bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Genomically and Clinically Annotated Patient Derived Xenograft (PDX) Resource for Preclinical Research in Non-Small Cell Lung Cancer
Authors: Woo Xing Yi , Srivastava Anuj , Mack Philip C. , Graber Joel H. , Sanderson Brian J. , Lloyd Michael W. , Chen Mandy , Domanskyi Sergii , Gandour-Edwards Regina , Tsai Rebekah A. , Keck James , Cheng Mingshan , Bundy Margaret , Jocoy Emily L. , Riess Jonathan W. , Holland William , Grubb Stephen C. , Peterson James G. , Stafford Grace A. , Paisie Carolyn , Neuhauser Steven B. , Karuturi R. Krishna Murthy , George Joshy , Simons Allen K. , Chavaree Margaret , Tepper Clifford G. , Goodwin Neal , Airhart Susan D. , Lara Primo N. , Openshaw Thomas H. , Liu Edison T. , Gandara David R. , Bult Carol J. 
Published: March 2022

AbstractPatient-derived xenograft models (PDXs) are an effective preclinical in vivo platform for testing the efficacy of novel drug and drug combinations for cancer therapeutics. Here we describe a repository of 79 genomically and clinically annotated lung cancer PDXs available from The Jackson Laboratory that have been extensively characterized for histopathological features, mutational profiles, gene expression, and copy number aberrations. Most of the PDXs are models of non-small cell lung cancer (NSCLC), including 37 lung adenocarcinoma (LUAD) and 33 lung squamous cell carcinoma (LUSC) models. Other lung cancer models in the repository include four small cell carcinomas, two large cell neuroendocrine carcinomas, two adenosquamous carcinomas, and one pleomorphic carcinoma. Models with both de novo and acquired resistance to targeted therapies with tyrosine kinase inhibitors are available in the collection. The genomic profiles of the LUAD and LUSC PDX models are consistent with those observed in patient tumors of the same tumor type from The Cancer Genome Atlas (TCGA) and to previously characterized gene expression-based molecular subtypes. Clinically relevant mutations identified in the original patient tumors were confirmed in engrafted tumors. Treatment studies performed for a subset of the models recapitulated the responses expected based on the observed genomic profiles.SignificanceThe collection of lung cancer Patient Derived Xenograft (PDX) models maintained at The Jackson Laboratory retain both the histologic features and treatment-relevant genomic alterations observed in the originating patient tumors and show expected responses to treatment with standard-of-care agents. The models serve as a valuable preclinical platform for translational cancer research. Information and data for the models are freely available from the Mouse Models of Human Cancer database (MMHCdb, http://tumor.informatics.jax.org/mtbwi/pdxSearch.do).
Low expression of EXOSC2 protects against clinical COVID-19 and impedes SARS-CoV-2 replication
Authors: Moll Tobias , Odon Valerie , Harvey Calum , Collins Mark O , Peden Andrew , Franklin John , Graves Emily , Marshall Jack N.G. , Santos Souza Cleide dos , Zhang Sai , Azzouz Mimoun , Gordon David , Krogan Nevan , Ferraiuolo Laura , Snyder Michael P , Shaw Pamela J , Rehwinkel Jan , Cooper-Knock Johnathan 
Published: March 2022

