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BACKGROUND: When considering hepatectomy for elderly HCC patients, it's essential to assess surgical safety and survival benefits. This study investigated the impact of preoperative frailty, assessed with the Clinical Frailty Scale (CFS), on outcomes for octogenarians undergoing HCC hepatectomy. METHODS: A retrospective cohort study of octogenarians who had hepatectomy for HCC between 2010 and 2022 at 16 hepatobiliary centers was conducted. Patients were categorized as frail or non-frail based on preoperative CFS, with frailty defined as CFS ≥5. The primary endpoints were overall survival (OS), recurrence-free survival (RFS), and cancer-specific survival (CSS), with perioperative outcomes as secondary endpoints. RESULTS: Among 240 octogenarians, 105 were characterized as being frail. Frail patients had a higher incidence of postoperative 30-day morbidity and postoperative 30-day and 90-day mortality versus non-frail patients. Meanwhile, 5-year OS, RFS and CSS among frail patients were lower compared with non-frail patients. Univariable and multivariable analysis revealed that preoperative frailty was an independent risk factor of postoperative 30-day morbidity (OR: 2.060), OS (HR: 2.384), RFS (HR: 2.190) and CSS (HR: 2.203). CONCLUSION: Preoperative frailty, as assessed by the CFS, was strongly associated with both short-term outcomes and long-term survival among octogenarians undergoing hepatectomy for HCC. Incorporating frailty assessment into the preoperative evaluation may help optimize patient selection and perioperative care.

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BACKGROUND: High-density lipoprotein cholesterol (HDL-C) is widely recognized for its protective effects against cognitive decline. However, recent studies have presented conflicting results, with some suggesting no significant cognitive benefits or even an increased risk of dementia associated with high HDL-C levels. For those who suffer from depression, the cognitive benefits of HDL-C may be diminished or reversed. The purpose of this study is to investigate the associations between HDL-C, cognitive ability, and depressive symptoms in middle-aged and older Chinese adults. METHODS: The datasets utilized were sourced from the China Health and Retirement Longitudinal Study (CHARLS) for the years 2011 and 2015, comprising 4,302 participants. Cross-lagged models were employed to explore the temporal sequence between cognitive performance and HDL-C levels, and to examine the interplay among depression, cognition, and HDL-C. Confounding factors such as sociodemographic characteristics, sleep conditions, and history of chronic diseases were controlled for. RESULTS: The analysis revealed unidirectional effects of baseline impaired cognition and greater severity of depression on increased HDL-C levels at follow-up (ß = - 0.036 and ß = 0.028, respectively, P < 0.05). However, higher baseline HDL-C levels did not significantly predict cognitive performance or depression 4 years later (ß = - 0.008 and ß = 0.023, respectively, P > 0.05). Depressive symptoms and cognition were found to have a significant bidirectional association (ß = - 0.026 and ß = - 0.053, respectively, P < 0.05). CONCLUSIONS: Cognitive impairment and depression are associated with higher HDL-C levels, whereas higher HDL-C levels do not appear to protect against cognitive decline or depressive symptoms. These findings underscore the importance of preserving cognitive and mental health, which may lower the likelihood of cardiovascular disease and dementia. Future studies should validate these findings and develop targeted interventions tailored to specific populations.

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Urea is a simple organic compound that is widely used in both the industry and daily life. Compared with conventional methods, the preparation of urea by electrochemical synthesis is more environmentally friendly and sustainable. However, after the reaction, low amounts of urea and high concentrations of inorganic ions, including [Formula: see text] concentration was achieved without interference. Thus, the developed method can be applied for the detection of trace urea and other related ions in urea-containing electrolyte products.

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Characterizing the nature of hydrodynamical transport properties in quantum dynamics provides valuable insights into the fundamental understanding of exotic non-equilibrium phases of matter. Experimentally simulating infinite-temperature transport on large-scale complex quantum systems is of considerable interest. Here, using a controllable and coherent superconducting quantum simulator, we experimentally realize the analog quantum circuit, which can efficiently prepare the Haar-random states, and probe spin transport at infinite temperature. We observe diffusive spin transport during the unitary evolution of the ladder-type quantum simulator with ergodic dynamics. Moreover, we explore the transport properties of the systems subjected to strong disorder or a tilted potential, revealing signatures of anomalous subdiffusion in accompany with the breakdown of thermalization. Our work demonstrates a scalable method of probing infinite-temperature spin transport on analog quantum simulators, which paves the way to study other intriguing out-of-equilibrium phenomena from the perspective of transport.

