bluuebunny/crossref_metadata_2025_split huggingface dataset:
Resolving an underrepresented circulating tumor cell population in lung cancer enabled by Hexokinase 2 analysis
Authors: Yang Liu , Yan Xiaowei , Chen Jie , Zhan Qiong , Hua Yingqi , Xu Shili , Dong Yu , Li Ziming , Wang Zhuo , Zuo Dongqing , Xue Min , Tang Yin , Herschman Harvey R. , Lu Shun , Shi Qihui , Wei Wei 
Published: April 2020

AbstractUnlike other epithelial cancer types, circulating tumor cells (CTCs) are less frequently detected in the peripheral blood of non-small cell lung cancer (NSCLC) patients using epithelial marker-based detection approaches, despite the aggressive nature of NSCLC. Here we demonstrate hexokinase-2 (HK2) as a metabolic function-associated marker for detection of CTCs, with significantly improved detection rates and high specificity, in 33 NSCLC patients. Use of the HK2 marker identified underrepresented cytokeratin-negative (HK2high/CKneg) CTCs present in many blood samples but rarely detected in pleural effusions or cerebrospinal fluids of NSCLC patients. HK2high/CKnegCTCs exhibited smaller sizes but consistent copy number variation profiles compared to CKposCTCs. Surprisingly, CK expression levels were found to be independent of CTC epithelial-to-mesenchymal transition (EMT) status as measured by single-cell transcriptome profiling, challenging the long-standing association between CK expression and EMT. Our approach improves sensitivity of CTC detection in NSCLC and can potentially resolve a more complete spectrum of CTCs, regardless of their CK expression levels or epithelial traits.
Comprehensive structure-function characterization of DNMT3B and DNMT3A reveals distinctivede novoDNA methylation mechanisms
Authors: Gao Linfeng , Emperle Max , Guo Yiran , Grimm Sara A , Ren Wendan , Adam Sabrina , Uryu Hidetaka , Zhang Zhi-Min , Chen Dongliang , Yin Jiekai , Dukatz Michael , Anteneh Hiwot , Jurkowska Renata Z. , Lu Jiuwei , Wang Yinsheng , Bashtrykov Pavel , Wade Paul A , Wang Gang Greg , Jeltsch Albert , Song Jikui 
Published: April 2020

AbstractMammalian DNA methylation patterns are established by twode novoDNA methyltransferases DNMT3A and DNMT3B, which exhibit both redundant and distinctive methylation activities. However, the related molecular basis remains undetermined. Through comprehensive structural, enzymology and cellular characterization of DNMT3A and DNMT3B, we here report a multi-layered substrate-recognition mechanism underpinning their divergent genomic methylation activities. A hydrogen bond in the catalytic loop of DNMT3B causes a lower CpG specificity than DNMT3A, while the interplay of target recognition domain and homodimeric interface fine-tunes the distinct target selection between the two enzymes, with Lysine 777 of DNMT3B acting as a unique sensor of the +1 flanking base. The divergent substrate preference between DNMT3A and DNMT3B provides an explanation for site-specific epigenomic alterations seen in ICF syndrome with DNMT3B mutations. Together, this study reveals crucial and distinctive substrate-readout mechanisms of the two DNMT3 enzymes, implicative of their differential roles during development and pathogenesis.
A data-driven geospatial workflow to improve mapping species distributions and assessing extinction risk under the IUCN Red List
Authors: Palacio Ruben Dario , Negret Pablo Jose , Velásquez-Tibatá Jorge , Jacobson Andrew P. 
Published: April 2020

