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Annals of Translational Medicine

AME Publishing Company

Preprints posted in the last 30 days, ranked by how well they match Annals of Translational Medicine's content profile, based on 18 papers previously published here. The average preprint has a 0.02% match score for this journal, so anything above that is already an above-average fit.

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Norepinephrine Induces Proliferation and Migration of Human Pulmonary Artery Smooth Muscle Cells via Endothelin 1

Wang, C.-C.; Jaw, F.-S.; Yen, T.-A.; Huang, H.-C.; Wu, E.-T.; Chou, H.-C.; TSAO, P.-N.; Chou, H.-W.; Huang, S.-C.; Chen, Y.-S.

2026-08-29 molecular biology 10.64898/2026.08.25.747161 medRxiv
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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.

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Global research trends and emerging fronts in refractory and macrolide-resistant Mycoplasma pneumoniae pneumonia in children: a bibliometric analysis (2000 2025)

Li, D.; Chen, H.; Shen, C.

2026-08-31 infectious diseases 10.64898/2026.08.25.26361371 medRxiv
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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

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Long term use and replacement of near vision glasses for presbyopia, in Punjab, Pakistan: a cross-sectional survey

Moin, M.; Younas, R.; Maqbool, S.; Awan, Z. H.; Bilal, M.; Katibeh, M.; Watts, E.; Latorre-Arteaga, S.; Freels, P. E.; Steinberg, A.; Bastawrous, A.

2026-08-17 ophthalmology 10.64898/2026.08.15.26360501 medRxiv
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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.

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Positive end-expiratory pressure versus sham valve/zero end-expiratory pressure in cardiopulmonary resuscitation during manual ventilation toimprove neurological outcomes in adult patients suffering an out-of-hospital cardiac arrest - an investigator-initiated, pragmatic, registry-based, multicenter, parallel-group, triple-blind randomized controlled superiority clinical trial in the ARREST registry (REVIVE-PEEP protocol Stage-1 Registered Report)

van Eijk, J.; Schober, P.; van Schuppen, H.; ter Schure, J.

2026-08-31 emergency medicine 10.64898/2026.08.27.26361533 medRxiv
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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.

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Clinical outcomes and its determinants among neonates with neonatal sepsis admitted to selected Governmental hospitals in Addis Ababa, Ethiopia.

Gutema, R. M.; Namara, G. T.

2026-08-12 pediatrics 10.64898/2026.08.10.26360094 medRxiv
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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.

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Methodologies for Manipulating Cardiomyocyte Physiology: In Vitro and In Vivo Perspectives

Yang, R.; Liu, D.-H.; Wang, D.-D.; Li, S.-M.; Liu, P.-P.; Li, S.-A.; Kang, J.-S.

2026-08-12 cell biology 10.64898/2026.08.11.744256 medRxiv
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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.

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Medial Plantar Nerve Shear Wave Elastography and Viscosity Imaging for Differentiating Mild from Moderate Diabetic Peripheral Neuropathy

Gao, X.; Li, Y.

2026-09-02 radiology and imaging 10.64898/2026.08.28.26361645 medRxiv
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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.

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Human milk feeding, fortification initiation, and clinical outcomes in neonates with critical congenital heart disease: A multi-institutional study

Elgersma, K. M.; Joy, B. F.; Huang, Z.; Radman, M. R.; Mills, K. I.; Schramm, J. E.; Wong, J. H.; Chlebowski, M. M.; Beshish, A. G.; Safa, R.; Mueller, D.; Shutes, B. L.; Pande, C.; Furlong-Dillard, J.; Narasimhulu, S. S.; Beach, A.; Goldstein, S. A.; Riley, C. M.; Reddy, R.; Goldshtrom, N.; Schneider, J.; Liao, G.; Asfari, A.; Karki, K. B.; Huibonhoa, R. M. T.; Mastropietro, C. W.; Cashen, K.

2026-08-23 pediatrics 10.64898/2026.08.20.26360934 medRxiv
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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.

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Breastfeeding intentions and breastfeeding reality among first-time mothers living with obesity: A qualitative thematic analysis

Aubry, E. M.; Keller, D.

2026-08-18 nursing 10.64898/2026.08.17.26360590 medRxiv
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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.

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Artificial Intelligence Model: Optimizing Cancer Risk Level Predictions Using Machine learning and deep learning approaches

Abd Aziz, A. B.; Arabiat, A.; Abu Owida, H.; Abuowaida, S.; Alshdaifa, N.; A. Mashagba, H.

