bluuebunny/crossref_metadata_2025 huggingface dataset:
The same but different. Multidimensional assessment of depression in students of natural science and music
Authors: Korte Michaela , Cerci Deniz , Wehry Roman , Timmers Renee , Williamson Victoria J.
Published: January 2023

Depression is one of the most common and debilitating health problems, however, its heterogeneity makes a diagnosis challenging. Thus far the restriction of depression variables explored within groups, the lack of comparability between groups, and the heterogeneity of depression as a concept limit a meaningful interpretation, especially in terms of predictability. Research established students in late adolescence to be particularly vulnerable, especially those with a natural science or musical study main subject. This study used a predictive design, observing the change in variables between groups as well as predicting which combinations of variables would likely determine depression prevalence. 102 under- and postgraduate students from various higher education institutions participated in an online survey. Students were allocated into three groups according to their main study subject and type of institution: natural science students, music college students and a mix of music and natural science students at university with comparable levels of musical training and professional musical identity. Natural science students showed significantly higher levels of anxiety prevalence and pain catastrophizing prevalence, while music college students showed significantly higher depression prevalence compared to the other groups. A hierarchical regression and a tree analysis found that depression for all groups was best predicted with a combination of variables: high anxiety prevalence and low burnout of students with academic staff. The use of a larger pool of depression variables and the comparison of at-risk groups provide insight into how these groups experience depression and thus allow initial steps towards personalized support structures.
Military sexual trauma-related posttraumatic stress disorder service-connection award denial across gender and race
Authors: Webermann Aliya R. , Gianoli Mayumi O. , Rosen Marc I. , Portnoy Galina A. , Haskell Sally G. , Runels Tessa , Black Anne C.
Published: January 2023

The current study characterizes a cohort of veteran claims filed with the Veterans Benefits Administration for posttraumatic stress disorder secondary to experiencing military sexual trauma, compares posttraumatic stress disorder service-connection award denial for military sexual trauma-related claims versus combat-related claims, and examines military sexual trauma -related award denial across gender and race. We conducted analyses on a retrospective national cohort of veteran claims submitted and rated between October 2017-May 2022, including 102,404 combat-related claims and 31,803 military sexual trauma-related claims. Descriptive statistics were calculated, logistic regressions assessed denial of service-connection across stressor type and demographics, and odds ratios were calculated as effect sizes. Military sexual trauma-related claims were submitted primarily by White women Army veterans, and had a two times higher odds of being denied (27.6%) than combat claims (18.2%). When controlling for demographics including age, race, and gender, men veterans had a 1.77 times higher odds of having military sexual trauma-related claims denied compared to women veterans (36.6% vs. 25.4%), and Black veterans had a 1.39 times higher odds of having military sexual trauma-related claims denied compared to White veterans (32.4% vs. 25.3%). Three-fourths of military sexual trauma-related claims were awarded in this cohort, however, there were disparities in awarding of claims across gender and race for men and Black veterans, which suggest the possibility of systemic barriers for veterans from underserved backgrounds and/or who may underreport military sexual trauma.
Female Saudi nursing students’ perspectives on pursuing a career in home healthcare: A qualitative study
Authors: Almegewly Wafa Hamad , Karavasileiadou Savvato , Alotaibi Taghreed Samel
Published: January 2023

Background

While the number of patients requiring home healthcare in Saudi Arabia is increasing, there is insufficient data on what attracts nurses to work in this field.

Objective

This qualitative study investigates how nursing students practicing in home healthcare perceive it as a future career.

Methods

A purposive sample was used to recruit fourth-year nursing students enrolled in an older adult nursing care course and trained in home healthcare settings. Data were gathered using five focus groups of five students each (a total of 25 students) and analyzed using thematic analysis.

Results

It was found that the majority of students did not perceive home healthcare as a viable career option compared to working in a hospital. They vacillated due to the nature of the work, safety concerns, working demands, invariability of health cases, and lack of opportunities for professional development. Nevertheless, some nursing students were amenable to pursuing a career in home healthcare due to the less working hours, sense of autonomy, and the ability to provide holistic care and educate patients and their families.

Conclusion

Population awareness programs are needed to overcome cultural barriers, increase student motivation and ultimately bolster the number of certified nurses working in home healthcare.
Addressing spatial misalignment in population health research: a case study of US congressional district political metrics and county health data
Authors: Nethery Rachel C. , Testa Christian , Tabb Loni P. , Hanage William P. , Chen Jarvis T. , Krieger Nancy
Published: January 2023

