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Lung Cancer (Amsterdam, Netherlands) Oct 2023ROS1 fusions are well treatable aberrations in NSCLC. Besides solvent-front mutations (SFM) in resistance to targeted therapy, small-scale ROS1 mutations are largely...
BACKGROUND
ROS1 fusions are well treatable aberrations in NSCLC. Besides solvent-front mutations (SFM) in resistance to targeted therapy, small-scale ROS1 mutations are largely unknown. We exploratively analyzed the clinical and molecular characteristics of small-scale ROS1 mutations in NSCLC patients without activating ROS1 fusions or SFMs.
METHODS
Next-generation sequencing was performed on tissue samples from NSCLC patients within the Network Genomic Medicine. Patients with ROS1 fusions and SFMs were excluded. We analyzed clinical characteristics of patients harboring small-scale ROS1-mutations, ROS1- and co-occurring mutations, and their response to systemic therapy.
RESULTS
Of 10,396 patients analyzed, 101 (1.0%) patients harbored small-scale ROS1 mutations. Most patients were male (73.3%) and smokers (96.6%). Nearly half of the patients presented with squamous-cell carcinoma (SqCC, 40.4%). Most mutations were transversions (50.5%), and 66% were in the kinase domain. Besides TP53 mutations (65.3%), KRAS (22.8%), EGFR (5.9%), PIK3CA (9.9%) and FGFR1-4 mutations (8.9%) co-occurred. In 10 (9.9%) patients, ROS1 mutation was the only aberration detected. Median overall survival (mOS) differed significantly in patients with or without KRAS co-mutations (9.7 vs 21.5 months, p = 0.02) and in patients treated with or without immune-checkpoint blockade (ICB) during treatment (21.5 vs 4.4 months, p = 0.003).
CONCLUSION
The cohort's clinical characteristics contrasted ROS1-fused cohorts. Co-occurrence of KRAS mutations led to shortened survival and patients benefited from ICB. Our data does not support the idea of ROS1 small-scale mutations as strong oncogenic drivers in NSCLC, but rather as relevant bystanders altering the efficacy of treatment approaches.
Topics: Humans; Male; Female; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Protein-Tyrosine Kinases; Proto-Oncogene Proteins p21(ras); Proto-Oncogene Proteins; Mutation
PubMed: 37579577
DOI: 10.1016/j.lungcan.2023.107344 -
Journal of Preventive Medicine and... Nov 2020This study conducted an age-period-cohort (APC) analysis of trends in healthy lifestyle behaviors in Japan.
OBJECTIVES
This study conducted an age-period-cohort (APC) analysis of trends in healthy lifestyle behaviors in Japan.
METHODS
We used National Health and Nutrition Survey data on salt intake and prevalence of smoking, drinking, and physical activity between 1995 and 2018 in Japan. Age groups were defined from 20 years to 69 years old in 10-year increments. Cohorts were defined for each age group of each year with a 1-year shift, and cohorts born in 1926-1935 (first cohort) until 1989-1998 (last cohort) were examined. We conducted a Bayesian APC analysis, calculating estimated values for each behavior by age group, period, and cohort.
RESULTS
Estimated salt intake decreased from cohorts born in the 1930s to the 1960s, but increased thereafter in both genders, and the magnitude of increase was larger for men. Estimated smoking prevalence increased in the cohorts starting from the 1930s for men and the 1940s for women, and then decreased starting in the cohorts born in the 1970s for both genders. Although estimated drinking prevalence decreased starting in the cohorts born in approximately 1960 for men, for women it increased until the cohorts born in approximately 1970. Estimated physical activity prevalence decreased starting in the cohorts born in the 1940s in both genders, but the magnitude of decrease was larger for women.
CONCLUSIONS
Trends in cohort effects differed by gender, which might be related to changes in the social environment for women. Improvements in dietary and exercise habits are required in more recently born cohorts of both genders.
Topics: Adult; Age Factors; Aged; Aged, 80 and over; Alcohol Drinking; Bayes Theorem; Cohort Studies; Eating; Exercise; Female; Healthy Lifestyle; Humans; Japan; Male; Middle Aged; Nutrition Surveys; Smoking
PubMed: 33296581
DOI: 10.3961/jpmph.20.159 -
Data in Brief Apr 2020Data from the routine surveillance systems have been extensively used to estimate the incidence of dengue. However, routine surveillance data frequently underestimate...
