bluuebunny/crossref_metadata_2025 huggingface dataset:
Nucleosome-binding by TP53, TP63, and TP73 is determined by the composition, accessibility, and helical orientation of their binding sites
Authors: Wilson Patrick D. , Yu Xinyang , Buck Michael J.
Published: May 2024

The p53 family of transcription factors plays key roles in driving development and combating cancer by regulating gene expression. TP53, TP63, and TP73—the three members of the p53 family—regulate gene expression by binding to their DNA binding sites, many of which are situated within nucleosomes. To thoroughly examine the nucleosome-binding abilities of the p53 family, we used Pioneer-seq, a technique that assesses a transcription factor’s binding affinity to its DNA binding sites at all possible positions within the nucleosome core particle. Using Pioneer-seq, we analyzed the binding affinity of TP53, TP63, and TP73 to 10 p53-family binding sites across the nucleosome core particle. We found that the affinity of TP53, TP63, and TP73 for nucleosomes was largely determined by the positioning of p53-family binding sites within nucleosomes; p53-family members bind strongly to the more accessible edges of nucleosomes but weakly to the less accessible centers of nucleosomes. We also found that the DNA-helical orientation of p53-family binding sites within nucleosomal DNA impacted the nucleosome-binding affinity of p53-family members. The composition of their binding sites also impacted each p53-family member’s nucleosome-binding affinities only when the binding site was located in an accessible location. Taken together, our results show that the accessibility, composition, and helical orientation of p53-family binding sites collectively determine the nucleosome-binding affinities of TP53, TP63, and TP73. These findings help explain the rules underlying p53-family-nucleosome binding and thus provide requisite insight into how we may better control gene-expression changes involved in development and tumor suppression.
A timed epigenetic switch balances T and ILC lineage proportions in the thymus
Authors: Pease Nicholas , Chen Lihua , Gerges Peter , Kueh Hao Yuan
Published: May 2024

How stem and progenitor cells give rise to multiple cell types in defined numbers and proportions is a central question in developmental biology. Epigenetic switches, acting at single gene loci, can generate extended delays in the activation timing of lineage-specifying genes, and thereby impact lineage decisions and cell type output of progenitors. Here, we analyzed a timed epigenetic switch controllingBcl11b, a transcription factor that drives T cell lineage commitment, but only after a long multi-day time delay in expression. To investigate roles for this delay in controlling lineage decision making, we analyzed progenitors with a deletion in a distalBcl11benhancer, that further extends this delay by ∼3 days. Strikingly, delayingBcl11bactivation reduces T cell output but enhances ILC generation in the thymus, and does so by redirecting progenitors to the ILC lineages at the T and ILC developmental branchpoint. Mechanistically, delayingBcl11bactivation promoted ILC redirection by up-regulating a PLZF-dependent ILC transcriptional program in progenitors. Despite up-regulating PLZF, committed ILC progenitors were still capable of later activatingBcl11b, which is also needed for specification of type 2 ILCs. These results show that epigenetic switches, by controlling the activation timing and order of lineage-specifying genes within regulatory networks, can modulate population sizes and proportions of differentiated cell types.
Hepatitis A virus whole genome sequencing strategy using NGS/Illumina technology
Authors: Sicilia Paola , Fantilli Anabella C. , Cuba Facundo , Di Cola Guadalupe , Barbás María Gabriela , Poklepovich Tomás , Ré Viviana E. , Castro Gonzalo , Pisano María Belén
Published: May 2024

Background

Molecular epidemiology of hepatitis A virus (HAV) plays a critical role in identifying outbreak origin and conducting surveillance. Although it is mostly carried out using short partial VP1/2A genomic sequences, utilizing whole-genome sequences (WGS) provides more accurate and robust information.

Objective

we aimed to develop an amplicon-based next-generation sequencing (NGS) strategy to obtain complete HAV genomes utilizing the COVIDSeq Test (Illumina), available in surveillance laboratories after the COVID19 pandemic.

Study design

25 primer pairs were designed and used to amplify partial genomic fragments (400bp) that comprise the entire HAV genome sequence from HAV previously positive serum and stool samples from Argentina. The DNA library was prepared using the Illumina COVIDSeq Test and sequenced in a MiSeq equipment. Phylogenetic analyses were performed with IQ-Tree using WGS and VP1/2A partial sequences of 1084pb and 422pb.

Results

11 samples could be successfully amplified and sequenced, with horizontal coverage between 79.3%-100% (>90% in 9 samples). Individual RT-PCRs and Sanger sequencing with specific primers had to be performed in 6 samples to cover gaps of Ns. Phylogenetic analyses of WGS and VP1/2A partial sequences yielded similar results (clustering with genotype IA), although 422pb fragments showed low accurate grouping definition.