Areal spatial misalignment, which occurs when data on multiple variables are collected using mismatched boundary definitions, is a ubiquitous obstacle to data analysis in public health and social science research. As one example, the emerging sub-field studying the links between political context and health in the United States faces significant spatial misalignment-related challenges, as the congressional districts (CDs) over which political metrics are measured and administrative units, e.g., counties, for which health data are typically released, have a complex misalignment structure. Standard population-weighted data realignment procedures can induce measurement error and invalidate inference, which has prompted the development of fully model-based approaches for analyzing spatially misaligned data. One such approach, atom-based regression models (ABRM), holds particular promise but has scarcely been used in practice due to the lack of appropriate software or examples of implementation. ABRM use “atoms”, the areas created by intersecting all sets of units on which variables of interest are measured, as the units of analysis and build models for the atom-level data, treating the atom-level variables (generally unmeasured) as latent variables. In this paper, we demonstrate the feasibility and strengths of the ABRM in a case study of the association between political representatives’ voting behavior (CD-level) and COVID-19 mortality rates (county-level) in a post-vaccine period. The adjusted ABRM results suggest that more conservative voting record is associated with an increase in COVID-19 mortality rates, with estimated associations smaller in magnitude but consistent in direction with those of standard realignment methods. The results also indicate that ABRM may enable more robust confounding adjustment and more realistic uncertainty estimates, properly representing the uncertainties arising from all analytic procedures. We also implement the ABRM in modern optimized Bayesian computing programs and make our code publicly available, which may enable these methods to be more widely adopted.
SURFBAT: a surrogate family-based association test building on large imputation reference panels
Authors: Herzig AF , Rubinacci S , Marenne G , Perdry H ,   FrEx Consortium,   FranceGenRef Consortium, Dina C , Redon R , Delaneau O , Génin E
Published: January 2023

Genotype-phenotype association tests are typically adjusted for population stratification using principal components that are estimated genome-wide. This lacks resolution when analysing populations with fine structure and/or individuals with fine levels of admixture. This can affect power and precision, and is a particularly relevant consideration when control individuals are recruited using geographic selection criteria. Such is the case in France where we have recently created reference panels of individuals anchored to different geographic regions. To make correct comparisons against case groups, who would likely be gathered from large urban areas, new methods are needed.

We present SURFBAT (a SURrogate Family Based Association Test) which performs an approximation of the transmission-disequilibrium test. Our method hinges on the application of genotype imputation algorithms to match similar haplotypes between the case and control groups. This permits us to approximate local ancestry informed posterior probabilities of un-transmitted parental alleles of each case individual. SURFBAT provides an association test that is inherently robust to fine-scale population stratification and opens up the possibility of efficiently using large imputation reference panels as control groups for association testing. The method is suitable when the control panel spans the local ancestry spectrum of the case-group population and each control has similar paternal and maternal ancestries. This is the case for our reference panels where individuals have their four grand-parents born in the same geographic area. In contrast to other methods for association testing that incorporate local-ancestry inference, SURFBAT does not require a set of ancestry groups to be defined, nor for local ancestry to be explicitly estimated.

We demonstrate the interest of our tool on simulated datasets created from the 1000 Genomes project and the FranceGenRef project, as well as on a real-data example for a group of case individuals affected by Brugada syndrome.
dentist: Computing uncertainty by sampling points around maximum likelihood estimates
Authors: Boyko James D. , O’Meara Brian C.
Published: January 2023

It is standard statistical practice to provide measures of uncertainty around parameter estimates. Unfortunately, this very basic and necessary enterprise is often absent in macroevolutionary studies.

dentist is an R package allows an estimate of confidence intervals around parameter estimates without an analytic solution to likelihood equations or an approximation based on local curvature at a peak. This package works by “denting” the likelihood surface by sampling points a specified distance around the maximum likelihood estimate following what is essentially a Metropolis-Hastings walk.

We describe the importance of estimating uncertainty around parameter estimates as well as demonstrate the ability of dentist to accurately estimate confidence intervals.

We introduce several plotting tools to visualize the results of a dentist analysis. dentist is freely available fromhttps://github.com/bomeara/dentist, written in the R language, and can be used for any given likelihood function.
Improved enzymatic labeling of fluorescent in situ hybridization probes applied to the visualization of retained introns in cells
Authors: Xiao Wen , Yeom Kyu-Hyeon , Lin Chia-Ho , Black Douglas L.
Published: January 2023

Fluorescence In Situ Hybridization (FISH) is a widely used tool for quantifying gene expression and determining the location of RNA molecules in cells. Here, we present an improved method for FISH probe production that yields high purity probes with a wide range of fluorophores using standard laboratory equipment at low cost. The method modifies an earlier protocol that uses terminal deoxynucleotidyl transferase to add fluorescently labeled nucleotides to synthetic deoxyoligonucleotides. In our protocol, Amino-11-ddUTP is joined to an oligonucleotide pool prior to its conjugation to a fluorescent dye, thereby generating pools of probes ready for a variety of modifications. This order of reaction steps allows for high labeling efficiencies regardless of the GC content or terminal base of the oligonucleotides. The Degree Of Labeling (DOL) for spectrally distinct fluorophores (Quasar, ATTO and Alexa dyes) was mostly greater than 90%, comparable to commercial probes. The ease and low cost of production allowed generation of probe-sets targeting a wide variety of RNA molecules. Using these probes, FISH assays in C2C12 cells showed the expected subcellular localization of mRNAs and pre-mRNAs forPolr2a(RNA polymerase II subunit 2a) andGapdh, and of the long noncoding RNAsMalat1andNeat1. Developing FISH probe sets for several transcripts containing retained introns, we found that retained introns in theGabbr1andNoc2ltranscripts are present in subnuclear foci separate from their sites of synthesis and partially coincident with nuclear speckles. This labeling protocol should have many applications in RNA biology.
Defective transfer of parental histone decreases frequency of homologous recombination in budding yeast
Authors: Karri Srinivasu , Yang Yi , Zhou Jiaqi , Dickson Quinn , Wang Zhiquan , Gan Haiyun , Yu Chuanhe
Published: January 2023

