Autism Spectrum Disorder (ASD) is a complex neurodevelopmental disorder that can be associated with intellectual disability (ID) and epilepsy (E). The etiology and the pathogenesis of this disorder is in most cases still to be clarified. Several studies have underlined that the EEG recordings in children with these clinical pictures are abnormal, however the precise frequency of these abnormalities and their relationship with the pathogenic mechanisms and in particular with epileptic seizures are still unknown. We retrospectively reviewed 292 routine polysomnographic EEG tracings of preschool children (age < 6 years) who had received a first multidisciplinary diagnosis of ASD according to DSM-5 clinical criteria. Children (mean age: 34.6 months) were diagnosed at IRCCS E. Medea . We evaluated: the background activity during wakefulness and sleep, the presence and the characteristics  of the slow-waves abnormalities and the interictal epileptiform discharges. In 78.0% of cases the EEG recordings were found to be abnormal, particularly during sleep. Paroxysmal slowing and epileptiform abnormalities were found in the 28.4% of the subjects, confirming the high percentage of abnormal polysomnographic EEG recordings in children with ASD. These alterations seem to be more correlated with the characteristics of the underlying pathology than with intellectual disability and epilepsy. In particular, we underline the possible significance of the prevalence of EEG abnormalities during sleep. Moreover, we analyzed the possibility that EEG data reduces the ASD clinical heterogeneity and suggests the exams to be carried out to clarify the etiology of the disorder. Autism Spectrum Disorder (ASD) is a complex neurodevelopmental disorder characterized by persistent deficits in social communication and interaction and by restricted, repetitive patterns of behavior, interests and/or activities. It becomes clinically evident during the early developmental period and leads to different degrees of impairment in personal, social and occupational functioning depending on the spectrum and severity of symptoms .In subjects with ASD, cognitive skills range widely; some individuals present with severe intellectual disability, others show high-level cognitive functioning. Neurological manifestations such as epilepsy, motor impairment and sleep disorders are common, and also associated with the more severe phenotypes of ASD. Thus, the early diagnosis and treatment of these comorbidities could improve the behavioral and cognitive difficulties .Based on the latest Centers for Disease Control and Prevention’s report (2018), in the US, 1 in every 44 children aged 8 years is affected by ASD, with an average ratio 4:1 for male: female and with an increasing trend of prevalence in recent years . In ItalDespite symptoms could appear in the first year of life, diagnosis of ASD is usually established in children between 2 and 4 years, according to DSM-5 clinical criteria, with the support of behavioral tests and parental interviews ,5.A number of environmental and biological factors may potentially contribute to the etiopathogenesis of the disorder. Most of them, such as congenital infections or toxicant exposures, act during fetal and perinatal periods, in the developmental phase of the central nervous system. A strong genetic component in ASD has also been confirmed .In the study by Donovan et al., 2017), several neuroanatomical abnormalities have been identified in brain structures and neuronal circuits such as cerebellum, limbic system, corpus callosum and frontal cortex of subjects affected by the disorder , several. To datep < 0.01), as well as an abnormal neurodevelopment during the first year of life to be related with epileptiform EEG abnormalities (p < 0.05) and epilepsy to be significantly associated with intellectual disability (p < 0.01) [p < 0.05 or p < 0.01): severe forms of autism, behavioral problems, motor stereotypies, intellectual disability and language impairment [An abnormal EEG characterizes 8–80% of non-epileptic ASD children and a mean of 39.1% of subjects with autism of all ages with or without epilepsy ,12. Abou < 0.01) . In NicoWithin this context, the primary aim of our study is to classify and quantify the EEG abnormalities recorded in a cohort of preschool children with ASD undergone to polysomnographic EEG (PSG-EEG) study at the IRCCS E. Medea, Bosisio Parini.Secondary aim is to estimate the prevalence of children with Paroxysmal Slowing and Interictal Epileptiform Discharges (PS-IEDs) on EEG recordings, both during wakefulness and sleep, to highlight any difference in their occurrence and to determine the prevalence of epilepsy within the same group.Tertiary aim is to explore a possible relationship between the EEG findings and the clinical phenotype of individuals with ASD, in term of intellectual disability, considering the potential usefulness of EEG data in the clinical classification, diagnostic and therapeutic management of these subjects.The data presented in this study were collected at the IRCCS E. Medea  a Scientific Institute funded by Italian Ministry of Health, dedicated to diagnosis, treatment and biomedical research of neurodevelopmental, neurological and neurodegenerative diseases of pediatric age. Clinical diagnosis of ASD was established in the children according to DSM-5 criteria by a multidisciplinary team , constitAt the IRCCS E. Medea in all children of early/pre-school age admitted to the Psychopathological Department, in which ASD has been diagnosed, a PSG-EEG is recorded during daytime spontaneous sleep, with average recording time of 40–70 min. This protocol is based on the Clinical Practice Guidelines by SINPIA and APA . These gParents are asked for consent to use of the data, collected through EEG recordings and other instrumental diagnostic tests, for research purposes in anonymous and aggregated form.In the light of the abovementioned recommendations and guidelines, we present in this paper a retrospective analysis of the PSG-EEG recordings collected over 30 months in order to describe the amount and characteristics of the abnormal data and explore the usefulness of this procedure in the diagnosis of ASD at an early age.All the PSG-EEG were digitally acquired (by MICROMED BQ32SYNCMASTER) at the Clinical Neurophysiology Unit of IRCCS E. Medea, with 20 scalp electrodes  and at least 2 surface electromyographic (EMG) electrodes (mainly placed over deltoids muscles of both sides).The recordings were analyzed by 3 expert clinical neurophysiologists, unaware of subjects’ clinical and diagnostic details.In all the recordings, features of the background activity during wakefulness and sleep were analyzed. Moreover, the presence and the location  of abnormal slow waves and PS-IEDs were assessed and classified according to the definitions of the International Glossary of clinical electroencephalography .We included in the study all children, younger than 6 years, who performed EEG-PSG recording in the context of diagnostic evaluation for ASD and in whom we obtained a sleep recording. All children in whom ASD was associated with a defined neurological and/or metabolic or genetic disease with a documented etiology were excluded.p)-value less than 0.05 (≤0.05) was considered statistically significant.We carried out exploratory statistical analyses only on categorical data, with contingency tables and one-tailed chi-square tests to evaluate the possible associations between PS-IEDs and neurodevelopmental delay and between neurodevelopmental delay and abnormal background activity at the EEG. We also calculated the prevalence of subjects with PS-IEDs only during sleep or even during wakefulness. We performed all data analysis with GraphPad Prism 8 (for Windows 64-bit). A probability . One child was diagnosed during the clinical workup with a type 1 Neurofibromatosis. Thus, 292 PSG-EEG recorded in 292 children with ASD were examined . Mean agNo child showed focal neurological signs, but 190 children (69.5%) presented with developmental delay. Only 1 individual (0.35%) received a diagnosis of epilepsy . Twenty-four subjects underwent MRI and abnormal findings were found in 15 cases  showed PS-IEDs.In 79 cases (95.2%) PS-IEDs were present only during sleep and in 4 cases (4.8%) also during wakefulness, specifically with a frequency 19.7 times higher during sleep. As far as the localization of PS-IEDs is concerned, 37.7% of the PS-IEDs were focal and 62.7% bilateral, diffuse. Focal PS-IEDs were in 48.4% of recordings over central areas, 32.3% over temporal areas and 19.3% over the frontal ones.During wakefulness, most of children (96.0%) did not show EEG alterations, while a minor percentage (4.00%) showed PS-IEDs or abnormal slow waves. On the other hand, in 76.0% of the subjects, slow or paroxysmal abnormalities were found during sleep. Examples are showed in We explored the relationship between developmental level impairment, abnormal features of background activity in sleep and the presence of PS-IEDs.p = 0.2787.As far as PS-IEDs are concerned, a developmental delay was found in 68.7% of individuals with PS-IEDs and in 64.1% of subjects without PS-IEDs with no significant association between the two factors: p = 0.0004.However, abnormal background activity during sleep was associated to developmental delay in 73.5% of the individuals, while normal background activity was related to developmental delay in 54.6% of the cases, with an extremely significant association between the two factors: There is a growing interest towards EEG features of ASD subjects, with particular focus on background abnormalities and IEDs, despite the lack of concluding evidence on the diagnostic, prognostic and therapeutic role of EEG data in ASD. Nevertheless, EEG features could be particularly useful in reducing heterogeneity in this spectrum of neuropsychiatric developmental disorders. PS-IEDs are frequent among ASD people, while are rare (1–4%) in healthy subjects . SeveralResults of our study confirm the high amount of EEG abnormalities in ASD children, with 28.4% of subjects showing PS-IEDs during sleep, while only a minor percentage showing PS-IEDs during wakefulness. These data are aligned with others studies reporting a prevalence of PS-IEDs of about 30% in a similar sample, i.e., children with ASD without epilepsy (mean age about 3 years) ,29. As already highlighted in some papers ,31, the In literature, abnormal background activity is statistically associated to developmental delay ,33. In oParticularly, the relevant finding of PS-IEDs mainly during sleep recordings, may suggests that these abnormal circuitries could be linked to the physiological, cyclical pattern of the neuronal firing during non-REM sleep , confirmWith our data we don’t want to suggest that the visual analysis of the EEG constitutes directly a diagnostic tool. Indeed, the diagnosis of ASD is a clinical one, based on the analysis of the developmental history and the observation of the child’s interaction with their parents and unfamiliar adults during a combination of structured and unstructured assessments .Nevertheless, the correlation of sleep EEG data with a clinical phenotype, such as the presence of developmental delay, can help in facilitating the definition of neurological endophenotypes with a reduction of