bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hereditary haemochromatosis beyond liver cancer: increased risk of prostate cancer during an 11-year follow-up
Authors: Atkins Janice L , Pilling Luke C , Torti Suzy V , Torti Frank M , Kuchel George A , Melzer David 
Published: March 2022

AbstractIn European ancestry populations, the iron overload disorder Hereditary Haemochromatosis (HH) is predominantly caused by the HFE p.C282Y mutation. Male p.C282Y homozygotes have markedly increased hepatic malignancy risks but risks for other cancers in both male and female homozygotes are unclear. We studied data from 451,143 UK Biobank European ancestry community participants (aged 40-70 years; 54.3% female) followed for a mean 11.6 years via hospital admission and national cancer registry data. We estimated risks of incident bladder, blood (with sub-analyses of leukemia and lymphoma), bone, brain, breast, colorectal, kidney, lung, melanoma, oesophageal, ovarian, pancreatic, prostate and stomach cancers in the 2,890 p.C282Y homozygotes, compared to participants without HFE mutations. Male p.C282Y homozygotes (12.1% with baseline diagnosed HH) had increased risks of prostate cancer (6.8% versus 5.4% without mutations, hazard ratio HR=1.32, 95% CI=1.07-1.63, p=0.01,). In lifetable estimates from ages 40-75 years, 14.4% of male p.C282Y homozygotes are projected to develop prostate cancer (versus 10.7% without mutations, excess 3.8%, 95% CI = 1.3-6.8). There was no excess of studied cancers in female p.C282Y homozygotes, or in p.C282Y/p.H63D compound heterozygotes of either sex. In a large community sample of male p.C282Y homozygotes, there was a 32% increase in prostate cancer risk, in addition to the known increased liver cancer risk. Those reporting HFE genotype status or monitoring p.C282Y homozygous males may need to ensure clinical monitoring for both liver and prostate cancers.Novelty and impact of the workMale HFE p.C282Y homozygotes, at risk of iron overload disorder hereditary haemochromatosis, have known increased liver cancer risks. We have shown, for the first time, that the male p.C282Y homozygotes also have a 32% increased risk of prostate cancer; with an excess proportion of 3.8% by age 75 compared to those without mutations. Those reporting HFE genotype status or monitoring p.C282Y homozygous males need to ensure vigilance for both excess liver and prostate cancers.
Knowledge-guided deep learning models of drug toxicity improve interpretation
Authors: Hao Yun , Romano Joseph D. , Moore Jason H. 
Published: March 2022

ABSTRACTIn drug development, a major reason for attrition is the lack of understanding of cellular mechanisms governing drug toxicity. The black-box nature of conventional classification models has limited their utility in identifying toxicity pathways. Here we developed DTox (Deep learning forToxicology), an interpretation framework for knowledge-guided neural networks, which can predict compound response to toxicity assays and infer toxicity pathways of individual compounds. We demonstrate that DTox can achieve the same level of predictive performance as conventional models with a significant improvement in interpretability. Using DTox, we were able to rediscover mechanisms of transcription activation by three nuclear receptors, recapitulate cellular activities induced by aromatase inhibitors and PXR agonists, and differentiate distinctive mechanisms leading to HepG2 cytotoxicity. Virtual screening by DTox revealed that compounds with predicted cytotoxicity are at higher risk for clinical hepatic phenotypes. In summary, DTox provides a framework for deciphering cellular mechanisms of toxicityin silico.
Generating publication ready visualizations for Single Cell transcriptomics using SCpubr
Authors: Blanco-Carmona Enrique 
Published: March 2022

