Nevin Manimala

Drug Saf. 2026 May 12. doi: 10.1007/s40264-026-01677-3. Online ahead of print.

ABSTRACT

Spontaneous reporting databases play a central role in pharmacovigilance for monitoring the safety of drugs and vaccines. Conventional statistical signal detection has relied primarily on disproportionality analyses based on reporting frequencies, whereas information on the timing of adverse event onset has not been fully exploited. Time to onset (TTO), defined as the interval between the initiation of drug administration and the occurrence of an adverse event, provides complementary information that captures temporal patterns of event manifestation beyond simple occurrence counts. This review summarizes the definition, calculation, characteristics, and limitations of TTO analyses in spontaneous reporting databases and provides an overview of statistical signal detection methods incorporating TTO information. In particular, nonparametric distribution-comparison approaches, such as the Kolmogorov-Smirnov and Anderson-Darling tests, are well suited to spontaneous reporting data, in which the underlying population and exposure size are unknown. These methods enable the detection of abnormalities in the temporal structure of adverse event onset that may not be identifiable through frequency-based analyses alone. Furthermore, disproportionality analysis and TTO-based approaches are not competing methods but complementary strategies that capture different dimensions of safety signals-reporting frequency and temporal patterns-and their combined use may improve both sensitivity and interpretability of signal detection. The review also discusses survival analysis-based methods and Weibull modeling for TTO data, outlining their theoretical background and applications while emphasizing their inherent limitations when applied to spontaneous reporting systems. Because of reporting bias, incomplete time information, and the absence of non-event cases, such methods should not be used to estimate population-level risks or to infer causality. In conclusion, TTO analyses using spontaneous reporting databases should be positioned as exploratory tools for characterizing onset patterns, generating hypotheses, and informing the design of subsequent epidemiological and safety studies, rather than as a direct basis for clinical or regulatory decision making.

PMID:42118500 | DOI:10.1007/s40264-026-01677-3

Discov Nano. 2026 May 12;21(1):185. doi: 10.1186/s11671-026-04610-w.

ABSTRACT

In industries like chemical processing, energy systems, metallurgy, filtration, and electronics cooling, activation energy in magneto-nanofluid flow with variant viscosity is essential for regulating reaction rates, maximizing heat and mass transfer, enhancing energy efficiency, and guaranteeing safe operation. This work is important because it advances our knowledge of heat and mass transmission in magnetized nanofluid flows, where the fluid viscosity varies nonlinearly with temperature or other physical parameters. The study’s primary goal is to create a numerical model capable of precisely analyzing the intricate relationship between magnetic forces, nonlinear viscosity, porous media, and nanoparticle transport. To get the perfect predictions, the governing model employed the efficacy of artificial neural networks with Levenberg Marquardt structure back propagation (ANN-LMSB), which is designed to investigate energy activation with exponential viscosity variant with temperature on magneto-hydrodynamic nanofluid flow past porous plate (MHD-NFPP). To articulate mathematical modeling, the Reynolds exponential model is used. By employing the model of Darcy-Brinkman-Forchheimer, the momentum equation is additionally formulated. Thermophoresis force and Brownian diffusion have been inspected by implementing Buongiorno model. Along with magnetic body force, mass conservation, nanoparticle concentration, momentum, and energy equations are expressed. Initially, the flow of fluid is denoted by the scheme of PDEs, which are transformed into the structure of ODEs. By employing Adams numerical method, a data set for suggested ANN-LMSB is produced for diverse scenarios by alteration of stretching parameter, the Hartmann number, the thermal and concentration Grashof numbers, the thermophoresis, the Brownian motion, Prandtl number, the chemical reaction constant, Schmidt number, and relative temperature parametric number. By training, testing, and validation procedures of ANN-LMSB, estimated solution of distinct cases is verified, and for the perfection of the suggested model, the comparison for verification is carried out. Afterwards, execution of suggested ANN-LMSB was validated by regression evaluation, mean square error, and histogram studies. Correctness level in range from 10^-9 to 10^-11 approves distinction of suggested methodology established on the closeness of the recommended and reference results.

PMID:42118499 | DOI:10.1186/s11671-026-04610-w

Psicol Reflex Crit. 2026 May 12. doi: 10.1186/s41155-026-00391-4. Online ahead of print.

ABSTRACT

BACKGROUND: The lack of development assessment instruments aimed at children with disabilities in the early years of life means that standardized items are used for accommodation.

OBJECTIVE: This study aimed to describe accommodations implemented in the administration of the Bayley Scales of Infant Development (BSID-III) cognitive scale and analyze their association with the cognitive performance of children affected by Congenital Zika Syndrome.

METHODS: A total of 125 children were assessed at 12 months using BSID-III. Twelve types of accommodation strategies were adopted and organized according to participants’ main disability conditions, such as sensory, motor, auditory, and general accommodations.

