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Photoplethysmography-based HRV analysis and machine learning for real-time stress quantification in mental health applications
No full text[[abstract]]Prolonged exposure to high-stress environments can lead to mental illnesses such as anxiety disorders, depression, and posttraumatic stress disorder. Here, a wearable device utilizing photoplethysmography (PPG) technology is developed to noninvasively measure physiological signals and analyze heart rate variability (HRV) parameters. Traditional normative HRV databases typically do not account for responses induced by specific stressors such as cognitive tasks. Therefore, machine learning is used to build a more dynamic stress assessment model. Machine learning can capture complex nonlinear relationships among HRV parameters during stress-inducing tasks, adapts to individual stress response variations, and provides real-time stress level predictions. Furthermore, machine learning models can integrate temporal patterns in HRV data to achieve nuanced stress level assessment. This study examines the feasibility of PPG signals and validates the developed stress model. The RR intervals derived from PPG signals were highly positively correlated with those from electrocardiography signals (correlation coefficient = 0.9920, R-squared = 0.9837); this confirms the usability of PPG signals for HRV analysis. The stress model is constructed via the open-source Swell dataset. In the experiments, participants complete the Depression Anxiety Stress Scales-21-Chinese (DASS-21-C) questionnaire to quantify levels of depression, anxiety, and stress over a week. Baseline and stress-state PPG data are collected, converted into HRV values, and input into the model for stress quantification. The Stroop test is used to elicit stress responses. After the experiment, the DASS-21-C stress scores were compared with the model's baseline, stress state, and combined scores. The highest correlation was observed between the model's baseline score and the DASS-21-C stress score (correlation coefficient = 0.92, R-squared = 0.8457), supporting the model's psychological significance in quantifying everyday stress. HRV parameter changes across experimental phases are discussed as well as sex differences in stress responses. In the future, this device may be applied in clinical scenarios for further validation and could be integrated with additional physiological indicators for broader application in daily health management and stress warning systems
Polygenic dissection of treatment-resistant depression with proxy phenotypes in the UK Biobank
No full text[[abstract]]Background: Treatment-resistant depression (TRD) affects one-third of major depressive disorder (MDD) patients. Previous pharmacogenetic studies suggest genetic variation may influence medication response but findings are heterogeneous. We conducted a comprehensive genetic investigation using proxy TRD phenotypes (TRDp) that mirror the treatment options of MDD from UK Biobank primary care records. Methods: Among 15,125 White British MDD patients, we identified TRDp with medication changes (switching or receiving multiple antidepressants [AD]); augmentation therapy (antipsychotics; mood stabilizers; valproate; lithium); or electroconvulsive therapy (ECT). Hospitalized TRDp patients (HOSP-TRDp) were also identified. We conducted genome-wide association analysis, estimated SNP-heritability (h2g), and assessed the genetic burden for nine psychiatric diseases using polygenic risk scores (PRS). Results: TRDp patients were more often female, unemployed, less educated, and had higher BMI, with hospitalization rates twice as high as non-TRDp. While no credible risk variants emerged, heritability analysis showed significant genetic influence on TRDp (liability h2g 21-24 %), particularly for HOSP-TRDp (28-31 %). TRDp classified by AD changes and augmentation carried an elevated yet varied polygenic burden for MDD, ADHD, BD, and SCZ. Higher BD PRS increased the likelihood of receiving ECT, lithium, and valproate by 1.27-1.80 fold. Patients in the top 10 % PRS relative to the average had a 12-36 % and 24-51 % higher risk of TRDp and HOSPTRDp, respectively. Conclusions: Our findings support a significant polygenic basis for TRD, highlighting genetic and phenotypic distinctions from non-TRD. We demonstrate that different TRDp endpoints are enriched with various spectra of psychiatric genetic liability, offering insights into pharmacogenomics and TRD's complex genetic architecture
KDM4C works in concert with GATA1 to regulate heme metabolism in head and neck squamous cell carcinoma