Recycling of parental histones is an important step in epigenetic inheritance. During DNA replication, DNA polymerase epsilon subunit DPB3/DPB4 and DNA replication helicase subunit MCM2 are involved in the transfer of parental histones to the leading and lagging DNA strands, respectively. SingleDpb3deletion (dpb3Δ) orMcm2mutation (mcm2-3A), which each disrupt one parental histone transfer pathway, leads to the other’s predominance. However, the impact of the two histone transfer pathways on chromatin structure and DNA repair remains elusive. In this study, we used budding yeastSaccharomyces cerevisiaeto determine the genetic and epigenetic outcomes from disruption of parental histone H3-H4 tetramer transfer. We found that adpb3Δ/mcm2-3Adouble mutant did not exhibit the singledpb3Δandmcm2-3Amutants’ asymmetric parental histone patterns, suggesting that the processes by which parental histones are transferred to the leading and lagging strands are independent. Surprisingly, the frequency of homologous recombination was significantly lower indpb3Δ, mcm2-3A, anddpb3Δ/mcm2-3Amutants relative to the wild-type strain, likely due to the elevated levels of free histones detected in the mutant cells. Together, these findings indicate that proper transfer of parental histones to the leading and lagging strands during DNA replication is essential for maintaining chromatin structure and that high levels of free histones due to parental histone transfer defects are detrimental to cells.
The QseB response regulator imparts tolerance to positively charged antibiotics by controlling metabolism and minor changes to LPS
Authors: Hurst Melanie N. , Beebout Connor J. , Hollingsworth Alexis , Guckes Kirsten R. , Purcell Alexandria , Bermudez Tomas A. , Williams Diamond , Reasoner Seth A. , Trent M. Stephen , Hadjifrangiskou Maria
Published: January 2023

The modification of lipopolysaccharide (LPS) inEscherichia coliandSalmonella spp. is primarily controlled by the two-component system PmrAB. LPS modification allows bacteria to avoid killing by positively charged antibiotics like polymyxin B. We previously demonstrated that in uropathogenicE. coli(UPEC), the sensor histidine kinase PmrB also activates a non-cognate transcription factor, QseB, and this activation somehow augments polymyxin B tolerance in UPEC. Here, we demonstrate – for the first time – that in the absence of the canonical LPS transcriptional regulator, PmrA, QseB can direct some modifications on the LPS. In agreement with this observation, transcriptional profiling analyses demonstrate regulatory overlaps between PmrA and QseB in terms of regulating LPS modification genes. However, both PmrA and QseB must be present for UPEC to mount robust tolerance to polymyxin B. Transcriptional and metabolomic analyses also reveal that QseB transcriptionally regulates the metabolism of glutamate and 2-oxoglutarate, which are consumed and produced during the modification of lipid A. We show that deletion ofqseBalters glutamate levels in the bacterial cells. TheqseBdeletion mutant, which is susceptible to positively charged antibiotics, is rescued by exogenous addition of 2-oxoglutarate. These findings uncover a previously unknown mechanism of metabolic control of antibiotic tolerance that may be contributing to antibiotic treatment failure in the clinic.

IMPORTANCE

Although antibiotic prescriptions are guided by well-established susceptibility testing methods, antibiotic treatments oftentimes fail. The presented work is significant, because it uncovers a mechanism by which bacteria transiently avoid killing by antibiotics. This mechanism involves two closely related transcription factors, PmrA and QseB, which are conserved across Enterobacteriaceae. We demonstrate that PmrA and QseB share regulatory targets in lipid A modification pathway and prove that QseB can orchestrate modifications of lipid A inE. coliin the absence of PmrA. Finally, we show that QseB controls glutamate metabolism during the antibiotic response. These results suggest that rewiring of QseB-mediated metabolic genes can lead to stable antibiotic resistance in subpopulations within the host, thereby contributing to antibiotic treatment failure.
COVID-19 NFL Injury Prevalence Analysis, A Follow-Up Study
Authors: Puga Troy B , Schafer Josh , Thiel Grace , Scigliano Nicholas , Ruan Tiffany , Toledo Andres , Agbedanu Prince N , Treffer Kevin
Published: January 2023

Background

In 2020, COVID-19 spread across the world and brought the world to a halt, causing the shutdown of nearly everything in order to prevent its spread. The NFL experienced the same effects of the shutdowns leaving athletes unable to train in some of the most advanced facilities with many of the best trainers in the world. Through a previous study,COVID-19 Return to Sport Injury Prevalence Analysis, it was determined that there was increased injury prevalence during the 2020 season likely due to decreased physiological adaptations within athletes bodies that resulted from facility shutdowns. Understanding injury epidemiology is vital in the prevention of injuries and the development of return-to-play protocols.

