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ObjectiveTo analyze the changing trends of the incidence and onset age of cervical cancer in Jiangsu Province by using cancer registration data from 2009 to 2019. MethodsThe information of national cancer registries with continuous data from 2009 to 2019 was selected, and the quality control indices of cancer registration must be up to standards. A total of 16 registries were included in this study. Statistical analysis indicators include the crude incidence rate of cervical cancer, age-standardized incidence rate, actual average onset age, age-standardized average onset age, and average annual percentage change (AAPC). A birth cohort model was constructed to analyze the incidence of cervical cancer among women born from 2009 to 2019 and its incidence trend. ResultsFrom 2009 to 2019, the crude and age-standardized incidence rates of cervical cancer among women in Jiangsu Province showed upward trends, with AAPCs of 5.62% (95%CI: 3.47−7.82) and 4.14% (95%CI: 2.06−6.27), respectively. The incidence rate of cervical cancer in rural areas (AAPC=4.46, 95%CI: 1.13−7.91) increased more than that in urban areas (AAPC=3.83, 95%CI: 2.81−4.86). The actual average onset age of cervical cancer increased from 51.53 years in 2009 to 55.07 years in 2019 (β=0.36, P

Abstract Background Major depressive disorder (MDD) is a highly heterogeneous disease, with differences in clinical manifestations among depression patients based on onset ages and genders. The neural mechanisms underlying these differences remain unclear. In this study, we utilized resting state functional imaging data from a large sample database and adopted the ReHo method to investigate gender differences in local brain function in MDD patients across different onset age groups. Methods The study included 364 MDD patients and 695 healthy participants who were part of the REST-meta-MDD project. Regional homogeneity (ReHo) assessed gender disparities in MDD and healthy individuals within groups delineated by gender and onset age (young group: 18–29 years; middle-aged group: 30–45 years). Results Among the young MDD groups, there were significant gender differences in the right superior frontal gyrus, right inferior frontal gyrus, left superior temporal gyrus, and right superior parietal lobule, with male MDD patients having higher ReHo values compared to females. When compared to healthy males, male MDD patients exhibited elevated ReHo values in the right superior parietal lobule. In the middle-aged groups, a marked ReHo difference was observed in the bilateral cerebellum posterior lobe, with female MDD patients showing higher ReHo values. Conclusions The functional mechanisms of MDD differ between genders and show distinct variations across different onset age groups. These findings underscore the importance of developing personalized interventions that address the unique needs of MDD patients, tailored to their gender and age, and necessitate the development of antidepressant medications targeted at each gender-age subgroup.

Background: Evidence on type 2 diabetes onset age and duration on mortality risk has been limited by short follow‐up, inadequate control for confounding, missing repeated measurements, and inability to cover the full range of onset age, duration, and major causes of death. Moreover, scarce data dissect how type 2 diabetes onset age and duration shape life expectancy. Methods: We evaluate prospectively these topics based on 270,075 eligible participants in the Nurses' Health Studies and Health Professionals Follow‐up Study, leveraging repeated measurements throughout up to 40 years of follow‐up. Cox models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Results: In fully adjusted analyses, incident early onset type 2 diabetes (diagnosed <40 years of age) was associated with significantly higher mortality from all‐causes (HR, 95% CI was 3.16, 2.64–3.79; vs. individuals without type 2 diabetes), cardiovascular disease (6.56, 4.27–10.1), respiratory disease (3.43, 1.38–8.51), neurodegenerative disease (5.13, 2.09–12.6), and kidney disease (8.55, 1.98–36.9). The relative risk elevations declined dramatically with each higher decade of age at diagnosis for deaths from most of these causes, though the absolute risk difference increased continuously. A substantially higher cumulative incidence of mortality and a greater loss in life expectancy were associated with younger age at type 2 diabetes diagnosis. Longer disease duration was associated with generally higher relative and absolute risk of mortality. Conclusion: Early onset of type 2 diabetes and longer disease duration are associated with substantially increased risk of all‐cause and cause‐specific mortality and greater loss in life expectancy. [ABSTRACT FROM AUTHOR]

Background: Major depressive disorder (MDD) is a highly heterogeneous disease, with differences in clinical manifestations among depression patients based on onset ages and genders. The neural mechanisms underlying these differences remain unclear. In this study, we utilized resting state functional imaging data from a large sample database and adopted the ReHo method to investigate gender differences in local brain function in MDD patients across different onset age groups. Methods: The study included 364 MDD patients and 695 healthy participants who were part of the REST-meta-MDD project. Regional homogeneity (ReHo) assessed gender disparities in MDD and healthy individuals within groups delineated by gender and onset age (young group: 18–29 years; middle-aged group: 30–45 years). Results: Among the young MDD groups, there were significant gender differences in the right superior frontal gyrus, right inferior frontal gyrus, left superior temporal gyrus, and right superior parietal lobule, with male MDD patients having higher ReHo values compared to females. When compared to healthy males, male MDD patients exhibited elevated ReHo values in the right superior parietal lobule. In the middle-aged groups, a marked ReHo difference was observed in the bilateral cerebellum posterior lobe, with female MDD patients showing higher ReHo values. Conclusions: The functional mechanisms of MDD differ between genders and show distinct variations across different onset age groups. These findings underscore the importance of developing personalized interventions that address the unique needs of MDD patients, tailored to their gender and age, and necessitate the development of antidepressant medications targeted at each gender-age subgroup. [ABSTRACT FROM AUTHOR]

Background The associations of age at orthostatic hypotension onset with incident myocardial infarction (MI), stroke, and dementia remain unknown. This study aimed to examine whether younger onset age of orthostatic hypotension was associated with higher risks of incident MI, stroke, and dementia. Methods Data were obtained from the UK Biobank. Information on the diagnosis of orthostatic hypotension, MI, stroke, and dementia was collected at baseline (2006–2010) and follow-ups (median = 13 years). The propensity score matching method and the Cox proportional hazard models were employed. Results A total of 448 374 adults (mean age: 56.8 ± 8.1 years), of whom 3 795 had orthostatic hypotension, were included. orthostatic hypotension patients exhibited higher risks of developing MI, stroke, and dementia than non-orthostatic hypotension participants. Importantly, among orthostatic hypotension patients, younger onset age (per 10-year decrement) was significantly associated with high risks of MI (HR = 3.15, 95% CI: 2.54–3.90, p  < .001), stroke (HR = 1.72, 95% CI: 1.33–2.23, p  < .001), and dementia (HR = 1.26, 95% CI: 1.02–1.57, p  = .034). After propensity score matching, orthostatic hypotension patients had significantly higher risks of MI, stroke, and dementia than matched controls among all onset age groups, and the HRs gradually increased with descending onset age. Conclusions Younger onset age of orthostatic hypotension was associated with higher risks of incident MI, stroke, and dementia, underscoring the necessity to pay additional attention to the cardiovascular health and neurocognitive status of individuals diagnosed with orthostatic hypotension at younger ages to attenuate subsequent risks of incident cardiovascular diseases and dementia. [ABSTRACT FROM AUTHOR]

Abstract Background Early-onset dementia (EOD, onset age

Psychiatric illnesses can affect the social transitions of adolescence and young adulthood, such as completing education and entering working life and relationships. However, associations between earlier onset age and long-term outcomes among those with early-onset psychoses (EOP) are unclear, as are the long-term outcomes of EOP compared to non-psychotic disorders. We used national register data of the Northern Finland Birth Cohort 1986 to detect persons with EOP and other early-onset psychiatric disorders. The long-term clinical and work-family outcomes of persons with onset age before 18 years (n = 41 psychoses, n = 495 non-psychoses) or between 18–22 years (n = 61 psychoses, n = 377 non-psychoses) were compared. Individuals with the onset of psychosis between 18–22 years had significantly more unfavourable long-term outcomes when compared to those with psychosis onset before 18 years. Persons with psychosis onset before the age of 18 years had similar outcomes to those with non-psychotic psychiatric disorder onset before 18 years regarding educational level, marital status, having children, and substance use disorders. Individuals with EOP were more often on a disability pension compared to those with other early-onset mental disorders. Adjusting for sex, educational level and substance use only slightly diluted these results. Unexpectedly, later onset age of EOP was associated with worse outcomes. Those with psychosis onset between 18–22 years of age are in a critical period, which underlines the importance of investing on interventions in this age group. Further studies on the effect of the onset age on later outcomes in EOP are needed. [ABSTRACT FROM AUTHOR]

