Cause Of Death Research Articles

Combination of miR-99b-5p and Enzalutamide or Abiraterone Synergizes the Suppression of EMT-Mediated Metastasis in Prostate Cancer

Prostate cancer (PCa) is the most frequently diagnosed cancer and second leading cause of cancer deaths among American men. Androgen deprivation therapy (ADT) has been systemically applied as a first-line therapy for PCa patients. Despite the initial responses, the majority of patients under ADT eventually experienced tumor progression to castration-resistant prostate cancer (CRPC), further leading to tumor metastasis to distant organs. Therefore, identifying the key molecular mechanisms underlying PCa progression remains crucial for the development of novel therapies for metastatic PCa. Previously, we identified that tumor-suppressive miR-99b-5p is frequently downregulated in aggressive African American (AA) PCa and European American (EA) CRPC, leading to upregulation of mTOR, androgen receptor (AR), and HIF-1α signaling. Given the fact that mTOR and HIF-1α signaling are critical upstream pathways that trigger the activation of epithelial–mesenchymal transition (EMT), we hypothesized that miR-99b-5p may play a critical functional role in regulating EMT-mediated PCa metastasis. To test this hypothesis, a series of cell biology, biochemical, and in vitro functional assays (wound healing, transwell migration, cell/ECM adhesion, and capillary-like tube formation assays) were performed to examine the effects of miR-99b-5p mimic on regulating EMT-mediated PCa metastasis processes. Our results have demonstrated that miR-99b-5p simultaneously targets MTOR and AR signaling, leading to upregulation of E-cadherin, downregulation of Snail/N-cadherin/Vimentin, and suppression of EMT-mediated PCa metastasis. MiR-99b-5p alone and in combination with enzalutamide or abiraterone significantly inhibits the EMT-mediated metastasis of AA PCa and EA CRPC.

IMPACTS OF TOBACCO USE AND EXPOSURE TO TOBACCO SMOKE ON HEALTH, SOCIETY, ECONOMY, AND ENVIRONMENT

Smoking represents a significant global public health challenge and is the primary preventable cause of disease and death. This problem is accentuated by the fact that a substantial 80% of adult smokers worldwide come from low- or middle-income countries. The aim of this paper is twofold: first, to highlight the health impacts associated with tobacco use, and second, to delineate the indirect damage caused to the environment during the life cycle of tobacco products - from production and distribution to consumption and waste generation. The reluctance of some countries to take decisive action, together with intense pressure from tobacco corporations, is hindering progress towards reducing the number of adult smokers and curbing tobacco use among minors. State interventions, supported by strict laws, are necessary to enforce the ban on indoor smoking, the ban on the sale of tobacco to minors, and the establishment of permanent interstate cooperation in the fight against cigarette smuggling. Educational initiatives aimed at raising awareness of the dangers of smoking and tobacco consumption are key to fostering a smoke-free culture. A strong media campaign, supported by state measures, could contribute to faster and more comprehensive targeting of target groups, especially younger age categories.

Predictive value of Cmmi-MHR combined with thromboelastography parameters in acute cerebral infarction.

Cerebral infarction is a common neurological disease with high rates of morbidity, mortality, and recurrence, posing a great threat to human life and health. Cerebral infarction is the second leading cause of death in the world and the leading cause of long-term disability in humans. The results of the third national retrospective sampling survey on causes of death in 2008 showed that cerebral infarction has become the leading cause of death in China and its mortality rate is 4-5 times that of European and American countries. Therefore, this article proposed a study on the predictive value of Cmmi-MHR combined with thromboelastography parameters that was performed for acute cerebral infarction. This paper mainly proposed a high frame rate imaging technology and analyzed its algorithm. In this article, in the experimental part, an in-depth analysis of the predictive value of the Monocyte-to-high-density lipoprotein cholesterol ratio (MHR) combined with thromboelastography parameters was performed for acute cerebral infarction. The final experimental results showed that HDL (OR = 1.695%, P-trend = 0.049) had a probability of death within 90days of hospitalization (OR = 0.81, 95% CI = 1.06-3.11, P-trend = 0.523). There were no significant differences in mortality rate after 90days. Regardless of adjusting for confounders such as age, gender, and NIHSS score, there was no significant difference in the risk of MHR or monocyte count within 90days of hospitalization. The conclusion indicates that the combination of Cmmi-MHR and thromboelastography parameters provides a new perspective and method for the diagnosis and treatment of cerebral infarction, and provides important support for personalized treatment and management of cerebral infarction.

