bluuebunny/crossref_metadata_2025_split huggingface dataset:
TRF2-mediated ORC recruitment underlies telomere stability upon DNA replication stress
Authors: Higa Mitsunori , Matsuda Yukihiro , Fujii Jumpei , Sugimoto Nozomi , Yoshida Kazumasa , Fujita Masatoshi 
Published: October 2021

Abstract
Telomeres are intrinsically difficult-to-replicate region of eukaryotic chromosomes. Telomeric repeat binding factor 2 (TRF2) binds to origin recognition complex (ORC) to facilitate the loading of ORC and the replicative helicase MCM complex onto DNA at telomeres. However, the biological significance of the TRF2–ORC interaction for telomere maintenance remains largely elusive. Here, we employed a TRF2 mutant with mutations in two acidic acid residues (E111A and E112A) that inhibited the TRF2–ORC interaction in human cells. The TRF2 mutant was impaired in ORC recruitment to telomeres and showed increased replication stress-associated telomeric DNA damage and telomere instability. Furthermore, overexpression of an ORC1 fragment (amino acids 244–511), which competitively inhibited the TRF2–ORC interaction, increased telomeric DNA damage under replication stress conditions. Taken together, these findings suggest that TRF2-mediated ORC recruitment contributes to the suppression of telomere instability.
VARIDT 2.0: structural variability of drug transporter
Authors: Fu Tingting , Li Fengcheng , Zhang Yang , Yin Jiayi , Qiu Wenqi , Li Xuedong , Liu Xingang , Xin Wenwen , Wang Chengzhao , Yu Lushan , Gao Jianqing , Zheng Qingchuan , Zeng Su , Zhu Feng 
Published: October 2021

AbstractThe structural variability data of drug transporter (DT) are key for research on precision medicine and rational drug use. However, these valuable data are not sufficiently covered by the available databases. In this study, a major update of VARIDT (a database previously constructed to provide DTs’ variability data) was thus described. First, the experimentally resolved structures of all DTs reported in the original VARIDT were discovered from PubMed and Protein Data Bank. Second, the structural variability data of each DT were collected by literature review, which included: (a) mutation-induced spatial variations in folded state, (b) difference among DT structures of human and model organisms, (c) outward/inward-facing DT conformations and (d) xenobiotics-driven alterations in the 3D complexes. Third, for those DTs without experimentally resolved structural variabilities, homology modeling was further applied as well-established protocol to enrich such valuable data. As a result, 145 mutation-induced spatial variations of 42 DTs, 1622 inter-species structures originating from 292 DTs, 118 outward/inward-facing conformations belonging to 59 DTs, and 822 xenobiotics-regulated structures in complex with 57 DTs were updated to VARIDT (https://idrblab.org/varidt/ and http://varidt.idrblab.net/). All in all, the newly collected structural variabilities will be indispensable for explaining drug sensitivity/selectivity, bridging preclinical research with clinical trial, revealing the mechanism underlying drug-drug interaction, and so on.
The human telomeric proteome during telomere replication
Authors: Lin Chih-Yi Gabriela , Näger Anna Christina , Lunardi Thomas , Vančevska Aleksandra , Lossaint Gérald , Lingner Joachim 
Published: October 2021

AbstractTelomere shortening can cause detrimental diseases and contribute to aging. It occurs due to the end replication problem in cells lacking telomerase. Furthermore, recent studies revealed that telomere shortening can be attributed to difficulties of the semi-conservative DNA replication machinery to replicate the bulk of telomeric DNA repeats. To investigate telomere replication in a comprehensive manner, we develop QTIP-iPOND - Quantitative Telomeric chromatin Isolation Protocol followed by isolation of Proteins On Nascent DNA - which enables purification of proteins that associate with telomeres specifically during replication. In addition to the core replisome, we identify a large number of proteins that specifically associate with telomere replication forks. Depletion of several of these proteins induces telomere fragility validating their importance for telomere replication. We also find that at telomere replication forks the single strand telomere binding protein POT1 is depleted, whereas histone H1 is enriched. Our work reveals the dynamic changes of the telomeric proteome during replication, providing a valuable resource of telomere replication proteins. To our knowledge, this is the first study that examines the replisome at a specific region of the genome.
GMrepo v2: a curated human gut microbiome database with special focus on disease markers and cross-dataset comparison
Authors: Dai Die , Zhu Jiaying , Sun Chuqing , Li Min , Liu Jinxin , Wu Sicheng , Ning Kang , He Li-jie , Zhao Xing-Ming , Chen Wei-Hua 
Published: October 2021

