bluuebunny/crossref_metadata_2025_split huggingface dataset:
Decadal Trends in Physical Activity Adherence Among Korean Older Adults: An Analysis of National Survey of Older Korean Data, 2011–2020
Authors: Lee Joonyoung , Kim Eun Seong , Lee Hyunyoung , Huh Jung Hoon 
Published: February 2024

Background/Objectives: This study investigated adherence to physical activity (PA) guidelines and associated sociodemographic factors among older Koreans from 2011 to 2020. Methods: Utilizing four public data sets from the National Survey of Older Koreans, the study included the data on 40,993 older adults 65 years and older in South Korea, collected between 2011 and 2020. Adherence to PA guidelines and sociodemographic factors were assessed through self-reported questionnaires. The data were analyzed using a two-way analysis of variance and post hoc tests. Results: Overall adherence increased from 39.1% in 2011 to 48.2% in 2017, then decreased to 37.6% in 2020 (p < .001). Men had higher adherence than women (p < .001). Age-related adherence peaked in the young-older group (65–74 years old) and was lowest in the oldest-old group (85+ years old) (p < .001). Marital status, education, and income were also significantly related to PA adherence (p < .001) across the years. Conclusion: Although continuous increase in adherence to PA among Koreans 65 years and older was observed, the decline in PA levels during the COVID era underscored the need for targeted interventions and well-informed health care policies to address demographic challenges. Still, considering that data were collected during the recommended social distancing period, a cautions interpretation of these findings is warranted. Significance/Implications: Health policies aiming to improve adherence to PA guidelines should prioritize Korean older adults who are female, belong to the oldest-old group, are single, and have low education and income levels, with the goal of enhancing health equity.
Sp1 facilitates continued HSV-1 gene expression in the absence of key viral transactivators
Authors: Sodroski Catherine N. , Oh Hyung Suk , Chou Shu-Fan , Knipe David M. 
Published: February 2024

ABSTRACT

Productive replication of herpes simplex virus (HSV) relies upon a well-ordered transcriptional cascade flowing from immediate-early (IE) to early (E) to late (L) gene products. While several virus-encoded transcriptional activators are involved in this process, IE and E gene promoters also contain multiple binding sites for the ubiquitously expressed cellular transcription factor Sp1. Sp1 has been previously implicated in activating HSV-1 gene transcription downstream of these sites, but why Sp1-binding sites are maintained in the promoters of genes activated by virus-encoded activators remains unclear. We hypothesized that Sp1 enables continued HSV-1 transcription and replication when viral transactivators are limited. We used a depletion-based approach in human foreskin fibroblasts to investigate the specific contribution of Sp1 to the initiation and progression of the HSV-1 lytic gene cascade. We found that Sp1 increased viral transcript levels, protein expression, and replication following infection with VP16- or ICP0-deficient viruses but had little to no effect on rescued viruses or during wild-type (WT) HSV-1 infection. Moreover, Sp1 promoted WT virus transcription and replication following interferon treatment of fibroblasts and thus may contribute to viral immune evasion. Interestingly, we observed reduced expression of Sp1 and Sp1-family transcription factors in differentiated sensory neurons compared to undifferentiated cells, suggesting that reduced Sp1 levels may also contribute to HSV-1 latent infection. Overall, these findings indicate that Sp1 can promote HSV-1 gene expression in the absence of key viral transactivators; thus, HSV-1 may use Sp1 to maintain its gene expression and replication under adverse conditions.

IMPORTANCE
Herpes simplex virus (HSV) is a common human pathogen that actively replicates in the epithelia but can persist for the lifetime of the infected host via a stable, latent infection in neurons. A key feature of the HSV replication cycle is a complex transcriptional program in which virus and host-cell factors coordinate to regulate expression of the viral gene products necessary for continued viral replication. Multiple binding sites for the cellular transcription factor Sp1 are located in the promoters of HSV-1 genes, but how Sp1 binding contributes to transcription and replication of wild-type virus is not fully understood. In this study, we identified a specific role for Sp1 in maintaining HSV-1 gene transcription under adverse conditions, as when virus-encoded transcriptional activators were absent or limited. Preservation of Sp1-binding sites in HSV-1 gene promoters may thus benefit the virus as it navigates diverse cell types and host-cell conditions during infection.
MOB-mediated regulation of septation initiation network (SIN) signaling is required for echinocandin-induced hyperseptation in
Aspergillus fumigatus
Authors: Thorn Harrison I. , Guruceaga Xabier , Martin-Vicente Adela , Nywening Ashley V. , Xie Jinhong , Ge Wenbo , Fortwendel Jarrod R. 
Published: February 2024

