bluuebunny/crossref_metadata_2025 huggingface dataset:
Telemedicine to Address Inequities in Access to Primary Health Care for Minority Groups: A protocol for a Systematic Review and Meta-Analysis
Authors: de Oliveira Laguna Silva Gabriela , Fernandes Gabriel Ricardo , Pereira Emmanuelle Moreira , da Rocha Jacqueline Castro , Aguilar Gabriela Tizianel , Linhares Tiago Sigal , Dode Andressa Dutra , Cabral Felipe Cezar , de Campos Moreira Taís , Chagas Maria Eulália Vinadé
Published: November 2024

Background

The present article outlines the protocol for a systematic review and meta-analysis aimed at consolidating the available evidence on how telemedicine can reduce inequities in access to Primary Health Care (PHC) among minority populations. The review seeks to identify barriers, facilitators, and factors that influence the effectiveness of this intervention across different settings.

Methods

This protocol for a systematic review and meta-analysis is reported in line with Prisma-P and the results will be reported using PRISMA-E flowchart. The eligibility criteria was defined using the PICOS approach. Population is minority groups that have used telemedicine, the intervention is synchronous and asynchronous telemedicine, the comparator will consist of minority groups that have received usual care, outcome is access to primary health care and we will include randomized controlled trials. We will search MEDLINE (via PubMed), Scopus, Latina American and Caribbean Health Sciences Literature (LILACS) databases. The risk of bias will be assessed using the ROBINS-I and the confidence in cumulative evidence will be assessed using the GRADE equity tool.

Discussion

It is expected to provide pragmatic results, such supporting decision-making regarding the creation and implementation of new public policies, the development of clinical guidelines, and the optimization of resources aimed at equitable access.

Systematic review registration

PROSPERO CRD42024581305
Large language models for extracting histopathologic diagnoses from electronic health records
Authors: Johnson Brian , Bath Tyler , Huang Xinyi , Lamm Mark , Earles Ashley , Eddington Hyrum , Jih Lily J. , Gupta Samir , Shah Shailja C. , Curtius Kit
Published: November 2024

Background & Aims

Accurate data resources are essential for impactful medical research. To date, most large-scale studies have relied on structured sources, such as International Classification of Diseases codes, to determine patient diagnoses and outcomes. However, these structured datasets are often incomplete or inaccurate. Recent advances in natural language processing, specifically the introduction of open-weight large language models (LLMs), enable more accurate data extraction from unstructured text in electronic health records (EHRs).

Methods

We created an approach using LLMs for identifying histopathologic diagnoses, including presence of dysplasia and cancer, in pathology reports from the Department of Veterans Affairs Healthcare System, including those patients with genotype data within the Million Veteran Program (MVP) biobank. Our approach requires no additional training and utilizes a simple ‘yes/no’ question prompt to obtain an answer. We validated the method on 3 diagnostic tasks by applying the same prompts to reports from patients with vs without diagnoses of inflammatory bowel disease (IBD) and calculating F-1 scores as a balanced accuracy measure.

Results

In patients without IBD in MVP, we achieved F1-scores of 99.3% for identifying any dysplasia, 98.2% for identifying high-grade dysplasia and/or colorectal adenocarcinoma (HGD/CRC), and 96.2% for identifying CRC using LLM Gemma-2. In IBD patients in MVP, we achieved F1-scores of 97.1% for identifying dysplasia, 96.4% for identifying HGD/CRC, and 97.1% for identifying CRC.

Conclusion

LLMs provide excellent accuracy in extracting diagnoses from EHRs and can be applied to a variety of tasks with no additional human-led development required. Our validated methods generalized to unstructured pathology notes, even withstanding challenges of resource-limited computing environments.
Cooperative [2Fe-2S] cluster-binding regulates the functional transitions of theAspergillus fumigatusiron regulator HapX for adaptation to iron starvation, sufficiency and excess
Authors: Oberegger Simon , Misslinger Matthias , Haas Hubertus
Published: November 2024

Accurate sensing of cellular iron levels is vital, as this metal is essential but toxic in excess. The iron-sensing transcription factor HapX is crucial for virulence ofAspergillus fumigatus,the predominant human mold pathogen. Its absence impairs growth under iron limitation and excess, but not under moderate iron availability, suggesting that HapX switches between three states to adapt to varying iron availability.

This study suggests that the HapX state transitions are regulated by the different propensities of four phylogenetically conserved cysteine-rich regions (CRRs) to coordinate [2Fe-2S] clusters resulting in cumulative occupancies that depend on iron availability. In the iron starvation state, CRR-B and -C lack [2Fe-2S] clusters, the iron sufficiency/”neutral” state features clusters in CRR-B and/or -C and the iron excess state has clusters in all CRR-A, B, and -C, while CRR-D plays a minor role. Combinatorial mutation of CRR-B and -C blocked growth by locking HapX in the iron starvation state, leading to uncontrolled iron uptake, iron accumulation, repression of iron-consuming pathways and impaired iron detoxification. Loss of the C-terminal 27 amino acid region of HapX, which is crucial for the iron starvation state and was found to contain a degron, rescued the severe growth defect. Noteworthy, the - Fe state of HapX induced several gene clusters encoding secondary metabolites.
Gut microbiota-derived GlcNAc-MurNAc is a TLR4 agonist that protects the host gut
Authors: Li Chenyu , Adamson Christopher , Ng Wee Ren Allan , Liang Yaquan , Hong Zebin , Loh Jia Tong , Ng Siu Kin , Kwan Mun Chung Jeric , Feng Shiliu , Ng Wei Long Evan , Kumar Nair Sajith , Ruedl Christiane , Wong Sunny Hei , Lam Kong-Peng , Qiao Yuan
Published: November 2024

