prevalence of impaired glucose regulation in the general population of developed countries in Europe. METHODS Five electronic databases were systematically searched in March 2014 to identify English language articles with general population samples aged 18 and over from developed countries in Europe. Values for the measures of interest were combined using a random effects model and analysis of the effects of moderator variables was carried out. RESULTS A total of 5594 abstracts were screened, with 46 studies included in the review. Overall prevalence of impaired glucose regulation was 22.3%. Mean prevalence of impaired glucose tolerance was 11.4% (10.1-12.8) and did not differ by gender. Sample age, diagnostic criteria and country were found to have a significant univariate effect on prevalence of impaired glucose tolerance but only diagnostic criteria remained significant in multivariate analysis. Mean prevalence of impaired fasting glucose was significantly higher in men at 10.1% (7.9-12.7) compared with 5.9% in women (4-8.7). The only moderator variable with a significant effect on impaired fasting glucose prevalence was country. CONCLUSIONS This meta-analysis shows a moderate prevalence of impaired glucose regulation in developed Europe with over one in five people meeting the criteria for either impaired glucose tolerance, impaired fasting glucose or both.
Multinational Assessment of Accuracy of Equations for Predicting Risk of Kidney Failure: A Meta-analysis.

IMPORTANCE Identifying patients at risk of chronic kidney disease (CKD) progression may facilitate more optimal nephrology care. Kidney failure risk equations, including such factors as age, sex, estimated glomerular filtration rate, and calcium and phosphate concentrations, were previously developed and validated in 2 Canadian cohorts. Validation in other regions and in CKD populations not under the care of a nephrologist is needed. OBJECTIVE To evaluate the accuracy of the risk equations across different geographic regions and patient populations through individual participant data meta-analysis. DATA SOURCES Thirty-one cohorts, including 721,357 participants with CKD stages 3 to 5 in more than 30 countries spanning 4 continents, were studied. These cohorts collected data from 1982 through 2014. STUDY SELECTION Cohorts participating in the CKD Prognosis Consortium with data on end-stage renal disease. DATA EXTRACTION AND SYNTHESIS Data were obtained and statistical analyses were performed between July 2012 and June 2015. Using the risk factors from the original risk equations, cohort-specific hazard ratios were estimated and combined using random-effects meta-analysis to form new pooled kidney failure risk equations. Original and pooled kidney failure risk equation performance was compared, and the need for regional calibration factors was assessed. MAIN OUTCOMES AND MEASURES Kidney failure (treatment by dialysis or kidney transplant). RESULTS During a median follow-up of 4 years of 721,357 participants with CKD, 23,829 cases kidney failure were observed. The original risk equations achieved excellent discrimination (ability to differentiate those who developed kidney failure from those who did not) across all cohorts (overall C statistic, 0.90; 95% CI, 0.89-0.92 at 2 years; C statistic at 5 years, 0.88; 95% CI, 0.86-0.90); discrimination in subgroups by age, race, and diabetes status was similar. There was no improvement with the pooled equations. Calibration (the difference between observed and predicted risk) was adequate in North American cohorts, but the original risk equations overestimated risk in some non-North American cohorts. Addition of a calibration factor that lowered the baseline risk by 32.9% at 2 years and 16.5% at 5 years improved the calibration in 12 of 15 and 10 of 13 non-North American cohorts at 2 and 5 years, respectively (P = .04 and P = .02). CONCLUSIONS AND RELEVANCE Kidney failure risk equations developed in a Canadian population showed high discrimination and adequate calibration when validated in 31 multinational cohorts. However, in some regions the addition of a calibration factor may be necessary.
Development of a generic fidelity measure for rehabilitation intervention research for children with physical disabilities

To increase research rigour and create a plausible way to assess clinical effectiveness, it is necessary to measure the degree to which interventions are delivered as intended (fidelity). Generic fidelity measures enable evaluation of more than one intervention through observation of unique and general characteristics relevant across interventions. This study describes the first generic fidelity measure in paediatrics.
Periodic analysis using two-way analysis of variance for the circadian rhythm of intraocular pressure in primary open angle glaucoma

The purpose of the article is to investigate the diurnal variation of intraocular pressure (IOP) in glaucoma patients by periodic regression analyses using two-way analysis of variance (ANOVA). Seventy-two open-angle glaucoma patients participated in this study and IOP measurements were taken in this group every 2 h during waking hours. Patients were categorized based on the Glaucoma staging system (GSS) into “severe” (GSS > stage 2) and “less severe” (GSS ≤ stage 2) groups. They were also categorized into high tension (IOP ≥ 19 mmHg) and low tension (IOP < 19 mmHg) groups. Diurnal IOP curves were plotted and analyzed for all patients and for each subgroup by periodic regression analysis with two-way ANOVA. Results showed that all diurnal IOP curves from all patients and all subgroups statistically fitted periodic regression curves within a 24-h period (p < 0.0001, two-way ANOVA for all categories). It is concluded that IOP exhibits a 24-h circadian rhythm in glaucoma patients during waking hours.
Association of early imaging for back pain with clinical outcomes in older adults.

