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1.
Bone Rep ; 22: 101799, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39252698

ABSTRACT

Studies show that statins users are at reduced risk of fracture and improved bone mineral density. However, the clinical effectiveness of statin use in patients with gout has not been investigated. This retrospective cohort study used data from Taiwan's National Health Insurance Research Database, consisting of 3443 patients with gout using statins aged 50 years and above and 6886 gout patients of non-statin users matched by sex, age and propensity score. The Cox proportional hazards regression analysis showed that statin use was associated with a reduced risk of hip fracture (adjusted hazard ratio [aHR] = 0.78, 95 % confidence interval [CI] = 0.64-0.94) after controlling for potential confounding factors. The association was significant in both genders aged 50-64 years, with aHRs of near 0.35, but not in the elderly. In addition, women aged 50-64 years who used statins also exhibited a lower risk of vertebral fracture (aHR = 0.70, 95 % CI = 0.50-0.99), but not men. In conclusion, the stating use in gout patients could reduce fracture risk for younger patients. Further research is warranted to confirm these findings.

2.
World J Surg Oncol ; 22(1): 242, 2024 Sep 11.
Article in English | MEDLINE | ID: mdl-39256833

ABSTRACT

BACKGROUND: Recent randomized phase III trials have demonstrated the efficacy of anti-programmed cell death 1 (PD-1) immune checkpoint inhibitors (ICIs) in treating patients with recurrent or metastatic head and neck squamous cell carcinoma (RMHNSCC). However, a large proportion of such patients still have poor response. This study aimed to identify biomarkers for predicting anti-PD-1 ICI treatment outcomes . METHODS: We retrospectively analyzed 144 patients with RMHNSCC who received anti-PD-1 ICIs after progression to platinum-based chemotherapy between January 2017 and December 2022 at Kaohsiung Chang Gung Memorial Hospital. Data on clinicopathological parameters, albumin levels, calcium levels, and other pretreatment peripheral blood biomarkers, including total lymphocyte count, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), and prognostic nutritional index (PNI) were collected and correlated with the treatment outcome of anti-PD-1 ICIs. RESULTS: Low tumor proportion score (TPS), low combined positive score (CPS), NLR ≥ 5, PLR ≥ 300, hypercalcemia, hypoalbuminemia, and PNI < 45 were significantly correlated with poor response of ICIs. The overall response rates were 25% and 3% in patients with calcium < 10 mg/dL and calcium ≥ 10 mg/dL, respectively (P = 0.007). The overall response rates were 6% and 33% in patients with albumin < 4 g/dL and albumin ≥ 4 g/dL, respectively (P < 0.001). Univariate survival analysis showed that low TPS, low CPS, NLR ≥ 5,, hypercalcemia, hypoalbuminemia, and PNI < 45 were significantly associated with worse progression-free survival (PFS) and inferior overall survival (OS). Multivariate analysis revealed that calcium ≥ 10 mg/dL and albumin < 4 g/dL were independent poor prognosticators for worse PFS and inferior OS. The two-year OS rates were 26% and 9% in patients with calcium < 10 mg/dL and ≥ 10 mg/dL, respectively (P < 0.001). The two-year OS rates were 10% and 33% in patients with albumin < 4 g/dL and ≥ 4 g/dL, respectively (P < 0.001). CONCLUSIONS: Hypercalcemia and hypoalbuminemia can potentially predict poor treatment outcomes of anti-PD-1 ICIs in patients with RMHNSCC. Blood calcium and albumin levels may be helpful in individualizing treatment strategies for patients with RMHNSCC.


Subject(s)
Head and Neck Neoplasms , Hypercalcemia , Hypoalbuminemia , Immune Checkpoint Inhibitors , Neoplasm Recurrence, Local , Squamous Cell Carcinoma of Head and Neck , Humans , Male , Female , Retrospective Studies , Immune Checkpoint Inhibitors/therapeutic use , Squamous Cell Carcinoma of Head and Neck/drug therapy , Squamous Cell Carcinoma of Head and Neck/blood , Squamous Cell Carcinoma of Head and Neck/pathology , Squamous Cell Carcinoma of Head and Neck/immunology , Middle Aged , Head and Neck Neoplasms/drug therapy , Head and Neck Neoplasms/pathology , Head and Neck Neoplasms/blood , Head and Neck Neoplasms/complications , Head and Neck Neoplasms/immunology , Aged , Hypercalcemia/drug therapy , Hypercalcemia/blood , Hypercalcemia/etiology , Neoplasm Recurrence, Local/drug therapy , Neoplasm Recurrence, Local/pathology , Prognosis , Survival Rate , Hypoalbuminemia/complications , Hypoalbuminemia/etiology , Adult , Follow-Up Studies , Aged, 80 and over , Programmed Cell Death 1 Receptor/antagonists & inhibitors , Biomarkers, Tumor/blood
3.
FEBS Lett ; 2024 Sep 19.
Article in English | MEDLINE | ID: mdl-39300280