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AIMS: To assess the validity and internal reliability of the International Trauma Questionnaire (ITQ) among patients diagnosed with major depressive disorder (MDD) and to explore the network structure of Complex post-traumatic stress disorder (CPTSD) among MDD patients in China. METHODS: Eligible individuals were recruited from a large tertiary hospital in Guangdong Province. Trained researchers conducted in-person interviews and administered self-report questionnaires, including demographics, medical information, and psychological assessments. Confirmatory factor analyses (CFA) and network analysis were performed, with calculations of Average Variance Extracted (AVE), Cronbach's α, and composite reliability. RESULTS: A total of 113 patients with MDD participated in this study. The correlated six-factor one-order model was a good representation of the latent structure of ITQ (χ2= 60.114, df = 39, P = 0.017, SRMR = 0.070, RMSEA = 0.050, TLI = 0.952, CFI = 0.972, BIC = 175.508). All ITQ subscales possessed acceptable convergent validity and internal reliability, except for affective dysregulation and re-experiencing. The square root of AVE for affective dysregulation was lower than its correlations with other clusters. Network analysis revealed that node C4 ('I feel worthless'), as a core symptom, was significantly associated with the development of CPTSD. CONCLUSIONS: The clinical applicability of the ITQ was demonstrated by its overall validity and reliability among patients with MDD. However, the affective dysregulation and re-experiencing clusters still need to be revised and enhanced. Timely screening, recognition, and diagnosis are critical due to the worse clinical outcomes seen in comorbid patients.

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Objectives: Analyzing and comparing COVID-19 infection and case-fatality rates across different regions can help improve our response to future pandemics. Methods: We used public data from the WHO to calculate and compare the COVID-19 infection and case-fatality rates in different continents and income levels from 2019 to 2023. Results: The Global prevalence of COVID-19 increased from 0.011 to 0.098, while case fatality rates declined from 0.024 to 0.009. Europe reported the highest cumulative infection rate (0.326), with Africa showing the lowest (0.011). Conversely, Africa experienced the highest cumulative case fatality rates (0.020), with Oceania the lowest (0.002). Infection rates in Asia showed a steady increase in contrast to other continents which observed initial rises followed by decreases. A correlation between economic status and infection rates was identified; high-income countries had the highest cumulative infection rate (0.353) and lowest case fatality rate (0.006). Low-income countries showed low cumulative infection rates (0.006) but the highest case fatality rate (0.016). Initially, high and upper-middle-income countries experienced elevated initial infection and case fatality rates, which subsequently underwent significant reductions. Conclusions: COVID-19 rates varied significantly by continent and income level. Europe and the Americas faced surges in infections and low case fatality rates. In contrast, Africa experienced low infection rates and higher case fatality rates, with lower- and middle-income nations exceeding case fatality rates in high-income countries over time.

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BACKGROUND: Research on gastrointestinal mucosal adenocarcinoma (GMA) is limited and controversial, and there is no reference tool for predicting postoperative survival. AIM: To investigate the prognosis of GMA and develop predictive model. METHODS: From the Surveillance, Epidemiology, and End Results database, we collected clinical information on patients with GMA. After random sampling, the patients were divided into the discovery (70% of the total, for model training), validation (20%, for model evaluation), and completely blind test cohorts (10%, for further model evaluation). The main assessment metric was the area under the receiver operating characteristic curve (AUC). All collected clinical features were used for Cox proportional hazard regression analysis to determine factors influencing GMA's prognosis. RESULTS: This model had an AUC of 0.7433 [95% confidence intervals (95%CI): 0.7424-0.7442] in the discovery cohort, 0.7244 (GMA: 0.7234-0.7254) in the validation cohort, and 0.7388 (95%CI: 0.7378-0.7398) in the test cohort. We packaged it into Windows software for doctors' use and uploaded it. Mucinous gastric adenocarcinoma had the worst prognosis, and these were protective factors of GMA: Regional nodes examined [hazard ratio (HR): 0.98, 95%CI: 0.97-0.98, P < 0.001)] and chemotherapy (HR: 0.62, 95%CI: 0.58-0.66, P < 0.001). CONCLUSION: The deep learning-based tool developed can accurately predict the overall survival of patients with GMA postoperatively. Combining surgery, chemotherapy, and adequate lymph node dissection during surgery can improve patient outcomes.