No full text[[abstract]]Head and neck squamous cell carcinoma (HNSCC), the sixth most common cancer worldwide, presents significant public health challenges due to its genetic instability and late-stage diagnosis. Despite advancements in treatment, the median overall survival remains below one year, emphasizing the need for improved detection, prognosis, and therapeutic strategies. This study investigates the role of KDM4C and its interaction with GATA1 in regulating heme metabolism and tumor progression in HNSCC. KDM4C knockdown (KDM4C-KD) hindered HNSCC cell migration using in vitro assays, inhibited metastasis through zebrafish xenotransplantation, and suppressed tumor growth in mouse xenograft models. RNA-seq and CUT&Tag-seq analyses on KDM4C-KD SAS cells identified KDM4C-regulated genes, including ferrochelatase (FECH), in heme metabolism. Immunoprecipitation and docking analyses confirmed the KDM4C-GATA1 interaction. Notably, FECH overexpression in KDM4C or GATA1 knockdown cells restored cell migration, invasion, and proliferation, highlighting FECH as a crucial downstream target. KDM4 inhibitors myricetin and BPRKD022S0 (22S0) increased H3K9me3 levels, downregulated heme metabolism genes, and reduced cell survival in HNSCC cells. Zebrafish and mouse models demonstrated that these inhibitors effectively suppressed tumor growth and metastasis. Immunohistochemical analysis of HNSCC patient samples revealed high KDM4C and GATA1 expression correlated with advanced clinical stages and poor survival outcomes. Our findings elucidate the critical role of the KDM4C/GATA1-FECH axis in HNSCC progression and suggest that targeting this pathway with KDM4 inhibitors shows promising therapeutic potential for HNSCC treatment
Osteomyelitis caused by moesziomyces aphidis in an immunocompetent adult: A case report and literature review
No full text[[abstract]]Osteomyelitis caused by Moesziomyces aphidis is exceedingly rare and, to our knowledge, has not been previously reported in immunocompetent individuals. This case represents the first documented instance. A 19-year-old woman developed osteomyelitis following an open right leg fracture sustained in a traffic accident. Initial cultures yielded an unidentified yeast, later identified as M. aphidis through internal transcribed spacer sequencing. The patient demonstrated clinical improvement with combination therapy of amphotericin B and following oral voriconazole. This case underscores the emerging pathogenic potential of Moesziomyces spp., particularly in the setting of trauma and open wounds, and highlights the importance of including this genus in the differential diagnosis of osteomyelitis. A literature review indicates that Moesziomyces infections are predominantly observed in immunocompromised patients, especially in Asia. However, our case underscores the need for greater awareness of this emerging pathogen in immunocompetent hosts as well
Gestational weight gain as a modifiable factor for the impact of pre-conceptional maternal shift work on postpartum weight retention
No full text[[abstract]]Objectives This study examined whether gestational weight gain (GWG) mediates the relationship between maternal shift work and postpartum weight retention (PPWR). Methods Mothers with singleton births in the Taiwan Birth Cohort Study were assessed for shift work, GWG, and PPWR. Propensity score matching balanced baseline characteristics. We applied multivariable generalized linear regression and causal mediation analysis for the associations, with GWG amount and excessive GWG as mediators. Results Shift work before pregnancy was associated with higher GWG (0.55 kg, 95% CI: 0.36-0.75) and increased odds of excessive GWG (adjusted OR: 1.18, 95% CI: 1.08-1.29). Excessive GWG mediated the relationship between shift work and PPWR, with shift workers retaining 0.37 kg more at 6 months postpartum. Conclusions Maternal shift work before pregnancy increases GWG, contributing to PPWR. Managing GWG is crucial to reduce shift work-related PPWR
Polycomb repressive complex 2 proteins SUZ12 and EZH2 contribute to TGFb1-induced disassembly of the nuclear envelope
No full text[[abstract]]Morphology of the cell nucleus is mostly spheroid or ellipsoid, but can be variable according to cell types or disease conditions. How the nuclear shape is regulated, and whether it is involved in cell signaling is less clear. We previously reported that TGFβ1 induces rupture and reform of the nuclear lamina mediated by SMAD signaling. the nuclear envelope (NE) proteins lamin B1 and SUN1, but not lamin A, SUN2 or Emerin, are required for TGFβ1-induced nuclear morphology change. the chromatin regions that lost NE coverage formed a supra-nucleosomal structure with increased incorporation of specific histone H1 variants and H3K27me3, the localization of which correlated well with a histone H3 variant H3.3. We further characterized that polycomb repressive complex 2 proteins such as SUZ12 and EZH2, are involved in the process of nuclear envelope disassembly induced by TGFβ1. Our results provide evidences that shape of the nucleus can be modulated through extracellular signaling molecules such as TGFβ1, followed by compositional changes in the histone modification enzymes, the histone variants, and the nuclear lamina
Chinese visceral adiposity index outperforms other obesity indexes in association with increased overall cancer incidence: Findings from prospective MJ cohort study