IMPORTANCE In contrast to the recommendations for younger adults, many guidelines allow for older adults with back pain to undergo imaging without waiting 4 to 6 weeks. However, early imaging may precipitate interventions that do not improve outcomes. OBJECTIVE To compare function and pain at the 12-month follow-up visit among older adults who received early imaging with those who did not receive early imaging after a new primary care visit for back pain without radiculopathy. DESIGN, SETTING, AND PARTICIPANTS Prospective cohort of 5239 patients 65 years or older with a new primary care visit for back pain (2011-2013) in 3 US health care systems. We matched controls 1:1 using propensity score matching of demographic and clinical characteristics, including diagnosis, pain severity, pain duration, functional status, and prior resource use. EXPOSURES Diagnostic imaging (plain films, computed tomography [CT], magnetic resonance imaging [MRI]) of the lumbar or thoracic spine within 6 weeks of the index visit. MAIN OUTCOME AND MEASURES PRIMARY OUTCOME back or leg pain-related disability measured by the modified Roland-Morris Disability Questionnaire (score range, 0-24; higher scores indicate greater disability) 12 months after enrollment. RESULTS Among the 5239 patients, 1174 had early radiographs and 349 had early MRI/CT. At 12 months, neither the early radiograph group nor the early MRI/CT group differed significantly from controls on the disability questionnaire. The mean score for patients who underwent early radiography was 8.54 vs 8.74 among the control group (difference, -0.10 [95% CI, -0.71 to 0.50]; mixed model, P = .36). The mean score for the early MRI/CT group was 9.81 vs 10.50 for the control group (difference,-0.51 [-1.62 to 0.60]; mixed model, P = .18). CONCLUSIONS AND RELEVANCE Among older adults with a new primary care visit for back pain, early imaging was not associated with better 1-year outcomes. The value of early diagnostic imaging in older adults for back pain without radiculopathy is uncertain.
Brain magnetic resonance imaging pattern and outcome in children with haemolytic‐uraemic syndrome and neurological impairment treated with eculizumab

The aim of this study was to describe the magnetic resonance imaging (MRI) findings and the neurological and neuropsychological outcomes in paediatric, diarrhoea‐associated haemolytic–uraemic syndrome (D+HUS) with central nervous system impairment treated with eculizumab, a monoclonal antibody.
Mulheres submetidas à coleta de Papanicolaou: perfil socioeconômico e reprodutivo

| Introduction: Cancer of the Uterine Cervix is the one with greatest potential for prevention and cure, and the Paptest is the main tracking method for this type of neoplasia. Goal: To identify the socioeconomic and reproductive profile of women submitted to the Paptest. Methods: Adescriptive, quantitative and cross study. Held in the Family Health Unit of the Porto de Santana, Cariacica/ES. The random sample consisted of 100 women registered at the unit, who underwent preventive collection in 2007. Data collection through interviews with registration form occurred in November 2008. Results: 52% of respondents had completed elementary schooling, 79% are within Class C, 26% had two pregnancies, 36% had 2 childbirths, 54% of deliveries were normal, 50% had their first sexual relation between 16 and 18 years old, 86% had up to 4 sexual partners, 83% have already made use of oral contraceptive, whereas 43% used for less than 5 years, 57% held the first arrangement between 16-18 years, 75% reported conducting preventive exams annually, 44% no made use of condoms during sexual intercourse. Conclusion: The jority of women subjected to the Paptest has low socioeconomic level and does not use a condom during sex. Keywords| Cancer of the uterine cervix; oman’s health; Family health.
Effects of Nicotine Patch vs Varenicline vs Combination Nicotine Replacement Therapy on Smoking Cessation at 26 Weeks: A Randomized Clinical Trial.

