Abdominal obesity (AO) is a well-known independent risk factor for stroke in the general population although it remains unclear in the case of the elderly, especially in Chinese older patients with obstructive sleep apnea (OSA), considering the obesity paradox. This study aimed to investigate the association between AO and stroke among Chinese older patients with OSA.Data were collected from January 2015 to October 2017, and 1,290 older patients (age 60–96 years) with OSA (apnea–hypopnea index ≥ 5 events/h on polysomnography) were consecutively enrolled from sleep centers at six hospitals, evaluated for AO defined as waist circumference (WC) using the standardized criteria for the Chinese population, and followed up prospectively for a median period of 42 months. Logistic regression and Cox regression analyses were used to determine the cross-sectional and longitudinal associations between AO and stroke risk in these participants and different groups of the severity of OSA.vs. 6.8% and 8.3% vs. 2.4%, respectively; both P < 0.05) was predicted. Cross-sectional analysis revealed an association between AO and stroke , which was stronger among participants with moderate OSA only . Cox regression analysis showed that, compared to participants without AO, participants with AO had a higher cumulative incidence of stroke  during a median follow-up of 42 months, and this association was observed in patients with severe OSA only  but not for individuals with mild OSA  and moderate OSA .Participants with AO had a higher prevalence of stroke at baseline. A higher incidence of stroke during a median follow-up period of 42 months in participants with AO than in participants without AO (12.4% The risk of stroke is associated with AO among Chinese older patients who have OSA, both at baseline and during follow-up, and the strength of the association varied by OSA severity. Active surveillance for early detection of AO could facilitate the implementation of stroke-preventive interventions in the Chinese older OSA population. Obstructive sleep apnea (OSA) is the most common sleep disorder and is a leading health concern due to its strong association with the increasing burden of major adverse cardiovascular and cerebrovascular diseases and all-cause mortality . FurtherAbdominal obesity (AO) is common in patients with OSA, and AO increases the risk of OSA. The results from two observational longitudinal studies confirmed a strong association between AO and OSA, whereas another study reported a stronger, more significant association in younger than in older individuals . MoreoveGiven that the majority of the patients with OSA have AO, this obesity paradox may contribute to stroke outcomes and should be considered an important confounding factor. Thus, the present study was conducted with an aim to assess the association between AO and the prevalence of stroke among Chinese older patients with OSA at baseline and to determine the long-term effect of AO on incident stroke in a cohort of older OSA patients without stroke at baseline.The project is a Chinese population-based, multicenter, prospective, observational study to assess the association of AO with stroke in older patients with OSA aged ≥ 60 years. The study began consecutively recruiting subjects on 1 January 2015 from sleep centers of six hospitals in China using a clinic’s electronic classification system, and the data were cutoff on 30 October 2017. This study collected baseline information including basic demographics, clinical medical characteristics, and sleep parameters. OSA was defined as an apnea-hypopnea index (AHI) ≥ 5 events/h.n = 313), the Peking University International Hospital (n = 238), and the Peking University People’s Hospital , the Beijing Chaoyang Hospital affiliated to Capital Medical University , the 960th Hospital of PLA , and the affiliated Hospital of Gansu University of Chinese Medicine , who had completed polysomnography (PSG) study within 7 days after admission, at baseline, during which we performed a cross-sectional analysis. After following up prospectively for approximately 4 years, we excluded 88 patients based on the following criteria for the longitudinal analysis: (1) previous history of myocardial infarction and hospitalization for unstable angina or heart failure (n = 34); (2) patients with malignant tumors (n = 3); (3) patients with aphasia mental disorders (n = 4); and those whose blood pressure was not controlled with antihypertensive agents (n = 47). Furthermore, we excluded 95 patients who were lost during the follow-up (n = 17) and patients with stroke at baseline (n = 78). Eventually, the final sample included in the prospective analysis contained 1,107 participants, and the study participant-selection flowchart is presented in For the current study, a total of 1,290 patients with OSA were enrolled in six hospitals in six areas of China, including the General Hospital of the Chinese People’s Liberation Army ; all participants provided written informed consent for study participation.2), lowest oxygen saturation (LSpO2), and total sleep time (TST). Apnea was defined as a complete cessation of respiratory airflow for more than 10 s, whereas hypopnea was defined as at least a 30% reduction of air flow accompanied by a 4% or greater decrease in SaO2 or arousal. The AHI was defined as the number of episodes of apnea and hypopnea per hour of sleep. Oxygen desaturation index (ODI) was defined as the average number of arterial oxygen saturation dips ≥ 4%/h. TST was defined as the time spent in all sleep stages. LSpO2 was defined as the lowest value of whole oxygen saturation observed during sleep. MSpO2 was defined as the mean value of whole oxygen saturation observed during sleep. TSA90 was defined as the total sleep time spent at oxygen saturation levels below 90%  in a sleep laboratory within 7 days after admission . Particielow 90% . Sleep selow 90% . The catelow 90% .Demographics included age, sex, BMI, waist–hip ratio, neck circumference, and WC. The waist circumference was measured according to the WHO recommended method . The subLifestyle variables included self-reported current smoking (consecutively or cumulatively smoking for > 6 months in the past year) and alcohol consumption .Comorbidities included CHD, diabetes, hypertension, hyperlipidemia, atrial fibrillation (AF), carotid atherosclerosis (CAS), chronic obstructive pulmonary disease (COPD), and hyperlipidemia. Hypertension was defined as a previous diagnosis of hypertension or the use of antihypertensive medication . HyperliAll participants underwent comprehensive clinical assessment at baseline, and the clinical data that were collected were screened, assessed, and extracted using predesigned electronic case report forms by at least two medical professionals who were blinded to the patients’ PSG results. The categories of covariates are listed in Abdominal obesity was defined as WC ≥ 90 cm and ≥85 cm in men and women, respectively, according to the standardized criteria for Chinese individuals . The stuvia telephonic follow-up, a clinic visit, or medical chart review, which was performed independently by at least two investigators who were blinded to the patients’ clinical condition, PSG results, and study group.All participants were followed-up prospectively for approximately 4 years after the full baseline assessment. Patients or their proxies were contacted initially at 1-, 3-, 6-, and 12-month intervals, and every 6 months thereafter (at least 3 months and up to 1 year) until December 2020 or death -reported medical history (shared by patients or their proxies). Next, during a clinic visit or by medical chart review, we obtained the participant’s CT or MRI report to verify the diagnosis of stroke. Study events of all participants were adjudicated by the clinical event committee.The predefined endpoint in our study was stroke. Strokes were recorded both at baseline and the median follow-up of 42-month. Older participants who reported two or more stroke events in multiple follow-up notes were uniformly counted as having one relevant event, and we extracted data from the longest follow-up period after the endpoint event. Stroke was defined as both ischemic and hemorrhagic stroke using the Diagnostic Criteria of Cerebrovascular Diseases in China (2019) . The preU or the chi-square test. Logistic regression analysis was performed to obtain the ORs and 95% confidence intervals (CIs) between AO and stroke risk in total participants and different OSA  groups that were stratified according to the AHI. Three models were created to examine the relationship between AO and stroke: Model 1, which was unadjusted; Model 2, adjusted for age and sex; and Model 3, further adjusted for BMI, neck circumference, drinking status, smoking status, WHR, WC, BMI, sleep parameters, and baseline self-reported comorbidities. We used three Cox regression models to examine the association between AO and hazard ratios (HRs) of stroke during a median follow-up of 42 months in the whole cohort as well as in different OSA groups. AO was considered both a continuous and categorical variable during the analysis of all models.Continuous variables at baseline are presented as mean ± SD or median (interquartile range 25th and 75th percentiles) in our study, and intergroup differences at baseline were compared using the Mann–Whitney 2, LSpO2, TST, TSA90, ODI, AHI, and baseline self-reported comorbidities of CHD, COPD, diabetes, carotid atherosclerosis, atrial fibrillation, and hypertension. All p-values were two-tailed, and statistical significance was set at 0.05. SPSS  was used for all analyses.Additionally, all older patients with hypertension received antihypertensive drugs according to Chinese guidelines for the management of hypertension during follow-up . In thisvs. 6.8%; P < 0.05), and this trend was consistent across different OSA groups and became stronger among participants with moderate OSA  who were included in the cross-sectional analysis underwent successful overnight PSG; at baseline, 23.7, 30.1, and 46.2% of the participants had mild, moderate, and severe OSA, respectively. The prevalence of stroke was 6.5, 10.8, and 11.2% for mild, moderate, and severe OSA, respectively, and was 10.0% for all participants. The prevalence of stroke in OSA patients with AO tended to increase compared with those without AO (12.4% P < 0.05). A statistically significant difference was observed between stroke and non-stroke older participants in the specific OSA subgroup as follows: older OSA patients with stroke had a higher median neck circumference than those without stroke (only in the moderate OSA group); the ratios of AO (in the mild and moderate OSA groups) and the proportion of comorbidities of hypertension (both in the moderate and in the severe OSA groups), CHD (only in the mild OSA group), hyperlipidemia (in the severe OSA group), AF (only in the severe OSA group), and COPD (only in the moderate OSA group) were significantly higher between older participants with stroke compared to those without stroke, whereas no statistically significant difference was noted between the stroke and non-stroke groups in specific OSA groups for all other selected characteristics (P > 0.05).Associations between AO and stroke that were detected in the cross-sectional analysis are shown in P < 0.05) after adjusting for age, sex, BMI, neck circumference, drinking status, smoking status, waist–hip ratio, WC, BMI, sleep parameters, and baseline self-reported comorbidities in the mild, moderate, and severe OSA groups. The OR of AO for stroke increased significantly  for the moderate OSA group in the fully adjusted model, although there were no significant associations between AO and odds of stroke in the mild and severe OSA groups.We observed that these associations between AO and stroke varied with the severity of OSA. A onefold increase in WC was associated with a 2, 3, and 2% increase in the odds of stroke (P < 0.05), and participants with severe OSA and concomitant AO were more likely to have experienced stroke . After adjusting for age, sex, BMI, neck circumference, drinking status, smoking status, waist–hip ratio, WC, BMI, sleep parameters, and baseline self-reported comorbidities, the differences were moderately attenuated but remained significant . P < 0.05; P < 0.05) but not in the mild and moderate OSA groups (P > 0.05).The results of the longitudinal analysis are shown in n = 915), the untreated OSA , and the CPAP-treated OSA . A comparative analysis was performed to examine the longitudinal association between AO and stroke among three groups according to the CPAP therapy ; also, other factors that are potentially affected by AO were not evaluated. Accordingly, future studies taking these issues into account are required to validate and expand the current findings. However, we do not consider that these limitations negate the value of our study.In this Chinese population-based multicenter study, we provide evidence in support that AO was associated with stroke both at baseline and during a prospective median follow-up of 42 months. Again, considering the specific OSA groups, the relation was varied because of the different categories of variables in AO. Our results showed that the “obesity paradox” cannot be regarded as a major concern in an older population with OSA. Additionally, stroke is associated with increased risks of all-cause mortality and other adverse outcomes; thus, special attention should be paid to the care of Chinese older OSA populations concomitant with AO, and early screening of AO should be scaled up to prevent and reduce the prevalence and incidence of stroke burden.The datasets presented in this article are not readily available for confidentiality reasons. Requests to access the datasets should be directed to the authors, without undue reservation.The Ethics Committee of Chinese PLA General Hospital (S2019-352-01) approved the study. Written informed consent was obtained from all participants.YHG, YG, JG, JL, and YY collected and analyzed the data. XS, KL, and LY wrote and participated in all aspects of this research, including the field investigation. LL, JH, and KC designed this study. All authors have read and approved the submitted manuscript.


