bluuebunny/crossref_metadata_2025 huggingface dataset:
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

Chinese 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

Identifying 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

Acoustic 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

Background

Polypharmacy 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.

Methods

A 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.

Results

In 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.

Conclusions

Pharmacist 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 Registration

CRD42019139679
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

Highlanders 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

Cell 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

Zika 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.
YAP–VGLL4 antagonism defines the major physiological function of the Hippo signaling effector YAP
Authors: Cai Jing , Choi Kyungsuk , Li Hongde , Pulgar Prieto Katiuska Daniela , Zheng Yonggang , Pan Duojia
Published: December 2022

The Hippo–YAP signaling pathway plays a critical role in development, homeostasis, regeneration, and tumorigenesis by converging on YAP, a coactivator for the TEAD family DNA-binding transcription factors, to regulate downstream transcription programs. Given its pivotal role as the nuclear effector of the Hippo pathway, YAP is indispensable in multiple developmental and tissue contexts. Here we report that the essentiality of YAP in liver and lung development can be genetically bypassed by simultaneous inactivation of the TEAD corepressor VGLL4. This striking antagonistic epistasis suggests that the major physiological function of YAP is to antagonize VGLL4. We further show that the YAP–VGLL4 antagonism plays a widespread role in regulating Hippo pathway output beyond normal development, as inactivation ofVgll4dramatically enhanced intrahepatic cholangiocarcinoma formation inNf2-deficient livers and ameliorated CCl4-induced damage in normal livers. Interestingly,Vgll4expression is temporally regulated in development and regeneration and, in certain contexts, provides a better indication of overall Hippo pathway output than YAP phosphorylation. Together, these findings highlight the central importance of VGLL4-mediated transcriptional repression in Hippo pathway regulation and inform potential strategies to modulate Hippo signaling in cancer and regenerative medicine.
Small-angle neutron scattering of long-wavelength magnetic modulations in reduced sample dimensions
Authors: Causer Grace L. , Chacon Alfonso , Heinemann André , Pfleiderer Christian
Published: December 2022

Magnetic small-angle neutron scattering (SANS) is ideally suited to providing direct reciprocal-space information on long-wavelength magnetic modulations, such as helicoids, solitons, merons or skyrmions. SANS of such structures in thin films or micro-structured bulk materials is strongly limited by the tiny scattering volume vis a vis the prohibitively high background scattering by the substrate and support structures. Considering near-surface scattering just above the critical angle of reflection, where unwanted signal contributions due to substrate or support structures become very small, it is established that the scattering patterns of the helical, conical, skyrmion lattice and fluctuation-disordered phases in a polished bulk sample of MnSi are equivalent for conventional transmission and near-surface SANS geometries. This motivates the prediction of a complete repository of scattering patterns expected for thin films in the near-surface SANS geometry for each orientation of the magnetic order with respect to the scattering plane.
2-Ethyl-4-methyl-1H-imidazol-3-ium bromide
Authors: Butcher Ray J. , Purdy Andrew P.
Published: December 2022

In the title molecular salt, C6H11N2
+·Br−, the components are linked by N—H...Br...H—N hydrogen bonds into C(8)chains of alternating cations and anions propagating in the b-axis direction; these chains are cross-linked in the c-axis direction by weak C—H...Br hydrogen bonds.
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

Purpose

Post-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/approach

The 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.

Findings

The 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 implications

Social 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/value

The 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

Purpose

The 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/approach

The 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.

Findings

The 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/implications

This research study used cross-sectional data, which fall short of meeting the requirement for proving causation.

Practical implications

The 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/value

This 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

Purpose

In 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/approach

This 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.

Findings

The 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/implications

Theoretically, 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/value

Because 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.
Factors associated with changes in illicit opioid use during the COVID-19 pandemic among incarcerated people who use drugs in Quebec, Canada
Authors: Park Hyejin , Linthwaite Blake , Dussault Camille , Halavrezos Alexandros , Chalifoux Sylvie , Sherman Jessica , Del Balso Lina , Buxton Jane A. , Cox Joseph , Kronfli Nadine
Published: December 2022

Purpose

People who use drugs (PWUD) have been disproportionately affected by the COVID-19 pandemic. This study aims to examine changes in illicit opioid use and related factors among incarcerated PWUD in Quebec, Canada, during the pandemic.

