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Construction of hot tumor classification models in gastrointestinal cancers
No full text[[abstract]]BackgroundGastrointestinal (GI) cancers account for more than one-third of cancer-related mortality, and the prognosis for late-stage patients remains poor. Immunotherapy has been proven to extend the survival of patients at advanced stages; however, challenges persist in patient selection and overcoming drug resistance. Tumor-infiltrating lymphocytes (TILs) and tertiary lymphoid structures (TLS) in the tumor microenvironment (TME) have been found to be associated with anti-tumor immune responses. 'Hot tumors' with high levels of infiltration tend to respond better to immune checkpoint inhibitor (ICI) therapy, making them potential biomarkers for ICI treatment.MethodsTo explore potential biomarkers for predicting immunotherapy response and prognosis in GI cancers, we downloaded the gene expression profiles of seven GI cancers from The Cancer Genome Atlas (TCGA) database and characterized their TME, classifying the samples into hot/cold tumor subgroups. Furthermore, we developed a computational framework to construct cancer-specific hot tumor classification models with only a few genes. External independent datasets and qPCR experiments were used to verify the performance of our few-gene models.ResultsWe constructed cancer-specific few-gene models to identify hot tumors for GI cancers with only two to nine genes. The results showed that B cells are important for hot tumor determination, and the identified hot tumors are significantly associated with TLS. They not only overexpress TLS marker genes but are also associated with the presence of TLS in whole-slide images. Further, a two-gene qPCR model was developed to effectively distinguish between hot and cold tumor subgroups in cholangiocarcinoma, providing an opportunity for stratifying patients with hot tumors in clinical settings.ConclusionsIn conclusion, our established few-gene models, which can be easily integrated into clinical practice, can distinguish hot and cold tumor subgroups, and may serve as potential biomarkers for predicting ICI response
Effects of SGLT2 inhibitors on transplant survival and key clinical outcomes in heart transplant recipients with diabetes
No full text[[abstract]]Background. Chronic kidney disease and heart allograft vasculopathy are the primary causes of morbidity and mortality after cardiac transplant. This study aimed to evaluate the impact of sodium-glucose cotransporter-2 inhibitors (SGLT2i) on transplant survival, cardiovascular events, dialysis, and all-cause mortality in diabetes patients who have undergone heart transplantation. Methods. In this research, we adopted data from the TriNetX collaborative network to observe outcomes in patients who underwent heart transplants between January 01, 2015 and December 31, 2022. A total of 6494 transplant recipients were identified, from which 1063 matched pairs of SGLT2i users and non-users were selected using propensity score matching. The Kaplan-Meier analysis and Cox proportional hazards models were applied to compare the risks of various outcomes between the study and control groups. Results. In propensity-matched cohorts, patients using SGLT2i exhibited a lower risk of dialysis [hazard ratio (HR) (95% confidence interval [CI]): 0.566 (0.385-0.833)], graft rejection and failure [0.873 (0.774-0.985)], hospitalizations [0.822 (0.739-0.916)], and all-cause death [0.767 (0.627-0.938)] compared to non-users. Yet, no significant differences were observed between the two groups in the risks of post-transplant infection or sepsis [0.891 (0.739-1.075)], ischemic heart disease (HR: 1.044, 95% CI: 0.939-1.161), and heart failure worsening [0.915 (0.733-1.144)]. Conclusion. This multicenter cohort study demonstrated that cardiac transplant recipients with diabetes who received SGLT2i had a significantly lower risk of dialysis, graft rejection, hospitalization, and all-cause mortality compared to those who did not receive SGLT2i
White matter microstructural integrity mediates associations between prenatal endocrine-disrupting chemicals exposure and intelligence in adolescents
