bluuebunny/crossref_metadata_2025_split huggingface dataset:
Retrospective analysis of cohort risk factors and feeding phase timing associated with noninfectious heart disease deaths in U.S. feedlot cattle
Authors: Johnson Blaine T , Amrine David E , Larson Robert L , Weaber Robert L , White Brad J 
Published: December 2021

Abstract
Heart disease, specifically congestive heart failure, has become of increased interest to geneticists and cattle feeders. Data on cohort associations of risk factors related to heart disease and when heart disease deaths occur in U.S. feedlot cattle are limited. The study objectives were to 1) determine potential associations between feedlot cohort demographics and the risk of at least one noninfectious heart disease (NIHD) death occurrence and 2) determine potential association between feedlot cohort demographics and the timing of NIHD deaths during the feeding phase. Data were downloaded from commercial feedyard software and analyzed by constructing a generalized linear mixed model for both analyses. A binomial and Gaussian distributions for risk of NIHD death and timing of NIHD were utilized as link functions for their respective models. Our study population consisted of 28,950 cohorts (representing 4,596,205 cattle) that were placed in 22 U.S. commercial feedlots from January 01, 2016, to January 01, 2019. There were 3,282 cases of NIHD deaths from a population of 75,963 cattle that died during the 3-yr study period. Average cohort arrival weight’s effect on NIHD probability was influenced by arrival quarter and arrival year of placement (P &lt; 0.01). Cohorts with steers were associated with a greater probability of at least one NIHD death (2.38%) compared with heifers (1.95%; P &lt; 0.01). Increasing cohort size was associated with an increased probability of a cohort having at least one NIHD death (P &lt; 0.01). The probability of a cohort having at least one NIHD death increased with increasing DOF categories from 1.51% in cattle fed 100 to 175 d, to 2.12% in cattle fed 176 to 250 d, and 2.87% for cattle fed 251 to 326 d. Cattle &gt; 326 DOF were no different in the probability of a NIHD death compared with the other feeding categories. Timing of a NIHD death had a mean and median occurrence of 110 DOF with an interquartile range of 64 to 153 DOF. The effect of arrival weight on days at death was influenced by year placed with heavier cattle generally decreasing the model adjusted means of DOF at NIHD death. Arrival quarter was influenced by year placed on model adjusted means on the timing of a NIHD death. Steers with NIHD died later compared with heifers (P &lt; 0.01) diagnosed with NIHD. In conclusion, multiple factors are associated with the probability and timing of a NIHD death. Probability of having at least one NIHD death within a cohort was low, and half of the deaths occurred before 110 DOF.
Effects of forage inclusion and cattle breed on apparent digestibility and ruminal pH of steers fed a whole shelled corn-based diet
Authors: Carvalho Pedro H V , Westphalen Mariana F , Silva Flavia A S , Felix Tara L 
Published: December 2021

Abstract
Objectives were to evaluate the effects of cattle breed, Holstein or Angus, and forage inclusion on total tract digestibility and ruminal pH in cattle fed a whole shelled corn-based diet. Six Holstein and six Angus steers were assigned to a 2 × 3 factorial arrangement of treatments. Factors included breed, Holstein or Angus, and forage inclusion at 0%, 8%, or 16% forage (dry matter [DM] basis). Steers were fed in a replicated 3 × 3 Latin square, split-plot design. Each period consisted of 14 d diet adaptation followed by 7 d of sample collection. Data were analyzed using the MIXED procedures in SAS (v9.4 SAS Inst. Inc., Cary, NC). Repeated measures were used to analyze changes in ruminal pH over time. There was no interaction of breed × diet (P ≥ 0.19) on dry matter intake (DMI) or digestibility; however, Holstein steers had greater (P = 0.03) DMI than Angus steers. Despite the impact of breed on intake, there was no effect (P ≥ 0.33) of breed on diet digestibility. Digestibility of DM increased (linear; P &lt; 0.01) as forage was removed from the diet, but there were no differences (P ≥ 0.32) in Neutral Detergent Fiber (NDF) and starch digestibility. However, due to the change in diet, NDF intake digested on a grams per day basis increased (P ≤ 0.01) and starch intake digested (g/d) decreased (P = 0.01) as forage inclusion increased. There was a tendency for breed × diet interaction (P = 0.08) on ruminal pH. Holstein steers fed 8% or 16% forage had greater ruminal pH than Holstein steers fed 0% forage; but, ruminal pH of Angus steers was not altered by diet.
Intellectual Curiosity and Action Initiation are Subtypes of Apathy Affected in Huntington Disease Gene Expansion Carriers
Authors: Hendel Rebecca K. , Hellem Marie N.N. , Hjermind Lena E. , Nielsen Jørgen E. , Vogel Asmus 
Published: December 2021