AbstractNew therapeutic targets are a valuable resource in the struggle to reduce the morbidity and mortality associated with the COVID-19 pandemic, caused by the SARS-CoV-2 virus. Genome-wide association studies (GWAS) have identified risk loci, but some loci are associated with co-morbidities and are not specific to host-virus interactions. Here, we identify and experimentally validate a link between reduced expression of EXOSC2 and reduced SARS-CoV-2 replication. EXOSC2 was one of 332 host proteins examined, all of which interact directly with SARS-CoV-2 proteins; EXOSC2 interacts with Nsp8 which forms part of the viral RNA polymerase. Lung-specific eQTLs were identified from GTEx (v7) for each of the 332 host proteins. Aggregating COVID-19 GWAS statistics for gene-specific eQTLs revealed an association between increased expression of EXOSC2 and higher risk of clinical COVID-19 which survived stringent multiple testing correction. EXOSC2 is a component of the RNA exosome and indeed, LC-MS/MS analysis of protein pulldowns demonstrated an interaction between the SARS-CoV-2 RNA polymerase and the majority of human RNA exosome components. CRISPR/Cas9 introduction of nonsense mutations within EXOSC2 in Calu-3 cells reduced EXOSC2 protein expression, impeded SARS-CoV-2 replication and upregulated oligoadenylate synthase (OAS) genes, which have been linked to a successful immune response against SARS-CoV-2. Reduced EXOSC2 expression did not reduce cellular viability. OAS gene expression changes occurred independent of infection and in the absence of significant upregulation of other interferon-stimulated genes (ISGs). Targeted depletion or functional inhibition of EXOSC2 may be a safe and effective strategy to protect at-risk individuals against clinical COVID-19.
Dietary Lipid Oxidization Products Alter Growth, Adiposity and Gut Microbial Ecology in Prepubertal Porcine Model
Authors: Arowolo Folagbayi K. , Willis Kent A. , Karabayir Ibrahim , Akbiligic Oguz , Blaser Morgan , Booth Jeffrey , Pierre Joseph F. , Shanmuganayagam Dhanansayan 
Published: March 2022

ABSTRACTElevated levels of dietary fats in westernized diets, associated with increased risk of obesity and other chronic diseases, are increasingly consumed by children in the United States. Cooking practices such as high heat frying and increased use of oxidizable sources of fats have introduced high levels of lipid oxidation products (LOPs) into these diets. The effects of these highly reactive dietary compounds on human biology are largely unstudied, especially in the gut where these compounds are likely present at higher concentrations. Given that the gut microbiome can be influenced by dietary components and then in turn have a systemic impact, we investigated the effects of consuming LOPs on gut bacterial and fungal communities and on growth and body composition during the prepubertal period in a porcine model. The presence of LOPs in the high fat diet reduced growth and body fat gain in the model. The gut microbiome was uniquely altered by both high fat and the presence of LOPs, with notable changes in the abundances ofTuricibacterales, Spriochaetales, RF39, Lactobacillales and Erysipelotrichales. The mycobiome was dominated byKazachstania, a porcine specific yeast, which was only minimally influenced by the dietary regimen. Application of machine learning identified dietary fat and LOPs as strong predictors of body fat. The genusMethanobrevibacterwas the key microbial predictor of body fat. This study highlights the need for further studies on the biological effects of LOPs which have become ubiquitous in human, livestock and pet diets in developed countries.
The neural code for ‘face cells’ is not face specific
Authors: Vinken Kasper , Prince Jacob S. , Konkle Talia , Livingstone Margaret 
Published: March 2022

1Abstract‘Face cells’ are visual neurons that respond more to faces than other objects. Clustered together in inferotemporal cortex, they are thought to carry out face processing specifically and are thus studied using faces almost exclusively. Analyzing neural responses in and around macaque face patches to hundreds of objects, we found graded response profiles for non-faces that were predictive of the degree of face selectivity and provided information on face-cell tuning that could not be characterized with actual faces. This relationship between non-face and face responses was not predicted by color and simple shape properties, but by information encoded in deep neural networks trained on general object classification rather than face identification. These findings contradict the long-standing assumption that face cells owe their category selectivity to face-specific features, instead providing evidence for the notion that category-selective neurons are best understood as tuning directions in an integrated, domain-general object space.
Individual stochasticity in the life history strategies of animals and plants
Authors: Varas-Enríquez Pablo José , van Daalen Silke , Caswell Hal 
Published: March 2022

