bluuebunny/crossref_metadata_2025_split huggingface dataset:
Presence of an EML4-ALK gene fusion detected by microfluidic chip DNA hybridization
Authors: Boparai Montek , Oberc Christopher , Li Paul C H 
Published: January 2021

ABSTRACTNon-small cell lung cancer (NSCLC) accounts for ∼80-85% of all lung cancer cases, and the EML4-ALK fusion oncogene is a well-known contributor to NSCLC cases. Expensive methods such as FISH, IHC, and NGS have been used to detect the EML4-ALK fusion oncogene. Here, a cost-effective and facile method of detecting and differentiating an EML4-ALK fusion oncogene from the wild-type gene has been accomplished by DNA hybridization using the microfluidic biochip. First, oligonucleotide probes were confirmed for successful detection of immobilized sense strands. Second, capture of the sense PCR product strands (fusion and WT) and their subsequent detection and differentiation were accomplished. Our proof-of-concept study shows the ability to detect 1% fusion products, among WT ones.
Development of an itraconazole resistance gene as a dominant selectable marker for transformation in Aspergillus oryzae and Aspergillus luchuensis
Authors: Tokashiki Jikian , Toyama Hirohide , Mizutani Osamu 
Published: January 2021

ABSTRACT
There are only a few combinations of antifungal drugs with known resistance marker genes in the Aspergillus species; therefore, the transformation of their wild-type strains is limited. In this study, to develop the novel dominant selectable marker for itraconazole, a fungal cell membrane synthesis inhibitor, we focused on Aspergillus luchuensis cyp51A (Alcyp51A), which encodes a 14-α-sterol demethylase related to the steroid synthesis pathway. We found that the G52R mutation in AlCyp51A and the replacement of the native promoter with a high-expression promoter contributed to itraconazole resistance in Aspergillus oryzae, designated as itraconazole resistant gene (itrA). The random integration in the A. luchuensis genome of the itrA marker cassette gene also allowed for transformation using itraconazole. Therefore, we succeed in developing a novel itraconazole resistance marker as a dominant selectable marker for transformation in A. oryzae and A. luchuensis.
Well Plate Maker: a user-friendly randomized block design application to limit batch effects in large-scale biomedical studies
Authors: Borges Hélène , Hesse Anne-Marie , Kraut Alexandra , Couté Yohann , Brun Virginie , Burger Thomas 
Published: January 2021

Abstract

Summary
Many factors can influence results in clinical research, in particular bias in the distribution of samples prior to biochemical preparation. Well Plate Maker is a user-friendly application to design single- or multiple-well plate assays. It allows multiple group experiments to be randomized and therefore helps to reduce possible batch effects. Although primarily fathered to optimize the design of clinical sample analysis by high throughput mass spectrometry (e.g. proteomics or metabolomics), it includes multiple options to limit edge-of-plate effects, to incorporate control samples or to limit cross-contamination. It thus fits the constraints of many experimental fields.

Availability and implementation
Well Plate Maker is implemented in R and available at Bioconductor repository (https://bioconductor.org/packages/wpm) under the open source Artistic 2.0 license. In addition to classical scripting, it can be used through a graphical user interface, developed with Shiny technology.
Continual representation learning for evolving biomedical bipartite networks
Authors: Jha Kishlay , Xun Guangxu , Zhang Aidong 
Published: January 2021

Abstract

Motivation
Many real-world biomedical interactions such as ‘gene-disease’, ‘disease-symptom’ and ‘drug-target’ are modeled as a bipartite network structure. Learning meaningful representations for such networks is a fundamental problem in the research area of Network Representation Learning (NRL). NRL approaches aim to translate the network structure into low-dimensional vector representations that are useful to a variety of biomedical applications. Despite significant advances, the existing approaches still have certain limitations. First, a majority of these approaches do not model the unique topological properties of bipartite networks. Consequently, their straightforward application to the bipartite graphs yields unsatisfactory results. Second, the existing approaches typically learn representations from static networks. This is limiting for the biomedical bipartite networks that evolve at a rapid pace, and thus necessitate the development of approaches that can update the representations in an online fashion.

