bluuebunny/crossref_metadata_2025 huggingface dataset:
A biomechanical switch promotes lysosomal remodelling and exocytosis in keloid fibroblasts
Authors: Ross Rosie , Guo Yiyang , Walker Rebecca N. , Bergamaschi Daniele , Shaw Tanya J. , Connelly John T.
Published: November 2023

Keloids are a severe form of scarring for which the underlying mechanisms are poorly understood, and treatment options are limited or inconsistent. While biomechanical forces are potential drivers of keloid scarring, the direct cellular responses to mechanical cues have yet to be defined. The aim of this study was to examine the distinct responses of normal dermal fibroblasts (NDFs) and keloid-derived fibroblasts (KDFs) to changes in extracellular matrix (ECM) stiffness. When cultured on hydrogels mimicking the elasticity of normal or scarred skin, KDFs displayed greater stiffness-dependent increases in cell spreading, F-actin stress fibre formation, and focal adhesion assembly. Elevated acto-myosin contractility in KDFs disrupted the normal mechanical regulation of ECM remodelling, leading to constitutive collagen and fibronectin deposition. Transcriptional profiling identified mechanically-regulated pathways in NDFs and KDFs, including the actin cytoskeleton, Hippo signalling, and autophagy. Further analysis of the autophagy pathway revealed that autophagic flux was intact in both fibroblast populations and depended on acto-myosin contractility. However, KDFs displayed marked changes in lysosome organisation and an increase in lysosomal exocytosis, which was mediated by acto-myosin contractility. Together, these findings demonstrate that KDFs possess an intrinsic increase in cytoskeletal tension, which heightens the response to ECM mechanics and promotes lysosomal exocytosis.
Population structure and history ofMycobacterium bovisEuropean 3 clonal complex reveal transmission across ecological corridors of unrecognised importance in Portugal
Authors: Pereira André C. , Lourenço José , Themudo Gonçalo , Botelho Ana , Cunha Mónica V.
Published: November 2023

Mycobacterium boviscauses animal tuberculosis in livestock and wildlife, with an impact on animal health and production, wildlife management, and public health. In this work, we sampled a multi-host tuberculosis community from the official hotspot risk area of Portugal over 16 years, generating the largest available dataset in the country. Using phylogenetic and ecological modelling, we aimed to reconstruct the history of circulating lineages across the livestock-wildlife interface to inform intervention and the implementation of genomic surveillance within the official eradication plan. We find evidence for the co-circulation ofM. bovisEuropean 1 (Eu1), Eu2, and Eu3 clonal complexes, with Eu3 providing sufficient temporal signal for further phylogenetic investigation. The Eu3 most recent common ancestor (bovine) was dated in the 90’s, subsequently transitioning to wildlife (red deer and wild boar). Isolate clustering based on sample metadata was used to inform phylogenetic inference, unravelling frequent transmission between two clusters that represent an ecological corridor of previously unrecognised importance in Portugal. The latter was associated with transmission at the livestock-wildlife interface towards locations with higher temperature and precipitation, lower agriculture and road density, and lower host densities. This is the first analysis ofM. bovisEu3 complex in Iberia, shedding light on background ecological factors underlying long-term transmission, and informing where efforts could be focused within the larger hotspot risk area of Portugal.

IMPORTANCE

Efforts to strengthen surveillance and control of animal tuberculosis (TB) are ongoing worlwide. Here, we developed an eco-phylodynamic framework based on discrete phylogenetic approaches informed byM. boviswhole genome sequence data representing a multi-host transmission system at the livestock-wildlife interface, within a rich ecological landscape in Portugal, to understand transmission processes and translate this knowledge into disease management benefits.

We find evidence for the co-circulation of severalM. bovisclades, with frequent transmission of the Eu3 lineage among cattle and wildlife populations. Most transition events between different ecological settings took place toward host, climate and land use gradients, underscoring animal TB expansion and a potential corridor of unrecognised importance forM. bovismaintenance.

Results stress that animal TB is an established wildlife disease without ecological barriers, showing that control measures in place are insufficient to prevent long-distance transmission and spillover across multi-host communities, demanding new interventions targeting livestock-wildlife interactions.
Phase Separation of a Novel form of Euchromatic Histone Methyltransferasel (EHMT1N/C) into cytoplasmic RNA viral Inclusion bodies facilitates their coalescence, thereby enhancing viral replication
Authors: Biligiri Kriti Kestur , Sharma Nishi Raj , Mohanty Abhishek , Sarkar Debi Prasad , Vemula Praveen Kumar , Rampalli Shravanti
Published: November 2023