ABSTRACTSpecies distribution maps are essential for assessing extinction risk and guiding conservation efforts. Here, we developed a data-driven, reproducible geospatial workflow to map species distributions and evaluate their conservation status consistent with the guidelines and criteria of the IUCN Red List. Our workflow follows five automated steps to refine the distribution of a species starting from its Extent of Occurrence (EOO) to Area of Habitat (AOH) within the species range. The ranges are produced with an Inverse Distance Weighted (IDW) interpolation procedure, using presence and absence points derived from primary biodiversity data. As a case-study, we mapped the distribution of 2,273 bird species in the Americas, 55% of all terrestrial birds found in the region. We then compared our produced species ranges to the expert-drawn IUCN/BirdLife range maps and conducted a preliminary IUCN extinction risk assessment based on criterion B (Geographic Range). We found that our workflow generated ranges with fewer errors of omission, commission, and a better overall accuracy within each species EOO. The spatial overlap between both datasets was low (28%) and the expert-drawn range maps were consistently larger due to errors of commission. Their estimated Area of Habitat (AOH) was also larger for a subset of 741 forest-dependent birds. We found that incorporating geospatial data increased the number of threatened species by 52% in comparison to the 2019 IUCN Red List. Furthermore, 103 species could be placed in threatened categories (VU, EN, CR) pending further assessment. The implementation of our geospatial workflow provides a valuable alternative to increase the transparency and reliability of species risk assessments and improve mapping species distributions for conservation planning and decision-making.
The impact of the Turkish (TK) population variome on the genomic architecture of rare disease traits
Authors: Coban-Akdemir Zeynep , Song Xiaofei , Ceballos Francisco C. , Pehlivan Davut , Karaca Ender , Bayram Yavuz , Mitani Tadahiro , Gambin Tomasz , Yozgatli Tugce Bozkurt , Jhangiani Shalini N. , Muzny Donna M. , Lewis Richard A. ,   Baylor Hopkins Center for Mendelian Genomics, Liu Pengfei , Boerwinkle Eric , Hamosh Ada , Gibbs Richard A. , Sutton V. Reid , Sobreira Nara , Carvalho Claudia M. B. , Shaw Chad A. , Posey Jennifer E. , Valle David , Lupski James R. 
Published: April 2020

ABSTRACTPurposeThe variome of the Turkish (TK) population, a population with a considerable history of admixture and consanguinity, has not been deeply investigated deeply for its potential impact on the genomic architecture of disease traits.MethodsWe generated and analyzed a database of variants derived from exome sequencing (ES) data of 773 TK unrelated, clinically affected individuals with various suspected Mendelian disease traits, and 643 unaffected relatives.ResultsUsing uniform manifold approximation and projection (UMAP), we showed that the TK genomes are more similar to those of Europeans and consist of two main subpopulations: clusters 1 and 2 (N=235 and 1,181) that differ in admixture proportion and variome (https://turkishvariomedb.shinyapps.io/tvdb/). Furthermore, the higher inbreeding coefficient (F) values observed in the TK affected compared to unaffected individuals correlated with a larger median span of long-sized (>2.64 Mb) runs of homozygosity (ROH) regions (p-value=2.09e-18). We show that long-sized ROHs are more likely to be formed on recently configured haplotypes enriched for rare homozygous deleterious variants in the TK-affected compared to TK-unaffected individuals (p-value= 3.35e-11). Analysis of genotype-phenotype correlations reveals that genes with rare homozygous deleterious variants in long-sized ROHs provide the most comprehensive set of molecular diagnoses for the observed disease traits with a systematic quantitative analysis of HPO (Human Phenotype Ontology) terms.ConclusionOur findings support the notion that novel rare variants on newly configured haplotypes arising within the recent past generations of a family or clan contribute significantly to recessive disease traits in the TK population.
Low-coverage sequencing cost-effectively detects known and novel variation in underrepresented populations
Authors: Martin Alicia R. , Atkinson Elizabeth G. , Chapman Sinéad B. , Stevenson Anne , Stroud Rocky E. , Abebe Tamrat , Akena Dickens , Alemayehu Melkam , Ashaba Fred K. , Atwoli Lukoye , Bowers Tera , Chibnik Lori B. , Daly Mark J. , DeSmet Timothy , Dodge Sheila , Fekadu Abebaw , Ferriera Steven , Gelaye Bizu , Gichuru Stella , Injera Wilfred E. , James Roxanne , Kariuki Symon M. , Kigen Gabriel , Koenen Karestan C. , Kwobah Edith , Kyebuzibwa Joseph , Majara Lerato , Musinguzi Henry , Mwema Rehema M. , Neale Benjamin M. , Newman Carter P. , Newton Charles R. J. C. , Pickrell Joseph K. , Ramesar Raj , Shiferaw Welelta , Stein Dan J. , Teferra Solomon , van der Merwe Celia , Zingela Zukiswa ,   NeuroGAP-Psychosis Consortium
Published: April 2020