Data from the routine surveillance systems have been extensively used to estimate the incidence of dengue. However, routine surveillance data frequently underestimate the diseases' incidence. Underreporting of dengue cases is related to the varying spectrum of its clinical presentation, with a large proportion of mild and asymptomatic infections, to its unspecific signs and symptoms, to the limitations of access to health care, and to the performance of the surveillance system itself [1-3]. In order to obtain accurate figures on dengue incidence, a cohort of children and adolescents was set up and followed during four years. The incidence of reported cases was used as a reference for the sample size calculation, which was stratified by age groups. A two-stage procedure was used to select the participants: census tracts were randomly selected, and within each one, a pre-determined number of children of each age group was randomly selected. The parents or legal guardians of the participating children and adolescents provided a written informed consent. In the first home visit, they responded to a questionnaire containing data on socio-demographic characteristics, housing, access to water, sewage, and garbage collection. Also, during the first visit a blood sample of the participating child/adolescent was collected for dengue baseline serology. Beginning in the week after the enrolment, the parent or legal guardian that was designated in the first visit received weekly phone calls for fever surveillance. If the child/adolescent had fever during the week, a nurse was dispatched to the family's home to collect more detailed data on the fever episode and collect a blood sample for dengue diagnosis (IgG, IgM, NS1 and PCR). If the dengue diagnosis was confirmed, a medical appointment was scheduled, and another blood sample for confirmatory tests was collected. It was also agreed that in every anniversary of their participation, they would receive another visit for a blood collection for dengue serology, regardless if they had a fever episode or a confirmed dengue diagnosis during the previous year. This article contains the description of the cohort's dataset. It is associated with the article published in Acta Tropica, under the title "A cohort study to assess the incidence of dengue, Brazil, 2014-2018" [4]. The associated article focused on the seroprevalence and incidence of dengue, and explored some associations between both outcomes and some explanatory variables.
PubMed: 32095494
DOI: 10.1016/j.dib.2020.105266 -
International Journal of Epidemiology Jun 2023Social media represent an unrivalled opportunity for epidemiological cohorts to collect large amounts of high-resolution time course data on mental health. Equally, the...
MOTIVATION
Social media represent an unrivalled opportunity for epidemiological cohorts to collect large amounts of high-resolution time course data on mental health. Equally, the high-quality data held by epidemiological cohorts could greatly benefit social media research as a source of ground truth for validating digital phenotyping algorithms. However, there is currently a lack of software for doing this in a secure and acceptable manner. We worked with cohort leaders and participants to co-design an open-source, robust and expandable software framework for gathering social media data in epidemiological cohorts.
IMPLEMENTATION
Epicosm is implemented as a Python framework that is straightforward to deploy and run inside a cohort's data safe haven.
GENERAL FEATURES
The software regularly gathers Tweets from a list of accounts and stores them in a database for linking to existing cohort data.
AVAILABILITY
This open-source software is freely available at [https://dynamicgenetics.github.io/Epicosm/].
Topics: Humans; Social Media; Software; Algorithms; Data Accuracy; Databases, Factual
PubMed: 36847716
DOI: 10.1093/ije/dyad020 -
PloS One 2016Longitudinal analysis investigates period (P), often as years. Additional scales of time are age (A) and birth cohort (C) Aim of our study was to use ecological APC...
Longitudinal analysis investigates period (P), often as years. Additional scales of time are age (A) and birth cohort (C) Aim of our study was to use ecological APC analysis for women breast cancer incidence and mortality in Germany. Nation-wide new cases and deaths were obtained from Robert Koch Institute and female population from federal statistics, 1999-2008. Data was stratified into ten 5-years age-groups starting 20-24 years, ten birth cohorts starting 1939-43, and two calendar periods 1999-2003 and 2004-2008. Annual incidence and mortality were calculated: cases to 100,000 women per year. Data was analyzed using glm and apc packages of R. Breast cancer incidence and mortality increased with age. Secular rise in breast cancer incidence and decline in mortality was observed for period 1999-2008. Breast cancer incidence and mortality declined with cohorts; cohorts 1950s showed highest incidence and mortality. Age-cohort best explained incidence and mortality followed by age-period-cohort with overall declining trends. Declining age-cohort mortality could be probable. Declining age-cohort incidence would require future biological explanations or rendered statistical artefact. Cohorts 1949-1958 could be unique in having highest incidence and mortality in recent time or future period associations could emerge relatively stronger to cohort to provide additional explanation of temporal change over cohorts.