Protein lysine methyltransferases (PKMTs) methylate histone and non-histone proteins to regulate biological outcomes such as development and disease including viral infection. While PKMTs have been extensively studied for modulating the antiviral responses via host gene regulation, their role in methylation of proteins encoded by viruses and its impact on host-pathogen interactions remain poorly understood. In this study, we discovered a distinct nucleo-cytoplasmic form of Euchromatic Histone Methyltransferase1(EHMT1N/C), a PKMT, that phase separates into viral inclusion bodies (IBs) upon cytoplasmic RNA-virus infection (Sendai Virus). EHMT1N/Cinteracts with cytoplasmic EHMT2 and methylates SeV-Nucleoprotein upon infection. Elevated nucleoprotein methylation during infection correlated with coalescence of small IBs into large mature platforms for efficient replication. Inhibition of EHMT activity by pharmacological inhibitors or genetic depletion of EHMT1N/Creduced the size of IBs with a concomitant reduction in replication. Since IB formation is conserved among all cytoplasmic RNA-viruses, our study will have strong implications in understanding the mechanisms regulating IB formation, discerning RNA viral pathogenesis and designing therapeutic strategies.
Implementation of an internet-based stress management program in micro- and small-sized enterprises: A study protocol for a pre-post feasibility study of the effectiveness-implementation hybrid type 2 trial
Authors: Sasaki Natsu , Shimazu Taichi , Takeno Hajime , Ogawa Sayaka , Sawada Utako , Tsutsumi Akizumi , Imamura Kotaro
Published: November 2023

Background

Text-based self-guided internet-based stress management programs can improve mental health among workers. However, such mental health programs have scarcely been implemented in micro– and small-sized enterprises (MSEs), which are lacking in occupational healthcare services.

Objectives

This paper describes a study protocol for a pre-post feasibility study of an effectiveness-implementation hybrid type 2 trial of text-based internet-based programs (“WellBe-LINE”) in MSEs with less than 50 employees. This feasibility study primarily aims to evaluate trial methods for future effectiveness-implementation hybrid type 2 trials.

Methods

For this study protocol, an internet– and text-based self-care intervention program using the LINE app (a popular message tool in Japan) will be prepared according to evidence-based psychoeducational topics. Based on our online survey findings, personalized algorithms will be implemented according to employees’ gender, age, and psychological distress levels. A pre-post design feasibility study will be conducted on ten companies to evaluate trial methods (e.g., recruitment, penetration, and procedures). The primary outcome will involve individual-level penetration, defined as the proportion of the number of employees who register for the program divided by the total number of invited employees at the company. The progression criterion specifies that more than 50% of the recruited companies obtain 60% individual penetration. Finally, acceptability, appropriateness, feasibility, and cost will be measured using quantitative internet-based questionnaires and qualitative interviews.

Discussion

This pre-post feasibility study for future effectiveness-implementation hybrid type 2 trials will provide in-depth knowledge about the successful implementation of text-based, semi-personalized, self-care mental health interventions in real-world settings using both quantitative and qualitative data.

Conclusions

This feasibility study will help validate the effectiveness of text-based interventions using a widely used social networking service (SNS) tool for employees in MSEs.

Trial registration

UMIN clinical trial registration: UMIN000046960 (registration date: February 21, 2022)

https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000053570

Contributions to the literature

Internet-based mental health interventions in micro– and small-sized enterprises have not been implemented yet.

This feasibility study plans to test the implementation strategies to achieve high penetration in employees.

This study can provide insights into occupational health implementation in a disadvantaged context.
Cognitive and inflammatory heterogeneity in severe mental illness: Translating findings from blood to brain
Authors: Sæther Linn Sofie , Szabo Attila , Akkouh Ibrahim A. , Haatveit Beathe , Mohn Christine , Vaskinn Anja , Aukrust Pål , Ormerod Monica B. E.G. , Steen Nils Eiel , Melle Ingrid , Djurovic Srdjan , Andreassen Ole A. , Ueland Torill , Ueland Thor
Published: November 2023

Recent findings link cognitive impairment and inflammatory-immune dysregulation in schizophrenia (SZ) and bipolar (BD) spectrum disorders. However, heterogeneity and translation between the periphery and central (blood-to-brain) mechanisms remains a challenge. Starting with a large SZ, BD and healthy control cohort (n=1235), we aimed to i) identify candidate peripheral markers (n=25) associated with cognitive domains (n=9) and elucidate heterogenous immune-cognitive patterns, ii) evaluate the regulation of candidate markers using human induced pluripotent stem cell (iPSC)-derived astrocytes and neural progenitor cells (n=10), and iii) evaluate candidate marker messenger RNA expression in leukocytes using microarray in available data from a subsample of the main cohort (n=776), and in available RNA-sequencing deconvolution analysis of postmortem brain samples (n=474) from the CommonMind Consortium (CMC). We identified transdiagnostic subgroups based on covariance between cognitive domains (measures of speed and verbal learning) and peripheral markers reflecting inflammatory response (CRP, sTNFR1, YKL-40), innate immune activation (MIF) and extracellular matrix remodelling (YKL-40, CatS). Of the candidate markers there was considerable variance in secretion of YKL-40 in iPSC-derived astrocytes and neural progenitor cells in SZ compared to HC. Further, we provide evidence of dysregulated RNA expression of genes encoding YKL-40 and related signalling pathways in a high inflammatory subgroup consisting predominantly of SZ in the postmortem brain samples. Our findings suggest a relationship between peripheral inflammatory-immune activity and cognitive impairment, and highlight YKL-40 as a potential marker of cognitive functioning in a subgroup of individuals with severe mental illness.
Different patterns of structural network impairments in two amyotrophic lateral sclerosis subtypes driven by 18F-FDG PET/MR hybrid imaging
Authors: Feng Feng , Feng Guozheng , Liu Jiajin , Hao Weijun , Huang Weijie , Bi Xiao , Li Mao , Wang Hongfen , Yang Fei , He Zhengqing , Bai Jiongming , Wang Haoran , Ma Guolin , Xu Baixuan , Shu Ni , Huang Xusheng
Published: November 2023

