bluuebunny/crossref_metadata_2025_split huggingface dataset:
Xpert MTB/XDR: A ten-color reflex assay suitable for point of care settings to detect isoniazid-, fluoroquinolone-, and second line injectable drug-resistance directly fromMycobacterium tuberculosispositive sputum
Authors: Cao Yuan , Parmar Heta , Gaur Rajiv L. , Lieu Deanna , Raghunath Shobana , Via Nova , Battagalia Simone , Cirillo Daniela M. , Denkinger Claudia , Georghiou Sophia , Kwiatkowski Robert , Persing David , Alland David , Chakravorty Soumitesh 
Published: September 2020

AbstractWe describe the design, development, analytical performance and a limited clinical evaluation of the 10-color Xpert MTB/XDR assay (CE-IVD only, not for sale in the US). This assay is intended as a reflex test to detect resistance to Isoniazid (INH), Fluoroquinolones (FLQ), Ethionamide (ETH) and Second Line Injectable Drugs Drugs (SLID) on unprocessed sputum samples and concentrated sputum sediments which are positive forMycobacterium tuberculosis. The Xpert MTB/XDR assay simultaneously amplifies eight genes and promoter regions inM. tuberculosisand analyzes melting temperatures (Tms) using sloppy molecular beacon probes (SMB) to identify mutations associated with INH, FLQ, ETH and SLID resistance. Results can be obtained under 90 minutes and requires 10-color GeneXpert modules. The assay can differentiate low versus high-level resistance to INH and FLQ as well as cross-resistance versus individual resistance to SLIDs by identifying mutation-specific Tms or Tm patterns generated by the SMB probes. The assay has a Limit of Detection comparable to the Xpert MTB/RIF assay and succesfully detected 16 clinically significant mutations in a challenge set of clinical isolate DNA. In a clinical study performed at two sites with 100 sputum and 214 clinical isolates, the assay showed a sensitivity of 94-100% and a specificity of 100% for all drugs except for ETH when compared to sequencing. The sensitivity and specificity when compared to phenotypic drug susceptibility testing were in the same range. Used in combination with a primary tuberculosis diagnostic test, this assay is expected to expand the capacity for detection of drug-resistant tuberculosis.
Nasal systems immunology identifies inflammatory and tolerogenic myeloid cells that determine allergic outcome following challenge
Authors: Voskamp Astrid L. , Gerdes Maarten L. , Menafra Roberta , Duijster Ellen , Kielbasa Szymon M. , Kormelink Tom Groot , Tak Tamar , Stam Koen A. , de Jong Nicolette W. , Hendriks Rudi W. , Kloet Suzanne L. , Yazdanbakhsh Maria , de Jong Esther C. , Gerth van Wijk Roy , Smits Hermelijn H. 
Published: September 2020

AbstractInnate mononuclear phagocytic system (MPS) cells preserve mucosal immune homeostasis. Here, we investigated their role at nasal mucosa following challenge with house dust mite. We combined single cell proteome and transcriptome profiling on immune cells from nasal biopsy cells of allergic rhinitis and non-allergic subjects, before and after repeated nasal allergen challenge. Nasal biopsies of patients showed infiltrating inflammatory HLA-DRhiCD14+monocytes and CD16+monocytes, and transcriptional changes in resident CD1C+CD1A+conventional dendritic cells (cDC)2 following challenge. Importantly, although clinically silent, non-allergic individuals displayed a distinct innate MPS response to allergen challenge: predominant infiltration of myeloid-derived suppressor cells (HLA-DRlowCD14+monocytes), as well as cDC2 clusters expressing increased inhibitory/tolerogenic transcripts. Therefore, we identified not only clusters involved in airway inflammation but also a non-inflammatory, homeostatic blueprint of innate MPS responses to allergens in non-allergic individuals. Future therapies should target innate MPS for treatment of inflammatory airway diseases.Abstract Figure
Evaluation of DISORDER: retrospective image motion correction for volumetric brain MRI in a pediatric setting
Authors: Vecchiato Katy , Egloff Alexia , Carney Olivia , Siddiqui Ata , Hughes Emer , Dillon Louise , Colford Kathleen , Green Elaine , Texeria Rui Pedro A.G. , Price Anthony N. , Ferrazzi Giulio , Hajnal Joseph V. , Carmichael David W , Cordero-Grande Lucilio , O’Muircheartaigh Jonathan 
Published: September 2020