RESULTS: This study identified that 59.2% of participants used some accommodation. “Lighting” (sensory accommodation) included the use of lighting during the test, and “not timing” includes disabling time tracking for tasks that involve time management. They were the most used accommodations, in addition to having presented a statistically significant association (p < = 0.05) with several items assessed by the instrument. A strong, statistically significant negative correlation (ρ = -0.73; p < 0.001) was found between the number of accommodations used and the cognitive performance score obtained by children. This indicates that the greater the use of accommodations, the lower the level of cognitive performance. It is understood that the more severe the congenital syndrome, the more accommodations are required during the assessment.

CONCLUSION: These findings are consistent with the guidelines provided in the accommodation procedures, which aim to offer opportunities for adequate assessment of children and allow for an explanation of their actual level of development, without any compensation. Assessment using accommodation provides more reliable data on children’s developmental strengths and weaknesses and has the potential to guide effective intervention programs. Such explanation favors a perspective of equity in the provision of care to children with disabilities.

PMID:42118492 | DOI:10.1186/s41155-026-00391-4

Environ Sci Pollut Res Int. 2026 May 12. doi: 10.1007/s11356-026-37813-w. Online ahead of print.

ABSTRACT

The cement industry is a typical high-carbon and overcapacity sector. In the context of global climate change, identifying productivity loss driven by resource misallocation is essential for controlling CO₂ emissions in the cement industry. We incorporate energy and CO₂ emissions into the Hsieh and Klenow (2009) model (HK model), reconstruct the analytical framework through which resource misallocation affects productivity, and empirically evaluate the resulting productivity loss in Hunan Province’s cement industry from 2016 to 2019. The results show that eliminating resource misallocation increases industry productivity by 22.14%, with CO₂ price distortion accounting for 12% of the productivity loss. The study also shows that in the cement industry, economically developed regions have lower resource use efficiency than less developed regions; large enterprises have higher efficiency than small enterprises; older enterprises perform better than newer ones; and state-owned enterprises have higher efficiency than non-state-owned enterprises.

PMID:42118488 | DOI:10.1007/s11356-026-37813-w

Mol Divers. 2026 May 12. doi: 10.1007/s11030-026-11584-5. Online ahead of print.

ABSTRACT

Bisphenol A (BPA), an environmental endocrine disruptor, is implicated in hepatocellular carcinoma (HCC), but its molecular mechanisms are unclear. This study employed an integrative computational framework to identify potential BPA-related molecular targets in HCC, assess their statistical clinical value, and generate hypotheses regarding their roles within the tumor microenvironment. BPA and HCC targets were retrieved from public databases and intersected with differentially expressed genes in HCC, identifying fifteen overlapping genes statistically enriched in cell cycle regulation, p53 signaling, and viral carcinogenesis. Six hub genes (MKI67, CCNA2, EZH2, CCNB1, CDK1, BIRC5) were significantly upregulated in HCC with high internal cross-validated diagnostic accuracy (AUC > 0.96), although these estimates may be susceptible to overfitting and require external validation. Molecular docking and dynamics simulations predicted stable BPA binding to six proteins (Ki67, Cyclin A2, EZH2, Cyclin B1, CDK1, Survivin), with van der Waals forces calculated as the primary driving energy contribution by MM-PBSA. The two-gene (CCNB1/EZH2) risk model showed statistical associations with patient survival, validated internally and externally, although its generalizability remains limited. Mendelian randomization provided genetic evidence consistent with a potential risk-associated role for CCNB1 and a protective-associated role for EZH2. Single-cell analysis localized high CCNB1 and EZH2 expression to malignant and proliferative T-cells, correlating with specific immune infiltration patterns and checkpoint expression. In conclusion, these computational findings suggest a statistical and structural association between BPA exposure and HCC-related core cell-cycle regulators (e.g., CCNB1/EZH2). The data generate the hypothesis that CCNB1 and EZH2 may serve as prognostic biomarkers and potential contributors to HCC biology, possibly through coordinated effects on cell cycle dysregulation and immune microenvironment remodeling, though direct evidence of in vivo molecular targeting by BPA or causal pathway activation is not established by this study. These findings provide novel insights into BPA’s putative role in hepatocarcinogenesis and offer clues for future experimental validation regarding risk assessment and therapeutic strategies.

PMID:42118483 | DOI:10.1007/s11030-026-11584-5

Clin Transl Oncol. 2026 May 12. doi: 10.1007/s12094-026-04359-9. Online ahead of print.

ABSTRACT

PURPOSE: Gastric cancer (GC) remains a major global health burden, with poor survival rates. HER2 is a key biomarker for targeted therapy, but discordance between primary tumors and metastases may impact treatment decisions. This meta-analysis evaluated the prevalence and clinical relevance of HER2 status differences between primary gastric cancers and metastatic lesions.

