bluuebunny/crossref_metadata_2025_split huggingface dataset:
COVID-19 Outcomes in Patients with Cancer: Findings from the University of California Health System Database
Authors: Kwon D. H. , Cadena Pico J. E. , Nguyen S. , Chan K. H. R. , Soper B. , Gryshuk A. L. , Ray P. , Huang F. W. 
Published: September 2021

AbstractBackgroundPatients with cancer are at risk for poor COVID-19 outcomes. We aimed to identify cancer-related risk factors for poor COVID-19 outcomes.Patients and MethodsWe conducted a retrospective cohort study using the University of California Health COVID Research Data Set. This database includes prospectively-collected, electronic health data of patients who underwent testing for SARS-CoV-2 at seventeen California medical centers. We identified adult patients tested for SARS-CoV-2 between February 1, 2020 and December 31, 2020, and selected a cohort of patients with cancer using diagnostic codes. We obtained demographic, comorbidity, laboratory, cancer type, and antineoplastic therapy data. The primary outcome was hospitalization within 30 days after first positive SARS-CoV-2 test. Secondary outcomes were SARS-CoV-2 positivity and composite endpoint for severe COVID-19 (intensive care, mechanical ventilation, or death within 30 days after first positive test). We used multivariable logistic regression to identify cancer-related factors associated with outcomes.ResultsWe identified 409,462 patients undergoing SARS-CoV-2 testing. Of 49,918 patients with cancer, 1,781 (3.6%) tested positive. Patients with cancer were less likely to test positive (OR 0.69, 95%CI 0.66-0.73, P<0.001). BCR-ABL-negative myeloproliferative neoplasms (polycythemia vera, essential thrombocythemia, and primary myelofibrosis) (OR 2.51, 95%CI 1.29-4.89, P=0.007); venetoclax (OR 3.63, 95%CI 1.02-12.92, P=0.046); methotrexate (OR 3.65, 95%CI 1.17-11.37, P=0.026); Asian race (OR 1.92, 95%CI 1.23-2.98, P=0.004); and Hispanic/Latino ethnicity (OR 1.96, 95%CI 1.41-2.73, P<0.001) were associated with increased hospitalization risk. Among 388 hospitalized patients with cancer and COVID-19, cancer type and therapy type were not associated with severe COVID-19.ConclusionsIn this large, diverse cohort of Californians, cancer was not a risk factor for SARS-CoV-2 positivity. Patients with BCR/ABL-negative myeloproliferative neoplasm and patients receiving methotrexate or venetoclax may be at an increased risk of hospitalization following SARS-CoV-2 infection. Further mechanistic and comparative studies are needed to explain and confirm our findings.
Increasing triacylglycerol formation and lipid storage by unsaturated lipids protects renal proximal tubules in diabetes
Authors: Pérez-Martí Albert , Ramakrishnan Suresh , Li Jiayi , Dugourd Aurelien , Molenaar Martijn R. , De La Motte Luigi R. , Grand Kelli , Mansouri Anis , Parisot Mélanie , Lienkamp Soeren S. , Saez-Rodriguez Julio , Simons Matias 
Published: September 2021

AbstractIn diabetic patients, dyslipidemia frequently contributes to organ damage such as diabetic kidney disease (DKD). DKD is associated with excessive renal deposition of triacylglycerol (TAG) in lipid droplets (LD). Yet, it is unclear whether LDs play a protective or damaging role and how this might be influenced by dietary patterns. By using a diabetes mouse model, we find here that high fat diet enriched in the unsaturated oleic acid (OA) caused more lipid storage in LDs in renal proximal tubular cells (PTC) but less tubular damage than a corresponding butter diet with the saturated palmitic acid (PA). Mechanistically, we identify endoplasmic reticulum (ER) stress as the main cause of PA-induced PTC injury. ER stress is caused by elevated cellular levels of saturated TAG precursors and to higher membrane order in the ER. The resulting cell death is preceded by a transcriptional rewiring of phospholipid metabolism. Simultaneous addition of OA rescues the cytotoxic effects by normalizing membrane order and by increasing the total TAG amount. The latter also stimulates the formation of LDs that in turn can release unsaturated lipids upon demand by lipolysis. Our study thus clarifies mechanisms underlying PA-induced cell stress in PTCs and emphasizes the importance of olive oil for the prevention of DKD.
State-wide Genomic Epidemiology Investigations of COVID-19 Infections in Healthcare Workers – Insights for Future Pandemic Preparedness
Authors: Watt Anne E. , Sherry Norelle L. , Andersson Patiyan , Lane Courtney R. , Johnson Sandra , Wilmot Mathilda , Horan Kristy , Sait Michelle , Ballard Susan A. , Crachi Christina , Beck Dianne J. , Marshall Caroline , Kainer Marion , Stuart Rhonda , McGrath Christian , Kwong Jason C. , Bass Pauline , Kelley Peter G. , Crowe Amy , Guy Stephen , Macesic Nenad , Smith Karen , Williamson Deborah A. , Seemann Torsten , Howden Benjamin P. 
Published: September 2021

