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Study designRetrospective cohort study of prospectively accrued data.ObjectiveTo evaluate a large, prospective, multicentre dataset of surgically treated degenerative cervical myelopathy (DCM) cases on the contemporary risk of C5 palsy with surgical approach.Summary of background dataThe influence of surgical technique on postoperative C5 palsy after decompression for DCM is intensely debated. Comprehensive, covariate-adjusted analyses are needed using contemporary data.MethodsPatients with moderate to severe DCM were prospectively enrolled in the multicenter, randomized, Phase III CSM-Protect clinical trial and underwent either anterior or posterior decompression between Jan 31, 2012 and May 16, 2017. The primary outcome was the incidence of postoperative C5 palsy, defined as the onset of muscle weakness by at least one grade in manual muscle test at the C5 myotome with slight or absent sensory disruption after cervical surgery. Two comparative cohorts were made based on the anterior or posterior surgical approach. Multivariate hierarchical mixed-effects logistic regression was used to estimate odds ratios (OR) with 95% confidence intervals (CI) for C5 palsy.ResultsA total of 283 patients were included, and 53.4% underwent posterior decompression. The total incidence of postoperative C5 palsy was 7.4% and was significantly higher in patients who underwent posterior decompression compared with anterior decompression (11.26% vs. 3.03%, P =0.008). After multivariable regression, the posterior approach was independently associated with greater than four times the likelihood of postoperative C5 palsy ( P =0.017). Rates of C5 palsy recovery were comparable between the two surgical approaches.ConclusionThe odds of postoperative C5 palsy are significantly higher after posterior decompression compared to anterior decompression for DCM. This may influence surgical decision-making when there is equipoise in deciding between anterior and posterior treatment options for DCM.Level of evidenceTherapeutic Level-II.

Background: The association between the frailty index (FI) and the risk of chronic lung diseases (CLDs) remains unexplored, warranting further research. Methods and materials: This study investigated the relationship between FI and CLD risk using data from the China Health and Retirement Longitudinal Study (CHARLS) and English Longitudinal Study of Ageing (ELSA), comprising a combined sample of 9642 individuals. Propensity score weighting was used to ensure similar distribution of covariates across FI groups. The Wilcoxon rank-sum test was used to analyze differences in FI scores between groups with and without CLD. Kaplan–Meier curves and Cox regression analysis were employed to explore the association between frailty status and CLD incidence, with sensitivity analyses conducted for validation. Results: Higher FI scores were significantly associated with increased CLD risk in both cohorts (p <.05). Kaplan–Meier survival and Cox regression analyses indicated that frail individuals have a significantly elevated risk of CLD compared to robust individuals, particularly in certain subgroups (e.g., female) within the CHARLS cohort (p <.05). The ELSA cohort yielded similar results (p <.05), affirming FI as a strong predictor of CLD. Additional risk factors identified included age, smoking, and unmarried status (p <.05). Frail individuals consistently exhibited the highest risk in both cohorts (CHARLS HR = 1.54, p =.003; ELSA HR = 6.64, p <.001). The sensitivity analysis did not substantially alter the significant associations. Conclusion: These findings emphasize the critical role of frailty in the development of CLD, suggesting that targeted interventions could reduce CLD risk. [ABSTRACT FROM AUTHOR]

Background: Although second-generation antipsychotics (SGAs) have proven to be effective therapeutic options for patients with schizophrenia, there is a notable lack of evidence on patients' subjective perspectives regarding their well-being, quality of life, and satisfaction with these medications. This study aimed to evaluate the treatment satisfaction and effectiveness of lurasidone on quality of life and functioning in adult patients with schizophrenia in real-world Italian clinical practice. Methods: This was a multicentre, national, non-interventional, single-arm, 3-month prospective study. Patients who were naive to lurasidone treatment and whose treating physician had decided to start them on this medication were enrolled and evaluated over a 3-month period. Eligible patients were adults (≥ 18 years of age) with a primary diagnosis of schizophrenia who were being treated with lurasidone (for the first time [i.e., they were lurasidone naive]) as part of routine clinical practice. Efficacy endpoints were changes in patient/caregiver treatment satisfaction (seven-point Likert scale from the Treatment Satisfaction Questionnaire for Medication), patient quality of life and functioning (QLS), investigator-rated global assessment of functioning (CGI-S, IAQ) after 6 weeks and 3 months of lurasidone, and number of relapses and hospitalizations. Results: Sixty-one patients were enrolled and 59 completed the study. The median dosage of lurasidone at baseline was 37.00 mg/day. The median duration of titration was 86.0 days (Min 28; Max 115 days); the median number of dosage changes was 1.0. At the end of 3-month observation period, the median dose of lurasidone was 74.00 mg/day. QoL and Functioning Score showed a trend of improvement over time, reaching a mean change from baseline of 9.8 at the end of the study. According to the CGI-S, the percentage of patients who were "markedly or severely ill" showed a continuous decrease from baseline to 3 months, from 62.29% to 8.20%. Patient satisfaction increased over time, with 80.32% of patients reporting that they were somewhat, fairly, or very satisfied (including 63.93% who were completely or very satisfied) at the end of the study. No relapses/hospitalizations for psychiatric reasons were reported. Lurasidone was well tolerated with no safety concerns or discontinuations due to AEs. Conclusions: Lurasidone represents a valid option for the treatment of schizophrenia and positively affects subjective well-being, quality of life and satisfaction. Trial registration: NCT06527885 retrospectively registered (01/08/2024). [ABSTRACT FROM AUTHOR]

Simple Summary: Bladder cancer is the ninth most commonly diagnosed form of cancer in both sexes worldwide and the fifth in Europe. The most common form, non-muscle-invasive bladder cancer, is highly prevalent with high recurrence rates and has wide range of outcomes that is partially due to the variability in the treatment delivered. Therefore, some recommendations have been done by the European Association of Urology to standardize their management. Several quality control indicators have been proposed to monitor the adherence of urologists and hospitals to these recommendations. A quality control indicator program has been initiated in the hospitals that are a part of the Flemish Hospital Network in June 2013 using a specific prospective registry. We have recently published the first analysis of these quality control indicators, which showed significant differences between the hospitals. Before publishing the second analysis with more patients and additional quality control indicators, we aimed to describe the characteristics of the cohort in this study. Purpose: Bladder cancer (BC) is a heterogeneous disease with varying outcomes, influenced by disease heterogeneity and variability in treatment and follow-up. Risk groups have been established for non–muscle-invasive BC (NMIBC) to standardize therapy, and several quality control indicators (QCIs) monitor adherence to these risk group-based guidelines. However, controversial results had been obtained regarding the oncological benefits of these QCIs until recent high-quality studies from large registries showed their usefulness. To improve adherence to the European Association of Urology (EAU) Guidelines and benchmark current care in Flemish hospitals within Vlaams Ziekenhuisnetwerk–KU Leuven (VZNKUL), a QCI program for NMIBC was initiated in 2013. This study aims to describe the demographic, clinical, and treatment data of patients enrolled in this program. Participants: The VZNKUL–NMIBC Quality Indicators Program Registry is a prospective cohort including patients treated and followed up with at seven academic and non-academic Flemish hospitals since June 2013. Data collection includes patient characteristics, tumor data, treatment, and oncological outcomes. Findings to date: From June 2013 to December 2020, 4744 transurethral resections of bladder tumors (TURBTs) from 2237 unique patients were analyzed. Most patients (80%) were men with a median age of 73. The median time from diagnosis to TURBT was 19 days. A single tumor was detected in 37% of TURBTs. Tumors larger than 3 cm were found in 20.8% of cases. In 46% of TURBTs, a reTURBT was scheduled according to guidelines. The complication rates were 7.5% and 2.4% for bladder perforation and bleeding, respectively. Postoperative single intravesical instillation of chemotherapy (SIVIC) was administered to 56.9% of 1533 indicated patients with a median time to administration of 4.7 h. Among the cohort, 60.4% had NMIBC, and 9.3% had muscle-invasive BC. Of 972 high-risk patients, 60.7% received adequate BCG induction, while 39.4% received adequate maintenance. After BCG induction ± maintenance, 39.7% were tumor-free, with 17.7% recurrence and 4% progression to muscle-invasive BC. BCG treatment was terminated early for 17% of patients due to intolerance. Early cystectomy was performed for 2.4% of the BCG-naïve patients, and 27.7% of patients with BCG failure underwent a BCG rechallenge. For intermediate-risk patients, 2.1% received adequate BCG, and 23% received intravesical chemotherapy. The median follow-up was 57 months. Five-year recurrence-free, progression-free, cancer-free, overall, and cancer-specific survival rates were 53%, 91.6%, 89%, 70.6%, and 95.6%, respectively, for the NMIBC patients. Of 400 non-metastatic MIBC patients, 217 (54.3%) underwent radical cystectomy (RC), of whom 46% received neoadjuvant chemotherapy, while 18 (4.5%) refused RC, and 74 (18.5%) were considered unfit for the surgery. Future plans: The VZNKUL–NMIBC Quality Indicators Program Registry will continue collecting data to evaluate QCIs and monitor treatment quality, enabling hospitals to benchmark their performance and improve patient care. Additionally, the registry's real-world data can support research and international collaboration. Trial registration: The study was registered on ClinicalTrials.gov (NCT04167332). [ABSTRACT FROM AUTHOR]

Several seismic gaps have been identified along the Xianshuihe-Xiaojiang fault zone and the Longmenshan fault zone in the Sichuan-Yunnan region, including the Daofu-Shimian gap on the Xianshuihe Fault, the Anninghe-Zemuhe gap, parts of the Xiaojiang Fault, and the Dayi gap between the Wenchuan and Lushan earthquakes. The seismic hazards of the Daofu-Shimian and Dayi gaps have aroused great concern and caused considerable debate. This paper reviews the recent geophysical observations and multidisciplinary studies conducted by domestic and international researchers in these areas, focusing on seismogenic structures, seismic activity, fault locking, stress fields, as well as earthquake triggering, and further analyzes the current controversial viewpoints about the seismic hazards in these regions. Based on the comprehensive analysis, we argue that the kinematic status along the Daofu-Shimian segment may vary significantly along the fault strike. Due to limitations in data and models, there is no consensus on the seismogenic potential of this area. Conversely, the Dayi seismic gap presents a high seismic potential. Furthermore, we delve into the scientific problems associated with major seismic gaps in the Sichuan-Yunnan region and make prospects for the strategy of future work. We propose a research framework that combines dense array and distributed acoustic sensing, artificial intelligence and big data technologies, joint inversion of multiple geophysical fields, as well as numerical simulation techniques for comprehensive seismic hazard analysis in seismic gaps. [ABSTRACT FROM AUTHOR]

