RESUMO
BACKGROUND: Evidence suggests a possible link between diabetes and gastric cancer risk, but the findings remain inconclusive, with limited studies in the Asian population. We aimed to assess the impact of diabetes and diabetes duration on the development of gastric cancer overall, by anatomical and histological subtypes. METHODS: A pooled analysis was conducted using 12 prospective studies included in the Asia Cohort Consortium. Among 558 981 participants (median age 52), after a median follow-up of 14.9 years and 10.5 years, 8556 incident primary gastric cancers and 8058 gastric cancer deaths occurred, respectively. Cox proportional hazard regression models were used to estimate study-specific hazard ratios (HRs) and 95% confidence intervals (CIs) and pooled using random-effects meta-analyses. RESULTS: Diabetes was associated with an increased incidence of overall gastric cancer (HR 1.15, 95% CI 1.06-1.25). The risk association did not differ significantly by sex (women vs men: HR 1.31, 95% CI 1.07-1.60 vs 1.12, 1.01-1.23), anatomical subsites (noncardia vs cardia: 1.14, 1.02-1.28 vs 1.17, 0.77-1.78) and histological subtypes (intestinal vs diffuse: 1.22, 1.02-1.46 vs 1.00, 0.62-1.61). Gastric cancer risk increased significantly during the first decade following diabetes diagnosis (HR 4.70, 95% CI 3.77-5.86), and decreased with time (nonlinear p < .01). Positive associations between diabetes and gastric cancer mortality were observed (HR 1.15, 95% CI 1.03-1.28) but attenuated after a 2-year time lag. CONCLUSION: Diabetes was associated with an increased gastric cancer incidence regardless of sex, anatomical subsite, or subtypes of gastric cancer. The risk of gastric cancer was particularly high during the first decade following diabetes diagnosis.
Assuntos
Diabetes Mellitus , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/epidemiologia , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Incidência , Masculino , Feminino , Ásia/epidemiologia , Pessoa de Meia-Idade , Diabetes Mellitus/epidemiologia , Diabetes Mellitus/mortalidade , Fatores de Risco , Estudos Prospectivos , Estudos de Coortes , Idoso , AdultoRESUMO
BACKGROUND: The family history of gastric cancer holds important implications for cancer surveillance and prevention, yet existing evidence predominantly comes from case-control studies. We aimed to investigate the association between family history of gastric cancer and gastric cancer risk overall and by various subtypes in Asians in a prospective study. METHODS: We included 12 prospective cohorts with 550,508 participants in the Asia Cohort Consortium. Cox proportional hazard regression was used to estimate study-specific adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between family history of gastric cancer and gastric cancer incidence and mortality, then pooled using random-effects meta-analyses. Stratified analyses were performed for the anatomical subsites and histological subtypes. RESULTS: During the mean follow-up of 15.6 years, 2258 incident gastric cancers and 5194 gastric cancer deaths occurred. The risk of incident gastric cancer was higher in individuals with a family history of gastric cancer (HR 1.44, 95% CI 1.32-1.58), similarly in males (1.44, 1.31-1.59) and females (1.45, 1.23-1.70). Family history of gastric cancer was associated with both cardia (HR 1.26, 95% CI 1.00-1.60) and non-cardia subsites (1.49, 1.35-1.65), and with intestinal- (1.48, 1.30-1.70) and diffuse-type (1.59, 1.35-1.87) gastric cancer incidence. Positive associations were also found for gastric cancer mortality (HR 1.30, 95% CI 1.19-1.41). CONCLUSIONS: In this largest prospective study to date on family history and gastric cancer, a familial background of gastric cancer increased the risk of gastric cancer in the Asian population. Targeted education, screening, and intervention in these high-risk groups may reduce the burden of gastric cancer.
Assuntos
Neoplasias Gástricas , Humanos , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/epidemiologia , Neoplasias Gástricas/genética , Masculino , Feminino , Incidência , Ásia/epidemiologia , Estudos Prospectivos , Pessoa de Meia-Idade , Fatores de Risco , Idoso , Adulto , Seguimentos , Predisposição Genética para DoençaRESUMO
The female predominance of gallbladder cancer (GBC) has led to a hypothesis regarding the hormone-related aetiology of GBC. We aimed to investigate the association between female reproductive factors and GBC risk, considering birth cohorts of Asian women. We conducted a pooled analysis of 331,323 women from 12 cohorts across 4 countries (China, Japan, Korea, and Singapore) in the Asia Cohort Consortium. Cox proportional hazard models were used to estimate the hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) to assess the association between reproductive factors (age at menarche, parity, age at first delivery, breastfeeding, and age at menopause) and GBC risk. We observed that a later age at menarche was associated with an increased risk of GBC (HR 1.4, 95% CI 1.16-1.70 for 17 years and older vs. 13-14 years), especially among the cohort born in 1940 and later (HR 2.5, 95% CI 1.50-4.35). Among the cohort born before 1940, women with a later age at first delivery showed an increased risk of GBC (HR 1.56, 95% CI 1.08-2.24 for 31 years of age and older vs. 20 years of age and younger). Other reproductive factors did not show a clear association with GBC risk. Later ages at menarche and at first delivery were associated with a higher risk of GBC, and these associations varied by birth cohort.