No full text[[abstract]]Per- and polyfluoroalkyl substances (PFAS) and phthalic acid esters (PAEs) are well-known endocrine-disrupting chemicals (EDCs) that potentially affect child neurodevelopment. We aimed to investigate the effects of prenatal exposure to PFAS and PAEs on macro- and micro-structural brain development and intelligence in adolescents using multimodal neuroimaging techniques. We employed structural magnetic resonance imaging (MRI) and various diffusion MRI techniques, including diffusion tensor imaging (DTI), diffusion kurtosis imaging (DKI), and neurite orientation dispersion and density imaging (NODDI), to assess the gray-matter macrostructure and whitematter microstructural integrity and complexity. Participants were drawn from a birth cohort of 52 mother-child pairs in central Taiwan recruited in 2001, and the adolescent intelligence quotient (IQ) scores were assessed using the Wechsler Intelligence Scale. Nine PFAS concentrations of cord blood and maternal serum samples were obtained from the children's mothers during the third trimester of pregnancy (27-40 weeks) using a liquid chromatography system coupled to a triple-quadrupole mass spectrometer, while maternal urinary phthalates were used to evaluate PAEs exposure. Our results showed significant associations between prenatal exposure to PFAS and phthalates with changes in specific fronto-parietal regions of the adolescent male brain, including reduced cortical thickness in the inferior frontal gyrus and right superior parietal cortex, which are involved in language, memory, and executive function. A dose-response association was observed, with higher levels of PFAS and PAE exposure modulating altered white-matter fiber integrity in the superior cerebellar peduncle and inferior cerebellar peduncle of the male and female adolescent brains. In addition, higher levels of prenatal exposure to EDCs were associated with lower IQ scores in adolescents. Mediation analyses further revealed that white-matter microstructure of inter-hemispheric and cerebellar fibers mediated the association between prenatal EDC exposure and adolescent IQ scores in female adolescents. Our multimodal human neuroimaging findings suggest that prenatal exposure to EDCs may have long-lasting effects on neuroanatomical development, neural fiber connectivity, and intelligence in adolescents, and highlight the importance of using advanced diffusion imaging techniques, including DKI and NODDI, to detect neurodevelopmental changes and their brainbehavioral consequences with the risks associated with these environmental exposures
Impacts of night shift on medical professionals: a pilot study of brain connectivity and gut microbiota
No full text[[abstract]]Night shift is a prevalent workstyle in medical hospitals, demanding continuous health monitoring and rapid decision making of medical professionals. Night shifts may cause serious health problems to medical staff, including cognitive impairments, poor sleep, and inflammatory responses, leading to the altered gut-brain axis. However, how night shifts impact gut-brain axis and how long the impact lasts remain to be studied. Hence, we investigated the dynamic changes of brain-microbiota relations following night shifts and subsequent recovery days among medical shift workers. Young medical staffs were recruited for the 3-session assessments over the scheduled night shifts (pre-shift, post-shift, and recovery) by measuring (a) sleep metrics, (b) brain functions, (c) gut bacteriome compositions, and (d) cognitive assessments. Participants experienced partial sleep deprivation only during the 5-day night shifts but rapidly returned to baseline after the 4-day recovery, so as the elevated brain fluctuations in the superior frontal gyrus after night shifts. Meanwhile, the night shifts caused elongated connectivity changes of default-mode and dorsal attention networks without recovery. Nevertheless, we did not find prevailing night-shift effects on cognition and gut bacteriome compositions, except the Gemellaceae concentration and the multi-task performance. Collectively, night shifts may induce prolonged alterations on brain connectivity without impacts on gut bacteriome, suggesting the vulnerable brain functions and the resilient gut bacteriome to the short-term night shifts among medical shift workers
