bluuebunny/crossref_metadata_2025_split huggingface dataset:
PIK3R3is a candidate regulator of platelet count in people of Bangladeshi ancestry
Authors: Burley Kate , Fitzgibbon Lucy , van Heel David ,   Genes & Health Research Team, Vuckovic Dragana , Mumford Andrew D 
Published: November 2022

AbstractPlatelets are mediators of cardiovascular disease and are regulated by complex sets of interacting genes. To reveal new regulatory loci for platelet count (PLT), we performed genome-wide association studies (GWAS) in 20,218 Bangladeshi (BAN) and 9,198 Pakistani (PAK) individuals from the Genes and Health study. Most significantly associated loci (p <5 ×10−8) replicated findings in prior transethnic GWAS. However, the BAN locus defined by rs946528 (chr1:46019890) did not associate with PLT in the PAK analysis but was in the same linkage disequilibrium block as PLT-associated variants in prior East Asian GWAS. The single independent association signal was refined to a 95% credible set of 343 variants spanning eight coding genes. Functional annotation, mapping to megakaryocyte regulatory regions and colocalization with whole blood eQTLs identified the most likely mediator of the PLT phenotype to bePIK3R3encoding a regulator of phosphoinositol 3-kinase, widely linked elsewhere to adverse cardiovascular phenotypes.
From Pigs to Silkworms: Cognition and Welfare across 10 Farmed Taxa
Authors: Miller Rachael , Schiestl Martina , Trevarthen Anna , Gaffney Leigh , Lavery J. Michelle , Fischer Bob , Schnell Alexandra 
Published: November 2022

AbstractBillions of animals across many taxa are extensively farmed, with critical impacts on animal welfare. Societal efforts to reduce animal suffering lack rigorous and systematic approaches that facilitate maximising welfare improvements, such as informed funding allocation decisions. We present a multi-measure, cross-taxa framework for modelling differences in pain, suffering, and related cognition to assess whether certain animals have larger welfare ranges (how well or badly animals can fare). Measures include behavioural flexibility, cognitive sophistication, and general learning. We evaluated 90 empirically detectable proxies for cognition and welfare range (henceforth ‘proxies’) in pigs, chickens, carp, salmon, octopus, shrimp, crabs, crayfish, bees, and silkworms. We grouped a subset of proxies into: A) 10 ideal proxies and B) 10 less ideal proxies but with sufficient data for interspecies comparisons. We graded the strength of evidence per proxy across taxa, and constructed a cognition and welfare range profile, with overall judgement scores (ranging from likely no/low confidence to yes/very high confidence). We discuss the implications of comparisons and highlight key avenues for future research. This work is timely, given recent indications of significant political will towards reducing animal suffering, such as the inclusion of cephalopods and decapods in the Animal Welfare (Sentience) Bill following a UK government-commissioned research review. Given the novelty and robustness of our review, we believe it sets a new standard for investigating interspecies comparisons of cognition and welfare ranges and helps inform future research. This should help streamline funding allocations and improve the welfare of millions of farmed animals.Graphical/ Visual Abstract and CaptionCognition and welfare in farmed animals - from pigs to silkworms (Free stock images:http://www.pixabay.com)
Preselection of QTL markers enhances accuracy of genomic selection in Norway spruce
Authors: Chen Zhi-Qiang , Klingberg Adam , Hallingbäck Henrik R. , Wu Harry X. 
Published: November 2022

AbstractGenomic prediction (GP) or genomic selection is a method to predict the accumulative effect of all quantitative trait loci (QTLs) effects by capturing the linkage disequilibrium between markers and QTLs. Thus, marker preselection is considered a promising method to capture Mendelian segregation effects, especially for an oligogenic trait. Using QTLs detected in the genome-wide association study (GWAS) could improve genomic prediction, including informative marker selection and adding a QTL with the largest effect size as a fixed effect. Here, we performed GWAS and genomic selection studies in a population with 904 clones from 32 full-sib families using a newly developed 50k SNP Norway spruce array. In total, GWAS identified 41 SNPs associated with budburst stage (BB) and the SNP with the largest effect size explained 5.1% of the phenotypic variation (PVE). For the other five traits like growth and wood quality traits, only 2 – 13 SNPs were detected and PVE of the strongest effects ranged from 1.2% to 2.0%. GP with approximately 100 preselected SNPs based on the smallestp-values from GWAS showed the largest predictive ability (PA) for the oligogenic trait BB. But for the other polygenic traits, approximate 2000-4000 preselected SNPs, indicated by the smallest Akaike information criterion to offer the best model fit, still resulted in PA being similar to that of GP models using all markers. Analyses on both real-life and simulated data also showed that the inclusion of a large QTL SNP in the model as a fixed effect could improve PA and accuracy of GP provided that the PVE of the QTL was ≥2.5%.
BeEM: fast and faithful conversion of mmCIF format structure files to PDB format
Authors: Zhang Chengxin 
Published: November 2022

