bluuebunny/crossref_metadata_2025 huggingface dataset:
Disparity in cognitive factors related to cancer screening uptake based on the theory of planned behavior
Authors: Mirzaei-Alavijeh Mehdi , Amini Mahin , Moradinazar Mehdi , Eivazi Mehdi , Jalilian Farzad
Published: July 2024

Introduction

Early detection of cancer is a highly effective way to decrease cancer-related deaths. The purpose of this study was to determine the disparity in cognitive factors related to cancer screening uptake based on the theory of planned behavior (TPB).

Methods

In this cross-sectional study, conducted in Kermanshah County, the west of Iran, during 2019, a total of 1760 people aged 30 to 75 years old, were randomly selected to participate voluntarily in the study. Participants filled out a questionnaire including the socio demographic variables, socioeconomic status (SES), TPB variables, and cancer screening uptake behaviors.

Results

The mean age of respondents was 45.28. 44.96% of the participants had undergone cancer screening at least once. Socioeconomic status (SES) and gender had the most significant impact on the disparity in cancer screening uptake, with contributions of 74.64% and 22.25% respectively. Women were 8.63 times more likely to be screened than men. Participants with a family history of cancer had a 2.84 times higher chance of being screened. Single individuals were significantly less likely to be screened compared to married individuals. The concentration index for attitude, subjective norms (SN), perceived behavior control (PBC), behavior intention, and cancer screening uptake was 0.0735, 0.113, 0.333, 0.067, and 0.132 respectively. Intention (Beta = 0.225 and P: < 0.001) is a significant predictor of cancer screening behaviors.

Conclusion

The findings of this study are highly valuable for health policymakers in Iran. They emphasize the significance of creating, executing, and assessing campaigns that promote intention, PBC and SN, particularly among disadvantaged individuals. By doing so, we can effectively decrease the disparity in cancer screening rates. It is crucial to prioritize men, single individuals, and disadvantaged groups in cancer screening promotion programs. This knowledge can be utilized to develop an intervention that is guided by theory and supported by evidence, with the aim of increasing cancer screening rates and minimizing disparities.
Public health education using social learning theory: a systematic scoping review
Authors: Liu Ting , Pang Patrick Cheong-Iao , Lam Chi-Kin
Published: July 2024

Background

Public health education (PHE) in social environments plays a crucial role in mitigating the impact of public health events, especially with the recent surge in global incidents. Social learning theory (SLT) provides a strong theoretical foundation for implementing PHE. The objective of this study is to conduct a systematic scoping review of PHE using SLT, synthesizing the target populations, types of research, main findings, and future directions.

Methods

The study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Extension for Scoping Review (PRISMA-ScR) guidelines. We conducted a comprehensive search of five electronic databases (Web of Science, Scopus, PubMed, ProQuest, and APA PsycInfo) for English articles related to PHE using SLT. Two reviewers independently screened the titles and abstracts. Descriptive statistics were utilized to analyze the characteristics of the articles included in the study, followed by a comprehensive narrative analysis of the results.

Results

Research on PHE using SLT mainly focuses on adolescents, students, special patients, and vulnerable populations. The study sample includes seven research types and nine commonly used experimental methods. Four modes of PHE using SLT are identified, along with four types of summarized research results.

Conclusion

PHE research based on SLT can be prioritized for preventing widespread infectious diseases, spreading fundamental public health information, and assisting patients with particular illnesses. To enhance the implementation of PHE, researchers and policymakers should integrate online and offline health education resources, ensure the accessibility of up-to-date information, and leverage digital technologies in PHE. More highly interactive and participatory health education courses will be established in social learning environments to encourage public participation in PHE.
Effect of pachinko parlour openings and closings on neighbourhood income-generating crimes in Japan: 6.5 years of observations
Authors: Yokotani Kenji , Abe Nobuhito , Yamamoto Tetsuya , Takamura Masahiro , Takahashi Hideyuki
Published: July 2024

Background

Electronic gambling machines (EGMs) in gambling venues cause gambling-related harm and are a public health concern. This study focused on pachinko parlours as gambling venues and income-generating crimes as gambling-related harm. We aimed to verify whether income-generating crime rates increase in proximity to pachinko parlours and during the opening and post-closing periods of pachinko parlours relative to the pre-opening periods.

