bluuebunny/crossref_metadata_2025_split huggingface dataset:
Video based educational intervention in waiting area to improve awareness about health screening among patients visiting family medicine clinics
Authors: Saeed Rabeeya , Ahmed Farah , Danish Syed Hasan , Talha Mohammad , Usmani Maha , Durrani Noureen , Ali Noman 
Published: July 2024

Abstract
Background
Multiple educational modalities have been utilized including leaflet, face-to-face counseling and watching videos in waiting areas for engaging patients. Considering the two challenges of waiting time frustration and lack of health screening awareness, Family Physicians’ waiting area are an ideal place to bridge this gap. The objective of this study is to evaluate the effectiveness of video-based health education intervention in improving knowledge about health screening among patients and their families sitting in waiting area of Family Medicine clinics.

Methods
It was a pre and post quasi-experimental study that was conducted in family medicine clinics located at main campus and Outreach centers of a tertiary care hospital. A total of 300 participants were approached during the six month period. The intervention consisted of an educational video on health screening. The content of the video was taken from the recommended preventive care guidelines from CDC and USPSTF. The pre-and post-intervention knowledge of the participants was assessed through a semi-structured coded questionnaire by an interviewer who was trained in data collection. Data was analyzed using SPSS version 26. Pre and post intervention knowledge adequacy was determined using MacNemar’s Chi-square test.

Results
Total 300 participants voluntarily participated into the study. Median age of the participants was 28 (IQR = 23.25–36.75) years. Majority of participants were males (56%). Following the intervention, there was significant increase in the proportion of participants (51.3% versus 68%) who had understanding of health screening check-up (p < 0.001). Following the study intervention, there was significant increase in proportion of participants who had adequate knowledge related to diabetes (p = 0.045), hypertension (p < 0.001), cholesterol (p < 0.001), cervical cancer (p < 0.001), colon cancer (p < 0.001) and hepatitis B & C (p < 0.001). No significant improvement in breast cancer related knowledge was observed (p = 0.074). Highest post-intervention increase in knowledge from baseline was observed for hypertension (13.3% versus 63.3%) followed by colon cancer (24.3% versus 59.3%), cholesterol (67 versus 96.7%), hepatitis b & C (56.7% versus 77.3%), diabetes (29.7% versus 48%), cervical cancer (1.7% versus 19%), and breast cancer (7.7% versus 18.3%).

Conclusion
This study highlighted a pivotal role of an educational video intervention in clinic waiting area to improve awareness regarding health screening among patients and their families. Further interventional community based or multicenter studies are warranted to assess the long-term impact of these educational videos on knowledge and utilization of health screening among adult population.
BUB1B monoallelic germline variants contribute to prostate cancer predisposition by triggering chromosomal instability
Authors: Silva Maria P. , Ferreira Luísa T. , Brás Natércia F. , Torres Lurdes , Brandão Andreia , Pinheiro Manuela , Cardoso Marta , Resende Adriana , Vieira Joana , Palmeira Carlos , Martins Gabriela , Silva Miguel , Pinto Carla , Peixoto Ana , Silva João , Henrique Rui , Maia Sofia , Maiato Helder , Teixeira Manuel R. , Paulo Paula 
Published: July 2024

Abstract
Background
Prostate cancer (PrCa) is the most frequently diagnosed cancer in men. Variants in known moderate- to high-penetrance genes explain less than 5% of the cases arising at early-onset (< 56 years) and/or with familial aggregation of the disease. Considering that BubR1 is an essential component of the mitotic spindle assembly checkpoint, we hypothesized that monoallelic BUB1B variants could be sufficient to fuel chromosomal instability (CIN), potentially triggering (prostate) carcinogenesis.

Methods
To unveil BUB1B as a new PrCa predisposing gene, we performed targeted next-generation sequencing in germline DNA from 462 early-onset/familial PrCa patients and 1,416 cancer patients fulfilling criteria for genetic testing for other hereditary cancer syndromes. To explore the pan-cancer role of BUB1B, we used in silico BubR1 molecular modeling, in vitro gene-editing, and ex vivo patients’ tumors and peripheral blood lymphocytes.

Results
Rare BUB1B variants were found in ~ 1.9% of the early-onset/familial PrCa cases and in ~ 0.6% of other cancer patients fulfilling criteria for hereditary disease. We further show that BUB1B variants lead to decreased BubR1 expression and/or stability, which promotes increased premature chromatid separation and, consequently, triggers CIN, driving resistance to Taxol-based therapies.

