bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hiplot: a comprehensive and easy-to-use web service boosting publication-ready biomedical data visualization
Authors: Li Jianfeng , Miao Benben , Wang Shixiang , Dong Wei , Xu Houshi , Si Chenchen , Wang Wei , Duan Songqi , Lou Jiacheng , Bao Zhiwei , Zeng Hailuan , Yang Zengzeng , Cheng Wenyan , Zhao Fei , Zeng Jianming , Liu Xue-Song , Wu Renxie , Shen Yang , Chen Zhu , Chen Saijuan , Wang Mingjie ,   Hiplot Consortium
Published: March 2022

AbstractModern web techniques provide an unprecedented opportunity for leveraging complex biomedical data generating in clinical, omics, and mechanism experiments. Currently, the functions for carrying out publication-ready biomedical data visualization represent primary technical hurdles in the state-of-art omics-based web services, whereas the demand for visualization-based interactive data mining is ever-growing. Here, we propose an easy-to-use web service, Hiplot (https://hiplot.com.cn), equipping with comprehensive and interactive biomedical data visualization functions (230+) including basic statistics, multi-omics, regression, clustering, dimensional reduction, meta-analysis, survival analysis, risk modeling, etc. We used the demo and real datasets to demonstrate the usage workflow and the core functions of Hiplot. It permits users to conveniently and interactively complete a few specialized visualization tasks that previously could only be done by senior bioinformatics or biostatistics researchers. A modern web client with efficient user interfaces and interaction methods has been implemented based on the custom components library and the extensible plugin system. The versatile output can also be produced in different environments via using the cross-platform portable command-line interface (CLI) program, Hctl. A switchable view between the editable data table and the file uploader/path selection could facilitate data importing, previewing, and exporting, while the plumber-based response strategy significantly reduced the time costs for generating basic scientific graphics. Diversified layouts, themes/styles, and color palettes in this website allow users to create high-quality and publication-ready graphics. Researchers devoted to both life and data science may benefit from the emerging web service.
Assessing performance and clinical usefulness in prediction models with survival outcomes: practical guidance for Cox proportional hazards models
Authors: McLernon David J , Giardiello Daniele , Van Calster Ben , Wynants Laure , van Geloven Nan , van Smeden Maarten , Therneau Terry , Steyerberg Ewout W 
Published: March 2022

AbstractRisk prediction models need thorough validation to assess their performance. Validation of models for survival outcomes poses challenges due to the censoring of observations and the varying time horizon at which predictions can be made. We aim to give a description of measures to evaluate predictions and the potential improvement in decision making from survival models based on Cox proportional hazards regression.As a motivating case study, we consider the prediction of the composite outcome of recurrence and death (the ‘event’) in breast cancer patients following surgery. We develop a Cox regression model with three predictors as in the Nottingham Prognostic Index in 2982 women (1275 events within 5 years of follow-up) and externally validate this model in 686 women (285 events within 5 years). The improvement in performance was assessed following the addition of circulating progesterone as a prognostic biomarker.The model predictions can be evaluated across the full range of observed follow up times or for the event occurring by a fixed time horizon of interest. We first discuss recommended statistical measures that evaluate model performance in terms of discrimination, calibration, or overall performance. Further, we evaluate the potential clinical utility of the model to support clinical decision making. SAS and R code is provided to illustrate apparent, internal, and external validation, both for the three predictor model and when adding progesterone.We recommend the proposed set of performance measures for transparent reporting of the validity of predictions from survival models.
Founder effect contributes to the unique pattern of SARS-CoV-2 variant B.1.1.519 emergence in Alaska
Authors: Haan Tracie J. , Smith Lisa K. , DeRonde Stephanie , House Elva , Zidek Jacob , Puhak Diana , Redlinger Matthew , Parker Jayme , Barnes Brian M. , Burkhead Jason L. , Knall Cindy , Bortz Eric , Chen Jack , Drown Devin M. 
Published: March 2022

