Vascular endothelial growth factor A (VEGFA) plays a critical role in the pathogenesis of diabetic macular edema (DME) in patients with type 2 diabetes mellitus (T2DM). Herein, we sought to determine whether palmitoylation modulates the stability and function of VEGFA in the context of DME.

VEGFA protein levels were measured by western blotting in retinal pigment epithelial (RPE) tissues from mice and in cultured RPE cell lines. Palmitoylation of VEGFA was assessed using acyl‑biotin exchange (ABE) and Click‑iT pulldown assays. Cell proliferation was evaluated with the Cell Counting Kit‑8 (CCK‑8) assay. The interaction between VEGFA and zinc finger DHHC-type containing 19 (ZDHHC19) was examined by co‑immunoprecipitation. Retinal histopathology in DME mice was evaluated by hematoxylin‑eosin (H&E) staining.

VEGFA levels were elevated in the RPE of DME mice compared with those of T2DM mice. Pharmacological inhibition of palmitoylation with 2‑bromopalmitate (2‑BP) reduced VEGFA protein expression in cultured cells. ZDHHC19 was identified as the palmitoyltransferase responsible for VEGFA. Wild‑type ZDHHC19 failed to palmitoylate the VEGFA‑C387A mutant, and the catalytically inactive ZDHHC19‑C142S mutant also lacked activity toward VEGFA. Overexpression of wild‑type VEGFA or ZDHHC19 significantly promoted RPE cell proliferation, whereas the VEGFA‑C387A and ZDHHC19‑C142S mutants had no effect. Consistent with these in vitro findings, wild‑type VEGFA or ZDHHC19 overexpression exacerbated DME development in mice, while the corresponding mutants did not significantly affect disease progression.

ZDHHC19‑mediated palmitoylation of VEGFA contributes to DME pathogenesis and may serve as a potential therapeutic target and biomarker for this disease.

The online version contains supplementary material available at 10.1007/s40200-026-02023-1.

Antibodies to Epstein-Barr virus (EBV) proteins can predict nasopharyngeal carcinoma (NPC) risk. We previously defined a prototype EBNA1 protein panel and multiplex immunoblot assay that distinguishes NPC risk several years pre-diagnosis. Assay throughput and specificity are critical to effectively implement a population-level screening program. Here, we developed a strip test assay-EBNA1 SeroStrip-HT-with an objective to increase throughput and maximize specificity. EBNA1 full-length (FL) and glycine-alanine repeat deletion mutants (dGAr) were purified from insect and mammalian cells to screen serum IgA/IgG from prospective cohorts in Singapore and Shanghai, China, with known time intervals to NPC diagnosis. Twenty pre-diagnostic sera within 4 years to diagnosis were compared to 96 healthy controls using a nested case-control study design. IgA to mammalian-derived EBNA1 dGAr achieved 85.0% sensitivity and 94.8% specificity (AUC, 0.939) for NPC status. IgA to insect-derived EBNA1 dGAr showed the same sensitivity (85.0%) and similar specificity (93.8%) (AUC, 0.941). IgA to insect-derived EBNA1 FL had a higher 90% sensitivity, but lower 91.7% specificity (AUC, 0.940). Combining EBNA1 FL and dGAr results showed that subjects positive for both proteins had a 243.67 odds ratio for NPC incidence compared to double-negative scores. This study demonstrated the efficacy of EBNA1 SeroStrip-HT for NPC risk assessment and stratification in high- and intermediate-risk populations, yielding high accuracy and a 12-fold increased throughput over the prototype. The insect system was appropriate for large-scale production of purified EBNA1. Larger, geographically diverse cohorts are warranted to confirm these results, especially in low-incidence populations.

The mechanisms underlying pharmacological treatments for stimulant use disorders are poorly understood. This study examined whether changes in craving, depressive symptoms, and/or impulsivity mediate treatment effect in pharmacotherapy with combined naltrexone and bupropion for methamphetamine use disorder (MUD).

The study was based on secondary analysis of data from the Accelerated Development of Additive Pharmacotherapy Treatment for methamphetamine disorder (ADAPT-2) trial which randomized adults with MUD to combined treatment with injectable naltrexone (380 mg every 3 weeks) plus oral bupropion (450 mg daily) versus placebo. A total of 403 adults with MUD participated in the first stage; 225 of first stage participants in the placebo arm who did not respond to treatment were re-randomized in the second stage. Mediation effects were examined using longitudinal multi-level structural equation modeling.