Cluster analysis of clinical phenotypes in idiopathic inflammatory myopathy patients complicated with cardiac involvement.

This study aimed to classify idiopathic inflammatory myopathy (IIM) patients with cardiac involvement (IIM-CI) into different categories based on their clinical phenotypes via cluster analysis and to explore their differences in outcomes. IIM-CI patients admitted to Peking Union Medical College Hospital from January 2015 to June 2021 were retrieved. The clinical data, laboratory examinations, and treatment were retrospectively reviewed, and the outcome was traced. A second-order clustering method was employed for categorization. A total of 88 IIM-CI patients were enrolled in this study and were classified into two categories through cluster analysis. Category I consisted of patients who exhibited distinct cardiac structural and functional changes, such as enlargement of atriums and/or ventricles, along with the remarkable heart insufficiency biomarkers, whereas patients of category II displayed more widely systemic injuries and intensive skeletal muscle weakness. In comparison, pulmonary hypertension (58.8% vs 16.7%, p < 0.01), arrhythmia (82.4% vs 27.8%, p < 0.01), and positive serum anti-mitochondrial-M2 antibody (52.9% vs 5.6%, p < 0.01) were more prevalent in category I than in category II, and serum N-terminal pro-B-type natriuretic peptide levels (1703.5 pg/L vs 364.0 pg/L, p = 0.02) were significantly elevated in category I, whereas skeletal muscle weakness (50.0% vs 74.1%, p = 0.02), interstitial lung disease (20.6% vs 63.0%, p < 0.01), skin rash (11.8% vs 48.1%, p < 0.01), arthralgia (2.9% vs 27.8%, p < 0.01), fever (2.9% vs 27.8%, p < 0.01), and dysphagia (2.9% vs 22.2%, p < 0.01) were more common in category II patients. Heart failure was the primary cause of death in category I, but severe pneumonia was predominantly responsible for deaths in category II. Two categories of IIM-CI were identified based on clinical features with distinctive characteristics. Two categories exhibited differences in clinical manifestations, autoantibody profiles, and the primary cause of death.

Association of low vitamin D level and full-term early-onset neonatal sepsis; a case-control study

BackgroundSepsis is one of the main causes of death in newborns worldwide. Vitamin D levels during fetal and neonatal periods have a significant role in the development of the immunological system. The study aims to evaluate the association between vitamin D levels and the risk of early-onset neonatal sepsis in full-term neonates in a developing country.MethodsThis case–control study was conducted at the Neonatal Intensive Care Units (NICUs) of Kasr Alainy Hospital, Cairo, Egypt. The study was composed of two groups; the sepsis group involved full-term neonates appropriate for gestational age with sepsis-related clinical signs. The control group included newborns with no signs of clinical/laboratory infection within 72 h of life. Blood samples were collected on admission during the first three days of life in both groups for the measurement of 25-hydroxyvitamin D levels, Complete Blood Count (CBC), C reactive protein (CRP), and blood culture.ResultsForty-five newborns with clinical and laboratory findings of early-onset neonatal sepsis within 72 h of life were enrolled, and the control group included forty-five newborns with no evidence of sepsis. Vitamin D levels in the sepsis group were significantly lower than in the control group. Apgar score at the first minute was significantly lower in the sepsis group. 57.8% of neonates with sepsis had positive blood cultures. There was a statistical difference between deficient, insufficient, and sufficient vitamin D levels regarding the duration of the NICU stay, which was longer in neonates with deficient vitamin D levels. CRP was significantly higher in neonates with deficient vitamin D levels. The area under the receiver operating characteristic curve for serum vitamin D in the prediction of neonatal sepsis was 0.76 at a cutoff < 19.7(ng/ml).ConclusionIn the current study, full-term newborns with EOS had considerably lower vitamin D levels than healthy controls. Through appropriate vitamin supplementation of the mothers during pregnancy, it could be possible to ensure adequate vitamin D levels for newborns. This may contribute to the reduction of the risk of EOS, together with the other well-known preventive measures (i.e. breastfeeding and intrapartum antibiotic prophylaxis).

