bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Paradigm For Calling Sequence In Families: The Long Life Family Study
Authors: Daw E. Warwick , Anema Jason A. , Schwander Karen , Lin Shiow Jiuan , Wang Lihua , Wojczynski Mary , Thyagarajan Bharat , Stitziel Nathan , Province Michael A. 
Published: May 2024

AbstractOver Several years, we have developed a system for assuring the quality of whole genome sequence (WGS) data in the LLFS families. We have focused on providing data to identify germline genetic variants with the aim of releasing as many variants on as many individuals as possible. We aim to assure the quality of the individual calls. The availability of family data has enabled us to use and validate some filters not commonly used in population-based studies. We developed slightly different procedures for the autosomal, X, Y, and Mitochondrial (MT) chromosomes. Some of these filters are specific to family data, but some can be used with any WGS data set. We also describe the procedure we use to construct linkage markers from the SNP sequence data and how we compute IBD values for use in linkage analysis.
Clonal evolution of hematopoietic stem cells after cancer chemotherapy
Authors: Uryu Hidetaka , Saeki Koichi , Haeno Hiroshi , Kapadia Chiraag Deepak , Furudate Ken , Nangalia Jyoti , Chapman Michael Spencer , Zhao Li , Hsu Joanne I. , Zhao Chong , Chen Shujuan , Tanaka Tomoyuki , Li Zongrui , Yang Hui , DiNardo Courtney , Daver Naval , Pemmaraju Naveen , Jain Nitin , Ravandi Farhad , Zhang Jianhua , Song Xingzhi , Thompson Erika , Tang Hongli , Little Latasha , Gumbs Curtis , Orlowski Robert Z. , Qazilbash Muzaffar , Bhalla Kapil , Colla Simona , Kantarjian Hagop , Shamanna Rashmi Kanagal , Ramos Carlos Bueso- , Nakada Daisuke , Futreal P. Andrew , Shpall Elizabeth , Goodell Margaret , Garcia-Manero Guillermo , Takahashi Koichi 
Published: May 2024

AbstractNormal hematopoietic stem and progenitor cells (HSPCs) inherently accumulate somatic mutations and lose clonal diversity with age, processes implicated in the development of myeloid malignancies1. The impact of exogenous stressors, such as cancer chemotherapies, on the genomic integrity and clonal dynamics of normal HSPCs is not well defined. We conducted whole-genome sequencing on 1,032 single-cell-derived HSPC colonies from 10 patients with multiple myeloma (MM), who had undergone various chemotherapy regimens. Our findings reveal that melphalan treatment distinctly increases mutational burden with a unique mutation signature, whereas other MM chemotherapies do not significantly affect the normal mutation rate of HSPCs. Among these therapy-induced mutations were several oncogenic drivers such asTET2andPPM1D. Phylogenetic analysis showed a clonal architecture in post-treatment HSPCs characterized by extensive convergent evolution of mutations in genes such asTP53andPPM1D. Consequently, the clonal diversity and structure of post-treatment HSPCs mirror those observed in normal elderly individuals, suggesting an accelerated clonal aging due to chemotherapy. Furthermore, analysis of matched therapy-related myeloid neoplasm (t-MN) samples, which occurred 1-8 years later, enabled us to trace the clonal origin of t-MNs to a single HSPC clone among a group of clones with competing malignant potential, indicating the critical role of secondary mutations in dictating clonal dominance and malignant transformation. Our findings suggest that cancer chemotherapy promotes an oligoclonal architecture with multiple HSPC clones possessing competing leukemic potentials, setting the stage for the selective emergence of a singular clone that evolves into t-MNs after acquiring secondary mutations. These results underscore the importance of further systematic research to elucidate the long-term hematological consequences of cancer chemotherapy.
Mechanism of structure-specific DNA binding by the FANCM branchpoint translocase
Authors: Abbouche Lara , Murphy Vincent J , Gao Jixuan , van Twest Sylvie , Sobinoff Alexander P , Auweiler Karen M , Pickett Hilda A , Bythell-Douglas Rohan , Deans Andrew J 
Published: May 2024

