bluuebunny/crossref_metadata_2025_split huggingface dataset:
Establishing a Framework for the Clinical Translation of Germline Findings in Precision Oncology
Authors: Dixon Katherine , Young Sean , Shen Yaoqing , Thibodeau My Linh , Fok Alexandra , Pleasance Erin , Zhao Eric , Jones Martin , Aubert Geraldine , Armstrong Linlea , Virani Alice , Regier Dean , Gelmon Karen , Renouf Dan , Chia Stephen , Bosdet Ian , Rassekh S Rod , Deyell Rebecca J , Yip Stephen , Fisic Ana , Titmuss Emma , Abadi Shirin , Jones Steven J M , Sun Sophie , Karsan Aly , Marra Marco , Laskin Janessa , Lim Howard , Schrader Kasmintan A 
Published: May 2020

Abstract
Inherited genetic variation has important implications for cancer screening, early diagnosis, and disease prognosis. A role for germline variation has also been described in shaping the molecular landscape, immune response, microenvironment, and treatment response of individual tumors. However, there is a lack of consensus on the handling and analysis of germline information that extends beyond known or suspected cancer susceptibility in large-scale cancer genomics initiatives. As part of the Personalized OncoGenomics program in British Columbia, we performed whole-genome and transcriptome sequencing in paired tumor and normal tissues from advanced cancer patients to characterize the molecular tumor landscape and identify putative targets for therapy. Overall, our experience supports a multidisciplinary and integrative approach to germline data management. This includes a need for broader definitions and standardized recommendations regarding primary and secondary germline findings in precision oncology. Here, we propose a framework for identifying, evaluating, and returning germline variants of potential clinical significance that may have indications for health management beyond cancer risk reduction or prevention in patients and their families.
Genetic basis of phenotypic plasticity and genotype × environment interactions in a multi-parental tomato population
Authors: Diouf Isidore , Derivot Laurent , Koussevitzky Shai , Carretero Yolande , Bitton Frédérique , Moreau Laurence , Causse Mathilde 
Published: May 2020

AbstractDeciphering the genetic basis of phenotypic plasticity and genotype × environment interactions (G×E) is of primary importance for plant breeding in the context of global climate change. Tomato (Solanum lycopersicum) is a widely cultivated crop that can grow in different geographical habitats and that displays a great capacity for expressing phenotypic plasticity. We used a multi-parental advanced generation intercross (MAGIC) tomato population to explore G×E and plasticity for multiple traits measured in a multi-environment trial (MET) comprising optimal cultural conditions together with water deficit, salinity, and heat stress over 12 environments. Substantial G×E was observed for all the traits measured. Different plasticity parameters were estimated by employing Finlay–Wilkinson and factorial regression models and these were used together with genotypic means for quantitative trait loci (QTL) mapping analyses. In addition, mixed linear models were also used to investigate the presence of QTL × environment interactions. The results highlighted a complex genetic architecture of tomato plasticity and G×E. Candidate genes that might be involved in the occurrence of G×E are proposed, paving the way for functional characterization of stress response genes in tomato and for breeding climate-adapted cultivars.
Phen2Gene: rapid phenotype-driven gene prioritization for rare diseases
Authors: Zhao Mengge , Havrilla James M , Fang Li , Chen Ying , Peng Jacqueline , Liu Cong , Wu Chao , Sarmady Mahdi , Botas Pablo , Isla Julián , Lyon Gholson J , Weng Chunhua , Wang Kai 
Published: May 2020

Abstract
Human Phenotype Ontology (HPO) terms are increasingly used in diagnostic settings to aid in the characterization of patient phenotypes. The HPO annotation database is updated frequently and can provide detailed phenotype knowledge on various human diseases, and many HPO terms are now mapped to candidate causal genes with binary relationships. To further improve the genetic diagnosis of rare diseases, we incorporated these HPO annotations, gene–disease databases and gene–gene databases in a probabilistic model to build a novel HPO-driven gene prioritization tool, Phen2Gene. Phen2Gene accesses a database built upon this information called the HPO2Gene Knowledgebase (H2GKB), which provides weighted and ranked gene lists for every HPO term. Phen2Gene is then able to access the H2GKB for patient-specific lists of HPO terms or PhenoPacket descriptions supported by GA4GH (http://phenopackets.org/), calculate a prioritized gene list based on a probabilistic model and output gene–disease relationships with great accuracy. Phen2Gene outperforms existing gene prioritization tools in speed and acts as a real-time phenotype-driven gene prioritization tool to aid the clinical diagnosis of rare undiagnosed diseases. In addition to a command line tool released under the MIT license (https://github.com/WGLab/Phen2Gene), we also developed a web server and web service (https://phen2gene.wglab.org/) for running the tool via web interface or RESTful API queries. Finally, we have curated a large amount of benchmarking data for phenotype-to-gene tools involving 197 patients across 76 scientific articles and 85 patients’ de-identified HPO term data from the Children’s Hospital of Philadelphia.
Where are G-quadruplexes located in the human transcriptome?
Authors: Vannutelli Anaïs , Belhamiti Sarah , Garant Jean-Michel , Ouangraoua Aida , Perreault Jean-Pierre 
Published: May 2020