Naltrexone-bupropion treatment was associated with decreases in drug use, craving, depressive symptoms, and impulsivity. The indirect effect of treatment through change in craving was significant (self-reported use = -0.21, 95% credible interval (CrI) = -0.35, -0.09; drug screen-ascertained use = -0.36, 95% CrI = -0.63, -0.16). Change in craving mediated 56% of the treatment effect on self-reported drug use and 45% of the effect on drug screen-ascertained use. Estimates for mediated effects for depressive symptoms and impulsivity were smaller in magnitude and nonsignificant.

Reduction in craving mediates the effect of naltrexone-bupropion pharmacotherapy in MUD. Craving may serve as a surrogate measure of treatment efficacy in short-term trials and help identify promising candidate medications to be tested in larger and longer-term trials.

ClinicalTrials.gov number: NCT03078075.

This study evaluates the usability, accessibility, and ergonomic design of six widely used Iranian mobile banking applications for older adults (aged 60 and above) to enhance digital inclusion and promote healthy aging through improved financial access.

An explanatory sequential mixed-methods approach was utilized, integrating quantitative usability testing with the System Usability Scale (SUS) and qualitative heuristic evaluation using the Smartphone's Usability Heuristics (SMASH) framework. Five Human-Computer Interaction (HCI) experts evaluated the applications in a controlled lab setting, while 1,200 older adults from diverse backgrounds participated in usability testing and semi-structured interviews. Statistical analysis involved ANOVA with post hoc Least Significant Difference (LSD) tests to compare SUS scores across applications and age groups, complemented by thematic analysis of qualitative data.

Heuristic evaluation identified 135 usability issues, with error prevention (mean severity: 2.27) and visibility of system status (mean severity: 2.22) being the most critical. SUS scores varied significantly (F(5, 1194)=42.36, P<0.001), ranging from 27.50 (SD=7.18) for Bank E to 59.02 (SD=7.94) for Bank A. Younger older adults (60-63 years) reported higher SUS scores (M=54.2) than those aged 72-75 (M=45.3, P<0.001). Qualitative findings highlighted cultural mismatches and cognitive overload as key barriers.

Poor usability in mobile banking apps widens the digital divide for older adults, hindering financial independence. Tailored designs with simplified interfaces, cultural relevance, and enhanced error prevention can improve digital health literacy, support equitable access and promote mental and social well-being among aging populations.

Background/Objectives: Accurate assessment of dietary behaviors is essential for understanding their impact on health and guiding nutritional policies. Given the escalating prevalence of noncommunicable diseases in the MENA region, the availability of culturally adapted and psychometrically validated Arabic-language instruments is essential for accurate health assessment. This systematic review aims to identify and evaluate studies that have translated, adapted, or validated dietary behavior measurement instruments into Arabic. Methods: Following the PRISMA guidelines and registered in PROSPERO (CRD420251157552), a search was conducted in PubMed, Scopus, and Web of Science. Studies including the validation, translation, or adaptation of instruments into Arabic among Arabic-speaking populations were included. Methodological quality was assessed using the COSMIN checklist. Results: Thirty-two studies were included, published between 2006 and 2025, primarily in Lebanon (n = 14) and Saudi Arabia (n = 6). The instruments measured various concepts: dietary intake, diet quality, eating disorders, etc. While internal consistency and structural validity were frequently assessed with adequate methodological quality, content validity, measurement error, and responsiveness were either under-reported or failed to meet COSMIN standards. Conclusions: Despite an increasing volume of publications, the methodological quality of Arabic instrument validation remains heterogeneous, with significant gaps in the assessment of longitudinal properties. Efforts are needed to improve the rigor of adaptation processes and to evaluate key properties such as responsiveness in order to ensure reliable tools for research and clinical practice in the MENA region.

Oligoasthenoteratozoospermia (OAT) is one of the most common multifactorial causes of male infertility. Platelet-rich plasma (PRP), a biological product, has emerged as a promising regenerative therapy in various fields of medicine, including reproductive health. Therefore, we investigated the effect of PRP administration on sperm DNA fragmentation in OAT men.

