Annals of Translational Medicine

Purpose: To analyze the effect of radiotherapy timing relative to surgery on patients' survival and mortality rates in uveal melanoma (UM). Design: Retrospective cohort study using registry data from the Surveillance, Epidemiology, and End Results (SEER) database. Subjects: A total of 1,198 patients with UM were extracted from the SEER database and divided into three groups: preoperative radiotherapy, intraoperative radiotherapy (IORT), and postoperative radiotherapy. Methods: UM cases were extracted from the SEER database. Survival curves were generated based on the Kaplan-Meier method. An extended Cox regression was used to estimate the cancer-specific and all-cause mortality. Main Outcome Measures: Overall survival (including median survival) and hazard reductions for cancer-specific and all-cause mortality. Results: Preoperative radiotherapy revealed the highest median survival (4.93 years), followed by postoperative radiotherapy (4.76 years), and IORT (4.02 years). The preoperative strategy reduced the hazard of all-cause mortality by 42%, 50%, and 60% at 5-, 7-, and 10-year follow-up, respectively, compared with IORT. Findings were consistent in the cancer-specific sensitivity analysis (45%, 53%, and 62% reductions at the same time points). However, postoperative radiotherapy did not significantly reduce the cancer-specific mortality in comparison to IORT. Conclusions: Preoperative radiotherapy was associated with higher median overall survival and lower all-cause and cancer-specific mortality than IORT over 10 years of follow-up. Postoperative radiotherapy showed intermediate outcomes that did not differ significantly from IORT. Prospective studies with more detailed data on the temporal relation of radiotherapy timing and surgery are needed to confirm these findings.

Background. A recent meta-analysis by Dang et al. [1] concluded that enteral supplementation with docosahexaenoic acid (DHA), with or without arachidonic acid (ARA) did not significantly affect retinopathy of prematurity (ROP) outcomes in preterm infants. Of four eligible trials that supplemented both DHA and ARA, only two contributed to each ROP outcome analyzed, and severe ROP was not assessed. Methods. We replicated the eligibility criteria and search strategy of Dang et al., restricted to trials that supplemented both DHA and ARA, and reanalyzed three ROP endpoints (any ROP, ROP requiring treatment, and severe ROP [stage 3 and/or treated]) using complete outcome records from all eligible trials. Crude risk ratios (RR) were pooled by Mantel-Haenszel fixed-effect meta-analysis. Gestational age-adjusted odds ratios (adjOR) were pooled on the log scale by inverse-variance random-effects meta-analysis with restricted maximum likelihood (REML) estimation of between-study variance and Hartung-Knapp confidence intervals. Results. Five trials were included; one trial was identified in our replicated search but was excluded by Dang et al. without a stated rationale. The pooled estimate for any ROP was consistent with Dang et al. (RR 0.87 [95% CI 0.71-1.08]; adjOR 0.70 [0.46-1.08]). For ROP requiring treatment, the crude RR suggested a lower risk but did not reach statistical significance (RR 0.60 [0.35-1.04]), whereas the gestational age-adjusted estimate indicated lower odds (adjOR 0.47 [0.23-0.94]). For severe ROP, DHA+ARA supplementation produced a significant protective effect in both unadjusted and adjusted models (RR 0.56 [0.36-0.86]; adjOR 0.42 [0.19-0.96]). Conclusions. When all eligible trials contribute to each endpoint and severe ROP is included as an outcome, enteral DHA+ARA supplementation reduces severe ROP and is associated with lower odds of ROP requiring treatment after adjustment for gestational age. These findings differ from the conclusions of Dang et al. and support reconsideration of DHA+ARA supplementation as a strategy to reduce sight-threatening ROP in preterm infants.