Assuntos
Neoplasias da Vesícula Biliar , Menarca , Humanos , Feminino , Neoplasias da Vesícula Biliar/epidemiologia , Neoplasias da Vesícula Biliar/etiologia , Pessoa de Meia-Idade , Fatores de Risco , Adulto , Ásia/epidemiologia , Idoso , Estudos de Coortes , História Reprodutiva , Modelos de Riscos Proporcionais , Menopausa , Fatores Etários , Adolescente , ParidadeRESUMO
Previous studies have investigated the association between reproductive factors and lung cancer risk; however, findings have been inconsistent. In order to assess this association among Asian women, a total of 308,949 female participants from 11 prospective cohorts and four Asian countries (Japan, Korea, China, and Singapore) were included. Cox proportional hazards regression models were used to estimate the hazard ratios (HR) and 95% confidence intervals (CIs). A total of 3,119 primary lung cancer cases and 2247 lung cancer deaths were identified with a mean follow-up of 16.4 years. Parous women had a lower risk of lung cancer incidence and mortality as compared with nulliparous women, with HRs of 0.82 (95% CI = 0.70-0.96) and 0.78 (95% CI = 0.65-0.94). The protective association of parity and lung cancer incidence was greater among ever-smokers (HR = 0.66, 95% CI = 0.49-0.87) than in never-smokers (HR = 0.90, 95% CI = 0.74-1.09) (P-interaction = 0.029). Compared with age at first delivery ≤20 years, older age at first delivery (21-25, ≥26 years) was associated with a lower risk of lung cancer incidence and mortality. Women who ever used hormone replacements had a higher likelihood of developing non-small cell lung cancer (HR = 1.31, 95% CI = 1.02-1.68), compared to those who never used hormone replacements. Future studies are needed to assess the underlying mechanisms, the relationships within these female reproductive factors, and the potential changes in smoking habits over time.
Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Gravidez , Feminino , Humanos , Incidência , Estudos Prospectivos , Neoplasias Pulmonares/epidemiologia , Ásia/epidemiologia , Hormônios , Fatores de Risco , Modelos de Riscos ProporcionaisRESUMO
BACKGROUND: The birth cohort effect has been suggested to influence the rate of breast cancer incidence and the trends of associated reproductive and lifestyle factors. We conducted a cohort study to determine whether a differential pattern of associations exists between certain factors and breast cancer risk based on birth cohorts. METHODS: This was a cohort study using pooled data from 12 cohort studies. We analysed associations between reproductive (menarche age, menopause age, parity and age at first delivery) and lifestyle (smoking and alcohol consumption) factors and breast cancer risk. We obtained hazard ratios (HRs) with 95% confidence intervals (CIs) using the Cox proportional hazard regression analysis on the 1920s, 1930s, 1940s and 1950s birth cohorts. RESULTS: Parity was found to lower the risk of breast cancer in the older but not in the younger birth cohort, whereas lifestyle factors showed associations with breast cancer risk only among the participants born in the 1950s. In the younger birth cohort group, the effect size was lower for parous women compared to the other cohort groups (HR [95% CI] 0.86 [0.66-1.13] compared to 0.60 [0.49-0.73], 0.46 [0.38-0.56] and 0.62 [0.51-0.77]). Meanwhile, a higher effect size was found for smoking (1.45 [1.14-1.84] compared to 1.25 [0.99-1.58], 1.06 [0.85-1.32] and 0.86 [0.69-1.08]) and alcohol consumption (1.22 [1.01-1.48] compared to 1.10 [0.90-1.33], 1.15 [0.96-1.38], and 1.07 [0.91-1.26]). CONCLUSION: We observed different associations of parity, smoking and alcohol consumption with breast cancer risk across various birth cohorts.