ABSTRACT

Aspergillus fumigatus
is a major invasive mold pathogen and the most frequent etiologic agent of invasive aspergillosis. The currently available treatments for invasive aspergillosis are limited in both number and efficacy. Our recent work has uncovered that the β-glucan synthase inhibitors, the echinocandins, are fungicidal against strains of
A. fumigatus
with defects in septation initiation network (SIN) kinase activity. These drugs are known to be fungistatic against strains with normal septation. Surprisingly, SIN kinase mutant strains also failed to invade lung tissue and were significantly less virulent in immunosuppressed mouse models. Inhibiting septation in filamentous fungi is therefore an exciting therapeutic prospect to both reduce virulence and improve current antifungal therapy. However, the SIN remains understudied in pathogenic fungi. To address this knowledge gap, we characterized the putative regulatory components of the
A. fumigatus
SIN. These included the GTPase, SpgA, it’s two-component GTPase-activating protein, ByrA/BubA, and the kinase activators, SepM and MobA. Deletion of
spgA
,
byrA,
or
bubA
resulted in no overt septation or echinocandin susceptibility phenotypes. In contrast, our data show that deletion of
sepM
or
mobA
largely phenocopies disruption of their SIN kinase binding partners,
sepL
and
sidB
, respectively. Reduced septum formation, echinocandin hypersusceptibility, and reduced virulence were generated by loss of either gene. These findings provide strong supporting evidence that septa are essential not only for withstanding the cell wall disrupting effects of echinocandins but are also critical for the establishment of invasive disease. Therefore, pharmacological SIN inhibition may be an exciting strategy for future antifungal drug development.

IMPORTANCE

Septa are important structural determinants of echinocandin susceptibility and tissue invasive growth for the ubiquitous fungal pathogen
Aspergillus fumigatus
. Components of the septation machinery therefore represent promising novel antifungal targets to improve echinocandin activity and reduce virulence. However, little is known about septation regulation in
A. fumigatus
. Here, we characterize the predicted regulatory components of the
A. fumigatus
septation initiation network. We show that the kinase activators SepM and MobA are vital for proper septation and echinocandin resistance, with MobA playing an essential role. Null mutants of
mobA
displayed significantly reduced virulence in a mouse model, underscoring the importance of this pathway for
A. fumigatus
pathogenesis.
Reconstructing the transcriptional regulatory network of probiotic
L. reuteri
is enabled by transcriptomics and machine learning
Authors: Josephs-Spaulding Jonathan , Rajput Akanksha , Hefner Ying , Szubin Richard , Balasubramanian Archana , Li Gaoyuan , Zielinski Daniel C. , Jahn Leonie , Sommer Morten , Phaneuf Patrick , Palsson Bernhard O. 
Published: February 2024

ABSTRACT

Limosilactobacillus reuteri
, a probiotic microbe instrumental to human health and sustainable food production, adapts to diverse environmental shifts via dynamic gene expression. We applied the independent component analysis (ICA) to 117 RNA-seq data sets to decode its transcriptional regulatory network (TRN), identifying 35 distinct signals that modulate specific gene sets. Our findings indicate that the ICA provides a qualitative advancement and captures nuanced relationships within gene clusters that other methods may miss. This study uncovers the fundamental properties of
L. reuteri
’s TRN and deepens our understanding of its arginine metabolism and the co-regulation of riboflavin metabolism and fatty acid conversion. It also sheds light on conditions that regulate genes within a specific biosynthetic gene cluster and allows for the speculation of the potential role of isoprenoid biosynthesis in
L. reuteri
’s adaptive response to environmental changes. By integrating transcriptomics and machine learning, we provide a system-level understanding of
L. reuteri
’s response mechanism to environmental fluctuations, thus setting the stage for modeling the probiotic transcriptome for applications in microbial food production.