Background: Pulmonary arterial hypertension (PAH) is a serious disease with poor prognosis, especially in infants or preterm babies and there is still no optimal treatment for this disease. Noradrenalin (NE) is a vasoactive mediator which is released by sympathetic ganglion. According to previous studies, NE/1-adrenoreceptors is not only in regulating normal physiologic responses, but also in the pathogenesis of PAH. However, the mechanisms of NE in PAH are not fully understood. Methods: Human PASMC (PASMC) was used in this study. Cell viability assay and Wound healing assay were used to evaluate the proliferation and migration of PASMC. Immunoprecipitation and western blots analysis were used to investigate the mechanisms which involved in NE-induced PASMC proliferation. Results: We investigated that NE could induce human PASMC proliferation and migration. Furthermore, we first find that endothelin 1 (ET-1) signaling pathway plays an important role in NE-induced PASMC proliferation. ET1 is a critical molecular which is known for regulating cell growth and migration. We investigated that NE could increase NE-1 secretion, further enhancing ET-1 bind to its receptors. For further clarifying the downstream signals in NE/ET-1 induced PASMC proliferation, we detected the phosphorylation and expression levels of ERK and JNK. Conclusions: By combining the results from ours and previous studies, we believed that JNK/c-jun pathway may play an important role in NE-induced PASMC proliferation. Key Words: Noradrenaline; Pulmonary Arterial Hypertension; Pulmonary Artery Smooth Muscle Cells; Endothelin-1; JNK/c-Jun Signaling.

Background: Refractory and macrolide-resistant Mycoplasma pneumoniae pneumonia (MPP) has emerged as a major challenge in pediatric respiratory medicine, amplified by the post-2023 resurgence. However, a systematic overview of the research landscape specific to treatment-refractory and drugresistant disease in children remains lacking. Methods: Research articles and reviews on pediatric refractory or macrolide-resistant MPP published between 2000 and 2025 were retrieved from OpenAlex using Boolean searches. After screening, 2,286 records were quantitatively analyzed for annual output, contributing countries/institutions, thematic clusters, and citation-burst dynamics using Python. Results: Annual publications grew exponentially, with a pronounced surge after 2023 (n=378 in 2025). China produced the highest volume (45.1%) but recorded fewer citations per publication than the US, Japan, and Canada. The literature resolved into four clusters: macrolide resistance/molecular basis, epidemiology, etiology/co-infection, and refractory disease management. Burst analysis showed an evolution from earlier fronts like 23S rRNA mutations and azithromycin to recent emerging trends like pandemic-related co-circulation, genotype surveillance, and co-infection. Conclusions: Research on pediatric refractory and resistant MPP is expanding rapidly, shifting in emphasis from etiologic descriptions toward resistance mechanisms and clinical management. Standardizing the treatment of macrolide-unresponsive disease and post-pandemic epidemiological surveillance represent the principal directions for future work. Keywords: Mycoplasma pneumoniae; children; macrolide resistance; refractory pneumonia; bibliometric analysis; research trends

Background: An estimated 826 million people have avoidable near vision impairment (NVI) due to lack of access to near vision glasses for presbyopia. Glasses use, uptake and replacement is essential to sustained NVI correction. Here we explore the uptake of second and subsequent pairs of near vision glasses and the willingness to pay. Methods: In this cross-sectional survey, 276 individuals who received near vision glasses through eye health screening programs in Punjab province, Pakistan from 2020 to 2022, were surveyed between February and July 2025, i.e. 3-5 years later. Results: 92.0% (n=254) of respondents were still using near vision glasses: a purchased replacement (41.3%, n=114), a free replacement (30.8%, n=85), or the original pair (19.9%, n=55). Male gender, higher age, and personal income were strongly associated with purchasing additional pairs, while women and those economically dependent on others relied more on free provision (all p values <0.05). Accessibility, indicated by shorter travel times and awareness of supply sources, also played a significant role in sustained replacement. Over 98% of participants expected to obtain (purchase or receive) a new pair of glasses in the future, and over 94% of participants expected to purchase their next pair. The mean willingness-to-pay (WTP) was 353 PKR (95% CI: 327-379) // 1.25 USD (95% CI: 1.16-1.34), while the average reported price paid was 416.67 PKR // 1.47 USD (95% CI: 351.39-481.94)). Conclusion: Sustained use of near vision glasses remained high 3-5 years after initial provision. Many recipients had purchased replacements, and willingness and ability to pay were high among participants, suggesting potential for sustained demand beyond initial subsidized distribution.