Speckle Plethysmograph-Based Blood Pressure Assessment

Continuous non-invasive blood pressure (CNBP) monitoring is of the utmost importance in detecting and managing hypertension, a leading cause of death in the United States. Extensive research has delved into pioneering methods for predicting systolic and diastolic blood pressure values by leveraging pulse arrival time (PAT), the time difference between the proximal and distal signal peaks. The most widely employed pairing involves electrocardiography (ECG) and photoplethysmography (PPG). Possessing similar characteristics in terms of measuring blood flow changes, a recently investigated optical signal known as speckleplethysmography (SPG) showed its stability and high signal-to-noise ratio compared with PPG. Thus, SPG is a potential surrogate to pair with ECG for CNBP estimation. The present study aims to unlock the untapped potential of SPG as a signal for non-invasive blood pressure monitoring based on PAT. To ascertain SPG’s capabilities, eight subjects were enrolled in multiple recording sessions. A third-party device was employed for ECG and PPG measurements, while a commercial device served as the reference for arterial blood pressure (ABP). SPG measurements were obtained using a prototype smartphone-based system. Following the completion of three scenarios—sitting, walking, and running—the subjects’ signals and ABP were recorded to investigate the predictive capacity of systolic blood pressure. The collected data were processed and prepared for machine learning models, including support vector regression and decision tree regression. The models’ effectiveness was evaluated using root-mean-square error and mean absolute percentage error. In most instances, predictions utilizing PATSPG exhibited comparable or superior performance to PATPPG (i.e., SPG Rest ± 12.4 mmHg vs. PPG Rest ± 13.7 mmHg for RSME, and SPG 8% vs. PPG 9% for MAPE). Furthermore, incorporating an additional feature, namely the previous SBP value, resulted in reduced prediction errors for both signals in multiple model configurations (i.e., SPG Rest ± 12.4 mmHg to ±3.7 mmHg for RSME, and SPG Rest 8% to 3% for MAPE). These preliminary tests of SPG underscore the remarkable potential of this novel signal in PAT-based blood pressure predictions. Subsequent studies involving a larger cohort of test subjects and advancements in the SPG acquisition system hold promise for further improving the effectiveness of this newly explored signal in blood pressure monitoring.

Cervical percutaneous interferential current stimulation improves citric acid cough tests in patients with Parkinson’s disease on medication

Aspiration pneumonia is the leading cause of death in patients with Parkinson’s disease. The incidence of silent aspiration is high in such patients owing to decreased pharyngeal and laryngeal sensation; thus, interventions for this condition may help prevent pneumonia. In this single-arm, open-label study, we used a cervical percutaneous interferential current stimulation device to activate pharyngeal and laryngeal sensory nerves. We evaluated its effectiveness in patients with Hoehn–Yahr stages 2–4 Parkinson’s disease. The primary endpoint was the proportion of patients with a normal cough reflex after consuming 1% citric acid at the end of the intervention compared with baseline measurements. In total, 25 patients received neck percutaneous interferential current stimulation for 20 min twice weekly for 8 weeks. Afterward, the proportion of patients with a normal cough reflex after 1% citric acid consumption increased significantly (p = 0.001), whereas other indicators, such as tongue pressure, peak expiratory flow, and penetration or aspiration during videofluoroscopic examination, remained unchanged. A longer duration of illness, higher Unified Parkinson’s Disease Rating Scale total scores, and higher levodopa equivalent daily doses were significantly associated with improved cough test outcomes. Hence, cervical percutaneous interferential current stimulation significantly improved cough reflexes and may improve silent aspiration. Trial Registration: Japan Registry of Clinical Trials, jRCTs062220013, first registered 09/05/2022.

Plasma and interstitial fluid antibiotic levels of subcutaneously implanted compounded florfenicol calcium sulfate beads in New Zealand White rabbits (Oryctolagus cuniculus).

