Nevin Manimala

Clin Epigenetics. 2025 Dec 19;17(1):202. doi: 10.1186/s13148-025-02019-3.

ABSTRACT

Orthostatic hypotension is a sharp decrease in blood pressure when an individual transitions from a supine to an upright position. OH affects at least 30% of older adults. It is attributed to the dysfunction of the autonomic innervation and decreased vascular bed capacity. Genomic (n = 2526), methylomic (n = 910), and transcriptomic (n = 391) data from centenarians aged 90 years and older were used to examine molecular and genetic factors for OH. No statistically significant genetic predictors of OH were identified. However, the study revealed numerous epigenetic markers of OH indicative of general aging, such as DNA hypomethylation. The predictive DNA methylation-based model for orthostatic hypotension demonstrated an average accuracy of 79%. The transcriptome analyses highlighted associations between OH and inflammation pathways, as well as other age-related biological processes. Integrated omics and clinical data have identified six key mechanisms associated with orthostatic hypotension: metabolic dysregulation, impaired muscle tone, altered cell proliferation, inflammation, humoral regulation, and neural regulation.

PMID:41419941 | DOI:10.1186/s13148-025-02019-3

J Transl Med. 2025 Dec 19. doi: 10.1186/s12967-025-07422-1. Online ahead of print.

NO ABSTRACT

PMID:41419940 | DOI:10.1186/s12967-025-07422-1

Cell Commun Signal. 2025 Dec 19. doi: 10.1186/s12964-025-02598-x. Online ahead of print.

ABSTRACT

RNA viruses can generate “defective” viral genomes during replication, which can interact with standard viral genomes affecting the course of infections. These non-standard viral genomes are related to milder clinical outcomes and are currently being tested as antivirals. Decades of research in influenza have focused on viral mechanisms affecting the production of deletion-containing viral genomes (DelVGs). Based on adaptations of influenza NS1 protein to manipulate host cell metabolism, we hypothesized host metabolic state could also alter the quantity and pattern of deletion-containing viral genomes and the particles that house them. To test this hypothesis, we manipulated host cell anabolic signaling activity and monitored the production of DelVGs and non-infectious particles by two influenza strains, using single-cell immunofluorescence and third-generation sequencing. We show that: 1) influenza infection activates PI3K signaling, with the A/H1N1 strain having roughly double the pAKT levels in single cells as the A/H3N2; 2) alpelisib, a PI3K receptor inhibitor, subverted the ability of both influenza strains to activate PI3K in a dose dependent manner; 3) DelVGs were increased roughly tenfold in polymerase complex segments and ~ 60% in the hemagglutinin segment of A/H1N1 at 20uM of alpelisib; and 4) the A/H3N2 strain did not show changes in DelVG production, but had a modest, statistically significant maximum increase of 11% in non-infectious particles. We find that host cell metabolism can increase the production of non-infectious particles and DelVGs during single rounds of infection, shifting potential interactions among virions. The differential results according to strain and alpelisib concentration suggest future directions examining strain differences in the NS1::p85β virus-host interaction and the specific metabolic state of the cell. Our study presents a new line of investigation into metabolic states associated with less severe flu infection and opens the possibility for potential induction of these states with metabolic drugs.

PMID:41419939 | DOI:10.1186/s12964-025-02598-x

Clinics (Sao Paulo). 2025 Dec 18;81:100853. doi: 10.1016/j.clinsp.2025.100853. Online ahead of print.

ABSTRACT

OBJECTIVE: To evaluate and monitor, through electrophysiological assessment of hearing, the integrity of the peripheral and central auditory pathways in infants with Peri-intraventricular hemorrhage and/or Periventricular Leukomalacia (PIVH/PVL) who stayed in a Neonatal Intensive Care Unit (NICU), aiming to verify the occurrence of possible neural dysfunctions in this system.

MATERIAL AND METHODS: This prospective longitudinal study evaluated preterm Newborns (NBs) and infants at the time of hospital discharge and after 3- and 6-months. The Study Group (SG) had 12 females and 11 males, with gestational age between 25- and 33-weeks, and a mean gestational age of 29.82-weeks at birth. The Control Group (CG) had 26 healthy NBs, distributed in 13 females and 13 males, with gestational age between 27- and 33-weeks and a mean of 30.67-weeks of gestational age at birth. All participants underwent Auditory Brainstem Response (ABR) and Cortical Auditory Evoked Potentials (CAEP) P1, N1, P2, at the time of hospital discharge, and 3- and 6-months after discharge. Each group’s results were compared using statistical tests.