IMPORTANCE

We have studied
Limosilactobacillus reuteri
, a beneficial probiotic microbe that plays a significant role in our health and production of sustainable foods, a type of foods that are nutritionally dense and healthier and have low-carbon emissions compared to traditional foods. Similar to how humans adapt their lifestyles to different environments, this microbe adjusts its behavior by modulating the expression of genes. We applied machine learning to analyze large-scale data sets on how these genes behave across diverse conditions. From this, we identified 35 unique patterns demonstrating how
L. reuteri
adjusts its genes based on 50 unique environmental conditions (such as various sugars, salts, microbial cocultures, human milk, and fruit juice). This research helps us understand better how
L. reuteri
functions, especially in processes like breaking down certain nutrients and adapting to stressful changes. More importantly, with our findings, we become closer to using this knowledge to improve how we produce more sustainable and healthier foods with the help of microbes.
Assessing trends and variability in outpatient dual testing for chronic kidney disease with urine albumin and serum creatinine, 2009–2018: a retrospective cohort study in the Veterans Health Administration System
Authors: Bhave Nicole M , Han Yun , Steffick Diane , Bragg-Gresham Jennifer , Zivin Kara , Burrows Nilka R , Pavkov Meda E , Tuot Delphine , Powe Neil R , Saran Rajiv 
Published: February 2024

BackgroundSimultaneous urine testing for albumin (UAlb) and serum creatinine (SCr), that is, ‘dual testing,’ is an accepted quality measure in the management of diabetes. As chronic kidney disease (CKD) is defined by both UAlb and SCr testing, this approach could be more widely adopted in kidney care.ObjectiveWe assessed time trends and facility-level variation in the performance of outpatient dual testing in the integrated Veterans Health Administration (VHA) system.Design, subjects and main measuresThis retrospective cohort study included patients with any inpatient or outpatient visit to the VHA system during the period 2009–2018. Dual testing was defined as UAlb and SCr testing in the outpatient setting within a calendar year. We assessed time trends in dual testing by demographics, comorbidities, high-risk (eg, diabetes) specialty care and facilities. A generalised linear mixed-effects model was applied to explore individual and facility-level predictors of receiving dual testing.Key resultsWe analysed data from approximately 6.9 million veterans per year. Dual testing increased, on average, from 17.4% to 21.2%, but varied substantially among VHA centres (0.3%–43.7% in 2018). Dual testing was strongly associated with diabetes (OR 10.4, 95% CI 10.3 to 10.5, p<0.0001) and not associated with VHA centre complexity level. However, among patients with high-risk conditions including diabetes, <50% received dual testing in any given year. As compared with white veterans, black veterans were less likely to be tested after adjusting for other individual and facility characteristics (OR 0.93, 95% CI 0.92 to 0.93, p<0.0001).ConclusionsDual testing for CKD in high-risk specialties is increasing but remains low. This appears primarily due to low rates of testing for albuminuria. Promoting dual testing in high-risk patients will help to improve disease management and patient outcomes.
Correlation between allostatic load index and cumulative mortality: a register-based study of Danish municipalities
Authors: Bruun-Rasmussen Neda Esmailzadeh , Napolitano George , Bojesen Stig E , Ellervik Christina , Holmager Therese Lucia Friis , Rasmussen Knud , Lynge Elsebeth 
Published: February 2024

ObjectivesThe aim of this study was to examine population-based allostatic load (AL) indices as an indicator of community health across 14 municipalities in Denmark.DesignRegister-based study.SettingData derived from: the Lolland-Falster Health Study, the Copenhagen General Population Study and the Danish General Suburban Population Study. Nine biomarkers (systolic blood pressure, diastolic blood pressure, pulse rate, total serum cholesterol, high-density lipoprotein cholesterol, waist-to-hip ratio, triglycerides, C-reactive protein and serum albumin) were divided into high-risk and low-risk values based on clinically accepted criteria, and the AL index was defined as the average between the nine values. All-cause mortality data were obtained from Statistics Denmark.ParticipantsWe examined a total of 106 808 individuals aged 40–79 years.Primary outcome measureLinear regression models were performed to investigate the association between mean AL index and cumulative mortality risk.ResultsMean AL index was higher in men (range 2.3–3.3) than in women (range 1.7–2.6). We found AL index to be strongly correlated with the cumulative mortality rate, correlation coefficient of 0.82. A unit increase in mean AL index corresponded to an increase in the cumulative mortality rate of 19% (95% CI 13% to 25%) for men, and 16% (95% CI 8% to 23%) for women but this difference was not statistically significant. The overall mean increase in cumulative mortality rate for both men and women was 17% (95% CI 14% to 20%).ConclusionsOur findings indicate the population-based AL index to be a strong indicator of community health, and suggest identification of targets for reducing AL.
Mobile health biometrics to prescribe immediate remote physical activity for enhancing uptake to cardiac rehabilitation (MOTIVATE-CR+): protocol for a randomised controlled feasibility trial
Authors: Crozier Anthony , Cocks Matthew , Hesketh Katie , Miller Gemma , Mcgregor Gordon , Thomas Laura , Jones Helen 
Published: February 2024