Assuntos
Neoplasias da Mama , Gravidez , Feminino , Humanos , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/etiologia , Coorte de Nascimento , Estudos de Coortes , Japão , Fatores de Risco , Estilo de Vida , China , República da CoreiaRESUMO
Body fatness is considered a probable risk factor for biliary tract cancer (BTC), whereas cholelithiasis is an established factor. Nevertheless, although obesity is an established risk factor for cholelithiasis, previous studies of the association of body mass index (BMI) and BTC did not take the effect of cholelithiasis fully into account. To better understand the effect of BMI on BTC, we conducted a pooled analysis using population-based cohort studies in Asians. In total, 905 530 subjects from 21 cohort studies participating in the Asia Cohort Consortium were included. BMI was categorized into four groups: underweight (<18.5 kg/m2 ); normal (18.5-22.9 kg/m2 ); overweight (23-24.9 kg/m2 ); and obese (25+ kg/m2 ). The association between BMI and BTC incidence and mortality was assessed using hazard ratios (HR) and 95% confidence intervals (CIs) by Cox regression models with shared frailty. Mediation analysis was used to decompose the association into a direct and an indirect (mediated) effect. Compared to normal BMI, high BMI was associated with BTC mortality (HR 1.19 [CI 1.02-1.38] for males, HR 1.30 [1.14-1.49] for females). Cholelithiasis had significant interaction with BMI on BTC risk. BMI was associated with BTC risk directly and through cholelithiasis in females, whereas the association was unclear in males. When cholelithiasis was present, BMI was not associated with BTC death in either males or females. BMI was associated with BTC death among females without cholelithiasis. This study suggests BMI is associated with BTC mortality in Asians. Cholelithiasis appears to contribute to the association; and moreover, obesity appears to increase BTC risk without cholelithiasis.
Assuntos
Neoplasias do Sistema Biliar , Colelitíase , Masculino , Feminino , Humanos , Obesidade/complicações , Obesidade/epidemiologia , Sobrepeso/epidemiologia , Fatores de Risco , Estudos de Coortes , Ásia/epidemiologia , Neoplasias do Sistema Biliar/epidemiologia , Colelitíase/complicações , Colelitíase/epidemiologia , Índice de Massa CorporalRESUMO
INTRODUCTION: Although lung cancer prediction models are widely used to support risk-based screening, their performance outside Western populations remains uncertain. This study aims to evaluate the performance of 11 existing risk prediction models in multiple Asian populations and to refit prediction models for Asians. METHODS: In a pooled analysis of 186,458 Asian ever-smokers from 19 prospective cohorts, we assessed calibration (expected-to-observed ratio) and discrimination (area under the receiver operating characteristic curve [AUC]) for each model. In addition, we developed the "Shanghai models" to better refine risk models for Asians on the basis of two well-characterized population-based prospective cohorts and externally validated them in other Asian cohorts. RESULTS: Among the 11 models, the Lung Cancer Death Risk Assessment Tool yielded the highest AUC (AUC [95% confidence interval (CI)] = 0.71 [0.67-0.74] for lung cancer death and 0.69 [0.67-0.72] for lung cancer incidence) and the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial Model had good calibration overall (expected-to-observed ratio [95% CI] = 1.06 [0.90-1.25]). Nevertheless, these models substantially underestimated lung cancer risk among Asians who reported less than 10 smoking pack-years or stopped smoking more than or equal to 20 years ago. The Shanghai models were found to have marginal improvement overall in discrimination (AUC [95% CI] = 0.72 [0.69-0.74] for lung cancer death and 0.70 [0.67-0.72] for lung cancer incidence) but consistently outperformed the selected Western models among low-intensity smokers and long-term quitters. CONCLUSIONS: The Shanghai models had comparable performance overall to the best existing models, but they improved much in predicting the lung cancer risk of low-intensity smokers and long-term quitters in Asia.
Assuntos
Neoplasias Pulmonares , Masculino , Humanos , Neoplasias Pulmonares/diagnóstico , Fumantes , Estudos Prospectivos , China/epidemiologia , Pulmão , Fatores de Risco , Medição de Risco , Detecção Precoce de CâncerRESUMO
Viruses are microscopic biological entities that can quickly invade and multiply in a living organism. Each year, over 36,000 people die and nearly 400 million are infected with the dengue virus (DENV). Despite dengue being an endemic disease, no targeted and effective antiviral peptide resource is available against the dengue species. Antiviral peptides (AVPs) have shown tremendous ability to fight against different viruses. Accelerating antiviral drug discovery is crucial, particularly for RNA viruses. DDX3X, a vital cell component, supports viral translation and interacts with TRPV4, regulating viral RNA metabolism and infectivity. Its diverse signaling pathway makes it a potential therapeutic target. Our study focuses on inhibiting viral RNA translation by blocking the activity of the target gene and the TRPV4-mediated Ca2+ cation channel. Six major proteins from camel milk were first extracted and split with the enzyme pepsin. The antiviral properties were then analyzed using online bioinformatics programs, including AVPpred, Meta-iAVP, AMPfun, and ENNAVIA. The stability of the complex was assessed using MD simulation, MM/GBSA, and principal component analysis. Cytotoxicity evaluations were conducted using COPid and ToxinPred. The top ten AVPs, determined by optimal scores, were selected and saved for docking studies with the GalaxyPepDock tools. Bioinformatics analyses revealed that the peptides had very short hydrogen bond distances (1.8 to 3.6 Å) near the active site of the target protein. Approximately 76% of the peptide residues were 5-11 amino acids long. Additionally, the identified peptide candidates exhibited desirable properties for potential therapeutic agents, including a net positive charge, moderate toxicity, hydrophilicity, and selectivity. In conclusion, this computational study provides promising insights for discovering peptide-based therapeutic agents against DENV.