Background:
Apathy is a prevalent behavioral syndrome of Huntington disease (HD) that can result in severe loss of function for the individual with HD and substantial caregiver distress. Research-based evidence of apathy is characterized by methodological differences, and there is a deficiency in the evidence concerning the subtypes of apathy.

Objective:
To characterize apathy in premanifest and motor-manifest HD gene expansion carriers and controls using the Short Problem Behaviors Assessment for Huntington’s Disease (PBA–s) and the Lille Apathy Rating Scale (LARS).

Method:
We included 82 HD gene expansion carriers (premanifest and motor manifest) and 32 controls (Mini-Mental State Examination score ≥24 and Montreal Cognitive Assessment score ≥19) in the study. We quantified apathy using the PBA–s and the LARS and performed correlation analyses between the global LARS score and motor function, cytosine-adenine-guanine repeat length, cytosine-adenine-guanine Age Product score, and neuropsychiatric and cognitive symptoms.

Results:
The motor-manifest HD gene expansion carriers scored significantly higher than the controls on the global score and the Intellectual Curiosity and Action Initiation subscales of the LARS. Apathy was present in 28% of the HD gene expansion carriers (including 7 premanifest). The apathetic participants had a significantly higher motor score, significantly higher scores on the neuropsychiatric instruments, and significantly lower cognitive scores compared with the controls.

Conclusion:
Apathy is a frequent syndrome that is found in individuals with HD. Apathy has a specific expression, with symptoms such as reduced initiation, voluntary actions, and interests, that might be related to the underlying neuropathology. Apathy is related to disease progression, neuropsychiatric symptoms, and cognitive impairments.
Genetic alteration of humanMYH6is mimicked by SARS-CoV-2 polyprotein: mapping viral variants of cardiac interest
Authors: Anand Praveen , Lenehan Patrick J. , Niesen Michiel , Yoo Unice , Patwardhan Dhruti , Montorzi Marcelo , Venkatakrishnan AJ , Soundararajan Venky 
Published: December 2021

AbstractAcute cardiac injury has been observed in a subset of COVID-19 patients, but the molecular basis for this clinical phenotype is unknown. It has been hypothesized that molecular mimicry may play a role in triggering an autoimmune inflammatory reaction in some individuals after SARS-CoV-2 infection. Here we investigate if linear peptides contained in proteins that are primarily expressed in the heart also occur in the SARS-CoV-2 proteome. Specifically, we compared the library of 136,704 8-mer peptides from 144 human proteins (including splicing variants) to 9,926 8-mers from all 17 viral proteins in the reference SARS-CoV-2 proteome. No 8-mers were exactly identical between the reference human proteome and the reference SARS-CoV-2 proteome. However, there were 45 8-mers that differed by only one amino acid when compared to the reference SARS-CoV-2 proteome. Interestingly, analysis of protein-coding mutations from 141,456 individuals showed that one of these 8-mers from the SARS-CoV-2 Replicase polyprotein 1a/1ab (KIALKGGK) is identical to aMYH6peptide encoded by the c.5410C>A (Q1804K) genetic variation, which has been observed at low prevalence in Africans/African Americans (0.08%), East Asians (0.3%), South Asians (0.06%) and Latino/Admixed Americans (0.003%). Furthermore, analysis of 4.85 million SARS-CoV-2 genomes from over 200 countries shows that viral evolution has already resulted in 20 additional 8-mer peptides that are identical to human heart-enriched proteins encoded by reference sequences or genetic variants. Whether such mimicry contributes to cardiac inflammation during or after COVID-19 illness warrants further experimental evaluation. We suggest that SARS-CoV-2 variants harboring peptides identical to human cardiac proteins should be investigated as ‘viral variants of cardiac interest’.
Trends and associated factors for Covid-19 hospitalisation and fatality risk in 2.3 million adults in England
Authors: Beaney T , Neves AL , Alboksmaty A , Flott K , Fowler A , Benger JR , Aylin P , Elkin S , Darzi A , Clarke J 
Published: December 2021