AbstractAlaska is the largest geographic state in the United States with the lowest population density and a mix of urban centers and isolated rural communities. The differences in population dynamics in Alaska from the contiguous United States may have contributed to a unique pattern of emergence and spread of SARS-CoV-2 variants observed in early 2021. Here we examined 2,323 virus genomes from Alaska and 278,635 virus genomes from the contiguous United States collected between the first week of December 2020 through the last week of June 2021. We focused on this timeframe because of the notable emergence and spread of the SARS-CoV-2 lineage B.1.1.519 observed in Alaska. We found that this variant was consistently detected in Alaska from the end of January through June of 2021 with a peak prevalence in April of 77.9% unlike the rest of the United States with a peak prevalence of 4.6%. In Alaska, the earlier emergence of B.1.1.519 coincided with a later peak of Alpha (B.1.1.7) when compared to the rest of the United States. We also observed differences in the composition of lineages and variants over time between the two most populated regions of Alaska. Although there was a modest increase in COVID-19 cases during the peak incidence of B.1.1.519, it is difficult to disentangle how social dynamics conflated changes in COVID-19 during this time. We suggest that the viral characteristics, such as amino acid substitutions in the spike protein, and a founder effect likely contributed to the unique spread of B.1.1.519 in Alaska.
SARS-CoV-2 virus dynamics in recently infected people – data from a household transmission study
Authors: Mellis Alexandra M. , Meece Jennifer K , Halasa Natasha B. , Chappell James D. , McLean Huong Q. , Grijalva Carlos G. , Hanson Kayla E. , Zhu Yuwei , Kim Ahra , Deyoe Jessica , Ivacic Lynn C. , Reed Carrie , Talbot H. Keipp , Rolfes Melissa A. 
Published: March 2022

AbstractWe used daily real-time reverse-transcription polymerase chain reaction (rRT-PCR) results from 67 cases of SARS-CoV-2 infection in a household transmission study to examine the trajectory of cycle threshold (Ct) values, an inverse correlate of viral RNA concentration, from nasal specimens collected between April 2020 and May 2021. Ct values varied over the course of infection, across RT-PCR platforms, and by participant age. Specimens collected from children and adolescents showed higher Ct values and adults aged ≥50 years showed lower Ct values than adults aged 18-49 years. Ct values were lower on days when participants reported experiencing symptoms.
From Delta to Omicron SARS-CoV-2 variant: switch to saliva sampling for higher detection rate
Authors: Cornette Margot , Decaesteker Bieke , Martens Geert Antoine , Vandecandelaere Patricia , Jonckheere Stijn 
Published: March 2022

AbstractBackgroundReal-time polymerase chain reaction (RT-PCR) testing on a nasopharyngeal swab is the current standard for SARS-CoV-2 virus detection. Since collection of this sample type is experienced uncomfortable by patients, saliva- and oropharyngeal swab collections should be considered as alternative specimens.ObjectivesEvaluation of the relative performance of oropharyngeal swab, nasopharyngeal swab and saliva for the RT-PCR based SARS-CoV-2 Delta (B.1.617.2) and Omicron (B.1.1.529) variant detection.Study designNasopharyngeal swab, oropharyngeal swab and saliva were collected from 246 adult patients who presented for SARS-CoV-2 testing at the screening centre in Ypres (Belgium). RT-PCR SARS-CoV-2 detection was performed on all three sample types separately. Variant type was determined for each positive patient using whole genome sequencing or Allplex SARS-CoV-2 variants I and II Assay.Results and conclusionsSaliva is superior compared to nasopharyngeal swab for the detection of the Omicron variant. For the detection of the Delta variant, nasopharyngeal swab and saliva can be considered equivalent specimens. Oropharyngeal swab is the least sensitive sample type and shows little added value when collected in addition to a single nasopharyngeal swab.HighlightsSaliva is the preferred sample type for Omicron variant (B.1.1.529) detectionNasopharyngeal swab and saliva are equivalent for Delta variant (B.1.617.2) detectionOropharyngeal swab is the least preferred sample type for SARS-CoV-2 detection
Updated population-level estimates of child restraint practices among children aged 0-12 years in Australia, ten years after introduction of age-appropriate restraint use legislation
Authors: Brown Julie , Albanese Bianca , Ho Catherine , Elkington Jane , Koppel Sjaan , Charlton Judith L. , Olivier Jake , Keay Lisa , Bilston Lynne E 
Published: March 2022