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OBJECTIVE: Prevention programs for eating disorders (EDs) and high body index mass (BMI) have the potential to reduce the onset of these interconnected public health concerns. However, it remains unclear whether routine implementation of such programs would be cost-effective. This study aims to determine the cost-effectiveness of an intervention that aims to prevent both ED and high BMI. METHOD: A Markov model was developed to evaluate the incremental cost-effectiveness of a targeted school-based program, Healthy Weight, that aims to prevent both EDs and high BMI among Australian adolescents with body image concerns (aged 15-18 years), versus a "no intervention" comparator. A cost-utility analysis was conducted from a "healthcare and education" sector perspective with costs (measured in 2019 Australian dollars) and health impacts modeled over the lifetime of the target population. An incremental cost-effectiveness ratio (ICER), expressed as cost per health-adjusted life year (HALY) gained, was calculated. Sensitivity analyses were done to test model assumptions. RESULTS: The mean intervention cost and HALYs gained were AUD$2.13 million (95% CI, AUD$1.83-2.43 million) and 146 (95% CI, 90-209), respectively. With healthcare cost-savings (AUD$3.97 million) included, the intervention was predicted to be cost-saving (AUD$1.83 million; 95% CI, AUD$0.51-3.21 million). Primary findings were robust to extensive sensitivity analyses. DISCUSSION: The Healthy Weight intervention is likely to represent good value-for-money. To ensure the successful implementation of this program at the population level, further research on its feasibility and acceptability among schools and the wider community is required.

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OBJECTIVES: To describe the health-related quality of life (HRQoL), estimate the associated health state utility values (HSUVs) and explore factors associated with HRQoL of patients with anxiety and/or depression in a resource-limited hospital setting. METHODS: A cross-sectional survey involving 462 participants was conducted in a hospital setting. The Amharic version of the EQ-5D-5 L assessed HRQoL, while the GAD-7 and PHQ-9 measured severity of anxiety and depression symptoms respectively. HSUVs were analysed based on clinical and demographic profiles; mean differences were compared using t-tests and one-way ANOVA; Scheffe's post hoc comparisons and effect sizes (Cohen's d statistic) were used to assess the magnitude of group differences. Factors associated with HRQoL were explored using regression analysis. RESULTS: The mean HSUV was 0.87 (SD = 0.17) and the EQ VAS was 71.4 (SD = 19.1). Patients with both anxiety and depression scored significantly lower (HSUV = 0.83 [0.16], EQ VAS = 64.4 [17.9]) compared to those with either anxiety only (HSUV = 0.88 [0.17], EQ VAS = 75.3 [17.9]) or depression only (HSUV = 0.89 [0.18], EQ VAS 74.4 [19.7]). Males had slightly higher mean scores than females, while those aged 18-35 years demonstrated the highest scores on both the EQ-5D-5 L and EQ VAS. Older age (ß=-0.002), higher PHQ-9 scores (ß=-0.008) and comorbid hypertension (ß=-0.07) associated with lower HSUVs. Lower EQ VAS scores were associated with being female (ß=-4.4), having comorbid hypertension (ß=-7.4) and higher PHQ-9 scores (ß=-0.86), while a positive association was found with having 'more than enough' income (ß = 11.8). CONCLUSIONS: Older age, severity or co-diagnosis of anxiety or depression and comorbid conditions were associated with lower HRQoL, highlighting the need for better interventions to improve the HRQoL of patients with anxiety and depression in Ethiopia.