Assuntos
Vírus da Dengue , Dengue , Humanos , Peptídeos Antimicrobianos , Antivirais/farmacologia , Antivirais/uso terapêutico , Antivirais/química , RNA Helicases DEAD-box/metabolismo , RNA Helicases DEAD-box/farmacologia , Dengue/tratamento farmacológico , Vírus da Dengue/genética , Peptídeos/farmacologia , Peptídeos/química , Peptídeos/metabolismo , RNA Viral/genética , Canais de Cátion TRPV , Replicação ViralRESUMO
Around 30% of acute myeloid leukemia (AML) patients have triggering mutations in Feline McDonough Sarcoma (FMS)-like tyrosine kinase 3 (FLT3), which has been suggested as a possible therapeutic candidate for AML therapy. Many tyrosine kinase inhibitors are available and have a wide variety of applications in the treatment of cancer by inhibiting subsequent steps of cell proliferation. Therefore, our study aims to identify effective antileukemic agents against FLT3 gene. Initially, well-known antileukemic drug candidates have been chosen to generate a structure-based pharmacophore model to assist the virtual screening of 217,77,093 compounds from the Zinc database. The final hits compounds were retrieved and evaluated by docking against the target protein, where the top four compounds have been selected for the analysis of ADMET. Based on the density functional theory (DFT), the geometry optimization, frontier molecular orbital (FMO), HOMO-LUMO, and global reactivity descriptor values have been evaluated that confirming a satisfactory profile and reactivity order for the selected candidates. In comparison to control compounds, the docking results revealed that the four compounds had substantial binding energies (-11.1 to -11.5 kcal/mol) with FLT3. The physicochemical and ADMET (adsorption, distribution, metabolism, excretion, toxicity) prediction results corresponded to the bioactive and safe candidates. Molecular dynamics (MD) confirmed the better binding affinity and stability compared to gilteritinib as a potential FLT3 inhibitor. In this study, a computational approach has been performed that found a better docking and dynamics score against target proteins, indicating potent and safe antileukemic agents, furthermore in-vivo and in-vitro investigations are recommended.Communicated by Ramaswamy H. Sarma.
Assuntos
Leucemia Mieloide Aguda , Simulação de Dinâmica Molecular , Humanos , Animais , Gatos , Simulação de Acoplamento Molecular , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/uso terapêutico , Tirosina Quinase 3 Semelhante a fms/metabolismo , Tirosina Quinase 3 Semelhante a fms/uso terapêutico , Leucemia Mieloide Aguda/tratamento farmacológico , Inibidores de Proteínas Quinases/químicaRESUMO
Importance: Despite evidence of an association between reproductive factors and endometrial cancer risk, prospective studies have been conducted mainly in non-Asian countries. Objective: To assess the association between reproductive factors, such as number of deliveries, age at menarche, or menopause, and endometrial cancer risk. Design, Setting, and Participants: This cohort study used pooled individual data from 13 prospective cohort studies conducted between 1963 and 2014 in the Asia Cohort Consortium. Participants were Asian women. Data analysis was conducted from September 2019 to April 2023. Exposures: Reproductive factors were assessed using a questionnaire in each cohort. Main Outcomes and Measures: The main outcome was time to incidence of endometrial cancer. A Cox proportional hazards model was used to calculate hazard ratios (HRs) and 95% CIs. Results: A total of 1005 endometrial cancer cases were detected among 332â¯625 women (mean [SD] age, 54.3 [10.4] years) during a mean (SD) of 16.5 (6.4) years of follow-up. Increasing number of deliveries was associated with a decreased endometrial cancer risk in a dose-response manner (≥5 deliveries vs nulliparous [reference]: HR, 0.37; 95% CI, 0.26-0.53; P for trend < .001). Compared with menarche at younger than 13 years, menarche at 17 years or older had an HR of 0.64 (95% CI, 0.48-0.86; P for trend < .001). Late menopause (age ≥55 years) showed an HR of 2.84 (95% CI, 1.78-4.55; P for trend < .001) compared with the youngest age category for menopause (<45 years). Age at first delivery, hormone therapy, and breastfeeding were not associated with endometrial cancer risk. Conclusions and Relevance: This large pooled study of individual participant data found that late menarche, early menopause, and a higher number of deliveries were significantly associated with a lower risk of endometrial cancer. These convincing results from Asian prospective studies add to the growing body of evidence for the association between reproductive factors and endometrial cancer.