No full text[[abstract]]Background: We assessed the associations of visceral adiposity indexes such as Chinese Visceral Adiposity Index (CVAI), Visceral Adiposity Index (VAI), Lipid Accumulation Product (LAP), waist circumference (WC), and waist-hip ratio (WHR) with overall and specific cancer incidence in a Chinese population. Methods: 332,297 individuals from the Taiwan MJ cohort (1996-2007) were included. We utilized multivariable Cox proportional hazards models to examine associations of baseline visceral adiposity indexes and cancer incidences. Sex-specific CVAI, VAI, and LAP were calculated, incorporating WC and triglycerides levels. CVAI and VAI also included body mass index and high-density lipoprotein, with CVAI further incorporating age. Results: Higher CVAI was consistently associated with higher overall cancer incidence, with HRs of 1.45 (95% CI: 1.2-1.76) and 2.03 (95% CI: 1.52-2.72) for males and females, respectively, comparing the fifth quintile to the first. The HRs for WC were 1.27 (95% CI: 1.08-1.49) and 1.19 (95% CI: 1.01-1.40) for males and females, WHR was significantly associated with cancer risk in males (HR:1.28; 95% CI: 1.13-1.45), and LAP was significantly associated with cancer risk in females (HR: 1.25; 95% CI: 1.04-1.5). VAI was not associated with overall cancer incidence. Discussion: CVAI is a superior clinical biomarker for predicting cancer incidence in the Chinese population compared to traditional visceral obesity indices
Validity of absolute risk estimates derived from case‒control studies and population incidence with applications to lung cancer screening
No full text[[abstract]]Absolute risk prediction models are important tools for disease prevention and early detection. They are best studied in prospective cohorts. However, when the disease incidence rate is low, such as that of lung cancer in never smokers, synthesizing data and information from multiple sources is an important strategy. A recent study exemplified this strategy by proposing a two-stage procedure to estimate a logistic regression model for predicting lung cancer occurrence among never-smoking females in Taiwan on the basis of age-matched case–control studies and age-specific lung cancer incidence rates among this population. The latter were obtained from the Taiwan Cancer Registry, Cause of Death Database, age-specific female population size and smoking rates, life tables, and others. The risk factors considered in the logistic regression model included age, body mass index, chronic obstructive pulmonary disease, educational level, and genetic variants. With additional information on the age-specific population distribution of these risk factors, in this paper, we established an asymptotic theory, used it to construct confidence intervals, examined its numerical performance via simulation studies, and applied it to estimate the numbers and confidence intervals of Taiwanese never-smoking females whose lung cancer risk was higher than the thresholds discussed in the literature regarding low-dose computed tomography lung cancer screening. This information is useful for health policy decision making
Prenatal and childhood infections and risk of epilepsy
No full text[[abstract]]Infections in utero and early childhood are associated with an increased epilepsy risk; however, confounding by familial predisposition has not been adequately accounted for in previous studies. We aimed to assess the epilepsy risk attributable to infections in utero and early childhood by performing population-based and sibling-comparison analyses to account for residual and unmeasured familial confounding factors. This nationwide birth cohort study included 2,609,289 individuals born 2001-2016 in Taiwan. Maternal infection during pregnancy and early childhood infection during the first year of life were defined. Maternal pre-pregnancy infection was used as negative control. In the population analyses, offspring exposed to any maternal infection during pregnancy had an increased epilepsy risk (hazard ratio (HR) = 1.36, 95% confidence interval (CI):1.27-1.45). However, the association with maternal infection was attenuated to the null (HR = 1.11, 95% CI:0.98-1.27), except for maternal infection in sepsis (HR = 2.54, 95% CI:1.74-3.70) and central nervous system (HR = 24.59, 95% CI:3.28-184.23), in the sibling analyses. The association of maternal pre-pregnancy infection with offspring epilepsy was observed in the population analyses, but not in the sibling analyses. Individuals exposed to childhood infection had an increased epilepsy risk (HR = 1.49, 95% CI:1.45-1.54) in the population analyses; the association was still observed in the sibling analyses (HR = 1.31, 95% CI:1.23-1.40). The association between maternal infection during pregnancy and epilepsy risk in the offspring appears largely because of familial confounding factors. Infections during early childhood may play a causal role in the subsequent epilepsy risk