bluuebunny/crossref_metadata_2025_split huggingface dataset:
Polygenic risk scores based on European GWAS correlate to disease prevalence differences around the world
Authors: Jain Pritesh R , Burch Myson , Martinez Melanie , Mir Pablo , Fichna Jakub , Zekanowski Cezary , Rizzo Renata , Tümer Zeynep , Barta Csaba , Yannaki Evangelia , Stamatoyannopoulos John , Drineas Petros , Paschou Peristera 
Published: November 2021

AbstractBackgroundComplex disorders are caused by a combination of genetic, environmental and lifestyle factors, and their prevalence can vary greatly across different populations. Genome wide association studies (GWAS) can help identify common variants that underlie disease risk. However, despite their increasing number, the vast majority of studies focuses on European populations, leading to questions regarding the transferability of findings to non-Europeans. Here, we investigated whether polygenic risk scores (PRS) based on European GWAS correlate to disease prevalence within Europe and around the world.ResultsGWAS summary statistics of 20 different disorders were used to estimate PRS in nine European and 24 worldwide reference populations. We estimated the correlation between average genetic risk for each of the 20 disorders and their prevalence in Europe and around the world. A clear variation in genetic risk was observed based on ancestry and we identified populations that have a higher genetic liability for developing certain disorders both within European and global regions. We also found significant correlations between worldwide disease prevalence and PRS for 13 of the studied disorders with obesity genetic risk having the highest correlation to disease prevalence. For these 13 disorders we also found that the loci used in PRS are significantly more conserved across the different populations compared to randomly selected SNPs as revealed by Fst and linkage disequilibrium structure.ConclusionOur results show that PRS of world populations calculated based on European GWAS data can significantly capture differences in disease risk and identify populations with the highest genetic liability to develop various conditions. Our findings point to the potential transferability of European-based GWAS results to non-European populations and provide further support for the validity of GWAS.
Viral load and infectivity of SARS-CoV-2 in paired respiratory and oral specimens from symptomatic, asymptomatic or post-symptomatic individuals
Authors: Tallmadge Rebecca L. , Laverack Melissa , Cronk Brittany , Venugopalan Roopa , Martins Mathias , Zhang XiuLin , Elvinger François , Plocharczyk Elizabeth , Diel Diego G. 
Published: November 2021

ABSTRACTIn the present study, we assessed the diagnostic sensitivity and determined the viral load and infectivity of SARS-CoV-2 in paired respiratory (nasopharyngeal and anterior nares) and oral samples (saliva and sublingual swab). Samples were collected from 77 individuals of which 75 were diagnosed with COVID-19 and classified as symptomatic (n=29), asymptomatic (n=31), or post-symptomatic (n=15). Specimens were collected at one time point from each individual, between day 1 to 23 after the initial COVID-19 diagnosis, and included self-collected saliva (S), or sublingual (SL) swab, and bilateral anterior nares (AN) swab, followed by healthcare provider collected nasopharyngeal (NP) swab. Sixty-three specimen sets were tested using five assay/platforms. The diagnostic sensitivity of each assay/platform and specimen type was determined. Of the 63 specimen sets, SARS-CoV-2 was detected in 62 NP specimens, 52 AN specimens, 59 saliva specimens, and 31 SL specimens by at least one platform. Infectious SARS-CoV-2 was isolated from 21 NP, 13 AN, 12 saliva, and one SL specimen out of 50 specimen sets. SARS-CoV-2 isolation was most successful up to 5 days after initial COVID-19 diagnosis using NP specimens from symptomatic patients (16 of 24 positives, 66.67%), followed by specimens from asymptomatic patients (5 of 17 positives, 29.41%), while it was not very successful with specimens from post-symptomatic patients. Benefits of self-collected saliva and AN specimens balance the loss of sensitivity relative to NP specimens. Therefore, saliva and AN specimens are acceptable alternatives for symptomatic SARS-CoV-2 diagnostic testing or surveillance with increased sampling frequency of asymptomatic individuals.ImportanceThe dynamics of infection with SARS-CoV-2 has a significant impact on virus infectivity and in the diagnostic sensitivity of molecular and classic virus detection tests. In the present study we determined the diagnostic sensitivity of paired respiratory (nasopharyngeal and anterior nares swabs) and oral secretions (saliva and sublingual swab) and assessed infectious virus shedding patterns by symptomatic, asymptomatic or post-symptomatic individuals. Understanding the diagnostic performance of these specimens and the patterns of infectious virus shedding in these bodily secretions provides critical information to control COVID-19, and may help to refine guidelines on isolation and quarantine of positive individuals and their close contacts identified through epidemiological investigations.
Age Based Trends for Unplanned Pediatric Rehospitalizations in the United States
Authors: Amritphale Nupur , Amritphale Amod , Vasireddy Deepa , Batra Mansi , Sehgal Mukul , Gremse David 
Published: November 2021

