bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prevalence and Outcome of Cardio-Embolic Stroke Patients Admitted at Referral Neurology Hospital in Bangladesh
Authors: Been Sayeed S K Jakaria , Haque A K M Mahmudul , Moniruzzaman Md. , Mahmud Reaz , Yusuf Md. Abdullah , Das Subir Chandra , Rashid Mohammad Bazlur , Rahman Sabrina , Nayeem Abu , Kabir A K M Humayon , Haque Chowdhury M S Jahirul , Rahman Md. Mujibur 
Published: February 2022

AbstractBackgroundStroke is the second leading cause of mortality worldwide; where the majority of stroke is ischemic. Among ischemic stroke, cardio-embolic has both higher severity and mortality.ObjectiveTo find out clinical outcomes and determine predictors of mortality related to cardio-embolic stroke.MethodologyThis prospective cohort study was conducted among patients of acute ischemic stroke of cardiac origin admitted at the National Institute of Neurosciences and Hospital, Bangladesh from 1st October 2020 to 30 September, 2021. Patients were kept under follow-up to 90 days from discharge.ResultsA total of 689 ischemic stroke patients were screened, 156 had confirmed Cardio-embolic stroke. So, the frequency of cardio-embolic stroke was 22.64%. Male to female ratio was 1.3:1, mean age of 63 years. Hypertension 119 (76.3%), atrial fibrillation 107 (68.6%), and IHD 40 (25.6%) were most common comorbidities. Interestingly, we found only 23 (14.7%) patients with chronic rheumatic heart diseases. NIH Stroke scale score (median, IQR) during admission was 13 [7-19]. Overall mortality was 47 (29.9%), among them 30 (19.2%) died within 48 hours of hospital admission while 17 (10.9%) within 90 days of hospital discharge. Modified Rankin score at 90 days was 2 [min 0, max 5] those who survived. Cumulative incidence of recurrent stroke was 9 (7.1%) and incidence of anticoagulant induced hemorrhage were 5 (3.2%) among them. Risk factors associated with mortality (odds ratio, [95% CI], p value) were acute myocardial infarction (1.6 [1.14 – 2.52], 0.04), raised Troponin (1.89 [1.16-2.99], 0.01), reduced ejection fraction (3.38 [2.17-5.27], <0.001), hypotension (3.12 [2.07 – 4.68], < 0.001), chronic kidney disease (1.82 [1.06 - 3.10], 0.04), raised Creatinine (2.41 [1.52 - 3.84], 0.01), raised blood sugar (1.82 [1.14 - 2.89], 0.02), severe stroke (9.45 [3.57 – 25.03], <0.001), large infarct (53.67 [7.59 - 379.47], < 0.001), hemorrhagic transformation (4.43 [2.89 – 6.84], < 0.001) and aspiration pneumonia (1.9 [1.28-2.39], 0.01).ConclusionOverall frequency, severity, functional disability, and mortality in cardio-embolic stroke are higher. Acute myocardial infarction, severe stroke, presence of hyperglycemia, hypotension, renal impairment, low ejection fraction, large infarct, hemorrhagic transformations, and aspiration pneumonia are both clinically and statistically significantly associated with mortality in cardio-embolic stroke.
Genetic influences on neurodevelopmental disorders and their overlap with co-occurring conditions in childhood and adolescence: A meta-analysis
Authors: Gidziela Agnieszka , Ahmadzadeh Yasmin I. , Michelini Giorgia , Allegrini Andrea G. , Agnew-Blais Jessica , Lau Lok Yan , Duret Megan , Procopio Francesca , Daly Emily , Ronald Angelica , Rimfeld Kaili , Malanchini Margherita 
Published: February 2022

