Acquired radioresistance remains a major obstacle to effective radiotherapy for cervical cancer, often driven by epithelial-mesenchymal transition (EMT). This study reveals TSPAN8 as a novel regulator of EMT-mediated radioresistance, offering new insights for overcoming treatment failure. Radioresistant subclones of HeLa-R25 and SiHa-R25 cells were established by repeated 2 Gy fractions. Radioresistance, apoptosis, EMT, and stemness were assessed by clonogenic survival, flow cytometry, immunoblotting, and immunofluorescence. Differentially expressed genes were identified by microarray, validated by protein-protein interaction analysis and co-immunoprecipitation, and functionally examined via TSPAN8 overexpression/knockdown, xenograft models, and immunohistochemistry of primary, metastatic, and recurrent post-radiotherapy specimens. Prognostic relevance was analyzed in the TCGA-CESC cohort. Fractionated irradiation induced EMT and radioresistance, with significantly higher clonogenic survival in R25 cells (P < 0.05), characterized by E-cadherin loss, N-cadherin/Vimentin upregulation, and increased CD44/Oct4. TSPAN8 was the most upregulated gene and directly interacted with E-cadherin. Overexpression enhanced EMT, invasion, and resistance to apoptosis, while knockdown reversed these effects and restored radiosensitivity in vivo. TSPAN8 knockdown in radioresistant xenografts significantly suppressed tumor growth (P < 0.05), and combined knockdown with irradiation further reduced tumor volume (P < 0.05). In patient samples, post-radiotherapy recurrences and metastases exhibited high TSPAN8 and vimentin with reduced E-cadherin. TCGA data confirmed that elevated TSPAN8 was associated with worse outcomes, including shorter disease-specific survival (HR = 2.02, 95% CI 1.01-3.71, P = 0.02) and progression-free survival (HR = 3.09, 95% CI 1.80-5.30, P < 0.001). These data suggest that TSPAN8 drives EMT-mediated radioresistance in cervical cancer, is associated with recurrence and poor survival, and represents a potential biomarker and therapeutic target. Targeting TSPAN8 may enhance radiosensitivity and improve personalized radiotherapy outcomes.

A close relationship exists between inflammation and cancer. Recent studies have highlighted inflammation as a significant contributor to the progression of bladder cancer. However, the role of alkyladenine DNA glycosylase homolog 2 (AlkBH2), an enzyme involved in DNA repair and a member of the AlkB family, in the context of bladder cancer inflammation remains largely unexplored. Our findings demonstrate that AlkBH2 promotes the proliferation, colony formation, migration, and invasion of bladder cancer cells. Mechanistically, AlkBH2 activates the nuclear factor-kappa B (NF-κB) signaling pathway, which in turn drives the progression of bladder cancer. These results suggest that AlkBH2 plays a critical oncogenic role in bladder cancer by modulating inflammation through the activation of the NF-κB pathway. These findings highlight the potential of AlkBH2 as a therapeutic target for bladder cancer treatment.

To evaluate the possible influence of gender and specialty on adverse drug reaction (ADR) reporting among physicians before and after the COVID-19 pandemic.

This retrospective nationwide register study analysed all ADR reports submitted by physicians to the Swedish Medical Products Agency during 2017 and 2023 (n = 4079 and 3740, respectively). The reporting rates were calculated and stratified by gender and specialty.

The highest reporting rate among physicians was observed in medical specialties, followed by primary care and psychiatry (27, 10, and 12, reports/100 physicians in 2017; 18, 15, and 9 in 2023). The lowest reporting rates were observed for surgical and hospital service specialties (8 and 1 in 2017; 6 and 1 in 2023). Male and female physicians reported ADRs to a similar extent and both reported more frequently on female patients. Gender concordance between physician and patient was associated with significantly higher reporting (p < 0.001 in 2017; p = 0.041 in 2023).

Reporting varied across specialties, and gender concordance emerged as a previously unrecognized factor influencing ADR reporting. These findings provide new opportunities for targeted interventions to enhance physician participation in pharmacovigilance.