Purpose: To implement a comprehensive knowledge-based algorithm (KBA) for pancreatic cancer staging based on the current Japanese guidelines and to evaluate its performance as a clinical decision support system in comparison with a retrieval-augmented large language model (LLM) system. Materials and methods: A KBA covering TNM classification, stage classification, and resectability classification was implemented as a web application. The correctness of the system outputs was exhaustively verified for all possible inputs. Subsequently, six non-board-certified radiologists performed pancreatic cancer staging for 12 simulated cases with imaging findings under three conditions: unassisted, LLM-assisted, and KBA-assisted. Staging accuracy and staging time were compared among the three conditions using pairwise proportion z-tests and Welch's t-tests, respectively. Results: In the comparative experiment, staging accuracy was 81.9%, 80.6%, and 98.6% in the unassisted, LLM-assisted, and KBA-assisted conditions, respectively. Mean staging time was 229.2, 401.9, and 196.2 s, respectively. The KBA-assisted condition showed higher accuracy than both the unassisted and LLM-assisted conditions (both p<0.001). Staging time was longer in the LLM-assisted condition than in the other two conditions (both p<0.001). Conclusion: A comprehensive KBA for pancreatic cancer staging based on the current Japanese guidelines was implemented and exhaustively verified. In a preliminary comparative experiment, KBA assistance improved staging accuracy without increasing staging time, whereas LLM assistance increased staging time without improving staging accuracy. These findings suggest that verified KBA systems may be feasible and useful for clinical tasks governed by explicit guideline-based rules.

We present our Stage-1 Registered Report as a full clinical trial article with all methods in past tense and including mock results, table and figures for the primary analysis. To remind the reader that this Stage-1 article is written before data collection, we highlight in color that these mock results are only for illustrative purposes and will be replaced by the actual results in the Stage-2 Registered Report. Background In patients experiencing out-of-hospital cardiac arrest, optimization of oxygen delivery during cardiopulmonary resuscitation is a critical. Although both positive end-expiratory pressure (PEEP) and zero end-expiratory pressure (ZEEP) are employed during CPR, their respective impacts on clinically relevant outcomes is yet to be clearly established. Methods This investigator-initiated, pragmatic, registry-based, multicenter, triple-blind randomized controlled superiority trial evaluates whether applying 8 cm H2O PEEP during cardiopulmonary resuscitation improves outcomes compared with ZEEP in adults with non-traumatic, non-drowning out-of-hospital cardiac arrest. Pre-randomized CPR kits (1:1 PEEP vs. sham) were used by ambulance sites during manual ventilation throughout the resuscitation process. The primary analysis was conducted in the principal stratum of patients who received either a supraglottic airway or endotracheal tube. The primary outcome was neurological status at hospital discharge measured by a utility-weighted score on the modified Rankin Scale. Secondary outcomes included prehospital return of spontaneous circulation, 30-day survival, and 6-month quality of life. The primary safety outcome was clinically significant pneumothorax.