AbstractA systematic understanding of the aetiology of neurodevelopmental disorders (NDDs), their co-occurrence, and co-occurrence with other conditions during childhood and adolescence remains incomplete. This meta-analysis bridges gaps in our knowledge. First, we meta-analysed the literature on the relative contribution of genetic and environmental factors to NDDs. Second, we considered the literature on the overlap between different NDD categories. Lastly, we synthesized the literature on the co-occurrence between NDDs and disruptive, impulse control and conduct disorders (DICCs). We performed multilevel, random-effects meta-analyses on 296 independent studies, including over 4 million children and adolescents. We found all NDDs to be substantially heritable (family-based heritability (h2) = 0.66; SNP h2 = 0.19). Meta-analytic genetic correlations between NDDs, and between NDDs and DICCs were moderate to strong. However, given the paucity of available studies covering the co-occurrence of NDDs and DICCs, these could only be estimated for a few disorders. While our work provides direct evidence to inform and potentially guide clinical and educational diagnostic procedures and practice, it also highlights the imbalance in the research effort that has characterized developmental genetics research.
The impact of theta-burst stimulation on cortical GABA and glutamate in treatment-resistant depression: A surface-based MRSI analysis approach
Authors: Spurny-Dworak B , Godbersen GM , Reed MB , Unterholzner J , Vanicek T , Baldinger-Melich P , Hahn A , Kranz GS , Bogner W , Lanzenberger R , Kasper S 
Published: February 2022

AbstractBackgroundTheta burst stimulation (TBS) belongs to one of the biological antidepressant treatment options. When applied bilaterally, excitatory intermittent TBS (iTBS) is commonly targeted to the left and inhibitory continuous TBS (cTBS) to the right dorsolateral prefrontal cortex. TBS was shown to influence neurotransmitter systems, while iTBS is thought to interfere with glutamatergic circuits and cTBS to mediate GABAergic neurotransmission.ObjectivesWe aimed to expand insights in the therapeutic effects of TBS on the GABAergic and glutamatergic system utilizing 3D-multivxovel magnetic resonance spectroscopy imaging (MRSI) in combination with a novel surface-based MRSI analysis approach to investigate changes of cortical neurotransmitter levels in patients with treatment resistant depression (TRD).MethodsTwelve TRD patients (5 female, mean age±SD=35±11 years) completed paired MRSI measurements, using a GABA-edited 3D-multivoxel MEGA-LASER sequence, before and after three weeks of bilateral TBS treatment. Changes in cortical distributions of GABA+/tNAA (GABA+macromolecules relative to total N-acetylaspartate) and Glx/tNAA (Glx=mixed signal of glutamate and glutamine), were investigated in a surface-based region-of-interest (ROI) analysis approach.ResultsANCOVAs revealed a significant increase in Glx/tNAA ratios in the left caudal middle frontal area (pcorr.=0.046, F=13.292), an area targeted by iTBS treatment. Whereas, contralateral treatment with cTBS evoked no alterations in glutamate or GABA concentrations.ConclusionThis study demonstrates surface-based adaptions in the stimulation area to the glutamate metabolism after excitatory iTBS but not after cTBS, using a novel surface-based analysis of 3D-MRSI data. The reported impact of facilitatory iTBS on glutamatergic neurotransmission provides further insight into the neurobiological effects of TBS in TRD.
Systematic review and meta-analysis to estimate the burden of fatal and non-fatal overdose among people who inject drugs
Authors: Shealey Jalissa , Hall Eric W. , Pigott Therese D. , Bradley Heather 
Published: February 2022

AbstractBackgroundPeople who inject drugs (PWID) have high overdose risk. To assess the burden of drug overdose among PWID in light of opioid epidemic-associated increases in injection drug use (IDU), we estimated rates of non-fatal and fatal overdose among PWID living in Organization for Economic Cooperation and Development (OECD) countries using data from 2010 or later.MethodsPubMed, Psych Info, and Embase databases were systematically searched to identify peer-reviewed studies reporting prevalence or rates of recent (past 12 months) fatal or non-fatal overdose events among PWID in OECD countries. Data were extracted and meta-analyzed using random effects models to produce pooled non-fatal and fatal overdose rates.Results57 of 13,307 identified reports were included in the review, with 33/57 studies contributing unique data and included in the meta-analysis. Other (24/57) studies presented overlapping data to those included in meta-analysis. The rates of non-fatal and fatal overdose among PWID in OECD countries were 24.74 per 100 person years (PY) (95% CI: 19.86 – 30.83; n=28; I2=98.5%) and 0.61 per 100 PY (95% CI: 0.32 – 1.16; n=8; I2=93.4%), respectively. The rate of non-fatal overdose was 27.79 in North American countries, 25.71 in Canada, 28.59 in the U.S., and 21.44 in Australia.ConclusionThese findings suggest there is a fatal overdose for every 40 non-fatal overdose events among PWID in OECD countries. The magnitude of overdose burden estimated here underscores the need for expansion of overdose prevention and treatment programs and serves as a baseline estimate for monitoring success of such programs.
Brachypodium antifreeze protein gene products inhibit ice recrystallization, attenuate ice nucleation, and reduce immune response
Authors: Juurakko Collin L. , diCenzo George C. , Walker Virginia K. 
Published: February 2022