Conclusions
Our study shows that different BUB1B variants may uncover a trigger for CIN-driven carcinogenesis, supporting the role of BUB1B as a (pan)-cancer predisposing gene with potential impact on genetic counseling and treatment decision-making.
Altered hypoxia-induced cellular responses and inflammatory profile in lung fibroblasts from COPD patients compared to control subjects
Authors: Martin Ryde , Nora Marek , Anna Löfdahl , Olivia Pekny , Leif Bjermer , Gunilla Westergren-Thorsson , Ellen Tufvesson , Anna-Karin Larsson-Callerfelt 
Published: July 2024

Abstract
Background
Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease characterized by chronic bronchitis, emphysema and vascular remodelling. The disease is associated with hypoxia, inflammation and oxidative stress. Lung fibroblasts are important cells in remodelling processes in COPD, as main producers of extracellular matrix proteins but also in synthesis of growth factors and inflammatory mediators.

Methods
In this study we aimed to investigate if there are differences in how primary distal lung fibroblasts obtained from COPD patients and healthy subjects respond to hypoxia (1% O2) and pro-fibrotic stimuli with TGF-β1 (10 ng/mL). Genes and proteins associated with oxidative stress, endoplasmic reticulum stress, remodelling and inflammation were analysed with RT-qPCR and ELISA.

Results
Hypoxia induced differences in expression of genes involved in oxidative stress (SOD3 and HIF-1α), ER stress (IRE1, PARK and ATF6), apoptosis (c-Jun and Bcl2) and remodelling (5HTR2B, Collagen7 and VEGFR2) in lung fibroblasts from COPD subjects compared to control subjects, where COPD fibroblasts were in general less responsive. The release of VEGF-C was increased after hypoxia, whereas TGF-β significantly reduced the VEGF response to hypoxia and the release of HGF. COPD fibroblasts had a higher release of IL-6, IL-8, MCP-1 and PGE2 compared to lung fibroblasts from control subjects. The release of inflammatory mediators was less affected by hypoxia, whereas TGFβ1 induced differences in inflammatory profile between fibroblasts from COPD and control subjects.

Conclusion
These results suggest that there is an alteration of gene regulation of various stress responses and remodelling associated mediator release that is related to COPD and hypoxia, where fibroblasts from COPD patients have a deficient response.
BMI variability and cardiovascular outcomes within clinical trial and real-world environments in type 2 diabetes: an IMI2 SOPHIA study
Authors: Massey Robert J. , Chen Yu , Panova-Noeva Marina , Mattheus Michaela , Siddiqui Moneeza K. , Schloot Nanette C. , Ceriello Antonio , Pearson Ewan R. , Dawed Adem Y. 
Published: July 2024

Abstract
Background
BMI variability has been associated with increased cardiovascular disease risk in individuals with type 2 diabetes, however comparison between clinical studies and real-world observational evidence has been lacking. Furthermore, it is not known whether BMI variability has an effect independent of HbA1c variability.

Methods
We investigated the association between BMI variability and 3P-MACE risk in the Harmony Outcomes trial (n = 9198), and further analysed placebo arms of REWIND (n = 4440) and EMPA-REG OUTCOME (n = 2333) trials, followed by real-world data from the Tayside Bioresource (n = 6980) using Cox regression modelling. BMI variability was determined using average successive variability (ASV), with first major adverse cardiovascular event of non-fatal stroke, non-fatal myocardial infarction, and cardiovascular death (3P-MACE) as the primary outcome.

Results
After adjusting for cardiovascular risk factors, a + 1 SD increase in BMI variability was associated with increased 3P-MACE risk in Harmony Outcomes (HR 1.12, 95% CI 1.08–1.17, P < 0.001). The most variable quartile of participants experienced an 87% higher risk of 3P-MACE (P < 0.001) relative to the least variable. Similar associations were found in REWIND and Tayside Bioresource. Further analyses in the EMPA-REG OUTCOME trial did not replicate this association. BMI variability’s impact on 3P-MACE risk was independent of HbA1c variability.