Abstract Background: Even though significant advances in diagnosis, treatment, and prevention strategies have been implemented, neonatal sepsis remains a common concern in clinical practice, especially in low-resource countries. It is one of the major causes of death during the first month of life. This study aimed to assess clinical outcomes and predictors of mortality among neonates with neonatal sepsis admitted to public hospitals in selected Hospitals in Addis Ababa, Ethiopia. Methods: A hospital-based prospective cohort study design was conducted among 466 neonates admitted with neonatal sepsis from September 2024 to January 2025. All neonates who were admitted to selected Hospitals of Addis Ababa city after being clinically or laboratory-diagnosed with neonatal sepsis by the attending physician were included in the study. Data were entered into EpiData 4.2 and analyzed by SPSS version 26. Bivariate and multivariate Cox regression were used to identify the relationship between dependent and independent variables. Finally, variables with p-value [&le;] 0.05 were taken as significant factors associated with poor clinical outcome. Results: The study was conducted among 466 neonates admitted with neonatal sepsis. Of all neonates admitted with neonatal sepsis, 372 (79.8%) were discharged with good outcomes, and 94 (20.2%) had a poor outcome/died. Duration of ruptured membrane being >12hr (AOR=7.02, 95 % (CI: 1.85, 26.57), marital status /divorced (AOR=3.12, 95 % (CI: 1.67, 7.45),rural residence (AOR= 6.05, 95 % (CI: 2.03-16.53), assisted instrumental delivery (AOR= 5.99, 95 % (CI: 1.46-17.11), meconium-stained amniotic fluid ((AOR= 9.48, 95 % (CI: 0.49-18.61)), no initiate exclusive breast feed within one hour (AOR= 3.20, 95 % (CI: 0.90-7.52), chest in drawing (AOR= 5.81, 95 % (CI: 1.75-11.23) were significantly associated with neonatal mortality. Conclusion: Neonatal mortality was moderately high. Meconium-stained amniotic fluid, prolonged duration of ruptured membrane (>12hr), Mode of delivery (instrumental delivery), and chest in drawing are among the predictors of neonatal mortality. Keywords: -Clinical outcome,Neonatal sepsis, Mortality, predictors, Ethiopia.

Cardiac tissue is primarily made up of cardiomyocytes, which are regulated by the autonomic nervous system. We have used and developed approaches such as patch clamping and electrical stimulation-combined calcium imaging, computer modeling, optogenetics and chemogenetics combining with video-based Short-Time Fourier transformation (STFT) method to study the physiological activities of cardiomyocytes. The action potential of cardiomyocytes was found to be synchronized with calcium signals, which can be grouped into two categories by STFT. A mathematical model was developed to simulate the changes in electrical activities within cardiomyocytes caused by energy depletion, especially for 2-deoxy-D-glucose (2DG) treatment. Optogenetic and chemogenetics tools, such as ChR2(H134R), OptoXR-{beta}2AR and hM3Dq accelerated beating, while GR, ACR1 and hM4Di inhibited cardiomyocytes beating. A video-based STFT method was developed to visualize the beating frequency during these manipulations. An in vitro co-culture method was developed to study the relationship between sympathetic neuronal firing and calcium dynamics in cardiomyocytes. In vivo, electrocardiograph (ECG) measurements showed that Clozapine N-oxide (CNO) caused heart rates increasement in cTnT-hM3Dq virus injected mouse. However, it had no impact on cTnT-hM4Di virus injected mouse. This study provides comprehensive methodologies for studying cardiomyocyte physiology and manipulating heart rates in vitro and in vivo.

ObjectiveIn recent years, the number of cats kept as companion animals has increased, leading to a growing demand for veterinary care. Although some histone deacetylase (HDAC) inhibitors are promising for the treatment of human cancers and neurological diseases, comprehensive systematic research on HDAC inhibitors in domestic cats remains insufficient. Therefore, this study aimed to investigate the effects of HDAC inhibitors on the transcriptome of feline cells. MethodsTwo types of cells derived from domestic cats, Crandell-Rees Feline Kidney (CRFK; kidney-derived) cells and PG-4 cells (astrocyte-derived), were treated with four HDAC inhibitors (panobinostat, trichostatin A, valproic acid, and vorinostat) for 24 h. Transcriptomic changes after treatment were examined using RNA sequencing. ResultsHDAC inhibitor treatment upregulated the expression of intercellular chemical interactions and signal transduction-related genes, similar to observations in human cells. Although HDAC inhibitors did not suppress the expression of cell cycle-related genes in CRFK cells, as observed in human cells, the inhibitors downregulated the expression of organogenesis-related genes. Consistent with observations in human cells, HDAC inhibitors suppressed the expression of cell cycle- and cancer-related genes in PG-4 cells. Importantly, valproic acid, which is thought to be more effective for neurological diseases than for cancer, suppressed the expression of more cancer-related genes in PG-4 cells than the other three HDAC inhibitors. Conclusion and relevanceOur findings revealed that the responses of cells derived from feline organs to various HDAC inhibitors varied considerably depending on the organ of origin and species. Since few studies, including human studies, have comprehensively compared transcriptomic responses to multiple HDAC inhibitor classes across multiple cell types, the results of this study provide a foundation for future research on the treatment and prevention of cancer and neurological diseases in domestic cats and other mammals.