Methods

We used crime records spanning 6.5 years, including data on the opening and closing days of pachinko parlours for 6.5 years. We also sampled the addresses of convenience stores, bowling alleys, and households with official land prices all over Japan. The dependent variable was the daily income-generating crime incidence rate. Areas within 0.5 km, 0.5–1 km, 1–5 km, and 5–10 km radii of the pachinko parlours were the independent variables. The pre-, opening-, and post-closing periods of the pachinko parlours were also independent variables. The covariates included the number of convenience stores and always open pachinko parlours near pachinko parlours. Data were analysed using an analysis of variance (ANOVA) and covariance (ANCOVA). We also used differences-in-differences analysis (DD) to reveal the increase in income-generating crime rates in neighbourhoods exposed to the opening or closing of pachinko parlours.

Results

The daily income-generating crime incidence rate was significantly higher in areas within 0.5–1 km and 1–5 km radii of pachinko parlours than in those within 0.5 km and 5–10 km radii of them. The daily income-generating crime incidence rate was also significantly higher during the opening and post-closing periods than during the pre-opening period, even when controlling for the number of convenience stores and always open pachinko parlours. In particular, fraud crime rates increased with the opening and closing of pachinko parlours.

Conclusions

The highest income-generating crime incidence rate was observed within a 0.5–1 km and 1–5 km radius of pachinko parlours. The opening of pachinko parlours also increased income-generating crime incidence rates, which increased after closing. Pachinko parlours are considered to be creating public harm because the corporate activities of these parlours make the youth in their neighbourhood perpetrators of fraud and older adults its victims. Future research should examine the current findings using official crime records.
Association of MRI findings with paraspinal muscles fat infiltration at lower lumbar levels in patients with chronic low back pain: a multicenter prospective study
Authors: Gu† Heyi , Hong† Jingrui , Wang Zhongwei , Chen Jiaxin , Yuan Feng , Jiang Yuanming , Yang Yingjuan , Luo Mingbin , Zhang Zhenguang , He Bo , Huang Yilong , Sun Li
Published: July 2024

Objective

In chronic low back pain (CLBP), the relationship between spinal pathologies and paraspinal muscles fat infiltration remains unclear. This study aims to evaluate the relationship between MRI findings and paraspinal muscles morphology and fat infiltration in CLBP patients by quantitative MRI.

Methods

All the CLBP patients were enrolled from July 2021 to December 2022 in four medical institutions. The cross-sectional area (CSA) and proton density fat fraction (PDFF) of the multifidus (MF) and erector spinae (ES) muscles at the central level of the L4/5 and L5/S1 intervertebral discs were measured. MRI findings included degenerative lumbar spondylolisthesis (DLS), intervertebral disc degeneration (IVDD), facet arthrosis, disc bulge or herniation, and disease duration. The relationship between MRI findings and the paraspinal muscles PDFF and CSA in CLBP patients was analyzed.

Results

A total of 493 CLBP patients were included in the study (198 females, 295 males), with an average age of 45.68 ± 12.91 years. Our research indicates that the number of MRI findings are correlated with the paraspinal muscles PDFF at the L4/5 level, but is not significant. Moreover, the grading of IVDD is the primary factor influencing the paraspinal muscles PDFF at the L4-S1 level (BES at L4/5=1.845, P < 0.05); DLS was a significant factor affecting the PDFF of MF at the L4/5 level (B = 4.774, P < 0.05). After including age, gender, and Body Mass Index (BMI) as control variables in the multivariable regression analysis, age has a significant positive impact on the paraspinal muscles PDFF at the L4-S1 level, with the largest AUC for ES PDFF at the L4/5 level (AUC = 0.646, cut-off value = 47.5), while males have lower PDFF compared to females. BMI has a positive impact on the ES PDFF only at the L4/5 level (AUC = 0.559, cut-off value = 24.535).

Conclusion

The degree of paraspinal muscles fat infiltration in CLBP patients is related to the cumulative or synergistic effects of multiple factors, especially at the L4/L5 level. Although age and BMI are important factors affecting the degree of paraspinal muscles PDFF in CLBP patients, their diagnostic efficacy is moderate.
Rare correlation of somatic PRKACA mutations with pregnancy-associated aldosterone- and cortisol-producing adenomas: a case report and literature review
Authors: Lin Jianfan , Li Yufei , Huang Zhenxing , Zhu Yingli , Li Li , Yang Haiyan , Liang Xinghuan , Qin Yingfen , Zhou Jia , Xian Jing , Liu Deyun , Lu Decheng , Luo Zuojie
Published: July 2024

Background

Somatic mutations have been observed to induce aldosterone-producing adenomas (APAs). These may be accelerated during pregnancy. Somatic PRKACA mutations are common in cortisol-producing adenomas (CPAs). However, their role in APAs, particularly aldosterone- and cortisol-producing adenomas (A/CPAs), is not well understood. This study aims to investigate the association between PRKACA mutations and the accelerated development of A/CPAs during pregnancy.