Type 2 diabetes (T2D) prevalence in adults at a younger age has increased but the disease status may go unnoticed. This study aimed to determine whether the onset age and subsequent diabetic complications can be attributed to the polygenic architecture of T2D in the Taiwan Han population. A total of 9,627 cases with T2D and 85,606 controls from the Taiwan Biobank were enrolled. Three diabetic polygenic risk scores (PRSs), PRS_EAS and PRS_EUR, and a trans-ancestry PRS (PRS_META), calculated using summary statistic from East Asian and European populations. The onset age was identified by linking to the National Taiwan Insurance Research Database, and the incidence of different diabetic complications during follow-up was recorded. PRS_META (7.4%) explained a higher variation for T2D status. And the higher percentile of PRS is also correlated with higher percentage of T2D family history and prediabetes status. More, the PRS was negatively associated with onset age (β = −0.91 yr), and this was more evident among males (β = −1.11 vs. −0.76 for males and females, respectively). The hazard ratio of diabetic retinopathy (DR) and diabetic foot were significantly associated with PRS_EAS and PRS_META, respectively. However, the PRS was not associated with other diabetic complications, including diabetic nephropathy, cardiovascular disease, and hypertension. Our findings indicated that diabetic PRS which combined susceptibility variants from cross-population could be used as a tool for early screening of T2D, especially for high-risk populations, such as individuals with high genetic risk, and may be associated with the risk of complications in subjects with T2D. NEW & NOTEWORTHY: Our findings indicated that diabetic polygenic risk score (PRS) which combined susceptibility variants from Asian and European population affect the onset age of type 2 diabetes (T2D) and could be used as a tool for early screening of T2D, especially for individuals with high genetic risk, and may be associated with the risk of diabetic complications among people in Taiwan. [ABSTRACT FROM AUTHOR]

Background: There is growing evidence that sex and onset age are important factors of clinical features in Parkinson's disease. Aim: The study aimed to identify nonmotor symptoms based on sex and onset age in people with Parkinson's disease. Design: This is a cross‐sectional descriptive study. Methods: A total of 210 participants were recruited from the university hospital and the Parkinson's disease association. This study measured the Korean version of the nonmotor symptoms questionnaire which includes gastrointestinal, urinary, apathy/attention/memory, hallucination/delusions, depression/anxiety, sexual function, cardiovascular, sleep disorder, and miscellaneous domains. Results: All participants reported at least one nonmotor symptom. The most commonly reported symptoms were nocturia (65.7%) and constipation (61.9%). The male participants reported more dribbling of saliva, constipation, and impaired sexual function, whereas the female reported more weight change. Young‐onset people with Parkinson's disease reported more depression than late‐onset people with Parkinson's disease. Conclusion: This study contributes to the understanding of symptom experience beyond motor‐related symptomatology for those with Parkinson's disease and adds to the current literature. Individualized symptom assessment and management should be provided by prioritizing prevalent sex or onset age‐specific symptoms, rather than addressing with all nonmotor symptoms. Summary statement: What is already known about this topic? Most people with Parkinson's disease experience nonmotor symptoms including autonomic nervous symptoms as the disease progresses.Nonmotor symptoms can affect quality of life of people with Parkinson's disease, but related factors are not fully understood. What this paper adds? This paper identified the presentations of nonmotor symptoms in people with Parkinson's disease based on sex and onset age. The implications of this paper: Nurses enable people with Parkinson's disease to actively engage in self‐care of their own symptoms by educating Parkinson's disease related and how to cope with the symptoms in advance.Individualized nursing care reflecting the disease characteristics is needed to improve patient engagement in symptom management. [ABSTRACT FROM AUTHOR]

Background: There is a rapidly increasing incidence of early-onset colorectal cancer (EO-CRC) which threatens the survival of young people, while aging also represents a challenging clinical problem. Objectives: We aimed to investigate the differences in the clinical characteristics and prognosis in stage III rectal cancer (RC), to help optimize treatment strategies. Design and methods: This study included 757 patients with stage III RC, all of whom received neoadjuvant chemoradiotherapy and total mesorectal excision. The whole cohort was categorized as very early onset (VEO, ⩽30 years old), early onset (EO, >30 years old, ⩽50 years old), intermediate onset (IO, >50 years, ⩽70 years), or late onset (LO, >70 years old). Results: There were more female VEO patients than males, more mucinous adenocarcinoma, signet-ring cell carcinoma, pre-treatment cT4 stage, and higher pre-treatment serum carbohydrate antigen 19-9 compared with the other three groups. VEO patients had the worst survival with the highest RC-related mortality (34.5%), recurrence (13.8%), and metastasis (51.7%). LO patients had the highest non-RC-related mortality rate (16.6%). The Cox regression model showed VEO was a negative independent prognostic factor for disease-free survival [DFS, hazard ratio (HR): 2.830, 95% confidence interval (CI): 1.633–4.904, p < 0.001], distant metastasis-free survival (DMFS, HR: 2.969, 95% CI: 1.720–5.127, p < 0.001), overall survival (OS, HR: 2.164, 95% CI: 1.102–4.249, p = 0.025), and cancer-specific survival (CSS, HR: 2.321, 95% CI: 1.145–4.705, p = 0.020). LO was a negative independent factor on DFS (HR: 1.800, 95% CI: 1.113–2.911, p = 0.017), DMFS (HR: 1.903, 95% CI: 1.150–3.149, p = 0.012), OS (HR: 2.856, 95% CI: 1.745–4.583, p < 0.001), and CSS (HR: 2.248, 95% CI: 1.282–3.942, p = 0.005). VEO patients had better survival in the total neoadjuvant therapy-like (TNT-like) pattern on DFS (p = 0.039). IO patients receiving TNT-like patterns had better survival on DFS, OS, and CSS (p = 0.006, p = 0.018, p = 0.006, respectively). Conclusion: In stage III RC, VEO patients exhibited unique clinicopathological characteristics, with VEO a negative independent prognostic factor for DFS, DMFS, OS, and CSS. VEO and IO patients may benefit from a TNT-like treatment pattern. [ABSTRACT FROM AUTHOR]

Background: Excessive weight gain and obesity are widely accepted as risk factors for diabetes mellitus, and the age at which obesity onsets may be related to the development of cardiovascular diseases and certain cancers. Here, we aimed to investigate associations between the onset-age of overweight/obesity and risk of developing diabetes mellitus in China. Methods: 42,144 people with the normal weight range and without diabetes at baseline, were enrolled from the Kailuan cohort which began on the 1st June 2006. All participants were followed-up, biennially, until 31st December 2017. During follow-up, 11,220 participants had become overweight/obese. For each case, one normal-weight control was matched according to age ( ± 1 year) and sex. Our final analysis included 10,858 case-control pairs. An age-scaled Cox model was implemented to estimate hazard ratios (HR) with corresponding 95% confidence intervals (CI) for diabetes mellitus incidence across age-groups. Results: At a median follow-up of 5.46 years, 1,403 cases of diabetes mellitus were identified. After multivariate adjustments, age-scaled Cox modelling suggested that risk gradually attenuated with every 10 year increase in age of onset of overweight/obesity. Diabetes mellitus adjusted HRs (aHRs) for new-onset overweight/obesity at <45years, 45-54 years, and 55-64 years were 1.47 (95%CI, 1.12-1.93), 1.38 (95%CI, 1.13-1.68), 1.32 (95%CI, 1.09-1.59), respectively. However, new-onset of overweight/obesity at >65 years did not relate to diabetes mellitus (aHR, 1.20; 95%CI, 0.92-1.57). This trend was not observed in women or the new-onset obesity subgroup but was evident in men and the new overweight onset subgroup. Conclusion: Participants with early onset of excessive weight gain issues are at considerably higher risk of developing diabetes mellitus compared to those who maintain a normal weight. [ABSTRACT FROM AUTHOR]