IntroductionCardiac rehabilitation (CR) can reduce cardiovascular mortality and improve health-related quality of life. In the United Kingdom, patient uptake of CR remains low (52%), falling well short of the target in the 2019 National Health Service long-term plan (85%). Mobile health (mHealth) technologies, offering biometric data to patients and healthcare professionals, may bridge the gap between supervised exercise and physical activity advice, enabling patients to engage in regular long-term physically active lifestyles. This randomised controlled trial (RCT) will evaluate the feasibility of mHealth technology when incorporated into a structured home-based walking intervention, in people with recent myocardial infarction.Methods and analysisThis is a feasibility, assessor blinded, parallel group RCT. Participants will be allocated to either CR standard care (control group) or CR standard care+mHealth supported exercise counselling (mHealth intervention group). Feasibility outcomes will include the number of patients approached, screened and eligible; the percentage of patients who decline CR (including reasons for declining), agree to CR and consent to being part of the study; the percentage of patients who enrol in standard CR and reasons for drop out; and the percentage of participants who complete clinical, physical and psychosocial outcomes to identify a suitable primary outcome for a future definitive trial.Ethics and disseminationThe trial was approved in the UK by the Northwest—Greater Manchester East Research Ethics Committee (22/NW/0301) and is being conducted in accordance with the Declaration of Helsinki and Good Clinical Practice. Results will be published in peer-reviewed journals and presented at national and international scientific meetings.Trial registration numbersNCT05774587
Community perspectives on the magnitude of Xeroderma pigmentosum and care-seeking practices in Micheweni district, Pemba: a mixed-methods cross-sectional study
Authors: Matemba Lucas E , Shayo Elizabeth H , Masemo Ame , Nassor Nahya K , Ally Mayassa S , Msovela Judith 
Published: February 2024

ObjectivesTo determine the community’s perception on the magnitude of Xeroderma pigmentosum (XP) disease and healthcare-seeking practices in Micheweni, Pemba in response to the public widespread information on the increased burden of the disease.DesignMixed-methods cross-sectional study.SettingMicheweni district, Pemba.Participants211 male and female adults in the household survey, three caretakers/parents of patients with XP in the case study, 20 key community leaders/influential people and health workers in in-depth interviews and 50 community members and other leaders in six focus groups.ResultsThis study has revealed that XP disease exists in few families of which some of them have more than one child affected. The record review showed that there were a total of 17 patients who were diagnosed with the disease for the past 3 years, however only 10 were alive during the time of the survey. Findings from the community members revealed that several patients were believed to have XP disease and perceived causes include inheritance, food types, beliefs and other sociocultural practices. Stigma and discrimination were reported by caretakers and religious leaders. However, some cases believed to be XP were identified as other skin conditions when clinical examination was performed by the team of our researchers. There is a great confusion about XP and other skin diseases.ConclusionThe study has shown that XP affects only few families, hence termed as concentrated rather than a generalised disease. Due to the rareness of the disease, majority of people in the district are unaware of the disease, hence confusing it with other skin conditions. There is a need for the government in collaboration with other stakeholders to provide educational programme to community members about the disease to address the misconception about the magnitude of the disease.
Prevalence and drivers of nurse and physician distress in cardiovascular and oncology programmes at a Canadian quaternary hospital network during the COVID-19 pandemic: a quality improvement initiative
Authors: Jelen Ahlexxi , Rodin Gary , Graham Leanna , Goldfarb Rebecca , Mah Kenneth , Satele Daniel V , Elliot Mary , Krzyzanowska Monika K , Rubin Barry B 
Published: February 2024

