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Adult attention deficit hyperactivity disorder (ADHD), a prevalent psychiatric disorder, significantly impacts social, academic, and occupational functioning. However, it has been relatively less prioritized compared to childhood ADHD. This study employed a functional near-infrared spectroscopy (fNIRS) during verbal fluency tasks in conjunction with machine learning (ML) techniques to differentiate between healthy controls (N =75) and ADHD individuals (N =120). Efficient feature selection in high-dimensional fNIRS datasets is crucial for improving accuracy. To address this, we propose a hybrid feature selection method that combines a wrapper-based and embedded approach, termed Bayesian-Tuned Ridge RFECV (BTR-RFECV). The proposed method facilitated streamlined feature selection and hyperparameter tuning in high-dimensional data, thereby reducing the number of features while enhancing accuracy. HbO features from the combined frontal and temporal regions were key, with the models achieving precision (89.89%), recall (89.74%), F-1 score (89.66%), accuracy (89.74%), MCC (78.36%), and GDR (88.45%). The outcomes of this study highlight the promising potential of combining fNIRS with ML as diagnostic tools in clinical settings, offering a pathway to significantly reduce manual intervention.

Abstract Background Nicotine use and nicotine use disorder (NUD) are the leading causes of preventable death in the United States. Persons with mental disorders (e.g., bipolar disorder) are differentially susceptible to nicotine use. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are indicated for type 2 diabetes mellitus (T2DM) and obesity and show preliminary evidence of efficacy in addiction-related behaviours. Herein, we synthesize extant preclinical and clinical evidence evaluating the effect of GLP-1RAs on neurobiological systems and behaviours salient to nicotine consumption and cessation. Methods Online databases (MedLine, Embase, AMED, PsychINFO, JBI EBP Database, PubMed, Web of Science, Google Scholar) were searched from inception to May 21, 2024. Relevant studies were also extracted from the reference lists of the obtained articles. All articles were screened against inclusion and exclusion criteria. Results Administration of GLP-1RAs reduced nicotine self-administration and nicotine-seeking behaviour in animal models that, in some cases, is sustained beyond exposure to the agent. GLP-1RAs also mitigated post-nicotine cessation weight gain, craving, withdrawal, and hyperphagia. The preceding effects are attributable to modulation of reward-related brain regions (e.g., mesolimbic dopamine system), resulting in nicotine aversion. GLP-1RAs were also efficacious as adjunctive therapies [e.g., in combination with nicotine replacement therapies (NRTs)]. Conclusion The multi-effect characteristics in NUD paradigms provide a compelling rationale for large, adequately powered, long-term, randomized controlled trials of GLP-1RAs in the treatment and prevention of NUD. The replicated effect on mitigating post-nicotine cessation weight gain is a differentiating feature of GLP-1RAs from extant proven therapies for NUD.

Background: Calcification of the ascending and/or descending thoracic aorta is easily measured via non-contrast cardiac computed tomography (CT), commonly performed for quantification of coronary artery calcium (CAC). We assessed whether thoracic aortic calcium (TAC) further improves long-term cardiovascular disease (CVD) risk stratification beyond CAC alone. Methods: Cardiac CT was performed among 6,783 asymptomatic Multi-Ethnic Study of Atherosclerosis participants at baseline. Cox proportional hazards regression assessed the association of TAC with incident CVD and all-cause mortality over a median follow-up of 17.7 years, adjusting for CVD risk factors and CAC. Results: The mean age was 62.1 years old, 53% were female, and 28% had TAC. Over a median follow-up of 17.7 years, 48% of participants with TAC ≥500 experienced CVD and 72% died. Compared to TAC=0, TAC ≥500 was significantly associated with an increased risk of CVD (HR=1.28, 95% CI: 1.06-1.54) and all-cause mortality (HR=1.44, 95% CI: 1.25–1.65), with the strongest association among persons with CAC=0 (CVD HR=1.79, 95% CI: 1.04–3.07; all-cause mortality HR=1.82, 95% CI: 1.29–2.56). The addition of TAC to traditional risk factors and CAC did not improve CVD discrimination (ΔC-statistic=+0.002, p=0.12), but incrementally improved prediction of all-cause mortality (CVD: ΔC-statistic=+0.002, p=0.02). Conclusions: Participants with TAC ≥500 had a high long-term risk for CVD and all-cause mortality. TAC primarily improved risk stratification among persons with CAC=0.

Groundbreaking strategies for preventive cardiology were showcased at the 2024 American Society for Preventive Cardiology (ASPC) Congress on Cardiovascular Disease (CVD) Prevention held in Salt Lake City, Utah, from August 2nd to 4th, 2024. The event featured 69 moderators and 13 scientific sessions comprised of 98 topics, 36 satellite events, 133 poster presentations, and 27 lifestyle classes.The conference highlighted innovative strategies focused on integrating cardiovascular, kidney, and metabolic health, presenting a cohesive approach for managing complex, interrelated conditions. Pivotal studies have addressed the role of lipid-lowering therapies, the benefits of early statin initiation, and the importance of precision medicine in preventing CVD.The ASPC's emphasis on translating this research into practical clinical tools has the potential to revolutionize preventive care strategies, making strides toward reducing the burden of CVD globally and improving long-term patient outcomes through personalized and early intervention approaches.

