Aim: Polypharmacy is a major health concern among older adults and is associated with increased vulnerability and adverse health outcomes. However, limited evidence exists regarding its association with sensory, oral, and dietary functions. This study examined the effects of polypharmacy on these functions using nationally representative data from the 2023 Korean Elderly Survey.

Methods: A total of 10,078 community-dwelling adults aged ≥ 65 years were analyzed. Polypharmacy was defined as the use of five or more medications. Sensory function (vision and hearing), oral function (chewing difficulty, swallowing difficulty, denture use, unmet dental needs), and dietary intake (meal frequency, fruit and vegetable consumption) were assessed using structured questionnaires. Chi-square tests and logistic regression analyses were performed. Model 1 adjusted for demographic factors, and Model 2 additionally adjusted for the number of chronic diseases.

Results: Older adults with polypharmacy showed substantially poorer sensory and oral function than those without polypharmacy. Higher prevalence was observed for vision difficulty (60.5% vs. 40.6%), hearing difficulty (48.7% vs. 20.6%), chewing difficulty (58.9% vs. 30.1%), swallowing difficulty (20.9% vs. 6.7%), and unmet dental care needs (9.6% vs. 3.0%) (all p < 0.001). In the fully adjusted model, polypharmacy remained significantly associated with hearing difficulty, chewing difficulty, swallowing difficulty, denture use, and unmet dental care needs. However, associations between polypharmacy and dietary intake indicators were not statistically significant after adjustment.

Conclusions: Polypharmacy is significantly associated with hearing and oral functional impairments among older adults, and these associations were attenuated but not fully explained after adjusting for chronic disease burden. These findings highlight the importance of comprehensive geriatric assessment and multidisciplinary care that integrates medication management and oral health. Strategies promoting rational prescribing and monitoring of functional outcomes are essential to mitigate the adverse effects of polypharmacy and support healthy aging.

Background: Irreversible pulpitis is commonly associated with reduced success of inferior alveolar nerve block (IANB) during root canal treatment, often leading to inadequate intraoperative pain control. Inflammatory mediators can decrease local anesthetic effectiveness and alter nerve response. Preoperative administration of anti-inflammatory drugs has been proposed as a strategy to improve anesthetic success. This review evaluates whether preoperative anti-inflammatory medication enhances the efficacy of IANB in patients with irreversible pulpitis.

Methods: Thirteen articles published between 2014 and 2024 were included in the qualitative analysis following a screening of titles, abstracts, and full texts. The quality of the studies was assessed using the ROBINS tool.

Results: Premedication with non-steroidal anti-inflammatory drugs or corticosteroids significantly improves the success of IANB in patients with symptomatic irreversible pulpitis. Success rates in treated groups generally range between 55% and 73%, compared to less than 40% in control groups. Ibuprofen, ketorolac, and dexamethasone were among the most effective agents.

Discussion: Premedication with non-steroidal anti-inflammatory drugs or corticosteroids, especially ibuprofen and dexamethasone, improves the efficacy of IANB in symptomatic irreversible pulpitis, enhancing anesthetic success and reducing intraoperative pain.

Aim: Interobserver variability continues to limit the consistency of breast ultrasound interpretation. This study compares two Vision Transformer (ViT) models and two Convolutional Neural Network (CNN) models for automated three-class breast ultrasound classification, with a specific focus on the tradeoff between predictive performance and computational efficiency.

Methods: Swin Transformer Base and DeiT Base were evaluated alongside InceptionV3 and MobileNetV3 Large using the public Breast Ultrasound Images (BUSI) dataset, which contains 780 images labeled as benign, malignant, and normal. A consistent on-the-fly augmentation pipeline was applied during training to promote robustness and reduce sensitivity to incidental image variations.

Results: Swin Transformer Base achieved the highest test accuracy (0.9167) and F1 score (0.8981). MobileNetV3 Large reached an accuracy of 0.8583 with substantially lower computational demand. The efficiency contrast was pronounced, with Swin requiring 30.33 GFLOPs versus 0.43 GFLOPs for MobileNetV3 Large.

Conclusions: On this benchmark, ViT models can yield higher classification performance, while lightweight CNNs offer a strong efficiency profile that may better match deployment-constrained settings. These results suggest that model selection should be guided by both predictive accuracy and operational feasibility within the target clinical workflow.

Cardiovascular disease remains the leading cause of global mortality with nearly 19 million deaths annually, while exponential growth in multimodal imaging, continuous monitoring, and electronic health record data has created analytical challenges exceeding traditional methods. This narrative review examines artificial intelligence (AI) and machine learning (ML) applications in cardiovascular medicine through a comprehensive literature analysis from 2019 to 2025, focusing on clinical validation and regulatory approvals. Current applications demonstrate significant clinical utility: automated ECG interpretation achieves > 90% accuracy in arrhythmia detection and predicts life-threatening arrhythmias up to two weeks before clinical onset; deep learning cardiac imaging analysis matches expert performance while reducing analysis time from 45 minutes to under 5 minutes; and ML risk prediction outperforms traditional scores with area under the curve values of 0.865 vs. 0.765. The FDA has approved 122 cardiology AI algorithms representing 14% of all clinical AI in the U.S. market, including ECG interpretation, echocardiographic measurement, and imaging analysis systems. Real-world implementations demonstrate 15–25% reductions in diagnostic errors and 20–30% faster emergency intervention times. However, substantial challenges persist: data quality limitations, algorithmic bias with 10–15% performance variation across populations, workflow integration barriers, and validation requirements. Future directions include multimodal systems, continuously learning algorithms, precision medicine applications, and equitable global implementation. Successful integration requires addressing limitations through diverse training datasets, transparent development, standardized validation, provider education, and maintaining physician autonomy. AI and ML represent powerful augmentation tools that, through evidence-based implementation, can transform cardiovascular care while preserving clinical expertise in decision-making.

Diabetes mellitus is one of the biggest public health issues of modern society, with a constant increase in prevalence. It is a complex metabolic disorder characterized by hyperglycemia, dyslipidemia, and impaired insulin signaling, leading to redox imbalance and, consequently, blood vessel dysfunction. One of the key factors in the regulation of vascular tone and contractility is the sodium/potassium adenosine triphosphatase (Na⁺/K⁺-ATPase), whose reduced expression and altered activity contribute to the development of vascular dysfunction in type 2 diabetes (T2D). Impaired redox balance and increased production of reactive oxygen species, which directly affect Na⁺/K⁺-ATPase activity, also affect the telomere-telomerase system, leading to telomere shortening, DNA damage, and cell apoptosis. Hyperbaric oxygen therapy is used to treat ischemic lesions and vascular complications of diabetes, but the molecular mechanisms underlying its effects on Na⁺/K⁺-ATPase and telomere length in T2D patients remain incompletely elucidated.

Large language models (LLMs) like ChatGPT are increasingly used in drafting scientific papers. While they can improve clarity and efficiency, a troubling issue has emerged: the inclusion of fabricated references-nonexistent citations that can mislead, especially in biomedical research where evidence integrity is crucial. Studies indicate that 69% of references in ChatGPT’s medical queries are false, and only 7% of AI-generated medical articles contain accurate references. These fake citations often mimic real authors and journals, making detection difficult. Such inaccuracies can compromise research integrity, skew citation metrics, and reduce trust in scientific literature. To address this, journals are adopting policies requiring disclosure of AI use and human verification of references. Nonetheless, detecting AI-related misinformation remains challenging, and many experts believe the problem is bigger than currently known. Going forward, authors should avoid relying solely on LLMs, and reviewers must scrutinize references carefully. The scientific community needs to balance AI’s usefulness with rigorous oversight, ensuring that the pursuit of efficiency doesn't undermine credibility. Ultimately, safeguarding research from AI-generated misinformation will require combined efforts of transparency, vigilance, and adherence to ethical principles, preserving the integrity of biomedical science.

Background: Climate change-driven wildfires are increasing in frequency and intensity. The 2025 Manitoba wildfire season, which burned over one million hectares, exposed rural and Indigenous lung cancer patients undergoing radiation therapy to unprecedented levels of fine particulate matter (PM_2.5) and triggered widespread evacuations, severely threatening treatment continuity and outcomes. This systematic review examines the evidence (2010–2023) on the impact of wildfire smoke exposure on radiation oncology outcomes in rural and Indigenous lung cancer patients, with particular attention to its applicability to the Manitoba context.

Methods: PRISMA-guided systematic review of PubMed, Scopus, and Web of Science (1 January 2010–31 July 2025). Studies were included if they addressed wildfire smoke or PM_2.5 exposure, lung cancer, radiation therapy outcomes, and rural or Indigenous populations. Quality was assessed using the Newcastle-Ottawa Scale for observational studies and CASP checklists for reviews/qualitative studies. Findings were narratively synthesized.