ABSTRACT

Heart failure (HF) is highly prevalent. Mechanisms underlying HF remain incompletely understood. Splicing factors (SF), which control pre-mRNA alternative splicing, regulate cardiac structure and function. This study investigated regulation of the splicing factor heterogeneous nuclear ribonucleoprotein-L (hnRNPL) in the failing heart. hnRNPL protein increased in left ventricular tissue from mice with transaortic constriction-induced HF and from HF patients. In left ventricular tissue, hnRNPL was detected predominantly in nuclei. Knockdown of the hnRNPL homolog Smooth in Drosophila induced cardiomyopathy. Computational analysis of predicted mouse and human hnRNPL binding sites suggested hnRNPL-mediated alternative splicing of tropomyosin, which was confirmed in C2C12 myoblasts. These findings identify hnRNPL as a sensor of cardiac dysfunction and suggest that disturbances of hnRNPL affect alternative splicing in HF.

4.
Psychoneuroendocrinology ; 170: 107169, 2024 Aug 21.
Article in English | MEDLINE | ID: mdl-39226626

ABSTRACT

Appetite hormones may play a significant role in neuronal excitability and synaptic plasticity and may also affect brain function development. This study aimed to explore the role of appetite hormones in attention deficit/hyperactivity disorder (ADHD), including aspects of pathophysiology, pharmacotherapy, and side effects. We recruited 119 patients with ADHD who were undergoing methylphenidate treatment (ADHD+MPH), 77 unmedicated ADHD patients (ADHD-MPH), and 87 healthy controls. Blood samples were collected from all participants to examine serum levels of orexin A, ghrelin, leptin, and adiponectin. Behavioral symptoms were assessed using the Swanson, Nolan, and Pelham Rating Scale, and visual and auditory attention were evaluated using computerized neuropsychological tests. The side effects of methylphenidate treatment were measured using Barkley's Side Effects Rating Scale. Orexin levels in the control group were significantly higher than in the ADHD-MPH (p=0.037) and ADHD+MPH (p<0.001) groups; additionally, orexin levels in the ADHD-MPH group were significantly higher than in the ADHD+MPH group (p=0.032). Leptin levels in both the ADHD+MPH (p=0.011) and ADHD-MPH (p=0.011) groups were significantly lower than in the control group. Ghrelin levels were positively associated with auditory attention across all ADHD groups (p=0.015). Furthermore, ghrelin levels were positively correlated with methylphenidate dosage (p=0.024), and negatively correlated with methylphenidate side effects (p=0.044) in the ADHD+MPH group. These findings provide further insight into the relationships between appetite hormones, pharmacotherapy, and ADHD. Orexin A and leptin are associated with the etiology of ADHD, while orexin A and ghrelin play important roles in attention deficits and methylphenidate usage in ADHD.

5.
Inorg Chem ; 63(33): 15516-15526, 2024 Aug 19.
Article in English | MEDLINE | ID: mdl-39102647

ABSTRACT

Water vapor inevitably exists in the environment, which causes adverse impacts on many crucial chemical reactions. However, high water vapor of up to 10 vol %─relevant to a broad spectrum of industrial practices-for catalytic implications has been less investigated or neglected. As such, we explored an industry-relevant, humidity-highly sensitive benzene oxidation only in the presence of 10 vol % water vapor using the well-established Pt/Co3O4 catalysts, to bring such an important yet ignored topic to the forefront. Results revealed that Pt/Co3O4 catalysts possessing higher contents of Pt nanoparticles exhibited marked tolerance to water vapor interference. Under an incomplete benzene conversion condition, the input of 10 vol % water vapor indeed impaired the catalytic performance of Pt/Co3O4 catalyst significantly, which, in fact, was caused by the unfavorable formation of carboxylate species covering the catalyst's surface engendering irrecoverable activity loss, instead of the well-accepted water competitive adsorption. While such activity loss can be restored by elevating the reaction to a higher temperature. This study helps us to understand the compromised catalytic activity caused by high humidity, urging the systematic evaluation of well-established catalyst systems in high water vapor-contained conditions and pressing the development of water-tolerant catalysts for real-life application consideration.