Gut microbiota-derived peptidoglycan fragments (PGNs) are key signaling molecules that regulate multiple aspects of the host’s health. Yet the exact structures of natural PGNs in hosts have not been fully elucidated. Herein, we developed an LC-HRMS/MS analytical platform for global quantification and profiling of natural PGN subtypes in host gut and sera, unexpectedly revealing the abundance of PGN-derived saccharide moieties that do not resemble canonical ligands of mammalian NOD1/2 receptors. Focusing on the disaccharide GlcNAc-MurNAc (GM), a natural gut PGN that does not activate NOD1/2 yet still exhibits robust immunostimulatory effects in host immune cells, we unambiguously established GM as a TLR4 agonist, adding to the growing knowledge of NOD-independent mechanisms of PGN sensing in hosts. Importantly, the administration of GM effectively mitigates colonic inflammation in the DSS-induced colitis model in mice via TLR4-dependent mechanisms, highlighting thein vivosignificance of natural gut microbiota-derived PGNs in maintaining host intestinal homeostasis.
A new class of binding protein-dependent solute transporter exemplified by the TAXI-GltS system fromBordetella pertussis
Authors: Jaques Lily M. , Davies Joseph F.S. , Leone Vanessa , Kelly David J. , Mulligan Christopher
Published: November 2024

Tripartite ATP-dependent periplasmic (TRAP) transporters are widespread in prokaryotes, but absent in eukaryotes, and facilitate the uptake of a wide variety of substrates. TRAP transporters are composed of a substrate binding protein (SBP) and two unequally sized membrane components that exist as either separate proteins or are fused into a single polypeptide. Almost all TRAP SBPs exist as monomeric globular proteins that bind substrate and present it to the membrane component. Here, we describe the discovery and characterisation of a novel TRAP SBP from the TAXI subfamily with a previously unidentified architecture. BP0403 from the human pathogenBordetella pertussisis a predicted lipoprotein composed of 3 distinct domains; an α/β globular domain with a unique fold, a long helical domain and a C-terminal TAXI SBP domain. Expression and purification of the full-length protein reveals that it forms a stable dimer. Structural modelling of the dimer interface and molecular weight analysis using size exclusion chromatography of the individual domains reveals that the interdomain helical region is solely responsible for dimerization. Differential scanning fluorimetry (DSF) and intrinsic tyrosine fluorescence reveal that BP0403 binds L-glutamate with nanomolar affinity. Unexpectedly, analysis of the genome context of BP0403 reveals the complete absence of characteristic genes for TRAP membrane components but co-localisation and translational coupling withgltS, encoding a Na+/glutamate symporter. In other bacteria, we identified fused BP0403-GltS homologues, strongly suggesting that this constitutes a completely novel SBP-dependent secondary active transporter. Structural comparisons suggest GltS operates by an elevator-type mechanism, like TRAP transporters; the association of an SBP with this class of secondary transporter is an emerging theme.
Simultaneous mapping of RNA secondary, tertiary, and quaternary structure in living cells by multi-site DMS probing
Authors: Saleem Irfana , Miller Thomas , Kearns Lucas , Mitchell David , Bose Ritwika , Weidmann Chase A. , Mustoe Anthony M.
Published: November 2024

Identifying tertiary structures and protein binding sites on RNA molecules remains a key challenge in RNA biology. We report a new chemical probing strategy termed multi-site DMS-MaP (msDMS-MaP) that exploits base tautomerization during mutational profiling reverse-transcription to measure typically invisible DMS-induced modifications at the N7 position of G. These N7-G modifications are now resolved concurrently with conventional N1 and N3 modifications with only minor modifications to established protocols, providing a multi-dimensional, single-molecule readout of RNA structure. We show that N7-G reactivity specifically reports on RNA tertiary and quaternary structure, enabling identification of diverse, functionally significant motifs such as cooperatively folding tertiary domains and protein binding sites in living cells. We apply msDMS-MaP to obtain a map of the quaternary structural ensemble of the 7SK non-coding snRNP, revealing unique protein binding sites across three 7SK structural isoforms. msDMS-MaP represents a broadly applicable strategy for enhanced RNA functional motif discovery and characterization.
Investigating understanding, experience and barriers to care for people living with chronic hepatitis B virus infection in Kilifi, Kenya
Authors: Downs Louise O , Odhiambo Juliet , Zaharani Mwanakombo , Chirro Oscar , Safari Benson , Aliyan Nadia , Matthews Philippa C , Kagwanja Nancy
Published: November 2024