AbstractFANCM is a DNA repair protein that recognizes stalled replication forks, and recruits downstream repair factors. FANCM activity is also essential for the survival of cancer cells that utilize the Alternative Lengthening of Telomeres (ALT) mechanism. FANCM efficiently recognizes stalled replication forks in the genome or at telomeres through its strong affinity for branched DNA structures. In this study, we demonstrate that the N-terminal translocase domain drives this specific branched DNA recognition. The Hel2i subdomain within the translocase is crucial for effective substrate engagement and couples DNA binding to catalytic ATP-dependent branch migration. Removal of Hel2i or mutation of key DNA-binding residues within this domain diminished FANCM’s affinity for junction DNA and abolished branch migration activity. Importantly, these mutant FANCM variants failed to rescue the cell cycle arrest, telomere-associated replication stress, or lethality of ALT-positive cancer cells depleted of endogenous FANCM. Our results reveal the Hel2i domain is key for FANCM to properly engage DNA substrates, and therefore plays an essential role in its tumour-suppressive functions by restraining the hyperactivation of the ALT pathway.
A reference-free algorithm discovers regulation in the plant transcriptome
Authors: Meyer Elisabeth , Saldivar Evan V. , Kokot Marek , Xue Bo , Deorowicz Sebastian , Rhee Seung Y. , Salzman Julia 
Published: May 2024

AbstractMost plant genomes and their regulation remain unknown. We used SPLASH - a new, reference-genome free sequence variation detection algorithm - to analyze transcriptional and post-transcriptional regulation from RNA-seq data. We discovered differential homolog expression during maize pollen development, and imbibition-dependent cryptic splicing in Arabidopsis seeds. SPLASH enables discovery of novel regulatory mechanisms, including differential regulation of genes from hybrid parental haplotypes, without the use of alignment to a reference genome.
Exploring the Architectural Biases of the Canonical Cortical Microcircuit
Authors: Balwani Aishwarya , Cho Suhee , Choi Hannah 
Published: May 2024

AbstractThe cortex plays a crucial role in various perceptual and cognitive functions, driven by its basic unit, thecanonical cortical microcircuit. Yet, we remain short of a framework that definitively explains the structure-function relationships of this fundamental neuroanatomical motif. To better understand how physical substrates of cortical circuitry facilitate their neuronal dynamics, we employ a computational approach using recurrent neural networks and representational analyses. We examine the differences manifested by the inclusion and exclusion of biologically-motivated inter-areal laminar connections on the computational roles of different neuronal populations in the microcircuit of two hierarchically-related areas, throughout learning. Our findings show that the presence of feedback connections correlates with the functional modularization of cortical populations in different layers, and provides the microcircuit with a natural inductive bias to differentiate expected and unexpected inputs at initialization. Furthermore, when testing the effects of training the microcircuit and its variants with a predictive-coding inspired strategy, we find that doing so helps better encode noisy stimuli in areas of the cortex that receive feedback, all of which combine to suggest evidence for a predictive-coding mechanism serving as an intrinsic operative logic in the cortex.
Incidence of prostate cancer in Medicaid beneficiaries with and without HIV in 2001-2015 in 14 states
Authors: Pirsl Filip , Calkins Keri , Rudolph Jacqueline E. , Wentz Eryka , Xu Xiaoqiang , Lau Bryan , Joshu Corinne E. 
Published: May 2024

