Nevin Manimala

J Hum Genet. 2025 Dec 17. doi: 10.1038/s10038-025-01443-w. Online ahead of print.

ABSTRACT

Transmembrane protein 53 (TMEM53) is an outer nuclear membrane protein that plays a crucial role in maintaining skeletal homeostasis. Pathogenic variants in TMEM53 have been identified as the genetic cause of craniotubular dysplasia, Ikegawa type (CTDI), a rare form of sclerosing bone dysplasia characterized by skull hyperostosis, cranial deformities, and increased bone density. To date, the causal association of bi-allelic pathogenic variants of TMEM53 in CTDI has been identified in 14 patients from eight unrelated families. Mechanistically, TMEM53 negatively regulates BMP-SMAD signaling by restricting the nuclear import of phosphorylated SMAD1/5/9, thereby modulating osteoblast differentiation and bone formation. This review summarizes the current understanding of TMEM53 function and the consequences of its deficiency. We aim to clarify genotype-phenotype correlations, outline therapeutic prospects for CTDI, and explore the distinct mechanisms underlying cranial and tubular bone formation.

PMID:41408477 | DOI:10.1038/s10038-025-01443-w

Intensive Care Med Exp. 2025 Dec 18;13(1):131. doi: 10.1186/s40635-025-00843-8.

ABSTRACT

BACKGROUND: Patients with severe acute pancreatitis (SAP) frequently develop hypoxic acute respiratory failure (AHRF), with a mortality rate as high as 37%. However, the optimal partial pressure of oxygen (PaO₂) for SAP patients remains unclear to date. This study aims to investigate whether partial pressure of oxygen is associated with mortality in SAP patients.

METHODS: A retrospective cohort study was conducted on patients with severe acute pancreatitis (SAP) admitted to the First Affiliated Hospital of Nanchang University from 2015 to 2024. Propensity score matching (based on whether arterial oxygen partial pressure PaO₂ ≥ 80 mmHg during the first 3 days after ICU admission, assigning patients to the liberal PaO₂ group or conservative PaO₂ group), univariate logistic regression analysis, Cox regression analysis, subgroup analysis, Kaplan-Meier (K-M curve) survival analysis, and sensitivity analysis were employed to thoroughly evaluate the association between PaO₂ and mortality in SAP patients. The primary outcome was 28-day mortality.

RESULTS: The study included 1585 patients. We found that higher PaO₂ was associated with lower 28-day mortality rates. In logistic regression analysis after propensity score matching, the incidence rates of adverse outcomes such as persistent circulatory failure (OR 0.50; 95% CI 0.35-0.69; P < 0.001) and persistent multiple organ failure (OR 0.60; 95% CI 0.47-0.78; P < 0.001) significantly decreased. The K-M curve demonstrated significant reductions in 28-day mortality (P = 0.02), 90-day mortality (P = 0.0079), and overall mortality (P = 0.008) in the liberal PaO₂ group, with all P values showing statistical significance. Subgroup analysis revealed that the association between higher PaO₂ and mortality in SAP patients varied across different age groups, BMI values, SIRS and APACHE II scores, and smoking status. Sensitivity analysis demonstrated stable results after excluding specific populations. On the third day of ICU admission (P = 0.016), higher PaO₂ correlated with improved outcomes compared to the conservative group, particularly when PaO₂ stabilized around 100 mmHg.

CONCLUSIONS: Early maintenance of higher PaO₂ (≥80 mmHg) during the initial ICU period was associated with lower mortality.

PMID:41408473 | DOI:10.1186/s40635-025-00843-8

Eur J Pediatr. 2025 Dec 18;185(1):25. doi: 10.1007/s00431-025-06680-x.

ABSTRACT

Limiting healthcare-associated infections (HAI) SARS-CoV-2 transmission has been a global challenge. We assessed characteristics of pediatric SARS-CoV-2 HAI outbreaks to better understand HAI transmission in pediatric care. We analyzed PCR-confirmed SARS-CoV-2 outbreak cases notified through statutory surveillance, at case level and at outbreak level, in Germany between 24 February 2020 and 31 December 2023 to describe SARS-CoV-2 HAI outbreaks in pediatric care and compare them with non-pediatric outbreaks. Pediatric outbreaks included any outbreak in pediatric care or with > 50% of cases among patients aged < 18 years. We calculated age-disaggregated median monthly incidences of SARS-CoV-2 HAI outbreak cases per 100,000 hospitalizations using reimbursement data. Among 36,371 SARS-CoV-2 HAI hospital outbreak cases from 3191 outbreaks, we identified 25 pediatric outbreaks with 241 cases. Of 218 cases with case status information, 181 (83%) were healthcare workers (HCW) and 37 (17%) were patients < 18 years old. Among all 241 cases, five (2%) were severe including one death case whereas 2580 (7%) of non-pediatric HAI cases were severe and 2736 (8%) deaths. Age-disaggregated median monthly outbreak case incidence < 18 years (0.3/100,000 hospitalizations; range 0.1-7.6) was markedly lower than among the non-pediatric age group of 18-59-year olds (14.8/100,000 hospitalizations; range 0.1-215.7).