2026-08-25 cancer biology 10.64898/2026.08.20.745910 medRxiv
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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.

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4-Hydroxybenzaldehyde Attenuates Isoproterenol-induced Cardiac Fibrosis via TGF-β-Smad2/3 Signaling Pathway

Liu, Z.; He, W.; Liu, F.; Mao, H.; chen, j.

2026-08-26 molecular biology 10.64898/2026.08.20.746132 medRxiv
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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.

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Cataract surgical burden and district level disparities in Bangladesh: A retrospective study

Ahmed, M. S.; Islam, M.; Albert, A.; Jahan, A. F.; Islam, N. L.; Shahnaz, T.; Mahdee, C. M.

2026-08-17 ophthalmology 10.64898/2026.08.15.26360490 medRxiv
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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.

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Ocular diagnostic patterns among patients attending community outreach eye camps in Bangladesh: a retrospective registry-based study

Ahmed, M. S.; Islam, M.; Albert, A.; Jahan, A. F.; Islam, N. L.; Shahnaz, T.; Mahdee, C. M.

2026-08-17 ophthalmology 10.64898/2026.08.15.26360489 medRxiv
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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.

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Prospective In-silico Simulation of the VESALIUS-CV Trial Using Biomedical Knowledge Graph and Real-World Data-Driven AI Modeling

Perlman, A.; Goldstein, N.; Goldman, M.; Shapiro, M.; Barash, E.; Bar, A.; Raveh, T.; Tordjman, E.; Schussheim, H.; Dormont, F.; Matalon, O.

2026-08-31 cardiovascular medicine 10.64898/2026.08.26.26361436 medRxiv
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Background. Cardiovascular-outcomes trials are lengthy, costly, and associated with substantial uncertainty prior to readout. In-silico trial simulation using real-world data (RWD) has emerged as a potential tool to support earlier decision-making; however, evidence of prospective predictive validity, generated prior to trial result disclosure, remains limited. Methods. We applied a semi-mechanistic machine learning framework integrating real-world patient data with biologically informed drug representations to prospectively simulate the VESALIUS-CV trial evaluating evolocumab versus placebo. The simulation model was trained on a combination of patient-level real-world data and a drug-centric knowledge graph and validated for both patient-level and trial-level retrospective predictive performance. The model was then used to simulate VESALIUS-CV before public disclosure of trial results, using a locked model and prespecified eligibility criteria and primary endpoint aligned with the clinical protocol. A patient-level time-to-event model was used to generate virtual trial arms, from which cumulative incidence curves, hazard ratios, confidence intervals, and p-values for major adverse cardiovascular events (MACE) were estimated. Results. In retrospective validation, the model demonstrated strong patient-level discrimination, with time-dependent ROC-AUC values ranging from 0.80 to 0.90 across follow-up horizons. For trial-level validation, 22 randomized cardiovascular-outcomes trials were simulated, and hazard ratios for 3-point MACE across 24 between-arm comparisons showed consistent directional agreement and quantitative correlation with published results such that the model accurately predicted trial success, achieving an F1 score of 0.83, with precision of 0.79 and sensitivity of 0.89. In a fully prospective application, the simulation predicted a statistically significant reduction in 3-point MACE with evolocumab versus placebo, estimating a hazard ratio of 0.78 (95% CI, 0.70-0.87) at 54 months. These predictions were consistent with the subsequently reported VESALIUS-CV results, which demonstrated a hazard ratio of 0.75 (95% CI, 0.65-0.86) at 55 months of median follow-up. Conclusions. In a fully prospective setting, a RWD-driven, AI-based simulation accurately predicted the direction, magnitude, and temporal dynamics of treatment effects observed in the VESALIUS-CV trial. These results demonstrate that in-silico trial simulation can anticipate clinical outcomes in the prospective setting, supporting its use as a complementary tool for early decision-making, trial design optimization, and de-risking in cardiovascular drug development.

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Morphological and phenotypic characterization of adipose-derived mesenchymal stem cells isolated from locally adapted Indonesian goat breed

Budipitojo, T.; Padeta, I.; Purwaningrum, M.; Budiariati, V.; Pirarat, N.