Resting heart rate - The forgotten risk factor? Comparison of resting heart rate and hypertension as predictors of all-cause mortality in 692,217 adults in Asia and Europe
No full text[[abstract]]BACKGROUND: Resting Heart Rate (RHR) is commonly viewed as a reflection of underlying co-morbidities and not an independent risk factor. Here we compared whether high RHR (80-99 beats/min) and hypertension (blood pressure, BP ≥140/90 mmHg) independently predict all-cause mortality in 692,217 adults from Asia and Europe. METHODS: Taiwan MJ cohort constituted of 636,064 adults (1994-2017) and the HUNT cohort of 56,153 Norwegian adults (1995-1997). Both cohorts were followed for about 25 years. We report adjusted hazard ratios (HRs) for all-cause mortality, and life expectancy were calculated. RESULTS: The prevalence of high RHR changed little between those aged 20-29 years (21.2 %) and ≥ 70 years (25.2 %, ns.), whereas hypertension prevalence increased from 4.5 % to 57.3 %, respectively. We observed similar all-cause mortality among those with a high RHR and a normal BP and those with hypertension and normal RHR of 60-69 beats/min. We observed higher all-cause mortality among those with normal BP (≤120/80 mmHg) but high RHR than among those with hypertension and normal RHR. All-cause mortality risk associated with hypertension was not significant for those <40 years of age, whereas risk associated with high RHR remained significant across all age groups. Reductions in life expectancy was larger among individuals with normal BP, but high RHR (10.29 years, 95 % CI 8.09-12.49) compared with those with hypertension but normal RHR (5.53 years, 95 % CI 3.57-7.59). CONCLUSIONS: Our data clearly demonstrate that elevated RHR should be considered as an independent risk factor for all-cause mortality. The observation that elevated RHR in young adulthood to middle age (20-50 years of age) served as better predictor of all-cause mortality than hypertension calls for a paradigm shift particularly among these age groups, and we suggest it is time that RHR should be regarded as a vital clinical sign measured and evaluated at all clinical visits
Associations of paternal age with offspring under-five mortality and perinatal outcomes: A cohort study using claims data in Taiwan
No full text[[abstract]]BACKGROUND: The causal relationship between advanced paternal age and offspring health is unclear, owing to familial confounders. This study examined the association of paternal age with offspring's under-five mortality and perinatal outcomes, using sibling comparison analyses to account for familial confounding factors. METHODS: A nationwide birth cohort study was designed based on Taiwan's single-payer compulsory National Health Insurance programme. Individuals born between 2001 and 2015 were included, resulting in 2454 104 live-born singletons. Among them, 1513 222 individuals had full sibling(s) who were included in the sibling-comparison analyses. Logistic regression analyses were used to evaluate the main study cohort whereas conditional logistic regressions were used in the sibling-comparison analyses. RESULTS: In the main cohort, paternal age categories showed a U-shaped relationship with offspring's under-five mortality in the crude analysis, which attenuated towards the null hypothesis after accounting for the measured potential confounders. There was an increased risk of premature birth (gestational age 35 years. Sibling-comparison analyses that accounted for unmeasured familial time-invariant confounders showed that younger siblings with older paternal age had a lower risk of under-five mortality, low birth weight, small for gestational age (10th percentile), congenital defects and low 5 min Apgar Score, and a higher risk of premature birth and large for gestational age. CONCLUSIONS: Children with older fathers had lower risks of under-five mortality, low birth weight, small for gestational age, congenital defects and low 5 min Apgar Score
Air pollution causes abnormal alanine aminotransferase levels in patients with chronic hepatitis B