Objective: To examine how medial plantar nerve shear wave speed (Cs) and viscosity coefficient (Vi) are associated with the severity of diabetic peripheral neuropathy (DPN), and to assess their ability to differentiate adjacent severity categories. Materials and Methods: Based on TCSS, the 113 patients with type 2 diabetes mellitus were assigned to the non-DPN (n = 33), mild DPN (n = 46), and moderate DPN (n = 34) groups. Medial plantar nerve Cs and Vi were measured using shear wave elastography and viscosity imaging. Receiver operating characteristic analysis evaluated Cs, Vi, and their logistic regression-based combination; areas under the curves (AUCs) were compared using DeLong tests. Results: Cs and Vi increased progressively across the three groups (both P < 0.001). For non-DPN versus mild DPN, the AUCs of Cs, Vi, and the combined model were 0.688 (95% CI, 0.604-0.772), 0.741 (0.660-0.822), and 0.745 (0.665-0.826), respectively, without significant pairwise differences. For mild versus moderate DPN, the corresponding AUCs were 0.707 (0.625-0.789), 0.794 (0.724-0.865), and 0.799 (0.731-0.867). The combined model outperformed Cs (P = 0.045), whereas Cs versus Vi and Vi versus the combined model did not differ significantly (P = 0.162 and 1.000, respectively). Conclusion: Medial plantar nerve Cs and Vi increased with DPN severity. Their combination improved discrimination between mild and moderate DPN compared with Cs alone but not with Vi alone. Quantitative medial plantar nerve viscoelastic assessment may complement clinical severity grading.

Background: A subset of uveal melanomas can be treated using either enucleation or proton beam therapy (PBT), which offer similar oncological outcomes. The most appropriate treatment depends on a patient's preference. To allow patients to genuinely determine their preference, it is recommended to describe options as neutrally as possible. This study assesses to what extent ocular oncologists use and perceive non-neutral framing behaviour, and if it is related to patient satisfaction with decision-making. Methods: Consultations of ocular oncologists with patients newly-diagnosed with uveal melanoma were audio recorded, transcribed verbatim, and coded for ocular oncologists' explicit and implicit non-neutral framing behaviours. Explicit non-neutral framing was defined as: explicitly mentioning a preferred option at least once, without relating it to the patient. Implicit non-neutral framing was defined as: describing an option (un)favourably, without providing a medically substantive clarification alongside. Results: 110 patients provided consent for the audio recordings. Non-neutral framing was found in 84% (n=92/110) of consultations. We found explicit behaviour in 38% (42/110) and implicit behaviour in 76% (84/110, median=1, range, 0-4) of consultations. The most frequent implicit framing was presenting options by positively or negatively emphasizing one option. Non-neutral framing behaviours were not significantly related to patient satisfaction with decision-making. Conclusion: This study shows that in most consultations some non-neutral framing was present, which did not impact patients' satisfaction with decision-making. Nonetheless, ocular oncologists should be aware that how they describe options may influence preferences in ways that do not align with the patient's values.

Background Neonates with critical congenital heart disease (CCHD) are vulnerable to feeding-related complications including necrotizing enterocolitis (NEC). Human milk and direct breastfeeding (BF) may offer protection, but multisite evidence is limited. We aimed to determine relationships between the proportion of human milk received (ie, human milk percentage) or BF frequency during the neonatal period and NEC, sepsis, infectious complications, or length of stay (LOS). We also determined whether bovine-derived fortification or formula initiation was associated with NEC. Methods This retrospective study included neonates from 25 US pediatric centers who underwent surgery with cardiopulmonary bypass. Outcomes were NEC (modified Bell's Stages II-III), sepsis, infection, and LOS. Disease risk score case-control matching and energy balancing weighted regression balanced multiple relevant covariates. Results Among 822 neonates, the percentage of human milk received during the neonatal period was not associated with NEC, sepsis or infection. Initiation of fortification or formula was associated with 3-fold higher odds of developing NEC within 5 days (OR:3.10, 95%CI:1.10-8.12, p=0.025). In energy balancing weighted regression models, higher neonatal human milk percentage and more frequent BF were strongly associated with shorter LOS: 100% versus 0% human milk with 9.33 days shorter (4.47-14.19, p<0.001); each additional BF session with 0.48 days shorter (0.31-0.65, p<0.001). Conclusions In this multisite cohort, fortification or formula initiation was associated with increased odds of NEC; and neonatal human milk percentage and BF with shorter LOS. Given limited evidence to guide practice, caution in introducing bovine-derived formula for high-risk infants with CCHD may be warranted.