AbstractAlthough mmCIF is the current official format for deposition of protein and nucleic acid structures to the Protein Data Bank (PDB) database, the legacy PDB format is still the primary supported format for many structural bioinformatics tools. Therefore, reliable software to convert mmCIF structure files to PDB files is needed. Unfortunately, existing conversion programs fail to correctly convert many mmCIF files, especially those with many atoms and/or long chain identifies. This study proposed BeEM, which converts any mmCIF format structure files to PDB format. BeEM conversion faithfully retains all atomic and chain information, including chain IDs with more than 2 characters, which are not supported by any existing mmCIF to PDB converters. The conversion speed of BeEM is at least ten times faster than existing converters such as MAXIT and Phenix. BeEM is available under the BSD licence athttps://github.com/kad-ecoli/BeEM/.
SARS-CoV-2 vaccination of laboratory rhesus monkeys (Macaca mulatta): Monitoring and efficacy
Authors: Oh Dan Qi Priscilla , Grothe Iris , Lukaß Herbert , Kreiter Andreas K. , Hoffmann Markus , Wegener Detlef 
Published: November 2022

AbstractThe availability of effective vaccines and a high vaccination rate allowed the recent mitigation, or even withdrawal, of many protective measures for containing the SARS CoV-2 pandemic. At the same time, new and highly mutated variants of the virus are found to have significantly higher transmissibility and reduced vaccine efficacy, thus causing high infection rates during the third year of the pandemic. The combination of reduced measures and increased infectivity poses a particular risk for unvaccinated individuals, including animals susceptible to the virus. Among the latter, non-human primates (NHPs) are particularly vulnerable. They serve as important models in various fields of biomedical research and because of their cognitive capabilities, they receive particular attention in animal welfare regulations around the world. Yet, although they played an extraordinarily important role for developing and testing vaccines against SARS-CoV-2, the protection of captive rhesus monkeys against Covid-19 has rarely been discussed. We here report upon twofold mRNA vaccination of a cohort of 19 rhesus monkeys (Macaca mulatta) against infection by SARS-CoV-2. All animals were closely monitored on possible side effects of vaccination, and were tested for neutralising antibodies against the virus. The data show that vaccination of rhesus monkeys is a safe and reliable measure to protect these animals against SARS-CoV-2.
OpenMEA: Open-Source Microelectrode Array Platform for Bioelectronic Interfacing
Authors: O’Leary Gerard , Khramtsov Iouri , Ramesh Rakshith , Perez-Ignacio Aidan , Shah Prajay , Moradi Chameh Homeira , Gierlach Adam , Genov Roman , Valiante Taufik A. 
Published: November 2022

AbstractBioelectronic interfaces have the potential to revolutionize the treatment of medical disorders and augment physiology. Implantable devices such as pacemakers and deep brain stimulators have already been deployed to control activity in diseases including Parkinson’s disease and epilepsy. These devices typically operate by delivering electrical stimulation at pre-programmed intervals (known as open-loop stimulation). Recent advances in machine learning and low-power integrated circuits have led to the emergence of personalized medical devices that monitor the user’s state and stimulate in response to measured biological activity (known as closed-loop stimulation). There are two key questions that require fundamental research to achieve breakthroughs in personalized devices: 1) What biomarkers and algorithms are best suited to detecting biological states (e.g. seizures in epilepsy)? and 2) What types of electrical stimuli are optimal for controlling these states? The answer to these questions can be exploredin vitrousing multielectrode array (MEA) systems that interface with biological tissue with reduced experimental complexity, better reproducibility, and fewer confounding variables present in whole organisms. However, existing MEA systems have functional limitations and closed-source designs that prevent researchers from developing improvements. This paper introduces OpenMEA, an open-source platform for closed-loop bioelectronics research. OpenMEA includes designs for the components necessary to build a benchtopin vitrolaboratory, including electrophysiological recording and stimulation electronics, a microfluidic perfusion system, and physical designs for multielectrode arrays. The system is demonstrated with the electrical recording and stimulation of epileptogenic human and rodent brain slices. The aim of OpenMEA is to democratize bioelectronic research tools to accelerate the deployment of devices for the treatment of disorders and beyond.
PSYCHOLOGICAL FACTORS PREDICTING OUTCOMES OF CONSERVATIVE TREATMENT IN FROZEN SHOULDER PATIENTS (PSY-FS)
Authors: Brindisino Fabrizio , Silvestri E , Fioretti A , Giovannico G , Di Giacomo G , Feller D , Chiarotto A 
Published: November 2022