Objective: Quantitative studies examining the occurrence of childbirth‐related posttraumatic stress disorder (CB‐PTSD) following severe perineal rupture are lacking. The objective of this population‐based study was to investigate the prospective associations between the degree of perineal tear during childbirth and CB‐PTSD symptoms, when adjusting for known covariates (maternal age, years of school education, premature birth, and parity). We hypothesized that women with different degrees of perineal tear will differ regarding (1) the level of CB‐PTSD symptoms at 8 weeks and 2 years postpartum and (2) the rate of change in CB‐PTSD symptoms from 8 weeks to 2 years postpartum. Method: Secondary data analysis from the Akershus Birth Cohort, a large population‐based prospective cohort study using self‐report questionnaires and hospital record data. Results: The degree of perineal tear was significantly associated with CB‐PTSD symptoms at 8 weeks and 2 years postpartum. However, the degree of perineal tear was not significantly associated with the change in CB‐PTSD symptoms over time. Similar patterns were found for both total CB‐PTSD symptoms as well as for avoidance and intrusion symptoms only. Conclusion: Results seem to support a dose–response model, suggesting that the higher the severity of the perineal tear, the higher the posttraumatic morbidity. [ABSTRACT FROM AUTHOR]

Nonsuicidal self-injury (NSSI) is rare in childhood but becomes prevalent in adolescence, which suggests that early intervention might be indicated. As childhood predictors of NSSI in adolescence are largely unknown, identifying these predictors was the aim of this study. In a birth cohort sample (n = 759) of Norwegian children, NSSI at 12, 14, or 16 years of age was regressed on predictors of NSSI at age 6 (parental factors: depression, parenting stress, negativity/hostility, emotional availability to the child; child factors: temperamental negative affectivity, emotion regulation, symptoms of emotional and behavioral disorders; external events: victimization from bullying, serious negative life events). Semistructured clinical interviews with adolescents and their parents were used to assess DSM-5 –defined NSSI and NSSI disorder. NSSI during the preceding 12 months at 12, 14, or 16 years of age was reported by 81 adolescents (10.0%, 95% CI 8.2-11.9), and NSSI disorder was reported by 20 adolescents (2.7%, 95% CI 1.9-3.8). In multivariable logistic regression analysis, female gender (odds ratio 11.6, 95% CI 4.0-33.5), parenting stress (odds ratio 4.8, 95% CI 1.4-16.5), and parental negativity/hostility (odds ratio 1.8, 95% CI 1.2-2.7) predicted NSSI, whereas child factors and external events were not predictive. Parental factors when the child is 6 years of age—parenting stress and negativity/hostility toward the child—predict NSSI in adolescence. Universal and indicated programs targeting these aspects of parenting during childhood might reduce NSSI in adolescence. Almost 1 in 4 adolescents engage in deliberate self-harm without wanting to die from it. However, childhood predictors of nonsuicidal self-injury are largely unknown. This study from Norway followed 759 children from birth until adolescence. The authors found that children who perceived their parents as more negative and hostile at 6 years old were at increased risk of engaging in self-injury when they became adolescents. Children whose parents reported more stress in the parenting role were also at increased risk of engaging in self-harm during adolescence. The authors conclude alleviating parental stress and improving parent-child relations at an early age might decrease the risk of adolescent self-harm. We worked to ensure race, ethnic, and/or other types of diversity in the recruitment of human participants. We worked to ensure sex and gender balance in the recruitment of human participants. We worked to ensure that the study questionnaires were prepared in an inclusive way. We actively worked to promote sex and gender balance in our author group. The author list of this paper includes contributors from the location and/or community where the research was conducted who participated in the data collection, design, analysis, and/or interpretation of the work. [ABSTRACT FROM AUTHOR]

Palmoplantar pustulosis (PPP) is often considered as pustular psoriasis of extremities. Benvitimod has been approved for mild to moderate psoriasis. We thus designed this study to evaluate the efficacy and safety of benvitimod for treating PPP. Of 47 PPP patients recruited from 4 hospitals, 40 finished 8 weeks visit and completed 4 weeks safety follow‐up visit. The Palmoplantar Pustular Psoriasis Area and Severity Index (PPPASI) and Dermatology Life Quality Index (DLQI) scores fell continuously. At week 8, mean ± SD PPPASI and DLQI were 3.39 ± 3.86 (p < 0.0001) and 2.49 ± 3.34 (p < 0.0001), respectively. At week 8, 70% (28/40) achieved PPPASI‐50 response, 35% (14/40) achieved PPPASI‐75 response, and 17.5% (7/40) achieved PPPASI‐90 response. Relapse occurred in 7.5% (3/40) of the patients. Of 47 patients enrolled, self‐reported compliance was 12.77% (6/47). Common drug‐related adverse events (5/47) included xerosis cutis. Only one patient's disease progressed during treatment. Our study demonstrated the efficacy and safety of benvitimod. [ABSTRACT FROM AUTHOR]

We tested the longitudinal associations between life space mobility (LSM) at baseline and cognitive performance in three domains (memory, reasoning, and speed of processing) over time. Our analytic sample includes 2,690 older adults (mean age = 73.0, 75.9% female) participating in the ACTIVE Study. We used multiple linear mixed-effects models to evaluate whether LSM, measured using the Life Space Questionnaire, at baseline was longitudinally associated with scores on eight cognitive tests and three composite scores across 10 years. In unadjusted models, there were significant main effects of baseline LSM on memory and reasoning domains, and one speed of processing test (beta: 0.019 to 0.055, p < 0.05). All effects were non-significant in adjusted models. Over time, baseline LSM was associated with one memory test score in adjusted models. Greater LSM at baseline is associated with marginally higher cognitive performance but does not appear to affect the rate of cognitive change at a clinically significant level. [ABSTRACT FROM AUTHOR]

Exposure to metals, a newly recognized risk factor for cardiovascular disease (CVD), could be related to atherosclerosis progression. The authors hypothesized that higher urinary levels of nonessential (cadmium, tungsten, uranium) and essential (cobalt, copper, zinc) metals previously associated with CVD would be associated with baseline and rate of change of coronary artery calcium (CAC) progression, a subclinical marker of CVD in MESA (Multi-Ethnic Study of Atherosclerosis). We analyzed data from 6,418 MESA participants with spot urinary metal levels at baseline (2000-2002) and 1 to 4 repeated, continuous measures of CAC over a 10-year period. We used linear mixed-effect models to assess the association of baseline urinary metal levels with baseline CAC and cumulative change in CAC over a 10-year period. Urinary metals (μg/g creatinine) and CAC were log transformed. Models were adjusted for baseline sociodemographic factors, estimated glomerular filtration rate, lifestyle factors, and clinical factors. At baseline, the median CAC was 6.3 (Q1-Q3: 0.7-58.2). Comparing the highest to lowest quartile of urinary cadmium, CAC levels were 51% (95% CI: 32%, 74%) higher at baseline and 75% (95% CI: 47%, 107%) higher over the 10-year period. For urinary tungsten, uranium, and cobalt, the corresponding CAC levels over the 10-year period were 45% (95% CI: 23%, 71%), 39% (95% CI: 17%, 64%), and 47% (95% CI: 25%, 74%) higher, respectively, with no difference for models with and without adjustment for clinical factors. For copper and zinc, the corresponding estimates dropped from 55% to 33% and from 85% to 57%, respectively, after adjustment for clinical factors. The associations of metals with CAC were comparable in magnitude to those for classical CVD risk factors. Exposure to metals was generally associated with extent of coronary calcification at baseline and follow-up. These findings support that metals are associated with the progression of atherosclerosis, potentially providing a novel strategy for the prevention and treatment of atherosclerosis progression. [ABSTRACT FROM AUTHOR]

Several epidemiologic studies have investigated the circulating levels of albumin, bilirubin, and uric acid (UA) in relation to cancer risk; however, they have provided equivocal evidence. In this prospective case-cohort study, we measured the plasma levels of albumin, bilirubin, and UA and investigated their association with cancer incidence in 3584 case patients and 4270 randomly selected participants with a median follow-up of 15.8 years. The adjusted hazard ratios (HRs) and 95% CIs of total cancer for the highest quartile (Q4) versus lowest quartile (Q1) was 0.77 (95% CI, 0.67-0.90; P <.001 for trend) for albumin. This association was attenuated after excluding liver cancer cases with lower plasma albumin levels. Plasma bilirubin levels were positively related to liver cancer but inversely to total cancer after excluding liver cancer with, for Q4 versus Q1, an adjusted HR of 0.86 (95% CI, 0.74-0.99; P  = .015 for trend). Plasma UA levels were not dose-responsively associated with total cancer risk. Higher plasma bilirubin levels were associated with a decreased risk of total cancer after excluding liver cancer, which is likely attributed to the antioxidant properties of bilirubin. [ABSTRACT FROM AUTHOR]

Whether or not women who harbor a germline pathogenic variant ('mutation') in the BRCA1 or BRCA2 genes are at elevated risk of developing endometrial cancer is yet to be determined. We conducted a prospective analysis of 4959 BRCA mutation carriers with no prior history of cancer (except for breast or melanoma) and an intact uterus. After a mean of 6.7 years of follow-up there were 38 incident cases of endometrial cancer diagnosed; 30 among BRCA1 carriers and eight among BRCA2 carriers. The mean age at diagnosis was 58.4 years (range 46.8–76.1). The majority were of the endometrioid subtype (n = 16), followed by mixed endometroid and serous (n = 4), serous (n = 3) or clear cell (n = 1) (missing = 13). The cumulative incidence from age 40 to age 70 was 3.4% for BRCA1 carriers and was 1.6% for BRCA2 mutation carriers. Prior tamoxifen use was associated with a significant two–fold increased risk (HR = 2.24; 95% CI 1.10–4.55). There was no significant association between exogenous hormone use, oophorectomy, smoking or BMI at age 40 and risk (P ≥ 0.32). Compared to the general population, we observed higher rates of endometrial cancer among young BRCA1 mutation carriers; however, lifetime risks were similar. Women with prior tamoxifen exposure were at a significantly increased risk. These findings were based. on a small number of incident cases and require confirmation with additional follow-up of our aging cohort. • We prospectively evaluated whether endometrial cancer is part of the BRCA - spectrum. • Cumulative incidence was 3.4% for BRCA1 and 1.6% for BRCA2 mutation carriers. • Tamoxifen use was a significant risk factor BRCA -endometrial cancer. • With few incident cases, we are not able to conclusively confirm an increased risk. • Hysterectomy at the time of preventive ophorectomy should be individualized. [ABSTRACT FROM AUTHOR]