AbstractObjectiveTo determine child restraint practices approximately 10 years after introduction of legislation requiring correct use of age-appropriate restraints for all children aged up to 7 years.MethodsA stratified cluster sample was constructed to collect observational data from children aged 0-12 years across the Greater Sydney region of NSW. Methods replicated those used in a similar 2008 study. Population weighted estimates for restraint practices were generated, and logistic regression used to examine associations between restraint type, and child age with correct use accounting for the complex sample.ResultsAlmost all children were appropriately restrained (99.3%, 95% CI 98.4-100). However, less than half were correctly restrained (No error = 27.3%, 95% CI 10.8-43.8, No serious error = 43.8%, 95% CI 35.0-52.7). Forany error, the odds of error decreased by 39% per year of age (OR 0.61, 95% 0.46-0.81), and for serious error by 25% per year (OR 0.75 95% CI 0.60-0.93).ConclusionThe findings demonstrate a substantial increase in appropriate child restraint, but no real change in correct use.Implications for Public HealthGiven the negative impact incorrect use has on crash protection, continuing high rates of incorrect use may reduce effectiveness of legislative change on injury reduction.
Maintaining hypoxia environment of subchondral bone alleviates osteoarthritis progression
Authors: Zhang Hao , Wang Lipeng , Cui Jin , Wang Sicheng , Han Yafei , Shao Hongda , Wang Cheng , Hu Yan , Li Xiaoqun , Zhou Qirong , Guo Jiawei , Zhuang Xinchen , Sheng Shihao , Zhang Tao , Zhou Dongyang , Chen Jiao , Wang Fuxiao , Gao Qianmin , Jing Yingying , Chen Xiao , Su Jiacan 
Published: March 2022

AbstractAbnormal subchondral bone remodeling featured by over-activated osteoclastogenesis leads to articular cartilage degeneration and osteoarthritis (OA) progression, but the mechanism is still unclear. In this study, we used lymphocyte cytosolic protein 1 (Lcp1) knock-out mice to suppress subchondral osteoclast formation in mice OA model with anterior cruciate ligament transection (ACLT) and Lcp1-/- mice showed decreased bone remodeling and sensory innervation in subchondral bone accompanied by retarded cartilage degeneration. For mechanisms, in wildtype mice with ACLT the activated osteoclasts in subchondral bone induced type-H vessels and elevated oxygen concentration which ubiquitylated hypoxia-inducible factor 1α (HIF-1α), vital for maintaining chondrocyte homeostasis in articular chondrocytes and led to cartilage degeneration. Deletion of Lcp1 impeded osteoclast-mediated angiogenesis, which maintained the low levels of oxygen partial pressure (pO2) in subchondral bone as well as the whole joint and delayed the OA progression. Stabilization of HIF-1α delayed cartilage degeneration and knockdown of Hif1a abolished the protective effects of Lcp1 knockout. Notably, we identified a novel subgroup of hypertrophic chondrocytes highly associated with OA by single cell sequencing analysis of human articular chondrocytes. Lastly, we showed that Oroxylin A, an Lcp1-encoded protein L-plastin (LPL) inhibitor, could alleviate OA progression. In conclusion, maintaining hypoxic environment in subchondral bone is an attractive strategy for OA treatment.TeaserInhibiting subchondral osteoclastogenesis alleviates OA progression via maintaining joint hypoxia environment.
DUF581-9 (At2g44670; FLZ3) negatively regulates SnRK1 activity by interference with T-loop phosphorylation
Authors: Bortlik Jennifer , Lühle Jost , Alseekh Saleh , Weiste Christoph , Fernie Alisdair R. , Dröge-Laser Wolfgang , Börnke Frederik 
Published: March 2022

SummaryIn plants, SUCROSE NON-FERMENTING RELATED KINASE 1 (SnRK1) is a key energy-sensor that orchestrates large-scale transcriptional reprogramming to maintain cellular homeostasis under energy deficit. SnRK1 activity is under tight negative control, although the exact mechanisms leading to its activation are far from being understood. We show that the Arabidopsis DOMAIN OF UNKNOWN FUNCTION (DUF581) protein DUF581-9/FLZ3 binds to the catalytic SnRK1α subunit KIN10 to inhibit its activation by GRIK-dependent T-loop phosphorylation. Overexpression of DUF581-9 in Arabidopsis dampens SnRK1 signalling and interferes with adaptation to dark-induced starvation. The presence of DUF581-9 significantly reduced SnRK1 activity in protoplasts and in vitro. This was accompanied by a reduction in T175 T-loop phosphorylation and also diminished KIN10 auto-phosphorylation. Furthermore, DUF581-9 reduced binding of the up-stream activating kinase GRIK2 to KIN10, explaining the reduced KIN10 T-loop phosphorylation. Ectopically expressed DUF581-9 protein was rapidly turned over by the proteasome when Arabidopsis plants were subjected to starvation treatment, likely releasing its inhibitory activity on the SnRK1 complex. Taken together, our results support a model in which DUF581-9 negatively regulates SnRK1 activity under energy sufficient conditions. Turnover over of the protein provides a rapid way for SnRK1 activation under energy deficit without the need of de-novo protein synthesis.
Establishment of an efficient transformation and CRISPR/Cas9-mediated gene editing system in Chinese local planting cassava (Manihot esculenta Crantz) cultivar SC8
Authors: Wang Yajie , Lu Xiaohua , Zhen Xinghou , Yang Hui , Che Yannian , Hou Jingyi , Li Ruimei , Liu Jiao , Geng Mengting , Hu Xinwen , Yao Yuan , Guo Jianchun 
Published: March 2022