Chronic hepatitis B infection (CHB) is a global health disaster with over 1 million people dying annually from this infection worldwide. A large burden of morbidity and mortality is in the WHO-African Region (WHO-AFRO) however here <5% of people are diagnosed and 0.2% on treatment. Community understanding of HBV is often poor and people living with HBV (PLWHB) can experience stigma and discrimination. However there has been little documentation on the impact of an HBV diagnosis on the lives of PLWHB. We explore the experience of PLWHB in Kilifi, Kenya, including their understanding of the disease, how their diagnosis has changed their lives and what barriers they have experienced when accessing care. We show overall understanding of HBV in this group is good, with most participants knowing transmission routes and available treatment. In the general community however, HBV understanding is poor - there is no local name for the infection other than the symptoms it causes such as swollen tummy and yellow eyes. Many participants felt shocked at their initial diagnosis and had mixed reactions from friends and family. Costs of transport and concerns about lost employment were seen as the biggest barrier to care with many people advocating for decentralised clinics. Stigma was also raised with people feeling isolated, rejected and discriminated against. There was also discomfort around the current integration of HBV and HIV services at KCRH, with concerns over increased stigma, longer waiting times and preferential treatment being given to those living with HIV.

Community education, provision of wider testing and advocacy by well-respected community members were mentioned as key methods to reduce HBV transmission. Decentralisation of clinics may improve access to care; however the patient voice must be considered when planning future interventions to ensure these are acceptable and accessible to the community.
The lived experience of social anxiety disorder: A conceptual model based on published literature and social media listening
Authors: Schmidt Ana Lucía , Staunton Hannah , Stein Murray B. , Hayes Anne Marie , Rodriguez-Esteban Raul , Fischer Kathrin , McIver Tammy , Suter Eugénie E.
Published: November 2024

Social anxiety disorder (SAD) affects up to 1 in 8 individuals over their lifetime and is characterized by an intense fear of social situations where there may be exposure to unfamiliar people or possible scrutiny. The analysis of social media data rather than traditional methods (interviews or focus groups) can provide a unique opportunity to understand the lived experience of individuals with SAD, for whom interacting with strangers is challenging. This retrospective observational study reviewed published literature from PubMed and data from Reddit using social media listening (SML). A stepwise analysis in line with US Food and Drug Administration Patient-Focused Drug Development guidelines was performed to develop a conceptual model for SAD. Natural language processing techniques and machine learning approaches were employed to extract symptoms and impacts described by individuals with SAD. Eleven publications from the literature and 535,544 posts from 118,040 Reddit users were included. Clinical and patient experts then refined the conceptual model covering three key symptom domains (physical, negative automatic thoughts, and emotions) and two impact domains (social functioning and occupational/educational functioning). This study provides insights into the lived experience of individuals with SAD and confirms the value of SML when traditional methods are inappropriate.
A Machine Learning Model of Perturb-Seq Data for Use in Space Flight Gene Expression Profile Analysis
Authors: Johnson Liam , Casaletto James , Costes Sylvain , Proctor Caitlin , Sanders Lauren
Published: November 2024

The genetic perturbations caused by spaceflight on biological systems tend to have a system-wide effect which is often difficult to deconvolute into individual signals with specific points of origin. Single cell multi-omic data can provide a profile of the perturbational effects but does not necessarily indicate the initial point of interference within a network. The objective of this project is to take advantage of large scale and genome-wide perturbational or Perturb-Seq datasets by using them to pre-train a generalist machine learning model that is capable of predicting the effects of unseen perturbations in new data. Perturb-Seq datasets are large libraries of single cell RNA sequencing data collected from CRISPR knock out screens in cell culture. The advent of generative machine learning algorithms, particularly transformers, make it an ideal time to re-assess large scale data libraries in order to grasp cell and even organism-wide genomic expression motifs. By tailoring an algorithm to learn the downstream effects of the genetic perturbations, we present a pre-trained generalist model capable of predicting the effects of multiple perturbations in combination, locating points of origin for perturbation in new datasets, predicting the effects of known perturbations in new datasets, and annotation of large-scale network motifs. We demonstrate the utility of this model by identifying key perturbational signatures in RNA sequencing data from spaceflown biological samples from the NASA Open Science Data Repository.
Structural basis for the synergistic assembly of the snRNA export complex
Authors: Dubiez Etienne , Garland William , Brask Maja Finderup , Erba Elisabetta Boeri , Jensen Torben Heick , Kadlec Jan , Cusack Stephen
Published: November 2024

The nuclear cap-binding complex (CBC) and its partner ARS2 play crucial roles in regulating Pol II transcript fate through mutually exclusive interactions with RNA effectors. One such effector, PHAX, mediates the nuclear export of U-rich small nuclear RNAs (snRNAs). Here we present the cryo-EM structure of the snRNA export complex comprising phosphorylated PHAX, CBC, CRM1, Ran-GTP and capped RNA. The central region of PHAX bridges the CBC-bound capped RNA to the CRM1-RanGTP, while also significantly reinforcing cap dinucleotide binding. Additionally, PHAX interacts with a distant region of CRM1 facilitating contacts of an essential phosphorylated region with the prominent basic surface of RanGTP. The importance of these interactions is confirmed byin vitroand in cell mutagenesis experiments. CBC engagement within the snRNA export complex is incompatible with its interactions with other RNA effectors such as ALYREF or NCBP3. Taken together, we demonstrate that snRNA export complex formation requires synergistic binding of all its components, which in turn displaces ARS2 from the CBC, and commits the complex for export.
A genome-scale single cell CRISPRi map oftransgene regulation across human pluripotent stem cell lines
Authors: Feng Claudia , Peets Elin Madli , Zhou Yan , Crepaldi Luca , Usluer Sunay , Dunham Alistair , Braunger Jana M , Su Jing , Strauss Magdalena E , Muraro Daniele , Xian Cheam Kimberly Ai , Bonder Marc Jan , Nogales Edgar Garriga , Cooper Sarah , Bassett Andrew , Leonard Steven , Gu Yong , Fussing Bo , Burke David , Parts Leopold , Stegle Oliver , Velten Britta
Published: November 2024