6.
Respir Investig ; 62(6): 942-950, 2024 Aug 24.
Article in English | MEDLINE | ID: mdl-39182399

ABSTRACT

BACKGROUND: Refractory chronic cough (RCC) causes significant impairments in the life quality of patients. Further research into the identification of etiologies and development of the treatment schedules for RCC is needed. PATIENTS AND METHODS: We established an multidisciplinary team (MDT) clinic, by integrating respiratory medicine, otorhinolaryngology, and gastroenterology departments, to investigate cough etiologies and the effectiveness of treatment. The therapeutic effect was assessed quantitatively using the Cough Visual Analog Scales (VAS), Leicester Cough Questionnaire (LCQ), and Reflux Symptoms Index (RSI) scores. RESULTS: In total, 213 patients attending the MDT outpatient clinic were examined, and 115 patients with RCC were included for analysis. The RCC diagnosis rate among the outpatient was 88.7%. Common causes of RCC included gastroesophageal reflux cough (63.5%), upper airway cough syndrome (UACS) (43.5%), and cough variant asthma (CVA) (14.8%). After an average treatment period of 2.17 ± 1.06 weeks (wk), 73.9% of the patients had partial cough remission, and 6.1% had complete cough remission. The cough VAS score before and after treatment was 6.11 ± 2.02 vs. 3.66 ± 2.22 (P < 0.05), respectively; LCQ total score before and after treatment was 10.24 ± 3.11 vs. 13.16 ± 3.59 (P < 0.05), respectively; and RSI score before and after treatment was 15.82 ± 7.01 vs. 10.71 ± 6.64 (P < 0.05), respectively. CONCLUSION: The etiologies of most patients with RCC could be identified in the MDT clinic, and the cough-related symptoms of a significant number of patients with RCC improved in a short period.

7.
Cancer Manag Res ; 16: 989-1001, 2024.
Article in English | MEDLINE | ID: mdl-39108298

ABSTRACT

Background: The aim of this study was to investigate the role of phthalate in patients with esophageal squamous cell carcinoma (ESCC). Methods: A total of 116 ESCC patients and 58 controls without any known histories of malignancies were enrolled. All eight urine phthalate metabolites were measured to assess phthalate levels. Clinical and urine phthalate metabolite profiles were compared between subgroups to identify differences, and the effects of phthalates on clinical ESCC outcomes were also examined. Results: The concentrations of some urine phthalate metabolites were higher in the ESCC group than in the control group, including mono-(3-carboxypropyl) phthalate (MCPP), mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP), and mono-n-butyl phthalate (MnBP). Higher concentrations of urine phthalate metabolites were associated with clinical T3-T4 status. Patients with higher concentration of mono-(2-ethyl-5-carboxypentyl) phthalate (MECPP), mono-2-ethylhexyl phthalate (MEHP), and MEOHP had lower 1-year and 2-year overall survival (OS) rates than those with lower concentrations of these metabolites in our univariate analysis. Multivariate analysis showed that urinary MEHP of ≥3 µg/L and clinical stage IVB were independent prognostic factors for worse OS. Conclusion: The results of our study showed that urine phthalate metabolites are elevated in ESCC patients and associated with advanced tumor stage, and that a high urinary concentration of MEHP is an independent prognostic factor of worse OS.

9.
Vaccine ; 42(25): 126131, 2024 Nov 14.
Article in English | MEDLINE | ID: mdl-39003103

ABSTRACT

Vaccine-induced immune thrombocytopenia and thrombosis (VITT) is a newly recognized syndrome mediated by anti-platelet factor 4 antibodies induced by Covid-19 adenovirus-vectored vaccines including ChAdOx1 nCoV-19 and Ad26.COV2.S. This study validated a proposed Brighton Collaboration case definition for VITT. A data collection form was developed and used to capture the variations in VITT criteria and assess their level of diagnostic certainty from adjudicated positive VITT case datasheets in Germany (n = 71), UK (n = 220), Australia (n = 203), and Taiwan (n = 56). We observed high prevalence of each component of the proposed VITT definition in positive cases (84%-100%), except for the occurrence of thrombosis or thromboembolism criterion in only 34% of VITT cases in Taiwan. The sensitivity of this proposed definition was 100% for Germany and UK, 92% for Australia, and 89% for Taiwan cases. These findings support the validity of this case definition for VITT.