Results: Fifteen moderate-to-high-quality studies were included (four cohort, two qualitative, five reviews, two meta-analysis, one scoping review, one observational). Wildfire-derived PM_2.5 exacerbates radiation-induced lung toxicities (e.g., pneumonitis reported in up to 30% of thoracic radiotherapy patients) via oxidative stress and inflammation. High PM_2.5 exposure is linked to increased mortality/complications (adjusted OR 1.15, 95% CI 1.05–1.26) and respiratory hospitalizations (RR 1.12, 95% CI 1.07–1.18). Treatment interruptions exceeding 7 days-common during wildfire evacuations-reduce local control by ~10% and elevate mortality risk (HR 1.14, 95% CI 1.03–1.26). Rural and Indigenous patients experience disproportionate barriers, including limited healthcare access, long travel distances, socioeconomic constraints, and culturally insensitive services.

Discussion: Wildfire smoke significantly worsens radiation therapy outcomes in rural lung cancer patients through synergistic pulmonary toxicity and treatment disruptions. No Manitoba-specific studies were identified, highlighting a critical evidence gap. Urgent interventions are needed: mobile radiation units, subsidized high-efficiency air filtration, culturally safe care models, telehealth expansion, and province-specific research to address climate-related health inequities in radiation oncology.

Background:The increasing use of electronic cigarettes and heated tobacco products has raised concerns regarding their potential effects on periodontal health. The objective of this systematic review was to assess the impact of these alternative nicotine delivery systems on periodontal inflammation, oral microbiota, and outcomes of non-surgical periodontal therapy.

Methods: A comprehensive literature search was conducted in PubMed, Web of Science, and Scopus, in accordance with PRISMA guidelines.

Results: The findings indicate that although electronic cigarettes and heated tobacco products may reduce exposure to certain harmful constituents compared with conventional cigarettes, they are not free of adverse effects. Their use has been associated with increased levels of pro-inflammatory cytokines, reduced anti-inflammatory mediators, delayed periodontal healing, and alterations in oral microbiota composition, which may contribute to the progression of periodontal disease. These biological changes may negatively influence the response to non-surgical periodontal therapy.

Discussion: From a clinical perspective, individuals using electronic cigarettes or heated tobacco products tend to exhibit less favorable treatment outcomes, often comparable to those observed in conventional cigarette smokers. Despite being promoted as harm-reduction alternatives, current evidence suggests that electronic cigarettes and heated tobacco products still pose significant risks to periodontal tissues. Overall, the available biological and clinical evidence supports the need for further investigation into the underlying mechanisms of tissue damage and reinforces the importance of promoting complete smoking cessation, including avoidance of electronic cigarettes and heated tobacco products, to preserve long-term oral health.

Opioid use disorder (OUD) is an emerging clinical and public health concern in cancer care. Although opioids remain essential for cancer pain management, a substantial subset of patients develops OUD, including many iatrogenic cases. This scoping review (ScR) synthesized evidence on the epidemiology, risk factors, screening approaches, and multidisciplinary management of OUD in adults with cancer. The review followed Joanna Briggs Institute (JBI) and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)-ScR guidelines. Four databases (PubMed, Medline, Scopus, ScienceDirect) were searched for English language randomized trials, quasi-experimental studies, and observational studies published from 2019–2025. Eligible studies included adults aged ≥ 18 years with cancer. Two independent reviewers conducted the study selection (OA and YI). The search identified 1,044 records; 403 abstracts were screened; 164 full-texts were assessed; and 46 studies met the inclusion criteria. OUD prevalence averaged 8% (range 6–50%), with 23.5% of patients classified as at risk. New persistent opioid use occurred in 19% within 8 weeks. Postoperative persistent opioid use was 33.3% overall, higher among patients with prior opioid exposure (48.3%) than opioid-naive individuals (18.5%). Reported risk factors included prior opioid use, younger age, male sex, substance use history, anxiety, and financial distress. Screening tools identified approximately 20% of patients as high risk. Multidisciplinary interventions-including buprenorphine/naloxone treatment and structured monitoring-were effective in managing concurrent cancer pain and OUD. OUD in cancer populations is preventable and manageable through systematic risk assessment and integrated multidisciplinary care. Early screening with validated tools, structured monitoring, and compassionate communication support safe opioid use while maintaining adequate analgesia. Evidence supports expanding access to medication-assisted therapies, psychosocial support, and harm-reduction strategies. These findings provide a foundation for improving clinical outcomes and guiding future research.

Background:Transcatheter mitral valve intervention, including repair (e.g., edge-to-edge repair) and replacement, is now a cornerstone of treatment for severe mitral regurgitation (MR) in high-risk patients, providing a less invasive alternative to surgical treatment. The purpose of this systematic review is to assess the efficacy and safety of different antithrombotic strategies to prevent thromboembolic events and bleeding complications after transcatheter mitral valve repair (TMVR).

Methods: According to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a systematic literature search on PubMed, Embase, Web of Science, Scopus, and Cochrane Library was conducted from January 2015 to January 2025. Eligible studies included adult patients who underwent transcatheter mitral valve intervention (including repair and replacement procedures) and compared different antithrombotic regimens, including direct oral anticoagulants (DOACs), vitamin K antagonists (VKAs), and antiplatelet therapies. Two reviewers independently extracted data and assessed quality. The studies were too heterogeneous, so a narrative synthesis was performed.

Results: Fifteen studies involving 20,956 patients were included. DOACs were associated with a lower risk of major bleeding compared to VKAs [hazard ratio (HR): 0.21, p = 0.02, in one large study], with similar rates of stroke. Mortality was lower with DOACs in several analyses (e.g., HR: 0.67). Triple therapy and dual antiplatelet therapy (DAPT) were associated with increased bleeding risk without providing additional thromboembolic protection.

Discussion: DOACs have a safer profile in post-TMVR patients, with reduced bleeding risk and lower mortality compared with VKAs. Triple therapy and DAPT should only be used in high-risk patients with specific indications due to their greater risk of bleeding. Optimizing outcomes requires a tailored approach to antithrombotic therapy, considering patient factors and procedural considerations. Definitive standards may still demand further investigation, such as multicenter randomized controlled trials evaluating antithrombotic treatments after TMVR.

New guidelines for high blood pressure (BP) by the European Society of Cardiology (ESC) now consider BP of 120–140/70–90 mmHg to be elevated (“high”) BP and recommend pharmacotherapy for BP > 130/80 mmHg if the estimated 10-year risk of cardiovascular events exceeds 10%, regardless of age. These recommendations are given with reference to two meta-analyses, but the studies included in the referred meta-analyses lack direct relevance, as patients in the first meta-analysis had established hypertension and several cardiovascular risk conditions. Further, the estimation of risk levels in the second meta-analysis was not done a priori with the recommended SCORE2 risk tool, but through a post hoc analysis of cardiovascular death in the placebo group. We argue that no randomized study has provided BP treatment based on such risk algorithms, nor from healthy participants with “elevated BP” (120–139/70–89 mmHg). A further problem is the use of a fixed risk threshold of 10% regardless of age, which will shift treatment to older patients without any major risk factors, while younger individuals with early onset of high BP and other metabolic syndrome characteristics usually will have a 10-year estimated cardiovascular risk far below this threshold, thus treatment may be delayed. This concept of the 2024 ESC hypertension guidelines is not evidence-based and should, in our opinion, not be implemented in Norway or in any other country. Norwegian doctors should follow the National Directorate of Health’s guidelines with age-adjusted intervention thresholds and consult European Society of Hypertension guidelines if they need to consider more extensive patient recommendations.

At the beginning of COVID-19 pandemic, due to the lack of guidance from evidence-based medicine on how to treat the infected patients, the medical class faced significant difficulties, not only with the unknown infection but also with the great number of cases. This led to a great number of hospitalizations and deaths. It would have been necessary to try drugs already available on the market, which might be effective against SARS-CoV-2. This is a short review of studies in the scientific literature dealing with the use of indomethacin as an antiviral drug against SARS-CoVs. We revised studies taken from the scientific literature in PubMed, Science Direct, Scopus, ResearchGate, Google Scholar etc., describing the effects of indomethacin as an antiviral drug against SARS-CoVs. To search for studies, we used the keywords: SARS-CoV, off-label drug, pandemic emergence, repurposed drug, Absence of EBM, Antiviral, Indomethacin, and Mechanisms. Among the studies reviewed, there is an interesting experimental study, published in 2006 by an Italian group, which considered the problem at the time of the previous SARS-CoV epidemic, that clearly demonstrated an antiviral effect of indomethacin, both in vitro and in vivo, against SARS-CoV. Two other studies, both clinical, one retrospective observational, and the other a prospective randomized trial comparing indomethacin with paracetamol, also showed good effects of indomethacin in the treatment of patients with COVID-19. On the basis of these notices, we wonder why, in such an emergency situation, indomethacin was not taken into consideration and was not tried in the treatment of COVID-19.