the heterogeneity in ASD study samples and may also be a clinical marker. The detection of focal EEG abnormalities recommends MRI investigations in individuals with ASD. Surely, a bias of our study is the low percentage of MRI performed, due to the fact that the above recommendation has not yet entered the diagnostic routine of the clinical practice. Other findings, such as excess of fast activity, asynchronous PS-IEDs over the central regions of the brain, detection of non-epileptic myoclonus, should prompt clinicians to perform tests aimed at identifying a possible genetic cause .In our sample, only one subject was diagnosed with an epileptic syndrome. This rate (0.35%) is very low compared to data reported in literature, although many children of our sample showed intellectual disability (66%), which is considered as a risk factor for developing epilepsy in ASD. Indeed, two peaks of epilepsy onset are described in ASD so far : the firAs far as the unexplained M:F ratio is concerned, it may be related to the fact that females have been found to be diagnosed with ASD at significantly later ages and to experience greater delays in the time from an initial evaluation to receiving a clinical ASD diagnosis ,38,39. QThe use of anti-seizures medications in individuals with PS-IEDs in the absence of clinical seizures is controversial . As we sFinally, the prognostic significance of PS-IEDs in young subjects with ASD on the possibility of later developing epileptic seizures can be only clarified with prospective studies with quite long follow-up.Another possible use of EEG data in subjects with ASD is the detailed study of the prognostic questions regarding the outcome of autism.ASD has a heterogeneous developmental time course . Indeed,Several studies have explored the relationship between EEG abnormalities and adaptive behavior, executive functioning, severity of ASD core symptoms and other psychiatric symptoms, finding that  childrenTherefore, EEG abnormalities, especially in early age, can have a negative impact on brain development, compromising both cognition and behavior .For this reason, several rehabilitation projects have been launched in our Institute on very young children who receive a diagnosis of ASD .Our data represent a starting point for setting up further prospective studies aiming correlating over time the outcome of these therapeutic procedures with PSG-EEG findings at the time of diagnosis.These studies may outline the profiles of children most at risk of having a worse prognosis and a lower response to rehabilitation interventions.Our study presents with some limitations. The first one is due to the initial selection of the subjects included. In order to better homogenize our cohort, we choose to include in our study only preschool children. Focusing on this early age, may have missed data on the development of epilepsy in older age.Moreover, clearly syndromic individuals and epileptic subjects are less likely to come to our attention as a first step.Based on these limitations, we chose to conduct only an exploratory analysis, we did not calculate sample size and we did not deal with confounding factors and other clinical variables, which we will examine in future perspective studies. However, we calculated study power post-hoc on the main outcome analysis, i.e., the contingency table crossing epileptiform abnormalities X delayed development, obtaining 10.9% power. Therefore, we can conclude that this study is not adequately powered to claim that there is no difference in the occurrence of epileptiform abnormalities between children with delayed and normal development. We calculated study power post-hoc also on the secondary outcome analysis, i.e., the contingency table crossing background activity X delayed development, obtaining 92.2% power.Our intention is to proceed with a detailed characterization of behavior, language, type of delay, adaptive skills, functionality and to perform a multivariable correlation, in a larger cohort, between the clinical and the neurophysiological data. Additionally, we will thoroughly characterize the dysmorphological, genetic and abnormal neuroradiological findings and their correlation with EEG data.Our study suggests that there is a high rate of EEG abnormalities in preschool children diagnosed with ASD. These alterations concern both features of the background activity and, most importantly, the presence of PS-IEDs. These EEG abnormalities seem to be much more noticeable in sleep than in wakefulness.If confirmed, these preliminary results could be particularly useful to better define the heterogeneity of ASD pictures and to direct further investigations, particularly genetic and neuroradiological, on the etiological aspects of the disease. They also suggest the need of further studies aiming at correlating EEG data with the prognostic matters and the outcomes of the rehabilitative interventions.


The T classification, which reflects the vertical growth pattern of the tumor, is one of the most important prognostic factors in colorectal cancer. We aimed to investigate the prognostic value of tumor length and width in patients with colorectal cancer (CRC).A total of 259 patients with stage I–III CRC who underwent curative resection were reevaluated according to tumor location. One-way ANOVA analysis was conducted to investigate the relationship between the tumor length times width (TLTW) and clinical parameters. Univariate and multivariate analyses were conducted to analyze the potential prognostic factors affecting overall survival (OS) of patients with stage I–III CRC. In the entire cohort, the TLTW was analyzed as a continuous variable.P = .003) and tumor location (P = .04) could be independent prognostic factors for patients with CRC. In addition, TLTW had an intimate relationship with tumor location (P < 0.001) and differentiation (P = .003). The mean TLTW of the right colon was significantly larger than mean TLTW of the left colon and rectal cancers. However, the mean TLTW of the left colon cancer was similar to that of the rectal cancer TLTW . Subgroup analysis of TLTW according to tumor location suggested that TLTW was an independent prognostic factor for patients with right colon cancer (RCC) (P = .007) rather than left colon cancer (LCC) (P = .49) or rectal cancer (P = .16). Kaplan-Meier (K-M) analysis based on tumor location suggested that the survival rate of RCC patients had a distinctly higher trend rate than LCC patients and RECC patients in the long-term rather than in the short-term.The results suggested that TLTW (TLTW is closely associated with tumor location in CRC. In addition, TLTW may be an independent prognostic factor for patients with RCC. The prognosis of patients with CRC has improved significantly over the past few decades owing to the application of advanced surgical techniques and superior postoperative chemotherapy regimens. The tumor-node-metastasis (TNM) staging system, the gold standard for various types of cancer, is currently the most significant factor for evaluating the prognosis of CRC patients. According to TNM stage, the T subcategory in CRC refers to vertical tumor penetration within or beyond the bowel wall rather than the maximum horizontal tumor diameter. The T stage of many solid tumors, such as renal, breast, and lung cancers is confirmed by tumor size, defined as the longest horizontal tumor diameter, namely tumor length. However, the T classification of CRC refers to the bowel wall layers that are vertically infiltrated by the tumor rather than the tumor size. Recently, the prognostic role of tumor length, one of the indicators reflecting the tumor extent, was again appraised in a series of studies in CRC.–8 However, these results indicated that the prognostic impact of tumor size remains controversial and needs further investigation. This phenomenon may be due to the fact that the tumor size of CRC alone is not able to reflect the actual degree of tumor growth, thus making it difficult to assess the prognosis of CRC patients. In addition, the prognostic value of the widest tumor width perpendicular to the tumor size was overlooked. Consequently, on the basis of existing literature data, we took advantage of tumor length times width (TLTW), aiming to reflect the degree of tumor growth more accurately, thus yielding a better prognosis evaluation for CRC patients.The incidence of colorectal cancer (CRC) is increasing, and it is the fourth most commonly diagnosed malignancy and the fifth most common cause of mortality among tumor sufferers in China.–12 The type of surgical operation of colorectal cancer is also based on the location of the tumor, namely right hemicolectomy, extended right hemicolectomy, left hemicolectomy, and anterior resection. The surgical approach according to the tumor location has been shown to have a great impact on the prognosis of CRC. In addition, further evidence indicates that embryological origins, histology, anatomy, genetics, and immunology of right colon cancer (RCC) differ from those of left colon cancer (LCC) and rectal cancer.,13 At present, the expression of certain genes in colorectal cancer is closely related to the prognosis of the tumor, such as K-RAS, N- RAS, B-RAF, MMR, and EGFR. Furthermore, many studies have been conducted to verify the prognostic value of tumor size, whereas few previous studies have considered the primary tumor location, and to date, no consensus has been reached.–8,14–16 Cai et al demonstrated that the tumor size of the colon is larger than that of rectal cancer. According to Kornprat et al, colon tumor size was significantly correlated with tumor location, and the optimal cut-off values of colon cancer decreased from the RCC to LCC, and ultimately to the rectum. Those results suggested the tumor extent may also vary according to different primary tumor locations. Therefore, the impact of primary tumor location should not be neglected when estimating the prognostic value of clinical parameters, including factors reflecting tumor dimension, such as tumor length and width.Accumulating evidence has verified that CRC characteristics such as epidemiology, pathological characteristics, and clinical outcomes differ according to primary tumor locations.In the present study, we aim to investigate the relationship between TLTW and clinical parameters of CRC patients. In addition, we further explore the prognostic role of TLTW for CRC patients in accordance with primary tumor locations.In our study, tumor length was defined as the longest horizontal tumor diameter, that is, tumor size. The longest horizontal tumor diameter perpendicular to the tumor size was defined as tumor width. In this study, we regarded the tumor shape as rhombus, as shown in the sketch map in Figure  The patients’ ages ranged from 26 to 90 years . All selected colon cancer tissues met the following inclusion criteria: (1) the patient underwent curative resection; (2) the patient had a regular follow-up; (3) patients with pathologically confirmed colorectal cancer; and (4) patients with stage I, II, or III CRC. Exclusion criteria were (1) history of previous malignant disease or a second primary tumor, (2) familial adenomatous polyposis, (3) preoperative chemotherapy and/or radiation, and (4) synchronous distant metastases at diagnosis.This study was approved