AbstractSingle Cell transcriptomic analysis has become a widespread technology of choice when it comes to understanding the differences at a transcriptomic level in heterogeneous samples. As a consequence, a plethora of analysis tools have been published to tackle the different analysis steps from count matrix generation to downstream analysis. Many of them provide ways to generate visualizations of the data. While some design choices are made, it is a common practice to provide the user with visualizations as raw as possible so that they can be customized to the user needs. However, in many cases these final customization steps are either time consuming or demand a very specific set of skills. This problem is addressed by SCpubr, which sacrifices some of this initial freedom of choice in aesthetics to provide the user a more streamlined way of generating high quality Single Cell transcriptomic visualizations.
Connexin 43-mediated Neurovascular Interactions Regulate Neurogenesis in the Adult Brain Subventricular Zone
Authors: Genet Nafiisha , Genet Gael , Fang Jennifer S. , Chavkin Nicholas W. , Vasavada Hema H. , Goldberg Joshua S. , Acharya Bipul R. , Bhatt Neha , Baker Kasey , McDonnell Stephanie , Huba Mahalia R. , Ma Gerry , Eichmann Anne , Thomas Jean Leon , ffrench-Constant Charles , Hirschi Karen K. 
Published: March 2022

AbstractThe subventricular zone (SVZ) is the largest neural stem cell (NSC) niche in the adult brain; herein, the blood-brain barrier is leaky, allowing direct interactions between NSCs and endothelial cells (ECs). Mechanisms by which direct NSC-EC interactions in the SVZ control NSC behavior are unclear. We found Cx43 to be highly expressed by both NSCs and ECs in the SVZ, and its deletion in either cell type leads to increased NSC proliferation and neuroblast generation, suggesting that Cx43-mediated NSC-EC interactions maintain NSC quiescence. This is further supported by in vitro studies showing co-culture with ECs decreases NSC proliferation and increases their expression of genes associated with quiescence in a Cx43-dependent manner. Cx43 mediates these effects in a channel-independent manner involving its cytoplasmic tail and ERK activation. Such insights further advance our understanding of NSC regulation in vivo and may inform NSC maintenance ex vivo for stem cell therapies for neurodegenerative disorders.
A nepenthesin insert allosterically controls catalysis in the malaria parasite protease plasmepsin V
Authors: Polino Alexander J. , Miller Justin J. , Bhakat Soumendranath , Bobba Suhas , Bowman Gregory R. , Goldberg Daniel E. 
Published: March 2022

AbstractPlasmepsin V (PM V) is a pepsin-like aspartic protease essential for growth of the malaria parasite Plasmodium falciparum. Previous work has shown PM V to be an ER-resident protease that processes parasite proteins destined for export into the host cell. Depletion or inhibition of the enzyme is lethal during asexual replication within red blood cells, as well as during the formation of sexual stage gametocytes. The structure of the P. vivax PM V has been characterized by x-ray crystallography, revealing a canonical pepsin fold punctuated by structural features uncommon to secretory aspartic proteases. Here we use parasite genetics to probe these structural features by attempting to rescue lethal PM V depletion with various mutant enzymes. We find an unusual nepenthesin 1-type insert to be essential for parasite growth and PM V activity. Mutagenesis of the nepenthesin insert suggests that both its amino acid sequence and one of the two disulfide bonds that undergird its structure are required for the nepenthesin insert’s role in PM V function. Molecular dynamics simulations paired with Markov state modelling suggest that the nepenthesin insert allosterically controls PM V catalysis through multiple mechanisms.
Model Selection in Occupancy Models: Inference versus Prediction
Authors: Stewart Peter S. , Stephens Philip A. , Hill Russell A. , Whittingham Mark J. , Dawson Wayne 
Published: March 2022

AbstractOccupancy models are a vital tool for applied ecologists studying the patterns and drivers of species occurrence, but their use requires a method for selecting between models with different sets of occupancy and detection covariates. The information-theoretic approach, which employs information criteria such as Akaike’s Information Criterion (AIC) is arguably the most popular approach for model selection in ecology and is often used for selecting occupancy models. However, the information-theoretic approach risks selecting models which produce inaccurate parameter estimates, due to a phenomenon called collider bias. Using simulations, we investigated the consequences of collider bias (using an illustrative example called M-bias) in the occupancy and detection processes of an occupancy model, and explored the implications for model selection using AIC and a common alternative, the Schwarz Criterion (or Bayesian Information Criterion, BIC). We found that when M-bias was present in the occupancy process, AIC and BIC selected models which inaccurately estimated the effect of the focal occupancy covariate, while simultaneously producing more accurate predictions of the site-level occupancy probability. In contrast, M-bias in the detection process did not impact the focal estimate; all models made accurate inferences, while the site-level predictions of the AIC/BIC-best model were slightly more accurate. Our results demonstrate that information criteria can be used to select occupancy covariates if the sole purpose of the model is prediction, but must be treated with more caution if the purpose is to understand how environmental variables affect occupancy. By contrast, detection covariates can usually be selected using information criteria regardless of the model’s purpose. These findings illustrate the importance of distinguishing between the tasks of parameter inference and prediction in ecological modelling. Furthermore, our results underline concerns about the use of information criteria to compare different biological hypotheses in observational studies.Open Research StatementCode to fully reproduce our simulations and analyses is available at:https://zenodo.org/badge/latestdoi/462801230
A systematic and critical review of leadership styles in contemporary hospitality: a roadmap and a call for future research
Authors: Elkhwesky Zakaria , Salem Islam Elbayoumi , Ramkissoon Haywantee , Castañeda-García José-Alberto 
Published: March 2022