AbstractBackgroundThe Covid-19 case fatality ratio varies between countries and over time but it is unclear whether variation is explained by the underlying risk in those infected. This study aims to describe the trends and risk factors for admission and mortality rates over time in England.MethodsIn this retrospective cohort study, we included all adults (≥18 years) in England with a positive Covid-19 test result between 1stOctober 2020 and 30thApril 2021. Data were linked to primary and secondary care electronic health records and death registrations. Our outcomes were i) one or more emergency hospital admissions and ii) death from any cause, within 28 days of a positive test. Multivariable multilevel logistic regression was used to model each outcome with patient risk factors and time.Results2,311,282 people were included in the study, of whom 164,046 (7.1%) were admitted and 53,156 (2.3%) died within 28 days. There was significant variation in the case hospitalisation and mortality risk over time, peaking in December 2020-February 2021, which remained after adjustment for individual risk factors. Older age groups, males, those resident in more deprived areas, and those with obesity had higher odds of admission and mortality. Of risk factors examined, severe mental illness and learning disability had the highest odds of admission and mortality.ConclusionsIn one of the largest studies of nationally representative Covid-19 risk factors, case hospitalisation and mortality risk varied significantly over time in England during the second pandemic wave, independent of the underlying risk in those infected.
Tracking bacteria at high density with FAST, the Feature-Assisted Segmenter/Tracker
Authors: Meacock Oliver J. , Durham William M. 
Published: November 2021

AbstractMost bacteria live attached to surfaces in densely-packed communities1,2. While new experimental and imaging techniques are beginning to provide a window on the complex processes that play out in these communities, resolving the behaviour of individual cells through time and space remains a major challenge. Although a number of different software solutions have been developed to track microorganisms3–8, these approaches typically rely on a large number of user-defined parameters that must be carefully tuned to effectively track cells. Testing a given parameter combination can take hours to days depending on the size of the dataset, making iterative optimisation impractical. To overcome these limitations, we have developed FAST, the Feature-Assisted Segmenter/Tracker, which uses unsupervised machine learning to optimise tracking while maintaining ease of use. Our approach, rooted in information theory, largely eliminates the need for users to iteratively adjust parameters manually and make qualitative assessments of the resulting cell trajectories. Instead, FAST measures multiple distinguishing “features” for each cell and then autonomously quantifies the amount of unique information each feature provides. We then use these measurements to determine how data from different features should be combined to minimize tracking errors. Comparing our algorithm with a naïve approach that uses cell position alone revealed that FAST produced 4 to 10 times fewer tracking errors. The modular design of FAST combines our novel tracking method with tools for segmentation, extensive data visualisation, lineage assignment, and manual track correction. It is also highly extensible, allowing users to extract custom information from images and seamlessly integrate it into downstream analyses. FAST therefore enables high-throughput, data-rich analyses with minimal user input. It has been released for use either in Matlab or as a compiled stand-alone application, and is available athttps://bit.ly/3vovDHn, along with extensive tutorials and detailed documentation.
Bagaza virus in wild birds, Portugal, 2021
Authors: Queirós João , Barros Sílvia , Sánchez-Cano Alberto , Henriques Margarida , Fagulha Teresa , dos Santos Fábio Abade , Duarte Margarida , Gonçalves Catarina , Gonçalves David , Rodrigues Marisa , Cabrera Teresa Cardona , de Mera Isabel G. Fernández , Gortazar Christian , Höfle Ursula , Célio Alves Paulo 
Published: November 2021