Acute paraplegia is a frequent and high-stake presentation in emergency departments. Spinal cord compression (SCC), particularly malignant epidural SCC, is a common oncologic emergency requiring urgent intervention, whereas Guillain-Barré syndrome (GBS) is a rarer but potentially life-threatening autoimmune polyradiculoneuropathy. Early differentiation between these conditions is essential, as delays in diagnosis and treatment are associated with irreversible neurological deficits and increased morbidity. Our objective is to synthesize recent evidence on the pathophysiology, clinical presentation, diagnosis, and management of SCC and GBS, with emphasis on early differentiation and multidisciplinary care strategies in emergency and rehabilitation settings. A scoping review was conducted following the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) guidelines. Electronic databases (PubMed, MEDLINE, Scopus, ScienceDirect, and CINAHL) were searched for English language studies published between January 2020 and June 2025. The review focused on clinical studies and reports addressing early differentiation and multidisciplinary management of SCC and GBS in emergency settings. Nineteen studies met the inclusion criteria. The review found that GBS diagnosis relies heavily on recognizing progressive symmetric weakness and preceding infectious triggers, while SCC requires immediate imaging and prompt corticosteroid administration. The limited number of studies highlights a gap in integrated emergency protocols for distinguishing these conditions. Surgical decompression remains the cornerstone of SCC management, with emerging evidence suggesting potential benefits even beyond the traditional 24-h window. This scoping review reinforces the critical need for early differentiation between SCC and GBS. Although the available literature is limited, it underscores the importance of coordinated multidisciplinary care. Clinicians must remain attentive to evolving diagnostic algorithms, particularly in light of new evidence supporting extended surgical windows for SCC.

Aim: This study aimed to develop and evaluate a stacking ensemble machine learning (SEML) model that integrates deep learning (DL) algorithms to improve the accuracy of prognostic predictions for patients with head and neck squamous cell carcinoma (HNSCC).

Methods: A cohort of 215 HNSCC patients’ CT images, featuring gross tumor volume (GTV) and planning target volume (PTV) contours, was analyzed. Radiomics features were extracted and converted into quantitative data. These features were then used to train and compare a novel SEML model against standard DL algorithms to predict patient prognosis.

Results: The proposed SEML model demonstrated superior predictive performance compared to the DL model, achieving 93% accuracy, 100% sensitivity, and 83% specificity. Statistical analysis using the chi-square test indicated no substantial difference in prediction performance between features derived from GTV and PTV contours (p > 0.05).

Conclusions: The SEML model effectively enhances the prognostic prediction accuracy for HNSCC based on radiomic features. This approach shows significant potential to inform clinical decision-making and support the development of customized treatment strategies for improved patient care.

The biopsychosocial model is the prevailing framework for chronic orofacial pain (COP). While COP is a heterogeneous clinical entity involving nociceptive and neuropathic components, it is increasingly defined by its nociplastic features-a systemic, non-nociceptive state in which psychological factors significantly influence symptoms. Current research frequently suffers from the conflation of constructs. Psychosocial predictors (e.g., self-efficacy) and outcome measures (e.g., pain interference) are often conceptually inseparable. To advance beyond this, we advocate for the integration of the brain-heart axis (BHA). The BHA provides objective, quantifiable markers of autonomic nervous system (ANS) dysregulation, the physical manifestation of chronic stress rooted in large-scale brain network imbalance. The present study proposes a theoretical framework in which psychological distress is reflected in corrected QT interval (QTc) changes, while low self-efficacy is mirrored by reduced heart rate variability (HRV). This integration is supported by the neurochemical roles of N-methyl-D-aspartate (NMDA) receptors in central sensitization and dopamine D2 receptor dysfunction in the basal ganglia. The present paper delineates a framework for research and clinical implementation within advanced dental training.

Background:Obstructive sleep apnea (OSA) is a syndrome characterized by episodes of complete cessation of breathing (apnea) or inadequate breathing (hypopnea) during sleep.

Methods: A systematic search of PubMed, Cochrane Library, Embase, Scopus, Web of Science, and Lilacs databases was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We identified 1,532 records; after screening, 9 randomized controlled trials (RCTs), published between 2009 and 2020, met the inclusion criteria. These studies included 698 participants aged 5–75 years.

Results: Nine randomized trials (n = 698; 2009–2020) showed that myofunctional therapy (MFT), alone or as an adjunct, for example, continuous positive airway pressure (CPAP) and nasal washing, reduced apnea-hypopnea index (AHI) versus control in adults and children. Snoring intensity improved in trials that measured it; several studies reported gains in oxygen saturation and mouth-breathing reduction. Protocols targeted the soft palate, tongue, and facial muscles with daily home exercises.

Discussion: MFT appears to be a promising non-invasive treatment for reducing AHI, especially in pediatric patients. Its benefits extend beyond AHI reduction, supporting orofacial function and nasal breathing. However, its clinical integration remains limited due to a lack of standardized protocols and inconsistent reporting of patient adherence. Most studies also have short follow-up periods, which makes it difficult to assess long-term efficacy. To advance evidence-based use of MFT, future research should adopt standardized outcomes, monitor adherence systematically, and include long-term follow-up.

Idiopathic pulmonary fibrosis (IPF) is a progressive, fatal interstitial lung disease of undefined etiology. In recent years, its global incidence has shown an upward trend, with a median survival of approximately 3–5 years after diagnosis. Currently, clinical treatment outcomes for this disease remain limited. Approved therapeutic agents are nintedanib, pirfenidone, and nerandomilast, all of which are predominantly administered orally. The oral route renders drugs susceptible to degradation in the gastrointestinal tract, leading to reduced drug bioavailability and limited therapeutic efficacy. In this work, we believe that nanodelivery systems (NDSs) represent a promising approach to address the limitations of traditional therapies. Most importantly, we emphasized that inhalation NDSs should be prioritized to enhance the accumulation efficiency of targeted drugs at pulmonary lesion sites. Collectively, this study aims to provide insights into the developmental prospects of NDSs for IPF, paving the way for more efficient and personalized therapeutic approaches to enhance treatment efficacy while minimizing side effects.

Aim: Polypharmacy is increasingly prevalent among older adults and has been suggested as a potential risk factor for adverse health outcomes, including cognitive impairment and functional decline. Therefore, this study aimed to investigate the associations of polypharmacy with cognitive impairment and functional status among community-dwelling older adults using nationally representative data from the 2023 Korean Elderly Survey.

Methods: A cross-sectional analysis was conducted using data from 9,898 community-dwelling older adults without a diagnosis of dementia. Polypharmacy was defined as the concurrent use of five or more physician-prescribed medications. Cognitive function was assessed using the Korean version of the Mini-Mental State Examination (K-MMSE), with cognitive impairment defined as a score ≤ 23. Functional status was evaluated using the Korean Activities of Daily Living (K-ADL) and Korean Instrumental Activities of Daily Living (K-IADL). Logistic regression was used to estimate odds ratios and 95% confidence intervals (CIs) for cognitive impairment, while multiple linear regression analyses examined associations with functional status. Models were sequentially adjusted for sociodemographic characteristics, health behaviors, and the number of chronic diseases.

Results: Polypharmacy was associated with increased odds of cognitive impairment in the crude model (OR = 1.70, 95% CI: 1.40–2.05); however, this association was attenuated and became non-significant after adjustment for sociodemographic and health-related factors. In contrast, polypharmacy remained independently associated with poorer functional status in fully adjusted models, showing higher K-ADL scores (B = 0.14, p = 0.007) and K-IADL scores (B = 0.43, p < 0.001).

Conclusions: Polypharmacy was independently associated with functional impairment but not with cognitive impairment after comprehensive adjustment, suggesting that functional decline may represent a more sensitive and immediate consequence of complex medication use in older adults. These findings underscore the need for comprehensive geriatric assessment approaches that integrate medication review with functional evaluation.

The involvement of the Internet of Things (IoT) technology and artificial intelligence (AI) in the matter of maternal healthcare has allowed monitoring pregnant women in real-time and predicting poor pregnancy outcomes, including stillbirth and premature birth. Nevertheless, to diminish the risks of devices, the introduction of such technologies has to be accompanied by harsh safety monitoring programs. Materiovigilance, as the systematic sensing and monitoring of adverse events associated with medical instruments, is also crucial to patient safety in high-risk obstetric environments. Wearable sensors, e.g., fetal Dopplers, smart fabrics, and adhesive patches, have enhanced the prediction of stillbirth by offering continuous acquisition of physiological data but presents a hazard of ill effects if not controlled adequately. The AI introduction into the sphere of Materiovigilance enhances regulatory conformity, real-time decision-making, and raises the possibility of risk identification. Despite the massive potential, issues such as inaccurate data, poor infrastructure, and underreporting persist, particularly in low- and middle-income countries. In such circumstances, the Materiovigilance Programme of India is another staged effort to enhance the device safety supervision and reporting systems. Engagement of different stakeholders such as clinicians, engineers, regulatory agencies, and technology developers provides an opportunity to secure the safety and efficacy of AI-equipped medical devices. Enhancement of Materiovigilance systems is required to preserve proper maternal-fetal health and sustain clinics in digital obstetrics, as any error in maternal-fetal monitoring may lead to preventable death.