Topics: Adult; Age Factors; Aged; Breast Neoplasms; Cohort Studies; Female; Germany; Humans; Incidence; Middle Aged; Young Adult
PubMed: 26933878
DOI: 10.1371/journal.pone.0150723 -
Environmental Research Oct 2021Organophosphate insecticides and the herbicide, 2,4-dichlorophenoxyacetic acid (2,4-D) are used to protect crops or control weeds. Pyrethroids are used to manage pests...
BACKGROUND
Organophosphate insecticides and the herbicide, 2,4-dichlorophenoxyacetic acid (2,4-D) are used to protect crops or control weeds. Pyrethroids are used to manage pests both in agriculture and in residences, and to reduce the transmission of insect-borne diseases. Several studies have reported inverse associations between exposure to organophosphates (as a larger class) and birth outcomes but these associations have not been conclusive for pyrethroids or 2,4-D, specifically. We aimed to investigate the association between birth outcomes and urinary biomarkers of pyrethroids, organophosphates and 2,4-D among healthy pregnant women living in New York City.
METHODS
We quantified urinary biomarkers of 2,4-D and of organophosphate and pyrethroid insecticides from 269 women from two cohorts: a) Thyroid Disruption And Infant Development (TDID) and b) Sibling/Hermanos cohort (S/H). We used weighted quantile sum regression and multivariable linear regression models to evaluate the associations between a mixture of urinary creatinine-adjusted biomarker concentrations and birth outcomes of length, birthweight and head circumference, controlling for covariates. We also used linear regression models and further classified biomarkers concentrations into three categories (i: non-detectable; ii: between the limit of detection and median; and iii: above the median) to investigate single pesticides' association with these birth outcomes. Covariates considered were delivery mode, ethnicity, marital status, education, income, employment status, gestational age, maternal age and pre-pregnancy BMI. Analyses were conducted separately for each cohort and stratified by child sex within each cohort.
RESULTS
In TDID cohort, we found a significant inverse association between weighted quantile sum of mixture of pesticides and head circumference among boys. We found that the urinary biomarkers of organophosphate chlorpyrifos, TCPy, and 2,4-D had the largest contribution to the overall mixture effect in the TDID cohort among boys (b = -0.57, 95%CI: -0.92, -0.22) (weights = 0.81 and 0.16 respectively) but not among girls. In the multivariable linear regression models, we found that among boys, for each log unit increase in 3,5,6-trichloro-2-pyridinol (TCPy, metabolite of organophosphate chlorpyrifos) in maternal urine, there was a -0.56 cm decrease in head circumference (95%CI: -0.92, -0.19). Among boys in the TDID cohort, 2,4-D was associated with smaller head circumference in the second (b = -1.57; 95%CI: -2.74, -0.39) and third (b = -1.74, 95%CI: -2.98, -0.49) concentration categories compared to the first. No associations between pyrethroid and organophosphate biomarkers and birth outcomes were observed in girls analyzed in WQS regression or individually in linear regression models in TDID cohort. In the S/H cohort, head circumference increased with higher concentrations of 3-phenoxybenzoic acid (3-PBA, a biomarker of several pyrethroids) (b = 0.53, 95%CI: 0.03, 1.04) among boys and head circumference was lower among girls in the high compared to low category of 2,4-D (b = -2.27, 95%CI: - 3.98, -0.56). Birth length was also positively associated with the highest concentration of 2,4-D compared to the lowest among boys (b = 4.01, 95%CI: 0.02,8.00).
CONCLUSIONS
Weighted quantile sum of pesticides was negatively associated with head circumference among boys in one cohort. Nonetheless, due to directional homogeneity assumption in WQS no positive associations were detected. In linear regression models with individual pesticides, concentrations of TCPy were inversely associated with head circumference in boys and higher concentrations of 2,4-D was inversely associated with head circumference among girls; 2,4-D concentrations were also associated with higher birth length among boys. Concentrations of 3-PBA was positively associated with head circumference among boys.
Topics: 2,4-Dichlorophenoxyacetic Acid; Birth Weight; Child; Chlorpyrifos; Female; Herbicides; Humans; Infant; Infant, Newborn; Insecticides; Male; Maternal Exposure; Parturition; Pregnancy; Pregnant Women; Prenatal Exposure Delayed Effects; Pyrethrins
PubMed: 34174256
DOI: 10.1016/j.envres.2021.111539 -
JAMA Network Open Apr 2023Type 2 diabetes increases the risk of progressive diabetic kidney disease, but reliable prediction tools that can be used in clinical practice and aid in patients'...