Purpose
The purpose of this paper is to provide an overview of leadership styles in the hospitality industry. It also demonstrates theories used in hospitality leadership styles research, identifies the main outcomes and highlights gaps for future research.

Design/methodology/approach
This paper presents a comprehensive review of the 79 articles on leadership styles in the hospitality context spanning over 13 years (2008–2020) and extends the scope in distinctive means.

Findings
This review has demonstrated that leadership styles research in hospitality has made progress in the past 13 years; however, there are conceptual and empirical overlaps among different leadership styles in hospitality. There is a lack of research on antecedents and integrating theories in studies. This review has revealed that several leadership styles have not been rigorously examined in hospitality research with their outcomes.

Research limitations/implications
The search strategy used to find articles published in Web of Science about leadership styles in hospitality was restricted to title to boost the accuracy of the subsequent literature.

Practical implications
By following the guidance presented in this review, the authors expect to advance and maintain hospitality leadership research to provide substantive insights into the context of hospitality leadership over the coming years.

Originality/value
To the best of the authors’ knowledge, this study is one of the first to undertake a comprehensive understanding of various leadership styles in the hospitality context. This study provides a comprehensive projected research agenda to demonstrate theoretical discourses and empirical research. Overall, this critical review presents a holistic idea of the focus of the prior studies and what should be highlighted in future studies.
Determinants of the intellectual capital efficiency of listed banks in Nigeria: a DEA approach
Authors: Olohunlana Aminat Olayinka , Odeleye Anthonia Taye , Isola Wakeel Atanda 
Published: March 2022

PurposeThis study empirically investigates the level of intellectual capital efficiency amongst the listed commercial banks in Nigeria and the factors influencing its efficient utilisation.Design/methodology/approachThe paper employs the data envelopment analysis (DEA) to determine intellectual capital efficiency for the listed banks in Nigeria using data obtained from their annual financial reports from 2013 to 2019. After obtaining the efficiency scores, the Tobit regression technique was used to analyse the impact of firm-specific factors on intellectual capital efficiency.FindingsThe study found that only 8.33% of the sampled Nigerian commercial banks are at optimum capacity in utilising their intellectual capital, while 91.67% are inefficient. It also finds that bank size and directors' shareholdings positively impact intellectual capital efficiency, while market and ownership concentration debar the attainment of optimum intellectual capital efficiency.Research limitations/implicationsThis study contributes to very scare literature on intellectual capital efficiency measurements by using the non-parametric analysis (DEA) to measure intellectual capital efficiency for listed banks in Nigeria.Practical implicationsThis study showcases the importance of measuring intellectual capital efficiency amongst listed banks in Nigeria. It provides more information to the regulators and stakeholders on the need to enforce the disclosure of the value created from intellectual capital investment.Originality/valueThis study contributes to the scarce literature on measuring intellectual capital efficiency using a non-parametric analysis (DEA). It also provides new insights into the factors that influence intellectual capital efficiency amongst listed commercial banks in Nigeria.
“What is going on in the ‘big tent’?” Current developments in (new) institutional theory and performance measurement and management research
Authors: Polzer Tobias 
Published: March 2022