AbstractBackgroundGenetic studies of biomedical phenotypes in underrepresented populations identify disproportionate numbers of novel associations. However, current genomics infrastructure--including most genotyping arrays and sequenced reference panels--best serves populations of European descent. A critical step for facilitating genetic studies in underrepresented populations is to ensure that genetic technologies accurately capture variation in all populations. Here, we quantify the accuracy of low-coverage sequencing in diverse African populations.ResultsWe sequenced the whole genomes of 91 individuals to high-coverage (≥20X) from the Neuropsychiatric Genetics of African Population-Psychosis (NeuroGAP-Psychosis) study, in which participants were recruited from Ethiopia, Kenya, South Africa, and Uganda. We empirically tested two data generation strategies, GWAS arrays versus low-coverage sequencing, by calculating the concordance of imputed variants from these technologies with those from deep whole genome sequencing data. We show that low-coverage sequencing at a depth of ≥4X captures variants of all frequencies more accurately than all commonly used GWAS arrays investigated and at a comparable cost. Lower depths of sequencing (0.5-1X) performed comparable to commonly used low-density GWAS arrays. Low-coverage sequencing is also sensitive to novel variation, with 4X sequencing detecting 45% of singletons and 95% of common variants identified in high-coverage African whole genomes.ConclusionThese results indicate that low-coverage sequencing approaches surmount the problems induced by the ascertainment of common genotyping arrays, including those that capture variation most common in Europeans and Africans. Low-coverage sequencing effectively identifies novel variation (particularly in underrepresented populations), and presents opportunities to enhance variant discovery at a similar cost to traditional approaches.
Asynchrony between virus diversity and antibody selection limits influenza virus evolution
Authors: Morris Dylan H. , Petrova Velislava N. , Rossine Fernando W. , Parker Edyth , Grenfell Bryan T. , Neher Richard A. , Levin Simon A. , Russell Colin A. 
Published: April 2020

AbstractSeasonal influenza viruses create a persistent global disease burden by evolving to escape immunity induced by prior infections and vaccinations. New antigenic variants have a substantial selective advantage at the population level, but these variants are rarely selected within-host, even in previously immune individuals. Using a mathematical model, we show that the temporal asynchrony between within-host virus exponential growth and antibody-mediated selection could limit within-host antigenic evolution. If selection for new antigenic variants acts principally at the point of initial virus inoculation, where small virus populations encounter well-matched mucosal antibodies in previously infected individuals, there can exist protection against reinfection that does not regularly produce observable new antigenic variants within individual infected hosts. Our results provide a theoretical explanation for how virus antigenic evolution can be highly selective at the global level but nearly neutral within host. They also suggest new avenues for improving influenza control.
Topologically correct synthetic reconstruction of pathogen social behavior found in deep tissue sites
Authors: Clark Stacie A. , Thibault Derek , Shull Lauren M. , Davis Kimberly M. , Aunins Emily , van Opijnen Tim , Isberg Ralph R. 
Published: April 2020

AbstractWithin deep tissue sites, extracellular bacterial pathogens often replicate in clusters that are surrounded by immune cells. Disease is modulated by interbacterial interactions as well as bacterial-host cell interactions resulting in microbial growth, phagocytic attack and secretion of host antimicrobial factors. To overcome the limited ability to manipulate these infection sites, we established a system forYersinia pseudotuberculosis(Yptb)growth in microfluidics-driven microdroplets that regenerates microbial social behavior in tissues. Chemical generation of nitric oxide (NO) in the absence of immune cells was sufficient to reconstruct microbial social behavior, as witnessed by expression of the NO-inactivating protein Hmp on the extreme periphery of microcolonies, mimicking spatial regulation in tissues. Similarly, activated macrophages that expressed inducible NO synthase (iNOS) drove peripheral expression of Hmp, allowing regeneration of social behavior observed in tissues. These results argue that topologically correct microbial tissue growth and associated social behavior can be reconstructed in culture.
The effects of high-altitude windborne migration on survival, oviposition and blood-feeding of the African malaria mosquito,Anopheles gambiaes.l
Authors: Sanogo ZL , Yaro AS , Dao A , Diallo M , Yossi O , Samaké D , Krajacich BJ , Faiman R , Lehmann T 
Published: April 2020

AbstractRecent results of high-altitude windborne mosquito migration raised questions about the viability of these mosquitoes despite ample evidence that many insect species, including other dipterans have been known to migrate regularly over tens or hundreds of kilometers on high-altitude winds and retain their viability. To address these concerns, we subjected wildAn. gambiaes.l. mosquitoes to a high-altitude survival assay, followed by oviposition (egg laying) and blood feeding assays. Despite carrying out the survival assay under exceptionally harsh conditions that probably provide the lowest survival potential following high altitude flight, a high proportion of the mosquitoes survived for six and even eleven hours assay durations at 120-250m altitudes. Minimal differences in egg laying success were noted between mosquitoes exposed to high altitude survival assay and those kept near the ground. Similarly, minimal differences were found in the female’s ability to take an additional blood meal after oviposition between these groups. We conclude that similar to other high-altitude migrating insects, mosquitoes are able to withstand extended high-altitude flight and subsequently reproduce and transmit pathogens by blood feeding on new hosts.
Eccentric-focused rehabilitation promotes myelin plasticity in individuals with chronic, incomplete spinal cord injury
Authors: Faw Timothy D. , Lakhani Bimal , Liu Hanwen , Nguyen Huyen T. , Schmalbrock Petra , Knopp Michael V. , Lohse Keith R. , Kramer John L.K. , McTigue Dana M. , Boyd Lara A. , Basso D. Michele 
Published: April 2020