by the Ethics Committee of the Affiliated Hospital of the Medical School of Ningbo University. Written informed consent was obtained from all the patients in this study. A total of 259 patients with CRC who underwent initial resection at the Hospital Affiliated to Ningbo University School of Medical from 2005 to 2017 were recruited. Patients with stage IV disease were excluded from this study. Tumor location including the cecum/appendix, ascending colon, hepatic flexure, and proximal transverse colon , was defined as RCC. Tumor location including the distal transverse colon , splenic flexure, descending colon, and sigmoid colon, was defined as LCC. Rectal cancer refers to rectosigmoid colon cancer to the dentate line.The following clinical variables were collected in this study: age at diagnosis, sex, differentiation, primary tumor location, cancer embolus, breakthrough serosa, lymph node metastasis, TLTW, depth of invasion, lymph metastasis, American Joint Committee on Cancer (AJCC) stage (TNM), and survival time. The tumor length was defined as the maximum horizontal tumor diameter. Similarly, tumor width was defined as the widest horizontal tumor diameter perpendicular to the tumor length. Tumor length and width were collected from the pathology reports of the resected CRC specimens. The length and width were then multiplied for the study. In addition, the products of the length multiplied by width were regarded as continuous variables in both univariate and multivariate analyses, and other parameters were analyzed as categorical variables. The primary tumor location was defined as RCC, LCC, or RECC. The stage of all patients was defined according to the seventh edition of the AJCC Cancer Staging Manual.In the first year, the patients were examined at the hospital every 3 months. For the second year, patients were examined every 6 months, and annually thereafter. Laboratory checks, Computed Tomography (CT) scans, and other examinations were performed according to the CRC treatment guidelines. The primary endpoint of this study was overall survival (OS), defined as the period from 1 month later after surgery to death from any cause. The secondary endpoint was follow-up.P < 0.05.SPSS software  was used to analyze the research data. One-way analysis of variance (ANOVA) tests were used to analyze the association between TLTW and clinical variables. The Cox proportional hazards model was used in the multivariate analysis of prognostic factors. The Kaplan-Meier method was used to investigate the overall survival rate of patients with colorectal cancer according to tumor location. Statistical significance was set at 2 and 121.00 cm2, and the median was 20.00 cm2. As shown in Table We recruited 259 patients with stage I–III who underwent initial curative resection at Taizhou Hospital affiliated with Wenzhou Medical University. The clinical parameters of this study are summarized in Table P < 0.001) and differentiation (P = .003) in CRC. However, the TLTWs were not significantly correlated with age (P = .63), sex (P = .63), cancer embolus (P = .26), depth of invasion (P = .11), breakthrough serosa (P = .11), lymph node metastasis (P = .20), lymph metastasis (P = .33), TNM stage (P = .08), and survival time (P = .13). Notably, the results indicated that TLTWs in RCC were significantly larger than those in LCC and rectal cancer. However, the mean TLTW in left-sided colon cancer was not significantly different from that of rectal cancer. In addition, the results demonstrated that the TLTWs of CRC were significantly associated with tumor differentiation (P = .003). The mean TLTW of well differentiation was smaller than that of moderate differentiation, and the mean TLTW of moderate differentiation was smaller than that of poor differentiation. In addition, there were no significant differences between poor differentiation and mucinous adenocarcinoma in the TLTWs.The correlation between TLTWs and various clinicopathological parameters, as shown in Table P = .003), breakthrough serosa (P = .002), lymph node metastasis (P = .002), tumor location (P < 0.001), T stage (P = .008), N stage (P = .000), and TNM stage (P = .001) were poor prognostic factors for CRC patients. Multivariate analysis of OS indicated that tumor location (P = .04), differentiation (P = .03), cancer embolus (P = .01), N stage (P = .006), and TLTW (P = .003) were independent risk factors for OS of patients with CRC.As shown in Table P = .03), N stage (P = .04), and TLTW (P = .007) were significantly associated with the survival rate of RCC patients. Overall, the results suggest that TLTW could be an independent prognostic factor for patients with RCC. The results suggested that TLTW had no significant association with overall survival rate in patients with LCC and RECC. When we combined patients with LCC or RECC into 1 subgroup, the results showed that TLTW had no significant association with survival time for patients with left-sided colorectal cancer (results not shown).To evaluate the prognostic role of TLTW in different colorectal cancer sites, subgroup analysis according to tumor location was conducted. As shown in Table P = .12, log-rank test)   . During the course of the study, 60 23.17%) patients with CRC died. Among these deaths, 18 , 20 , and 22  deaths occurred in patients with RCC, LCC, and RECC, respectively. Among these deaths, the 8-year survival rate of patients with colorectal cancer, analyzed in accordance with tumor location, did not show a significant difference  statistics,17 and X-tile programs, have been implemented to determine the significant cut-off points of tumor size, the results of which suggest that the cut-off points for tumor size are not widely applicable. Consequently, in our retrospective analysis, we first combined the tumor length and width by multiplying them, and the results showed that TLTW was significantly associated with the prognosis of CRC patients. The conclusion of this study is inconsistent with those of some previous studies, which may be a reason why tumor size, as opposed to TLTW, cannot accurately reflect the degree of tumor growth.Tumor size plays an important role in the prognostic evaluation system of many solid cancers. Tumor length and width are simple horizontal growth index metrics that are standardized in different hospital systems and are usually reported in routine pathological examinations. However, although many efforts have been made to illuminate the prognostic value of the largest horizontal tumor extent, the results were controversial. Although the rectum is also derived from the same part of the gut as the left-sided colon, RECC has occasionally been investigated separately. Consequently, CRC was classified into 3 subgroups based on their primary tumor location, namely RCC, LCC and RECC. Moreover, increasing evidence has shown that the epidemiology, pathological features, and clinical outcomes of CRC are different in accordance with primary tumor locations.–12 Modest et al inferred that stage III RCC patients had significantly shorter progression-free survival and OS than stage III LCC patients. Recently, in a meta-analysis of 66 clinical studies with 1.4 million patients, tumor location was shown to have a significant association with prognosis of patients with CRC. Based on accumulated findings, the issue of whether to consider CRC as 3 separate tumor entities according to anatomical site has been discussed. Interestingly, Takahashi et al demonstrated the most striking result that the optimal cut-off value of tumor size with respect to outcome decreases from the right colon to the left colon, with the smallest cut-off value for rectal cancer. Similarly, Moda et al showed that the mean tumor size on the right side is significantly larger than that in left-sided cancers (6.1 vs 4.8 cm). In a study analyzing the distribution characteristics of tumor location and tumor size among 3369 Chinese colorectal cancer patients during colonoscopy, the results also showed that colon cancer was significantly larger than rectal cancer. Recently, Lim et al also verified that RCC exhibited a greater average tumor size than LCC. Remarkably, our current study similarly revealed that TLTW had a significant correlation with tumor anatomical location (P = .000). Our results showed that the mean TLTW in RCC was significantly larger than mean TLTW in LCC and RECC. However, the mean TLTW in LCC was not significantly different from the mean TLTW in RECC. Based on the above evidence, we investigated the prognostic value of TLTW for patients with CRC based on the tumor site. This is a reasonable way to eliminate the effect of tumor location on TLTW when analyzing the prognostic role of TLTW in patients with CRC. In our current study, the results indicated that TLTW was an independent prognostic factor for RCC patients but not for LCC and RECC patients. Moreover, our results also suggested that tumor location could be an independent prognostic factor for CRC patients (P = .000). In addition, our K-M survival analysis suggested that the prognosis of RCC patients was better than that of LCC and RECC patients in the long-term when compared with the short-term. Our results are correlate somewhat with their investigation.,35 Consequently, it is reasonable to consider RCC, LCC, and RECC as 3 separate tumor entities and consider the prognostic role of clinical factors based on tumor location, especially for factors reflecting tumor growth extent, such as tumor size, TLTW, and tumor volume.Evidence suggests that RCC and LCC are derived from different parts of the gut.To our knowledge, this is the first study to demonstrate the prognostic value of TLTW in CRC with different primary tumor locations. However, the present study has several limitations. First, our investigation was a single-center retrospective study, and the number of recruited CRC patients was relatively small (n = 259). Second, adjuvant chemotherapy, laboratory examinations, and other vital factors were not included in this study. Third, the optimal cut-off value of TLTW in accordance with the primary tumor location was not determined. Nevertheless, the current study has a significant advantage in that we identified a novel prognostic factor for patients with RCC. In addition, our study provides a new perspective for investigating the prognostic role of tumor size. Further multicenter prospective investigations on TLTW should be conducted, and additional baseline parameters should be considered.In conclusion, TLTW, which reflects the extent of tumor growth, was closely associated with tumor location. TLTW was an independent factor for OS in patients with stage I–III RCC but not in patients with LCC and RECC. In addition, we should consider the prognostic role of clinical factors based on tumor location, especially for factors reflecting the extent of tumor growth. In the future, we will continue to study the role of TLTW in CRC patients.Encheng Zhou, Jianhui Chen, and Shuwang Peng collected the clinical samples. Jianhui Chen and Ting Fei analysed the data. Qing Huang, Changlei Qi, and Encheng Zhou conceived and supervised the project, analysed the data and drafed the manuscript. Encheng Zhou, Jingfeng Chen, and Xiaojun Wang analysed the data and helped write the manuscript. All authors have approved the final article.