Design/methodology/approach

The authors conducted an observational, cross-sectional study in three Quebec provincial prisons. Participants completed self-administered questionnaires. The primary outcome, “changes in illicit opioid consumption,” was measured using the question “Has your consumption of opioid drugs that were not prescribed to you by a medical professional changed since March 2020?” The association of independent variables and recent changes (past six months) in opioid consumption were examined using mixed-effects Poisson regression models with robust standard errors. Crude and adjusted risk ratios with 95% confidence intervals (95% CIs) were calculated.

Findings

A total of 123 participants (median age 37, 76% White) were included from January 19 to September 15, 2021. The majority (72; 59%) reported decreased illicit opioid consumption since March 2020. Individuals over 40 were 11% less likely (95% CI 14–8 vs 18–39) to report a decrease, while those living with others and with a history of opioid overdose were 30% (95% CI 9–55 vs living alone) and 9% (95% CI 0–18 vs not) more likely to report decreased illicit opioid consumption since March 2020, respectively.

Originality/value

The authors identified possible factors associated with changes in illicit opioid consumption among incarcerated PWUD in Quebec. Irrespective of opioid consumption patterns, increased access to opioid agonist therapy and enhanced discharge planning for incarcerated PWUD are recommended to mitigate the harms from opioids and other drugs.
Managing unbounded digital transformation: exploring the role of tensions in a digital transformation initiative in the forestry industry
Authors: Koukouvinou Panagiota , Simbi Nadia , Holmström Jonny
Published: December 2022

Purpose

Prior research has highlighted the pervasive importance of digital technologies in business and societal settings, but their enabling role in digital transformation, and effective forms of organization to address tensions that arise during attempts to promote it, have been insufficiently explored. Therefore, the purpose of this paper is to investigate how and why tensions affect clusters established to foster digital transformation.

Design/methodology/approach

Empirical data were acquired through a qualitative exploratory holistic single case study, focused on the Swedish Cluster of Forest Technology. This included interviews with informants, selected by homogeneous purposive sampling, and event observation to investigate the personal perspectives of representatives of every company engaged in the cluster, followed by a thematic analysis of their comments.

Findings

The case study revealed three major tensions, between knowledge flow, collaboration and competition, but also others that were interrelated with those major tensions, related to matters such as trust and protection of intellectual property, power equality and hierarchy, and networks that must be managed in digital transformation efforts.

Originality/value

The paper extends understanding of the tensions that arise, and their management, in digital transformation processes.
An investigation into how value incongruence became misfit
Authors: Sun Yuwei , Billsberry Jon
Published: December 2022

Purpose

The purpose of this review is to argue that the way that perceived employee misfit (PEM) has been measured in quantitative studies does not capture the construct identified in qualitative studies.

Design/methodology/approach

Through reverse citation analysis, this study reveals how low levels of value congruence became the currency of PEM in quantitative studies.

Findings

This study finds that in the absence of alternatives, researchers have taken low scores of value congruence as a measure of misfit. However, there is limited evidence to show that PEM relates to values, supplementary conceptualization or interactions with the organization (rather than interactions with other employees, tasks, etc.). In addition, the most commonly used instruments measure degrees of similarity, not disparity, making the interpretation of PEM-related data unclear. Combined, these factors raise construct validity concerns about most quantitative studies of PEM.

Research limitations/implications

Given the upsurge of interest in PEM, there is an urgent need for greater clarification on the nature of the construct. From the analysis, this study identifies two key dimensions of studying PEM that create four distinctly different ways of conceptualizing the construct.

Originality/value

This study highlights a series of major methodological weaknesses in the study of PEM and reveal that almost all published quantitative studies of PEM are actually studying something else; something whose nature is very unclear.
Is Ramadan model of intermittent fasting related to hedonic hunger?
Authors: Tengilimoglu-Metin M. Merve , METİN Ziya Erokay
Published: December 2022

Purpose

The purpose of this study was to examine hedonic hunger at the end of the Ramadan fasting.

Design/methodology/approach

Data were collected by the Power of Food Scale (PFS), Food Craving Questionnaire-Trait (FCQ-T) and the Visual Analogue Scale. All data were taken twice at the beginning and end of Ramadan fasting.