Population-scale resources of genetic, molecular, and cellular information form the basis for understanding human genomes, charting the heritable basis of disease, and tracing the effects of mutations. Pooled perturbation assays applied to cellular models, probing the effect of many perturbations coupled with an scRNA-seq readout (Perturb-seq), are especially potent references for interpreting disease-linked mutations or gene expression changes. However, the utility of existing maps has been limited by the comprehensiveness of perturbations possible, and the relevance of their cell line context. Here, we present the first genome-scale CRISPR interference (CRISPRi) perturbation map with single-cell RNA sequencing readout across many human genetic backgrounds in human pluripotent cells. To do so, we establish large-scale CRISPRi screening in human induced pluripotent stem cells from healthy donors, using over 20,000 guide RNAs to target 7,226 genes across 34 cell lines from 26 genetic backgrounds, and gather expression data from nearly 2 million cells. We comprehensively maptransexpression changes induced by the target knockdowns, which complement co-expression patterns in unperturbed cells and facilitate the functional annotation of target genes to biological processes and complexes. Consistency of targeting protein complex members point to protein complexes as a nexus for aggregating transcriptional variation, revealing novel interaction partners. We characterise variation in perturbation effects across donors, with expression quantitative trait loci linked to higher genetic modulation of perturbation effects but overall low replication of trans effects due to knockdown of their corresponding cis regulators. This study pioneers population-scale CRISPR perturbations with single cell readouts that will fuel foundation models for the future of effective modulation of cellular disease phenotypes.
Multi-omics analysis reveals key immunogenic signatures induced by oncolytic Zika virus infection of paediatric brain tumour cells
Authors: Sherwood Matt , Mitsugi Thiago G. , Kaid Carolini , Coke Brandon , Zatz Mayana , Maringer Kevin , Okamoto Oswaldo K. , Ewing Rob M.
Published: November 2024

Brain tumours disproportionately affect children and are the largest cause of paediatric cancer-related death. Despite decades of research, paediatric standard-of-care therapy still predominantly relies on surgery, radiotherapy, and systemic use of cytotoxic chemotherapeutic agents, all of which can result in debilitating acute and late effects. Novel therapies that engage the immune system, such as oncolytic viruses (OVs), hold great promise and are desperately needed. Zika virus (ZIKV) infects and destroys aggressive cells from paediatric medulloblastoma, atypical teratoid rhabdoid tumour (ATRT), diffuse midline glioma (DMG), ependymoma and neuroblastoma. Despite this, the molecular mechanisms underpinning this therapeutic response are grossly unknown. By profiling the transcriptome across a time-course, we comprehensively investigated the response of paediatric medulloblastoma and ATRT brain tumour cells to ZIKV infection at the transcriptome level for the first time. We observed conserved TNF signalling pathway and cytokine signalling-related signatures following ZIKV infection. We demonstrated that the canonical TNF-alpha signalling pathway is implicated in oncolysis by reducing the viability of ZIKV-infected brain tumour cells and is a likely contributor to the anti-tumoural immune response through TNF-alpha secretion. Our findings have highlighted TNF-alpha as a potential prognostic marker for oncolytic ZIKV virotherapy. Performing a 49-plex ELISA, we generated the most comprehensive ZIKV-infected cancer cell secretome to date. We demonstrated that ZIKV infection induces a clinically relevant and diverse pro-inflammatory brain tumour cell secretome, thus circumventing the need for transgene modification to boost efficacy. We assessed publicly available scRNA-Seq data to model how the ZIKV-induced secretome may (i) interact with medulloblastoma tumour microenvironment (TME) cells via paracrine signalling and (ii) polarise lymph node immune cells via endocrine signalling. Our modelling has provided significant insight into the cytokine response that orchestrates the diverse anti-tumoural immune response during oncolytic ZIKV infection of brain tumours. Our findings have significantly contributed to understanding the molecular mechanisms governing oncolytic ZIKV infection and will help pave the way towards ZIKV-based virotherapy.
Biomimetic porous silicon for rationally engineered combination therapy to induce immunogenic cell death
Authors: Saarela Silja , Happonen Emilia , Laari Milla-Iida , Mohammed Zakir , Saba Shaghayegh , Liu Ruixian , Klefström Juha , Lehto Vesa-Pekka , Xu Wujun
Published: November 2024

