bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multimodal measures of spontaneous brain activity reveals both common and divergent patterns of cortical functional organization
Authors: Vafaii Hadi , Mandino Francesca , Desrosiers-Grégoire Gabriel , O’Connor David , Shen Xilin , Ge Xinxin , Herman Peter , Hyder Fahmeed , Papademetris Xenophon , Chakravarty Mallar , Crair Michael C. , Constable R. Todd , Lake Evelyn MR. , Pessoa Luiz 
Published: December 2022

AbstractWork in humans and animals shows that the brain can be decomposed into large-scale functional networks. Whereas most studies, especially in humans, use the blood-oxygenation-level-dependent (BOLD) signal, the relationship between BOLD and neuronal activity is complex and incompletely understood. This limits our ability to interpret and apply measures derived from fMRI-BOLD. Here, we employ wide-field Ca2+imaging simultaneously recorded with fMRI-BOLD in highly-sampled mice expressing GCaMP6f in excitatory neurons. These unique data enabled us to characterize the similarities and differences between networks discoverable by each modality. Importantly, we applied a network partitioning approach that uses a mixed-membership algorithm, which allows brain regions to participate in multiple networks with varying strengths. This contrasts with assuming regions belong to only one network. Our findings demonstrate that (1) most BOLD networks are detected via Ca2+signals. (2) There is considerable overlapping—as opposed to disjoint—network organization that is evident from both modalities. (3) Large-scale networks determined by Ca2+signals at low temporal frequencies (0.01 – 0.5Hz)—as opposed to higher frequencies (0.5 – 5Hz)—are more similar to those determined by BOLD. (4) Despite many similarities, differences emerge across modes including the spatial distribution of membership diversity (the extent to which regions affiliate with multiple networks). In sum, Ca2+imaging of excitatory neurons confirms that the mouse cortex is functionally organized into overlapping large-scale networks in a manner that reflects many, but not all, properties observable with simultaneous fMRI-BOLD; affirming the neural origins of patterns of brain organization that are evident in a clinically accessible neuroimaging modality.
Identification of hyperosmotic stress-responsive genes in Chinese hamster ovary cells via genome-wide virus-free CRISPR/Cas9 screening
Authors: Kim Su Hyun , Shin Seunghyeon , Baek Minhye , Xiong Kai , Karottki Karen Julie la Cour , Hefzi Hooman , Grav Lise Marie , Pedersen Lasse Ebdrup , Kildegaard Helene Faustrup , Lewis Nathan E. , Lee Jae Seong , Lee Gyun Min 
Published: December 2022

AbstractChinese hamster ovary (CHO) cells are the preferred mammalian host cells for therapeutic protein production that have been extensively engineered to possess the desired attributes for high-yield protein production. However, empirical approaches for identifying novel engineering targets are laborious and time-consuming. Here, we established a genome-wide CRISPR/Cas9 screening platform for CHO-K1 cells with 111,651 guide RNAs (gRNAs) targeting 21,585 genes using a virus-free recombinase-mediated cassette exchange-based gRNA integration method. Using this platform, we performed a positive selection screening under hyperosmotic stress conditions and identified 180 genes whose perturbations conferred resistance to hyperosmotic stress in CHO cells. Functional enrichment analysis identified hyperosmotic stress responsive gene clusters, such as tRNA wobble uridine modification and signaling pathways associated with cell cycle arrest. Furthermore, we validated 32 top-scoring candidates and observed a high rate of hit confirmation, demonstrating the potential of the screening platform. Knockout of the novel target genes,ZfrandPnp, in monoclonal antibody (mAb)-producing recombinant CHO (rCHO) cells and bispecific antibody (bsAb)-producing rCHO cells enhanced their resistance to hyperosmotic stress, thereby improving mAb and bsAb production. Overall, the collective findings demonstrate the value of the screening platform as a powerful tool to investigate the functions of genes associated with hyperosmotic stress and to discover novel targets for rational cell engineering on a genome-wide scale in CHO cells.
Neuropsychiatric Disorder Subtyping Via Clustered Deep Learning Classifier Explanations
Authors: Ellis Charles A. , Miller Robyn L. , Calhoun Vince D. 
Published: December 2022