Findings

A total number of 105 volunteers (43.8% female and 56.2% male) participated in a cross-sectional study. Ramadan fasting associated with PFS food tasted sub-factor, whereas no association was found on PFS aggregate and other PFS domain factors. Participants had higher PFS food tasted domain score at the end of the Ramadan fasting than before Ramadan fasting (p < 0.001). Total FCQ-T score as well as all sub-domains did not differ significantly. Females desired to consume carbonated beverages more, whereas in male (p = 0.04), ice cream was the most craved food.

Originality/value

The findings of this study provide data to the literature about the relation between Ramadan fasting and hedonic hunger. Ramadan fasting appears to have an influence on pleasure at first bite. The effect of Ramadan fasting on hedonic hunger should be tested with larger samples and controlled trials.
(Re)constructing performative anti-racist education courses: from the experiences of Black feminist graduate assistants
Authors: Adeniji Danelle , Foster Marquita
Published: December 2022

Purpose

The purpose of this study is to describe the authors’ experiences as Black feminist graduate assistants assigned to teach diversity courses led by white professors.

Design/methodology/approach

The authors draw from Black feminist approach to provide authentic, liberatory anti-racist pedagogy, ensuring that the identities and cultural knowledge of Black, indigenous and people of color (BIPOC) pre-service teachers (PSTs) are given space in anti-racist education and social studies courses.

Findings

The study’s findings show that creating systems for (re)constructing performative anti-racist courses disrupt whiteness and whitewashed pedagogy in teacher preparation programs.

Originality/value

The implications of the authors’ experiences reflect that centering abolitionist teaching methods can bolster BIPOC PSTs anti-racist identities and future practices in diverse classrooms.
Genome size does not influence extinction risk in the world's amphibians
Authors: Pincheira‐Donoso Daniel , Harvey Lilly P. , Johnson Jack V. , Hudson Dave , Finn Catherine , Goodyear Luke E. B. , Guirguis Jacinta , Hyland Edel M. , Hodgson Dave J.
Published: December 2022

Variation in genome size spans multiple orders of magnitude among animals. Despite the longstanding debate regarding the adaptive value or costs of genomic complexity, genome size has been proposed to influence extinction risk under the rapidly changing environments of the Anthropocene.

The main hypothesis suggests that genome enlargement increases the accumulation of deleterious mutations while reducing rates of organismal growth and development. These combined effects of larger genome size are predicted to trigger population declines that can lead to extinction, especially under rapidly changing environments that disrupt demographic resilience.

Comparative evidence from terrestrial plants and across vertebrates has provided mixed support for this hypothesis. However, large‐scale comparative studies based on explicit phylogenetic approaches remain lacking. Using a global‐scale amphibian dataset and two recognised proxies of extinction risk (International Union for Conservation of Nature IUCN conservation categories and population trends), we test the prediction that genomes are larger (as estimated by C‐value) in species facing extinction risk. We combine these analyses with life‐history traits widely known to be implicated with extinctions (body size, fecundity), along with a range of environmental factors.

Our phylogenetic analyses consistently failed to identify an effect of genome size on either of the two proxies for extinction risk. The only consistent predictor of extinction risk observed across models performed for amphibians combined and for orders separately was decreasing geographical range size. We also identified a role for larger body size, decreasing range of environmental temperature (for anurans) and increasing levels of UV‐B radiation (for salamanders) as drivers of increasing threat.

Our study provides no support for the prediction that species with larger genomes suffer heightened risk of extinction. We discuss some fundamental limitations underlying the genome size‐extinction hypothesis, and suggest that it is not a promising avenue to elucidate the causes of biodiversity declines in the Anthropocene.

Read the freePlain Language Summaryfor this article on the Journal blog.
A pattern recognition receptor C‐type lectin TcCTL14 contributes to immune response and development in the red flour beetle, Tribolium castaneum
Authors: Zhang Yonglei , Ai Huayi , Wang Yihan , Zhang Ping , Du Liheng , Wang Jiatao , Wang Suisui , Gao Han , Li Bin
Published: December 2022