Conclusions
In individuals with type 2 diabetes, increased BMI variability was found to be an independent risk factor for 3P-MACE across cardiovascular outcome trials and real-world datasets. Future research should attempt to establish a causal relationship between BMI variability and cardiovascular outcomes.
Data-independent LC-MS/MS analysis of ME/CFS plasma reveals a dysregulated coagulation system, endothelial dysfunction, downregulation of complement machinery
Authors: Nunes Massimo , Vlok Mare , Proal Amy , Kell Douglas B. , Pretorius Etheresia 
Published: July 2024

Abstract
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating chronic condition that is characterized by unresolved fatigue, post-exertion symptom exacerbation (PESE), cognitive dysfunction, orthostatic intolerance, and other symptoms. ME/CFS lacks established clinical biomarkers and requires further elucidation of disease mechanisms. A growing number of studies demonstrate signs of hematological and cardiovascular pathology in ME/CFS cohorts, including hyperactivated platelets, endothelial dysfunction, vascular dysregulation, and anomalous clotting processes. To build on these findings, and to identify potential biomarkers that can be related to pathophysiology, we measured differences in protein expression in platelet-poor plasma (PPP) samples from 15 ME/CFS study participants and 10 controls not previously infected with SARS-CoV-2, using DIA LC-MS/MS. We identified 24 proteins that are significantly increased in the ME/CFS group compared to the controls, and 21 proteins that are significantly downregulated. Proteins related to clotting processes – thrombospondin-1 (important in platelet activation), platelet factor 4, and protein S – were differentially expressed in the ME/CFS group, suggestive of a dysregulated coagulation system and abnormal endothelial function. Complement machinery was also significantly downregulated, including C9 which forms part of the membrane attack complex. Additionally, we identified a significant upregulation of lactotransferrin, protein S100-A9, and an immunoglobulin variant. The findings from this experiment further implicate the coagulation and immune system in ME/CFS, and bring to attention the pathology of or imposed on the endothelium. This study highlights potential systems and proteins that require further research with regards to their contribution to the pathogenesis of ME/CFS, symptom manifestation, and biomarker potential, and also gives insight into the hematological and cardiovascular risk for ME/CFS individuals affected by diabetes mellitus.

Graphical abstract
Efficacy and toxicity of KRASG12C inhibitors in advanced solid tumors: a meta-analysis
Authors: Dang Shoutao , Zhang Shuyang , Zhao Jingyang , Li Wei 
Published: July 2024

Abstract
Background
The efficacy and toxicity of KRASG12C inhibitors were evaluated for advanced solid tumors in several studies; however, the results were not fully consistent.

Methods
Clinical trials evaluating KRASG12C inhibitors for advanced solid tumors were searched from PubMed, Embase, and Cochrane Library online databases up to 31st December 2023. The characteristics of the studies and the results of objective response rate (ORR), disease control rate (DCR), duration of response (DoR), progression-free survival (PFS) rate, overall survival (OS) rate, and treatment-related adverse events (trAEs) were extracted.

Results
Ten studies with 925 heavily pretreated advanced patients harboring KRASG12C mutation were included. For total population, the pooled analysis of ORR was 28.6% (95%CI, 21.2-36.6%), DCR was 85.5% (95%CI, 82.2-88.6%), PFS rate at 6 months (PFS6) was 49.6% (95%CI, 41.4-57.9%), PFS rate at 12 months (PFS12) was 26.7% (95%CI, 19.8-34.1%), OS rates at 6 months (OS6) was 76.2% (95%CI, 68.8-82.9%), OS rates at 12 months (OS12) was 47.8% (95%CI, 38.6-57.0%). The pooled analysis of any grade trAEs was 79.3% (95%CI, 66.2-90.0%) and grade three or more trAEs was 24.4% (95%CI, 16.7-32.9%). The median time to response and DoR results from individual data were 1.39 months (95%CI, 1.37–1.41 months) and 10.54 months (95%CI, 7.72–13.36 months). Sotorasib had significantly lower pooled incidences of any trAEs (OR, 0.07, 95%CI, 0.03–0.14) and grade three or more trAES (OR, 0.34, 95%CI, 0.24–0.49) compared with adagrasib.

Conclusions
KRASG12C inhibitors have good ORR, DCR, PFS rate, OS rate, tolerable trAEs, and early response with long duration in advanced solid tumors; however, most of the pooled results were heterogeneous. Sotorasib has shown better safety results.
De-implementation strategy to reduce unnecessary antibiotic prescriptions for ambulatory HIV-infected patients with upper respiratory tract infections in Mozambique: a study protocol of a cluster randomized controlled trial
Authors: Faiela Candido , Moon Troy D. , Sidat Mohsin , Sevene Esperança 
Published: July 2024

Abstract
Background
Antibiotics are globally overprescribed for the treatment of upper respiratory tract infections (URTI), especially in persons living with HIV. However, most URTIs are caused by viruses, and antibiotics are not indicated. De-implementation is perceived as an important area of research that can lead to reductions in unnecessary, wasteful, or harmful practices, such as excessive or inappropriate antibiotic use for URTI, through the employment of evidence-based interventions to reduce these practices. Research into strategies that lead to successful de-implementation of unnecessary antibiotic prescriptions within the primary health care setting is limited in Mozambique. In this study, we propose a protocol designed to evaluate the use of a clinical decision support algorithm (CDSA) for promoting the de-implementation of unnecessary antibiotic prescriptions for URTI among ambulatory HIV-infected adult patients in primary healthcare settings.