The demand for palm sugar has been consistently increasing each year, particularly due to the growing public awareness of health benefits. Palm sugar is considered a safer sweetener option due to its low glycemic index and absence of side effects. The primary objective of this research is to analyze consumer perceptions regarding the attributes of palm sugar. This analysis is crucial in assessing consumer satisfaction and loyalty toward palm sugar consumption. Consequently, the findings will contribute to enhancing the marketing mix strategies for palm sugar. The survey method was employed to conduct this research, with a sample size of 30 consumer respondents selected through random sampling. Additionally, an opinion poll was conducted with key individuals to gather insights on the development of palm sugar products. The collected data were then analyzed using a prospective analysis approach. The research results indicate that specific attributes significantly influence consumer perceptions when purchasing palm sugar. Consumer perceptions in purchasing palm sugar are based on details of the marketing mix attributes which are the determining attributes, namely: taste, quality, palm sugar color, texture, popularity of craftsmen, and price. The marketing development implications of this research are improvements to three attribute components, namely raw material composition information, product standards, hygiene, partnerships, and technology. This serves as a consideration for craftsmen to improve consumer perceptions of palm sugar. [ABSTRACT FROM AUTHOR]

This research investigates the prospective variables that can influence the success of agribusiness in the coastal regions of East Java, particularly in terms of how this success contributes to food security. The study explores interrelated dimensions, including environmental, social, economic, institutional, regulatory, and technological aspects. Utilizing MICMAC analysis, the research identifies and analyzes the relationships between variables within a complex system, involving 150 experts in coastal agribusiness. The results highlight several key success variables, including the availability and enforcement of laws related to sustainable fishing practices, technological innovation in marine and coastal resource management, coastal zoning regulations and conservation area management, the adoption rate of sustainable agricultural and fisheries technologies, coastal land utilization, and community awareness of environmental sustainability. This research makes novel contributions to the existing literature by integrating multiple dimensions—environmental, social, economic, institutional, regulatory, and technological—into a comprehensive framework for understanding agribusiness success in coastal areas. The application of MICMAC analysis provides a methodological advancement by emphasizing the dynamic dependencies within the agribusiness ecosystem. Furthermore, the study offers region-specific insights, particularly for East Java’s coastal regions, addressing a research gap in the sustainability of coastal agribusinesses. These findings emphasize the necessity of a holistic approach that accounts for various aspects to enhance the resilience and sustainability of agribusinesses, guiding policymakers and practitioners in strengthening agribusiness sustainability in coastal regions. [ABSTRACT FROM AUTHOR]

Background: The exploration of optimizing cardiopulmonary function and athletic performance through high-intensity metabolic exercises (HIMEs) is paramount in sports science. Despite the acknowledged efficacy of HIMEs in enhancing cardiopulmonary endurance, the high metabolic stress imposed on the cardiopulmonary system, especially for amateurs, necessitates a scaled approach to training. Objective: The aim of this study is to ascertain whether adjustments in the initiation posture and the adoption of an appropriate breathing strategy can effectively mitigate the cardiopulmonary stress induced by HIMEs without compromising training efficacy. Methods: Twenty-two subjects were recruited into this study. The post-exercise heart rate (PHR) and post-exercise oxygen consumption rate (POCR) were collected within 30 min after exercise. A two-way ANOVA, multi-variable Cox regression, and random survival forest machine learning algorithm were used to conduct the statistical analysis. Results: Under free breathing, only the maximum POCR differed significantly between standing and prone positions, with prone positions showing higher stress (mean difference = 3.15, p < 0.001). In contrast, the regulated breathing rhythm enhanced performance outcomes compared to free breathing regardless of the starting position. Specifically, exercises initiated from prone positions under regulated breathing recorded a significantly higher maximum and average PHR than those from standing positions (maximum PHR: mean difference = 13.40, p < 0.001; average PHR: mean difference = 6.45, p < 0.001). The multi-variable Cox regression highlighted the starting position as a critical factor influencing the PHR and breathing rhythm as a significant factor for the POCR, with respective variable importances confirmed by the random survival forest analysis. These results underscore the importance of controlled breathing and starting positions in optimizing HIME outcomes. Conclusions: Regulated breathing in high-intensity exercises enhances performance and physiological functions, emphasizing the importance of breathing rhythm over starting position. Effective training should balance exercise volume and technique to optimize performance and minimize stress, reducing overtraining and injury risks. [ABSTRACT FROM AUTHOR]

The primary purpose of this study was to investigate whether anxiety and depression change following total knee arthroplasty (TKA). A secondary objective was to explore the association between preoperative variables and changes in anxiety and depression. This was a prospective, multicenter, cohort study. Participants (n = 1,852, age 64 ± 8.7 years, a body mass index of 31.3, a modified Comorbidity Index of 1.0 ± 1.3, and 61.7% were women) completed the EuroQol 5-dimension 5-level preoperatively and at 1- and 3-month postoperatively. Fulfillment of physical activity expectations and preparedness to resume activities was assessed at 3 months. The anxiety or depression dimension was analyzed using the Paretian classification profile changes and compared with the sign Fisher's exact test. Logistic regressions were used to analyze the relationship between patient characteristics, preoperative anxiety or depression, activity expectations, preparedness to resume activities, and changes in anxiety/depression. The percentage of patients reporting Level 1 (no anxious or depressed feelings) significantly (P <.0001) increased from preoperative (62.2%) to 3 months (77.1%) postoperative, while levels 2 to 5 (slightly through extremely anxious or depressed) all decreased. The percentage of worsening anxiety and depression was significantly (P <.0001) greater in patients who did not feel they were well prepared to resume activities of daily living (17.7 versus 4.4%) and physical recreation (12.9 versus 3.9%). Preoperative anxiety and depression (odds ratio [OR] 52.27, 95% confidence interval [CI]: 34.98, 80.67), EuroQol 5-dimension 5-level (OR: 2.55, 95% CI: 1.04, 6.34), activity of daily living (OR: 1.57, 95% CI: 1.19, 2.06), and body mass index (OR: 1.05, 95% CI: 1.02, 1.08) were significant (P <.05) predictors of an improving Paretian change profile at 3 months postoperative. Anxiety and depression decrease following TKA, and these changes appear heavily dependent on a patient's preoperative psychological well-being and postoperative preparedness to resume daily activities. Physicians' awareness of preoperative patient psychological well-being and management of patient preparedness and expectations to resume physical activity may modulate postoperative anxiety and depression. [ABSTRACT FROM AUTHOR]

Background Dizziness is common in older adults, especially in those attending falls services. Yet, the extent to which dizziness is associated with future falls has not been reviewed. This systematic review and meta-analysis assessed the association between dizziness and future falls and related injuries in older adults. Methods EMBASE, CINAHL Plus, SCOPUS and PsycINFO databases were searched from inception to 5 February 2024. The review was registered on PROSPERO (registration ID: CRD42022371839). Meta-analyses were conducted for the associations of dizziness with future falls (including recurrent and injurious falls). Three meta-analyses were performed on different outcomes: any-type falls (≥1 falls), recurrent falls (≥2 falls) and injurious falls. Results Twenty-nine articles were included in the systematic review (N  = 103 306 participants). In a meta-analysis of 14 articles (N  = 46 795 participants), dizziness was associated with significantly higher odds of any-type future falls (OR = 1.63, 95% CI = 1.44–1.84). In another meta-analysis involving seven articles (N  = 5630 participants), individuals with dizziness also had significantly higher odds of future recurrent falls (OR = 1.98, 95% CI = 1.62–2.42). For both meta-analyses, significant overall associations were observed even when adjusted for important confounding variables. In contrast, a meta-analysis (three articles, N  = 46 631 participants) revealed a lack of significant association between dizziness and future injurious falls (OR = 1.12, 95% CI = 0.87–1.45). Conclusions Dizziness is an independent predictor of future falls in older adults. These findings emphasise the importance of recognising dizziness as a risk factor for falls and implementing appropriate interventions. [ABSTRACT FROM AUTHOR]

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Geriatric nurses are both ageing and at high risk for developing burnout symptoms. Burnout symptomatology relates to lower job performance and lower care quality. Developing impairments in cognitive functioning might explain such relationships. We examined prospective relationships of burnout symptoms and cognitive functioning (memory and executive functions objectively assessed). We included age as well as several control variables as predictors and searched for interaction effects to explain prior inconsistencies. German nurses (N = 191) from geriatric care filled out self-administered questionnaires at the workplace (t1) and performed a comprehensive cognitive test battery in the lab six months later at t2. Results showed expected age effects on executive functions but no relationships between burnout symptoms and cognitive functioning nor any interaction effects with age. Exhausted subjects had a slightly better performance in updating. The nearly robust null findings in this study indicate that the relationship of burnout symptoms and decreased cognitive functioning may be a predominantly clinical issue. [ABSTRACT FROM AUTHOR]

Abstract Identifying high-risk patients for developing postoperative delirium (POD) is essential for optimizing the medical field’s human and financial resources through specialty-relevant geriatric assessments that can aid in establishing prehabilitation strategies. This study aims to identify geriatric screening tools to predict preoperative delirium and explore the high-risk elderly patients undergoing oral maxillofacial surgery. A comprehensive geriatric assessment encompassing 23 instruments was used to evaluate inpatients undergoing surgery under general anaesthesia, preoperatively and postoperatively. Selective intraoperative and postoperative variables were also assessed for their relation to POD occurrence. This prospective study included 90 patients (mean age 79.0 years) from August 2022 to August 2023. The POD rate in this cohort was (8.9% n = 8). The Clock-Drawing Test (CDT) was significantly associated with POD occurrence (p = 0.005). Significant associations were found between POD occurrence and operation type (p = 0.018), duration (p = 0.026), length of stay ( p = 0.002), and postoperative hemoglobin levels (p = 0.027). This study highlights the importance of comprehensive geriatric assessments in predicting POD in elderly patients. Future research should build on these findings to enhance preoperative care strategies and improve outcomes. Trial registration: German Register of Clinical Studies, DRKSID DRKS00028614.

