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Beta-ketothiolase deficiency (BKTD), also called mitochondrial acetoacetyl-CoA thiolase (T2) deficiency, is a rare autosomal recessive inborn error of metabolism affecting isoleucine catabolism and ketone body utilization. Although recurrent ketoacidotic crises are the hallmark of the disease, neurological complications-particularly basal ganglia injury-are increasingly recognized. We report a 2-year-old girl with known BKTD who presented with severe euglycemic ketoacidosis and acute encephalopathy. Initial CT showed symmetric hypodensity confined to the bilateral globus pallidi. Follow-up CT during ongoing metabolic instability demonstrated interval progression to involve the bilateral putamina and cerebral peduncles. MRI, obtained after referral, revealed nonenhancing T2/FLAIR hyperintense, T1 hypointense globus pallidus lesions without diffusion restriction but with punctate SWI hypointensities consistent with microcystic cavitary degeneration and microhemorrhage. There were additional diffusion-restricting lesions in the bilateral cerebral peduncles, small nonrestricting white matter foci in the frontal and right parietal lobes, and generalized cerebral atrophy. A baseline MRI 17 months earlier had been normal. This case illustrates the evolution from acute pallidal injury to irreversible basal ganglia necrosis with microhemorrhage and concurrent acute/subacute tract involvement, and highlights how CT and MRI together can characterize the spectrum of BKTD-related brain injury.

Palliative care is an essential health service for patients with chronic and life-threatening conditions. Although palliative care has been formally recognized in Georgia's legislation and state programs since the mid-2000s, evidence regarding the development, accessibility, and integration of services remains limited. The WHO framework, Assessing the Development of Palliative Care Worldwide: A Set of Actionable Indicators, and its application in the EAPC Atlas of Palliative Care in the European Region 2025 provide an opportunity for a comprehensive assessment of the national palliative care system. This study evaluated the development of palliative care in Georgia using WHO actionable indicators and compared the findings with the EAPC 2025 Atlas to identify system-level gaps and priorities for improvement. This study employed a descriptive health systems assessment and policy analysis of palliative care development in Georgia. The evaluation was guided by the World Health Organization's 2021 framework, Assessing the Development of Palliative Care Worldwide: A Set of Actionable Indicators. Fourteen indicators across six domains were operationalized using national administrative data, policy documents, institutional reports, and published literature from 2021 to 2024. Quantitative and qualitative findings were triangulated and benchmarked against the European Association for Palliative Care (EAPC) Atlas of Palliative Care in the European Region 2025 to assess service availability, accessibility, geographical distribution, coverage, and system capacity. While palliative care is legally recognized and partially embedded in national health policy, implementation remains limited and uneven. Service provision is highly centralized in Tbilisi, with restricted outpatient and home-based services in regions. In 2024, only 16.7% of the estimated national palliative care need was met. Opioid consumption remains in the very low range, reflecting restrictive regulations, limited medicine availability, and insufficient prescriber training. Similarly, the EAPC 2025 Atlas shows low performance across key WHO indicators, particularly in governance, monitoring mechanisms, service integration, research, and education. Despite early legislative advances, Georgia's palliative care system remains fragmented and inadequately integrated into primary health care. Strengthening governance, financing, education, and monitoring in line with WHO and EAPC benchmarks is essential to achieve equitable, sustainable, and comprehensive palliative care coverage.

Myeloid sarcoma (MS) is a rare extramedullary tumor of immature myeloid cells. Intracranial MS occurring as an extramedullary relapse without concurrent systemic acute myeloid leukemia (AML), is exceptionally rare and poses a considerable diagnostic challenge due to its non-specific clinical and radiological features, often mimicking more common intracranial neoplasms like meningioma. We report a case of isolated intracranial MS in a 61-year-old female with a prior history of FLT3-ITD mutated AML (M2), who had been in sustained complete hematologic remission for four years. She presented with a two-week history of diminished responsiveness and apathy. Cranial MRI revealed a well-defined, homogenously enhancing left frontal mass with a dural tail sign and significant peritumoral edema, initially suggestive of a meningioma. However, diffusion-weighted imaging (DWI) demonstrated restricted diffusion. The tumor was resected. Histopathological examination revealed diffuse sheets of immature myeloid cells. Immunohistochemistry was positive for CD117, CD34, and CD68, with weak MPO expression, confirming the diagnosis of MS. Post-operatively, the patient was referred for systemic chemotherapy. This case illustrates that intracranial MS can be a form of extramedullary relapse in AML patients even during long-term remission and can closely mimic a meningioma radiologically. Key diagnostic clues include a prior history of AML and radiographic features such as restricted diffusion on DWI and prominent peritumoral edema. However, these findings are non-specific, and a definitive diagnosis relies on histopathological and immunohistochemical analysis. The management of MS should be based on systemic AML therapy principles rather than surgery alone. This report highlights the necessity of considering MS in the differential diagnosis of new intracranial masses in patients with a history of AML to ensure timely and appropriate treatment.