Conclusion

the amplicon-based NGS whole genome sequencing tool developed by adapting the COVIDSeq test to HAV, proved to be efficient in generating new complete and near-complete viral sequences. The study of the 1084bp fragment of the VP1/2A region would constitute a useful alternative option for outbreak investigation with public health impact.
Retrospective Comparison of Outcomes and Cost of a Virtual vs. Center-Based Cardiac Rehabilitation Program
Authors: Shah Neil D. , Banta Conor W. , Berger Andrea L. , Hattenberger Andrea , Zimmerman Alex , Martin Bryan E. , Wu Edward , Majumdar Usnish , Kirchner H. Lester , Matsumura Martin E.
Published: May 2024

Background

Despite robust evidence supporting an association with improved outcomes in eligible patients, cardiac rehabilitation (CR) remains underutilized, with a minority of eligible patients participating. Virtual cardiac rehabilitation (VCR) has been proposed as an alternative to traditional center-based CR (CBCR) to improve utilization rates. However, data supporting the efficacy and cost-effectiveness of VCR is limited. In the present study, we compared the outcomes and cost of a VCR vs. traditional CBCR program.

Methods

Retrospective cohort study comparing VCR vs. CBCR. CBCR data were collected from a period of January 2018 to September 2023. VCR data were collected from program initiation in July 2021 to September 2023. Primary health outcomes measured were 1-year mortality rates, recurrent MI, all-cause hospital readmission, and emergency department visits. Primary cost outcomes were analyzed as cost ratios related to VCR vs. CBCR assessing total medical costs allowed, pharmacy costs, and total costs of care over the 12 months post-CR enrollment.

Results

VCR was associated with a significant reduction in 1-year all-cause hospital readmission (incident rate ratio (IRR)=0.616, 95% confidence interval (CI): 0.489, 0.777, p<0.001) and ED admission (IRR=0.557, 95% CI: 0.452, 0.687, p<0.001) at 1 year. The IRR of MI and all-cause mortality did not significantly differ between VCR and CBCR. In addition, VCR was associated with significant reductions in medically related (cost ratio=0.814, 95% CI: 0.690, 0.960, p=0.0144) and total costs (cost ratio=0.838, 95% CI: 0.725, 0.970, p=0.0176).

Conclusion

VCR is a viable alternative to CBCR with at least comparable efficacy and cost, and as such, represents a key mechanism for improving access to and participation in CR for eligible patients.
Universal protection of allogeneic cell therapies from natural killer cells via CD300a agonism
Authors: Zhang Shu-Qi , Thomas Faith , Fang Justin , Austgen Kathryn , Cowan Chad , Welstead G. Grant
Published: May 2024

Immunogenicity limits the persistence of off-the-shelf, allogeneic cell therapies and transplants. While ablation of human leukocyte antigen (HLA) removes most T cell and humoral alloreactivity, no solution has enabled universal protection against the resulting natural killer (NK) cell response. Here, we engineered Trans Antigen Signaling Receptors (TASR) as a new class of NK inhibitory ligands and discovered CD300a, a previously inaccessible receptor, as a functional target. CD300a TASR outperformed leading alternative strategies in focused screens, including CD47 and HLA-E, and was solely capable of universally protecting allogeneic T cells against a large human cohort (45/45 donors), spanning diverse demographics and NK cell phenotypes. A model allogeneic T cell therapy co-expressing an anti-CD19 Chimeric Antigen Receptor (CAR) and CD300a TASR, produced using multiplexed non-viral integration, exhibited enhanced B cell killing potency under allogeneic immune pressure. CD300 TASR represents a universal solution to NK alloreactivity, broadening the population that could be effectively treated by next-generation allogeneic cell therapies.

Category

Immunobiology and Immunotherapy

Key Points

An engineered CD300a agonist ligand (CD300a TASR) universally protects HLA-deficient allogeneic T cells from NK-mediated rejection.

CD300a TASR is more protective in CMV seropositive hosts than HLA-E ligand and enhances CAR-T efficacy under allogeneic immune pressure.
Gym-Based Modified Powerlifting Exercises for People with Early Onset Parkinson’s Disease: Study Protocol
Authors: Harris Dale M , Thwaites Claire , Callisaya Michelle L , Blazé Richard , Morris Meg E
Published: May 2024

Background

Although powerlifting has been shown to increase strength and function in some adults, the safety and feasibility of powerlifting exercises modified for people with early onset Parkinson’s disease is not known.

Methods

People with early onset Parkinson’s disease (age <50 years) will be invited to engage in eight consecutive weeks of twice-weekly modified powerlifting exercises in a community gymnasium. The primary outcome is the feasibility of powerlifting exercises modified for people with early onset Parkinson’s disease, quantified by measures of safety, adverse events, adherence, access, and cost. Secondary outcomes include motor disability, quality of life, psychosocial status, and strength. Semi-structured interviews with participants and exercise trainers will capture experiences, beliefs, and attitudes towards this type of community-based strength training.

Discussion

Powerlifting may be beneficial for those with early onset Parkinson’s disease as it can improve muscle strength, coordination, and balance, and may have neuroprotective effects, potentially slowing down the progression of the disease. However, there is a need to first measure feasibility and safety of modified powerlifting in a small number of individuals before the efficacy can be tested in larger randomised controlled trials.