AbstractIdentifying subtypes of neuropsychiatric disorders based on characteristics of their brain activity has tremendous potential to contribute to a better understanding of those disorders and to the development of new diagnostic and personalized treatment approaches. Many studies focused on neuropsychiatric disorders examine the interaction of brain networks over time using dynamic functional network connectivity (dFNC) extracted from resting-state functional magnetic resonance imaging data. Some of these studies involve the use of either deep learning classifiers or traditional clustering approaches, but usually not both. In this study, we present a novel approach for subtyping individuals with neuropsychiatric disorders within the context of schizophrenia (SZ). We train an explainable deep learning classifier to differentiate between dFNC data from individuals with SZ and controls, obtaining a test accuracy of 79%. We next make use of cross-validation to obtain robust average explanations for SZ training participants across folds, identifying 5 SZ subtypes that each differ from controls in a distinct manner and that have different degrees of symptom severity. These subtypes specifically differ from one another in their interaction between the visual network and the subcortical, sensorimotor, and auditory networks and between the cerebellar network and the cognitive control and subcortical networks. Additionally, there are statistically significant differences in negative symptom scores between the subtypes. It is our hope that the proposed novel subtyping approach will contribute to the improved understanding and characterization of SZ and other neuropsychiatric disorders.
Tuning in on auditory details is difficult: Individuals with aphasia show impaired acoustic and phonemic processing
Authors: Kries Jill , De Clercq Pieter , Lemmens Robin , Francart Tom , Vandermosten Maaike 
Published: December 2022

AbstractAcoustic and phonemic processing are understudied in aphasia, a language disorder that can affect different levels and modalities of language processing. For successful speech comprehension, processing of the speech envelope is necessary, which relates to amplitude changes over time (e.g., the rise times). Moreover, to identify speech sounds (i.e., phonemes), efficient processing of spectro-temporal changes as reflected in formant transitions is essential. Given the lack of aphasia studies on these aspects, we tested rise time processing and phoneme identification in 29 individuals with post-stroke aphasia and 23 healthy age-matched controls. We found significantly lower performance in the aphasia group than in the control group on both tasks, even when controlling for individual differences in hearing levels and cognitive functioning. Further, by conducting an individual deviance analysis, we found a low-level acoustic or phonemic processing impairment in 76% of individuals with aphasia. Additionally, we investigated whether this impairment would propagate to higher-level language processing and found that rise time processing predicts phonological processing performance in individuals with aphasia. These findings show that it is important to develop diagnostic and treatment tools that target low-level language processing mechanisms.
The effectiveness and cost of integrating pharmacists within general practice to optimize prescribing and health outcomes in primary care patients with polypharmacy: A systematic review
Authors: Croke Aisling , Cardwell Karen , Clyne Barbara , Moriarty Frank , McCullagh Laura , Smith Susan M. 
Published: December 2022

AbstractBackgroundPolypharmacy and associated potentially inappropriate prescribing (PIP) place a considerable burden on patients and represent a challenge for general practitioners (GPs). Integration of pharmacists within general practice (herein ‘pharmacist integration’) may improve medications management and patient outcomes. This systematic review assessed the effectiveness and costs of pharmacist integration.MethodsA systematic search of ten databases from inception to January 2021 was conducted. Studies that evaluated the effectiveness or cost of pharmacist integration were included. Eligible interventions were those that targeted medications optimization compared to usual GP care without pharmacist integration (herein ‘usual care’). Primary outcomes were PIP (as measured by PIP screening tools) and number of prescribed medications. Secondary outcomes included health-related quality of life, health service utilization, clinical outcomes, and costs. Randomised controlled trials (RCTs), non-RCTs, interrupted-time-series, controlled before-after trials and health-economic studies were included.Screening and risk of bias using Cochrane EPOC criteria were conducted by two reviewers independently. A narrative synthesis and meta-analysis of outcomes where possible, were conducted; the certainty of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluation approach.ResultsIn total, 23 studies (28 full text articles) met the inclusion criteria. In ten of 11 studies, pharmacist integration probably reduced PIP in comparison to usual care (moderate certainty evidence). A meta-analysis of number of medications in seven studies reported a mean difference of -0.80 [-1.17, -0.43], which indicated pharmacist integration probably reduced number of medicines (moderate certainty evidence). It was uncertain whether pharmacist integration improved health-related quality of life because the certainty of evidence was very low. Twelve health-economic studies outlined costs and potential cost-effectiveness.ConclusionsPharmacist integration probably reduced PIP and number of medications however, there was no clear effect on other patient outcomes; and while interventions in a small number of studies appeared to be cost-effective, further robust, well-designed cluster RCTs with economic evaluations are required to determine cost-effectiveness of pharmacist integration within general practice.PROSPERO RegistrationCRD42019139679
Positive selection in the genomes of two Papua New Guinean populations at distinct altitude levels
Authors: André Mathilde , Brucato Nicolas , Hudjasov Georgi , Pankratov Vasili , Yermakovich Danat , Kreevan Rita , Kariwiga Jason , Muke John , Boland Anne , Deleuze Jean-François , Meyer Vincent , Evans Nicholas , Cox Murray P. , Leavesley Matthew , Dannemann Michael , Org Tõnis , Metspalu Mait , Mondal Mayukh , Ricaut François-Xavier 
Published: December 2022

