bluuebunny/crossref_metadata_2025_split huggingface dataset:
Studying Clinical, Biologic and Echocardiography Criteria to Predict a Resistant Kawasaki Disease in Children
Authors: Robert Anne-Cécile , Parmentier Anne-Laure , Schulze Olivier , Verney Cindy , Huet Frédéric , Thiriez Gérard , Anxionnat Raphaël 
Published: July 2021

Background:
Resistant Kawasaki disease (KD) represents 10%–15% of KD patients and increases risk of coronary artery abnormalities (CAAs). Different scores exist to predict resistant KD but only in Japanese population, although a French team has recently proposed a new scoring system. The principal objective of this study is to establish criteria to predict resistant KD in our representative French population. The second objective is an attempt to develop a predictive score of resistant KD.

Methods:
We conducted a retrospective multicenter study including 2 universities and five secondary hospitals in Eastern France. Patients were included over a period from January 1, 2010 through December 31, 2019. Diagnosis of KD was recorded to the European Single Hub and Access point for pediatric Rheumatology in Europe (SHARE) initiative criteria.

Results:
Two hundred two eligible patients had KD and 194 patients were analyzed: 160 sensitive KD and 34 (17.5%) resistant KD. In univariate model, serum sodium <133 mmol/L (odds ratio [OR] 2.97 [1.40–6.45]), hemoglobin level <110 g/L (OR 3.17 [1.46–7.34]), neutrophils >80% (OR 2.36 [1.03–5.25]), C reactive protein level >150 mg/L (OR 4.47 [2.07–10.19]), CAA (OR 3.85 [1.67–8.79]) or myocarditis (OR 6.98 [1.47–36.95]) at the diagnosis were statistically significant, but only serum sodium was an independent factor of resistant KD.

Conclusion:
This study shows an association between resistant KD and biologic and echocardiography criteria, but only serum sodium is an independent predictive factor. A score to predict resistant KD could not yet be established.
Vitamin A in Children Hospitalized for Measles in a High-income Country
Authors: Lo Vecchio Andrea , Cambriglia Maria Donata , Bruzzese Dario , Guarino Alfredo 
Published: July 2021

Background:
Worldwide medical authorities recommend vitamin A supplementation for severe measles requiring hospitalization; however, evidence supporting its use in high-income countries is lacking. A nationwide vitamin A shortage reported in concomitance with a recent measles outbreak in Italy provided an opportunity to test the effectiveness of vitamin A in a high-income setting, approximating an unbiased allocation.

Methods:
We conducted a prospective controlled cohort study involving children admitted for measles to a tertiary-care hospital in Southern Italy. The primary outcome was the duration of fever. Secondary outcomes included the length of hospitalization, rate of complications, need for antibiotic treatment and body temperature.

Results:
A total of 108 inpatient children (36% female, median age 16.3 months) were enrolled; 36 received 2 doses of oil-based vitamin A according to age, and 72 matched controls received standard care. There were no significant differences between the study groups in the duration of fever (7.03 ± 2.67 vs. 6.82 ± 3.27, P = 0.72), length of hospitalization (median, 5.0 vs. 5.0 days, P = 0.50), maximum body temperature (median, 39°C in both groups, P = 0.23), rate of organ (69.4% vs. 63.9%, P = 0.72) and hematologic complications (41.7% vs. 59.7%, P = 0.12), or need for antibiotic treatment (66.7% vs. 61.1%, P = 0.72). Overall, vitamin A supplementation did not reduce the risk of any complications (relative risk, 1.33; 95% confidence intervals: 0.59–2.96).

Conclusion:
Vitamin A does not change the clinical course of measles infection or the rate of complications in children hospitalized in a high-income country.

Study registration number:
EU PAS 31805.
Assessment of Disease-related Knowledge Among Children With Inflammatory Bowel Disease and their Family Using IBD-KID2: Evaluating Tool Generalizability
Authors: Vernon-Roberts Angharad , Lopez Robert N. , Lewindon Peter , Lemberg Daniel A. , Bowcock Nerissa L. , Alex George , Otley Anthony , Jacobson Kevan , Roberts Amin J. , Evans Helen M. , Gearry Richard B. , Day Andrew S. 
Published: July 2021

Background:
Children with inflammatory bowel disease (IBD) and their families benefit from improved knowledge of their disease and treatment. Knowledge levels of individual family members are infrequently studied but may identify where education is best directed. We aimed to assess disease-specific knowledge among children with IBD, parents, and siblings, using a validated assessment tool (IBD-KID2), and to establish generalizability of IBD-KID2.