RESULTS: Evolutionary study of mean ABR and CAEP latencies in infants in the study and control group showed a similar pattern over the six months after hospital discharge.

CONCLUSION: The comparison of brainstem and cortical potentials showed that auditory function is symmetrical in the peripheral and central portions of the auditory pathway in both groups. The maturation of the ABR and CAEP waves in both groups developed in a very similar way over the six months after hospital discharge.

PMID:41418391 | DOI:10.1016/j.clinsp.2025.100853

Infant Behav Dev. 2025 Dec 18;82:102174. doi: 10.1016/j.infbeh.2025.102174. Online ahead of print.

ABSTRACT

Negative affect (NA) is a central dimension of infant temperament and an early marker of risk for later psychopathology. While maternal mental health has been associated with increased infant NA, few studies have explored how maternal mental health symptoms relate to the specific subdomains of NA throughout infancy. This study examined longitudinal associations between maternal mental health and infant NA, comparing the general domain with its specific subdomains. We analyzed data from 557 mother-infant dyads enrolled in the Germina cohort in São Paulo, Brazil. Maternal symptoms of depression, anxiety, and stress, along with infant NA and its subdomains-sadness, fear, distress to limitations, and falling reactivity-were assessed at 3, 5-9, and 10-16 months postpartum. Longitudinal associations were examined using linear mixed-effects models with successive-differences contrasts, adjusting for sociodemographic covariates. Maternal stress consistently predicted higher NA and its subdomains-sadness, fear, and distress-across infancy, and was linked to reduced falling reactivity. Depression was associated with increased NA, distress, and decreased reactivity throughout infancy. Anxiety exhibited a time-varying association with distress, increasing from 3 to 9 months before declining, but showed no link with overall NA. Subdomain-specific analyses uncovered maternal mental health associations not evident in general NA models. Examining NA subdomains provides a more detailed understanding of their evolving, dynamic relationships with maternal mental health across infancy. These insights highlight the importance of integrating NA subdomains into screening and intervention strategies to more effectively support at-risk children.

PMID:41418383 | DOI:10.1016/j.infbeh.2025.102174

Eur J Obstet Gynecol Reprod Biol. 2025 Dec 13;318:114891. doi: 10.1016/j.ejogrb.2025.114891. Online ahead of print.

ABSTRACT

PURPOSE: To investigate whether psychosocial care during in vitro fertilization (IVF) treatment affects the emotional capacity and well-being of women undergoing fertility treatment.

METHODS: This randomized controlled, single-blind study was conducted between February 2020 and March 2021. A total of 112 women undergoing IVF were recruited based on predefined inclusion and exclusion criteria. After a 24.1 % loss to follow-up (n = 27), data from 85 participants (42 in the experimental group, 43 in the control group) were analyzed. The control group received routine care, while the intervention group attended a structured seven-session counseling program that included coping strategies such as Emotional Freedom Technique (EFT) and breathing exercises. Psychological outcomes were measured at three time points using Screening Tool on Distress in Fertility Treatment (SCREENIVF), Fertility Quality of Life Tool (FertiQol), COMPI Fertility Problem Stress Scales (COMPI-FPSS), and Subjective Units of Distress (SUD) scale. Group comparisons were analyzed with appropriate statistical methods.

RESULTS: Baseline characteristics did not differ between groups (p > 0.05). The experimental group had a higher positive hCG rate on day + 13 of IVF (42.9 % vs. 18.6 %, p = 0.015). Post-intervention, they showed greater reductions in anxiety (Cohen’s d = -0.72, 95 % CI [-1.15 to -0.28], p = 0.001) and helplessness (Cohen’s d = 1.26, 95 % CI [0.79-1.72], p < 0.001), and increased acceptance (p < 0.001), while depression decreased non-significantly (p = 0.167). Personal and social stress decreased (Cohen’s d = -0.99, 95 % CI [-1.43 to -0.54], p < 0.001; social domain p = 0.003), but marital stress did not (p = 0.619). FertiQOL total and Treatment Environment scores improved (Cohen’s d = -1.89, 95 % CI [-2.39 to -1.39], p < 0.001; Cohen’s d = -1.71, 95 % CI [-2.20 to -1.22], p < 0.001), whereas Treatment Tolerance did not differ (p = 0.001). SUD scores decreased after sessions 2, 4, and 5 (r = -0.62 to -0.63, 95 % CI [-0.77 to -0.46], p < 0.001). Effect sizes indicate medium to large clinical relevance. Participants at risk per SCREENIVF showed marked stress reduction and improved quality of life, with referrals to mental health services as needed.

