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This study is the first attempt to assess the presence of 16 priority polycyclic aromatic hydrocarbons (PAHs) enlisted by the US Environmental Protection Agency in PM2.5 and PM10 from industrial areas of Odisha State, India. During 2017–2018, bimonthly sampling of PM10 and PM2.5 was carried out for 24 h in the industrial and mining areas of Jharsuguda and Angul in Odisha during the pre-monsoon, monsoon, and post monsoon seasons. Highest mean concentration of ∑16PAHs in PM2.5 was observed during the post monsoon (170 ng/m3) period followed by pre-monsoon (48 ng/m3) and monsoon (16 ng/m 3) periods, respectively. A similar trend of ∑16PAHs was also observed in PM10 with higher levels observed during post monsoon (286 ng/m3) followed by pre-monsoon (81 ng/m3) and monsoon (27 ng/m3) seasons. Diagnostic ratios and principal component analysis suggested diesel, gasoline and coal combustion as the major contributors of atmospheric PAH pollution in Odisha. Back trajectory analysis revealed that PAH concentration was affected majorly by air masses originating from the northwest direction traversing through central India. Toxic equivalents ranged between 0.24 and 94.13 ng TEQ/m3. In our study, the incremental lifetime cancer risk ranged between 10–5 and 10–3, representing potential cancer risk.

Purpose: Family may play an important role in Hematopoietic stem cell transplantation (HSCT) recovery; however, little is known about the effect of family functioning on an individual’s health. The purpose of this study was to examine the effect of family cohesion (family functioning) on the trajectory of HSCT recipients’ symptom distress (symptom frequency and symptom bother) before, during, and after HSCT. Methods: Secondary analysis was conducted using data collected from178 individuals who underwent HSCT. Longitudinal parallel-process (LPP) modeling was used to examine how family cohesion and HSCT associated symptoms (symptom frequency and symptom bother) change over time; and how these longitudinal changes relate to each other. Results: The trajectory of family cohesion predicted the trajectories of HSCT associated symptom frequency and bother. HSCT recipients who experienced higher family cohesion at baseline (T1) showed lower symptom frequency (pConclusion: Findings indicate that higher family cohesion predicts decrease in symptom distress over the HSCT trajectory. Interventions aimed at enhancing family cohesion have the potential to lower HSCT recipients’ symptom distress. Further research is needed to understand the critical role of family cohesion and family functioning and their relationship with HSCT symptom distress prevention, early detection, and risk stratification.

Exploring typical and atypical brain developmental trajectories is very important for understanding the normal pace of brain development and the mechanisms by which mental disorders deviate from normal development. A precise and sex‐specific brain age prediction model is desirable for investigating the systematic deviation and individual heterogeneity of disorders associated with atypical brain development, such as autism spectrum disorders. In this study, we used partial least squares regression and the stacking algorithm to establish a sex‐specific brain age prediction model based on T1‐weighted structural magnetic resonance imaging and resting‐state functional magnetic resonance imaging. The model showed good generalization and high robustness on four independent datasets with different ethnic information and age ranges. A predictor weights analysis showed the differences and similarities in changes in structure and function during brain development. At the group level, the brain age gap estimation for autistic patients was significantly smaller than that for healthy controls in both the ABIDE dataset and the healthy brain network dataset, which suggested that autistic patients as a whole exhibited the characteristics of delayed development. However, within the ABIDE dataset, the premature development group had significantly higher Autism Diagnostic Observation Schedule (ADOS) scores than those of the delayed development group, implying that individuals with premature development had greater severity. Using these findings, we built an accurate typical brain development trajectory and developed a method of atypical trajectory analysis that considers sex differences and individual heterogeneity. This strategy may provide valuable clues for understanding the relationship between brain development and mental disorders., We established a sex‐specific brain age prediction model based on T1‐weighted structural magnetic resonance imaging and resting‐state functional magnetic resonance imaging and This model showed good generalization and high robustness on four independent datasets with different ethnic information and age ranges. A predictor weights analysis showed the differences and similarities in changes in structure and function during brain development. Within the ABIDE dataset, the premature development group had significantly higher Autism Diagnostic Observation Schedule (ADOS) scores than those of the delayed development group, implying that individuals with premature development had greater severity.

Objectives We investigated the association between maternal depression trajectories from pregnancy until 2 years postpartum, and problematic internet use in children at nine years of age. Methods A total of 1132 mother-child pairs from the Panel Korea Study for Children were used. Maternal depression was assessed repeatedly using the Kessler scale (K-scale) (during pregnancy, and at 6, 12, and 24 months of age). Problematic internet use was assessed in children 9 years old using the K-scale. The children's behavioral problems were assessed using the Child Behavior Checklist at nine years old. Latent profile analysis was used to identify the group trajectories of maternal depression. We compared the severity of problematic internet use of the children according to the maternal depression trajectories. We also identified behavioral problems in children with problematic internet use in each maternal depression trajectory. Results Trajectory analysis identified three group trajectories of maternal depression: no symptoms (n = 478), mild symptoms (n = 534), and moderate symptoms (n = 120). The mild and moderate maternal depression trajectory groups were more associated with high-risk internet use in 9-year-old children compared to the non-depressed group. In children with high-risk internet use, more severe behavioral problems were reported when their mothers had depression. Conclusion Maternal depression up to two years after childbirth affected problematic internet use in middle childhood.

Introduction Most studies modeling adolescent cigarette smoking trajectories use age as the time axis, possibly obscuring depiction of the natural course of cigarette smoking. We used a simulated example and real data to contrast smoking trajectories obtained from models that used time since smoking onset or calendar time (age) as the time axis. Methods Data were drawn from a longitudinal investigation of 1293 grade 7 students (mean age 12.8 years) recruited from 10 high schools in Montreal, Canada in 1999–2000, who were followed into young adulthood. Cigarette consumption was measured every 3 months during high school, and again at mean ages 20.4 and 24.0. Analyses using time since onset of smoking as the time metric was restricted to 307 incident smokers; analysis using calendar time included 645 prevalent and incident smokers. Smoking status and nicotine dependence (ND) were assessed at mean ages 20.4 and 24.0. Simulated data mimicked the real study during high school. Results Use of different time metrics resulted in different numbers and shapes of trajectories in the simulated and real datasets. Participants in the calendar time analyses reported more ND in young adulthood, reflecting inclusion of 388 prevalent smokers who had smoked for longer durations. Conclusions Choosing the right time metric for trajectory analysis should be balanced against research intent. Trajectory analyses using the time since onset metric depict the natural course of smoking in incident smokers. Those using calendar time offer a snapshot of smoking across ages during a given time period. Implications This study uses simulated and real data to show that trajectory analyses of cigarette smoking that use calendar time (e.g., age) versus time since onset as the time axis metric tell a different story. Trajectory analyses using the time since onset metric depict the natural course of smoking in incident smokers. Those using calendar time offer a snapshot of smoking across ages during a given time period. Choosing the right time metric should be balanced against research intent.