Introduction: Specific pathogen infections associated with acute rhinosinusitis (ARS) in infants are risk factors for allergic asthma in adolescents. However, the risk factors for ARS onset remain largely unknown in asthmatic children. In this study, we aim to investigate the risk factors for ARS in childhood asthma. Methods: This study retrospectively compared and analyzed the clinical characteristics of asthmatic children with (n = 194) or without ARS (n = 799). Univariate regression analyses were performed to identify ARS-associated risk factors in asthmatic children, and subsequent multivariate backward stepwise logistic regression analyses were performed to identify independent risk factors. Results: The onset age, values of blood eosinophils (EOS) (%), and total IgE were significantly lower in patients with ARS than in those without ARS. Moreover, the proportions of patients allergic to Dermatophagoides pteronyssinus (d1) and Dermatophagoides farinae (d2) were significantly smaller in children with ARS (all p values <0.05). Univariate analyses showed that an older onset age, a higher body mass index, a higher value of blood EOS (%) were protective factors, while a higher value of blood lymphocytes (%) and a higher degree of sensitization to d1 and d2 were risk factors for ARS. Further backward stepwise multivariate logistic regression analyses confirmed that a younger onset age and allergic sensitization to d1 were independent risk factors for ARS in childhood asthma. Conclusion: Younger onset age and allergic sensitization to d1 are risk factors for the onset of ARS in childhood asthma, so allergen intervention should be performed as early as possible in asthmatic children. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the clinical characteristics and the risk factors associated with excessive daytime sleepiness (EDS) in patients with early- and late-onset narcolepsy. Methods: Patients with narcolepsy were consecutively recruited. All patients were separated into early- and late-onset groups according to the onset age of disease ≤ 15 and > 15 years, respectively. Demographic, clinical, and sleep parameters were compared between the two groups. Linear regressions were performed to examine the risk factors of subjective and objective EDS in patients with early- and late-onset narcolepsy. Results: A total of 101 patients with narcolepsy (median age at recruitment = 18.0 years) were classified into an early-onset group (67 patients with median age at onset = 12.0 years) and a late-onset group (34 patients with median age at onset = 28.5 years). Compared with early-onset group, late-onset group scored significantly higher on Epworth Sleepiness Scale (ESS), Ullanlinna Narcolepsy Scale (UNS), sleep paralysis, rapid eye movement (REM) sleep behavior disorder (RBD) questionnaire-Hong Kong (all P < 0.050). UNS-cataplexy and sleep paralysis had significantly positive associations with subjective EDS, and N1%, arousal index, and periodic limb movements index were positively associated with objective EDS in the early-onset group (all P < 0.050). However, these associations were not observed in late-onset narcolepsy. Conclusion: Late onset narcolepsy had more severe self-reported narcolepsy symptoms. REM sleep related symptoms and disrupted nighttime sleep were associated with EDS in early-onset narcolepsy. These findings suggest that early- and late-onset narcolepsy may represent two distinct phenotypes. [ABSTRACT FROM AUTHOR]

Background: Identifying more homogenous subtypes of patients with obsessive–compulsive disorder (OCD) using biological evidence is critical for understanding complexities of the disorder in this heterogeneous population. Age of onset serves as a useful subtyping scheme for distinguishing OCD into two subgroups that aligns with neurodevelopmental perspectives. The underlying neurobiological markers for these distinct neurodevelopmental differences can be identified by investigating gyrification changes to establish biological evidence-based homogeneous subtypes. Methods: We compared whole-brain cortical gyrification in 84 patients with early-onset OCD, 84 patients with late-onset OCD, and 152 healthy controls (HCs) to identify potential markers for early neurodevelopmental deficits using the local gyrification index (lGI). Then, the relationships between lGI in clusters showing significant differences and performance in visuospatial memory and verbal fluency, which are considered trait-related neurocognitive impairments in OCD, were further examined in early-onset OCD patients. Results: The early-onset OCD patients exhibited significantly greater gyrification than those with late-onset OCD patients and HCs in frontoparietal and cingulate regions, including the bilateral precentral, postcentral, precuneus, paracentral, posterior cingulate, superior frontal, and caudal anterior cingulate gyri. Moreover, impaired neurocognitive functions in early-onset OCD patients were correlated with increased gyrification. Conclusions: Our findings provide a neurobiological marker to distinguish the OCD population into more neurodevelopmentally homogeneous subtypes, which may contribute to the understanding of the neurodevelopmental underpinnings of an etiology in early-onset OCD consistent with the accumulated phenotypic evidence of greater neurodevelopmental deficits in early-onset OCD than in late-onset OCD. [ABSTRACT FROM AUTHOR]

The objective of the study was to assess whether determinants of quality of life are different or similar for married and unmarried substance user men from Pakistan? A sample of 218 inpatient substance user men (M age = 27.73 & SD = 5.25; Married N = 116; Unmarried N = 102) was assessed on WHO-QOL assessing four quality of life domains. It was found that within subject differences across four QoL domains were significant with all participants reporting better physical, psychological, and social QoL than environmental QoL. Also, married compared to unmarried participants scored higher on psychological and environmental QoL domains. Furthermore, age and substance use duration were negative correlates but education and onset age were positive correlates of specific QoL domains. Interaction effects showed that age and substance use duration were stronger negative predictors of psychological and environmental QoL in married compared to unmarried substance user men. It was concluded that older and married substance user men compared to younger and unmarried substance user men and those with more duration were at a higher risk of poor QoL due to substance use. [ABSTRACT FROM AUTHOR]

Background The association of age at coronary heart disease (CHD) onset with incident dementia remains unexplored. This study aimed to examine whether younger onset age of CHD is associated with a higher risk of incident dementia. Methods and Results Data were obtained from the UK Biobank. Information on the diagnosis of CHD and dementia was collected at baseline and follow‐ups. Propensity score matching method and Cox proportional hazards models were used to evaluate the association between different ages at CHD onset and incident dementia. A total of 432 667 adults (mean±SD age, 56.9±8.1 years) were included, of whom 11.7% had CHD. Compared with participants without CHD, participants with CHD exhibited higher risks of developing all‐cause dementia, Alzheimer's disease, and vascular dementia. More importantly, younger age at CHD onset (per 10‐year decrease) was significantly associated with elevated risks of all‐cause dementia (hazard ratio [HR], 1.25 [95% CI, 1.20–1.30]; P

Psoriasis is an immune‐mediated chronic, relapsing, inflammatory, systemic disease induced by a combination of genetics and environment. Currently, there are limited reports on the epidemiological and clinical characteristics of geriatric psoriatic patients in mainland China. This study analyzed the epidemiological characteristics, clinical features, and comorbidity rates of geriatric patients with psoriasis and evaluated the influence of age of onset on disease characteristics. This retrospective study enrolled 1259 geriatric patients with psoriasis in hospitals affiliated with the National Standardized Psoriasis Diagnosis and Treatment Center in China from September 2011 to July 2020 to analyze the epidemiological characteristics, clinical features, and prevalence of comorbidity in geriatric psoriasis. The cases were classified according to the age of onset into two groups to compare differences: early‐onset psoriasis (EOP) and late‐onset psoriasis (LOP). The mean age of geriatric patients with psoriasis was 67, with a 1.8:1 male‐to‐female ratio and 10.7% positive family history. The clinical manifestations of plaque psoriasis accounted for a high proportion (82.0%) and 85.1% of patients had moderate to severe disease. Overweight (27.8%), hypertension (18.0%), joint involvement (15.8%), diabetes (13.7%), and coronary heart disease (4.0%) were the first five common comorbidities. The LOP group had significantly more patients (79.9%) than the EOP group (20.1%). Positive family history was significantly associated with the EOP group (21.7%) than the LOP group (7.9%). The scalp (60.2%) was the most affected area, followed by the nails (25.3%), palmoplantar region (25.0%), and genitals (12.7%). This study analyzed the epidemiological and clinical characteristics of geriatric psoriasis in China and found that age of onset had no effect on disease characteristics or other comorbidities, except for toenail involvement, diabetes, and joint damage. [ABSTRACT FROM AUTHOR]

Schizophrenia is a heritable neurocognitive disorder affecting about 1% of the population, and usually has an onset age at around 21-25 in males and 25-30 in females. Recent advances in genetics have helped to identify many common and rare variants for the liability to schizophrenia. Earlier evidence appeared to suggest that younger onset age is associated with higher genetic liability to schizophrenia. Clinical longitudinal research also found that early and very-early onset schizophrenia are associated with poor clinical, neurocognitive, and functional profiles. A recent study reported a heritability of 0.33 for schizophrenia onset age, but the genetic basis of this trait in schizophrenia remains elusive. In the preGenome-Wide Association Study (GWAS) era, genetic loci found to be associated with onset age were seldom replicated. In the post-Genome-Wide Association Study era, new conceptual frameworks are needed to clarify the role of onset age in genetic research in schizophrenia, and to identify its genetic basis. In this review, we first discussed the potential of onset age as a characterizing/subtyping feature for psychosis, and as an important phenotypic dimension of schizophrenia. Second, we reviewed the methods, samples, findings and limitations of previous genetic research on onset age in schizophrenia. Third, we discussed a potential conceptual framework for studying the genetic basis of onset age, as well as the concepts of susceptibility, modifier, and "mixed" genes. Fourth, we discussed the limitations of this review. Lastly, we discussed the potential clinical implications for genetic research of onset age of schizophrenia, and how future research can unveil the potential mechanisms for this trait. [ABSTRACT FROM AUTHOR]

