bluuebunny/crossref_metadata_2025_split huggingface dataset:
The association between frailty and survival in patients with pleural disease: a retrospective cohort study
Authors: Barton Eleanor , Verduri A. , Carter B. , Hughes J. , Hewitt J. , Maskell N. A. 
Published: April 2024

Abstract
Background
There are currently no data on the relationship between frailty and mortality in pleural disease. Understanding the relationship between frailty and outcomes is increasingly important for clinicians to guide decisions regarding investigation and management. This study aims to explore the relationship between all-cause mortality and frailty status in patients with pleural disease.

Methods
In this retrospective analysis of a prospectively collected observational cohort study, outpatients presenting to the pleural service at a tertiary centre in Bristol, UK with a radiologically confirmed, undiagnosed pleural effusion underwent comprehensive assessment and were assigned a final diagnosis at 12 months. The modified frailty index (mFI) was calculated and participants classified as frail (mFI ≥ 0.4) or not frail (mFI ≤ 0.2).

Results
676 participants were included from 3rd March 2008 to 29th December 2020. The median time to mortality was 490 days (IQR 161–1595). A positive association was found between 12-month mortality and frailty (aHR = 1.72, 95% CI 1.02–2.76, p = 0.025) and age ≥ 80 (aHR = 1.80, 95% CI 1.24–2.62, p = 0.002). Subgroup analyses found a stronger association between 12-month mortality and frailty in benign disease (aHR = 4.36, 95% CI 2.17–8.77, p < 0.0001) than in all pleural disease. Malignancy irrespective of frailty status was associated with an increase in all-cause mortality (aHR = 10.40, 95% CI 6.01–18.01, p < 0.0001).

Conclusion
This is the first study evaluating the relationship between frailty and outcomes in pleural disease. Our data demonstrates a strong association between frailty and 12-month mortality in this cohort. A malignant diagnosis is an independent predictor of 12-month mortality, irrespective of frailty status. Frailty was also strongly associated with 12-month mortality in patients with a benign underlying cause for their pleural disease. This has clinical relevance for pleural physicians; evaluating patients’ frailty status and its impact on mortality can guide clinicians in assessing suitability for invasive investigation and management.

Trial registration
This study is registered with the Health Research Authority (REC reference 08/H0102/11) and the NIHR Portfolio (Study ID 8960).
Etiology of bacterial pneumonia and multi-drug resistance pattern among pneumonia suspected patients in Ethiopia: a systematic review and meta-analysis
Authors: Tilahun Mihret , Belete Melaku Ashagrie , Gedefie Alemu , Debash Habtu , Alemayehu Ermiyas , Gebretsadik Daniel , Ebrahim Hussein , Mohammed Ousman 
Published: April 2024

Abstract
Background
Bacterial pneumonia can affect all age groups, but people with weakened immune systems, young children, and the elderly are at a higher risk. Streptococcus pneumoniae, Klebsiella pneumoniae, Haemophilus influenzae, and Pseudomonas aeruginosa are the most common causative agents of pneumonia, and they have developed high MDR in recent decades in Ethiopia. This systematic review and meta-analysis aimed to determine the pooled prevalence of bacterial pneumonia and multidrug resistance in Ethiopia.

Methods
The articles were searched extensively in the electronic databases and grey literature using entry terms or phrases. Studies meeting the eligibility criteria were extracted in MS Excel and exported for statistical analysis into STATA version 14 software. The pooled prevalence of bacterial pneumonia and multidrug resistance were calculated using a random-effects model. Heterogeneity was assessed by using the I2 value. Publication bias was assessed using a funnel plot and Egger’s test. A sensitivity analysis was done to assess the impact of a single study on the pooled effect size.

Result
Of the 651 studies identified, 87 were eligible for qualitative analysis, of which 11 were included in the meta-analysis consisting of 1154 isolates. The individual studies reported prevalence of bacterial pneumonia ranging from 6.19 to 46.3%. In this systematic review and metanalysis, the pooled prevalence of bacterial pneumonia in Ethiopia was 37.17% (95% CI 25.72–46.62), with substantial heterogeneity (I2 = 98.4%, p < 0.001) across the studies. The pooled prevalence of multidrug resistance in bacteria isolated from patients with pneumonia in Ethiopia was 67.73% (95% CI: 57.05–78.40). The most commonly isolated bacteria was Klebsiella pneumoniae, with pooled prevalence of 21.97% (95% CI 16.11–27.83), followed by Streptococcus pneumoniae, with pooled prevalence of 17.02% (95% CI 9.19–24.86), respectively.