AbstractThe life histories of organisms are expressed as rates of development, reproduction, and survival. However, individuals may experience differential outcomes for the same set of rates. Such individual stochasticity generates variance around familiar mean measures of life history traits, such as life expectancy and the reproductive number R0. By writing life cycles as Markov chains, we calculate variance and other indices of variability for longevity, lifetime reproductive output (LRO), age at offspring production, and age at maturity for 83 animal and 332 plant populations from the Comadre and Compadre matrix databases. We find that the magnitude within and variability between populations in variance indices in LRO, especially, are surprisingly high. We furthermore use principal components analysis to assess how the inclusion of variance indices affects life history constraints. We find that these indices, to a similar or greater degree than the mean, explain the variation in life history strategies among plants and animals.
PTEN is required for human Treg suppression of costimulation
Authors: Lam Avery J. , Haque Manjurul , Ward-Hartstonge Kirsten A. , Uday Prakruti , Wardell Christine M. , Gillies Jana K. , Speck Madeleine , Mojibian Majid , Geltink Ramon I. Klein , Levings Megan K. 
Published: March 2022

AbstractRegulatory T cell (Treg) therapy is under clinical investigation for the treatment of transplant rejection, autoimmune disease, and graft-versus-host disease. With the advent of genome editing, attention has turned to reinforcing Treg function for therapeutic benefit. A hallmark of Tregs is dampened activation of PI3K-AKT signalling, of which PTEN is a major negative regulator. Loss-of-function studies of PTEN, however, have not conclusively shown a requirement for PTEN in upholding Treg function and stability. Using CRISPR-based genome editing in human Tregs, we show that PTEN ablation does not cause a global defect in Treg function and stability; rather, it selectively blocks their ability to suppress antigen-presenting cells. PTEN-KO Tregs exhibit elevated glycolytic activity, upregulate FOXP3, maintain a Treg phenotype, and have no discernable defects in lineage stability. Functionally, PTEN is dispensable for human Treg-mediated inhibition of T cell activity in vitro and in vivo but is required for suppression of costimulatory molecule expression by antigen-presenting cells. These data are the first to define a role for a signalling pathway in controlling a subset of human Treg activity. Moreover, they point to the functional necessity of PTEN-regulated PI3K-AKT activity for optimal human Treg function.
Newly synthesized mRNA escapes translational repression during the acute phase of the mammalian unfolded protein response
Authors: Alzahrani Mohammed R. , Guan Bo-Jhih , Zagore Leah L. , Wu Jing , Licatalosi Donny D. , Baker Kristian E. , Hatzoglou Maria 
Published: March 2022

AbstractEndoplasmic Reticulum (ER) stress, caused by the accumulation of misfolded proteins in the ER, elicits a homeostatic mechanism known as the Unfolded Protein Response (UPR). The UPR reprograms gene expression to promote adaptation to chronic ER stress. The UPR comprises an acute phase involving inhibition of bulk protein synthesis and a chronic phase of transcriptional induction coupled with the partial recovery of protein synthesis. However, the role of transcriptional regulation in the acute phase of the UPR is not well understood. Here we analyzed the fate of newly synthesized mRNA encoding the protective and homeostatic transcription factor X-box binding protein 1 (XBP1) during this acute phase. We have previously shown that global translational repression induced by the acute UPR was characterized by decreased translation and increased stability of XBP1 mRNA. We demonstrate here that this stabilization is independent of new transcription. In contrast, we show XBP1 mRNA newly synthesized during the acute phase accumulates with long poly(A) tails and escapes translational repression. Inhibition of nascent RNA polyadenylation during the acute phase decreased cell survival with no effect in unstressed cells. Furthermore, during the chronic phase of the UPR, levels of XBP1 mRNA with long poly(A) tails decreased in a manner consistent with co-translational deadenylation. Finally, additional pro-survival, transcriptionally-induced mRNAs show similar regulation, supporting the broad significance of the pre-steady state UPR in translational control during ER stress. We conclude that the biphasic regulation of poly(A) tail length during the UPR represents a previously unrecognized pro-survival mechanism of mammalian gene regulation.
A review of recent clinical measures that can be used to support psychological therapies with adults with intellectual disabilities
Authors: Gourley Thomas Richard , Yates Luke 
Published: March 2022