The structural network damages in amyotrophic lateral sclerosis (ALS) patients are evident but contradictory due to the high heterogeneity of disease. We hypothesized that patterns of structural network impairments would be different in ALS subtypes by a data-driven method using 18F-FDG PET/MR hybrid imaging. 50 patients with ALS and 23 healthy controls (HCs) were collected PET, structural MRI and diffusion tensor imaging data by a 18F-FDG PET/MR hybrid. Two ALS subtypes were identified as the optimal cluster based on gray matter volume and standardized uptake value ratio. Network metrics at the global, local and connection levels were compared to explore the impaired patterns of structural network in the identified subtypes. Compared with HCs, the two ALS subtypes displayed a pattern of a locally impaired structural network centralized in the sensorimotor network and a pattern of an extensively impaired structural network in the whole brain. When comparing the two ALS subgroups by a support vector machine classifier based on the decreases in nodal efficiency of structural network, the individualized network scores were obtained in every ALS patient and demonstrated a positive correlation with disease severity. We clustered two ALS subtypes by a data-driven method, which encompassed different patterns of structural network impairments. Our results imply that ALS may possess the intrinsic damaged pattern of white matter network and thus provide a latent direction for stratification in clinical research.
Analyzing Chinese interest in osteoporosis-related diseases by using the Baidu index
Authors: Wu Jianjun , Lin Yanping , Chen Jingyi , Huang Jiachun , Huang Hongxing
Published: November 2023

Purpose

Understanding the public’s concern about osteoporosis in China is crucial for guiding public health campaigns and educational efforts, as it is significant public health concern in country. Using the Baidu index, this study aims to examine the Chinese fascination with diseases associated with osteoporosis.

Methods

The research gathered information on the search frequency of osteoporosis-related terms on Baidu between January 2012 and December 2022. To gauge the popularity of subjects associated with osteoporosis, the Baidu index was utilized. The study analyzed the trends and patterns of search volume and identified the most popular topics related to osteoporosis.

Results

The study found an increasing trend in interest in osteoporosis-related diseases in China over the past ten years. The search volume for osteoporosis-related keywords increased steadily from 2012 to 2022. The most popular diseases related to osteoporosis were hyperosteogeny, fracture, osteoarthritis, and metabolic diseases.

Conclusions

The study offers valuable information about the level of understanding and awareness among the general population in China regarding diseases associated with osteoporosis. The growing fascination with subjects related to osteoporosis indicates that the general population is developing a greater understanding of the significance of maintaining bone health. The results of the study can provide valuable guidance for public health campaigns and educational efforts focused on enhancing the prevention and management of osteoporosis-related conditions in China.
Forecasting COVID-19 New Cases Using Transformer Deep Learning Model
Authors: Patil Saurabh , Mollaei Parisa , Farimani Amir Barati
Published: November 2023

Making accurate forecasting of COVID-19 cases is essential for healthcare systems, with more than 650 million cases as of 4 January,1making it one of the worst in history. The goal of this research is to improve the precision of COVID-19 case predictions in Russia, India, and Brazil, a transformer-based model was developed. Several researchers have implemented a combination of CNNs and LSTMs, Long Short-Term Memory (LSTMs), and Convolutional Neural Networks (CNNs) to calculate the total number of COVID-19 cases. In this study, an effort was made to improve the correctness of the models by incorporating recent advancements in attention-based models for time-series forecasting. The resulting model was found to perform better than other existing models and showed improved accuracy in forecasting. Using the data from different countries and adapting it to the model will enhance its ability to support the worldwide effort to combat the pandemic by giving more precise projections of cases.
Gestational diabetes as a risk factor for GBS maternal rectovaginal colonization: a systematic review and meta-analysis
Authors: Mercado-Evans Vicki , Zulk Jacob J. , Hameed Zainab A. , Patras Kathryn A.
Published: November 2023

Background

Maternal rectovaginal colonization by group BStreptococcus(GBS) increases the risk of perinatal GBS disease that can lead to death or long-term neurological impairment. Factors that increase the risk of rectovaginal GBS carriage are incompletely understood resulting in missed opportunities for detecting GBS in risk-based clinical approaches. There is a lacking consensus on whether gestational diabetes mellitus (GDM) is a risk factor for rectovaginal GBS. This systematic review and meta-analysis aims to address current conflicting findings and determine whether GDM should be clinically considered as a risk factor for maternal GBS colonization.

Methods

Peer-reviewed studies that provided GDM prevalence and documented GBS vaginal and/or rectal colonization in women with and without GDM were included in this analysis.

From study inception to October 30, 2023, we identified 6,275 relevant studies from EMBASE and PUBMED of which 19 were eligible for inclusion. Eligible studies were analyzed and thoroughly assessed for risk of bias with a modified Newcastle-Ottawa Scale that interrogated representativeness and comparability of cohorts, quality of reporting for GDM and GBS status, and potential bias from other metabolic diseases. Results were synthesized using STATA 18 and analyzed using random-effects meta-analyses.