Abstract
GMrepo (data repository for Gut Microbiota) is a database of curated and consistently annotated human gut metagenomes. Its main purposes are to increase the reusability and accessibility of human gut metagenomic data, and enable cross-project and phenotype comparisons. To achieve these goals, we performed manual curation on the meta-data and organized the datasets in a phenotype-centric manner. GMrepo v2 contains 353 projects and 71,642 runs/samples, which are significantly increased from the previous version. Among these runs/samples, 45,111 and 26,531 were obtained by 16S rRNA amplicon and whole-genome metagenomics sequencing, respectively. We also increased the number of phenotypes from 92 to 133. In addition, we introduced disease-marker identification and cross-project/phenotype comparison. We first identified disease markers between two phenotypes (e.g. health versus diseases) on a per-project basis for selected projects. We then compared the identified markers for each phenotype pair across datasets to facilitate the identification of consistent microbial markers across datasets. Finally, we provided a marker-centric view to allow users to check if a marker has different trends in different diseases. So far, GMrepo includes 592 marker taxa (350 species and 242 genera) for 47 phenotype pairs, identified from 83 selected projects. GMrepo v2 is freely available at: https://gmrepo.humangut.info.
Genome-wide analysis of 8-oxo-7,8-dihydro-2'-deoxyguanosine at single-nucleotide resolution unveils reduced occurrence of oxidative damage at G-quadruplex sites
Authors: An Jiao , Yin Mengdie , Yin Jiayong , Wu Sizhong , Selby Christopher P , Yang Yanyan , Sancar Aziz , Xu Guo-Liang , Qian Maoxiang , Hu Jinchuan 
Published: October 2021

Abstract8-Oxo-7,8-dihydro-2′-deoxyguanosine (OG), one of the most common oxidative DNA damages, causes genome instability and is associated with cancer, neurological diseases and aging. In addition, OG and its repair intermediates can regulate gene transcription, and thus play a role in sensing cellular oxidative stress. However, the lack of methods to precisely map OG has hindered the study of its biological roles. Here, we developed a single-nucleotide resolution OG-sequencing method, named CLAPS-seq (Chemical Labeling And Polymerase Stalling Sequencing), to measure the genome-wide distribution of both exogenous and endogenous OGs with high specificity. Our data identified decreased OG occurrence at G-quadruplexes (G4s), in association with underrepresentation of OGs in promoters which have high GC content. Furthermore, we discovered that potential quadruplex sequences (PQSs) were hotspots of OGs, implying a role of non-G4-PQSs in OG-mediated oxidative stress response.
PLAZA 5.0: extending the scope and power of comparative and functional genomics in plants
Authors: Van Bel Michiel , Silvestri Francesca , Weitz Eric M , Kreft Lukasz , Botzki Alexander , Coppens Frederik , Vandepoele Klaas 
Published: October 2021

Abstract
PLAZA is a platform for comparative, evolutionary, and functional plant genomics. It makes a broad set of genomes, data types and analysis tools available to researchers through a user-friendly website, an API, and bulk downloads. In this latest release of the PLAZA platform, we are integrating a record number of 134 high-quality plant genomes, split up over two instances: PLAZA Dicots 5.0 and PLAZA Monocots 5.0. This number of genomes corresponds with a massive expansion in the number of available species when compared to PLAZA 4.0, which offered access to 71 species, a 89% overall increase. The PLAZA 5.0 release contains information for 5 882 730 genes, and offers pre-computed gene families and phylogenetic trees for 5 274 684 protein-coding genes. This latest release also comes with a set of new and updated features: a new BED import functionality for the workbench, improved interactive visualizations for functional enrichments and genome-wide mapping of gene sets, and a fully redesigned and extended API. Taken together, this new version offers extended support for plant biologists working on different families within the green plant lineage and provides an efficient and versatile toolbox for plant genomics. All PLAZA releases are accessible from the portal website: https://bioinformatics.psb.ugent.be/plaza/.
ViRBase v3.0: a virus and host ncRNA-associated interaction repository with increased coverage and annotation
Authors: Cheng Jun , Lin Yunqing , Xu Linfu , Chen Kechen , Li Qi , Xu Kaixin , Ning Lin , Kang Juanjuan , Cui Tianyu , Huang Yan , Zhao Xiaoyang , Wang Dong , Li Yanhui , Su Xi , Yang Bin 
Published: October 2021