Background: Maternal obesity is associated with lower breastfeeding initiation, shorter breastfeeding duration and lower rates of exclusive breastfeeding. Although breastfeeding intention predicts initiation, little is known about how first-time mothers living with obesity experience the transition from antenatal intention to postpartum reality. Aim: This qualitative study explored breastfeeding expectations, intentions, attitudes and early breastfeeding challenges among first-time mothers living with obesity in Switzerland. Methods: Seven semi-structured interviews were conducted with first-time mothers living with obesity in German-speaking Switzerland. Interviews were audio-recorded, transcribed verbatim and analysed using reflexive thematic analysis according to Braun and Clarke. Results: All participants intended to breastfeed and described breastfeeding as part of motherhood. However, most experienced a postpartum reality that differed from their expectations. Three themes were developed: antenatal engagement with and expectations of breastfeeding, postpartum breastfeeding reality, and everyday breastfeeding life. Women received little antenatal breastfeeding counselling and faced challenges related to medicalised birth, delayed lactogenesis II, breast anatomy, pain, insufficient milk supply, pumping and inconsistent professional support. Several women described feelings of failure when breastfeeding did not work as hoped. Conclusion: First-time mothers living with obesity may have strong breastfeeding intentions but still experience major challenges after birth. Breastfeeding support should start during pregnancy and be realistic, respectful and weight-inclusive.

This study emphasizes the potential of computational techniques in cancer risk assessment, lighting opportunities for specific and data-driven healthcare solutions. This study examines the use of artificial intelligence (AI), machine learning (ML), and deep learning (DL) approaches to improve cancer risk assessment using a Kaggle dataset. The study uses Java-based ML software to create and evaluate multiple predictive models, taking advantage of its powerful libraries and frameworks for processing and analyzing cancer risk indicators. This work analyzes model performance using 10-fold cross-validation, resulting in reliable generalization and accuracy estimates. Several classification techniques, such as Random Forest (RF) logistic regression (LR), decision trees (DT), Naive Bayes (NB), and Multi-layer perceptron (MLP), are used to assess their efficacy in predicting risk levels for various cancer types. To measure classification effectiveness, key performance metrics such as accuracy, precision, recall, and F1 score are produced, in addition to multi-class confusion matrices. The results show that the RF model is the best classifier for classification, with accuracy of 99.85%, F-measure of 99.80%, precision of 99.80%, and sensitivity of 99.90%. These findings demonstrate the model's ability to effectively estimate cancer risk levels among individuals. of cancer risk estimations, allowing for earlier discovery and more effective medical care.