Assuntos
Neoplasias do Endométrio , Humanos , Feminino , Gravidez , Pessoa de Meia-Idade , Estudos Prospectivos , Estudos de Coortes , Neoplasias do Endométrio/epidemiologia , Neoplasias do Endométrio/etiologia , História Reprodutiva , ParidadeRESUMO
Importance: Smoking causes considerable noncommunicable diseases, perinatal morbidity, and mortality. Objective: To investigate the associations of population-level tobacco-control policies with health outcomes. Data Sources: PubMed, EMBASE, Web of Science, Cumulated Index to Nursing and Allied Health Literature, and EconLit were searched from inception to March 2021 (updated on 1 March 2022). References were manually searched. Study Selection: Studies reporting on associations of population-level tobacco control policies with health-related outcomes were included. Data were analyzed from May to July 2022. Data Extraction and Synthesis: Data were extracted by 1 investigator and cross-checked by a second investigator. Analyses were conducted using the Preferred Reporting Items for Systematic Reviews and Meta-analyses reporting guideline. Main Outcomes and Measures: The primary outcomes were respiratory system disease (RSD), cardiovascular disease (CVD), cancer, mortality, hospitalization, and health care utilization. The secondary outcomes were adverse birth outcomes, such as low birth weight and preterm birth. Random-effects meta-analysis was used to estimate pooled odds ratios (ORs) and 95% CIs. Results: Of 4952 records identified, 144 population-level studies were included in the final analysis; 126 studies (87.5%) were of high or moderate quality. The most frequently reported policies were smoke-free legislation (126 studies), followed by tax or price increases (14 studies), multicomponent tobacco control programs (12 studies), and a minimum cigarette purchase age law (1 study). Smoke-free legislation was associated with decreased risk of all CVD events (OR, 0.90; 95% CI, 0.86-0.94), RSD events (OR, 0.83; 95% CI, 0.72-0.96), hospitalization due to CVD or RSD (OR, 0.91; 95% CI, 0.87-0.95), and adverse birth outcomes (OR, 0.94; 95% CI, 0.92-0.96). These associations persisted in all sensitivity and subgroup analyses, except for the country income category, for which a significant reduction was only observed in high-income countries. In meta-analysis, there was no clear association of tax or price increases with adverse health outcomes. However, for the narrative synthesis, all 8 studies reported statistically significant associations between tax increases and decreases in adverse health events. Conclusions and Relevance: In this systematic review and meta-analysis, smoke-free legislation was associated with significant reductions in morbidity and mortality related to CVD, RSD, and perinatal outcomes. These findings support the need to accelerate the implementation of smoke-free laws to protect populations against smoking-related harm.
Assuntos
Doenças Cardiovasculares , Complicações na Gravidez , Nascimento Prematuro , Gravidez , Feminino , Recém-Nascido , Humanos , Controle do Tabagismo , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/prevenção & controleRESUMO
Lung cancer is the primary reason of cancer deaths worldwide, and the percentage of death rate is increasing step by step. There are chances of recovering from lung cancer by detecting it early. In any case, because the number of radiologists is limited and they have been working overtime, the increase in image data makes it hard for them to evaluate the images accurately. As a result, many researchers have come up with automated ways to predict the growth of cancer cells using medical imaging methods in a quick and accurate way. Previously, a lot of work was done on computer-aided detection (CADe) and computer-aided diagnosis (CADx) in computed tomography (CT) scan, magnetic resonance imaging (MRI), and X-ray with the goal of effective detection and segmentation of pulmonary nodule, as well as classifying nodules as malignant or benign. But still, no complete comprehensive review that includes all aspects of lung cancer has been done. In this paper, every aspect of lung cancer is discussed in detail, including datasets, image preprocessing, segmentation methods, optimal feature extraction and selection methods, evaluation measurement matrices, and classifiers. Finally, the study looks into several lung cancer-related issues with possible solutions.
