bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Retrospective Stressor Analysis (RSA): a novel qualitative tool for identifying causes of burnout and mitigation strategies during residency
Authors: Chrouser Kristin L. , Zebib Laura , Webb Blake F. , Bagian Tandi , Arnold Timothy 
Published: May 2024

Abstract
Background
Resident physicians are at an increased risk of burnout due to their high-pressure work environments and busy schedules which can lead to poor mental health outcomes and decreased performance quality. Given variability among training programs and institutions across the United States, stressors likely differ, and interventions must be tailored to the local context, but few tools exist to assist in this process.

Methods
A tool commonly used in adverse event analysis was adapted into a “retrospective stressor analysis” (RSA) for burnout prevention. The RSA was tested in a group of chief residents studying quality improvement and patient safety in veteran’s hospitals across the United States. The RSA prompted them to identify stressors experienced during their residencies across four domains (clinical practice, career development, personal life, and personal health), perceived causes of the stressors, and potential mitigation strategies.

Results
Fifty-eight chief residents completed the RSA. Within the clinical domain, they describe the stress of striving for efficiency and clinical skills acquisition, all while struggling to provide quality care in high pressure environments. In the career domain, identifying mentors and opportunities for research engagement was stressful. Within their personal lives, a lack of time-constrained their ability to maintain hobbies, relationships, and attend meaningful social events while also reducing their engagement in healthy behaviors such as exercise, optimal nutrition, and attending medical appointments. Within each of these domains, they identified and described stress mitigation strategies at the individual, departmental, and national levels.

Conclusion
The RSA is a novel tool that can identify national trends in burnout drivers while simultaneously providing tailored prevention strategies for residents and their training sites.
Association between regulator inspection and ratings on primary care prescribing: an observational study in England 2014 to 2019
Authors: Allen Thomas , Walshe Kieran , Proudlove Nathan , Sutton Matt 
Published: May 2024

Abstract
Background
Healthcare regulators in many countries undertake inspections of healthcare providers and publish inspection outcomes with the intention of improving quality of care. Comprehensive inspections of general practices in England by the Care Quality Commission began for the first time in 2014. It is assumed that inspection and rating will raise standards and improve care, but the presence and extent of any improvements is unknown. We aim to determine if practice inspection ratings are associated with past performance on prescribing indicators and if prescribing behaviour changes following inspection.

Methods
Longitudinal study using a dataset of 6771 general practices in England. Practice inspection date and score was linked with monthly practice-level data on prescribing indicators relating to antibiotics, hypnotics and non-steroidal anti-inflammatory drugs. The sample covers practices receiving their first inspection between September 2014 and December 2018. Regression analysis and the differential timing of inspections is used to identify the impact on prescribing.

Results
Better-rated practices had better prescribing in the period before inspections began. In the six months following inspections, no overall change in prescribing was observed. However, the differences between the best and worse rated practices were reduced but not fully. The same is also true when taking a longer-term view. There is little evidence that practices responded in anticipation of inspection or reacted differently once the ratings were made public.

Conclusion
While some of the observed historic variation in prescribing behaviour has been lessened by the process of inspection and ratings, we find this change is small and appears to come from both improvements among lower-rated practices and deteriorations among higher-rated practices. While inspection and rating no doubt had other impacts, these prescribing indicators were largely unchanged.
Expression of glucocorticoid receptor and HDACs in airway smooth muscle cells is associated with response to steroids in COPD
Authors: Zhou Liang , Roth Michael , Papakonstantinou Eleni , Tamm Michael , Stolz Daiana 
Published: May 2024

Abstract
Background
Steroid insensitivity in Chronic Obstructive Pulmonary Disease (COPD) presents a problem for controlling the chronic inflammation of the airways. The glucocorticoid receptor (GR) mediates the intracellular signaling of inhaled corticosteroids (ICS) by interacting with transcription factors and histone deacetylases (HDACs). The aim of this study was to assess if COPD patients’ response to ICS in vivo, may be associated with the expression of GR, the complex of GR with transcription factors, and the expression of various HDACs in vitro.