Ethics and dissemination

We will publish the findings in peer-reviewed journals and presentations at conferences. The consumer engagement council will guide communication of findings to individuals with early onset Parkinson’s disease, ensuring information is accessible and actionable for the target audience.
The African American Dementia and Aging Project (AADAPt): An Oregon-based Longitudinal Study
Authors: Lindauer Allison , Croff Raina , Duff Kevin , Mattek Nora , Fuller Patrice , Pierce Aimee , Bonds Kalisha , Kaye Jeffrey
Published: May 2024

Objectives

The vast majority of studies on aging, cognition, and dementia focus on non-Hispanic white subjects. This paper adds to the extant literature by providing insight into the African American aging experience. Here we describe the study design and baseline characteristics of the African American Dementia and Aging Project (AADAPt) study, which is exploring aging and cognition in African American older adults in Oregon.

Methods

African American older adults (n=177) participated in AADAPt, a longitudinal study that collected data on cognitive, physical, and social functioning in annual visits since 2000.

Results

AADAPt participants had risk factors for developing dementia in future, such as hypertension and hyperlipidemia, but also reported protective factors such as high social engagement.

Conclusions

The AADAPt project offers new insights into aging in older African Americans that includes data on cognition, social engagement, and physical health, which are crucial for understanding the experience of under-represented groups and making future studies more inclusive. These findings reflect a window of time for a geographically-focused cohort, and the lessons learned from this study likely have broader implications for shaping the health of these older African American adults. Keywords: African American, Dementia, Observational Study
Filling the gaps: leveraging large language models for temporal harmonization of clinical text across multiple medical visits for clinical prediction
Authors: Choi Inyoung , Long Qi , Getzen Emily
Published: May 2024

Electronic health records offer great promise for early disease detection, treatment evaluation, information discovery, and other important facets of precision health. Clinical notes, in particular, may contain nuanced information about a patient’s condition, treatment plans, and history that structured data may not capture. As a result, and with advancements in natural language processing, clinical notes have been increasingly used in supervised prediction models. To predict long-term outcomes such as chronic disease and mortality, it is often advantageous to leverage data occurring at multiple time points in a patient’s history. However, these data are often collected at irregular time intervals and varying frequencies, thus posing an analytical challenge. Here, we propose the use of large language models (LLMs) for robust temporal harmonization of clinical notes across multiple visits. We compare multiple state-of-the-art LLMs in their ability to generate useful information during time gaps, and evaluate performance in supervised deep learning models for clinical prediction.
Functional and multi-omic aging rejuvenation with GLP-1R agonism
Authors: Huang Junzhe , Kwok Andrew J. , Li Jason Chak Yan , Chiu Clement Lek Hin , Ip Bonaventure Y. , Tung Lok Yi , Zheng Xianyi , Chow Hoi Tung , Lo Michelle P. S. , Li Zhongqi , Chan Roy C. H. , Lin Nenghan , Wang Ziyu , Wang Manyu , Yan Leo Y. C. , Chan Danny C. W. , Wu William K. K. , Chow Kim Hei-Man , Lin Wei-Jye , Tang Yamei , Ng Billy Wai-Lung , Wong Sunny H. , Leung Thomas W. , Mok Vincent C. T. , Ko Ho
Published: May 2024

Identifying readily implementable methods that can effectively counteract aging is urgently needed for tackling age-related degenerative disorders. Here, we conducted functional assessments and deep molecular phenotyping in the aging mouse to demonstrate that glucagon-like peptide-1 receptor agonist (GLP-1RA) treatment attenuates body-wide age-related changes. Apart from improvements in physical and cognitive performance, the age-counteracting effects are prominently evident at multiple omic levels. These span the transcriptomes and DNA methylomes of various tissues, organs and circulating white blood cells, as well as the plasma metabolome. Importantly, the beneficial effects are specific to aged mice, not young adults, and are achieved with a low dosage of GLP-1RA which has a negligible impact on food consumption and body weight. The molecular rejuvenation effects exhibit organ-specific characteristics, which are generally heavily dependent on hypothalamic GLP-1R. We benchmarked the GLP-1RA age-counteracting effects against those of mTOR inhibition, a well-established anti-aging intervention, observing a strong resemblance across the two strategies. Our findings have broad implications for understanding the mechanistic basis of the clinically observed pleiotropic effects of GLP-1RAs, the design of intervention trials for age-related diseases, and the development of anti-aging-based therapeutics.
Autologous ovarian tissue transplantation and longevity improvement (experimental mice model)
Authors: Ruhliada Nikolai
Published: May 2024

In the study we showed the improvement in life longevity in mice after step-by step autologous ovarian transplantation. This has proven to be more efficient than “traditional” hormonal replacement therapy. Despite the highest speed and effectiveness of estradiol replacement deficiency in blood by its oral or transdermal use, one did not receive a significant increase in the life longevity in animals and possibly in women (Canderelli R., Leccesse L. et al. 2007). The function of transplanted fragment is usually limited to 6-12 months. This is enough for oncofertility purposes, sometimes, but not for longevity improvement. We performed periodical tissue return (autologous transplantation), containing both cortex and medulla in mice experimental model, that resulted in statistically reliable improvement of longevity. The experimental model we suggested could be projected and to other mammals or humans, as the cortical transplantation gives the same results for reproduction restoration in mice and humans and even on hormone levels normalization, but there is still lack of information about anti-ageing factors containing in ovarian medulla and cortex. That is why we consider that the most important factor for anti-ageing transplantation technology is to preserve both medulla and cortex.