Purpose: Identifying the onset age of cancer is essential for its early intervention. The aim of this study was to characterize the features and investigate the variation tendency of first primary colorectal cancer (CRC) onset age in the USA. Methods: For this retrospective population-based cohort analysis, data on patients diagnosed with first primary CRC (n = 330,977) between 1992 and 2017 were obtained from the Surveillance, Epidemiology, and End Results dataset. Annual percent changes (APC) and average APCs were calculated to examine the changes in average age at CRC diagnosis using the Joinpoint Regression Program. Results: From 1992 to 2017, the average age at CRC diagnosis decreased from 67.0 to 61.2 years, declining by 0.22% and 0.45% annually before and after 2000. The age at diagnosis was lower in the distal than in the proximal CRC cases and the age has the downward trends in all subgroups of sex, race, and stage. Over one-fifth of CRC patients were initially diagnosed with distantly metastatic CRC, with the age lower than that in localized CRC cases (63.5 vs 64.8 years). Conclusions: The first primary CRC onset age has decreased significantly in the USA over the last 25 years and the modern lifestyle may be responsible for the decline. Specifically, the age of proximal CRC is invariably higher than that of distal CRC. Moreover, the age of advanced stage is lower than that of the early stage. Clinicians should adopt earlier screening age and more effective screening techniques for CRC. [ABSTRACT FROM AUTHOR]

Abstract Aims/Introduction To assess the relationship between type 2 diabetes mellitus onset age and vascular complications in China. Materials and Methods A retrospective review of 3,568 patients with type 2 diabetes mellitus using a propensity score‐matched (PSM) cohort analysis was carried out in two different age of onset groups (age 40 and 60 years). These groups were then subdivided into two groups, early‐onset diabetes (EOD40 and EOD60; the onset age before 40 and 60 years, respectively) and late‐onset diabetes (LOD40 and LOD60: the onset age after 40 and 60 years, respectively). Macrovascular and microvascular complications were analyzed before and after PSM. Results Patients categorized in both the early‐onset disease (EOD) groups had a higher risk of developing macro‐ and microvascular complications before PSM. After PSM, no differences existed between the EOD and late‐onset disease groups in the risk of macrovascular complications. Compared with the late‐onset disease group, the odds ratio of having a microvascular complication of diabetic retinopathy, chronic kidney disease and diabetic peripheral neuropathy in the 40‐year‐old EOD group increased to 2.906, 1.967 and 1.672 (P

Summary: Background: The aim of the study is to estimate the incidence of pancreatic cancer among individuals with new-onset type 2 Diabetes (T2DM) and evaluate the relationship of pancreatic cancer risk with age at diabetes onset and diabetes duration. Methods: This longitudinal cohort study included 428,362 new-onset T2DM patients in Shanghai and Mendelian randomization (MR) in the east-Asian population were used to investigate the association. Incidence rates of pancreatic cancer in all patients and by subgroups were calculated and compared to the general population. Findings: A total of 1056 incident pancreatic cancer cases were identified during eight consecutive years of follow-up. The overall pancreatic cancer annual incidence rate was 55·28/100,000 person years in T2DM patients, higher than that in the general population, with a standardized incidence ratio (SIR) of 1·54 (95% confidence interval [CI], 1·45–1·64). The incidence of pancreatic cancer increased with age and a significantly higher incidence was observed in the older groups with T2DM. However, the relative pancreatic cancer risk was inversely related to age of T2DM onset, and a higher SIR of 5·73 (95%CI, 4·49–7·22) was observed in the 20–54 years old group. The risk of pancreatic cancer was elevated at any diabetes duration. Fasting blood glucose ≥10·0 mmol/L was associated with increased risk of pancreatic cancer. MR analysis indicated a positive association between T2DM and pancreatic cancer risk. Interpretation: Efforts toward early and close follow-up programs, especially in individuals with young-onset T2DM, and the improvement of glucose control might represent effective strategies for improving the detection and results of treatment of pancreatic cancer. Funding: Chinese National Natural Science Foundation.

With the development of 16S rRNA technology, gut microbiome evaluation has been performed in many diseases, including gastrointestinal tumors. Among these cancers, gastric cancer (GC) exhibits high morbidity and mortality and has been extensively studied in its pathogenesis and diagnosis techniques. The current researches have proved that the gut microbiome may have the potential to distinguish GC patients from healthy patients. However, the change of the gut microbiome according to tumor node metastasis classification (TNM) has not been clarified. Besides, the characteristics of gut microbiome in GC patients and their ages of onset are also ambiguous. To address the above shortcomings, we investigated 226 fecal samples and divided them according to their tumor stage and onset age. The findings revealed that surgery and tumor stage can change the characteristic of GC patients' gut microbiota. In specific, the effect of surgery on early gastric cancer (EGC) was greater than that on advanced gastric cancer (AGC), and the comparison of postoperative microflora with healthy people indicated that EGC has more differential bacteria than AGC. Besides, we found that Collinsella, Blautia, Anaerostipes, Dorea, and Lachnospiraceae_ND3007_group expressed differently between EGC and AGC. More importantly, it is the first time revealed that the composition of gut microbiota in GC is different between different onset ages. Key points: •Gut microbiota of gastric cancer (GC) patients are either highly associated with TNM stage and surgery or not. It shows surgery has more significant changes in early gastric cancer (EGC) than advanced gastric cancer (AGC). •There existed specific gut microbiota between EGC and AGC which may have potential to distinguish the early or advanced GC. •Onset age of GC may influence the gut microbiota: the composition of gut microbiota of early-onset gastric cancer (EOGC) and late-onset gastric cancer (LOGC) is significantly different. [ABSTRACT FROM AUTHOR]

Objective: To identify genetic variants associated with Stanford A thoracic aortic aneurysm and dissection (ATAAD) using whole-exome sequencing (WES) and analyze positive mutation rates among patients of different onset ages. Methods: WES was performed on 62 sporadic Chinese ATAAD patients (51-74 years old), and then grouped based on onset age together with 73 previously reported TAAD patients (19-50 years old): ≤35, 36-45, 46-55, and >55 years. The proportion of patients with pathogenic/likely pathogenic (P/LP) variants in TAAD causal genes was compared across groups. Results: The average onset age of the 62 patients was 57.66 years. Eight P/LP variants were identified (two novel, six previously described) in five known TAAD causal genes ( FBN1 , SMAD3 , TGFBR2 , TGFB2 , and MYLK ) in eight individuals. P/LP variant positive rates among patients across age groups were: 22.73% for ≤35 years, 32% for 36-45 years, 15.52% for 46-55 years, and 3.33% for >55 years. Significant differences ( p = 0.0077) were observed between 36-45 and >55 years group. Conclusions: ATAAD patients aged 36-45 years old at diagnosis had a higher chance of having a P/LP variant and patients >55 years old had the lowest P/LP diagnostic rate. Therefore, gene screening in ATAAD patients ≤55 years old is key to improved diagnostic rate.

Lin Wan, Jing Wei Department of Psychological Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People’s Republic of ChinaCorrespondence: Jing WeiDepartment of Psychological Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Shuaifuyuan 1, Dongcheng District, Beijing, People’s Republic of ChinaTel +86-10-61956061Email weijing@pumch.cnBackground: Patients with early-onset schizophrenia usually exhibit more severe symptoms, revealing a potentially distinctive disease phenotype. Methylenetetrahydrofolate reductase (MTHFR) is a critical enzyme in folate conversion and methylation modification associated with the disease. We aimed to investigate the potential effects of MTHFR polymorphisms and related methylation patterns in patients with early-onset schizophrenia, which implies special phenotypes of schizophrenia.Methods: In 177 patients with schizophrenia, MTHFR polymorphism at three sites (C677T, A1298C, and G1793A) and the Positive and Negative Syndrome Scale (PANSS) were tested. Differential methylation positions (DMPs) and enrichment of genes and related pathways were analyzed by testing the genomic methylation level. Catechol-O-methyltransferase (COMT), solute carrier family 6 member 4 (SLC6A4), neuregulin1 (NRG1), and brain-derived neurotrophic factor (BDNF) were selected to evaluate the methylation levels of specific CpG regions by pyrosequencing.Results: Higher levels of symptom severity and MTHFR polymorphisms and lower levels of global DNA methylation in patients with early-onset schizophrenia were observed in this study. SLC6A4 was hypermethylated, and BDNF was hypomethylated in specific regions of patients with early-onset schizophrenia.Conclusion: Aggravating symptoms, increased MTHFR polymorphisms, and reduced genomic methylation levels may be characteristics and underlying mechanisms of early-onset schizophrenia, which implies a special disease phenotype. Beyond that, specific genes and biological pathways may imply the potential phenotype of schizophrenia.Keywords: schizophrenia, phenotype, onset age, MTHFR, polymorphism, methylation

