Category: Nevin Manimala

Chin Med. 2026 Jul 29;21(1):204. doi: 10.1186/s13020-026-01476-z.

ABSTRACT

BACKGROUND: Multiple sclerosis (MS) is a debilitating neuroinflammatory disease. Experimental autoimmune encephalomyelitis (EAE) is a commonly used rodent model for MS. Forsythoside A (FA), a natural compound derived from Forsythia suspensa, exhibits anti-inflammatory and neuroprotective properties; however, its efficacy in EAE and its underlying mechanism remain unclear.

PURPOSE: To explore the therapeutic effect of FA on EAE and its mechanism.

METHODS: EAE was induced in C57BL/6 mice treated with FA (20/60 mg/kg) from day 7. Clinical scores, histopathology (H&E, LFB, immunofluorescence), flow cytometry, and spinal cord RNA sequencing were analyzed. Network pharmacology, molecular docking, molecular dynamics (MD) simulations, and surface plasmon resonance (SPR) were employed to identify and validate the target of FA. In vitro studies using BV2 microglia with Tnfaip2 knockdown/overexpression confirmed the mechanism via qRT-PCR and Western blot.

RESULTS: FA treatment dose-dependently alleviated clinical severity. While the 20 mg/kg dose showed a trend toward improvement without statistical significance, the 60 mg/kg dose significantly reduced CNS inflammation and demyelination. FA decreased peripheral Th1 cells in EAE mice. It suppressed microglial activation and pro-inflammatory markers (IL-1β, TNF-α, iNOS) expression. Transcriptomics and network analysis pinpointed TNF-α-induced protein 2 (Tnfaip2) in the TNF pathway. FA directly bound Tnfaip2 (K_D = 28 µM), validated by docking, MD simulations, and SPR. In vitro, FA inhibited LPS-induced pro-inflammatory polarization and the Tnfaip2/NF-κB pathway in BV2 cells. Tnfaip2 overexpression abolished the anti-inflammatory effects of FA.

CONCLUSION: FA ameliorates EAE by suppressing pro-inflammatory microglial polarization via directly targeting Tnfaip2 and inhibiting the NF-κB pathway. This identifies the Tnfaip2/NF-κB axis as a potential therapeutic target for MS.

PMID:42527947 | DOI:10.1186/s13020-026-01476-z

BMC Zool. 2026 Jul 28;11(1):24. doi: 10.1186/s40850-026-00280-4.

ABSTRACT

BACKGROUND: Activity budgets provide insights into how primates respond to habitat variation. Through behavioural flexibility, primates, including blue monkeys, can adjust their activity patterns and resource use under changing environmental conditions. This study compared the activity budgets of two Boutourlini’s blue monkey groups inhabiting different forest zones of Saja Forest: the core and transition zones. We collected Behavioral data from August 2024 to October 2025 using the instantaneous scan sampling method.

RESULTS: A total of 19,725 behavioral observations were recorded. Feeding was the dominant activity (29.6%), while times allocated for other activities were a smaller proportion (7.5%). The core-zone group spent significantly more time on feeding (33.0%), whereas those in the transition study group spent more time on movement (29.5%), and both showed statistically significant differences. Social activity was also higher in the transition zone group (13.5%), but it was not significant. Feeding was higher in the dry season (32.11%), whereas moving was higher in the wet season (28.67%). Diurnal patterns were observed, with feeding peaking in the morning and afternoon, while resting was highest at midday. Activity budgets varied among sex-age categories, with adult females showing the highest proportion of feeding activity (33.3%).

CONCLUSIONS: These findings provide baseline information on the activity budgets of two Boutourlini’s blue monkey groups occupying different forest zones. The observed variation in activity budgets between study groups and across seasons suggests behavioural flexibility under different environmental conditions. Future studies involving multiple independent groups per habitat type and direct measurements of habitat characteristics are needed to better understand the ecological factors influencing behavioural variation and to support conservation planning.

PMID:42527926 | DOI:10.1186/s40850-026-00280-4

BMC Nurs. 2026 Jul 27;25(1):667. doi: 10.1186/s12912-026-05093-x.

ABSTRACT

BACKGROUND: Patient safety is a major priority in intensive care units (ICUs), particularly among mechanically ventilated patients receiving intravenous sedation. Although sedative agents are essential for maintaining comfort and ventilator synchrony, inappropriate sedation practices may contribute to adverse clinical outcomes. Understanding the factors influencing nurses’ sedation practices is therefore essential to promote safe and effective patient care. This study aimed to explore the factors influencing critical care nurses’ intravenous sedation practices and examine their relationship with patient safety outcomes.