BackgroundUnguided internet-based cognitive behavioral therapy (ICBT) has been proven effective for major depressive disorder (MDD). However, few studies have examined its cost-effectiveness in low-resource countries and under nonspecialist routine care. ObjectiveThis study aimed to evaluate the short- and long-term cost utility of unguided ICBT compared to a waitlist control for persons with MDD from the perspectives of society and the health care system. MethodsThis analysis was implemented alongside an 8-week 2-arm randomized controlled trial with a 12-month follow-up period conducted in Shenzhen, China. Outcomes including cost and health utility were collected at the pretreatment and posttreatment time points and 3, 6, and 12 months after the intervention. Direct medical costs and indirect costs were prospectively collected using the hospital information system and the Sheehan Disability Scale. Health outcomes were measured using the Chinese version of the Short-Form Six-Dimension health index. The primary outcome was incremental cost utility ratio (ICUR) expressed as the difference in costs between 2 therapies by the difference in quality-adjusted life years (QALYs). The seemingly unrelated regression model and the bootstrap method were performed to estimate adjusted ICURs. Cost-effectiveness planes and cost-effectiveness acceptability curves were used to demonstrate uncertainty. A series of scenario analyses were conducted to verify the robustness of base-case results. ResultsIn total, 244 participants with MDD were randomly allocated to the ICBT (n=122, 50%) or waitlist control (n=122, 50%) groups. At the pretreatment time point, no statistically significant difference was observed in direct medical cost (P=.41), indirect cost (P=.10), or health utility (P=.11) between the 2 groups. In the base-case analysis, the ICBT group reported higher direct medical costs and better quality of life but lower total costs at the posttreatment time point. The adjusted ICURs at the posttreatment time point were CN ¥–194,720.38 (US $–26,551.50; 95% CI CN ¥–198,766.78 to CN ¥–190,673.98 [US $–27,103.20 to US $–25,999.70]) and CN ¥49,700.33 (US $6776.99; 95% CI CN ¥46,626.34-CN ¥52,774.31 [US $6357.83-$7196.15]) per QALY from the societal and health care system perspectives, respectively, with a probability of unguided ICBT being cost-effective of 75.93% and 54.4%, respectively, if the willingness to pay was set at 1 time the per-capita gross domestic product. In the scenario analyses, the probabilities increased to 76.85% and 77.61%, respectively, indicating the potential of ICBT to be cost-effective over the long term. ConclusionsUnguided ICBT is a cost-effective treatment for MDD. This intervention not only helps patients with MDD improve clinically but also generates societal savings. These findings provide health economic evidence for a potential scalable MDD treatment method in low- and middle-income countries. Trial RegistrationChinese Clinical Trial Registry (ChiCTR) ChiCTR2100046425; https://tinyurl.com/bdcrj4zv

Background Up to 15% of survivors of COVID-19 infection experience long-term health effects, including fatigue, myalgia and impaired cognitive function, termed post-COVID-19 condition or long COVID. Several trials that study the benefits and harms of various interventions to manage long COVID have been published and hundreds more are planned or are ongoing. Trustworthy systematic reviews that clarify the benefits and harms of interventions are critical to promote evidence-based practice.Objective To create and maintain a living systematic review and network meta-analysis addressing the benefits and harms of pharmacologic and non-pharmacologic interventions for the treatment and management of long COVID.Methods Eligible trials will randomise adults with long COVID to pharmacologic or non-pharmacologic interventions, placebo, sham or usual care. We will identify eligible studies by searching MEDLINE, EMBASE, CINAHL, PsycINFO, AMED and CENTRAL from inception, without language restrictions.Reviewers will work independently and in duplicate to screen search records, collect data from eligible trials, including trial and patient characteristics and outcomes of interest and assess risk of bias. Our outcomes of interest will include patient-reported fatigue, pain, postexertional malaise, changes in education or employment status, cognitive function, mental health, dyspnoea, quality of life, physical function, recovery and serious adverse events.For each outcome, when possible, we will perform a frequentist random-effects network meta-analysis. When there are compelling reasons to suspect that certain interventions are only applicable or effective for a subtype of long COVID, we will perform separate network meta-analyses. The Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach will guide our assessment of the certainty of evidence.We will update our living review biannually, on the publication of a seminal trial, or when new evidence emerges that may change clinical practice.Conclusion This living systematic review and network meta-analysis will provide comprehensive, trustworthy and up-to-date summaries of the evidence addressing the benefits and harms of interventions for the treatment and management of long COVID. We will make our findings available publicly and work with guideline-producing organisations to inform their recommendations.Ethics and dissemination The study describes the protocol for a systematic review that uses data from published trial reports. Therefore, the study is exempt from ethics review. We intend to deposit all data in a public repository and publish each iteration of the living review online.