Methods:
Children with IBD and family members were recruited from tertiary IBD clinics in New Zealand, Australia, and Canada. All participants completed IBD-KID2 online at baseline, and the children with IBD again after 2 weeks to assess reliability.

Results:
Participants included 130 children with IBD, 118 mothers, 55 fathers, and 37 siblings. Children with IBD had a mean score of 9.1 (SD 2.9) (maximum 15 points), significantly lower than parents (P < 0.005) and higher than siblings (P < 0.005). Scores of children with IBD were positively associated with current age (P < 0.005), age at diagnosis (P = 0.04) and fathers education level (P = 0.02). Significant score correlations were seen between children with IBD and their mother (P < 0.005) but not father. Sibling scores were not correlated with either parent. Test–retest reliability was high. The cohorts from each country were comparable, and no difference in group scores was seen between countries.

Conclusion:
IBD-KID2 is a generalizable and reliable tool for the assessment of disease and treatment knowledge for children with IBD and their families. Score correlations between parents and children with IBD suggest transfer of knowledge, but sibling knowledge is low and targeted education may be beneficial.
Evolution of master sex determiners: TGF-β signalling pathways at regulatory crossroads
Authors: Pan Qiaowei , Kay Tomas , Depincé Alexandra , Adolfi Mateus , Schartl Manfred , Guiguen Yann , Herpin Amaury 
Published: July 2021

To date, more than 20 different vertebrate master sex-determining genes have been identified on different sex chromosomes of mammals, birds, frogs and fish. Interestingly, six of these genes are transcription factors (Dmrt1- orSox3- related) and 13 others belong to the TGF-β signalling pathway (Amh,Amhr2,Bmpr1b,GsdfandGdf6). This pattern suggests that only a limited group of factors/signalling pathways are prone to become top regulators again and again. Although being clearly a subordinate member of the sex-regulatory network in mammals, the TGF-β signalling pathway made it to the top recurrently and independently. Facing this rolling wave of TGF-β signalling pathways, this review will decipher how the TGF-β signalling pathways cope with the canonical sex gene regulatory network and challenge the current evolutionary concepts accounting for the diversity of sex-determining mechanisms.This article is part of the theme issue ‘Challenging the paradigm in sex chromosome evolution: empirical and theoretical insights with a focus on vertebrates (Part I)’.
Viscoelastic Parameterization of Human Skin Cells to Characterize Material Behavior at Multiple Timescales
Authors: Parvini Cameron H. , Cartagena-Rivera Alexander X. , Solares Santiago D. 
Published: July 2021

AbstractCountless biophysical studies have sought distinct markers in the cellular mechanical response that could be linked to morphogenesis, homeostasis, and disease. Here, a novel iterative-fitting methodology is used to investigate the viscoelastic behavior at multiple relaxation times of human skin cells under physiologically relevant conditions. Past investigations often involved parameterizing linear elastic relationships and assuming purely Hertzian contact mechanics. However, linear elastic treatment fails to capture and properly account for the rich temporal information available in datasets. We demonstrate the performance superiority of the proposed iterative viscoelastic characterization method over standard open-search approaches. Our viscoelastic measurements revealed that 2D adherent metastatic melanoma cells exhibit reduced elasticity compared to normal counterparts—melanocytes and fibroblasts, whereas are significantly less viscous than only fibroblasts over timescales spanning three orders of magnitude. Interestingly, melanocytes are stiffer than melanoma cells, while being the less viscous cells measured. The measured loss angle indicates clear differential viscoelastic responses across multiple timescales between the measured cells. We propose the use of viscoelastic properties at multiple timescales as a mechanical biomarker of diseases. Altogether, this method provides new insight into the complex viscoelastic behavior of metastatic melanoma cells relevant to better understanding cancer metastasis aggression.
A patient-driven clinicogenomic partnership through the Metastatic Prostate Cancer Project
Authors: Crowdis Jett , Balch Sara , Sterlin Lauren , Thomas Beena S. , Camp Sabrina Y. , Dunphy Michael , Anastasio Elana , Shah Shahrayz , Damon Alyssa L. , Ramos Rafael , Sosa Delia M. , Small Ilan K. , Tomson Brett , Nguyen Colleen M. , McGillicuddy Mary , Chastain Parker S. , He Meng Xiao , Cheung Alexander T.M. , Wankowicz Stephanie , Tewari Alok K. , Kim Dewey , AlDubayan Saud H. , Dowdye Ayanah , Zola Benjamin , Nowak Joel , Manarite Jan , Gunn Major Idola Henry , Olson Bryce , Lander Eric S. , Painter Corrie A. , Wagle Nikhil , Van Allen Eliezer M. 
Published: July 2021