OBJECTIVE To visualize the postoperative clinical course using the comprehensive complication index (CCI) and to propose an early alarming sign for subsequent serious outcomes in perihilar cholangiocarcinoma. BACKGROUND Surgery for this disease carries a high risk of morbidity and mortality. The developmental course of the overall morbidity burden and its clinical utility are unknown. METHODS Patients who underwent major hepatectomy for perihilar cholangiocarcinoma between 2010 and 2019 were reviewed retrospectively. All postoperative complications were evaluated according to the Clavien-Dindo classification (CDC), and the CCI was calculated on a daily basis until postoperative day 14 to construct an accumulating graph as a trajectory. Group-based trajectory modeling was conducted to categorize the trajectory into clinically distinct patterns and the predictive power of early CCI for a subsequent serious course was assessed. RESULTS A total of 4230 complications occurred in the 484 study patients (CDC grade I, n=27; II, n=132; IIIa, n=290; IIIb, n=4; IVa, n=21; IVb, n=1; and V, n=9). The trajectory was categorized into 3 patterns: mild (n=209), moderate (n=235), and severe (n=40) morbidity courses. The 90-day mortality rate significantly differed among the courses: 0%, 0.9%, and 17.5%, respectively (P

It is essential to study the behaviour of soot particles in the engine cylinder, including movement and physical properties during engine operation, for further analysis of performance characteristics and engine emissions. This research aims to determine the size distribution of soot particles near the cylinder wall, leading to soot in lubricating oil. The research was carried out numerically using in-house MATLAB routines to post-process CFD simulation results. In this analysis, the soot particle size was calculated using the Hiroyasu soot formation, Nagle & Strickland-Constable oxidation, and Wersborg soot coagulation models. In addition, the simulation time and computing effort were minimized by using a post-processed soot particle size estimate. According to the findings, soot particles smaller than 50 nm were found in the squish area, especially near the cylinder wall. The average value of the final location of the particles tracked from all zones in the trajectory analysis varies between 0.4 and 3.1% of the magnitude closer to the cylinder wall relative to the particles tracked without the thermophoresis factor.

Genetic background has been considered one of the important contributors to the rate of cognitive decline among patients with Alzheimer's disease (AD). We conducted a 4-year longitudinal follow-up study, recruited 255 AD and 44 mild cognitive impairment (MCI) patients, and used a data-driven trajectory analysis to examine the influence of selected AD risk genes on the age for and the rate of cognitive decline in Han Chinese population. Genotyping of selected single-nucleotide polymorphisms in the APOE, ABCA7, SORL1, BIN1, GAB2, and CD33 genes was conducted, and a Bayesian hierarchical model was fitted to analyze the trajectories of cognitive decline among different genotypes. After adjusting for sex and education years, the APOE e4 allele was associated with an earlier mean change of -2.39 years in the age at midpoint of cognitive decline, the G allele in ABCA7 rs3764650 was associated with an earlier mean change of -1.75 years, and the T allele in SORL1 rs3737529 was associated with a later mean change of 2.6 years. Additionally, the rate of cognitive decline was associated with the APOE e4 allele and SORL1 rs3737529. In summary, APOE and SORL1 might be the most important genetic factors related to cognitive decline in Han Chinese population.

Introduction Management of chronic kidney disease (CKD) entails high medical complexity and often results in high hospitalization burden. There are limited data on the associations of longitudinal hospital utilization patterns with adverse clinical outcomes in individuals with CKD. Methods We derived cumulative all-cause hospitalization trajectory groups using latent class trajectory analysis in 3012 participants of the Chronic Renal Insufficiency Cohort (CRIC) Study who were alive and did not reach end-stage kidney disease (ESKD) within 4 years of study entry. Cox proportional hazards models tested the associations between hospitalization trajectory groups and risks of ESKD and death prior to the onset of ESKD (ESKD-censored death). Results Within 4 years of study entry, there were 5658 hospitalizations among 3012 participants. We identified 3 distinct subgroups of individuals with CKD based on cumulative all-cause hospitalization trajectories over 4 years: low-utilizer (n = 1066), intermediate-utilizer (n = 1802), and high-utilizer (n = 144). High-utilizers represented a patient population of lower socioeconomic status who had a greater prevalence of comorbid conditions and lower kidney function compared with intermediate- and low-utilizers. After the 4-year ascertainment period to form the trajectory subgroups, there were 544 ESKD events and 437 ESKD-censored deaths during a median follow-up time of 5.1 years. Compared with low-utilizers, intermediate-utilizers and high-utilizers were at 1.49-fold (95% confidence interval [CI] 1.22–1.84) and 1.75-fold (95% CI 1.20–2.56) higher risk of ESKD in adjusted analyses, respectively. Compared with low-utilizers, intermediate-utilizers and high-utilizers were at 1.48-fold (95% CI 1.17–1.87) and 2.58-fold (95% CI 1.74–3.83) higher risk of ESKD-censored death in adjusted analyses, respectively. Conclusions Trajectories of cumulative all-cause hospitalization identify subgroups of individuals with CKD who are at high risk of ESKD and death., Graphical abstract

Evidence was limited on trajectory of body mass index (BMI) through adulthood and its association with hypertension. We aimed to evaluate their association by sex in large-scale study. Data were obtained from the China Health and Nutrition Survey (CHNS) from 1991 to 2015. Latent class trajectory analysis (LCTA) was used to capture BMI change trajectories. Hazard risks (HRs) were estimated from Cox proportion hazard regression. Among 14,262 participants (mean age, 38.8; 47.8% men), 5138 hypertension occurred (2687 men and 2451 women) occurred during a mean follow-up 9.6 years. Four body mass trajectory groups were identified as BMI loss, stable, moderate and substantial gain. Appropriately half of participants (48.0%) followed 1 of the 2 BMI gain trajectories, where BMI increased at least 3 kg/m2 overtime. Compared with participants with stable BMI, those gaining BMI substantially had higher risk of hypertension by 65% (HR 1.65, 95% CI 1.45–1.86) in male and 83% (HR 1.83, 95% CI 1.58–2.12) in female. The HRs in BMI loss patterns were 0.74 (0.62–0.89) in men and 0.87 (0.75–1.00) in women. Our findings imply that majority of Chinese adults transited up to a higher BMI level during follow-up. Avoiding excessive weight gain and maintaining stable weight might be important for hypertension prevention.