Chronic lateral ankle instability is a relatively frequent consequence after acute ankle sprain. In case of unsuccessful conservative treatment, surgical therapy is recommended to prevent osteoarthritis of the ankle joint. To date, different surgical methods have evolved. Yet, it remains unclear which approach reveals the best results. We hypothesized that the modified Broström–Gould procedure with suture anchor ligament fixation leads to superior postoperative results compared to the Broström–Gould procedure or the periosteal flap technique.

The recent advances in technological capabilities have led to a massive production of time‐series data and remarkable progress in longitudinal designs and analyses within psychological research. However, implementing time‐series analysis can be challenging due to the various characteristics and complexities involved, as well as the need for statistical expertise. This paper introduces a statistical pipeline on time‐series analysis for studying the changes in a single process over time at either a population or individual level, both retrospectively and prospectively. This is achieved through systemization and extension of existing modelling and inference techniques. This analytical approach enables practitioners not only to track but also to model and evaluate emerging trends and apparent seasonality. It also allows for the detection of unexpected events, quantifying their deviations from baseline and forecasting future values. Given that other discernible population‐ and individual‐level changes in psychological and behavioural processes have not yet emerged, continued surveillance is warranted. A near real‐time monitoring tool of time‐series data could guide community psychological responses across multiple ecological levels, making it a valuable resource for field practitioners and psychologists. An empirical study is conducted to illustrate the implementation of the introduced analytical pipeline in practice and to demonstrate its capabilities. [ABSTRACT FROM AUTHOR]

BACKGROUND Vitamin D may prevent the development of hypertension through down-regulation of renin–angiotensin system. However, epidemiologic studies assessing the interrelation of vitamin D-related biomarkers with hypertension are sparse. METHODS We examined the prospective associations between vitamin D-related biomarkers and the risk of hypertension in a nested case-control study. In each of the Women's Health Study (WHS) and Physicians' Health Study (PHS) II, 500 incident hypertension cases and 500 age and race-matched controls were randomly selected. Baseline plasma 25(OH)-vitamin D [25(OH)D], parathyroid hormone (PTH), and total renin concentrations were measured. RESULTS Among controls, 25(OH)D and PTH were inversely correlated, but neither was correlated with total renin. In the crude model, there was a trend of association between increasing quintiles of 25(OH)D and lower risk of hypertension in women, with relative risks and 95% CIs of 1.00, 1.24 (0.84–1.83), 0.82 (0.53–1.25), 0.75 (0.48–1.16), and 0.81 (0.52–1.27) (P , trend:.07). Adjustment for body mass index and other hypertension risk factors eliminated this association (relative risk of 5th quintile: 1.03). No associations were found in men. Baseline PTH and ratio of 25(OH)D to PTH were not associated with the risk of hypertension in women or men. When men and women were included in the same model, vitamin D insufficiency (defined as 25(OH)D <20 ng/mL) also was not associated with an increased risk of hypertension. No interactions were found across subgroups. CONCLUSIONS Our study found no association of baseline plasma 25(OH)D or PTH with the risk of hypertension or total renin concentration in middle-aged and older men and women. [ABSTRACT FROM AUTHOR]

Abstract Background Data have shown that vitamin B12 has immunomodulatory effects via different pathways, which could influence the pathophysiology of sepsis. The objective of this study was to investigate whether vitamin B12 levels, assessed by the measurement of holotranscobalamin (HTC), total vitamin B12 (B12), and methylmalonic acid (MMA, which accumulates in case of B12 deficiency), are associated with the development of sepsis in patients with onset of bacterial infection. Methods This was a single-center, prospective observational pilot study. Adult patients who presented to the emergency department with bacterial infection confirmed by a positive microbiological culture result were included in the study and followed up for 6 days to assess whether they developed sepsis or not. The primary objective was to compare HTC concentration in patients who developed sepsis to those who did not develop sepsis. Secondary objectives were the evaluation of B12 and MMA concentrations in those two groups. Multiple logistic regression models were used, with presence of sepsis as the outcome variable, and HTC, B12, and MMA concentrations as predictor variables, separately, and adjusted for potential confounders. Results From 2019 to 2022, 2131 patients were assessed for eligibility, of whom 100 met the inclusion criteria. One patient was excluded from the analysis due to missing data. Of the 99 patients, 29 developed sepsis. There was no evidence for an association between HTC or B12 concentration and the development of sepsis (OR 0.65, 95% CI 0.31–1.29, p = 0.232, OR 0.84, 95% CI 0.44–1.54, p = 0.584, respectively). There was an association between MMA concentration and the development of sepsis, with a positive effect, i.e. with increasing MMA, the odds for sepsis increased (OR 2.36, 95% CI 1.21–4.87, p = 0.014). This association remained significant when adjusted for confounders (OR 2.72, 95% CI 1.23–6.60, p = 0.018). Conclusions Our study found an association between elevated MMA concentration and the development of sepsis. We did not find an association between HTC and B12 concentrations and the development of sepsis. Further, larger studies are warranted, as it could lead to interventional trials investigating whether B12 supplementation provides a clinical benefit to patients with infection or sepsis. Trial registration The study was registered on ClinicalTrials.gov under the identifier NCT04008446 on June 17, 2019.

Abstract Objective In Europe, cenobamate has been approved for use as an adjunctive therapy in adult patients with epilepsy (PWE) with focal‐onset seizures (FOS) who have not responded satisfactorily to treatment with at least two antiseizure medications (ASMs). Pivotal trials and real‐world observational studies have demonstrated a high efficacy of cenobamate, even in very difficult‐to‐treat epilepsies. Our aim was to investigate the efficacy of add‐on cenobamate in adult PWE who were prospectively monitored. We compared these results with those previously obtained for add‐on lacosamide, perampanel, and brivaracetam therapy. Methods Patients were enrolled from the CENKORK study, which is a prospective, non‐interventional, open‐label, monocenter cohort study of adult PWE experiencing FOS. The titration of cenobamate was performed according to the guidelines outlined in the summary of product characteristics. The primary outcome measure was the retention rate at 6 months and 1 year. In addition, we assessed seizure‐free rates, the proportion of patients achieving at least a 50% seizure reduction, adverse events, and the reasons for treatment discontinuation. These outcome measures were compared with historical controls treated with adjunctive lacosamide, perampanel, or brivaracetam at our center. Results Between June 2021 and 2022, 172 PWE with ongoing FOS were included. 22 cases were lost to follow‐up, leaving 150 cases for the 1‐year assessment. The retention rates at 6 months and 1 year were 88.7% and 80%, respectively. Seizure freedom was achieved in 14% of patients at both the 6‐month and 1‐year marks, while the ≥50% responder rates were 50% and 61%, respectively. The 6‐month retention rate was significantly higher in cenobamate than in other ASMs (p

Objective To evaluate the impact of atypical sensory response patterns on the development of initiating joint attention （IJA） abilities in toddlers， further exploring the early developmental mechanisms of autism spectrum disorder （ASD）. Methods Forty infants at 12 months of age were followed up and divided into three groups at 24 months of age： ASD， developmental differences （D/D）， and typical development （TD） groups. The Toddler Sensory Profile Second Edition （TSP-2） was used to assess the degree of atypical sensory response patterns. Interactive videos were coded to evaluate IJA abilities. Linear regression analysis was employed to assess the relationship between sensory responsiveness and IJA abilities. Results The sensory seeking and registration scores at 12 months of age and the sensory seeking score at 24 months of age in ASD toddlers were negatively correlated with IJA frequency （rs = -0.735， P = 0.015； rs = -0.635， P = 0.048； rs = -0.680， P = 0.030）， while the sensory sensitivity and avoiding scores at 12 months were positively correlated with the development of IJA frequency（rp= 0.674， P = 0.047； rp= 0.818， P = 0.007）. Conclusions Higher levels of sensory seeking and registration in ASD toddlers will affect their current IJA abilities. However， higher levels of sensory sensitivity and avoiding predict a better developmental trend in IJA abilities.

Abstract Background Liver disease and dementia are both highly prevalent and share common pathological mechanisms. We aimed to investigate the associations between metabolic dysfunction-associated fatty liver disease (MAFLD), metabolic dysfunction-associated steatotic liver disease (MASLD) and the risk of all-cause and cause-specific dementia. Methods We conducted a prospective study with 403,506 participants from the UK Biobank. Outcomes included all-cause dementia, Alzheimer’s disease, and vascular dementia. Multivariable Cox proportional hazards models were used for analyses. Results 155,068 (38.4%) participants had MAFLD, and 111,938 (27.7%) had MASLD at baseline. During a median follow-up of 13.7 years, 5,732 participants developed dementia (2,355 Alzheimer’s disease and 1,274 vascular dementia). MAFLD was associated with an increased risk of vascular dementia (HR 1.32 [95% CI 1.18–1.48]) but a reduced risk of Alzheimer’s disease (0.92 [0.84–1.0]). Differing risks emerged among MAFLD subtypes, with the diabetes subtype increasing risk of all-cause dementia (1.8 [1.65–1.96]), vascular dementia (2.95 [2.53–3.45]) and Alzheimer’s disease (1.46 [1.26–1.69]), the lean metabolic disorder subtype only increasing vascular dementia risk (2.01 [1.25–3.22]), whereas the overweight/obesity subtype decreasing risk of Alzheimer’s disease (0.83 [0.75–0.91]) and all-cause dementia (0.9 [0.84–0.95]). MASLD was associated with an increased risk of vascular dementia (1.24 [1.1–1.39]) but not Alzheimer’s disease (1.0 [0.91–1.09]). The effect of MAFLD on vascular dementia was consistent regardless of MASLD presence, whereas associations with Alzheimer’s disease were only present in those without MASLD (0.78 [0.67–0.91]). Conclusions MAFLD and MASLD are associated with an increased risk of vascular dementia, with subtype-specific variations observed in dementia risks. Further research is needed to refine MAFLD and SLD subtyping and explore the underlying mechanisms contributing to dementia risk.