ABSTRACTMolecular profiling studies have enabled numerous discoveries for metastatic prostate cancer (MPC), but they have mostly occurred in academic medical institutions focused on select patient populations. We developed the Metastatic Prostate Cancer Project (MPCproject, mpcproject.org), a patient-partnered initiative to empower MPC patients living anywhere in the U.S. and Canada to participate in molecular research and contribute directly to translational discovery. Here we present clinicogenomic results from our partnership with the first 706 MPCproject participants. We found that a patient-centered and remote research strategy enhanced engagement with patients in rural and medically underserved areas. Furthermore, patient-reported data achieved 90% consistency with abstracted health records for therapies and provided a mechanism for patient-partners to share information about their cancer experience not documented in medical records. Among the molecular profiling data from 333 patient-partners (n = 573 samples), whole exome sequencing of 63 tumor samples obtained from hospitals across the U.S. and Canada and 19 plasma cell-free DNA (cfDNA) samples from blood donated remotely recapitulated known findings in MPC and enabled longitudinal study of prostate cancer evolution. Inexpensive ultra-low coverage whole genome sequencing of 318 cfDNA samples from donated blood revealed clinically relevant genomic changes like AR amplification, even in the context of low tumor burden. Collectively, this study illustrates the power of a longitudinal partnership with patients to generate a more representative clinical and molecular understanding of MPC.NoteTo assist our patient-partners and the wider MPC community interpret the results of this study, we have included a glossary of terms in the Supplementary Materials.
Protein-Protein Interaction Site Prediction Based on Attention Mechanism and Convolutional Neural Networks
Authors: Lu Shuai , Li Yuguang , Ma Qiang , Nan Xiaofei , Zhang Shoutao 
Published: July 2021

AbstractProteins usually perform their cellular functions by interacting with other proteins. Accurate identification of protein-protein interaction sites (PPIs) from sequence is import for designing new drugs and developing novel therapeutics. A lot of computational models for PPIs prediction have been developed because experimental methods are slow and expensive. Most models employ a sliding window approach in which local neighbors are concatenated to present a target residue. However, those neighbors are not been distinguished by pairwise information between a neighbor and the target. In this study, we propose a novel PPIs prediction model AttCNNPPISP, which combines attention mechanism and convolutional neural networks (CNNs). The attention mechanism dynamically captures the pairwise correlation of each neighbor-target pair within a sliding window, and therefore makes a better understanding of the local environment of target residue. And then, CNNs take the local representation as input to make prediction. Experiments are employed on several public benchmark datasets. Compared with the state-of-the-art models, AttCNNPPISP significantly improves the prediction performance. Also, the experimental results demonstrate that the attention mechanism is effective in terms of constructing comprehensive context information of target residue.
Remodeling of organelles and microtubules during spermiogenesis in the liverwort Marchantia polymorpha
Authors: Minamino Naoki , Norizuki Takuya , Mano Shoji , Ebine Kazuo , Ueda Takashi 
Published: July 2021

AbstractGametogenesis is an essential biological event for sexual reproduction in various organisms. Bryophytes and some other plants employ motile sperms (spermatozoids) as male gametes, which self-locomote to the egg cells to accomplish fertilization. Spermatozoids of bryophytes harbor distinctive morphological characteristics, including the cell body with a helical slender shape and two motile flagella at the anterior edge. During transformation from a spermatid to spermatozoid (spermiogenesis), the shape and cellular contents of spermatids are dynamically reorganized. However, how each organelle is reorganized during plant spermiogenesis remains obscure. In this study, we classified the developmental processes during spermiogenesis in the liverwort Marchantia polymorpha according to cellular and nuclear shapes and flagella development. We then examined the remodeling of microtubules and reorganization of endomembrane organelles during spermiogenesis. The results indicate that the state of post-translational modification of tubulin is dynamically changed during the formation of the flagella and spline, and the plasma membrane and endomembrane organelles are drastically reorganized in a precisely regulated manner during spermiogenesis. These findings are expected to provide useful indexes to classify developmental and subcellular processes of spermiogenesis in bryophytes.Summary statementWe classified developmental processes of spermatozoids into 1 + 5 stages and characterized remodeling of organelles and microtubules during spermiogenesis in the liverwort Marchantia polymorpha.
Ancient Darwinian replicators nested within eubacterial genomes
Authors: Bertels Frederic , Rainey Paul B. 
Published: July 2021