AbstractBackground and PurposeHead motion causes image degradation in brain MRI examinations, negatively impacting image quality, especially in pediatric populations. Here, we used a retrospective motion correction technique in children and assessed image quality improvement for 3D MRI acquisitions.Material and MethodsWe prospectively acquired brain MRI at 3T using 3D sequences, T1-weighted MPRAGE, T2-weighted Turbo Spin Echo and FLAIR, in 32 unsedated children, including 7 with epilepsy (age range 2–18 years). We implemented a novel motion correction technique: Distributed and Incoherent Sample Orders for Reconstruction Deblurring using Encoding Redundancy (DISORDER). For each subject and modality, we obtained 3 reconstructions: as acquired (Aq), after DISORDER motion correction (Di), and Di with additional outlier rejection (DiOut).We analyzed 288 images quantitatively, measuring 2 objective no-reference image quality metrics: Gradient Entropy (GE) and MPRAGE White Matter Homogeneity (WM-H). As a qualitative metric, we presented blinded and randomized images to 2 expert neuroradiologists who scored them for clinical readability.ResultsBoth image quality metrics improved after motion correction for all modalities and improvement correlated with the amount of intrascan motion. Neuroradiologists also considered the motion corrected images as of higher quality (Wilcoxon’s z = −3.164 MPRAGE, z = −2.066 TSE, z = −2.645 FLAIR, for all p < 0.05).ConclusionsRetrospective image motion correction with DISORDER increased image quality both from an objective and qualitative perspective. In 75% of sessions, at least one sequence was improved by this approach, indicating the benefit of this technique in unsedated children for both clinical and research environments.
Targeting Neuroplasticity to Improve Motor Recovery after Stroke
Authors: Norman Sumner L. , Wolpaw Jonathan R. , Reinkensmeyer David J. 
Published: September 2020

AbstractAfter neurological injury, people develop abnormal patterns of neural activity that limit motor recovery. Traditional rehabilitation, which concentrates on practicing impaired skills, is seldom fully effective. New targeted neuroplasticity (TNP) protocols interact with the CNS to induce beneficial plasticity in key sites and thereby enable wider beneficial plasticity. They can complement traditional therapy and enhance recovery. However, their development and validation is difficult because many different TNP protocols are conceivable, and evaluating even one of them is lengthy, laborious, and expensive. Computational models can address this problem by triaging numerous candidate protocols rapidly and effectively. Animal and human empirical testing can then concentrate on the most promising ones. Here we simulate a neural network of corticospinal neurons that control motoneurons eliciting unilateral finger extension. We use this network to (1) study the mechanisms and patterns of cortical reorganization after a stroke, and (2) identify and parameterize a TNP protocol that improves recovery of extension force. After a simulated stroke, standard training produced abnormal bilateral cortical activation and suboptimal force recovery. To enhance recovery, we interdigitated standard trials with trials in which the teaching signal came from a targeted population of sub-optimized neurons. Targeting neurons in secondary motor areas on 5-20% of the total trials restored lateralized cortical activation and improved recovery of extension force. The results illuminate mechanisms underlying suboptimal cortical activity post-stroke; they enable identification and parameterization of the most promising TNP protocols. By providing initial guidance, computational models could facilitate and accelerate realization of new therapies that improve motor recovery.
Estimating Trends in Fertility in Kenya from Non Birth History Data
Authors: Ngugi Paul Waweru 
Published: September 2020