AbstractBackgroundCOVID-19 has resulted in many infections in healthcare workers (HCWs) globally. We performed state-wide SARS-CoV-2 genomic epidemiological investigations to identify HCW transmission dynamics and provide recommendations to optimise healthcare system preparedness for future outbreaks.MethodsGenome sequencing was attempted on all COVID-19 cases in Victoria, Australia. We combined genomic and epidemiologic data to investigate the source of HCW infections across multiple healthcare facilities (HCFs) in the state. Phylogenetic analysis and fine-scale hierarchical clustering were performed for the entire Victorian dataset including community and healthcare cases. Facilities provided standardised epidemiological data and putative transmission links.FindingsBetween March and October 2020, approximately 1,240 HCW COVID-19 infection cases were identified; 765 are included here. Genomic sequencing was successful for 612 (80%) cases. Thirty-six investigations were undertaken across 12 HCFs. Genomic analysis revealed that multiple introductions of COVID-19 into facilities (31/36) were more common than single introductions (5/36). Major contributors to HCW acquisitions included mobility of staff and patients between wards and facilities, and characteristics and behaviours of individual patients including super-spreading events. Key limitations at the HCF level were identified.InterpretationGenomic epidemiological analyses enhanced understanding of HCW infections, revealing unsuspected clusters and transmission networks. Combined analysis of all HCWs and patients in a HCF should be conducted, supported by high rates of sequencing coverage for all cases in the population. Established systems for integrated genomic epidemiological investigations in healthcare settings will improve HCW safety in future pandemics.FundingThe Victorian Government, the National Health and Medical Research Council Australia, and the Medical Research Future Fund.
The phenomenology of tics and tic-like behavior in TikTok
Authors: Vera Alonso Zea , Bruce Adrienne , Garris Jordan , Tochen Laura , Bhatia Poonam , Lehman Rebecca K , Lopez Wendi , Wu Steve W. , Gilbert Donald L. 
Published: September 2021

ABSTRACTBackground and ObjectivePediatricians and pediatric subspecialists worldwide have reported a marked increase in functional (conversion) disorders with tic-like behaviors during the COVID-19 pandemic. These patients often report frequent viewing of Tourette Syndrome (TS) TikTok videos, suggesting disease modeling. We aimed to evaluate tic phenomenology in videos posted on TikTok.MethodsThe 100 most-viewed videos under #tourettes in TikTok were randomly assigned to two primary reviewers (n=3; <2 years independent practice), all pediatric neurologists specializing in movement disorders, for extraction and classification of tic phenomenology. Initial disagreements were solved by consensus. If not resolved, a senior reviewer (n=5; >2 years independent pediatric movement-disorder practice) served as tiebreaker. In addition, two primary and one senior reviewer rated each video on a Likert scale from 1= “All the tics are typical of TS” to 5= “None of the tics are typical of TS”. Mean scores and Spearman correlation between primary and senior reviewers were calculated.ResultsSix videos without tic-like behaviors were excluded. Most videos depicted coprophenomena (coprolalia: 53.2%; copropraxia: 20.2%), often with unusual characteristics. Frequently, videos demonstrated atypical phenomenology such as very strong influence by the environment (motor: 54.3%; phonic: 54.3%), aggression (19.1%), throwing objects (22.3%), self-injurious behaviors (27.7%), and long phrases (>3 words; 45.7%). Most videos portrayed atypical, non-tic behaviors (Median [IQR] Likert ratings: Primary 4.5 [4-5]; Senior 5 [3-5]). Primary vs. senior rater scores demonstrated moderate agreement (r = 0.46; p<0.001).ConclusionsTS symptoms portrayals on highly-viewed TikTok videos are predominantly not representative or typical of TS.HighlightsMany teenagers with functional tic-like disorder have been reported during the COVID-19 pandemic.These patients report increased viewing of Tourette Syndrome TikTok videos, a popular social media platform, and present with similar tic-like behaviors.Current TikTok videos are poorly representative of Tourette syndrome and more consistent with functional tic-like behavior.We provide a detailed description of the phenomenology tics and tic-like behavior portrayed in TikTok.
OpenClinicalAI: enabling AI to diagnose diseases in real-world clinical settings
Authors: Huang Yunyou , Wang Nana , Tang Suqin , Ma Li , Hao Tianshu , Jiang Zihan , Zhang Fan , Kang Guoxin , Miao Xiuxia , Guan Xianglong , Zhang Ruchang , Zhang Zhifei , Zhan Jianfeng ,   for the Alzheimer’s Disease Neuroimaging Initiative
Published: September 2021

