Nevin Manimala

BMC Neurol. 2025 Dec 11;25(1):499. doi: 10.1186/s12883-025-04523-8.

ABSTRACT

BACKGROUND: Stroke-associated pneumonia (SAP) significantly impacts mortality and functional outcomes in acute stroke care. While multiple risk prediction scores have been developed internationally, their performance in Japanese healthcare settings-characterized by high nurse-to-patient ratios and systematic multidisciplinary protocols-remains unexplored. This study aimed to determine SAP incidence in Japanese acute stroke care and validate established risk prediction scores.

METHODS: We conducted a retrospective cohort study of consecutive patients with first-ever acute stroke admitted within 7 days of onset to a 199-bed acute care hospital with a dedicated 24-bed stroke care unit (April 2022-March 2023). SAP was diagnosed using modified CDC criteria requiring radiographic evidence. Three validated risk scores (A²DS², Pneumonia score, ISAN) were calculated and compared using receiver operating characteristic analysis. Independent predictors were identified through multivariable logistic regression using directed acyclic graph-based variable selection.

RESULTS: Among 847 patients analyzed (median age 75 years, 54.2% male), SAP developed in 22 patients (2.6%, 95% CI 1.5-3.7). Most cases (77.3%) occurred within 72 h. All three scores demonstrated good discrimination: A²DS² achieved the highest AUROC of 0.825 (95% CI 0.78-0.88), followed by Pneumonia score and ISAN (both AUROC 0.798). No statistically significant differences were observed between scores. An A²DS² cutoff ≥ 6 provided optimal balance (sensitivity 86.4%, specificity 65.8%, NPV 99.5%). Independent predictors included male sex (OR 3.87, 95% CI 1.41-10.61), NIHSS score (OR 1.08 per point, 95% CI 1.03-1.12), dysphagia (OR 5.31, 95% CI 1.16-24.34), and mechanical ventilation (OR 5.33, 95% CI 1.28-22.18).

CONCLUSIONS: SAP incidence in Japanese acute stroke care (2.6%) was substantially lower than international reports, likely reflecting high nursing standards and systematic preventive protocols. Despite low baseline risk, the A²DS² score demonstrated excellent discrimination and high negative predictive value, enabling reliable risk stratification. The predominance of early SAP onset supports intensive monitoring during the critical first 72 h. These findings support implementation of A²DS²-based risk stratification protocols in Japanese stroke care settings.

PMID:41382279 | DOI:10.1186/s12883-025-04523-8

Mol Med. 2025 Dec 11. doi: 10.1186/s10020-025-01409-w. Online ahead of print.

ABSTRACT

BACKGROUND: Immunotherapy is a promising treatment for drug-resistant cancers. However, its effectiveness against head and neck squamous cell carcinoma (HNSCC) is limited. This indicates the need to explore additional factors that can predict tumor response to new therapies and improve or supplement their effects. Therefore, we aimed to investigate whether the post-radiation usage of anti-TIGIT and/or anti-CD96 could enhance the antitumor response in HNSCC.

METHODS: HNSCC tissues, as well as human and mouse cell lines, were examined to evaluate the effects of radiation on immune checkpoint receptors (TIGIT, CD96, and CD226) and tumor ligands (CD155, CD112, CD113, and CD111). Overall and disease-free survival, along with factors related to these immune checkpoint receptors and ligands, were detected. Moreover, we investigated the effects of radiation dose and exposure time on the expression of these receptors and ligands in vitro and in vivo. Tumor growth and survival rates were then evaluated using TIGIT and/or CD96 inhibitors injected intraperitoneally after exposure to radiation. Finally, various proliferative and immunological parameters of the tumor microenvironment were determined using immunohistochemistry and flow cytometry. Statistical analyses were performed using Student’s t-test, one-way analysis of variance, or two-way analysis of variance.