Aims/Introduction: To assess the relationship between type 2 diabetes mellitus onset age and vascular complications in China. Materials and Methods: A retrospective review of 3,568 patients with type 2 diabetes mellitus using a propensity score‐matched (PSM) cohort analysis was carried out in two different age of onset groups (age 40 and 60 years). These groups were then subdivided into two groups, early‐onset diabetes (EOD40 and EOD60; the onset age before 40 and 60 years, respectively) and late‐onset diabetes (LOD40 and LOD60: the onset age after 40 and 60 years, respectively). Macrovascular and microvascular complications were analyzed before and after PSM. Results: Patients categorized in both the early‐onset disease (EOD) groups had a higher risk of developing macro‐ and microvascular complications before PSM. After PSM, no differences existed between the EOD and late‐onset disease groups in the risk of macrovascular complications. Compared with the late‐onset disease group, the odds ratio of having a microvascular complication of diabetic retinopathy, chronic kidney disease and diabetic peripheral neuropathy in the 40‐year‐old EOD group increased to 2.906, 1.967 and 1.672 (P < 0.05), respectively. The odds ratio of diabetic retinopathy and diabetic peripheral neuropathy in the 60‐year‐old EOD group was 1.763 and 1.675 (P < 0.05), respectively. Conclusions: The earlier the onset of type 2 diabetes mellitus, the higher risk of microvascular, but not necessarily macrovascular, complications. It is not too late to prevent diabetes at any age. Pre‐emptive microvascular treatment or preventative measures in EOD patients who do not yet show symptoms, might be beneficial. [ABSTRACT FROM AUTHOR]

Abstract Objectives To evaluate the relationship between age at onset of cannabis use and cannabis abuse in a sample of Portuguese cannabis users, testing the mediating role of the number of friends using cannabis and comparing these relationships between male and female subsets. Method A sample of 529 Portuguese cannabis users comprising 276 males and 244 females aged from 14 to 21 years completed a sociodemographic questionnaire, the Cannabis Abuse Screening Test (CAST), and answered four questions related to cannabis use. Data were analyzed using the PROCESS macro in SPSS version 26.0. Results Age at onset of cannabis use was negatively related to the number of friends using cannabis, while the number of friends using cannabis had a positive relationship with cannabis abuse. As predicted, the number of friends using cannabis seems to have a mediating role in the relationship between cannabis onset age use and cannabis abuse, since the indirect effect was found to be significant. The pattern of the relationships among the variables observed was found to be similar for both male and female subsets of the sample. However, males reported higher cannabis abuse than females. Conclusion The results highlight the mediating role of friends’ use of cannabis in the relationship between age at onset of cannabis use and users’ abuse. These results highlight the importance of early intervention in cannabis use. In particular, the pattern of the relationships observed among the studied variables emphasizes the need to monitor and conduct peer training interventions or interventions to promote of social skills.

Background: Metabolic syndrome (MetS) is associated with an increased risk of incident cardiovascular diseases (CVD), but the association between the new-onset MetS at different ages and the CVD risk remain unclear. Methods: This was a prospective study comprising a total of 72,986 participants without MetS and CVD who participated in the Kailuan study baseline survey (July 2006 to October 2007). All participants received the biennial follow-up visit until December 31, 2019. In addition, 26,411 patients with new-onset MetS were identified from follow-up, and one control participant was randomly selected for each of them as a match for age (± 1 year) and sex. In the end, a total of 25,125 case-control pairs were involved. Moreover, the Cox proportional hazard model was established to calculate the hazard ratios (HR) for incident CVD across the onset age groups. Results: According to the median follow-up for 8.47 years, 2,319 cases of incident CVD occurred. As MetS onset age increased, CVD hazards gradually decreased after adjusting for potential confounders. Compared with non-MetS controls, the HR and the 95% confidence interval (CI) for CVD were 1.84 (1.31–2.57) in the MetS onset age <45 years group, 1.67 (1.42–1.95) for the 45–54 years group, 1.36 (1.18–1.58) for the 55–64 years group, and 1.28 (1.10–1.50) for the ≥65 years group, respectively (p for interaction = 0.03). Conclusions: The relative risks of CVD differed across MetS onset age groups, and the associations was more intense in the MetS onset group at a younger age. [ABSTRACT FROM AUTHOR]

Objectives To further investigate the clinical characteristics and circulating lymphocyte profiles of patients with early-onset primary Sjögren's syndrome (pSS). Method Data of 333 patients with pSS were analysed retrospectively. Early onset was defined as a pSS diagnosis at an age of 35 years or younger. The clinical, laboratory and immunophenotypic profiles of peripheral blood lymphocyte subsets were compared between early- and later-onset pSS. Results Thirty-six (10.81%) patients matched the definition of early-onset pSS, with age at disease onset being 28.97  (5.53) years. Elevated serum IgG level (77.14% vs 31.16%, P <0.001), low C3 (41.67% vs 20.20%, P =0.004) and C4 levels (27.78% vs 6.40%, P <0.001), anti-SSA positivity (91.67% vs 51.85%, P <0.001) and anti-SSB positivity (50% vs 20.54%, P <0.001) were more frequent in early-onset patients. The frequencies of hematological (80.56% vs 52.53%, P =0.001), renal (19.44% vs 5.05%, P =0.005) and mucocutaneous involvement (50% vs 22.56%, P <0.001) were significantly higher in the early-onset pSS group, which showed a higher 2010 EULAR SS Disease Activity Index (ESSDAI) [11(6.25–17) vs 7(3–12); P =0.003], compared with the later-onset group. In addition, profound CD4+ T-cell lymphopenia was found in patients with early-onset. Conclusions Patients with early-onset pSS have distinctive clinical manifestations and greater activation of the cellular immune system, present with more severe clinical symptoms and immunological features, have increased activation of circulating T cells and have an unfavourable prognosis. Thus, they require more positive treatment with glucocorticoids and/or immunosuppressants and merit closer follow-up and regular monitoring. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the relationship between age at onset of cannabis use and cannabis abuse in a sample of Portuguese cannabis users, testing the mediating role of the number of friends using cannabis and comparing these relationships between male and female subsets. Method: A sample of 529 Portuguese cannabis users comprising 276 males and 244 females aged from 14 to 21 years completed a sociodemographic questionnaire, the Cannabis Abuse Screening Test (CAST), and answered four questions related to cannabis use. Data were analyzed using the PROCESS macro in SPSS version 26.0. Results: Age at onset of cannabis use was negatively related to the number of friends using cannabis, while the number of friends using cannabis had a positive relationship with cannabis abuse. As predicted, the number of friends using cannabis seems to have a mediating role in the relationship between cannabis onset age use and cannabis abuse, since the indirect effect was found to be significant. The pattern of the relationships among the variables observed was found to be similar for both male and female subsets of the sample. However, males reported higher cannabis abuse than females. Conclusion: The results highlight the mediating role of friends' use of cannabis in the relationship between age at onset of cannabis use and users' abuse. These results highlight the importance of early intervention in cannabis use. In particular, the pattern of the relationships observed among the studied variables emphasizes the need to monitor and conduct peer training interventions or interventions to promote of social skills. [ABSTRACT FROM AUTHOR]

Abstract Background Though outcome differences between children and adults with immunoglobulin A vasculitis (IgAV) has been well documented, it remains unclear if disease features in pediatric IgAV patients vary with onset age. We aimed to explore clinical features and prognosis of pediatric IgAV stratified by onset age. Methods We retrospectively reviewed records of patients under 18 years old diagnosed with IgAV from January 1999 to December 2018 in one tertiary medical center in Taiwan. Patients were grouped by onset age: ≤ 6 years old, 6–12 years old (> 6, ≤ 12), and 12–18 years old (> 12,