Step-by step autologous ovarian transplantation provides the improvement in life longevity in female mice. This technology could be even more efficient, compared to estrogen hormonal replacement therapy in hormone levels improvement (FSH, estradiol). While menopausal hormonal therapy (MHT) with estrogens doesn’t improve longevity in mice, step-by-step autologous transplantation of ovarian cryopreserved tissue statistically reliably prolongs lifespan in mice.
The TWK-26 potassium channel governs nutrient absorption in theC. elegansintestine
Authors: Torzone Sarah K. , Breen Peter C. , Cohen Natalie R. , Simmons Kaylee N. , Dowen Robert H.
Published: May 2024

Ion channels are necessary for proper water and nutrient absorption in the intestine, which supports cellular metabolism and organismal growth. While a role for Na+co-transporters and pumps in intestinal nutrient absorption is well defined, how individual K+uniporters function to maintain ion homeostasis is poorly understood. UsingCaenorhabditis elegans, we show that a gain-of-function mutation intwk-26, which encodes a two-pore domain K+ion channel orthologous to human KCNK3, facilitates nutrient absorption and suppresses the metabolic and developmental defects displayed by impaired intestinal MAP Kinase (MAPK) signaling. Mutations indrl-1andflr-4,which encode two components of this MAPK pathway, cause severe growth defects, reduced lipid storage, and a dramatic increase in autophagic lysosomes, which mirror dietary restriction phenotypes. Additionally, these MAPK mutants display structural defects of the intestine and an impaired defecation motor program. We find that activation of TWK-26 reverses the dietary restriction-like state of the MAPK mutants by restoring intestinal nutrient absorption without correcting the intestinal bloating or defecation defects. This study provides unique insight into the mechanisms by which intestinal K+ion channels support intestinal metabolic homeostasis.
Local structural dynamics of Rad51 protomers revealed by cryo-electron microscopy of Rad51-ssDNA filaments
Authors: Liu Jie , Gore Steven , Heyer Wolf-Dietrich
Published: May 2024

Homologous recombination (HR) is a high-fidelity repair mechanism for double-strand breaks. Rad51 is the key enzyme that forms filaments on single-stranded DNA (ssDNA) to catalyze homology search and DNA strand exchange in recombinational DNA repair. In this study, we employed single-particle cryo-electron microscopy (cryo-EM) to ascertain the density map of the budding yeast Rad51-ssDNA filament bound to ADP-AlF3, achieving a resolution of 2.35 Å without imposing helical symmetry. The model assigned 6 Rad51 protomers, 24 nt of DNA, and 6 bound ADP-AlF3. It shows 6-fold symmetry implying monomeric building blocks, unlike the structure of the Rad51-I345T mutant filament with three-fold symmetry implying dimeric building blocks, for which the structural comparisons provide a satisfying mechanistic explanation. This image analysis enables comprehensive comparisons of individual Rad51 protomers within the filament and reveals local conformational movements of amino acid side chains. Notably, Arg293 in Loop1 adopts multiple conformations to facilitate Leu296 and Val331 in separating and twisting the DNA triplets. We also analyzed the predicted structures of yeast Rad51-K342E and two tumor-derived human RAD51 variants, RAD51-Q268P and RAD51-Q272L, using the Rad51-ssDNA structure from this study as a reference.
Interleukin 21 is a marker of Human African Trypanosomiasis Infection and a contributor to pathology in mice
Authors: Capewell Paul , Ilboudo Hamidou , Cooper Anneli , Kaboré Windingoudi Justin , Noyes Harry , Neill Kerry O’ , Camara Mamadou , Jamonneau Vincent , MacLeod Annette , Bucheton Bruno ,   TrypanoGEN+ research group of the H3Africa consortium
Published: May 2024

Background

Human African trypanosomiasis (HAT) is an important disease of sub-Saharan Africa that is approaching elimination in many regions. However, the disease has previously returned from similarly low case numbers in the past, making it important to identify issues that hinder elimination efforts. One important factor is likely to be the recent characterization of individuals with latent HAT infections that are able to tolerate HAT with few symptoms and to control blood parasitaemia to levels that are undetectable by microscopy. Although animal trypanotolerance has been examined in detail, it is unclear how the latent phenotype is maintained in humans.