To determine antibiotic levels in plasma and interstitial fluid (ISF) after SC placement of compounded florfenicol (FF) calcium sulfate beads (CSBs) in New Zealand White rabbits (Oryctolagus cuniculus). 6 juvenile female rabbits (n = 5 treatment and 1 control). An ultrafiltration probe and CSBs were placed SC in 6 rabbits (n = 5 for FF CSBs and 1 for control CSBs). Plasma (3, 6, 12, 24, and 48 hours and 7, 14, and 21 days) and ISF (daily for 21 days) samples were collected, and FF was measured by HPLC for pharmacokinetic analysis. Hematology, biochemistry, and histopathology were assessed. Means ± SD for the area under the curve, maximum concentration, time of maximum concentration, terminal half-life, and mean residence time to the last data point for plasma and ISF were 16.63 ± 8.16 and 17,902 ± 7,564 h·µg/mL, 0.79 ± 0.38 and 245 ± 223 µg/mL, 2.90 ± 0.3 and 59 ± 40 hours, 30.81 ± 16.9 and 27.3 ± 9.39 hours, 23.4 ± 10 and 73.7 ± 13 hours, respectively. Plasma FF was < 2 µg/mL at all time points. The ISF FF remained > 8 μg/mL for 109.98 to 231.58 hours. One rabbit death occurred during treatment, but the cause of death was undetermined. Local tissue inflammation was present, but no clinically significant systemic adverse effects were found on hematology, biochemistry, or histopathology in the remaining rabbits. Florfenicol CSBs maintained antibiotic concentrations in ISF at levels likely to be effective against bacteria sensitive to > 8 µg/mL for 5 to 10 days while maintaining low (< 2 µg/mL) plasma levels. Florfenicol CSBs may be effective for local antibiotic treatment in rabbit abscesses.

Targeting the autophagy-miRNA axis in prostate cancer: toward novel diagnostic and therapeutic strategies.

Since prostate cancer is one of the leading causes of cancer-related death, a better understanding of the molecular pathways guiding its development is imperative. A key factor in prostate cancer is autophagy, a cellular mechanism that affects both cell survival and death. Autophagy is essential in maintaining cellular homeostasis. Autophagy is a physiological mechanism wherein redundant or malfunctioning cellular constituents are broken down and recycled. It is essential for preserving cellular homeostasis and is implicated in several physiological and pathological conditions, including cancer. Autophagy has been linked to metastasis, tumor development, and treatment resistance in prostate cancer. The deregulation of miRNAs related to autophagy appears to be a crucial element in the etiology of prostate cancer. These miRNAs influence the destiny of cancer cells by finely regulating autophagic mechanisms. Numerous investigations have emphasized the dual function of specific miRNAs in prostate cancer, which alter autophagy-related pathways to function as either tumor suppressors or oncogenes. Notably, miRNAs have been linked to the control of autophagy and the proliferation, apoptosis, and migration of prostate cancer cells. To create customized therapy approaches, it is imperative to comprehend the dynamic interplay between autophagy and miRNAs in prostate cancer. The identification of key miRNAs provides potential diagnostic and prognostic markers. Unraveling the complex network of lncRNAs, like PCA3, also expands the repertoire of molecular targets for therapeutic interventions. This review explores the intricate interplay between autophagy and miRNAs in prostate cancer, focusing on their regulatory roles in cellular processes ranging from survival to programmed cell death.

Theoretical Exploration of the Antioxidant Activity, Chemopreventive, and Antineoplastic Potentials of Molecules Present in Morinda lucida, Momordica charantia, and Vernonanthura polyanthes