METHODS: A cross-sectional descriptive exploratory study was conducted among 105 nurses working in critical care units. Participants were recruited using a consecutive sampling technique and were directly involved in caring for mechanically ventilated patients receiving intravenous sedation. Data were collected using the Nurses’ Profile Questionnaire and the Nurse Sedation Practices Scale (NSPS). Descriptive statistics and multiple regression analysis were performed to identify predictors of nurses’ sedation practices. Statistical significance was considered at p < 0.05.

RESULTS: Sedation orders and goals achieved the highest mean score (81.5%), followed by sedation practices (74.2%) and attitudes toward sedation (72.4%). Subjective norms showed moderate scores (67.6%), while perceived behavioral control demonstrated lower scores (60.1%). Intention to sedate recorded the lowest score (41.1%), suggesting a preference for individualized sedation approaches. Multiple regression analysis identified subjective norms, perceived behavioral control, and intention to sedate as significant predictors of nurses’ sedation practices. Subjective norms were the strongest predictor (B = 0.328, p < 0.001), followed by perceived behavioral control (B = 0.210, p = 0.002). Intention to sedate showed a significant negative association with sedation practices (B = -0.139, p = 0.010).

CONCLUSION: Improving sedation practices among critical care nurses requires strengthening perceived behavioral control and promoting patient-centered sedation approaches to enhance patient safety outcomes in mechanically ventilated patients.

PMID:42527923 | DOI:10.1186/s12912-026-05093-x

Environ Health. 2026 Jul 29;25(1):66. doi: 10.1186/s12940-026-01324-5.

ABSTRACT

Conflicting views in experimental carcinogenesis often arise due to differences in study design among reported studies. For carcinogenicity assessments, regulatory agencies, such as the US Food and Drug Administration (FDA), and intergovernmental advisory organizations, such as the Organization for Economic Co-operation and Development (OECD), specify the use of at least three dose levels plus control group for trend analyses, with the highest dose inducing a measurable toxic response. In addition, there needs to be a sufficient number of animals per group to have adequate power to detect a true carcinogenic effect. Departure from such recommendations can weaken the interpretations of study results. We examine here two recent carcinogenicity studies from Japan and Korea that were conducted following the positive carcinogenicity study of radiofrequency radiation (RFR) in experimental animals by the National Toxicology Program (NTP). The Japan and Korea follow-up studies used fewer animals per group, a single RFR exposure group, and a lower exposure level than the NTP study. Not surprisingly, while the NTP study revealed the carcinogenicity of RFR, the Japanese and Korean studies, which had reduced statistical power compared to the NTP study, issued conclusions conflicting with those of the more substantial NTP study on the health effects of RFR. In general, carcinogenicity studies with weaker doses, fewer exposure groups, and reduced statistical power should not be used to test the validity of more robust studies.

PMID:42527916 | DOI:10.1186/s12940-026-01324-5

BMC Neurol. 2026 Jul 22;26(1):484. doi: 10.1186/s12883-026-05163-2.

ABSTRACT

BACKGROUND: The treatment of neuromyelitis optica spectrum disorder (NMOSD) has entered the era of targeted biological agents. While relapse control has improved substantially, patient-reported outcomes (PROs) remain understudied. This study aimed to explore real-world patient-reported perceptions of inebilizumab therapy in AQP4-IgG-positive NMOSD.

METHODS: We conducted a nationwide cross-sectional survey of AQP4-IgG-positive NMOSD patients receiving inebilizumab using an anonymous online questionnaire (April-September 2025). Data collected included demographics, medication history, and multidimensional quality-of-life changes following inebilizumab initiation. Descriptive statistics and correlation analyses were performed. Key outcomes were patient-reported without objective validation.

RESULTS: A total of 275 valid questionnaires were analyzed. Respondents were predominantly female (90.5%) with a mean age of 39.7 ± 11.8 years. Mean inebilizumab treatment duration was 14.5 ± 8.4 months. Of all patients, 33.1% received inebilizumab as initial maintenance therapy, 42.9% had previously used conventional immunosuppressants, and 24.0% had switched from other biologics. Among respondents, 92.4% reported meaningful symptom improvement across multiple domains including bodily pain and mental health. Overall, 96.4% expressed willingness to continue therapy, with symptom improvement cited as the predominant reason (91.7%). Correlation analysis revealed weak associations between treatment duration and satisfaction (r = 0.12, p < 0.05) and between medication cost burden and satisfaction (r = – 0.24, p < 0.01).

CONCLUSIONS: In this cross-sectional survey, Chinese patients with AQP4-IgG-positive NMOSD receiving inebilizumab reported high satisfaction, perceived multidimensional benefit, and strong treatment continuation willingness. These findings provide exploratory patient-reported evidence regarding the acceptability of inebilizumab in routine practice. However, the observed improvements are self-reported and associative rather than causal; interpretation should account for the cross-sectional, non-comparative design, potential selection and recall biases, and lack of objective outcome validation. Prospective controlled studies are required to confirm these preliminary findings.