Case presentation

A patient with primary aldosteronism (PA) associated with severe Cushing’s syndrome (CS) underwent surgical resection of an adrenal tumor one year after delivery. Pathologic examination revealed an adrenocortical adenoma characterized primarily by zona glomerulosa hyperplasia. Somatic mutation analysis revealed the presence of the somatic PRKACA mutation, which was validated as a deleterious mutation by various computational databases. Immunohistochemical results showed positive staining for cytochrome P450 family 11 subfamily B member 1 (CYP11B1), cytochrome P450 family 11 subfamily B member 2 (CYP11B2), and luteinizing hormone/chorionic gonadotropin receptor (LHCGR). Our study included a review of 20 previously documented cases of aldosterone- and cortisol-producing adenomas (A/CPAs), two of which were concurrently positive for both CYP11B1 and CYP11B2, consistent with our findings.

Conclusion

Somatic mutations in PRKACA may correlate with the upregulation of LHCGR, which synergistically drives the accelerated growth of co-secretion tumors during pregnancy, thereby exacerbating disease progression.
Electronic oral health surveillance system for Egyptian preschoolers using District Health Information System (DHIS2): design description and time motion study
Authors: Abdelrahman Hams H. , Hamza Maha , Essam Wafaa , Adham May , AbdulKafi Abdulrahman , Baniode Mohammad
Published: July 2024

Background

Early childhood caries (ECC) is a major global health issue affecting millions of children. Mitigating this problem requires up-to-date information from reliable surveillance systems. This enables evidence-based decision-making to devise oral health policies. The World Health Organization (WHO) advocates the adoption of mobile technologies in oral disease surveillance because of their efficiency and ease of application. The study describes developing an electronic, oral health surveillance system (EOHSS) for preschoolers in Egypt, using the District Health Information System (DHIS2) open-source platform along with its Android App, and assesses its feasibility in data acquisition.

Methods

The DHIS2 Server was configured for the DHIS2 Tracker Android Capture App to allow individual-level data entry. The EOHSS indicators were selected in line with the WHO Action Plan 2030. Two modalities for the EOHSS were developed based on clinical data capture: face-to-face and tele/asynchronous. Eight dentists in the pilot team collected 214 events using modality-specific electronic devices. The pilot’s team's feedback was obtained regarding the EOHSS's feasibility in collecting data, and a time-motion study was conducted to assess workflow over two weeks. Independent t-test and Statistical Process Control techniques were used for data analysis.

Results

The pilot team reported positive feedback on the structure of the EOHSS. Workflow adaptations were made to prioritize surveillance tasks by collecting data from caregivers before acquiring clinical data from children to improve work efficiency. A shorter data capture time was required during face-to-face modality (4.2 ± 0.7 min) compared to telemodality (5.1 ± 0.9 min), p < 0.001). The acquisition of clinical data accounted for 16.9% and 21.1% of the time needed for both modalities, respectively. The time required by the face-to-face modality showed random variation, and the tele-modality tasks showed a reduced time trend to perform tasks.

Conclusions

The DHIS2 provides a feasible solution for developing electronic, oral health surveillance systems. The one-minute difference in data capture time in telemodality compared to face-to-face indicates that despite being slightly more time-consuming, telemodality still shows promise for remote oral health assessments that is particularly valuable in areas with limited access to dental professionals, potentially expanding the reach of oral health screening programs.
Using an internet-based platform to provide online and offline healthcare services for discharged patients
Authors: Cui Lei , Tong Zirong , Wang Rong , Fang Xiaoping , Liu Longxiu
Published: July 2024

Background

Continuing care is needed for the growing number of chronically ill patients who struggle with health problems after discharge. This study aims to elucidate the development process, functionalities, service protocols, and utilization of an Internet Plus Care (IPC) platform devised by our hospital to offer healthcare services to discharged patients.