PurposeIn a recent paper that was published inJournal of Public Budgeting, Accounting and Financial Management, Modell (2021) takes stock of the institutional research on performance measurement and management (PMM) in the public sector and proposes a number of avenues for further inquiry in the area. The aim of this comment is to contextualise some of his observations against the backdrop of current developments in (new) institutional theory.Design/methodology/approachThe recent scholarly debate about whether institutional theory needs any redirecting is the point of departure for this comment. Three of the themes from this debate are revisited and implications for research on PMM in the public sector are outlined.FindingsFirst, against the backdrop of an emerging plethora of organisational forms in the public sector, this comment focusses on the locus or “where” PMM can be analysed and how organisational forms affect PMM. The second point addresses the “what” of analysis, where it is argued that PMM instruments are embedded in an ecology of concepts and a relational perspective on diffusion is introduced. A third observation is related to methodological issues and discusses the “how”: how best to study manifestations of PMM systems.Originality/valueThe comment illustrates a number of implications of the current developments in (new) institutional theory for research on PMM. In so doing, the wider ambition is to stimulate an exchange between public-sector accounting and organisation studies.
Personal thermal comfort models: a deep learning approach for predicting older people’s thermal preference
Authors: Arakawa Martins Larissa , Soebarto Veronica , Williamson Terence , Pisaniello Dino 
Published: March 2022

PurposeThis paper presents the development of personal thermal comfort models for older adults and assesses the models’ performance compared to aggregate approaches. This is necessary as individual thermal preferences can vary widely between older adults, and the use of aggregate thermal comfort models can result in thermal dissatisfaction for a significant number of older occupants. Personalised thermal comfort models hold the promise of a more targeted and accurate approach.Design/methodology/approachTwenty-eight personal comfort models have been developed, using deep learning and environmental and personal parameters. The data were collected through a nine-month monitoring study of people aged 65 and over in South Australia, who lived independently. Modelling comprised dataset balancing and normalisation, followed by model tuning to test and select the best hyperparameters’ sets. Finally, models were evaluated with an unseen dataset. Accuracy, Cohen’s Kappa Coefficient and Area Under the Receiver Operating Characteristic Curve (AUC) were used to measure models’ performance.FindingsOn average, the individualised models present an accuracy of 74%, a Cohen’s Kappa Coefficient of 0.61 and an AUC of 0.83, representing a significant improvement in predictive performance when compared to similar studies and the “Converted” Predicted Mean Vote (PMVc) model.Originality/valueWhile current literature on personal comfort models have focussed solely on younger adults and offices, this study explored a methodology for older people and their dwellings. Additionally, it introduced health perception as a predictor of thermal preference – a variable often overseen by architectural sciences and building engineering. The study also provided insights on the use of deep learning for future studies.
Immunoglobulin A vasculitis post‐severe acute respiratory syndrome coronavirus 2 vaccination and review of reported cases
Authors: Hashizume Hideo , Ajima Sayaka , Ishikawa Yuto 
Published: March 2022

AbstractImmunoglobulin (Ig)A vasculitis/nephropathy is a systemic immune complex‐mediated vasculitis. Although severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) vaccination is widely recommended in individuals without specific allergy to the vaccine components, it is arguable whether vaccination is advisable for patients with IgA vasculitis or for predisposed individuals. We and others have presented cases of IgA vasculitis occurring after SARS‐CoV‐2 vaccination. In total, these 19 cases, including ours, involved predominantly female patients, and half of them were suffering from de novo vasculitis onset. The most frequent manifestation was gross hematuria (89.5%) while skin lesions were relatively infrequent, occurring in only five cases (26.3%), of which three (15.8%) were confirmed to be IgA vasculitis. Taken together, these cases suggest that SARS‐CoV‐2 vaccination might be a trigger for development/deterioration of IgA vasculitis/nephropathy.
Gene expression in lung epithelial cells following interaction with Pneumocystis carinii and its specific life forms yields insights into host gene responses to infection
Authors: Kottom Theodore J. , Carmona Eva M. , Limper Andrew H. 
Published: March 2022