This paper quantitatively reveals the state-of-the-art and state-of-the-practice AI systems only achieve acceptable performance on the stringent conditions that all categories of subjects are known, which we call closed clinical settings, but fail to work in real-world clinical settings. Compared to the diagnosis task in the closed setting, real-world clinical settings pose severe challenges, and we must treat them differently. We build a clinical AI benchmark named Clinical AIBench to set up real-world clinical settings to facilitate researches. We propose an open, dynamic machine learning framework and develop an AI system named OpenClinicalAI to diagnose diseases in real-world clinical settings. The first versions of Clinical AIBench and OpenClinicalAI target Alzheimer’s disease. In the real-world clinical setting, OpenClinicalAI significantly out-performs the state-of-the-art AI system. In addition, OpenClinicalAI develops personalized diagnosis strategies to avoid unnecessary testing and seamlessly collaborates with clinicians. It is promising to be embedded in the current medical systems to improve medical services.One-Sentence SummaryWe propose a clinical AI benchmark and an open, dynamic machine learning framework to enable AI diagnosis systems to land in real-world clinical settings.
Wound Complications Following Surgery to the Lymph Nodes: A protocol for a systematic review and meta-analysis
Authors: Nzenwa Ikemsinachi C. , Iqbal Hassan A. , Hardie Claire , Smith George E , Matteucci Paolo L , Totty Joshua P 
Published: September 2021

AbstractBackgroundMalignancies that spread to the lymph nodes may be identified through surgical biopsy, and treatment of metastatic disease may be through lymph node dissection. These surgeries, however, may be associated with significant adverse outcomes, particularly wound complications, the true incidence of which remains unknown. Multiple studies have reported their individual rates of complications in isolation. The aim of this study will be to systematically evaluate data that presents the incidence of wound complications in patients undergoing these surgeries.MethodsWe have designed and registered a protocol for a systematic review and meta-analysis of studies presenting incidence data. We will search MEDLINE, EMBASE and CENTRAL for relevant articles published before March 30th, 2021. Meta-analysis will be undertaken to synthesise an overall incidence of surgical site infection, wound dehiscence, haematoma and seroma. Subgroup analyses will investigate the effects of anatomical location, primary malignancy and study design on pooled incidence. Risk of bias will be evaluated for each included study using bespoke tools matched to the study design.DiscussionThe results of this study will provide the incidence of wound complications and secondary complications following lymph node surgery. This will directly impact upon the consent process, and may influence the nature of future research studies aimed at reducing post-operative complications.
Comprehensive analysis of DNA replication timing in genetic diseases and gene knockouts identifies MCM10 as a novel regulator of the replication program
Authors: Caballero Madison , Ge Tiffany , Rebelo Ana Rita , Seo Seungmae , Kim Sean , Brooks Kayla , Zuccaro Michael , Kanagaraj Radhakrishnan , Vershkov Dan , Kim Dongsung , Smogorzewska Agata , Smolka Marcus , Benvenisty Nissim , West Stephen C , Egli Dieter , Mace Emily M , Koren Amnon 
Published: September 2021