BackgroundThis study aimed to identify the trajectories of work ability over 16 years preceding the individual pensionable age and to examine the association with retirement timing.MethodsThe study population consisted of 2612 public sector employees from the Finnish Retirement and Aging study and the Finnish Public Sector study. Participants were grouped into ‘no-extension’ (retired at the individual pensionable date or worked no longer than 6 months after that date) and ‘extension’ (worked more than 6 months after individual pensionable age). Trajectories of self-reported work ability score (0–10) in maximum of eight measurement points over 16 years preceding retirement were examined using the group-based latent trajectory analysis. Log-binomial regression was used to analyse the association between trajectory groups and extended employment.ResultsFour stable (‘Stable excellent’, 7%; ‘Stable high’, 62%; ‘Stable medium’, 24%; ‘Low’, 4%) and one decreasing (‘Declining’, 3%) work ability trajectories were identified. After taking into account gender, age, occupational status, marital status and self-rated health, ‘Stable excellent’ trajectory was associated with a higher likelihood of extended employment compared with the ‘Low’ (risk ratio (RR) 2.38, 95% CI 1.21 to 4.68) and to the ‘Declining’ (RR 2.82, 95% CI 1.32 to 6.01) trajectories. There was no difference in retirement timing between ‘Declining’, ‘Low’ and ‘Stable medium’ trajectories.ConclusionWork ability remained relatively stable among majority of the participants over 16 years of follow-up. Stable excellent work ability from mid-life to late career was associated with higher likelihood of extending employment beyond individual pensionable age than those with low or declining work ability.

The Fukushima Daiichi Nuclear Power Station (NPS) accident, which occurred in March 2011, is having long-term effects on children. About 3 years after the accident, we identified three patterns of peer relationship problems and four patterns of emotional symptoms using group-based trajectory modeling. As a result, we reported that different factors might be related to very severe trajectories of peer relationship problems and emotional symptoms. In this study, we used five waves of data from fiscal year (FY) 2011 to FY2015 from the Mental Health and Lifestyle Survey, a detailed survey of the Fukushima Health Management Survey started in FY2011. We analyzed 7013 residents within the government-designated evacuation zone (aged 6–12 years old as of 11 March 2011) with responses to all items of psychological distress in at least one wave from FY2011 and FY2015. We planned this study to describe the trajectories of peer relationship problems and emotional symptoms in children and to examine potential risks and protective factors over the 5 years following the NPS accident. We identified four patterns of peer relationship problems and five patterns of emotional symptoms using latent class growth analysis. For peer relationship problems, male sex, experiencing the NPS explosion and lack of exercise habits were associated with the severe trajectory group. For emotional symptoms, experiencing the NPS explosion, experiencing the tsunami disaster and lack of exercise habits were associated with the severe trajectory group. Exercise habits are very important for the mental health of evacuees after a nuclear disaster.

OBJECTIVE: People with HIV continue to exhibit cognitive symptoms after suppressive antiretroviral therapy (ART). It remains unclear if initiating ART during acute HIV-1 infection (AHI) uniformly improves cognitive outcomes. METHODS: Sixty-seven individuals (96% men, median age 28 years) initiated ART immediately after AHI diagnosis and maintained viral suppression for 6 years. They underwent a four-test neuropsychological battery that measured fine motor speed and dexterity, psychomotor speed, and executive functioning at baseline (pre-ART AHI), weeks 12, 24 and 96, and annually thereafter through week 288. Performances were standardized to calculate an overall (NPZ-4) score and frequencies of impaired cognitive performance (≤-1 SD on at least two tests, or ≤-2 SD on at least one test). Group-based trajectory analysis (GBTA) was applied to identify distinct neuropsychological trajectories modelled from baseline to week 288. Posthoc analyses examined HIV-1 and demographic factors that differed between trajectory subgroups. RESULTS: NPZ-4 scores improved from baseline to week 96 (P

The aim of this study was to determine the predictability of clinical complications by analyzing the perfusion index historical behavior patterns with polynomial group-based trajectory model.

ObjectiveIncreasing numbers of patients are developing rheumatoid arthritis (RA) at an older age, and optimal treatment of patients with elderly-onset RA (EORA) is attracting greater attention. This study aimed to analyze the efficacy and safety of biologic/targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) in EORA and non-EORA elderly patients.MethodsA cohort of patients with RA treated with b/tsDMARDs were retrospectively analyzed. Only patients aged ≥ 60 years were included. Among them, patients who developed RA aged ≥ 60 years were categorized as EORA, whereas those aged < 60 years were categorized as non-EORA elderly. Disease activity was compared between the EORA and non-EORA elderly groups.ResultsIn total, 1040 patients were categorized as EORA and 710 as non-EORA elderly. There were no significant differences in characteristics at baseline between the 2 groups. The proportion of patients with low and high disease activity was comparable at Weeks 2, 22, and 54 between the EORA and the non-EORA elderly group. There were no significant differences in the reasons for the discontinuation of b/tsDMARDs between the 2 groups. Elderly RA onset did not affect changes in Clinical Disease Activity Index (CDAI) and Health Assessment Questionnaire–Disability Index, nor did it affect the reasons for b/tsDMARD discontinuation between the 2 groups. The trajectory analysis on CDAI responses to b/tsDMARDs for 54 weeks identified 3 response patterns. The proportion of patients categorized into each group and CDAI response trajectories to b/tsDMARDs were very similar between EORA and non-EORA elderly patients.ConclusionCDAI response patterns to b/tsDMARDs and HR of adverse events were similar between EORA and non-EORA elderly patients.