Evidence is accumulating that pattern recognition receptor (PRR) C‐type lectins (CTL) play essential roles in recognition of pathogens. TcCTL14 (accession no. TC00871) contains the most domains among all CTL of Tribolium castaneum. Yet the biological function of TcCTL14 remains unclear. In this study, TcCTL14 exhibiting typical motif and domain of CTL was cloned from T. castaneum. The expression pattern analysis showed that TcCTL14 was highly expressed in late pupae and central nervous system, and was upregulated after treatment with Escherichia coli and Staphylococcus aureus, respectively. Analysis of binding affinity revealed that recombinant TcCTL14 not only could bind to lipopolysaccharide and peptidoglycan in a dose‐dependent fashion, but possibly could bind to and agglutinate different bacteria in a Ca2+‐dependent fashion. Knockdown of TcCTL14 before injection with bacteria led to the downregulation of nuclear factor‐κB transcription factors of Toll/IMD and 4 antimicrobial peptides. Knockdown of TcCTL14 also caused suppressed metamorphosis, reduced fecundity, and delayed embryogenesis of T. castaneum. Further observation discovered that knockdown of TcCTL14 inhibited the development of ovaries and embryos. The detection of signaling pathways revealed that TcCTL14 may be involved in metamorphosis and fecundity by impacting 20‐hydroxyecdysone and vitellogenin, respectively. Overall, these results indicate that TcCTL14 may contribute to immune response by agglutination or regulating the expression of antimicrobial peptides by the Toll/IMD pathway, and is required for T. castaneum development including metamorphosis, fecundity, and embryogenesis. These findings will improve the functional cognition of PRR CTL in insects and provide the new strategy for pest control.
Genomic differentiation with isolation by distance along a latitudinal gradient in the spotted‐leg treefrogPolypedates megacephalus
Authors: JIN Long , ZHENG Yuchi , LUAN Xiaofeng , LIAO Wenbo
Published: December 2022

The patterns of isolation by distance (IBD) entailing increased genetic differentiation among populations have aroused extensive concerns for evolutionary biologists. Although the IBD may act on spatial processes contributing to the genetic differentiation among populations in anuran species, the factors shaping the IBD of frogs among populations in natural systems are largely unknown. Here, we studied the genetic differentiation among six populations with 24 individuals of the spotted‐leg treefrog along a latitudinal gradient (1860.31 km) based on 1020 single nucleotide polymorphisms from restriction site‐associated DNA sequencing. The results showed that the genetic diversity differed significantly among populations and that the insular populations had higher genetic diversity than the mainland populations. Furthermore, we also found a significant genetic differentiation among populations (FST= 0.277) and no sign of inbreeding (FUNI= −0.145). The IBD was detected for all populations, and a higher degree of the IBD was indicated when controlling for the effects of the isolation between Hainan and mainland populations caused by the Qiongzhou Strait. Our findings suggest that the form of the Qiongzhou Strait plays a key role in shaping the genetic diversity and population differentiation in treefrogs.
Screening of dephytinization reaction of chlorophyll pigments with citrus acetone powder by UPLC–DAD–MS
Authors: Li Yunchang , Agarry Israel Emiezi , Ding Desheng , Zalán Zsolt , Huang Pimiao , Cai Tian , Chen Kewei
Published: December 2022

The preparation of dephytylated chlorophyll standards is inefficient and the process is complicated, which hinders chlorophyll determination and related bioactive property investigation. In this paper, chlorophyll derivatives from four phytylated chlorophylls (chlorophyll a, chlorophyll b, pheophytin a, and pheophytin b) before and after the enzymatic reaction were qualitatively and quantitatively characterized by UPLC–DAD–MS. A simple index was proposed to characterize chlorophyll pigments from their oxidized counterparts by the λmax of the typical peak of chlorophyll derivatives in UV–visible spectrum and their signal intensity ratios. The optimal reaction conditions for the enzymatic reaction of four chlorophyll pigments were optimized, and kinetic models were fitted. The results showed that the optimal temperatures for the enzymatic reactions of chlorophyll a, chlorophyll b, pheophytin a, and pheophytin b were 30, 30, 60, and 60°C, respectively, and their optimal reaction time was 2, 3, 1, and 3 h, respectively. Kinetic models were fitted under optimal reaction conditions to study the Km and Vm values of the enzymatic reactions.