Methods
This study is a multicenter, two-arm, cluster randomized controlled trial, involving six primary health care facilities in Maputo and Matola municipalities in Mozambique, guided by an innovative implementation science framework, the Dynamic Adaption Process. In total, 380 HIV-infected patients with URTI symptoms will be enrolled, with 190 patients assigned to both the intervention and control arms. For intervention sites, the CDSAs will be posted on either the exam room wall or on the clinician´s exam room desk for ease of reference during clinical visits. Our sample size is powered to detect a reduction in antibiotic use by 15%. We will evaluate the effectiveness and implementation outcomes and examine the effect of multi-level (sites and patients) factors in promoting the de-implementation of unnecessary antibiotic prescriptions. The effectiveness and implementation of our antibiotic de-implementation strategy are the primary outcomes, whereas the clinical endpoints are the secondary outcomes.

Discussion
This research will provide evidence on the effectiveness of the use of the CDSA in promoting the de-implementation of unnecessary antibiotic prescribing in treating acute URTI, among ambulatory HIV-infected patients. Findings will bring evidence for the need to scale up strategies for the de-implementation of unnecessary antibiotic prescription practices in additional healthcare sites within the country.

Trial registration
ISRCTN, ISRCTN88272350. Registered 16 May 2024, https://www.isrctn.com/ISRCTN88272350
Analysis of risk factors for complications in echocardiography-guided percutaneous intramyocardial septal radiofrequency ablation
Authors: Wang Hanzhi , Cheng Jifang , Chen Qi , Pu Zhaoxia , Li Huajun 
Published: July 2024

Abstract
Background
The feasibility of percutaneous intramyocardial septal radiofrequency ablation (PIMSRA) for the treatment of hypertrophic obstructive cardiomyopathy (HOCM) has been previously reported. However, limited investigation has been conducted regarding the complications associated with this procedure.

Objective
This study aims to analyze the risk factors affecting the occurrence of complications during PIMSRA, such as pericardial effusion, ventricular premature beats, and interventricular septal perforation. In this study, the optimal cut-off values for these risk factors are also explored, and corresponding strategies for prevention are proposed.

Methods
A total of 101 patients diagnosed with HOCM who underwent the PIMSRA procedure from 2021 to 2022 were included in this retrospective analysis. Patients were classified into subgroups with or without complications based on procedural records. Univariate and multivariate regression analyses were conducted to identify independent risk factors for complications during the PIMSRA procedure.

Results
There were 48 patients with complications and 53 patients without complications. The heart rate at the start of the procedure and the maximum left ventricular outflow tract gradient (LVOTG) were independent risk factors related to PIMSRA complications. The optimal cut-off values for predicting complication occurrence were a heart rate > 49 bpm at the start of the procedure (OR: 3.79, 95% CI: 1.64–8.78, p = 0.002) and a maximum LVOTG > 92 mmHg (OR: 2.57, 95% CI: 1.15–5.75, p = 0.022), respectively.

Conclusions
The occurrence of PIMSRA complications is primarily associated with the heart rate at the start of the procedure and the maximum LVOTG. It is recommended to establish a comprehensive control plan to minimize the risk of complications during PIMSRA procedures.
Operator independent continuous ultrasound monitoring of diaphragm excursion predicts successful weaning from mechanical ventilation: a prospective observational study
Authors: Demoule Alexandre , Fossé Quentin , Mercat Alain , Bergum Daniel , Virolle Sara , Bureau Côme , Mellemseter Marit , Guichou Rafaël , Similowski Thomas , Dres Martin , Mortaza Satar 
Published: July 2024

Abstract
Background
In mechanically ventilated patients, diaphragm ultrasound can identify diaphragm weakness and predict weaning failure. We evaluated whether a novel operator-independent ultrasound-based medical device allowing continuous monitoring of the diaphragm (CUSdi) could reliably (1) measure diaphragm excursion (EXdi) and peak contraction velocity (PCVdi), (2) predict weaning outcome, and (3) approximate transdiaphragmatic pressure (Pdi).