RESULTS: Elevated levels of TIGIT, CD96, CD155, CD112, CD113, and CD111 were observed in both HNSCC tissues and the cell lines. Radiation increased the expression of these inhibitory receptors and ligands. Thus, anti-TIGIT and anti-CD96 were used to target the upregulated expression of the receptors TIGIT and CD96, respectively. This treatment combination inhibited tumor growth by boosting apoptosis, reducing tumor cell proliferation, and restoring the cytotoxic functions of CD4⁺ and CD8⁺ T cells after radiation therapy.

CONCLUSION: Our findings suggest that TIGIT and CD96 could be markers of the clinical stage and treatment response of HNSCC. Therefore, administering anti-TIGIT and anti-CD96 after radiotherapy may provide a novel approach for incorporating immunoradiotherapy into HNSCC treatment.

PMID:41382272 | DOI:10.1186/s10020-025-01409-w

BMC Infect Dis. 2025 Dec 11. doi: 10.1186/s12879-025-12316-0. Online ahead of print.

ABSTRACT

BACKGROUND: COVID-19 patients frequently present with various comorbidities. Two developed antiviral medications, nirmatrelvir/ritonavir and molnupiravir, have been utilized in COVID-19 patients; but comparisons of the effectiveness between nirmatrelvir/ritonavir and molnupiravir in COVID-19 patients with different comorbidities remain unknown. This study aims to compare the effectiveness, including invasive ventilation and mortality, of nirmatrelvir/ritonavir and molnupiravir in the overall population and populations with various comorbidities in Taiwanese patients during the omicron BA.2 wave.

METHODS: We retrospectively collected electronic medical records from the Taipei Medical University Clinical Research Database between January and December 2022 and conducted an analysis of adult patients diagnosed with SARS-CoV-2 infection. For data management, we performed propensity score matching to minimize the imbalance between two groups; the standardized mean difference > 0.1 or a p value < 0.05 considered statistically significant. Variables, which remained imbalanced after matching, were adjusted by cox regression model. To identify the risk associated with these variables, a Cox proportional hazards model were performed. Kaplan-Meier method was applied to estimate invasive ventilation and mortality, comparing survival curves between nirmatrelvir/ritonavir users and molnupiravir users.

RESULTS: Our cohort was recruited from a database, including patients who receive nirmatrelvir/ritonavir or molnupiravir treatment. Out of a total of 35,617 patients, 968 patients received nirmatrelvir/ritonavir and 1198 patients received molnupiravir after matching. Patients with chronic liver disease or mental disease on nirmatrelvir/ritonavir had lower risks of intubation than those on molnupiravir. Overall, nirmatrelvir/ritonavir reduced mortality risk by 65% (adjusted hazard ratio (aHR): 0.35, 95% confidence interval (CI): 0.14-0.88, p = 0.026). For patients with diabetes mellitus (aHR: 0.29, 95% CI: 0.11-0.78, p = 0.014), with chronic kidney disease (aHR: 0.26, 95% CI: 0.10-0.68, p = 0.007), or aged over 65 years (aHR: 0.30, 95% CI: 0.13-0.70, p = 0.005), nirmatrelvir/ritonavir demonstrated superior efficacy in reducing mortality risk compared to molnupiravir.

CONCLUSIONS: Data revealed that both nirmatrelvir/ritonavir and molnupiravir demonstrated clinical benefits in treating COVID-19 patients in a real-world setting. Moreover, nirmatrelvir/ritonavir was associated with a lower risk of mortality in COVID-19 patients with specific circumstances.

CLINICAL TRIAL: Clinical trial number is not applicable.

PMID:41382264 | DOI:10.1186/s12879-025-12316-0

BMC Health Serv Res. 2025 Dec 11. doi: 10.1186/s12913-025-13820-4. Online ahead of print.

ABSTRACT

BACKGROUND: Pakistan’s healthcare system faces critical challenges, including limited infrastructure and disparities in access between urban and rural regions. Telehealth has emerged as a promising solution to improve accessibility, but patient-centered evidence on its effectiveness and cost-efficiency remains limited.