METHODS: A systematic search of PubMed, Embase, and Cochrane was conducted for studies assessing HER2 status in matched primary and metastatic gastric cancer samples. Pooled proportions and 95% confidence intervals (CIs) were calculated using random-effects models. Subgroup analyses by metastatic site were performed. Statistical analyses were conducted using R software, version 4.2.3.

RESULTS: This meta-analysis included 3,515 patients across 20 studies. The pooled proportion of HER2-positive expression in primary gastric tumors was 13% (95% CI: 12-15%; I² = 68.7%), while HER2-negative tumors accounted for 74% (95% CI: 72%-76%; I² = 94.9%). In metastatic sites, the overall pooled proportion of HER2-positive lesions was 18% (95% CI: 16%-20%; I² = 77.3%), with notable variation across anatomical locations: 38% in lung metastases, 31% in liver metastases, 19% in lymph nodes, and 7% in peritoneum. Conversely, HER2-negative metastases accounted for 82% overall (95% CI: 80%-84%; I² = 78.2%), with proportions of 93% in peritoneum, 81% lymph nodes, 69% in liver metastases, and 62% in lung.

CONCLUSIONS: Significant heterogeneity in HER2 expression between primary and metastatic gastric cancer underscores the need for reassessment of HER2 status in metastatic sites. Relying solely on primary tumor samples may lead to underestimation of HER2 positivity and suboptimal therapeutic decisions. Incorporating site-specific HER2 testing into clinical practice may enhance patient selection for HER2-targeted therapies and improve treatment outcomes.

PMID:42118480 | DOI:10.1007/s12094-026-04359-9

Clin Exp Optom. 2026 May 12:1-9. doi: 10.1080/08164622.2026.2669529. Online ahead of print.

ABSTRACT

CLINICAL RELEVANCE: Quantitative assessment of pupillary dynamics provides an objective measure of autonomic and retinal function, with potential utility in the clinical evaluation of ocular and neurological conditions.

BACKGROUND: Increasing myopia severity may alter pupillary mechanisms, and smartphone-based pupillometry provides a non-invasive method to quantify these changes. The purpose of this study was to investigate alterations in static and dynamic pupillary parameters among emmetropes, low, moderate, and high myopia groups using smartphone-based pupillometry.

METHODS: This comparative study included 160 participants (40 per group) aged 18-35 years. Pupillary dynamics were recorded with the Reflex Pro application under standardised illumination. Parameters analysed were latency, constriction velocity, maximum constriction speed, constriction amplitude, release amplitude, constriction time, and average pupil diameter. Intergroup differences were assessed using one-way ANOVA followed by Tukey’s post hoc analysis, with p < 0.05 considered statistically significant.

RESULTS: Latency was significantly prolonged with increasing severity of myopia, ranging from 0.25 ± 0.05 s in emmetropes to 0.36 ± 0.08 s in high myopes (p < 0.001). Constriction velocity and maximum constriction speed showed progressive reduction, with high myopes exhibiting the slowest dynamics (2.9 ± 0.3 mm/s and 3.1 ± 0.3 mm/s, respectively; p < 0.001). Constriction amplitude and release amplitude also declined significantly across groups (p < 0.001). Constriction time was prolonged in high myopes (0.74 ± 0.09 s) compared to emmetropes (0.65 ± 0.08 s, p = 0.01). Average pupil diameter showed a trend towards increase in high myopes (5.8 ± 0.6 mm) but did not reach overall statistical significance (p = 0.06). Post hoc analysis confirmed that differences between emmetropes and high myopes were consistently significant for most parameters (p < 0.001).

CONCLUSION: Pupillary dynamics vary with myopia severity, with smartphone-based pupillometry offering a potential non-invasive assessment tool, though causality requires longitudinal validation.

PMID:42117369 | DOI:10.1080/08164622.2026.2669529

Vet Rec. 2026 May 12. doi: 10.1002/vetr.70736. Online ahead of print.

ABSTRACT

BACKGROUND: Floppy rabbit syndrome (FRS) is known as an idiopathic neurological condition with a peracute onset of tetraparesis. While there are several anecdotal reports mentioning this phenomenon, scientific literature on this subject is scarce. The aim of this study was to assess clinical and clinicopathological data as well as the outcome of patients with FRS.

METHODS: This retrospective study included pet rabbits that presented with a peracute progressive symmetric lower motor neuron tetraparesis characterised by generalised weakness in all four limbs and decreased muscle tone and spinal reflexes. History, clinical signs, laboratory results, treatment and outcome were analysed.

RESULTS: The data revealed nine rabbits with non-ambulatory tetraparesis resembling FRS. Otherwise, the rabbits presented clinically unremarkably. All the animals showed significantly increased serum creatine kinase (CK) concentrations. Eight out of nine rabbits fully recovered within a short period.