Combined chemo-photothermal therapy (CHT-PTT) is a promising treatment for metastatic cancers. It enables the synergistic induction of immunogenic cell death (ICD), while sensitising suppressive tumour microenvironment to immunotherapy. To induce ICD, the rational design of a combined CHT-PTT regimen remains unclear. In the present study, black porous silicon nanoparticles (BPSi NPs) were utilized as both drug carriers and photothermal conversion agents. To enhance their colloidal stability and homotypic targeting, BPSi NP surfaces were modified with polyethylene glycol and further coated with cancer cell membranes (CMs). Six chemotherapeutic drugs with different cell growth inhibition mechanisms were tested against metastatic MDA-MB-231 breast cancer cells to evaluate their ICD induction potentials. Finally, in the combined CHT-PTT, the effect of temperature was evaluated. Based on the analysis of ICD markers, high-mobility group box 1 and calreticulin proteins, we found that bromodomain-containing protein 4 inhibitor, (+)-JQ-1 (JQ1) was the optimal drug, and the mild-hyperthermia temperature of 45 °C was the best temperature setting in the combined CHT-PTT to induce ICD. Thus, our study provides rationally designed CHT-PTT regimen for efficient cancer treatment with high efficacy and low side effects.
Pesticide degradation capacity of a novel strain belonging toSerratia sarumanii(GBS19) with its genomic profile
Authors: Alatassi Gülperi , Baysal Ömür , Silme Ragıp Soner , Örnek Gülçin Pınar , Örnek Hakan , Can Ahmet
Published: November 2024

The use of pesticides in agricultural pest control and the potential for biological degradation of these chemicals are significant factors in environmental conservation. Sustainable pest control strategies should prioritize the preservation of non-target organisms and the maintenance of soil ecosystem dynamics. Initiation from this point, this study aimed to identify microorganisms capable of pesticide biodegradation commonly used in our region’s intensive agricultural fields. The microorganism with the broadest degradation spectrum was identifiedin vitrostudies, and whole-genome sequence analyses indicated that some genomic regions were able to degrade pesticides, which was also confirmed with LC-MS analysis. Detailed genomic analyses linked to allele sequence definitions for ribosomal MLST have classified this strain asSerratia sarumaniiunder theSerratiagenus. Moreover, our findings showed that the introduction of this microorganism can stimulate the degradation of certain pesticides in the environment while, interestingly, simultaneously enhancing the potency of low concentrations of some other pesticides through a synergistic effect. To validate of GBS19 biodegradation capacity, additional studies carried out on 25 pesticide active chemicals using LC-MS chromatographic analysis revealed that theSerratia sarumaniiGBS19 strain is able to biodegrade some active compounds of various pesticides (fludioxonil, fenhexamid, pyrimethanil, and spirodiclofen) by up to 54%, 52%, 46%, and 23%, respectively. These results highlight the degrative properties of our prominent original strain as a gene pool which can be put into practice by transforming into competent strain using recombinant DNA technology.
Structural Basis for Catalysis and Substrate Specificity of a LarA Racemase with a Broad Substrate Spectrum
Authors: Gatreddi Santhosh , Urdiain-Arraiza Julian , Desguin Benoit , Hausinger Robert P. , Hu Jian
Published: November 2024

The LarA family consists of diverse racemases/epimerases that interconvert the diastereomers of a variety of α-hydroxyacids by using a nickel-pincer nucleotide (NPN) cofactor. The hidden redox reaction catalyzed by the NPN cofactor makes LarA enzymes attractive engineering targets for applications. However, how a LarA enzyme binds its natural substrate and recognizes different α-hydroxyacids has not been elucidated. Here, we report three high-resolution structures of the enzyme-substrate complexes of a broad-spectrum LarA enzyme fromIsosphaera pallida(LarAIp). The substrate binding mode reveals an optimal orientation and distance between the hydride donor and acceptor, strongly supporting the proposed proton-coupled hydride transfer mechanism. The experimentally solved structures, together with the structural models of other LarA enzymes, allow us to identify the residues/structural elements critically involved in the interactions with different α-hydroxyacid substrates. Collectively, this work provides a critical structural basis for catalysis and substrate recognition of the diverse enzymes in the LarA family, thus building a foundation for enzyme engineering.
TFEB/HLH-30-mediated expansion of neuronal lysosomal capacity in early adulthood protects dendrite maintenance during aging inCaenorhabditis elegans
Authors: Zhong Ruiling , Richardson Claire E.
Published: November 2024

Lysosomes are essential for neuronal homeostasis, providing degradation and recycling functions necessary to support neurons’ complex operations and long lifespans. However, the regulation of lysosomal degradative capacity in healthy neurons is poorly understood. Here, we investigate the role of HLH-30, the soleCaenorhabditis eleganshomolog of Transcription Factor EB (TFEB), a master regulator of lysosome biogenesis and autophagy that it is thought to predominantly function in the context of starvation or stress. We demonstrate that HLH-30 is dispensable for neuronal development but acts cell-intrinsically to expand lysosomal degradative capacity during early adulthood. Loss of HLH-30 leads to lysosomal dysfunction and delayed turnover of synaptic vesicle proteins from the synapse. Notably, we show that basal HLH-30 activity is sufficient to expand neuronal lysosomal capacity without nuclear enrichment, in contrast to the nuclear translocation associated with starvation- and stress-induced activation of TFEB and HLH-30. Furthermore, we show that neuronal lysosomal function declines with age in wild-type animals, and this corresponds to a decrease in basal HLH-30-mediated transcription. We further demonstrate that basal HLH-30 activity is crucial for neuron maintenance: lysosomal dysfunction due to inadequate HLH-30 activity leads to dendrite degeneration and aberrant outgrowths. In summary, our study establishes a critical role for HLH-30/TFEB in promoting lysosomal capacity to preserve neuronal homeostasis and structural integrity of mature neuronsin vivo.
Are senior management with academic experience more cautious? Empirical evidence from corporate risk-taking
Authors: He Ping , Zou Ying
Published: November 2024