Instructions for the KD were given to eligible participants, with a typical plan and a menu for all the main meals, snacks, and drinks permitted over seven days. They were also free to change meals according to their preferences provided that they followed the plan. The participants attended six times throughout the intervention for measurements of their anthropometric indices, BHB levels, interleukin-1beta (1L-1β) levels, and completion of a questionnaire . Following the KD caused significant weight loss, a reduction in waist circumference and BHB levels, as well as a reduction in BMI and appetite. Cholesterol, triglycerides (TG), and high-density lipoprotein cholesterol (HDL-C) increased slightly. However, low-density lipoprotein cholesterol (LDL-C) in serum increased significantly (p < 0.05), and 1L-1β decreased significantly (p < 0.0001). The results show that the KD effectively encouraged weight loss and NLRP3 inflammasome inhibition. Based on the questionnaire results, it was found that a variety of physical symptoms, including overall energy, physical activity, mood, sleep, focus, skin conditions, and menstruation, had significantly improved.The effects of a ketogenic diet (KD) on anthropometric indices, the lipid profile, and the benefits of the ketone body beta-hydroxybutyrate (BHB) as an inhibitor of the NOD-like receptor pyrin domain-containing 3 (NLRP3) inflammasome in obese women were investigated in this study. From January to March 2021, 23 obese adult women ( Despite the efforts of the medical community, obesity is a pandemic that is rapidly spreading and remains a major health problem . ObesitySaudi Arabia has been Westernizing over the past few decades, and as a result, it now has one of the highest prevalence rates of obesity and overweight people ,6. AccorObesity is associated with the emergence of a chronic low-grade inflammatory response brought on by adipocyte enlargement and fat mass expansion, which allows macrophages to infiltrate adipose tissue . As a reRegulated calorie intake combined with the ketogenic diet (KD) has gained popularity in recent years after being recommended as a successful weight loss strategy . The KD The inflammatory NOD-like receptor protein 3 (NLRP3) complex is a tightly controlled inflammatory response to both internal and external cellular abnormalities and microbial components . It is a2, were free of disabilities and chronic diseases, and were prepared to consume the meals included in the study. At the Nutrition Clinic of the Buraydah Central Hospital, all participants underwent medical evaluations to exclude those with cardiovascular disorders, uncontrolled hypertension, impaired kidney function, liver failure, or who were pregnant or breastfeeding. All the participants signed consent forms.Advertisements on “WhatsApp” were used to recruit participants from the Saudi Arabian city of Buraydah. The eligibility requirements for the participants were as follows: Saudi women in their 20 s to 50 s who were “physically well”, had a BMI greater than 30 kg/mFrom January to March 2021, the study was carried out at the Buraydah Central Hospital. This was a repeated-measurement uncontrolled intervention research. The prospective participants listened to a presentation on a very low carbohydrate or ketogenic diet, which provided details of the diet, the significance of nutritional composition, recommended eating times each day, the benefits of the diet, and the high-fat diet. All potential participants were asked to consume a KD for eight weeks while maintaining their normal physical activity levels. The study protocol and potential risks were fully explained to the participants before their written consent was obtained. Participants were asked to attend six sessions during the intervention period, at baseline (pre-intervention), weeks 1, 2, and 4 (mid-intervention), week 6, and week 8 (post-intervention) for an assessment of their body weight, height, BMI, waist circumference, and BHB levels.The session was held at the Nutrition Clinic of the Buraydah Central Hospital. A very low carbohydrate or ketogenic diet with caloric restriction was used as the experimental intervention. At the start of the intervention, all participants attended a two-hour lecture about a KD, nutritional composition, the proper times to eat, and the beneficial effects of a KD, as well as an educational session about their prescribed diet plan. The participants were given a list of very low-carbohydrate foods to choose from in order to consume 20 g of carbohydrates per day. They were provided with a typical plan and a menu for all main dishes, snacks, and drinks allowed for seven days, with instructions to limit their carbohydrate intake to 5–10% of energy intake (EI) and to derive at least 75% of it from fat, incorporate a protein intake of 20%, and follow a very low-energy diet with a deliberate caloric deficit . Unlimited quantities of meat, poultry, fish, shellfish, and eggs were permitted, as were two cups of salad and vegetables per day, one cup of low-carbohydrate vegetables per day, four ounces of hard cheese, and limited amounts of cream, avocado, olives, and lemon juice. Transformed fats were prohibited, but fats and oils were not. Detailed explanations of how to apply the KD principles in practice and appropriate tracking and monitoring procedures were provided. The participants were instructed not to use drugs or antioxidants to eliminate the possibility of confounding effects. BHB levels were measured weekly to assess adherence to the dietary regimen.A structured questionnaire validated by nutrition experts was designed for use before and after participation. Each questionnaire consisted of three parts:The first section contained demographic data  and anthropometric measurements . The second section covered diseases or allergies caused by a specific food. The third section covered their diet, appetite, physical activity, and nutritional knowledge, particularly of the KD.The first section of the questionnaire used after the diet included anthropometric measurements . The second part focused on the participant’s level of commitment to the program and their diet in terms of health, appetite, and the number of meals they consumed per day. The third section explored the psychological state of participants after completing the KD, including mood, focus, general energy, skin condition, menstruation, and athletic activity.In accordance with Flint et al. , with sl2 (m2) was the formula used to calculate BMI (kg/m2). Obesity was defined as having a BMI greater than 30 [Anthropometric measurements were taken between 8 a.m. and 11 a.m., after an overnight fast (8 to 10 h), in standardized conditions and by the same examiner at the beginning and end of the intervention. The heights, BMIs, and waist circumferences of the participants were measured while they were standing with their heads and knees straight, wearing light clothing and no shoes or headgear. Weight (kg)/height than 30 .Blood analysis was performed twice: once before (0 weeks) and once after the end of the study (8 weeks). After an overnight fast of at least 8 h, blood samples of 5 mL were collected and coagulated for at least 30 min at room temperature before being centrifuged at 3500 rpm for 7 min. For each sample, 1 mL of separated serum was placed in a microtube and frozen. The frozen serum was analyzed by the Buraydah Central Hospital Laboratories using a Chemistry Analyzer . In accordance with Choi et al. , the anaKetosis was identified using a portable meter (FreeStyle Optium Neo Blood Glucose and Ketone Monitoring meters) to measure the ketone bodies, specifically beta-hydroxybutyrate (BHB), in the capillaries. All capillary ketonemia diagnoses were performed after an overnight fast of 8 to 10 h, as with the anthropometric assessments. Each participant performed these measurements in five sessions  throughout the KD diet, and the corresponding values were reviewed on the machine memory to control adherence .Cloud-Clone Corporation  provided the enzyme-linked immunosorbent assay (ELISA) kits, including an IL-1β kit. The ELISA was carried out following the manufacturer’s instructions. Immediately after the blood collection, the serum was separated by centrifugation for 20 min in 5 mL collection tubes, and the samples were stored in aliquots at −20 °C for later use. Before use, the samples were brought to room temperature (18–25 °C), and 100 μL of serum was added to the appropriate wells and incubated for one hour at 37 °C. After removing the