Results
In this research, we propose a novel representation learning approach that accurately preserves the intricate bipartite structure, and efficiently updates the node representations. Specifically, we design a customized autoencoder that captures the proximity relationship between nodes participating in the bipartite bicliques (2 × 2 sub-graph), while preserving both the global and local structures. Moreover, the proposed structure-preserving technique is carefully interleaved with the central tenets of continual machine learning to design an incremental learning strategy that updates the node representations in an online manner. Taken together, the proposed approach produces meaningful representations with high fidelity and computational efficiency. Extensive experiments conducted on several biomedical bipartite networks validate the effectiveness and rationality of the proposed approach.
Accurate haplotype-resolved assembly reveals the origin of structural variants for human trios
Authors: Xu Mengyang , Guo Lidong , Du Xiao , Li Lei , Peters Brock A , Deng Li , Wang Ou , Chen Fang , Wang Jun , Jiang Zhesheng , Han Jinglin , Ni Ming , Yang Huanming , Xu Xun , Liu Xin , Huang Jie , Fan Guangyi 
Published: January 2021

Abstract

Motivation
Achieving a near complete understanding of how the genome of an individual affects the phenotypes of that individual requires deciphering the order of variations along homologous chromosomes in species with diploid genomes. However, true diploid assembly of long-range haplotypes remains challenging.

Results
To address this, we have developed Haplotype-resolved Assembly for Synthetic long reads using a Trio-binning strategy, or HAST, which uses parental information to classify reads into maternal or paternal. Once sorted, these reads are used to independently de novo assemble the parent-specific haplotypes. We applied HAST to cobarcoded second-generation sequencing data from an Asian individual, resulting in a haplotype assembly covering 94.7% of the reference genome with a scaffold N50 longer than 11 Mb. The high haplotyping precision (∼99.7%) and recall (∼95.9%) represents a substantial improvement over the commonly used tool for assembling cobarcoded reads (Supernova), and is comparable to a trio-binning-based third generation long-read-based assembly method (TrioCanu) but with a significantly higher single-base accuracy [up to 99.99997% (Q65)]. This makes HAST a superior tool for accurate haplotyping and future haplotype-based studies.

Availability and implementation
The code of the analysis is available at https://github.com/BGI-Qingdao/HAST

Supplementary information
Supplementary data are available at Bioinformatics online.
Can Genomics Remove Uncertainty from Adoption? Social Workers’ and Medical Advisors’ Accounts of Genetic Testing
Authors: Arribas-Ayllon Michael , Shelton Katherine , Clarke Angus 
Published: January 2021

Abstract
Genetic testing is controversial in adoption with professionals taking different positions on whether children should be protected from genetic information or whether it can be used to assist adoption. In this article, we argue that advances in ‘genome-wide’ testing add further complications to these debates. Although next-generation sequencing (NGS) and microarray-based technologies can offer high-quality molecular diagnoses for a variety of conditions, they also increase the burden of interpretation. For these reasons, adoption professionals will need to understand the relevance and complexity of biomedical information. Our study explores the accounts of social workers’ and medical advisors’ knowledge and reasoning about genetic testing in adoption. Twenty participants, including social workers, managers, medical advisors and paediatricians, were recruited from adoption services in England and Wales. A key finding revealed that medical professionals reported increasing pressure to test children prior to adoption, whilst social workers justified testing on the basis that it reduced uncertainty and therefore assisted adoption. Professionals’ accounts of genetic testing suggest that social workers may not be aware of the potential indeterminacy of microarray and NGS technologies. This has important implications for adoption because increases in genomic uncertainty can stigmatise children and disadvantage their prospects for adoption.
Research End-User Perspectives about Using Social Work Research in Policy and Practice
Authors: Tilbury Clare , Hughes Mark , Bigby Christine , Fisher Mike 
Published: January 2021

Abstract
Research funding and assessment initiatives that foster engagement between researchers and research end-users have been adopted by governments in many countries. They aim to orient research towards achieving measurable impacts that improve economic and social well-being beyond academia. This has long been regarded as important in social work research, as it has in many fields of applied research. This study examined research engagement and impact from the perspective of research end-users working in human services. In-person or telephone interviews were conducted with forty-three research end-users about how they used research and interacted with researchers. Content analysis was undertaken to identify engagement strategies and thematic coding was employed to examine underpinning ideas about research translation into practice. Participants were involved in many types of formal and informal research engagements. They viewed research translation as a mutual responsibility but indicated that researchers should do more to improve the utility of their research for industry. The findings highlight the iterative nature of engagement and impact and raise questions about the infrastructure for scaling up impact beyond relationships between individual researchers and their industry partners.
The Role of Self-efficacy in the Recovery Trajectory of Mental Health Consumers
Authors: Wu Hui-Ching , Yang Chiao-Yu , Chen Yi-Ching 
Published: January 2021