In conclusion, high adulthood SES, but not childhood SES, may be considered to be a protective factor against CVD in urban populations in high-CVD-risk regions. No effects of critical periods in early life were observed on CVD risk. In later life, social mobility was found to affect CVD mortality in both men and women. In men, a protective effect of upward mobility was confirmed, whereas in women, an increased CVD risk was related to downward mobility. It can be concluded that CVD prevention may be beneficial if socioeconomic potentials are strengthened in later life.Although the inverse association between socioeconomic status (SES) and cardiovascular disease (CVD) is well established, research on the effect of changes in the SES throughout life on CVD risk in populations with different social backgrounds remains scarce. This study aimed to assess the relationship between childhood SES, adulthood SES, and changes in SES over time, and CVD incidence and mortality in a Polish urban population. In addition, the predictive performance of the SES index was compared with education alone. A cohort study with a 10-year follow-up was conducted, in which a random sample of 10,728 residents in Kraków aged 45–69 years were examined. The SES was assessed at baseline using data on education, parents’ education, housing standard at the age of 10 years, professional activity, household amenities, and difficulties in paying bills and buying food. SES categories  were extracted using cluster analyses. Information on new CVD cases was obtained from questionnaires in subsequent phases of the study and confirmed by reviewing clinical records. Data on deaths and causes were obtained from the residents’ registry, Central Statistical Office, and the participants’ families. The effect of the SES index on the risk of CVD was assessed using Cox proportional hazard models. In male and female participants, the CVD incidence and mortality were observed to be 27,703 and 32,956 person-years (384 and 175 new CVD cases) and 36,219 and 40,048 person-years (159 and 92 CVD deaths), respectively. Childhood SES was not associated with CVD incidence and mortality. A protective effect of high adulthood SES against CVD mortality was observed in men and women . In women, downward social mobility was related to 2.24 and 3.75 times higher CVD incidence and mortality, respectively. In men, a protective effect against mortality was observed in upward mobility . Model discrimination was similar for the SES index and education alone for the association with CVD incidence. In women, the SES index was a slightly better predictor of CVD mortality than education alone (C-index = 0.759, SE = 0.0282 vs. C-index = 0.783, SE = 0.0272;  The association between socioeconomic status (SES) and cardiovascular disease (CVD) is well known ,2. KnowlThis ambiguity in the significance of SES characteristics in CVD risk assessment may be due to differences in SES assessment methods. For example, education is a widely used indicator of SES in population studies and is known to be related with CVD mortality; however, its use is undoubtedly a simplification of the assessment. Education alone, as well as other simplified single measures of SES, may not necessarily reflect multidimensional SES characteristics. In studies on social inequalities in health, there is still no consensus on the best single measure of SES ,11. GiveFurthermore, the SES affects the lives and health of individuals from early childhood throughout their life. Socioeconomic circumstances increase CVD risk through various mechanisms. On the one hand, childhood might be the critical period in which low socioeconomic conditions determine later poor health; on the other hand, accumulating lifelong exposure to low SES may be even more important . The effIn this context, Central and Eastern Europe provide an interesting setting for studying the SES. In the 1990s and early 2000s, Central and Eastern European countries experienced political and economic transitions. Hence, many people experienced changes in social position. During the same time, after a long period of high and increasing CVD mortality, the trend was reversed.This study aimed to determine the relationship between childhood SES, adulthood SES, and changes in SES over time , and CVD incidence and mortality in high-cardiovascular-risk region, with particular emphasis on the comprehensive assessment of the SES. In addition, the predictive performance of the SES index was compared with education alone.The Polish cohort of the Health, Alcohol and Psychosocial factors In Eastern Europe (HAPIEE) study was established in Krakow. A random population sample of men and women aged 45–69 years at baseline, stratified by gender and 5-year age groups, was contacted. The baseline examination was completed between 2002 and 2005. In total, 10,728 participants were recruited (with a 61% response rate), and all participants gave written consent. At baseline, trained nurses interviewed the participants in their homes using a standardized questionnaire. Detailed information on socioeconomic characteristics, health, and health behaviors was collected. Then, all participants were invited to the clinic for anthropometric and blood pressure measurements and blood sample collection for biochemical tests .Childhood SES was assessed using questions about the level of education of the participants’ parents and housing standard at about 10 years of age . Adulthood SES was assessed using the information on the participants’ education, professional activity, household amenities, and difficulties in paying bills and buying food. The SES index was constructed as described in detail elsewhere ; a summaThe participants were classified into homogeneous groups of childhood SES and adulthood SES using a two-stage clustering algorithm. Three groups of childhood SES  were generated, with reasonable evidence of cluster structure (silhouette coefficient (s(i)) = 0.51). Similarly, three groups of adulthood SES  were identified (s(i) = 0.55). Using the data on childhood and adulthood SES of each participant, the following social mobility categories were generated: (1) always low; (2) downward mobility if childhood SES was middle or high but adulthood SES was low; (3) upward mobility if childhood SES was low and adulthood SES was middle or high; and (4) always middle or high. The description of the SES clusters and the distribution of the characteristics used for the SES index are presented in New cases of nonfatal CVD events, i.e., myocardial infarction, stroke, coronary artery bypass graft, percutaneous coronary interventions, and unstable coronary disease (confirmed using coronary angiography), were identified in reexamination interviews (2006–2008) and in three postal questionnaires . Both reexamination interviews and postal questionnaires had an identical series of questions about whether the participant had had myocardial infarction, stroke, coronary angiography, coronary artery bypass graft, or percutaneous coronary interventions since the last contact. In each case, when the participant reported the presence of the disease, the study team verified the clinical diagnosis by reviewing the medical documentation. Data on deaths by cause were obtained from the mortality register of the residents of the city of Krakow, Central Statistical Office, and by contacting the participants’ families. CVD deaths were accepted for codes from I.00 to I.99, according to the 10th revision of International Statistical Classification of Diseases and Health Problems (ICD-10). For each participant, their status at the end of the observation was determined, and the exact survival time was calculated. The follow-up was completed on 31 December 2013. For participants who were lost at follow-up, the censorship date was considered as the date of the last contact.2 ≥ 30), hypercholesterolemia (low density lipoprotein concentration ≥3 mmol/L or receiving lipid-lowering treatment), hypertension (blood pressure ≥140/90 mm Hg or receiving hypotensive treatment), and diabetes (fasting plasma glucose ≥7 mmol/L or having diabetes diagnosed by the doctor).Covariates measured at baseline included age, marital status (married/cohabiting vs. single/separated/divorced/widowed), and five main CVD risk factors according to the latest ESC guidelines on clinical practice: smoking status, obesity  with 95% confidence intervals (CIs). All analyses were carried out in sex groups. The goodness-of-fit of the preformed model with the SES index and that of the model with education alone were compared using Harrell’s C-index. Two-sided p-Values < 0.05 were considered to be statistically significant. Analyses were performed using IBM Corp. software released in 2021  or R Core Team (2013) .Continuous variables were reported as means (standard deviation) or medians (first and third quartiles (Q1–Q3)), as appropriate. The Kolmogorov–Smirnov test was used to test the normal distribution of variables. Categorical variables were reported as numbers and percentages. The differences in the variables were tested using Student’s test or the analysis of variance and the χThe observation for CVD incidence included 27,703 and 32,956 person-years in men and women, respectively. The date of censorship for nonfatal CVD cases was the latest date the participant was confirmed to be free of CVD. A total of 384 and 175 new CVD cases were observed in men and women, respectively. The date of censorship for mortality analyses was 31 December 2013, which included 36,219 and 40,048 person-years in men and women, respectively. A total of 159 and 92 CVD deaths were reported in men and women, respectively .p < 0.001) than women. The distribution of childhood SES was similar in men and women, with about one-fourth of the participants having a high SES. Sex differences in adulthood SES distribution were more pronounced, as a higher number of men had a high SES. Similarly, the distribution of social mobility was more advantageous in men, who had at least a middle SES significantly more often  throughout their life and experienced upward mobility more frequently . Men were more likely to smoke and have hypertension and diabetes (p < 0.001), whereas women were more often obese . No significant differences were observed in the prevalence of hypercholesterolemia (The mean baseline age of participants was 56 years (SD = 6.9). In this study, men were more likely to be married or cohabiting  in men and 60% (p < 0.001) in women. Further adjustment for main CVD risk factors attenuated the association in men, so it was insignificant in fully adjusted models. In women, the attenuation was slighter, and compared with women with low SES, more than 40% reduced risk of CVD was observed in women with high SES (HR of 0.57 and 95% CI of 0.35–0.94). In the assessment of social mobility, although a reduction in CVD risk was observed in men with always middle or high SES and in men who experienced upward social mobility after adjustment for age and marital status, these associations were not confirmed in the fully adjusted models. However, in women, associations with social mobility were observed only on different levels of exposure. A higher than twofold increase in the risk of CVD was observed for downward mobility (HR of 2.24 and 95% CI of 1.25–4.02 in fully adjusted models). In women, no associations between always middleor high SES or upward mobility and CVD incidence were observed (The association between childhood SES and CVD incidence was not significant . In the observed .p < 0.001) in men and 78% (p < 0.001) in women. In the fully adjusted models, the HRs were only slightly attenuated . The significant effect of social mobility on CVD mortality was observed in both men and women. In men, a strong protective effect of maintaining middle or high SES and upward mobility was observed . The effect size was similar for maintaining middle or high SES and upward mobility and indicated about 50% risk reduction compared with always-low SES. In women, the relationship between social mobility and CVD mortality was demonstrated only as the negative impact of deteriorating SES .Associations between SES and CVD mortality are presented in The associations between adulthood SES and education alone, and CVD incidence are presented in Childhood SES was not significantly associated with either the risk of CVD or the risk of CVD death at the 10-year follow-up. However, high adulthood SES was confirmed as a protective factor for both fatal and nonfatal CVD. In men, the protective effect of maintaining middle or high SES or upward mobility was observed. In women, the harmful effect of downward mobility might confirm the relationship between low SES and CVD at different levels of exposure. The relationships were independent of the main CVD risk factors. The SES index seemed to be a better measure than education alone as it was significantly related to mortality, which was not observed for education.Similar to this study, a Finnish-population-based cohort study reported that not poor childhood living conditions but low adult SES was a strong determinant of myocardial infarction incidence and fatality . SimilarIn the present study, a cluster method was used to identify SES groups and capture the detailed heterogeneity of the variables describing SES. This approach seems to be suitable for countries in Central Europe, in which social classes are less clearly separated from each other. The cluster method enabled the observation of significant differences in the education level and current professional position between participants with high SES and those with middle or low SES. Sex differences in SES distribution were substantial, and differences in the associations between social mobility and CVD risk between sexes may have been due to baseline differences in SES distribution. Significant associations in men were observed for higher SES categories, in which men were better represented. However, significant associations in women were observed in lower SES, which was more common in women.However, it seems that even studies that include multiple SES measures cannot examine all potentially important socioeconomic characteristics. The present analysis compared predictive values of the SES index with education alone against CVD incidence and mortality. In terms of the associations with CVD incidence and mortality, the SES index was only slightly better than education alone. However, the improvement in model discrimination was rather small; thus, using education as a simple measure of adulthood SES for the assessment of CVD risk might be justified.There are several limitations in the interpretation of the presented results that should be considered. First, data on childhood SES were based on the distant recall of amenities available decades earlier, which increases the probability of recall bias and may also be the source of random errors. Also known is the effect of overestimation of SES in childhood, assessed using parental education. Secondly, data on the income of the participants were not available, so only indirect assessment through the declared problems with payments was used. Thirdly, the SES index incorporating several data crucial for SES assessment was used to assure a comprehensive SES assessment; however, the use of this method may be somewhat limited for other authors, as the classification may be, to some extent, dependent on the data. Finally, it should be considered that the register of new CVD cases, based on the participants’ reports in subsequent questionnaires, may have been incomplete.The study had relevant strengths, including a population-based study sample, prospective design, long follow-up time, and standardized research methods to guarantee the high quality of the data obtained. A comprehensive approach was applied to SES assessment, and data on a higher number of characteristics were included compared with previous studies, for both childhood and adulthood. The comparison of the SEX index with the simplest and most common method of quick SES assessment in terms of CVD prediction was performed, which—to the best of our knowledge—has not been performed before for the population of a region.In conclusion, high adulthood SES but not childhood SES may be regarded as a protective factor against CVD in urban populations in high-CVD-risk regions. The effect of the critical period in early life for CVD risk was not observed. In later life, the effect of social mobility was observed on different levels of exposure in both men and women. In men, a protective effect of upward mobility was confirmed, whereas in women, increased CVD risk related to downward mobility was confirmed. CVD prevention may be beneficial if socioeconomic potentials are strengthened in later life.