ABSTRACTFrozen shoulder contracture syndrome (FSCS) is characterized by underhand onset, severe shoulder daily and night pain, active and passive range of motion (ROM) limitation, disturbing sleep, and shoulder-related disability.FSCS has a cryptogenetics etiology and is more prevalent in people with diabetes, autoimmune and thyroid disease, with higher prevalence in the age range between 50 and 60. Notably no deal is about higher incidence in people with physically low activity and female sex. Moreover, although some patients report complete symptom recovery, others report residual motion impairments and pain.Research on prognostic factors was applied on FSCS, and Eljabu et colleagues (2016) stated that diabetes, comorbidities, bilateral presentation and onset higher pain and disability are negative prognostic factors that could direct patient to early surgery; however, little is known about the prognostic influence of psychological factors in FSCS patients. On the other hand, in other shoulder pathologies, the presence of psychological factors is well documented, and evidence confirms that some of these features could represent prognostic factors that impact the prognosis.A recent systematic review reported that psychological factors were associated with increased pain perception and decreased function and quality of life at baseline in patients with FSCS, and pain-beliefs seem to be associated with a worst perception of arm function; however, little is known about the prognostic value of such factors in FSCS recovery.Knowing about the presence and the role of all types of prognostic factors is important because they can aid treatment and lifestyle decisions, improving individual risk prediction, providing novel targets for new treatments, and enhancing collaboration between different professionals.This study aims to determine if pain, function, disability, quality of life, ROM and time for recovery were influenced by psychological factors in FSCS patients.
Attendance-related healthcare resource utilisation and costs in patients with long QT syndrome in Hong Kong: A retrospective cohort study
Authors: Chung Cheuk To , Chou Oscar Hou In , Lee Teddy Tai Loy , Radford Danny , Jeevaratnam Kamalan , Wong Wing Tak , Cheng Shuk Han , Mok Ngai Shing , Liu Tong , Tse Gary , Lee Sharen 
Published: November 2022

AbstractIntroductionThe understanding of healthcare resource utilisation and its related costs is crucial for optimizing resource allocation in the healthcare setting. There is currently a paucity of published studies investigating healthcare costs related to long QT syndrome (LQTS).MethodThis was a retrospective study of LQTS patients from Hong Kong, China. The healthcare resource utilisation for Accident and Emergency (A&E), inpatient and specialist outpatient settings across a 19-year period was extracted and analysed. Costs in US dollars were calculated using unit costs.ResultsThe cohort consists of 125 LQTS patients with a mean presentation age of 26.7 ± 22.0 years old. Of these, 45 patients presented with ventricular tachycardia/ventricular fibrillation (VT/VF) and 44 patients had an implantable cardioverter-defibrillator (ICD) implementation. At the individual patient level, the median annualised costs were $69 (30-183) at the A&E setting, $10270 (2248-64006) at the inpatient setting and $675 (393-1329) at the special outpatient setting. Patients who presented with VT/VF initially had significantly higher annualised median costs in the inpatient ($59843 [13812-214930] vs. $5480 [1162-23111], p<0.0001) and specialist outpatient setting ($823 [539-1694] vs $609 [383-1269], p=0.133) compared to patients without VT/VF initially.ConclusionThere is an increasing healthcare demand in the inpatient and specialist outpatient settings for LQTS patients. The most expensive attendance type was inpatient setting stay at $10270 per year. The total median annualised cost of LQTS patients without VT/VF was 90% lower compared to patients with VT/VF.
Decoding the variant-to-function relationship forLIPA, a risk locus for coronary artery disease
Authors: Li Fang , Flynn Elise , Ha Philip , Zebak Mazal N. , Cheng Haoxiang , Xue Chenyi , Shi Jianting , Wu Xun , Wang Ziyi , Meng Yujiao , Cui Jian , Zhu Yizhou , Rozenblyum Annie , Chun Jeana , Hernandez-Ono Antonio , Javaheri Ali , Razani Babak , Westerterp Marit , Bauer Robert C , Suh Yousin , Hao Ke , Lappalainen Tuuli , Zhang Hanrui 
Published: November 2022

