bluuebunny/crossref_metadata_2025_split huggingface dataset:
FutureTox IV Workshop Summary: Predictive Toxicology for Healthy Children
Authors: Knudsen Thomas B , Fitzpatrick Suzanne Compton , De Abrew K Nadira , Birnbaum Linda S , Chappelle Anne , Daston George P , Dolinoy Dana C , Elder Alison , Euling Susan , Faustman Elaine M , Fedinick Kristi Pullen , Franzosa Jill A , Haggard Derik E , Haws Laurie , Kleinstreuer Nicole C , Buck Louis Germaine M , Mendrick Donna L , Rudel Ruthann , Saili Katerine S , Schug Thaddeus T , Tanguay Robyn L , Turley Alexandra E , Wetmore Barbara A , White Kimberly W , Zurlinden Todd J 
Published: January 2021

Abstract
FutureTox IV, a Society of Toxicology Contemporary Concepts in Toxicology workshop, was held in November 2018. Building upon FutureTox I, II, and III, this conference focused on the latest science and technology for in vitro profiling and in silico modeling as it relates to predictive developmental and reproductive toxicity (DART). Publicly available high-throughput screening data sets are now available for broad in vitro profiling of bioactivities across large inventories of chemicals. Coupling this vast amount of mechanistic data with a deeper understanding of molecular embryology and post-natal development lays the groundwork for using new approach methodologies (NAMs) to evaluate chemical toxicity, drug efficacy, and safety assessment for embryo-fetal development. NAM is a term recently adopted in reference to any technology, methodology, approach, or combination thereof that can be used to provide information on chemical hazard and risk assessment to avoid the use of intact animals (U.S. Environmental Protection Agency [EPA], Strategic plan to promote the development and implementation of alternative test methods within the tsca program, 2018, https://www.epa.gov/sites/production/files/2018-06/documents/epa_alt_strat_plan_6-20-18_clean_final.pdf). There are challenges to implementing NAMs to evaluate chemicals for developmental toxicity compared with adult toxicity. This forum article reviews the 2018 workshop activities, highlighting challenges and opportunities for applying NAMs for adverse pregnancy outcomes (eg, preterm labor, malformations, low birth weight) as well as disorders manifesting postnatally (eg, neurodevelopmental impairment, breast cancer, cardiovascular disease, fertility). DART is an important concern for different regulatory statutes and test guidelines. Leveraging advancements in such approaches and the accompanying efficiencies to detecting potential hazards to human development are the unifying concepts toward implementing NAMs in DART testing. Although use of NAMs for higher level regulatory decision making is still on the horizon, the conference highlighted novel testing platforms and computational models that cover multiple levels of biological organization, with the unique temporal dynamics of embryonic development, and novel approaches for estimating toxicokinetic parameters essential in supporting in vitro to in vivo extrapolation.
Addressing Quality of Care in Pediatric Units using a Digital Tool: Implementation Experience from 18 SNCU of India
Authors: Saboth MD Prasant Kumar , Sarin PhD Enisha , Alwadhi MD Varun , Jaiswal MPH Avinash , Mohanty MD Jaya Swarup , Choudhary DCH Nidhi , Bisht MBBS Nitin , Gupta MBBS Anil , Kumar BSc Arvind , Gupta MD Sachin , Kumar MD Harish 
Published: January 2021

AbstractLack of quality care is associated with newborn mortality and stillbirth. India launched the Special newborn care unit (SNCU) Quality of Care Index (SQCI) for measuring quality indicators in SNCU. The USAID Vriddhi project provided support to the use of SQCI in 19 SNCU across aspirational districts of Jharkhand, Uttarakhand, Himachal Pradesh, Punjab and Haryana. The objective was to provide holistic support to quality care processes by generating analyzed quarterly reports for action with the goal toward sustainability by capacitating SNCU personnel and program officers to use SQCI, over a 1period from April 2019 to June 2020. The composite index has seven indicators and converts them into indices, each having a range from 0.1 to 1, to measure performance of SNCU.7 of the 18 SNCU improved their composite scores from the first to the last quarter. Rational use of antibiotics showed improvement in 12 SNCU. Survival in newborns &gt;2500 g and &lt;2500, low birth weight admission and optimal bed utilization had the most variations between and within facilities. Based on quarterly data analysis, all facilities introduced KMC, 10 facilities improved equipment and drug supply, 9 facilities launched in-house capacity building to improve asphyxia management. The SQCI implementation helped to show a process of using SQCI data for identifying bottlenecks and addressing quality concerns. The project has transitioned to complete responsibility of SQCI usage by the district and facility teams. Use of an existing mechanism of quality monitoring without any major external support makes the SQCI usable and doable.
The Cotton Lignin Biosynthetic Gene Gh4CL30 Regulates Lignification and Phenolic Content and Contributes to Verticillium Wilt Resistance
Authors: Xiong Xian-Peng , Sun Shi-Chao , Zhu Qian-Hao , Zhang Xin-Yu , Li Yan-Jun , Liu Feng , Xue Fei , Sun Jie 
Published: January 2021