Patients with acute respiratory distress syndrome (ARDS) and acute kidney injury (AKI) requiring continuous renal replacement therapy (CRRT) represent a complex clinical scenario. Permissive hypercapnia during lung-protective ventilation may cause severe acidemia and limit further reductions in ventilatory intensity. Extracorporeal carbon dioxide removal integrated into the CRRT circuit may enhance carbon dioxide clearance while providing renal support, but its physiological effects and safety in this population remain uncertain. We conducted a systematic review and meta-analysis of adult studies evaluating ECCO2R integrated with continuous RRT in patients with ARDS and AKI. Literature searches were performed in PubMed, Embase (Ovid), and Cochrane CENTRAL from inception to May 15, 2026, without language or date restrictions, and were supplemented by reference screening, forward citation tracking, and trial registry searches. The primary outcomes were changes in PaCO2 and arterial pH after treatment initiation. Secondary outcomes included changes in ventilatory parameters, clinical outcomes, and safety events. Pre-post changes were pooled using random-effects models with restricted maximum likelihood estimation. Seven observational studies comprising 105 patients were included. ECCO2R integrated with RRT was associated with sustained reductions in PaCO2 at 2 h (mean difference [MD] -8.22 mmHg; 95% CI -12.00 to -4.44), 6 h (MD -9.02 mmHg; 95% CI -15.69 to -2.34), and 24 h (MD -9.10 mmHg; 95% CI -13.59 to -4.61). These changes were accompanied by increases in arterial pH at 2 h (MD + 0.05; 95% CI 0.02 to 0.08) and 24 h (MD + 0.06; 95% CI 0.02 to 0.11). Ventilatory variables also improved, with reductions in tidal volume normalized to predicted body weight (MD -1.14 mL/kg PBW; 95% CI -1.74 to -0.54), driving pressure (MD -3.61 cmH2O; 95% CI -4.87 to -2.35), and mechanical power (MD -6.82 J/min; 95% CI -9.12 to -4.51). Safety and patient-centered outcomes were limited and heterogeneously reported. ECCO2R integrated with CRRT was associated with early PaCO2 reduction, pH improvement, and lower ventilatory intensity in patients with ARDS and AKI. These findings support the physiological feasibility of this combined approach, although prospective comparative studies are needed to define its clinical role, safety, and impact on patient-centered outcomes. PROSPERO CRD420251234033.