Methods
In 49 mechanically ventilated patients, CUSdi was recorded during a 30-min spontaneous breathing trial (SBT), and EXdi and PCVdi were measured. In subgroups of patients, standard ultrasound measurement of EXdi and PCVdi was performed (n = 36), and Pdi derived parameters (peak and pressure time product, n = 30) were measured simultaneously.

Results
The agreement bias between standard ultrasound and CUSdi for EXdi was 0.1 cm (95% confidence interval -0.7–0.9 cm). The regression of Passing-Bablok indicated a lack of systematic difference between EXdi measured with standard ultrasound and CUSdi, which were positively correlated (Rho = 0.84, p < 0.001). Weaning failure was observed in 54% of patients. One, two and three minutes after the onset of the SBT, EXdi was higher in the weaning success group than in the failure group. Two minutes after the onset of the SBT, an EXdi < 1.1 cm predicted weaning failure with a sensitivity of 0.83, a specificity of 0.68, a positive predictive value of 0.76, and a negative predictive value of 0.24. There was a weak correlation between EXdi and both peak Pdi (r = 0.22, 95% confidence interval 0.15 – 0.28) and pressure time product (r = 0.13, 95% confidence interval 0.06 – 0.20). Similar results were observed with PCVdi.

Conclusions
Operator-independent continuous diaphragm monitoring quantifies EXdi reliably and can predict weaning failure with an identified cut-off value of 1.1 cm.
Trial registration clinicaltrial.gov, NCT04008875 (submitted 12 April 2019, posted 5 July 2019) and NCT03896048 (submitted 27 March 2019, posted 29 March 2019).
Effect of lung volume preservation during spontaneous breathing trial on successful extubation in patients receiving mechanical ventilation: protocol for a multicenter clinical trial
Authors: Subirà Carles , Rognoni Gina , Baquerizo Herbert , García Carolina , Cabañes Sara , de la Torre Maria , Quevedo Beatriz , Pedrós Cristina , Tizón Ana I. , Murillo Natalia , Parro Laura , Eiras Fernando , Rialp Gemma , Altaba Susana , González-Castro Alejandro , Pacheco Andrés F. , Bayoumi Pablo , Gómez-Medrano Norma , Vallverdú Imma , Higón Áurea , Navarro María D. , Falcón Alirio , Keough Elena , Arizo David , Martínez Juan F. , Durán Núria , Rodríguez Raquel , Popoviciu-Koborzan Melinda R. , Guerrero Isabel , Concha Pablo , Barral Patricia , Batlle Montserrat , Cano Sílvia , Garcia-Castrillon Silvia , Andorrà Xavier , Tua Yenifher , Arnau Anna , Fernández Rafael 
Published: July 2024

Abstract
Background
In standard weaning from mechanical ventilation, a successful spontaneous breathing test (SBT) consisting of 30 min 8 cmH2O pressure-support ventilation (PSV8) without positive end-expiratory pressure (PEEP) is followed by extubation with continuous suctioning; however, these practices might promote derecruitment. Evidence supports the feasibility and safety of extubation without suctioning. Ultrasound can assess lung aeration and respiratory muscles. We hypothesize that weaning aiming to preserve lung volume can yield higher rates of successful extubation.

Methods
This multicenter superiority trial will randomly assign eligible patients to receive either standard weaning [SBT: 30-min PSV8 without PEEP followed by extubation with continuous suctioning] or lung-volume-preservation weaning [SBT: 30-min PSV8 + 5 cmH2O PEEP followed by extubation with positive pressure without suctioning]. We will compare the rates of successful extubation and reintubation, ICU and hospital stays, and ultrasound measurements of the volume of aerated lung (modified lung ultrasound score), diaphragm and intercostal muscle thickness, and thickening fraction before and after successful or failed SBT. Patients will be followed for 90 days after randomization.

Discussion
We aim to recruit a large sample of representative patients (N = 1600). Our study cannot elucidate the specific effects of PEEP during SBT and of positive pressure during extubation; the results will show the joint effects derived from the synergy of these two factors. Although universal ultrasound monitoring of lungs, diaphragm, and intercostal muscles throughout weaning is unfeasible, if derecruitment is a major cause of weaning failure, ultrasound may help clinicians decide about extubation in high-risk and borderline patients.

Trial registration
The Research Ethics Committee (CEIm) of the Fundació Unió Catalana d’Hospitals approved the study (CEI 22/67 and 23/26). Registered at ClinicalTrials.gov in August 2023. Identifier: NCT05526053.