Methods

To identify immune components involved in latent HAT, we used targeted RNASeq to examine the expression of 495 immune-related transcripts in blood collected from 287 individuals at active disease foci in Guinea. These samples included latent infections, HAT clinical cases, and uninfected controls. Thein vivoeffects of IL21 functional blockade was investigated using a murine model of trypanosomiasis.

Results

Differential expression analysis revealed transcripts involved in T cell activation and B cell development that associated with trypanosome infection, includingPD1,CD70, andCD80. In particular,IL21was found to be elevated in infected individuals, although it was significantly higher in clinical cases relative to latent infections. This pattern was replicated at the protein level when patient sera were examined by ELISA. Reducing IL21 pathway activity in mice infected withTrypanosoma bruceiled to increased survivorship and reduced parasitaemia in the model animals.

Conclusion

Our data show that IL21 is a potential biomarker of Human African Trypanosomiasis and is a cause rather than a consequence of symptoms severity. Further investigation of IL21 will contribute to understanding the factors involved in developing latent HAT, improving control efforts to identify and predict such infections. In the future, the factors identified in this study may also serve as intervention targets to control the symptoms of trypanosomiasis.
Evaluating later or expanded premises hours for alcohol in the night-time economy (ELEPHANT): statistical analysis plan
Authors: Sheikh Nurnabi , Henriques-Cadby Ines , Haghpanahan Houra , Angus Colin , O'Donnell Rachel , Emslie Carol , Fitzgerald Niamh , Lewsey Jim
Published: May 2024

This document provides the statistical analysis plan (SAP) for the ELEPHANT study (Evaluating later or expanded premises hours for alcohol in the night-time economy), an interrupted time series study following a natural experiment design, for evaluating the impact of late-night trading hours of alcohol premises in the night-time economy.
In uteroadeno-associated virus (AAV)-mediated gene delivery targeting sensory and supporting cells in the embryonic mouse inner ear
Authors: Barbosa-Spinola Carla Maria , Boutet de Monvel Jacques , Safieddine Saaid , Lahlou Ghizlène , Etournay Raphaël
Published: May 2024

In vivo gene delivery to tissues using adeno-associated vector (AAVs) has revolutionized the field of gene therapy. Yet, while sensorineural hearing loss is one of the most common sensory disorders worldwide, gene therapy applied to the human inner ear is still in its infancy. Recent advances in the development recombinant AAVs have significantly improved their cell tropism and transduction efficiency across diverse inner ear cell types to a level that renders this tool valuable for conditionally manipulating gene expression in the context of developmental biology studies of the mouse inner ear. Here, we describe a protocol forin uteromicro-injection of AAVs into the embryonic inner ear, using the AAV-PHP.eB and AAV-DJ serotypes that respectively target the sensory hair cells and the supporting cells of the auditory sensory epithelium. We also aimed to standardize procedures for imaging acquisition and image analysis to foster research reproducibility and allow accurate comparisons between studies. We find that AAV-PHP.eB and AAV-DJ provide efficient and reliable tools for conditional gene expression targeting cochlear sensory and supporting cells in the mouse inner ear, from late embryonic stages on.
Age-specific dynamics of neutralizing antibodies, cytokines, and chemokines in response to La Crosse virus infection in mice
Authors: Alatrash Reem , Vaidya Varun , Herrera Bobby Brooke
Published: May 2024

La Crosse virus (LACV) is a primary cause of pediatric arboviral encephalitis in the United States, particularly affecting children aged 16 years or younger. This age-related susceptibility extends to murine models, where weanling mice (3 weeks old) succumb to LACV infection, while adults (≥6 weeks old) demonstrate resistance. Despite its clinical relevance, the host immune response to LACV is not fully understood. In this study, we investigated the roles of neutralizing antibodies (nAbs), cytokines, and chemokines in weanling and adult mice following infection with 5x105plaque forming units (PFU) of LACV. We observed significant age-related differences in viral titers and survival. Weanling mice demonstrated early disease onset with elevated peripheral viremia, but passive transfer of adult serum, confirmed to have nAbs, to naïve weanlings prior to infection completely rescued them from death. Cytokine and chemokine profiling revealed distinct kinetics and age-specific immune responses. Adult mice had increased Th1 cytokines, Th9/Th17/Th22/Treg cytokines, and many chemokines. In contrast, weanlings had higher Th2 cytokines, correlating with symptoms onset. Flow cytometry and intracellular cytokine staining further demonstrated that weanling mice produced higher levels of IL-4 by CD4+and CD8+T cells compared to adults, regardless of infection status. Conversely, LACV-infected adult mice had increased IFN-γ production by CD8+T cells compared to uninfected adults. Finally, adoptive transfer of splenocytes from immune adult mice to naïve weanlings delayed neurological symptoms and improved survival, highlighting the protective role of immune adult cells against LACV. In conclusion, this study links nAbs and cytokine and chemokine responses to protective immunity in adult mice, contrasting with the pathogenesis seen in weanlings. These findings underscore the importance of further research into innate and adaptive immune mechanisms in LACV infection.
Self-Assembled Monolayer Transporters Enable Reagentless Analysis of Small Molecule Analytes
Authors: Flynn Connor D. , Riordan Kimberly T. , Young Tiana L. , Chang Dingran , Wu Zhenwei , Isaacson Scott E. , Yousefi Hanie , Das Jagotamoy , Kelley Shana O.
Published: May 2024