2026-08-24 cell biology 10.64898/2026.08.23.746531 medRxiv
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Adipose-derived mesenchymal stem cells (gAD-MSCs) are promising candidates for veterinary regenerative medicine, yet the characterization of gAD-MSCs from locally adapted Indonesian goat breeds remains limited. This study aimed to isolate and characterize gAD-MSCs from Peranakan Ettawa (PE) goats using tissue explant culture. Subcutaneous adipose tissue was collected from the base of the tail of healthy PE goats (n=3). Primary cell outgrowth from explants was observed by Day 5, displaying characteristic fibroblast-like, spindle-shaped morphology and strong plastic adherence. Serial passaging to Passage 3 (P3) yielded a morphologically stable, homogeneous cell population. Assessment of cellular metabolic activity via the resazurin assay demonstrated sustained cell viability and a statistically significant increase in metabolic activity between Day 3 and Day 5 (p < 0.05). Furthermore, functional clonogenic capacity, evaluated using the colony-forming unit (CFU) assay, showed continuous temporal expansion of colonies over 14 days, yielding an average of 52.0 + - 4.1 colonies per dish. These findings confirm that expanded gAD-MSCs P3from PE goats maintain characteristic mesenchymal morphology, sustained metabolic activity, and clonogenic capacity. This work provides a baseline cellular profile of PE goat gAD-MSCs, supporting their potential use in veterinary regenerative medicine and tissue engineering.

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Factors associated with ocular injury among patients admitted with head injury at Mulago National Referral Hospital a tertiary hospital in Uganda

Olupot, A.; Oguttu, F.; Shiuma, J.; Lyazzi, O. J.; Odong, B.; Jumanne, M. R.; Frank, K.; Ntende, J.; Mukunya, D.; Otiti, J. S.; Ampaire, A. M.; Lusobya, R. C.; Nsibirwa, S. G.; Atukunda, I.

2026-08-21 ophthalmology 10.64898/2026.08.18.26360753 medRxiv
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Background Given the close anatomical proximity of the eye and its adnexae to the cranium, ocular injury frequently coexists with head trauma. However, specific factors predisposing patients with head injury to ocular involvement in Uganda remain poorly defined. Objective This study aimed to determine the factors associated with ocular injury among patients with head injury at Mulago National Referral Hospital (MNRH), a tertiary referral facility in Kampala, Uganda. Methods We conducted a cross-sectional study among 383 adult patients admitted with head injury to the Accidents and Emergency Department of MNRH from 15/05/2025 to 30/07/2025. All participants underwent a standardized ophthalmic evaluation. Bivariable and multivariable Poisson regression analyses were used to identify factors associated with ocular injury, reported as adjusted prevalence ratios (APR). Results Ocular injury was identified in 268 of 383 patients (70.0%; 95% CI: 65.1-74.5). On multivariable analysis, age 26-44 years (APR 1.18; 95% CI: 1.11-1.43; p=0.013), commercial motorcyclist (boda-boda rider) occupation (APR 1.25; 95% CI: 1.06-1.47; p=0.007), road traffic accident mechanism of injury (APR 1.19; 95% CI: 1.02-1.38; p=0.03), severe head injury (APR 1.70; 95% CI: 1.44-2.01; p<0.0001), and the presence of facial fractures (APR 1.61; 95% CI: 1.44-1.81; p<0.0001) significantly increased the likelihood of ocular injury. Conversely, intracranial hemorrhagic lesions were inversely associated with ocular injury (APR 0.80; 95% CI: 0.68-0.93; p=0.004). Conclusion Ocular injuries are common among patients with head injury. Patients aged 26 to 44 years, commercial motorcyclist occupation, road traffic injury, severe head injury, and facial fractures have a higher risk of ocular injury. We recommend prioritizing ophthalmic evaluation of for patients admitted with head injury to minimize preventable visual impairment.

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Beyond BMI: an interpretable integrated body composition index from low-dose chest CT for all-cause mortality risk stratification: a multicentre study

Yi, J.; Patel, K. K.; Miller, R. J. H.; Marcinkiewicz, A. M.; Kamagate, A.; Shanbhag, A.; Hijazi, W.; Lemley, M.; Zhou, J.; Liang, J. X.; Ramirez, G.; Mostafavi, S.; Urs, M.; Spielvogel, C. P.; Slipczuk, L.; Travin, M.; Alexanderson, E.; Caraval-Juarez, I.; Packard, R. R.; Al-Mallah, M.; Ruddy, T. D.; Einstein, A. J.; Feher, A.; Miller, E. J.; Acampa, W.; Knight, S.; Le, V. T.; Mason, S.; Calsavara, V. F.; Chareonthaitawee, P.; Wopperer, S.; Kwan, A. C.; Wang, L.; Li, D.; Fishman, E. K.; Lopez-Ramirez, F.; Berman, D. S.; Kwiecinski, J.; Dey, D.; Di Carli, M. F.; Slomka, P.