AbstractBagaza virus (BAGV) emerged in Spain, in 2010. Since then, BAGV was not reported in other European countries until September 2021, when BAGV was diagnosed by molecular methods in one corn bunting and several red-legged partridges, after abnormal mortality in Southern Portugal. Sequencing revealed high similarity with strains reported previously.
Long-term consequences of alcohol use in early adolescent mice: focus on neuroadaptations in GR, CRF and BDNF
Authors: Sampedro-Piquero P. , Moreno-Fernández R.D. , Begega A. , López M. , Santín L.J. 
Published: November 2021

AbstractOur aim was to assess the cognitive and emotional state, as well as related-changes in the glucocorticoid receptor (GR), the corticotropin-releasing factor (CRF) and the brain-derived neurotrophic factor (BDNF) expression of adolescent C57BL/6J male mice after a five-week two-bottle choice protocol (postnatal day (pd) 21 to pd52). Additionally, we wanted to analyse whether the behavioural and neurobiological effects observed in late adolescence (pd62) lasted until adulthood (pd84). Behavioural testing revealed that alcohol during early adolescence increased anxiety-like and compulsive-related behaviours, which was maintained in adulthood. Concerning cognition, working memory was only altered in late adolescent mice, whereas object location test performance was impaired in both ages. In contrast, novel object recognition remained unaltered. Immunohistochemical analysis showed that alcohol during adolescence diminished BDNF+ cells in the cingulate cortex, the hippocampal CA1 layer and the central amygdala. Regarding hypothalamic-pituitary-adrenal axis (HPA) functioning, alcohol abuse increased the GR and CRF expression in the hypothalamic paraventricular nucleus and the central amygdala. Besides this, GR density was also higher in the prelimbic cortex and the basolateral amygdala, regardless of the animals’ age. Our findings suggest that adolescent alcohol exposure led to long-term behavioural alterations, along with changes in BDNF, GR and CRF expression in limbic brain areas involved in stress response, emotional regulation, and cognition.
Evolution of resistance to Irinotecan in cancer cells involves generation of topoisomerase-guided mutations in non-coding genome that reduce the chances of DNA breaks
Authors: Kumar Santosh , Gahramanov Valid , Patel Shivani , Yaglom Julia , Kaczmarczyk Lukasz , Alexandrov Ivan , Gerlitz Gabi , Salmon-Divon Mali , Sherman Michael Y. 
Published: November 2021

AbstractResistance to chemotherapy is a leading cause of treatment failure. Drug-resistance mechanisms involve mutations in specific proteins or changes in their expression levels. It is commonly understood that resistance mutations happen randomly prior to treatment and are selected during the treatment. However, selection of drug-resistant mutants in culture could be achieved by multiple drug exposures of cloned genetically identical cells, and thus cannot result from selection of pre-existent mutations. Accordingly, adaptation must involve generation of mutations de-novo upon drug treatment. Here we explored the origin of resistance mutations to a widely used Top1 inhibitor irinotecan, which triggers DNA breaks, causing cytotoxicity. Resistance mechanism involved gradual accumulation of recurrent mutations in non-coding regions of DNA at Top1-cleavage sites. Surprisingly, cancer cells had higher number of such sites than reference genome, which may define their increased sensitivity to irinotecan. Homologous recombination repair of DNA double strand breaks at these sites following initial drug exposures gradually reverted cleavage-sensitive “cancer” sequences back to cleavage-resistant “normal” sequences. These mutations reduced generation of DNA breaks upon subsequent exposures, thus gradually increasing the drug resistance. Together, large target size for mutations and their Top1-guided generation lead to their gradual and rapid accumulation, synergistically accelerating development of resistance.Abstract Figure
Simultaneous pathway engagement of translation in astrocytes, circadian rhythm in GABAergic neurons and cytoskeleton in glutamatergic neurons precede electroencephalographic changes in neurodegenerative prion disease
Authors: Kaczmarczyk Lech , Schleif Melvin , Dittrich Lars , Williams Rhiannan , Koderman Maruša , Bansal Vikas , Rajput Ashish , Schulte Theresa , Jonson Maria , Krost Clemens , Testaquadra Fabio , Bonn Stefan , Jackson Walker S. 
Published: November 2021