Background: Data have shown that vitamin B12 has immunomodulatory effects via different pathways, which could influence the pathophysiology of sepsis. The objective of this study was to investigate whether vitamin B12 levels, assessed by the measurement of holotranscobalamin (HTC), total vitamin B12 (B12), and methylmalonic acid (MMA, which accumulates in case of B12 deficiency), are associated with the development of sepsis in patients with onset of bacterial infection. Methods: This was a single-center, prospective observational pilot study. Adult patients who presented to the emergency department with bacterial infection confirmed by a positive microbiological culture result were included in the study and followed up for 6 days to assess whether they developed sepsis or not. The primary objective was to compare HTC concentration in patients who developed sepsis to those who did not develop sepsis. Secondary objectives were the evaluation of B12 and MMA concentrations in those two groups. Multiple logistic regression models were used, with presence of sepsis as the outcome variable, and HTC, B12, and MMA concentrations as predictor variables, separately, and adjusted for potential confounders. Results: From 2019 to 2022, 2131 patients were assessed for eligibility, of whom 100 met the inclusion criteria. One patient was excluded from the analysis due to missing data. Of the 99 patients, 29 developed sepsis. There was no evidence for an association between HTC or B12 concentration and the development of sepsis (OR 0.65, 95% CI 0.31–1.29, p = 0.232, OR 0.84, 95% CI 0.44–1.54, p = 0.584, respectively). There was an association between MMA concentration and the development of sepsis, with a positive effect, i.e. with increasing MMA, the odds for sepsis increased (OR 2.36, 95% CI 1.21–4.87, p = 0.014). This association remained significant when adjusted for confounders (OR 2.72, 95% CI 1.23–6.60, p = 0.018). Conclusions: Our study found an association between elevated MMA concentration and the development of sepsis. We did not find an association between HTC and B12 concentrations and the development of sepsis. Further, larger studies are warranted, as it could lead to interventional trials investigating whether B12 supplementation provides a clinical benefit to patients with infection or sepsis. Trial registration: The study was registered on ClinicalTrials.gov under the identifier NCT04008446 on June 17, 2019. [ABSTRACT FROM AUTHOR]

BACKGROUND: - Hypertension can be both, a cause and a consequence of habitual order complaint (CKD). thus, blood pressure control is an integral element in treatment of hypertensive CKD cases as it can decelerate down complaint progression and reduce associated cardiovascular complaint threat. OBJECTS: - To dissect application pattern of antihypertensive medicines in hypertensive CKD cases in a tertiary care sanatorium. METHODS: - This was a cross sectional study carried out in Department of Nephrology, VIMSAR, Burla, over a period of 4 months. Applicable data from 120 unique conventions (OPD and IPD) of 120 different hypertensive CKD cases, all above 18 times of age, was collected. These cases were clinically diagnosed with CKD and hypertension as per the NKF- KDOQI and JNC 8 guidelines independently. The medicine application pattern was studied with respect to age, gender, type of antihypertensive used, chance use of multidrug remedy, medicines specified from Essential medicine List (EDL) and conventions with general name, as per WHO Drug application criteria. RESULTS: - Of 120 cases, 68(56.7) were males and 52(43.3) were ladies. maturity of the cases was in the age group 60- 80 times (45).29.3 of these cases were diabetic. Calcium channel blockers were the most constantly specified medicines (53.75) followed by diuretics (17.5). 55 cases were on multidrug antihypertensive remedy.63.46 antihypertensive medicines were specified with general name. CONCLUSION: - Analysis of the conventions indicated that use of antihypertensives in CKD cases, was in agreement with NKF- KDOQI and JNC 8 guidelines. utmost cases were on multidrug antihypertensive remedy and calcium channel blockers followed by diuretics were the most constantly specified antihypertensive group of medicines. [ABSTRACT FROM AUTHOR]

Current prospective reports suggest a pandemic-related increase in adolescent mental health problems. We examine whether age-related change over 11–14 years accounts for this increase. Mothers and adolescents in a UK-based birth cohort (Wirral Child Health and Development Study; WCHADS; N = 737) reported on adolescent depression and behavioural problems pre-pandemic (December 2019–March 2020), mid-pandemic (June 2020–March 2021) and late pandemic (July 2021–March 2022). Analysis used repeated measures models for over-dispersed Poisson counts with an adolescent-specific intercept with age as a time-varying covariate. Maturational curves for girls, but not for boys, showed a significant increase in self-reported depression symptoms over ages 11–14 years. Behavioural problems decreased for both. After adjusting for age-related change, girls' depression increased by only 13% at mid-pandemic and returned to near pre-pandemic level at late pandemic (mid versus late – 12%), whereas boys' depression increased by 31% and remained elevated (mid versus late 1%). Age-adjusted behavioural problems increased for both (girls 40%, boys 41%) and worsened from mid- to late pandemic (girls 33%, boys 18%). Initial reports of a pandemic-related increase in depression in young adolescent girls could be explained by a natural maturational rise. In contrast, maturational decreases in boys' depression and both boys' and girls' behavioural problems may mask an effect of the pandemic. [ABSTRACT FROM AUTHOR]

Infectious encephalitis in children is fairly uncommon, but unfavorable outcomes are seen in many survivors. The aim of this study was to prospectively describe the long-term neurocognitive consequences following infectious encephalitis in childhood. Children admitted to a primary and tertiary hospital in Sweden between 2011 and 2016 were asked to participate. Fifty-nine children were assessed at a median time of 18 months (IQR 18–20) after hospitalization. Follow-up included measures of intellectual functioning, attention, working memory, and executive functions. Caregiver ratings of executive functioning and behavioral – emotional symptoms were assessed with standardized questionnaires. Neurocognitive outcome and measures of executive functions and behavioral–emotional symptoms varied greatly among participants. Basic auditory attention, working memory, and mental processing speed were affected and significantly lower compared to a standardized mean. Other domains identified as areas of vulnerability included executive functions, sustained attention, and the exert of self-control. Behavioral–emotional symptoms were less common; however, somatic complaints and behaviors related to conduct problems were seen in about one-third of individuals. This study highlights the importance of a comprehensive neurocognitive examination to identify children with unfavorable outcomes. [ABSTRACT FROM AUTHOR]

Sediments are an integral component of aquatic systems, linking multiple water uses, functions, and services. Contamination of sediments by chemicals is a worldwide problem, with many jurisdictions trying to prevent future pollution (prospective) and manage existing contamination (retrospective). The present review assesses the implementation of sediment toxicity testing in environmental regulations globally. Currently, the incorporation of sediment toxicity testing in regulations is most common in the European Union (EU), North America, and Australasian regions, with some expansion in Asia and non‐EU Europe. Employing sediment toxicity testing in prospective assessments (i.e., before chemicals are allowed on the market) is most advanced and harmonized with pesticides. In the retrospective assessment of environmental risks (i.e., chemicals already contaminating sediments), regulatory sediment toxicity testing practices are applied inconsistently on the global scale. International harmonization of sediment toxicity tests is considered an asset and has been successful through the widespread adoption and deployment of Organisation for Economic Co‐operation and Development guidelines. On the other hand, retrospective sediment assessments benefit from incorporating regional species and protocols. Currently used toxicity testing species are diverse, with temperate species being applied most often, whereas test protocols are insufficiently flexible to appropriately address the range of environmental contaminants, including nanomaterials, highly hydrophobic contaminants, and ionized chemicals. The ever‐increasing and ‐changing pressures placed on aquatic resources are a challenge for protection and management efforts, calling for continuous sediment toxicity test method improvement to insure effective use in regulatory frameworks. Future developments should focus on including more subtle and specific toxicity endpoints (e.g., incorporating bioavailability‐based in vitro tests) and genomic techniques, extending sediment toxicity testing from single to multispecies approaches, and providing a better link with ecological protection goals. Environ Toxicol Chem 2024;43:1697–1716. © 2024 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC. [ABSTRACT FROM AUTHOR]

STUDY QUESTION What is the prospective risk of Type 2 diabetes (T2D) in Nordic women with polycystic ovary syndrome (PCOS) compared to controls? SUMMARY ANSWER A diagnosis of PCOS and BMI ≥30 kg/m2 is a high-risk phenotype for a prospective risk of T2D diagnosis across Nordic countries. WHAT IS KNOWN ALREADY The risk of T2D in women with PCOS is increased. The risk of T2D is related to BMI and the magnitude of risk in normal weight women with PCOS has been discussed. However, prospective data regarding risk of T2D in population-based cohorts of women with PCOS are limited. STUDY DESIGN, SIZE, DURATION This national register-based study included women with PCOS and age-matched controls. The main study outcome was T2D diagnosis occurring after PCOS diagnosis. T2D was defined according to ICD-10 diagnosis codes and/or filled medicine prescriptions of anti-diabetic medication excluding metformin. PARTICIPANTS/MATERIALS, SETTING, METHODS The study cohort included women originating from Denmark (PCOS Denmark, N = 27 016; controls, N = 133 994), Finland (PCOS Finland, N = 20 467; controls, N = 58 051), and Sweden (PCOS Sweden, N = 52 409; controls, N = 254 010). The median age at cohort entry was 28 years in PCOS Denmark, Finland, and Sweden with a median follow-up time (interquartile range) in women with PCOS of 8.5 (4.0–14.8), 9.8 (5.1–15.1), and 6.0 (2.0–10.0) years, respectively. Cox regression analyses were adjusted for BMI and length of education. MAIN RESULTS AND THE ROLE OF CHANCE The crude hazard ratio (HR, 95% CI) for T2D diagnosis in women with PCOS was 4.28 (3.98–4.60) in Denmark, 3.40 (3.11–3.74) in Finland, and 5.68 (5.20–6.21) in Sweden. In adjusted regression analyses, BMI ≥30 vs <25 kg/m2 was associated with a 7.6- to 11.3-fold risk of T2D. In a combined meta-analysis (PCOS, N = 99 892; controls, N = 446 055), the crude HR for T2D in PCOS was 4.64 (3.40–5.87) and, after adjustment for BMI and education level, the HR was 2.92 (2.32–3.51). LIMITATIONS, REASONS FOR CAUTION Inclusion of more severe cases of PCOS in the present study design could have lead to an overestimation of risk estimates in our exposed population. However, some women in the control group would have undiagnosed PCOS, which would lead to an underestimation of T2D risk in women with PCOS. BMI data were not available for all participants. The present study should be repeated in study cohorts with higher background risks of T2D, particularly in populations of other ethnicities. WIDER IMPLICATIONS OF THE FINDINGS The prospective risk for diagnosis of T2D is increased in women with PCOS, and the risk is aggravated in women with BMI ≥30 kg/m2. STUDY FUNDING/COMPETING INTEREST(S) Funding in Denmark was from the Region of Southern Denmark, Overlægerådet, Odense University Hospital. Funding in Finland was from Novo Nordisk Foundation, Finnish Research Council and Sigrid Juselius Foundation, the National Regional Fund, Sakari Alhopuro Foundation and Finnish Diabetes Research Foundation. E.E. has received a research grant from Ferring Pharmaceuticals (payment to institution) and serves as medical advisor for Tilly AB, not related to this manuscript. The remaining authors declare no conflict of interest. TRIAL REGISTRATION NUMBER N/A. [ABSTRACT FROM AUTHOR]