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BACKGROUND: T2*BOLD is based on myocardial deoxyhemoglobin content to reflect the state of myocardial oxygenation. Quantitative flow ratio is a tool for assessing coronary blood flow based on invasive coronary angiography. PURPOSE: This study aimed to evaluate the correlation between T2*BOLD and QFR in the diagnosis of stenotic coronary arteries in patients with multi-vessel coronary artery disease. METHODS: Fifty patients with MVCAD with at least 1 significant coronary artery stenosis (diameter stenosis > 50%) and 21 healthy control subjects underwent coronary angiography combined with QFR measurements and cardiovascular magnetic resonance (CMR). QFR ≤ 0.80 was considered to indicate the presence of hemodynamic obstruction. RESULTS: Totally 60 (54%) obstructive vessels had hemodynamic change. Between stenotic coronary arteries (QFR ≤ 0.8) and normal vessels, T2*BOLD showed AUCs of 0.97, 0.69, and 0.91 for left anterior descending (LAD), left circumflex (LCX) and right coronary (RCA) arteries and PI displayed AUCs of 0.89, 0.77 and 0.90 (all p > 0.05, except for LAD). The AUCs of T2*BOLD between stenotic coronary arteries (QFR > 0.8) and normal vessels were 0.86, 0.72, and 0.85 for LAD, LCX and RCA; while, PI showed AUCs of 0.93, 0.86, and 0.88, respectively (p > 0.05). Moreover, T2*BOLD displayed AUCs of 0.96, 0.74, and 0.91 for coronary arteries as before between coronary arteries with stenosis (QFR ≤ 0.8 and > 0.8), but the mean PI of LAD, LCX and RCA showed no significant differences between them. CONCLUSION: T2* BOLD and QFR have good correlation in diagnosing stenotic coronary arteries with hemodynamic changes in patients with stable multi-vessel CAD. T2* BOLD is superior to semi-quantitative perfusion imaging in analyzing myocardial ischemia without stress.

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Patient activation, broadly defined as the ability of individuals to manage their health and navigate the healthcare system effectively, is crucial for achieving positive health outcomes. The Patient Activation Measure (PAM), a popularly used tool, was developed to assess this vital component of health care. This review is the first to systematically examine the validity of the PAM, as well as study its reliability, factor structure, and validity across various populations. Following the PRISMA and COSMIN guidelines, a search was conducted in MEDLINE, EMBASE, and Cochrane Library, from inception to 1 October 2023, using combinations of keywords related to patient activation and the PAM. The inclusion criteria were original quantitative or mixed methods studies focusing on PAM-13 or its translated versions and containing data on psychometric properties. Out of 3007 abstracts retrieved, 39 studies were included in the final review. The PAM has been extensively studied across diverse populations and geographical regions, including the United States, Europe, Asia, and Australia. Most studies looked at populations with chronic conditions. Only two studies applied the PAM to community-dwelling individuals and found support for its use. Studies predominantly showed a high internal consistency (Cronbach's alpha > 0.80) for the PAM. Most studies supported a unidimensional construct of patient activation, although cultural differences influenced the factor structure in some cases. Construct validity was established through correlations with health behaviors and outcomes. Despite its strengths, there is a need for further research, particularly in exploring content validity and differential item functioning. Expanding the PAM's application to more diverse demographic groups and community-dwelling individuals could enhance our understanding of patient activation and its impact on health outcomes.