Background: Childhood trauma (CT) exposure is associated with a more pernicious course in bipolar disorder (BD). However, few studies have reported differences between BD I and BD II regarding CT exposure. We explore the differences in the CT trajectories in bipolar disorders. Methods: A retrospective cohort study of individuals with BD (BD I = 73 vs BD II = 73) was carried out. Early age at onset (EAO) and suicide ideation/behavior were used as severity outcomes. Timespan between EAO and treatment was documented and the associations between CT and comorbid alcohol used disorder (AUD), anxiety disorders (AD), and post-traumatic stress disorder (PTSD) were also described. Univariate, bivariate analyses, and a Poisson regression model with bootstrap resampling were used. Results: Higher scores of CT, physical abuse (PA), and sexual abuse (SA) were statistically significant for BD II than BD I (p < 0.001, p = 0.048, p < 0.001, respectively). Early age at onset, suicide ideation/behavior and treatment delay were associated with CT in both BD I and BD II. However, AUD and PTSD showed association with CT only for BD I. Limitations: Sample size, non-comparison control group, and recall bias. Conclusions: There are differences in CT subtype exposure between BD I and BD II with regards to early age onset, suicide ideation/behavior, delayed time to treatment, and comorbid mental disorders. These results claim for early access to strategies such as CT exposure screening in individuals with BD to detect possible pernicious course and improve the quality of life and clinical outcomes.

Abstract There is insufficient evidence to guide dose and frequency optimization with repeated-dose ketamine for depression. This study assessed the value of symptomatic non-improvement after the first few ketamine infusions as a predictor of overall non-response in depression for early decision-making to discontinue treatment. A total of 135 individuals with major depressive disorder or bipolar disorder experiencing a current major depressive episode were administered six repeated doses of intravenous ketamine. Depressive symptoms were assessed using the Montgomery-Åsberg Depression Rating Scale (MADRS) at baseline, 4 h after the first infusion, and 24 h after each infusion. Improvement, partial response, and response were defined as a reduction rate of ≥ 20%, 30%, and 50% in MADRS scores, respectively. This study examined the relationship between improvement (as opposed to non-improvement after each infusion or consecutive non-improvements after the first few infusions) and partial response and response after the sixth infusion. This analysis was summarized using sensitivity, specificity, and other diagnostic test parameters. The sensitivities of improvement at 24 h post-infusion 4 and improvement at 24 h post-infusion 3, vs. three consecutive non-improvements, as predictors for overall partial response and response exceeded 90%. No significant reduction in depressive symptoms was seen in non-improvers following the remaining infusions after the above-identified point. Our study suggests that non-improvement after four infusions, or more conservatively three consecutive non-improvements after three infusions, could serve as a signal of overall non-response to repeated-dose intravenous ketamine for depression and that subsequent treatments would not be warranted.

These 4 hypothetical cases highlight new features of the American Heart Association cardiovascular-kidney-metabolic (CKM) health construct. The cases incorporate the CKM staging system, estimates from the PREVENT risk calculator, and clinical approaches related to CKM stages and individual risk profiles. Topics include management considerations for (1) a patient with stage 1 obesity and impaired glucose tolerance, (2) a patient with metabolic risk factors and moderate-risk chronic kidney disease (CKD), (3) a patient with subclinical atherosclerotic cardiovascular disease and multiple comorbid conditions, and (4) a patient with metabolic risk factors, prior myocardial infarction, new-onset heart failure, atrial fibrillation, and CKD.

Background Prepregnancy diabetes and obesity are associated with hypertensive disorders of pregnancy (HDPs). However, the proportion of cases of HDP in the population explained by diabetes and obesity (population attributable fraction), especially among American Indian and Alaska Native and Native Hawaiian and Other Pacific Islander, is not well characterized. Methods and Results We conducted a cross‐sectional analysis of data on individuals with a live singleton birth from the US National Vital Statistics System between 2016 and 2019. We used adjusted logistic regression to estimate the prevalence odds ratios of HDPs and tested interaction for race and ethnicity. We calculated the population attributable fraction for the effect of obesity and diabetes on HDPs. Among 13 201 338 birthing individuals, (mean age, 29±6 years), 7% had HDP. The prevalence of HDP was highest among American Indian and Alaska Native individuals (9.1%). Prepregnancy diabetes (prevalence odds ratio, 2.63 [95% CI, 2.59–2.67]) and obesity (prevalence odds ratio, 2.95 [95% CI, 2.93–2.97]) were associated with HDPs. Compared with non‐Hispanic White individuals, the association of diabetes with HDPs was strongest among Native Hawaiian and Other Pacific Islander (prevalence odds ratio, 3.05 [95% CI, 2.48–3.77]), and the association of obesity with HDP was strongest among Asian individuals (prevalence odds ratio, 3.44 [95% CI, 3.35–3.54]; all P for interaction

IntroductionThis study addresses the rising cardiovascular disease (CVD) rates in the United Arab Emirates (UAE) by investigating the occurrence and impact of genetic variants in CVD-related genes.MethodsWe collected all genes linked to heritable CVD from public and diagnostic databases and mapped them to their corresponding biological processes and molecular pathways. We then evaluated the types and burden of genetic variants within these genes in 343 individuals from the Emirati Mendelian Study Cohort and 3,007 national electronic health records.ResultsWe identified a total of 735 genes associated with heritable CVD, covering a range of cardiovascular conditions. Enrichment analysis revealed key biological processes and pathways, including Apelin, FoxO, and Ras signaling, that are implicated across all forms of heritable CVD. Analysis of a UAE cohort of 3,350 individuals showed a predominance of rare and unique CVD variants specific to the population. The study found a significant burden of pathogenic variants in families with CVD within the Emirati Mendelian cohort and re-assessed the pathogenicity of 693 variants from national health records, leading to the discovery of new CVD-causing variants.DiscussionThis study underscores the importance of continuously updating our understanding of genes and pathways related to CVD. It also highlights the significant underrepresentation of the UAE population in public databases and clinical literature on CVD genetics, offering valuable insights that can inform future research and intervention strategies.