AbstractCassava starch is a widely used raw material for industrial production. South Chinese cassava cultivar 8 (Manihot esculenta Crantz cv. SC8) is one of the main locally planted cultivars. In this study, an efficient transformation system for cassava SC8 mediated with Agrobacterium strain LBA4404 was presented for the first time, in which the factors of Agrobacterium strain cell infection (density OD600 = 0.65), 250 µM acetosyringone induction, and agro-cultivation with wet friable embryogenic callus (FEC) for 3 days in dark conditions were found to increase the transformation efficiency through the binary vector pCAMBIA1304 harboring GUS- and GFP-fused genes driven by the CaMV35S promoter. Based on the optimized transformation protocol, approximately 120-140 independent transgenic lines per mL settled FEC cell volume (SCV) by gene transformation in approximately five months, and 45.83% homozygous mono-allelic mutations of the MePDS gene with a YAO promoter-driven CRISPR/Cas9 system were generated. This study will open a more functional avenue for the genetic improvement of cassava SC8.
Maternal H3K36 and H3K27 HMTs protect germline immortality via regulation of the transcription factor LIN-15B
Authors: Cockrum Chad , Strome Susan 
Published: March 2022

ABSTRACTMaternally synthesized products play critical roles in development of offspring. A premier example is the C. elegans H3K36 methyltransferase MES-4, which is essential for germline survival and development in offspring. How maternal MES-4 protects germline immortality is not well understood, but its role in H3K36 methylation hinted that it may regulate gene expression in Primordial Germ Cells (PGCs). We tested this hypothesis by profiling transcripts from single pairs of PGCs dissected from wild-type and mes-4 mutant (lacking maternal and zygotic MES-4) newly hatched larvae. We found that mes-4 PGCs display normal turn-on of most germline genes and normal repression of somatic genes, but dramatically up-regulate hundreds of genes on the X chromosome. We demonstrated that X mis-expression is the cause of germline death by generating and analyzing mes-4 mutants that inherited different endowments of X chromosome(s). Intriguingly, removal of the THAP transcription factor LIN-15B from mes-4 mutants reduced X mis-expression and prevented germline death. lin-15B is X-linked and mis-expressed in mes-4 PGCs, identifying it as a critical target for MES-4 repression. The above findings extend to the H3K27 methyltransferase MES-2/3/6, the C. elegans version of Polycomb Repressive Complex 2. We propose that maternal MES-4 and PRC2 cooperate to protect germline survival by preventing synthesis of germline-toxic products encoded by genes on the X chromosome, including the key transcription factor LIN-15B.
Structure and functional mapping of the KRAB-KAP1 repressor complex
Authors: Stoll Guido A. , Pandiloski Ninoslav , Douse Christopher H. , Modis Yorgo 
Published: March 2022

AbstractTransposable elements (TEs) are a genetic reservoir from which new genes and regulatory elements can emerge. Expression of TEs can be pathogenic, however, and is tightly regulated. KRAB domain-containing zinc finger proteins (KRAB-ZFPs) recruit co-repressor KRAB-associated protein 1 (KAP1/TRIM28) to regulate many TEs but how KRAB-ZFPs and KAP1 interact remains unclear. Here, we report the crystal structure of the KAP1 tripartite motif (TRIM) in complex with the KRAB domain from a human KRAB-ZFP, ZNF93. Structure-guided mutations in the KAP1-KRAB binding interface abolished repressive activity in an epigenetic TE silencing assay. Deposition of H3K9me3 over thousands of loci is lost genome-wide in cells expressing a KAP1 variant with mutations that abolish KRAB binding. Our work identifies and functionally validates the KRAB-KAP1 molecular interface, which forms the nexus of a transcriptional control axis vital to vertebrates and underpins programmable gene repression by CRISPRi.
The faecal microbiome of the wild European badger Meles meles; a comparison against other wild omnivorous mammals from across the globe
Authors: Scott-Baumann James , Friedersdorff Jessica C A , Villarreal-Ramos Bernardo , King Jonathan , Hopkins Beverley , Pizzey Richard , Rooke David , Hewinson Glyn , Mur Luis A. J. 
Published: March 2022