Background:Sickle cell disease (SCD) is a group of heritable conditions with significant morbidity, burden of disease management and healthcare delivery issues. Medical mistrust (MM) is a psychological outcome of healthcare delivery issues. The purpose of this review was to assess the concept of MM in the literature on SCD, summarize the findings and gaps, and was guided by three questions: 1) How has MM been measured and/or described in patients with SCD? 2) What factors have been described in the literature that predispose patients with SCD to develop MM? 3) What consequences or outcomes have been described because of MM in patients with SCD?

Methods: The methodological framework of Arksey and O’Malley was used to review articles from PubMed, Scopus, Web of Science, CINAHL, PsycInfo, and EMBASE. Inclusion criteria were quantitative, qualitative, and mixed methods peer-reviewed studies published in English between 1994 and 2025; articles focused on patients with SCD and those that described concepts found in the existing MM instruments.

Results: Forty-two studies were included; 26 were strictly qualitative, 11 were mixed methods, and 5 were strictly quantitative. No study used an existing MM measure; yet concepts from MM measures were described: group disparities and suspicion. Negative healthcare staff communication, poor pain control, transition of care, and lack of provider transparency predisposed patients toward MM. Outcomes of MM included avoidance of care, nonadherence, psychological distress, and maladaptive coping.

Discussion: This review highlights the predictors and outcomes of MM in patients with SCD and identifies the notable gaps in the state of the SCD MM literature. More studies are needed to assess the development and consequences of MM in patients with SCD. The findings highlight the experiences of patients with SCD and offer researchers insights into possible interventions to decrease MM and improve outcomes.

Hepatocellular carcinoma (HCC) is an aggressive primary liver malignancy with a high propensity for extrahepatic spread, most commonly to the lungs, lymph nodes, and bones. Metastases to atypical sites like the orbital and oral cavity are uncommon and often underrecognized. We report the case of a 74-year-old male with hepatitis C-related cirrhosis who was diagnosed with HCC and initially treated with locoregional therapies. Disease progression was marked by the development of biopsy-confirmed pulmonary metastases, followed by treatment with durvalumab plus tremelimumab immunotherapy and external beam radiation. Despite therapy, further progression occurred with mediastinal lymphadenopathy. The patient subsequently developed visual disturbances, and ophthalmologic evaluation identified a solitary choroidal mass consistent with metastatic HCC. Around the same time, he presented with recurrent oral bleeding, and a biopsy of a maxillary gingival lesion confirmed metastatic HCC. This case highlights the aggressive nature of advanced HCC and its potential for unusual metastatic spread. To our knowledge, this is among the few reported cases of HCC with orbital and oral metastases. Awareness of atypical metastatic presentations and a multidisciplinary approach are essential for timely diagnosis and optimal management.

Aim: Adherence to antihypertensive medication is essential for positive outcomes among patients diagnosed with hypertension. Yet, up to 72% of individuals prescribed antihypertensives do not take medication as prescribed. Understanding mechanisms of behavior change (MoBCs) for antihypertensive adherence provides essential insight for how to change adherence behavior. This study examined the association between 4 potential MoBCs and self-reported antihypertensive adherence.

Methods: This exploratory, cross-sectional study recruited 101 patients prescribed antihypertensive medications to complete self-report questionnaires on adherence and potential mechanisms of nonadherence. Antihypertensive adherence was assessed using the Hill-Bone Compliance to High Blood Pressure Therapy Scale (HB-HBP). The 4 putative MoBCs for nonadherence included self-efficacy, self-regulation, behavioral automaticity, and hypertension knowledge. Associations between self-reported antihypertensive adherence and MoBCs were examined using independent samples t-tests and multivariate median regression with covariate adjustment for participant characteristics.

Results: The sample had a mean age of 61.7 years (SD = 13.1 years), was 59.4% female (n = 60), 66.3% White (n = 67), and 7.9% Hispanic (n = 8). Low adherence was reported by 16.8% of the study sample. Participants who reported low adherence to antihypertensive medications had lower scores on the self-efficacy questionnaire (p < 0.001) and hypertension knowledge (p = 0.045). Self-efficacy and hypertension knowledge remained significantly associated with self-reported adherence in multivariate regression with covariate adjustment.

Conclusions: The current study supports the hypothesis that self-efficacy for adherence and additionally hypertension knowledge are the MoBCs most strongly associated with self-reported adherence behavior. Behavioral interventions to improve medication adherence should consider focusing on self-efficacy and hypertension knowledge as potentially important target MoBCs. The authors recommend that future research should consider tailored intervention approaches that target specific mechanisms of adherence and specific self-reported reasons for nonadherence.

Aim: Myxofibrosarcoma (MFS) is characterized by high local recurrence and complex microenvironmental interactions. Although three-dimensional (3D) culture systems better mimic in vivo tumor architecture than conventional two-dimensional (2D) monolayer cultures, the global proteomic consequences of dimensionality in MFS remain incompletely defined.

Methods: We performed quantitative mass spectrometry-based proteomic profiling of eight independently established patient-derived MFS cell lines cultured under 2D monolayer and 3D spheroid conditions. Differential protein expression and pathway enrichment analyses were conducted to delineate dimensionality-driven molecular programs.

Results: Culture dimensionality emerged as the principal determinant of proteomic variation across all cell lines. Compared with monolayers, 3D spheroids exhibited significant enrichment of hypoxia response, autophagy-related processes, extracellular matrix organization, and PI3K-Akt signaling pathways. In contrast, 2D cultures preferentially upregulated DNA replication, RNA processing, and cell-cycle-associated pathways. These findings indicate that 3D architecture alone is sufficient to induce coordinated stress-adaptive and survival-oriented proteomic reprogramming in MFS cells.

Conclusions: This study provides a comprehensive proteomic atlas defining dimensionality-dependent molecular states in MFS. While functional validation was beyond the scope of this work, the pathway rewiring identified here establishes a mechanistic framework for future hypothesis-driven investigations targeting autophagy- and PI3K-Akt-associated vulnerabilities in 3D MFS models.

Although emotions play a fundamental role in modulating pain perception, their objective assessment in clinical contexts remains challenging. Recent advances in artificial intelligence (AI) have opened new opportunities to measure emotional states through facial expression analysis, physiological signal modeling, natural language processing (NLP), and multimodal data integration. In affective computing, the field that focuses on technologies designed to recognize, interpret, process, and simulate human emotions, facial expression-based emotion recognition has progressed from traditional machine learning methods to advanced deep learning approaches, including convolutional neural networks (CNNs), attention-based hybrid models, and transformer architectures. Similarly, recurrent neural networks and self-supervised learning methods have been implemented for developing models from physiological signals such as electrocardiography, photoplethysmography, galvanic skin response, and related biosignals. Additionally, NLP systems can extract affective information from naturalistic text, using both lexicon-based and transformer-based models. Finally, multimodal fusion and alignment techniques allow the integration of heterogeneous data streams, providing richer and more ecologically valid emotion representations. Collectively, these strategies offer powerful tools for advancing automatic pain assessment (APA) in cancer care, with the potential to support personalized, emotion-aware therapeutic approaches. However, from an AI perspective, several open challenges remain, including multimodal representation learning under weak supervision, robustness to missing or degraded modalities, limited explainability of affective inference models, lack of standardized benchmarking protocols, and the presence of bias and domain shift in emotion datasets. Given the inherently subjective, context-dependent, and culturally mediated features of the emotional experience, further research is needed to address these technical limitations, integrating technological advances with the intrinsic complexity of emotion interpretation.

The recent improvements of the ultrasounds technology and the probes have led the dental community to start to apply this technology at macrovascular and microvascular level. This scoping review aims to investigate the diagnostic and research applications of ultrasonography in periodontics. A comprehensive literature search was conducted in PubMed, Scopus, and Web of Science, to identify relevant studies in periodontology: The search strategy included the following terms: “ultrasonography”, “echography”, “ultrasound”, “dentistry”. The review was conducted in accordance with the PRISMA-ScR guidelines. In addition, a manual search was conducted through the following journals from the last 10 years: Journal of Clinical Periodontology, the Journal of Dental Research and Oral Surgery, and Oral Medicine, Oral Pathology and Oral Radiology. Ten studies were included, covering different applications of ultrasonography in periodontology. Ultrasonography was employed in peri-implant and periodontal diagnosis, assessment of soft tissue thickness and vascularization, palatal wound and bone healing. This review highlights the effectiveness of ultrasonography in diagnosis and surgical evaluation. Further research, standardized protocols, and randomized clinical trials are needed, expanding the investigation to more fields relevant to the maxillofacial district.

Aim: Adult-onset Still’s disease (AOSD) is a rare systemic inflammatory disorder marked by fever, rash, joint pain, and hyperferritinemia. While immune dysregulation is implicated in AOSD, the exact causal mechanisms remain unclear. This study aimed to investigate the genetic causal relationship between 731 immune cell phenotypes and AOSD, and to identify protective or risk-associated profiles.