Verticillium wilt is a vascular disease causing tremendous damage to cotton production worldwide. However, our knowledge of the mechanisms of cotton resistance or susceptibility to this disease is very limited. In this study, we compared the defense transcriptomes of cotton (Gossypium hirsutum) cultivars Shidalukang 1 (Verticillium dahliae resistant, HR) and Junmian 1 (V. dahliae susceptible, HS) before and after V. dahliae infection, identified hub genes of the network associated with responses to V. dahliae infection, and functionally characterized one of the hub genes involved in biosynthesis of lignin and phenolics. We identified 6,831 differentially expressed genes (DEGs) between the basal transcriptomes of HR and HS; 3,685 and 3,239 of these DEGs were induced in HR and HS, respectively, at different time points after V. dahliae infection. KEGG pathway analysis indicated that DEGs were enriched for genes involved in lignin biosynthesis. In all, 23 hub genes were identified based on a weighted gene coexpression network analysis of the 6,831 DEGs and their expression profiles at different time points after V. dahliae infection. Knockdown of Gh4CL30, one of the hub genes related to the lignin biosynthesis pathway, by virus-induced gene silencing, led to a decreased content of flavonoids, lignin, and S monomer but an increased content of G monomer, G/S lignin monomer, caffeic acid, and ferulic acid, and enhanced cotton resistance to V. dahliae. These results suggest that Gh4CL30 is a key gene modulating the outputs of different branches of the lignin biosynthesis pathway, and provide new insights into cotton resistance to V. dahliae. [Formula: see text] Copyright © 2021 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
What’s in a Name? A Mixed Method Study on How Young Women Who Sell Sex Characterize Male Partners and Their Use of Condoms
Authors: Busza Joanna , Hensen Bernadette , Birdthistle Isolde , Chabata Sungai T. , Hargreaves James R. , Floyd Sian , Chiyaka Tarisai , Mushati Phillis , Cowan Frances M. 
Published: January 2021

Introduction:
Young women who sell sex (YWSS) are at disproportionate risk of HIV. Reducing YWSS' vulnerability requires engaging their male sexual partners. To achieve this, we need to understand the characteristics and dynamics of their sexual partnerships to inform effective interventions.

Methods:
We conducted a mixed-methods study to compare YWSS' qualitative descriptions of male partners with categories reported in a behavioral survey. Data were drawn from enrollment into an evaluation of the DREAMS initiative in Zimbabwe in 2017. As part of a respondent-driven sampling survey, we recruited 40 seed participants from 2 intervention and 4 comparison sites. We conducted semistructured interviews with 19 “seeds,” followed by a behavioral survey with 2387 YWSS. We interpreted quantitative and qualitative data together to understand how YWSS perceived male sexual partners, assess how well survey variables related to narrative descriptions, and describe patterns of risk behavior within partnerships.

Results:
Qualitative data suggest survey categories “husband” and “client” reflect YWSS' perceptions but “regular partner/boyfriend” and “casual partner” do not. In interviews, use of the term “boyfriend” was common, describing diverse relationships with mixed emotional and financial benefits. More than 85% of male partners provided money to YWSS, but women were less likely to report condomless sex with clients than regular partners (11% vs 37%) and more likely to report condomless sex with partners who ever forced them to have sex (37% vs 21%).