The purpose of this summary is to explain key findings from a study that included people with bipolar I disorder, as described in two separate articles (see the ‘Further Information’ section for more details). The study compared a new formulation of aripiprazole, given as an injection once every 2 months, with a once‑monthly injection of aripiprazole.

Plastogens are a class of therapeutics that function by rapidly promoting changes in neuroplasticity. A notable example, ketamine, is receiving great attention due to its combined rapid and long-term antidepressant effects. Ketamine is an N-methyl-D-aspartate receptor (NMDAR) antagonist, and, in addition to its therapeutic activity, it is associated with psychotomimetic and dissociative side effects. Stinels—rapastinel, apimostinel, and zelquistinel—are also plastogens not only with rapid and long-term antidepressant effects but also with improved safety and tolerability profiles compared to ketamine. Previous descriptions of the mechanism by which stinels modulate NMDAR activity have been inconsistent and, at times, contradictory. The purpose of this review is to clarify the mechanism of action and contextualize stinels within a broader class of NMDAR-targeting therapeutics. In this review, we present the rationale behind targeting NMDARs for treatment-resistant depression and other psychiatric conditions, describe the various mechanisms by which NMDAR activity is regulated by different classes of therapeutics, and present evidence for the stinel mechanism. In contrast with previous descriptions of glycine-like NMDAR partial agonists, we define stinels as positive allosteric modulators of NMDAR activity with a novel regulatory binding site.

Climate change is a public health crisis predominantly due to fossil fuel combustion, that challenges planetary and human health. Considerable evidence exists to demonstrate the impact climate change has on cardiovascular disease primarily through air pollution, and non-optimal temperature. Conversely, healthcare systems themselves contribute substantially to climate change. Many clinicians personally report a sense of responsibility to reduce the detrimental impact of parts of our healthcare system on the environment. Roadmaps exist to guide decarbonization and reduce pollution in the healthcare sector. The first step in minimizing the climate impact of the provision of cardiovascular care is to determine the carbon footprint of highly resource dependent sectors such as critical care cardiology as well as the cardiac catheterization and electrophysiology laboratories. This should be followed by sustainable changes to address healthcare waste and energy use. Engagement from healthcare leadership, governmental organizations and major cardiac societies will be necessary to impact meaningful change.

Objective: Elevated lipoprotein(a) [Lp(a)] is an independent, genetically determined risk factor for atherosclerotic cardiovascular disease (ASCVD). We evaluated the frequency of testing for elevated Lp(a) and subsequent management at the Johns Hopkins Hospital, a large academic medical center, over a 5-year period. Methods: The Johns Hopkins Hospital (JHH) electronic medical record was queried to identify patients with an encounter between 2017 and 2021, either with established ASCVD or at increased risk, defined as being on any lipid lowering medication or having LDL-C ≥ 190 mg/dL. The frequency of Lp(a) testing and of elevated levels were identified for each year. Results: Among 111,350 unique adult patients, 2,785 (2.5 %) had at least one Lp(a) test. Patients with Lp(a) testing, compared to those without testing, were younger (mean age 56 years vs. 66 years), more often female (49 % vs. 44 %), Black (24.7 % vs. 24.6 %) or “other” race/ethnicity (12 % vs 10 %), and had higher LDL-C levels (median 118 vs. 91 mg/dL; p < 0.001). The number and frequency of Lp(a) testing increased from 167 (0.57 %) in 2017 to 1155 (5.67 %) in 2021. Lp(a) levels were abnormal in 43.4 % of patients (moderate [75–125 nmol/L]: 10.3 %, high [126–600 nmol/L]: 32.2 %, severe [>600 nmol/L]: 0.9 %). Among 920 patients with high or severe Lp(a) levels, 200 (22 %) had a subsequent referral to cardiology or lipid specialist, and 180 (20 %) had a new lipid-lowering medication prescribed in the subsequent 18 months. Conclusion: Based on a single-center experience, the frequency of incident Lp(a) testing among increased-risk patients was low but increased significantly over 5-years, likely due to Lipid Clinic referrals with reflex Lp(a) testing and greater awareness about this risk factor. Future work should target appropriate population based Lp(a) testing strategies and clinical decision-making regarding risk management once Lp(a) elevation is diagnosed.

The American Heart Association (AHA) has devised Life's Essential 8, a set of eight evidence-based health behaviors that play a crucial role in optimizing cardiovascular health and overall well-being. In addition to Life's Essential 8, enhanced screening for Cardiovascular-Kidney-Metabolic (CKM) Syndrome risk factors into routine athlete screening also provides a more comprehensive approach for ensuring athlete safety and long-term health. Incorporating Life's Essential 8 and CKM Syndrome metrics into athlete health evaluations will improve the sports performance of athletes and help optimize their long-term health.