AbstractAntifreeze proteins (AFPs) from the model crop, Brachypodium distachyon, allow freeze survival and attenuate pathogen-mediated ice nucleation. Intriguingly, each Brachypodium AFP gene encodes two proteins, an autonomous AFP and a leucine-rich repeat (LRR). We present structural models suggesting that ice-binding motifs on the ~13 kDa AFPs can “spoil” nucleating arrays on the ~120 kDa bacterial ice nucleating proteins that form ice at high sub-zero temperatures, consistent with decreases in ice nucleating activity by lysates from wildtype compared to transgenic Brachypodium lines. Strikingly, the expression of Brachypodium LRRs in transgenic Arabidopsis inhibited an immune response to pathogen flagella peptides (flg22), with structural modelling suggesting this was due to affinity of the LRR domains to flg22. Thus, these genes play distinctive roles in connecting freeze survival and anti-pathogenic systems via their encoded proteins’ ability to adsorb to ice as well as attenuating bacterial ice nucleation and the host immune response.
Using landscape genomics to infer genomic regions involved in environmental adaptation of soybean genebank accessions
Authors: Haupt Max , Schmid Karl 
Published: February 2022

AbstractUnderstanding how crops adapt to specific environmental conditions is becoming increasingly important in the face of accelerating climate change, but the genetics of local adaptation remain little understood for many crops. Landscape genomics can reveal patterns of genetic variation that indicate adaptive diversification during crop evolution and dispersal. Here, we examine genetic differentiation and association signatures with environmental gradients in soybean (Glycine max) germplasm groups from China that were inferred from the USDA Soybean Germplasm Collection (N = 17,019 accessions) based on population structure and passport information. We recover genes previously known to be involved in soybean environmental adaptation and report numerous new candidate genes in selection signatures implicated by genomic resources such as the genome annotation and gene expression datasets to function in flowering regulation, photoperiodism and stress reaction cascades. Linkage disequilibrium network analysis suggested functional relationships between genomic regions with selection signatures, consistent with the polygenic nature of environmental adaptation. We tested whether haplotypes associated with environmental adaptation in China were present in 843 North American and 160 European soybean cultivars and found that haplotypes in major genes for early maturity have been selected during breeding, but also that a large number of haplotypes exhibiting putative adaptive variation for cold regions at high latitudes are underrepresented in modern cultivars. Our results demonstrate the value of landscape genomics analysis in genebank germplasm as a starting point for the study of crop environmental adaptation and have the potential to inform future research efforts focused on improved soybean adaptation. Functional validation of candidate genes will support understanding of their adaptive roles and likely enable the transfer of beneficial adaptive variation into modern breeding germplasm.
Evaluating Chinese Handwriting Performance of Primary School Students Using the Smart Handwriting Analysis and Recognition Platform (SHARP)
Authors: Li-Tsang Cecilia W. P. , Li Tim M. H. , Yang C.N. , Leung Howard W. H. , Zhang Eve W. L. 
Published: February 2022

AbstractBackgroundHandwriting is one of the fundamental skills for school-aged children, and it is an intricate and interacting process. An innovative computerized handwriting assessment system, the Smart Handwriting Analysis and Recognition Platform (SHARP) was used to provide a comprehensive and quantitative analysis of Chinese handwriting performance and identify children with handwriting difficulties objectively, accurately, and efficiently.Aims/ObjectivesThe purpose of this study is to provide quantitative data on children’s Chinese handwriting process and products using SHARP; to investigate the handwriting difficulties in children with neurodevelopmental problems, and to explore the associations between handwriting and sensorimotor performance, including fine motor skills, visual perceptual skills, visual-motor integration, and oculomotor proficiency.Material and MethodsTypically developing students and students with neurodevelopmental problems were recruited through teachers and therapists from six primary schools in Hong Kong. SHARP and tests of sensorimotor skills were performed.ResultsThe quantitative analysis using the SHARP system showed a progressive developmental change in handwriting performance among the typically developing children at their primary education. There were also significant differences between the typically developing students group and those with neurodevelopmental problems, both in handwriting speed and writing errors. Significant associations between the handwriting process parameters and fine motor skills were identified, while handwriting product parameters were closely correlated with visual-perceptual skills of these typical developing students.Conclusions and SignificanceSHARP appears to provide a comprehensive, quantitative and objective evaluation of students’ handwriting performances, thus assisting both teachers and parents in comparing students’ performance objectively, thus identifying students with handwriting difficulties as early as P1 level. It was observed that handwriting performance has strong relationships with young children’s visual perceptual skills and fine motor skills. The findings could help to facilitate early intervention for those students with handwriting problems.
When Vibrios Take Flight: A Meta-analysis of Pathogenic Vibrios Species in Wild and Domestic Birds
Authors: Ayala Andrea J. , Ogbunugafor C. Brandon 
Published: February 2022