There is limited high-quality data on antibiotic prescribing in low and middle-income countries, particularly in the private sector. Here, we use large-scale healthcare surveys to assess antibiotic prescribing levels and the factors influencing prescribing decisions for common infections in primary care and outpatient settings, predominantly within the private sector, in Pakistan, Egypt and Indonesia.

We analysed surveys completed by prescribers in Pakistan, Egypt and Indonesia, collected in primary care and outpatient settings, predominantly within the private sector, by IQVIA between 2017 and 2021, namely IQVIA's proprietary Medical Data Index (Medical Index of Pakistan (MIP), Egypt Medical Data Index (EMDI) and Indonesia Medical Data Index (IMDI)). IQVIA market research information reflects estimates of real-world activity and should be treated accordingly. We evaluated antibiotic prescribing categorised by WHO AWaRe and Essential Medicines List (EML) classifications for common infections. We used mixed-effects regression analyses to identify factors influencing prescribing decisions.

Among the 384 975 infection-related health consultation records analysed, antibiotics were prescribed in 82.0% of consultations in Pakistan, 81.2% in Egypt and 69.1% in Indonesia. Watch antibiotics accounted for 70.2% of antibiotic prescriptions in Pakistan, 52.9% in Egypt and 53.6% in Indonesia. Non-WHO EML antibiotics accounted for 26.8% of prescriptions in Pakistan, 39.9% in Egypt and 33.0% in Indonesia. Consultations for patients presenting with lower respiratory tract infections, urinary tract infections, multiple infections or differentiated fever had higher odds of receiving any or a Watch antibiotic. Consultations by respiratory-related specialists in Pakistan and Egypt and by most specialities in Indonesia were more likely to receive Watch antibiotics.

Similar patterns of high levels of total and Watch antibiotic prescribing for common infections-including those that generally do not require any antibiotics-were identified among prescribers in primary care and outpatient settings within the private sector in Pakistan, Egypt and Indonesia.

The aim of this study is to evaluate existing evidence on the effectiveness of amoxicillin and amoxicillin-clavulanate for community-acquired pneumonia in children and adults.

Systematic review and meta-analysis.

PubMed, Cochrane Library, Web of Science and Ovid-MEDLINER were searched with no language restrictions through 16 July 2024.

We included studies comparing the effectiveness of amoxicillin or amoxicillin-clavulanate versus other antibiotics or placebo.

Only randomised controlled trials comparing amoxicillin or amoxicillin-clavulanate with another antibiotic or placebo with a primary outcome of clinical resolution or clinical failure were eligible for our review. We used random-effects and fixed-effects logistic regression models to estimate the pooled treatment effect size. Heterogeneity of the studies was evaluated using the τ statistic. We performed an unplanned frequentist random-effects network meta-analysis for the indirect comparison between amoxicillin and amoxicillin-clavulanate. The revised Cochrane risk of bias tool for randomised trials was used to assess and categorise studies into low risk of bias, some concerns or high risk of bias.

We extracted data from 44 studies including 45 400 patients. We found no evidence of a differential effect on clinical resolution when comparing amoxicillin with other antibiotics (n=15 trials; pooled OR 0.88; 95% CI 0.56 to 1.38, where >1 favours amoxicillin) or amoxicillin-clavulanate with other antibiotics (n=17; OR 0.89; 95% CI 0.76 to 1.04). Similarly, evidence of difference in clinical failure between amoxicillin and other antibiotics was unclear and unable to rule out clinically important benefits or harms (n=8; OR 0.76; 95% CI 0.55 to 1.06, where <1 favours amoxicillin). We found no evidence of a differential effect on clinical resolution between adults treated with amoxicillin and amoxicillin-clavulanate (n=28; OR 1.04; 95% CI 0.64 to 1.70, where >1 favours amoxicillin-clavulanate). Sixty-three per cent and 29% of amoxicillin and amoxicillin-clavulanate studies, respectively, had low risk of bias according to the Cochrane risk of bias tool for randomised trials.