Subject(s)
COVID-19 Vaccines , ChAdOx1 nCoV-19 , Purpura, Thrombocytopenic, Idiopathic , Thrombosis , Humans , COVID-19 Vaccines/adverse effects , COVID-19 Vaccines/immunology , Thrombosis/immunology , Thrombosis/etiology , ChAdOx1 nCoV-19/immunology , ChAdOx1 nCoV-19/adverse effects , Germany/epidemiology , Australia/epidemiology , Purpura, Thrombocytopenic, Idiopathic/diagnosis , Purpura, Thrombocytopenic, Idiopathic/etiology , Purpura, Thrombocytopenic, Idiopathic/immunology , Purpura, Thrombocytopenic, Idiopathic/chemically induced , Purpura, Thrombocytopenic, Idiopathic/epidemiology , Taiwan/epidemiology , Male , Middle Aged , Female , United Kingdom/epidemiology , COVID-19/prevention & control , COVID-19/diagnosis , COVID-19/immunology , Adult , Aged , Ad26COVS1/adverse effects , SARS-CoV-2/immunology , Platelet Factor 4/immunology
10.
BMC Microbiol ; 24(1): 275, 2024 Jul 25.
Article in English | MEDLINE | ID: mdl-39048954

ABSTRACT

BACKGROUND: Extreme precipitation events often cause sudden drops in salinity, leading to disease outbreaks in shrimp aquaculture. Evidence suggests that environmental stress increases animal host susceptibility to pathogens. However, the mechanisms of how low salinity stress induces disease susceptibility remain poorly understood. METHODS: We investigated the acute response of shrimp gut microbiota exposed to pathogens under low salinity stress. For comparison, shrimp were exposed to Vibrio infection under two salinity conditions: optimal salinity (Control group) and low salinity stress (Stress group). High throughput 16S rRNA sequencing and real-time PCR were employed to characterize the shrimp gut microbiota and quantify the severity level of Vibrio infection. RESULTS: The results showed that low salinity stress increased Vibrio infection levels, reduced gut microbiota species richness, and perturbed microbial functions in the shrimp gut, leading to significant changes in lipopolysaccharide biosynthesis that promoted the growth of pathogens. Gut microbiota of the bacterial genera Candidatus Bacilliplasma, Cellvibrio, and Photobacterium were identified as biomarkers of the Stress group. The functions of the gut microbiota in the Stress group were primarily associated with cellular processes and the metabolism of lipid-related compounds. CONCLUSIONS: Our findings reveal how environmental stress, particularly low salinity, increases shrimp susceptibility to Vibrio infection by affecting the gut microbiota. This highlights the importance of avoiding low salinity stress and promoting gut microbiota resilience to maintain the health of shrimp.


Subject(s)
Dysbiosis , Gastrointestinal Microbiome , Penaeidae , RNA, Ribosomal, 16S , Salt Stress , Vibrio Infections , Vibrio parahaemolyticus , Animals , Penaeidae/microbiology , Vibrio parahaemolyticus/physiology , RNA, Ribosomal, 16S/genetics , Vibrio Infections/microbiology , Vibrio Infections/veterinary , Dysbiosis/microbiology , Salinity , Aquaculture , Bacteria/classification , Bacteria/genetics , Bacteria/isolation & purification
11.
Thorac Cancer ; 15(24): 1805-1814, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39045786

ABSTRACT

BACKGROUND: Organophosphate flame retardants (OPFRs) are extensively distributed in our environment, prompting concerns about potential health hazards, including lung injuries resulting from OPFR exposure. METHODS: The present study recruited 125 lung cancer patients, assessing their exposure to 10 OPFR compounds through urine samples. The final analysis comprised 108 participants after excluding those lacking epidermal growth factor receptor (EGFR) status and those with chronic kidney disease. Demographic and clinical characteristics, as well as urinary OPFR concentrations, were compared based on OPFR detection. Spearman correlation was conducted to explore the relationship between OPFR compounds, while logistic regression was used to identify OPFR compounds associated with EGFR mutation. RESULTS: The study revealed widespread OPFR exposure among lung cancer patients, with an overall detection frequency of 99.07%. Tris(2-butoxyethyl) phosphate (TBEP) exhibited a strong correlation to its metabolite bis(2-butoxyethyl) phosphate (r = 0.88, p < 0.01). Patients with TBEP in their urine had higher percentage of wild-type EGFR and the detection of TBEP was associated with a reduced likelihood of mutant EGFR expression. CONCLUSIONS: OPFR exposure was prevalent in lung cancer patients, with TBEP detection identified as a factor with lower EGFR mutation expression. This study contributes to the understanding of OPFR exposure in lung cancer patients and underscores the significance of TBEP in evaluating EGFR mutation in this population.