Background: This study aimed to explore the longitudinal associations of rumination with suicidal ideation and suicide attempts in individuals with major depressive disorder (MDD). Methods: Participants were derived from the Depression Cohort in China study (DCC). Those who completed at least one follow-up visit during the 12 months were included in the analysis. Dimensions of rumination including brooding and reflection were each measured using five items of the Ruminative Responses Scale. Suicidal ideation was assessed using the Beck Scale for Suicide Ideation. Suicide attempts were also assessed and all were analyzed with generalized estimating equations. Results: Our final sample included 532 participants aged 18 to 59 years (mean [SD], 26.91 [6.94] years) consisting of 148 (27.8%) males and 384 (72.2%) females. After adjusting for temporal trend and potential confounders, individuals with higher levels of reflection were more likely to report suicidal ideation (AOR =1.11, 95% CI:1.01–1.22). However, no statistically significant association was found between brooding and suicidal ideation (AOR =1.06, 95% CI:0.96–1.17). Conversely, individuals with higher levels of brooding were more likely to report suicide attempts (AOR =1.13, 95% CI:1.02–1.24), while no statistically significant association was observed between reflection and suicide attempts (AOR =0.91, 95% CI:0.82–1.01). Conclusion: Rumination reflects a disturbance in cognitive emotional processing and manifests in different dimensions. Our findings suggest that high levels of reflection and brooding may be associated with a higher likelihood of having suicidal ideation and suicide attempts, respectively. However, it should be interpreted with caution, given that effect sizes are small.

Abstract Hypertension (HTN) affects over 1.2 billion individuals worldwide and is defined as systolic blood pressure (BP) ≥ 140 mmHg and diastolic BP ≥ 90 mmHg. Hypertension is also considered a high risk factor for cerebrovascular diseases, which may lead to vascular cognitive impairment (VCI). VCI is associated with executive dysfunction and is also a transitional stage between hypertension and vascular dementia. Hence, it is essential to establish a reliable approach to diagnosing the severity of VCI. In 28 HTN (51–83 yrs; 18 males, 10 females) and 28 healthy controls (HC) (51–75 yrs; 7 males, 21 females), we investigated which regions demonstrate alterations in the resting-state functional connectome due to vascular cognitive impairment in HTN by using the amplitude of the low-frequency fluctuations (ALFF), regional homogeneity (ReHo), graph theoretical analysis (GTA), and network-based statistic (NBS) methods. In the group comparison between ALFF/ReHo, HTN showed reduced spontaneous activity in the regions corresponding to vascular or metabolic dysfunction and enhanced brain activity, mainly in the primary somatosensory cortex and prefrontal areas. We also observed cognitive dysfunction in HTN, such as executive function, processing speed, and memory. Both the GTA and NBS analyses indicated that the HTN demonstrated complex local segregation, worse global integration, and weak functional connectivity. Our findings show that resting-state functional connectivity was altered, particularly in the frontal and parietal regions, by hypertensive individuals with potential vascular cognitive impairment.

Abstract Understanding the mechanisms that drive TDP-43 pathology is integral to combating amyotrophic lateral sclerosis (ALS), frontotemporal lobar degeneration (FTLD) and other neurodegenerative diseases. Here we generated a longitudinal quantitative proteomic map of the cortex from the cytoplasmic TDP-43 rNLS8 mouse model of ALS and FTLD, and developed a complementary open-access webtool, TDP-map ( https://shiny.rcc.uq.edu.au/TDP-map/ ). We identified distinct protein subsets enriched for diverse biological pathways with temporal alterations in protein abundance, including increases in protein folding factors prior to disease onset. This included increased levels of DnaJ homolog subfamily B member 5, DNAJB5, which also co-localized with TDP-43 pathology in diseased human motor cortex. DNAJB5 over-expression decreased TDP-43 aggregation in cell and cortical neuron cultures, and knockout of Dnajb5 exacerbated motor impairments caused by AAV-mediated cytoplasmic TDP-43 expression in mice. Together, these findings reveal molecular mechanisms at distinct stages of ALS and FTLD progression and suggest that protein folding factors could be protective in neurodegenerative diseases.

Abstract Background Post-COVID-19 Condition (PCC), as defined by the World Health Organization (WHO), currently lacks any regulatory-approved treatments and is characterized by persistent and debilitating cognitive impairment and mood symptoms. Additionally, metabolic dysfunction, chronic inflammation and the associated risks of elevated body mass index (BMI) have been reported. In this study, we aim to investigate the efficacy of vortioxetine in improving cognitive deficits in individuals with PCC, accounting for the interaction of metabolic dysfunction, elevated inflammation and BMI. Methods This is a post-hoc analysis of an 8-week randomized, double-blind, placebo-controlled trial that was conducted among adults aged 18 years and older living in Canada who were experiencing WHO-defined PCC symptoms. The recruitment of participants began in November 2021 and concluded in January 2023. A total of 200 individuals were enrolled, where 147 were randomized in a 1:1 ratio to receive either vortioxetine (5–20 mg, n = 73) or placebo (n = 74) for daily treatment under double-blind conditions. The primary outcome measure was the change in the Digit Symbol Substitution Test (DSST) score from baseline to endpoint. Results Our findings showed significant effects for time (χ2 = 7.771, p = 0.005), treatment (χ2 = 7.583, p = 0.006) and the treatment x time x CRP x TG-HDL x BMI interaction (χ2 = 11.967, p = 0.018) on cognitive function. Moreover, the between-group analysis showed a significant improvement with vortioxetine at endpoint (mean difference = 0.621, SEM = 0.313, p = 0.047). Conclusion Overall, vortioxetine demonstrated significant improvements in cognitive deficits among individuals with baseline markers of metabolic dysfunction, elevated inflammation and higher BMI at endpoint as compared to placebo. Trial Registration NCT05047952 (ClinicalTrials.gov; Registration Date: September 17, 2021).