Methods
Primary airway smooth muscle cells (ASMC) were established from endobronchial biopsies obtained from patients with asthma (n = 10), patients with COPD (n = 10) and subjects that underwent diagnostic bronchoscopy without pathological findings and served as controls (n = 6). ASMC were also established from 18 COPD patients, 10 responders and 8 non-responders to ICS, who participated in the HISTORIC study, an investigator-initiated and driven clinical trial that proved the hypothesis that COPD patients with high ASMC in their endobronchial biopsies respond better to ICS than patients with low ASMC. Expression of GR and its isoforms GRα and GRβ and HDACs was investigated in primary ASMC in the absence or in the presence of dexamethasone (10− 8M) by western blotting. The complex formation of GR with transcription factors was assessed by co-immunoprecipitation.

Results
Expression of GR and its isoform GRα but not GRβ was significantly reduced in ASMC from COPD patients as compared to controls. There were no significant differences in the expression of GR, GRα and GRβ between responders and non-responders to ICS. However, treatment with dexamethasone upregulated the expression of total GR (p = 0.004) and GRα (p = 0.005) after 30 min in responders but not in non-responders. Τhe formation of the complex GR-c-Jun was increased 60 min after treatment with dexamethasone only in responders who exhibited significantly lower expression of HDAC3 (p = 0.005) and HDAC5 (p < 0.0001) as compared to non-responders.

Conclusions
These data suggest that ASMC from COPD patients who do not respond to treatment with ICS, are characterized by reduced GR-c-Jun complex formation and increased expression of HDAC3 and HDAC5.

Trial registration
ISRCTN11017699 (Registration date: 15/11/2016).
Is GFR decline induced by SGLT2 inhibitor of clinical importance?
Authors: Günes-Altan Merve , Bosch Agnes , Striepe Kristina , Bramlage Peter , Schiffer Mario , Schmieder Roland E. , Kannenkeril Dennis 
Published: May 2024

Abstract
Background
Use of sodium-glucose-cotransporter-2 (SGLT2) inhibitors often causes an initial decline in glomerular filtration rate (GFR). This study addresses the question whether the initial decline of renal function with SGLT2 inhibitor treatment is related to vascular changes in the systemic circulation.

Methods
We measured GFR (mGFR) and estimated GFR (eGFR) in 65 patients with type 2 diabetes (T2D) at baseline and after 12 weeks of treatment randomized either to a combination of empagliflozin and linagliptin (SGLT2 inhibitor based treatment group) (n = 34) or metformin and insulin (non-SGLT2 inhibitor based treatment group) (n = 31). mGFR was measured using the gold standard clearance technique by constant infusion of inulin. In addition to blood pressure (BP), we measured pulse wave velocity (PWV) under standardized conditions reflecting vascular compliance of large arteries, as PWV is considered to be one of the most reliable vascular parameter of cardiovascular (CV) prognosis.

Results
Both mGFR and eGFR decreased significantly after initiating treatment, but no correlation was found between change in mGFR and change in eGFR in either treatment group (SGLT2 inhibitor based treatment group: r=-0.148, p = 0.404; non-SGLT2 inhibitor based treatment group: r = 0.138, p = 0.460). Noticeably, change in mGFR correlated with change in PWV (r = 0.476, p = 0.005) in the SGLT2 inhibitor based treatment group only and remained significant after adjustment for the change in systolic BP and the change in heart rate (r = 0.422, p = 0.018). No such correlation was observed between the change in eGFR and the change in PWV in either treatment group.

Conclusions
Our main finding is that after initiating a SGLT2 inhibitor based therapy an exaggerated decline in mGFR was related with improved vascular compliance of large arteries reflecting the pharmacologic effects of SGLT2 inhibitor in the renal and systemic vascular bed. Second, in a single patient with T2D, eGFR may not be an appropriate parameter to assess the true change of renal function after receiving SGLT2 inhibitor based therapy.