METHODS: This cross-sectional survey included patients (n = 532) who completed telehealth consultations with EZShifa between May and December 2023. A structured questionnaire assessed socio-demographics, comfort, trust, perceived quality of care, and patient-reported costs. Descriptive statistics summarised characteristics. Ordinal regression identified predictors of telehealth acceptance. Patient-reported telehealth and in-person care costs were compared, and incremental cost-effectiveness ratios (ICERs) were estimated using acceptance and comfort scores as effectiveness measures.

RESULTS: Most participants were aged 26-50 and from Punjab or Sindh. High satisfaction was reported for provider professionalism and consultation quality, though some concerns about connectivity and privacy remained. Ordinal regression showed that higher comfort (OR 4.15-20.3, p = 0.008) and perceived quality of care (OR 2.59, p = 0.004) significantly predicted acceptance, while sociodemographic factors were non-significant. The mean reported telehealth cost (PKR 2,000) was substantially lower than in-person visits (PKR 4,800). ICER analysis indicated telehealth was dominant, offering cost savings and greater patient-reported effectiveness.

CONCLUSIONS: Telehealth demonstrates strong acceptance, satisfaction, and economic benefits in Pakistan’s primary healthcare system. Despite self-reported costs and cross-sectional design limitations, findings highlight telehealth’s potential for scaling chronic disease management and reducing healthcare disparities.

PMID:41382260 | DOI:10.1186/s12913-025-13820-4

Hum Genomics. 2025 Dec 11. doi: 10.1186/s40246-025-00876-w. Online ahead of print.

NO ABSTRACT

PMID:41382250 | DOI:10.1186/s40246-025-00876-w

Eur J Med Res. 2025 Dec 11. doi: 10.1186/s40001-025-03610-3. Online ahead of print.

ABSTRACT

PURPOSE: Keratorefractive lenticule extraction (KLEx) is widely used for myopia correction. This study aims to investigate the relationships among the designed lenticular area (DLA), lenticule stretched preparation (LSP), and the achieved functional optical zone (AFOZ) to identify factors influencing these discrepancies.

SETTING: The study was conducted at the Eye & ENT Hospital of Fudan University, Shanghai.

DESIGN: The study was a non-randomized, prospective analysis of patients’ surgical parameters.

METHODS: 29 young adults who underwent KLEx for myopia correction were included. Preoperative data, including spherical equivalent and axial length, were recorded. The removed lenticule was stained, flattened, and measured using ImageJ software to calculate the LSP area. Postoperative AFOZ was assessed using Pentacam topography. Statistical analysis compared LSP, DLA, and AFOZ and correlated differences with clinical parameters.

RESULTS: The mean age of the patients was 23.07 ± 4.76 years, with a median spherical equivalent of – 4.3755.375, (- 5.375, – 3.188) D. The AFOZ was smaller than the DLA (35.26 (35.260, 35.260) mm² vs. 36.32 (35.790, 36.320) mm²), likely due to corneal remodeling. Axial length significantly correlated with the LSP-DLA discrepancy (P = 0.005), with longer axial lengths associated with smaller differences, suggesting that increased axial length reduces corneal elasticity. Spherical equivalent also correlated significantly with the AFOZ-DLA discrepancy (P = 0.047).

CONCLUSIONS: Anatomical factors such as axial length and myopia severity affect the AFOZ in KLEx. Future research should incorporate additional biomechanical and imaging parameters to enhance the accuracy of outcome predictions.

PMID:41382247 | DOI:10.1186/s40001-025-03610-3

Acta Neuropathol Commun. 2025 Dec 11. doi: 10.1186/s40478-025-02202-w. Online ahead of print.