Results

Studies encompassed 266,706 women from 10 different countries, with study periods spanning from 1981 to 2020. Meta-analysis revealed that gestational diabetes is associated with a 16% increased risk of rectovaginal GBS carriage (OR 1.16, CI 1.07-1.26,P= 0.003). We also performed subgroup analyses to assess independent effects of pregestational vs. gestational diabetes on risk of maternal GBS carriage. Pregestational diabetes (Type 1 or Type 2 diabetes mellitus) was also associated with an increased risk of 76% (pooled OR 1.76, CI 1.27-2.45,P= 0.0008).

Conclusions

This study achieved a consensus among previously discrepant observations and demonstrated that gestational diabetes and pregestational diabetes are significant risk factors for maternal rectovaginal carriage of GBS. Recognition of GDM as a risk factor during clinical decisions about GBS screening and intrapartum antibiotic prophylaxis may decrease the global burden of GBS on maternal-perinatal health.
“We can’t develop standards for a thing which doesn’t belong to us”:Assessment of infrastructure, behaviours and user satisfaction of Guardian Waiting Shelters for secondary level hospitals in southern Malawi
Authors: Panulo Mindy , Lamb Jennifer , Chidziwisano Kondwani , White Blessings , Dreibelbis Robert , Morse Tracy
Published: November 2023

Background

Guardian Waiting Shelters (GWSs) are an essential component of the Malawi’s health care system as they serve as a temporary home for patient guardians while taking care of their relatives admitted to the hospital. Despite GWSs valuable role in healthcare settings, there have been few studies on the specific experiences, infrastructure, and conditions provided at these facilities. The study examines GWS management structures and conditions, as well as guardian satisfaction and perception of health risks related to GWS use.

Methods

In this cross-sectional, mixed-methods study, we assessed 12 GWSs from 12 districts in the southern region of Malawi. Qualitative data included interviews (n=149) and focus group discussions with patient guardians (n=72), as well as interviews with GWS caretakers (n=5), representatives from Hospital Management (n=12) and Hospital Advisory Committees (n=11). Quantitative data included structured assessments (n=12) of infrastructure present and used at GWSs. Descriptive statistics and qualitative thematic analysis were utilized for data analysis, and a problem tree analysis was used to triangulate and summarize the findings.

Results

249 participants, including 221 being patient guardians, participated across the 12 GWSs. Each GWS had an average of 100 users daily, primarily middle-aged females (71%). There was a lack of clear and consistent management and responsibility for GWS operation and maintenance. GWS infrastructure conditions were poor, with inadequate functional sleeping rooms, insufficient access to water and sanitation facilities, and limited facilities for hygienic food preparation. Notably, 50% of the GWSs lacked water access, and a quarter had non-functional toilets. Overall, guardians felt unsafe and at risk of disease transmission when staying within GWS.

Conclusion

Study findings highlight lack of clear, consistent GWS ownership as a root cause of challenges in GWSs. Clear policy and operational standards must be established for effective management and smooth functioning of GWSs in Malawi.
radioGWAS: link radiome to genome to discover driver genes with somatic mutations for heterogeneous tumor image phenotype in pancreatic cancer
Authors: Zheng Dandan , Grandgenett Paul M. , Zhang Qi , Baine Michael , Shi Yu , Du Qian , Liang Xiaoying , Wong Jeffrey , Iqbal Subhan , Preuss Kiersten , Kamal Ahsan , Yu Hongfeng , Du Huijing , Hollingsworth Michael A. , Zhang Chi
Published: November 2023

Addressing the significant level of variability exhibited by pancreatic cancer necessitates the adoption of a systems biology approach that integrates molecular data, biological properties of the tumors, and clinical features of the patients. In this study, a comprehensive multi-omics methodology was employed to examine a distinctive collection patient dataset containing rapid autopsy tumor and normal tissue samples as well as longitudinal imaging with a focus on pancreatic cancer. By performing a whole exome sequencing analysis on tumor and normal tissues to identify somatic gene variants and a radiomics feature analysis to tumor CT images, the genome-wide association approach established a connection between pancreatic cancer driver genes and relevant radiomics features, enabling a thorough and quantitative assessment of the heterogeneity of pancreatic tumors. The significant association between sets of genes and radiomics features revealed the involvement of genes in shaping tumor morphological heterogeneity. Some results of the association established a connection between the molecular level mechanism and their outcomes at the level of tumor structural heterogeneity. Because tumor structure and tumor structural heterogeneity are related to the patients’ overall survival, patients who had pancreatic cancer driver gene mutations with an association to a certain radiomics feature have been observed to experience worse survival rates than cases without these somatic mutations. Furthermore, the outcome of the association analysis has revealed potential gene mutations and radiomics feature candidates that warrant further investigation in future research endeavors.
The potential health impact and healthcare cost savings of different sodium reduction strategies in Canada
Authors: Flexner Nadia , Jones Amanda C. , Amies-Cull Ben , Cobiac Linda , Nilson Eduardo , L’Abbe Mary R.
Published: November 2023

Background

High dietary sodium is the main dietary risk factor for non-communicable diseases due to its impact on cardiovascular diseases, the leading cause of death globally. The Government of Canada has taken measures to reduce average dietary sodium intakes, such as setting voluntary sodium reduction targets for packaged foods and recently approving regulations mandating ‘high in’ front-of-pack labeling (FOPL) symbols.