AbstractIntegrative mobile genetic elements (MGEs), such as transposons and insertion sequences, propagate within bacterial genomes, but persistence times in individual lineages are short. For long-term survival, MGEs must continuously invade new hosts by horizontal transfer. Theoretically, MGEs that persist for millions of years in single lineages, and are thus subject to vertical inheritance, should not exist. Here we draw attention to an exception — a class of MGE termed REPIN. REPINs are non-autonomous MGEs whose duplication depends on non-jumping RAYT transposases. Comparisons of REPINs and typical MGEs show that replication rates of REPINs are orders of magnitude lower, REPIN population size fluctuations correlate with changes in available genome space, REPIN conservation depends on RAYT function, and REPIN diversity accumulates within host lineages. These data lead to the hypothesis that REPINs form enduring, beneficial associations with eubacterial chromosomes. Given replicative nesting, our hypothesis predicts conflicts arising from the diverging effects of selection acting simultaneously on REPINs and host genomes. Evidence in support comes from patterns of REPIN abundance and diversity in two distantly related bacterial species. Together this bolsters the conclusion that REPINs are the genetic counterpart of mutualistic endosymbiotic bacteria.
The functional form of specialized predation dramatically affects whether Janzen-Connell effects can prevent competitive exclusion
Authors: Smith Daniel J. B. 
Published: July 2021

AbstractJanzen Connell Effects (JCEs), specialized predation of seeds and seedlings near conspecific trees, are hypothesized to promote high species richness. While past modeling studies show JCEs can maintain higher diversity than a neutral community, recent theoretical work indicates JCEs may weakly inhibit competitive exclusion when species exhibit interspecific fitness variation. However, recent models make somewhat restrictive assumptions about the functional form of specialized predation – that JCEs occur at a fixed rate when seeds/seedlings are within a fixed distance of a conspecific tree. Using a theoretical model, I show that the functional form of JCEs largely impacts their ability to promote coexistence. If specialized predation pressure increases additively with adult tree density and decays exponentially with distance, JCEs maintain considerably higher diversity than predicted by recent models. Parameterizing the model with values from a Panamanian tree community indicates JCEs can maintain high diversity in communities exhibiting high interspecific fitness variation.
Bacteria are everywhere, even in your COI marker gene data!
Authors: Zafeiropoulos Haris , Gargan Laura , Hintikka Sanni , Pavloudi Christina , Carlsson Jens 
Published: July 2021