ABSTRACT

Spinal hemangioblastomas (sHB) are rare vascular tumors, with distinct clinical courses between von Hippel-Lindau (VHL)-associated and sporadic cases. The MIB-1 labeling index has been proposed as a surrogate marker for tumor proliferation, but its prognostic value remains unclear in this context. In this subgroup analysis from a multicenter retrospective study, we analyzed 116 primary sHB patients with available MIB-1 indices. Patients were stratified by VHL status. Statistical comparisons included ROC analyses for local progression-free survival (PFS) prediction and Kaplan-Meier survival curves for local PFS, stratified by a MIB-1 index cut-off derived from Youden’s index. The MIB-1 index was significantly lower in VHL-associated tumors compared to sporadic ones (mean 2.17% vs. 3.02%, p = 0.008). In VHL-associated sHB, a higher MIB-1 index (≥ 2%) correlated with an increased risk of local tumor progression (AUC 0.74, 95% CI 0.49-0.98), whereas this was not observed in sporadic cases (AUC 0.56, 95% CI 0.23-0.88). Kaplan-Meier analysis showed that VHL patients with MIB-1 ≥ 2% had significantly shorter PFS (p = 0.05), while no significant association was found in sporadic tumors (p = 0.87). Our findings suggest that while VHL-associated sHB exhibit lower proliferative indices overall, elevated MIB-1 labeling indices might serve as a prognostic marker of shorter local PFS in this subgroup. In contrast, MIB-1 index appears to have limited prognostic relevance in sporadic sHB. These results highlight the importance of further molecular stratification and proliferation assessment in sHB to better inform clinical decision-making.

PMID:41382243 | DOI:10.1186/s40478-025-02202-w

Popul Health Metr. 2025 Dec 11. doi: 10.1186/s12963-025-00440-7. Online ahead of print.

ABSTRACT

The aim of the study was to analyze changes and demographic inequalities in the mortality of the Lithuanian population in 2020 and 2021 compared to the period of 2015-2019, assess the major causes of death that contributed to the changes, and identify the groups of the society that suffered most.

METHODS: Mortality rates for 2015-2021 from all causes, cardiovascular diseases, malignant neoplasms, external causes, diseases of the digestive system, diseases of the respiratory system, and COVID-19 in Lithuania by sex and age were calculated per 100,000 population. Mortality changes compared with the previous year and between the average of 2015-2019 years were calculated. The average annual percentage change was calculated to determine the aggregated 2015-2019 change in mortality from the leading causes of death. Coefficients of linear regression multiplied by 100 were presented as average annual changes, which were statistically significant at p < 0.05. Mortality rate differences between 2020 and 2021 years and the average of 2015-2019 years were calculated.

RESULTS: Lithuania has recorded 9.4% higher overall mortality among males in 2020 and 18% higher mortality in 2021 compared with a period unaffected by the COVID-19 pandemic (p < 0.05). Among females – 10.7% higher mortality in 2020 and 22.6% in 2021 (p < 0.05). Male and female mortality from COVID-19 in all age groups in 2021 was higher than that in 2020, and mortality rates increased with an increase in age. Negative changes in mortality from 2015 to 2019 to 2020 among males and females of all age groups were mainly determined by COVID-19. The most significant impact of COVID-19 in 2021 on the overall mortality changes was estimated in the 55-64 and 65-74 male age groups, while female overall mortality was in the 45-54 and 65-74 age groups.

CONCLUSIONS: Negative changes in mortality from 2015 to 2019 to 2020 among males and females of all age groups were mainly determined by COVID-19. The most significant impact of COVID-19 in 2021 on the overall mortality changes was estimated in the 55-74 male age group, while on female overall mortality in the 45-54 and 65-74 age groups.

PMID:41382237 | DOI:10.1186/s12963-025-00440-7

J Ovarian Res. 2025 Dec 11. doi: 10.1186/s13048-025-01884-z. Online ahead of print.

ABSTRACT

PURPOSE: Polycystic Ovary Syndrome (PCOS) is a common endocrine disorder, with dysregulated lipid metabolism and immune dysfunction. However, it remains unclear whether immune phenotypes mediate the relationship between lipidomes and PCOS.