Abstract
This study examined the relative contributions of consumer–provider trust, health care choice, empowerment as well as possible mediation by self-efficacy, to a recovery trajectory model in an Asian collective cultural context. We interviewed 310 adults with severe mental illnesses referred from community rehabilitation centers in Taiwan. They were administered six scales, including the Satisfaction with Services (SS), Quality of Life (QL), Self-Efficacy Scale, Working Alliance Inventory-Short Form, Information and Advice Scale and Personal Empowerment Scale. Quantitative path analysis was used to evaluate the effects of the predictors on the QL and SS. The study revealed a satisfactory model fit. Self-efficacy and trust had significant direct effects and empowerment had a significant indirect effect on subjective QL, while empowerment, health care choices, and trust had significant direct effects on SS. Self-efficacy mediated the influence of empowerment on the QL. In conclusion, SS might be improved by building a trusting relationship, providing information regarding health care choices, and improving consumer empowerment and QL can be improved by strengthening self-efficacy and empowerment. The recovery-promoting competitive model should take cultural characteristics including traditional dependence on authority figures, into consideration in an Asian context.
A CADM3 variant causes Charcot-Marie-Tooth disease with marked upper limb involvement
Authors: Rebelo Adriana P , Cortese Andrea , Abraham Amit , Eshed-Eisenbach Yael , Shner Gal , Vainshtein Anna , Buglo Elena , Camarena Vladimir , Gaidosh Gabriel , Shiekhattar Ramin , Abreu Lisa , Courel Steve , Burns Dennis K , Bai Yunhong , Bacon Chelsea , Feely Shawna M E , Castro Diana , Peles Elior , Reilly Mary M , Shy Michael E , Zuchner Stephan 
Published: January 2021

Abstract
The CADM family of proteins consists of four neuronal specific adhesion molecules (CADM1, CADM2, CADM3 and CADM4) that mediate the direct contact and interaction between axons and glia. In the peripheral nerve, axon-Schwann cell interaction is essential for the structural organization of myelinated fibres and is primarily mediated by the binding of CADM3, expressed in axons, to CADM4, expressed by myelinating Schwann cells. We have identified—by whole exome sequencing—three unrelated families, including one de novo patient, with axonal Charcot-Marie-Tooth disease (CMT2) sharing the same private variant in CADM3, Tyr172Cys. This variant is absent in 230 000 control chromosomes from gnomAD and predicted to be pathogenic. Most CADM3 patients share a similar phenotype consisting of autosomal dominant CMT2 with marked upper limb involvement. High resolution mass spectrometry analysis detected a newly created disulphide bond in the mutant CADM3 potentially modifying the native protein conformation. Our data support a retention of the mutant protein in the endoplasmic reticulum and reduced cell surface expression in vitro. Stochastic optical reconstruction microscopy imaging revealed decreased co-localization of the mutant with CADM4 at intercellular contact sites. Mice carrying the corresponding human mutation (Cadm3Y170C) showed reduced expression of the mutant protein in axons. Cadm3Y170C mice showed normal nerve conduction and myelin morphology, but exhibited abnormal axonal organization, including abnormal distribution of Kv1.2 channels and Caspr along myelinated axons. Our findings indicate the involvement of abnormal axon-glia interaction as a disease-causing mechanism in CMT patients with CADM3 mutations.
Metabolic and Hemodynamic Resting-State Connectivity of the Human Brain: A High-Temporal Resolution Simultaneous BOLD-fMRI and FDG-fPET Multimodality Study
Authors: Jamadar Sharna D , Ward Phillip G D , Liang Emma X , Orchard Edwina R , Chen Zhaolin , Egan Gary F 
Published: January 2021