Conclusion
The pooled prevalence of bacterial isolates from bacterial pneumonia and their multidrug resistance were high among Ethiopian population. The initial empirical treatment of these patients remains challenging because of the strikingly high prevalence of antimicrobial resistance.
Light environment affects the efficiency of surgical suture training
Authors: Gu Yuan , Xie Lihua , Huang Xianzhe , Liu Chan , Ouyang Zhengxiao , Yuan Liqin , Li Wenzhao 
Published: April 2024

Abstract
Background
Suture knotting is the basis of surgical skills. In the process of surgical skills learning, the surrounding environment, especially the light, will affect the efficiency of learning. This study investigated the effect of optical environment on the learning of stitching and knotting skills.

Methods
A total of 44 medical students were randomly divided into four groups and participated in the study of suture knotting in four different optical environments. During the process, we assess objective pressure level by testing salivary amylase activity Likert scale and objective structured clinical examination (OSCE) was used to estimate the subjective psychological state and overall skill mastery in surgical suturing respectively.

Results
Under high illumination conditions (700 lx), the salivary amylase activity of the high color temperature group (6000 K) was significantly higher than that of the low color temperature group (4000 K) (p < 0.0001). Similarly, under low illumination (300 lx), the salivary amylase activity of the high color temperature group was also significantly higher than that of the low color temperature group (p < 0.05). The student under high illumination conditions (700 lx) and the low color temperature (6000 K) have an autonomy score between 37–45, which is significantly higher compared to the other three groups (p < 0.0001). Group 2 has an average OSCE score of 95.09, which were significantly higher than those of the other three groups (p < 0.05).

Conclusion
High illumination combined with low color temperature is considered as the optimal training conditions, promoting trainees' optimism, reducing stress levels, and enhancing learning efficiency. These results highlight the pivotal role of light environment in improving the quality and efficiency of surgical skills training.
Grace Under Pressure: a mixed methods impact assessment of a verbatim theatre intervention to improve healthcare workplace culture
Authors: Hooker Claire , Karageorge Aspasia , Scott Karen M. , Lim Renee , Nash Louise 
Published: April 2024

Abstract
Background
Healthcare workplace mistreatment has been documented globally. Poor workplace behaviour, ranging from incivility to bullying and harassment, is common in healthcare, and contributes significantly to adverse events in healthcare, poor mental health among healthcare workers, and to attrition in the healthcare workforce, particularly in junior years. Poor workplace behaviour is often normalised, and is difficult to address. Verbatim theatre, a form of research informed theatre in which plays are created from informants’ exact words only, is particularly suited to facilitating workplace culture change by raising awareness about issues that are difficult to discuss. The objective of this study was to assess the impact of the verbatim theatre play ‘Grace Under Pressure’ on workplace culture in NSW hospitals.

Methods
The intervention was conducted in 13 hospitals from 8 Local Health Districts (LHDs) in NSW, Australia, in October and November 2019, with aggregated impact across all sites measured by a bespoke survey (‘Pam McLean Centre (PMC) survey’) at the conclusion of the intervention. This study was conducted in 3 Local Health Districts (one urban, one regional, one remote), with data collection conducted in November–December 2019 and December 2020. The study design was a mixed methods assessment of the play’s impact using (1) validated baseline measures of psychosocial risk, analysed descriptively, (2) overall findings from the PMC survey above, analysed descriptively, (3) interviews conducted within a month of the intervention, analysed thematically and (4) interviews conducted one year later, analysed thematically.

Results
Half (51.5%) of the respondents (n = 149) to the baseline survey had scores indicating high risk of job strain and depressive symptoms. Of 478 respondents to the PMC survey (response rate 57%), 93% found the play important, 92% recommended others see the play, 89% considered that it stimulated thinking about workplace behaviour, and 85% that it made discussing these issues easier. Thematic analysis of interviews within one month (n = 21) showed that the play raised awareness about poor workplace behaviour and motivated behaviour change. Interviews conducted one year later (n = 6) attributed improved workplace culture to the intervention due to improved awareness, discussion and capacity to respond to challenging issues.