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Background: The utility of pre- and post-operative alpha-fetoprotein (AFP) and des-gamma (γ)-carboxy prothrombin (DCP) expression patterns and their dynamic changes as predictors of the outcome of hepatic resection for hepatocellular carcinoma (HCC) has yet to be well elucidated. Methods: From a multicenter database, AFP and DCP data during the week prior to surgery and the first post-discharge outpatient visit (within 1-2 months after surgery) were collected from patients with HCC who underwent hepatectomy. AFP-DCP expression patterns were categorized according to the number of positive tumor markers (AFP ≥ 20ng/mL, DCP ≥ 40mAU/mL), including double-negative, single-positive, and double-positive. Changes in the AFP-DCP expression patterns were delineated based on variations in the number of positive tumor markers when comparing pre- and post-operative patterns. Results: Preoperatively, 53 patients (8.3%), 337 patients (52.8%), and 248 patients (38.9%) exhibited double-negative, single-positive, and double-positive AFP-DCP expression patterns, respectively. Postoperatively, 463 patients (72.6%), 130 patients (20.4%), and 45 patients (7.0%) showed double-negative, single-positive, and double-positive AFP-DCP expression patterns, respectively. Survival analysis showed a progressive decrease in recurrence-free (RFS) and overall survival (OS) as the number of postoperative positive tumor markers increased (both P < 0.001). Multivariate analysis showed that postoperative AFP-DCP expression pattern, but not preoperative AFP-DCP expression pattern, was an independent risk factor for RFS and OS. Further analysis showed that for patients with positive preoperative markers, prognosis gradually improves as positive markers decrease postoperatively. In particular, when all postoperative markers turned negative, the prognosis was consistent with that of preoperative double-negative patients, regardless of the initial number of positive markers. Conclusions: AFP-DCP expression patterns, particularly postoperative patterns, serve as vital sources of information for prognostic evaluation following hepatectomy for HCC. Moreover, changes in AFP-DCP expression patterns from pre- to post-operation enable dynamic prognostic risk stratification postoperatively, aiding the development of individualized follow-up strategies.

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The lymphocyte-specific protein tyrosine kinase (LCK) plays a crucial role in both T-cell development and activation. Dysregulation of LCK signaling has been demonstrated to drive the oncogenesis of T-cell acute lymphoblastic leukemia (T-ALL), thus providing a therapeutic target for leukemia treatment. In this study, we introduced a sophisticated virtual screening strategy combined with biological evaluations to discover potent LCK inhibitors. Our initial approach involved utilizing the PLANET algorithm to assess and contrast various scoring methodologies suitable for LCK inhibitor screening. After effectively evaluating PLANET, we progressed to devise a virtual screening workflow that synergistically combines the strengths of PLANET with the capabilities of Schrödinger's suite. This integrative strategy led to the efficient identification of four potential LCK inhibitors. Among them, compound 1232030-35-1 stood out as the most promising candidate with an IC50 of 0.43 nM. Further in vitro bioassays revealed that 1232030-35-1 exhibited robust antiproliferative effects on T-ALL cells, which was attributed to its ability to suppress the phosphorylations of key molecules in the LCK signaling pathway. More importantly, 1232030-35-1 treatment demonstrated profound in vivo antileukemia efficacy in a human T-ALL xenograft model. In addition, complementary molecular dynamics simulations provided deeper insight into the binding kinetics between 1232030-35-1 and LCK, highlighting the formation of a hydrogen bond with Met319. Collectively, our study established a robust and effective screening strategy that integrates AI-driven and conventional methodologies for the identification of LCK inhibitors, positioning 1232030-35-1 as a highly promising and novel drug-like candidate for potential applications in treating T-ALL.

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OBJECTIVES: Endocardial trabeculae undergo varicose changes and hyperplasia in response to hemodynamic influences and are a variable phenotype reflecting changes in disease. Fractal analysis has been used to analyze the complexity of endocardial trabeculae in a variety of cardiomyopathies. The aim of this paper was to quantify the myocardial trabecular complexity through fractal analysis and to investigate its predictive value for the diagnosis of heart failure with preserved ejection fraction (HFpEF) in patients with multivessel coronary artery disease (CAD). METHODS: The retrospective study population consisted of 97 patients with multivessel CAD, 39 of them were diagnosed with HFpEF, while 46 healthy volunteers were recruited as controls. Fractal dimension (FD) was obtained through fractal analysis of endocardial trabeculae on LV short-axis cine images. Logistic regression analyses were used to confirm the predictors and compare different prediction models. RESULTS: Mean basal FD was significantly higher in patients with HFpEF than in patients without HFpEF or in the healthy group (median: 1.289; IQR: 0.078; p < 0.05). Mean basal FD was also a significant independent predictor in univariate and multivariate logistic regression (OR: 1.107 and 1.043, p < 0.05). Furthermore, adding FD to the prediction model improved the calibration and accuracy of the model (c-index: 0.806). CONCLUSION: The left ventricular FD obtained with fractal analysis can reflect the complexity of myocardial trabeculae and has an independent predictive value for the diagnosis of HFpEF in patients with multivessel CAD. Including FD into the diagnostic model can help improve the diagnosis. CRITICAL RELEVANCE STATEMENT: Differences show in the complexity of endocardial trabeculae in multivessel coronary artery disease patients, and obtaining fractal dimensions (FD) by fractal analysis can help identify heart failure with preserved ejection fraction (HFpEF) patients. KEY POINTS: The complexity of myocardial trabeculae differs among patients with multivessel coronary artery disease. Left ventricular fractal dimensions can reflect the complexity of the myocardial trabecular. Fractal dimensions have predictive value for the diagnosis of heart failure with preserved ejection fraction.