CONCLUSION: Our results suggest limited SARS-CoV-2 HAI transmission in pediatric care. The high proportion of cases among HCW in pediatric outbreaks underlines the need to protect HCW from infections to further limit HAI transmission. Our findings highlight the value of outbreak surveillance for monitoring HAI transmission patterns in vulnerable sub-groups such as pediatric patients.

WHAT IS KNOWN: • Children and adolescents experience less severe SARS-CoV-2 illness. • Pediatric care poses unique infection prevention and control challenges.

WHAT IS NEW: • Pediatric outbreaks were very rare with few severe cases suggesting that pediatric care was less affected by SARS-CoV-2 outbreaks. • Most cases in pediatric outbreaks occurred among healthcare workers pointing to the need to protect HCW from infections and a limited role of pediatric patients and caregivers.

PMID:41408457 | DOI:10.1007/s00431-025-06680-x

Dig Dis Sci. 2025 Dec 17. doi: 10.1007/s10620-025-09620-9. Online ahead of print.

ABSTRACT

BACKGROUND: The proton pump inhibitors (PPIs) are widely prescribed for the treatment of dyspepsia and heartburn. However, their use carries the long-term potential for drug-drug interactions, osteopenia, opportunistic infections, adverse cardiovascular outcomes, and altered gut microbiome. Proper indication for and PPI dose optimization would be clinically beneficial.

AIMS: Examine the use of endoscopy with esophageal 96-h ambulatory pH monitoring with patients off- and on-PPI, to guide clinicians in prescribing PPI, thereby minimizing inappropriate use, or adverse effects. Specifically, examine (1) the prevalence of normal and abnormal acid exposure time (AET) in PPI users and non-users; (2) the degree, if any, of restrictive diet on AET in the presence or absence of PPI use. We hypothesized that such patients would have inadequate esophageal pH control and that restrictive diet would be beneficial.

PATIENTS AND METHODS: Retrospective cohort study of consecutive patients presenting with PPI-refractory symptoms of gastroesophageal reflux disease (GERD). All patients underwent an endoscopy with wireless esophageal ambulatory pH monitoring performed either off-PPI or on-PPI therapy for 96 h, following a “liberal diet” for the first 48 h and a “restricted diet” for the latter 48 h of the study. AET was defined as the % time the pH in the distal esophagus was < 4.0; values ≥ 6% per 24 h defined an abnormal AET off-PPI. Control of AET on-PPI was defined as distal esophageal pH < 4 < 1.6% total time. For each patient, the average from the first 2 days (on liberal diet) was considered as the baseline AET and was compared with the average from the latter 2 days (on restricted diet). Depending on the baseline (first 48 h) AET, patients were further divided into 2 groups: those with normal and those with abnormal AET.

RESULTS: We studied 54 consecutive patients with PPI-refractory GERD symptoms. There were 2 groups: those who underwent pH monitoring off-PPI (n = 32) and those who were studied on-PPI (n = 22). In the off-PPI group, there were 26 women (81%) and 6 men (19%), median age 59 years (range 43-76). In the on-PPI group, there were 16 women (73%) and 6 men (27%), median age 66 years, (range 44-78). Of the 32 patients studied off-PPI, 12 (38%) exhibited abnormal AET (% > 6), while the remaining 20 (62%) had normal AET. Of the 22 patients studied on-PPI, 7 (32%) exhibited abnormal AET (% > 1.6), while 15 (68%) had normal AET. The dietary restriction had a statistically significant impact on reducing and (often normalizing) AET in both PPI users and non-users.

CONCLUSIONS: Together with endoscopy, ambulatory 96-h pH monitoring, is feasible and well-tolerated. Most patients (62-68%) with symptomatically PPI-refractory GERD studied either off- or on-PPI, exhibit normal AET. Restrictive diet has a favorable impact on AET in most such patients, but its long-term impact remains unknown.