The detection of small molecules beyond glucose remains an ongoing challenge in the field of biomolecular sensing owing to their small size, diverse structures, and lack of alternative non-enzymatic sensing methods. Here, we present a new reagentless electrochemical approach for small molecule detection that involves directed movement of electroactive analytes through a self-assembled monolayer to an electrode surface. Using this method, we demonstrate detection of several physiologically relevant small molecules as well as the capacity for the system to operate in several biological fluids. We anticipate that this mechanism will further improve our capacity for small molecule measurement and provide a new generalizable monolayer-based technique for electrochemical assessment of various electroactive analytes.
A new framework for exploratory network mediator analysis in omics data
Authors: Cai Qingpo , Fu Yinghao , Lyu Cheng , Wang Zihe , Rao Shun , Alvarez Jessica A. , Bai Yun , Kang Jian , Yu Tianwei
Published: May 2024

Omics methods are widely used in basic biology and translational medicine research. More and more omics data are collected to explain the impact of certain risk factors on clinical outcomes. To explain the mechanism of the risk factors, a core question is how to find the genes/proteins/metabolites that mediate their effects on the clinical outcome. Mediation analysis is a modeling framework to study the relationship between risk factors and pathological outcomes, via mediator variables. However, high-dimensional omics data are far more challenging than traditional data: (1) From tens of thousands of genes, can we overcome the curse of dimensionality to reliably select a set of mediators? (2) How do we ensure that the selected mediators are functionally consistent? (3) Many biological mechanisms contain nonlinear effects. How do we include nonlinear effects in the high-dimensional mediation analysis? (4) How do we consider multiple risk factors at the same time? To meet these challenges, we propose a new exploratory mediation analysis framework, medNet, which focuses on finding mediators through predictive modeling. We propose new definitions for predictive exposure, predictive mediator, and predictive network mediator, using a statistical hypothesis testing framework to identify predictive exposures and mediators. Additionally, two heuristic search algorithms are proposed to identify network mediators, essentially subnetworks in the genome-scale biological network that mediate the effects of single or multiple exposures. We applied medNet on a breast cancer data set and a metabolomics data set combined with food intake questionnaire data. It identified functionally consistent network mediators for the exposures’ impact on the outcome, facilitating data interpretation.
Importance sampling method for Feldman-Cousins confidence intervals
Authors: Berns Lukas
Published: May 2024

In various high-energy physics contexts, such as neutrino-oscillation experiments, several assumptions underlying the typical asymptotic confidence interval construction are violated, such that one has to resort to computationally expensive methods like the Feldman-Cousins method for obtaining confidence intervals with proper statistical coverage. By construction, the computation of intervals at high confidence levels requires fitting millions or billions of pseudoexperiments, while wasting most of the computational cost on overly precise intervals at low confidence levels. In this work, a simple importance sampling method is introduced that reuses pseudoexperiments produced for all tested parameter values in a single mixture distribution. This results in a significant error reduction on the estimated critical values, especially at high confidence levels, and simultaneously yields a correct interpolation of these critical values between the parameter values at which the pseudoexperiments were produced. The theoretically calculated performance is demonstrated numerically using a simple example from the analysis of neutrino oscillations. The relationship to similar techniques applied in statistical mechanics and p-value computations is discussed.

Published by the American Physical Society
2024
Probing the dark matter velocity distribution via daily modulation
Authors: Heikinheimo Matti , Nordlund Kai , Sassi Sebastian , Tuominen Kimmo
Published: May 2024

We consider dark matter velocity distributions with an anisotropic component, and analyze how the velocity structure can be probed in a solid-state ionization detector with no directional detection capability using a daily modulation effect due to the anisotropic response function of the target. We show that with an energy resolution of <10  eV it is possible to identify the presence of an anisotropic component consistent with observations for sub-GeV dark matter, and that introduction of daily modulation information substantially improves the sensitivity in a narrow mass range.

Published by the American Physical Society
2024
Female CEOs and SME’s financing decision: evidence from firm-level data
Authors: Hussain Muntazir , Rehman Ramiz , Bashir Usman
Published: May 2024

Purpose

This study investigates the relationship between female CEOs and SMEs’ financing decisions. The study also examined the moderating role of ownership structure (female, foreign, and state ownership) in female CEO-SMEs’ financing decisions.

Design/methodology/approach

The study has applied Generalized Least Square (GLS) and Binomial Logistic Regression. The study has used firm-level data from 2,700 Small and Medium Enterprises (SMEs) in the Chinese economy.