Practical Application

Dephytylated chlorophylls, such as chlorophyllide and pheophorbide, are frequently determined in food industry and are always required to be prepared in lab with acetone powder from plant tissue. Moreover, chlorophyll pigments are easy to undergo oxidations, which make the characterization of dephytylated chlorophyll pigments more complicated and difficult. In this paper, four types of phytylated chlorophylls were investigated respectively about the dephytinization process with the citrus acetone powder, and the reaction mixture was analyzed with UPLC–DAD–MS, which can provide an important reference for relevant chlorophyll determination studies and the development of chlorophyll identification protocols.
Effects of ethanol on mechanical allodynia and dynamic weight bearing in male and female mice with spared nerve injury
Authors: Nothem Mitchell A. , Wickman Jason R. , Giacometti Laura L. , Barker Jacqueline M.
Published: December 2022

Background

Men and women with chronic pain report increased alcohol use and are more likely to be diagnosed with alcohol use disorder. The relationship between alcohol use and pain is bidirectional. Alcohol is used as an analgesic, but chronic alcohol intake increases pain. Sex differences in the relationship between chronic pain and alcohol are reported in the clinical and preclinical literature, but due to this bidirectional relationship, it is challenging to investigate the mechanisms that contribute to these differences. Thus, animal models of chronic pain are needed to characterize the efficacy of ethanol as an analgesic in males and females. The current experiments tested the hypothesis that ethanol differentially reduces pain behaviors in male and female mice in chronic neuropathic pain.

Methods

The spared nerve injury (SNI) model was used to investigate the analgesic effects of multiple doses of ethanol (0.5, 1, 2, g/kg i.p.) in male and female mice using von Frey and dynamic weight‐bearing (DWB) assays.

Results

In both male and female mice, SNI led to robust allodynia and shifts in dynamic weight bearing. In male SNI mice, all three doses of ethanol fully reversed mechanical allodynia and shifts in DWB. In SNI females, only the highest dose (2.0 g/kg) was fully antiallodynic in the von Frey assay, while shifts in weight bearing were reversed at the 1.0 and 2.0 g/kg doses. The differences between male and females were not due to lower blood ethanol concentrations in female mice.

Conclusion

These data indicate that while ethanol has antiallodynic and antinociceptive effects in male and female mice, the doses and time course of these effects are distinct. Studies investigating the relationship between pain and ethanol exposure in mice should consider sex as a key variable. These data also inform reported sex differences in rodent models of chronic pain and in chronic pain patients.
The effect of corruption on firm investment in the presence of missing data
Authors: Dastan Seyedmasood , Gibson John
Published: December 2022

Greater availability of firm‐level surveys in developing countries has enabled researchers to consider the effects of corruption at the firm level. One often overlooked issue with these surveys is nonresponse by firms. We examine the impact of corruption on firm investment and demonstrate that failing to account for nonresponse leads to an overestimation of the impact of corruption.
Cognitive aids in the management of clinical emergencies: a systematic review
Authors: Greig P. R. , Zolger D. , Onwochei D. N. , Thurley N. , Higham H. , Desai N.
Published: December 2022

Clinical emergencies can be defined as unpredictable events that necessitate immediate intervention. Safety critical industries have acknowledged the difficulties of responding to such crises. Strategies to improve human performance and mitigate its limitations include the provision and use of cognitive aids, a family of tools that includes algorithms, checklists and decision aids. This systematic review evaluates the usefulness of cognitive aids in clinical emergencies. Following a systematic search of the electronic databases, we included 13 randomised controlled trials, reported in 16 publications. Each compared cognitive aids with usual care in the context of an anaesthetic, medical, surgical or trauma emergency involving adults. Most trials used only clinicians in the development and testing of the cognitive aids, and only some trials provided familiarisation with the cognitive aids before they were deployed. The primary outcome was the completeness of care delivered to the patient. Cognitive aids were associated with a reduction in the incidence of missed care steps from 43.3% to 11% (RR (95%CI) 0.29 (0.15–0.16); p < 0.001), and the quality of evidence was rated as moderate. The use of cognitive aids was related to decreases in the incidence of errors, increases in the rate of correctly performed steps and improvement in the clinical teamwork skills scores, non‐technical skills scores, subjective conflict resolution scores and the global assessment of team performance. Cognitive aids had an inconsistent influence on the time to first intervention and time to complete care of the patient's condition. It is possible that this was a reflection of how common or rare the crisis in question was as well as the experience and expertise of the clinicians and team. Sufficient thought should be applied to the development of the content and design of cognitive aids, with consideration of the pre‐existing guideline ecosystem. Cognitive aids should be tested before their deployment with adequate clinician and team training.
Experience with sotrovimab treatment of SARS‐CoV‐2‐infected patients in Denmark
Authors: Rasmussen Line Dahlerup , Lebech Anne‐Mette , Øvrehus Anne , Poulsen Birgitte Klindt , Christensen Hanne Rolighed , Nielsen Henrik , Johansen Isik Somuncu , Omland Lars Haukali , Wiese Lothar , Helleberg Marie , Storgaard Merete , Dalager‐Pedersen Michael , Rasmussen Thomas A. , Benfield Thomas , Petersen Tonny Studsgaard , Andersen Åse Bengård , Gram Mie Agermose , Stegger Marc , Edslev Sofie Marie , Obel Niels
Published: December 2022