INTRODUCTION The optimal ablation approach for persistent atrial fibrillation (AF) remains unclear. METHODS AND RESULTS Objective was to compare the long-term rates of freedom from AF/AT in patients that underwent STAR mapping guided ablation against outcomes of patients undergoing conventional ablation procedures. Patients undergoing ablation for persistent AF as part of the Stochastic Trajectory Analysis of Ranked signals (STAR) mapping study were included. Outcomes following 'pulmonary vein isolation (PVI) plus STAR mapping guided ablation (STAR mapping cohort) were compared to patients undergoing PVI alone ablation during the same time period and also a propensity-matched cohort undergoing PVI plus the addition of complex fractionated electrogram (CFAE) and/or linear ablation ("conventional ablation"). Rates of procedural AF termination and freedom from AF/AT during follow-up were compared. Sixty-five patients were included in both the STAR cohort and propensity matched conventional ablation cohort. AF termination rates were significantly higher in the STAR cohort (51/65, 78.5%) than conventional ablation cohort (10/65, 15.4%) and PVI alone ablation cohort (13/50, 26.0%; STAR cohort vs. other 2 cohorts both p

To identify low back pain (LBP) trajectories from early adolescence through to early adulthood and to investigate whether sustained levels of elevated subclinical C-reactive protein (CRP) are linked with these LBP trajectories. We analysed longitudinal data from 1513 participants who were enrolled in the Raine Study cohort. Data on LBP with impact on daily living and CRP were collected at the ages of 14, 17, 20, and 22. We constructed group-based trajectory models to identify discrete trajectories of LBP with impact. We then evaluated how the CRP trajectories and the LBP with impact trajectories evolved jointly over time using a multi-trajectory analysis. The model identified three LBP trajectories. One subgroup included almost half the participants (46.1%) who had a consistently low probability of LBP. Another subgroup comprising 43.5% of participants had an increasing probability of LBP, while one in ten participants (10.4%) had a decreasing probability of LBP. There were no associations between elevated CRP and LBP trajectory subgroup membership. Although young people follow distinct trajectories of LBP, CRP trajectories do not appear to be a distinguishing factor of the LBP trajectories. Previously reported associations between CRP and LBP may be explained by comorbidity or other factors. Future studies undertaking trajectory analysis should consider comorbidity clusters. Diagnostic: individual cross-sectional studies with the consistently applied reference standard and blinding

The Kingdom of Bahrain announced its first case of COVID-19 infection on February 24, 2020. Since that time, the government has imposed several restrictions such as closures, banning gatherings, and closing border crossings to limit the spread of the pandemic and relieve pressure on the healthcare system. This article provides an overview of the current trajectory of the pandemic in the Kingdom of Bahrain. In addition, the article introduces and applies a methodology to analyze the impact of the interventions and precautionary measures enforced by the government to limit the COVID-19 disease propagation. The results show that most of the enforced precautionary measures were effective in reducing the spread of the disease by a percentage ranging from 20.2% to 41.8%. A religious occasion in Bahrain—involving large gatherings—had increased the spread of the disease by 28.7%. Not enough evidence is found to conclude that reopening interventions had caused the disease to spread again.

Organophosphate esters (OPEs) are contaminants of emerging concern, and studies have concluded that urban areas are a significant source of OPEs. Samples were collected from six ground-based sites located in Chengdu, a typical rapidly developing metropolitan area in Southwest China, and were analyzed for seven OPEs in atmospheric PM 2.5 ( Σ7 OPEs). The concentrations of Σ7 OPEs in PM 2.5 ranged from 5.83 to 6.91 ng m −3 , with a mean of 6.6 ± 3.3 ng m −3 , and the primary pollutants were tris-(2-butoxyethyl) phosphate (TBEP), tri-n-butyl phosphate (TnBP), tris-(2-chloroethyl) phosphate (TCEP) and tris-(2-chloroisopropyl) phosphate (TCPP), which together made up more than 80 % of the Σ7 OPEs. The concentrations of Σ7 OPEs were higher in autumn and winter than in summer. Nonparametric tests showed that there was no significant difference in Σ7 OPE concentrations among the six sampling sites, but the occurrence of unexpectedly high levels of individual OPEs at different sites in autumn might indicate noteworthy emissions. A very strong correlation ( R2 = 0.98, p 0.01) between the OPEs in soil and in PM 2.5 was observed. Backward trajectory analysis indicated that the OPEs in PM 2.5 were mainly affected by local sources. Principal component analysis (PCA) revealed that the OPEs in PM 2.5 were largely sourced from the plastics industry, interior decoration and traffic emission (34.5 %) and the chemical, mechanical and electrical industries (27.8 %), while the positive matrix factorization (PMF) model revealed that the main sources were the plastics industry and indoor source emissions, the food and cosmetics industry and industrial emissions. In contrast to coastal cities, sustained and stable high local emissions in the studied inland city were identified, which is particularly noteworthy. Chlorinated phosphates, especially TCPP and TCEP, had a high content, and their usage and source emissions should be controlled.

Many studies have validated cartilage thickness as a biomarker for knee osteoarthritis (OA); however, few studies investigate beyond cross-sectional observations or comparisons across two timepoints. By characterizing the trajectory of cartilage thickness changes over 8 years in healthy individuals from the OA initiative data set, this study discovers associations between the dynamics of cartilage changes and OA incidence. A fully automated cartilage segmentation and thickness measurement method were developed and validated against manual measurements: mean absolute error = 0.11-0.14 mm (n = 4129 knees) and automatic reproducibility = 0.04-0.07 mm (n = 316 knees). The mean thickness for the medial and lateral tibia (MT, LT), central weight-bearing medial and lateral femur (cMF, cLF), and patella (P) cartilage compartments were quantified for 1453 knees at seven timepoints. Trajectory subgroups were defined per cartilage compartment such as stable, thinning to thickening, accelerated thickening, plateaued thickening, thickening to thinning, accelerated thinning, or plateaued thinning. For tibiofemoral compartments, the stable (22%-36%) and plateaued thinning (22%-37%) trajectories were the most common, with an average initial velocity (μm/month), acceleration (μm/month2 ) for the plateaued thinning trajectories LT: -2.66, 0.0326; MT: -2.49, 0.0365; cMF: -3.51, 0.0509; and cLF: -2.68, 0.041. In the patella compartment, the plateaued thinning (35%) and thickening to thinning (24%) trajectories were the most common, with an average initial velocity, acceleration for each -4.17, 0.0424; 1.95, -0.0835. Knees with nonstable trajectories had higher adjusted odds of OA incidence than stable trajectories: accelerated thickening, accelerated thinning, and plateaued thinning trajectories of the MT had adjusted odds ratio (OR) of 18.9, 5.48, and 1.47, respectively; in the cMF, adjusted OR of 8.55, 10.1, and 2.61, respectively.

Glioblastoma (GBM) is the most common and lethal primary brain tumor. In this study, we aimed to investigate the differentiation states of GBM cells and their clinical relevance. Integrated single-cell RNA-sequencing (scRNA-seq) data and bulk RNA-seq data from GBM samples were used for analysis. Two subsets of GBM cells in distinct differentiation states were characterized, and 498 GBM cell differentiation-related genes (GDRGs) were identified. GDRGs were significantly correlated with immune regulation and metabolic pathways. We classified the GBM patients into two groups based on the expression of GDRGs in tumors and found that the cell differentiation-based classification successfully predicted patient overall survival (OS), immune checkpoint expression and likelihood of immunotherapy response in GBMs. FN1, APOE, RPL7A and GSTM2 were the 4 most significant survival-predicting GDRGs, and patients with different expression levels of each of these genes had distinct survival outcomes. Finally, a nomogram composed of the GDRG signature, age, pharmacotherapy, radiotherapy, IDH mutations and MGMT promoter methylation was generated and validated in two large GBM cohorts to predict GBM prognosis. This study highlights the significant roles of cell differentiation in predicting the clinical outcomes of GBM patients and their potential response to immunotherapy, suggesting promising therapeutic targets for GBM.