PMID:41408433 | DOI:10.1007/s10620-025-09620-9

J Cancer Res Clin Oncol. 2025 Dec 17;152(1):14. doi: 10.1007/s00432-025-06377-6.

ABSTRACT

BACKGROUND: Thyroid cancer (TC) is one of the most prevalent endocrine malignancies, and its recurrence presents a major clinical challenge that can adversely affect patient prognosis and treatment outcomes. Despite the progress in diagnostic methods, traditional statistical models still face limitations in accurately predicting TC recurrence due to the intricate interactions between clinical and pathological factors.

METHODS: To address this challenge, the study presented a novel stacking ensemble learning framework for TC recurrence prediction. The dataset included a total of 383 patients, comprising 108 recurrence and 275 non-recurrence cases, and was stratified into training set (n = 268) and testing set (n = 115) using a 70:30 ratio. The proposed stacking framework integrated three heterogeneous base learners, namely Stochastic Gradient Descent (SGD), Extra Trees (ET), and Decision Trees (DT) with eXtreme Gradient Boosting (XGBoost) as the meta learner. The hyperparameter optimization of various learners was performed through 5-fold cross-validation on the training set. The model performance was evaluated on testing set using accuracy, precision, recall, F1-score, AUC, and Brier score (BS). To enhance the model’s interpretability, the Shapley Additive Explanations (SHAP) method was utilized to identify the overall top influential factor and provide local interpretation for specific individual patient based model outcome.

RESULTS: The proposed stacking model achieved accuracy of 96.52%, precision of 96.67%, recall of 90.62%, and F1-Score of 93.55%, AUC of 0.9921 on the testing set. The SHAP analysis revealed the top 5 critical factors to TC recurrence, including treatment response, age, N-stage, risk stratification, and adenopathy. Furthermore, an interactive and user-friendly prediction tool, TCCheck, was developed based on optimized stacking model, accessible online at https://tccheck-prediction-tool.streamlit.app/ .

CONCLUSION: The study presented an effective and interpretable stacking ensemble learning framework for predicting TC recurrence. By deploying the proposed framework as a web prediction tool, it enables explainable and individualized clinical decision support, thereby enhancing its translational value in real-world settings. Furthermore, the framework serves as a methodological reference for recurrence prediction in other cancer types.

PMID:41408410 | DOI:10.1007/s00432-025-06377-6

Sci Rep. 2025 Dec 17. doi: 10.1038/s41598-025-32491-z. Online ahead of print.

ABSTRACT

Host population genetics can shape disease spread in wildlife, yet it is rarely integrated into epizootic investigations. To explore whether connectivity patterns in wild boar populations may have influenced the spread of African swine fever (ASF) in north-western Italy, we characterised the genetic structure of the local population. Microsatellite genotyping was performed on 578 wild boar sampled from 26 hunting districts across thirteen loci and analysed using Bayesian clustering, correspondence analysis and spatial PCA. In parallel, 2,414 ASF detections recorded between December 2021 and March 2025 were examined through retrospective spatiotemporal scan statistics and directional spread analysis. We identified two main genetic clusters, one largely corresponding to Piedmont and the other more prevalent in Liguria regions, with zones of admixture along their border and a connectivity corridor through the Ligurian Apennines. Over the 38-month period, 16 significant ASF clusters were detected. The outbreak spread eastward and north-eastward from the initial focus at the Liguria-Piedmont border. Four clusters showed significant directionality, and recurrent clustering in certain areas suggested local persistence. Notably, several ASF clusters overlapped with genetic admixture zones and connectivity hubs. Our findings suggest two mechanisms underpinning disease spread: short-range transmission within genetically related groups and longer-range movement along ecological corridors. Embedding genetic monitoring into routine surveillance may enhance the effectiveness of ASF control by guiding carcass removal, search efforts and spatial prioritisation toward high-risk transition zones.

PMID:41408392 | DOI:10.1038/s41598-025-32491-z

Int J Retina Vitreous. 2025 Dec 17. doi: 10.1186/s40942-025-00777-z. Online ahead of print.

ABSTRACT

BACKGROUND: Swept-source OCT (SS-OCT) and OCT angiography (SS-OCTA) enable high-resolution assessment of retinal and choroidal biomarkers in diabetic macular edema (DME). However, prospective analyses of how these biomarkers correlate before and after anti-VEGF therapy in treatment-naïve eyes are limited. The aim of this study was to prospectively evaluate biomarker correlations following aflibercept treatment using state-of-the-art, high-resolution imaging with SS-OCT and SS-OCTA during 4 months of follow-up.