No full text[[abstract]]Background: To investigate the association between air pollution and abnormal alanine aminotransferase levels in patients with chronic hepatitis B treated with nucleotide/nucleoside analogs. Methods: This cross-sectional study enrolled 1,275 patients with chronic hepatitis B treated with nucleotide/nucleoside analogs from 2019 to 2022 in Kaohsiung and analyzed the incidence and risk factors for abnormal alanine aminotransferase levels. Daily air pollutant concentrations were estimated for the year prior to enrolment. Results: Abnormal alanine aminotransferase levels were observed in 1,127 patients (88.4%) before treatment with nucleotide/nucleoside analogs (NAs). Logistic regression analysis revealed that the strongest factor associated with abnormal alanine aminotransferase levels was the level of hepatitis B virus DNA (odds ratio/confidence interval: 1.40/1.25-1.57; p<0.001), followed by concentration of particulate matter ≤2.5 µm in diameter (1.05/1.02-1.08; p<0.001) and liver cirrhosis (0.27/0.17-0.42; p<0.001). Among patients without cirrhosis, logistic regression analysis revealed that the strongest factors associated with abnormal alanine aminotransferase levels were the level of hepatitis B virus DNA (odds ratio/confidence interval: 1.52/1.28-1.82; p<0.001) and concentration of particulate matter ≤2.5 µm in diameter (1.06/1.101-1.11; p=0.01). Among patients with cirrhosis, logistic regression analysis revealed that the strongest factor associated with abnormal alanine aminotransferase levels was hepatitis B virus DNA level (odds ratio/confidence interval: 1.28/1.12-1.48; p=0.001). Conclusion: Higher concentrations of particulate matter ≤2.5 µm in diameter caused elevated baseline alanine aminotransferase levels in patients with chronic hepatitis B receiving nucleotide/nucleoside analog therapy. The impact of particulate matter ≤2.5 µm in diameter on abnormal alanine aminotransferase levels was particularly pronounced in patients without cirrhosis
5-methoxytryptophan protects against toll-like receptor 2-mediated renal tissue inflammation and fibrosis in a murine unilateral ureteral obstruction model
No full text[[abstract]]INTRODUCTION: 5-Methoxytryptophan (5-MTP) is a cellular metabolite with anti-inflammatory properties. Several recent reports indicate that 5-MTP protects against post-injury tissue fibrosis. It was unclear how 5-MTP controls tissue fibrosis. We postulated that 5-MTP attenuates renal interstitial fibrosis by blocking toll-like receptor 2 (TLR2) and transforming growth factor β (TGFβ) signaling pathways. METHODS: In vivo experiments were carried out in a well-established unilateral ureteral obstruction (UUO) model in wild-type (WT) and tlr2-/- mice. The effect of 5-MTP on renal fibrosis was evaluated by pretreatment of WT UUO mice with intraperitoneal administration of 5-MTP. To determine whether 5-MTP attenuates fibrosis by inhibiting TLR2 and TGFβ signaling pathways, we evaluated the effect of 5-MTP on TLR2-induced fibroblast phenotypic switch in NRK-49F fibroblasts and TLR2 and TGFβ signaling pathways in human proximal tubular epithelial cells (HPTECs) and RAW264.7 macrophages stimulated with Pam3CSK4 (Pam3) or TGFβ1. RESULTS: UUO-induced renal fibrosis was abrogated in tlr2-/- mice consistent with a crucial role of TLR2 in UUO-induced renal fibrosis. UUO-induced macrophage infiltration and pro-fibrotic cytokine production in renal tissues were suppressed by tlr2 knockout. 5-MTP administration attenuated renal tissue fibrosis accompanied by reduction of macrophage infiltration and IL-6 and TGFβ levels. 5-MTP inhibits TLR2 upregulation and blocks TLR2-MyD88-TRAF6 signaling pathway in macrophages. Furthermore, 5-MTP blocked Pam3- and TGFβ1-induced phenotypic switch of NRK-49F to myofibroblasts and inhibited Pam3- and TGFβ1-induced signaling pathways in HPTECs and RAW264.7 cells. CONCLUSION: 5-MTP is effective in protecting against UUO-induced renal interstitial fibrosis by blocking TLR2 and TGFβ signaling pathways. INTRODUCTION: 5-Methoxytryptophan (5-MTP) is a cellular metabolite with anti-inflammatory properties. Several recent reports indicate that 5-MTP protects against post-injury tissue fibrosis. It was unclear how 5-MTP controls tissue fibrosis. We postulated that 5-MTP