AbstractHighlanders and lowlanders of Papua New Guinea (PNG) have faced distinct environmental conditions. These environmental differences lead to specific stress on PNG highlanders and lowlanders, such as hypoxia and environment-specific pathogen exposure, respectively. We hypothesise that these constraints induced specific selective pressures that shaped the genomes of both populations. In this study, we explored signatures of selection in newly sequenced whole genomes of 54 PNG highlanders and 74 PNG lowlanders. Based on multiple methods to detect selection, we investigated the 21 and 23 genomic top candidate regions for positive selection in PNG highlanders and PNG lowlanders, respectively. To identify the most likely candidate SNP driving selection in each of these regions, we computationally reconstructed allele frequency trajectories of variants in each of these regions and chose the SNP with the highest likelihood of being under selection with CLUES. We show that regions with signatures of positive selection in PNG highlanders genomes encompass genes associated with the hypoxia-inducible factors pathway, brain development, blood composition, and immunity, while selected genomic regions in PNG lowlanders contain genes related to immunity and blood composition. We found that several candidate driver SNPs are associated with haematological phenotypes in the UK biobank. Moreover, using phenotypes measured from the sequenced Papuans, we found that two candidate SNPs are significantly associated with altered heart rates in PNG highlanders and lowlanders. Furthermore, we found that 16 of the 44 selection candidate regions harboured archaic introgression. In four of these regions, the selection signal might be driven by the introgressed archaic haplotypes, suggesting a significant role of archaic admixture in local adaptation in PNG populations.
Cleavage of cFLIP restrains cell death during viral infection and tissue injury and favors tissue repair
Authors: Martinez Lagunas Kristel , Savcigil Deniz Pinar , Zrilic Matea , Carvajal Fraile Carlos , Craxton Andrew , Self Emily , Uranga-Murillo Iratxe , de Miguel Diego , Arias Maykel , Willenborg Sebastian , Piekarek Michael , Albert Marie Christine , Nugraha Kalvin , Lisewski Ina , Janakova Erika , Igual Natalia , Tonnus Wulf , Hildebrandt Ximena , Ibrahim Mohammed , Ballegeer Marlies , Saelens Xavier , Kueh Andrew , Meier Pascal , Linkermann Andreas , Pardo Julian , Eming Sabine , Walczak Henning , MacFarlane Marion , Peltzer Nieves , Annibaldi Alessandro 
Published: December 2022

AbstractCell death coordinates repair programs following pathogen attack and tissue injury. However, aberrant cell death can interfere with such programs and cause organ failure. cFLIP is a crucial regulator of cell death and a substrate of Caspase-8. Yet, the physiological role of cFLIP cleavage by Caspase-8 remains elusive. Here, we discovered an essential role for cFLIP cleavage in restraining cell death in different pathophysiological scenarios. Mice expressing a cleavage-resistant cFLIP mutant,CflipD377A, exhibited increased sensitivity to SARS-CoV-induced lethality, impaired skin wound healing and increased tissue damage caused bySharpindeficiency.In vitro, abrogation of cFLIP cleavage sensitizes cells to TNF-induced necroptosis and apoptosis by favoring complex-II formation. Mechanistically, the cell death-sensitizing effect of the D377A mutation depends on Gln(Q)469. These results reveal a crucial role for cFLIP cleavage in controlling the amplitude of cell death responses occurring upon tissue stress, to ensure the execution of repair programs.
Discovery And Characterization of Small Molecule Inhibitors of Zika Virus Replication
Authors: Kumar Ankur , Kumar Deepak , Kumar Prateek , Jones Brittany L. , Mysorekar Indira U , Giri Rajanish 
Published: December 2022

AbstractZika virus (ZIKV) is a flavivirus, and ZIKV infections in the past 15 years have been linked to Guillain-Barre syndrome and severe complications during pregnancy associated with congenital Zika syndrome. There are no approved therapies or vaccines for ZIKV. In recent years, advances in structure-based drug design methodologies have accelerated drug development pipelines for identifying promising inhibitory compounds against viral diseases. Among ZIKV proteins, NS2B-NS3 protease is an attractive target for antiviral drug development due to its vital role in the proteolytic processing of the single polyprotein. To find potential inhibitors against ZIKV, we used molecular docking at the NS2B-NS3 protease active site as a virtual screening approach with small molecules diverse scaffold-based library with rigorous druglikeness filters. The top-hit compounds with stable molecular dynamics trajectories were then subjected to in-vitro efficacy testing against ZIKV. In docking and molecular dynamics simulation studies, compound F1289-0194 showed stable binding to the NS2B-NS3 protease active site. Furthermore, viral load assays, immunofluorescence, and plaque reduction assays demonstrated that compound F1289-0194 significantly reduced ZIKV load and replication in Vero cells while maintaining cellular integrity. Thus, the compound F1289-0194 merits further investigation as a novel inhibitor against ZIKV replication.
Financial inclusion and post-harvest losses in West African economic and Monetary Union
Authors: Akpa Armand Fréjuis , Osabohien Romanus , Ashraf Junaid , Al-Faryan Mamdouh Abdulaziz Saleh 
Published: December 2022