excess cytokines, 100 μL of the antibody solution (A) was added to the wells and incubated for one hour at 37 °C. Following incubation, the wells were washed three times with a washing solution, then 100 μL of the antibody solution (B) was added to the wells and incubated for one hour at 37 °C. After repeated washing, 90 μL of the substrate solution was added to each well and incubated for 30 min. The reaction was stopped after incubation by adding a stop solution to each well. Finally, cytokine levels were estimated using a microplate reader to measure absorbance at 450 nm .t-tests and chi-square tests were used to compare the means at baseline and in the weeks before and after. Repeated analysis of variance measurements was used to investigate the effects of the KD on changes in the anthropometric measurements over time. p < 0.05 was chosen as the statistical significance level [For data entry and analysis, IBM’s Statistical Package for Social Science (SPSS) version 23  was used. For the quantitative data analysis, basic frequencies and percentages and the means and standard deviations were used to describe and compare responses among individuals. Paired ce level .n = 23) before and after following the ketogenic diet. The average age and height of the participants were 35.3 years and 156.83 cm, respectively. The majority of the participants were overweight, with an average body mass index (BMI) of 33.96 and a waist circumference of 99.04 cm. The nutritional intervention resulted in a significant (p < 0.0001) reduction in body weight, BMI, and waist circumference. After the first month, the body weight of all participants decreased progressively throughout the study. BMI and waist circumference decreased significantly (p < 0.0001) and continued to decrease progressively throughout the study.Out of 40 volunteers, 23 obese females aged from 18 to 48 years were found to be eligible for the study and passed the preliminary tests. p < 0.0001) at the first session (1.235 mmol/L) and continued to increase up to week 8 (0.2565 mmol/L) as shown in p < 0.05) increase in LDL-C. The ketogenic diet significantly (p < 0.0001) decreased the IL-1β cytokine from 121.38 to 20.70 ng/mL.Depending on the baseline, the level of ketone bodies in the blood increased significantly (This study aimed to find out how a very low-carbohydrate diet (KD) affected the anthropometric indices of obese Saudi women and how beta-hydroxybutyrate (BHB) stimulation affected the inhibition of the NLRP3 inflammasome and IL-1β. The majority of participants were married, had a college education, and earned an average income. Even though the majority of participants were young, educated, healthy, and had a decent monthly income, their knowledge of food regimes was very poor. A person with a good education can control their eating habits to promote moderate rather than excessive consumption and to highlight healthy food options rather than rigid diet regimens. This could have been because most participants lacked sufficient free time to attend symposiums or lectures concerning diet.Our results demonstrate that the KD intervention led to a significant reduction in the participants’ weights, BMIs, and waist circumferences, as well as a drop in IL-1β levels, as reported by Zhu et al. . The invBiochemically, the results reveal that although the total cholesterol, TG, and HDL levels all slightly improved, high levels of LDL-C were found following the intervention. This was probably because blood LDL-C levels are sensitive to higher fat intake, but this was likely to reduce in subsequent weeks as the diet in this study only lasted two months, as is customary. An experimental ketogenic study supported our findings that a low-carbohydrate, high-fat diet (LCKD) with supplementation improved blood lipid subgroups but had no effect on the total LDL-C other than to change it from small dense LDL-C to large buoyant LDL-C, which may reduce the risk of cardiovascular disease .According to the study by Noakes and Windt , a high-The results of this study demonstrate that dietary changes through the use of a KD considerably raised the levels of BHB in the serum of participants, which produced several favorable effects, including weight loss, a smaller waist circumference, and the alleviation of several symptoms. Notably, the intervention decreased the level of IL-1β, a cytokine that triggers the immune system to combat NLRP3, which when its level is increased, results in a range of inflammatory illnesses. According to a prior study that concurred with this one, elevated BHB levels prevented the neutrophils of elderly subjects from secreting IL-1β, did not worsen their condition, and instead decreased their bacterial burden . AccordiThe findings show that the NLRP3 inflammasome in macrophages is independently suppressed by fasting, exercise, and the ketogenic diet-induced metabolite BHB. While preserving ATP for ketone-dependent organs, including the brain and heart, metabolic signals such as BHB may decrease innate immune responses in ketogenic diet settings. The findings also illuminate the immunological functions of metabolic signals such as BHB, suggesting that dietary or pharmaceutical therapies to increase BHB without inducing a general starvation response may lessen the severity of NLRP3-mediated chronic inflammatory disorders and have a variety of beneficial effects.Genetic, environmental, metabolic, and behavioral variables all contribute to obesity. It has been thought that food addiction is likely to be a contributory factor to obesity and weight gain following weight-loss therapy . TherefoThis finding is consistent with a study  that exaThe sleep conditions of the participants improved, which is significant because it is connected to morbidity and death linked to obesity and is crucial for health . The parThis study has some limitations. First, because this was a two-month short-term intervention, its long-term impact, and safety could not be determined. Second, although the ketogenic diet used in this trial had some positive effects on weight loss and inflammation reduction, compliance was low, and the drop-out rate was high, necessitating strict monitoring. Third, the study sample size was small because it focused on a specific region of Saudi Arabia, making it difficult to cover the entire country, and there was no control group. Fourth, in order to evaluate the effects of the KD, the study did not include a control group that consumed an isocaloric but non-ketogenic diet. For comparison, data from the same participants prior to starting the diet were used. Another problem is that the results of this study cannot be compared with a standard low-calorie nonketogenic diet.In conclusion, a KD was conducted for 8 weeks to track participants’ progress in terms of their health. The study discovered that a KD induced by very low carbohydrate intake significantly reduced the weights, BMIs, and waist circumferences of the participants. Furthermore, there was a significant increase in the level of BHB in the participants’ serum, and the level of IL-1β was significantly decreased, demonstrating the inhibition of NLRP3-mediated chronic inflammation diseases. After the intervention, the total cholesterol, TG, and HDL-C levels improved slightly, but the LDL-C levels increased slightly. The KD positively impacted appetite suppression, fullness maintenance, and improvements in health status, physical activity, skin conditions, menstruation, sleeping, mood, and focus. The findings shed light on the immunological functions of metabolic signals such as BHB, implying that dietary or pharmaceutical therapies to increase BHB without inducing a general starvation response may alleviate the severity of NLRP3-mediated chronic inflammatory disorders, resulting in a variety of beneficial symptoms. Our findings support short-term KD diets as appropriate interventions to combat obesity in adults; however, due to the complexity of the potential mechanisms, their interactions, and the lack of data from controlled long-term studies (>1 year), an evidence-based recommendation to support KD diets as a preventive measure to help reduce cardiovascular risks or type 2 diabetes risks is premature. Furthermore, because transient unfavorable effects involving raised LDL-C have been reported, recommendations to consume the healthiest fat sources and reduce saturated fats should be made with caution. Diabetes patients who follow this diet should be under close medical supervision or capable of adjusting their medication.