Objectives

To estimate the number of avoidable ischemic heart disease (IHD) and stroke incidence cases, and their associated healthcare cost and Quality-Adjusted Life Year (QALY) savings resulting from different sodium reduction strategies and recommendations in Canada.

Methods

We used the PRIMEtime model, a proportional multi-state lifetable model. Outcomes were modeled over the lifetime of the population alive in 2019, at a 1.5% discount rate, and from the public healthcare system perspective. Nationally representative data were used as inputs for the model.

Results

Fully meeting Health Canada’s sodium reduction targets was estimated to prevent 219,490 (95% UI, 73,409–408,630) cases of IHD, and 164,435 (95% UI, 56,121–305,770) strokes. This led to a gain of 276,185 (95% UI, 85,414–552,616) QALYs, and healthcare costs savings of CAD$ 4,212(95% UI, 1,303–8,206) million over the lifetime of the 2019 cohort. Sodium reduction intake through FOPL regulations has the potential to prevent between 35,930 (95% UI, 8,058– 80,528) and 124,744 (95% UI, 40,125–235,643) cases of IHD, and between 26,869 (95% UI, 5,235–61,621) and 93,129 (95% UI, 30,296–176,014) strokes. This results in QALY gains ranging from 45,492 (95% UI, 10,281–106,579) to 157,628 (95% UI, 46,701–320,622), and healthcare costs savings ranging from CAD$ 695 (95% UI, 160–1,580) to CAD$ 2,415 (95% UI, 722–4,746) million over the lifetime of the 2019 Canadian cohort. Greater health and healthcare costs gains were estimated if Canadians were to meet the population-level sodium intake recommendations of the World Health Organization (2,000 mg/day) and the Adequate Intake recommendation (1,500 mg/day). All sodium reduction strategies tested were cost saving.

Conclusions

Reducing population-level sodium intakes is feasible and has the potential to improve health outcomes and save healthcare costs in Canada. From interventions tested, most health and healthcare costs gains were attributed to fully meeting sodium reduction targets, which highlights the importance of changing the voluntary nature of these targets to mandatory. A combination of strategies, mandatory sodium reduction targets and implementation of the ‘high in’ FOPL symbol would provide the most benefit from a public health standpoint.
Management and Clinical Outcomes of Neonatal Hypothermia in the Newborn Nursery
Authors: Dang Rebecca , Patel Anisha I. , Weng Yingjie , Schroeder Alan R. , Aby Janelle , Frymoyer Adam
Published: November 2023

Background and Objectives

Neonatal hypothermia has been shown to be commonly detected among late preterm and term infants. In preterm and very low birth weight infants, hypothermia is associated with increased morbidity and mortality. Little is known about the clinical interventions and outcomes in hypothermic late preterm and term infants. This study fills this gap in the evidence.

Methods

Single-center retrospective cohort study using electronic health record data on infants ≥35 weeks’ gestation admitted to a newborn nursery from 2015-2021. Hypothermia was categorized by severity: none, mild (single episode, 36.0-36.4°C), and moderate/severe (recurrent episodes and/or <36.0°C). Bivariable and multivariable logistic regression examined associations between hypothermia and interventions/outcomes. Stratified analyses by effect modifiers were conducted when appropriate.

Results

Among 24,009 infants, 1,111 had moderate/severe hypothermia. These hypothermic infants had higher odds of NICU transfer (aOR 2.10, 95% CI 1.68-2.60), sepsis evaluation (aOR 2.23, 95% CI 1.73-2.84), and antibiotic use (aOR 1.73, 95% CI 1.15-2.50) than infants without hypothermia. No infants with hypothermia had culture-positive sepsis and receipt of antibiotics ≥72 hours (surrogate for culture-negative sepsis and/or higher severity of illness) was not more common in hypothermic infants. Hypothermic infants also had higher odds of blood glucose measurement and hypoglycemia, higher percent weight loss and longer lengths of stay.

Conclusion

Late preterm and term infants with hypothermia in the nursery have potentially unnecessary increased resource utilization. Evidence-based and value-driven approaches to hypothermia in this population are needed.

What’s Known on This Subject

Neonatal hypothermia has been associated with morbidity and mortality in high-risk (preterm and very low birth weight) infants. The clinical implications of hypothermia in otherwise healthy late preterm and term infants admitted to the newborn nursery are poorly defined.