AbstractCellular proliferation depends on the accurate and timely replication of the genome. Several genetic diseases are caused by mutations in key DNA replication genes; however, it remains unclear whether these genes influence the normal program of DNA replication timing. Similarly, the factors that regulate DNA replication dynamics are poorly understood. To systematically identify trans-acting modulators of replication timing, we profiled replication in 184 cell lines from three cell types, encompassing 60 different gene knockouts or genetic diseases. Through a rigorous approach that considers the background variability of replication timing, we concluded that most samples displayed normal replication timing. However, mutations in two genes showed consistently abnormal replication timing. The first gene was RIF1, a known modulator of replication timing. The second was MCM10, a highly conserved member of the pre-replication complex. MCM10 mutant cells demonstrated replication timing variability comprising 46% of the genome and at different locations than RIF1 knockouts. Replication timing alterations in MCM10-mutant cells was predominantly comprised of replication initiation defects. Taken together, this study demonstrates the remarkable robustness of the human replication timing program and reveals MCM10 as a novel modulator of DNA replication timing.
TAAC - TMS Adaptable Auditory Control: a universal tool to mask TMS click
Authors: Russo S. , Sarasso S. , Puglisi G.E. , Dal Palù D. , Pigorini A. , Casarotto S. , D’Ambrosio S. , Astolfi A. , Massimini M. , Rosanova M. , Fecchio M. 
Published: September 2021

AbstractBackgroundCoupling transcranial magnetic stimulation with electroencephalography (TMS-EEG) allows recording the EEG response to a direct, non-invasive cortical perturbation. However, obtaining a genuine TMS-evoked EEG potential requires controlling for several confounds, among which a main source is represented by the auditory evoked potentials (AEPs) associated to the TMS discharge noise (TMS click). This contaminating factor can be in principle prevented by playing a masking noise through earphones.New methodHere we release TMS Adaptable Auditory Control (TAAC), a highly flexible, open-source, Matlab®-based interface that generates in real-time customized masking noises. TAAC creates noises starting from the stimulator-specific TMS click and tailors them to fit the individual, subject-specific click perception by mixing and manipulating the standard noises in both time and frequency domains.ResultsWe showed that TAAC allows us to provide standard as well as customized noises able to effectively and safely mask the TMS click.Comparison with existing methodsHere, we showcased two customized noises by comparing them to two standard noises previously used in the TMS literature (i.e., a white noise and a noise generated from the stimulator-specific TMS click only). For each, we quantified the Sound Pressure Level (SPL; measured by a Head and Torso Simulator - HATS) required to mask the TMS click in a population of 20 healthy subjects. Both customized noises were effective at safe (according to OSHA and NIOSH safety guidelines), lower SPLs with respect to standard noises.ConclusionsAt odds with previous methods, TAAC allows creating effective and safe masking noises specifically tailored on each TMS device and subject. The combination of TAAC with tools for the real-time visualization of TEPs can help control the influence of auditory confounds also in non-compliant patients. Finally, TAAC is a highly flexible and open-source tool, so it can be further extended to meet different experimental requirements.
APOK3, a pollen killer antidote in Arabidopsis thaliana
Authors: Simon Matthieu , Durand Stéphanie , Ricou Anthony , Vrielynck Nathalie , Mayjonade Baptiste , Gouzy Jérôme , Boyer Roxane , Roux Fabrice , Camilleri Christine , Budar Françoise 
Published: September 2021

AbstractAccording to the principles of heredity, each parental allele of hybrids equally participates in the progeny. At some loci, however, it happens that one allele is favored to the expense of the other. Gamete killers are genetic systems where one allele (the killer) triggers the death of the gametes carrying the other (killed) allele. They have been found in many organisms, and are of major interest to understand mechanisms of evolution and speciation. Gamete killers are particularly prevalent in plants, where they can compromise crop breeding. Here, we deciphered a pollen killer in Arabidopsis thaliana by exploiting natural variation, de novo genomic sequencing and mutants, and analyzing segregations in crosses. We found that the killer allele carries an antidote gene flanked by two elements mandatory for the killing activity. We identified the gene encoding the antidote, a chimeric protein addressed to mitochondria. This gene appeared in the species by association of domains recruited from other genes, and it recently underwent duplications within a highly variable locus, particularly in the killer genotypes. Exploring the species diversity, we identified sequence polymorphisms correlated with the antidote activity.
The genetic and social contributions to sex differences in lifespan in Drosophila serrata
Authors: Narayan Vikram P. , Wilson Alastair J. , Chenoweth Stephen F. 
Published: September 2021