Renal collecting duct carcinoma (CDC) is an extremely rare disease with few studies, and the current understanding of its prognosis is limited. We used the Surveillance, Epidemiology, and End Results (SEER) registry data to explore the prognostic factors and effect of treatment modalities on the overall survival (OS) and cancer-specific survival (CSS) in patients with CDC.Patients’ information of CDCs diagnosed by pathological examination between 2000 and 2018 was extracted from the SEER database. The Kaplan–Meier method was used to calculate OS and CSS and log-rank tests to evaluate the differences in OS and CSS. The associations between clinicopathological variables and survival outcomes were assessed with the Cox proportional hazard model. A directed acyclic graph (DAG) was drawn to recognize confounding factors and to obtain the multivariable regression model, and the impact of surgery, radiotherapy, and chemotherapy on OS and CSS was analyzed, respectively.A total of 242 patients with CDC were enrolled. The median OS and CSS time were 17 and 21 months, respectively. The OS rates at 1, 2, and 5 years were 56.9%, 41.9%, and 30.0%, respectively, while the CSS rates at 1, 2, and 5 years were 60.1%, 47.5%, and 34.8%, respectively. Patients who had a large tumor size, poor pathological grade, and advanced TNM classification exhibited worse survival outcomes. Univariable and multivariable Cox regression analyses revealed that surgery, chemotherapy, T stage, N stage, and M stage were independent prognostic factors for OS and CSS. The DAG-guided multivariate Cox regression model revealed that surgery and chemotherapy improved OS and CSS.CDC is an exceedingly rare disease and has malignant behavior. Most patients have a high pathological grade and advanced TNM stage at diagnosis and exhibited poor survival. Resection of all visible tumors including metastatic lesions or chemotherapy can be beneficial to prognosis, while healthier benefits are less likely to receive radiotherapy. More relevant studies with larger samples are needed to verify the value of surgery and adjuvant therapy in the treatment of CDCs. Collecting duct carcinoma (CDC) is a rare subtype of renal cell carcinoma (RCC), which is a malignant renal epithelial tumor, originating from the principal cells of the distal segment of the renal medullary collecting duct , 2. CDCsRobust studies about surgical treatment and prognostic factors of CDCs are lacking. Although some studies based on public databases have verified relevant prognostic factors affecting survival , 9, 10, https://seer.cancer.gov/seerstat/), the “Incidence-SEER Research Plus Data, 18 Registries, Nov 2020 Sub (2000-2018)” database was linked and the clinical and follow-up data of patients diagnosed with CDCs by postoperative pathology from 2000 to 2018 were retrieved and exported. According to the code of ICD-0-3: 8319/3: Collecting duct carcinoma, the patients were recruited into this study. The inclusion/exclusion criteria for patients were as follows: (1) survival data of patients were complete and available; (2) diagnosis was confirmed by histology; (3) the year of diagnosis was between 2000 and 2018; (4) laterality only contained left or right; (5) patient information came from the medical institution; (6) in terms of surgery, patients only receiving tumor destruction were not considered; and (7) cases with incomplete clinical information related to the study were excluded. Finally, a total of 242 patients with CDCs who met the criteria were recruited in this study.Much information on cancer incidence and survival outcomes was collected in the SEER database, and about 35% of the US population was covered . By runnInformation of demographic characteristics including age, sex, and race was obtained. The data of tumor features containing tumor size, TNM stage, pathological grade, and laterality of tumor were also chosen. Next, the treatment strategies of CDCs which consisted of surgery, chemotherapy, or radiotherapy were extracted. Radiotherapy and chemotherapy were categorized into “no/unknown” or “yes.” Notably, the intent of radiotherapy for these cases is unclear and a significant proportion of patients were probably given radiotherapy for palliation. Additionally, OS was calculated from the date of diagnosis confirmed to any cause of death, regarded as the primary survival outcome. Additionally, CSS was defined as the time from the date of diagnosis to the date of death caused by CDCs.p < 0.05 (two-sided) was considered to be statistically significant.All statistical analyses were performed, using R 3.6.3 software . Continuous variables with a normal distribution were described as mean ± standard deviation (SD) while clinical characteristics conforming to the skewed distribution were exhibited by the median and interquartile range (IQR). Categorical variables were recorded in numbers and percentages during descriptive statistics. The Kaplan–Meier method was used to conduct survival curves, and log-rank tests were applied to compare differences between survival curves. The univariable and multivariable Cox proportional hazards regression model was used to analyze independent prognostic factors affecting OS and CSS. Moreover, under the guidance of DAG, three different multivariable regression models were constructed to explore the impact of surgery, chemotherapy, and radiotherapy on OS and CSS, respectively. A total of 242 patients diagnosed with CDCs were enrolled in this study, and their baseline clinicopathological features are shown in The maximum tumor diameter ranged from 4.1 to 8.5 cm, and the median tumor size was 6.3 cm. According to the TNM stage system, 77 (31.8%) cases were in T1, 16 (6.6%) in T2, 121 (50.0%) in T3, and 21 (8.7%) in T4. Respectively, 94 (38.9%) and 86 (35.5%) patients had clinical lymph node metastasis and/or distant metastases at presentation. Based on the AJCC 6th edition staging system for renal carcinoma, there were 57 (23.6%) stage I, 11 (4.6%) stage II, 57 (23.6%) stage III, and 111 (45.9%) stage IV tumors, while pathological grade revealed that 3.72%, 10.7%, 38.0%, and 26.4% of the patients were in stages I, II, III, and IV disease, respectively. During the treatment, most patients (85.1%) with CDCs underwent surgical resection and the remaining patients (14.9%) received conservative treatment. However, only a few patients received radiotherapy or chemotherapy, accounting for 25 (10.3%) and 64 (26.4%), respectively.p < 0.001, and median CSS: 11 vs. 32 months, p < 0.001) than those with smaller tumor sizes       . The overall 1-, 2-, and 5-year survival rates were 56.9%, 41.9%, and 30.0%, respectively, and for CSS, its 1-, 2-, and 5-year survival rates were 60.1%, 47.5%, and 34.8%, respectively. Patients with larger tumor sizes had shorter survival   (p < 0.001) (p < 0.001)     S2G. Intp < 0.001, and median CSS: 10 vs. 4 months, p < 0.001)   . All factors with statistical significance (p < 0.05) in univariate analysis were selected and submitted to multivariable Cox regression model analysis. Next, we detected multicollinearity between these variables and found that the variance inflation factors of the AJCC stage which was included in the model were more than 5. Therefore, the factor of the AJCC stage was not enrolled in the multivariable Cox regression model. In multivariate analysis, advanced T stage , N stage , M stage , surgery , chemotherapy  remained significant prognostic factors for OS and CSS. The above findings of the Cox regression analysis of prognostic factors for OS and CSS are presented in The Cox regression models were used to recognize the independent predictors of OS and CSS. By univariate analysis, the result showed that tumor size, pathological grade, AJCC stage, T stage, N stage, M stage, surgery, radiotherapy, and chemotherapy were closely related to OS and CSS (p = 0.004) and CSS  (p < 0.001) and CSS  (p = 0.680) and CSS  , chemotherapy and survival outcomes, or radiotherapy and survival outcomes, respectively, and the confounding factor in the Cox regression model were identified correctly. In the light of the relationship between each exposure factor and outcomes, a total of three DAGs were produced to direct the multivariable regression analysis model. When surgery was deemed as the main exposure factor, chemotherapy and radiotherapy as intermediate variables should be excluded from the Cox regression model (= 0.002) Table 3.CDC, also called Bellini duct carcinoma, is a very rare subtype of renal malignancies and presents an aggressive clinical course, with low incidence and worse outcomes , 10. CurIn the present study, we reconfirmed that CDCs showed some aggressive behavioral characteristics, and patients with CDCs had a poor prognosis. Many studies have reported that the majority of patients had high pathological grade, advanced T stage, positive lymph node, and distant metastasis at diagnosis and these factors were the independent predictor of CDCs. In our previous study , most paFor the treatment of CDC, patients with CDC could benefit from surgical treatment and chemotherapy. When we included patients in all stages for the survival analysis, patients who received chemotherapy and radiotherapy displayed shorter survival than those who did not. However, in the next subgroup analysis, we found that patients with advanced CDC who underwent chemotherapy had longer survival than those who did not, while patients with advanced CDC who received radiotherapy had the same survival time as those who did not. The reason for this phenomenon is that for most patients receiving chemotherapy or radiotherapy, their intent of chemotherapy or radiotherapy was likely palliative and these patients themselves had a poorer prognosis than those in the earlier stages. Although no explicit treatment strategy is established, there is no doubt that surgery is still the primary treatment. Generally, patients with CDCs after surgery can obtain a longer survival , 10, 15.Undoubtedly, there exist several limitations in the present study. First, despite the data we used in this study from the SEER database, the number of cases included is still small. Second, this study belongs to a retrospective study and potential selection bias is inevitable. Third, chemotherapy schedule and administration time are unclear and the effect of specific chemotherapeutic drugs on the survival of CDCs remains to be studied. Fourth, the type of surgery is unknown and the role of NSS and RN in the treatment of patients with early CDCs is also folded. Equally importantly, the intent of radiotherapy—palliative or curative—is not known and the value of radiotherapy is not clear. Additionally, because pathological sections are not centrally re-confirmed by professional pathologists, CDC is easily misdiagnosed as others, including medullary carcinoma and FH-deficient RCC. These defects are unavoidable. However, this study is of tremendous value to help clinicians comprehend the prognosis of CDCs and make the right treatment strategies for this tumor.CDC is an extremely rare renal carcinoma, with an invasive biological behavior. Most patients have a high pathological grade and advanced TNM stage at diagnosis and exhibited poor survival. Larger tumor size, advanced TNM stage, later AJCC stage, and higher pathological grade may indicate an extremely detrimental prognosis. Healthier benefits are more likely to undergo surgery or chemotherapy than more comorbid ones. Certainly, to make systemic therapeutic options for this tumor, long-term large-scale prospective trials are necessary.The original contributions presented in the study are included in the article/XYQ, JQZ and SGW conceived and designed the study. JZX, and CQL collected and assembled the data. XYQ, MLZ, and SYH, contributed to data processing, interpretation of results, and drafting. XYQ, JNZ, and CQ critically revised the manuscript. All authors read and approved the manuscript.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.