AbstractAs a means to aid in the investigation of viral infection mechanisms and identification of more effective antivirus targets, the availability of a source which continually collects and updates information on the virus and host ncRNA-associated interaction resources is essential. Here, we update the ViRBase database to version 3.0 (http://www.virbase.org/ or http://www.rna-society.org/virbase/). This update represents a major revision: (i) the total number of interaction entries is now greater than 820,000, an approximately 70-fold increment, involving 116 virus and 36 host organisms, (ii) it supplements and provides more details on RNA annotations (including RNA editing, RNA localization and RNA modification), ncRNA SNP and ncRNA-drug related information and (iii) it provides two additional tools for predicting binding sites (IntaRNA and PRIdictor), a visual plug-in to display interactions and a website which is optimized for more practical and user-friendly operation. Overall, ViRBase v3.0 provides a more comprehensive resource for virus and host ncRNA-associated interactions enabling researchers a more effective means for investigation of viral infections.
Homologous recombination-mediated irreversible genome damage underlies telomere-induced senescence
Authors: Ghadaouia Sabrina , Olivier Marc-Alexandre , Martinez Aurélie , Kientega Tibila , Qin Jian , Lambert-Lanteigne Patrick , Cardin Guillaume B , Autexier Chantal , Malaquin Nicolas , Rodier Francis 
Published: October 2021

Abstract
Loss of telomeric DNA leads to telomere uncapping, which triggers a persistent, p53-centric DNA damage response that sustains a stable senescence-associated proliferation arrest. Here, we show that in normal cells telomere uncapping triggers a focal telomeric DNA damage response accompanied by a transient cell cycle arrest. Subsequent cell division with dysfunctional telomeres resulted in sporadic telomeric sister chromatid fusions that gave rise to next-mitosis genome instability, including non-telomeric DNA lesions responsible for a stable, p53-mediated, senescence-associated proliferation arrest. Unexpectedly, the blocking of Rad51/RPA-mediated homologous recombination, but not non-homologous end joining (NHEJ), prevented senescence despite multiple dysfunctional telomeres. When cells approached natural replicative senescence, interphase senescent cells displayed genome instability, whereas near-senescent cells that underwent mitosis despite the presence of uncapped telomeres did not. This suggests that these near-senescent cells had not yet acquired irreversible telomeric fusions. We propose a new model for telomere-initiated senescence where tolerance of telomere uncapping eventually results in irreversible non-telomeric DNA lesions leading to stable senescence. Paradoxically, our work reveals that senescence-associated tumor suppression from telomere shortening requires irreversible genome instability at the single-cell level, which suggests that interventions to repair telomeres in the pre-senescent state could prevent senescence and genome instability.
Reciprocal Effects Between Depressive Symptoms and Pain in Veterans over 50 Years of Age or Older
Authors: Griffin Sarah C , Young Jonathan R , Naylor Jennifer C , Allen Kelli D , Beckham Jean C , Calhoun Patrick S 
Published: October 2021

Abstract

Objective
Depression and chronic pain are major problems in American veterans, yet there is limited long-term research examining how they relate to one another in this population. This study examined the relationship between depressive symptoms and pain in U.S. veterans 50 years of age or older.

Methods
This study used data on veterans from the 2002–2016 waves of the Health and Retirement Study (n = 4,302), a large-scale observational study of Americans 50 years of age or older. Measures included a short form of the Center for Epidemiologic Studies Depression scale and two items assessing the presence and degree of pain. Analyses included random-intercept cross-lagged panel models (RI-CLPM).

Results
In the RI-CLPM, there were roughly equivalent cross-lagged effects between depressive symptoms and pain. There was also evidence that depressive symptoms and pain have a trait-like component and that these trait-like characteristics are associated.