Methods

This was a mixed study. After describing the development process, function and usage of IPC platform, we retrospectively collect data such as the general information of service recipients and service providers, service items, and service prices through the IPC platform from January 2021 to September 2023 to characterize these services.

Results

69 nurses delivered a total of 788 services to 211 patients through the IPC platform. The majority of services (N = 652, 82.7%) were delivered offline, with almost half of the recipients (N = 384, 48.7%) being elderly individuals. 46.4% of nurses provided services ≥ 3 times. Furthermore, 26.5% of patients received services three or more times. Notably, patients’ care requirements exhibited variations across age groups, with wound care (n = 243, 63.3%), pressure injuries care (n = 50, 13.0%), and replacement of indwelling nasogastric tubes (n = 20, 5.2%) emerging as the top three services favored by the elderly.

Conclusions

The IPC platform demonstrates potential in delivering diverse health services to patients; however, the involvement of nurses and patients needs to be enhanced. It is necessary to implement relevant safeguard policies to promote the effective use of IPC platform for health management of discharged patients in the future.

What does this paper contribute to the wider global clinical community?

The prevalence of chronic diseases is on the rise, and patients with chronic diseases continue to struggle with health problems after discharge and require extended treatment and rehabilitation. Our study proves that IPC platform presents a promising avenue for addressing these challenges.

It is anticipated that governmental authorities will undertake comprehensive policy, legislative, and medical insurance reforms to facilitate the extensive adoption of IPC platform-based services.
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

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

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

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

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

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

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

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

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

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

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.
Drug repurposing of pyrazolotriazine derivatives as potential anti-SARS-CoV-2 agents: in vitro and in silico studies
Authors: Oudah Khulood H. , Najm Mazin A. A. , Barghash Reham F. , Kutkat Omnia , GabAllah Mohamed , Albohy Amgad , Abouzid Khaled A. M.
Published: July 2024

The search for new molecules targeting SARS-CoV-2 has been a priority since 2020. The continuous evolution of new mutants increases the need for more research in the area. One way to find new leads is to repurpose existing drugs and molecules against the required target. Here, we present the in vitro and in silico screening of ten previously synthesized and reported compounds as anti-COVID 19 agents. The compounds were screened in vitro against VERO-E6 cells to find their Cytotoxic Concentration (CC50) and their Inhibitory Concentration (IC50). Compounds 1, 2, and 5 revealed a promising anti-SARS-CoV-2 of (IC50 = 2.4, 11.2 and 2.8 µM), respectively while compounds 3 and 7 showed moderate activity of (IC50 = 17.8 and 26.1 µM) compared to Chloroquine which showed an IC50 of 24.9 µM. Among tested compounds, 1 showed the highest selectivity (CC50/IC50) of 192.8. Docking, molecular dynamics and ADME studies were done to investigate potential interactions between compounds and SARS-CoV-2 targets as well as to study the possibility of using them as lead compounds.
Engineering cyanobacteria as a new platform for producing taxol precursors directly from carbon dioxide
Authors: Zhong Jialing , Wang Yushu , Chen Zhuoyang , Yalikun Yaliqin , He Lin , Liu Tiangang , Ma Gang
Published: July 2024

Taxol serves as an efficient natural anticancer agent with extensive applications in the treatment of diverse malignancies. Although advances in synthetic biology have enabled the de novo synthesis of taxol precursors in various microbial chassis, the total biosynthesis of taxol remains challengable owing to the restricted oxidation efficiency in heterotrophic microbes. Here, we engineered Synechocystis sp. PCC 6803 with modular metabolic pathways consisting of the methylerythritol phosphate pathway enzymes and taxol biosynthetic enzymes for production of taxadiene-5α-ol (T5α-ol), the key oxygenated intermediate of taxol. The best strain DIGT-P560 produced up to 17.43 mg/L of oxygenated taxanes and 4.32 mg/L of T5α-ol. Moreover, transcriptomic analysis of DIGT-P560 revealed that establishing a oxygenated taxane flux may enhance photosynthetic electron transfer efficiency and central metabolism in the engineered strain to ameliorate the metabolic disturbances triggered by the incorporation of exogenous genes. This is the first demonstration of photosynthetic production of taxadiene-5α-ol from CO2 in cyanobacteria, highlighting the broad prospects of engineered cyanobacteria as ﻿bio-solar cell factories for valuable terpenoids production and expanding the ideas for further rational engineering and optimization.
CREdb: A comprehensive database of Cis-Regulatory Elements and their activity in human cells and tissues
Authors: Hartl Chris , Zhuang Jiali , Tyler Aaron , Zhou Bing , Wong Emily , Merberg David , Farrell Brad , DeBoever Chris , Bryant Julie , Diogo Dorothée
Published: July 2024