AbstractIt has been demonstrated that RNA G-quadruplexes (G4) are structural motifs present in transcriptomes and play important regulatory roles in several post-transcriptional mechanisms. However, the full picture of RNA G4 locations and the extent of their implication remain elusive. Solely computational prediction analysis of the whole transcriptome may reveal all potential G4, since experimental identifications are always limited to specific conditions or specific cell lines. The present study reports the first in-depth computational prediction of potential G4 region across the complete human transcriptome. Although using a relatively stringent approach based on three prediction scores that accounts for the composition of G4 sequences, the composition of their neighboring sequences, and the various forms of G4, over 1.1 million of potential G4 (pG4) were predicted. The abundance of G4 was computationally confirmed in both 5′ and 3′UTR as well as splicing junction of mRNA, appreciate for the first time in the long ncRNA, while almost absent of most of the small ncRNA families. The present results constitute an important step toward a full understanding of the roles of G4 in post-transcriptional mechanisms.
CRISPRi-mediated functional analysis of lung disease-associated loci at non-coding regions
Authors: Stuart William D , Guo Minzhe , Fink-Baldauf Iris M , Coleman Alan M , Clancy John P , Mall Marcus A , Lim Foong-Yen , Brewington John J , Maeda Yutaka 
Published: May 2020

AbstractGenome-wide association studies have identified lung disease-associated loci; however, the functions of such loci are not well understood in part because the majority of such loci are located at non-coding regions. Hi-C, ChIP-seq and eQTL data predict potential roles (e.g. enhancer) of such loci; however, they do not elucidate the molecular function. To determine whether these loci function as gene-regulatory regions, CRISPR interference (CRISPRi; CRISPR/dCas9-KRAB) has been recently used. Here, we applied CRISPRi along with Hi-C, ChIP-seq and eQTL to determine the functional roles of loci established as highly associated with asthma, cystic fibrosis (CF), chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF). Notably, Hi-C, ChIP-seq and eQTL predicted that non-coding regions located at chromosome 19q13 or chromosome 17q21 harboring single-nucleotide polymorphisms (SNPs) linked to asthma/CF/COPD and chromosome 11p15 harboring an SNP linked to IPF interact with nearby genes and function as enhancers; however, CRISPRi indicated that the regions with rs1800469, rs2241712, rs12603332 and rs35705950, but not others, regulate the expression of nearby genes (single or multiple genes). These data indicate that CRISPRi is useful to precisely determine the roles of non-coding regions harboring lung disease-associated loci as to whether they function as gene-regulatory regions at a genomic level.
Deep soft K-means clustering with self-training for single-cell RNA sequence data
Authors: Chen Liang , Wang Weinan , Zhai Yuyao , Deng Minghua 
Published: May 2020

Abstract
Single-cell RNA sequencing (scRNA-seq) allows researchers to study cell heterogeneity at the cellular level. A crucial step in analyzing scRNA-seq data is to cluster cells into subpopulations to facilitate subsequent downstream analysis. However, frequent dropout events and increasing size of scRNA-seq data make clustering such high-dimensional, sparse and massive transcriptional expression profiles challenging. Although some existing deep learning-based clustering algorithms for single cells combine dimensionality reduction with clustering, they either ignore the distance and affinity constraints between similar cells or make some additional latent space assumptions like mixture Gaussian distribution, failing to learn cluster-friendly low-dimensional space. Therefore, in this paper, we combine the deep learning technique with the use of a denoising autoencoder to characterize scRNA-seq data while propose a soft self-training K-means algorithm to cluster the cell population in the learned latent space. The self-training procedure can effectively aggregate the similar cells and pursue more cluster-friendly latent space. Our method, called ‘scziDesk’, alternately performs data compression, data reconstruction and soft clustering iteratively, and the results exhibit excellent compatibility and robustness in both simulated and real data. Moreover, our proposed method has perfect scalability in line with cell size on large-scale datasets.
Simultaneous changes in seed size, oil content and protein content driven by selection of SWEET homologues during soybean domestication
Authors: Wang Shoudong , Liu Shulin , Wang Jie , Yokosho Kengo , Zhou Bin , Yu Ya-Chi , Liu Zhi , Frommer Wolf B , Ma Jian Feng , Chen Li-Qing , Guan Yuefeng , Shou Huixia , Tian Zhixi 
Published: May 2020