Using data from a representative sample of the Children of Immigrants Longitudinal Study (N = 3344), the current study revealed that parental hostility, emotional rejection, and harsh family interactions with parents significantly impaired successful college graduation of immigrant youths in young adulthood, with the decreased odds of 20.1% to 30.22%. Furthermore, academic aspirations of immigrant youths in late adolescence not only significantly mediated the abovementioned relationships but also contributed to the higher odds of immigrant youths’ college graduation by 2.226 to 2.257 times. Findings of this study related to educational innovations, family services, and policy implications are discussed herein.Parental hostility and emotional rejection—or aggregated as general harsh family interactions with parents—have received little research attention due to such parent-child interactions being counted as minor forms of parental maltreatment and regarded as being less harmful. However, recent research showed that these minor forms of parental maltreatment on youth development are far from negligibility on account of their frequency, chronicity, and incessancy. In this longitudinal study, we investigated how parental hostility, emotional rejection, and harsh family interactions with parents of in early adolescence of immigrant youths (wave-1 M Adolescence is a critical formative and transitional period for youths to prepare for adulthood ,2, in whImmigrant youths, compared to their non-immigrant counterparts, are at greater risk of being harshly disciplined and maltreated by their parents due to lower parental education levels, disadvantaged social status, and cultural differences . This isHarsh parenting and parental maltreatment can occur in various forms and types, which are commonly referred to parents or main caregivers using abusive, hostile, disdainful, and neglectful responses toward their offspring behaviorally, psychologically, and emotionally ,7,18. EmPertinently, the family transmission model evinces that parents are the main socialization figures responsible for providing care, support, resources, and the social and cultural capital necessary for the healthy cognitive development of their offspring . HoweverAccordingly, as immigrant parents are of disadvantaged social status, economic deprivation, and cultural differences, they may be more prone to employ harsh discipline and unsupportive parenting ,27,37. TDuring adolescence, youths may ask the questions, “Who am I?” and “What will I do in the future?”, which are closely related to their formation of self-concept and identity, a process referring to the establishment of the “possible self” in relation to the future . Youths As academic aspirations of youths are mainly shaped by the process of family socialization and experiences in early years ,15, it hContextual differences of the living environment can undeniably have distinct structural effects on youth development, including educational success. However, prior research has seldom considered contextual influences on educational achievement of both immigrant and non-immigrant youths when studying harsh parental discipline and maltreatment, such as parental hostility, emotional rejection, and harsh family interactions with parents. This is important because youths’ educational achievement is highly susceptible to their living contexts of their family, cultural, and school environments ,44, whicThe aim of this study was to investigate the effects of immigrant youths’ experiences of parental hostility, emotional rejection, and harsh family interactions with parents—aggregated as parental hostility and emotional rejection—in early adolescence on their successful college graduation in young adulthood through the mediation of immigrant youths’ academic aspirations in late adolescence. This study builds on prior pertinent research with the following advantages. First, it is a longitudinal study covering a long-range time period across the 10-year life course development of immigrant youths from early adolescence to young adulthood. This is valuable, as prior studies mainly limited their focus on educational performance of children and youths in primary or high school years ,12,14. SH1. Parental hostility, emotional rejection, and harsh family interactions with parents—aggregated as parental hostility and emotional rejection—in early adolescence of immigrant youths would negatively predict their successful college graduation in young adulthood.H2. Parental hostility, emotional rejection, and harsh family interactions with parents in early adolescence of immigrant youths would negatively predict their academic aspirations in late adolescence, even controlling their initial level of academic aspirations in early adolescence.H3. Academic aspirations of immigrant youths in late adolescence would mediate the effects of parental hostility, emotional rejection, and harsh family interactions with parents in early adolescence of immigrant youths on their successful college graduation in young adulthood.H4. Compared to parental hostility and emotional rejection, harsh family interactions with parents in early adolescence of immigrant youths would more strongly predict their academic aspirations in late adolescence and successful college graduation in young adulthood.In order to preclude confounding effects, in this study, we adjusted for gender, age, number of siblings, generation status, standardized English and math test scores, and ethnic origins of immigrant youths. Immigration research indicates that female immigrant youths generally perform better academically than their male counterparts  and thatage = 14 years old) in 8th and 9th grades studying in 49 public and private schools, representative of the population of immigrant youths in the study regions. In 1995–1996, the wave-2 survey of CILS involved reinterviewing 4288 immigrant youths (81.5%) of the original sample at the time of their high school graduation (age = 17 years old). In 2002, the wave-3 survey of CILS was conducted when the immigrant youths were in their young adulthood (age = 24 years old), including a sample of 3613 immigrant youths representing 68.9% and 84.3% of the wave-1 and 2 samples, respectively. In the present study, we used data across the three waves of CILS covering a 10-year life course of immigrant youths’ adaptation and development. Data analysis in the present study was based on a sample of 3344 immigrant youths who had given information regarding the study variables concerned. The rates of missing values were very low in the drawn sample of 3344 immigrant youths, ranging from 0.6% to 0.9%. The missing values were largely due to missing responses of immigrant youths to one of the question items used to construct the composite scores of parental emotional rejection and academic aspirations. The technique of expectation maximization imputation (EM) was used to replace the missing values rather than employing mean substitution, as the former involves a two-step iterative process whereby regression analysis and maximum likelihood are used to impute missing values through simulation with reference to all the available data as predictions to effectively avoid the problems of restricted variances and biased estimates associated with mean substitution [The data used in this longitudinal study were obtained from the Children of Immigrants Longitudinal Study (CILS), which is one of the largest longitudinal surveys on the development and adjustment of immigrant youths conducted in the United States . CILS retitution .Successful college graduation of immigrant youths in young adulthood was measured with a single question item asking whether the CILS immigrant youth participants had graduated from a college with a four-year undergraduate degree at the time of the wave-3 CILS survey. A dichotomous response to the question item was used, in which 1 = yes and 0 = no.Academic aspirations of immigrant youths were measured by two question items included in the wave-1 and wave-2 CILS surveys, which asked the immigrant youth (1) the highest education level he/she would like to achieve and (2) the highest education level he/she thinks they would realistically achieve. A 5-point scale was used to rate participants’ responses to the two items, ranging from 1 = less than high school to 5 = finish a graduate degree. The two items were averaged in the wave-1 and wave-2 CILS surveys to represent the academic aspirations of immigrant youths in early and late adolescence, respectively ,42; highParental hostility of immigrant youths in early adolescence was measured in the wave-1 CILS survey, in which immigrant youths were asked whether the processes of family socialization and communication with parents were full of clashes and hostility from their parents. The response was provided on a 4-point scale, where 1 = all of the time, 2 = most of the time, 3 = sometimes, and 4 = never, which was inversely coded, so higher scores represent more parental hostility. Although it is more desirable to employ validated scales to measure parental hostility, such as the Parental Acceptance–Rejection Questionnaire , CILS isr = 0.439, p < 0.001, and the Cronbach alpha was α = 0.611, representing an adequate level.Parental emotional rejection of immigrant youths in early adolescence was measured with two items in the wave-1 CILS survey asking immigrant youths (1) whether their parents did not like him/her much and (2) whether their parents were not interested in him/her; these items were rated on a 4-point scale, where 1 = very true, 2 = partly true, 3 = not very true, and 4 = not true at all. Again, although the use of validated scales to measure parental emotional rejection is more informative, the latest relevant studies used similar items comparable to the items adopted in the current study to measure parental emotional rejection ,37, supppc = 0.600. In addition, the average correlation coefficient among the three items was adequate: r = 0.316, p < 0.001. Hence, harsh family interactions with parents were measured by combining the three items as a composite score.Harsh family interactions with parents in early adolescence of immigrant youths were measured by combining the items used to indicate the aggregate of parental hostility and emotional rejection. This is justified, as the indicators and dimensions of parental harsh discipline and maltreatment were found to be closely interrelated, with more harmful effects on child and youth development when they occurred in combination ,26,37. BFor contextual variables obtained from the wave-1 CILS survey, family composition was measured as a dummy variable with reference to whether the immigrant youths were living with both their biological father and mother (1 = two-parent family and 0 = otherwise). Parental SES was included as a unit-weighted standardized variable by averaging occupational socioeconomic index, parental education, and home ownership, with higher scores representing better socioeconomic levels . Mode ofFor sociodemographic variables of immigrant youths, gender was measured as a dummy variable , and age and number of siblings were included as count variables. In addition, immigrant generation status was classified as 1.5 generation (immigrated with both parents to the U.S.), 2 generation (born in the U.S. with two immigrant parents), or 2.5 generation (born in the U.S. with one immigrant parent and one native parent) served as a reference . Standariμ) to iY in a function of the linear predictor (iη). Therefore, we can have:Due to the clustered nature of the CILS data nested in schools, multilevel modeling was applied; a generalized linear mixed modeling (GLMM) approach was employed because successful college graduation of immigrant youths in young adulthood was a dichotomous outcome, which can express as:Mplus 8.5 [For this, GLMM generates the form asocedures . The modplus 8.5 .N = 3344) who took part in the three waves of the CILS. Slightly more female immigrant youths participated than their male counterparts, accounting for 54.1% of the total sample (n = 1809). The mean age of immigrant youths in the wave-1 survey was 14.23 years, with an average of 1.79 siblings in the home. Moreover, 1.5-generation  and 2-generation  immigrant youths were more represented in the sample than their 2.5-generation counterparts . The standardized English and math test scores of the participants averaged 700.762 and 669.111, respectively. In terms of family composition, approximately one-quarter of the immigrant youths came from non-two-parent households , and the average score of parental SES, calculated according to the Duncan Socioeconomic Index (SEI), was 34.25 that is much lower than the means of the American public obtained from the General