This study aims to investigate the cardioprotective effects of 4-Hydroxybenzaldehyde (4-HBA) against isoproterenol (ISO)-induced cardiac fibrosis and to elucidate the underlying mechanisms. In vivo, cardiac fibrosis was induced in C57BL/6 mice by subcutaneous injection of ISO, and the mice were treated with 4-HBA or a TGF-{beta} inhibitor. Assessments using echocardiography, histopathology, and Western blotting demonstrated that 4-HBA significantly alleviated ISO-induced cardiac dysfunction, reduced collagen deposition, and attenuated apoptosis in mice. Mechanistically, 4-HBA inhibited TGF-{beta} expression and Smad2/3 phosphorylation. In vitro, ISO was applied to cardiomyocytes (HL-1) and cardiac fibroblasts (MCFs), with or without 4-HBA or TGF-{beta} inhibitor intervention. The results showed that 4-HBA suppressed HL-1 apoptosis and fibroblast proliferation, and significantly reduced the expression of extracellular matrix genes, TGF-{beta} levels, and Smad2/3 phosphorylation in MCFs. These findings indicate that 4-HBA reduces myocardial injury while targeting the TGF-{beta}/Smad2/3 pathway to attenuate cardiac fibrosis, highlighting its potential as a therapeutic agent for fibrotic cardiomyopathy.This study aims to investigate the cardioprotective effects of 4-Hydroxybenzaldehyde (4-HBA) against isoproterenol (ISO)-induced cardiac fibrosis and to elucidate the underlying mechanisms. In vivo, cardiac fibrosis was induced in C57BL/6 mice by subcutaneous injection of ISO, and the mice were treated with 4-HBA or a TGF-{beta} inhibitor. Assessments using echocardiography, histopathology, and Western blotting demonstrated that 4-HBA significantly alleviated ISO-induced cardiac dysfunction, reduced collagen deposition, and attenuated apoptosis in mice. Mechanistically, 4-HBA inhibited TGF-{beta} expression and Smad2/3 phosphorylation. In vitro, ISO was applied to cardiomyocytes (HL-1) and cardiac fibroblasts (MCFs), with or without 4-HBA or TGF-{beta} inhibitor intervention. The results showed that 4-HBA suppressed HL-1 apoptosis and fibroblast proliferation, and significantly reduced the expression of extracellular matrix genes, TGF-{beta} levels, and Smad2/3 phosphorylation in MCFs. These findings indicate that 4-HBA reduces myocardial injury while targeting the TGF-{beta}/Smad2/3 pathway to attenuate cardiac fibrosis, highlighting its potential as a therapeutic agent for fibrotic cardiomyopathy.

Background. Lung metastases in osteosarcoma (OS) are the main cause of the death. The accuracy of the diagnosis of nodules by computed tomography (CT) of the lungs is critically important for determining the disseminated stage of the disease and planning surgical treatment. The use of artificial intelligence (AI) in the search for lung nodules increases the accuracy of diagnosis and reduces the chance of missing metastases. Objective: to evaluate the accuracy of lung nodules diagnosis in adolescents with OS using AI. Methods. A retrospective assessment of CT scans of adolescents with OS was performed. A pathological nodule with an average size of [&ge;]4 mm was considered a target finding. The diagnostic accuracy of an AI algorithm previously trained on an adult dataset was evaluated, and the number of false positives (FP) and false negatives (FN) was determined. Sensitivity, specificity, accuracy, area under the ROC curve (AUC), positive predictive value, negative predictive value, and F1-measure were calculated. Based on the obtained results, the effectiveness of the algorithm was assessed. Results. 248 CT scans of adolescents with OS were evaluated. The following results were obtained: in 5 cases, the AI algorithm showed a FP result (2.02%), in 34 cases, it showed a FN result (13.71%), and in 209 cases, a correct result (both true positive and true negative) (84.27%). The diagnostic accuracy of the algorithm was 0.843 (95% CI 0.794-0.887). The application of the AI algorithm in the practice of an X-ray doctor in a specific clinical task would allow to increase the sensitivity from 0.805 to 0.891, while ensuring an absolute decrease in the number of FN results by 8.59% and a relative decrease by 44%. Conclusion. The obtained results confirm the practical value of the application of the AI algorithm and justify the implementation of AI-assisted systems in the diagnostic protocols for lung metastases in adolescents with OS.