Conclusions
Verbatim theatre is effective in raising awareness about difficult workplace behaviour in ways that motivate behaviour change, and hence can be effective in catalysing real improvements in healthcare workplace culture. Creative approaches are recommended for addressing similarly complex challenges in healthcare workforce retention.
GATA3 functions downstream of BRCA1 to promote DNA damage repair and suppress dedifferentiation in breast cancer
Authors: Wang Xuejie , Bai Feng , Liu Xiong , Peng Bin , Xu Xingzhi , Zhang Hongquan , Fu Li , Zhu Wei-Guo , Wang Bin , Pei Xin-Hai 
Published: April 2024

Abstract
Background
Inadequate DNA damage repair promotes aberrant differentiation of mammary epithelial cells. Mammary luminal cell fate is mainly determined by a few transcription factors including GATA3. We previously reported that GATA3 functions downstream of BRCA1 to suppress aberrant differentiation in breast cancer. How GATA3 impacts DNA damage repair preventing aberrant cell differentiation in breast cancer remains elusive. We previously demonstrated that loss of p18, a cell cycle inhibitor, in mice induces luminal-type mammary tumors, whereas depletion of either Brca1 or Gata3 in p18 null mice leads to basal-like breast cancers (BLBCs) with activation of epithelial-mesenchymal transition (EMT). We took advantage of these mutant mice to examine the role of Gata3 as well as the interaction of Gata3 and Brca1 in DNA damage repair in mammary tumorigenesis.

Results
Depletion of Gata3, like that of Brca1, promoted DNA damage accumulation in breast cancer cells in vitro and in basal-like breast cancers in vivo. Reconstitution of Gata3 improved DNA damage repair in Brca1-deficient mammary tumorigenesis. Overexpression of GATA3 promoted homologous recombination (HR)-mediated DNA damage repair and restored HR efficiency of BRCA1-deficient cells. Depletion of Gata3 sensitized tumor cells to PARP inhibitor (PARPi), and reconstitution of Gata3 enhanced resistance of Brca1-deficient tumor cells to PARP inhibitor.

Conclusions
These results demonstrate that Gata3 functions downstream of BRCA1 to promote DNA damage repair and suppress dedifferentiation in mammary tumorigenesis and progression. Our findings suggest that PARP inhibitors are effective for the treatment of GATA3-deficient BLBCs.
Engineering Streptomyces sp. CPCC 204095 for the targeted high-level production of isatropolone A by elucidating its pathway-specific regulatory mechanism
Authors: Zhang Cong , Xu Qianqian , Fu Jie , Wu Linzhuan , Li Yihong , Lu Yuan , Shi Yuanyuan , Sun Hongmin , Li Xingxing , Wang Lifei , Hong Bin 
Published: April 2024

Abstract
Background
Isatropolone A and C, produced by Streptomyces sp. CPCC 204095, belong to an unusual class of non-benzenoid aromatic compounds and contain a rare seven-membered ring structure. Isatropolone A exhibits potent activity against Leishmania donovani, comparable to the only oral drug miltefosine. However, its variably low productivity represents a limitation for this lead compound in the future development of new anti-leishmaniasis drugs to meet unmet clinical needs.

Results
Here we first elucidated the regulatory cascade of biosynthesis of isatropolones, which consists of two SARP family regulators, IsaF and IsaJ. Through a series of in vivo and in vitro experiments, IsaF was identified as a pathway-specific activator that orchestrates the transcription of the gene cluster essential for isatropolone biosynthesis. Interestingly, IsaJ was found to only upregulate the expression of the cytochrome P450 monooxygenase IsaS, which is crucial for the yield and proportion of isatropolone A and C. Through targeted gene deletions of isaJ or isaS, we effectively impeded the conversion of isatropolone A to C. Concurrently, the facilitation of isaF overexpression governed by selected promoters, prompted the comprehensive activation of the production of isatropolone A. Furthermore, meticulous optimization of the fermentation parameters was conducted. These strategies culminated in the attainment of an unprecedented maximum yield—980.8 mg/L of isatropolone A—achieved in small-scale solid-state fermentation utilizing the genetically modified strains, thereby establishing the highest reported titer to date.