What This Study Adds

Infants with moderate/severe hypothermia have higher odds of diagnostic interventions and NICU transfers than infants without hypothermia. No infants with hypothermia had culture-positive sepsis. With the lack of a strong evidence base, hypothermia may drive unnecessary resource overutilization.
Blood-based epigenome-wide analyses of chronic low-grade inflammation across diverse population cohorts
Authors: Hillary Robert F. , Ng Hong Kiat , McCartney Daniel L. , Elliott Hannah R. , Walker Rosie M. , Campbell Archie , Huang Felicia , Direk Kenan , Welsh Paul , Sattar Naveed , Corley Janie , Hayward Caroline , McIntosh Andrew M. , Sudlow Cathie , Evans Kathryn L. , Cox Simon R. , Chambers John C. , Loh Marie , Relton Caroline L. , Marioni Riccardo E. , Yousefi Paul D. , Suderman Matthew
Published: November 2023

Chronic inflammation is a hallmark of ageing and age-related disease states. The effectiveness of inflammatory proteins such as C-reactive protein (CRP) in assessing long-term inflammation is hindered by their phasic nature. DNA methylation (DNAm) signatures of CRP may act as more reliable markers of chronic inflammation. We show that inter-individual differences in DNAm capture 50% of the variance in circulating CRP (N=17,936, Generation Scotland). We develop a series of DNAm predictors of CRP using state-of-the-art algorithms. An elastic net regression-based predictor outperformed competing methods and explained 18% of phenotypic variance in the LBC1936 cohort, doubling that of existing DNAm predictors. DNAm predictors performed comparably in four additional test cohorts (ALSPAC, HELIOS, SABRE, LBC1921), including individuals of diverse genetic ancestry and from different age groups. The newly-described predictor surpassed assay-measured CRP and a genetic score in its associations with 26 health outcomes. Our findings forge new avenues for assessing chronic low-grade inflammation in diverse populations.
Determinants of treatment success among drug-susceptible tuberculosis patients in Ghana: A prospective cohort study
Authors: Djochie Richard Delali Agbeko , Anto Berko Panyin , Aduele Opare-Addo Mercy Naa
Published: November 2023

Background

Achieving optimal rates of success in tuberculosis treatment is vital not just for the individual patient’s well-being but also for preventing the rise of drug-resistant tuberculosis strains. Unfavourable treatment outcomes pose significant challenges for healthcare systems worldwide. Identifying the factors that determine treatment success is crucial for implementing effective interventions that enhance treatment outcomes and contribute to the eradication of the disease. As a result, this study aimed to assess tuberculosis treatment outcomes and identify factors associated with treatment success.

Methods

Patients diagnosed with active tuberculosis were closely monitored from the start of their treatment until its completion from January 2021 to June 2022. A data collection tool, developed using Redcap and aligned with the study objectives, was utilized to gather demographic information, and adverse reactions to antitubercular medicines and track the treatment outcomes of the participants. The participants’ quality of life was assessed using the Short-form 12 version 2 questionnaire at baseline, as well as at the end of the second and sixth months. Logistic regression was employed to evaluate the association between various participant characteristics and treatment success, with odds ratios used to quantify the strength of the associations.

Results

Among 378 participants, 77.3% had successful TB treatment, while 13.5% were lost to follow-up, 0.5% experienced treatment failure, and 8.7% died. Factors influencing treatment success included initial body weight, weight gain during treatment, HIV status, drug adverse reactions, and mental well-being at the beginning of treatment. Multivariate analysis showed that gaining at least 3kg during treatment and having no risk of depression at the beginning significantly increased the likelihood of successful treatment.

Conclusion

Patients with tuberculosis who experience compromised physical and mental health-related quality of life, encounter adverse reactions to antitubercular drugs and have concurrent HIV infection should receive close monitoring and personalized interventions to improve their chances of treatment success.
The intrinsically disordered transcriptional activation domain of CIITA is functionally tuneable by single substitutions: An exception or a new paradigm?
Authors: Sreenivasan Shwetha , Heffren Paul , Suh Kyung-Shin , Rodnin Mykola V. , Kosa Edina , Fenton Aron W. , Ladokhin Alexey S. , Smith Paul E. , Fontes Joseph D. , Swint-Kruse Liskin
Published: November 2023

During protein evolution, some amino acid substitutions modulate protein function (“tuneability”). In most proteins, the tuneable range is wide and can be sampled by a set of protein variants that each contains multiple amino acid substitutions. In other proteins, the full tuneable range can be accessed by a set of variants that each contains a single substitution. Indeed, in some globular proteins, the full tuneable range can be accessed by the set of site-saturating substitutions at an individual “rheostat” position. However, in proteins with intrinsically disordered regions (IDRs), most functional studies – which would also detect tuneability – used multiple substitutions or small deletions. In disordered transcriptional activation domains (ADs), studies with multiple substitutions led to the "acidic exposure" model, which does not anticipate the existence of rheostat positions. In the few studies that did assess effects of single substitutions on AD function, results were mixed: The ADs of two full-length transcription factors didnotshow tuneability, whereas a fragment of a third AD was tuneable by single substitutions. Here, we tested tuneability in the AD of full-length human class II transactivator (CIITA). Sequence analyses and experiments showed that CIITA’s AD is an IDR. Functional assays of singly-substituted AD variants showed that CIITA’s function was highly tuneable, with outcomes not predicted by the acidic exposure model. Four tested positions showed rheostat behaviour for transcriptional activation. Thus, tuneability of different IDRs can vary widely. Future studies are needed to illuminate the biophysical features that govern whether an IDR is tuneable by single substitutions.
Modelling hepatitis C infection acquired from blood transfusions in the UK between 1970 and 1991 for the Infected Blood Inquiry
Authors: Hayes Sarah , McCabe Ruth , Angelis Daniela De , Donnelly Christl A , Evans Stephen JW , Medley Graham F , Spiegelhalter David J , Bird Sheila M
Published: November 2023

The Statistics Expert Group was convened at the request of the Infected Blood Inquiry to provide estimates of the number of infections and deaths from bloodborne infections including hepatitis B virus; human immunodeficiency virus; hepatitis C virus and variant Creutzfeldt Jakob disease, as a direct result of contaminated blood and blood products administered in the United Kingdom of Great Britain and Northern Ireland (UK). In the absence of databases of HCV infections and related deaths for all nations of the UK, a statistical model was required to estimate the number of infections and subsequent deaths from HCV acquired from blood transfusions throughout January 1970 – August 1991.