Objective: In Europe, cenobamate has been approved for use as an adjunctive therapy in adult patients with epilepsy (PWE) with focal‐onset seizures (FOS) who have not responded satisfactorily to treatment with at least two antiseizure medications (ASMs). Pivotal trials and real‐world observational studies have demonstrated a high efficacy of cenobamate, even in very difficult‐to‐treat epilepsies. Our aim was to investigate the efficacy of add‐on cenobamate in adult PWE who were prospectively monitored. We compared these results with those previously obtained for add‐on lacosamide, perampanel, and brivaracetam therapy. Methods: Patients were enrolled from the CENKORK study, which is a prospective, non‐interventional, open‐label, monocenter cohort study of adult PWE experiencing FOS. The titration of cenobamate was performed according to the guidelines outlined in the summary of product characteristics. The primary outcome measure was the retention rate at 6 months and 1 year. In addition, we assessed seizure‐free rates, the proportion of patients achieving at least a 50% seizure reduction, adverse events, and the reasons for treatment discontinuation. These outcome measures were compared with historical controls treated with adjunctive lacosamide, perampanel, or brivaracetam at our center. Results: Between June 2021 and 2022, 172 PWE with ongoing FOS were included. 22 cases were lost to follow‐up, leaving 150 cases for the 1‐year assessment. The retention rates at 6 months and 1 year were 88.7% and 80%, respectively. Seizure freedom was achieved in 14% of patients at both the 6‐month and 1‐year marks, while the ≥50% responder rates were 50% and 61%, respectively. The 6‐month retention rate was significantly higher in cenobamate than in other ASMs (p < 0.001 for each comparator). Adverse events were significantly more common with perampanel (p < 0.001). Significance: Add‐on cenobamate proved to be particularly efficacious compared to our experience with other recently introduced ASMs. Plain Language Summary: This observational study was carried out in 172 adult patients with difficult‐to‐treat epilepsy who were treated with adjunctive cenobamate. After 1 year, the data of 150 patients could be analyzed. Seizure freedom, in the preceding 3 months, was achieved in 14%. The rate of PWE continuing cenobamate was 80%. In our hands, cenobamate showed promising efficacy and tolerability even when compared to other recently introduced antiseizure medications. [ABSTRACT FROM AUTHOR]

This aim of this study is to characterize the nature and pathophysiology of dysphagia after ACDF surgery by precisely and comprehensively capturing within-subject changes on videofluoroscopy between preoperative and postoperative time points. 21 adults undergoing planned primary ACDF procedures were prospectively recruited and enrolled. Participants underwent standardized preoperative and six-week postoperative videofluoroscopic swallow studies. Videos were blindly rated using the Penetration-Aspiration Scale (PAS) and analysis of total pharyngeal residue (%C2-42), swallowing timing, kinematics, and anatomic change was completed. Linear mixed-effects modeling was used to explore the relationships between possible predictor variables and functional outcomes of interest that changed across timepoints. There was no change in PAS scores across timepoints. Total pharyngeal residue (%C2-C42) was increased postoperatively (p < 0.001). Our statistical model revealed significant main effects for timepoint (p = 0.002), maximum pharyngeal constriction area (MPCAN) (p < 0.001), and maximum thickness of posterior pharyngeal (PPWTMAX) (p = 0.004) on the expression of total pharyngeal residue. There were significant two-way interactions for timepoint and MPCAN (p = 0.028), timepoint and PPWTMAX (p = 0.005), and MPCAN and PPWTMAX (p = 0.010). Unsurprisingly, we found a significant three-way interaction between these three predictors (p = 0.027). Our findings suggest that in planned ACDF procedures without known complications, swallowing efficiency is more likely to be impaired than airway protection six weeks after surgery. The manifestation of impaired swallowing efficiency at this timepoint appears to be driven by a complex relationship between reduced pharyngeal constriction and increased prevertebral edema. [ABSTRACT FROM AUTHOR]

Purpose: To build an Mult-Task Learning (MTL) based Artificial Intelligence(AI) model that can simultaneously predict clinical stage, histology, grade and LNM for cervical cancer before surgery. Methods: This retrospective and prospective cohort study was conducted from January 2001 to March 2014 for the training set and from January 2018 to November 2021 for the validation set at Beijing Chaoyang Hospital, Capital Medical University. Preoperative clinical information of cervical cancer patients was used. An Artificial Neural Network (ANN) algorithm was used to build the MTL-based AI model. Accuracy and weighted F1 scores were calculated as evaluation indicators. The performance of the MTL model was compared with Single-Task Learning (STL) models. Additionally, a Turing test was performed by 20 gynecologists and compared with this AI model. Results: A total of 223 cervical cancer cases were retrospectively enrolled into the training set, and 58 cases were prospectively collected as independent validation set. The accuracy of this cervical cancer AI model constructed with ANN algorithm in predicting stage, histology, grade and LNM were 75%, 95%, 86% and 76%, respectively. And the corresponding weighted F1 score were 70%, 94%, 86%, and 76%, respectively. The average time consumption of AI simultaneously predicting stage, histology, grade and LNM for cervical cancer was 0.01s (95%CI: 0.01–0.01) per 20 patients. The mean time consumption doctor and doctor with AI were 581.1s (95%CI: 300.0-900.0) per 20 patients and 534.8s (95%CI: 255.0-720.0) per 20 patients, respectively. Except for LNM, both the accuracy and F-score of the AI model were significantly better than STL AI, doctors and AI-assisted doctors in predicting stage, grade and histology. (P < 0.05) The time consumption of AI was significantly less than that of doctors' prediction and AI-assisted doctors' results. (P < 0.05 Conclusion: A multi-task learning AI model can simultaneously predict stage, histology, grade, and LNM for cervical cancer preoperatively with minimal time consumption. To improve the conditions and use of the beneficiaries, the model should be integrated into routine clinical workflows, offering a decision-support tool for gynecologists. Future studies should focus on refining the model for broader clinical applications, increasing the diversity of the training datasets, and enhancing its adaptability to various clinical settings. Additionally, continuous feedback from clinical practice should be incorporated to ensure the model's accuracy and reliability, ultimately improving personalized patient care and treatment outcomes. [ABSTRACT FROM AUTHOR]

Objectives: To determine the associations between waterpipe use, duration, and intensity of use with prevalence and incidence of metabolic syndrome and its components (increased waist circumference, triglycerides, fasting glucose, blood pressure and decreased high-density lipoprotein cholesterol). Methods: We conducted cross-sectional and prospective analyses using data from the Pars Cohort Study in southern Iran, encompassing 9,264 participants at the baseline, and 5,002 randomly selected in a repeated follow-up. We used multivariate logistic regression models adjusted for age, sex, education, wealth score, physical activity and cigarette pack-years to report odds ratios (OR) and 95% confidence intervals (CI). Results: Among 9,264 participants, 3,119 (33.7%) had metabolic syndrome, and 3,482 (37.6%) had ever smoked waterpipe, with both more common in women than in men. In adjusted models, former waterpipe use was significantly associated with prevalence (OR = 1.43, 95% CI: 1.23–1.68) and incidence (OR = 1.57, 95% CI: 1.19–2.06) of the metabolic syndrome while current waterpipe use was not. Past use was associated with increased risk in all components of metabolic syndrome; current use was associated with increases in all except high blood glucose and hypertension. Past waterpipe users had higher waterpipe use intensity (before quitting) in comparison with current users (2.3 vs. 2.0 waterpipes per day, p < 0.01) and had started waterpipe smoking at a younger age (27.2 vs. 30.1 years, p < 0.01). Conclusion: Waterpipe use was associated with metabolic syndrome and its components, especially among former users potentially due to higher intensity and earlier initiation of use. [ABSTRACT FROM AUTHOR]