ABSTRACTOf the over 100 species in the genus Vibrio, approximately twelve are associated with clinical disease, such as cholera and vibriosis. Crucially, eleven of those twelve—V. alginolyticus, V. cholerae, V. cincinnatiensis, V. hollinsae, e.g., Grimontia hollinsae, V. furnissii, V. mimicus, V. parahaemolyticus, V. vulnificus, V. harveyi, V. scophthalmi and V. metschnikovi—have also been isolated from birds. Since 1965, pathogenic Vibrio species have been consistently isolated from aquatic and ground-foraging bird species, which has implications for public health, as well as the One Health paradigm defined as an ecology-inspired, integrative framework for the study of health and disease, inclusive of environmental, human, and animal health. In this meta-analysis, we identified 76 studies from the primary literature which report on or examine birds as hosts for pathogenic Vibrio species. We found that the burden of disease in birds was most commonly associated with V. cholerae, followed by V. metschnikovi and V. parahaemolyticus. Meta-analysis wide prevalences of the Vibrio pathogens varied from 19% for V. parahaemolyticus to 1% for V. mimicus. Wild and domestic birds were both affected, which may have implications for conservation, as well as agriculturally associated avian species. As pathogenic Vibrios become more abundant throughout the world as a result of warming estuaries and oceans, susceptible avian species should be continually monitored as potential reservoirs for these pathogens.
scAnnotate: an automated cell type annotation tool for single-cell RNA-sequencing data
Authors: Ji Xiangling , Tsao Danielle , Bai Kailun , Tsao Min , Xing Li , Zhang Xuekui 
Published: February 2022

AbstractMotivationSingle-cell RNA-sequencing (scRNA-seq) technology enables researchers to investigate a genome at the cellular level with unprecedented resolution. An organism consists of a heterogeneous collection of cell types, each of which plays a distinct role in various biological processes. Hence, the first step of scRNA-seq data analysis is often to distinguish cell types so they can be investigated separately. Researchers have recently developed several automated cell type annotation tools, requiring neither biological knowledge nor subjective human decisions. Dropout is a crucial characteristic of scRNA-seq data widely used in differential expression analysis. However, dropout information is not explicitly used by any current cell annotation method. Fully utilizing dropout information for cell type annotation motivated this work.ResultsWe present scAnnotate, a cell annotation tool that fully utilizes dropout information. We model every gene’s marginal distribution using a mixture model, which describes both the dropout proportion and the distribution of the non-dropout expression levels. Then, using an ensemble machine learning approach, we combine the mixture models of all genes into a single model for cell-type annotation. This combining approach can avoid estimating numerous parameters in the high-dimensional joint distribution of all genes. Using fourteen real scRNA-seq datasets, we demonstrate that scAnnotate is competitive against nine existing annotation methods. Furthermore, because of its distinct modelling strategy, scAnnotate’s misclassified cells are very different from competitor methods. This suggests using scAnnotate together with other methods could further improve annotation accuracy.AvailabilityWe implemented scAnnotate as an R package and made it publicly available from CRAN.ContactXuekui Zhang: xuekui@uvic.ca and Li Xing: li.xing@math.usask.ca
Long-read sequencing of diagnosis and post-therapy medulloblastoma reveals complex rearrangement patterns and epigenetic signatures
Authors: Rausch Tobias , Snajder Rene , Leger Adrien , Simovic Milena , Stegle Oliver , Birney Ewan , Bonder Marc Jan , Ernst Aurelie , Korbel Jan O. 
Published: February 2022