Purpose

Based on upper echelons theory, this study aims to explore the impact of senior management’s academic experience on corporate risk-taking and analyze the pathways and potential moderating effects of this relationship.

Design/methodology/approach

This study uses panel data of Chinese A-share listed companies in the Shenzhen Stock Exchange and Shanghai Stock Exchange from 2008 to 2020. An ordinary least squares model is used to test the hypothesis.

Findings

The results indicate that senior management’s academic experience suppresses corporate risk-taking, with investment level and cash reserves being two important channels. The moderation effect test shows that the inhibitory effect becomes more pronounced when senior managers with academic backgrounds occupy chief executive officer or chief financial officer roles. Conversely, when academic executives possess overseas/financial backgrounds or increase their compensation incentives, the strength of this disincentive effect diminishes. Moreover, our extended research finds that this inhibitory effect is more pronounced in state-owned companies and those within a strong Confucian cultural environment. Additionally, senior management’s academic experience positively correlates with both current and future market returns and company value.

Originality/value

This study contributes to the development of top management team building and corporate governance practices. Additionally, it furnishes investors with valuable insights into assessing the risk level of companies through the characteristics of their top management teams, thereby facilitating informed investment decision-making and improving capital market resource allocation efficiency.
Pace Control Systems: investigating people issues
Authors: Gulia Aditya , Pandey Jatin
Published: November 2024

Learning outcomes

After completion of the case study, the students will be able to understand lead and lag indicators, understand job performance and its linkage with job satisfaction, calculate the cost of turnover and design solutions to the problem of attrition and low satisfaction.

Case overview/synopsis

Pace Control Gears was a small-scale enterprise based out of Sonipat, India. It was an entrepreneurial venture by Rajesh Kumar, who had set Pace in 2010 to manufacture low-voltage electrical apparatus. Recently, Pace had begun to experience issues with quality control that were largely the result of human error. The company was facing a drop in satisfaction levels and higher attrition levels among the employees. Kumar had to find a solution quickly to address the problem, as it had direct implications for the company’s margins and the assurance of quality that it was associated with in the market.

Complexity academic level

This case study is suited to undergraduate and postgraduate courses in human resource management and general management.

Supplementary materials

Teaching notes are available for educators only.

Subject code

CSS 6: Human Resources Management.
Examining the mediating role of organizational pride on the relationship of human values and work outcomes of facilities managers
Authors: Ling Florence Yean Yng , Ng Yong Jun , Zhai Wujuan
Published: November 2024

Purpose

This study aims to explore the relationship between facilities managers’ human values, organizational pride and work outcomes, with the aim of discovering ways to boost their work outcomes.

Design/methodology/approach

A two-pronged research design comprising an online survey followed by in-depth interviews was adopted. Partial least square structural equation modeling (PLS-SEM) was used to model the data.

Findings

All 18 human values and 7 organizational pride emotions are present to a significant extent in facilities managers. The PLS-SEM showed that human values positively affect work outcomes of facilities managers significantly. In addition, work outcomes are further boosted when organizational pride is present.

Research limitations/implications

The degree of human values that an individual possesses may not be easily measured using a five-point Likert scale as there might be social desirability bias.

Practical implications

The implication is that organizations should select and hire facilities managers with high human values and introduce programs and initiatives to improve facilities managers’ organizational pride as these lead to higher work outcomes. Some recommendations on how to achieve these are provided.

Originality/value

The findings extend existing knowledge by empirically showing the mediating influence of organizational pride on the relationship between human values and facilities managers’ work outcomes. When organizational pride is present, work outcomes of facilities managers is boosted.
Decision-making approach based on bipolar complex fuzzy Hamacher power aggregation operators for classifying computer forensics
Authors: Sun Dechao , Mahmood Tahir , Rehman Ubaid ur , Zeng Shouzhen
Published: November 2024

Purpose

Gathering, analyzing and securing electronic data from various digital devices for use in legal or investigative procedures is the key process of computer forensics. Information retrieved from servers, hard drives, cellphones, tablets and other devices is all included in this. This article tackles the challenging problem of how to prioritize different kinds of computer forensics and figure out which kind is most useful in cases of cybercrime, fraud, theft of intellectual property, harassment and espionage.