Background and objective Congenital hyperinsulinemic hypoglycemia (CHH) is the leading cause of persistent hypoglycemia in neonates and infants. In high-resource settings, diagnosis and management depend on rapid genetic testing and advanced imaging to differentiate focal from diffuse disease. However, in low-resource settings, limited diagnostic capacity and lack of access to medications often necessitate early surgical intervention. This study aimed to evaluate the clinical features, surgical intervention, and outcomes in infants undergoing pancreatectomy for congenital hyperinsulinism at Al Ribat University Hospital, Sudan. Methods A retrospective descriptive study was conducted, involving all pediatric patients who underwent pancreatectomy for CHH from January 2019 to December 2024. Data were extracted from operative logs and medical records, including demographics, diagnostic investigations, medical therapy, surgical procedures, postoperative complications, histopathology, and one-year outcomes. Descriptive statistics and appropriate inferential statistical tests were used for the analysis. Results Thirty-two patients were included, of whom 19 (59.4%) were female. The majority were diagnosed during the first week of life (n = 19, 59.4%). Diazoxide was administered to 30 (93.75%) patients, with only eight (26.7%) showing a therapeutic response. Restricted access to genetic testing (n = 8, 25%) and imaging (n = 6, 18.8%) resulted in the predominance of near-total pancreatectomy (n = 31, 96.9%). Intraoperative complications were minimal, with bleeding occurring in two cases (6.25%) and vascular injury in one case (3.1%). Early postoperative hypoglycemia was noted in 13 patients (40.6%), whereas hyperglycemia was noted in one patient (3.1%). Surgical complications included wound infection in seven patients (21.9%) and intestinal obstruction in one patient (3.1%). Histopathology confirmed CHH in all cases, with diffuse disease in 27 patients (84.4%). During a one-year follow-up period, three patients (9.4%) died, including two (6.3%) due to recurrent hypoglycemia. Conclusions Near-total pancreatectomy remains a practical and life-saving option for infants with medically unresponsive CHH in low-resource settings where diagnostic and pharmacologic limitations restrict individualized care. Despite limited access to preoperative localization and the predominance of diffuse disease, surgical outcomes were acceptable, with low intraoperative morbidity and manageable rates of postoperative complications. Persistent postoperative hypoglycemia and late mortality highlight the need for structured endocrine follow-up and improved access to medical therapy. Strengthening diagnostic capacity, ensuring medication availability, and establishing coordinated multidisciplinary care pathways are essential to improving long-term outcomes for children with CHH in resource-limited environments.

Menopause is a major psychoneuroendocrine transition which can impact emotional functioning and mental health. Although emotion regulation (ER) is fundamental for mental health, intrinsic neural connectivity supporting ER across the menopausal transition remains unexplored. Addressing this gap, this study provides the first examination of intrinsic effective connectivity within an ER-related network across menopausal stages. Resting-state fMRI data were acquired from 76 healthy premenopausal (n = 32), perimenopausal (n = 19), and postmenopausal (n = 25) women. Effective connectivity within a predefined ER network was examined using spectral dynamic causal modeling. Further, we assessed how intrinsic connectivity predicts self-reported ER ability within each group. While self-reported ER ability did not differ across groups, resting-state effective connectivity within the ER network varied in a stage-specific manner, with the most heterogeneous effects observed between pre- and perimenopause, suggesting a non-monotonic pattern of between-group differences. Perimenopause was characterized by distinct frontal interaction patterns, reflecting a stage-specific redistribution of network organization rather than a gradual intermediate between pre- and postmenopausal connectivity profiles. Differences regarding postmenopause were restricted to greater weighting of temporo-parietal network components. Connectivity-ER ability associations revealed stage-specific predictive profiles, with distributed fronto-temporal connectivity predicting ER ability in premenopause, frontal-restricted connectivity in perimenopause, and a single frontal connection with reversed predictive direction in postmenopause. Our findings demonstrate that comparable levels of trait-based ER ability are associated with divergent intrinsic network configurations rather than a uniform architecture. Identifying perimenopause as distinct stage of intrinsic network organization advances hormone-sensitive models of intrinsic connectivity and provides a framework for understanding how baseline network organization may adapt during psychoneuroendocrine transitions in women.

Evaluate the effectiveness and safety of adding metformin to insulin (M+I) versus insulin alone for pregnant women with type 2 diabetes mellitus (T2DM) or gestational diabetes mellitus (GDM), focusing on stillbirth as the primary outcome. PubMed, Embase, and Cochrane Central were searched. No date limits. Last search: January 2025. Randomized clinical trials including women with T2DM or GDM were eligible. Trials restricted to type 1 diabetes were excluded. Two reviewers extracted maternal and neonatal outcomes and assessed risk of bias with the Cochrane RoB 2 tool. Evidence certainty was graded using GRADE. Data were pooled with random-effects models and reported as risk ratios (RRs) or mean differences (MDs) with 95% confidence intervals. Nine RCTs (2,420 women) were included, most with GDM and some with T2DM. Moderate-quality evidence indicated reduced stillbirth risk with M+I (6 RCTs, 2,196 participants; RR 0.36, 95% CI 0.14-0.90; NNT 111). Low-quality evidence suggested lower risks of gestational hypertension (4 RCTs; RR 0.68, 95% CI 0.48-0.97) and neonatal hypoglycemia (7 RCTs; RR 0.49, 95% CI 0.30-0.80). No significant differences were found for cesarean section, preterm delivery, or other neonatal outcomes. Heterogeneity, baseline imbalances, and small samples limited certainty. M+I may reduce stillbirth and some adverse outcomes compared with insulin alone, but most evidence remains low certainty. Further high-quality RCTs are needed.Registered in PROSPERO: CRD42024617330.