Cancer is one of the leading causes of death worldwide and one of the top four causes of premature death in most countries. Several studies have shown that secondary metabolites found in medicinal plants have anticancer, antimutagenic, anti-genotoxic, and chemopreventive effects. Ethnobotany knowledge points to Morinda lucida, Momordica charantia, and Vernonanthura polyanthes as anticancer plants, turning them into promising candidates for cancer treatment. This study analyzed M. lucida, M. charantia, and V. polyanthes compounds to identify potential antioxidant, chemopreventive, and anticancer agents through in silico analysis. We performed pharmacokinetics, biological activities, and toxicological predictions besides molecular docking. Theoretical calculations on thermodynamic grounds of the antioxidant properties were determined using density functional theory. The molecules damnacanthal, momordicin I, and quercetin-3-[Formula: see text]-rutinoside identified in M. lucida, M. charantia, and V. polyanthes, respectively, presented good anticancer potential and were chosen for the molecular docking study and DFT calculations. According to Lipinski’s criteria, damnacanthal, momordicin I, and quercetin-3-[Formula: see text]-rutinoside were classified as potential drugs, especially for the pharmacokinetics criteria. Damnacanthal and momordicin I had high absorption in the gastrointestinal treatment, while quercetin-3-[Formula: see text]-rutinoside had low absorption. These compounds also demonstrated antineoplastic, antimutagenic, and cancer-preventive activity, according to the in silico analysis. In this sense, damnacanthal, momordicin I, and quercetin-3-[Formula: see text]-rutinoside were chosen to test their potential interactions with the beta estrogen receptor, vascular endothelial growth factor receptor 2, and xanthine dehydrogenase, respectively, and intermolecular interactions were determined. Regarding the antioxidant potential of the structures, two different mechanisms were scrutinized with the help of their respective molecular descriptors, such as hydrogen atom transfer (HAT) and one-electron transfer (ET). In conclusion, this computational study revealed that damnacanthal, momordicin I, and quercetin-3-[Formula: see text]rutinoside are promising chemoprotective and anticancer molecules with favorable pharmacokinetics and toxicological properties.

Historical Control Data of Spontaneous Pathological Findings in C57BL/6J Mice Used in 18-Month Dietary Carcinogenicity Assays.

A retrospective analysis in C57BL6/J mice used in dietary carcinogenicity studies was performed to determine the survival rate, causes of death and incidences of spontaneous non-tumoral and tumoral findings. Data were collected from 1600 mice from control dose groups of sixteen 18-month carcinogenicity assays performed between 2003 and 2021 at the same test facility with similar environmental conditions and experimental procedures. The survival rate was high in both sexes (81%-85%) and the causes of humane euthanasia or death were mainly non-tumoral (chronic ulcerative dermatitis, atrial thrombosis). Benign tumors were more frequent than malignant tumors and females were more affected than males. Pituitary gland adenoma in females, lymphoma, bronchioloalveolar adenoma, and harderian gland adenoma in both sexes were the most common tumors. Systemic amyloidosis, the most frequent non-tumoral lesion, was observed variably across studies without sex predilection. The analysis by cohort (3 time periods of 6 years) showed a tendency toward higher incidences of lymphoma and pituitary gland adenoma and lower incidences of amyloidosis over time. The results presented here provide for the first time a robust set of control historical data in untreated C57BL/6J mice kept for 18 months contributing to build in depth knowledge of this animal model.

Canine Euthanasia’s Trend Analysis during Thirty Years (1990–2020) in Italy: A Veterinary Hospital as Case Study

This study aimed to investigate changes in the number of, and reasons for, requests for dogs’ euthanasia over the last thirty years. Data (breed, age, gender, neuter status, manner, and cause of death) from dogs’ euthanasia registered between 1990 and 2020 in a small animals’ veterinary hospital were analyzed. The overall period examined has been split into two terms (T1 = 1990–2004 and T2 = 2005–2020) considering the introduction and enforcement of Law 189/2004. During the whole period examined, a significant increasing trend in euthanasia cases has been recorded (p = 0.027). Comparing the two terms, we observed significant differences regarding variables such as age, breed, reproductive status, and ownership. The number of euthanized dogs was significantly higher in T1 than in T2. Dogs euthanized in T2 were older than dogs in T1. A high percentage of the euthanized dogs were crossbred and stray dogs. Additionally, the number of neutered/spayed dogs was significantly higher. Regarding the cause of death, a significantly higher percentage of neoplastic processes was detected in T2. The data here reported suggest a potential influence of Law 189/2004. This law in Italy has proven to be a legal milestone that has influenced the decision-making process between euthanasia and natural death.

Machine Learning-Based Prediction of Suicidal Thinking in Adolescents by Derivation and Validation in 3 Independent Worldwide Cohorts: Algorithm Development and Validation Study.