AbstractThis study aimed at determining the extent to which methods for estimating trends in fertility without use of birth history could be used on Kenyan surveys data by employing the own-children method (OCM) and reverse survival (RS) method in estimating fertility trend in the country. The study used data from 2015/16 Kenya Integrated Household and Budget Survey (KIHBS) and 2014 Kenya Demographic and Health Survey (KDHS). Data evaluation was done in order to obtain optimal fertility estimates. 2015/16 KIHBS data reported a Whipples index of 49.0 and 57.5 for terminal digits 0 and 5 respectively. Myer’s blended index was 2.9 and this was an indication that in general the data was accurate and therefore did not require any adjustment to improve its quality before use. Results from 2015/16 KIHBS showed that RS estimated Total Fertility Rate to be 3.5 as compared to OCM that estimated it to be 3.8. The results from 2014 KDHS dataset were consistent when using both RS and OCM. The two indirect methods can give consistent fertility estimates when the reference period is closer to the survey period but in the fourth and fifth year RS tends to systematically overstate fertility as compared to OCM. This study found out that in the absence of full birth history data, RS and OCM can reliably estimate consistent fertility estimates and trend.
Leveraging T-cell receptor – epitope recognition models to disentangle unique and cross-reactive T-cell response to SARS-CoV-2 during COVID-19 progression/resolution
Authors: Postovskaya Anna , Vujkovic Alexandra , de Block Tessa , van Petersen Lida , van Frankenhuijsen Maartje , Brosius Isabel , Bottieau Emmanuel , Van Dijck Christophe , Theunissen Caroline , van Ierssel Sabrina H. , Vlieghe Erika , Bartholomeus Esther , Adriaensen Wim , Vanham Guido , Ogunjimi Benson , Laukens Kris , Vercauteren Koen , Meysman Pieter 
Published: September 2020

ABSTRACTDespite the general agreement on the importance of T cells during SARS-CoV-2 infection, the clinical impact of specific and cross-reactive T-cell responses remains uncertain, while this knowledge may indicate how to adjust vaccines and maintain robust long-term protection against continuously emerging variants. To characterize CD8+ T-cell response to epitopes unique to SARS-CoV-2 (SC-unique) or shared with other coronaviruses (CoV-common), we trained a large number of TCR-epitope recognition models for MHC-I-presented SARS-CoV-2 epitopes from publicly available data. Applying those models to longitudinal COVID-19 TCR repertoires of critical and non-critical COVID-19 patients, we discovered that notwithstanding comparable CD8+ T-cell depletion and the sizes of putative CoV-common CD8+ TCR repertoires in all symptomatic patients at the initial stage of the disease, the temporal dynamics of putative SC2-unique TCRs differed depending on the disease severity. Only non-critical patients had developed large and diverse SC2-unique CD8+ T-cell response by the second week of the disease. Additionally, only this patient group demonstrated redundancy in CD8+ TCRs putatively recognizing unique and common SARS-CoV-2 epitopes. Our findings thus emphasize the role of thede novoCD8+ T-cell response and support the argument against the clinical benefit of pre-existing cross-reactive CD8+ T cells. Now, the analytical framework of this study can not only be employed to track specific and cross-reactive SARS-CoV-2 CD8+ T cells in any TCR repertoire but also be generalized to more epitopes and be employed for adaptive immune response assessment and monitoring to inform public health decisions.
Global genome decompaction leads to stochastic activation of gene expression as a first step toward fate commitment in human hematopoietic stem cells
Authors: Romuald Parmentier , Alice Moussy , Sophie Chantalat , Laëtitia Racine , Ravi Sudharshan , Nan Papili Gao , Daniel Stockholm , Guillaume Corre , Geneviève Fourel , Jean-François Deleuze , Rudiyanto Gunawan , Andras Paldi 
Published: September 2020