The aim was to evaluate the effect of intratesticular injection of PRP on DNA fragmentation index (DFI) in men with idiopathic OAT and assess its potential as a novel therapeutic intervention to enhance sperm DNA integrity.

This randomized controlled trial study involved 160 infertile men diagnosed with OAT without underlying diseases who were referred to the infertility center of Fatemieh Infertility Center, Hamadan, Iran, from July 2023 to July 2024. The participants were randomly assigned to intervention and control groups using a block randomization method. The intervention group received 1-2 cc of PRP in each testicle. Sperm parameters and DFI were measured; a hormonal study was also performed before and after the procedure.

The results revealed a significant difference in concentration (p = 0.030), progressive motility (p < 0.001), DNA fragmentation (p < 0.001), normal morphology (p < 0.001), and also testosterone levels (p < 0.001) between groups after PRP injection.

PRP Injection into the testis appears to be a safe, minimally invasive, and potentially effective therapeutic approach in enhancing sperm quality and reducing DFI in men with OAT.

Accurate application of reference standards (RSs) is essential for correct decision-making in areas governed by such standards. Yet in real-world practice, even fully trained users often apply RSs inconsistently, due to cognitive overload, stress, or other contextual factors, generating misleading evidence. This problem is exemplified by the fact that up to 80% of board-certified hematologists mislabel patients with Sjögren syndrome (SS), a connective tissue disorder (CTD) associated with the greatest risk of lymphoproliferative disorders compared to other CTDs. Embedding RS-based consultations with full objectivity into the decision-making layers of digitalized and non-digitalized settings is critical for improving both decision-making and the quality of resulting evidence. The aim of this proof-of-concept (POC) study is to apply a newly developed framework, the Fully Expert Human-based Retrieval Augmented Generation (FEH-RAG) framework, to provide such a foundation for augmenting SS case labeling in routine daily clinical practice.

In this POC study, using the nine steps of the FEH-RAG framework, seven expert end-users systematically selected the most widely used SS classification criteria (SSCC) and extracted their elements, including items, definitions, item weights, and inter-item relationships. Extracted items were profiled based on their usage in routine clinical practice. A pathway layout and decision tables were developed accordingly. Following pathway generation, the residual misalignment of the outputs with the SSCC was assessed in a cohort of patients at risk of SS. The experts predefined that the residual misalignment rate of the FEH-RAG outputs with the SSCC must be ≤2% (95% confidence, using the rule of three).

The FEH-RAG framework objectively generated RS-based, transparent, and traceable outputs, including decision tables, an SS classification pathway, and a list of misinterpretations of the SSCC. These misinterpretations involved definitions of dry eye and dry mouth, application of secondary SS criteria, handling SS criteria-specific exclusion rules, and interpretation of serological and objective test results. This POC study achieved its expert-defined maximum misalignment threshold of ≤2% with 95% confidence (0 misalignment in 150 consecutive patients at risk of SS).

This POC study established the needed foundation for improving SS case labeling in daily clinical practice across both digital and non-digital settings. As shown here, publishing FEH-RAG outputs while highlighting potential RS misinterpretations offers a transparent and traceable basis for augmenting decision-making in domains governed by RSs.

As obesity, diabetes and other diet-related metabolic disorders continue to rise, non-nutritive artificial sweeteners (NASs) are widely used as sugar substitutes in free-sugar reduction and weight-management strategies, but their effects on the gut microbiota, host metabolism and related health outcomes remain debated. To clarify this evidence landscape, this review synthesizes current knowledge on the effects of major NAS on the gut microbiota and host metabolic and health-related outcome. A bibliometric analysis was conducted to characterize the development, knowledge structure and thematic evolution of this research area. For the eight NAS exposure categories included in this review (saccharin, cyclamate, aspartame, acesulfame potassium, sucralose, neotame, neohesperidin dihydrochalcone and mixed NAS), we performed a compound-specific analysis integrating physicochemical characteristics, regulatory status, and research findings from in vitro, ex vivo, animal and human studies on gut microbiota alterations, host metabolic and health-related outcomes. These findings were further compared through four interpretive dimensions: exposure conditions, research model background, outcome assessment and interpretation of discordant results. Current research evidence does not support a class-wide conclusion that NAS are uniformly harmful or safe. To make research findings searchable, we developed the NAS-MAP knowledge graph, an interactive non-nutritive artificial sweetener-microbiota-associated phenotype knowledge graph. Overall, this review consolidates current knowledge, clarifies the sources of inconsistent findings, and provides a framework for more mechanistically informative studies, standardized evidence reporting, and more precise sweetener-, exposure- and population-specific dietary and public health guidance.