CONCLUSION: Psychosocial care during IVF treatment appears to reduces psychological distress and enhances treatment-related well-being in women undergoing fertility procedures. These findings support the incorporation of psychosocial interventions into standard fertility care.

PMID:41418369 | DOI:10.1016/j.ejogrb.2025.114891

Ecotoxicol Environ Saf. 2025 Dec 18;309:119587. doi: 10.1016/j.ecoenv.2025.119587. Online ahead of print.

ABSTRACT

Environmental remediation including mercury (Hg) source closure, cage-farming prohibition, and sediment capping has been implemented at Baihua Reservoir (BHR) since 2007, which strongly influences Hg bioaccumulation in fish. In this study, total Hg (THg) and methylmercury (MeHg) concentrations were determined in abiotic matrices and fish in 2015-2016 and 2018-2019 and compared with data extracted from previous studies referring to 2002-2006 and 2008-2009. Following these remediation measures, the water quality improved, eutrophication declined, and environmental Hg levels dropped dramatically. By 2018-2019, the aqueous THg and MeHg decreased by 82 % and 89 %, and sediment THg and MeHg decreased by 99 % and 86 %, respectively, compared to 2002-2006 levels. However, prohibition of cage fish farming in BHR shifted fish diets toward plankton, slowing their growth rate and lengthening the food chain by one level. Paradoxically, average fish THg during 2008-2019 increased significantly by 73-168 %, whereas the increase in MeHg (33-137 %) was not statistically significant. The relative proportion of MeHg to THg (%MeHg) in fish transiently peaked at 56 ± 23 % in 2015-2016. The bioaccumulation factor for fish Hg was high, while the trophic magnification rates of Hg were lower and remained low compared to global averages, reflecting efficient initial uptake into the food web but constrained transfer efficiency. This unexpected rise in fish Hg is likely due to the dietary shift to Hg-rich plankton, reduced somatic growth dilution in wild fish, and enhanced Hg trophic transfer. Therefore, ongoing monitoring and updated fish consumption advisories are recommended to mitigate potential health risks.

PMID:41418362 | DOI:10.1016/j.ecoenv.2025.119587

Biomed Phys Eng Express. 2025 Dec 19. doi: 10.1088/2057-1976/ae2f65. Online ahead of print.

ABSTRACT

OBJECTIVE: To classify digital mammograms based on radiological findings using morphology and texture descriptors with artificial neural networks (ANN) for breast cancer detection.

APPROACH: The mammography dataset from High Specialty Regional Hospital of Oaxaca (HRAEO) (median patient age (mpa), 48 years [interquartile range (IQR), 41-54 years]) with radiological findings was retrospectively analyzed. All patients underwent breast biopsy and were not previously treated. External testing was performed using mammograms from the National Cancer Institute (INCAN) (mpa: 47 years [IQR, 37-62 years]). The morphology was analyzed using a circularity descriptor (), and the texture was analyzed using the mean height/width ratio of the extrema descriptor (). These results were compared with cancer/benign histopathology, which was binarily classified using ANNs. The F1-score, Cohen’s kappa (K), and area under the ROC curve (AUC) were employed as evaluation metrics, and the Wilcoxon rank-sum test was used for statistical analysis (h = 0, with p > 0.05, was considered as not statistically significant).

MAIN RESULTS: 216 raw mammograms from HRAEO and 33 mammograms from INCAN (95+16 breast cancer and 121+17 benign findings) were included. The best internal testing results were obtained with a one-hidden-layer ANN with 100 neurons, achieving a F1-score of 0.95, K of 0.91, and an AUC of 0.953 (95% confidence interval [CI]: 0.917, 0.977) (h=0, p>0.99). However, the external testing results were significantly lower: 0.38 F1-score, 0.02 K, and 0.509 AUC (95% CI: 0.344, 0.664) (h=0, p=0.14) due to not exactly meeting the inclusion criteria and possible demographic and spectrum bias, or domain-adaptation issues.

SIGNIFICANCE: The proposed morphology () and texture () descriptors show promise for detecting breast cancer in raw mammograms, with radiological findings, in a local context. However, their poor external performance highlights the need for substantial further work before this approach can be deemed suitable for broader diagnostic applications.