SummaryWhen human cord blood derived CD34+ cells are induced to differentiatein vitro, they undergo rapid and dynamic morphological and molecular transformations that are critical for fate commitment. Using ATAC-seq and single-cell RNA sequencing, we detected two phases in this process. In the first phase, we observed a rapid and global chromatin opening that makes most of the gene promoters in the genome accessible, followed by widespread upregulation of gene transcription and a concomitant increase in the cell-to-cell variability of gene expression. The second phase is marked by a slow chromatin closure and a subsequent overall downregulation of gene transcription and emergence of coherent expression profiles corresponding to distinct cell subpopulations. These observations are consistent with a model based on the spontaneous probabilistic organization of the cellular process of fate commitment.
The Costs and Benefits of a Modified Biomedical Science Workforce
Authors: Schaller Michael D. 
Published: September 2020

ABSTRACTAnalyses of the biomedical research workforce, the biomedical research enterprise and its sustainability have identified a number of threats and offered many solutions to alleviate the problems. While, a number of these solutions have been implemented, one solution that has not been broadly adopted, despite being widely recommended, is to increase the number of staff scientists and reduce dependency on trainees. The perceived impediment of this is the cost. This paper explores the costs associated with laboratory personnel and the benefits, in terms of productivity, associated with different positions in the workforce. The results of this cost-benefit analysis depend upon the values assigned to different metrics of productivity by individuals and institutions. If first and senior author publications are the most important metrics of productivity, a trainee dependent workforce is much more cost effective. If total publications is the most valued metric of productivity, the cost effectiveness of trainee and staff scientists is reasonably equitable. This analysis provides data for consideration when making personnel decisions and for the continued discussion of modification of the biomedical research workforce. It also provides insight into the incentives for modification of the workforce at the grass roots, which must be considered by institutions genuinely committed to workforce modification to sustain the biomedical research enterprise.
Regulatory crosstalk between motility and interbacterial communication inSalmonellaTyphimurium
Authors: Plitnick Jonathan , Chevance Fabienne F.V. , Stringer Anne , Hughes Kelly T. , Wade Joseph T. 
Published: September 2020

ABSTRACTFliA is a broadly conserved σ factor that directs transcription of genes involved in flagellar motility. We previously identified FliA-transcribed genes inEscherichia coliandSalmonella entericaserovar Typhimurium, and we showed thatE. coliFliA transcribes many unstable, non-coding RNAs from intragenic promoters. Here, we show that FliA inS. Typhimurium also directs transcription of large numbers of unstable, non-coding RNAs from intragenic promoters, and we identify two previously unreported FliA-transcribed protein-coding genes. One of these genes,sdiA, encodes a transcription factor that responds to quorum sensing signals produced by other bacteria. We show that FliA-dependent transcription ofsdiAis required for SdiA activity, highlighting a regulatory link between flagellar motility and intercellular communication.IMPORTANCEInitiation of bacterial transcription requires association of a σ factor with the core RNA polymerase to facilitate sequence-specific recognition of promoter elements. FliA is a widely conserved σ factor that directs transcription of genes involved in flagellar motility. We previously showed thatEscherichia coliFliA transcribes many unstable, non-coding RNAs from promoters within genes. Here, we demonstrate the same phenomenon inSalmonellaTyphimurium. We also show thatS. Typhimurium FliA directs transcription of thesdiAgene, which encodes a transcription factor that responds to quorum sensing signals produced by other bacteria. FliA-dependent transcription ofsdiAis required for transcriptional control of SdiA target genes, highlighting a regulatory link between flagellar motility and intercellular communication.
Stanniocalcin 1a is a Ca2+-regulated switch controlling epithelial cell quiescence-proliferation balance and Ca2+uptake
Authors: Li Shuang , Liu Chengdong , Goldstein Allison , Xin Yi , Ke Caihuan , Duan Cunming 
Published: September 2020