Subject(s)
ErbB Receptors , Flame Retardants , Lung Neoplasms , Organophosphates , Humans , Male , Female , Lung Neoplasms/genetics , ErbB Receptors/genetics , Middle Aged , Aged , Environmental Exposure/adverse effects , Mutation , Adult
12.
Sci Rep ; 14(1): 16280, 2024 07 15.
Article in English | MEDLINE | ID: mdl-39009643

ABSTRACT

This retrospective study investigated the incidence, medication use, and outcomes in pediatric autosomal-dominant polycystic kidney disease (ADPKD) using Taiwan's National Health Insurance Research Database (NHIRD). A 1:4 matched control group of individuals included in the NHIRD during the same period was used for comparative analyses. A total of 621 pediatric patients were identified from 2009 to 2019 (mean age, 9.51 ± 6.43 years), and ADPKD incidence ranged from 2.32 to 4.45 per 100,000 individuals (cumulative incidence, 1.26-1.57%). The incidence of newly developed hypertension, anti-hypertensive agent use, nephrolithiasis, and proteinuria were significantly higher in the ADPKD group than the non-ADPKD group (0.7 vs. 0.04, 2.26 vs. 0.30, 0.4 vs. 0.02, and 0.73 vs. 0.05 per 100 person-years, respectively). The adjusted hazard ratios for developing hypertension, proteinuria, nephrolithiasis and anti-hypertensive agent use in cases of newly-diagnosed pediatric ADPKD were 12.36 (95% CI 4.92-31.0), 13.49 (95% CI 5.23-34.79), 13.17 (95% CI 2.48-69.98), and 6.38 (95% CI 4.12-9.89), respectively. The incidence of congenital cardiac defects, hematuria, urinary tract infections, gastrointestinal diverticulosis, dyslipidemia, and hyperuricemia were also higher in the ADPKD group. Our study offers valuable insights into the epidemiology of pediatric ADPKD in Taiwan and could help in formulating guidelines for its appropriate management.


Subject(s)
Polycystic Kidney, Autosomal Dominant , Humans , Taiwan/epidemiology , Polycystic Kidney, Autosomal Dominant/epidemiology , Polycystic Kidney, Autosomal Dominant/therapy , Polycystic Kidney, Autosomal Dominant/drug therapy , Child , Male , Female , Adolescent , Retrospective Studies , Child, Preschool , Incidence , Hypertension/epidemiology , Hypertension/drug therapy , Proteinuria/epidemiology , Nephrolithiasis/epidemiology , Treatment Outcome , Antihypertensive Agents/therapeutic use , Infant , Databases, Factual
13.
Vaccine ; 42(24): 126079, 2024 Oct 24.
Article in English | MEDLINE | ID: mdl-38909000

ABSTRACT

INTRODUCTION: Standardizing case definitions for priority vaccine safety conditions facilitates uniform evaluation and consolidation of data obtained from different settings. The Brighton Collaboration case definitions (BCCD) were created to support this harmonization and enable classification from level 1 (most certain) to level 5 (not a case) of certainty. Assessing the performance of BCCD in practice is critical, particularly in resource-limited settings, where many new vaccines may be introduced without prior monitoring in high-income countries. We assessed the performance of BCCD in Addis Ababa, Ethiopia, as applicable to COVID-19 and other vaccines. METHODS: Active surveillance was conducted at Tikur Anbessa Specialized Hospital, the largest referral hospital in Ethiopia. During June 1, 2022-May 31, 2023, three trained physicians prospectively identified patients eligible for COVID-19 vaccination (regardless of vaccine receipt) who presented with one or more of eleven pre-specified adverse events of special interest (AESI) from the emergency department and inpatient wards. Standardized data collection forms were used to capture patient information and assign level of certainty (LOC), regardless of vaccination status for COVID-19. We conducted descriptive analysis to characterize cases and the LOCs reached for each AESI. RESULTS: We detected 203 AESI cases. The most detected conditions were thrombosis and thromboembolism (n = 100, 49 %) and generalized convulsions (n = 38, 19 %). Ninety-six percent of the cases were confirmed at levels 1-3 (n = 187) or level 5 (n = 9) LOC. Non-classifiable (level 4) cases were observed for pericarditis (n = 2), encephalitis (n = 2), myelitis (n = 2), and generalized convulsion (n = 1). CONCLUSION: The BCCD were successfully applied in > 95 % of cases in a large referral hospital in Ethiopia, with generalized convulsion, pericarditis, and encephalomyelitis as the exceptions. We recommend further evaluation in other low-resource settings, particularly in rural or non-referral hospitals, to gain additional insights into performance of these definitions for revision or adaptation, as needed.