SummaryCancer genomes harbor a broad spectrum of structural variants (SV) driving tumorigenesis, a relevant subset of which are likely to escape discovery in short reads. We employed Oxford Nanopore Technologies (ONT) sequencing in a paired diagnostic and post-therapy medulloblastoma to unravel the haplotype-resolved somatic genetic and epigenetic landscape. We assemble complex rearrangements and such associated with telomeric sequences, including a 1.55 Megabasepair chromothripsis event. We uncover a complex SV pattern termed ‘templated insertion thread’, characterized by short (mostly <1kb) insertions showing prevalent self-concatenation into highly amplified structures of up to 50kbp in size. Templated insertion threads occur in 3% of cancers, with a prevalence ranging to 74% in liposarcoma, and frequent colocalization with chromothripsis. We also perform long-read based methylome profiling and discover allele-specific methylation (ASM) effects, complex rearrangements exhibiting differential methylation, and differential promoter methylation in seven cancer-driver genes. Our study shows the potential of long-read sequencing in cancer.Graphical abstractI) We investigate a single patient with chromothriptic sonic hedgehog medulloblastoma (Li-Fraumeni syndrome), with tissue samples taken from blood, the primary tumor at diagnosis, and a post-treatment (relapse) tumor. II) Data on the three samples has been collected from four sources, 1) Illumina whole-genome, 2) Illumina transcriptome sequencing, 3) Illumina Infinium HumanMethylation450k, as well as 4) long-read whole-genome sequencing using Oxford Nanopore Technologies (ONT) sequencing. III) An integrative analysis combines genomic, epigenomic as well as transcriptomic data to provide a comprehensive analysis of this heavily rearranged tumor sample. Long and short read sequencing data is used to inform the analysis of complex structural genomic variants and methylation called from haplotyped ONT reads and validated through the methylation array data allows for a haplotype-resolved study of genomic and epigenomic variation, which can then be examined for transcriptional effect. IV) This integrative analysis allows us to identify a large number of inter- and intra-chromosomal genomic rearrangements (A) including a complex rearrangement pattern we term templated insertion threads (B), as well as sample-specific and haplotype specific methylation patterns of known cancer genes (C).
Keratinocyte-Associated Protein 3 is a novel gene for adiposity with differential effects in males and females
Authors: Szalanczy Alexandria M , Goff Emily , Seshie Osborne , Deal Aaron , Grzybowski Michael , Klotz Jason , Key Chia-Chi C , Geurts Aron M , Solberg Woods Leah C 
Published: February 2022

AbstractObjectiveDespite the obesity crisis in the United States, the underlying genetics are poorly understood. Our lab previously identified Keratinocyte-associated protein 3, Krtcap3, as a candidate gene for adiposity where increased expression of Krtcap3 correlated with decreased fat mass. Here we seek to confirm that Krtcap3 expression affects adiposity traits.MethodsWe developed an in vivo whole-body Krtcap3 knock-out (KO) rat model. Wild-type (WT) and KO rats were placed onto a high-fat or low-fat diet at six weeks of age and were maintained on diet for 13 weeks, followed by assessments of metabolic health. We hypothesized that Krtcap3-KO rats will have increased adiposity and a worsened metabolic phenotype relative to WT.ResultsWe found that KO male and female rats have significantly increased body weight versus WT. KO females ate more, had more fat mass, but were also more insulin sensitive than WT. Alternatively, KO males weighed more and were more insulin resistant than WT, with no differences in eating or fat mass.ConclusionsThis study validates Krtcap3 in body weight regulation and demonstrates sex-specific effects on food intake, adiposity, and insulin sensitivity. Future studies will investigate how Krtcap3 is acting and seek to better understand these sex differences.Study Importance QuestionsWhat is already known about this subject?
Over 900 low-risk, common genetic variants for BMI have been identified, but these still only explain a fraction of the heritability and many of the underlying causal genes remain unknownKrtcap3 has been identified as a candidate gene for obesity in both rats and humans, but no verification or functional studies have been doneWhat are the new findings in your manuscript?
Identified Krtcap3 as a novel gene that impacts feeding behavior and adiposity in female ratsDetermined that Krtcap3 impacts insulin sensitivity differentially in male and female ratsHow might your results change the direction of research or the focus of clinical practice?
This work may lead to identification of new pathways that contribute to obesity without metabolic complications, which will advance understanding of the biology of obesity and potentially identify novel drug targetsThis work highlights the need to investigate sex differences in the genetics of obesity