We present this statistical model in detail alongside the results of its application to each of the four nations in the UK. We estimated that 26,800 people (95% uncertainty interval 21,300 – 38,800) throughout the UK were chronically infected with HCV because of contaminated blood transfusions between January 1970 and August 1991. The number of deaths up to the end of 2019 that occurred as a result of this chronic infection is estimated to be 1,820 (95% uncertainty interval 650 – 3,320).
Winning hearts and minds: the charismatic leader’s role in SME productivity
Authors: Salloum Charbel , Jarrar Hajer , Chaanine Nathalie , Al Sayah Maher , Verdie Jean-François
Published: November 2023

Purpose

This study focuses on exploring charismatic leadership within Lebanese Information Technology (IT) small and medium-sized enterprises (SMEs) and its influence on productivity. Through an in-depth analysis of the charismatic qualities and behaviors exhibited by leaders in these organizations, this research aims to delineate how such attributes may shape productivity levels. This study aims to deepen our understanding of leadership dynamics within the context of Lebanese IT SMEs, providing essential insights that can contribute to the enhancement of organizational performance and success.

Design/methodology/approach

This fundamental research used a quantitative approach and a purposive sampling method to select 342 Lebanese IT SMEs for primary data collection through a survey. Statistical regression analysis was then applied to treat the collected data.

Findings

The findings of this study reveal a positive correlation between charismatic leadership and increased innovation behavior among group or board members. This correlation can be strengthened by fostering a sense of ownership toward innovation and by ensuring a healthy work-life balance. Furthermore, the creation of an environment that emphasizes open communication and trust can enhance this correlation.

Practical implications

The implications of these findings are significant for organizations seeking to enhance their innovation capabilities. They suggest that investing in the development of charismatic leadership skills can be a valuable strategy for fostering innovation and creativity.

Originality/value

This study offers a unique and practical assessment of the role that charismatic leadership plays in maintaining resilient firm structures, especially during periods of political and economic instability.
An integrated model predicting the drivers of mobile payment outcomes: evidence from emerging markets
Authors: Elsotouhy Mohamed M. , Mobarak Abdelkader M.A. , Dakrory Mona I. , Ghonim Mohamed A. , Khashan Mohamed A.
Published: November 2023

Purpose

Because the success of m-payment services depends on the enablers and barriers that affect user satisfaction, the present research explores the effects of perceived value and sacrifices on users' satisfaction with m-payment services. The predicted relationships among perceived value, perceived sacrifices, users' satisfaction, continuance intention, word-of-mouth (WOM), shopping effectiveness, quality of life (QOL) and stickiness were established based on the mobile technology acceptance model (MTAM) and the value-based adoption model (VAM).

Design/methodology/approach

A representative data sample of 430 Egyptian banking clients was analyzed to test the hypotheses using partial least squares-structural equation modeling (PLS-SEM).

Findings

The findings revealed that all perceived value constructs significantly positively affect users' satisfaction. Moreover, all perceived sacrifice constructs significantly negatively affect users' satisfaction. Users' satisfaction, in turn, has a significant positive effect on continuance intention, WOM, shopping effectiveness, QOL and stickiness with m-payment services.

Originality/value

This is the first study to examine several levels of m-payment outcomes, including m-payment, consumer and bank outcomes, based on the integration of MTAM and VAM models.
Cross-country comparison of operant resources in logistics outsourcing relationships
Authors: Munim Ziaul Haque , Maditati Dhanavanth Reddy , Kummer Sebastian , Schramm Hans-Joachim
Published: November 2023

Purpose

This study aims to explore the gaps concerning the organizational operant resources (OORs) of logistics service providers (LSPs) expected in outsourcing relationships. The study considers the views of both manufacturing firms (M-firms) and LSPs in India and DACH region (Germany, Austria and Switzerland) seeking gaps within and across regions.

Design/methodology/approach

This research employed a survey targeting executives from large M-firms and LSPs in both India and DACH. The perceptions about the importance and improvement expectations of 17 OORs are analyzed. A modified version of importance-improvement analysis (A-B), a novel comparative A-B analysis (CABA) method, has been proposed to identify the importance and improvement gaps in OORs between M-firms and LSPs within and across India and the DACH region.

Findings

There are more gaps between M-firms and LSPs in India compared to DACH. Cross-country comparisons reveal that LSPs in India and DACH have similar perceptions concerning the OORs, but M-firms in India have significantly higher improvement expectations than those in DACH.