AbstractBackgroundProstate cancer is projected to be the most common cancer among people living with HIV; however, incidence of prostate cancer has been reported to be lower in men with HIV compared to men without HIV with little evidence to explain this difference. We describe prostate cancer incidence by HIV status in Medicaid beneficiaries, allowing for comparison of men with and without HIV who are similar with respect to socioeconomic characteristics and access to healthcare.MethodsMedicaid beneficiaries (N=15,167,636) aged 18-64 with ≥7 months of continuous enrollment during 2001-2015 in 14 US states were retained for analysis. Diagnoses of HIV and prostate cancer were identified using inpatient and other non-drug claims. We estimated cause-specific (csHR) and sub-distribution hazard ratios comparing incidence of prostate cancer by HIV status, adjusted for age, race-ethnicity, state of residence, year of enrollment, and comorbid conditions. Models were additionally stratified by age and race-ethnicity.ResultsThere were 366 cases of prostate cancer observed over 299,976 person-years among beneficiaries with HIV and 17,224 cases over 22,298,914 person-years in beneficiaries without HIV. The hazard of prostate cancer was lower in men with HIV than men without HIV (csHR=0.89; 95% CI: 0.80, 0.99), but varied by race-ethnicity, with similar observations among non-Hispanic Black (csHR=0.79; 95% CI: 0.69, 0.91) and Hispanic (csHR=0.85; 95% CI: 0.67, 1.09), but not non-Hispanic white men (csHR=1.17; 95% CI: 0.91, 1.50). Results were similar in models restricted to ages 50-64 and 40-49, except for a higher hazard of prostate cancer in Hispanic men with HIV in their 40s, while the hazard of prostate cancer was higher in men with HIV across all models for men aged 18-39.ConclusionReported deficits in prostate cancer incidence by HIV status may be restricted to specific groups defined by age and race-ethnicity.
Fine-scale spatial and social patterns of SARS-CoV-2 transmission from identical pathogen sequences
Authors: Tran-Kiem Cécile , Paredes Miguel I. , Perofsky Amanda C. , Frisbie Lauren A. , Xie Hong , Kong Kevin , Weixler Amelia , Greninger Alexander L. , Roychoudhury Pavitra , Peterson JohnAric M. , Delgado Andrew , Halstead Holly , MacKellar Drew , Dykema Philip , Gamboa Luis , Frazar Chris D. , Ryke Erica , Stone Jeremy , Reinhart David , Starita Lea , Thibodeau Allison , Yun Cory , Aragona Frank , Black Allison , Viboud Cécile , Bedford Trevor 
Published: May 2024

AbstractPathogen genomics can provide insights into underlying infectious disease transmission patterns, but new methods are needed to handle modern large-scale pathogen genome datasets and realize this full potential. In particular, genetically proximal viruses should be highly informative about transmission events as genetic proximity indicates epidemiological linkage. Here, we leverage pairs of identical sequences to characterise fine-scale transmission patterns using 114,298 SARS-CoV-2 genomes collected through Washington State (USA) genomic sentinel surveillance with associated age and residence location information between March 2021 and December 2022. This corresponds to 59,660 sequences with another identical sequence in the dataset. We find that the location of pairs of identical sequences is highly consistent with expectations from mobility and social contact data. Outliers in the relationship between genetic and mobility data can be explained by SARS-CoV-2 transmission between postal codes with male prisons, consistent with transmission between prison facilities. We find that transmission patterns between age groups vary across spatial scales. Finally, we use the timing of sequence collection to understand the age groups driving transmission. Overall, this work improves our ability to leverage large pathogen genome datasets to understand the determinants of infectious disease spread.
Mobile Phone Dependence Syndrome and its influencing factors among middle school students in Guangzhou, China: a cross-sectional study
Authors: Wang Chang , Zhu Haiyuan , Lin Rong , Liu Hui , Li Jinrong , Sun Minying , Lin Weiquan , Zhou Qin , Huang Bing , Zhao Jierong , Yang Yingyu , Li Ying , Zhang Runquan , Wu Qiqi , Dong Xiaomei 
Published: May 2024

AbstractBackgroundMobile Phone Dependence Syndrome (MPDS), a kind of addiction caused by extra phone use, is characterized by impairment of physical, mental, and social functioning. This study aimed to assess the prevalence of MPDS, injury due to overfocusing on phone, and explore MPDS’s associated factors among middle school students in Guangzhou, China.Methods1928 questionnaires were collected from April 2023 to May 2023 in Liwan and Nansha districts of Guangzhou through multi-stage cluster sampling. We used the Mobile Phone Dependence Scale for Middle School Students (MPDS Scale) and analyzed its reliability and validity. Frequency distribution, Chi-square test, fisher exact test and binary logistic regression were performed in data analysis.ResultsThe reliability and validity of the MPDS Scale were good. The prevalence of MPDS was 10.0% and injury rate because of overfocusing on phone is 11.9%. Binary logistic regression demonstrated that gender, grade, personality, father’s parenting style, time of mobile phone use on rest days, and the most important motivation for using phone might influence occurrence of MPDS among middle school students (P<0.05).ConclusionPrevalence of MPDS among middle school students in Guangzhou was at a low level relatively. Students with MPDS had higher injury proportion than students with no MPDS. Female gender, grade of senior high school, introverted character, fathers with authoritarian parenting styles, spending 6 hours above on phone on rest days, and motivation of entertainment for using phone were associated with occurrence of MPDS. These findings can help develop measures to reduce occurrence of MPDS.
The characteristics and risk factors of burnout for public servants in North China
Authors: Jia Zhiyi , Chen Jinping , Dang Yalong 
Published: May 2024