ABSTRACTBACKGROUND AND OBJECTIVESHospital readmission rate helps to highlight the effectiveness of post-discharge care. There remains a paucity of plausible age based categorization especially for ages below one year for hospital readmission rates.METHODSData from 2017 Healthcare cost and utilization project National readmissions database was analyzed for ages 0-18 years. Logistic regression analysis was performed to identify predictors for unplanned early readmissions.RESULTSWe identified 5,529,389 inpatient pediatric encounters which were further divided into age group cohorts. The overall rate of readmissions was identified at 3.2%. Beyond infancy, the readmission rate was found to be 6.7%. Across all age groups, the major predictors of unplanned readmission were cancers, diseases affecting transplant recipients and sickle cell patients. It was determined that reflux, milk protein allergy, hepatitis and inflammatory bowel diseases were significant comorbidities leading to readmission. Anxiety, depression and suicidal ideation depicted higher readmission rates in those older than 13 years. Across ages 1-4 yrs, dehydration, asthma and bronchitis were negative predictors of unplanned readmission.CONCLUSIONSThirty-day unplanned readmissions remain a problem leading to billions of tax-payer-dollars lost per annum. Effective strategies for mandatory outpatient follow-up may help the financial aspect of care while also enhancing the quality of care.
Implementation of Unassisted and Community-Based HIV Self-Testing (HIVST) during the COVID-19 pandemic among Men-who-have-sex-with-Men (MSM) and Transgender Women (TGW): A Demonstration Study in Metro Manila, Philippines
Authors: Rosadiño John Danvic T. , Pagtakhan Ronivin G. , Briñes Matthew T. , Dinglasan Jeanno Lorenz G. , Cruz Denis P. , Corciega John Oliver L. , Pagtakhan Aeronne B. , Regencia Zypher Jude G. , Baja Emmanuel S. 
Published: November 2021

ABSTRACTObjectiveThe study aimed to demonstrate the feasibility of an unassisted and community-based HIV self-testing (HIVST) distribution model and to evaluate its acceptability among men-having-sex-with-men (MSM) and transgender women (TGW).MethodsOur observational study focused on implementing the HIVST service in Metro Manila, Philippines. Convenience sampling was done with the following inclusion criteria: MSM or TGW, at least 18 years old, and had no previous HIV diagnosis. Individuals taking HIV Pre-exposure Prophylaxis (PrEP), on Antiretroviral Therapy (ART), or female sex at birth were excluded. The implementation of the study was online using a virtual assistant and delivery system via courier due to COVID-19-related lockdowns. Feasibility was measured by the number of HIVST kits successfully delivered and utilized and the HIV point prevalence rate. Moreover, acceptability was evaluated by a 10-item system usability scale (SUS). HIV prevalence was estimated with linkage to care prioritized for reactive participants.ResultsOut of 1,690 kits distributed, only 953 (56.4%) participants reported their results. Overall HIV point prevalence was 9.8%, with 56 (60.2%) reactive participants linked to further testing. Furthermore, 27.4% of respondents self-reported, and 13.4% of the reactive participants were first-time testers. The HIVST service had an overall mean ± standard deviation SUS score of 81.0 ± 13.0, rendering the HIVST kits very acceptable.ConclusionsHIVST is acceptable and feasible to MSM and TGW. Online platforms are an innovative and effective way to deliver HIVST service during a pandemic. However, messaging to entice people to use the kit must be differentiated based on their age, gender identity and expression, and previous HIVST experience to offer the service efficiently to the target populations.
Cryo-EM structure of the Inner Ring fromXenopus laevisNuclear Pore Complex
Authors: Huang Gaoxingyu , Zhan Xiechao , Zeng Chao , Liang Ke , Zhu Xuechen , Zhao Yanyu , Wang Pan , Wang Qifan , Zhou Qiang , Tao Qinghua , Liu Minhao , Lei Jianlin , Yan Chuangye , Shi Yigong 
Published: November 2021