Postnatal care is the aspect of maternity care with which women in England are least satisfied. Little is known about first-time mothers’ expectations of postnatal care, or how these expectations relate to their experiences and appraisal of care. Thirty-two first-time mothers took part in a longitudinal qualitative descriptive study, based on two semi-structured interviews—the first in pregnancy, and the second 2 to 3 months after birth. Trajectory analysis was used to identify the thematic patterns in the relationships between postnatal care expectations, needs, experiences, and confidence. Five trajectories were identified, showing that mothers’ satisfaction with postnatal care and confidence were primarily influenced not by the extent to which their expectations were met but the varied extent to which their individual postnatal needs were met. Rapid and responsive assessment of needs both antenatally and postnatally, and appropriate adjustment of care, is key in supporting women effectively at this time.

Purpose Study objectives were to examine: (a) biomarker trajectories (change from presurgical baseline values of Lymphedema index (L‐Dex) units and arm volume difference) and symptom cluster scores 24 months after breast cancer surgery and (b) associations of these objective biomarkers and symptom cluster scores. Patient/treatment characteristics influencing trajectories were also evaluated. Methods A secondary analysis of data from the published interim analysis of a randomized parent study was undertaken using trajectory analysis. Five hundred and eight participants included in the prior analysis with 24 months of postsurgical follow‐up were initially measured with bioelectric impedance spectroscopy (BIS) and tape measure (TM) and completed self‐report measures. Patients were reassessed postsurgery for continuing eligibility and then randomized to either BIS or TM groups and measured along with self‐report data at regular and optional* visits 3, 6,12,15*,18, 21*, and 24‐months. Results Three subclinical trajectories were identified for each biomarker (decreasing, stable, increasing) and symptom cluster scores (stable, slight increase/decrease, increasing). Subclinical lymphedema was identified throughout the 24‐month period by each biomarker. An L‐Dex increase at 15 months in the BIS group was noted. The self‐report sets demonstrated contingency coefficients of 0.20 (LSIDS‐A soft tissue, P = .031) and 0.19 (FACTB+4, P = .044) with the L‐Dex unit change trajectories. Conclusions These data support the need for long‐term (24 months) prospective surveillance with frequent assessments (every 3 months) at least 15 months after surgery. Statistically significant convergence of symptom cluster scores with L‐Dex unit change supports BIS as beneficial in the early identification of subclinical lymphedema., Long‐term (24 months) lymphedema prospective surveillance with frequent assessments (every 3 months) at least through 15‐months post‐surgery is indicated. Convergence of symptom cluster scores with L‐Dex unit change supports Bioelectric Impedance Spectroscopy as beneficial in the early identification of sub‐clinical lymphedema.

In robot-assisted endoscopic nasal surgery, due to the slender and complicated nasal cavity and sinus anatomical structure, the nasal endoscope of robot end-effector is prone to injure surrounding tissues during surgical approaches. In order to improve the movement safety of the endoscope in robot-assisted endoscopic nasal surgery, a path planning method for endoscopic surgical approaches based on medical image pixel map searching is proposed in this paper, and safe surgical paths from the nasal entrance point to the operating areas are obtained. Firstly, through the trajectory analysis of nasal endoscope tip during surgery, the path planning requirements of endoscope tip are analyzed and obtained. Then, considering the slender and complicated anatomy of the nasal cavity, a binarized three-dimensional grid map containing the spatial anatomy of the nasal cavity is constructed based on the patient's CT medical image sequence. The endoscopic surgical approaches are searched and optimized by introducing the A-star algorithm, and safe surgical paths from the nasal entrance point to the operating areas are obtained. Finally, a virtual nasal endoscopy system is developed and tested on a head model containing nasal tissue, and the effectiveness of the planned surgical paths is verified by automatic virtual nasal endoscopy browsing experiment.

This paper presents a design and evaluation of a customized finger prosthesis that generates a natural finger motion. The design of the prosthesis followed two primary requirements: i) The size of the prosthesis should reflect that of an amputee’s finger; ii) the prosthesis should enable the natural finger motion of the amputee. To achieve these aims, two methods were employed: i) An incomplete fourbar mechanism by utilizing the remaining joint of a subject as the joint in the mechanism; ii) a fingertip trajectory analysis in polar coordinates to model the natural finger motion. In this paper, we focused on the design of the finger prosthesis so that the prototype was manufactured based on the finger information of a normal subject before applying it to the actual finger amputee. The performance of the proposed system was verified by intensive experiments for grasping and manipulation with the proposed system.

Objectives Gaining knowledge of dynamic processes of mechanisms underlying mindfulness-based cognitive therapy (MBCT) for recurrent depression could help to improve treatment efficacy. The current study examined the overall course and week-to-week associations of mindfulness and positive/negative affect during MBCT for recurrent depression. Methods Using data from the MOMENT study, 235 patients with recurrent depression in (partial) remission allocated to MBCT were included. Prior to each MBCT session, self-reports were obtained on mindfulness, positive affect, and negative affect. Results Autoregressive latent trajectory (ALT) modeling revealed that, across the MBCT course, larger increases in mindfulness were associated with larger increases in positive affect (r = .80,p < .050). Higher general levels of negative affect were associated with smaller increases in mindfulness over time (r = -.26,p < .001). Week-to-week effects showed no reciprocal cross-lagged effects between mindfulness and positive affect or negative affect, except for positive affect at session 2 which was positively associated with mindfulness at session 3 (r = .11,p < .050). Conclusions The current study supports a positive association in strength of increase between mindfulness and positive affect, while higher general levels of negative affect might be associated with smaller increases of mindfulness during MBCT for recurrent depression. For future research, experience sampling methods (ESMs) are recommended to capture dynamics on a smaller time scale. ALT modeling techniques are advised to be better able to interpret the processes of stability and change during MBCT for recurrent depression.