Objective

The objective of this study is to perform a follow up study toCOVID-19 Return to Sport Injury Prevalence Analysisin order to to examine the longitudinal effects of the COVID-19 pandemic on injury epidemiology. This study will examine if there was a recovery to baseline or lingering effects from the COVID-19 pandemic-induced spike in injuries.

Methods

Injury tallies collected from the 17-week-long 2020 NFL regular season, played after COVID-19 restrictions, were compared with the injury tallies collected from the 18-week-long NFL regular seasons (2021, 2022), in order to determine if there was a change in injury prevalence. An unpaired t-test was conducted to compare the mean injuries per team per week between each of the 2020, 2021, and 2022 regular seasons.

Results

The 2022 and 2021 NFL regular seasons produced lower numbers of total injuries than the 2020 NFL regular season that was impacted by COVID-19. The comparison of the mean number of injuries per team per week of the 2020 season compared with the 2021 regular season was statistically significant (P=.03). The comparison of the 2020 and 2022 regular seasons was also statistically significant (P=.02).

Conclusions

The results of this follow-up study and our previous study show that extended training interruptions have the ability to induce detraining and lead to increased injuries.

Additionally, the results of this study show that retraining can occur and lead to injury protective factors. This is the first large scale opportunity to demonstrate the effects of these principles and how they are important to understanding injury epidemiology.
Personalized virtual brains of Alzheimer’s Disease link dynamical biomarkers of fMRI with increased local excitability
Authors: Yalçınkaya Bahar Hazal , Ziaeemehr Abolfazl , Fousek Jan , Hashemi Meysam , Lavanga Mario , Solodkin Ana , McIntosh Anthony R. , Jirsa Viktor K. , Petkoski Spase
Published: January 2023

Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by the accumulation of abnormal beta-amyloid (Aβ) and hyperphosphorylated Tau (pTau). These proteinopathies disrupt neuronal activity, causing, among others, an excessive and hypersynchronous neuronal firing that promotes hyperexcitability and leads to brain network dysfunction and cognitive deficits. In this study, we used computational network modeling to build a causal inference framework to explain AD-related abnormal brain activity. We constructed personalized brain network models with a set of working points to enable maximum dynamical complexity for each brain. Structural brain topographies were combined, either with excitotoxicity, or postsynaptic depression, as two leading mechanisms of the Aβ and pTau on neuronal activity. By applying various levels of these putative mechanisms to the limbic regions that typically present, with the earliest and largest protein burden, we found that the excitotoxicity is sufficient and necessary to reproduce empirical biomarkers two biometrics associated with AD pathology: homotopic dysconnectivity and a decrease in limbic network dynamical fluidity. This observation was shown not only in the clinical groups (aMCI and AD), but also in healthy subjects that were virtually-diseased with excitotoxicity as these abnormal proteins can accumulate before the appearance of any cognitive changes. The same findings were independently confirmed by a mechanistic deep learning inference framework. Taken together, our results show the crucial role of protein burden-induced hyperexcitability in altering macroscopic brain network dynamics, and offer a mechanistic link between structural and functional biomarkers of cognitive dysfunction due to AD.
T7 phage-assisted evolution of riboswitches using error-prone replication and dual selection
Authors: Goicoechea Eduardo , Jaramillo Alfonso
Published: January 2023

Leveraging riboswitches, non-coding mRNA fragments pivotal to gene regulation, poses a challenge in effectively selecting and enriching these functional genetic sensors, which can toggle between ON and OFF states in response to their cognate inducers. Here, we show our engineered phage T7, enabling the evolution of a theophylline riboswitch. We have replaced T7’s DNA polymerase with a transcription factor controlled by a theophylline riboswitch and have created two types of host environments to propagate the engineered phage. Both types host an error-prone T7 DNA polymerase regulated by a T7 promoter along with another critical gene - either cmk or pifA, depending on the host type. The cmk gene is necessary for T7 replication and is used in the first host type for selection in the riboswitch’s ON state. Conversely, the second host type incorporates the pifA gene, leading to abortive T7 infections and used for selection in the riboswitch’s OFF state. This dual-selection system, termed T7AE, was then applied to a library of 65,536 engineered T7 phages, each carrying randomized riboswitch variants. Through successive passage in both host types with and without theophylline, we observed an enrichment of phages encoding functional riboswitches that conferred a fitness advantage to the phage in both hosts. The T7AE technique thereby opens new pathways for the evolution and advancement of gene switches, including non-coding RNA-based switches, setting the stage for significant strides in synthetic biology.
Pathway choice in the alternative telomere lengthening in neoplasia is dictated by replication fork processing mediated by EXD2’s nuclease activity
Authors: Broderick Ronan , Cherdyntseva Veronica , Nieminuszczy Jadwiga , Dragona Eleni , Kyriakaki Maria , Evmorfopoulou Theodora , Gagos Sarantis , Niedzwiedz Wojciech
Published: January 2023