Trial registration
clinicaltrials.gov (NCT02752113).
Correlation between the triglyceride-glucose index and left ventricular global longitudinal strain in patients with chronic heart failure: a cross-sectional study
Authors: Zhang Shuai , Liu Yan , Liu Fangfang , Ye Qing , Guo Dachuan , Xu Panpan , Wei Tianhao , Zhang Cheng , Lu Huixia 
Published: May 2024

Abstract
Background
Left ventricular global longitudinal strain (GLS) holds greater diagnostic and prognostic value than left ventricular ejection fraction (LVEF) in the heart failure (HF) patients. The triglyceride-glucose (TyG) index serves as a reliable surrogate for insulin resistance (IR) and is strongly associated with several adverse cardiovascular events. However, there remains a research gap concerning the correlation between the TyG index and GLS among patients with chronic heart failure (CHF).

Method
427 CHF patients were included in the final analysis. Patient demographic information, along with laboratory tests such as blood glucose, lipids profiles, and echocardiographic data were collected. The TyG index was calculated as Ln [fasting triglyceride (TG) (mg/dL) × fasting plasma glucose (FPG) (mg/dL)/2].

Results
Among CHF patients, GLS was notably lower in the higher TyG index group compared to the lower TyG index group. Following adjustment for confounding factors, GLS demonstrated gradual decrease with increasing TyG index, regardless of the LVEF level and CHF classification.

Conclusion
Elevated TyG index may be independently associated with more severe clinical left ventricular dysfunction in patients with CHF.
Long non-coding RNA PXN-AS1 promotes glutamine synthetase-mediated chronic myeloid leukemia BCR::ABL1-independent resistance to Imatinib via cell cycle signaling pathway
Authors: Li Yifei , Yuan Shiyi , Zhou Ying , Zhou Jingwen , Zhang Xuan , Zhang Ping , Xiao Wenrui , Zhang Ying , Deng Jianchuan , Lou Shifeng 
Published: May 2024

Abstract
Background
Chronic myeloid leukemia (CML) is a common hematological malignancy, and tyrosine kinase inhibitors (TKIs) represent the primary therapeutic approach for CML. Activation of metabolism signaling pathway has been connected with BCR::ABL1-independent TKIs resistance in CML cells. However, the specific mechanism by which metabolism signaling mediates this drug resistance remains unclear. Here, we identified one relationship between glutamine synthetase (GS) and BCR::ABL1-independent Imatinib resistance in CML cells.

Methods
GS and PXN-AS1 in bone marrow samples of CML patients with Imatinib resistance (IR) were screened and detected by whole transcriptome sequencing. GS expression was upregulated using LVs and blocked using shRNAs respectively, then GS expression, Gln content, and cell cycle progression were respectively tested. The CML IR mice model were established by tail vein injection, prognosis of CML IR mice model were evaluated by Kaplan–Meier analysis, the ratio of spleen/body weight, HE staining, and IHC. PXN-AS1 level was blocked using shRNAs, and the effects of PXN-AS1 on CML IR cells in vitro and in vivo were tested the same as GS. Several RNA-RNA tools were used to predict the potential target microRNAs binding to both GS and PXN-AS1. RNA mimics and RNA inhibitors were used to explore the mechanism through which PXN-AS1 regulates miR-635 or miR-635 regulates GS.

Results
GS was highly expressed in the bone marrow samples of CML patients with Imatinib resistance. In addition, the lncRNA PXN-AS1 was found to mediate GS expression and disorder cell cycle in CML IR cells via mTOR signaling pathway. PXN-AS1 regulated GS expression by binding to miR-635. Additionally, knockdown of PXN-AS1 attenuated BCR::ABL1-independent Imatinib resistance in CML cells via PXN-AS1/miR-635/GS/Gln/mTOR signaling pathway.

Conclusions
Thus, PXN-AS1 promotes GS-mediated BCR::ABL1-independent Imatinib resistance in CML cells via cell cycle signaling pathway.