Suicide is the second-leading cause of death among adolescents and is associated with clusters of suicides. Despite numerous studies on this preventable cause of death, the focus has primarily been on single nations and traditional statistical methods. This study aims to develop a predictive model for adolescent suicidal thinking using multinational data sets and machine learning (ML). We used data from the Korea Youth Risk Behavior Web-based Survey with 566,875 adolescents aged between 13 and 18 years and conducted external validation using the Youth Risk Behavior Survey with 103,874 adolescents and Norway's University National General Survey with 19,574 adolescents. Several tree-based ML models were developed, and feature importance and Shapley additive explanations values were analyzed to identify risk factors for adolescent suicidal thinking. When trained on the Korea Youth Risk Behavior Web-based Survey data from South Korea with a 95% CI, the XGBoost model reported an area under the receiver operating characteristic (AUROC) curve of 90.06% (95% CI 89.97-90.16), displaying superior performance compared to other models. For external validation using the Youth Risk Behavior Survey data from the United States and the University National General Survey from Norway, the XGBoost model achieved AUROCs of 83.09% and 81.27%, respectively. Across all data sets, XGBoost consistently outperformed the other models with the highest AUROC score, and was selected as the optimal model. In terms of predictors of suicidal thinking, feelings of sadness and despair were the most influential, accounting for 57.4% of the impact, followed by stress status at 19.8%. This was followed by age (5.7%), household income (4%), academic achievement (3.4%), sex (2.1%), and others, which contributed less than 2% each. This study used ML by integrating diverse data sets from 3 countries to address adolescent suicide. The findings highlight the important role of emotional health indicators in predicting suicidal thinking among adolescents. Specifically, sadness and despair were identified as the most significant predictors, followed by stressful conditions and age. These findings emphasize the critical need for early diagnosis and prevention of mental health issues during adolescence.

Identifying p56lck SH2 Domain Inhibitors Using Molecular Docking and In Silico Scaffold Hopping

Bacterial infections are the second-leading cause of death, globally. The prevalence of antibacterial resistance has kept the demand strong for the development of new and potent drug candidates. It has been demonstrated that Src protein tyrosine kinases (TKs) play an important role in the regulation of inflammatory responses to tissue injury, which can trigger the onset of several severe diseases. We carried out a search for novel Src protein TK inhibitors, commencing from reported highly potent anti-bacterial compounds obtained using the Mannich reaction, using a combination of e-pharmacophore modeling, virtual screening, ensemble docking, and core hopping. The top-scoring compounds from ligand-based virtual screening were modified using protein structure-based design approaches, and their binding to the Src homology-2 domain of p56lck TK was predicted using ensemble molecular docking. We have prepared a database of 202 small molecules and have identified six novel top hits that can be subjected to further investigation. We have also performed in silico ADMET property prediction for the hit compounds. This combined computer-aided drug design approach can serve as a starting point for identifying novel TK inhibitors that could be further subjected to in vitro studies and validation of antimicrobial activity.

Effects of a Tai Chi rehabilitation program implemented using a hybrid online and offline mode on oxidative stress and inflammatory responses in patients with coronary heart disease: a randomized controlled trial

BackgroundCoronary heart disease (CHD) is the leading cause of death in both developed and many developing countries. Exercise training is a fundamental component of cardiac rehabilitation programs for patients with CHD. This study aims to investigate the effects of a Tai Chi rehabilitation program, which is provided through a hybrid online and offline mode, on oxidative stress and inflammatory responses in patients with CHD.MethodsA total of 34 patients with coronary heart disease were randomly assigned to two groups: an experiment group (n = 14, age 62.07 ± 9.076 years) and a control group (n = 20, age 61.90 ± 9.700 years). The experiment group underwent a 12-week Tai Chi cardiac rehabilitation program (TCCRP), while the control group followed a conventional exercise rehabilitation program (CERP) consisting of 1-h sessions, 3 times per week, for a total of 36 sessions. Participants were studied at baseline and post-intervention. The main assessments include the levels of Malondialdehyde (MDA), Superoxide dismutase (SOD), Tumor necrosis factor (TNF-α) and Interleukin-10 (IL − 10) in blood samples. Pearson correlation analysis was used, and the differences between the two groups were subsequently tested using two-way repeated ANOVA. Statistical significance was defined as a two-sided p-value of &amp;lt;0.05.ResultsThe key finding of the study reveals that MDA was significantly reduced by 1.027 nmoL/mL. Additionally, the TCCRP showed significant improvements in SOD and IL-10, with values of 10.110 U/mL and 2.441 pg./mL, respectively. Notably, a significant positive correlation was found between SOD and IL-10 (r = 0.689, p = 0.006), while MDA showed a significant positive correlation with TNF-a (r = 0.542, p = 0.045). In contrast, the ECRP group only showed a significant improvement in SOD.ConclusionThe study conducted a 12-week program on TCCRP, which utilized a hybrid online and offline model for individuals with coronary heart disease. The program showed promising results in alleviating oxidative stress and inflammation, possibly by regulating the balance between oxidative and antioxidative factors, as well as pro-inflammatory and anti-inflammatory factors.