[INLINE:1] Strong evidence has accumulated to show a correlation between depression symptoms and inflammatory responses. Moreover, anti-inflammatory treatment has shown partial effectiveness in alleviating depression symptoms. Lycium barbarum polysaccharide (LBP), derived from Goji berries, exhibits notable antioxidative and anti-inflammatory properties. In our recent double-blinded randomized placebo-controlled trial, we found that LBP significantly reduced depressive symptoms in adolescents with subthreshold depression. It is presumed that the antidepressant effect of LBP may be associated with its influence on inflammatory cytokines. In the double-blinded randomized controlled trial, we enrolled 29 adolescents with subthreshold depression and randomly divided them into an LBP group and a placebo group. In the LBP group, adolescents were given 300 mg/d LBP. A 6-week follow up was completed by 24 adolescents, comprising 14 adolescents from the LBP group (15.36 ± 2.06 years, 3 men and 11 women) and 10 adolescents from the placebo group (14.9 ± 1.6 years, 2 men and 8 women). Our results showed that after 6 weeks of treatment, the interleukin-17A level in the LBP group was lower than that in the placebo group. Network analysis showed that LBP reduced the correlations and connectivity between inflammatory factors, which were associated with the improvement in depressive symptoms. These findings suggest that 6-week administration of LBP suppresses the immune response by reducing interleukin-17A level, thereby exerting an antidepressant effect.

Abstract Emerging research indicates that high HDL-C levels might not be cardioprotective, potentially worsening cardiovascular disease (CVD) outcomes. Yet, there is no data on HDL-C's association with other CVD risk factors like myocardial fibrosis, a key aspect of cardiac remodeling predicting negative outcomes. We therefore aimed to study the association between HDL-C levels with interstitial myocardial fibrosis (IMF) and myocardial scar measured by CMR T1-mapping and late-gadolinium enhancement (LGE), respectively. There were 1863 participants (mean age of 69 years) who had both serum HDL-C measurements and underwent CMR. Analysis was done among those with available indices of interstitial fibrosis (extracellular volume fraction [ECV]; N = 1172 and native-T1; N = 1863) and replacement fibrosis by LGE (N = 1172). HDL-C was analyzed as both logarithmically-transformed and categorized into

Abstract The Russo-Ukrainian War has led to a humanitarian crisis, and many people volunteered to help affected refugees. This cross-sectional survey study investigates the relationships between the psychological impact of participation, coping mechanisms, and motivational functions of volunteering during the Russo-Ukrainian War among 285 Ukrainian and 435 Polish volunteers (N = 720). Multivariate linear regression was used to examine relationships between motivational functions and psychosocial and demographic characteristics. Ukrainian volunteers reported significantly higher Hyperarousal and Avoidance, Depression, Anxiety, and Stress, Problem-focused, Emotion-focused, and Avoidant coping, as well as total scores of Hardiness and Psychological Capital than Polish counterparts. Linear regression analysis found that Impact of the Event Scale results, Coping with Stress, being a female, unemployed, and religious were significantly associated with higher motivational functions. Ukrainian volunteers could significantly reduce negative feelings and strengthen social networks and religious faith by volunteering, while Polish volunteers were significantly more likely to gain skills and psychosocial development from helping others.

Abstract Amyotrophic lateral sclerosis (ALS) is a severely debilitating neurodegenerative condition that is part of the same disease spectrum as frontotemporal dementia (FTD). Mutations in the CCNF gene, encoding cyclin F, are present in both sporadic and familial ALS and FTD. However, the pathophysiological mechanisms underlying neurodegeneration remain unclear. Proper functioning of the endoplasmic reticulum (ER) and Golgi apparatus compartments is essential for normal physiological activities and to maintain cellular viability. Here, we demonstrate that ALS/FTD-associated variant cyclin FS621G inhibits secretory protein transport from the ER to Golgi apparatus, by a mechanism involving dysregulation of COPII vesicles at ER exit sites. Consistent with this finding, cyclin FS621G also induces fragmentation of the Golgi apparatus and activates ER stress, ER-associated degradation, and apoptosis. Induction of Golgi fragmentation and ER stress were confirmed with a second ALS/FTD variant cyclin FS195R, and in cortical primary neurons. Hence, this study provides novel insights into pathogenic mechanisms associated with ALS/FTD-variant cyclin F, involving perturbations to both secretory protein trafficking and ER-Golgi homeostasis.