Lysosomal viscosity is a key biomarker of cancer progression and chemotherapy response, but real-time, precise monitoring remains challenging. To address this challenge, we develop a novel chemosensing platform based on a molecular rotor architecture for specific, dynamic detection of lysosomal viscosity. The platform operates via an "off-on" switching mechanism: in low-viscosity environments, rapid rotor rotation through the twisted intramolecular charge transfer effect quenches fluorescence; in high-viscosity conditions, restricted rotation triggers strong emission, enabling an ultra-sensitive and selective response. Using systematic molecular engineering and screening within this platform, the probe PMA-H is identified as the optimal candidate, demonstrating a remarkable 187-fold fluorescence enhancement in response to viscosity (from 0.54 to 1410 cP), excellent environmental stability with minimal interference from pH, polarity, or biomolecules, and precise lysosomal targeting. Subsequently, PMA-H is employed to track lysosomes in HeLa cells, and it reveals alterations in lysosomal viscosity, morphology, and abundance during apoptosis, ferroptosis, cuproptosis, and zinc-induced cell death. In general, this platform allows real-time tracking of lysosomal viscosity fluctuations induced by various chemotherapeutic agents, highlighting its significant potential as a powerful tool for early cancer diagnostics and fundamental lysosomal research.

Urosepsis is a critical condition originating from urinary tract infections, characterized by rapid progression and high mortality. The Pan-immune-inflammation Value (PIV), a novel composite index reflecting integrated immune and inflammatory status, has shown prognostic value in various critically ill and septic populations. However, its independent prognostic value in urosepsis remains inadequately explored. This study therefore aims to systematically evaluate the ability of PIV to predict 28-day adverse outcomes in patients with urosepsis. This study employed a retrospective dual-cohort design. The internal training cohort comprised adult ICU patients with urosepsis from the MIMIC-IV database, while the external validation cohort was derived from the electronic medical record system of Anshun Municipal People's Hospital. To investigate the association between the PIV and short-term adverse outcomes in urosepsis patients, we utilized a range of statistical methods, including multivariable Cox regression, restricted cubic spline (RCS) analysis, subgroup analysis, and Kaplan-Meier survival curves. To develop a parsimonious predictive model, the internal cohort was randomly split into training and testing sets at a 7:3 ratio. Within the training set, an ensemble machine learning strategy-incorporating the Boruta algorithm, LASSO-Cox regression, random forest (RF), gradient boosting (GBDT), and support vector machine (SVM)-was applied to identify key predictive variables from serological tests, comorbidities, demographic characteristics, and vital signs. Based on the selected features, prognostic models were constructed using multivariable Cox regression in the training, testing, and external validation sets, respectively. The discriminatory power of these models against traditional disease severity scores was assessed using receiver operating characteristic (ROC) curves, with the area under the curve (AUC) quantifying predictive performance. A total of 1,686 patients with severe urosepsis were included in this study. In the fully adjusted model, both continuous PIV and PIV quartiles were independently associated with 28-day adverse outcomes. For 28-day ICU mortality, each unit increase in continuous PIV was associated with a 76.4% higher risk (HR 1.764, 95% CI 1.340-2.323, p < 0.001); compared with the lowest quartile (Q1), the highest quartile (Q4) showed a significantly increased risk of 84.3% (HR 1.843, 95% CI 1.186-2.846, p = 0.007). For 28-day in-hospital mortality, the HR for continuous PIV was 1.639 (95% CI 1.214-2.214, p < 0.001), and the HR for Q4 was 1.789 (95% CI 1.110-2.885, p = 0.039). In the external validation cohort, the predictive value of PIV for 28-day ICU mortality remained consistent and was even more pronounced (continuous PIV: HR 1.79, 95% CI 1.21-2.64, p = 0.004). Restricted cubic spline analysis further confirmed a significant positive dose-response relationship between PIV and mortality (overall p < 0.001). The risk prediction model based on PIV demonstrated good discriminative ability, with areas under the receiver operating characteristic curve of 0.71, 0.73, and 0.76 in the training, internal testing, and external validation sets, respectively, all of which were higher than those of traditional severity scores (e.g., SOFA, APACHE II). This study confirms PIV as an independent predictor of 28-day mortality risk in patients with urosepsis across two cohorts. The prediction model incorporating PIV and four other clinical variables exhibited good discrimination and calibration, with prognostic performance superior to that of traditional disease severity scores. Future prospective, multicenter studies involving diverse geographic and ethnic populations are needed to further validate the generalizability of this model, thereby facilitating precise risk stratification for patients with urosepsis.