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Background: The application of Pringle maneuver (PM) during hepatectomy reduces intraoperative blood loss and the need for perioperative transfusion, but its effect on long-term recurrence and survival for patients with hepatocellular carcinoma (HCC) remains controversial. We sought to determine the association between the application of PM and post-hepatectomy oncologic outcomes for patients with HCC. Methods: Patients who underwent curative hepatectomy for HCC at 9 Chinese hospitals from January 2010 to December 2018 were identified. Using two propensity score methods [propensity score matching (PSM) and inverse probability of treatment weight (IPTW)], cumulative recurrence rate and cancer-specific mortality (CSM) were compared between the patients in the PM and non-PM groups. Multivariate competing-risks regression models were performed to adjust for the effect of non-cancer-specific mortality and other prognostic risk factors. Results: Of the 2,798 included patients, 2,404 and 394 did and did not adopt PM (the PM and non-PM groups), respectively. The rates of intraoperative blood transfusion, postoperative 30-day mortality and morbidity were comparable between the two groups (all P>0.05). In the PSM cohort by the 1:3 ratio, compared to 382 patients in the non-PM group, 1,146 patients in the PM group also had the higher cumulative 5-year recurrence rate and CSM (63.9% and 39.1% vs. 55.3% and 31.6%, both P<0.05). Similar results were also yielded in the entire cohort and the IPTW cohort. Multivariate competing-risks regression analyses demonstrated that no application of the PM was independently associated with lower recurrence rate and CSM based on various analytical cohorts [hazard ratio (HR), 0.82 and 0.77 in the adjusted entire cohort, HR 0.80 and 0.73 in the PSM cohort, and HR 0.80 and 0.76 in the IPTW cohort, respectively]. Conclusions: The findings suggested that no application of PM during hepatectomy for patients with HCC reduced the risk of postoperative recurrence and cancer-specific death by approximately 20-25%.

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BACKGROUND: Despite the Barcelona Clinic Liver Cancer system discouraging hepatectomy for intermediate/advanced hepatocellular carcinoma, the procedure is still performed worldwide, particularly in Asia. This study aimed to develop and validate nomograms for predicting survival and recurrence for these patients. METHODS: We analyzed patients who underwent curative-intent hepatectomy for intermediate/advanced hepatocellular carcinoma between 2010 and 2020 across 3 Chinese hospitals. The Eastern Hepatobiliary Surgery Hospital cohort was used as the training cohort for the nomogram construction, and the Jilin First Hospital and Fujian Mengchao Hepatobiliary Hospital cohorts served as the external validation cohorts. Independent preoperative predictors for survival and recurrence were identified through univariable and multivariable Cox regression analyses. Predictive accuracy was measured using the concordance index and calibration curves. The predictive performance between nomograms and conventional hepatocellular carcinoma staging systems was compared. RESULTS: A total of 1,328 patients met the inclusion criteria. The nomograms for predicting survival and recurrence were developed using 10 and 6 independent variables, respectively. Nomograms' concordance indices in the training cohort were 0.777 (95% confidence interval 0.759-0.800) and 0.719 (95% confidence interval 0.697-0.742) for survival and recurrence, outperforming 4 conventional staging systems (P < .001). Nomograms accurately stratified risk into low, intermediate, and high subgroups. These results were validated well by 2 external validation cohorts. CONCLUSION: We developed and validated nomograms predicting survival and recurrence for patients with intermediate/advanced hepatocellular carcinoma, contradicting Barcelona Clinic Liver Cancer surgical guidelines. These nomograms may facilitate clinicians to formulate personalized surgical decisions, estimate long-term prognosis, and strategize neoadjuvant/adjuvant anti-recurrence therapy.