Abstract
Soybean accounts for more than half of the global production of oilseed and more than a quarter of the protein used globally for human food and animal feed. Soybean domestication involved parallel increases in seed size and oil content, and a concomitant decrease in protein content. However, science has not yet discovered whether these effects were due to selective pressure on a single gene or multiple genes. Here, re-sequencing data from &gt;800 genotypes revealed a strong selection during soybean domestication on GmSWEET10a. The selection of GmSWEET10a conferred simultaneous increases in soybean-seed size and oil content as well as a reduction in the protein content. The result was validated using both near-isogenic lines carrying substitution of haplotype chromosomal segments and transgenic soybeans. Moreover, GmSWEET10b was found to be functionally redundant with its homologue GmSWEET10a and to be undergoing selection in current breeding, leading the the elite allele GmSWEET10b, a potential target for present-day soybean breeding. Both GmSWEET10a and GmSWEET10b were shown to transport sucrose and hexose, contributing to sugar allocation from seed coat to embryo, which consequently determines oil and protein contents and seed size in soybean. We conclude that past selection of optimal GmSWEET10a alleles drove the initial domestication of multiple soybean-seed traits and that targeted selection of the elite allele GmSWEET10b may further improve the yield and seed quality of modern soybean cultivars.
Access Through the Anatomical Snuffbox for Neuroendovascular Procedures: A Single Institution Series
Authors: Weinberg Joshua H , Sweid Ahmad , Khanna Omaditya , Mouchtouris Nikolaos , Asada Ashlee , Das Somnath , Curtis Darcy , Kim Julie , Romo Victor , Gooch Michael Reid , Herial Nabeel , Tjoumakaris Stavropoula , Zarzour Hekmat , Rosenwasser Robert H , Jabbour Pascal 
Published: May 2020

Abstract

BACKGROUND
Distal transradial catheterization in the anatomic snuffbox is an alternate route of access that has started to gain consideration for neuroendovascular procedures.

OBJECTIVE
To assess the feasibility and outcomes and present our institution's experience in performing neuroendovascular procedures via distal transradial access (dTRA).

METHODS
We conducted a retrospective analysis and identified 120 patients who underwent consecutive neuroendovascular procedures via dTRA in the anatomic snuffbox. Data collection was performed on indication for procedure, sheath size, number of vessels selectively catheterized, fluoroscopy time, procedure duration, radiation exposure, conversion to femoral approach, access site complication, and procedure success.

RESULTS
Of 120 patients with an average age of 54.7 yr ± 14.7, 73 (60.8%) underwent diagnostic angiograms, 38 (31.7%) underwent follow-up angiograms, and 9 (7.5%) underwent therapeutic procedures. The overall mean number of vessels catheterized was 2.5 ± 0.1 per procedure, the mean procedure time was 68.3 min ± 43.4, the mean fluoroscopy time was 10.8 min ± 7.6, the mean contrast dose was 70.6 mL ± 39.1, and the mean radiation exposure was 27 672.2 mGycm2 ± 42 728.4. Successfully completed therapeutic procedures included aneurysm 1 (0.8%), arteriovenous malformation (AVM)/arteriovenous fistula/carotid cavernous fistula 7 (5.8%), and 1 (0.8%) other treatment. Three patients (2.5%) required adjunct transfemoral endovenous access for AVM embolization. Two minor complications (1.67%) were a local wrist hematoma and a radial artery vasospasm without any sequelae.