AbstractBackgroundMyelin plasticity has emerged as a novel mechanism by which the nervous system can change with experience, offering new potential for rehabilitation-induced recovery after neurotrauma. This first-in-human study investigated whether innovative, downhill locomotor rehabilitation promotes myelin plasticity in individuals with chronic, incomplete spinal cord injury (SCI).MethodsOf 20 individuals with SCI that enrolled, 4 passed the imaging screen and had myelin water imaging (MWI) before and after a 12-week (3 times/week) downhill locomotor treadmill training program (SCI+DH). One individual was excluded for imaging artifacts. Uninjured control participants (n=7) had two MWI sessions within the same day. Changes in myelin water fraction (MWF), a histopathologically-validated myelin biomarker, were analyzed ina priorimotor learning and non-motor learning brain regions and the cervical spinal cord using statistical approaches appropriate for small sample sizes.ResultsWithin SCI+DH individuals, significantly more motor learning regions showed increased MWF than non-motor learning regions (p<.05). Compared to Control, MWF in the SCI+DH group increased in white matter underlying postcentral and precuneus cortices, combined motor learning brain regions, and ventral spinal cord (p<.05). To account for small sample size, an estimation-based approach showed the pattern of MWF increase was specific to training and region.ConclusionDownhill training increased MWF in brain regions specifically associated with motor learning and in the ventral spinal cord.Trial RegistrationClincialTrials.gov(NCT02498548,NCT02821845)FundingNational Institutes of Health [F31NS096921 (TDF), R21HD082808 (DMB)], Craig H. Neilsen Foundation [316282 (DMB)], Foundation for Physical Therapy Research [Promotion of Doctoral Studies Level II Scholarship (TDF)]
The natural history and transmission potential of asymptomatic SARS-CoV-2 infection
Authors: Van Vinh Chau Nguyen , Lam Vo Thanh , Dung Nguyen Thanh , Yen Lam Minh , Minh Ngo Ngoc Quang , Hung Le Manh , Ngoc Nghiem My , Dung Nguyen Tri , Man Dinh Nguyen Huy , Nguyet Lam Anh , Nhat Le Thanh Hoang , Nhu Le Nguyen Truc , Ny Nguyen Thi Han , Hong Nguyen Thi Thu , Kestelyn Evelyne , Dung Nguyen Thi Phuong , Xuan Tran Chanh , Hien Tran Tinh , Phong Nguyen Thanh , Tu Tran Nguyen Hoang , Geskus Ronald B. , Thanh Tran Tan , Truong Nguyen Thanh , Binh Nguyen Tan , Thuong Tang Chi , Thwaites Guy , Van Tan Le ,   for OUCRU COVID-19 research group
Published: April 2020

ABSTRACTBackgroundLittle is known about the natural history of asymptomatic SARS-CoV-2 infection or its contribution to infection transmission.MethodsWe conducted a prospective study at a quarantine centre for COVID-19 in Ho Chi Minh City, Vietnam. We enrolled quarantined people with RT-PCR-confirmed SARS-CoV-2 infection, collecting clinical data, travel and contact history, and saliva at enrolment and daily nasopharyngeal throat swabs (NTS) for RT-PCR testing. We compared the natural history and transmission potential of asymptomatic and symptomatic individuals.ResultsBetween March 10th and April 4th, 2020, 14,000 quarantined people were tested for SARS-CoV-2; 49 were positive. Of these, 30 participated in the study: 13(43%) never had symptoms and 17(57%) were symptomatic. 17(57%) participants acquired their infection outside Vietnam. Compared with symptomatic individuals, asymptomatic people were less likely to have detectable SARS-CoV-2 in NTS samples collected at enrolment (8/13 (62%) vs. 17/17 (100%) P=0.02). SARS-CoV-2 RNA was detected in 20/27 (74%) available saliva; 7/11 (64%) in the asymptomatic and 13/16 (81%) in the symptomatic group (P=0.56). Analysis of the probability of RT-PCR positivity showed asymptomatic participants had faster viral clearance than symptomatic participants (P<0.001 for difference over first 19 days). This difference was most pronounced during the first week of follow-up. Two of the asymptomatic individuals appeared to transmit the infection to up to four contacts.ConclusionsAsymptomatic SARS-CoV-2 infection is common and can be detected by analysis of saliva or NTS. NTS viral loads fall faster in asymptomatic individuals, but they appear able to transmit the virus to others.
ArchR: An integrative and scalable software package for single-cell chromatin accessibility analysis
Authors: Granja Jeffrey M. , Corces M. Ryan , Pierce Sarah E. , Bagdatli S. Tansu , Choudhry Hani , Chang Howard Y. , Greenleaf William J. 
Published: April 2020