A panel of four plasma amino acids is a promising biomarker for newly diagnosed bladder cancer

BackgroundMetastasis and recurrence are the main causes of death in post-operative bladder cancer (BC), emphasizing the importance of exploring early-stage diagnostic markers. Serum biomarkers constitute a promising diagnostic approach for asymptomatic stage cancer as they are non-invasive, have high accuracy and low cost. AimsTo correlate concentrations of plasma amino acids with BC progression to assess their utility as an early-stage diagnostic. MethodsNewly diagnosed BC patients (n=95) and normal controls (n=96) were recruited during the period from 1 December 2018 to 30 December 2020. General and food frequency questionnaires established their basic information and dietary intake data. Venous blood samples were collected from fasting subjects and used to detect levels of plasma amino acids by liquid chromatography-mass spectrometry. Verification was performed on the GSE13507 transcriptome gene expression matrix of BC from Gene Expression Omnibus (GEO) database. ResultsEleven amino acids have been identified as altered in the plasma of newly diagnosed BC patients compared to controls (P < 0.05). Adjusted by gender, education, smoking and other factors, plasma ornithine level (OR = 0.256, 95% CI: 0.104 ∼ 0.630) is a protective factor for BC, plasma levels of methionine (OR = 3.460, 95% CI: 1.384 ∼ 8.651), arginine (OR = 3.851, 95% CI: 1.542 ∼ 9.616), and glutamate (OR = 3.813, 95% CI: 1.543 ∼ 9.419) are all risk factors for BC. ROC analysis demonstrated that the combination of plasma ornithine, methionine, arginine and glutamate could accurately diagnose BC (AUC = 0.84, 95% CI: 0.747 ∼ 0.833). In addition, the mRNA level of arginase 1 was decreased (P < 0.05), while the inducible nitric oxide synthase was increased significantly, which may be linked with the disturbance of arginine metabolism in BC patients. Further analysis of GEO database confirmed the role of arginine metabolism. ConclusionA biomarker panel containing four amino acids may provide a feasible strategy for the early diagnosis of BC. However, further validation is required through prospective studies.

A Comparison Study on the Metabolites in PC-3, RWPE-1, and Chrysin-Treated PC-3 Cells

Prostate cancer is frequently diagnosed and the leading cause of death in men worldwide. Prostate-specific antigen (PSA) blood tests and biopsies are the primary methods for diagnosing prostate cancer; however, their accuracy is less than 50%. Therefore, there is a need to develop diagnostic tests that minimize patient discomfort during examination and adequate biomarkers that are more accurate, sensitive, and specific for the detection of prostate cancer. This study investigated the application of metabolomics to identify biomarkers in prostate cancer biofluids. In addition, changes in prostate cancer metabolite levels induced by chrysin, a natural anticancer compound, were evaluated and compared with those in non-treated prostate cancer cells. Gas chromatography-mass spectrometry (GC-MS)-based metabolomic profiling was performed to investigate the differences in metabolic alterations among prostate cancer, normal prostate, and chrysin-treated prostate cancer cells. Pairwise comparisons of the extracellular fluid metabolomes were performed using principal component analysis (PCA), partial least squares–discriminant analysis (PLS-DA), and Student’s t-test. The results revealed significantly different patterns among the metabolite groups, including alcohols, amino acids, carboxylic acids, organic acids, sugars, and urea. The RWPE-1- and chrysin-treated PC-3 (PC-3 Chr) cell groups showed similar tendencies for 23 metabolites, while the groups showed significant differences from the PC-3 group. Most amino acids showed higher concentrations in PC-3 cells than in the normal cell line RWPE-1 cells and PC-3 Chr cells. Our results revealed that GC-MS might be an effective diagnostic tool to detect prostate cancer and contribute to finding new tumor markers for prostate cancer as the basis for new ideas.