Background: Sleep and affective states are closely intertwined. Nevertheless, previous methods to evaluate sleep-affect associations have been limited by poor ecological validity, with a few studies examining temporal or dynamic interactions in naturalistic settings. Objectives: First, to update and integrate evidence from studies investigating the reciprocal relationship between daily sleep and affective phenomena (mood, affect, and emotions) through ambulatory and prospective monitoring. Second, to evaluate differential patterns based on age, affective disorder diagnosis (bipolar, depression, and anxiety), and shift work patterns on day-to-day sleep-emotion dyads. Third, to summarise the use of wearables, actigraphy, and digital tools in assessing longitudinal sleep-affect associations. Method: A comprehensive PRISMA-compliant systematic review was conducted through the EMBASE, Ovid MEDLINE(R), PsycINFO, and Scopus databases. Results: Of the 3024 records screened, 121 studies were included. Bidirectionality of sleep-affect associations was found (in general) across affective disorders (bipolar, depression, and anxiety), shift workers, and healthy participants representing a range of age groups. However, findings were influenced by the sleep indices and affective dimensions operationalised, sampling resolution, time of day effects, and diagnostic status. Conclusions: Sleep disturbances, especially poorer sleep quality and truncated sleep duration, were consistently found to influence positive and negative affective experiences. Sleep was more often a stronger predictor of subsequent daytime affect than vice versa. The strength and magnitude of sleep-affect associations were more robust for subjective (self-reported) sleep parameters compared to objective (actigraphic) sleep parameters. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusions Symptoms of anxiety and attention‐deficit/hyperactivity disorder (ADHD) are prospectively related from childhood to adolescence. However, whether the two dimensions of ADHD—inattention and hyperactivity‐impulsivity—are differentially related to anxiety and whether there are developmental and sex/gender differences in these relations are unknown.Two birth cohorts of Norwegian children were assessed biennially from ages 4 to 16 (N = 1,077; 49% girls) with diagnostic parent interviews used to assess symptoms of anxiety and ADHD. Data were analyzed using a random intercept cross‐lagged panel model, adjusting for all unobserved time‐invariant confounding effects.In girls, increased inattention, but not hyperactivity‐impulsivity, predicted increased anxiety 2 years later across all time‐points and increased anxiety at ages 12 and 14 predicted increased inattention but not hyperactivity‐impulsivity. In boys, increased hyperactivity‐impulsivity at ages 6 and 8, but not increased inattention, predicted increased anxiety 2 years later, whereas increased anxiety did not predict increased inattention or hyperactivity‐impulsivity.The two ADHD dimensions were differentially related to anxiety, and the relations were sex‐specific. In girls, inattention may be involved in the development of anxiety throughout childhood and adolescence and anxiety may contribute to girls developing more inattention beginning in early adolescence. In boys, hyperactivity‐impulsivity may be involved in the development of anxiety during the early school years. Effective treatment of inattention symptoms in girls may reduce anxiety risk at all time‐points, while addressing anxiety may decrease inattention during adolescence. Similarly, treating hyperactivity‐impulsivity may reduce anxiety risk in boys during late childhood (at ages 8–10). [ABSTRACT FROM AUTHOR]

Chronic subdural hematomas (CSDHs) are a relatively common condition defined as an abnormal collection of blood and its break down products in the subdural space, usually accompanied by a history of preceding mild head trauma. Surgical management remains the mainstay of treatment. The objective of this study was to assess the surgical treatment outcome of patients operated on for CSDH at University of Gondar Comprehensive Specialized Hospital, Northwest Ethiopia. This comprehensive novel study serves as a benchmark for assessing therapeutic outcomes among patients with CSDH in the context of Ethiopia. Institution-based prospective observational study was conducted among patients operated on for symptomatic CSDH at University of Gondar Comprehensive Specialized Hospital from January 1, 2023, to December 31, 2023 G C. A total of 107 patients (70 males (65.4%) and 37 females (34.6%) with a male to female ration of 1.9:1 and mean age of 62.4 and a standard deviation of 13.7 (range from 23 to 92) were studied. Fifyt-one (47.7%) of the patients had a history of antecedent trauma. In terms of clinical symptoms, 86 (80.4%) patients had weakness as the chief complaint, followed by headache in 81 (75.7%). Among complications, recurrence is the most common, which was seen in 16 (15%) patients, followed by altered mental status (confusion, delirium) in 18 (16.8%) patients. The mean duration of the hospital stay was 6 days, with a standard deviation of 4 days. The majority of the patients had a good recovery with the resumption of normal life: 92 (86%), 10 (9.3%) patients had moderate disability, were disabled but independent, 2 (1.8%) patients had severe disability, were dependent on daily support, and 3 (2.8%) patients died. CSDHs are a relatively common condition characterized by an abnormal collection of blood. Antecedent trauma is the usual risk factor. Complication can happen following surgical intervention; however, patients with CSDH generally have a good prognosis. [ABSTRACT FROM AUTHOR]

The incidence of inflammatory bowel disease (IBD) is increasing. The prevalence of overweight and obesity is increasing in parallel with IBD and could contribute to IBD development. The aim of this study was to assess the relationship between weight change and the risk for IBD. Data gathered from 55,896 adult participants in the three first population-based Trøndelag Health Studies (HUNT1-3), Norway, performed in 1984–2008 was used. The exposure was change in body mass index between two HUNT studies. The outcome was a new IBD diagnosis recorded during a ten-year follow-up period after the exposure assessment. The risk of IBD by weight change was assessed by Cox regression analyses reporting hazard ratios (HRs) and 95% confidence intervals (CIs), adjusted for sex, age, and smoking status. There were 334 new cases of ulcerative colitis (UC) and 54 of Crohn's disease (CD). Weight loss decreased the risk of a new UC diagnosis by 38% (adjusted HR 0.62, 95% CI 0.39–0.97) and seemed to double the risk of getting a new CD diagnosis (adjusted HR 2.01, 95% CI 0.91–4.46). Weight gain was not associated with a new diagnosis of neither UC (adjusted HR 1.00, 95% CI 0.78–1.26) nor CD (adjusted HR 1.08, 95% CI 0.56–2.08). In this study, weight loss was associated with decreased risk of UC. However, no associations were seen between weight gain and the risk of UC or CD, suggesting that the increasing weight in the general population cannot explain the increasing incidence of IBD. [ABSTRACT FROM AUTHOR]

• 12 months after SARS-CoV-2 infection, around 7 % of children and young people report 'brain fog' i.e., cognitive impairment. • 2.4% of children and young people experienced persistent cognitive impairment at 3-, 6- and 12-months after SARS-CoV-2 infection. • 12 months after SARS-CoV-2 infection, more females, white ethnicities, and older at the time of first infection, children and young people reported cognitive impairment. • Cognitive impairment co-occurs with poorer mental health, fatigue and sleep problems. Cognitive impairment is often reported after SARS-CoV-2 infection, yet evidence gaps remain. We aimed to (i) report the prevalence and characteristics of children and young people (CYP) reporting "brain fog" (i.e., cognitive impairment) 12-months post PCR-proven SARS-CoV-2 infection and determine whether differences by infection status exist and (ii) explore the prevalence of CYP experiencing cognitive impairment over a 12-month period post-infection and investigate the relationship between cognitive impairment and poor mental health and well-being, mental fatigue and sleep problems. The Omicron CLoCk sub-study, set up in January 2022, collected data on first-time PCR-test-positive and PCR-proven reinfected CYP at time of testing and at 3-, 6- and 12-months post-testing. We describe the prevalence of cognitive impairment at 12-months, indicating when it was first reported. We characterise CYP experiencing cognitive impairment and use chi-squared tests to determine whether cognitive impairment prevalence varied by infection status. We explore the relationship between cognitive impairment and poor mental health and well-being, mental fatigue and trouble sleeping using validated scales. We examine associations at 3-, 6- and 12-months post-testing by infection status using Mann-Whitney U and chi-square tests. At 12-months post-testing, 7.0 % (24/345) of first-positives and 7.5 % (27/360) of reinfected CYP experienced cognitive impairment with no difference between infection-status groups (p = 0.78). The majority of these CYP experienced cognitive impairment for the first time at either time of testing or 3-months post-test (no difference between the infection-status groups; p = 0.60). 70.8 % of first-positives experiencing cognitive impairment at 12-months, were 15-to-17-years-old as were 33.3 % of reinfected CYP experiencing cognitive impairment (p < 0.01). Consistently at all time points post-testing, CYP experiencing cognitive impairment were more likely to score higher on all Strengths and Difficulties Questionnaire subscales, higher on the Chalder Fatigue sub-scale for mental fatigue, lower on the Short Warwick-Edinburgh Mental Wellbeing Scale and report more trouble sleeping. CYP have a fluctuating experience of cognitive impairment by 12-months post SARS-CoV-2-infection. Cognitive impairment is consistently correlated with poorer sleep, behavioural and emotional functioning over a 12-month period. Clinicians should be aware of cognitive impairment post-infection and its co-occurring nature with poorer sleep, behavioural and mental health symptoms. [ABSTRACT FROM AUTHOR]

With >1300 civilians murdered, the terrorist attack of October 7 is one of the deadliest terrorist attacks in modern history. Previous research documented a sharp increase in depression in the aftermath of the attacks and the military conflict that followed. In this national prospective cohort study, we examined to what extent perceived belongingness (PB) moderates the association between depression and suicide ideation (SI) in the wake of the October 7th terrorist attack. A representative sample of 710 Israeli adults (of them, 362 females, 51.1 %), Jews (557, 79.9 %), and Arabs (153, 20.1 %), aged 18–85 (M = 41.01 , SD = 13.72) completed questionnaires assessing depression, current SI, and perceived belongingness at two timepoints: T1 (in August 2023) and T2 (in November 2023). Perceived belongingness at T1 predicted SI at T2 beyond demographic and trauma-related characteristics. Importantly, we found a significant interaction in which a PB at T1 moderated the link between depression and current SI at T2. Specifically, the level of depression at T2 contributed to current SI-T2 more strongly for individuals with low PB levels than for individuals with high PB levels. Our study highlights the impact of PB on SI following the October 7th terrorist attack. Clinicians treating individuals coping with depression should attend to their patients' sense of belongingness, as low PB comprises a significant risk factor for current SI. Moreover, community and national initiatives that could increase levels of PB among the citizens may help to diminish suicide risk in the aftermath of the attack. • This is the first prospective study on suicide ideation after the October 7th terrorist attack in Israel. • Belongingness pre-attack predicted suicide ideation post October 7th attack. • Belongingness found to moderate the contribution of depression on current SI following the attack. [ABSTRACT FROM AUTHOR]