IMPORTANCE
Type 2 diabetes increases the risk of progressive diabetic kidney disease, but reliable prediction tools that can be used in clinical practice and aid in patients' understanding of disease progression are currently lacking.
OBJECTIVE
To develop and externally validate a model to predict future trajectories in estimated glomerular filtration rate (eGFR) in adults with type 2 diabetes and chronic kidney disease using data from 3 European multinational cohorts.
DESIGN, SETTING, AND PARTICIPANTS
This prognostic study used baseline and follow-up information collected between February 2010 and December 2019 from 3 prospective multinational cohort studies: PROVALID (Prospective Cohort Study in Patients with Type 2 Diabetes Mellitus for Validation of Biomarkers), GCKD (German Chronic Kidney Disease), and DIACORE (Diabetes Cohorte). A total of 4637 adult participants (aged 18-75 years) with type 2 diabetes and mildly to moderately impaired kidney function (baseline eGFR of ≥30 mL/min/1.73 m2) were included. Data were analyzed between June 30, 2021, and January 31, 2023.
MAIN OUTCOMES AND MEASURES
Thirteen variables readily available from routine clinical care visits (age, sex, body mass index; smoking status; hemoglobin A1c [mmol/mol and percentage]; hemoglobin, and serum cholesterol levels; mean arterial pressure, urinary albumin-creatinine ratio, and intake of glucose-lowering, blood-pressure lowering, or lipid-lowering medication) were selected as predictors. Repeated eGFR measurements at baseline and follow-up visits were used as the outcome. A linear mixed-effects model for repeated eGFR measurements at study entry up to the last recorded follow-up visit (up to 5 years after baseline) was fit and externally validated.
RESULTS
Among 4637 adults with type 2 diabetes and chronic kidney disease (mean [SD] age at baseline, 63.5 [9.1] years; 2680 men [57.8%]; all of White race), 3323 participants from the PROVALID and GCKD studies (mean [SD] age at baseline, 63.2 [9.3] years; 1864 men [56.1%]) were included in the model development cohort, and 1314 participants from the DIACORE study (mean [SD] age at baseline, 64.5 [8.3] years; 816 men [62.1%]) were included in the external validation cohort, with a mean (SD) follow-up of 5.0 (0.6) years. Updating the random coefficient estimates with baseline eGFR values yielded improved predictive performance, which was particularly evident in the visual inspection of the calibration curve (calibration slope at 5 years: 1.09; 95% CI, 1.04-1.15). The prediction model had good discrimination in the validation cohort, with the lowest C statistic at 5 years after baseline (0.79; 95% CI, 0.77-0.80). The model also had predictive accuracy, with an R2 ranging from 0.70 (95% CI, 0.63-0.76) at year 1 to 0.58 (95% CI, 0.53-0.63) at year 5.
CONCLUSIONS AND RELEVANCE
In this prognostic study, a reliable prediction model was developed and externally validated; the robust model was well calibrated and capable of predicting kidney function decline up to 5 years after baseline. The results and prediction model are publicly available in an accompanying web-based application, which may open the way for improved prediction of individual eGFR trajectories and disease progression.
Topics: Male; Adult; Humans; Diabetes Mellitus, Type 2; Glomerular Filtration Rate; Prospective Studies; Renal Insufficiency, Chronic; Disease Progression
PubMed: 37017968
DOI: 10.1001/jamanetworkopen.2023.1870 -
Therapeutics and Clinical Risk... 2022In a lack of similar research, we meant to retrospectively investigate the prognostic significance of pre-chemoradiotherapy (C-CRT) platelet-to-albumin ratio (PAR) on...
PURPOSE
In a lack of similar research, we meant to retrospectively investigate the prognostic significance of pre-chemoradiotherapy (C-CRT) platelet-to-albumin ratio (PAR) on the survival results of locally advanced unresectable pancreatic adenocarcinoma (LAPC) patients.
PATIENTS AND METHODS
The present analysis included 139 LAPC patients who received C-CRT in total. The utility of pre-C-CRT cutoff(s) reshaping survival data was explored using receiver operating characteristic (ROC) curve analysis. The primary and secondary objectives were the associations between PAR levels and overall survival (OS) and progression-free survival (PFS) outcomes.