ABSTRACTThe advent of large-scale single-cell chromatin accessibility profiling has accelerated our ability to map gene regulatory landscapes, but has outpaced the development of robust, scalable software to rapidly extract biological meaning from these data. Here we present a software suite for single-cellanalysis of regulatorychromatin inR(ArchR;www.ArchRProject.com) that enables fast and comprehensive analysis of single-cell chromatin accessibility data. ArchR provides an intuitive, user-focused interface for complex single-cell analyses including doublet removal, single-cell clustering and cell type identification, robust peak set generation, cellular trajectory identification, DNA element to gene linkage, transcription factor footprinting, mRNA expression level prediction from chromatin accessibility, and multi-omic integration with scRNA-seq. Enabling the analysis of over 1.2 million single cells within 8 hours on a standard Unix laptop, ArchR is a comprehensive analytical suite for end-to-end analysis of single-cell chromatin accessibility data that will accelerate the understanding of gene regulation at the resolution of individual cells.
Frequency of Hepatitis B, C and HIV infections among transfusion-dependent Beta Thalassemia patients in Dhaka
Authors: Bhuyan Golam Sarower , Zaman Noor Aftab Uz , Sultana Rosy , Noor Farjana Akther , Sultana Nusrat , Sarker Suprovath Kumar , Islam Md Tarikul , Sayeed Md. Abu , Ul Khabir Md. Imam , Hossain A K M Ekramul , Qadri Syeda Kashfi , Qadri Syed Saleheen , Qadri Firdausi , Mannoor Kaiissar 
Published: April 2020

AbstractTransfusion transmitted infections (TTIs) have remained a major deterrent to public health, particularly among the patients with transfusion-dependent Beta thalassemia in developing countries. Although proper donor selection through adoption of WHO-advised infection panel has lowered the rate of infections, the multi-transfused patients are not free of risk. The present study screened 148 transfusion-dependent Beta thalassemia patients to determine the frequency of HCV, HBV and HIV using ELISA method. Among these patients, infected cases with HCV, HBV and HIV were 13.51%, 3.37% and 0%, respectively. Moreover, 2% of the patients had co-infections with both HBV and HCV. The percentage of infections in the patients with frequent transfusion interval (≤30 days) was significantly higher (P<0.0005) than that in the patients with less frequent transfusion intervals (>30 days). Immunochromatography (ICT)-based rapid test kits are usually used to screen and confirm these infections in the blood of the patients. However, ICT-based tests are not sensitive enough to detect the infections. So, a combination of both Nucleic Acid testing (NAT) and serological testing are suggested to significantly reduce the risk of viral infections during blood transfusion.
Trust and commitment as mediators between economic and non-economic satisfaction in business relationships: a sales perspective
Authors: Høgevold Nils , Svensson Goran , Otero-Neira Carmen 
Published: April 2020

Purpose
This paper aims to test trust and commitment as mediators between economic and non-economic satisfaction in seller business relationships in contrast to previous studies on buyer business relationships.

Design/methodology/approach
Based on a cross-industry sample of Norwegian companies with sales or marketing managers/directors or key account managers. Key informants were selected to participate who adhered to specific criteria, such as their designations should be sales or marketing managers/directors or key account managers.

Findings
Trust and commitment mediate between economic and non-economic satisfaction in seller business relationships in line with what has been previously tested and retested across contexts and through time in buyer business relationships.

Research limitations/implications
This study helps in establishing an extended foundation to assess the structural properties between economic and non-economic satisfaction, as well as trust and commitment, in business relationships based on seller and or buyer perspectives.

Practical implications
The tested seller business relationship research model provides a corporate foundation for assessing the seller perspective of business relationships. It also provides a corporate foundation for combining the seller perspective with that of the customer perspective.

Originality/value
To the best of the authors’ knowledge, it is the first study based on seller business relationships that validates the research model reported in multiple previous studies based on buyer business relationships.