OBJECTIVE: To examine the hypothesis that PTSD with delayed expression in some cases occurs without subthreshold PTSD symptoms above background levels bridging the gap between the traumatic exposure(s) and the clinical diagnosis.METHODS: We performed systematic searches of peer-reviewed papers in English referenced in Pubmed, Embase, or PsycINFO and ascertained 34 prospective studies of PTSD symptom trajectories identified by latent class growth statistical modeling. Studies with delayed and low-stable trajectories provided appropriate data for this study. We computed the difference between the delayed trajectory PTSD symptom sumscore and the low-stable PTSD sumscore at the observed points in time after the traumatic event(s).RESULTS: In 29 study populations, the latent class growth analyses displayed delayed trajectories, and in these, we identified 110 data points (% PTSD sumscore difference/months since traumatic exposure). The median PTSD symptom sumscore was 25% higher during the initial 6 months among individuals in the delayed trajectory compared to those in low-stable trajectory. From this level, the difference widened and reached a plateau of 40-50% higher. The variation was large, and the baseline participation rate and loss to follow-up were exceeding 25% in the majority of the studies. Heterogeneity of populations, measures, and analyses precluded formal meta-analysis.CONCLUSION: Delayed PTSD is preceded by PTSD symptoms during the first year in most cases. Still, few individuals may experience an asymptomatic delay. The results underpin the rationale for monitoring PTSD symptoms and may inform forensic assessments in that delayed PTSD without symptoms bridging the traumatic event is rare.

Objective In this study, we aimed to inform clinical practice by identifying distinct subgroups of U.S. veteran psychiatry inpatients on their alcohol and drug use severity, posttraumatic stress disorder (PTSD) symptoms, and suicidal ideation over time. Method Participants were 406 patients with co-occurring substance use and mental health disorders. A parallel latent growth trajectory model was used to characterize participants' symptom severity across 15 months posttreatment intake. Results Four distinct classes were identified: 47% "normative improvement," 32% "high PTSD," 11% "high drug use," and 9% "high alcohol use." Eighty percent of the sample had reduced their drinking and drug intake by half from baseline to 3 months, and those levels remained stable from 3 to 15 months. The High PTSD, High Drug Use, and High Alcohol Use classes all reported levels of PTSD symptomatology at baseline consistent with a clinical diagnosis, and symptom levels remained high and stable across all 15 months. The Normative Improvement class showed declining drug and alcohol intake and was the only class exhibiting reductions in PTSD symptomatology over time. High substance use classes showed initial declines in suicidal ideation, then an increase from 9 to 15 months. Conclusions The reduction in frequency of drinking and drug use for 80% of the sample was substantial and supports the potential efficacy of current treatment approaches. However, the high and stable levels of PTSD for more than 50% of the sample, as well as the reemergence of suicidal ideation in a sizable subgroup, underscore the difficulty in finding and linking patients to effective interventions to decrease symptomatology over time.

The salamander vertebral column is largely undifferentiated with a series of more or less uniform rib-bearing presacral vertebrae traditionally designated as the trunk region. We explored regionalization of the salamander trunk in seven species and two subspecies of the salamander genus Lissotriton by the combination of microcomputed tomography scanning and geometric morphometrics. The detailed information on trunk vertebral shape was subjected to a multidimensional cluster analysis and a phenotypic trajectory analysis. With these complementary approaches, we observed a clear morphological regionalization. Clustering analysis showed that the anterior trunk vertebrae (T1 and T2) have distinct morphologies that are shared by all taxa, whereas the subsequent, more posterior vertebrae show significant disparity between species. The phenotypic trajectory analysis revealed that all taxa share a common pattern and amount of shape change along the trunk region. Altogether, our results support the hypothesis of a conserved anterior-posterior developmental patterning which can be associated with different functional demands, reflecting (sub)species' and, possibly, regional ecological divergences within species.

BACKGROUND The current study aimed to investigate the patterns of postoperative pain trajectories over time and their associated risk factors in patients receiving video-assisted thoracoscopic surgery (VATS) and epidural analgesia (EA) for non-small cell lung cancer (NSCLC). METHODS This retrospective study was conducted at a tertiary medical center and included patients undergoing VATS for stage I NSCLC between 2011 and 2015. Maximal pain intensity was recorded daily during the first postoperative week. Group-based trajectory analysis was performed to categorize variations in pain scores over time. Associations between pain trajectory classification and amount of EA administered and length of hospital stay (LOS) after surgery were also evaluated. RESULTS A total of 635 patients with 4,647 pain scores were included in the analysis, and two postoperative pain trajectory groups were identified: group 1, mild pain trajectory (78%); and group 2, rebound pain trajectory (22%). Risk factors for rebound pain trajectory were a surgical time longer than 3 hours (odds ratio, OR: 1.97; 95% confidence interval, CI: 1.27 - 3.07), female sex (OR: 1.62; 95% CI: 1.04 - 2.53) and higher pain score on postoperative day 0 (OR: 1.21; 95% CI: 1.08 - 1.36, linear effect). Although group 2 had a longer LOS (p < 0.001), they did not receive more EA than group 1 (p = 0.805). CONCLUSION Surgical time, sex and pain intensity after surgery were major determinants of rebound pain trajectory, and more aggressive pain control strategies should be considered in high-risk patients.

An integrated care model for people living with Parkinson’s disease (PD) offers the promise of meeting complex care needs in a person-centered way that addresses fragmentation and improves quality of life. The purpose of our research was to co-design a care delivery model that supports both social and medical care from the perspective of patients and care partners. In the first step of our co-design approach, participants from five countries were invited to share their experiences of living with PD during a narrative interview. A qualitative analysis of these narrative interviews based on the Corbin and Strauss model was done to map out patients’ trajectories. Three typical trajectories were identified: (a) the “unpredictable” trajectory, (b) the “situated” trajectory, and (c) the “demanding” trajectory. Based on the analysis of these trajectories, we were able to integrate various patient experiences into the design of an integrated care network. publishedVersion

Pediatric sepsis is a heterogeneous disease with varying physiological dynamics associated with recovery, disability, and mortality. Using risk scores generated from a sepsis prediction model to define illness states, we used Markov chain modeling to describe disease dynamics over time by describing how children transition among illness states. We analyzed 18,666 illness state transitions over 157 pediatric intensive care unit admissions in the 3 days following blood cultures for suspected sepsis. We used Shannon entropy to quantify the differences in transition matrices stratified by clinical characteristics. The population-based transition matrix based on the sepsis illness severity scores in the days following a sepsis diagnosis can describe a sepsis illness trajectory. Using the entropy based on Markov chain transition matrices, we found a different structure of dynamic transitions based on ventilator use but not age group. Stochastic modeling of transitions in sepsis illness severity scores can be useful in describing the variation in transitions made by patient and clinical characteristics.