Conclusions:
Reducing HIV risk among YWSS requires prevention messages and tools that recognize diverse and changing vulnerability within and between sexual relationships with different male partners.
A novel adhesive complex at the base of intestinal microvilli
Authors: Hartmann Christian , Thüring Eva-Maria , Michels Birgitta E. , Pajonczyk Denise , Leußink Sophia , Greune Lilo , Brinkmann Frauke , Glaesner-Ebnet Mark , Wardelmann Eva , Zobel Thomas , Schmidt M. Alexander , Gerke Volker , Ebnet Klaus 
Published: January 2021

AbstractIntestinal epithelial cells form dense arrays of microvilli at the apical membrane to enhance their functional capacity. Microvilli contain a protocadherin-based intermicrovillar adhesion complex localized at their tips which regulates microvillar length and packaging. Here, we identify a second adhesive complex in microvilli of intestinal epithelial cells. This complex is localized at the basal region of microvilli and consists of the adhesion molecule TMIGD1, the phosphoprotein EBP50 and the F-actin – plasma membrane cross-linking protein ezrin. Ternary complex formation requires unmasking of the EBP50 PDZ domains by ezrin binding and is strongly enhanced upon mutating Ser162 located in PDZ domain 2 of EBP50. Dephosphorylation of EBP50 at S162 is mediated by PP1α, a serine/threonine phosphatase localized at the microvillar base and involved in ezrin phosphocycling. Importantly, the binding of EBP50 to TMIGD1 enhances the dynamic turnover of EBP50 at microvilli in a Ser162 phosphorylation-dependent manner. We identify an adhesive complex at the microvillar base and propose a potential mechanism that regulates microvillar dynamics in enterocytes.
Genetic analysis of mitochondrial DNA copy number and associated traits identifies loci implicated in nucleotide metabolism, platelet activation, and megakaryocyte proliferation, and reveals a causal association of mitochondrial function with mortality
Authors: Longchamps RJ , Yang SY , Castellani CA , Shi W , Lane J , Grove ML , Bartz TM , Sarnowski C , Burrows K , Guyatt AL , Gaunt TR , Kacprowski T , Yang J , De Jager PL , Yu L ,   CHARGE Aging and Longevity Group, Bergman A , Xia R , Fornage M , Feitosa MF , Wojczynski MK , Kraja AT , Province MA , Amin N , Rivadeneira F , Tiemeier H , Uitterlinden AG , Broer L , Van Meurs JBJ , Van Duijn CM , Raffield LM , Lange L , Rich SS , Lemaitre RN , Goodarzi MO , Sitlani CM , Mak ACY , Bennett DA , Rodriguez S , Murabito JM , Lunetta KL , Sotoodehnia N , Atzmon G , Kenny Y , Barzilai N , Brody JA , Psaty BM , Taylor KD , Rotter JI , Boerwinkle E , Pankratz N , Arking DE 
Published: January 2021

AbstractMitochondrial DNA copy number (mtDNA-CN) measured from blood specimens is a minimally invasive marker of mitochondrial function that exhibits both inter-individual and intercellular variation. To identify genes involved in regulating mitochondrial function, we performed a genome-wide association study (GWAS) in 465,809 White individuals from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium and the UK Biobank (UKB). We identified 133 SNPs with statistically significant, independent effects associated with mtDNA-CN across 100 loci. A combination of fine-mapping, variant annotation, and co-localization analyses were used to prioritize genes within each of the 133 independent sites. Putative causal genes were enriched for known mitochondrial DNA depletion syndromes (p= 3.09 x 10−15) and the gene ontology (GO) terms for mtDNA metabolism (p= 1.43 x 10−8) and mtDNA replication (p= 1.2 x 10−7). A clustering approach leveraged pleiotropy between mtDNA-CN associated SNPs and 41 mtDNA-CN associated phenotypes to identify functional domains, revealing three distinct groups, including platelet activation, megakaryocyte proliferation, and mtDNA metabolism. Finally, using mitochondrial SNPs, we establish causal relationships between mitochondrial function and a variety of blood cell related traits, kidney function, liver function and overall (p= 0.044) and non-cancer mortality (p= 6.56 x 10−4).
Elevation-related climate trends dominate fungal co-occurrence patterns on Mt. Norikura, Japan
Authors: Yang Ying , Shi Yu , Kerfahi Dorsaf , Ogwu Matthew C , Wang Jianjun , Dong Ke , Takahashi Koichi , Moroenyane Itumeleng , Adams Jonathan M. 
Published: January 2021