LIMITATIONS: The study is limited by the small number of patients and the absence of muscle biopsy results and electromyography.

CONCLUSION: FRS can be clearly diagnosed due to its typical consistent clinical presentation and neurological examination. Clinical pathology, including the determination of serum CK concentrations, may aid in differentiating FRS from other diseases. FRS is typically self-limiting idiopathic neuromuscular disease that does not require specific treatment; therefore, euthanasia should be avoided.

PMID:42117365 | DOI:10.1002/vetr.70736

Vet Rec. 2026 May 12. doi: 10.1002/vetr.70741. Online ahead of print.

ABSTRACT

BACKGROUND: Large language models (LLMs) are emerging as decision-support tools in human medicine; however, their evaluation in veterinary anaesthesiology remains limited.

METHODS: We retrospectively analysed 225 anonymised feline and canine cases (American Society of Anaesthesiologists [ASA] classifications 1‒5) from Atatürk University Veterinary Hospital. ChatGPT-4o, ChatGPT-5 and Gemini 2.5 Pro independently assigned ASA classifications and generated anaesthetic protocols using standardised prompts. Protocol adequacy was evaluated for all cases, regardless of ASA classification agreement, by two experienced veterinary anaesthesiologists using a four-point scale. Statistical analyses included Friedman and Bonferroni-adjusted Wilcoxon tests, effect sizes and inter-panelist reliability (assessed by quadratic-weighted Cohen’s kappa and intraclass correlation coefficient).

RESULTS: ChatGPT-5 achieved the highest ASA classification accuracy (53.3%), followed by ChatGPT-4o (46.7%) and Gemini 2.5 Pro (30.7%). The performance was strongest for ASA 3‒5, whereas ASA 1 cases were frequently misclassified, mainly due to ASA overestimation. ChatGPT-5 generated the most clinically sufficient anaesthetic protocols, outperforming the other models.

LIMITATIONS: The retrospective, single-centre design and inclusion of only feline and canine cases may limit generalisability.

CONCLUSIONS: LLMs can generate clinically relevant ASA classifications and anaesthetic protocols in veterinary anaesthesiology, although performance varies across models. However, expert oversight remains essential.

PMID:42117364 | DOI:10.1002/vetr.70741

Curr Cardiol Rev. 2026;22(3):e1573403X351298. doi: 10.2174/011573403X351298250717031928.

ABSTRACT

INTRODUCTION: There are strong guidelines regarding the importance of SGLT-2 inhibitors (SGLT2i) in reducing mortality in patients with heart failure with reduced ejection (HFrEF). However, the role of SGLT2i in the management of patients with heart failure with preserved ejection fraction (HFpEF) and heart failure with mildly reduced ejection fraction (HFmrEF) remains ambiguous.

METHODS: A systematic review and meta-analysis of SGLT2i randomized controlled trials (RCTs) in HFpEF and HFmrEF, with and without diabetes was conducted (Prospero ID – CRD42023464479). Databases including Clinicaltrials.gov, PubMed, Biomed Central, Scopus, and Science Direct were searched from 2018 to 2024. Hospitalization due to heart failure (HFH) with HFpEF and HFmrEF was the primary outcome analyzed, followed by a subgroup analysis of HFH in HFpEF only. Secondary outcomes analyzed included cardiovascular (CV) death, all-cause mortality, and serious adverse effects.

RESULTS: In seven RCTs involving 31,057 participants, meta-analysis using random effects models showed that SGLT2i treated patients had a statistically significant reduction in HFH risk (OR=0.74, p<0.00001) compared to placebo or standard of care (SOC). A subgroup analysis, in HFpEF only patients, also showed a statistically significant reduction (OR=0.72, p<0.0001) in HFH odds. Statistical analysis of secondary outcomes showed a statistically non-significant difference in CV death risk (OR=0.92, p=0.13), all-cause mortality (OR=0.94, p=0.13), and any serious adverse events (OR=0.92, p=0.10).

DISCUSSION: This meta-analysis demonstrates that SGLT2i significantly reduce the risk of heart failure hospitalization in patients with preserved and mildly reduced ejection fraction, regardless of diabetes status. While reductions in cardiovascular and all-cause mortality, as well as serious adverse events, were observed, these did not reach statistical significance. These findings align with emerging evidence suggesting a broader cardioprotective role for SGLT2i across the heart failure spectrum, although further studies are needed to clarify their mortality benefit and long-term safety in HFpEF and HFmrEF populations.

CONCLUSION: This meta-analysis found a significant reduction in HFH with the use of SGLT2i in patients with HFpEF and HFmrEF. Secondarily, there was a statistically non-significant reduction in allcause mortality, CV death risk, and serious adverse events with the use of SGLT2i.

PMID:42117353 | DOI:10.2174/011573403X351298250717031928