Abstract Background X chromosome inactivation (XCI) is the mechanism by which the X-linked gene dosage is adjusted between the sexes. Evidence shows that many sex-specific diseases have their basis in X chromosome biology. While female schizophrenia patients often have a delayed age of disease onset and clinical phenotypes that are different from those of males, it is unknown whether the sex differences in schizophrenia are associated with X-linked gene dosage and the choice of X chromosome silencing in female cells. Previous studies demonstrated that sex chromosome aneuploidies may be related to the pathogeneses of some psychiatric diseases. Here, we examined the changes in skewed XCI in patients with schizophrenia. Methods A total of 109 female schizophrenia (SCZ) patients and 80 age- and sex-matched healthy controls (CNTLs) were included in this study. We evaluated clinical features including disease onset age, disease duration, clinical symptoms by the Positive and Negative Syndrome Scale (PANSS) and antipsychotic treatment dosages. The XCI skewing patterns were analyzed by the methylation profile of the HUMARA gene found in DNA isolated from SCZ patient and CNTL leukocytes in the three age groups. Results First, we found that the frequency of skewed XCI in SCZ patients was 4 times more than that in the age- and sex-matched CNTLs (p < 0.01). Second, we found an earlier onset of severe XCI skewing in the SCZ patients than in CNTLs. Third, we demonstrated a close relationship between the severity of skewed XCI and schizophrenic symptoms (PANSS score ≥ 90) as well as the age of disease onset. Fourth, we demonstrated that the skewed XCI in SCZ patients was not transmitted from the patients’ mothers. Limitations The XCI skewing pattern might differ depending on tissues or organs. Although this is the first study to explore skewed XCI in SCZ, in the future, samples from different tissues or cells in SCZ patients might be important for understanding the impact of skewed XCI in this disease. Conclusion Our study, for the first time, investigated skewed XCI in female SCZ patients and presented a potential mechanism for the sex differences in SCZ. Our data also suggested that XCI might be a potential target for the development of female-specific interventions for SCZ.

Background: Easy Z-score imaging system (eZIS)-assisted SPECT accurately detects decreases in cerebral blood flow in the posterior cingulate cortex (PCC), precuneus, and parietal lobe, the cerebral regions deeply implicated in Alzheimer’s disease (AD). Several studies suggested onset age-dependent decreases in cerebral blood flow in these regions in AD, but these studies did not screen for amyloid accumulation, suggesting inclusion of non-AD patients in their subjects. Objective: By applying eZIS-SPECT to patients with amyloid deposition, it was the aim of this study to clarify onset age-dependent decreases in cerebral blood flow in the regions critical to AD. Methods: We retrospectively analyzed eZIS-SPECT data on 34 AD patients with amyloid retention confirmed by 11C-Pittsburgh compound B-PET. The subjects were divided into an early-onset group (n = 16) and a late-onset group (n = 18). The three indicators of the eZIS that had discriminated between AD patients and normal controls in previous studies were compared between the two groups. Results: The mean values for the respective indicators were significantly higher in the early-onset group than in the late-onset group. Also, the proportion of patients with abnormalities in all indicators was significantly higher in the early-onset group (93.8%) than in the late-onset group (50.0%). Conclusions: The present study, applying eZIS-SPECT to amyloid-positive AD patients, suggests that reduced cerebral blood flow in the PCC, precuneus, and parietal lobe is more pronounced in the early-onset type than in the late-onset type of the disease.

BackgroundMetabolic syndrome (MetS) is associated with an increased risk of incident cardiovascular diseases (CVD), but the association between the new-onset MetS at different ages and the CVD risk remain unclear.MethodsThis was a prospective study comprising a total of 72,986 participants without MetS and CVD who participated in the Kailuan study baseline survey (July 2006 to October 2007). All participants received the biennial follow-up visit until December 31, 2019. In addition, 26,411 patients with new-onset MetS were identified from follow-up, and one control participant was randomly selected for each of them as a match for age ( ± 1 year) and sex. In the end, a total of 25,125 case-control pairs were involved. Moreover, the Cox proportional hazard model was established to calculate the hazard ratios (HR) for incident CVD across the onset age groups.ResultsAccording to the median follow-up for 8.47 years, 2,319 cases of incident CVD occurred. As MetS onset age increased, CVD hazards gradually decreased after adjusting for potential confounders. Compared with non-MetS controls, the HR and the 95% confidence interval (CI) for CVD were 1.84 (1.31–2.57) in the MetS onset age

Background: Metabolic syndrome (MetS) at baseline increases the risks of cardiovascular diseases (CVD) and all-cause mortality. However, MetS status is changeable during follow-up. The associations of dynamic changes of MetS with CVD and all-cause mortality remain unclear.Methods: Thirty-one thousand four hundred eighty-one eligible subjects were included from the Kailuan cohort. Dynamic changes of MetS were divided into four patterns as MetS-free, MetS-developed, MetS-recovery and MetS-stable. The outcomes were CVD, all-cause mortality, and the subtypes of CVD as myocardial infarction (MI), stroke and heart failure. Multiple Cox regression models were used to calculate the adjusted hazard ratios (HRs) and confidence intervals (95% CIs).Results: Altered risks of CVD, the subtypes of CVD, and all-cause mortality were observed among different dynamic patterns of MetS. Compared with the MetS-free group, MetS-developed group increased the risks of CVD (HR = 1.78, 95% CI = 1.51–2.11), MI (HR = 1.54, 95% CI = 1.01–2.34), stroke (HR = 1.78, 95% CI = 1.45–2.18), and heart failure (HR = 1.63, 95% CI = 1.11–2.39). MetS-recovery group decreased these risks with the HRs of 0.59 (95% CI = 0.48–0.72) for CVD, 0.62 (95% CI = 0.41–0.96) for MI, 0.59 (95% CI = 0.46–0.75) for stroke, and 0.56 (95% CI = 0.34–0.91) for heart failure compared with the MetS-stable group. However, the increased risk in the MetS-developed group and the decreased risk in the MetS-recovery group were not significant for all-cause mortality. When stratified by the onset age of MetS status change, early development of MetS (

The onset age of ulcerative colitis has been increasing in several countries. Furthermore, the number of elderly patients with ulcerative colitis has been increasing in an aging society. We investigated the incidence of ulcerative colitis patients in Japan using a large-scale health insurance claims database to survey the ulcerative colitis incidence ratio and the clinical characteristics in late-onset ulcerative colitis patients. Newly diagnosed 2,791 ulcerative colitis between 2015 and 2018 was investigated. Medical treatment within 12 months of diagnosis was analyzed among 0-19, 20-39, 40-59 and 60-75 age groups. The mean age at diagnosis was 40.3 years (SD: 12.9), and the incidence ratio peaked in the 40's. Most of patients received 5-aminocylitic acid (91.7%), a subset of patients received prednisolone (20.1%), and a small number of patients took immunomodulator (6.8%), cytapheresis (3.3%), anti-TNFa therapy (4.3%), and colectomy (1.0%) within 12 months after diagnosis. All treatments except colectomy were most frequent in the 0-19 age group; however, colectomy was most frequent in 60-75 age group. The clinical course of ulcerative colitis that developed in adults did not differ significantly in terms of medical treatment within 12 months from the onset; meanwhile, the surgery rate was high in elderly patients. It is necessary to pay close attention to future trends regarding the aging of the onset age and the treatment, especially for late-onset ulcerative colitis patients. [ABSTRACT FROM AUTHOR]

The incidence of melanoma is one of the fastest growing of all tumor types in the United States and the number of cases worldwide has doubled in the past 30 years. Melanoma, which arises from melanocytes, is an extremely aggressive tumor that invades the vascular and lymphatic systems to establish tumors elsewhere in the body. Melanoma is a particularly resilient cancer and systemic therapy approaches have achieved minimal success against metastatic melanoma resulting in only a few FDA-approved treatments with limited benefit. Leading treatments offer minimal efficacy with response rates generally under 15% in the long term with no clear effect on melanoma-related mortality. Even the recent success of the specific BRAF mutant inhibitor vemurafenib has been tempered somewhat since acquired resistance is rapidly observed. Thus, understanding the mechanism(s) of melanoma carcinogenesis is paramount to combating this deadly disease. Not only for the treatment of melanoma but, ultimately, for prevention. In this report, we will summarize our work to date regarding the characterization of ultraviolet radiation (UVR)-mediated melanomagenesis and highlight several promising avenues of ongoing research. © 2014 Elsevier B.V. All rights reserved.