Abstract Background Dilated cardiomyopathy (DCM) is a severe, non-ischemic heart disease which ultimately results in heart failure (HF). Decades of research on DCM have revealed diverse aetiologies. Among them, familial DCM is the major form of DCM, with pathogenic variants in LMNA being the second most common form of autosomal dominant DCM. LMNA DCM is a multifactorial and complex disease with no specific treatment thus far. Many studies have demonstrated that perturbing candidates related to various dysregulated pathways ameliorate LMNA DCM. However, it is unknown whether these candidates could serve as potential therapeutic targets especially in long term efficacy. Methods We evaluated 14 potential candidates including Lmna gene products (Lamin A and Lamin C), key signaling pathways (Tgfβ/Smad, mTor and Fgf/Mapk), calcium handling, proliferation regulators and modifiers of LINC complex function in a cardiac specific Lmna DCM model. Positive candidates for improved cardiac function were further assessed by survival analysis. Suppressive roles and mechanisms of these candidates in ameliorating Lmna DCM were dissected by comparing marker gene expression, Tgfβ signaling pathway activation, fibrosis, inflammation, proliferation and DNA damage. Furthermore, transcriptome profiling compared the differences between Lamin A and Lamin C treatment. Results Cardiac function was restored by several positive candidates (Smad3, Yy1, Bmp7, Ctgf, aYAP1, Sun1, Lamin A, and Lamin C), which significantly correlated with suppression of HF/fibrosis marker expression and cardiac fibrosis in Lmna DCM. Lamin C or Sun1 shRNA administration achieved consistent, prolonged survival which highly correlated with reduced heart inflammation and DNA damage. Importantly, Lamin A treatment improved but could not reproduce long term survival, and Lamin A administration to healthy hearts itself induced DCM. Mechanistically, we identified this lapse as caused by a dose-dependent toxicity of Lamin A, which was independent from its maturation. Conclusions In vivo candidate evaluation revealed that supplementation of Lamin C or knockdown of Sun1 significantly suppressed Lmna DCM and achieve prolonged survival. Conversely, Lamin A supplementation did not rescue long term survival and may impart detrimental cardiotoxicity risk. This study highlights a potential of advancing Lamin C and Sun1 as therapeutic targets for the treatment of LMNA DCM. Graphical Abstract

Following the publication of results from multiple landmark cardiovascular outcome trials of antihyperglycemic medications over the past 8 years, there has been a major shift in the focus of care for people with type 2 diabetes, from control of hyperglycemia to managing cardiovascular risk. Multiple international cardiology and diabetes society guidelines and recommendations now endorse sodium‐glucose cotransporter‐2 inhibitors and glucagon‐like protein‐1 receptor agonists as first‐line therapies to mitigate cardiovascular risk. The most recent publication is the 2023 European Society of Cardiology guideline on the management of cardiovascular disease in those with type 2 diabetes that, for the first time, recommends use of both classes of medications for the mitigation of cardiovascular risk for those with or at high risk for atherosclerotic cardiovascular disease, heart failure, and chronic kidney disease. Here, we review the evidence behind contemporary society guidelines and recommendations for the management of type 2 diabetes and cardiovascular risk.

Objective: Many studies support the notion that polygenic risk scores (PRS) improve risk prediction for coronary heart disease (CHD) beyond conventional risk factors. However, PRS are not yet considered risk-enhancing factor in guidelines. Our objective was to determine the predictive performance of a commercially available PRS (CARDIO inCode-Score®) compared with the Pooled Cohorts Equations (PCE) in a contemporary, multi-ethnic cohort. Methods: Participants (n = 63,070; 67 % female; 18 % non-European) without prior CHD were followed from 2007 through 12/31/2022. The association between the PRS and incident CHD was assessed using Cox regression adjusting for genetic ancestry and risk factors. Event rates were estimated by categories of PCE and by low/intermediate/high genetic risk within PCE categories; risk discrimination and net reclassification improvement (NRI) were also assessed. Results: There were 3,289 incident CHD events during 14 years of follow-up. Adjusted hazard ratio (aHR) for incident CHD per 1 SD increase in PRS was 1.18 (95 % CI:1.14–1.22), and the aHR for the upper vs lower quintile of the PRS was 1.66 (95 % CI:1.49–1.86). The association was consistent in both sexes, in European participants compared with all minority groups combined and was strongest in the first 5 years of follow-up. The increase in the C-statistic was 0.004 (0.747 vs. 0.751; p < 0.0001); the NRI was 2.4 (0.9–3.8) for the entire cohort and 9.7 (7.5–12.0) for intermediate PCE risk individuals. After incorporating high genetic risk, a further 10 percent of participants at borderline/intermediate PCE risk would be candidates for statin therapy. Conclusion: Inclusion of polygenic risk improved identification of primary prevention individuals who may benefit from more intensive risk factor modification.