Conclusions
These findings indicate that depressive symptoms and pain in veterans are stable characteristics in American veterans 50 years of age or older. There appear to be reciprocal effects between the two, whereby deviations in one’s typical depressive symptoms predict subsequent deviations in one’s pain level and vice versa; however, the size of these effects is very small. These findings suggest that clinicians should treat both depressive symptoms and pain, rather than assume that treatment benefits in one domain will lead to major benefits in another.
Bearing a Disproportionate Burden: Racial/Ethnic Disparities in Experiences of U.S.-Based Social Workers during the COVID-19 Pandemic
Authors: Ross Abigail M , Cederbaum Julie A , de Saxe Zerden Lisa , Zelnick Jennifer R , Ruth Betty J , Guan Ting 
Published: October 2021

AbstractWhile social workers have served as frontline workers responding to the needs of vulnerable populations during COVID-19 pandemic, little is known about how social work professionals themselves have been impacted. This article explored the impact of COVID-19 on social work professionals’ mental health, physical health, and access to personal protective equipment (PPE). This was a cross-sectional web-based survey of social workers practicing in the United States (N = 3,118); data on demographic and workplace characteristics, physical and mental health, and safety concerns were collected between June and August of 2020. Univariate statistics were used to characterize the sample. Ordinal logistic and multinomial regression were used to achieve the research aims. The majority of participants reported either moderate or severe concerns related to mental (55 percent) and physical (55 percent) health; 36 percent of respondents indicated concerns about PPE access. Respondents’ concerns differed by demographic (e.g., race, age) and workplace characteristics (e.g., setting, role, region). Social workers of color are experiencing COVID-19-related concerns of significantly greater severity relative to their White counterparts. Findings highlight an immediate need to deepen understanding of the factors that contribute to these trends and identify mechanisms to support the frontline social work workforce most impacted.
Development of a Screening Tool for Pediatric Neuropathic Pain and Complex Regional Pain Syndrome
Authors: Mesaroli Giulia , Campbell Fiona , Hundert Amos , Birnie Kathryn A. , Sun Naiyi , Davidge Kristen M. , Lalloo Chitra , Davies-Chalmers Cleo , Harris Lauren , Stinson Jennifer 
Published: October 2021

Objective:Neuropathic pain (NP) and complex regional pain syndrome (CRPS) in children can result in significant disability and emotional distress. Early assessment and treatment could potentially improve pain, function, quality of life, and reduce costs to the health care system. Currently, there are no screening tools for pediatric NP and CRPS. This research aimed to develop and establish the content validity of a screening tool for pediatric NP and CRPS using a phased approach.Materials and Methods:Phase I surveyed clinical experts using a modified Delphi procedure to elicit disease concepts for inclusion. In phase II, a consensus conference including clinicians, researchers, and people with lived experience, informed the initial item pool. Consensus for item inclusion was achieved using a nominal group technique for voting. Phase III used iterative rounds of cognitive interviews with children aged 8 to 18 years with CRPS or NP to evaluate the tool’s comprehensiveness and individual item relevance and comprehensibility. Descriptive statistics were used to describe participant characteristics. Content analysis was used to analyze patient interviews.Results:Phase I (n=50) generated an initial item pool (22 items). Phase II generated a comprehensive item pool (50 items), after which an initial version of the screening tool was drafted. Following phase III (n=26) after item revision and elimination, 37 items remained.Discussion:The Pediatric PainSCAN is a novel screening tool that has undergone rigorous development and content validity testing. Further research is needed to conduct item reduction, determine scoring, and test additional measurement properties.
Neighborhood Socioeconomic Disadvantage and Disability After Critical Illness*
Authors: Falvey Jason R. , Murphy Terrence E. , Leo-Summers Linda , Gill Thomas M. , Ferrante Lauren E. 
Published: October 2021

OBJECTIVES:
Factors common to socioeconomically disadvantaged neighborhoods, such as low availability of transportation, may limit access to restorative care services for critical illness survivors. Our primary objective was to evaluate whether neighborhood socioeconomic disadvantage was associated with an increased disability burden after critical illness. Our secondary objective was to determine if the effect differed for those discharged to the community compared with those discharged to a facility.

DESIGN:
Longitudinal cohort study with linked Medicare claims data.

SETTING:
United States.

PATIENTS:
One hundred ninety-nine older adults, contributing to 239 ICU admissions, who underwent monthly assessments of disability for 12 months following hospital discharge in 13 different functional tasks from 1998 to 2017.