Background

Cis-regulatory elements (CREs) play a pivotal role in gene expression regulation, allowing cells to serve diverse functions and respond to external stimuli. Understanding CREs is essential for personalized medicine and disease research, as an increasing number of genetic variants associated with phenotypes and diseases overlap with CREs. However, existing databases often focus on subsets of regulatory elements and present each identified instance of element individually, confounding the effort to obtain a comprehensive view. To address this gap, we have created CREdb, a comprehensive database with over 10 million human regulatory elements across 1,058 cell types and 315 tissues harmonized from different data sources. We curated and aligned the cell types and tissues to standard ontologies for efficient data query.

Results

Data from 11 sources were curated and mapped to standard ontological terms. 11,223,434 combined elements are present in the final database, and these were merged into 5,666,240 consensus elements representing the combined ranges of the individual elements informed by their overlap. Each consensus element contains curated metadata including the number of elements supporting it and a hash linking to the source databases. The inferred activity of each consensus element in various cell-type and tissue context is also provided. Examples presented here show the potential utility of CREdb in annotating non-coding genetic variants and informing chromatin accessibility profiling analysis.

Conclusions

We developed CREdb, a comprehensive database of CREs, to simplify the analysis of CREs by providing a unified framework for researchers. CREdb compiles consensus ranges for each element by integrating the information from all instances identified across various source databases. This unified database facilitates the functional annotation of non-coding genetic variants and complements chromatin accessibility profiling analysis. CREdb will serve as an important resource in expanding our knowledge of the epigenome and its role in human diseases.
Sex hormone binding globulin (SHBG) serum levels and insulin resistance in men on chronic hemodialysis
Authors: Nikolaou Evdokia , Tziastoudi Maria , Gougoura Sofia G. , Filippidis Georgios , Dousdampanis Periklis , Bargiota Alexandra , Mertens Peter Rene , Eleftheriadis Theodoros , Hadjigeorgiou Georgios M. , Koukoulis Georgios N. , Stefanidis Ioannis
Published: July 2024

Background

In males with end stage renal disease biochemical hypogonadism is a frequent finding. Testosterone and sex hormone binding globulin (SHBG) have been associated with insulin resistance, a well-known condition in uremia. The aim of the present study was to investigate in males on chronic hemodialysis the relationship of testosterone and SHBG serum levels with insulin resistance.

Methods

In a cross-sectional study we enrolled men treated with chronic hemodialysis who did not suffer from an acute illness or other endocrinopathy, as well as primary hypogonadism, and were not hospitalised. Diabetes mellitus, diabetic nephropathy or previous transplantation were not exclusion criteria. As controls we used a community-based group of healthy males matched for age and Body Mass Index (BMI). We assessed the BMI (kg/m2) from body weight and height, the body fat content (%) by bioelectrical impedance and serum testosterone (ng/ml), SHBG (nmol/L) and estradiol (pg/ml) by standard methods. Testosterone < 3.25 ng/ml defined biochemical hypogonadism. In non-diabetic males, we calculated the homeostasis model assessment index (HOMA-R), an estimate of insulin resistance, from serum fasting insulin and glucose.

Results

27 men (age 54.4 ± 19 years) on chronic hemodialysis (treatment duration 29.1 ± 14.4 months) and 51 healthy men (age 47.1 ± 9.6 years) were included. In men on hemodialysis vs. healthy men there were increased serum levels of SHBG (40.9 ± 26.9 vs. 27.6 ± 11.9 nmol/L; p = 0.031) and a significantly enhanced frequency of biochemical hypogonadism (22.2 vs. 3.9%; p = 0.011). In cases without diabetes (n = 22) a significant correlation was observed between the HOMA-R (r = -0.586, p = 0.004) and the fasting insulin levels (r = -0.650, p = 0.001) on the one hand and the serum SHBG levels on the other.

Conclusions

Our findings confirm enhanced prevalence of biochemical hypogonadism in males on chronic hemodialysis. In non-diabetic cases the serum levels of SHBG correlated with serum insulin and insulin resistance.