Current evidence is unclear as to whether amoxicillin or amoxicillin-clavulanate differs from other antibiotics, or from each other, in the treatment of community-acquired pneumonia, owing to the small number of trials and substantial heterogeneity in comparators used across study settings.

CRD42024568554.

In Australia, asthma is the most common chronic childhood disease, with prevalence and care varying across communities. In three local government areas (LGAs) in Melbourne's inner west, we compared childhood asthma-related emergency department (ED) visits to Victoria overall, and explored parents' perceived enablers and barriers to community-based asthma care.

We used an administrative dataset (2007-19) and a cross-sectional survey of parents across six primary schools in the three LGAs (2022-23). Descriptive analysis was conducted to present childhood asthma-related ED rates, and asthma control, management practices, parental perceived asthma care enablers and barriers. Differences in these measures across LGAs were also examined.

Childhood asthma-related ED visit rates were 26-53% higher in the three LGAs compared with Victoria overall. Parents (n = 545) identified general practitioners (GPs), pharmacists and EDs as the most helpful resources, but faced barriers to community-based asthma care, such as fear during asthma flare-ups, difficulty accessing GPs, and concerns about medication side effects.  DISCUSSION: Melbourne's inner west has disproportionately higher asthma-related ED presentation rates. This warrants further investigation and development of strategies to improve community-based asthma care and reduce triggers, including air pollution.

Over the last 3 decades, Australian general practice has undergone profound digital transformation. From handwritten prescriptions and paper files to comprehensive practice management systems, each technological wave has promised efficiency while introducing new layers of complexity.

Over the last 3 decades, Australian general practice has undergone profound digital transformation. From handwritten prescriptions and paper files to comprehensive practice management systems, each technological wave has promised efficiency while introducing new layers of complexity.

The COVID-19 pandemic acted as a catalyst, embedding telehealth and e-prescriptions as core elements of routine care. The emergence of cloud systems and artificial intelligence represents a new frontier, offering opportunities to streamline workflows and refocus care on the patient. Drawing lessons from past implementation efforts, this paper argues that success will depend on designing technologies grounded in usability, interoperability, equity and trust to ensure that innovation strengthens rather than fragments the therapeutic relationship.

The spread of misinformation during the COVID-19 pandemic highlighted the importance of evidence-based information. The SANGYAN podcast promotes evidence-based knowledge on health-related issues in multiple languages in a simple, cost-effective, and concise manner. This provides individuals access to the appropriate information in an accessible manner.

The study's goal is to assess user preferences for health information on a digital health platform designed to address COVID-19 misinformation.

SANGYAN was developed by integrating the principles of social cognitive theory and information processing theory. The SANGYAN podcast was created to promote the importance of evidence-based information in order to address the spread of misinformation. The study design was a quasi-experimental study; prior to introducing the SANGYAN podcast, participants' sociodemographic information was collected, and health literacy was assessed using the Rapid Estimate of Adult Literacy in Medicine, Revised scale. After listening to the podcast, participants were interviewed about its usability, and they completed the System Usability Scale and the Client Satisfaction Questionnaire - 8. Data were collected from a total of 500 participants, 250 each from the Rural Health Training Center and Panimalar Medical College Hospital & Research Institute. The participants were older than 18 years when they were included. Descriptive and bivariate analyses were performed.

A total of 500 participants were enrolled in the study, 50% (250/500) from rural areas and 50% (250/500) from urban areas. The majority of the participants were 45 years to 64 years old (155/500, 31%), were women (289/500, 57.8%), had poor health literacy (384/500, 76.8%), and had a high school education or less than a high school certification (241/500, 48.2%). The mean overall System Usability System score was 70.9 (SD 17.73), with those aged 18 years to 24 years having the highest mean score (81.2, SD 15.48). High user satisfaction was present, with 97.6% (487/499) obtaining the desired information from the platform.

The study revealed that the SANGYAN podcast provides information to diverse individuals, as it is multilingual, and was found useful by the participants.