Multiple myeloma patients with a long remission after autologous hematopoietic stem cell transplantation

Autologous stem cell transplantation (autoHCT) is considered standard of care for newly diagnosed multiple myeloma (MM). Although most patients eventually progress after autoHCT, a small proportion achieve a durable response. In this retrospective study we included 1576 patients, 244 (15%) of whom were long-term responders (LTR), defined as having a progression-free survival (PFS) of ≥8 years after transplant. Patients in the LTR group were younger than the non-LTR group (median age 58.4 vs. 59.5 years; p = 0.012), less likely to have high-risk cytogenetics (4% vs. 14%; p < 0.001), more often had <50% bone marrow plasma cells (67% vs. 58%; p = 0.018) and R-ISS stage I disease (43% vs. 34%). More patients in the LTR group received post-transplant maintenance (63% vs. 52%; p = 0.002). Patients in the LTR group had higher rates of complete response (CR) at day100 (41% vs. 27%; p < 0.001) and at best post-transplant response (70% vs. 37%; p < 0.001), compared to the non-LTR group. Patients in the LTR groups had a median PFS of 169.3 months and the median overall survival (OS) had not been reached. The leading cause of death in the LTR was disease progression. In conclusion, 15% of patients in the cohort were LTR after upfront autoHCT, with distinct characteristics and a median PFS of more than 14 years.

Potential suicide risk among the college student population: machine learning approaches for identifying predictors and different students’ risk profiles

BackgroundSuicide is one of the leading causes of death among young people and university students. Research has identified numerous socio-demographic, relational, and clinical factors as potential predictors of suicide risk, and machine learning techniques have emerged as promising ways to improve risk assessment.ObjectiveThis cross-sectional observational study aimed at identifying predictors and college student profiles associated with suicide risk through a machine learning approach.MethodsA total of 3102 students were surveyed regarding potential suicide risk, socio-demographic characteristics, academic career, and physical/mental health and well-being. The classification tree technique and the multiple correspondence analysis were applied to define students’ profiles in terms of suicide risk and to detect the main predictors of such a risk.ResultsAmong the participating students, 7% showed high potential suicide risk and 3.8% had a history of suicide attempts. Psychological distress and use of alcohol/substance were prominent predictors of suicide risk contributing to define the profile of high risk of suicide: students with significant psychological distress, and with medium/high-risk use of alcohol and psychoactive substances. Conversely, low psychological distress and low-risk use of alcohol and substances, together with religious practice, represented the profile of students with low risk of suicide.ConclusionsMachine learning techniques could hold promise for assessing suicide risk in college students, potentially leading to the development of more effective prevention programs. These programs should address both risk and protective factors and be tailored to students’ needs and to the different categories of risk.

PFAS and their association with the increased risk of cardiovascular disease in postmenopausal women.

Cardiovascular diseases (CVD) are one of the major causes of death globally. In addition to traditional risk factors such as unhealthy lifestyles (smoking, obesity, sedentary) and genetics, common environmental exposures, including persistent environmental contaminants, may also influence cardiovascular disease risk. Per- and polyfluoroalkyl substances (PFAS) are a class of highly fluorinated chemicals used in household consumer and industrial products known to persist in our environment for years, causing health concerns that are now linked to endocrine disruptions and related outcomes in women, including interference of the cardiovascular and reproductive systems. In postmenopausal women, higher levels of PFAS are observed than in premenopausal women due to the cessation of menstruation, which is crucial for PFAS excretion. Because of these findings, we explored the association between Perfluorooctanoic acid (PFOA), Perfluorooctane sulfonate (PFOS), Perfluorobutanesulfonic acid (PFBS) in postmenopausal women from our previously established CVD study. We used liquid chromatography with tandem mass spectrometry (LC-MS-MS), supported by machine learning approaches, and the detection and quantification of serum metabolites and proteins. Here, we show that PFOS can be a good predictor of coronary artery disease, while PFOA can be an intermediate predictor of coronary microvascular disease. We also found that the PFAS levels in our study are significantly associated with inflammation-related proteins. Our findings may provide new insight into the potential mechanisms underlying the PFAS-induced risk of cardiovascular diseases in this population.