Graphic Abstract
Ownership and use of insecticide-treated nets in Myanmar: insights from a nationally representative demographic and health survey
Authors: Win Kyawt Mon , Show Kyaw Lwin , Sattabongkot Jetsumon , Aung Pyae Linn 
Published: May 2024

Abstract
Background
Malaria poses a substantial public health threat in Myanmar, indicating the need for rigorous efforts to achieve elimination of the disease nationwide by 2030. The use of insecticide-treated nets (ITNs) forms part of a pivotal strategy for preventing transmission. This study explored the ownership and use of ITNs in Myanmar and identified factors associated with non-use of ITNs.

Methods
Household datasets from the 2015–2016 Myanmar Demographic and Health Survey were utilised, which encompassed all household members except children under the age of five. Descriptive statistics and inferential tests, including simple and multiple logistics regression models and Pearson correlations, were employed for analysis. All analyses, taking the two-stage stratified cluster sampling design into account, used weighting factors and the “svyset” command in STATA. The ownership and use of bed nets were also visualised in QGIS maps.

Results
Among the 46,507 participants, 22.3% (95% CI 20.0%, 24.5%) had access to ITNs, with only 15.3% (95% CI 13.7, 17.1%) sleeping under an ITN the night before the survey. Factors associated with the non-use of ITNs included age category (15–34 years—aOR: 1.17, 95% CI 1.01, 1.30; 50+ years—aOR: 1.19, 95% CI 1.06, 1.33), location (delta or lowland—aOR: 5.39, 95% CI 3.94, 7.38; hills—aOR: 1.80, 95% CI 1.20, 2.71; plains—aOR: 3.89, 95% CI 2.51, 6.03), urban residency (aOR: 1.63, 95% CI 1.22, 2.17), and wealth quintile (third—aOR: 1.38, 95% CI 1.08, 1.75; fourth—aOR: 1.65, 95% CI 1.23, 2.23; fifth—aOR: 1.47, 95% CI 1.02, 2.13). A coherent distribution of the ownership and use of ITNs was seen across all states/regions, and a strong correlation existed between the ownership and use of ITNs (r: 0.9795, 95% CI 0.9377, 0.9933, alpha < 0.001).

Conclusions
This study identified relatively low percentages of ITN ownership and use, indicating the need to increase the distribution of ITNs to achieve the target of at least one ITN per every two people. Strengthening the use of ITNs requires targeted health promotion interventions, especially among relatively affluent individuals residing in delta or lowland areas, hills, and plains.
Prevalence of Leber hereditary optic neuropathy in the Community of Madrid (Spain), estimation with a capture-recapture method
Authors: Esteban-Vasallo María D. , Domínguez-Berjón M. Felicitas , Chalco-Orrego Juan Pablo , González Martín–Moro Julio 
Published: May 2024

Abstract
Background
Leber hereditary optic neuropathy (LHON) typically presents in young adults as bilateral painless subacute visual loss. Prevalence data are scarce. The aim of this study was to examine the validity of different ascertainment sources used in population-based rare diseases registries to detect cases, and to explore the impact of a capture-recapture method in the estimation of the prevalence of LHON in the Autonomous Community of Madrid (ACM) in 2022.

Methods
Descriptive cross-sectional population-based study. Potential LHON cases were detected by automatic capture from the healthcare information sources usually explored for the Regional Registry for Rare Diseases (SIERMA). Ophthalmologists provided data from their clinical registry. Positive predictive values (PPV) and sensitivity with 95% confidence intervals (CI) were estimated. Global and by sex prevalences were calculated with confimed cases and with those estimated by the capture-recapture method.

Results
A total of 102 potential LHON cases were captured from healthcare information sources, 25 of them (24.5%) finally were confirmed after revision, with an overall PPV of 24.5% (95%CI 17.2–33.7). By source, the electronic clinical records of primary care had the highest PPV (51.2, 95%CI 36.7–65.4). The ophthalmologists clinical registry provided 22 cases, 12 of them not detected in the automatic capture sources. The clinical registry reached a sensitivity of 59.5% (95%CI 43.5–73.6) and the combination of automatic capture sources reached a 67.6% (95%CI: 51.5–80.4). The total confirmed cases were 37, with a mean age of 48.9 years, and a men: women ratio of 2.4:1. Genetic information was recovered in 27 cases, with the m.3460 mutation being the most frequent (12 cases). The global prevalence was 0.55 cases/100,000 inhabitants (95%CI 0.40–0.75), and with the capture-recapture method reached 0.79 cases/100,000 (95%CI 0.60–1.03), a 43.6% higher, 1.15 cases/100,000 (95%CI 0.83–1.58) in men and 0.43 cases/100,000 (95%CI 0.26–0.70) in women.