AbstractSimultaneous [18F]-fluorodeoxyglucose positron emission tomography functional magnetic resonance imaging (FDG-PET/fMRI) provides the capacity to image 2 sources of energetic dynamics in the brain—glucose metabolism and the hemodynamic response. fMRI connectivity has been enormously useful for characterizing interactions between distributed brain networks in humans. Metabolic connectivity based on static FDG-PET has been proposed as a biomarker for neurological disease, but FDG-sPET cannot be used to estimate subject-level measures of “connectivity,” only across-subject “covariance.” Here, we applied high-temporal resolution constant infusion functional positron emission tomography (fPET) to measure subject-level metabolic connectivity simultaneously with fMRI connectivity. fPET metabolic connectivity was characterized by frontoparietal connectivity within and between hemispheres. fPET metabolic connectivity showed moderate similarity with fMRI primarily in superior cortex and frontoparietal regions. Significantly, fPET metabolic connectivity showed little similarity with FDG-sPET metabolic covariance, indicating that metabolic brain connectivity is a nonergodic process whereby individual brain connectivity cannot be inferred from group-level metabolic covariance. Our results highlight the complementary strengths of fPET and fMRI in measuring the intrinsic connectivity of the brain and open up the opportunity for novel fundamental studies of human brain connectivity as well as multimodality biomarkers of neurological diseases.
Developmental Differences Between the Limbic and Neocortical Telencephalic Wall: An Intrasubject Slice-Matched 3 T MRI-Histological Correlative Study in Humans
Authors: Bobić-Rasonja Mihaela , Pogledić Ivana , Mitter Christian , Štajduhar Andrija , Milković-Periša Marija , Trnski Sara , Bettelheim Dieter , Hainfellner Johannes A , Judaš Miloš , Prayer Daniela , Jovanov-Milošević Nataša 
Published: January 2021

Abstract
The purpose of the study was to investigate the interrelation of the signal intensities and thicknesses of the transient developmental zones in the cingulate and neocortical telencephalic wall, using T2-weighted 3 T-magnetic resonance imaging (MRI) and histological scans from the same brain hemisphere. The study encompassed 24 postmortem fetal brains (15–35 postconceptional weeks, PCW). The measurements were performed using Fiji and NDP.view2. We found that T2w MR signal-intensity curves show a specific regional and developmental stage profile already at 15 PCW. The MRI-histological correlation reveals that the subventricular-intermediate zone (SVZ-IZ) contributes the most to the regional differences in the MRI-profile and zone thicknesses, growing by a factor of 2.01 in the cingulate, and 1.78 in the neocortical wall. The interrelations of zone or wall thicknesses, obtained by both methods, disclose a different rate and extent of shrinkage per region (highest in neocortical subplate and SVZ-IZ) and stage (highest in the early second half of fetal development), distorting the zones’ proportion in histological sections. This intrasubject, slice-matched, 3 T correlative MRI-histological study provides important information about regional development of the cortical wall, critical for the design of MRI criteria for prenatal brain monitoring and early detection of cortical or other brain pathologies in human fetuses.
Outcomes of open and endovascular repair of Kommerell diverticulum
Authors: Bloom Jordan P , Attia Rizwan Q , Sundt Thoralf M , Cameron Duke E , Hedgire Sandeep S , Bhatt Ami B , Isselbacher Eric M , Srivastava Sunita D , Kwolek Christopher J , Eagleton Matthew J , Mohebali Jahan , Jassar Arminder S 
Published: January 2021

Abstract

OBJECTIVES
Kommerell diverticulum (KD) is a rare congenital vascular anomaly often associated with an aberrant subclavian artery (ASCA). Definitive indications for intervention remain unclear. We present open and endovascular (EV) operative outcomes in a large contemporary series and propose a management algorithm.

METHODS
Between 2004 and 2020, 224 patients presented with ASCA and associated KD to our institution. Of the 43 (19.2%) patients who underwent operative repair, 31 (72.1%) had open surgical (OS) repair via thoracotomy and 12 (27.9%) had EV repair. Univariable and bivariable statistical analyses were conducted stratified by approach. The median follow-up time was 5.4 years (IQR, 2.9–9.7).