Precise enhancement of endogenous protein synthesis offers a reversible therapeutic strategy without permanent genomic modification. However, existing Cas13-mediated translational activation systems are limited by modest potency and restricted modular expandability. Here, we developed the Enhanced Targeted Translational Activation System (ETTAS), a modular RNA-guided platform that combines dCas13a, the SINEB2 translational activation element, and an independently recruitable aptamer-mediated auxiliary module. Systematic ortholog screening identified dCas13a as the most effective scaffold for SINEB2-mediated translational activation, whereas direct tandem duplication of SINEB2 elements impaired rather than enhanced activity. To overcome this architectural limitation, we used aptamer-mediated recruitment to spatially separate target recognition from auxiliary activation. A binding-validated, non-interfering dCas13a-binding aptamer enabled construction of a dual-module system in which an aptamer-recruited SINEB2 element enhanced translation without altering target mRNA abundance or stability. Compared with the previously reported dCasRx-SINEB2 system, ETTAS produced stronger reporter activation, stronger endogenous induction of P53 and PTEN, and greater antiproliferative and pro-apoptotic effects in bladder cancer cells. Proteomic analyses showed selective target protein upregulation with limited global perturbation. In vivo, dual-AAV delivery of ETTAS activated endogenous P53 and suppressed tumor growth. ETTAS establishes a programmable framework for modular post-transcriptional upregulation of endogenous proteins.

Lafosse type III and IV subscapularis tendon injuries are severe rotator cuff tears. Current repair uses anterolateral, anterior, and lateral portals, which have restricted visualization and difficult maneuverability. This technical note describes an L-shaped three-portal (LST) combination: anterosuperolateral, anteroinferolateral, and anteroinferomedial portals. The L-shaped three-portal configuration establishes an unobstructed surgical field free from bony interference, allowing comprehensive subscapularis tendon exposure. It optimizes anchor insertion angles and suture passing path, promoting accurate anchor fixation and effective suture management. Ultimately, it minimizes surgical complications and improves double-row repair efficiency for Lafosse type III/IV injuries, presenting a secure and efficient approach. This article outlines the technique, highlighting procedural aspects, potential risks, advantages, and limitations.

Obesity stands as a formidable 21st-century public health crisis, with its capacity to aggravate depressive symptoms gaining increasing clinical attention. Traditional treatment models often treat these two conditions separately. However, recent research evidence suggests a complex network linking obesity and depressive symptoms across metabolism, behavior, and mental health, with dietary patterns proposed as a key upstream modulator of both metabolic and psychological pathways. The specific mechanisms by which diet influences obesity and depressive symptoms remain unclear. Therefore, this narrative review focuses on analyzing molecular connections between diet, obesity, and depressive symptoms, including adipose tissue inflammation, the gut-brain axis, the hypothalamus-pituitary-adrenal axis, insulin and brain-derived neurotrophic factor levels, and neuroplasticity. We discuss the possible pathways and effects of different diet therapies in regulating metabolism and simultaneously impacting mental health, including calorie restriction diet, intermittent fasting, ketogenic diet, low glycemic index diet, plant-based diet, Mediterranean diet, Dietary Approaches to Stop Hypertension, among others. This review aims to provide a scientific basis for precision nutrition and personalized, sustainable diet therapies in clinical practice, promoting awareness and improving treatment strategies for depressive symptoms in obese patients.