CONCLUSION
Distal radial artery catheterization in the anatomic snuffbox is a safe and effective access site to perform neuroendovascular procedures. Complications and conversion rate are low making it a safe alternative.
Triggered high-mass star formation in the H iiregion W 28 A2: A cloud–cloud collision scenario
Authors: Hayashi Katsuhiro , Yoshiike Satoshi , Enokiya Rei , Fujita Shinji , Yamada Rin , Sano Hidetoshi , Torii Kazufumi , Kohno Mikito , Nishimura Atsushi , Ohama Akio , Yamamoto Hiroaki , Tachihara Kengo , Wong Graeme , Maxted Nigel , Braiding Catherine , Rowell Gavin , Burton Michael , Fukui Yasuo 
Published: May 2020

AbstractWe report on a study of the high-mass star formation in the H ii region W 28 A2 by investigating the molecular clouds that extend over ∼5–10 pc from the exciting stars using the 12CO and 13CO (J = 1–0) and 12CO (J = 2–1) data taken by NANTEN2 and Mopra observations. These molecular clouds consist of three velocity components with CO intensity peaks at VLSR ∼ −4 km s−1, 9 km s−1, and 16 km s−1. The highest CO intensity is detected at VLSR ∼ 9 km s−1, where the high-mass stars with spectral types O6.5–B0.5 are embedded. We found bridging features connecting these clouds toward the directions of the exciting sources. Comparisons of the gas distributions with the radio continuum emission and 8 μm infrared emission show spatial coincidence/anti-coincidence, suggesting physical associations between the gas and the exciting sources. The 12CO J = 2–1 to 1–0 intensity ratio shows a high value (≳0.8) toward the exciting sources for the −4 km s−1 and +9 km s−1 clouds, possibly due to heating by the high-mass stars, whereas the intensity ratio at the CO intensity peak (VLSR ∼ 9 km s−1) decreases to ∼0.6, suggesting self absorption by the dense gas in the near side of the +9 km s−1 cloud. We found partly complementary gas distributions between the −4 km s−1 and +9 km s−1 clouds, and the −4 km s−1 and +16 km s−1 clouds. The exciting sources are located toward the overlapping region in the −4 km s−1 and +9 km s−1 clouds. Similar gas properties are found in the Galactic massive star clusters RCW 38 and NGC 6334, where an early stage of cloud collision to trigger the star formation is suggested. Based on these results, we discuss the possibility of the formation of high-mass stars in the W 28 A2 region being triggered by cloud–cloud collision.
Peripheral Nerve Stimulation for the 21st Century: Sural, Superficial Peroneal, and Tibial Nerves
Authors: Hanyu-Deutmeyer Aaron , Pritzlaff Scott G 
Published: May 2020

Abstract

Objective
Peripheral nerve stimulation (PNS) of the lower extremity has progressed significantly over the last decade. From the proof of concept that ultrasound-guided, percutaneous implantation was possible to advances in waveforms, the field has been rapidly evolving. While most nerves in the lower extremity can be PNS targets, consideration must be given to the ergonomics of pulse generator placement, patient comfort, and avoidance of lead migration. For this paper, we examine some of the conditions amenable to lower extremity PNS, review the evidence and history behind PNS for these conditions, and describe approaches for the tibial, sural, and superficial peroneal nerves.

Methods
A literature search was conducted using PubMed. Search terms used were “peripheral nerve stimulation,” “lower extremity entrapment neuropathies,” “sural nerve,” “superficial peroneal nerve,” “tibial nerve,” and “tarsal tunnel syndrome.” Emphasis was placed on randomized controlled studies, anatomical dissections, and comprehensive review articles. Approaches to nerves and ultrasound images were based on anecdotal PNS cases from an experienced implanter (SP).

Conclusions
The development of ultrasound as a viable method of image guidance for percutaneous peripheral nerve stimulation has led to an exponential growth in the field. Lower extremity percutaneous lead placement is both feasible and an appropriate treatment modality for certain pain conditions.
MEASUREMENT AND ANALYSIS OF THE NEUTRON ENERGY SPECTRUM AND ASSOCIATED OCCUPATIONAL EXPOSURE FROM A SHIELDED241AM-BE SOURCE
Authors: Stringer Jimmy Steele , Spitz Henry , Glover Samuel 
Published: May 2020

Abstract
A set of five Bonner spheres was used to measure the ambient neutron H*(10) dose around an orphan 241Am-Be neutron source shielded with different arrangements and types of neutron-absorbing materials. These results were compared to measurements obtained using a portable radiation dosemeter. The Bonner sphere measurement results identified the presence of a large thermal and intermediate neutron component from the shielded 241Am-Be source that was not revealed using the portable instrument.
Hallucinations in Older Adults: A Practical Review
Authors: Badcock Johanna C , Larøi Frank , Kamp Karina , Kelsall-Foreman India , Bucks Romola S , Weinborn Michael , Begemann Marieke , Taylor John-Paul , Collerton Daniel , O’Brien John T , El Haj Mohamad , Ffytche Dominic , Sommer Iris E 
Published: May 2020