Assuntos
Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Pulmão/patologia , Tomografia Computadorizada por Raios X/métodos , Diagnóstico por Computador/métodos , Tórax , Interpretação de Imagem Radiográfica Assistida por Computador/métodosRESUMO
BACKGROUND: This study was performed to investigate the association between body mass index (BMI) and gastric cancer in East and Southeast Asia where most of gastric cancer is non-cardia gastric cancer. METHODS: On the basis of 8,997 gastric cancer cases among the Asia Cohort Consortium participants from China, Japan, Korea, and Singapore (N = 538,835), we assessed gastric cancer risk according to BMI by calculating hazard ratios (HR) and 95% confidence intervals (CI) using the Cox proportional hazard regression model. RESULTS: A U-shaped associations between BMI and gastric cancer risk were observed. Gastric cancer risks in underweight group (<18.5 kg/m2) and in obesity group (≥27.5 kg/m2) were higher than reference BMI group (23-24.9 kg/m2; HR, 1.15; 95% CI, 1.05-1.25 for underweight; HR, 1.12; 95% CI, 1.03-1.22 for obesity, respectively). The associations of underweight and obesity with gastric cancer risk were consistent in the analyses for non-cardia gastric cancer, intestinal-type gastric cancer, and late-onset gastric cancer. No significant association of underweight and obesity with the risk of cardia gastric cancer, diffuse-type gastric cancer, and early-onset gastric cancer was observed. In addition, we found that the U-shaped association between BMI and gastric cancer risk remained in nonsmokers, while only underweight was related to increased gastric cancer risk in smokers. CONCLUSIONS: BMI has a U-shaped association with gastric cancer risk in East and Southeast Asian population, especially for the non-cardia gastric cancer, intestinal-type gastric cancer, and late-onset gastric cancer. IMPACT: Future studies with consideration of anatomic location and histology of gastric cancer are needed to establish the association of underweight as well as obesity with gastric cancer risk.
Assuntos
Neoplasias Intestinais , Neoplasias Gástricas , Índice de Massa Corporal , Humanos , Obesidade/complicações , Obesidade/epidemiologia , Fatores de Risco , Neoplasias Gástricas/epidemiologia , Neoplasias Gástricas/patologia , MagrezaRESUMO
Importance: Marital status has been shown to be associated with mortality, but evidence in Asian populations is limited. Objective: To examine the association of marital status with total and cause-specific mortality. Design, Setting, and Participants: This cohort study included individual participant data from 16 prospective studies in the Asia Cohort Consortium conducted between 1963 and 2015. Asian participants with complete information on marital and vital status were included. Study-specific hazard ratios (HRs) and 95% CIs were estimated using Cox proportional hazards model and then pooled using a random-effects meta-analysis. The analysis began in February 2021 and ended in August 2021. Exposures: Marital status. Main Outcomes and Measures: All-cause and cause-specific mortality. Results: Of 623â¯140 participants (326â¯397 women [52.4%] and 296â¯743 men [47.6%]; mean [SD] age, 53.7 [10.2] years; mean [SD] follow-up time, 15.5 [6.1] years), 123â¯264 deaths were ascertained. Compared with married individuals, those who were unmarried had pooled HRs of 1.15 (95% CI, 1.07-1.24) for total mortality, 1.12 (95% CI, 1.03-1.22) for cerebrovascular disease mortality, 1.20 (95% CI, 1.09-1.31) for coronary heart disease mortality, 1.17 (95% CI, 1.07-1.28) for circulatory system diseases mortality, 1.06 (95% CI, 1.01-1.11) for cancer mortality, 1.14 (95% CI, 1.05-1.23) for respiratory diseases mortality, and 1.19 (95% CI, 1.05-1.34) for external causes of death. Positive associations with total mortality were also observed for those who were single (HR, 1.62; 95% CI, 1.41-1.86), separated (HR, 1.35; 95% CI, 1.13-1.61), divorced (HR, 1.38; 95% CI, 1.13-1.69), and widowed (HR, 1.09; 95% CI, 1.04-1.13). In subgroup analyses, the positive association persisted across baseline health conditions, and the risk of death was more pronounced among men or people younger than 65 years. Conclusions and Relevance: This large pooled cohort study of individual participant data provides strong evidence that being unmarried, as well as belonging to the unmarried subcategories, was positively associated with total and cause-specific mortality. Investment of targeted social support services might need to be considered in light of the mortality differences between married and unmarried individuals.
Assuntos
Estudos de Coortes , Ásia/epidemiologia , Causas de Morte , Feminino , Humanos , Masculino , Estado Civil , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
Colorectal cancer (CRC) is the second most common cause of death worldwide, affecting approximately 1.9 million individuals in 2020. Therapeutics of the disease are not yet available and discovering a novel anticancer drug candidate against the disease is an urgent need. Thymidylate synthase (TS) is an important enzyme and prime precursor for DNA biosynthesis that catalyzes the methylation of deoxyuridine monophosphate (dUMP) to deoxythymidine monophosphate (dTMP) that has emerged as a novel drug target against the disease. Elevated expression of TS in proliferating cells promotes oncogenesis as well as CRC. Therefore, this study aimed to identify potential natural anticancer agents that can inhibit the activity of the TS protein, subsequently blocking the progression of colorectal cancer. Initially, molecular docking was implied on 63 natural compounds identified from Catharanthus roseus and Avicennia marina to evaluate their binding affinity to the desired protein. Subsequently, molecular dynamics (MD) simulation, ADME (Absorption, Distribution, Metabolism, and Excretion), toxicity, and quantum chemical-based DFT (density-functional theory) approaches were applied to evaluate the efficacy of the selected compounds. Molecular docking analysis initially identified four compounds (PubChem CID: 5281349, CID: 102004710, CID: 11969465, CID: 198912) that have better binding affinity to the target protein. The ADME and toxicity properties indicated good pharmacokinetics (PK) and toxicity ability of the selected compounds. Additionally, the quantum chemical calculation of the selected molecules found low chemical reactivity indicating the bioactivity of the drug candidate. The global descriptor and HOMO-LUMO energy gap values indicated a satisfactory and remarkable profile of the selected molecules. Furthermore, MD simulations of the compounds identified better binding stability of the compounds to the desired protein. To sum up, the phytoconstituents from two plants showed better anticancer activity against TS protein that can be further developed as an anti-CRC drug.