Radiotherapy (RT) is a crucial component of childhood cancer management; however, its global availability and technological capacity remain highly heterogeneous. Despite increasing international attention to childhood cancer care, comprehensive analyses of pediatric RT infrastructure across different economic settings remain limited. This scoping review aimed to characterize the global landscape of pediatric RT infrastructure, treatment technologies, and operational challenges, while highlighting Morocco as an illustrative low- and middle-income country (LMIC) case study. A systematic search identified 1361 records, of which 41 studies published between 2016 and 2025 were included following PRISMA-ScR methodological guidance. Of these, 51.2% originated from LMICs, whereas only 19.5% were conducted in high-income countries (HIC). Advanced treatment modalities, such as intensity-modulated RT, volumetric modulated arc therapy, and proton therapy, remain largely concentrated in HICs, whereas many LMICs continue to rely on limited infrastructure and constrained technical resources. These structural limitations may contribute to delayed treatment initiation and restricted access to pediatric RT. The Moroccan context illustrates both ongoing national efforts to modernize RT services and the persistent scarcity of pediatric-specific data in the literature. Addressing these disparities will be essential to improving equitable access to pediatric RT worldwide.

The menisci play a critical role in load transmission and shock absorption and serve as important secondary stabilizers of the knee. Unfortunately, meniscal repair is not always feasible, and resection may be required. Meniscal allograft transplantation is an established method of meniscal substitution; however, its use remains limited by graft sizing challenges, high costs, and restricted availability. The semitendinosus tendon has the capacity to remodel and revascularize within the intra-articular environment. The purpose of this technical note is to describe the surgical technique for meniscal substitution using a semitendinosus tendon autograft.

Osteoarthritis (OA) is increasingly recognized as an immune-associated whole-joint disorder characterized by chronic low-grade inflammation, which contributes to joint degeneration, structural deterioration, and persistent pain. Innate and adaptive immune cells, including macrophages, T cells, neutrophils, and mast cells, participate in OA pathogenesis by releasing pro-inflammatory cytokines, reactive oxygen species, and matrix-degrading enzymes, as well as by interacting with chondrocytes, synovial fibroblasts, and subchondral bone cells. Natural products, because of their multi-target pharmacological properties, have emerged as potential modulators of this complex immune microenvironment. This review critically appraises current evidence on natural-product interventions modulating OA-associated immune-cell responses, with particular emphasis on mechanistic evidence, evidence maturity, and translational potential. It further compares evidence across immune-cell populations to identify shared mechanisms, population-specific differences, and key translational gaps. Macrophage- and T-cell-associated responses have the most developed evidence base, with relatively consistent evidence supporting modulation of M1-like/M2-like macrophage phenotypes and the T helper 17 (Th17)/regulatory T (Treg) cell balance. Neutrophil- and mast-cell-associated responses represent emerging or auxiliary areas of evidence, as these immune-cell populations may amplify inflammation and pain through reactive oxygen species production, neutrophil extracellular trap formation, degranulation, and inflammatory mediator release. Evidence for B cells, dendritic cells (DCs), and natural killer (NK) cells remains limited; therefore, these immune-cell populations should currently be regarded as potential research directions rather than established therapeutic targets. Most available data derive from in vitro and animal studies, whereas clinical evidence is largely restricted to peripheral immune-marker changes and short-term symptom improvement. Future studies should integrate local joint immune profiling, functional validation, and stratified clinical designs to clarify the translational potential of natural products in OA immunomodulation.

Juvenile idiopathic arthritis (JIA) remains a clinical challenge when conventional and biological therapies fail. This report describes a case of highly refractory JIA and evaluates the efficacy of the Janus kinase (JAK) inhibitor upadacitinib, providing a potential therapeutic reference for difficult-to-treat pediatric autoimmune diseases. A 16-year-old female presented with a 3-year history of polyarticular swelling and pain that worsened over 1 month. Physical examination revealed extensive tenderness in the small joints of the hands, feet, and knees. Functional impairment was noted in the shoulder joints (restricted abduction and lifting) and wrist joints (limited flexion and extension). Laboratory results showed an erythrocyte sedimentation rate of 26&#x2005;mm/h and a C-reactive protein level of 18.39&#x2005;mg/L. Musculoskeletal ultrasound indicated grade 1 synovitis with effusion in the bilateral metacarpophalangeal, proximal interphalangeal, and distal interphalangeal joints, as well as both wrist joints. Effusion was also observed in the suprapatellar bursae of both knees. The patient's condition was classified as refractory, with prior failure of multiple lines of therapy, including conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), various biologic DMARDs (bDMARDs) (such as TNF, IL-6, and IL-1 inhibitors), and targeted synthetic DMARDs, such as tofacitinib. Following initiation of upadacitinib, the patient achieved marked clinical remission and improved joint mobility. Upadacitinib demonstrated potent efficacy in a pediatric patient with JIA who was nonresponsive to multiple bDMARDs and tofacitinib. These findings suggest that upadacitinib may be a viable salvage therapy for refractory JIA.