PMID:42527908 | DOI:10.1186/s12883-026-05163-2

BMC Bioinformatics. 2026 Jul 24;27(1):162. doi: 10.1186/s12859-026-06538-5.

ABSTRACT

BACKGROUND: Single-cell foundation models such as scGPT and Geneformer learn rich representations of gene expression programs, but whether these representations encode gene regulatory relationships beyond expression-level confounds remains unclear. Attention patterns in these models have been shown to capture co-expression rather than direct regulation, leaving open the question of whether deeper representations-particularly the residual stream-contain genuine regulatory information.

RESULTS: We systematically investigated residual-stream geometry in scGPT and Geneformer across four tissue contexts from the Tabula Sapiens atlas, evaluating whether geometric proximity between gene vectors provides incremental predictive value for curated TRRUST transcription factor-target edges beyond expression confounds. Under repeated stratified cross-validation, geometric features provided significant incremental signal in kidney and immune settings, validated by label-permutation and geometry-shuffle null controls; centered-cosine similarity, PCA projection and multi-layer bundling recovered comparable signal in lung tissues, and the multi-layer bundle improved every domain (kidney ΔAUROC = + 0.122, immune + 0.042, lung + 0.028, external lung + 0.027; geometry-augmented AUROC 0.60-0.69). The effect was fully robust to leave-TF-out and leave-target-out cross-validation and to harder degree- and expression-matched negative edges, but under the stricter leave-both-out split-no transcription factor and no target shared between folds-it collapsed to near-zero (ΔAUROC at most + 0.003, and not statistically significant in kidney or immune), marking the ceiling of out-of-entity generalization. With a comparable per-layer residual-stream extraction applied to both models, the apparent Geneformer advantage mostly disappeared (small residual gaps remained in three of four domains), indicating it largely reflected representation-construction choices rather than a substantial architectural difference. Asymmetric geometric features predicted regulatory edge orientation (AUROC 0.80-0.90), and the geometric signal added incremental value on top of expression-based gene regulatory network (GRN) inference (GENIE3, co-expression).

CONCLUSION: Foundation model residual streams carry incremental, regulatory-relevant geometric signal that is distributed across layers and that complements expression-based GRN inference for retrospective edge prioritization. The signal is statistical enrichment rather than a stand-alone regulatory classifier: absolute performance is modest and out-of-entity generalization is limited, so its practical role is as an orthogonal evidence channel for edge re-ranking and hypothesis prioritization in multi-evidence frameworks.

PMID:42527907 | DOI:10.1186/s12859-026-06538-5

BMC Emerg Med. 2026 Jul 29;26(1):204. doi: 10.1186/s12873-026-01697-3.

ABSTRACT

PURPOSE: Artificial intelligence (AI) can support and enhance radiologists in musculoskeletal imaging, but evidence of clinical benefit is still lacking. This prospective study aimed to estimate the range of expected effect size on patient recall rates whether after implementation of an AI system for fracture detection affects in a paediatric emergency setting during out-of-hourse care.

METHODS: Children and adolescents (2-18 years) undergoing appendicular skeletal radiography between April and September 2025 during on-call hours at a tertiary referral hospital were eligible. On every second day, automated fracture detection by a commercial AI system (TechCare Kids, Milvue, Paris, France) was available for the treating physician. Endpoints were the rate of diagnostic revisions leading to patient recall the next day, therapeutic changes, length of stay at the emergency department, need for senior consultation, subjective diagnostic confidence, and AI accuracy.

RESULTS: Among 1515 screened patients, 667 were enrolled (median age 11.0 years, 61% male). Fractures were present in 296 cases (44.3%). AI accuracy was 95.1%. Diagnostic revisions occurred in 8.6% without AI, in 5.7% with AI support (risk ratio 0.66; 95% CI 0.37-1.19). Resulting therapeutic changes were rare in both groups (2.0% vs. 0.4%; p = 0.10). No significant differences were observed for secondary endpoints, including need for senior consultation (14.3% vs. 12.5%), subjective diagnostic confidence, or length of stay (2.3 h vs. 2.4 h).

CONCLUSION: Given the small effect size for patient recall rates in an academic medical setting, it is questionable whether the efforts conducting a confirmatory study with adequate statistical power would be justified by the expected incremental benefit for the investigated outcomes.

PMID:42527905 | DOI:10.1186/s12873-026-01697-3

BMC Ophthalmol. 2026 Jul 29;26(1):448. doi: 10.1186/s12886-026-05095-y.