Social Survey of 1994 [n = 906). In terms of ethnic origins, Cuban and Southeast Asian immigrant youths were most prevalent in the sample , and immigrant youths from Northeast/East Asia (2.3%), the Middle East/Africa (1.9%), and Europe (1.9%) were the least represented in the sample, with immigrant youths of Central/South American (16.6%), Mexican (12.4%), and Caribbean (10.9%) origins falling in the middle.t-tests conducted via the biased-corrected and accelerated (BCa) method (ĵ = 1000) showed that the drawn and original samples did not differ in terms of age , number of siblings , immigrant generations , standardized English scores , standardized math scores , or parental SES . In addition, Chi-square bootstrapping tests conducted via the biased-corrected and accelerated (BCa) method (ĵ = 1000) revealed that compared to the original sample, the drawn sample comprised slightly higher proportions of female immigrant youths  = 6.805, p < 0.01, 95%CIs = 0.007 to 0.051), immigrant youths from two-parent families  = 23.577, p < 0.001, 95%CIs = 0.033 to 0.075), positive/neutral reception  = 8.426, p < 0.01, 95%CIs = 0.011 to 0.055), and immigrant youths attending suburban schools  = 13.719 (1), p < 0.001, 95%CIs = 0.019 to 0.064). Nevertheless, Cohen’s effects sizes showed that the significant differences were minimal, ranging from ω = 0.029 to 0.054. Moreover, Chi-square bootstrapping tests conducted via the biased-corrected and accelerated (BCa) method (ĵ = 1000) did not reveal significant differences between the drawn and original samples in terms of ethnic origins (X2(7) = 9.080, p = 0.247, 95%CIs = 0.000 to 0.034), school type (X2(1) = 1.910, p = 0.167, 95%CIs = 0.000 to 0.037), or minority school status (X2(1) = 0.367, p = 0.545, 95%CIs = 0.000 to 0.028). Accordingly, there is no solid evidence to show the differences between the drawn and original samples. Nevertheless, on account of the theoretical and empirical importance of the sociodemographic and contextual variables of immigrant youths compared above, immigrant youths’ gender, age, number of siblings, standardized English and math scores, family composition, parental SES, reception mode, ethnic origin, school type, school location, and minority school status were all adjusted in the modeling procedures to preclude the possibility of confounding effects.As the current study was based on the drawn sample of 3344 immigrant youths who provided relevant information regarding the study variables across the three waves of the CILS, it is important to compare their differences with the original sample of 5262 immigrant youth participants in terms of sociodemographic and contextual variables obtained in the wave-1 CILS survey, although we cannot examine their differences in terms of the main study variables due to attrition of the original sample. Independent samples bootstrapping b = −0.224, p < 0.001), meaning that a unit increase in parental hostility resulted in the decreased odds of successful college graduation of immigrant youths by 20.1%. In model 2, parental emotional rejection significantly and negatively predicted successful college graduation of immigrant youths in young adulthood , explicating that each unit of increased parental emotional rejection induced the decreased odds of immigrant youths’ successful college graduation by 21.9%. Moreover, harsh family interactions with parents were significantly and strongly predictive of the reduced rates of successful college graduation of immigrant youths in young adulthood , meaning that each unit increased in harsh family interactions with parents in early adolescence led to the decreased odds of college graduation of immigrant youths in young adulthood by 30.2%. In fact, the significant negative effects of parental hostility, emotional rejection, and harsh family interactions with parents on successful college graduation of immigrant youths in young adulthood were sustained, even controlling for the various sociodemographic and contextual covariates mentioned above.With respect to whether parental hostility, emotional rejection, and harsh family interactions with parents in early adolescence negatively predict immigrant youths’ successful college graduation in young adulthood, GLMM results revealed that parental hostility in early adolescence significantly and negatively predicted successful college graduation of immigrant youths in young adulthood model 1,  . In addition, parental emotional rejection predicted significantly lower academic aspirations of immigrant youths in late adolescence . Notably, the academic aspirations of immigrant youths in early adolescence were robustly and significantly positively contributive to their academic aspirations in late adolescence across the three models . In terms of the effects of sociodemographic and contextual covariates, female and 1.5- and 2-generation immigrant youths significantly had higher academic aspirations in late adolescence than their male and 2.5-gernation counterparts. Moreover, immigrant youths from two-parent families and with higher parental SES significantly had higher academic aspirations in late adolescence than their counterparts from non-two-parent and economically poorer families. Furthermore, public school and inner-city school status significantly contributed to lower academic aspirations of immigrant youths in late adolescence at the school level.b = −0.191 and 0.814, p < 0.001); for each unit of increase in parental hostility, the odds of immigrant youths’ successful college graduation decreased by 17.4%, and for each unit of increase in academic aspirations of immigrant youths in late adolescence, the odds of successful college graduation increased by 2.257 times. Moreover, model 2 revealed that academic aspirations of immigrant youths in late adolescence significantly and positively predicted their successful college graduation , whereas parental emotional rejection in early adolescence significantly and negatively predicted successful college graduation of immigrant youths ; for each unit of increase in academic aspirations of immigrant youths in late adolescence, the odds of educational success of immigrant youths in young adulthood increased by 2.242 times, and for each unit of increase in parental emotional rejection, the odds of immigrant youths’ successful college graduation in young adulthood decreased by 16.6%. In model 3, both the academic aspirations of immigrant youths in late adolescence and harsh family interactions with parents in early adolescence of immigrant youths significantly predicted successful college graduation of immigrant youths in young adulthood ; for each unit of increase in academic aspirations of immigrant youths in late adolescence, the odds of successful college gladiation in young adulthood increased by 2.226 times, whereas for each unit of increase in harsh family interactions with parents, the odds of immigrant youths successfully obtaining a college degree in young adulthood decreased by 25.1%.βind = −0.156, p < 0.001) and total indirect effect . In addition, academic aspirations of immigrant youths in late adolescence significantly mediated the effect of parental emotional rejection on college graduation of immigrant youths in young adulthood, with an indirect effect  and total indirect effect . Lastly, it was found that immigrant youths’ academic aspirations in late adolescence significantly mediated the effect of harsh family interactions with parents in early adolescence of immigrant youths on their successful college graduation in young adulthood, with an indirect effect  and total indirect effect .This study represents a first attempt to investigate how harsh family experiences of immigrant youths in early adolescence adversely impact their educational achievement in young adulthood through the mediation of academic aspirations of immigrant youths in late adolescence, which is of research importance, due to the disadvantaged social conditions and cultural differences of immigrant families ,49. SomeMoreover, harsh family interactions with parents, the aggregate of parental hostility and emotional rejection, were found to more strongly compromise both successful college graduation of immigrant youths in young adulthood and their development of academic aspirations in late adolescence than the single minor form of parental hostility and emotional rejection, revealing the accumulative detriment of minor forms of parental maltreatment with respect to the positive development of immigrant youths. This is congruous with the claim by some researchers that concurrent exposure to multiple types of harsh parental discipline and maltreatment could result in destructive impacts on youth development ,36. TherIn addition, the results of this study show that parental hostility, emotional rejection, and harsh family interactions with parents significantly impaired the development of academic aspirations of immigrant youths in late adolescence, which, in turn, mediated the relationships between their experiences of harsh family socialization in early adolescence and successful college graduation in young adulthood. Similarly, recent research pointed out that the “future self” is an extension of the “current self” . Hence, On the other hand, some sociodemographic and contextual covariates of immigrant youths were found to be consistently and significantly predictive of both immigrant youths’ successful college graduation in young adulthood and academic aspirations in late adolescence. Specifically, female and 1.5- and 2-generation immigrant youths showed higher rates of successful college graduation and academic aspirations than their male and 2.5-generation counterparts. Prior immigration research reported that female and less assimilated immigrant youths have higher achievement drive, which critically propels their higher educational and social attainments ,46, as cIn summary, the current study reveals and supports a clear message that even minor forms of parental maltreatment and parental harshness in the early years of immigrant youths, such as parental hostility, emotional rejection, and harsh family interactions with parents in aggregate, may adversely affect immigrant youths’ educational success in adulthood; this significant relationship was persisted, even after adjusting for various important sociodemographic and contextual confounding covariates of immigrant youths, including gender, age, family characteristics, immigration generation, standardized test scores, ethnicity, school type, and locality at the individual and school levels. In addition, academic aspirations of youths were found to mediate the effects of parental hostility, emotional rejection, and harsh family interactions with parents in the early adolescence of immigrant youths on their later successful college graduation in adulthood. However, the current study is subject to several limitations that should be addressed in future investigations. First, although the current study included a large and representative sample of immigrant youths sampled from the two immigrant-receiving regions in the United States, these immigrant youths cannot represent the whole population of immigrant youths in other parts of the United States. Secondly, other serious types of parental maltreatment, e.g., sexual and physical abuse, and some important intrapersonal constructs of immigrant youths, such as self-esteem and life meaning, that may mediate the studied relationships, were not examined. Therefore, future research should investigate the accumulative effects of different maltreatment experiences of immigrant youths in relation to their educational achievement through the development of multiple cognitive and intrapersonal mediators. Thirdly, CILS data were collected twenty years ago and may not reflect the recent political economic, societal, and immigration policy changes in Western immigrant-receiving countries that are profoundly related to educational development of immigrant youths ,59. TherIn general, helping immigrant families to develop and cultivate nurturant and supportive parent–child relationships and enhancing immigrant youths’ establishment of positive academic aspirations in early years are pivotal for their educational success in adulthood, all of which are important determinants of their well-being and health in later life trajectories. Therefore, policy maker, educators, and human service professionals should pay more attention to these negative family experiences of immigrant youths when designing policy, programming, and interventions. In conclusion, we believe that if timely and adequate interventions and service supports are provided to harshly disciplined and maltreated immigrant youths and their families, these youths can thrive academically and socially.