PurposePsychometrically sound measures are essential for clinical practice to provide appropriate therapeutic input. Vlissideset al.(2016) reviewed measures used in psychological therapies with people who have intellectual disabilities (ID). This paper aims to review the evidence for the psychometric properties of recent clinical measures published since/overlooked by Vlissideset al.(2016).Design/methodology/approachA literature search was conducted to identify relevant clinical measures. Experts in the field also were contacted. Twenty papers were identified, relating to five novel clinical measures: psychological therapies outcome scale – intellectual disabilities, clinical outcome in routine evaluation – learning disabilities scale 30, quality of early relatedness rating scale, scale of emotional development – short and the Frankish assessment of the impact of trauma.FindingsEvidence was found supporting a proportion of the psychometric properties of each measure, and some measures were found to be useful in directing interventions and informing clinical decisions. None of the measures identified, however, are yet to be fully psychometrically investigated, requiring further research.Originality/valueTo the best of the authors’ knowledge, this paper is the first to review the evidence of psychometric properties for these five emerging clinical measures and as such contributes an original perspective on their current state and requirements for future development.
Who shares wins? Understanding barriers to information sharing in managing supply chain risk
Authors: Hannibal Claire , Rowan Jack , Durowoju Olatunde , Bryde David , Holloway Jake , Adeyemi Omolola , Shamim Saira 
Published: March 2022

PurposeCurrently there is no universally accepted approach to supply chain risk management and assurance. To begin to shed more light on the practical operational challenges presented when considering supply chain risk mitigation through the sharing of information, this paper discusses the results of an empirical study conducted with manufacturing supply chain professionals. The study examines state-of-the-art challenges to managing risk in today's supply chains by reporting on data collected in 2021.Design/methodology/approachTo develop a rich picture of the challenges of information sharing in multi-tier supply chains, the authors adopted a qualitative research design. The authors conducted 14 interviews with supply chain professionals and ran two focus groups that were industry specific: one focused on the nuclear industry and the other on automotive.FindingsThe study identifies contemporary practical challenges to information sharing in supply chains – specifically challenges related to data quality and the acceptance of sub-optimal normative supply chain practices, which have consequences for supplier assurance fatigue and supply chain transparency.Originality/valueThe topical and contemporary study shows how an acceptance of the normative practices of a supply chain can have a cumulative effect on the likelihood of supply chain disruption due to shortcomings in approaches to information sharing. The notion of the acceptance of the status quo in this context has received limited research attention, and hence offers an extension to current discourse on supply chain risk and resilience.
Employees' reactions to supervisors' fulfillment/non-fulfillment of psychological contract promises: an experimental field study
Authors: Ababneh Khaldoun I. , Dedousis Evangelos , Braendle Udo 
Published: March 2022