Telomerase-independent cancer proliferationviathe alternative lengthening of telomeres (ALT) relies upon two distinct, largely uncharacterized, break-induced-replication (BIR) processes. How cancer cells initiate and regulate these terminal repair mechanisms is unknown. Here, we establish that the EXD2 nuclease is recruited to ALT telomeres to direct their productive repair. We demonstrate that EXD2 loss leads to telomere shortening, elevated telomeric sister chromatid exchanges, C-circle formation as well as BIR-mediated telomeric replication. We discover that EXD2 fork-processing activity triggers a switch between RAD52-dependent and -independent ALT-associated BIR. The latter is suppressed by EXD2 but depends specifically on the fork remodeler SMARCAL1 and the MUS81 nuclease. Thus, our findings suggest that processing of stalled replication forks orchestrates elongation pathway choice at ALT telomeres. Finally, we show that co-depletion of EXD2 with BLM, DNA2 or POLD3 confers synthetic lethality in ALT cells, identifying EXD2 as a potential druggable target for ALT-reliant cancers.
Single-cell response to Wnt activation in human embryonic stem cells reveals uncoupling of Wnt target gene expression
Authors: Söderholm Simon , Jauregi-Miguel Amaia , Pagella Pierfrancesco , Ghezzi Valeria , Zambanini Gianluca , Nordin Anna , Cantù Claudio
Published: January 2023

Wnt signaling drives nuclear translocation of β-catenin and its subsequent association with the DNA-bound TCF/LEF transcription factors, which dictate target gene specificity by recognizing Wnt responsive elements across the genome. β-catenin target genes are therefore thought to be collectively activated upon Wnt pathway stimulation. However, this appears in contrast with the non-overlapping patterns of Wnt target gene expression in several contexts, including early mammalian embryogenesis. Here we followed Wnt target gene expression in human embryonic stem cells after Wnt pathway stimulation at a single-cell resolution. Cells changed gene expression program over time consistent with three key developmental events: i) loss of pluripotency, ii) induction of Wnt target genes, and iii) mesoderm specification. Contrary to our expectation, not all cells displayed equal amplitude of Wnt target gene activation; rather, they distributed in a continuum from strong to weak responders when ranked based on the expression of the targetAXIN2. Moreover, highAXIN2did not always correspond to elevated expression of other Wnt targets, which were activated in different proportions in individual cells. This uncoupling of Wnt target gene expression, which was also identified in single colorectal cancer cells with hyper-activated Wnt signaling, underlines the necessity to identify additional mechanisms that explain the heterogeneity of the Wnt/β-catenin-mediated transcriptional outputs in single cells.
Natural selection differences detected in key protein domains between non-pathogenic and pathogenic Feline Coronavirus phenotypes
Authors: Zehr Jordan D. , Kosakovsky Pond Sergei L. , Millet Jean K. , Olarte-Castillo Ximena A. , Lucaci Alexander G. , Shank Stephen D. , Ceres Kristina M. , Choi Annette , Whittaker Gary R. , Goodman Laura B. , Stanhope Michael J.
Published: January 2023

Feline Coronaviruses (FCoVs) commonly cause mild enteric infections in felines worldwide (termed Feline Enteric Coronavirus [FECV]), with around 12% developing into deadly Feline Infectious Peritonitis (FIP; Feline Infectious Peritonitis Virus [FIPV]). Genomic differences between FECV and FIPV have been reported, yet the putative genotypic basis of the highly pathogenic phenotype remains unclear. Here, we used state-of-the-art molecular evolutionary genetic statistical techniques to identify and compare differences in natural selection pressure between FECV and FIPV sequences, as well as to identify FIPV and FECV specific signals of positive selection. We analyzed full length FCoV protein coding genes thought to contain mutations associated with FIPV (Spike, ORF3abc, and ORF7ab). We identified two sites exhibiting differences in natural selection pressure between FECV and FIPV: one within the S1/S2 furin cleavage site, and the other within the fusion domain of Spike. We also found 15 sites subject to positive selection associated with FIPV within Spike, 11 of which have not previously been suggested as possibly relevant to FIP development. These sites fall within Spike protein subdomains that participate in host cell receptor interaction, immune evasion, tropism shifts, host cellular entry, and viral escape. There were 14 sites (12 novel) within Spike under positive selection associated with the FECV phenotype, almost exclusively within the S1/S2 furin cleavage site and adjacent C domain, along with a signal of relaxed selection in FIPV relative to FECV, suggesting that furin cleavage functionality may not be needed for FIPV. Positive selection inferred in ORF7b was associated with the FECV phenotype, and included 24 positively selected sites, while ORF7b had signals of relaxed selection in FIPV. We found evidence of positive selection in ORF3c in FCoV wide analyses, but no specific association with the FIPV or FECV phenotype. We hypothesize that some combination of mutations in FECV may contribute to FIP development, and that is unlikely to be one singular “switch” mutational event. This work expands our understanding of the complexities of FIP development and provides insights into how evolutionary forces may alter pathogenesis in coronavirus genomes.
Intranasal mRNA-LNP vaccination protects hamsters from SARS-CoV-2 infection
Authors: Vaca Gabriela Baldeon , Meyer Michelle , Cadete Ana , Hsiao Chiaowen Joyce , Golding Anne , Jeon Albert , Jacquinet Eric , Azcue Emily , Guan Chenxia Monica , Sanchez-Felix Xavier , Pietzsch Colette A. , Mire Chad E. , Hyde Matthew A. , Comeaux Margaret E. , Williams Julie M. , Sung Jean C. , Carfi Andrea , Edwards Darin K. , Bukreyev Alexander , Bahl Kapil
Published: January 2023