Assuntos
Antineoplásicos , Avicennia , Catharanthus , Neoplasias Colorretais , Antineoplásicos/química , Antineoplásicos/farmacologia , Avicennia/metabolismo , Catharanthus/metabolismo , Neoplasias Colorretais/tratamento farmacológico , Humanos , Simulação de Acoplamento Molecular , Timidilato Sintase/metabolismoRESUMO
In our previous study, we revealed the ameliorative therapeutic effect of dexamethasone (Dex) for Lupus nephritis lesions in the MRL/MpJ-Fas lpr/lpr (Lpr) mouse model. The female Lpr mice developed a greater number of mediastinal fat-associated lymphoid clusters (MFALCs) and inflammatory lung lesions compared to the male mice. However, the effect of Dex, an immunosuppressive drug, on both lung lesions and the development of MFALCs in Lpr mice has not been identified yet. Therefore, in this study, we compared the development of lung lesions and MFALCs in female Lpr mice that received either saline (saline group "SG") or dexamethasone (dexamethasone group "DG") in drinking water as a daily dose along with weekly intraperitoneal injections for 10 weeks. Compared to the SG group, the DG group showed a significant reduction in the levels of serum anti-dsDNA antibodies, the size of MFALCs, the degree of lung injury, the area of high endothelial venules (HEVs), and the number of proliferating and immune cells in both MFALCs and the lungs. A significant positive correlation was observed between the size of MFALCs and the cellular aggregation in the lungs of Lpr mice. Therefore, this study confirmed the ameliorative effect of Dex on the development of lung injury and MFALCs via their regressive effect on both immune cells' proliferative activity and the development of HEVs. Furthermore, the reprogramming of MFALCs by targeting immune cells and HEVs may provide a therapeutic strategy for autoimmune-disease-associated lung injury.
Assuntos
Doenças Autoimunes , Lesão Pulmonar , Nefrite Lúpica , Animais , Anticorpos Antinucleares , Dexametasona/farmacologia , Dexametasona/uso terapêutico , Modelos Animais de Doenças , Feminino , Humanos , Lesão Pulmonar/patologia , Nefrite Lúpica/patologia , Masculino , Mediastino/patologia , CamundongosRESUMO
Background: Although previous meta-analyses have suggested a dose-response relationship between body mass index (BMI) and thyroid cancer risk, limited evidence has been presented about Asian populations. To assess this association among Asian populations, where underweight is more prevalent than in other regions, a pooled analysis from the Asia Cohort Consortium was conducted. Methods: Baseline height and weight were measured in five cohorts and self-reported in eight cohorts. Thyroid cancer incidence was ascertained by linkage to local cancer registries. Cohorts were treated as a stratum in the Cox proportional hazard model to estimate the pooled hazard ratios (HRs) and corresponding confidence intervals (CIs) from the estimates for each cohort. All analyses were stratified by sex. Results: A total of 538,857 men and women from 13 cohorts from mainland China, Korea, Japan, and Singapore were included in the analysis. During a mean of 15.1 years of follow-up, 1132 thyroid cancer cases were ascertained. Using a BMI of 18.5-22.9 kg/m2 as a reference, an elevated risk of thyroid cancer was observed for groups with a BMI between 25 and 29.9 kg/m2 (HR: 1.31, [CI: 0.95-1.80]) and a BMI of 30 kg/m2 and greater (HR: 1.84, [CI: 0.89-3.81]) in men. Thyroid cancer risk was elevated in women with a BMI of 23-24.9 kg/m2 (HR: 1.26, [CI: 1.07-1.48]). The HRs for 5-U increment of BMI showed a linear association among men (HR: 1.25, [CI 1.10-1.55]) but not among women (HR: 1.07, [CI: 0.97-1.18]). Although the overall thyroid cancer risk was lower among underweight men and women, the papillary cancer risk may be elevated among underweight men (HR: 2.24, [CI: 0.75-6.66]). Conclusion: While higher BMI is associated with an elevated risk of thyroid cancer in both men and women, the association of underweight BMI may differ by sex and histological subtype.