PurposePost-harvest losses are major problems faced by farmers and this is due to their poor access to credit considered as a low rate of financial inclusion. This paper aims at analysing the relationship between financial inclusion and post-harvest losses in the West African Economic and Monetary Union (WAEMU).Design/methodology/approachThe study engaged data from the Food and Agriculture Organisation [FAO] for post-harvest losses. Also, it engaged data from Banque Centrale des Etats de l’Afrique de l’Ouest [BCEAO] for financial inclusion over the period 2000 to 2020. The study applied the Instrumental Variable Two-Stage Least Squares (IV-2SLS) and Generalised Method of Moments (GMM) to test the robustness of the results.FindingsThe results show that financial inclusion reduces post-harvest losses by 1.2%. Therefore, given this result, policies to improve farmers’ access to credit by increasing the rate of financial inclusion, is a necessary condition for the reduction of post-harvest losses.Social implicationsSocial implication of this study is that it contributes to the policy debate on the enhancement of food security by reducing post-harvest losses. The reduction in post-harvest losses and food security, will improve the welfare and livelihood of the society. This aims for the actualization of sustainable development goal of food and nutrition security (SDG-2).Originality/valueThe findings imply that efforts by governments and policymakers to improve farmers’ access to credit by increasing the rate of financial inclusion would reduce post-harvest losses in West African countries that are members of the WAEMU. Also, investment in education, ICT and building warehouse for farmers will help in reducing post-harvest losses. It implies that educated farmers have more opportunities to be financially inclusive than those who are not educated.
Psychological capital and employee job attitudes: the critical significance of work-life balance
Authors: Parray Zahoor Ahmad , Shah Tanveer Ahmad , Islam Shahbaz Ul 
Published: December 2022

PurposeThe major goal of this research is to examine the work-life balance as a mediating factor in the association between psychological capital and employee attitudes including job satisfaction, organizational commitment and turnover intentions.Design/methodology/approachThe authors gathered data from prestigious healthcare institutes in North Indian states to test the suggested study model. Data were gathered from 613 personnel employed in public and private healthcare organizations via an online Google form. Structural Equation Modelling (SEM) was applied for analyzing the data.FindingsThe findings validated the expected relations, demonstrating that the association between psychological capital and employee job attitudes is completely mediated by work-life balance.Research limitations/implicationsThis research study used cross-sectional data, which fall short of meeting the requirement for proving causation.Practical implicationsThe findings of this study will help organizations and practitioners, particularly healthcare administrators and policymakers, better recognize the value of psychological capital and work-life balance, and how they impact job attitudes.Originality/valueThis research study added to the existing self-determination theory (SDT) model developed by Deci et al. (2017) by incorporating psychological capital and work-life balance as autonomous intrinsic and workplace context factors, respectively, into the SDT model to study work behaviors in terms of job outcomes. In addition, the study added to the existing body of knowledge in organizational behavior literature about the role of mediating variables in understanding the indirect effect of personal resources on job attitudes.
Integrating and determining Fintech value chain financing: a perspective of Islamic financial institutions
Authors: Maryam Sayeda Zeenat , Ahmad Ashfaq 
Published: December 2022

PurposeIn the current era of technological advancement, it is becoming essential for financial institutions to serve through financial technology (Fintech). This study aims to integrate Fintech with value chain in existing system of Islamic financial institutions (IFIs) and to determine the adoption of Fintech value chain financing (FVCF) by IFIs in the presence of mediators.Design/methodology/approachThis paper examines a conceptual model by performing a self-administration survey for 393 sample size. After the completion of data collection 263 suitable responses are used for analysis. The hypotheses are tested by applying algorithm, bootstrapping and blindfolding techniques.FindingsThe findings of structural model demonstrate that trust, information sharing (IS) and information and communication technology (ICT) are important for adoption of FVCF in the perspective of IFIs. Secondly, innovativeness is partially mediating the relationship of trust, IS and ICT for adoption of FVCF. Thirdly, competitiveness is fully mediating the relationship of trust, IS and ICT with agility for adoption of FVCF by IFIs.Research limitations/implicationsTheoretically, this research is developing a conceptual model that is providing a new way to integrate value chain partners. This study is demonstrating the sequential mediation for the adoption of FVCF. Practically, this research is giving meaningful insight to policymakers of IFIs by suggesting a way forward to adopt FVCF. However, there is need to know the perception of other stakeholders that may involve in FVCF.Originality/valueBecause there exists limited work in the context of integration and adoption of Fintech by organizations, this study is a pioneer that is taking the perspective of financial institutions for FVCF.