Reversible splenium lesions during febrile illness (RESLEF) are found in a spectrum. There are two types of corpus callosum (CC) lesions: CC-only type, with limited lesions and the CC (+) type, with extensive white-matter lesions. This retrospective study aimed to describe the differences in clinical findings between CC-only and CC (+) lesions and the association between onset age and clinico-radiological features in RESLEF. Fifty-two episodes of CC-only or CC (+) lesions accompanied by neurological symptoms, e.g., seizures, delirious behavior (DB), and disturbance of consciousness (DC), from January 2008 to October 2019 were included. We analyzed the etiology (pathogen), clinical course, laboratory data, magnetic resonance imaging and electroencephalography findings, therapy, and prognosis. The rate of DC in the CC (+) was significantly higher than that in the CC-only group (5/6 [83%] vs 7/46 [15%]; p = 0.0016). The median number of seizures in the CC (+) was also significantly higher than that in the CC-only group (4 [0–7] vs 0 [0–7]; p = 0.034). Further, in RESLEF, the median onset age (months) in the seizure was significantly lower than that in the no-seizure group (39 [12–74] vs 83 [28–174]; p = 0.0007). The median onset age (months) in the DB was significantly higher than that in the no-DB group (74.5 [26–174] vs 28 [12–139]; p = 0.003). In RESLEF, CC (+) is a more severe neurological symptom than CC-only. Furthermore, the onset age is related to the type of neurological symptoms that appear. [ABSTRACT FROM AUTHOR]

Background: The average age at onset of heart failure (HF) shows a progressive decrease in recent years; however, the association between age at onset of HF and risk of subsequent dementia remains undetermined., Objectives: This study sought to examine whether younger onset age of HF is associated with a higher risk of incident dementia., Methods: Individual-level data from the UK Biobank cohort study were analyzed in the present study. Cox regression models and the propensity score matching method were used to analyze the associations of HF and its onset age with subsequent all-cause dementia, Alzheimer disease (AD), and vascular dementia (VD)., Results: Compared with 442,791 participants without HF, those with HF had a higher risk of all-cause dementia (HR: 1.14). Among 14,413 participants with HF, multivariable-adjusted HRs for all-cause dementia, AD, and VD were 1.18, 1.64, and 1.27, respectively, per 10-year decrease in age at HF onset. The propensity score matching analyses found that the strength of association between HF and all-cause dementia increased with decreasing onset age of HF (≥75 years, HR: 1.05; 65-74 years, HR: 1.10; <65 years, HR: 1.67) after multivariable adjustment. Similarly, participants with onset age of HF <65 years had the greatest HRs for incident AD and VD, compared with their matched control subjects., Conclusions: Younger age at HF onset was associated with increased risk of dementia. Individuals with an onset age of HF before 65 years of age may represent a particularly vulnerable population for dementia irrespective of subtypes and need careful monitoring and timely intervention to attenuate subsequent risk of incident dementia., Competing Interests: Funding Support and Author Disclosures This work was supported by the National Natural Science Foundation of China (project number 82373665 and 81974490), the Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences (2021-RC330-001), and the 2019 Irma and Paul Milstein Program for Senior Health Research Project Award. The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

ObjectivesLate-life depression (LLD) has negative impacts on somatic, emotional and cognitive domains of the lives of patients. Elucidating the abnormality in the brain networks of LLD patients could help to strengthen the understanding of LLD pathophysiology, however, the studies exploring the spontaneous brain activity in LLD during the resting state remain limited. This study aimed at identifying the voxel-level whole-brain functional connectivity changes in LLD patients.MethodsFifty patients with late-life depression (LLD) and 33 healthy controls were recruited. All participants underwent a resting-state functional magnetic resonance imaging scan to assess the voxel-wise degree centrality (DC) changes in the patients. Furthermore, DC was compared between two patient subgroups, the late-onset depression (LOD) and the early-onset depression (EOD).ResultsCompared with the healthy controls, LLD patients showed increased DC in the inferior parietal lobule, parahippocampal gyrus, brainstem and cerebellum (p < 0.05, AlphaSim-corrected). LLD patients also showed decreased DC in the somatosensory and motor cortices and cerebellum (p < 0.05, AlphaSim-corrected). Compared with EOD patients, LOD patients showed increased centrality in the superior and middle temporal gyrus and decreased centrality in the occipital region (p < 0.05, AlphaSim-corrected). No significant correlation was found between the DC value and the symptom severity or disease duration in the patients after the correction for multiple comparisons.ConclusionsThese findings indicate that the intrinsic abnormality of network centrality exists in a wide range of brain areas in LLD patients. LOD patients differ with EOD patients in cortical network centrality. Our study might help to strengthen the understanding of the pathophysiology of LLD and the potential neural substrates underlie related emotional and cognitive impairments observed in the patients.

Background: X chromosome inactivation (XCI) is the mechanism by which the X-linked gene dosage is adjusted between the sexes. Evidence shows that many sex-specific diseases have their basis in X chromosome biology. While female schizophrenia patients often have a delayed age of disease onset and clinical phenotypes that are different from those of males, it is unknown whether the sex differences in schizophrenia are associated with X-linked gene dosage and the choice of X chromosome silencing in female cells. Previous studies demonstrated that sex chromosome aneuploidies may be related to the pathogeneses of some psychiatric diseases. Here, we examined the changes in skewed XCI in patients with schizophrenia. Methods: A total of 109 female schizophrenia (SCZ) patients and 80 age- and sex-matched healthy controls (CNTLs) were included in this study. We evaluated clinical features including disease onset age, disease duration, clinical symptoms by the Positive and Negative Syndrome Scale (PANSS) and antipsychotic treatment dosages. The XCI skewing patterns were analyzed by the methylation profile of the HUMARA gene found in DNA isolated from SCZ patient and CNTL leukocytes in the three age groups. Results: First, we found that the frequency of skewed XCI in SCZ patients was 4 times more than that in the age- and sex-matched CNTLs (p < 0.01). Second, we found an earlier onset of severe XCI skewing in the SCZ patients than in CNTLs. Third, we demonstrated a close relationship between the severity of skewed XCI and schizophrenic symptoms (PANSS score ≥ 90) as well as the age of disease onset. Fourth, we demonstrated that the skewed XCI in SCZ patients was not transmitted from the patients' mothers. Limitations: The XCI skewing pattern might differ depending on tissues or organs. Although this is the first study to explore skewed XCI in SCZ, in the future, samples from different tissues or cells in SCZ patients might be important for understanding the impact of skewed XCI in this disease. Conclusion: Our study, for the first time, investigated skewed XCI in female SCZ patients and presented a potential mechanism for the sex differences in SCZ. Our data also suggested that XCI might be a potential target for the development of female-specific interventions for SCZ. [ABSTRACT FROM AUTHOR]

Background: Atopic dermatitis (AD) in adults is not uncommon, and its prevalence has been increasing in the recent decades. However, there is a paucity of data about the differences between early-onset and late-onset adult AD. Objective: The objective of this study is to investigate the clinical and laboratory characteristics of adult AD, focusing on the differences between early-onset and late-onset adult AD. Methods: We retrospectively reviewed the medical records and clinical photos of 214 adult AD patients (≥18 years of age) over a 3-year period. We classified the patients into 2 groups: early-onset (first onset of AD before 12 years of age) and late-onset (first onset of AD at 12 years of age or later). Results: Among 214 patients, 151 patients (70.6%) belonged to the early-onset group (mean age 24.5 years), while 63 patients belonged to the late-onset group (mean age 29.5 years). An association with allergic asthma or rhinitis, a family history of atopic disease, elevated total serum IgE, and sensitivity to food allergens were more commonly seen in the early-onset group. The late-onset group had a significant likelihood of nonflexural involvement (38.1% vs 13.2%). There was no significant difference in the mean eczema area severity index score, eosinophil count, and sensitivity to aeroallergens between 2 groups. Conclusion: Adult AD shows different clinical and laboratory characteristics depending on the age of onset. This study could help to create awareness about the heterogeneity of AD in adulthood and encourage further studies on clinical outcomes and different therapeutic methods depending on the age of onset. [ABSTRACT FROM AUTHOR]