AbstractNuclear pore complex (NPC) mediates nucleocytoplasmic shuttling. Here we present single-particle cryo-electron microscopy (cryo-EM) structure of the inner ring (IR) subunit fromXenopus laevisNPC at an average resolution of 4.4 Å. The symmetric IR subunit comprises a cytoplasmic half and a nuclear half. A homo-dimer of Nup205 resides at the center of the IR subunit, flanked by two molecules of Nup188. Four molecules of Nup93 each places an extended helix into the axial groove of Nup205 or Nup188, together constituting the central scaffold. The channel nucleoporin heterotrimer (CNT) of Nup54/58/62 is anchored on the central scaffold. Six Nup155 molecules interact with the central scaffold and together with the NDC1-ALADIN hetero-dimers anchor the IR subunit to the nuclear envelope and to outer rings. The scarce inter-subunit contacts may allow sufficient latitude in conformation and diameter of the IR. Our structure of vertebrate IR reveals key insights that are functionally important.
Reliable population signal of subjective economic value from unreliable neurons in primate orbitofrontal cortex
Authors: Ferrari-Toniolo Simone , Schultz Wolfram 
Published: November 2021

ABSTRACTBehavior-related neuronal signals often vary between neurons. Despite the unreliability of individual neurons, brains are able to accurately represent and drive behavior. The notion may also apply to economic (‘value-based’) choices and the underlying reward signals. Reward value is subjective and can be defined by nonlinear weighting of magnitude (utility) and probability. Using a wide variety of reward magnitude and probability, we assessed subjective reward value at choice indifference between safe and risky rewards as prescribed by the continuity axiom that provides stringent criteria for meaningful choice. We found that individual neurons in the orbitofrontal cortex (OFC) of monkeys carry unreliable and heterogeneous neuronal signals for subjective value that largely fails to match the animal’s choice. However, the averaged neuronal signals matched well the animals’ choices, suggesting reliable subjective economic value encoding by the observed population of unreliable neurons.HighlightsDifferent from widely held views, reliable neuronal information processing may not require reliable processors.Neurons in monkey orbitofrontal cortex (OFC) process reward magnitude and probability heterogeneously and unreliably.Despite unreliable neuronal processing, OFC population activity codes choices reliably.Reliability systems performance from unreliable elements seems to be a broad feature of neuronal reward coding.In briefUsing stringent concepts of behavioral choice, Ferrari-Toniolo and Schultz describe unreliable individual reward neurons in monkey orbitofrontal cortex whose activity combines to a reliable population code for economic choice.
Uncovering natural variation in root system architecture and growth dynamics using a robotics-assisted phenomics platform
Authors: LaRue Therese , Lindner Heike , Srinivas Ankit , Exposito-Alonso Moises , Lobet Guillaume , Dinneny José R. 
Published: November 2021