Conclusions
The prevalence of LHON estimated in the ACM was lower than in other European countries. Population-based registries of rare diseases require the incorporation of confirmed cases provided by clinicians to asure the best completeness of data. The use of more specific coding for rare diseases in healthcare information systems would facilitate the detection of cases. Further epidemiologic studies are needed to assess potential factors that may influence the penetrance of LHON.
Social media threats and health among adolescents: evidence from the health behaviour in school-aged children study
Authors: Lahti Henri , Kokkonen Marja , Hietajärvi Lauri , Lyyra Nelli , Paakkari Leena 
Published: May 2024

Abstract
Background
Social media are immensely popular among adolescents. Thus, concerns have been raised about the threats adolescents encounter on social media and the possible negative health consequences, such as depressive symptoms and anxiety. This study investigated the prevalence of nine social media threats: (1) cyberbullying, (2) sexual harassment, (3) racism, (4) unauthorized distribution of sensitive material, (5) phishing attempts, (6) misinformation, (7) the sale or distribution of drugs, (8) harmful or dangerous social media challenges, (9) content causing appearance pressures. The study also investigated how individual and social factors, problematic social media use (PSMU), and online communication with strangers are associated with social media threat exposure, as well as the association between social media threats and self-rated health, depressive feelings, and anxiety symptoms.

Methods and findings
Nationally representative Health Behaviour in School-aged Children (HBSC) data from Finland were obtained from 2288 respondents aged 11, 13, and 15 years. Fixed effects regression models were applied. The most common threat, encountered daily and weekly, was misinformation. Regression models showed that individual and social factors, PSMU, and online communication with strangers explained adolescent exposure to social media threats in differing ways. Furthermore, certain factors (e.g., emotional intelligence, family support) were associated with encountering social media threats less frequently, whereas other factors (e.g., PSMU, online communication with strangers) were associated with more frequent encounters. Daily and weekly exposure to social media threats was systematically associated with poor self-rated health, frequent depressive feelings, and anxiety symptoms.

Conclusions
Our study highlights the need for intervention and health promotion efforts to mitigate adolescent exposure to social media threats and ensuing negative health consequences.
Late-onset dyshormonogenic goitrous hypothyroidism due to a homozygous mutation of the SLC26A7 gene: a case report
Authors: Sciarroni Elisabetta , Montanelli Lucia , Di Cosmo Caterina , Bagattini Brunella , Comi Simone , Pignata Luisa , Brancatella Alessandro , De Marco Giuseppina , Ferrarini Eleonora , Nencetti Chiara , Sessa Maria Rita , Latrofa Francesco , Santini Ferruccio , Tonacchera Massimo , Agretti Patrizia 
Published: May 2024

Abstract
Background
In this study, we used targeted next-generation sequencing (NGS) to investigate the genetic basis of congenital hypothyroidism (CH) in a 19-year-old Tunisian man who presented with severe hypothyroidism and goiter.

Case presentation
The propositus reported the appearance of goiter when he was 18. Importantly, he did not show signs of mental retardation, and his growth was proportionate. A partial organification defect was detected through the perchlorate-induced iodide discharge test. NGS identified a novel homozygous mutation in exon 18 of the SLC26A7 gene (P628Qfs*11), which encodes for a new iodide transporter. This variant is predicted to result in a truncated protein. Notably, the patient's euthyroid brother was heterozygous for the same mutation. No renal acid–base abnormalities were found and the administration of 1 mg of iodine failed to correct hypothyroidism.

Conclusions
We described the first case of goitrous CH due to a homozygous mutation of the SLC26A7 gene diagnosed during late adolescence.