Methods: Using a two-sample Mendelian randomization (TSMR) approach, we applied inverse variance weighted (IVW) as the primary method, supplemented by MR-Egger, weighted median, simple mode, and weighted mode methods for robustness. Genetic instrumental variables for immune traits were sourced from recent genome-wide association studies (GWAS), and AOSD genetic predispositions were derived from the finn-b-STILL_ADULT cohort, comprising 201,947 individuals of European ancestry (3,403 AOSD cases and 198,544 controls).

Results: We identified 49 immune cell-related traits showing nominally significant associations with AOSD (all adjusted P > 0.05 after FDR correction). Among these, 34 traits showed nominally protective trends, while 15 showed nominally risk-associated trends. Reciprocally, AOSD showed nominally suggestive effects on 40 immune cell traits, with 25 exhibiting a trend toward decreased levels and 15 toward increased levels. Additionally, we conducted multiple sensitivity analyses to explore potential heterogeneity and pleiotropy, though the primary findings did not survive FDR correction.

Conclusions: These nominally significant associations between immune cell traits and AOSD, though not surviving FDR correction, may offer hypothesis-generating insights for future therapeutic research. The observed directional trends-with certain traits showing nominally protective or risk-associated patterns-suggest potential avenues for further exploration in the development of targeted treatment approaches for AOSD.

Tricuspid valve endocarditis has potential associations with various conditions, but it is commonly related to intravenous drug abuse. Often, its eradication can become very challenging due to high post-operative mortality and high rate of recurrence due to persistence of drug abuse habits. The bidirectional Glenn shunt (BGS), typically employed in congenital heart surgery, combined with tricuspid valvectomy, has occasionally been used for recurrent endocarditis. Herein, we present a 31-year-old woman with drug addiction scheduled for her fourth reintervention due to the early degeneration and infection of a previous pulmonary homograft used for recurring tricuspid valve endocarditis. The final surgical strategy was valvectomy and BGS, aimed at eliminating all potential sources of infection and providing more time for the patient to overcome drug addiction, enabling further treatment if necessary.

The increasing survival rates among paediatric and adolescent cancer patients has increased attention on long-term consequences of chemotherapy, particularly male fertility. This review addresses age- and dose-dependent gonadotoxicity and drug type on reproductive potential. It further investigates the damage, including disruption of the hypothalamic-pituitary-gonadal axis and epigenetic alterations that may pose transgenerational risks. A systematic search of PubMed, Scopus, Web of Science, and Google Scholar was conducted for studies from database inception to April 2025. Inclusion criteria included paediatric and adolescent male cancer patients or adult survivors of childhood cancer and reported chemotherapy-related effects on fertility. Preclinical animal models were included to elucidate epigenetic changes. Due to heterogeneity of study designs, a narrative synthesis was performed to categorize findings into hormonal, cellular, and clinical outcomes. Chemotherapy-induced infertility is highly dependent on the developmental stage and specific regimen. Alkylating agents and platinum-based therapies were consistently associated with impaired spermatogenesis, hormonal disruption, and azoospermia or oligospermia. Chemotherapy and cranial irradiation were altered hormonal system that regulates male reproduction and persists epigenetic changes in germ cells. Fertility preservation for postpubertal males is through sperm cryopreservation, while prepubertal boys relied on experimental strategies such as testicular tissue cryopreservation and in vitro spermatogenesis. Chemotherapy induces epigenetic after-effects, including altered DNA methylation patterns that persist even after spermatogenesis recovers. Chemotherapy compromises male fertility through cytotoxic damage and potential long-term genomic instability. The findings highlight that reproductive recovery does not guarantee genomic recovery (epigenetically intact sperm). Consequently, oncofertility care must adapt a reproductive health model that prioritizes early, customized counselling and use of biomarkers to better predict and preserve fertility in young survivors. Although sperm banking remains a standard approach for postpubertal, promising experimental may expand fertility options for prepubertal boys in future.

Obesity during the menopausal transition accelerates vascular aging through systemic inflammation, insulin resistance, and estrogen loss. These pathological processes impair endothelial function and arterial compliance, thereby increasing cardiovascular risk while simultaneously disrupting cerebral circulation, neurovascular regulation, and neuroendocrine stability that contribute to cognitive decline and psychological vulnerability. Regular exercise has emerged as an important non-pharmacological strategy to counteract these multidimensional impairments. Particular attention has been given to the modifying role of hormonal status and the differential adaptations observed between premenopausal and postmenopausal states. Evidence indicates that aerobic and multimodal programs enhance nitric oxide bioavailability, vascular elasticity, and cerebral perfusion, whereas resistance training contributes to musculoskeletal strength, metabolic regulation, and psychological resilience. Novel approaches such as interval-based or hypoxic exercise may provide additional benefits for postmenopausal women but require individualized supervision. Importantly, exercise-induced vascular improvements extend beyond cardiovascular protection, restoring cerebral blood flow, promoting hippocampal plasticity, and stabilizing hypothalamic–pituitary–adrenal axis function. These adaptations mediate enhancements in memory, executive performance, mood regulation, and stress resilience. This review synthesizes current findings across aerobic training, resistance training, combined training, high-intensity interval training, and hypoxic conditioning, and proposes an integrative vascular–cognitive–mental health framework that unifies these domains into a coherent model, with vascular function as a central mechanistic pathway linking exercise to cognitive and psychological outcomes, while underscoring the need for precision exercise prescriptions tailored to hormonal status, vascular risk, and functional capacity in obese women.

Aim: To evaluate ultrasound-derived congestion phenotypes in acute decompensated heart failure with preserved ejection fraction (HFpEF) and their association with cardiac remodeling and in-hospital outcomes.

Methods: This prospective study included 235 patients (median age 77.0 years, 75.3% women) with acute decompensated HFpEF. Within 2 hours of admission, all patients underwent echocardiography, lung ultrasound (B-lines), venous excess ultrasound score (VExUS) assessment, and bioimpedance analysis. Patients were classified into three phenotypes based on pulmonary (B-lines > 3) and systemic venous congestion (VExUS): low-low (no significant pulmonary or systemic congestion), pulmonary-dominant, and mixed severe. The primary endpoint was in-hospital mortality.

Results: Moderate-to-severe venous congestion (VExUS grade 2–3) was present in 60.8% of patients. The mixed severe phenotype predominated (60.9%) and was associated with higher body mass index (BMI) and waist (p < 0.001). This group demonstrated more advanced cardiac dysfunction, including higher E/e’ (14.9 vs. 11.9; p < 0.001), greater left atrial remodeling (left atrial volume index 45.0 vs. 39.0 mL/m²; p < 0.001), and increased left ventricular mass index (p = 0.010). Right ventricular (RV) involvement was more pronounced, with lower TAPSE (18.0 vs. 20.0 mm; p < 0.001) and higher tricuspid regurgitation velocity (p < 0.001). Markers of congestion showed a gradient, with higher NT-proBNP (3,072.5 vs. 1,197.0 pg/mL; p < 0.001), increased extracellular water (129% vs. 101%; p < 0.001), and lower phase angle (4.9 vs. 5.5; p < 0.001). In-hospital mortality was highest in the mixed severe phenotype [11.2% vs. 3.0% and 1.7%; p = 0.039; odds ratio (OR) 5.67]. B-lines correlated with tricuspid regurgitation velocity, E/e’, and extracellular water (all r ≥ 0.50).

Conclusions: Ultrasound-derived congestion phenotyping in HFpEF identifies distinct profiles associated with atrial and ventricular remodeling and worse in-hospital outcomes. Future studies are required to determine whether phenotype-guided decongestive strategies can improve outcomes beyond risk stratification.

Recent studies argue that other physiological solutions are superior to normal saline, which is due to their physiological features, better outcomes in critical care, and lower risk of hyperchloremia and acidosis; nonetheless, it is still a mystery how normal saline has dominated the field of fluid therapy worldwide. Moreover, there is an ongoing debate on whether harm to human health may limit its spread in the future. Additionally, new evidence revealed some of the deleterious effects of normal saline, including coagulopathy, metabolic acidosis, acute kidney injury (AKI), and higher mortality in ICU. The predominant cause for these outcomes appears to be the excess chloride concentration of normal saline relative to plasma. Therefore, it appears relevant to suggest that a normal saline solution should be normalized to that of human serum to overcome these pitfalls. An ideal normal saline solution shall be similar to human serum in its pH, osmolarity, and content of sodium, chloride, and essential minerals.

Artificial intelligence (AI) has rapidly advanced in radiology, demonstrating high performance across a wide range of diagnostic tasks. However, clinical adoption remains slower and more uneven than anticipated. This discrepancy reflects a fundamental gap between algorithm validation and clinical implementation. Current validation strategies primarily rely on controlled datasets and performance metrics such as accuracy and area under the curve, which often fail to capture the complexity of clinical environments. This article examines the nature of this “validation gap” and argues that it reflects a broader structural mismatch between how AI systems are evaluated and how clinical care operates. We propose a conceptual framework comprising three levels of validation: technical validity, workflow validity, and clinical validity. While most studies focus on technical performance, limited attention is given to integration into clinical workflows and impact on patient outcomes. Key factors contributing to this gap include limited generalizability across diverse populations and imaging protocols, poor alignment with clinical workflows, and the underrepresentation of uncertainty in model outputs. These limitations hinder effective implementation and may reduce trust in AI systems. Bridging this gap requires a shift toward more comprehensive validation strategies, including multicenter and prospective studies, improved workflow integration, and explicit incorporation of uncertainty and human–AI interaction. Ultimately, the clinical value of AI in radiology should be assessed not only by its performance in controlled settings but also by its ability to support decision-making and improve patient outcomes in real-world practice.