Objectives:Caregiving and becoming widowed are risk factors for depression in older adults, but few studies have examined their combined effect on depressive symptom trajectories. In a cohort of ol...

The combined role of objectively assessed moderate-vigorous intensity physical activity (MVPA) and sedentary behaviour (SB) is unclear in obesity prevention. This study aimed to identify latent groups for MVPA and SB trajectories from childhood to adolescence and examine their relationship with obesity risk at adolescence. From the Gateshead Millennium Study, accelerometer-based trajectories of time spent in MVPA and SB at ages 7, 9, 12, and 15 were derived as assigned as the predictor variable. Fat mass index (FMI), using bioelectrical impedance at age 15, was the outcome variable. From 672 children recruited, we identified three distinct multiple trajectory groups for time spent in MVPA and SB. The group with majority membership (54% of the cohort) had high MVPA and low SB at childhood, but MVPA declined and SB increased by age 15. One third of the cohort (31%) belonged to the trajectory with low MVPA and high time spent sedentary throughout. The third trajectory group (15% of the cohort) that had relatively high MVPA and relatively low SB throughout had lower FMI (−1.7, 95% CI (−3.4 to −1.0) kg/m2, p = 0.034) at age 15 compared to the inactive throughout group. High MVPA and low SB trajectories when combined are protective against obesity.

Free-range pigs are in the highest risk to acquire cysticercosis in endemic rural locations, although the behavioral and physiological responses to the infection are known to vary widely between pigs. Those animals reared in semi-confinement showed a group behavior that allows us to follow the herd to assess the risks of contact with the parasite. This study is aimed to determine the movement and feeding habits of pig groups raised under semi-confinement conditions, using minimally invasive procedures, applying trajectory analysis to different herds in rural settings. Pig population and subpopulations were characterized, and their movement was evaluated in two seasons of the year, using a global positioning system (GPS). Our results indicate that pig groups are formed based on human ownership and the establishment of family bonds with each other. Each group interacts with other groups in specific sites of the village. Significant differences were found in the time and distance covered by pigs in the dry and rainy seasons (P < 0.05), and the distance travelled by different groups were found to take place in repetitive, well-defined spaces that include moving through sewage, landfills, and open defecation sites. Due to this stability, the trajectories covered by pigs could be useful as indicators of risk factors linked to the exposure of pigs to Taenia solium

BACKGROUND: The current state of the science regarding the care and prognosis of patients with disorders of consciousness is limited. Scientific advances are needed to improve the accuracy, relevance, and approach to prognostication, thereby providing the foundation to develop meaningful and effective interventions. METHODS: To address this need, an interdisciplinary expert panel was created as part of the Coma Science Working Group of the Neurocritical Care Society Curing Coma Campaign. RESULTS: The panel performed a gap analysis which identified seven research needs for prognostic modeling and trajectory analysis (“recovery science”) in patients with disorders of consciousness: (1) to define the variables that predict outcomes; (2) to define meaningful intermediate outcomes at specific time points for different endotypes; (3) to describe recovery trajectories in the absence of limitations to care; (4) to harness big data and develop analytic methods to prognosticate more accurately; (5) to identify key elements and processes for communicating prognostic uncertainty over time; (6) to identify health care delivery models that facilitate recovery and recovery science; and (7) to advocate for changes in the health care delivery system needed to advance recovery science and implement already-known best practices. CONCLUSION: This report summarizes the current research available to inform the proposed research needs, articulates key elements within each area, and discusses the goals and advances in recovery science and care anticipated by successfully addressing these needs.

Background Young people living in remote Aboriginal communities experience some of the highest rates of chlamydia (CT) and gonorrhoea (NG) infection globally. A cluster-randomised controlled trial (TTANGO) in 11 remote primary health services demonstrated point-of-care (POC) testing for CT/NG was acceptable, accurate, improved the uptake and timeliness of treatment, and was cost-saving. Subsequently, POC testing was scaled-up and implemented in a further 20 remote health services (TTANGO2 program) across four jurisdictions (31 in total). We determine whether the uptake of POC testing observed in the trial was also achieved and sustained during the long-term program. Methods We conducted descriptive, interrupted time series and trajectory analyses to compare POC testing patterns over two time periods (trial: 2013–15 and program: 2016–19). For the trajectory analysis, we applied a Poisson model to identify and fit health services to testing groups. Results Among the 11 services who participated in both the trial and program, 7871 tests were conducted in total. The median number of tests per month in the trial was 241(IQR:178–305) and 408(IQR:294–538) in the program, with no significant trend in the trial (5.6 tests per month, p=0.190) but a significant increasing trend in the program (10.52 tests per month, p Conclusions Our findings suggest POC testing can be scaled-up and sustained as part of a routinely implemented program, achieving greater than expected testing numbers to support the clinical and public health benefits of more timely treatment. Further research is underway to investigate barriers among the ‘low’ testing sites. These findings support the proposed transition from syndromic management towards aetiological diagnosis and treatment in low- and middle-income countries.

Wandering is considered to be one of the most common behavioral symptoms of dementia. Designing robust models which are capable of detecting wandering episodes in people living with dementia would allow the prevention of the consequences of this behavior. To tackle this problem, this study proposes a framework where the skeletal trajectories are used to extract patterns from the movements of the participants. These patterns are utilized to classify a movement between wandering and non-wandering behavior using three machine learning methods. The proposed models were assessed based on two datasets collected in different environments consisting of trajectories that are associated with lapping, pacing, and random movements that represent wandering episodes. The predictive model based on the LSTM network achieved the best classification results in terms of macro F1-scores on both datasets with an overall accuracy higher than 70%. The findings of this study present the potential of LSTM-based predictive models in addressing the wandering recognition problem in a real-world scenario with patients suffering from dementia.

Introduction Type 2 diabetes mellitus (T2DM) frequently associates with increasing multi-morbidity/treatment complexity. Some headway has been made to identify genetic and non-genetic risk factors for T2DM. However longitudinal clinical histories of individuals both before and after diagnosis of T2DM are likely to provide additional insight into both diabetes aetiology/further complex trajectory of multi-morbidity. Methods This study utilised diabetes patients/controls enrolled in the DARE (Diabetes Alliance for Research in England) study where pre- and post-T2DM diagnosis longitudinal data was available for trajectory analysis. Longitudinal data of 281 individuals (T2DM n=237 vs matched non-T2DM controls n=44) were extracted, checked for errors and logical inconsistencies and then subjected to Trajectory Analysis over a period of up to 70 years based on calculations of the proportions of most prominent clinical conditions for each year. Results For individuals who eventually had a diagnosis of T2DM made, a number of clinical phenotypes were seen to increase consistently in the years leading up to diagnosis of T2DM. Of these documented phenotypes, the most striking were diagnosed hypertension (more than in the control group) and asthma. This trajectory over time was much less dramatic in the matched control group. Immediately prior to T2DM diagnosis a greater indication of ischaemic heart disease proportions was observed. Post-T2DM diagnosis, the proportions of T2DM patients exhibiting hypertension and infection continued to climb rapidly before plateauing. Ischaemic heart disease continued to increase in this group as well as retinopathy, impaired renal function and heart failure. Conclusion These observations provide an intriguing and novel insight into the onset and natural progression of T2DM. They suggest an early phase of potentially-related disease activity well before any clinical diagnosis of diabetes is made. Further studies on a larger cohort of DARE patients are underway to explore the utility of establishing predictive risk scores.