The optimal parameters for each ensemble model were selected based on trial-and-error methods. The aforementioned models were trained on 70% of the entire dataset, while the remaining data  were used for the validation of the developed models. The evaluation was conducted on the basis of reliable accuracy indices. The minimum value of correlation of determination (R2 = 0.82) was observed for the testing data of the RF regression model. In contrast, the highest (R2 = 0.942) was obtained for LIGHT GBM for the training data. Overall, the three models showed robust performance in terms of correlation and error evaluation; however, the trend of accuracy was obtained as follows: LIGHT GBM > XGBoost > RF regression. Owing to the superior performance of LIGHT GBM, it may be considered a reliable ML prediction technique for computing the bond strength of FRP laminates and concrete prisms. The performance of the models was further supplemented by comparing the slopes of regression lines between the observed and predicted values, along with error analysis , and root-mean-square error (RMSE)), predicted-to-experimental ratio, and Taylor diagrams. Moreover, the SHAPASH analysis revealed that the elastic modulus x thickness of FRP and width of FRP plate are the factors most responsible for IBS in FRP.The corrosion of steel reinforcement necessitates regular maintenance and repair of a variety of reinforced concrete structures. Retrofitting of beams, joints, columns, and slabs frequently involves the use of fiber-reinforced polymer (FRP) laminates. In order to develop simple prediction models for calculating the interfacial bond strength (IBS) of FRP laminates on a concrete prism containing grooves, this research evaluated the nonlinear capabilities of three ensemble methods—namely, random forest (RF) regression, extreme gradient boosting (XGBoost), and Light Gradient Boosting Machine (LIGHT GBM) models—based on machine learning (ML). In the present study, the IBS was the desired variable, while the model comprised five input parameters: elastic modulus x thickness of FRP ( Repairing and reinforcing structures has traditionally been a dynamic and complex aspect of building work. The use of fiber-reinforced polymer (FRP) bars, sheets, and strips to enhance RC or even steel structural components is one of the prevalent approaches for these kinds of repairs. Because of the corrosion of traditional steel reinforcement that leads to deterioration, RC structures require periodic maintenance and repair ,2,3. As Recent laboratory studies indicate that the potential for brittle debonding failures is alarming in FRP laminates, depending on the composite action in the FRP as well as the concrete prism ,16. To iTo attain improved lamination, it is pertinent to mention that the damaged surface layer of the concrete is removed while preparing the surface and exposing the coarse aggregates ,18,19,20Single-lap shear tests (SSTs) for FRP laminates that are externally attached to the concrete prism as well as externally attached to its grooves are depicted in 2 = 0.96, and other performance metrics were also lower). Su et al. [2 > 0.9 for all cases) and good model fitting effect, where XGBoost possessed the highest prediction accuracy. While predicting the creep performance of concrete, Liang et al. [In a variety of engineering challenges, machine learning (ML) or artificial intelligence (AI) is commonly utilized to discover the best solution to regression and classification problems. These ML models are not only trained with a large series of experimental findings, but they are also verified using unseen data. Furthermore, they have seen a wide range of applications in composite constructions, particularly over the past couple of years. This study takes into consideration three AI methods, i.e., Light Gradient Boost Machine (LIGHT GBM), extreme gradient boosting (XGBoost), and random forest (RF) regression. Liang et al.  predicteu et al.  used mulu et al.  revealedu et al.  conducteg et al.  modelledg et al. ,36. In cg et al. .To summarize, for the sake of improving the expense of civil engineering projects, AI models based on known experimental findings are required to estimate the IBS of FRP plates on a concrete prism. Due to highly nonlinear correlations between bond strength and a multitude of contributing parameters, typical prediction models for FRP–concrete coupling need further investigation . The autLIGHT GBM is a Microsoft open-source gradient boosting machine learning framework that employs a decision tree as a training method . LIGHT GConsider an input data including In particular, with regard to adopting GOSS for sampling, LIGHT GBM leverages the EFB to accelerate the training procedure without compromising precision. Several applications include attributes that are mutually incompatible, such as high-dimensional and limited inputs. Such attributes can be aggregated into a single attribute bundle by EFB. To use an attribute scanning method, the statistics of such attribute bundles and specific attributes can be compiled. In brief, LIGHT GBM is a new machine learning (ML) method that employs GOSS for internal node splits based on variability gain and EFB to reduce the dimensions of the input attributes. As a decision-tree-based approach, LIGHT GBM has the significant benefit of being sensitive to multicollinearity . TherefoThe optimization of hyperparameters is a crucial step in training machine learning (ML) techniques, as it can improve the generalization and prediction robustness of ML models, prevent overfitting and underfitting, and minimize the complexity of the model. In this way, grid search techniques have been used to optimize the hyperparameters for LIGHT GBM, XGBoost, and random forests (RFs) in order to achieve improved performance, efficiency, and precision. This technique is used to determine the efficacy of every combination of the specified hyperparameters and associated value ranges, and thereafter selects the optimal hyperparameter values. Moreover, a portion of the data samples are kept entirely masked from the models and utilized only as “testing set” to improve the results of the ML models and prevent the occurrence of underfitting and overfitting. The optimized hyperparameters of our analysis indicated improved results for identifying and predicting ultimate capacity of FRP laminates bonded to concrete. The hyperparameters for RF regression, LIGHT GBM, and XGBoost are listed in fTfE, GPa-mm), the width of the FRP laminate , the concrete’s compressive strength , the width of the groove , and the depth of the groove . The database contained 136 tested specimens of single-lap shear tests (SSTs) that were obtained from a previous work [fTfE had a skewness of 0.58 and a range of 12.90 to 78.90. The database used in this study was originally created by Moghaddas et al. [fb, as shown in 2 were also investigated. To demonstrate changes in concrete strength, three distinct mix designs with concrete strengths of 25, 35, or 45 MPa were used in accordance with ACI 211.1-91. The gradation and quality of coarse and fine aggregates were compiled as per ASTM C33/C33M. As shown in The descriptive statistics of the inputs as well as the target variable employed in the investigation are depicted in ous work , as alreous work . Betweens et al. . The ori2), root-mean-square error (RMSE), mean absolute error (MAE), relative squared error (RSE), relative root-mean-square error (RRMSE), Nash–Sutcliffe efficiency (NSE), and performance index (ρ), in accordance with previous literature [The performance of the developed models was evaluated using frequently used statistical indices, including the coefficient of determination  revealed that LIGHT GBM and RF regression had the best performance in the training and testing phases, respectively. The results of the statistical analysis revealed a close agreement between the experimental and predicted values amongst the three models. However, LIGHT GBM performed the best overall, with the highest recorded R2 and error parameters very close to zero, making it a reliable predictor of interfacial bond strength between the FRP laminates, in close agreement with previous findings [To predict the interfacial bond strength of FRP laminates with a concrete prism and its grooves, we evaluated the robustness, effectiveness, and relative analysis of the RF, XGBoost, and LIGHT GBM models. When comparing robust performance and strongly linked models, the distribution of data points must have a slope higher than 0.8 , a minimthan 0.8 , and a pthan 0.8 . Table 5findings . (i) Comparison of regression slopes  (ii) Error analysis  We also analyzed the errors from the model predictions, and the results were plotted for the training and testing datasets, as shown in (iii) Predicted-to-experimental ratio analysis  As part of the statistical methods used to evaluate the models’ performance, the ratio of the predicted values to the experimental values was also used so as to clearly highlight the accuracy of the model in more detail. Some researchers  predicte(iv) Taylor Diagrams  In fTfE is the most significant variable, followed by bf, cf′, hg, and bg , maximal depth (7), and number of trees (90) were found to govern the final RF predictions. The same magnitude of optimal learning rate was obtained for the other two ML methods  as well. In contrast to the RF regression, the maximal tree depth was found to be 3 for the other two models.fTfE is the most prominent input attribute, followed by the width of the FRP laminates. This is in good agreement with the Pearson’s linear correlation yielded for these two parameters as well as the ultimate axial capacity of FRP laminates. This suggests validation of the formulated models and consistency in terms of the importance of the variables using different statistical evaluation methods.The sensitivity via SHAPASH analysis indicated that Moreover, all of the models showed reliable performance in terms of correlation and error evaluation; however, LIGHT GBM outclassed the other two models. In LIGHT GBM, the values of R, RMSE, and MAE were 0.942, 3.40, and 0.80 for the training data, respectively, and 0.865, 3.56, and 1.3 for the testing data, respectively. For the training and validation datasets, the slopes of the regression lines were 0.9348 and 0.7678, respectively. This shows that the experimental and predicted values were in close agreement with one another.FRP laminates are widely utilized to retrofit a variety of reinforced concrete elements ; therefore, it is crucial to assess their bond strength with concrete structural members. Single-lap shear strength tests, performed on the FRP laminates bonded to a concrete prism and its grooves, were used to develop three ensemble models—namely, random forest (RF) regression, extreme gradient boosting (XGBoost), and Light Gradient Boosting Machine (LIGHT GBM) models—based on machine learning (ML). It is notable that the developed models were applicable for the extreme values of the input variables used in the present study. It is also worth mentioning that the tested specimens included single-lap-sheared samples bonded to the concrete using Sikadur 300 epoxy as an adhesive material. The following conclusions can be drawn from this research:The LIGHT GBM framework exhibits robust training speed, greater efficacy, higher accuracy, and is capable of handling large-scale data. It is also highly applicable in the binary and multi-classification problems. However, the associated drawbacks include overfitting and compatibility with the datasets. In addition, the SHAPASH analysis is highly versatile  and works with the aforementioned classification problems as well as with regression problems.