AbstractHere we investigate the faecal microbiome of wild European badgers Meles meles using samples collected at post-mortem as part of the All Wales Badger Found Dead study based on sequencing the V3-V4 region of the 16S rRNA gene. This is the first published characterisation of the badger microbiome. We initially undertook a sex-matched age comparison between the adult and cub microbiomes. Analysis used the QIIME 2 pipeline utilising DADA2 and the Silva database for taxonomy assignment. Fusobacteria appeared to be more abundant in the microbiomes of the cubs than the adults although no significant difference was seen in alpha or beta diversity between the adult and cub badger microbiomes. Comparisons were also made against other wild, omnivorous, mammals’ faecal microbiomes using publicly available data. Significant differences were seen in both alpha and beta diversity between the microbiomes from different species. As a wildlife species of interest to the disease bovine tuberculosis, knowledge of the faecal microbiome could assist in identification of infected badgers. Our work here suggests that if comparisons were made between the faeces of bTB infected and non-infected badgers, its possible age may not have a significant impact on the microbiome.
Distinguishing fine structure and summary representation of sound textures from neural activity
Authors: Berto Martina , Ricciardi Emiliano , Pietrini Pietro , Weisz Nathan , Bottari Davide 
Published: March 2022

ABSTRACTThe auditory system relies on both local and summary representations; acoustic local features exceeding system constraints are compacted into a set of summary statistics. Such compression is pivotal for sound-object recognition. Here, we assessed whether computations subtending local and statistical representations of sounds could be distinguished at the neural level. A computational auditory model was employed to extract auditory statistics from natural sound textures (i.e., fire, rain) and to generate synthetic exemplars where local and statistical properties were controlled. Twenty-four human participants were passively exposed to auditory streams while the EEG was recorded. Each stream could consist of short, medium, or long sounds to vary the amount of acoustic information. Short and long sounds were expected to engage local or summary statistics representations, respectively. Data revealed a clear dissociation. Compared to summary-based ones, auditory-evoked responses based on local information were selectively greater in magnitude in short sounds. Opposite patterns emerged for longer sounds. Neural oscillations revealed that local features and summary statistics rely on neural activity occurring at different temporal scales, faster (beta) or slower (theta-alpha). These dissociations emerged automatically without explicit engagement in a discrimination task. Overall, this study demonstrates that the auditory system developed distinct coding mechanisms to discriminate changes in the acoustic environment based on fine structure and summary representations.SIGNIFICANCE STATEMENTPrior to this study, it was unknown whether we could measure auditory discrimination based on local temporal features or spectrotemporal statistics properties of sounds from brain responses. Results show that the two auditory modes of sound discrimination (local and summary statistics) are automatically attuned to the temporal resolution (high or low) at which a change has occurred. In line with the temporal resolutions of auditory statistics, faster or slower neural oscillations (temporal scales) code sound changes based on local or summary representations. These findings expand our knowledge of some fundamental mechanisms underlying the function of the auditory system.
High-resolution secretory timeline from vesicle formation at the Golgi to fusion at the plasma membrane in S. cerevisiae
Authors: Gingras Robert M. , Sulpizio Abigail M. , Park Joelle , Bretscher Anthony 
Published: March 2022

AbstractMost of the components in the yeast secretory pathway have been studied, yet a high resolution temporal timeline of their participation is lacking. Here we define the order of acquisition, lifetime, and release of critical components involved in late secretion from the Golgi to the plasma membrane. Of particular interest is the timing of the many reported effectors of the secretory vesicle Rab protein Sec4, including the myosin-V Myo2, the exocyst complex, the lgl homolog Sro7, and the small yeast-specific protein Mso1. At the trans-Golgi network (TGN) Sec4’s GEF, Sec2, is recruited to Ypt31-positive compartments, quickly followed by Sec4 and Myo2 and vesicle formation. While transported to the bud tip, the entire exocyst complex, including Sec3, is assembled on to the vesicle. Before fusion, vesicles tether for 5s, during which the vesicle retains the exocyst complex and stimulates lateral recruitment of Rho3 on the plasma membrane. Sec2 and Myo2 are rapidly lost, followed by recruitment of cytosolic Sro7, and finally the SM protein Sec1, which appears for just 2 seconds prior to fusion. Perturbation experiments reveal an ordered and robust series of events during tethering that provide insights into the function of Sec4 and effector exchange.