AbstractThe mechanisms governing cell quiescence-proliferation balance are poorly defined. Using a zebrafish model, here we report that Stc1a, a glycoprotein known as a hypocalcemic hormone, not only inhibits epithelial calcium uptake but also functions as a Ca2+-regulated switch controlling epithelial cell quiescence-proliferation balance. Among the 4stcgenes, only thestc1aexpression is [Ca2+]-dependent. Genetic deletion ofstc1a, but notstc2b, resulted in elevated body Ca2+contents, ectopic Ca2+deposit, body swelling, and premature death. Reducing epithelial calcium channel Trpv6-mediated Ca2+uptake alleviated these phenotypes. Loss of Stc1a also promoted quiescent epithelial cells to re-enter the cell cycle. This action was accompanied by local IGF signaling activation and increased expression inpapp-aa, a zinc metalloproteinase degrading Igfbp5a. Genetic deletion ofpapp-aaorigfbp5aabolished the elevated epithelial cell reactivation instc1a-/-mutants. Likewise, inhibition of IGF1 receptor, PI3 kinase, Akt, and Tor signaling abolished epithelial cell reactivation. These results reveal that Stc1a plays dual roles in regulating epithelial calcium uptake and cell quiescence-proliferation balance and implicate Trpv6 and Papp-aa-Igfbp5a-IGF signaling in these functions.
Casino employees' intention to participate in corporate community involvement activities – an extended value-attitude-intention model
Authors: Huang G.H. , To Wai Ming 
Published: September 2020

PurposeThe success of corporate community involvement depends on employees' perception of and intention to participate in the associated activities. This paper explores personal and perceived organizational factors that influence casino employees' intention to participate in community involvement activities using the extended value-attitude-intention model.Design/methodology/approachBased on a literature review on corporate community involvement in the hospitality industry and the value-attitude-intention hierarchy, a theoretical model that links perceived societal value to employees' behavioral intention was established. The model was tested using responses from 322 Macao's casino employees.FindingsResults of structural equation modeling showed that perceived societal value of corporate community involvement and perceived societal pressure significantly influenced employees' attitude toward community involvement while perceived societal pressure also significantly influenced perceived facilitating conditions. Additionally, employees' attitude toward corporate community involvement and perceived facilitating conditions affected their intention to participate in corporate community involvement activities.Originality/valueCasinos use corporate community involvement as a way of counteracting the negative impacts of commercial gaming and supporting local communities. Hence, it is vital to understand the mechanism of engaging casino employees in corporate community involvement activities.
Investigation of waste diversion rates in the construction and demolition sector in Australia
Authors: Ratnasabapathy Shiyamini , Alashwal Ali , Perera Srinath 
Published: September 2020

PurposeWaste diversion rate (WDR) is a key indicator of effective waste management and circular economy. However, it has not yet been widely used in the construction and demolition waste (C&DW) sector. This study aims to promote the application of WDR as an effective measure for waste management through the investigation of the current status of C&DW diversion in the Australian construction industry.Design/methodology/approachA mixed-method approach, which combines a desk study and a case study of 12 residential projects was used in this study. Data retrieved from the National Waste Database (NWD) were used for the descriptive analysis.FindingsThe analysis of the national waste data revealed that the national average WDR in Australia is 64%. WDR varies based on material types and across the states. The analysis facilitated the forecasting of the possible future trend of waste diversion in Australia. The studied projects from two states in Australia presented slightly different results. Most of the waste stream, except mixed waste, presented above 95% of WDR in each project.Research limitations/implicationsAlthough the studied projects showed a higher recycling rate, this study claims that achieving a higher rate of recovery by diverting the waste could not be assured unless accurate estimation is carried out with reliable and verifiable data. Lack of reliable data is considered as the limitation of this study. While the scope of descriptive analysis of waste generation and diversion covers the whole country, the case study analysis is limited to the states of New South Wales and Victoria.Originality/valueThe study highlights the significance of WDR in assessing the performance of effective waste management in the C&DW sector. WDR is a comprehensive measure that takes the output of the waste life cycle into account for benchmarking waste management. The results provide a critique of the current practices of waste management and the essence of the consistent, transparent and verifiable waste data to enable accurate WDR estimation in Australia. The outcome is useful for waste managers and policymakers in developing potential waste management strategies and C&DW specific legislation for building a more ecologically sustainable industry.