Design/methodology/approach

Therefore, we first introduce enhanced versions of Hamacher power aggregation operators (AOs) within the framework of bipolar complex fuzzy (BCF) sets. These include BCF Hamacher power averaging (BCFHPA), BCF Hamacher power-weighted averaging (BCFHPWA), BCF Hamacher power-ordered weighted averaging (BCFHPOWA), BCF Hamacher power geometric (BCFHPG), BCF Hamacher power-weighted geometric (BCFHPWG) and BCF Hamacher power-ordered-weighted geometric (BCFHPOWG) operators. Employing the devised AOs, we devise a technique of decision-making (DM) for dealing with DM dilemmas with the BCF set (BCFS).

Findings

We prioritize different types of computer forensic by taking artificial data in a numerical example and getting the finest computer forensic. Further, by this example, we reveal the applicability of the proposed theory. This work provides a more elaborate and versatile procedure for classifying computer forensics with dual aspects of criteria and extra fuzzy information. It allows for better and less biased DM in the more intricate digital investigations, which may lead to better DM and time-saving in real-life forensic scenarios. To demonstrate the significance and impression of the devised operators and techniques of DM, they are compared with existing ones.

Originality/value

This research is the first to combine Hamacher and power AOs in BCFS for computer forensics DM. It presents new operators and a DM approach that is not encountered in the existing literature and is specifically designed to deal with the challenges and risks associated with the classification of computer forensics. The framework’s capacity to accommodate bipolar criteria and extra fuzzy information is a major development in the field of digital forensics and decision science.
The esports experience economy: a multiple-case study of esports events, peripherals and fashion
Authors: Brock Tom , Crawford Garry
Published: November 2024

Purpose

This study aims to examine the cultural and economic circumstances that shape esports consumer agency through case studies of “experiential consumption” (Miles, 2021).

Design/methodology/approach

A multiple-case study approach (Stake, 2006) is deployed alongside participant observation and document analysis to identify three cases of experiential consumption in esports – an esports tournament, a large online community for gaming peripherals and accessories, and an esportswear fashion brand.

Findings

The research identifies three aspects of experiential consumption relevant to esports. First, tournaments are sensory and emotional “spectacles”, immersing consumers in memorable experiences. Second, online gaming communities enable consumers to express themselves through “self-work”. Third, esportswear companies engage consumers with exclusive, authentic fashion experiences via “lifestyle branding”.

Research limitations/implications

The case studies highlight the need for future cross-cultural research on esports experiences, particularly how regional differences shape consumer behaviour. The impact of emerging technologies like virtual reality (VR), augmented reality (AR), blockchain and AI on personalising experiences, enhancing interactivity and related ethical considerations should be further explored.

Practical implications

Esports stakeholders can enhance esports events with real-time data analytics, VR and AR to create immersive experiences. They can also diversify income streams via personalised and exclusive apparel lines that reflect consumer identity, collaborating with mainstream fashion or entertainment brands. Compelling, emotionally resonant storytelling can deepen fan engagement and help build brand loyalty.

Originality/value

This article presents a new theoretical understanding of esports consumption through multiple case studies of experiential consumption, revealing the central role that “experience” plays in shaping the design and choice of esports products and services.
Does corporate environmental responsibility make firms greener in innovation? The role of knowledge flows
Authors: Xiong Deping , Liu Hanxiao , Yang Meng , Duan Yunlong
Published: November 2024

Purpose

In the context of severe environmental pollution and resource shortage, this study aims to examine how knowledge flows affect the green activities of firms. Specifically, this paper explored whether the firms’ knowledge flows, namely, knowledge inflow (KIF) and knowledge outflow (KOF), play a moderating role in relationship between corporate environmental responsibility (CER) and green innovation in Chinese high-polluting firms.

Design/methodology/approach

The analysis was carried out based on a panel data set of 305 heavy-polluting Chinese listed firms from 2010 to 2020. Meanwhile, this paper adopted the fixed model to empirically attest the proposed hypotheses regarding the relationships among CER, knowledge flows and green innovation.

Findings

The results indicate that there is a U-shaped relationship between CER and green innovation, while the two dimensions of knowledge flows exert opposing effects on the nonlinear link between CER and green innovation. Specifically, KIF positively moderates the effect of CER on green innovation, whereas KOF negatively moderates the effect of CER on green innovation.

Originality/value

This study demonstrates how green innovation can be influenced by CER and, moreover, provides a more nuanced understanding of the value of knowledge management (KM) in firms’ green activities. In this way, this paper answers the call for understanding the importance of green transformation in the context of KM.
Data-driven approach to fault detection for hospital HVAC system
Authors: Aghili Seyed Abolfazl , Khanzadi Mostafa , Haji Mohammad Rezaei Amin , Rahbar Morteza
Published: November 2024

Purpose

Hospital heating, ventilation and air conditioning (HVAC) systems are essential to patient safety and wellness. System malfunctions, however, may result in energy waste and even pose health dangers. This project aims to provide a fault detection and diagnostics framework designed primarily for HVAC systems in hospitals.

Design/methodology/approach

In order to identify problems in hospital air handling units, the study uses a data-driven methodology that makes use of Long Short-Term Memory (LSTM) and Gated Recurrent Units (GRU) models. To address the problem of uneven data, the dataset is balanced. Other machine learning classifiers, such as Logistic Regression, Multilayer Perceptron, Support Vector Machine, Random Forest, Gradient Boosting and eXtreme Gradient Boosting, are compared to see how well the LSTM and GRU models perform.