Artificial intelligence (AI) is transforming clinical decision-making across cranio-maxillofacial trauma, oral health, and systemic disease. These domains are increasingly recognised as biologically and clinically interconnected, yet they are often studied and managed independently. This perspective introduces the concept of an integrative triangle linking facial trauma, oral health, and systemic disease, with AI serving as the computational bridge that enables cross-domain modelling and coordinated care. AI applications within this framework include imaging-based fracture detection, patient-specific implant design, automated oral disease diagnosis, multimodal risk prediction, and longitudinal outcome modelling. By integrating imaging, clinical, laboratory, and behavioural data, AI can identify shared inflammatory and metabolic pathways influencing trauma recovery and chronic disease progression. This closed-loop paradigm supports continuous learning, allowing outcomes in one domain to inform prediction and intervention in the others. The integrative triangle provides a translational roadmap for precision medicine, moving from isolated prediction toward coordinated prevention and intervention. Future development will require multimodal data integration, prospective validation, and responsible governance to ensure explainable and equitable AI deployment. This framework positions facial trauma and oral health as central components of systemic precision medicine and highlights AI as a catalyst for integrated, patient-centred care.

Aim: Tremor is one of the most common neurological movement disorders, arising from dysfunction in the neuromuscular system. However, comprehensive analyses of peripheral blood elements, red blood cells (RBC) and white blood cells (WBC) counts, as well as liver and kidney function in patients with tremor remain limited. This cross-sectional study investigated alterations in serum elements, complete blood counts, and liver function in patients with tremor. The study sought to identify independent risk factors and evaluate their diagnostic performance.

Methods: Blood samples from 79 patients with tremor and 82 healthy controls were analyzed. Serum elements, RBC, WBC, platelet (PLT), liver function, and renal function were measured using the QL8000 element analyzer, XN 2800 automated hematology analyzer, and Roche Cobas 8000 system.

Results: Serum copper (Cu) and lead (Pb) levels were significantly elevated in tremor patients. These patients also showed increased monocytes, decreased eosinophils, and impaired liver function, including elevated aspartate aminotransferase and globulin with reduced albumin.

Conclusions: Tremor patients show distinct alterations in Cu, Pb, monocyte counts, eosinophil counts, and liver function markers. These findings suggest that these parameters may serve as potential diagnostic indicators and therapeutic targets. Cu and Pb were identified as independent risk factors, and their combination significantly improved diagnostic efficiency.

Early-life oxidative stress, resulting from an imbalance between reactive oxygen species (ROS) and reactive nitrogen species (RNS) and antioxidant defenses, has increasingly been proposed as an important contributor to the developmental origins of childhood asthma. Prenatal and early postnatal exposures-including pollutants, tobacco smoke, maternal distress, nutritional imbalance, and allergen-derived oxidase activity-may disrupt epithelial integrity and redox-regulated immune pathways, potentially predisposing the developing lung to allergic inflammation. To synthesize current mechanistic and epidemiologic evidence on how oxidative stress during early life may contribute to asthma development, with particular focus on environmental drivers, redox–immune interactions, and gene-environment susceptibility. A structured review of PubMed, Scopus, and Embase identified peer-reviewed English-language studies from birth cohorts, mechanistic models, and biomarker analyses evaluating oxidative stress, antioxidant capacity, and asthma-related outcomes. Environmental oxidants and nutritional deficiencies may increase ROS production, promoting epithelial injury, activation of redox-sensitive pathways such as NF-κB and MAPK, and the release of epithelial alarmins including IL-33, IL-25, and thymic stromal lymphopoietin (TSLP). These signals can influence innate immune activation and antigen-presenting cell function, favoring Th2/Th17-biased immune responses. Genetic variants in antioxidant pathways, including GSTM1, GSTP1, and Nrf2, may further modify susceptibility to oxidant exposures. Epidemiologic studies from birth cohorts report associations between early-life oxidative exposures, reduced lung growth, wheezing, allergic sensitization, and asthma risk. Current mechanistic and epidemiologic evidence suggests that oxidative stress may represent an important biological pathway linking early-life environmental exposures with asthma susceptibility, although further studies are needed to clarify its role within the complex network of factors contributing to asthma development.

Aim: Diabetes mellitus is a growing non-communicable disease (NCD) imposing major health and economic burdens in Ethiopia. While prior national and subnational estimates have been published using Global Burden of Disease (GBD) 2019 data, this study provides novel, updated estimates reflecting newly delineated regional boundaries and recent socio-demographic shifts using GBD 2023 data. We aimed to estimate the national and subnational burden and trends of diabetes mellitus in Ethiopia from 1990 to 2023.

Methods: This analysis is part of the GBD 2023 study, a collaborative effort between the Ethiopian Public Health Institute and the Institute for Health Metrics and Evaluation. Estimates were generated using standard GBD modeling tools [DisMod-MR 2.1 and Cause of Death Ensemble modeling (CODEm)] for incidence, prevalence, mortality, years of life lost (YLLs), years lived with disability (YLDs), and DALYs [with 95% uncertainty intervals (UI)] across Ethiopia’s regions and city administrations.

Results: In 2023, Ethiopia’s age-standardized prevalence of all forms of diabetes mellitus (type 1 and type 2 combined) was 2,996.4 (95% UI: 2,704.8–3,269.5) cases per 100,000 population. Type 2 diabetes accounted for nearly 99% of cases. The Somali region had the lowest prevalence (2,243.1 per 100,000), about 45% lower than in Sidama (4,066.4 per 100,000), highlighting marked regional disparities. The age-standardized DALY rate was 1,124.2 per 100,000. While high fasting plasma glucose was the leading proximal risk factor, high body mass index ranked as the top upstream modifiable risk factor (264.1 DALYs per 100,000).

Conclusions: This study highlights the substantial and unevenly distributed burden of diabetes mellitus in Ethiopia, driven predominantly by type 2 diabetes and modifiable metabolic risk factors. These findings call for tailored, region-specific strategies, such as targeted obesity prevention in high-prevalence urban centers and strengthened health system capacity in high-mortality pastoral regions to curb the future burden and align with global NCD targets.

Aim: Human Immunodeficiency Virus (HIV) and Acquired Immunodeficiency Syndrome (AIDS) have attained a manageable chronic status as more infected people experience increases in their life quality and expectancy. Health system factors affect adherence to Antiretroviral Therapy (ART) among persons living with HIV (PLHIV). Nonetheless, literature on health-system factors and ART adherence among PLHIV is sparse. This study therefore aimed to elucidate clinical and health system factors associated with ART adherence among PLHIV in Tamale Metropolis.

Methods: We conducted a facility-based cross-sectional survey of 418 PLHIV in the Tamale Metropolis, selected by convenience sampling from three major ART centres. Each factor associated with ART adherence, considered statistically significant at a p-value of < 0.05 with a 95% confidence interval, was analysed using both binary and multivariate logistic regression. Adherence was assessed by self-report of missed doses in the past 30 days, categorised as good (≥ 95% of prescribed doses taken) or poor (< 95% of prescribed doses taken).

Results: The overall ART adherence rate was 93.1% (95% CI: 90.3%–95.2%). Clinical and health system factors significantly associated with higher adherence included the absence of post-pill fatigue (AOR = 0.09; 95% CI: 0.02–0.37), absence of complaints regarding pill size (AOR = 3.71; 95% CI: 1.23–11.18), lower cost of accessing therapy (AOR = 0.27; 95% CI: 0.10–0.73), uninterrupted ART supply (AOR = 7.76; 95% CI: 1.02–59.30), and strong social support systems (AOR = 6.62; 95% CI: 1.18–37.21).

Conclusions: An adherence rate of 93% was obtained which falls short of the 95% global benchmark. Clinical factors promoting adherence included the absence of fatigue and concerns related to pill size, while health system-related factors promoting adherence included reduced cost of access, consistent ART supply, and good social support. The Ghana AIDS Commission and its implementing partners are urged to strengthen community-based social support networks, expand ART distribution points, and develop targeted educational initiatives to improve therapy adherence and contribute to achieving epidemic control. Limitations of this study include the use of self-reported adherence (potential recall and social desirability bias) and the cross-sectional design, which precludes causal inference.