BackgroundEpilepsy is a chronic neurologic condition with different risk factors and genetic predispositions. It is characterized by the occurrence of an epileptic seizure. To our knowledge, most studies have focused on revealing epilepsy prevalence in Saudi Arabia, but the etiological prevalence is still not well-studied in the region. Thus, this research aims to raise awareness and provide more insights into the etiological prevalence of this disorder.MethodologyA cross-sectional study was performed among 431 adult patients diagnosed with epilepsy in the Neurology Department at King Abdulaziz Medical City in Jeddah, Saudi Arabia. Patients’ data were retrospectively collected from electronic medical files covering the period between May 2016 and April 2021. Epilepsy etiologies were classified as suggested by the International League Against Epilepsy 2017.ResultsThe most commonly identified seizures were generalized (25.3%) and focal (8.9%). However, 66.1% of seizure types were unidentifiable. The most common etiology was structural (42.9%), followed by genetic (7.2%), with strokes (24.3%) and tumors (23.8%) being the most prevalent structural etiologies. However, 47.6% of the patients were classified under unknown etiology.ConclusionsThis study suggested that epilepsy diagnosed as generalized was by far the most common seizure type in our cohort. Structural etiology was evident in most patients, with stroke being the highest presented etiology. Epilepsy is a chronic neurological disorder characterized by the occurrence of recurrent seizures associated with permanent brain changes, according to the International League Against Epilepsy (ILAE) . SeizureThe prevalence and incidence of epilepsy vary between high-income and low-middle-income countries. In high-income countries, around 48.9 per 100,000 individuals are diagnosed with epilepsy annually, whereas the incidence has been reported to be 139 per 100,000 in low-middle-income countries . This obEpilepsy etiology and seizure types are crucial in determining its treatment and prognosis. In 2017, the ILAE published a revised classification of epilepsy etiology as genetic, structural, metabolic, infectious, immunological, and unknown. In addition, the seizure type was classified based on onset as focal, generalized, or unknown .Numerous studies have reported different seizure types, etiologies of epilepsy, and their prevalence. In a 2016 systematic review and meta-analysis of the prevalence and incidence of epilepsy, active generalized epilepsy was found to be the most prevalent , while active focal seizures accounted for 2.99 per 1,000 individuals. However, unknown seizures were reported to be the least common . In addition, epilepsy of an unknown etiology was the most common , and structural/metabolic epilepsy was the most known etiology  , head inTo our knowledge, few studies have focused on revealing the prevalence of epilepsy in Saudi Arabia, but the etiological prevalence is still not investigated in the region ,10-12. TStudy design and samplingAn observational, cross-sectional study was conducted at the Neurology Department of King Abdulaziz Medical City (KAMC), Jeddah. This study included all adult patients, 15 years and older of both genders, who were diagnosed with epilepsy in the outpatient Neurology Clinic between May 2016 and April 2021. Pediatric patients with epilepsy were excluded from the study. A simple random sampling technique was used to obtain a representative sample of these patients. From a total of 1,855 adult patients, the required minimum sample size was determined to be 319 at the 95% confidence level and a margin of error of ±5%. A total of 431 patients with epilepsy were included in the analysis.Definitions and classificationFor this research, following the practical definitions of ILAE, epilepsy was defined as a disease of the brain deﬁned by any of the following conditions: 1) at least two unprovoked (or reﬂex) seizures occurring >24 hours apart; (2) one unprovoked (or reﬂex) seizure and a probability of further seizures similar to the general recurrence risk (at least 60%) after two unprovoked seizures occurring over the next 10 years; and (3) diagnosis of an epilepsy syndrome [ at leastData collectionThe data were collected by the investigators after obtaining approval. Patients’ files were selected from the medical records using the BESTCare system at KAMC, Jeddah. A data collection sheet was used to gather eligible patients’ information. Data were collected on patients’ demographics, etiology of epilepsy, and type of seizure.Statistical analysisThe statistical analysis was performed using a 95% confidence interval using JMP Pro software version 15 . The categorical variables were analyzed as proportion, frequency, and percentage. Numerical variables were presented as median and range. The graphical representation for the categorical variables was in simple bar charts and tables. A p-value <0.05 was considered a significant value.Ethical considerationsThe study was conducted following the ethical approval of the Institutional Review Board committee of King Abdullah International Medical Research Center (KAIMRC) with the approval number RSS21J/009/06.Patients’ demographicsOverall, 431 patients with different types of epilepsy were included in this study. Male patients (50.6%) were slightly higher than female patients (49.4%). The patients’ ages ranged between 15 and 96 years  = 51-24). In this study, the most commonly identified seizures were generalized (25.3%) and focal (8.9%). However, 66.1% of seizure types were unidentifiable in patients’ medical records , with stroke (24.3%) and tumors (23.8%) being the most common structural etiologies in our study sample. Consistent findings have been reported in the literature as a cause of epilepsy. In a Norwegian study, the prevalence and causes of epilepsy were reported in 43.3% of the patients with structural-metabolic epilepsy, with stroke being the most prevalent cause , which iThis study has some limitations. First, the BestCare system started in 2016, and many patients with epilepsy were diagnosed before the start of the system; thus, many digital files had undocumented data explaining why many patients had unknown etiology, seizure type, or age at the time of diagnosis. Second, as this study was a single-center, retrospective, cross-sectional study, certain important aspects of epilepsy were not reported, such as family history, risk factors, comorbidities, and genetic testing. Third, patient follow-up could not be confirmed due to the retrospective nature of the study.Our findings were in accordance with similar international and local studies. Epilepsy diagnosed as generalized was by far the most common seizure type in our patient cohort. Structural etiology was evident in most patients, with stroke being the most reported etiology. Future studies reporting the pediatric population are recommended to shed light on the etiology in this age group. Neuroimaging data and electroencephalography are also necessary for further classification and reporting.