Findings

The results suggest that female CEOs use debt financing. However, the financing decision of female CEOs varies if we account for female ownership, foreign ownership, state ownership, firm association with big firms, and the industry in which the firm operates. This study also provides robust evidence that female CEOs utilize debt financing under certain conditions and that female CEOs prefer long-term debt financing to short-term debt financing when considering debt maturity choices.

Originality/value

Recent studies report a negative relationship between female CEOs and financing decisions based on the rationale that females are risk-averse and choose less risky financing compared to their male counterparts. This study posits new evidence that female CEO financing decisions are not always risk averse if we consider female ownership, foreign ownership, state ownership, firm association with big firms, and the industry in which the firm operates. Thus, we contribute to the corporate governance literature, and this study implies a corporate financing policy.
Nexus of knowledge oriented leadership and knowledge worker performance in Chinese higher education institutions: a post-pandemic behavioral analysis
Authors: Nawaz Amjad , Gu Aihua , Jiang Tao
Published: May 2024

Purpose

In the wake of the COVID-19 outbreak understanding the behavioral dynamics and role of knowledge-oriented leadership (KOL) in driving knowledge worker performance (KWP) is paramount for organizations striving to adapt and thrive in the post-pandemic era. Drawing on the path-goal theory, this study explores the impact of KOL on KWP. In addition, this study seeks to examine both the direct and indirect influences of KOL on KWP via digital orientation (DO) and digital citizenship practices (DCP), especially for higher education institutions (HEIs) located in China.

Design/methodology/approach

The sample consisted of 319 academic staff from HEIs in China. The study used Smart-PLS 4.0 for analytical examination.

Findings

The results indicate that the impact of knowledge-oriented leadership on KWP is negligible. Furthermore, DCP and DO partially mediate the relationship between KOL and KWP. The findings of this research have practical implications for Chinese HEIs and organizations across industries, providing insights into how to navigate the complexities of the post-pandemic work environment and effectively harness digitalization to optimize the KWP.

Research limitations/implications

The implications of this research extend beyond the HEIs, providing organizations in various industries with evidence-based strategies to promote effective leadership, foster digital skills, and cultivate a culture of digital citizenship in the post-pandemic work landscape.

Originality/value

Despite the increasing significance of KOL in the higher education sector, there is a dearth of studies establishing a relationship between KOL and KWP in HEIs. The present study seeks to fill this gap by examining the association among KOL, KWP, DO, and DCP in HEIs during the post-pandemic. This research provides significant contributions to the existing literature on the topic by scientifically exploring the association between KOL and KWP by examining the intervention mechanism of both digital citizenship practices and digital orientation.
Critical conscious leadership for decolonisation: a Black consciousness perspective of authentically transforming leadership
Authors: Seyama-Mokhaneli Sadi
Published: May 2024

Purpose

This paper draws on African anti-colonial thought and Black consciousness to propose critical conscious leadership (CCL) as a decolonising leadership approach appropriate for pursuing emancipation, social justice and innovation in a new African university.

Design/methodology/approach

I utilised the method of critical discourse analysis to study Ihron Rensburg’s language as he reflected on his leadership at the University of Johannesburg (UJ). The study engaged with Rensburg’s writings and texts on his account of leading the merger and transformation of UJ. The primary text draws from his book “Serving Higher Purposes” (2020).

Findings

Through the construction of CCL, the paper proposes alternative tenets for leading transformation towards a new African university. CCL grounds a decolonised and pluriversal new African university’s character premised on a consciously revitalised alternative thinking that will carry the communitarian spirit of Africa in knowledge production, dissemination and consumption in humanising all and serving the greater good. And it operates within the dialectical tensions of the social and economic purpose of higher education (HE), African and global relevance, African and Western paradigms, excellent performance and attainment of social justice.

Originality/value

The proposed CCL offers an alternative leadership approach that responds to the call to “Dethrone the Empire” by centring Blackness in HE leadership, which is crucial for authentic transformation and decolonisation.
Artificial intelligence in talent acquisition: a multiple case study on multi-national corporations
Authors: Roppelt Julia Stefanie , Greimel Nina Sophie , Kanbach Dominik K. , Stubner Stephan , Maran Thomas K.
Published: May 2024

Purpose

The aim of this paper is to explore how multi-national corporations (MNCs) can effectively adopt artificial intelligence (AI) into their talent acquisition (TA) practices. While the potential of AI to address emerging challenges, such as talent shortages and applicant surges in specific regions, has been anecdotally highlighted, there is limited empirical evidence regarding its effective deployment and adoption in TA. As a result, this paper endeavors to develop a theoretical model that delineates the motives, barriers, procedural steps and critical factors that can aid in the effective adoption of AI in TA within MNCs.

Design/methodology/approach

Given the scant empirical literature on our research objective, we utilized a qualitative methodology, encompassing a multiple-case study (consisting of 19 cases across seven industries) and a grounded theory approach.

Findings

Our proposed framework, termed the Framework on Effective Adoption of AI in TA, contextualizes the motives, barriers, procedural steps and critical success factors essential for the effective adoption of AI in TA.