We aimed to describe the clinical features of patients with pure autonomic failure (PAF) preceding phenoconversion that could be useful as predictive markers for advancing α-synuclein-associated neurodegeneration of the brain. Patients diagnosed with PAF were evaluated at eight centres (seven US-based and one European) and enrolled in a longitudinal observational cohort study (NCT01799915). Subjects underwent detailed assessments of motor, sleep, olfactory, cognitive and autonomic function and were followed prospectively to determine whether they developed parkinsonism or dementia for up to 10 years. We identified incident cases of Parkinson's disease (PD), dementia with Lewy bodies (DLB) or multiple system atrophy (MSA) and computed hazard ratios for phenoconversion as functions of clinical features. A total of 209 participants with PAF with a median disease duration of 6 years (IQR: 3–10) were enrolled. Of those, 149 provided follow-up information at an office or telemedicine visit. After a mean follow-up duration of 3 years, 48 (33%) participants phenoconverted (42% to PD, 35% to DLB and 23% to MSA). Faster phenoconversion from study enrolment to any diagnosis was associated with urinary and sexual dysfunction [hazard ratio (HR) 5.9, 95% confidence interval (CI): 1.6–22 and HR: 3.6, 95% CI: 1.1–12] followed by subtle motor signs (HR: 2.7, 95% CI: 1.2–6), trouble swallowing (HR 2.5, 95% CI: 1.4–4.5) and changes in speech (HR:2.4, 95% CI:1.1–4.8) at enrolment. Subjects reporting deterioration of handwriting were more likely to phenoconvert to PD (HR: 2.6, 95% CI: 1.1–5.9) and those reporting difficulty handling utensils were more likely to phenoconvert to DLB (HR: 6.8, 95% CI: 1.2–38). Patients with a younger age of PAF onset (HR: 11, 95% CI: 2.6–46), preserved olfaction (HR: 8.7, 95% CI: 1.7–45), anhidrosis (HR: 1.8, 95% CI: 1–3.1, P = 0.042) and severe urinary problems (HR 1.6, 95% CI: 1–2.5, P = 0.033) were more likely to phenoconvert to MSA. The best autonomic predictor of PD was a blunted heart rate increase during the tilt-table test (HR: 6.1, 95% CI: 1.4–26). Patients with PAF have an estimated 12% (95% CI: 9–15%) per year annual risk following study entry of phenoconverting to a manifest CNS synucleinopathy. [ABSTRACT FROM AUTHOR]

Sleep quality is directly related to general health and quality of life. Caregivers' sleep disturbances affect not only their own health, but also the optimal care of their patients, with negative consequences such as neglect and medication errors. This study was conducted prospectively in the palliative care unit. The participants were divided into two groups: the caregivers and the control group. The caregiver groups were categorized into two subgroups: family and paid caregivers. The sleep quality of the caregivers was evaluated with the Pittsburgh Sleep Quality Index (PSQI). The demographics, body mass index, educational level, the presence of chronic diseases and medications, need for spiritual support, daytime sleepiness, duration of caregiving, nighttime awakening, and tea/coffee consumption were recorded. The study included 250 caregivers (female: 74.8%, mean age: 50.6 ± 12.1) and 103 control group members. Family caregivers significantly had an advanced age, lower educational level, more chronic diseases, and medications, need for spiritual support, and longer duration of caregiving compared to the paid caregivers (p = 0.018, < 0.001, 0.001, 0.005, < 0.001, and 0.003, respectively). The total PSQI scores of caregivers were significantly higher in the FDR, family group, females, those with need of spiritual support, and tea/coffee consumption close to bedtime (p = 0.002 < 0.004. 0.026. < 0.001, and 0.022, respectively). The fact that the sleep quality of family group caregivers is worse than that of paid caregivers may prevent healthy medical service delivery. The provision of care by paid professional caregivers will improve quality of care and quality of life. [ABSTRACT FROM AUTHOR]

Several studies have discussed the features and characteristics of research on English language teaching in Indonesia by both lecturers and students. However, there is very little research that discusses topics, research methods, designs, and reasons for choosing topics, as well as the efforts to improve the quality of research conducted by prospective EFL teachers in the Indonesian context. The study aims to identify, assess, and characterize the research conducted by prospective Indonesian EFL teachers. The study used mixed research methods utilizing 477 research works as the objects of study, while the research participants were 67 prospective Indonesian EFL teachers and 5 heads of the English education program. The results showed that students' selected research topics were the process of learning English at the secondary school level and that their preferred methodologies were quantitative research, qualitative research, and classroom action research (mixed methods). The most popular topics in English language learning research were methods for learning, classroom action research, textbook analysis, media for learning English, and viewpoints on English teaching concerns. The reasons for choosing certain research topics and methods were dominated by issues of ease of research completion. The results contribute as a basis for future research to select variables, designs, issues, or study subjects to explore as well as for directing and defining the themes and research topics in the English Education study program. [ABSTRACT FROM AUTHOR]

Background: Nowadays, different therapeutic options are available for the first-line treatment of metastatic renal cell carcinoma (mRCC). Immuno-combinations are the standard first-line therapy in all mRCC patients regardless of the International Metastatic RCC Database Consortium (IMDC) risk category, even though TKI monotherapy is still a therapeutic option in selected patients. However, comparisons between the different first-line treatment strategies are lacking and few real-world data are available in this setting. For this reason, the regimen choice represents an important issue in clinical practice and the optimal treatment sequence remains unclear. Methods: The REGAL study is a multicentric prospective observational study enrolling mRCC patients treated with first-line systemic therapy according to clinical practice in a real-world setting. A retrospective cohort of mRCC patients who received first-line systemic therapy from the 1st of January 2021 will also be included. The primary objective is to identify potential prognostic and predictive factors that could help guide the treatment choice; secondary objectives included the assessment of the prognostic performance of the novel prognostic Meet-URO score (IMDC score + neutrophil-to-lymphocyte ratio + bone metastases) compared with the IMDC score and the comparison between treatment strategies according to response and survival outcomes and toxicity profile. Discussion: Considering the high number of therapeutic first-line strategies available for mRCC, the identification of clinical prognostic and predictive factors to candidate patients to a preferable systemic therapy is still an unmet clinical need. The Meet-URO 33 study aims to provide a large-scale real-world database on mRCC patients, to identify the clinical predictive and prognostic factors and the different performances between the ICI-based combinations according to response, survival and toxicity. Trial Registration: CESC IOV 2023-78. [ABSTRACT FROM AUTHOR]

Background: Liver disease and dementia are both highly prevalent and share common pathological mechanisms. We aimed to investigate the associations between metabolic dysfunction-associated fatty liver disease (MAFLD), metabolic dysfunction-associated steatotic liver disease (MASLD) and the risk of all-cause and cause-specific dementia. Methods: We conducted a prospective study with 403,506 participants from the UK Biobank. Outcomes included all-cause dementia, Alzheimer's disease, and vascular dementia. Multivariable Cox proportional hazards models were used for analyses. Results: 155,068 (38.4%) participants had MAFLD, and 111,938 (27.7%) had MASLD at baseline. During a median follow-up of 13.7 years, 5,732 participants developed dementia (2,355 Alzheimer's disease and 1,274 vascular dementia). MAFLD was associated with an increased risk of vascular dementia (HR 1.32 [95% CI 1.18–1.48]) but a reduced risk of Alzheimer's disease (0.92 [0.84–1.0]). Differing risks emerged among MAFLD subtypes, with the diabetes subtype increasing risk of all-cause dementia (1.8 [1.65–1.96]), vascular dementia (2.95 [2.53–3.45]) and Alzheimer's disease (1.46 [1.26–1.69]), the lean metabolic disorder subtype only increasing vascular dementia risk (2.01 [1.25–3.22]), whereas the overweight/obesity subtype decreasing risk of Alzheimer's disease (0.83 [0.75–0.91]) and all-cause dementia (0.9 [0.84–0.95]). MASLD was associated with an increased risk of vascular dementia (1.24 [1.1–1.39]) but not Alzheimer's disease (1.0 [0.91–1.09]). The effect of MAFLD on vascular dementia was consistent regardless of MASLD presence, whereas associations with Alzheimer's disease were only present in those without MASLD (0.78 [0.67–0.91]). Conclusions: MAFLD and MASLD are associated with an increased risk of vascular dementia, with subtype-specific variations observed in dementia risks. Further research is needed to refine MAFLD and SLD subtyping and explore the underlying mechanisms contributing to dementia risk. [ABSTRACT FROM AUTHOR]

Background: Metabolic syndrome (MetS) elevates cancer risk. However, a single MetS assessment does not fully reveal the long‐term association with cancer. Inflammation, alongside MetS, could synergistically expedite both the onset and advancement of cancer. This study aims to investigate MetS score trajectories and cancer risk in a large, prospective cohort study. Methods: The authors prospectively examined the relationship between MetS score trajectory patterns and new‐onset cancer in 44,115 participants. Latent mixture modeling was used to identify the MetS score trajectories. Cox proportional hazards regression models were used to evaluate the association between MetS score trajectory patterns and the risk of overall and site‐specific cancers. Results: Four MetS score trajectory patterns were identified: low‐stable (n = 4657), moderate‐low (n = 18,018), moderate‐high (n = 18,288), and elevated‐increasing (n = 3152). Compared to participants with a low‐stable trajectory pattern, the elevated‐increasing trajectory pattern was associated with an elevated risk of overall (hazard ratio [HR], 1.27; 95% confidence interval [CI], 1.04–1.55), breast (HR, 2.11; 95% CI, 1.04–4.34), endometrial (HR, 3.33; 95% CI, 1.16–6.77), kidney (HR, 4.52; 95% CI, 1.17–10.48), colorectal (HR, 2.54; 95% CI, 1.27–5.09), and liver (HR, 1.61; 95% CI, 1.09–4.57) cancers. Among participants with chronic inflammation (C‐reactive protein levels ≥3 mg/L), the elevated‐increasing trajectory pattern was significantly associated with subsequent breast, endometrial, colorectal, and liver cancers. Conclusions: Trajectories of MetS scores are associated with the occurrence of cancers, especially breast, endometrial, kidney, colorectal, and liver cancers, emphasizing the importance of long‐term monitoring and evaluation of MetS. Plain Language Summary: The association between long‐term elevated metabolic syndrome (MetS) scores and a heightened risk of various cancers is a pivotal finding of our study.Our research further indicates that individuals with MetS, particularly when coupled with chronic inflammation, are at an increased risk of cancer.We propose that sustained monitoring and management of MetS could be beneficial in reducing cancer risk. Metabolic syndrome (MetS) score trajectories have been linked to an increased risk of several cancers, including breast, endometrial, kidney, colorectal, and liver cancers. This highlights the critical need for long‐term monitoring and evaluation of MetS. [ABSTRACT FROM AUTHOR]