ObjectivesTo assess the prevalence and drivers of distress, a composite of burnout, decreased meaning in work, severe fatigue, poor work–life integration and quality of life, and suicidal ideation, among nurses and physicians during the COVID-19 pandemic.DesignCross-sectional design to evaluate distress levels of nurses and physicians during the COVID-19 pandemic between June and August 2021.SettingCardiovascular and oncology care settings at a Canadian quaternary hospital network.Participants261 nurses and 167 physicians working in cardiovascular or oncology care. Response rate was 29% (428 of 1480).Outcome measuresSurvey tool to measure clinician distress using the Well-Being Index (WBI) and additional questions about workplace-related and COVID-19 pandemic-related factors.ResultsAmong 428 respondents, nurses (82%, 214 of 261) and physicians (62%, 104 of 167) reported high distress on the WBI survey. Higher WBI scores (≥2) in nurses were associated with perceived inadequate staffing (174 (86%) vs 28 (64%), p=0.003), unfair treatment, (105 (52%) vs 11 (25%), p=0.005), and pandemic-related impact at work (162 (80%) vs 22 (50%), p<0.001) and in their personal life (135 (67%) vs 11 (25%), p<0.001), interfering with job performance. Higher WBI scores (≥3) in physicians were associated with perceived inadequate staffing (81 (79%) vs 32 (52%), p=0.001), unfair treatment (44 (43%) vs 13 (21%), p=0.02), professional dissatisfaction (29 (28%) vs 5 (8%), p=0.008), and pandemic-related impact at work (84 (82%) vs 35 (56%), p=0.001) and in their personal life (56 (54%) vs 24 (39%), p=0.014), interfering with job performance.ConclusionHigh distress was common among nurses and physicians working in cardiovascular and oncology care settings during the pandemic and linked to factors within and beyond the workplace. These results underscore the complex and contextual aspects of clinician distress, and the need to develop targeted approaches to effectively address this problem.
AI assisted reader evaluation in acute CT head interpretation (AI-REACT): protocol for a multireader multicase study
Authors: Fu Howell , Novak Alex , Robert Dennis , Kumar Shamie , Tanamala Swetha , Oke Jason , Bhatia Kanika , Shah Ruchir , Romsauerova Andrea , Das Tilak , Espinosa Abdalá , Grzeda Mariusz Tadeusz , Narbone Mariapaola , Dharmadhikari Rahul , Harrison Mark , Vimalesvaran Kavitha , Gooch Jane , Woznitza Nicholas , Salik Nabeeha , Campbell Alan , Khan Farhaan , Lowe David J , Shuaib Haris , Ather Sarim 
Published: February 2024

IntroductionA non-contrast CT head scan (NCCTH) is the most common cross-sectional imaging investigation requested in the emergency department. Advances in computer vision have led to development of several artificial intelligence (AI) tools to detect abnormalities on NCCTH. These tools are intended to provide clinical decision support for clinicians, rather than stand-alone diagnostic devices. However, validation studies mostly compare AI performance against radiologists, and there is relative paucity of evidence on the impact of AI assistance on other healthcare staff who review NCCTH in their daily clinical practice.Methods and analysisA retrospective data set of 150 NCCTH will be compiled, to include 60 control cases and 90 cases with intracranial haemorrhage, hypodensities suggestive of infarct, midline shift, mass effect or skull fracture. The intracranial haemorrhage cases will be subclassified into extradural, subdural, subarachnoid, intraparenchymal and intraventricular. 30 readers will be recruited across four National Health Service (NHS) trusts including 10 general radiologists, 15 emergency medicine clinicians and 5 CT radiographers of varying experience. Readers will interpret each scan first without, then with, the assistance of the qER EU 2.0 AI tool, with an intervening 2-week washout period. Using a panel of neuroradiologists as ground truth, the stand-alone performance of qER will be assessed, and its impact on the readers’ performance will be analysed as change in accuracy (area under the curve), median review time per scan and self-reported diagnostic confidence. Subgroup analyses will be performed by reader professional group, reader seniority, pathological finding, and neuroradiologist-rated difficulty.Ethics and disseminationThe study has been approved by the UK Healthcare Research Authority (IRAS 310995, approved 13 December 2022). The use of anonymised retrospective NCCTH has been authorised by Oxford University Hospitals. The results will be presented at relevant conferences and published in a peer-reviewed journal.Trial registration numberNCT06018545.