This paper presents a qualitative evidence synthesis investigating men's clinical experiences, psychosocial challenges, and decision-making related to help-seeking and treatment for erectile dysfunction (ED).&#xa0;The findings suggest that ED affects relationship experiences, self-esteem, psychosocial well-being, and help-seeking behaviors. Studies identified through Scopus, PubMed, and PsycINFO were synthesized qualitatively, focusing on adult men's experiences of ED, disclosure, treatment engagement, and decision-making.&#xa0;The review protocol was not prospectively registered. Searches were conducted in March 2026, and the included studies represented diverse clinical contexts, including general ED care, diabetes care, cancer survivorship, and cardiovascular rehabilitation. Eight qualitative studies involving 209 participants were included, and four major themes emerged: masculinity, stigma, and self-silencing; relational consequences influencing help-seeking and disclosure; healthcare communication as a barrier or facilitator to care; and treatment trade-offs, adherence, and acceptability. Men frequently reported negative effects on emotional well-being and help-seeking behaviors due to ED. Delay and hesitation in disclosure and help-seeking were attributed to fear of judgment, lack of support, and negative effects on confidence and self-esteem. Participants valued respectful communication from healthcare professionals and preferred supportive, individualized approaches that included relationship support. Decisions to seek treatment were influenced not only by perceived effectiveness but also by side effects, emotional burden, relationship concerns, and communication experiences.&#xa0;The findings should be interpreted with consideration of the limited number of included studies and the&#xa0;restriction to English-language publications. These findings suggest that ED care should incorporate respectful, stigma-sensitive communication and individualized counseling to facilitate treatment-seeking and improve treatment engagement.

Triple-negative breast cancer (TNBC) is an aggressive subtype lacking estrogen, progesterone, and HER2 receptors, which restricts targeted therapies and contributes to poor survival. Conventional chemotherapeutics such as doxorubicin and cisplatin show limited efficacy, significant toxicity, and resistance, underscoring the need for alternative strategies. Nerium oleander, a traditional medicinal plant, has demonstrated anticancer activity through leaf extracts; however, the role of exosome-like nanoparticles derived from its flowers (NELNs) remains unexplored. The therapeutic efficacy of NELNs was evaluated in the MDA-MB-231 TNBC cell line using in vitro and in silico approaches. Cytotoxicity was assessed by the MTT assay, while AO/EtBr and DCFDA staining examined apoptosis and ROS generation through fluorescence microscopy. Flow cytometry was employed for apoptosis confirmation and cell cycle analysis. Network pharmacology integrating target prediction, PPI network construction, and functional enrichment analysis was performed, followed by molecular docking of NELN-encapsulated metabolites against predicted targets. NELNs induced significant cytotoxicity, promoted apoptosis, and increased intracellular ROS levels in MDA-MB-231 cells. Flow cytometry confirmed apoptotic induction and revealed alterations in cell cycle progression. Pathway enrichment analysis of previously identified NELN-associated metabolites computationally highlighted arachidonic acid and linoleic acid metabolism, with cytochrome P450 enzymes (CYP1A2, CYP2C9, CYP3A4) emerging as putative targets. Molecular docking predicted favorable binding interactions of NELN metabolites to these targets. This study provides preliminary evidence that flower-derived NELNs exerted antiproliferative and pro-apoptotic activity against MDA-MB-231 cells under the tested experimental conditions. Furthermore, network pharmacology analyses generated putative mechanistic insights into pathways relevant to TNBC.