Findings

Regarding defect detection, the LSTM and GRU models outperform traditional classifiers in terms of both accuracy and computation speed, with high accuracy rates surpassing 90%. Due to its simpler design, GRU achieves higher accuracy and performs faster calculations than LSTM. These recurrent models work well to identify temporal relationships in time-series data, which is crucial for detecting HVAC system problems.

Originality/value

This study closes a research gap by concentrating on issue identification in hospital HVAC systems using actual data. It illustrates how deep learning may increase the precision of fault identification and computational efficiency in medical settings by utilizing LSTM and GRU models.
3‐Deoxyanthocyanidins: Extraction, stability, and food applications
Authors: Zhou Xuefu , Zhang Pangzhen , Ying Danyang , Duan Xu , Fang Zhongxiang
Published: November 2024

3‐Deoxyanthocyanidins, a rare class of anthocyanins, have gained increasing popularity due to their notable stability and bioactive properties. The enhanced stability of these colorants is attributed to the absence of a hydroxyl group at the C‐3 position. This absence leads to unique response mechanisms to environmental factors, such as pH, temperature, and light exposure. It also results in different interactions with biopolymers and co‐pigments. Sorghum is the only dietary source of 3‐deoxyanthocyanidins, which predominantly accumulate in the bran where the cell walls are extensively cross‐linked. This restricts their extraction, which is the premise of application. Therefore, this review compares the extraction efficiencies of 3‐deoxyanthocyanidins using conventional and innovative methods, discusses the qualification and quantification of such colorants, and summarizes factors affecting their stability, highlighting the differences in the behavior of anthocyanins and 3‐deoxyanthocyanidins influenced by these factors. This work provides insights for extracting and stabilizing 3‐deoxyanthocyanidins and proposes their potential applications in the food system.
Joint value creation: A functional, proactive approach to contract governance
Authors: Hurmerinta‐Haanpää Anna , Berger‐Walliser Gerlinde
Published: November 2024

The recurrent series of crises demonstrates that supply chains are frequently susceptible to disruption. It is imperative they adapt to evolving economic, ecological, social, and geopolitical circumstances. Economists and management scholars have introduced contract governance models that facilitate adaptation and collaboration; however, these models have been largely ignored in the legal field. This article addresses a significant gap in the existing literature on commercial contracts, which is currently fragmented between legal, economic, and organizational perspectives. The article proposes a functional, proactive contracting framework focused on joint value creation. The framework integrates insights from transaction cost economics, relational contract theory, relational view, functional contracting, proactive contracting, and legal design. It provides an instrument for contracting parties to co‐create contracts that enhance performance, reduce transaction costs, devise contingency plans, and utilize contracts as user‐centric tools to support relational governance practices and sustainability. A case study on Finnish Alliance Model Contract Clauses demonstrates the benefits of this approach in fostering more collaborative and resilient commercial contracts.
Knockdown of RUVBL2 improves hnRNPA2/B1‐stress granules dynamics to inhibit perioperative neurocognitive disorders in aged mild cognitive impairment rats
Authors: Wang Zixuan , Yang Chenyi , Wang Xinyi , Liao Huihui , Liu Xing , Liu Huan , Zhang Miao , Zhang Lin , Wang Haiyun
Published: November 2024

Perioperative neurocognitive disorders (PND) is common in aged mild cognitive impairment (MCI) patients and can accelerate the progression to dementia. This process involves heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNPA2/B1)‐mediated aggregates of stress granules (SGs), while RUVBL2 influences the dynamics of these SGs. Our research explored a new target for modulating hnRNAPA2/B1‐SGs dynamics to accelerate their disassembly and potentially delay MCI progression due to PND. We assessed the effect of hippocampal RUVBL2 knockdown on hnRNPA2/B1‐SGs in aged MCI rats through behavioral studies, biochemical experiments and MRI. We also examined hnRNPA2/B1‐SGs dynamics using immunofluorescence staining and fluorescence recovery after photobleaching (FRAP) in rat primary hippocampal neurons. Our results revealed that hnRNPA2/B1 in the hippocampus of aged MCI rats translocates to the cytoplasm to form SGs following anesthesia. RUVBL2 knockdown promotes the disappearance of hnRNPA2/B1‐SGs, allowing hnRNPA2/B1 to return to the nucleus and enhancing functional activity in the brain regions of aged MCI rats. In primary hippocampal neurons, RUVBL2 deletion facilitated hnRNPA2/B1‐SGs transition from hydrogel to liquid, promoting disassembly. We compared three commonly used general anesthetics—3% sevoflurane, 40 mg·kg−1·h−1 propofol, and 9% desflurane. Sevoflurane upregulated RUVBL2, which decreased the intraneuronal pH and disrupted energy metabolism. These changes resulted in greater stabilization of hnRNPA2/B1‐ SGs. In conclusion, our findings indicated that the knockdown of RUVBL2 expression contributes to the transition of hnRNPA2/B1‐SGs from the hydrogel phase to the liquid phase. Targeted interference with RUVBL2 may represent a novel approach to delay the progression to dementia due to PND in aged MCI patients.