Research limitations/implications

This study proposes an analytical approach that enables managers to identify improvement areas and better align with their outsourcing relationship partners. It also highlights aspects that need to be considered while entering emerging markets such as India.

Originality/value

The analysis approach using CABA is novel. Also, among the cross-country studies, this is the first to compare outsourcing relationships in India with the DACH region while involving both users' and service providers' perspectives.
Relationship between different resource and capability configurations and competitiveness – comparative study of Hungarian family and nonfamily firms
Authors: Kárpáti Zoltán , Ferincz Adrienn , Felsmann Balázs
Published: November 2023

Purpose

The purpose of this paper is to identify different types of resource and capability configurations among Hungarian family and nonfamily firms and explore which compositions can be considered competitive. In a rivalrous, dynamic world, understanding which sets of resources and capabilities lead to a higher level of competitiveness is vital.

Design/methodology/approach

This paper is based on a quantitative competitiveness survey carried out between November 2018 and July 2019 in Hungary. The authors used the Firm Competitiveness Index (FCI) to measure competitiveness and the resource-based view (RBV) approach to understand which configurations of resources and capabilities are responsible for a higher level of competitiveness based on 32 variables. An exploratory factor and cluster analysis were conducted to analyze the ownership's effect on firm competitiveness. The final sample size contained 111 companies, of which 53 were identified as family and 58 as nonfamily firms.

Findings

Factor analysis reveals five factors determining resources and capabilities: “operational,” “leadership,” “knowledge management,” “transformation” and “networking.” Based on these factors, the cluster analysis identified five groups in terms of types of family and nonfamily firms: “Lagging capabilities,” “Knowledge-based leadership,” “Innovativeness and transformation-oriented management,” “Relationship-oriented management” and “Business operation-oriented management.” Results show that nonfamily businesses focus on operational and leadership capabilities, reaching a higher FCI than family businesses, which are likely to invest more in their networking, transformation and knowledge management capabilities.

Originality/value

By defining the different configurations family and nonfamily firms rely on to reach competitiveness, the paper applies an essential element to the Hungarian and Middle Eastern European contexts of family business research. The findings contribute to developing family business literature and point out specific resources and capabilities family firms should focus on to shift toward reaching a higher level of professionalization and competitiveness. The characterization of different types of competitiveness comparing family and nonfamily firms enables the firms to assess customized implications.
Modeling dependence structure between green sukuk spread in Malaysia and the uncertainty factors before and during the COVID-19 pandemic
Authors: Hariz Fatma , Mezghani Taicir , Abbes Mouna Boujelbène
Published: November 2023

Purpose

This paper aims to analyze the dependence structure between the Green Sukuk Spread in Malaysia and uncertainty factors from January 1, 2017, to May 23, 2023, covering two main periods: the pre-COVID-19 and the COVID-19 periods.

Design/methodology/approach

This study contributes to the current literature by explicitly modeling nonlinear dependencies using the Regular vine copula approach to capture asymmetric characteristics of the tail dependence distribution. This study used the Archimedean copula models: Student’s-t, Gumbel, Gaussian, Clayton, Frank and Joe, which exhibit different tail dependence structures.

Findings

The empirical results suggest that Green Sukuk and various uncertainty variables have the strongest co-dependency before and during the COVID-19 crisis. Due to external uncertainties (COVID-19), the results reveal that global factors, such as the Infect-EMV-index and the higher financial stress index, significantly affect the spread of Green Sukuk. Interestingly, in times of COVID-19, its dependence on Green Sukuk and the news sentiment seems to be a symmetric tail dependence with a Student’s-t copula. This result is relevant for hedging strategies, as investors can enhance the performance of their portfolio during the COVID-19 crash period.

Originality/value

This study contributes to a better understanding of the dependency structure between Green Sukuk and uncertainty factors. It is relevant for market participants seeking to improve their risk management for Green Sukuk.
Examining the influence of specific IC elements on alliance formation of new ventures
Authors: Zane Lee J. , Tribbitt Mark A.
Published: November 2023

Purpose

Intellectual capital (IC) is essential to the success of new technology-based firms. However, young firms only possess some of the resources and capabilities needed to develop, produce and market their innovative products and services. Hence, many form alliances to access complementary resources. This paper investigates the signaling effect of technology-based start-ups’ stock of IC on alliance formation.

Design/methodology/approach

This study analyzes primary data concerning specific classes of IC and the alliances formed. Data were collected from founders of 233 technology-based new ventures in the USA. Hypotheses were tested via hierarchical linear regression.

Findings

This study demonstrates that firms' IC, in the form of founders with doctorates and patents, is positively related to the classes of alliances formed. These stocks of IC send signals about credibility to the market for alliance partners, enabling the firms to form alliances and gain access to complementary resources. The number of founders with doctorates was positively related to R&D alliances and alliance partners in a similar place in the value chain as the focal firm. In contrast, the number of patents was positively related to total alliances, production-oriented alliances and alliances considered upstream from the focal firm.

Originality/value

This paper collects retrospective data from founders of technology-based new ventures. The research contributes to the literature with its results that founder human capital and patent portfolios are essential for technology-based firms' innovation and growth. However, little research has investigated how firms' possession of IC facilitates alliance formation. This paper investigates this connection explicitly.