MEASUREMENTS AND MAIN RESULTS:
Neighborhood disadvantage was assessed using the area deprivation index, a 1–100 ranking evaluating poverty, housing, and employment metrics. Those living in disadvantaged neighborhoods (top quartile of scores) were less likely to self-identify as non-Hispanic White compared with those in more advantaged neighborhoods. In adjusted models, older adults living in disadvantaged neighborhoods had a 9% higher disability burden over the 12 months following ICU discharge compared with those in more advantaged areas (rate ratio, 1.09; 95% Bayesian credible interval, 1.02–1.16). In the secondary analysis adjusting for discharge destination, neighborhood disadvantage was associated with a 14% increase in disability burden over 12 months of follow-up (rate ratio, 1.14; 95% credible interval, 1.07–1.21). Disability burden was 10% higher for those living in disadvantaged neighborhoods and discharged home as compared with those discharged to a facility, but this difference was not statistically significant (interaction rate ratio, 1.10; 95% credible interval, 0.98–1.25).

CONCLUSIONS:
Neighborhood socioeconomic disadvantage is associated with a higher disability burden in the 12 months after a critical illness. Future studies should evaluate barriers to functional recovery for ICU survivors living in disadvantaged neighborhoods.
IGenomic answers for children: Dynamic analyses of >1000 pediatric rare disease genomes
Authors: Cohen Ana SA , Farrow Emily G , Abdelmoity Ahmed T , Alaimo Joseph T , Amudhavalli Shivarajan M , Anderson John T , Bansal Lalit , Bartik Lauren , Baybayan Primo , Belden Bradley , Berrios Courtney D , Biswell Rebecca L , Buczkowicz Pawel , Buske Orion , Chakraborty Shreyasee , Cheung Warren A , Coffman Keith A , Cooper Ashley M , Cross Laura A , Curran Thomas , Dang Thuy Tien T , Elfrink Mary M , Engleman Kendra L , Fecske Erin D , Fieser Cynthia , Fitzgerald Keely , Fleming Emily A , Gadea Randi N , Gannon Jennifer L , Gelineau-Morel Rose N , Gibson Margaret , Goldstein Jeffrey , Grundberg Elin , Halpin Kelsee , Harvey Brian S , Heese Bryce A , Hein Wendy , Herd Suzanne M , Hughes Susan S , Ilyas Mohammed , Jacobson Jill , Jenkins Janda L , Jiang Shao , Johnston Jeffrey J , Keeler Kathryn , Korlach Jonas , Kussmann Jennifer , Lambert Christine , Lawson Caitlin , Le Pichon Jean-Baptiste , Leeder Steve , Little Vicki C , Louiselle Daniel A , Lypka Michael , McDonald Brittany D , Miller Neil , Modrcin Ann , Nair Annapoorna , Neal Shelby H , Oermann Christopher M , Pacicca Donna M , Pawar Kailash , Posey Nyshele L , Price Nigel , Puckett Laura MB , Quezada Julio F , Raje Nikita , Rowell William J , Rush Eric T , Sampath Venkatesh , Saunders Carol J , Schwager Caitlin , Schwend Richard M , Shaffer Elizabeth , Smail Craig , Soden Sarah , Strenk Meghan E , Sullivan Bonnie R , Sweeney Brooke R , Tam-Williams Jade B , Walter Adam M , Welsh Holly , Wenger Aaron M , Willig Laurel K , Yan Yun , Younger Scott T , Zhou Dihong , Zion Tricia N , Thiffault Isabelle , Pastinen Tomi 
Published: October 2021

ABSTRACTPURPOSETo provide comprehensive diagnostic and candidate analyses in a pediatric rare disease cohort through the Genomic Answers for Kids (GA4K) program.METHODSExtensive analyses of 960 families with suspected genetic disorders including short-read exome (ES) and genome sequencing (srGS); PacBio HiFi long-read GS (HiFi-GS); variant calling for small-nucleotide (SNV), structural (SV) and repeat variants; and machine-learning variant prioritization. Structured phenotypes, prioritized variants and pedigrees are stored in PhenoTips database, with data sharing through controlled access (dbGAP).RESULTSDiagnostic rates ranged from 11% for cases with prior negative genetic tests to 34.5% in naïve patients. Incorporating SVs from GS added up to 13% of new diagnoses in previously unsolved cases. HiFi-GS yielded increased discovery rate with >4-fold more rare coding SVs than srGS. Variants and genes of unknown significance (VUS/GUS) remain the most common finding (58% of non-diagnostic cases).CONCLUSIONComputational prioritization is efficient for diagnostic SNVs. Thorough identification of non-SNVs remains challenging and is partly mitigated by HiFi-GS sequencing. Importantly, community research is supported by sharing real-time data to accelerate gene validation, and by providing HiFi variant (SNV/SV) resources from >1,000 human alleles to facilitate implementation of new sequencing platforms for rare disease diagnoses.