AbstractThe mitochondrial cytochrome C oxidase subunit I gene (COI) is commonly used in eDNA metabarcoding studies, especially for assessing metazoan diversity. Yet, a great number of COI operational taxonomic units or/and amplicon sequence variants are retrieved from such studies and referred to as “dark matter”, and do not get a taxonomic assignment with a reference sequence. For a thorough investigation of this dark matter, we have developed the Dark mAtteR iNvestigator (DARN) software tool. A reference COI-oriented phylogenetic tree was built from 1,240 consensus sequences covering all the three domains of life, with more than 80% of those representing eukaryotic taxa. With respect to eukaryotes, consensus sequences at the family level were constructed from 183,330 retrieved from the Midori reference 2 database. Similarly, sequences from 559 bacterial genera and 41 archaeal were retrieved from the BOLD database. DARN makes use of the phylogenetic tree to investigate and quantify pre-processed sequences of amplicon samples to provide both a tabular and a graphical overview of phylogenetic assignments. To evaluate DARN, both environmental and bulk metabarcoding samples from different aquatic environments using various primer sets were analysed. We demonstrate that a large proportion of non-target prokaryotic organisms such as bacteria and archaea are also amplified in eDNA samples and we suggest bacterial COI sequences to be included in the reference databases used for the taxonomy assignment to allow for further analyses of dark matter. DARN source code is available on GitHub at https://github.com/hariszaf/darn and you may find it as a Docker at https://hub.docker.com/r/hariszaf/darn.Author summaryDARN is a software approach aiming to provide further insight in the COI amplicon data coming from environmental samples. Building a COI-oriented reference phylogeny tree is a challenging task especially considering the small number of microbial curated COI sequences deposited in reference databases; e.g ~4,000 bacterial and ~150 archaeal in BOLD. Apparently, as more and more such sequences are collated, the DARN approach improves. To provide a more interactive way of communicating both our approach and our results, we strongly suggest the reader to visit this Google Collab notebook where all steps are described step by step and also this GitHub page where our results are demonstrated. Our approach corroborates the known presence of microbial sequences in COI environmental sequencing samples and highlights the need for curated bacterial and archaeal COI sequences and their integration into reference databases (i.e. Midori, BOLD, etc). We argue that DARN will benefit researchers as a quality control tool for their sequenced samples in terms of distinguishing eukaryotic from non-eukaryotic OTUs/ASVs, but also in terms of understanding the unknown unknowns.
A statistical framework for differential pseudotime analysis with multiple single-cell RNA-seq samples
Authors: Hou Wenpin , Ji Zhicheng , Chen Zeyu , Wherry E. John , Hicks Stephanie C. , Ji Hongkai 
Published: July 2021

ABSTRACTPseudotime analysis with single-cell RNA-sequencing (scRNA-seq) data has been widely used to study dynamic gene regulatory programs along continuous biological processes. While many computational methods have been developed to infer the pseudo-temporal trajectories of cells within a biological sample, methods that compare pseudo-temporal patterns with multiple samples (or replicates) across different experimental conditions are lacking. Lamian is a comprehensive and statistically-rigorous computational framework for differential multi-sample pseudotime analysis. It can be used to identify changes in a biological process associated with sample covariates, such as different biological conditions, and also to detect changes in gene expression, cell density, and topology of a pseudotemporal trajectory. Unlike existing methods that ignore sample variability, Lamian draws statistical inference after accounting for cross-sample variability and hence substantially reduces sample-specific false discoveries that are not generalizable to new samples. Using both simulations and real scRNA-seq data, including an analysis of differential immune response programs between COVID-19 patients with different disease severity levels, we demonstrate the advantages of Lamian in decoding cellular gene expression programs in continuous biological processes.
High rate of mutational events in SARS-CoV-2 genomes across Brazilian geographical regions, February 2020 to June 2021
Authors: Souza U.J.B. , Santos R.N. , Campos F.S. , Lourenço K.L. , Fonseca F.G. , Spilki F.R. ,   Corona-ômica.BR/MCTI Network
Published: July 2021

AbstractBrazil has been considered as one of the emerging epicenters of the coronavirus pandemic in 2021, experiencing over 3,000 daily deaths caused by the virus at the peak of the second wave. In total, the country has more than 19.2 million confirmed cases of Covid-19, including over 533,509 fatalities. A set of emerging variants arose in the country, some of them posing new challenges for COVID-19 control. The goal of this study was to describe mutational events across samples from Brazilian SARS-CoV-2 sequences openly publicly obtainable on the Global Initiative on Sharing Avian Influenza Data-EpiCoV (GISAID-EpiCoV) platform and generate an index of new mutant by each genome. A total of 16,953 SARS-CoV-2 genomes were obtained and are not proportionally representative of the five Brazilian geographical regions. A comparative sequence analysis was conducted to identify common mutations located at 42 positions of the genome (38 were in coding regions whereas two in 5’ and two in 3’ UTR). Moreover, 11 were synonymous and 27 missense variants, and more than 44.4% were located in the spike gene. Across the total of single nucleotide variations (SNVs) identified, 32 were found in genomes obtained from all five Brazilian regions. While a high genomic diversity is reported in Europe given the large number of sequenced genomes, Africa is emerging as a hotspot for new variants. In South America, Brazil and Chile, rates are similar to those found in South Africa and India, giving enough space to generate new viral mutations. Genomic surveillance is the central key to identifying the emerging variants of SARS-CoV-2 in Brazil and has shown that the country is one of the “hotspots” in the generation of new variants.