Because cancer is a multifactorial disease, it is difficult to identify the specific agents responsible for the disease’s progression and development, but lifestyle and diet have been shown to play a significant role. Diverse natural compounds are demonstrating efficacy in the development of novel cancer therapies, including sulforaphane (1-isothiocyanate-4-(methylsulfinyl)butane), a compound found in broccoli and other cruciferous vegetables that promotes key biological processes such as apoptosis, cell cycle arrest, autophagy, and suppression of key signalling pathways such as the PI3K/AKT/mTOR pathway in breast cancer cells. However, one of the primary challenges with sulforaphane treatment is its low solubility in water and oral bioavailability. As a consequence, several investigations were conducted using this component complexed in nanoparticles, which resulted in superior outcomes when combined with chemotherapy drugs. In this study, we discuss the properties and benefits of sulforaphane in cancer therapy, as well as its ability to form complexes with nanomolecules and chemotherapeutic agents that synergize the antitumour response in breast cancer cells. Breast cancer is the most frequent malignancy in women and the second most common cancer worldwide, characterized by the aberrant proliferation of cells and deregulation of cell cycle control ,2,3. BreIn 2013, an epidemiological study with a cohort of 69,120 participants described one of the first approaches to the relationship between dietary patterns and cancer development. The dietary patterns considered different food ingestion, and the results suggested a protective effect of a vegetarian-like diet showing a protection for overall cancer incidence, and interestingly, the lacto-ovo-vegetarian regiment appears to be a gastro-intestinal prevention factor . VariousThe glucosinolates are a class of sulphur containing glycosides, common glucosilates are glucoraphanin, glucoerucin, glucoraphasatin, and gluconasturtiin among others—these glucosinolates are found in broccoli, recked salad, radish and watercress respectively . Such moThere is a stable correlation of isothiocyanate formation with a pH range of 6–7, despite the fact that glucosinolates possess a β-hydroxy-isothiocyanate that being unstable spontaneously cyclises to oxazolidine-2-thiones  and indole isothiocyanates after lysis generates the corresponding alcohol as indole-3-carbinol. In contrast to a pH between 4 and 7 the presence of the nitrile generates principally ascorbigen and thiocyanate, nevertheless the mechanism of ‘nitrile-forming factor’ is not clear .2+ overload leading to cell apoptosis 24 h after treatment. Additionally, sustained treatment for 7 days led to a significant reduction in tumour size observed in mice tumours [TNFR1, cIAP-1, cIAP-2, Bax, and mitochondrial membrane potential decreased after co-treatment, suggesting apoptosis activation [LAMP2), which decreases sulforaphane’s capacity to trigger apoptotic cell death, at least in prostate cancer. LAMP2 knockdown enhanced apoptosis in PC-3 and 22Rv1 cells treated with 20 μm/L sulforaphane. Finally, another mechanism of apoptosis related to sulforaphane is the activation of p34cdc2 kinase by dephosphorylation—the activation induced apoptosis in 25% and 35% of treated cells after 24 and 48 h. In addition the authors suggested that the induction of the proteasome by ubiquitination is essential to induce the mechanism of apoptosis in treatment with sulforaphane [The main method of treatment related to cancer involves increasing the susceptibility of apoptosis in cancer cells. Sulforaphane treatment studies provide a consistent mechanism of action that is related to a reduced mitochondrial membrane potential that promotes apoptosis in cancer cells and tumour xenografts. Cancer research shows that sulforaphane treatment increases caspase-9 and poly-ADP ribose polymerase (PARP-1) activity, as well as cyclooxygenase IV (COX IV) activity, sensitizing cancer cells to mitochondria-mediated apoptosis . Interes tumours . Remarka tumours . The stutivation . On the tivation . Caspasetivation . Other eoraphane .NOS2 and NOS3 expression, triggering increased nitric oxide. Furthermore, the study reveals the upregulation of HSP-90AB1, PRKAR1B, ALOX12, PRG3, and NCF2. On the other hand, sulforaphane treatment led to downregulation of genes such as CCNA1, SOD3, and GPX4 among other genes related to maintenance of redox balance [Understanding oncogenesis and apoptosis reveals the critical function of cell cycle control in malignant transformation. When normal cells acquire DNA damage or mutations, checkpoints are activated to stop cell cycle progression and promote DNA repair or induce cell apoptosis. For example, Sundaram et al. showed apoptotic changes such as nuclear condensation, fragmentation, and formation of apoptotic bodies probably due to the induction of  balance . However balance . In addi balance . Another balance .Other research has shown sulforaphane might decrease the expression of cell cycle proteins such as Cyclin D1, Cyclin A, and C-Myc 4 h after treatment with 50 μM of sulforaphane in HT-29 cells. In contrast, higher expression of cell cycle inhibitory proteins such as p21 was reported. Interestingly, the MAPK pathway, ERK, JNK, and p38 activation were linked with sulforaphane therapy. However, the molecular mechanism that permits inhibition of cell growth by these pathways and proteins is not well known since they are contradictorily connected with cell growth . P21 expHSP90AA1, MAP1LC3B, MAP1LC3A, EIF2AK3, HSPA8, and UVRAG which are upregulated and ATG4C, FAS, PTEN, ATG10, PRKAA1, TP53, and NF-κB 1 as downregulated genes [Cell autophagy is a tightly controlled catabolic process by which cells recycle their internal components by sending them to lysosomes. Autophagy has been shown in several studies to perform a broad range of physiological and pathological functions in cells. Autophagy acts as a tumour suppressor in cancer, enabling cells to eliminate damaged cellular contents, consequently reducing ROS and DNA damage . In termed genes .The PI3K/AKT/mTOR signalling pathway is constitutively active in several cancer processes and plays an important role in carcinogenesis and development. Second, the PI3K/AKT/mTOR pathway regulates cancer cell survival, proliferation, migration, and therapy response . A numbeBreast cancer is the most prevalent cancer in women, with an incidence rate that has increased by 0.5% per year. In the case of breast cancer, the mechanism of action of sulforaphane is multi-targeted, as we show in ZEB1, claudin, and fibronectin, was seen at doses of 20, 30, and 40 μM at 72 h after sulforaphane therapy [(ALDH1A1), NANOG, GDF3, and the embryonic pluripotency-maintaining transcription factor Forkhead box D3 (FOXD3) [CCND1) and CDK4 expression promoting cell cycle arrest in G1/S phase progress [NF-κB 1 gene, suggesting that sulforaphane indirectly influences the regulation of the NF-κB pathway; These results were replicated by the same research team on in vivo models observing a 30–52% decrease in plasma levels of certain proteins such as CTSK, RANKL, and IL8 [Sulforaphane’s anticancer activity seems to be dose-dependent in breast cancer. For example, sulforaphane of 40 µM promotes the induction of early/late apoptotic and necrotic cells in MDA-MB 231. Down-regulation of genes involved in the epithelial-mesenchymal transition, such as  (FOXD3) . Consistprogress . The impprogress . Finally and IL8 .Currently, the combination of chemotherapeutic medications with various natural molecular components has shown multiple advantages such as improved effectiveness and reduced adverse effects. In the case of sulforaphane, considerable benefits have been shown when combined with several chemotherapeutic drugs in basic scientific study . For exa3O4, PEGylated Fe3O4, monomethoxypol, and based on Fe2+ and Fe3+ for the administration of sulforaphane in breast cancer, has recently been documented [BAX and Bak and the downregulation of anti-apoptotic bcl-2 and bcl-xL. Furthermore, sulforaphane-coated selenium and tellurium nanoparticles appear to specifically target tumour cells, whereas normal cells, MCF-10A, have a better tolerance to treatment, as observed in the MTT assay [Nanotechnology has been actively researched and used in cancer therapy as nanoparticles potentially play an important role as a drug delivery method. Nanoparticle-based drug delivery provides distinct benefits over traditional drug delivery, including greater stability and biocompatibility, increased permeability and retention effect, and precision targeting. The implementation of nanoparticles for sulforaphane delivery systems might overcome its primary limitations, which are its poor solubility in water and oral bioavailability. Not surprisingly, new perspectives of sulforaphane administration through nano-composite-based therapies have promising results. For instance, the use of nanoparticles of selenium, tellurium, gold-coated Fecumented ,73,74,75TT assay ,66,67. SAccording to the findings described in breast cancer lines like MDA-MB-231 and MCF7, the combination of sulforaphane + DOX was entrapped in liposomes nanoparticles at 9.375 mg/g of DOX, while for sulforaphane, it was 487.5 mg/g. Cell viability was statistically lower after the application of the DOX/sulforaphane nanoparticle combination. In addition, cell viability is reduced by 50% when sulforaphane and DOX are combined and seem to be effective in terms of their ability to inhibit tumour cell growth . AdditioA decrease in tumour growth from day 24 to day 36 was observed in the treated group, and in conjunction with these results, the nanoparticle showed anticancer activity in stem cells, with approximately 140 mammospheres per 2000 cells formed per 2000 cells compared to 210 mammospheres formed per 2000 cells in the untreated groups . The resSulforaphane is a relatively accessible and easy-to-acquire molecule, compared to other organic components that can be used to treat cancer. Since its discovery, it has been identified as a potent phytopharmaceutical capable of altering the resistance of carcinogenic cells. Although more studies are still needed to fully understand the molecular processes that this molecule triggers, the experimental evidence generated and compiled in this review demonstrates that in addition to being a compound that is consumed indirectly in the diet, it is a component with a high specificity for cancer cells. The experimental evidence generated and compiled in this review demonstrates that in addition to being a compound that is consumed indirectly in the diet, it is a component that presents a high specificity for cancer cells, thus proving to be a potential candidate for the treatment of different cancer types. Additionally, its efficiency when complexed with various types of nanoparticles improves the prospects for its use in the development of targeted and specialized therapies for each patient. Apart from this evidence, it has also been observed that the use of sulforaphane in conjunction with strategies currently implemented in the treatment of cancer enhances their therapeutic effects, also improving the tolerability of the side effects in these therapies. In this regard the clinical studies that exist regarding the use of sulforaphane in the treatment of breast cancer, have not yet obtained a nanoparticulate as a candidate for phase 3 studies and subsequent therapy. However, overall, the experimental studies demonstrate a high safety and bioavailability of the nanocomplexes studied by different authors, each with different perspectives and different chemical and physical characteristics that allow new perspectives for the use of these nanoparticles to be generated. These can be focused not only on the controlled release of sulforaphane but also in approaches that involve treatment in conjunction with physical methods. The research of new molecular targets and signalling pathways of sulforaphane will allow the development of its clinical applications for the prevention and treatment of breast cancer. In the evidence described in this review, we have emphasized the antioncogenetic sulforaphane role and its possible use in cancer treatment as adjuvant or complexed with different nanomaterials.