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BACKGROUND AND AIMS: Alcohol use and anxiety often co-occur, causing increased severity impairment. This protocol describes a randomized controlled trial (RCT) that aims to test the efficacy and cost-effectiveness of a web-based, self-guided alcohol and anxiety-focused program, compared with a web-based brief alcohol-focused program, for young adults who drink at hazardous levels and experience anxiety. It will also test moderators and mechanisms of change underlying the intervention effects. DESIGN: This RCT will be conducted with a 1:1 parallel group. SETTING: The study will be a web-based trial in Australia. PARTICIPANTS: Individuals aged 17-30 years who drink alcohol at hazardous or greater levels and experience at least mild anxiety (n = 500) will be recruited through social media, media (TV, print) and community networks. INTERVENTION AND COMPARATOR: Participants will be randomly allocated to receive a web-based, integrated alcohol-anxiety program plus technical and motivational telephone/e-mail support (intervention) or a web-based brief alcohol-feedback program (control). MEASUREMENTS: Clinical measures will be assessed at baseline, post-intervention (2 months), 6 months (primary end-point), 12 months and 18 months. Co-primary outcomes are hazardous alcohol consumption and anxiety symptom severity. Secondary outcomes are binge-drinking frequency; alcohol-related consequences; depression symptoms; clinical diagnoses of alcohol use or anxiety disorder (at 6 months post-intervention), health-care service use, educational and employment outcomes; and quality of life. Mediators and moderators will also be assessed. Efficacy will be tested using mixed models for repeated measures within an intention-to-treat framework. The economic evaluation will analyze individual-level health and societal costs and outcomes of participants between each trial arm, while mediation models will test for mechanisms of change. COMMENTS: This will be the first trial to test whether a developmentally targeted, web-based, integrated alcohol-anxiety intervention is effective in reducing hazardous alcohol use and anxiety severity among young adults. If successful, the integrated alcohol-anxiety program will provide an accessible intervention that can be widely disseminated to improve wellbeing of young adults, at minimal cost.

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Purpose: Results from studies of extended capecitabine after the standard adjuvant chemotherapy in early stage triple-negative breast cancer (TNBC) were inconsistent, and only low-dose capecitabine from the SYSUCC-001 trial improved disease-free survival (DFS). Adjustment of the conventional adjuvant chemotherapy doses affect the prognosis and may affect the efficacy of subsequent treatments. This study investigated whether the survival benefit of the SYSUCC-001 trial was affected by dose adjustment of the standard adjuvant chemotherapy or not. Patients and Methods: We reviewed the adjuvant chemotherapy regimens before the extended capecitabine in the SYSUCC-001 trial. Patients were classified into "consistent" (standard acceptable dose) and "inconsistent" (doses lower than acceptable dose) dose based on the minimum acceptable dose range in the landmark clinical trials. Cox proportional hazards model was used to investigate the impact of dose on the survival outcomes. Results: All 434 patients in SYSUCC-001 trial were enrolled in this study. Most of patients administered the anthracycline-taxane regimen accounted for 88.94%. Among patients in the "inconsistent" dose, 60.8% and 47% received lower doses of anthracycline and taxane separately. In the observation group, the "inconsistent" dose of anthracycline and taxane did not affect DFS compared with the "consistent" dose. Moreover, in the capecitabine group, the "inconsistent" anthracycline dose did not affect DFS compared with the "consistent" dose. However, patients with "consistent" taxane doses benefited significantly from extended capecitabine (P=0.014). The sufficient dose of adjuvant taxane had a positive effect of extended capecitabine (hazard ratio [HR] 2.04; 95% confidence interval [CI] 1.02 to 4.06). Conclusion: This study found the dose reduction of adjuvant taxane might negatively impact the efficacy of capecitabine. Therefore, the reduction of anthracycline dose over paclitaxel should be given priority during conventional adjuvant chemotherapy, if patients need dose reduction and plan for extended capecitabine.