METHODS: A two-step Mendelian Randomization analysis was employed to explore the causal relationship between plasma lipidomes and PCOS and to investigate the mediating role of immune cells. A total of 179 plasma lipidomes and 731 immune phenotypes were analyzed. We used single nucleotide polymorphisms (SNPs) associated with plasma lipidome levels as instrumental variables and applied statistical methods, including the inverse-variance weighted approach, to assess potential causal relationships.The function of immune phenotypes in regulating the relationship between lipids and PCOS was evaluated through mediation analysis.

RESULTS: Ten lipid-immune pathways mediating the association between plasma lipidomes and PCOS were identified. Elevated levels of phosphatidylcholines and triacylglycerols increased the risk of PCOS by modulating immune markers such as HLA DR on B cells and CD28 on regulatory T cells. Conversely, phosphatidylinositol (18:1_18:2) demonstrated a protective effect against PCOS through CD33 on myeloid-derived suppressor cells. Six specific plasma lipidomes were causally linked to PCOS risk, including phosphatidylcholine (18:1_20:4) and triacylglycerol (50:4), which increased risk, and phosphatidylinositol (18:1_18:2), which lowered risk. Additionally, 31 immune phenotypes were identified as causally associated with PCOS, with 27 increasing risk and 4 offering protective effects.

CONCLUSION: This study provides evidence that immune phenotypes mediate the relationship between plasma lipidomes and PCOS. These findings highlight the potential of targeting both lipid metabolic processes and immune pathways as novel therapeutic strategies for managing PCOS.

PMID:41382225 | DOI:10.1186/s13048-025-01884-z

Cell Commun Signal. 2025 Dec 11. doi: 10.1186/s12964-025-02573-6. Online ahead of print.

ABSTRACT

BACKGROUND: Given the role of metabolism in brain health and disease, the investigation of the role of insulin (INS) and insulin-like growth factors (IGFs) as potential therapeutic strategies for neurodegenerative diseases is currently underway. Yet, the signaling pathways associated with INS and IGFs in the brain remain elusive, particularly for the human brain. Unraveling these pathways is critical for harnessing their therapeutic potential in metabolism-associated brain disorders.

METHODS: This study employed phosphoproteomics using a human neuroblastoma cell line, SH-SY5Y, to unravel the signaling networks of INS, IGF-1, and IGF-2. Briefly, cells were stimulated for 10 and 60-minutes with the ligands, followed by protein extraction, trypsin digestion, tandem mass tag (TMT) labelling and phosphopeptide enrichment using an immobilized metal affinity chromatography (IMAC) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. The data were processed using R statistical software. Protein annotations were obtained from the UniprotKB database, and pathway enrichment analysis was performed using Ingenuity Pathway Analysis (IPA).

RESULTS: Phosphoproteomics performed at 10 and 60 min identified 34,358 phosphosites, of which 3,284 were significant at 10 min and 2,374 at 60 min (p.adj < 0.05) across all three ligands. Ligand stimulation induced modulation in phosphorylation at both the receptor level and downstream targets at serine (S), threonine (T), and tyrosine (Y) residues. LIMA1-Y229, a regulator of actin-cytoskeletal function, was the most prominent Y phosphosite across all ligands. IPA identified Rho GTPase as the most significantly enriched pathway, with IGF-1 predominantly driving phosphorylation of Rho GTPase effectors such as Rho guanine nucleotide exchange factors (ARHGEFs), Rho GTPase activating proteins (ARHGAPs) and CDC42. Myocardin-related transcription factor A (MRTFA), a transcriptional target of Rho GTPase, was increased in ligand-stimulated cells at 10 min, and inhibition of the Rho/SRF pathway and PI3K by CCG1423 and wortmannin, respectively, prevented nuclear localization of IGF-1-induced MRTFA.

CONCLUSIONS: This study demonstrates that INS, IGF-1, and IGF-2 regulate Rho GTPase and MRTFA activation, thereby contributing to the control of actin cytoskeletal dynamics in neuronal cells. Given the role of INS and IGFs in neuronal survival and neurodegenerative conditions, elucidating these mechanisms is of critical importance, as it offers insights into disease pathogenesis and potential therapeutic targets.

PMID:41382216 | DOI:10.1186/s12964-025-02573-6