PMID:41418324 | DOI:10.1088/2057-1976/ae2f65

JMIR Form Res. 2025 Dec 19;9:e75607. doi: 10.2196/75607.

ABSTRACT

BACKGROUND: Multiple-choice questions (MCQs) are essential in medical education for assessing knowledge and clinical reasoning. Traditional MCQ development involves expert reviews and revisions, which can be time-consuming and subject to bias. Large language models (LLMs) have emerged as potential tools for evaluating MCQ accuracy and efficiency. However, direct comparisons of these models in orthopedic MCQ assessments are limited.

OBJECTIVE: This study compared the performance of ChatGPT and DeepSeek in terms of correctness, response time, and reliability when answering MCQs from an orthopedic examination for medical students.

METHODS: This cross-sectional study included 209 orthopedic MCQs from summative assessments during the 2023-2024 academic year. ChatGPT (including the “Reason” function) and DeepSeek (including the “DeepThink” function) were used to identify the correct answers. Correctness and response times were recorded and compared using a χ2 test and Mann-Whitney U test where appropriate. The two LLMs’ reliability was assessed using the Cohen κ coefficient. The MCQs incorrectly answered by both models were reviewed by orthopedic faculty to identify ambiguities or content issues.

RESULTS: ChatGPT achieved a correctness rate of 80.38% (168/209), while DeepSeek achieved 74.2% (155/209; P=.04). ChatGPT’s Reason function also outperformed DeepSeek’s DeepThink function (177/209, 84.7% vs 168/209, 80.4%; P=.12). The average response time for ChatGPT was 10.40 (SD 13.29) seconds, significantly shorter than DeepSeek’s 34.42 (SD 25.48) seconds (P<.001). Regarding reliability, ChatGPT demonstrated an almost perfect agreement (κ=0.81), whereas DeepSeek showed substantial agreement (κ=0.78). A completely false response was recorded in 7.7% (16/209) of responses for both models.

CONCLUSIONS: ChatGPT outperformed DeepSeek in correctness and response time, demonstrating its efficiency in evaluating orthopedic MCQs. This high reliability suggests its potential for integration into medical assessments. However, our results indicate that some MCQs will require revisions by instructors to improve their clarity. Further studies are needed to evaluate the role of artificial intelligence in other disciplines and to validate other LLMs.

PMID:41418321 | DOI:10.2196/75607

J Med Internet Res. 2025 Dec 19;27:e75337. doi: 10.2196/75337.

ABSTRACT

BACKGROUND: The link between social media use and depressive symptoms remains bidirectional. Findings in this area are often compromised by methodological limitations related to measurement and sample size. As a result, it is challenging to assess dose-response relationships and potential causal pathways.

OBJECTIVE: This study aims to use objective measurement methods to assess the dose-response relationship and potential mechanisms between social media use and depressive symptoms.

METHODS: This study was conducted in 6 universities in 2022. Social media use duration was assessed based on the monitoring of mobile phone systems, and depressive symptoms were evaluated by the Self-Rating Depression Scale. Logistic regression and restricted cubic spline were used to assess the relationship between social media use and depressive symptoms. Mediation analysis was used to elucidate the biological pathways of sleep quality in the abovementioned relationship.

RESULTS: A total of 7401 college students were included in the final analysis, with 4.93% of moderate to severe depressive symptoms. After adjusting for variables such as sociodemographic characteristics and health-related characteristics, there was a significant association between individuals with longer weekly social media use time and depressive symptoms (odds ratio [OR>48h] 1.769, 95% CI 1.303-2.400). Similarly, the association between instant messaging-based social media use duration and depressive symptoms was also significant (OR>24h 1.728, 95% CI 1.225-2.437), while no associations were observed for content-based social use (OR>24h 1.251, 95% CI 0.932-1.680). Restricted cubic splines regression demonstrated a J-type relationship between social media use duration and depressive symptoms. Additionally, sleep quality played a partial mediating role in the relationship between social media use duration and depressive symptoms, with the mediating effect values ranging from 24.10% to 25.25%.

CONCLUSIONS: Prolonged social media use duration might be associated with an increased prevalence of depressive symptoms in emerging adulthood and may increase the odds of depression by affecting sleep quality, suggesting that early prevention and intervention regarding social media use might help to ameliorate depressive symptoms.

PMID:41418287 | DOI:10.2196/75337