AbstractObjectiveBurnout significantly affected the working efficiency of public servants. This study aimed to identify the characteristics and risk factors of burnout among public servants in North China.MethodsA cross-sectional online and anonymous survey was conducted between March 2024 and April 2024. The inclusion criteria included active public servants aged between 18 and 60 years with fluency in Chinese. Participants with mental disorders were excluded. The study utilized the Maslach Burnout Inventory-General Survey with Chinese adaptation to measure burnout across three dimensions: exhaustion, cynicism, and professional efficacy. The survey consisted of 16 seven-point Likert scale questions, with response options ranging from “never” to “daily,” and scored from 1 to 7. Participants with burnout had to meet at least one of the following criteria: 1) scoring in the upper third for exhaustion, 2) scoring in the upper third for cynicism, or 3) scoring in the lower third for professional efficacy. Severe burnout was defined as meeting all three criteria, moderate burnout was defined as meeting two criteria, and mild burnout was defined as meeting one criterion.ResultsThe study included 1064 participants from seventeen provinces in North China. The breakdown of burnout levels among the participants was as follows: 34.3% (365/1064) experienced no burnout, 29.5% (314/1064) had mild burnout, 35.6% (379/1064) had moderate burnout, and 0.6% (6/1064) experienced severe burnout. The study revealed no significant differences in burnout risk based on gender, age, academic degrees, occupation types, and length of service. However, significant variations were observed in burnout risk based on job position, salary, income satisfaction, job security, work stress, and interpersonal ability.ConclusionIn North China, two-thirds of public servants experienced occupational burnout. Job position, salary, income satisfaction, job security, work stress, and interpersonal ability were identified as the risk factors.
Tolerability of Long-acting Diquafosol Ophthalmic Solution as per Tear Film and Meibomian Glands Findings
Authors: Arita Reiko , Fukuoka Shima , Kaido Minako 
Published: May 2024

AbstractLong-acting diquafosol (DQS) ophthalmic solution (DQS-LX) has significant advantages regarding patient adherence owing to the reduced frequency of required eye drops; however, some patients prefer conventional DQS over DQS-LX. Herein, to clarify the characteristics of patients according to their preference for ophthalmic solutions, dry eye (DE) and meibomian gland (MG) findings were retrospectively investigated. This study enrolled 341 patients with DE (mean age, 62.1 ± 11.7 years) treated at the Itoh Clinic between November 8, 2022, and July 31, 2023, who switched from DQS to DQS-LX. Patients were divided into two groups: those who continued DQS-LX administration (DQS-LX group) and those who wished to revert to conventional DQS (DQS group). Data regarding subjective symptoms assessed using the Standard Patient Evaluation of Eye Dryness (SPEED) questionnaire, tear film breakup time (BUT), tear meniscus height (TMH), corneal and conjunctival fluorescein staining (CFS), conjunctival hyperemia/papilla, meiboscore, plugging, vascularity, meibum grade, and Schirmer’s score at the time of DQS-LX switch were evaluated. Of the 341 patients, 31 (9.1%) wished to revert to conventional DQS. In total, 32 eyes of 16 patients in the DQS group and 64 eyes of 32 patients in the DQS-LX group—for whom complete data were available—were included in the analysis. Compared with the DQS group, the DQS-LX group had significantly higher SPEED scores, shorter BUTs, lower TMHs, greater CFS findings, larger meibum grades (allP< 0.001), lower Schirmer scores (P= 0.008), and more pluggings (P= 0.001) than the DQS group. More allergic conjunctivitis-related complications were observed in the DQS group (P= 0.034). In conclusion, patients with low tear film volume and DE complicated by moderate or severe MG dysfunction preferred DQS-LX, while those with allergic findings preferred conventional DQS.
Comparison of actionable alterations in cancers with kinase fusion, mutation, and amplification
Authors: Suzuki Shinsuke , Akahane Toshiaki , Tanimoto Akihide , Higashi Michiyo , Kitazono Ikumi , Kirishima Mari , Nishigaki Masakazu , Ikeda Toshiro , Kanemitsu Shuichi , Nakazawa Junichi , Akahane Erina , Nishihara Hiroshi , Uozumi Kimiharu , Yoshimitsu Makoto , Ishitsuka Kenji , Ueno Shin-ichi 
Published: May 2024