Acute wheeze is one of the most common paediatric presentations to emergency care. Although blood eosinophils (BEO) are an established biomarker of type 2 inflammation in stable asthma, their role in guiding acute management-particularly systemic corticosteroid use-remains unclear. The aim of this review was to map and synthesise the existing evidence on the measurement and clinical utility of BEO sampled during acute wheeze exacerbations in children. A scoping review was conducted in accordance with Joanna Briggs Institute methodology and Preferred Reporting Items for Systematic Reviews and Meta-Analysis extension for scoping reviews (PRISMA-ScR) guidelines. Medline, Embase, Cochrane Library and Web of Science were searched for studies published in the last 20 years involving children under 16 years presenting acutely with wheeze and undergoing eosinophil testing. Prospective and retrospective studies were included. Data were summarised descriptively according to eosinophil measurement methods, reported values, cut-offs and associations with characteristics and treatment response. Eight heterogeneous studies (n = 855) met inclusion criteria, comprising five observational or retrospective studies and three randomised controlled trials. BEO reporting varied widely, with inconsistent units, cut-offs and poorly described sampling timing. No study utilised point-of-care testing. Across studies, eosinophil dynamics differed by age, wheeze phenotype, disease severity and viral aetiology, preventing meaningful comparison. Evidence supporting eosinophil-guided corticosteroid use was limited. Two studies demonstrated improved outcomes with systemic corticosteroids in children with rhinovirus-associated wheeze and higher BEO, while lower BEO were observed in respiratory syncytial virus (RSV)-associated wheeze. There is a paucity of high-quality data describing BEO during acute wheeze exacerbations in children. Current evidence underpinning eosinophil-guided care is largely derived from stable outpatient cohorts and may not be directly applicable to acute settings. Prospective studies with standardised sampling of BEO during acute presentations are needed to inform precision-based corticosteroid use.

Aim: To determine the level of agreement between remote and in-person assessment for the Timed Up and Go test (TUG), the Lateral Step-Up test (LSU), the Five-Times-Sit-To-Stand test (FTSTS), and the Pediatric Balance Scale (PBS) in children with cerebral palsy (CP).

Methods: Fifteen children diagnosed with unilateral and bilateral spastic CP and Gross Motor Function Classification System levels I–II underwent these four tests in two distinct environments. These assessments were conducted 24 to 48 hours apart, first in person at the physiotherapy clinic and then remotely at home via the VSee platform. Before the remote assessment, all parents attended a preliminary training session that covered technical proficiency with VSee, the proper setup of home equipment, and essential safety protocols.

Results: Children had a median age of 7 (IQR = 6–10) years old. All children successfully finished all four tests in both the home and clinic settings without any reported safety issues. The agreement was good for the time of repetitions in the FTSTS: ICC = 0.884 (95% CI: 0.654 to 0.961; MD = –1.26 seconds, 95% CI: –2.81 to 0.28, p = 0.102), and excellent for the total time of the TUG: ICC = 0.998 (95% CI: 0.990 to 0.999; MD = –0.42 seconds, 95% CI: –0.76 to –0.08, p = 0.017), the total score in the PBS: ICC = 0.998 (95% CI: 0.992 to 0.999; MD = 0.26 units, 95% CI: 0.01 to 0.52, p = 0.041), and the total number of steps in the LSU: ICC = 0.988 (95% CI: 0.965 to 0.996; MD = 0.53 steps, 95% CI: –0.68 to 1.75, p = 0.364).

Conclusions: Remote evaluation of the FTSTS, TUG, LSU, and PBS demonstrates good-to-excellent agreement with in-person assessment. However, wide limits of agreement indicated individual variability.

Oxidative stress-an imbalance between reactive oxygen/nitrogen species and antioxidant defenses-contributes not only to the developmental origins of asthma but also to poor control, airway remodeling, and corticosteroid-resistant inflammation in children. Persistent oxidant exposure, nutritional insufficiency, and mitochondrial dysfunction sustain redox imbalance in pediatric asthma, suggesting potential roles for environmental, dietary, and nutraceutical strategies-defined here as natural bioactive compounds providing health benefits beyond basic nutrition, including polyphenols such as curcumin, quercetin, and resveratrol, and essential minerals such as zinc and selenium-that complement standard therapy. To summarize evidence on preventive and therapeutic approaches that modulate oxidative stress in pediatric asthma, focusing on environmental control, antioxidant-rich dietary patterns, single and multi-component nutraceuticals, and mitochondria-targeted interventions. A structured review of PubMed, Scopus, and Embase (1995–2025) identified peer-reviewed English-language epidemiologic studies, mechanistic models, and clinical trials evaluating oxidative stress, antioxidant status, and asthma outcomes in children and, when relevant, adults. Reference lists of major reviews were screened to identify additional studies. Interventions that reduce exposure to air pollutants and tobacco smoke, combined with antioxidant-rich diets such as high fruit/vegetable intake and Mediterranean-style patterns, are consistently associated with improved lung function, fewer symptoms, and reduced inflammation. Clinical trials of single antioxidants (vitamin D, vitamin E, zinc, selenium, magnesium) show modest, context-dependent benefits, primarily in children with baseline deficiencies. Emerging research suggests that multi-component nutraceuticals-including polyphenols and coordinated micronutrient formulations-may enhance redox balance and improve pulmonary or vascular outcomes, though current evidence is limited by small sample sizes and heterogeneity. Experimental data strongly support mitochondria-targeted mechanisms, but pediatric clinical validation remains sparse. Strategies that reduce oxidative burden or strengthen antioxidant defenses appear biologically plausible adjuncts to standard asthma therapy. Further large, biomarker-guided trials are needed to clarify efficacy, identify responsive phenotypes, and determine the role of multi-component approaches relative to single-nutrient supplementation.

Aim: Hypertension and obesity frequently coexist and increase cardiovascular risk through vascular dysfunction, autonomic imbalance, and metabolic dysregulation. This study investigated the effects of an 8-week mat Pilates program on body composition, blood pressure, vascular function, autonomic nervous system activity, and health-related physical fitness in obese men with elevated or stage 1 hypertension.

Methods: Twenty-three men with elevated or stage 1 hypertension and a body mass index (BMI) ≥ 25 kg/m² were initially recruited and randomly assigned to a control group (CON) or an experimental group (EXP). After withdrawal or loss to follow-up, 20 participants completed the study and were included in the final analysis (CON, n = 10; EXP, n = 10). The EXP performed mat Pilates three times per week for eight weeks, while CON maintained their usual lifestyle. Outcomes were assessed before and after the intervention.

Results: Significant group × time interaction effects were observed for body weight, BMI, fat mass, hemodynamic variables, vascular indices, selected heart rate variability measures, and health-related physical fitness. Lean body mass and percent body fat improved significantly within the EXP, although the corresponding interaction effects were not significant. Overall, the EXP showed more favorable changes than the CON in several cardiometabolic and fitness-related outcomes.

Conclusions: An 8-week mat Pilates program was associated with favorable changes in body composition, blood pressure and vascular function, autonomic nervous system indices, and health-related physical fitness in obese men with elevated or stage 1 hypertension. However, because body weight and fat mass also decreased and the sample size was small, these findings should be interpreted cautiously. This study cannot determine whether the changes resulted from the Pilates intervention itself, concurrent body composition changes, or their combined effects. Trial registration: KCT0010502; https://cris.nih.go.kr/cris/index/index.do.

Antimicrobial resistance has intensified the search for alternatives to conventional antibiotics, particularly against multidrug-resistant bacterial pathogens that increasingly compromise treatment outcomes in hospitals and community settings. This narrative review examines bacteriophage therapy as an alternative for combating multidrug-resistant bacteria. Recent literature is discussed thematically, with emphasis on original studies, clinical datasets, translational experiments, and regulatory documents. The current evidence base consists predominantly of compassionate-use reports, small cohorts, and early-phase trials, including CRISPR-enhanced and inhaled phage platforms, which report safety observations, compartment-specific responses, and microbiome effects in individual studies. Mechanistic considerations discussed in the review include route-specific delivery, phage–host ecological interactions, resistance trade-offs, and phage–antibiotic synergy. While microbiological and clinical responses have been reported in individual studies, no confirmatory randomized trial has demonstrated clinical efficacy for any phage therapy indication. Manufacturing, standardization, and regulatory pathways for scaled deployment also remain unresolved. Regulatory developments in Europe, the United Kingdom, the United States, and Australia remain heterogeneous and predominantly access-based or compassionate-use-based rather than approval-based. Specific technical challenges include incomplete standardization of susceptibility testing and the need for robust monitoring of immune neutralization, endotoxin burden, and long-term ecological effects. Routine clinical adoption of phage therapy will ultimately depend on outcomes of adequately powered confirmatory trials, alongside resolution of manufacturing, regulatory, and standardization challenges.