RESULTS
Patients in EV group were older (68 years vs 47 years, P &lt; 0.001) and had larger aneurysms (base diameter 3.2 cm vs 21.5 cm, P = 0.007). All patients with dysphagia lusoria were treated with open surgery (n = 20). Asymptomatic patients with incidentally detected KD (50% vs 16.1%), those with chest or back pain (50% vs 19.4%) and patients who presented with an aortic emergency (25% vs 6.5%) were more likely to be treated endovascularly (P = 0.001). Carotid-to-subclavian bypass was used in 38 (88.4%) patients. There were no operative mortalities. In-hospital mortality was similar between groups (3.2% vs 16.7%, P = 0.121). Mid-term mortality was higher in the EV group [4 (33.8%) vs 0, P &lt; 0.001]. There were 2 (15.4%) postoperative strokes in the EV group. There were no statistically significant differences in other postoperative complications or hospital length of stay between groups.

CONCLUSIONS
KD can be managed using open or EV approaches with low morbidity and mortality. Treatment strategy should depend on clinical presentation and patient factors.
Prevalence of cardiac arrhythmias in cannabis use disorder related hospitalizations in teenagers from 2003 to 2016 in the United States
Authors: Umapathi Krishna Kishore , Thavamani Aravind , Dhanpalreddy Harshitha , Nguyen Hoang H 
Published: January 2021

Abstract

Aims
Cannabis is an increasingly common recreational substance used by teenagers. However, there is limited data probing association of cardiac arrhythmias with marijuana use in this population.

Methods and Results
We provide prevalence trends, disease burden and healthcare utilization of cardiac arrhythmias associated with cannabis use disorder (CUD) in hospitalized teenagers (13–20 years) using a large national administrative database in the United States from 2003–2016. We used partial least square regression analysis for assessing trends in prevalence of cardiac arrhythmias and multiple logistic regression to elucidate independent predictors of arrhythmias associated with CUD. Among all CUD related hospitalizations (n = 876, 431), 0.5% had arrhythmias. Prevalence trends of arrhythmias among CUD increased six-fold during the study period (P &lt; 0.001). CUD was more prevalent in males and older teens (both P &lt; 0.001). There was a significant risk for mortality when CUD was associated with arrhythmia (7.4% vs. 0.1%, P &lt; 0.001). While mean length-of-stay (LOS) was shorter (4.4 vs. 5.4 days, P &lt; 0.001) for patients with CUD, they incurred three times higher mean hospitalization charges when compared to CUD patients without arrhythmia ($45 959 vs. $18 986, P &lt; 0.001). Both LOS and hospitalization charges showed an uptrend during the study period (P &lt; 0.001). Congenital heart disease, congestive heart failure, hypertension, and obesity independently predicted arrhythmias in CUD while other substance abuse did not change the risk of arrhythmia in CUD.

Conclusion
Arrhythmia burden is increasing among teenagers with CUD, and co-occurrence of arrhythmia and CUD worsens hospital outcomes.
Mitochondrial P2X7 Receptor Localization Modulates Energy Metabolism Enhancing Physical Performance
Authors: Sarti Alba Clara , Vultaggio-Poma Valentina , Falzoni Simonetta , Missiroli Sonia , Giuliani Anna Lisa , Boldrini Paola , Bonora Massimo , Faita Francesco , Di Lascio Nicole , Kusmic Claudia , Solini Anna , Novello Salvatore , Morari Michele , Rossato Marco , Wieckowski Mariusz R , Giorgi Carlotta , Pinton Paolo , Di Virgilio Francesco 
Published: January 2021

AbstractBasal expression of the P2X7 receptor (P2X7R) improves mitochondrial metabolism, Adenosine 5′-triphosphate (ATP) synthesis, and overall fitness of immune and non-immune cells. We investigated P2X7R contribution to energy metabolism and subcellular localization in fibroblasts (mouse embryo fibroblasts and HEK293 human fibroblasts), mouse microglia (primary brain microglia, and the N13 microglia cell line), and heart tissue. The P2X7R localizes to mitochondria, and its lack (1) decreases basal respiratory rate, ATP-coupled respiration, maximal uncoupled respiration, resting mitochondrial potential, mitochondrial matrix Ca2+ level, (2) modifies expression pattern of oxidative phosphorylation enzymes, and (3) severely affects cardiac performance. Hearts from P2rx7-deleted versus wild-type mice are larger, heart mitochondria smaller, and stroke volume, ejection fraction, fractional shortening, and cardiac output, are significantly decreased. Accordingly, the physical fitness of P2X7R-null mice is severely reduced. Thus, the P2X7R is a key modulator of mitochondrial energy metabolism and a determinant of physical fitness.