2026-08-10 radiology and imaging 10.64898/2026.08.05.26359437 medRxiv
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Background: Body composition is recognized as a major determinant of health outcomes, but its multidimensional nature makes clinical adoption challenging. We sought to develop and validate a body composition index (BCI) for all-cause mortality risk assessment, integrating variables of six body composition tissues. Methods: We analyzed 28509 consecutive patients undergoing myocardial perfusion imaging with routine low-dose chest CT attenuation correction (CTAC) scans acquired during myocardial perfusion imaging (MPI) at 12 centers across four countries. An artificial intelligence-based BCI was developed in a cohort of 15037 patients CTACs by integrating the CT-derived metrics of bone, skeletal muscle, and four adipose tissue compartments, coronary artery calcium score, and basic demographic variables (age, sex, BMI). The performance of BCI for mortality prediction was validated in an internal cohort of 6444 patients and an external cohort of 7028 patients by prognosis, calibration, net benefit, and explainability. Model-based simulation of tissue metrics modification was performed to evaluate estimated mortality risk reduction. Findings: During a median of 3.5 (IQR [1.9, 5.1]) years, 4697 (16%) patients died. In the external testing cohort, the BCI demonstrated excellent discrimination for mortality (area under receiver operating characteristic curve 0.78 (95% CI [0.76, 0.79]) and Harrell concordance index 0.75 [0.73, 0.76]), calibration, and net benefit overall and across pre-specified subgroups stratified by patient characteristics and imaging protocols. Visceral adipose tissue attenuation was the most influential body composition measure, followed by skeletal muscle volume. Simulated improvement in body composition was associated with significant mortality risk reduction. Interpretation: An index combining six body composition measures obtained opportunistically from routine chest CT provides robust mortality risk stratification. By converting complex body composition information into a single interpretable score, the BCI can facilitate clinical implementation of opportunistic CT biomarkers and guide individualized preventive strategies.

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Prediction of Subsolid Pulmonary Nodule Evolution from Baseline CT Using Temporal Imaging Models

Bondarenko, M.; Qi, K.; Nowroozi, A.; Kim, J.; Kunzang, B.; Lee, A.; Liu, J.; Tran, N.; Weng, S.; Vella, M.; Chaudhari, G.; Schnizler, T.; Innanje, A.; Chen, T.; Sohn, J. H.

2026-08-13 radiology and imaging 10.64898/2026.08.12.26360292 medRxiv
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Background: Prediction of subsolid pulmonary nodule (SSN) progression from baseline CT may improve risk stratification and surveillance planning, but prior approaches have largely relied on fixed follow-up intervals. Methods: This retrospective single-center study evaluated interval-aware temporal imaging models for predicting future SSN growth and morphology across heterogeneous surveillance durations. A total of 24,946 longitudinal scan pairings derived from 2,543 clinician-reviewed SSNs in 426 patients were analyzed. A discriminative deep learning model predicted interval growth from baseline CT, segmentation masks, and interscan interval information, while a temporally conditioned generative model predicted future lesion morphology. Results: The discriminative model achieved an area under the receiver operating characteristic curve of 0.772 (95% confidence interval: 0.704-0.818), with sensitivity of 80.2% and specificity of 58.7% on the test cohort. The generative model predicted future lesion morphology with a Dice similarity coefficient of 0.706 +/-0.186. Prediction performance decreased with increasing follow-up duration, although both models generalized across intervals ranging from months to years. Conclusion: Interval-aware temporal imaging models enable the prediction of future SSN growth and morphology from baseline CT while accounting for variable surveillance intervals. These findings suggest a framework for time-aware, personalized risk assessment that may support individualized surveillance strategies and future AI-assisted management of pulmonary adenocarcinoma spectrum lesions.

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Predictors of Time to Start of Trophic Feeding in Preterm Neonates Admitted to Neonatal Intensive Care Unit of Adama Hospital Medical College, Ethiopia: A Retrospective Cohort Study

Misha, B.; Dassie, G. A.; Mohammad, I.