Objective To evaluate the effect of onset age of diabetes on metabolic control in adult patients with type 1 diabetes mellitus (T1DM). Methods Adults with T1DM from Guangdong type 1 diabetes translational study between Janurary 2011 to December 2017 were enrolled in this cross‐over survey. Patients were eligible if they were aged ≥18 years with diabetes duration longer than 1 years. Demographic data, glycated hemoglobin A1c (HbA1c), body mass index (BMI), lipid level, blood pressure (BP) and other metabolic indicators were collected. Insulin resistance in adults with T1DM was evaluated by estimate glucose disposal rate (eGDR) model calculation. The effects of onset age of diabetes on metabolic control and insulin resistance in adult patients with T1DM were evaluated. Partial correlation analysis was used to analyze the correlation between the onset age of diabetes and HbA1c or insulin resistance after eliminating the influence of the course of diabetes. Results (1) A total of 872 T1DM adults including 508 (58.3%) female patients with disease duration over 1 year were enrolled. The mean age was (33±11) years old, the mean onset age was (27±12) years and the mean diabetic duration was (8±6) years. (2) The overall mean HbA1c level for all patients was (8.9±2.6)%, and 23.8% (n=208) of them had HbA1c <7%. The mean BMI for all patients was (20.8±2.8) kg/m², and 89.7% (n=782) of them had BMI 18.5 to 23.9 kg/m². 26.3% (n=61) patients were dyslipidemia (TG≥1.7 mmol/L or HDL‐C<1.04 mmol/L). The mean BP for all patients was (116±15)/(73±9) mmHg (1 mmHg=0.133 kPa), and 88.4% (n=691) of them achieved the recommended BP control target. Only 26 patients (3.0%) reached the control standard in blood glucose, body weight, blood pressure and blood lipids. The overall eGDR was 8.84 (6.84,10.79) mg·kg－1·min－1. (3) Children and adolescent onset patients had a higher mean HbA1c(F= 4.863,P<0.05) and a severer insulin resistance (F=3.177,P<0.05) compared with adult onset diabetic patients. The control rate of HbA1c and serum lipid in children onset patients were lower compared with those in the other two groups (F=2.943 and 3.404, all P<0.05). Conclusion Earlier onset age of diabetes is associated with poor metabolic control and insulin resistance in T1DM adult patients in China Guangdong province. Individual management should take the diabetes onset age into account. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to investigate the effect of age at helmet therapy onset on treatment efficacy in moderate-to-severe deformational plagiocephaly (DP) and combined DP and asymmetrical brachycephaly (AB) in infants. Methods: Ninety-eight infants who were referred to our institution and who underwent helmet therapy between 2014 and 2018 were retrospectively reviewed. Patients with DP [cranial vault asymmetry index (CVAI) > 7% and DD > 10 mm] and AB [CVAI > 7% and cephalic ratio (CR) ≥ 94] were included. Pre- and post-treatment calvarial asymmetries (difference among DD, CVAI, and CR) were measured using 3D screening systems (SmartSoc and Omega Scanner 3D). Infants were classified according to age at treatment onset: group 1 (age, < 6 months) and group 2 (age, ≥ 6 months). Results: CVAI was statistically different between treatment onset and end in subgroups. Moreover, the regression of CVAI between groups DP1 (− 7.5% ± 1.2%) versus DP2 (− 5.4% ± 1.5%; p = 0.001) and groups AB1 (− 6.6% ± 1.4%) versus AB2 (− 4.4 ± 2.5; p = 0.0013) was statistically significant. CVAI was < 3.5% and CR was ≤ 89 (assumed as normal cranial shape) after treatment in 48%, 40%, 32%, and 6% of infants in groups DP1, DP2, AB1, and AB2, respectively. Conclusion: These findings emphasize the efficacy of helmet therapy for DP and AB. Helmet is an appropriate treatment option particularly for infants with severe DP and AB, and early onset of helmet therapy before the age of 6 months is advised. [ABSTRACT FROM AUTHOR]

Objectives: Late-life depression (LLD) has negative impacts on somatic, emotional and cognitive domains of the lives of patients. Elucidating the abnormality in the brain networks of LLD patients could help to strengthen the understanding of LLD pathophysiology, however, the studies exploring the spontaneous brain activity in LLD during the resting state remain limited. This study aimed at identifying the voxel-level whole-brain functional connectivity changes in LLD patients. Methods: Fifty patients with late-life depression (LLD) and 33 healthy controls were recruited. All participants underwent a resting-state functional magnetic resonance imaging scan to assess the voxel-wise degree centrality (DC) changes in the patients. Furthermore, DC was compared between two patient subgroups, the late-onset depression (LOD) and the early-onset depression (EOD). Results: Compared with the healthy controls, LLD patients showed increased DC in the inferior parietal lobule, parahippocampal gyrus, brainstem and cerebellum (p < 0.05, AlphaSim-corrected). LLD patients also showed decreased DC in the somatosensory and motor cortices and cerebellum (p < 0.05, AlphaSim-corrected). Compared with EOD patients, LOD patients showed increased centrality in the superior and middle temporal gyrus and decreased centrality in the occipital region (p < 0.05, AlphaSim-corrected). No significant correlation was found between the DC value and the symptom severity or disease duration in the patients after the correction for multiple comparisons. Conclusions: These findings indicate that the intrinsic abnormality of network centrality exists in a wide range of brain areas in LLD patients. LOD patients differ with EOD patients in cortical network centrality. Our study might help to strengthen the understanding of the pathophysiology of LLD and the potential neural substrates underlie related emotional and cognitive impairments observed in the patients. [ABSTRACT FROM AUTHOR]

As the oligoclonal band in the cerebrospinal fluid (CSF-OCB) in predicting relapsing-remitting multiple sclerosis (RRMS) is less sensitive in Asian populations than that in westerners, it remains elusive whether the IgG index could serve as an alternative. The purpose of this study was to compare these two methods of differentiating between RRMS and neuromyelitis optica spectrum disorder (NMOSD) in Chinese patients. A total of 171 patients (81 RRMS and 90 NMOSD) were retrospectively recruited, of whom 82 (56 RRMS and 26 NMOSD) received the CSF-OCB testing additionally. When the onset age was ≤38.5 years, IgG index with the threshold of 0.67 had a significant agreement (k = 0.4, p < 0.001) with the diagnosis while CSF-OCB failed to discriminate (k = 0.1, p = 0.578). However, when the onset age was >38.5 years, both IgG index with the threshold of 0.8 and CSF-OCB were moderately consistent with the diagnosis (both k > 0.4, p < 0.05). In total, our optimized algorithm had the sensitivity, specificity, and predictive accuracy of 0.778, slightly outperforming the CSF-OCB model. Accordingly, a combination of the onset age and IgG index could serve as an alternative to CSF-OCB for differentiating between RRMS and NMOSD in Chinese patients.

Von Hippel–Lindau (VHL) disease is a rare autosomal-dominant inherited tumor syndrome. We aimed to analyze the correlations between frequent VHL mutations and phenotypes in Chinese VHL families. We screened 540 patients from 187 unrelated Chinese VHL families for 19 frequent VHL mutations. The penetrance and mean age at onset for VHL-associated susceptible organs were calculated and compared. The overall survival of VHL patients was described with Kaplan–Meier curves. Among the 19 frequent germline mutations, there were four hotspot mutation sites (194, 481, 499, and 500). Missense mutations were the most common types of mutations (70.0%) followed by nonsense mutations (20.0%) and splicing mutations (10.0%). Due to the diversity of these mutations, the penetrance for each organ and the age at onset are distinct. Even in cases of similar mutations, variance in the penetrance and age at onset was observed. The mean age at death for the patients in this cohort was 42.4 ± 13.5 years, and variability was observed in the Kaplan–Meier curves. We present a precise summary of the phenotypes for the frequent VHL mutations in the largest Chinese VHL cohort, which provides valuable strategies for genetic counseling and clinical surveillance of VHL individuals.

Von Hippel–Lindau (VHL) disease is a rare autosomal-dominant inherited tumor syndrome. We aimed to analyze the correlations between frequent VHL mutations and phenotypes in Chinese VHL families. We screened 540 patients from 187 unrelated Chinese VHL families for 19 frequent VHL mutations. The penetrance and mean age at onset for VHL-associated susceptible organs were calculated and compared. The overall survival of VHL patients was described with Kaplan–Meier curves. Among the 19 frequent germline mutations, there were four hotspot mutation sites (194, 481, 499, and 500). Missense mutations were the most common types of mutations (70.0%) followed by nonsense mutations (20.0%) and splicing mutations (10.0%). Due to the diversity of these mutations, the penetrance for each organ and the age at onset are distinct. Even in cases of similar mutations, variance in the penetrance and age at onset was observed. The mean age at death for the patients in this cohort was 42.4 ± 13.5 years, and variability was observed in the Kaplan–Meier curves. We present a precise summary of the phenotypes for the frequent VHL mutations in the largest Chinese VHL cohort, which provides valuable strategies for genetic counseling and clinical surveillance of VHL individuals. [ABSTRACT FROM AUTHOR]