Conclusion
In Streptomyces sp. CPCC 204095, the production of isatropolone A and C is modulated by the SARP regulators IsaF and IsaJ. IsaF serves as a master pathway-specific regulator for the production of isatropolones. IsaJ, on the other hand, only dictates the transcription of IsaS, the enzyme responsible for the conversion of isatropolone A and C. By engineering the expression of these pivotal genes, we have devised a strategy for genetic modification aimed at the selective and high-yield biosynthesis of isatropolone A. This study not only unveils the unique regulatory mechanisms governing isatropolone biosynthesis for the first time, but also establishes an essential engineering framework for the targeted high-level production of isatropolone A.
Considering inequities in national dementia strategies: breadth, depth, and scope
Authors: Godard-Sebillotte Claire , Navani Sanjna , Hacker Georgia , Vedel Isabelle 
Published: April 2024

Abstract
Background
Considering that dementia is an international public health priority, several countries have developed national dementia strategies outlining initiatives to address challenges posed by the disease. These strategies aim to improve the care, support, and resources available to meet the needs of persons living with dementia and their care partners and communities. Despite the known impact of social determinants of health on dementia risk, care, and outcomes, it is unclear whether dementia strategies adequately address related inequities. This study aimed to describe whether and how national dementia strategies considered inequities associated with social determinants of health.

Methods
We conducted an environmental scan of the national dementia strategies of countries that are part of the Organisation for Economic Cooperation and Development (OECD). Included strategies had to be accessible in English or French. Sub-national or provincial plans were excluded. We synthesised information on strategies’ considerations of inequity through a thematic analysis.

Results
Of the 15 dementia strategies that met inclusion criteria, 13 mentioned at least one inequity (M = 2.4, median = 2, range:0–7) related to Race/Ethnicity; Religion; Age; Disability; Sexual Orientation/Gender Identity; Social Class; or Rurality. Age and disability were mentioned most frequently, and religion most infrequently. Eleven strategies included general inequity-focused objectives, while only 5 had specific inequity-focused objectives in the form of tangible percentage changes, deadlines, or allocated budgets for achieving equity-related goals outlined in their strategies.

Conclusions
Understanding if and how countries consider inequities in their dementia strategies enables the development of future strategies that adequately target inequities of concern. While most of the strategies mentioned inequities, few included tangible objectives to reduce them. Countries must not only consider inequities at a surface-level; rather, they must put forth actionable objectives that intend to lessen the impact of inequities in the care of all persons living with dementia.
Blood lipids mediate the effects of gut microbiome on endometriosis: a mendelian randomization study
Authors: Su Chang , Wan Su , Ding Jin , Ni Guantai , Ding Huafeng 
Published: April 2024

Abstract
Background
There is evidence for an association between the gut microbiome and endometriosis. However, their causal relationship and the mediating role of lipid metabolism remain unclear.

Methods
Using genome-wide association study (GWAS) data, we conducted a bidirectional Mendelian randomization (MR) analysis to investigate the causal relationships between gut microbiome and endometriosis. The inverse variance weighted (IVW) method was used as the primary model, with other MR models used for comparison. Sensitivity analysis based on different statistical assumptions was used to evaluate whether the results were robust. A two-step MR analysis was further conducted to explore the mediating effects of lipids, by integrating univariable MR and the multivariate MR method based on the Bayesian model averaging method (MR-BMA).

Results
We identified four possible intestinal bacteria genera associated with the risk of endometriosis through the IVW method, including Eubacterium ruminantium group (odds ratio [OR] = 0.881, 95% CI: 0.795–0.976, P = 0.015), Anaerotruncus (OR = 1.252, 95% CI: 1.028–1.525, P = 0.025), Olsenella (OR = 1.110, 95% CI: 1.007–1.223, P = 0.036), and Oscillospira (OR = 1.215, 95% CI: 1.014–1.456, P = 0.035). The further two-step MR analysis identified that the effect of Olsenella on endometriosis was mediated by triglycerides (proportion mediated: 3.3%; 95% CI = 1.5−5.1%).