AbstractThe plant kingdom contains a stunning array of complex morphologies easily observed above ground, but largely unexplored below-ground. Understanding the magnitude of diversity in root distribution within the soil, termed root system architecture (RSA), is fundamental to determining how this trait contributes to species adaptation in local environments. Roots are the interface between the soil environment and the shoot system and therefore play a key role in anchorage, resource uptake, and stress resilience. Previously, we presented the GLO-Roots (Growth and Luminescence Observatory for Roots) system to study the RSA of soil-grownArabidopsis thalianaplants from germination to maturity (Rellán-Álvarez et al. 2015). In this study, we present the automation of GLO-Roots using robotics and the development of image analysis pipelines in order to examine the natural variation of RSA in Arabidopsis over time. This dataset describes the developmental dynamics of 93 accessions and reveals highly complex and polygenic RSA traits that show significant correlation with climate variables.
Poly ADP-ribosylation of SET8 leads to aberrant H4K20 methylation in mammalian nuclear genome
Authors: Estève Pierre-Olivier , Sen Sagnik , Vishnu US , Ruse Cristian , Chin Hang Gyeong , Pradhan Sriharsa 
Published: November 2021

AbstractIn mammalian cells, SET8 mediated Histone H4 Lys 20 monomethylation (H4K20me1) has been implicated in regulating mitotic condensation, DNA replication, DNA damage response, and gene expression. Here we show SET8, the only known enzyme for H4K20me1 is post-translationally poly ADP-ribosylated by PARP1 on lysine residues. PARP1 interacts with SET8 in a cell cycle-dependent manner. Poly ADP-ribosylation on SET8 renders it catalytically compromised, and degradation via ubiquitylation pathway. Knockdown of PARP1 led to an increase of SET8 protein levels, leading to aberrant H4K20me1 and H4K20me3 domains genome-wide. H4K20me1 is associated with higher gene transcription levels while the increase of H4K20me3 levels was predominant in DNA repeat elements correlating with modulation of chromatin states. Hence, SET8 mediated chromatin remodeling in mammalian cells are modulated by poly ADP-ribosylation by PARP1.
Vγ usage distinguishes pro- and anti-tumor intestinal γδ T cell subsets
Authors: Reis Bernardo S. , Darcy Patrick W. , Khan Iasha Z. , Eleso Olawale , Zhu Caixia , Schernthanner Marina , Lockhart Ainsley , Reed Aubrey , Bortolatto Juliana , Castro Tiago B. R. , Bilate Angelina M. , Grivennikov Sergei , Mucida Daniel 
Published: November 2021

Abstractγδ T cells physiologically scan the intestinal epithelium, representing a substantial fraction of infiltrating lymphocytes in colorectal cancer (CRC), albeit their role in CRC remains unclear. Using murine CRC models, we found that most γδ T cells in pre- or non-tumor colon express Vγ1+ or Vγ7+ and exhibit a cytotoxic profile. Targeting these γδ T cell subsets, as well as conditionally interfering with γδ T cell function at early stages of tumorigenesis led to heightened tumor development, suggesting anti-CRC functions for Vγ1+ and Vγ7+ subsets. In contrast, RORγt+ γδ T cell subsets, including Vγ4+ and microbiotadependent Vγ6+, accumulated during CRC progression. Conditional deletion of RORγt or Vγ chains revealed redundant roles for IL-17–producing Vγ4+ and Vγ6+ γδ T cells in promoting tumor growth. Our results uncover pro- and anti-tumor roles for γδ T cell subsets.
Cost-effectiveness analysis of BNT162b2 COVID-19 booster vaccination in the United States
Authors: Li Rui , Liu Hanting , Fairley Christopher K , Zou Zhuoru , Xie Li , Li Xinghui , Shen Mingwang , Li Yan , Zhang Lei 
Published: November 2021