AbstractOlder adults experience hallucinations in a variety of social, physical, and mental health contexts. Not everyone is open about these experiences, as hallucinations are surrounded with stigma. Hence, hallucinatory experiences in older individuals are often under-recognized. They are also commonly misunderstood by service providers, suggesting that there is significant scope for improvement in the training and practice of professionals working with this age group. The aim of the present article is to increase knowledge about hallucinations in older adults and provide a practical resource for the health and aged-care workforce. Specifically, we provide a concise narrative review and critique of (1) workforce competency and training issues, (2) assessment tools, and (3) current treatments and management guidelines. We conclude with a brief summary including suggestions for service and training providers and future research.
Brief Report: Hormonal Contraception Use and Cabotegravir Pharmacokinetics in HIV-Uninfected Women Enrolled in HPTN 077
Authors: Blair Cheríe S. , Li Sue , Chau Gordon , Cottle Leslie , Richardson Paul , Marzinke Mark A. , Eshleman Susan H. , Adeyeye Adeola , Rinehart Alex R. , Margolis David , McCauley Marybeth , Hendrix Craig W. , Landovitz Raphael J. ,   on behalf of the HPTN 077 Study Team
Published: May 2020

Objectives:
To evaluate whether hormonal contraceptive use among cisgender women is associated with differences in pharmacokinetic (PK) parameters of a long-acting injectable formulation of the integrase strand transfer inhibitor, cabotegravir (CAB-LA).

Setting:
This is a secondary analysis of 85 cisgender women enrolled in HPTN 077, a phase 2a multicenter study that enrolled HIV-uninfected, low-risk individuals in Malawi, Brazil, South Africa, and the United States.

Methods:
Participants received 4-week daily oral cabotegravir lead-in, followed by CAB-LA 800 mg injection every 12 weeks (cohort 1) or 600 mg every 8 weeks (after 4-week initial interval between injections, cohort 2), over 41 weeks. Participants were followed 52–76 weeks subsequent to final injection. Generalized estimating equations and linear regression were used to evaluate differences in CAB-LA PK parameters (peak concentration, trough concentration, area under the curve, apparent terminal half-life, and time to lower limit of quantification) and self-reported hormonal contraceptive stratified by type (oral, injectable, implants, and other), controlling for body mass index and cohort.

Results:
Compared to women reporting no hormonal contraception (n = 6), oral contraceptive use (n = 18) was associated with lower CAB-LA peak concentration but was not associated with differences in other PK parameters. No other hormonal contraceptive type (injectable, implants, and other) was associated with significant differences in CAB-LA PK parameters.

Conclusion:
Although oral contraceptive use was associated with differences in CAB-LA peak concentration, no differences were observed in other PK parameters, suggesting that this association is not likely to be clinically significant. However, these data highlight the need for further research exploring potential drug–drug interactions between CAB-LA and hormonal contraceptives.
Can a herd immunity strategy become a viable option against COVID-19? A model-based analysis on social acceptability and feasibility
Authors: Akamatsu Takashi , Nagae Takeshi , Osawa Minoru , Satsukawa Koki , Sakai Takara , Mizutani Daijiro 
Published: May 2020

AbstractThis paper studies the social acceptability and feasibility of “herd immunity” strategies against coronavirus disease 2019 (COVID-19). To this end, we propose a control scheme that aims to develop herd immunity while satisfying the following two basic requirements for a viable policy option. The first requirement is social acceptability: the overall deaths should be minimized for social acceptance. The second is feasibility: the healthcare system should not be overwhelmed to avoid diverse adverse effects. Exploiting the fact that the severity of the disease increases considerably with age, the proposed control scheme protects high-risk individuals that mainly consist of the elderly. The protection of high-risk individuals reduces the average severity of the disease in the unprotected population, thereby substantially reducing mortality and avoiding the collapse of the healthcare system. Social acceptability (in terms of the resulting mortality) and feasibility (in terms of the healthcare system capacity) of the proposed herd immunity strategy are summarized into two respective, easily computable conditions by building on a simple susceptible–infected–recovered (SIR) model. For its parsimony, the proposed framework can provide a rule of thumb that applies to various populations for studying the viability of herd immunity strategies against COVID-19. For Japan, herd immunity may be developed by the considered control scheme ifand the severity rates of the disease are 1/10 times smaller than the previously reported value, although as high mortality as seasonal influenza is expected.