attenuates renal interstitial fibrosis by blocking toll-like receptor 2 (TLR2) and transforming growth factor β (TGFβ) signaling pathways. METHODS: In vivo experiments were carried out in a well-established unilateral ureteral obstruction (UUO) model in wild-type (WT) and tlr2-/- mice. The effect of 5-MTP on renal fibrosis was evaluated by pretreatment of WT UUO mice with intraperitoneal administration of 5-MTP. To determine whether 5-MTP attenuates fibrosis by inhibiting TLR2 and TGFβ signaling pathways, we evaluated the effect of 5-MTP on TLR2-induced fibroblast phenotypic switch in NRK-49F fibroblasts and TLR2 and TGFβ signaling pathways in human proximal tubular epithelial cells (HPTECs) and RAW264.7 macrophages stimulated with Pam3CSK4 (Pam3) or TGFβ1. RESULTS: UUO-induced renal fibrosis was abrogated in tlr2-/- mice consistent with a crucial role of TLR2 in UUO-induced renal fibrosis. UUO-induced macrophage infiltration and pro-fibrotic cytokine production in renal tissues were suppressed by tlr2 knockout. 5-MTP administration attenuated renal tissue fibrosis accompanied by reduction of macrophage infiltration and IL-6 and TGFβ levels. 5-MTP inhibits TLR2 upregulation and blocks TLR2-MyD88-TRAF6 signaling pathway in macrophages. Furthermore, 5-MTP blocked Pam3- and TGFβ1-induced phenotypic switch of NRK-49F to myofibroblasts and inhibited Pam3- and TGFβ1-induced signaling pathways in HPTECs and RAW264.7 cells. CONCLUSION: 5-MTP is effective in protecting against UUO-induced renal interstitial fibrosis by blocking TLR2 and TGFβ signaling pathways
Deidentification and temporal normalization of the electronic health record notes using large language models: The 2023 SREDH/AI-Cup competition for deidentification of sensitive health information
No full text[[abstract]]Electronic Medical Records (EMR) implementation benefits the medical industry with streamlined data analysis, increased patient medication safety, reduced expenses for pathology report storage, and improved medical care efficiency. The EMR text notes hold a patient’s clinical record, comprising notes written by the medical staff and further analyzed by the doctor following diagnosis. However, utilizing the EMR text note in its raw form can expose sensitive personal data belonging to patients and medical personnel. Therefore, safeguarding this private information is of utmost importance. Furthermore, the expression of time information in EMR text notes varies across institutions, which can significantly impact the accuracy and reliability of temporal information analysis. Therefore, normalizing temporal information is also a critical issue. The study presents a competition titled Privacy Protection and Standardization of Electronic Medical Record Competition that addresses recognizing Sensitive health information (SHI) recorded in EMR text notes and normalizing temporal information that poses a risk of identity theft. The competition released a corpus containing synthesized SHIs and normalized temporal information. The highest performance for the SHI recognition (subtask 1) and temporal information normalization (subtask 2) are micro-/macro-F of 0.949/0.912 and 0.844/0.869, respectively. Overall, the average micro/macro score for subtasks 1 and 2 were 0.666/0.496 and 0.6/0.394
MicroRNA-mediated regulation of Fatty Acid Oxidation Pathway in oral cancer
No full text[[abstract]]Cancer treatment requires a multifaceted approach. MicroRNAs play crucial roles in cancer by regulating key processes, understanding which is greatly beneficial for cancer prevention and treatment. In this study, we discovered a MicroRNA whose expression in oral cancer cells is suppressed by methylation. The decreased expression of this MicroRNA leads to dysregulation of its target genes. Specifically, the expression of the key rate-limiting enzyme in fatty acid oxidation, CPT1A, is significantly increased in oral cancer. The abundant expression of CPT1A enables cancer cells to promote proliferation, invasion, and migration by generating more ATP through fatty acid oxidation. Overall, the MicroRNA/CPT1A pathway may serve as a potential target for the treatment and prevention of oral cancer, warranting further investigation and application