Subject(s)
COVID-19 Vaccines , COVID-19 , Humans , Ethiopia/epidemiology , COVID-19/epidemiology , COVID-19/prevention & control , Female , Prospective Studies , Adult , Male , Middle Aged , Adolescent , Young Adult , COVID-19 Vaccines/administration & dosage , Aged , Child , Child, Preschool , SARS-CoV-2/immunology , Vaccination/statistics & numerical data , Infant , Hospitals/statistics & numerical data
14.
Sci Rep ; 14(1): 13270, 2024 06 10.
Article in English | MEDLINE | ID: mdl-38858540

ABSTRACT

Smoking has multiple negative effects on health; therefore, the Taiwanese government provides smoking cessation clinics to smokers. This study aimed to explore the trajectory of smoking cessation after smokers received treatment and the variables related to different trajectories. A retrospective longitudinal study was conducted, in which 735 adult smokers who received smoking cessation medications were recruited. The participants' demographic characteristics, chronic diseases, smoking characteristics, and cigarette dependence were collected from chart review. The amount of smoking was collected at baseline, and at 1 week, 1 month, 3 months, and 6 months after treatment. The Proc Traj procedure for group-based modeling and multinomial logistic regression were used for statistical analysis. Three trajectories were identified: early quitters (28.03%), late quitters (11.43%) and reducers (60.54%). Compared with early quitters, reducers were younger and had a higher probability of severe cigarette dependence. Compared with early quitters, late quitters had a higher number of taking smoking cessation medications. The findings revealed that approximately 60% of participants who received smoking cessation treatment could not completely quit smoking, and that age, number of medications taken, and cigarette dependence were significant predictors of different trajectories.


Subject(s)
Smoking Cessation , Humans , Smoking Cessation/methods , Smoking Cessation/statistics & numerical data , Male , Taiwan/epidemiology , Female , Middle Aged , Adult , Longitudinal Studies , Retrospective Studies , Smoking , Tobacco Use Disorder/therapy , Tobacco Use Disorder/epidemiology , Smoking Cessation Agents/therapeutic use
15.
Ecotoxicol Environ Saf ; 281: 116625, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38908056

ABSTRACT

Humans are extensively exposed to organophosphate flame retardants (OPFRs), an emerging group of organic contaminants with potential nephrotoxicity. Nevertheless, the estimated daily intake (EDI) and prognostic impacts of OPFRs have not been assessed in individuals with chronic kidney disease (CKD). In this 2-year longitudinal study of 169 patients with CKD, we calculated the EDIs of five OPFR triesters from urinary biomonitoring data of their degradation products and analyzed the effects of OPFR exposure on adverse renal outcomes and renal function deterioration. Our analysis demonstrated universal OPFR exposure in the CKD population, with a median EDIΣOPFR of 360.45 ng/kg body weight/day (interquartile range, 198.35-775.94). Additionally, our study revealed that high tris(2-chloroethyl) phosphate (TCEP) exposure independently correlated with composite adverse events and composite renal events (hazard ratio [95 % confidence interval; CI]: 4.616 [1.060-20.096], p = 0.042; 3.053 [1.075-8.674], p = 0.036) and served as an independent predictor for renal function deterioration throughout the study period, with a decline in estimated glomerular filtration rate of 4.127 mL/min/1.73 m2 (95 % CI, -8.127--0.126; p = 0.043) per log ng/kg body weight/day of EDITCEP. Furthermore, the EDITCEP and EDIΣOPFR were positively associated with elevations in urinary 8-hydroxy-2'-deoxyguanosine and kidney injury molecule-1 during the study period, indicating the roles of oxidative damage and renal tubular injury in the nephrotoxicity of OPFR exposure. To conclude, our findings highlight the widespread OPFR exposure and its possible nephrotoxicity in the CKD population.


Subject(s)
Flame Retardants , Organophosphates , Renal Insufficiency, Chronic , Humans , Flame Retardants/toxicity , Longitudinal Studies , Renal Insufficiency, Chronic/chemically induced , Renal Insufficiency, Chronic/urine , Male , Female , Middle Aged , Organophosphates/toxicity , Organophosphates/urine , Aged , Adult , Kidney/drug effects , Environmental Exposure/statistics & numerical data , Organophosphorus Compounds/urine , Organophosphorus Compounds/toxicity , Environmental Monitoring , Environmental Pollutants/toxicity , Environmental Pollutants/urine
16.
J Mol Neurosci ; 74(2): 38, 2024 Apr 04.
Article in English | MEDLINE | ID: mdl-38573391