BackgroundAcne vulgaris is a common chronic inflammatory disease of the pilosebaceous units associated with long-term sequelae and complications. Currently, acne in women is classified into adolescent and post-adolescent forms. However, comparative studies evaluating the clinical and laboratory parameters across various age groups in women with acne are lacking.The aim of the study is to compare the clinical and laboratory characteristics of different groups of women with acne vulgaris.Patients and methodsOver 3 years (2018-2021), a cross-sectional study was carried out on 340 women with acne consulting the Dermatology and Venereology Outpatient Clinic, Basrah Teaching Hospital, Basrah, Iraq. Eligible patients were carefully evaluated and fully examined, emphasizing on signs of hyperandrogenism and scoring of acne severity. Hormonal assays of serum total testosterone (TST), dehydroepiandrosterone sulfate (DHEAS), luteinizing hormone (LH), follicular stimulating hormone (FSH), and serum prolactin (PRL) were done. Pelvic ultrasonography was performed to identify any pelvic pathology. The patients were classified according to their age of onset. Clinical and laboratory data were compared among groups.ResultsThree groups were recognized: 160 patients (47%) with adolescent acne (AA) (mean age SD: 17.2±1.6 years), 80 (23.5%) with early adult-onset acne (EA) (mean age SD: 21.4±1.2 years), and 100 (29.4%) with post-adolescent acne (PA) (mean age SD: 28.7±2.9 years), which were further sub-grouped into late-onset acne , and persistent acne . The mean body mass index was normal in the AA group and overweight in the EA and PA groups. Moderate obesity was more frequent in PA . While 78.5% of AA was mild to moderate acne, 77.5% of EA was moderate to moderately severe, and 72% of PA was moderately severe to severe. Clinical and biochemical markers of hyperandrogenism were seen in all groups, however, they were more frequent in PA and EA groups than in the AA group (p<005).ConclusionClinical and biochemical hyperandrogenism were present in a significant proportion of women with acne; their prevalence was higher in post-adolescent acne than in adolescent acne. Acne that began between the ages of 20 and 25 was classified as "early adult-onset acne," and showed variable features of hyperandrogenism. A complete evaluation, regardless of age, for every female with acne, including a hormonal analysis and pelvic ultrasound examination to detect hormonal imbalances as early therapy, can help to prevent and reduce the risk of consequences. Acne vulgaris is a chronic inflammatory disease of the pilosebaceous unit, characterized clinically by open and closed comedones, erythematous papules and pustules, and in more severe cases, nodules, deep pustules, pseudocysts, and possible scarring . It primCutibacterium acnes certain strain with proinflammatory potential; and lastly, the inflammatory mediators released into the skin including IL‑1β, IL‑8, IL‑10 and tumor necrosis factor [The prevalence of acne varies among different age groups, with estimates ranging from 35% to close to 100% of adolescents having acne at some point . While is factor .Acne can be classified according to severity as mild, moderate, or severe and according to the age of the patient and the onset of the disease . It is cAccording to the time of onset, two subtypes of adult women with acne are recognized: persistent acne and late-onset acne. Persistent acne is a continuation or relapse of the disease from adolescence into adulthood and middle age. While the late-onset type involves patients aged 25 years and older who have not previously been affected by acne, late-onset acne is thought to be less common than persistent acne . It is aAdult acne pathogenesis involves several endogenous and exogenous factors and may include endocrine disorders, the chronic stimulation of innate immunity, and genetic predispositions; the exogenous factors include cosmetics, stress, and tobacco , 14. AcnThe aim of the study is to investigate and compare the clinical and biochemical parameters of hyperandrogenism of acne vulgaris in a sample of Iraqi women across various age groups, and to determine whether there was a connection between certain age groups and the severity of the clinical and hormonal profiles.A cross-sectional prospective study was conducted to compare the clinical and laboratory parameters of different groups of women with acne attending the Dermatology and Venereology outpatient clinic at Basrah Teaching Hospital, Basrah, Iraq, over the period from May 2018 to April 2021. The study inclusion criteria were any female patients presenting with acne vulgaris aged 12 years and above. They were divided into different groups according to the age of the onset of acne symptoms. The main exclusion criteria were any patients who had taken any systemic anti-acne medications like anti-androgens, oral contraceptive pills, systemic antibiotics, or isotretinoin for 6 months prior to enrollment. The method of random sampling was employed to collect the patients' data. The sample size was calculated using a simple statistical formula for cross-sectional studies, with a 95% level of confidence and a precision of 5%. We assumed that the prevalence of clinical and biochemical hyperandrogenism was 50% based on the wide range of their prevalence in the available literature (18% to 80%), and a sample size of 176 patients is required for each group.An anamnesis and careful examination were carried out for each patient. Data was collected using a questionnaire sheet that was arranged after we reviewed the most recent literature. The questionnaire included socio-demographic information, causes and exacerbating factors, first-degree family history, menstrual, gynecological, and obstetrical history, flaring of acne , and associated symptoms of hyperandrogenism  and obesity. Hirsutism is defined as excessive growth of terminal hair in the male distribution pattern and scored ≥8 on the Ferriman and Gallwey scale . AndrogeIn total, 340 females with various types of acne were included during the study period, and their ages ranged from 14 to 45 years (mean±SD=21.6±5.4 years). According to the age of onset of acne, three groups were identified: adolescent acne , early adult-onset acne , and post-adolescent acne , which was further divided into two subgroups: late-onset acne (40%) and persistent acne (60%) , with a highly statistically significant difference (p=0.0098).The mean level of BMI in all groups was within the normal range, with no statistical difference between groups. However, moderate obesity by BMI was more frequently encountered in PA (24%) compared to other groups, with a statistically significant difference (p=0.03). Regarding the Fitzpatrick phototype of the skin, there was no significant association between the phototypes and any particular group.The distribution of acne lesions is shown in Table The prevalence of oily skin (seborrhea) was noticed in all groups, with no statistical difference between them. Hirsutism was found in 36.25%, 32.5%, and 50% of patients in the AA, EA, and PA groups, respectively, and the prevalence in the PA group was higher than in other groups with a statistically significant difference (p=0.01). On the other hand, female pattern hair loss (FPHL) was encountered in all groups but was significantly higher in either the PA or EA groups than in the AA group (p=0.005); however, there was no statistically significant difference between the EA and PA groups.Although a high percentage of irregular menstrual cycles was found in all groups, it was more frequent in the PA group than in the AA and EA groups , with a highly significant association (p=0.0001). Furthermore, the premenstrual flare-up was noticed in a substantial proportion of patients in all groups, and it was significantly higher in the PA group than in other groups (P = 0.02) (Table Scoring of acne severity showed that the majority of patients with AA (78.5%) had mild to moderate acne, while 77.5% of EA patients had moderate to moderately severe acne, and 72% of PA patients had moderately severe to severe acne, with a statistically significant association between severity score in each group (p=0.0001).Different types of scars were seen in all groups; overall, 72% of patients in the PA had scars on their faces. while 57.5% of the EA and 31.25% of the AA groups had scars. It is clearly shown that the prevalence of scarring in the PA group was significantly higher than in the EA and AA groups (p=0.02), and in the EA group more than in the AA group p=0.048). The pitted scar was the most frequent type of scarring in all age groups compared to other scars like rolling or boxcar. There was no hypertrophic scar was noticed in all studied groups. Post-inflammatory hyperpigmentation (PIH) and macular erythema were noticed in all groups, but they were statistically higher in the AA and EA groups than in the PA group (p=0.05) , as shown in Table Based on the age at which acne indications first appeared, three patient groups were identified in this study: adolescent acne (AA), early adult onset acne (EA), and post-adolescent acne (PA). After age 25, PA can either develop slowly or late, or it can persist from AA or EA. The majority of patients in this group (60%) had PA that was persistent from AA or EA, which was consistent with the Scroza et al. study, in which 82% of the PA group was persistent acne . However, there is still debate over how to categorize women with acne depending on their age of onset. Some authors referred that AA's age of onset may be prolonged to the age of 24 years and PA begun beyond the age of 25 years ,20, whilIn this study, the mean body weight of the AA group was within the normal range, while that of the EA and PA groups was overweight. Even more so than in other groups, moderate obesity was more prevalent in PA, indicating a possible link between obesity and the emergence of adult acne. Obesity has been shown to increase the secretion of androgens, insulin, insulin-like growth factor 1 (IGF-1), and growth hormones. In acne patients, a correlation between the serum levels of IGF-1, DHEA-S, and dehydroepiandrosterone, as well as the number of acne lesions and sebum production, has also been reported. Acne is indeed a result of IGF-1 activation of 5-reductase, adrenal and gonadal androgen synthesis, and sebocyte stimulation .According to this study, there is a correlation between age and an increase in acne severity and associated problems. Mild to moderate acne was more prevalent in AA, moderate to moderately severe acne was more prevalent in EA, and severe to extremely severe acne was more prevalent in PA. These results support earlier research that has been published . AA is oWe found in this study that clinical symptoms and biochemical indicators of hyperandrogenism were present in all groups, albeit to varying degrees. In the PA group, as opposed to the EA and AA groups, hirsutism, FPHL, irregular menstruation, and premenstrual flare are more frequently observed. There is a statistically significant correlation between hirsutism, FPHL, and the severity and aggravation of