AbstractAlthough many studies have explored patterns of fungal community diversity and composition along various environmental gradients, the trends of co-occurrence networks across similar gradients remain elusive. Here, we constructed co-occurrence networks for fungal community along a 2300 m elevation gradient on Mt Norikura, Japan, hypothesizing a progressive decline in network connectivity with elevation due to reduced niche differentiation caused by declining temperature and ecosystem productivity. Results agreed broadly with predictions, with an overall decline in network connectivity with elevation for all fungi and the high abundance phyla. However, trends were not uniform with elevation, most decline in connectivity occurred between 700 m and 1500 m elevation, remaining relatively stable above this. Temperature and precipitation dominated variation in network properties, with lower mean annual temperature (MAT) and higher mean annual precipitation (MAP) at higher elevations giving less network connectivity, largely through indirect effects on soil properties. Among keystone taxa that played crucial roles in network structure, the variation in abundance along the elevation gradient was also controlled by climate and also pH. Our findings point to a major role of climate gradients in mid-latitude mountain areas in controlling network connectivity. Given the importance of the orographic precipitation effect, microbial community trends seen along elevation gradients might not be mirrored by those seen along latitudinal temperature gradients.ImportanceAlthough many studies have explored patterns of fungal community diversity and composition along various environmental gradients, it is unclear how the topological structure of co-occurrence networks shifts across environmental gradients. In this study, we found that the connectivity of the fungal community decreased with increasing elevation, and that climate was the dominant factor regulating co-occurrence patterns, apparently acting indirectly through soil characteristics. Assemblages of keystone taxa playing crucial roles in network structure varied along the elevation gradient and were also largely controlled by climate. Our results provide insight into the shift of soil fungal community co-occurrence structure along elevational gradients, and possible driving mechanisms behind this.Graphic abstract
Detecting therapy-guiding RNA aberrations in platelets of non-small cell lung cancer patients
Authors: Meng Pei , Rybczynska Anna A. , Wei Jiacong , Terpstra Miente Martijn , Timens Wim , Schuuring Ed , Hiltermann T. Jeroen N. , Groen Harry J.M. , van der Wekken Anthonie J. , van den Berg Anke , Kok Klaas 
Published: January 2021

AbstractBackgroundNowadays, the detection of therapy-guiding aberrations such as EGFR mutations and ALK fusion genes in tumor tissue is common practice for lung cancer patients. The aim of this study is to explore the feasibility of detecting common therapy-guiding aberrations in RNA isolated from platelets.MethodsWe applied a single primed enrichment-based targeted next generation sequencing (NGS) approach on 10 platelet RNA samples isolated from patients with active disease. In parallel, we applied RNA-based ddPCR focusing on EGFR p.(T790M), p.(L858R) and E19del, on KRAS codon 12 and 13 and on ALK-EML4/KIF5B fusions on 22 platelet RNA samples from patients with tumors known to harbor one of these drivers. For 11 cases ddPCR analysis of circulating cell free (cf)DNA from the same blood sample was performed in parallel.ResultsDespite having good quality NGS data, none of the variants detected in the tumor biopsy were observed in platelet-derived RNA samples. Using the more sensitive ddPCR, we detected known aberrations in three of 22 platelet-derived RNA samples. EGFR mutant droplets were not observed in any of the seven platelet samples, while these mutations were detected in three of six cfDNA samples of which five were extracted from the same blood sample. KRAS mutant droplets were detected in three out of nine platelet RNA samples with fractional abundances of 0.07%, 0.11% and 0.55%. Analysis of five cfDNA samples from the same blood samples revealed KRAS-mutant droplets in four of them. Two of the four corresponding platelet RNA samples were also positive for mutant KRAS. No ALK fusion droplets were detected in seven platelet derived RNA samples.ConclusionsThe level of tumor-derived RNA transcripts in platelets of non-small cell lung cancer patients was too low to be measured reliably for clinically relevant alterations in EGFR, KRAS and ALK fusion gene transcripts.
Lack of Accuracy of the GRACE score to Predict Coronary Anatomy in Acute Coronary Syndromes
Authors: Viana Mateus dos Santos , Silva Thomaz Emanoel Azevedo , Bagano Gabriela Oliveira , de Sá Barreto Pontes Bruna , de Melo Milton Henrique Vitoria , Filgueiras Pedro Henrique Correia , Meireles Andre Costa , de Andrade Lopes Paula Oliveira , de Oliveira Junior Andre Luiz Freitas , de Oliveira Porto João Vitor Miranda , de Almeida Correia Vitor Calixto , Correia Luis Claudio Lemos 
Published: January 2021