This study aims to describe the epidemiology, clinical features, microbiology and management of paediatric patients (<18 years) admitted to Christchurch Hospital with periorbital or orbital infections over a 10-year period.

A retrospective review was conducted of all patients under 18 years admitted with periorbital and orbital infections between 2013 and 2023. Cases were identified using surgical theatre records and discharge coding, with data extracted from electronic medical records. Clinical, demographic, microbiological and management data were analysed descriptively.

A total of 495 paediatric cases were identified, with 93% presenting with periorbital cellulitis and 7% with orbital cellulitis. Sinusitis was the predominant predisposing factor for postseptal disease, present in 83% of those cases. Orbital signs such as proptosis, pain with eye movement, reduced visual acuity and ophthalmoplegia were more frequent in orbital cellulitis. Orbital cases had longer hospital stays with a median of 4.5 days (range 2-33 days) compared to periorbital disease with a median of 1 day (range 0-8 days). Orbital cases also had a higher rate of surgical intervention (47%), most commonly functional endoscopic sinus surgery. Staphylococcus aureus was the most frequently isolated organism in both groups (45% periorbital, 42% orbital). Māori and Pacific children were disproportionately affected (comprising 20% and 10% respectively of periorbital cases and 17% and 19% of orbital cases).

The presence of orbital signs should prompt urgent imaging to exclude orbital disease. Sinusitis remains a key risk factor for orbital cellulitis, and Māori and Pacific children are disproportionately affected.

The expansion of telehealth services, particularly during the COVID-19 pandemic, has transformed health care delivery in the United States. Telehealth promises greater access and resource efficiency by reducing wait times and appointment lengths, especially in specialties like psychiatry, behavioral health, bariatrics, and sleep medicine. However, disparities exist in adoption based on demographics, geography, and socioeconomic status, raising concerns about equitable access and optimal resource use.

This study aims to evaluate how telehealth impacts health care resource use across 4 specialties by examining 2 key metrics: patient-to-provider ratios and appointment durations. It seeks to understand how factors such as patient demographics, facility characteristics, and social determinants influence telehealth adoption and efficiency using a national dataset spanning from 2018 to 2023.

We analyzed a deidentified dataset from Epic Cosmos, covering outpatient visits across 48 US states (2018-2023). After data preprocessing and feature engineering, we applied 3 machine learning (ML) models (random forest, extreme gradient boosting, and deep neural networks) to predict resource use. Using the model performing the best, feature importance was assessed using Shapley Additive Explanations values. We then used k-means clustering to group facilities into clusters per specialty. Comparative analyses were conducted to evaluate differences in use among clusters, during and after the pandemic.

Telehealth use peaked in 2020 and has remained above prepandemic levels since then. In 2018-2023, telehealth adoption reached 36.9% (4,543,021/12,311,710) in psychiatry, 23.9% (5,321,099/22,264,013) in behavioral health, 21.2% (924,333/4,360,061) in bariatrics, and 16.8% (851,803/5,070,256) in sleep medicine. Telehealth visits were consistently shorter than office visits (mean reduction 12.24 minutes; SD 3.33 minutes; P=.18), while patient-to-provider ratios varied significantly across specialties. Among ML models, extreme gradient boosting regression achieved the best performance (patient-to-provider ratios: R²=0.96-0.99; appointment durations: R²=0.61-0.69). Shapley Additive Explanations analysis identified visit type, telehealth use, facility size, rurality, and Social Vulnerability Index household vulnerability as the strongest predictors. Comparative analyses showed significant differences across clusters (all P<.05).

Telehealth has become a sustainable component of health care, enhancing access and efficiency across both rural and urban areas. However, its impact varies across specialties and regions, highlighting the need for targeted strategies such as staffing support for vulnerable populations, infrastructure investments in rural facilities, and reimbursement models that reflect telehealth's resource use. This study provides robust evidence from ML and clustering analyses, demonstrating how telehealth shapes resource use and offering actionable insights for equitable and sustainable integration.