acne. This is consistent with Khunger and Kumar's study . FurtherLH:FSH ratio and prolactin levels increased across all study groups, although there was no statistically significant difference between them. Khunger and Kumar conducted a hormonal study using serum levels of TST, DHEA-S, LH, FSH, and prolactin (PRL), which was consistent with our findings . The levRegarding PCO, EA and PA groups showed more frequent PCO than the AA group. The same results were mentioned by others, who reported PCO in 52-82% of patients with adult acne , and by The major limitation of the current study was that our results were based on the finding of a single center (southern Iraq), and the external validity of the study conclusion needs to be confirmed in a larger multi-centric study. Second, although patients on well-known systemic anti-acne medications were excluded from the study, we cannot rule out the potential effect of the long list of topical medications that may have been used by the patients on the signs and symptoms of acne, and this could have confounded the grading of acne severity. Third, the predetermined sample size for each group was not met during the study period, which could be due to a variety of factors, including the emergence of the COVID-19 pandemic and the entire closure at that time, which could confound the study's conclusions. Fourth, other laboratory tests for assessing androgen status, including 17-hydroxyprogesterone, free testosterone, and sex hormone-binding globulin, were not available.In conclusion, three main groups of female acne patients were identified: the adolescent acne (AA) group with ages ranging from 12 to 19 years; the early adult-onset acne (EA) group with ages ranging from 20 to 25 years; and the group, which encompasses females above the age of 25 years. Clinical and biochemical evidence of hyperandrogenism was observed in all groups, albeit to varying degrees. Patients with PA tended to be more severe than the other two groups, with considerably greater levels of androgens. EA patients share clinical characteristics with the AA group in that they are mild to moderate in severity as well as have an androgenic profile of post-adolescent acne (PA) with a high prevalence of increased androgens levels. A prospective investigation with a larger sample number of patients is needed to corroborate these findings. Full evaluation, regardless of age, for every female with acne, including a hormonal analysis and pelvic ultrasound examination to detect hormonal imbalances, and early treatment is highly recommended as this will help to prevent the condition from becoming severe and reduce the risk of consequences.


Many laboratory studies have shown that tea consumption protected against the development of esophageal cancer (EC). However, in epidemiological studies, inconsistent or even contradictory results were frequently observed, especially when drinking tea at higher temperatures.We conducted a meta-analysis based on published observational studies to explore whether hot tea consumption was a risk factor of EC. Relevant studies were searched in PubMed, Embase, and Web of science up to October 13, 2021, and we also manually retrieved the literature in the included studies and recent reviews.p = 0.00). Except for esophageal adenocarcinoma (EAC), this increased risk was also found in the majority of subgroups, which are the European and Australian populations.A total of 23 eligible reports were identified, including 5,050 cases and 10,609 controls, and a meta-analysis with Comprehensive Meta-Analysis (CMA) software (version 2.0) was conducted. A statistically significant increased EC risk was observed when drinking tea at higher temperature (odds ratios (ORs) = 1.79, 95% CI: 1.48–2.15, This meta-analysis showed that people who drank hot tea had a significantly increased risk of Esophageal squamous cell carcinoma (ESCC), but no significant association for EAC. Esophageal cancer (EC) is the seventh most commonly diagnosed cancer and the sixth cause of cancer mortality worldwide, with approximately 70% of cases occurring in men and a 2- to 3-fold difference in the incidence and mortality rates between different regions . EsophagAlthough the definitive mechanism of EC development is still unclear, many studies have shown that dietary habits are significantly associated with the development of EC –9. For eTea beverages are usually a mixture of boiling water and tea leaves. So, the potential thermal injury should be considered because very hot beverages are identified by the International Agency for Research on Cancer (IARC) monograph as Category 2A carcinogens for ESCC . Given tPublished studies related to hot tea consumption and EC risk were searched in the databases of Embase, PubMed, and Web of Science up to October 13, 2021. The search terms used were as follows: (a) “hot” or “high temperature,” (b) “esophageal cancer” or “esophageal carcinoma” or “esophageal neoplasm,” (c) “tea” or “beverage” or “drinking;” these searched keywords were combined with “and/or” without restrictions. In addition, we also retrieved papers in the reference lists and recent reviews.The studies included in the meta-analysis should satisfy all of the following criteria: (a) It was a case-control or cohort study; (b) The ORs or adjusted OR values and relevant corresponding 95% CIs were reported, or provided sufficient information to calculate it; (c) The study was about tea individually or tea was definitely included in the study; (d) The study tested the relationship between EC risk and tea temperature; (e) The diagnoses were confirmed as EC; and (f) It was published in English.The quality of included studies was evaluated by two reviewers independently with the Newcastle-Ottawa Scale (NOS) recommended by the Cochrane Non-Randomized Studies Methods Working Group . This waTwo researchers completed the selection process independently to review the eligibility of all the studies and extract the required information, including the first author's family name, year of publication, country, study design, type of cancer, gender of subjects, number of cases, and controls, temperatures of tea, ORs and 95% CIs, and adjusted confounders. Reduplicative references were deleted using the Endnote software, and then, we read the titles and abstracts to check whether the articles met the inclusion criteria. If it is difficult to determine the eligibility of one paper according to the title and abstract solely, the full text is downloaded and checked for the final decision. Any disagreements about research choices among researchers were resolved through discussion.Adjusted ORs were extracted preferentially to non-adjusted ones; however, unadjusted ORs and 95% CIs were accepted when adjusted ORs were not provided. The one with the most adjusted variables was selected when more than one adjusted OR was reported. Where multiple risk estimates were available in the same study, for example, studies providing ORs for both ESCC and EAC, they were included as two separate studies. Where different temperatures were reported, the highest qualitatively described temperature was chosen, such as “hot,” “scalding,” and “very hot”.p < 0.05. The heterogeneity was assessed with chi-square based on Cochran's Q statistic  version 2.0, like combing the effect size of ORs and 95% CIs, generating forest plots and funnel plots, and determining whether there was a statistical association. The statistical significance threshold was set at tatistic , and theogeneity . Generalion bias , 28.We retrieved 210 unique articles from the databases of PubMed, Embase, and Web of Science, 61 of which were identified as potentially relevant. After reviewing the full text, we determined that 23 reports met our inclusion criteria , 29–48. Finally, 23 articles  were identified in this meta-analysis including 5,050 cases and 10,609 controls. The detailed characteristics of the included studies are shown in The qualities of the studies included were all evaluated by the NOS method, and all eligible studies scored highly , so the random-effects model was selected. The overall results of this meta-analysis showed that people who drink hot tea have a higher risk of EC than those who do not drink hot tea, with a combined OR value of 1.77 , indicating that hot tea drinking can significantly increase the risk of EC (Significant heterogeneity was observed among the included studies (Isk of EC .p < 0.001) for ESCC, was 1.93  for combined EC. Five studies were included in the meta-analysis for EAC, comprising 680 cases and 1,313 controls. There was a statistically non-significant decreased risk of EAC in patients who consumed hot tea, with a pooled OR of.76 (95% CI = 0.58–1.01). There was no statistically heterogeneity  for EAC.When we stratified the included studies according to the cancer types, the results of ESCC and EC were consistent within the overall articles. The pooled OR was 2.33 , HB-CC studies , and PS-CH studies  were all consistent within the overall conclusions , Africa , and the Americas  were consistent with the overall conclusion, while the results of those conducted in Europe  and Australia  were the opposite  to help detect influential studies. Interestingly, when we omitted one study in turn, the ORs varied from 1.70 to 1.84, and the p-value was always < 0.001, which indicated that the overall result was robust .p = 1) and Begg's rank correlation test .Based on the visualization of the funnel plot , it was This meta-analysis assessed the relationship between hot tea drinking and EC risk, according to 23 published case-control and cohort studies. The overall result indicated that drinking hot tea could significantly increase the risk of EC. A recent study also confirmed it was the temperature effect, but not polycyclic aromatic hydrocarbons (PAH) exposure that posed an EC risk . The incSignificant heterogeneity was observed in the overall meta-analysis for EC, and we failed to identify any individual study that was an important contributor to the heterogeneity by omitting one study in turn in the sensitivity analysis.The subgroup analyses generated by stratifying the studies according to study design or sex were both consistent with the overall result. Publication bias was not present in both the ESCC and EAC subgroup analyses. However, the studies performed in Europe and Australia indicated a risk reduction trend, while in Asia, Africa, and America showed a significant trend of increased risk. The reason may be that EAC represents the majority of EC subtypes in these countries and this subtype is not easily influenced by hot temperature . FurtherNotably, the association between hot tea drinking and EC risk may be affected by other confounding factors. For example, in Western populations, heavy tobacco smoking and alcohol consumption are the main risk factors for ESCC , 53. TheIn previous studies, the tea temperature was mainly estimated by self-reported perception, the results may vary across individuals and could not be objectively verified. Besides, the existing evidence in humans for the carcinogenicity of drinking hot beverages is limited. According