ABSTRACTIntroductionCoronary anatomy is one of the strongest risk predictors in Acute Coronary Syndromes (ACS), which justifies early coronary angiography. Diagnostic scores for predicting outcomes are usually superior to clinical judgment. Despite being validated for prognosis, the GRACE score has been used to discriminate patients with high or low probability of anatomical severity.ObjectiveTo test the hypothesis that the GRACE score actually predicts anatomical severity.MethodsThe study was carried out by assessing consecutive patients with ACS who underwent invasive angiography. Severe anatomical disease was defined as obstructive involvement (≥ 70% in diameter) in (1) left main coronary artery or (2) double or triple vessel disease involving proximal left anterior descending artery or (3) subocclusion. The GRACE score was evaluated under numerical and dichotomous tests.ResultsA total of 733 patients were evaluated, aged 63 ± 14 years, 61% male and GRACE score of 119 ± 37. Obstructive coronary disease was observed in 81% of the patients, classified as one, two or three vessel disease, or left main coronary artery involvement in 28%, 23%, 26% and 4%, respectively. The area under the ROC curve of the GRACE score was 0.65 (95% CI = 0.61 - 0.69) for predicting severe disease. The cutoff point below which the first GRACE tertile is defined (109) was used to dichotomize low-risk (N = 318) and medium-high-risk (N = 415) samples. This standard definition of intermediate-high risk by the GRACE score (> 109) revealed sensitivity of 67% in detecting severe anatomy (95% CI = 61% - 72%) and specificity of 50% (95% CI = 46% - 55%), resulting in positive likelihood ratio of 1.3 (95% CI = 1.2 - 1.5) and negative likelihood ratio of 0.66 (95% CI = 0.55 - 0.80). There was a weak correlation between GRACE and anatomical scores such as SYNTAX (r = 0.36, P < 0.001) and Gensini (r = 0.36, P < 0.001).ConclusionDespite statistical association with extent of anatomical coronary disease, the GRACE Score is not accurate to predict severity of disease before coronary angiography.
Individual factors underlie temperature variation in sickness and in health: influence of age, BMI and genetic factors in a multi-cohort study
Authors: Penfold Rose S. , Zazzara Maria Beatrice , Osterdahl Marc F. ,   GSTT CovidCollaborative, Welch Carly , Lochlainn Mary Ni , Freidin Maxim B. , Bowyer Ruth C.E. , Thompson Ellen , Antonelli Michela , Tan Yu Xian Rachel , Sudre Carole H. , Modat Marc , Murray Benjamin , Wolf Jonathan , Ourselin Sebastien , Veenith Tonny , Lord Janet M. , Steves Claire J. 
Published: January 2021

AbstractIntroductionAgeing affects immune function resulting in aberrant fever response to infection. We assess the effects of biological variables on basal temperature and temperature in COVID-19 infection, proposing an updated temperature threshold for older adults.MethodsParticipants:Unaffected twin volunteers: 1089 adult TwinsUK participants.London hospitalised COVID-19+: 520 adults with emergency admission.Birmingham hospitalised COVID-19+: 757 adults with emergency admission.Community-based COVID-19+: 3972 adults self-reporting a positive test using the COVID Symptom Study mobile application.AnalysisHeritability assessed using saturated and univariate ACE models; Linear mixed-effect and multivariable linear regression analysing associations between temperature, age, sex and BMI; multivariable logistic regression analysing associations between fever (≥37.8°C) and age; receiver operating characteristic (ROC) analysis to identify temperature threshold for adults ≥ 65 years.ResultsAmong unaffected volunteers, lower BMI (p=0.001), and older age (p<0.001) associated with lower basal temperature. Basal temperature showed a heritability of 47% (95% Confidence Interval 18-57%).In COVID-19+ participants, increasing age associated with lower temperatures in cohorts (c) and (d) (p<0.001). For each additional year of age, participants were 1% less likely to demonstrate a fever (OR 0.99; p<0.001).Combining healthy and COVID-19+ participants, a temperature of 37.4°C in adults ≥65 years had similar sensitivity and specificity to 37.8°C in adults <65 years for discriminating fever in COVID-19.ConclusionsAgeing affects temperature in health and acute infection. Significant heritability indicates biological factors contribute to temperature regulation.Our observations indicate a lower threshold (37.4°C) should be considered for assessing fever in older adults.Key PointsOlder adults, particularly those with lower BMI, have a lower basal temperature and a lower temperature in response to infectionBasal temperature is heritable, suggesting biological factors underlying temperature regulationOur findings support a lower temperature threshold of 37.4°C for identifying possible COVID-19 infection in older adultsThis has implications for case detection, surveillance and isolation and could be incorporated into observation assessment