RESULTS
At a median follow-up of 15.7 months (95% CI: 11.6-19.8), the overall cohort's median and 5-year OS rates were 14.4 months (95% CI: 11.8-17) and 14.7%, respectively, while the corresponding PFS rates were 7.8 months (95% CI: 6.5-9.1) and 11.2%. Because the ROC curve analysis found 4.9 as the optimal PAR cutoff for both OS and PFS [area under the curve (AUC): 75.4%; sensitivity: 72.4%; specificity: 70.3%], we divided the patients into two PAR cohorts: PAR<4.9 (N=60) and PAR≥4.9 (N=79). Comparative analysis per PAR group exhibited significantly worse OS (11.2 vs 18.6 months, and 9.8% vs 20.9% at 5 years, P=0.003) and DFS (7 vs 14.3 months, and 7.6% vs 16.2% at 5 years, P=0.001) with PAR≥4.9 versus PAR<4.9, respectively. In multivariate analysis, the N0 nodal status, CA 19-9≤90 U/mL, and PAR<4.9 were found to be independent predictors of improved OS and PFS.
CONCLUSION
The pre-C-CRT high PAR (≥4.9) robustly and independently prognosticated significantly worse OS and PFS results in inoperable LAPC patients who underwent definitive C-CRT.
PubMed: 35444422
DOI: 10.2147/TCRM.S359553 -
EBioMedicine Aug 2023Although the infant gut microbiota has been extensively studied, comprehensive assessment on the microbiota determinants including technical variables has not been...
BACKGROUND
Although the infant gut microbiota has been extensively studied, comprehensive assessment on the microbiota determinants including technical variables has not been performed in large infant cohorts.
METHODS
We studied the effect of 109 variables on the 16S rRNA gene amplicon-based gut microbiota profiles of infants sampled longitudinally from three weeks to two years of life in the Finnish HELMi birth cohort. Spot faecal samples from both parents were included for intra-family analyses, totalling to 7657 samples from 985 families that were evaluated for beta-diversity patterns using permutational multivariate analysis on Bray-Curtis distances, and differential abundance testing and alpha-diversity for variables of interest. We also assessed the effect of different taxonomic levels and distance methods.
FINDINGS
In time point-specific models, the largest share of variation explained, up to 2-6%, were seen in decreasing order for the DNA extraction batch, delivery mode and related perinatal exposures, defecation frequency and parity/siblings. Variables describing the infant gastrointestinal function were continuously important during the first two years, reflecting changes in e.g., feeding habits. The effect of parity/siblings on infant microbiota was modified by birth mode and exposure to intrapartum antibiotics, exemplifying the tight interlinkage of perinatal factors relevant for infant microbiota research. In total, up to 19% of the biological microbiota variation in the infant gut could be explained. Our results highlight the need to interpret variance partitioning results in the context of each cohort's characteristics and microbiota processing.
INTERPRETATION
Our study provides a comprehensive report of key factors associated with infant gut microbiota composition across the two first years of life in a homogenous cohort. The study highlights possible important future research areas and confounding factors to be considered.
FUNDING
This research was supported by Business Finland, Academy of Finland, Foundation for Nutrition Research and the Doctoral Program in Microbiology and Biotechnology, University of Helsinki, Finland.
PubMed: 37399600
DOI: 10.1016/j.ebiom.2023.104695 -
Gaceta Sanitaria 2021To describe a surveillance and monitoring system based on the analysis of the incidence rate of permanent disability (PD) and premature mortality (PM) in a sample of...
OBJECTIVE
To describe a surveillance and monitoring system based on the analysis of the incidence rate of permanent disability (PD) and premature mortality (PM) in a sample of members of the Spanish Social Security.
METHOD
Study of three birth cohorts (1950-1959, 1960-1969 and 1970-1979) of people affiliated to the general Social Security system, included in the Continuous Sample of Labour Lives, who has been active for at least one day between 2004 and 2015 (N = 753,341). For each cohort, the annual incidence rates of PD and MP were estimated according to occupation and economic activity in women and men.
RESULTS
Between 2004 and 2015 the rates of PI and MP showed higher values in men with respect to women in practically all cohorts of births, occupations and economic activities groups. The trend throughout the observation period was increasing, both in the incidence of PD and PM in men and women, for the three birth cohorts and for all occupational categories.
CONCLUSIONS
The results derived from this work allows the continuous monitoring of the temporal evolution of the incidence of permanent disability and premature mortality in a representative sample of social security affiliates.
Topics: Disabled Persons; Female; Humans; Income; Male; Mortality, Premature; Occupations; Social Security
PubMed: 31959365
DOI: 10.1016/j.gaceta.2019.09.011