2026-08-31 epidemiology 10.64898/2026.08.26.26361481 medRxiv
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Background: Early trophic feeding promotes gut maturation, feeding tolerance, and growth in preterm neonates. However, delays remain common despite recommendations for initiation within 24 hours of birth, especially in resource-limited settings. Evidence on feeding initiation timing and predictors among Ethiopian preterm neonates is limited. Objective: To determine time to trophic feeding initiation and identify predictors among preterm neonates admitted to Adama Hospital Medical College, Ethiopia. Methods: A hospital-based retrospective cohort study was performed on 436 randomly chosen preterm neonates admitted to NICU. Data extraction was performed using a structured checklist. Time to trophic feeding initiation was analyzed using Kaplan-Meier estimates, log-rank tests, and bivariable and multivariable Cox regression models . Adjusted hazard ratios with 95% CIs were reported. Results:The sample comprised 416 preterm neonates, of whom 311 (74.8%) started trophic feeding during follow-up, and 105 (25.2%) were censored. The rate of initiation of trophic feeding was 1.92 per 100 person-hours (95% CI 1.72 to 2.15). Median time to initiation was 42 hours (interquartile range 24 to 50). Independent predictors of feeding initiation were determined by multivariable analysis and included gestational age, birth weight, maternal anaemia, respiratory distress syndrome and necrotising enterocolitis. Neonates born at 34-36 weeks had earlier initiation than those born at <34 weeks (AHR 1.39; 95 % CI 1.09 to 1.78). Similarly, neonates with a birth weight of [&ge;]1500 g had an earlier initiation than those with a birth weight of <1500 g (AHR 1.41; 95% CI 1.04 to 1.91). Delayed initiation was associated with maternal anaemia (AHR 0.70; 95% CI 0.51-0.95), respiratory distress syndrome (AHR 0.67; 95% CI 0.51-0.88) and necrotising enterocolitis (AHR 0.48; 95% CI 0.33-0.69). Conclusions: Delayed trophic feeding remains common among preterm neonates. Standardized feeding protocols, strengthened maternal care, and individualized nutrition strategies are needed to improve neonatal outcomes in study area.

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Glaucoma and Diabetes Mellitus: A Comparative Evaluation of Comorbid Effect on Tear Quantity among Patients in Owerri, Imo State, Nigeria.

Chukwuoha, C. M.; Ovenseri-Ogbomo, G.; Azuamah, Y. C.; Odimegwu, N. E.; Obioma-Elemba, J. E.; Ugwoke, G.; Nkeremuzor, E. C.; Eronini, Y.; Ikoro, N. C.; Esenwah, E. C.

2026-09-02 ophthalmology 10.64898/2026.08.30.26361782 medRxiv
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Abstract Objective: Glaucoma is a chronic disorder that impairs ocular health and may exacerbate ocular surface disease leading to tear film instability, dry eye symptoms and decreased quality of life. This study compared changes in tear quantity among glaucoma subjects living with and without diabetes mellitus, attending an eye clinic in Nigeria. Methods: A comparative cross sectional research design was used. 157 subjects which comprised 74 glaucoma subjects living with diabetes mellitus and 83 glaucoma subjects living without diabetes mellitus participated in the study. Tear quantity assessment included the Schirmer I test and tear meniscus height (TMH) measurement. Descriptive statistics, independent samples t-test and Chi-square test were used to examine the data at 0.05 level of significance. Results: Glaucoma subjects living with diabetes mellitus showed substantially decreased tear production (11.4 +/- 6.8 mm) compared with glaucoma subjects living without diabetes mellitus (19.6 +/- 9.6 mm; p < 0.001). Tear meniscus height in glaucoma subjects living with diabetes mellitus (0.8 +/- 0.3 mm) was significantly greater than in subjects living without diabetes mellitus (0.7 +/- 0.3 mm; p = 0.034). Conclusion: Diabetes mellitus dramatically deteriorates the ocular surface function in glaucoma subjects by decreasing tear production, altering the tear meniscus height and increasing the severity of ocular surface symptoms. Routine glaucoma care, especially in patients with diabetes mellitus, should include a full ocular surface evaluation including Schirmer I test, TBUT, TMH, and OSDI assessment to allow early detection and management of ocular surface disease, better treatment adherence, and improved visual outcomes. Keywords: Glaucoma, Diabetes Mellitus, Tear production, Tear Meniscus Height, Ocular Surface Disease.