Aims

To evaluate the experience with use of sotrovimab following severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) infection in high‐risk groups.

Methods

In a nationwide, population‐based cohort study, we identified all individuals treated with sotrovimab (N = 2933) and stratified them by 4 high‐risk groups: (A) malignant haematological disease, (B) solid organ transplantation, (C) anti‐CD20 therapy ≤1 year and (D) other risks. Cox regression analysis was used to calculate hazard ratios for hospitalization, death and associated prognostic factors.

Results

Of 2933 sotrovimab‐treated individuals, 83% belonged to high‐risk groups (37.6% haematological malignancy, 27.4% solid organ transplantation and 17.5% treatment with anti‐CD20 ≤1 year). Only 17.8% had other risks (11.8% were pregnant, 10.7% primary immunodeficiency, 21.2% other malignancy, 4.3% received anti‐CD20 >1 year and 52.0% other/unknown causes). Within 90 days of infusion, 30.2% were hospitalized and 5.3% died. The main prognostic factors were the predefined high‐risk groups, mainly malignant haematological disease and age ≥65 years. Number of COVID‐19 vaccines (≥3) was associated with a decreased risk of hospitalization. The Delta but not the Omicron BA.2 variant was associated with a higher risk of death compared to the BA.1 variant.

Conclusion

More than 90% of the patients treated with sotrovimab belonged to the very high‐risk groups as described in the Danish guidelines. Sotrovimab‐treated individuals remained at a high risk of hospitalization and death which was strongly associated with the underlying immunocompromised state and age. Having received >3 COVID‐19 vaccines was association with decreased risk of death and hospitalization.
HKDC1 upregulation promotes glycolysis and disease progression, and confers chemoresistance onto gastric cancer
Authors: Wang Mei‐Qian , Chen Yi‐Ru , Xu Hui‐Wen , Zhan Jia‐Rong , Suo Da‐Qin , Wang Ji‐Jin , Ma Yuan‐Zhen , Guan Xin‐Yuan , Li Yan , Zhu Sen‐Lin
Published: December 2022

There is increasing evidence that hexokinase is involved in cell proliferation and migration. However, the function of the hexokinase domain containing protein‐1 (HKDC1) in gastric cancer (GC) remains unclear. Immunohistochemistry analysis and big data mining were used to evaluate the correlation between HKDC1 expression and clinical features in GC. In addition, the biological function and molecular mechanism of HKDC1 in GC were studied by in vitro and in vivo assays. Our study indicated that HKDC1 expression was upregulated in GC tissues compared with adjacent nontumor tissues. High expression of HKDC1 was associated with worse prognosis. Functional experiments demonstrated that HKDC1 upregulation promoted glycolysis, cell proliferation, and tumorigenesis. In addition, HKDC1 could enhance GC invasion and metastasis by inducing epithelial–mesenchymal transition (EMT). Abrogation of HKDC1 could effectively attenuate its oncogenic and metastatic function. Moreover, HKDC1 promoted GC proliferation and migration in vivo. HKDC1 overexpression conferred chemoresistance to cisplatin, oxaliplatin, and 5‐fluorouracil (5‐Fu) onto GC cells. Furthermore, nuclear factor kappa‐B (NF‐κB) inhibitor PS‐341 could attenuate tumorigenesis, metastasis, and drug resistance ability induced by HKDC1 overexpression in GC cells. Our results highlight a critical role of HKDC1 in promoting glycolysis, tumorigenesis, and EMT of GC cells via activating the NF‐κB pathway. In addition, HKDC1‐mediated drug resistance was associated with DNA damage repair, which further activated NF‐κB signaling. HKDC1 upregulation may be used as a potential indicator for choosing an effective chemotherapy regimen for GC patients undergoing chemotherapy.