Breast cancer survival is shaped by a complex interaction of tumor-specific, biological, and patient-related factors. Stage at diagnosis remains the strongest predictor of outcome. Tumor size, nodal involvement, and histologic grade further aid in prognostic prediction by reflecting the biological aggressiveness of the disease. Since the early 2000s, molecular characteristics gained importance in risk stratification. Hormone receptor-positive cancers generally respond well to endocrine therapy, while HER2-positive tumors, once associated with poor outcomes, now benefit from targeted therapy. Newer agents and combinations such as CDK4/6 and PI3K/AKT/mTOR inhibitors are being investigated recently. Patient factors, including age, comorbidities, and overall health, also influence outcome and treatment tolerance. Cardiovascular toxicity from chemotherapy and radiotherapy has become an important consideration, particularly in the elderly. Although modern radiotherapy techniques have reduced cardiac risks, long-term cardiovascular mortality remains a competing cause of death in many survivors. Studies comparing breast-conserving therapy with mastectomy suggest improved overall survival with the former, partly due to reduced treatment morbidity. Early detection through mammography, ultrasound, and awareness campaigns greatly improves survival, yet access remains unequal in low-resource settings. Strengthening healthcare systems, tailoring treatments, expanding multidisciplinary care and improving public education are essential. Affordable personalized therapies, better infrastructure, and international collaboration can reduce disparities and enhance global breast cancer outcomes. Our international team researched literature information as well as summarizing up-to-date opinions from global experts, including those with limited resources and war-torn regions.

Bacterial co-infection in patients with coronavirus disease 2019 (COVID-19) can complicate diagnosis because of overlapping clinicoradiologic findings among pathogens. We report a case of suspected triple co-infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Legionella pneumophila (L. pneumophila), and Streptococcus pneumoniae (S. pneumoniae) after hot-spring travel in a post-splenectomy patient. A man in his 70s with a history of subtotal esophagectomy and concomitant splenectomy for esophageal cancer was admitted with fever, worsening productive cough, and altered sensorium. He had recently traveled to a hot spring with a group that included his wife, who also developed a fever and was diagnosed with COVID-19. On admission, results of urinary antigen tests for L. pneumophila and S. pneumoniae were positive, a SARS-CoV-2 nucleic acid amplification test was positive, and sputum culture yielded S. pneumoniae. Chest computed tomography revealed multifocal bilateral ground-glass opacities, small bilateral pleural effusions, and relatively well-defined right middle-lobe consolidation with air bronchograms in a peribronchovascular distribution. These microbiological and radiological findings supported a suspected triple co-infection rather than COVID-19 alone. Treatment with remdesivir, ceftriaxone, and levofloxacin was initiated, and the patient’s condition improved, with better oxygenation and decreased inflammatory markers. Remdesivir and ceftriaxone were discontinued after 5 days, whereas levofloxacin was continued for 14 days. Follow-up imaging revealed marked improvement, and the patient was discharged. Public health investigations did not detect Legionella at the hot-spring facility or identify any additional linked cases. This case highlights the importance of prompt pathogen-directed evaluation when COVID-19 pneumonia is accompanied by a relevant exposure history, host risk factors, and atypical imaging findings.

Background: Ankyloglossia is a congenital condition characterized by restricted tongue mobility, which may influence oral functions such as speech, swallowing, and oral motor coordination. This systematic review aimed to evaluate oral functional outcomes following surgical and/or myofunctional interventions in individuals with lingual hypomobility. A secondary aim was to assess variability and consistency of functional improvements across different therapeutic approaches.

Methods: This systematic review was conducted in accordance with PRISMA guidelines. PubMed, Scopus, and Web of Science were searched between 15 June 2025 and 10 August 2025. Eligible clinical studies (randomized controlled trials, cohort studies, and case series/reports) evaluated lingual frenotomy, frenulectomy, or frenuloplasty, alone or combined with orofacial myofunctional therapy, and reported oral functional outcomes, including tongue mobility, oral posture, swallowing-related tasks, neuromuscular measures, and patient-reported function. Risk of bias was assessed using validated tools (ROBINS-I and RoB 2). Due to heterogeneity in study design and outcome measures, a narrative synthesis was performed.

Results: Ten studies involving more than 1,300 participants across pediatric, adolescent, and adult populations were included. The evidence comprised randomized controlled trials, observational studies, and case series. Surgical intervention alone was primarily associated with immediate anatomical and mobility-related improvements. In contrast, combined surgical and myofunctional approaches were more consistently associated with improvements in functional outcomes, including tongue mobility, resting posture, and swallowing-related functions. However, the consistency of these improvements varied across age groups, intervention protocols, and outcome assessment methods. Risk of bias was variable and frequently influenced by heterogeneous diagnostic criteria, nonstandardized interventions, and nonuniform outcome measures.

Discussion: Combined surgical and myofunctional interventions appear to be associated with improvements in oral functional outcomes compared with stand-alone approaches. However, due to substantial methodological heterogeneity and limited high-quality evidence, these findings should be interpreted with caution and are primarily applicable to the specific functional domains evaluated.

Aim: To investigate interobserver variability in programmed cell death ligand 1 (PD-L1) combined positive score (CPS) assessment in head and neck squamous cell carcinoma (HNSCC) and to develop an artificial intelligence (AI)-based model for predicting PD-L1 expression and patient prognosis from hematoxylin and eosin (H&E)-stained slides.

Methods: Fifty HNSCC specimens were independently evaluated for PD-L1 by pathologists with different experience levels. Agreement was assessed using Fleiss’ and Cohen’s κ. Whole-slide images were processed into tiles for deep learning using DenseNet121. Tile-level features were integrated via two machine learning pipelines to construct whole-slide prediction models. Multiple algorithms were tested, with performance evaluated in validation and testing cohorts. Prognostic value was analyzed using AI-derived risk stratification.

Results: Interobserver agreement was low (Fleiss’ κ = 0.34), indicating substantial variability in CPS assessment. DenseNet121 achieved moderate predictive performance (AUC 0.641 in validation, 0.616 in testing). AI models significantly improved prediction accuracy, with logistic regression demonstrating the best performance (AUC 0.900 in validation, 0.851 in testing). AI-derived prediction scores effectively stratified overall survival, with multiple models showing significant prognostic discrimination (P < 0.05).

Conclusions: AI models integrating deep learning and machine learning can accurately predict PD-L1 expression and stratify prognosis in HNSCC, outperforming tile-level deep learning alone.

Aim: Hypocoagulability and associated alterations in myocardial mechanics seen in hemophilia could theoretically impact valvular geometry. Therefore, the purpose of the present study was to characterize mitral and tricuspid annular dimensions and functions in patients with hemophilia via 3D speckle-tracking echocardiography.

Methods: Of the 17 hemophilia patients originally assessed, four were excluded due to inadequate image quality. The remaining cohort consisted of 13 males with hemophilia (mean age: 40.8 ± 16.3 years; 11 with hemophilia A and 2 with hemophilia B). Thirty age- and gender-matched healthy males (mean age: 40.4 ± 9.2 years) served as the control group.

Results: Hemophilia patients presented with significant dilation of end-diastolic and end-systolic mitral annulus (MA) dimensions (diameter, area, and perimeter), leading to a reduction in MA fractional area change (MAFAC) compared with control subjects. In contrast, among the tricuspid annulus (TA) parameters, dilation was confined to end-diastolic values, while end-systolic dimensions were preserved.

Conclusions: Dilated MA, along with its functional deterioration, is present in patients with hemophilia compared to matched controls. TA dilation seems less pronounced.

Aim: Chronic kidney disease (CKD) is a major global health burden. Emerging evidence links water quality with kidney outcomes, but ecological panel evidence remains limited and context dependent. We examined hypothesis-generating associations between surface water quality indicators and CKD burden in China, Canada, and Ireland during 2010–2017.

Methods: We integrated age-standardized CKD rates from the Institute for Health Metrics and Evaluation (IHME) GBD Results Tool (DALYs, deaths, incidence, prevalence, years lived with disability (YLDs), and years of life lost (YLLs) per 100,000 population; country-year estimates were restricted to 2010–2017) for China, Canada, and Ireland with 284,965 surface water quality observations. The downloaded IHME citation identified the release as Global Burden of Disease Study 2023 (GBD 2023) Results, while the estimates used in this analysis were limited to 2010–2017. Country-specific ordinary least-squares regression was used for the primary analysis; random-effects meta-analysis was used only to summarize country-specific estimates, and restricted cubic spline (RCS) analyses explored non-linear patterns. Standardized beta coefficients were added to improve comparability across countries and water-quality scales.

Results: CKD DALYs rates declined in China (–13.5%) and Ireland (–5.4%) but rose in Canada (+9.0%). In country-specific models, nitrate was inversely associated with CKD DALYs (beta = –12.10; 95% CI: –19.80 to –4.41; P = 0.002; standardized beta = –0.25) and deaths (beta = –0.94; P = 0.006; standardized beta = –0.26) in Ireland. Total nitrogen was inversely associated with CKD incidence in Canada (beta = –0.63; P = 0.006; standardized beta = –0.20). These associations occurred over narrow exposure ranges and should be interpreted cautiously. Random-effects pooled estimates were not statistically significant, and heterogeneity across outcomes ranged from none to substantial (I²: 0–78.4%).

Conclusions: Surface water nitrate and nitrogen showed inconsistent, country-specific associations with CKD burden and did not yield robust pooled estimates. These hypothesis-generating ecological findings underscore the need for individual-level studies with measured drinking-water exposure, harmonized diagnostic information, and latency-aware designs.