IMPORTANCE Smoking cessation medications are routinely used in health care; it is vital to identify medications that most effectively treat this leading cause of preventable mortality. OBJECTIVE To compare the efficacies of varenicline, combination nicotine replacement therapy (C-NRT), and the nicotine patch for 26-week quit rates. DESIGN, SETTING, AND PARTICIPANTS Three-group randomized intention-to-treat clinical trial occurring from May 2012 to November 2015 among smokers recruited in the Madison, Wisconsin, and Milwaukee, Wisconsin, communities; 65.5% of smokers offered the study (2687/4102) refused participation prior to randomization. INTERVENTIONS Participants were randomized to one of three 12-week open-label smoking cessation pharmacotherapy groups: (1) nicotine patch only (n = 241); (2) varenicline only (including 1 prequit week; n = 424); and (3) C-NRT (nicotine patch + nicotine lozenge; n = 421). Six counseling sessions were offered. MAIN OUTCOMES AND MEASURES The primary outcome was carbon monoxide-confirmed self-reported 7-day point-prevalence abstinence at 26 weeks. Secondary outcomes were carbon monoxide-confirmed self-reported initial abstinence, prolonged abstinence at 26 weeks, and point-prevalence abstinence at weeks 4, 12, and 52. RESULTS Among 1086 smokers randomized (52% women; 67% white; mean age, 48 years; mean of 17 cigarettes smoked per day), 917 (84%) provided 12-month follow-up data. Treatments did not differ on any abstinence outcome measure at 26 or 52 weeks, including point-prevalence abstinence at 26 weeks (nicotine patch, 22.8% [55/241]; varenicline, 23.6% [100/424]; and C-NRT, 26.8% [113/421]) or at 52 weeks (nicotine patch, 20.8% [50/241]; varenicline, 19.1% [81/424]; and C-NRT, 20.2% [85/421]). At 26 weeks, the risk differences for abstinence were, for patch vs varenicline, -0.76% (95% CI, -7.4% to 5.9%); for patch vs C-NRT, -4.0% (95% CI, -10.8% to 2.8%); and for varenicline vs C-NRT, -3.3% (95% CI, -9.1% to 2.6%). All medications were well tolerated, but varenicline produced more frequent adverse events than did the nicotine patch for vivid dreams, insomnia, nausea, constipation, sleepiness, and indigestion. CONCLUSIONS AND RELEVANCE Among adults motivated to quit smoking, 12 weeks of open-label treatment with nicotine patch, varenicline, or C-NRT produced no significant differences in biochemically confirmed rates of smoking abstinence at 26 weeks. The results raise questions about the relative effectiveness of intense smoking pharmacotherapies. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01553084.
Association of Seafood Consumption, Brain Mercury Level, and APOE ε4 Status With Brain Neuropathology in Older Adults.

IMPORTANCE Seafood consumption is promoted for its many health benefits even though its contamination by mercury, a known neurotoxin, is a growing concern. OBJECTIVE To determine whether seafood consumption is correlated with increased brain mercury levels and also whether seafood consumption or brain mercury levels are correlated with brain neuropathologies. DESIGN, SETTING, AND PARTICIPANTS Cross-sectional analyses of deceased participants in the Memory and Aging Project clinical neuropathological cohort study, 2004-2013. Participants resided in Chicago retirement communities and subsidized housing. The study included 286 autopsied brains of 554 deceased participants (51.6%). The mean (SD) age at death was 89.9 (6.1) years, 67% (193) were women, and the mean (SD) educational attainment was 14.6 (2.7) years. EXPOSURES Seafood intake was first measured by a food frequency questionnaire at a mean of 4.5 years before death. MAIN OUTCOMES AND MEASURES Dementia-related pathologies assessed were Alzheimer disease, Lewy bodies, and the number of macroinfarcts and microinfarcts. Dietary consumption of seafood and n-3 fatty acids was annually assessed by a food frequency questionnaire in the years before death. Tissue concentrations of mercury and selenium were measured using instrumental neutron activation analyses. RESULTS Among the 286 autopsied brains of 544 participants, brain mercury levels were positively correlated with the number of seafood meals consumed per week (ρ = 0.16; P = .02). In models adjusted for age, sex, education, and total energy intake, seafood consumption (≥ 1 meal[s]/week) was significantly correlated with less Alzheimer disease pathology including lower density of neuritic plaques (β = -0.69 score units [95% CI, -1.34 to -0.04]), less severe and widespread neurofibrillary tangles (β = -0.77 score units [95% CI, -1.52 to -0.02]), and lower neuropathologically defined Alzheimer disease (β = -0.53 score units [95% CI, -0.96 to -0.10]) but only among apolipoprotein E (APOE ε4) carriers. Higher intake levels of α-linolenic acid (18:3 n-3) were correlated with lower odds of cerebral macroinfarctions (odds ratio for tertiles 3 vs 1, 0.51 [95% CI, 0.27 to 0.94]). Fish oil supplementation had no statistically significant correlation with any neuropathologic marker. Higher brain concentrations of mercury were not significantly correlated with increased levels of brain neuropathology. CONCLUSIONS AND RELEVANCE In cross-sectional analyses, moderate seafood consumption was correlated with lesser Alzheimer disease neuropathology. Although seafood consumption was also correlated with higher brain levels of mercury, these levels were not correlated with brain neuropathology.
Long-term randomised comparison of clinical outcomes following ART initiation with triple-nucleoside (Combivir/Abacavir) or NNRTI-based (Combivir/Nevirapine) therapy in Africa: the NORA substudy of the DART trial.

— these may occur more frequently than is recognised, as here, so using weighting to adjust for post-baseline changes should be considered more ISCRTN 13968779 ISCRTN 13968779 Long-term randomised comparison of clinical outcomes following ART initiation with triple-nucleoside (Combivir/Abacavir) or NNRTI-based (Combivir/Nevirapine) therapy in Africa: the NORA substudy of the DART trial AS Walker1, P Munderi2, C Kityo3, AG Babiker1, F Ssali3, A Reid4, H Grosskurth2, P Mugyenyi3, DM Gibb1, CF Gilks5 & the DART Trial Team