Research limitations/ implications

This paper contributes to literature on effective adoption of AI in TA and adoption theory.

Practical implications

Additionally, it provides guidance to TA managers seeking effective AI implementation and adoption strategies, especially in the face of emerging challenges.

Originality/value

To the best of the authors' knowledge, this study is unparalleled, being both grounded in theory and based on an expansive dataset that spans firms from various regions and industries. The research delves deeply into corporations' underlying motives and processes concerning the effective adoption of AI in TA.
Financial innovation intra Muslim capital markets and inter global counterparts: implications of differences
Authors: Norton Simon D.
Published: May 2024

Purpose

This study aims to investigate the implications for financial innovation and product development of differences between schools of jurisprudence (fiqh) pertaining across regional Muslim markets, and the consequences for global financial institutions.

Design/methodology/approach

The methodology is qualitative, drawing upon several sources. Firstly, differences in interpretation regarding the economic and moral responsibilities of financial institutions in Islamic and secular contexts. Secondly, contrasting tenets of schools of Islamic jurisprudence regarding the permissibility of products traded intra Muslim markets. Thirdly, characteristics of complex financial instruments traded in global secular markets prior to the credit crisis of 2007–2008.

Findings

Differences between Islamic and global secular interpretations regarding responsibilities of financial institutions militate against integrated markets across which products can be seamlessly traded. Global financial institutions should recognise that different Islamic schools of jurisprudence prioritise either legal form or substance of financial products, but not both simultaneously. This should be considered when designing new products for regional Muslim markets.

Practical implications

Global financial institutions which focus upon the legal (micro) form of new Islamic products should relate in investor prospectuses and marketing materials the extent to which these accommodate Islamic jurisprudence’s equal (macro) concern for public interest or maslahah. This may comprise the reallocation of risk from those unable to bear it to those willing to assume it for a price, reinforcing rather than compromising economic stability.

Originality/value

This study evaluates implications for product development and marketing for global financial institutions active in regional Muslim markets across which different Islamic schools of jurisprudence apply.
Determining the stationary digital twins implementation barriers for sustainable construction projects
Authors: Mohandes Saeed Reza , Singh Atul Kumar , Fazeli Abdulwahed , Banihashemi Saeed , Arashpour Mehrdad , Cheung Clara , Ejohwomu Obuks , Zayed Tarek
Published: May 2024

Purpose

Previous research has demonstrated that Digital Twins (DT) are extensively employed to improve sustainable construction methods. Nonetheless, their uptake in numerous nations is still constrained. This study seeks to identify and examine the digital twin’s implementation barriers in construction building projects to augment operational performance and sustainability.

Design/methodology/approach

An iterative two-stage approach was adopted to explore the phenomena under investigation. General DT Implementation Barriers were first identified from extant literature and subsequently explored using primary questionnaire survey data from Hong Kong building industry professionals.

Findings

Survey results illustrated that Lack of methodologies and tools, Difficulty in ensuring a high level of performance in real-time communication, Impossibility of directly measuring all data relevant to the DT, need to share the DT among multiple application systems involving multiple stakeholders and Uncertainties in the quality and reliability of data are the main barriers for adopting digital twins' technology. Moreover, Ginni’s mean difference measure of dispersion showed that the stationary digital twin’s barriers adoption is needed to share the DT among multiple application systems involving multiple stakeholders.

Practical implications

The study’s findings offer valuable guidance to the construction industry. They help stakeholders adopt digital twins' technology, which, in turn, improves cost efficiency and sustainability. This adoption reduces project expenses and enhances environmental responsibility, providing companies a competitive edge in the industry.

Originality/value

This research rigorously explores barriers to Digital Twin (DT) implementation in the Hong Kong construction industry, employing a systematic approach that includes a comprehensive literature review, Ranking Analysis (RII) and Ginni’s coefficient of mean difference (GM). With a tailored focus on Hong Kong, the study aims to identify, analyze and provide novel insights into DT implementation challenges. Emphasizing practical relevance, the research bridges the gap between academic understanding and real-world application, offering actionable solutions for industry professionals, policymakers and researchers. This multifaceted contribution enhances the feasibility and success of DT implementation in construction projects within the Architecture, Engineering and Construction (AEC) sector.
Aggregate analyst characteristics and forecasting performance
Authors: Wilson Mark , Wu Yi (Ava)
Published: May 2024

This paper examines the advantages of aggregate measures of analyst characteristics to researchers and investors interested in explaining differences in analysts' forecasting performance. We show while single‐characteristic and factor‐based measures reflecting attributes such as forecasting experience, access to resources and portfolio complexity vary significantly in the extent to which each explains analyst forecasting performance, equal‐weighted composite measures based on single characteristics or on factors extracted from those characteristics are consistently associated with forecasting bias arising from a range of indicators of reduced earnings quality. These aggregate measures of analyst characteristics require no additional data beyond traditional archival sources and offer a useful method of testing the impact of analyst characteristics on their forecasting performance.