Intranasal vaccination represents a promising approach for preventing disease caused by respiratory pathogens by eliciting a mucosal immune response in the respiratory tract that may act as an early barrier to infection and transmission. This study investigated immunogenicity and protective efficacy of intranasally administered messenger RNA (mRNA)–lipid nanoparticle (LNP) encapsulated vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Syrian golden hamsters. Intranasal mRNA-LNP vaccination systemically induced spike-specific binding (IgG and IgA) and neutralizing antibodies with similar robustness to intramuscular controls. Additionally, intranasal vaccination decreased viral loads in the respiratory tract, reduced lung pathology, and prevented weight loss after SARS-CoV-2 challenge. This is the first study to demonstrate successful immunogenicity and protection against respiratory viral infection by an intranasally administered mRNA-LNP vaccine.
Mitotic events depend on regulation of PLK-1 levels by the mitochondrial protein SPD-3
Authors: Chen Yu-Zen , Zimyanin Vitaly , Redemann Stefanie
Published: January 2023

In metazoans, Polo Kinase (Plk1) controls several mitotic events including nuclear envelope breakdown, centrosome maturation and kinetochore assembly. Here we show that mitotic events regulated by Polo Like Kinase (PLK-1) in earlyC. elegansembryos depend on the mitochondrial-localized protein SPD-3.spd-3mutant one-cell embryos contain abnormally positioned mitotic chromosomes and prematurely and asymmetrically disassemble the nuclear lamina. Nuclear envelope breakdown (NEBD) inC. elegansrequires direct dephosphorylation of lamin by PLK-1. Inspd-3mutants PLK-1 levels are ~6X higher in comparison to control embryos and PLK-1::GFP was highly accumulated at centrosomes, the nuclear envelope, nucleoplasm, and chromosomes prior to NEBD. Partial depletion ofplk-1inspd-3mutant embryos rescued mitotic chromosome and spindle positioning defects indicating that these phenotypes result from higher PLK-1 levels and thus activity. Our data suggests that the mitochondrial SPD-3 protein controls NEBD and chromosome positioning by regulating the endogenous levels of PLK-1 during early embryogenesis inC. elegans. This finding suggests a novel link between mitochondria and mitotic events by controlling the amount of a key mitotic regulator, PLK-1 and thus may have further implications in the context of cancers or age-related diseases and infertility as it provides a novel link between mitochondria and mitosis.
The natural tannins oligomeric proanthocyanidins and punicalagin are potent inhibitors of infection by SARS-CoV-2 in vitro
Authors: Chen Hsiao-Fan , Wang Wei-Jan , Chen Chung-Yu , Chang Wei-Chao , Hsueh Po-Ren , Peng Shin-Lei , Wu Chen-Shiou , Chen Yeh , Huang Hsin-Yu , Shen Wan-Jou , Wang Shao-Chun , Hung Mien-Chie
Published: January 2023

The COVID-19 pandemic continues to infect people worldwide. While the vaccinated population has been increasing, the rising breakthrough infection persists in the vaccinated population. For living with the virus, the dietary guidelines to prevent virus infection are worthy of and timely to develop further. Tannic acid has been demonstrated to be an effective inhibitor of coronavirus and is under clinical trial. Here we found that two other members of the tannins family, oligomeric proanthocyanidins (OPCs) and punicalagin, are also potent inhibitors against SARS-CoV-2 infection with different mechanisms. OPCs and punicalagin showed inhibitory activity against omicron variants of SARS-CoV-2 infection. The water extractant of the grape seed was rich in OPCs and also exhibited the strongest inhibitory activities for viral entry of wild-type and other variants in vitro. Moreover, we evaluated the inhibitory activity of grape seed extractants (GSE) supplementation against SARS-CoV-2 viral entry in vivo and observed that serum samples from the healthy human subjects had suppressive activity against different variants of SARS-CoV-2 vpp infection after taking GSE capsules. Our results suggest that natural tannins acted as potent inhibitors against SARS-CoV-2 infection, and GSE supplementation could serve as healthy food for infection prevention.

Highlights

OPCs and Punicalagin had inhibitory activity against omicron variants of SARS-CoV-2 infection.

OPCs serve as a dual inhibitor of the viral Mpro and the cellular TMPRSS2 protease.

Punicalagin possesses the most potent activity to suppress the Mpro and block the interaction of the viral spike protein and human ACE2.