AbstractSelective vulnerability is an enigmatic feature of neurodegenerative diseases (NDs), whereby a widely expressed protein causes lesions in specific brain regions and cell types. This selectivity may arise from cells possessing varying capacities to regain proteostasis when stressed by cytotoxic protein conformers. Using the RiboTag method in mice, translational responses of five neural subtypes to acquired prion disease (PrD) were measured. Pre-onset and disease onset timepoints were chosen based on longitudinal electroencephalography (EEG) that revealed a gradual increase in theta power between 10- and 18-weeks after prion injection, resembling a clinical feature of human PrD. At disease onset, marked by significantly increased theta power and histopathological lesions, mice had pronounced translatome changes in all five cell types despite having a normal outward appearance. Remarkably, at a pre-onset stage, prior to EEG and neuropathological changes, we found that 1) translatomes of astrocytes indicated a sharply reduced synthesis of ribosomal and mitochondrial components, 2) excitatory neurons showed increased expression of cytoskeletal genes, and 3) inhibitory neurons revealed reduced expression of circadian rhythm network genes. Further assessment for the role of circadian rhythms using a jet lag paradigm modestly exacerbated disease. These data demonstrate that early translatome responses to neurodegeneration emerge prior to other signs of disease and are unique to different cell types. Therapeutic strategies may need to target multiple pathways, each in specific populations of cells, early in the disease process.
BCM3D 2.0: Accurate segmentation of single bacterial cells in dense biofilms using computationally generated intermediate image representations
Authors: Zhang Ji , Wang Yibo , Donarski Eric D. , Toma Tanjin T. , Miles Madeline T. , Acton Scott T. , Gahlmann Andreas 
Published: November 2021

AbstractAccurate detection and segmentation of single cells in three-dimensional (3D) fluorescence timelapse images is essential for observing individual cell behaviors in large bacterial communities called biofilms. Recent progress in machine-learning-based image analysis is providing this capability with every increasing accuracy. Leveraging the capabilities of deep convolutional neural networks (CNNs), we recently developed bacterial cell morphometry in 3D (BCM3D), an integrated image analysis pipeline that combines deep learning with conventional image analysis to detect and segment single biofilm-dwelling cells in 3D fluorescence images. While the first release ofBCM3D(BCM3D 1.0) achieved state-of-the-art 3D bacterial cell segmentation accuracies, low signal-to-background ratios (SBRs) and images of very dense biofilms remained challenging. Here, we presentBCM3D 2.0to address this challenge.BCM3D 2.0is entirely complementary to the approach utilized inBCM3D 1.0. Instead of training CNNs to perform voxel classification, we trained CNNs to translate 3D fluorescence images into intermediate 3D image representations that are, when combined appropriately, more amenable to conventional mathematical image processing than a single experimental image. Using this approach, improved segmentation results are obtained even for very low SBRs and/or high cell density biofilm images. The improved cell segmentation accuracies in turn enable improved accuracies of tracking individual cells through 3D space and time. This capability opens the door to investigating timedependent phenomena in bacterial biofilms at the cellular level.
Thousands of human mutation clusters are explained by short-range template switching
Authors: Löytynoja Ari 
Published: November 2021

AbstractVariation within human genomes is unevenly distributed, and variants show spatial clustering. DNA- replication-related template switching is a poorly known mutational mechanism capable of causing major chromosomal rearrangements as well as creating short inverted sequence copies that appear as local mutation clusters in sequence comparisons. I reanalyzed haplotype-resolved genome assemblies representing 25 human populations and multinucleotide variants aggregated from 140,000 human sequencing experiments. Local template switching could explain thousands of complex mutation clusters across the human genome, the loci segregating within and between populations. I developed computational tools for identification of template switch events using both short-read sequencing data and genotype data, and for genotyping candidate loci using short-read data. The characteristics of template-switch mutations complicate their detection and, worryingly, widely used analysis pipelines for short-read sequencing data, normally capable of identifying single nucleotide changes, were found to miss template-switch mutations of tens of base pairs, potentially invalidating medical genetic studies searching for a causative allele behind genetic diseases. Combined with the massive sequencing data now available for humans, the novel tools described here enable building catalogs of affected loci and studying the cellular mechanisms behind template switching in both healthy organisms and disease.