AbstractSex differences in lifespan remain an intriguing puzzle for evolutionary biologists. A possible explanation for lower lifespan in males is the unconditional expression of recessive deleterious alleles in heterogametic X chromosomes in males (the unguarded X hypothesis). Empirical evidence, however, has yielded controversial results that can be attributed to differences in both genetic and social background. Here, we test the unguarded X hypothesis in Drosophila serrata using a factorial design to quantify the effects of genotype, sex, social environment, and their interactions on phenotypic variation for lifespan. Using an experimental approach, we manipulated two inbred laboratory genotypes and their reciprocal F1s, while controlling for different levels of density and mating status to account for any potential social effects. Our results also show subtle but significant genotype dependent effects for both density and mating, but ultimately find the unguarded X hypothesis insufficient to fully explain sexual dimorphism in D. serrata lifespan.
Comparing Heritability Estimators under Alternative Structures of Linkage Disequilibrium
Authors: Min Alan , Thompson Elizabeth , Basu Saonli 
Published: September 2021

AbstractSNP heritability of a trait is the proportion of its variance explained by the additive effects of the genome-wide single nucleotide polymorphisms (SNPs). The existing approaches to estimate SNP heritability can be broadly classified into two categories. One set of approaches model the SNP effects as fixed effects and the other treats the SNP effects as random effects. These methods make certain assumptions about the dependency among individuals (familial relationship) as well as the dependency among markers (linkage disequilibrium, LD) to provide consistent estimates of SNP heritability as the number of individuals increases. While various approaches have been proposed to account for such dependencies, it remains unclear which estimates reported in the literature are more robust against various model mis-specifications. Here we investigate the impact of different structures of LD and familial relatedness on heritability estimation. We show that the performance of different methods for heritability estimation depends heavily on the structure of the underlying pattern of LD and the degree of relatedness among sampled individuals. However, contrary to the claim in the current literature, we did not find significant differences in the performance of these fixed-SNP-effects and random-SNP-effects approaches. Moreover, we established the equivalence between the two method-of-moments estimators, one from each of these two lines of approaches.
The genome of the endangeredMacadamia janseniidisplays little diversity but represents an important genetic resource for plant breeding
Authors: Sharma Priyanka , Murigneux Valentine , Haimovitz Jasmine , Nock Catherine J. , Tian Wei , Masouleh Ardashir Kharabian , Topp Bruce , Alam Mobashwer , Furtado Agnelo , Henry Robert J. 
Published: September 2021

SummaryMacadamia, a recently domesticated expanding nut crop in the tropical and subtropical regions of the world, is one of the most economically important genera in the diverse and widely adapted Proteaceae family. All four species ofMacadamiaare rare in the wild with the most recently discovered,M. jansenii, being endangered. TheM. janseniigenome has been used as a model for testing sequencing methods using a wide range of long read sequencing techniques. Here we report a chromosome level genome assembly, generated using a combination of Pacific Biosciences sequencing and Hi-C, comprising 14 pseudo-molecules, with a N50 of 58 Mb and a total 758 Mb genome assembly size of which 56% is repetitive. Completeness assessment revealed that the assembly covered 96.9% of the conserved single copy genes. Annotation predicted 31,591 protein coding genes and allowed the characterization of genes encoding biosynthesis of cyanogenic glycosides, fatty acid metabolism and anti-microbial proteins. Re-sequencing of seven other genotypes confirmed low diversity and low heterozygosity within this endangered species. Important morphological characteristics of this species such as small tree size and high kernel recovery suggest thatM. janseniiis an important source of these commercial traits for breeding. As a member of a small group of families that are sister to the core eudicots, this high-quality genome also provides a key resource for evolutionary and comparative genomics studies.
Mechanoaccumulation of non-muscle myosin IIB during mitosis requires its translocation activity
Authors: Wang Chao , Ding Jingjing , Wei Qiaodong , Du Shoukang , Gong Xiaobo , Chew Ting Gang 
Published: September 2021

AbstractNon-muscle myosin II (NMII) is a force-generating mechanosensitive enzyme that responds to mechanical forces exerted on cells. Mechanoresponse of NMIIs confers mechanical adaptability to cells growing and dividing in a physically complex microenvironment. In response to mechanical forces, NMIIs mechanoaccumulate at the cell cortex with applied stress. Much less is known about how NMII mechanoaccumulation is mechanistically regulated. In this study, we subject cells in mitosis to compressive forces and show that mitotic cells promote active RhoA mechanoaccumulation, and via ROCK signaling, activate and stabilize NMIIB at the cell cortex. In line with RhoA in activating the myosin motor activity, we further show that the motor activity driving actin filament translocation, but not just the actin-binding function of NMIIB plays a dominant regulatory role in NMIIB mechanoaccumulation. Thus, the motor activity coordinates structural movement and nucleotide state changes to fine-tune actin-binding affinity optimal for NMIIs to generate and respond to forces.