Assuntos
Neoplasias da Glândula Tireoide , Ásia/epidemiologia , Índice de Massa Corporal , Estudos de Coortes , Feminino , Humanos , Incidência , Masculino , Fatores de Risco , Neoplasias da Glândula Tireoide/epidemiologiaRESUMO
BACKGROUND: Accumulating evidence suggests that consuming coffee may lower the risk of death, but evidence regarding tea consumption in Asians is limited. We examined the association between coffee and tea consumption and mortality in Asian populations. METHODS: We used data from 12 prospective cohort studies including 248 050 men and 280 454 women from the Asia Cohort Consortium conducted in China, Japan, Korea and Singapore. We estimated the study-specific association of coffee, green tea and black tea consumption with mortality using Cox proportional-hazards regression models and the pooled study-specific hazard ratios (HRs) using a random-effects model. RESULTS: In total, 94 744 deaths were identified during the follow-up, which ranged from an average of 6.5 to 22.7 years. Compared with coffee non-drinkers, men and women who drank at least five cups of coffee per day had a 24% [95% confidence interval (CI) 17%, 29%] and a 28% (95% CI 19%, 37%) lower risk of all-cause mortality, respectively. Similarly, we found inverse associations for coffee consumption with cardiovascular disease (CVD)-specific and cancer-specific mortality among both men and women. Green tea consumption was associated with lower risk of mortality from all causes, CVD and other causes but not from cancer. The association of drinking green tea with CVD-specific mortality was particularly strong, with HRs (95% CIs) of 0.79 (0.68, 0.91) for men and 0.78 (0.68, 0.90) for women who drank at least five cups per day of green tea compared with non-drinkers. The association between black tea consumption and mortality was weak, with no clear trends noted across the categories of consumption. CONCLUSIONS: In Asian populations, coffee consumption is associated with a lower risk of death overall and with lower risks of death from CVD and cancer. Green tea consumption is associated with lower risks of death from all causes and CVD.
Assuntos
Doenças Cardiovasculares , Neoplasias , Ásia/epidemiologia , Café/efeitos adversos , Estudos de Coortes , Feminino , Humanos , Masculino , Modelos de Riscos Proporcionais , Estudos Prospectivos , Fatores de Risco , Inquéritos e Questionários , CháRESUMO
Breast cancer is now the most frequently diagnosed cancer in women, and its percentage is gradually increasing. Optimistically, there is a good chance of recovery from breast cancer if identified and treated at an early stage. Therefore, several researchers have established deep-learning-based automated methods for their efficiency and accuracy in predicting the growth of cancer cells utilizing medical imaging modalities. As of yet, few review studies on breast cancer diagnosis are available that summarize some existing studies. However, these studies were unable to address emerging architectures and modalities in breast cancer diagnosis. This review focuses on the evolving architectures of deep learning for breast cancer detection. In what follows, this survey presents existing deep-learning-based architectures, analyzes the strengths and limitations of the existing studies, examines the used datasets, and reviews image pre-processing techniques. Furthermore, a concrete review of diverse imaging modalities, performance metrics and results, challenges, and research directions for future researchers is presented.
RESUMO
Cotton rats (Sigmodon hispidus, CRs) are commonly used as animal models in biomedical research. However, the reproductive characteristics and ovarian development in the CRs has not been widely investigated. We have previously shown that female CRs, in particular, show several unique phenotypes associated with the urogenital system, such as chronic kidney disease and pyometra. Our investigation revealed unique morphologies in CR ovaries, particularly in oocytes. Cotton rat ovaries at 6-8 weeks of age were obtained from the Hokkaido Institute of Public Health, and their sections analyzed by light microscopy and transmission electron microscopy. Although the general histology and folliculogenesis of CR ovaries were similar to those of other experimental rodents, multi-oocyte follicles (MOFs) and double nucleated oocytes (DNOs) were also observed. Although MOFs were found at all stages of follicular development, a greater frequency of MOFs was observed in the primary and secondary stages. However, DNOs tended to be frequently observed in primordial follicles. Almost all MOF oocytes and a few DNOs possessed a clear zona pellucida, expressed DEAD (Asp-Glu-Ala-Asp) box polypeptide 4 and Forkhead box protein 2, a representative marker of oocytes and follicular epithelial cells. Thus, our investigations revealed the unique phenotypes of the CR ovary. As MOFs and DNOs are occasionally observed in human patients with infertility, the CR would be a useful animal model to study for gaining a better understanding of folliculogenesis and oocytogenesis, as well as their abnormalities in humans and other animals.