Objectives Genetic testing is increasingly used in the diagnosis and management of respiratory conditions, including pulmonary fibrosis (PF). The perspectives of people with PF and healthcare professionals (HCP) on the use of genetic testing remain largely unexplored. Methods A qualitative study was undertaken. People living with PF, their caregivers, and HCP were invited to undertake a semi-structured interview. Interviews were conducted via videoconference or telephone, audio-recorded, and transcribed verbatim. Data were analysed by two researchers using inductive thematic analysis. Results Thirty-eight participants; 15 people living with PF, 1 caregiver, and 22 HCPs were interviewed. Analysis revealed three key themes. Genetic testing in PF was valued by all groups; people with PF wanted testing now, whilst respiratory physicians were cautious, citing their uncertainty regarding clinical value. All groups desired more information and support; people with PF desired a better understanding of terminology, whilst genetic counsellors wanted to better understand PF. No single model for returning genetic results in PF was identified, however resources, multidisciplinary care, and timely return of results was considered important. Conclusion Genetic testing is valued by people with PF and their HCP, but uncertainties remain regarding whether it should be offered and how results should be best communicated.

Objective: To describe trends in cataract surgical volume, district-level surgical burden, and early postoperative visual outcomes among patients treated through a multi-district outreach programme in Bangladesh. Methods and Analysis: This retrospective study was conducted using data from patients undergoing cataract surgery through the outreach eye-camp programme of Bashundhara Eye Hospital and Research Institute across eight districts of Bangladesh, between 2016 and 2025 (excluding 2021 because of COVID-19). Annual surgical volume trend was assessed using Poisson regression. Postoperative visual outcome on day 1 was categorized as good, borderline, or poor per WHO criteria. Univariable and multivariable ordinal logistic regression identified predictors of worse outcome. Results: 1,929 cataract-surgery records were included. Surgical volume rose from 34 cases in 2016 to a peak of 677 in 2023 (IRR = 1.20; 95% CI: 1.180, 1.220; p-value< 0.001). Small incision cataract surgery (SICS) was used in 99.43% cases. On postoperative day 1, 70.09% of eyes had a good outcome, 19.44% borderline, and 10.47% poor. Increasing age was independently associated with worse outcome, with 2 to 3 times higher odds among patients over 70. District was independently associated with outcome, with Chapainawabganj and Kushtia having lower odds of worse outcome than Brahmanbaria. Sex was significant only in unadjusted analysis. Conclusion: Surgical volume rose substantially over time. About seven in ten eyes achieved a good outcome on day 1, with age and district as the main predictors of worse outcome. Limitations include a single early assessment, exclusion of incomplete records, no standardized refraction, and unmeasured predictors.

Introduction: Community outreach eye camps extend eye care to underserved rural populations across South Asia, but published data mostly describe surgical yield rather than the full range of presenting conditions. This study described the pattern of ocular diagnoses among patients attending community eye camps in Bangladesh and examined how these patterns varied by year, age, and sex. Methodology: This was a retrospective, registry-based study of patients screened through the outreach eye-camp programme of Bashundhara Eye Hospital and Research Institute, Bangladesh, between 2020 and 2024 (2021 excluded due to COVID-19). Age, sex, and provisional diagnosis were recorded for every patient and grouped into five categories: cataract and lens disorders, refractive errors and presbyopia, ocular surface inflammatory disorders, lacrimal system disorders, and miscellaneous disorders. Multivariable logistic regression models estimated the adjusted odds and predicted prevalence of each diagnostic category by calendar year (adjusted for age group and sex) and by age group and sex (adjusted for calendar year). Results: Among 7,267 patients, refractive errors and presbyopia were the most common category (51.31%), followed by cataract and lens disorders (23.54%), miscellaneous disorders (13.86%), ocular surface inflammatory disorders (8.59%), and lacrimal disorders (2.70%). Ocular surface disorders declined significantly over time (adjusted OR: 0.80/year; p-value<0.001). Cataract showed a borderline decline (adjusted OR: 0.94; p-value=0.065). Cataract prevalence rose steeply with age, from 3-6% below 18 years to 49-55% at 60 and older, while refractive errors/presbyopia peaked at 40-59 years (64-68%) before declining thereafter (30-37%). Ocular surface disorders were most frequent among children. Lacrimal disorders remained uncommon (2-5%), with no significant interaction. Conclusion: Refractive errors and presbyopia were the leading reason for presentation, with distinct age patterns across diagnostic categories. Outreach eye camps should be resourced for both comprehensive refraction, primary eye care and cataract-surgical referral, reflecting actual community-level diagnostic needs.