Conclusion
This MR study found evidence for specific gut microbiomes associated with the risk of endometriosis, which might partially be mediated by triglycerides.
Associations of U.S. state-level COVID-19 policies intensity with cannabis sharing behaviors in 2020
Authors: Assaf Ryan D. , Hamad Rita , Javanbakht Marjan , Arah Onyebuchi A. , Shoptaw Steven J. , Cooper Ziva D. , Gorbach Pamina M. 
Published: April 2024

Abstract
Background
Cannabis use before the COVID-19 pandemic for many involved sharing prepared cannabis for inhalation, practices that were less prevalent during the pandemic. State-level COVID-19 containment policies may have influenced this decrease. This study examined the extent to which the intensity of state-level COVID-19 policies were associated with individual-level cannabis sharing. Findings have the potential to guide harm reduction policies for future respiratory pandemics and seasonal respiratory virus waves.

Methods
This study used cross-sectional individual-level data from the COVID-19 Cannabis Study, an anonymous U.S.-based web survey on cannabis use disseminated during the early phase of the pandemic (Full sample N = 1,883). We combined individual-level data with state-level policy data from Kaiser Family Foundation’s State COVID-19 Data and Policy Actions for three time-points from June to August 2020 that overlapped with the survey period. Cannabis sharing was dichotomized as any versus no sharing. We adapted a previously published coding framework to score the intensity of COVID-19 policies implemented in each U.S. state and averaged the policy score across the time period. We then used Poisson regression models to quantify the associations of the average state-level COVID-19 policy score with cannabis sharing during the pandemic.

Results
Participants (n = 925) reporting using inhalation as a mode for cannabis use were included in this analysis. Most respondents were male (64.1%), non-Hispanic White (54.3%), with a mean age of 33.7 years (SD 8.8). A large proportion (74.9%) reported sharing cannabis during the pandemic. Those who shared cannabis more commonly lived in states with a lower average policy score (16.7, IQR 12.3–21.5) compared to those who did not share (18.6, IQR 15.3–25.3). In adjusted models, the prevalence ratio of any cannabis sharing per every 5-unit increase in the average COVID-19 policy score was 0.97 (95% CI 0.93, 1.01).

Conclusions
Fewer individuals shared cannabis in states with more intense COVID-19 containment policies compared to those in states with less intense policies. Individuals who use cannabis may be willing to make changes to their behavior and may further benefit from specific and directed public health messaging to avoid sharing during respiratory infection outbreaks.
Health state utility estimates for value assessments of novel treatments in Huntington’s disease: a systematic literature review
Authors: Sawant Ruta , Paret Kyle , Petrillo Jennifer , Koenig Aaron , Wolowacz Sorrel , Ronquest Naoko , Rickards Hugh 
Published: April 2024

Abstract
Background
Huntington’s disease (HD) is a progressive neurodegenerative disease with a devastating impact on patients and their families. Quantifying how treatments affect patient outcomes is critical for informing reimbursement decisions. Many countries mandate a formal value assessment in which the treatment benefit is measured as quality-adjusted life-years, calculated with the use of utility estimates that reflect respondents’ preferences for health states.

Objective
To summarize published health state utility data in HD and identify gaps and uncertainties in the data available that could be used to inform value assessments.

Methods
We conducted a systematic literature review of studies that used preference-based instruments (e.g., EQ-5D and SF-6D) to estimate utility values for people with HD. The studies were published between January 2012 and December 2022.

Results
Of 383 articles screened, 16 articles reported utility values estimated in 11 distinct studies. The utility measure most frequently reported was EQ-5D (9/11 studies). Two studies reported SF-6D data; one used time trade-off methods to value health state descriptions (vignettes). Although utility scores generally worsened to a lower value with increased HD severity, the estimates varied considerably across studies. The EQ-5D index range was 0.89 − 0.72 for mild/prodromal HD and 0.71 − 0.37 for severe/late-stage disease.

Conclusions
This study uncovered high variability in published utility estimates, indicating substantial uncertainty in existing data. Further research is needed to better understand preferences and valuation across all stages and domains of HD symptoms and the degree to which generic utility measures capture the impact of cognitive changes on quality of life.