OPCs-enriched grape seed extractant exhibited inhibitory activities for viral entry of wild-type and other variants of SARS-CoV-2.

The daily intake of grape seed extractants may be able to prevent SARS-CoV-2 infection.
Cohesin-mediated DNA loop extrusion resolves sister chromatids in G2 phase
Authors: Batty Paul , Langer Christoph C.H. , Takács Zsuzsanna , Tang Wen , Blaukopf Claudia , Peters Jan-Michael , Gerlich Daniel W.
Published: January 2023

Genetic information is stored in linear DNA molecules, which fold extensively inside cells. DNA replication along the folded template path yields two sister chromatids that initially occupy the same nuclear region in a highly intertwined arrangement. Dividing cells must disentangle and condense the sister chromatids into separate bodies such that a microtubule-based spindle can move them to opposite poles. While the spindle-mediated transport of sister chromatids has been studied in detail, the chromosome-intrinsic mechanics pre-segregating sister chromatids have remained elusive. Here, we show that human sister chromatids resolve extensively already during interphase, in a process dependent on the loop-extruding activity of cohesin, but not that of condensins. Increasing cohesin’s looping capability increases sister DNA resolution in interphase nuclei to an extent normally seen only during mitosis, despite the presence of abundant arm cohesion. That cohesin can resolve sister chromatids so extensively in the absence of mitosis-specific activities indicates that DNA loop extrusion is a generic mechanism for segregating replicated genomes, shared across different Structural Maintenance of Chromosomes (SMC) protein complexes in all kingdoms of life.
Do national culture and board attributes influence corporate investment decisions?
Authors: Agyei-Mensah Ben Kwame
Published: January 2023

Purpose

The purpose of this paper is to study the relationship between board attributes and national culture on firms’ investment decisions.

Design/methodology/approach

The study used data from listed firms from seven Sub-Saharan Africa countries. Descriptive analysis was performed to provide the background statistics of the variables examined. This was followed by regression analysis, which constitutes the main data analysis.

Findings

The multiple regression analysis results indicate a negative relationship between uncertainty avoidance (UAI) and corporate investment decisions. The study also found that there is a negative relationship between the interaction between UAI and the number of independent board members and corporate investment decisions.

Originality/value

This study is one of the few to measure the influence of governance variables and national culture on corporate investment decisions in Sub-Sahara Africa.
Disruptive innovation in effective learning systems: the impact of personalized instructor-created software-aided assessments to increase retention and knowledge
Authors: Nadan Joseph S. , Walton Abram , Tabaei Behzad , Bryant Charles Edward , Shah Natalie
Published: January 2023

Purpose

This paper aims to propose an innovative method for deploying a personalized instructor-created software-aided assessment system, that will disrupt traditional learning environments by allowing students to confidentially and with indirect supervision from the instructor, assess their knowledge and ability to achieve the course outcomes.

Design/methodology/approach

Through empirical evaluation in real-world educational settings, the authors examine the impact of augmenting human activity in the classroom with an innovative software platform to transform the learning process.

Findings

Findings indicate that this software-aided assessment system effectively augments human interactivity by providing timely instructor-designed feedback to increase knowledge retention and skillsets.

Practical implications

This study has shown that incorporating disruptive innovation through the use of software-aided assessment systems increases the effectiveness of the faculty in the classroom and enhances student learning and retention. Thus, a transformative software-aided assessment system design that incorporates artificial intelligence into the learning pathway should be pursued. These software-aided assessments are disruptive innovation as they are formative, frequent and require little direct involvement from the instructor.

Originality/value

To the best of the authors’ knowledge, this study is the first of its kind to incorporate artificial intelligence into the assessment process by analyzing results of pilot programs at several universities. The results demonstrate how using software-aided transformative assessments in various courses have helped instructors assess students’ preparedness and track their learning progress. These software-aided systems are the first step in bringing disruptive innovation to the classroom as these software-aided assessment instruments rapidly assess learners’ knowledge and skills based on short, easily created, multiple-choice tests, with little direct engagement from the faculty.
Mobile payment service quality: a new approach for continuance intention
Authors: Hijazi Rawa , Abu Daabes Ajayeb , Al-Ajlouni Mohammed Iqbal
Published: January 2023

Purpose

This paper assesses the continuance intention (CI) for mobile-based payment (M-payment) services following the COVID-19 pandemic by combining the self-efficacy construct with the electronic service quality model.

Design/methodology/approach

This exploratory, cross-sectional research employs qualitative and quantitative research methods; specifically, a questionnaire and interviews. A total of 403 Jordanian participants completed valid questionnaires. Mediation and moderation evaluations assessed the M-payment service quality (MPSQ), self-efficacy and health concerns (HC) to determine CI.

Findings

The results verify the significance of MPSQ and self-efficacy in developing CI and show the mediating influence of self-efficacy between MPSQ and CI. Moreover, HC negatively impact the self-efficacy/CI link.

Practical implications

This research benefits M-payment service providers seeking to secure customer loyalty via improved M-payment services. The behavioral intention investigation will provide rich information about potential customers' CI and illuminate areas for development.