AbstractKinase-related gene fusion and point mutations play pivotal roles as drivers in cancer, necessitating optimized targeted therapy against these alterations. The efficacy of molecularly targeted therapeutics varies depending on the specific alteration, with great success reported for such therapeutics in the treatment of cancer with kinase fusion proteins. However, the involvement of actionable alterations in solid tumors, especially in relation to kinase fusions, remains incompletely understood. This study aimed to compare the number of actionable alterations in patients with tyrosine or serine/threonine kinase domain fusions, mutations, and amplifications. We analyzed 613 patients with 40 solid cancer types who visited our division between June 2020 and April 2024. To detect alterations involving multiple-fusion calling, we performed comprehensive genomic sequencing using FoundationOne®companion diagnostic (F1CDx) and FoundationOne®Liquid companion diagnostic (F1LCDx). Patient characteristics and genomic profiles were analyzed to assess the frequency and distribution of actionable alterations across different cancer types. Of the 613 patients, 44 had fusions involving kinases, transcriptional regulators, or tumor suppressors. F1CDx and F1LCDx detected 13 with kinase-domain fusions. We identified 117 patients with kinase-domain mutations and 58 with kinase-domain amplifications. The number of actionable alterations in patients with kinase-domain fusion, mutation, or amplification (median [interquartile range; IQR]) was 2 (1–3), 5 (3–7), and 6 (4–8), respectively. Patients with kinase fusion had significantly fewer actionable alterations than those with kinase-domain mutations and amplifications. However, those cancers with fusion involving tumor suppressors tended to have more actionable alterations (median [IQR]; 4 [2–9]). Cancers with kinase fusions tended to exhibit fewer actionable alterations than those with kinase mutations and amplifications. These findings underscore the importance of detecting kinase alterations and indicate the pivotal role of kinase fusions are strong drivers of cancer development, highlighting their potential as prime targets for molecular therapeutics.
Health and economic impact of caregiving on informal caregivers of people with chronic diseases in Sub-Saharan Africa: A systematic review
Authors: Kisangala Ephraim , Mbivnjo Etheldreda Leinyuy , Webb Edward JD , Barrett Barbara , Rukundo Godfrey Zari , Namisango Eve , Heslin Margaret 
Published: May 2024

AbstractBackgroundWith a disproportionate burden of chronic diseases and severe shortage of health workers in sub-Saharan Africa (SSA), the region implicitly relies on informal caregivers (ICGs) to support the patients both within and outside the health facilities. The aim of this review is to explore the health and economic impact of caregiving on ICGs of patients with chronic diseases in SSA.MethodsMedline (Ovid), CINAHL (EBSCOhost), PsycINFO (Ovid), Embase (Ovid), Global Health and Web of Science databases were systematically searched to identify original articles that considered the economic and/or health impacts of caregiving in SSA. The results from the included studies were synthesised narratively.ResultsAfter screening 4,372 articles, 47 were included for synthesis. The articles were from all sub-regions of SSA with more than half (25/47) of the articles focussing on caregivers for patients with cancer. Although the primary motivation for becoming caregivers was love and responsibility, the caring responsibilities described in twenty articles, had profound effects on the caregiver’s lives. Healthwise, ICGs experienced changes in their physical and mental health like developing musculoskeletal problems and depression. Economically, caregiving was expensive, and financially draining. The opportunity cost of caregiving included loss of jobs, loss of income, foregoing planned important activities and missed education opportunities.ConclusionICGs reported a range of mainly negative health and economic effects of the work they do. Health care systems should consider how to better support ICGs in terms of their own physical and mental wellbeing and governments should consider how to better financially support ICGs.