ABSTRACT

Disulfidptosis is a newly discovered form of regulatory cell death. However, the identification of disulfidptosis-related molecular subtypes and potential biomarkers in gliomas and their prognostic predictive potential need to be further elucidated. RNA sequencing profiles and the relevant clinical data were obtained from the Cancer Genome Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA). Disulfidptosis-related clusters were identified by unsupervised clustering analysis. Immune cell infiltration analysis and drug sensitivity analysis were used to explore the differences between clusters. Gene set enrichment analysis (GSEA) of differential genes between clusters was performed to explore the potential biological functions and signaling. A disulfidptosis-related scoring system (DRSS) was constructed based on a combined COX and LASSO analysis. Mendelian randomization (MR) analyses were used to further explore the causal relationship between levels of genes in DRSS and an increased risk of glioma. A prognosis nomogram was constructed based on the DRSS and 3 clinical features (age, WHO stage, and IDH status). The accuracy and stability of the prognosis nomogram were also validated in different cohorts. We identified two clusters that exhibited different prognoses, drug sensitivity profiles, and tumor microenvironment infiltration profiles. The overall survival (OS) of Cluster2 was significantly better than Cluster1. Cluster1 had an overall greater infiltration of immune cells compared to Cluster2. However, the Monocytes, activated B cells had higher infiltration abundance in Cluster2. GSEA results showed significant enrichment of immune-related biological processes in Cluster1, while Cluster2 was more enriched for functions related to neurotransmission and regulation. PER3, RAB34, NKX3-2, GPX7, FRA10AC1, and TGIF1 were finally included to construct DRSS. DRSS was independently related to prognosis. There was a significant difference in overall survival between the low-risk score group and the high-risk score group. Among six genes in DRSS, GPX7 levels were demonstrated to have a causal relationship with an increased risk of glioma. GPX7 may become a more promising biomarker for gliomas. The prognosis nomogram constructed based on the DRSS and three clinical features has considerable potential for predicting the prognosis of patients with glioma. Free online software for implementing this nomogram was established:  https://yekun-zhuang.shinyapps.io/DynNomapp/ . Our study established a novel glioma classification based on the disulfidptosis-related molecular subtypes. We constructed the DRSS and the prognosis nomogram to accurately stratify the prognosis of glioma patients. GPX7 was identified as a more promising biomarker for glioma. We provide important insights into the treatment and prognosis of gliomas.


Subject(s)
Glioma , Humans , Biomarkers , Cell Death , Glioma/diagnosis , Glioma/genetics , Tumor Microenvironment
17.
BMC Cancer ; 24(1): 547, 2024 Apr 30.
Article in English | MEDLINE | ID: mdl-38689252

ABSTRACT

OBJECTIVE: The purpose of this study was to develop an individual survival prediction model based on multiple machine learning (ML) algorithms to predict survival probability for remnant gastric cancer (RGC). METHODS: Clinicopathologic data of 286 patients with RGC undergoing operation (radical resection and palliative resection) from a multi-institution database were enrolled and analyzed retrospectively. These individuals were split into training (80%) and test cohort (20%) by using random allocation. Nine commonly used ML methods were employed to construct survival prediction models. Algorithm performance was estimated by analyzing accuracy, precision, recall, F1-score, area under the receiver operating characteristic curve (AUC), confusion matrices, five-fold cross-validation, decision curve analysis (DCA), and calibration curve. The best model was selected through appropriate verification and validation and was suitably explained by the SHapley Additive exPlanations (SHAP) approach. RESULTS: Compared with the traditional methods, the RGC survival prediction models employing ML exhibited good performance. Except for the decision tree model, all other models performed well, with a mean ROC AUC above 0.7. The DCA findings suggest that the developed models have the potential to enhance clinical decision-making processes, thereby improving patient outcomes. The calibration curve reveals that all models except the decision tree model displayed commendable predictive performance. Through CatBoost-based modeling and SHAP analysis, the five-year survival probability is significantly influenced by several factors: the lymph node ratio (LNR), T stage, tumor size, resection margins, perineural invasion, and distant metastasis. CONCLUSIONS: This study established predictive models for survival probability at five years in RGC patients based on ML algorithms which showed high accuracy and applicative value.