AbstractBackgroundOver 86% of older adults aged ≥65 years are fully vaccinated against SARS-COV-2 in the United States (US). Waning protection of the existing vaccines promotes the new vaccination strategies, such as providing a booster shot for those fully vaccinated.MethodsWe developed a decision-analytic Markov model of COVID-19 to evaluate the cost-effectiveness of a booster strategy of Pfizer-BioNTech BNT162b2 (administered 6 months after 2nd dose) in those aged ≥65 years, from a healthcare system perspective.FindingsCompared with 2-doses of BNT162b2 without a booster, the booster strategy in a 100,000 cohort of older adults would incur an additional cost of $3.4 million, but save $6.7 million in direct medical costs in 180 days. This corresponds to a benefit-cost ratio of 1.95 and a net monetary benefit of $3.4 million. Probabilistic sensitivity analysis indicates that with a COVID-19 incidence of 9.1/100,000 person-day, a booster strategy has a high chance (67%) of being cost-effective. The cost-effectiveness of the booster strategy is highly sensitive to the population incidence of COVID-19, with a cost-effectiveness threshold of 8.1/100,000 person-day. This threshold will increase with a decrease in vaccine and booster efficacies. Doubling the vaccination cost or halving the medical cost for COVID-19 treatment alone would not alter the conclusion of cost-effectiveness, but certain combinations of the two might render the booster strategy not cost-effective.InterpretationOffering BNT162b2 boosters to older adults aged ≥65 years in the US is likely to be cost-effective. Less efficacious vaccines and boosters may still be cost-effective in settings of high SARS-COV-2 transmission.FundingNational Natural Science Foundation of China. Berlina and Bill Gates Foundation
F0-F1 coupling and symmetry mismatch in ATP synthase resolved in every F0 rotation step
Authors: Kubo Shintaroh , Niina Toru , Takada Shoji 
Published: November 2021

AbstractThe F0F1 ATP synthase, essential for cellular energy production, is composed of the F0 and F1 rotary motors. While both F0 and F1 have pseudo-symmetric structures, their symmetries do not match. How the symmetry mismatch is solved remains elusive due to missing intermediate structures of rotational steps. Here, for ATP synthases with 3- and 10-fold symmetries in F1 and F0, respectively, we uncovered the mechanical couplings between F0 and F1 at every 36° rotation step via molecular dynamics simulations and comparison of cryo-electron microscopy structures from three species. We found that the frustration is shared by several elements. The F1 stator partially rotates relative to the F0 stator via elastic distortion of the b-subunits. The rotor can be distorted. The c-ring rotary angles can be deviated from symmetric ones. Additionally, the F1 motor may take non-canonical structures relieving stronger frustration. Together, we provide comprehensive understanding to solve the symmetry mismatch.
Fluctuating heat stress during development exposes reproductive costs and putative benefits
Authors: Rodrigues Leonor R. , McDermott Hayley A. , Villanueva Irene , Djukarić Jana , Ruf Lena C. , Amcoff Mirjam , Snook Rhonda R. 
Published: November 2021

Abstract

Temperature and thermal variability are increasing worldwide, with well‐known survival consequences. However, effects on other potentially more thermally sensitive reproductive traits are less understood, especially when considering thermal variation. Studying the consequences of male reproduction in the context of climate warming and ability to adapt is becoming increasingly relevant.

Our goals were to test how exposure to different average temperatures that either fluctuated or remained constant impacts different male reproductive performance traits and to assess adaptive potential to future heat stress.

We took advantage of a set of Drosophila melanogaster isogenic lines of different genotypes, exposing them to four different thermal conditions. These conditions represented a benign and a stressful mean temperature, applied either constantly or fluctuating around the mean and experienced during development when heat stress avoidance is hindered because of restricted mobility. We measured subsequent male reproductive performance for mating success, fertility, number of offspring produced and offspring sex ratio, and calculated the influence of thermal stress on estimated heritability and evolvability of these reproductive traits.

Both costs and benefits to different thermal conditions on reproductive performance were found, with some responses varying between genotypes. Mating success improved under fluctuating benign temperature conditions and declined as temperature stress increased regardless of genotype. Fertility and productivity were severely reduced at fluctuating mean high temperature for all genotypes, but some genotypes were unaffected at constant high mean temperature. These more thermally robust genotypes showed a slight increase in productivity under the fluctuating benign condition compared to constant high temperature, despite both thermal conditions sharing the same temperature for 6 hr daily. Increasing thermal stress resulted in higher heritability and evolvability.

Overall, the effects of temperature on reproductive performance depended on the trait and genotype; performance of some traits slightly increased when high temperatures were experienced for short periods but decreased substantially even when experiencing a benign temperature for a portion of each day. While thermal stress increased genetic variation that could provide adaptive potential against climate warming, this is unlikely to compensate for the overall severe negative effect on reproductive performance as mean temperature and variance increase.