Volatile organic compounds (VOCs) play an important role in air pollution. In this study, we conducted comprehensive field observations to investigate wintertime air pollution in Beijing, Wangdu, and Dezhou in the Beijing-Tianjin-Hebei region during 2017 and 2018. The average VOC concentrations of the three sites were 35.6 ± 26.6, 70.9 ± 56.3, and 50.5 ± 40.0 ppbv, respectively. The species with the highest concentration were similar in all three sites and included ethane, ethylene, acetylene, acetone, and toluene. The VOC mixing ratios of the three sites showed synchronous growth during pollution episodes and were 1.2-2 times higher than those during clean periods. Moreover, the OH loss rates (LOH) during pollution episodes were 1.2-1.7 times that during clean periods. The crucial reactive species in the three sites were ethylene, propylene, and acetaldehyde, contributing approximately 70% to the total LOH during pollution periods. According to the source apportionment analysis, vehicle exhausts were the largest source of VOCs in Beijing, accounting for more than 50% of the total emissions. During the pollution episodes, Beijing's industrial emissions decreased, but the secondary and background sources increased. Coal combustion was significant (approximately 40%) in Wangdu and should therefore be prioritized in emission reduction policies. In Dezhou, industrial emissions had a considerable impact on the VOC mixing ratio during pollution periods and should therefore be prioritized. The backward trajectory analysis showed that VOCs from the southern region likely contribute to Beijing's VOC pollution, highlighting the importance of regional integration for air quality management.

How people view their social groups' history has important implications at both the collective and the individual levels. It has been established that collective memories, the representations of one's groups' history, differ between generations and individuals. Yet, it remains unclear how collective memories change in reaction to dramatic social change. Using temporal collective relative deprivation (TCRD), which reflects how individuals perceive their group's situation in history, we hypothesize that TCRD trajectories change over time and that highly identified individuals will be less likely to change their trajectory. Kyrgyz nationals (N = 166) responded immediately after the Tulip Revolution and one year later to TCRD measurements. Dual group-based trajectory analysis indicates that a third of the sample modified their memories about their group's situation one year after a dramatic social change and that low identification with the group predicted this change. These results support the idea that collective memory is revised at the individual level after dramatic social change.

Background Gallbladder cancer (GC) is a malignant disease characterized with highly cellular heterogeneity and poor prognosis. Determining the intratumoral heterogeneity and microenvironment (TME) can provide novel therapeutic strategies for GC. Methods We performed the single‐cell RNA sequencing on the primary and lymph node metastatic gallbladder tumors and the adjacent normal tissues of five patients. The transcriptomic atlas and ligand–receptor‐based intercellular communication networks of the single cells were characterized. Results The transcriptomic landscape of 24,887 single cells was obtained and characterized as 10 cellular clusters, including epithelial, neuroendocrine tumor cells, T&NK cells, B cells, RGS5+ fibroblasts, POSTN+ fibroblasts, PDGFRA+ fibroblasts, endothelial, myeloid cells, and mast cells. Different types of GC harbored distinct epithelial tumor subpopulations, and squamous cell carcinoma could be differentiated from adenocarcinoma cells. Abundant immune cells infiltrated into adenocarcinoma and squamous cell carcinoma, rather than neuroendocrine neoplasms, which showed significant enrichment of stromal cells. CD4+/FOXP3+ T‐reg and CD4+/CXCL13+ T helper cells with higher exhausting biomarkers, as well as a dynamic lineage transition of tumor‐associated macrophages from CCL20hi/CD163lo, CCL20lo/CD163hi to APOE+, were identified in GC tissues, suggesting the immunosuppressive and tumor‐promoting status of immune cells in TME. Two distinct endothelial cells (KDR+ and ACKR1+), which were involved in angiogenesis and lymphangiogenesis, showed remarkable ligand–receptor interactions with primary GC cells and macrophages in gallbladder tumors. Conclusions This study reveals a widespread reprogramming across multiple cell populations in GC progression, dissects the cellular heterogeneity and interactions in gallbladder TME, and provides potential therapeutic targets for GC., Abundant immune cells in adenocarcinoma and squamous cell carcinoma while stromal cells in neuroendocrine neoplasms were enriched.Immunosuppressive microenvironment characterized as exhausted T cells and APOE+ macrophages.Endothelial cells (KDR+ and ACKR1+) indicated that angiogenesis and lymphangiogenesis were involved in GC.There were remarkable ligand–receptor interactions between endothelial, primary GC cells, and macrophages.

International audience; Growth Hormone (GH) under its human recombinant homologue (rhGH), may be abused by athletes to take advantage of its well-known anabolic and lipolytic properties; hence it is prohibited in sports by the World Anti-Doping Agency. Due to the rapid turnover of rhGH, anti-doping screening tests have turned to monitor two endocrine biomarkers (IGF-I and P-III-NP), but unfortunately, they show population-wise variability, limiting the identification rate of rhGH users. Previous studies have evidenced the numerous effects of GH on human physiology, especially in hematopoiesis and steroidogenesis. In this work, aiming to discover novel physiological rhGH biomarkers, we analyzed the complete blood count and the steroidomics profile of healthy, physically active, young males treated either with EPO + rhGH or EPO + placebo. The time-trends of these two physiological routes have been analyzed through geometric trajectory analysis (GTA) and OPLS-DA. Individuals supplemented with micro-doses of rhGH exhibited different leukopoietic and steroidal profiles compared to the control population, suggesting a role of the rhGH in both pathways. In the article, hypotheses on the observed differences are discussed according to the most recent literature and compared to results in animal models. The use of leukopoietic and steroidal biomarkers together with endocrine biomarkers (IGF-1 and P-III-NP) allows to correctly classify over 98% of samples with no false positives, miss-classifying only one single sample (false negative) over a total of 56; a promising result, if compared to the current rhGH detection strategies.