Originality/value

This research makes an original contribution to the existing M-payment literature by investigating the impact of customers' perception of service quality on their CI to utilize M-payment services, balanced with self-efficacy and HC.
Are principles of recovery-oriented practice evident in staff and service user perspectives on seclusion?
Authors: Stíobhairt Antaine , Staunton David , Guerin Suzanne
Published: January 2023

Purpose

This paper aims to explore the extent to which principles of recovery-oriented practice are evident in the published perspectives and experiences of health professionals and service users on seclusion in adult mental health services.

Design/methodology/approach

A systematic review informed by PRISMA guidelines was conducted, drawing from four databases, which were searched in August 2018 and August 2022. Only original empirical studies rated as having “major” relevance were included. Data were extracted from 31 studies and qualitatively synthesised through deductive analysis using recovery principles as themes.

Findings

There was limited evidence of perceptions of seclusion being being consistent with recovery principles, with greater evidence of perceptions that directly opposed them. Studies of service user perspectives highlighted this more often than staff perspectives. The findings highlight paradoxical relationships between care and control and conflicting rights and emphasise the need to openly acknowledge the complexity of seclusion and its interface with recovery.

Research limitations/implications

This review was developed in line with international best practice and the protocol was registered. Using a search string with only three components maximised sensitivity during searches and minimised the risk of relevant literature being missed. Limitations include the focus on studies where the full text was published in English.

Originality/value

This review makes a unique contribution, highlighting that, to the best of the authors’ knowledge, no studies to date have explicitly explored the perspectives and experiences of staff and service users on the use of seclusion in the context of recovery-oriented practice. The findings are relevant to clinical practice, policy and future research, including amending procedures and practices to partially reconcile seclusion and recovery where the seclusion is deemed necessary.
When do M&As with Fintech Firms Benefit Traditional Banks?
Authors: Collevecchio Francesca , Cappa Francesco , Peruffo Enzo , Oriani Raffaele
Published: January 2023

In the last decade, fintech has emerged in the financial sector, introducing numerous innovations that have severely impacted traditional banks. To respond to fintech firms and meet the new needs of consumers, banks seek to align their offerings by integrating fintech knowledge through mergers and acquisitions (M&As) within an open innovation framework. However, it is still not clear when exactly M&As with fintech firms benefit banks. This paper examines the contingency factors that make M&As beneficial for acquirer banks by using a holistic approach that considers the type of firm, type of deal and the context in which M&As occur. We analysed the effect produced by acquirer sustainability, minority acquisitions and institutional distance between the fintech and the bank's country of incorporation by applying an event study methodology using cumulative abnormal returns to gauge effects on expected performance. We have shown which are the conditions that allow us to maximize the acquirer bank's expected performance. Our research advances the scientific understanding of M&A contingency factors, and more generally of open innovation, in the specific context of fintech and banks. Moreover, we provide managers and policymakers with initial advice on the effects fintech M&As have on traditional banks, showing that they can be beneficial under specific conditions.
Good conduct in a context of rationing: A case study of how frontline professionals deal with distributive dilemmas of novel gene therapies
Authors: Wadmann Sarah , Hauge Amalie Martinus , Emdal Navne Laura
Published: January 2023

Classical dilemmas of how to distribute limited resources have been rekindled by the rise of advanced, high‐cost therapies. Building on a case study of a novel gene therapy in neuropaediatric care, this article explores the dilemmas that explicit priority setting can create for frontline professionals and develops a typology of professionals’ responses to these dilemmas. Despite political attempts to centralise priority setting and spare health professionals from having to consider treatment costs at the ‘bedside’, this study shows that concern for economic efficiency and budget control nonetheless need to be handled and balanced against other accountabilities in the daily work of frontline professionals. Contributing to the sociological debate on priority setting and rationing, this study develops an analytical perspective attuned to the relational aspects of frontline work and the challenges related to the balancing of diverging ideas of good conduct. Further, focussing on an empirical field at the forefront of genomic medicine, this study brings the sociological debate on priority setting and rationing up to date with current developments in precision medicine.
The UK GDPR, the Immigration Exception and Brexit: Interrogating Open Rights Group v Secretary of State for the Home Department and its Aftermath
Authors: Erdos David
Published: January 2023

This note explores the holding, context and aftermath of the judgments which declared the so‐called ʻimmigration exceptionʼ set out in the UK Data Protection Act 2018 incompatible with, and assumed it subject to, the (UK) General Data Protection Regulation (GDPR) restrictions clause (article 23). The subsequent limitation of this exemption's use to the government is impactful in itself. However, this case has much wider significance. Firstly, the finding that the restrictions clause mandates granular specificity places in jeopardy many exemptions not only in the UK but also in EU States. Secondly, the assumption that this article was engaged is questionable since, as reworded post‐Brexit, it is restricted to limitations laid down in delegated legislation. Nevertheless, this rewording depended on powers limited to addressing post‐Brexit technical ʻdeficienciesʼ and so is ultra vires. The Court of Appeal should have addressed this in order to vindicate the rule of law and separation of powers.