Mobile applications can enhance diabetes self-management by visualizing glucose trends and promoting engagement. However, evidence on their behavioral and clinical effectiveness in environments with constrained resources remains limited. This study evaluated the impact of the Iranian Asan-Chek mobile app on glycemic outcomes and user experiences among adults with type 1 diabetes mellitus (T1DM).

In a 12-week quasi-experimental mixed-methods study, 148 adults with T1DM were recruited. Seventy-four participants used the Bluetooth-enabled Asan-Chek app (intervention group) and 74 performed structured self-monitoring of blood glucose (control group). Primary outcomes included changes in HbA1c and qualitative insights into user engagement and experience. Semi-structured interviews with 15 purposively selected participants (13 app users, 2 controls, varied in age and diabetes duration) explored attitudes, perceived benefits, and barriers. Transcripts were analyzed thematically.

HbA1c decreased by 0.62% in the app group and by 0.41% in the control group (both P < 0.001), without any notable divergence between the intervention and control participants (P = 0.202). Changes in BMI, insulin requirements, and glycemic variability during the course of the study exhibited no statistical disparity between the two groups. Qualitative analysis uncovered three motifs: (i) heightened self efficacy and perceived control arising from instant feedback; (ii) stronger motivation prompted by color coded trend charts and reminders and (iii) usability and economic barriers: interface complexity, data driven anxiety, test strip cost, and finger prick fatigue.

Over twelve weeks, qualitative results highlighted that the Asan-Chek app provided motivational and behavioral advantages for individuals with T1DM but did not outperform structured SMBG in attaining HbA1c targets. Addressing challenges through optimized app interface, comprehensive user training, affordable supplies via reimbursement, and AI-driven feedback may help convert these behavioral gains into lasting glycemic improvement.

Diabetes mellitus causes microvascular alterations that contribute to the development of diabetic retinopathy. Hemodynamic changes in retrobulbar circulation may occur before clinically detectable retinal damage.

This study aimed to compare Doppler hemodynamic indices of the ophthalmic artery (OA) and central retinal artery (CRA) between diabetic participants and non-diabetic controls.

This cross-sectional observational study included 76 participants (38 diabetic participants and 38 non-diabetic controls), comprising 152 eyes analyzed at the eye level. Color Doppler imaging was used to measure peak systolic velocity (PSV), end-diastolic velocity (EDV), resistive index (RI), and systolic/diastolic (S/D) ratio in the OA and CRA. Group comparisons were performed using an independent samples t-test, with statistical significance set at p < 0.05.

Diabetic participants demonstrated significantly higher vascular resistance in retrobulbar arteries. OA-RI was significantly higher in diabetic participants (0.80 ± 0.03) than in non-diabetic controls (0.71 ± 0.01; p < 0.001). CRA-RI was similarly elevated (0.70 ± 0.04 vs. 0.62 ± 0.01; p < 0.001). Retrobulbar blood flow velocities were significantly reduced in diabetic participants, including OA-PSV (19.38 ± 2.71 vs. 29.18 ± 1.42 cm/s; p < 0.001) and OA-EDV (3.84 ± 1.04 vs. 8.49 ± 0.53 cm/s; p < 0.001). CRA-PSV (9.02 ± 1.23 vs. 13.28 ± 0.64 cm/s; p < 0.001) and CRA-EDV (2.87 ± 0.82 vs. 5.05 ± 0.33 cm/s; p < 0.001) were also significantly reduced. S/D ratios were significantly elevated in both vessels among diabetic participants.

Diabetes is associated with increased vascular resistance and reduced blood flow velocities in the OA and CRA. These findings suggest that color Doppler imaging may help identify early hemodynamic alterations in the ocular circulation associated with diabetic retinal disease.