AbstractTranslating human genomic discoveries into mechanistic insights requires linking genetic variations to candidate genes and their causal functional phenotypes. Genome-wide association studies have consistently identifiedLIPAas a risk locus for coronary artery disease (CAD), with previous expression quantitative trait loci (eQTL) analyses prioritizingLIPAas a candidate causal gene. However, functional studies elucidating the causal variants, regulatory mechanisms, target cell types, and their causal impact on atherosclerosis have been lacking. To address this gap, we applied functional genomics and experimental mouse models to establish the variant-to-function relationship at theLIPAlocus. Our findings show that CAD risk alleles in theLIPAlocus increase LIPA expression and enzyme activity specifically in monocytes/macrophages by enhancing PU.1 binding to an intronic enhancer region that interacts with theLIPApromoter. In myeloidLipa-overexpressing mice, we observed larger atherosclerotic lesions accompanied by altered macrophage function, including increased macrophage accumulation due to enhanced monocyte recruitment, reduced neutral lipid accumulation, and upregulation of integrin and extracellular matrix pathways. Our work establishes a direct causal link betweenLIPArisk alleles and increased monocyte/macrophage LIPA that exacerbates atherosclerosis, bridging human functional genomic evidence to the mechanistic understanding of CAD.Graphical Abstract
An ensemble deep learning model with empirical wavelet transform feature for oral cancer histopathological image classification
Authors: Deo Bhaswati Singha , Pal Mayukha , Panigrahi Prasanta K. , Pradhan Asima 
Published: November 2022

ABSTRACTOral squamous cell carcinoma (OSCC) has become quite prevalent across many countries and poor prognosis is one of the major reasons for the ensuing high mortality rate. It mainly occurs in sites such as tongue, tonsil, oropharynx, gum, floor and other parts of the mouth. For early detection, the widely used approach is biopsy, in which a small portion of the tissue is taken from the mouth and examined under a disinfected and secure microscope. However, these observations do not effortlessly distinguish between normal and cancerous cells. Diagnosis of OSCC is generally done by pathologists who mostly rely on their years of empirical experience from tissue biopsy sections. The possibilities of human errors increase while detecting the cells using microscopy biopsy images physically. With the growth of artificial intelligence, deep learning models have gained immense importance in recent years and have become one of the core technologies in numerous fields including the prediction of lung cancer, breast cancer, oral cancer, and various medical diagnosis. It not only enhances accuracy, but also fastens the image classification process, as a result, lowering human errors and workload. Here, we have made use of a customized deep-learning model for aiding pathologists in better OSCC detection from histopathological images. We accumulated and analyzed a complete set of 696 histopathological oral images, amongst them 80% have been taken in the training set, 10% of the images are included in the validation set, and the rest 10% for testing purposes. In this study, 2D empirical wavelet transform is used to extract features from the images; later an ensemble of two pre-trained models, namely Resnet50 and Densenet201 are used for the classification of images into normal and OSCC classes. The efficacy of the model is assessed and compared in terms of accuracy, sensitivity, specificity, and ROC AUC scores. The simulation results show that the proposed model has achieved an accuracy of 92.00%. Thus, this method may be utilized for assisting in the binary classification of oral histopathological images.
Simulated tempering-enhanced umbrella sampling improves convergence of free energy calculations of drug membrane permeation
Authors: Sousa Carla F. , Becker Robert A. , Lehr Claus-Michael , Kalinina Olga V. , Hub Jochen S. 
Published: November 2022