PurposeDrawing upon social exchange theory and psychological contract (PC) research, this study aims to examine the impact of supervisors' fulfillment/non-fulfillment of transactional psychological contract (TPC) and relational psychological contract (RPC) promises on employees' reactions (e.g. feelings of violation, trust in the supervisor and organizational commitment) in a non-Western context, namely, the United Arab Emirates (UAE).Design/methodology/approachAn experimental field design was used with a sample of employees (N = 234) from a wide range of nationalities and work backgrounds. Four conditions were developed by manipulating the fulfillment of three TPC promises (e.g. competitive salary) and three RPC promises (e.g. sufficient power and responsibility). Participants were randomly assigned to the four conditions and asked to complete the study materials as if they were experiencing a real employment situation with a real organization. Hypotheses were tested using multivariate analysis of covariance and follow-up univariate analysis with Bonferronipost hoccomparisons.FindingsThis study demonstrated that a supervisor's failure to fulfill promises pertinent to both TPC and RPC, or one of them, generated negative reactions among participants. Based on a comparison of means analysis, this study also established that breach of TPC promises produced a higher negative impact than breach of RPC promises on perceptions of breach, feelings of violation, trust in the supervisor, organizational perceptions, organizational commitment and recommendation intentions. Furthermore, these findings revealed that a supervisor's breach of RPC promises has no significant incremental (additive) effect above a supervisor's breach of TPC promises. On the other hand, a supervisor's breach of TPC promises has a significant incremental (additive) effect above a supervisor's breach of RPC promises.Originality/valueThis study is one of the very few studies that examined and established, under a controlled setting, the differential effects of fulfillment/non-fulfillment of both TPC and RPC promises on employees' breach perceptions, emotions, attitudes and behavioral intentions.
Systems thinking approach for disaster resilient and climate smart agriculture in Bangladesh
Authors: Islam Sheikh Tawhidul , Akand Md. Kamruzzaman , Islam Md. Nurul , Samad Soumic , Rishal Faiyad H. 
Published: March 2022

Purpose
Linear and narrow focus of climate change and disaster impact assessments on agriculture turns out as a limiting factor to understand how impact conditions trigger changes in the whole system resulting to make problems complicated. The paper aims to identify the micro-level challenges of the agriculture sector and then shows how macro-level planning could be developed and may help the rural peasants of Bangladesh to better cope with the adverse conditions generated as a result of disaster impacts and/or climate change-induced threats.

Design/methodology/approach
The paper, based on a secondary literature review and primary data generated by the author, shows that agriculture happens as a system where many microelements and processes contribute and benefits from it do not only confine into the final product generation. Using both the primary and secondary data, the paper shows how simplistic approaches to assess disaster impacts on agriculture in Bangladesh are taking place and thus leaving scopes to read properly the more complex and cyclic forms of hazard impacts in the sector by using the systems thinking approach and complex systems methodology.

Findings
The paper finally suggests how a better and comprehensive understanding of disaster and climate change impacts on agriculture would provide arguments for mainstreaming climate change adaptation and disaster risk reduction actions into regular development planning of the government.

Originality/value
The authors declare that this submission is their own work, and, to the best of the authors’ knowledge, it contains no materials previously published or written by another person or substantial proportions of material which have been accepted for the award of anywhere else.
Work and active aging: is there a relationship between health and meaning in life?
Authors: Torres Isabel , Gaspar Tânia , Rodrigues Paula 
Published: March 2022

PurposeThis study aims to explain the health impact of work demands and organization, job content, leadership and values in the workplace. It also explores the extent to which health conditions influence the meaning in life in late career.Design/methodology/approachThe sample consisted of 1,330 Portuguese-based individuals aged 55–75 years. The structural equation modeling (SEM) was used for the data analysis and to test the research questions.FindingsThe results showed that stress and burnout are influenced by work demands and organization, job content, leadership and values in the workplace. Employment status had no influence. Health status affects the meaning in life.Research limitations/implicationsAlthough participants were asked to answer the questionnaire bearing in mind their last work experience, retirees could have had difficulty reporting on their last work; therefore, in future research, the use of a qualitative methodology could also be equated as to complement richer information regarding past experiences in the work context.Practical implicationsConsidering the main goals of the United Nations 2030 Agenda for sustainable development, this study contributes, namely, to the third one – Ensure healthy lives and promote well-being for all at all ages. In fact, directing a look at the condition in which older people work and at their health contributes not only to more productive organizations, to less spending of public money on health, but also to a more inclusive society. Bearing in mind workers are progressively retiring later and that the exposure to certain work conditions during the late career is problematic for organizations and for society in general, this study has practical and social implication.Originality/valueConsidering demographic changes and the aging of the active population in Portugal and the scarce studies carried out in the country concerning this relevant theme, the authors believe that the conclusions may constitute an important input for workplace policies regarding older workers. In addition, little research has focused on the effect of health in meaning in life.