METHODS: This was a prospective interventional case series that included 28 eyes from 25 treatment-naïve patients with DME. All eyes received three monthly intravitreal aflibercept injections. Patients were reassessed one month after the loading phase (4-month visit). The evaluated biomarkers included best-corrected visual acuity (BCVA), central macular thickness (CMT), central choroidal thickness (CCT), vessel density (VD), and avascular area of the superficial plexus (AASP) and deep plexus (AADP). Pre- and post-treatment values were compared, and correlations were analyzed using Pearson’s or Spearman’s methods.

RESULTS: Significant changes in BCVA (0.7250 ± 0.23 to 0.3957 ± 0.21; p < 0.000), CMT μm (339.04 ± 66.19 to 265.21 ± 55.75; p < 0.000), CCT μm (221.71 ± 69.69 to 209.07 ± 70.92; p < 0.000), VD (17.90 ± 7.82 to 15.35 ± 5.80; p < 0.038), AASP μm² (235,374 ± 91,299 to 157,326 ± 77,815; p < 0.000) and AADP μm² (1996,335 ± 1,000,047 to 362,161 ± 277,225; p < 0.000) were detected. Very high correlations were observed for the CCT pre vs CCT post (r = 0.98; p < 0.001), and AADP pre vs AADP reduction (r = -0.93; p < 0.001), high correlation: VD pre vs VD reduction (r = -0.72; p < 0.001. In total, 2 correlations were very high, 1 high, 4 moderate, and 9 were low; all the correlations were statistically significant.

CONCLUSIONS: Treatment-naïve DME eyes treated with aflibercept showed significant structural, vascular, and functional improvements, with several baseline biomarkers acting as potential predictive indicators of post-treatment outcomes. The very high correlation of CCT and AADP and the high correlation of VD suggest that SS-OCT and SS-OCTA can provide clinically useful information for identifying how patients will respond to treatment. These correlations support the role of SS-OCT and SS-OCTA not only as diagnostic tools but also as potential predictive indicators of therapeutic response, facilitating more personalized DME management in clinical practice. Notably, this is the first prospective study to evaluate correlations between SS-OCT and SS-OCTA biomarkers in naïve DME eyes treated with aflibercept.

PMID:41408379 | DOI:10.1186/s40942-025-00777-z

J Health Popul Nutr. 2025 Dec 17. doi: 10.1186/s41043-025-01141-5. Online ahead of print.

ABSTRACT

BACKGROUND: There’s still a gap in research on phosphorus intake for elderly patients with chronic kidney disease. Processed and ultra-processed foods provide convenient dietary options but are significant source of harmful inorganic phosphorus. This study attempts to evaluate total phosphorus intake in elderly chronic kidney disease (CKD) patients across different stages, focusing on dietary contribution of inorganic phosphorus, stratified into tertiles, from processed and ultra-processed foods.

METHODS: Cross-sectional analytical study conducted using an adapted food frequency questionnaire to assess weekly consumption phosphorus patterns over the last year among 232 participants. The study investigates the frequency and types of natural high-phosphorus foods, as well as processed and ultra-processed foods commonly available in the Egyptian market. It focused on elderly chronic kidney disease patients aged over 65 years, covering various stages of chronic kidney disease, including those receiving haemodialysis, and compared their dietary intake to their caregivers and an age-matched group of individuals over 65 years without CKD.

RESULTS: Phosphorus intake among elderly CKD subgroups showed considerable inter-individuals difference, ranging 880 – 16,804 mg/week. The total median weekly phosphorus intake in CKD patients > 65 years was lower compared to caregivers, with a statistically significant difference (p = 0.011) for patients aged 65-74 years. Phosphorus intake declined as CKD progressed from stage II to V. Among CKD, patients with a diploma education& who cook for themselves were significantly more likely to exceed the Dietary Reference Intake, (p < 0.05).Weekly inorganic phosphorous intake showed significant proportionate with frailty score (p = 0.024). Phosphorus intake from processed food/UPF was categorized into tertiles (low (< 694.39 mg), moderate (694.39-2382.53 mg), and high (> 2382.53 mg). 41% CKD patients > 75 years were classified as low inorganic phosphorus consumers compared to 33.3% in CKD aged 65-74 years. Education level, BMI showed a significant association, p < 0.05. Patients undergoing three dialysis sessions per week consumed more than twice the inorganic phosphorus (1,314.9 mg) compared to those receiving two sessions (552.1 mg), (p > 0.05). CKD patients > 75 years had significantly lower consumption of nuts, legumes, and beans than caregivers (p = 0.048).