ABSTRACTMolecular dynamics simulations have been widely used to study solute permeation across biological membranes. The potential of mean force (PMF) for solute permeation is typically computed using enhanced sampling techniques such as umbrella sampling (US). For bulky drug-like permeants, however, obtaining converged PMFs remains challenging and often requires long simulation times, resulting in an unacceptable computational cost. Here, we augmented US with simulated tempering, introducing Simulated Tempering-enhanced US (STeUS), to improve the convergence of PMF calculations for the permeation of methanol and three common drug molecules. Simulate tempering helps to enhance sampling by varying the temperature of the system along a pre-defined temperature ladder. To obtain sufficient sampling of the umbrella histograms, which were computed only from the ground temperature, we modified the simulation time fraction spent at the ground temperature between 1/Kand 50%, whereKis the number of ST temperature states. We found that STeUS accelerates convergence compared to standard US, and the benefit of STeUS is system-dependent. For bulky molecules, for which standard US poorly converged, the application of ST was highly successful, leading to a more than five-fold accelerated convergence of the PMFs. For the small methanol solute, for which conventional US converges moderately, the application of ST is only beneficial if 50% of the STeUS simulation time is spent at the ground temperature. This study establishes STeUS as an efficient and simple method for PMF calculations, thereby strongly reducing the computational cost of routine high-throughput studies of drug permeability.
A Microfluidic Device to Simulate the Impact of Gut Microbiome in Cancer
Authors: Mittal Ekansh , Kang Youngbok (Abraham) 
Published: November 2022

AbstractThe gut microbiome has a role in the growth of many diseases such as cancer due to increased inflammation. There is an unmet need to identify novel strategies to investigate the effect of inflammation mediated by gut microbiome on cancer cells. However, there are limited biomimetic co-culture systems that allow to test causal relationship of microbiome on cancer cells. Here we developed a microfluidic chip that can simulate the interaction of the gut microbiome and cancer cells to test the effects of bacteria and inflammatory stress on cancer cells in vitro. To quantify the effect of bacteria on the growth of colorectal cancer cells, we cultured colorectal cancer cell line with Bacillus or lipopolysaccharide (LPS), which is a purified bacterial membrane and induce major inflammatory response, in the PDMS microfluidic device. We found that both LPS and Bacillus significantly accelerate the growth of colorectal cancer cells. These results show that the increased presence of certain bacteria can promote cancer cell growth and that these microfluidic chips can be used to test the specific correlation between bacteria and cancer cell growth. These microfluidic devices can have future implications for various cancer types and to identify treatment strategies.
Identification of variation inFibromelanosisregion on chromosome 20 for determining the purity of Indonesian Cemani chicken
Authors: Dharmayanthi Anik Budhi , Kinoshita Keiji , Khaerunnisa Isyana , Safitry Rona Saumy , Iryanto Syam Budi , Yohanna  , Sutikno  , Lompengeng Ishak Andi Baso , Zein M Syamsul Arifin , Satta Yoko , Akiyama Toyoko , Sumantri Cece 
Published: November 2022

ABSTRACTAyam Cemani is a local Indonesian chicken with heavy pigmentation in plumage colour, skin, eyes, and inner body organs. This trait with dermal hyperpigmentation is identical toFibromelanosis(Fm) mutation in a Silkie chicken. The causal mutation of theFmtrait is due to an inverted duplication and junction of two genomic regions involving the Endothelin3 (EDN3) gene on chromosome 20. There are two duplication boundaries; one is specific to theFmallele, the other is common for bothFmandfm+allele. Determining birds that are homozygous or heterozygous at this locus is useful for unifying theFmtrait of Cemani populations. This study develops a method for determining the presence or absence ofFmmutation by PCR amplification using the inverted sequences specific to theFmallele. Further, it develops the restriction fragment length polymorphism (RFLP) method in regions common to theFmand wild-typefm+allele. We aim to establish a simple method for detecting homozygous (Fm/Fm) and heterozygous (Fm/fm+) individuals withFmmutation and to clarify the degree of fixation of theFmtrait in the Ayam Cemani populations and the association between the phenotype and genotype. The result showed that mostly, the phenotype for Cemani withFm/fm+genotype is reddish black in their comb; meanwhile, the Cemani with (Fm/Fm) genotype showed heavy black pigmentation. Our study concluded that using the PCR-RFLP method. We can discriminate betweenFmhomozygous and heterozygous birds in the Cemani population. Thus, this briefly genotyping method effectively maintains and protects the pure line of Cemani chicken.