Subject(s)
Machine Learning , Stomach Neoplasms , Humans , Stomach Neoplasms/pathology , Stomach Neoplasms/surgery , Stomach Neoplasms/mortality , Male , Female , Middle Aged , Prognosis , Retrospective Studies , Aged , Gastrectomy , Gastric Stump/pathology , ROC Curve , Risk Assessment/methods , Algorithms
18.
World J Urol ; 42(1): 173, 2024 Mar 20.
Article in English | MEDLINE | ID: mdl-38507059

ABSTRACT

PURPOSE: To identify predictive factors for satisfactory treatment outcome of the patients with IC/BPS using urine biomarkers and machine-learning models. METHODS: The IC/BPS patients were prospectively enrolled and provide urine samples. The targeted analytes included inflammatory cytokines, neurotrophins, and oxidative stress biomarkers. The patients with overall subjective symptom improvement of ≥ 50% were considered to have satisfactory results. Binary logistic regression, receiver-operating characteristic (ROC) curve, machine-learning decision tree, and random forest models were used to analyze urinary biomarkers to predict satisfactory results. RESULTS: Altogether, 57.4% of the 291 IC/BPS patients obtained satisfactory results. The patients with satisfactory results had lower levels of baseline urinary inflammatory cytokines and oxidative biomarkers than patients without satisfying results, including interleukin-6, monocyte chemoattractant protein-1 (MCP-1), C-X-C motif chemokine 10 (CXCL10), oxidative stress biomarkers 8-hydroxy-2'-deoxyguanosine (8-OHDG), 8-isoprostane, and total antioxidant capacity (TAC). Logistic regression and multivariable analysis revealed that lower levels of urinary CXCL10, MCP-1, 8-OHDG, and 8-isoprostane were independent factors. The ROC curve revealed that MCP-1 level had best area under curve (AUC: 0.797). In machine-learning decision tree model, combination of urinary C-C motif chemokine 5, 8-isoprostane, TAC, MCP-1, and 8-OHDG could predict satisfactory results (accuracy: 0.81). The random forest model revealed that urinary 8-isoprostance, MCP-1, and 8-OHDG levels had the most important influence on accuracy. CONCLUSION: Machine learning decision tree model provided a higher accuracy for predicting treatment outcome of patients with IC/BPS than logistic regression, and levels of 8-isoprostance, MCP-1, and 8-OHDG had the most important influence on accuracy.


Subject(s)
Cystitis, Interstitial , Humans , Cystitis, Interstitial/diagnosis , Biomarkers/urine , Chemokines , Cytokines , Treatment Outcome , Antioxidants
19.
Front Public Health ; 12: 1340261, 2024.
Article in English | MEDLINE | ID: mdl-38525338

ABSTRACT

Organophosphate flame retardants (OPFRs) are emerging environmental pollutants that can be detected in water, dust, and biological organisms. Certain OPFRs can disrupt lipid metabolism in animal models and cell lines. However, the effects of OPFRs on human lipid metabolism remain unclear. We included 1,580 participants (≥20 years) from the 2013-2014 National Health and Nutrition Examination Survey (NHANES) to explore the relationship between OPFR exposure and lipid metabolism biomarkers. After adjusting for confounding factors, results showed that one-unit increases in the log levels of diphenyl phosphate (DPhP) (regression coefficient = -5.755; S.E. = 2.289; p = 0.023) and log bis-(1-chloro-2-propyl) phosphate (BCPP) (regression coefficient = -4.637; S.E. = 2.019; p = 0.036) were negatively associated with the levels of total cholesterol (TC) in all participants. One-unit increases in the levels of DPhP (regression coefficient = -2.292; S.E. = 0.802; p = 0.012), log bis (1,3-dichloro-2-propyl) phosphate (BDCPP) (regression coefficient = -2.046; S.E. = 0.825; p = 0.026), and log bis-2-chloroethyl phosphate (BCEP) (regression coefficient = -2.604; S.E. = 0.704; p = 0.002) were negatively associated with the levels of high-density lipoprotein cholesterol (HDL-C). With increasing quartiles of urine BDCPP levels, the mean TC levels significantly decreased in all participants (p value for trend = 0.028), and quartile increases in the levels of DPhP (p value for trend = 0.01), BDCPP (p value for trend = 0.001), and BCEP (p value for trend<0.001) were negatively corelated with HDL-C, with approximately 5.9, 9.9, and 12.5% differences between the upper and lower quartiles. In conclusion, DPhP, BDCPP, and BCEP were negatively related to HDL-C concentration, whereas DPhP and BCPP levels were negatively associated with TC level. Thus, exposure to OPFRs may interfere with lipid metabolism.


Subject(s)
Flame Retardants , Organophosphates , Organophosphorus Compounds , Animals , Humans , Organophosphates/metabolism , Flame Retardants/metabolism , Nutrition Surveys , Lipid Metabolism , Phosphates , Cholesterol
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