to the IARC classification system of carcinogens, “drinking very hot beverages at above 65°C” has been classified as “probably carcinogenic” (Group 2A), rather than “carcinogenic” to humans (Group 1) . Indeed,There were several limitations in this meta-analysis. Firstly, the heterogeneity could be eliminated, neither in overall results nor in most the subgroup analyses. For example, some studies only provided the unadjusted ORs, while others reported the adjusted ones. Moreover, the adjusted confounders were not always the same in different studies. All of these factors could explain the heterogeneity in the meta-analysis to some extent. Secondly, sufficient data were not provided in some literature. Lastly, most of the questionnaires used in the included studies were qualitative regarding the temperature of tea consumption, which was relied on self-reporting by the participants. Thus, we could not extract the exact temperature of tea drinking, and a more precise analysis could not be performed.This meta-analysis indicates that hot tea consumption is associated with a significantly increased risk in EC, particularly in ESCC. Given that hot tea consumption is prevalent in modern society, the results of our meta-analysis have important implications for EC etiology research as well as EC prevention.The original contributions presented in the study are included in the article/HL designed the research, performed the literature search and statistical analysis, interpreted the data, and drafted the manuscript. HG designed the research, performed the literature search, handled funding, and made critical revisions of the manuscript. All authors read and approved the final manuscript.This work was supported by the National Natural Science Foundation of China (no. 81773230) and the Science and Technology Research Plan of Henan (no. 212102310619).The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Adherence to a healthy lifestyle  is recommended in current guidelines for hypertension prevention. However, evidence regarding the association between sleep behaviors, independently and jointly with traditional lifestyle factors, and the risk of hypertension is limited.This prospective study included 165,493 participants who are free of hypertension at baseline from the UK Biobank. Sleep behaviors, including chronotype, sleep duration, insomnia, snoring, and daytime sleepiness were used to construct a healthy sleep score. We also derived a healthy lifestyle score based on smoking status, diet quality, physical activity, and body mass index (BMI). Cox proportional hazards regression models and competing risk analyses were used to estimate the associations of the healthy sleep score and healthy lifestyle score with the risk of hypertension. The population attributable risk percent (PAR%) was estimated for increased cases of hypertension due to poor adherence to a healthy sleep pattern or a healthy lifestyle.A total of 10,941 incident hypertension cases were documented during a median of 11.8 years of follow-up. The multivariable-adjusted hazard ratio (HR) for hypertension was 0.58  for participants with a sleep score of 5 compared with 0–1, and 0.48  for participants with a lifestyle score of 4 compared with those who scored 0. For joint association, those with a poor sleep pattern and a poor lifestyle had the highest risk of hypertension [HR: 2.41 ]. PAR% was 14.7% , 20.1% , and 31.7%  for poor adherence to a healthy sleep pattern, a healthy lifestyle, and the combination of a healthy sleep pattern and a healthy lifestyle.Both a healthy sleep pattern and a healthy lifestyle were associated with a lower risk of hypertension, and the benefits of adhering to a healthy sleep pattern complement the well-established lifestyle for the optimal primary prevention of hypertension. These findings support the current perspective that a healthy sleep pattern is an important part of a healthful and productive lifestyle for hypertension prevention. Hypertension is the leading risk factor for cardiovascular morbidity and mortality and accounted for 10.8 million  attributable deaths in 2019 globally –6 and cuTherefore, we aimed to estimate the association of the combination of the five sleep behaviors and overall lifestyle with the risk of hypertension independently and jointly. Meanwhile, we calculated the population attributable risk percent (PAR%) to estimate the percentage of hypertension events that theoretically will not occur if all participants had a healthy sleep pattern, a healthy lifestyle, or both at the same time.1 At baseline recruitment, participants completed touch-screen questionnaires and a standardized interview, had physical measurements taken, and provided biological samples. Data from the health care system were also collected. The UK Biobank study was approved by the North West Multi-centre Research Ethics Committee (REC reference for UK Biobank 11/NW/0382), and all participants provided written informed consent.The study design and population of the UK Biobank have been reported in detail previously . Brieflyn = 31), those who were pregnant or unsure of their pregnancy status at baseline (n = 371), those with hypertension at baseline , and those with missing value on variables used to define a healthy sleep pattern  and a healthy lifestyle , finally, 165,493 participants were included in this analysis . For participants with at least one missing automated BP reading, the mean of two manual BP measurements , or a single automated BP reading , or a single manual BP measurement  was used instead. A threshold of ≥ 140/90 mm Hg was used to determine baseline hypertension according to the 2018 European Society of Cardiology (ESC)/European Society of Hypertension (ESH) Guidelines for the management of arterial hypertension  and diastolic blood pressure (DBP) from two automated BP readings . The ICD code and UK Biobank Field ID of hypertension are shown in n = 884). Self-reported age of hypertension diagnosis was used to help calculate the period of the disease.Incident hypertension was ascertained based on hospital admission and diagnosis data and death registry records linked to the UK Biobank according to ICD-9 and ICD-10  and 95% confidence interval (CI) with the years of follow-up as the time metric, and competing risk analyses with cause-specific hazard function were conducted. The time of events was calculated from the baseline recruitment date to the date of the first diagnosis of hypertension, death, lost of follow-up, or censoring date , whichever came first. We first investigated the association of healthy sleep scores and healthy lifestyle scores with the risk of hypertension separately, and then we examined the joint association and interaction between sleep pattern categories and lifestyle categories on hypertension events.P-value for interaction was obtained by the joint test to estimate the statistical significance of the difference between subgroups (Three stepwise models were established to adjust for known or suspected risk factors for hypertension. Model 1 was adjusted for age (continuous) and sex . Model 2 was adjusted for Model 1 covariates and ethnicity , education , Townsend deprivation index quintiles, household income , baseline mean arterial pressure , moderate alcohol consumption [0–14 g/day for women and 0–28 g/day for men ], and liubgroups . We calcubgroups . We condP-value < 0.05 was considered statistically significant.Subgroup analyses and several sensitivity analyses were conducted. We performed stratified analyses to test the association of healthy sleep score with incident hypertension across age, sex, baseline CVD, CKD, diabetes, cancer, and each component of the healthy lifestyle. For sensitivity analyses, we first analyzed the association of healthy sleep scores and healthy lifestyle scores with the risk of hypertension among participants without CVD at baseline recruitment. Second, we excluded those who developed hypertension or died within 2 years from baseline and re-ran the analyses to minimize the reverse causation. Third, we further adjusted for lipid-lowering medication use and diabetes medication use in the regression model. Finally, considering the interrelationship between sleep, hypertension, and obstructive sleep apnea (OSA), we further adjusted for baseline OSA risk based on Berlin Questionnaire in the final model . All staThe baseline characteristics of all participants are shown in P trend < 0.0001), and a 1 score increment in healthy sleep score was associated with a 12% lower risk of hypertension . Similarly, the healthy lifestyle score was inversely associated with the risk of hypertension, and the fully adjusted HR was 0.48  in participants with a lifestyle score of 4 compared with those with a score of 0 (P trend < 0.0001). A 1 score increment in healthy lifestyle score was associated with a 16% lower risk of hypertension . In terms of individual factors of sleep patterns and lifestyles, short or long sleep duration, self-reported insomnia, snoring, and excessive daytime sleepiness, as well as smoking, physical inactivity, poor-quality diet, and not optimal body weight, were all associated with the risk of hypertension in the fully adjusted model .We further examined the joint association of sleep patterns and lifestyles with the risk of hypertension . A healtP for interaction > 0.05, P for interaction < 0.0001), without CVD (P for interaction = 0.005), and without diabetes at baseline , therefore, recall bias and misclassification of exposures were possible. However, misclassifications would likely bias our estimates toward the null. Second, the healthy sleep score did not include other sleep factors, such as periodic limb movement disorder and restless leg syndrome, which might be involved in the occurrence and development of hypertension . Third, Our findings indicated that adherence to a healthy sleep pattern and a healthy lifestyle is associated with a low risk of hypertension, and the benefits of adhering to a healthy sleep pattern complement the well-established lifestyle for the optimal primary prevention of hypertension. These findings suggest that a healthy sleep pattern is an important part of a healthful and productive lifestyle for hypertension prevention.www.ukbiobank.ac.uk/register-apply.Publicly available datasets were analyzed in this study. This data can be found here: The studies involving human participants were reviewed and approved by the North West Multi-center Research Ethics Committee (REC reference for UK Biobank 11/NW/0382). The patients/participants provided their written informed consent to participate in this study.LC had full assess to all of the data in the study and took responsibility for the integrity of the data and the accuracy of the data analysis. LL was the supervisor of this study. LC and LL conceived and designed the study. YL and LC were in charge of the statistical analyses and had primary responsibility for writing the manuscript. LC, GJ, XT, and WB critically reviewed the manuscript for important intellectual content. All authors approved the final version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.