CONCLUSION: Age, CKD diagnosis and stage may be additional factors in the observed variations in phosphorus-containing food intake patterns.

PMID:41408372 | DOI:10.1186/s41043-025-01141-5

Genome Med. 2025 Dec 17. doi: 10.1186/s13073-025-01561-2. Online ahead of print.

ABSTRACT

BACKGROUND: Psoriasis is a common inflammatory skin disease with heterogeneous presentation. Up to 30% of individuals have severe disease with a greater surface area of skin involvement, co-morbidity burden and impact on quality of life. Prognostic biomarkers of psoriasis severity could improve allocation of clinical resources and enable earlier intervention to prevent disease progression, and a genetic biomarker would be cost-effective, stable over time, and unaffected by treatment or comorbidity.

METHODS: Psoriasis severity was studied in four European population-based biobanks (Estonian Biobank, HUNT, FinnGen, UK Biobank) and classified based on level of clinical intervention received, with criteria for severe disease including hospitalisation due to psoriasis, use of systemic immunomodulating therapy or phototherapy. Common genetic variants, polygenic risk scores and traditional epidemiological risk factors were tested for association with severe psoriasis in each of the constituent biobanks and combined through meta-analysis. The distribution of psoriasis polygenic risk was also evaluated in a cohort of 4151 participants in the UK-based severe psoriasis registry, BSTOP, and a cohort of 1461 participants from Novartis clinical trials of secukinumab for psoriasis.

RESULTS: In the population-based datasets, 9738 of 44,904 individuals with psoriasis (21.7%) were classified as having severe disease. Genetic variants within the major histocompatibility complex (MHC) and the TNIP1 and IL12B psoriasis susceptibility loci were associated with severe disease at genome-wide significance (P < 5.0 × 10^-8). Furthermore, a strong positive correlation was observed between psoriasis susceptibility and severity effect sizes across all psoriasis susceptibility loci. An individual’s genetic liability to psoriasis as measured with a polygenic risk score (PRS) strongly associated with disease severity, with a magnitude of effect comparable to established severity risk factors such as obesity and smoking. The top 5% of psoriasis cases by genetic liability to psoriasis were 1.23-to-2.00 times as likely than the average psoriasis case to have severe disease. Psoriasis cases in our external validation datasets (BSTOP registry and Novartis clinical trials) were enriched for a PRS that exceeded the 95th percentile established among UK Biobank psoriasis cases by 3.06-fold and 2.32-fold respectively.

CONCLUSIONS: The psoriasis susceptibility PRS demonstrates utility and may be more effective than established epidemiological factors, as a stratification tool to identify those individuals that are at greatest risk of severe disease and may benefit most from early intervention.

PMID:41408349 | DOI:10.1186/s13073-025-01561-2

BMC Psychol. 2025 Dec 18. doi: 10.1186/s40359-025-03849-9. Online ahead of print.

ABSTRACT

BACKGROUND: This study investigates dementia-related search behaviors using Google Trends and national data from Taiwan, examining temporal trends, seasonal patterns with a focus on both Taiwan and global comparisons.

METHODS: We collected Google Trends data for dementia-related search terms from 2014 to 2024 and retrieved official Taiwanese dementia diagnosis data. Analytical approaches included descriptive statistics, Fourier-based regression for seasonal trend analysis, seasonal-trend decomposition, and Pearson correlation to assess the relationship between GT search volume and diagnosed dementia cases.

RESULTS: Search interest in dementia increased both globally and in Taiwan over the study period, with sharper fluctuations and a pronounced surge in Taiwan beginning in 2023. Seasonal trends revealed consistent peaks in certain months. In Taiwan, top and rising queries reflected clinical and caregiving concerns, while global searches were more general. A strong positive correlation was observed between Google Trends scores and diagnosed dementia cases in Taiwan (r ≈ 0.8).

CONCLUSIONS: Google Trends offers valuable insights into public interest in dementia and holds promise as a monitoring tool, particularly in aging societies and during health crises such as the COVID-19 pandemic.

PMID:41408340 | DOI:10.1186/s40359-025-03849-9