AbstractPneumocystis spp. interacts with epithelial cells in the alveolar spaces of the lung. It is thought that the binding of Pneumocystis to host cell epithelium is needed for life cycle completion and proliferation. The effect of this interaction on lung epithelial cells has previously shown that the trophic form of this organism greatly inhibits p34cdc2 activity, a serine/threonine kinase required for transition from the G2 to M phase in the cell cycle. To gain further insight into the host response during Pneumocystis pneumonia infection, we used microarray technology to profile epithelial cell (A549) gene expression patterns following Pneumocystis carinii interaction. Furthermore, we isolated separate populations of cyst and trophic forms of P. carinii, which were then applied to the lung epithelial cells. Differential expression of genes involved in various cellular functions dependent on the specific P. carinii life form in contact with the A549 cell was identified. The reliability of our data was further confirmed by Northern blot analysis on a number of selected upregulated or downregulated transcripts. The transcriptional response to P. carinii was dominated by cytokines, apoptotic, and antiapoptosis‐related genes. These results reveal several previously unknown effects of P. carinii on the lung epithelial cell and provide insight into the complex interactions of host and pathogen.
An ArsRC fusion protein enhances arsenate sensing and detoxification
Authors: Chen Jian , Galván Adriana E. , Nadar Venkadesh Sarkarai , Yoshinaga Masafumi , Rosen Barry P. 
Published: March 2022

SummaryArsenical resistance (ars) operons encode genes for arsenic resistance and biotransformation. The majority are composed of individual genes, but fusion of ars genes is not uncommon, although it is not clear if the fused gene products are functional. Here we report identification of a four‐gene ars operon from Paracoccus sp. SY that has two arsR‐arsC gene fusions. ArsRC1 and ArsRC2 are related proteins that consist of an N‐terminal ArsR arsenite (As(III))‐responsive repressor with a C‐terminal ArsC arsenate reductase. The other two genes in the operon are gapdh and arsJ. GAPDH, glyceraldehyde 3‐phosphate dehydrogenase, forms 1‐arseno‐3‐phosphoglycerate (1As3PGA) from 3‐phosphoglyceraldehyde and arsenate (As(V)), ArsJ is an efflux permease for 1As3PGA that dissociates into extracellular As(V) and 3‐phosphoglycerate. The net effect is As(V) extrusion and resistance. ArsRs are usually selective for As(III) and do not respond to As(V). However, the substrates and products of this operon are pentavalent, which would not be inducers of the operon. We propose that ArsRC fusions overcome this limitation by channelling the ArsC product into the ArsR binding site without diffusion through the cytosol, a de facto mechanism for As(V) induction. This novel mechanism for arsenate sensing can confer an evolutionary advantage for detoxification of inorganic arsenate.
Some like it cold: the cellular organization and physiological limits of cold‐tolerant nitrite‐oxidizing Nitrotoga
Authors: Keuter Sabine , Koch Hanna , Sass Katharina , Wegen Simone , Lee Natuschka , Lücker Sebastian , Spieck Eva 
Published: March 2022

SummaryChemolithoautotrophic production of nitrate is accomplished by the polyphyletic functional group of nitrite‐oxidizing bacteria (NOB). A widely distributed and important NOB clade in nitrogen removal processes at low temperatures is Nitrotoga, which however remains understudied due to the scarcity of cultivated representatives. Here, we present physiological, ultrastructural and genomic features of Nitrotoga strains from various habitats, including the first marine species enriched from an aquaculture system. Immunocytochemical analyses localized the nitrite‐oxidizing enzyme machinery in the wide irregularly shaped periplasm, apparently without contact to the cytoplasmic membrane, confirming previous genomic data suggesting a soluble nature. Interestingly, in two strains we also observed multicellular complexes with a shared periplasmic space, which seem to form through incomplete cell division and might enhance fitness or survival. Physiological tests revealed differing tolerance limits towards dissolved inorganic nitrogen concentrations and confirmed the generally psychrotolerant nature of the genus. Moreover, comparative analysis of 15 Nitrotoga genomes showed, e.g. a unique gene repertoire of the marine strain that could be advantageous in its natural habitat and confirmed the lack of genes for assimilatory nitrite reduction in a strain found to require ammonium for growth. Overall, these novel insights largely broaden our knowledge of Nitrotoga and elucidate the metabolic variability, physiological limits and thus potential ecological roles of this group of nitrite oxidizers.