ABSTRACT

BACKGROUND: Bipolar disorder and depression are associated with structural and functional changes in the retina, including a thinner retinal nerve fibre layer (RNFL). Lithium is widely considered the most effective treatment for bipolar disorder, but its mechanism of action is not fully understood. We assessed research looking at the effect of lithium on structural or functional retinal outcomes in humans.

METHODS: Searches using the terms ‘Lithium’ AND ‘retina’ were carried out to identify peer reviewed studies assessing the impact of lithium on retinal structure or function. These included those with or without a control group comparison, pre- and post- lithium comparisons and observational studies. There were no exclusions based on the quantity or preparation of lithium administered, or the length of administration. Risk of bias was assessed using the Joanna Briggs Institute (JBI) critical appraisal tool for Analytical Cross Sectional Studies, and a narrative synthesis and tabulated summary of the included studies was completed.

RESULTS: Seven studies assessing structural outcomes and 10 reporting functional ones were identified, all highly heterogenous and with multiple limitations. Structural outcomes were derived exclusively from optical coherence tomography (OCT) with retinal nerve fibre layer (RNFL) being the most common measurement. There was no evidence of differences in the RNFL between participants with bipolar disorder taking lithium and healthy controls in two larger studies. In six studies looking at differences in those with bipolar disorder taking lithium and those taking valproate, two showed no signs of difference and four showed evidence of thicker RNFL in the lithium group. Studies reporting functional outcomes reported a statistically significant effect of lithium on at least one functional measure, derived from electrooculography, electroretinography, and dark adaptation thresholds.

CONCLUSIONS: Current evidence suggests that lithium is likely to have an effect on the retina but limitations in all studies mean better designed and adequately powered prospective studies are required.

REGISTRATION: PROSPERO database (Number-CRD42024516635).

PMID:42527898 | DOI:10.1186/s12886-026-05095-y

Pediatr Blood Cancer. 2026 Jul 29:e70449. doi: 10.1002/1545-5017.70449. Online ahead of print.

ABSTRACT

BACKGROUND: Cerebellar ataxia after pediatric brain tumor treatment can cause persistent gait, balance, and speech impairment, yet no established rehabilitation strategy exists. Somato-cognitive coordination therapy (SCCT) is a virtual reality-guided intervention designed to promote sensorimotor integration through visually constrained reaching tasks. We evaluated the safety, feasibility, and preliminary functional observations of SCCT in this population.

METHODS: This single-center retrospective pilot study included 12 consecutive pediatric patients with cerebellar ataxia following brain tumor treatment who underwent outpatient SCCT between August 2023 and April 2025. SCCT sessions comprised approximately 10 min of alternating reaching tasks with limited visual feedback. Safety, acceptability, and changes in routinely documented selected scale for the assessment and rating of ataxia (SARA) subscale scores (gait, stance, and speech) were reviewed.

RESULTS: Patients received a median of 1 SCCT session (range, 1-7). No serious adverse events occurred. Although two patients reported transient fatigue, all respondents expressed willingness to continue, and 11 patients (92%) spontaneously described the intervention as enjoyable. Preliminary functional changes were observed even after a single 10-min session. The median pooled SARA subscale score showed a statistically significant reduction from 3.0 [interquartile range, 1.0-4.0] to 1.0 [1.0-2.0] (p < 0.001). One patient with cerebellar mutism showed speech-score reduction accompanied by longitudinal diffusion tractography changes.

CONCLUSIONS: SCCT appeared feasible and was not associated with serious adverse events in this retrospective pilot cohort. Exploratory functional observations warrant further evaluation in prospective randomized controlled trials to evaluate therapeutic efficacy and long-term durability.

PMID:42527885 | DOI:10.1002/1545-5017.70449

Pediatr Blood Cancer. 2026 Jul 29:e70477. doi: 10.1002/1545-5017.70477. Online ahead of print.

ABSTRACT

Selumetinib, a mitogen-activated protein kinase kinase inhibitor, was the first Food and Drug Administration-approved treatment for children with neurofibromatosis type 1-associated inoperable plexiform neurofibromas. We evaluated hematologic effects in 98 pediatric participants from the SPRINT Phase 1/2 trial (NCT01362803) with a median follow-up of 5.1 years (range: 0.2-11 years). Over 90% of values for white blood cell count, platelet count, absolute neutrophil count, and absolute lymphocyte count remained within normal limits across timepoints. There was a statistically significant, but unlikely clinically significant, decrease in absolute lymphocyte count and an increase in mean corpuscular volume. Selumetinib was not associated with apparent clinically significant hematologic changes.

PMID:42527881 | DOI:10.1002/1545-5017.70477