Objective: Lipoprotein(a) [Lp(a)] is an atherogenic and prothrombotic lipoprotein associated with atherosclerotic cardiovascular disease (ASCVD). We assessed the association between regular aspirin use and ASCVD mortality among individuals with versus without elevated Lp(a) in a nationally representative US cohort. Methods: Eligible participants were aged 40–70 years without clinical ASCVD, reported on aspirin use, and had Lp(a) measurements from the Third National Health and Nutrition Examination Survey (NHANES III, 1988–1994), the only cycle of this nationally representative US cohort to measure Lp(a). Regular aspirin use was defined as taking aspirin ≥30 times in the previous month. Using NHANES III linked mortality records and weighted Cox proportional hazards regression, the association between regular aspirin use and ASCVD mortality was observed in those with and without elevated Lp(a) (≥50 versus

BackgroundObesity has become an important threat to children’s health, with physical and psychological impacts that extend into adulthood. Limited physical activity and sedentary behavior are associated with increased obesity risk. Because children spend approximately 6 h each day in school, researchers increasingly study how obesity is influenced by school-day physical activity and energy expenditure (EE) patterns among school-aged children by using wearable devices that collect data at frequent intervals and generate complex, high-dimensional data. Although clinicians typically define obesity in children as having an age-and sex-adjusted body mass index (BMI) value in the high percentiles, the relationships between school-based physical activity interventions and BMI are analyzed using traditional linear regression models, which are designed to assess the effects of interventions among children with average BMI, limiting insight regarding the effects of interventions among children categorized as overweight or obese.MethodsWe investigate the association between wearable device–based EE measures and age-and sex-adjusted BMI values in data from a cluster-randomized, school-based study. We express and analyze EE levels as both a scalar-valued variable and as a continuous, high-dimensional, functional predictor variable. We investigate the relationship between school-day EE (SDEE) and BMI using four models: a linear mixed-effects model (LMEM), a quantile mixed-effects model (QMEM), a functional mixed-effects model (FMEM), and a functional quantile mixed-effects model (FQMEM). The LMEM and QMEM include SDEE as a summary measure, whereas the FMEM and FQMEM allow for the modeling of SDEE as a high-dimensional covariate. The FMEM and FQMEM allow the influence of the time of day at which physical activity is performed to be assessed, which is not possible using the LMEM or the QMEM. The FMEM assesses how frequently collected SDEE data influences mean BMI, whereas the FQMEM assesses the effects on quantile levels of BMI.ResultsThe LMEM and QMEM detected a statistically significant effect of overall mean SDEE on log (BMI) (the natural logarithm of BMI) after adjusting for intervention, age, race, and sex. The FMEM and FQMEM provided evidence for statistically significant associations between SDEE and log (BMI) for only a short time interval. Being a boy or being assigned a stand-biased desk is associated with a lower log (BMI) than being a girl or being assigned a traditional desk. Across our models, age was not a statistically significant covariate, and white students had significantly lower log (BMI) than non-white students in quantile models, but this significant effect was observed for only the 10th and 50th quantile levels of BMI. The functional regression models allow for additional interpretations of the influence of EE patterns on age-and sex-adjusted BMI, whereas the quantile regression models enable the influence of EE patterns to be assessed across the entire BMI distribution.ConclusionThe FQMEM is recommended when interest lies in assessing how device-monitored SDEE patterns affect children of all body types, as this model is robust and able to assess intervention effects across the full BMI distribution. However, the sample size must be sufficiently large to adequately power determinations of covariate effects across the entire BMI distribution, including the tails.

We discuss 12 misperceptions, misstatements, or mistakes concerning the use of covariates in observational or nonrandomized research. Additionally, we offer advice to help investigators, editors, reviewers, and readers make more informed decisions about conducting and interpreting research where the influence of covariates may be at issue. We primarily address misperceptions in the context of statistical management of the covariates through various forms of modeling, although we also emphasize design and model or variable selection. Other approaches to addressing the effects of covariates, including matching, have logical extensions from what we discuss here but are not dwelled upon heavily. The misperceptions, misstatements, or mistakes we discuss include accurate representation of covariates, effects of measurement error, overreliance on covariate categorization, underestimation of power loss when controlling for covariates, misinterpretation of significance in statistical models, and misconceptions about confounding variables, selecting on a collider, and p value interpretations in covariate-inclusive analyses. This condensed overview serves to correct common errors and improve research quality in general and in nutrition research specifically.

Background Coronary artery disease (CAD) is a leading cause of death among the 38.4 million people with HIV globally. The extent to which cardiovascular polygenic risk scores (PRSs) derived in non‐HIV populations generalize to people with HIV is not well understood. Methods and Results PRSs for CAD (GPSMult) and lipid traits were calculated in a global cohort of people with HIV treated with antiretroviral therapy with low‐to‐moderate atherosclerotic cardiovascular disease risk enrolled in REPRIEVE (Randomized Trial to Prevent Vascular Events in HIV). The PRSs were associated with baseline lipid traits in 4495 genotyped participants, and with subclinical CAD in a subset of 662 who underwent coronary computed tomography angiography. Among participants who underwent coronary computed tomography angiography (mean age, 50.9 [SD, 5.8] years; 16.1% women; 41.8% African, 57.3% European, 1.1% Asian), GPSMult was associated with plaque presence with odds ratio (OR) per SD in GPSMult of 1.42 (95% CI, 1.20–1.68; P=3.8×10−5), stenosis >50% (OR, 2.39 [95% CI, 1.48–3.85]; P=3.4×10−4), and noncalcified/vulnerable plaque (OR, 1.45 [95% CI, 1.23–1.72]; P=9.6×10−6). Effects were consistent in subgroups of age, sex, 10‐year atherosclerotic cardiovascular disease risk, ancestry, and CD4 count. Adding GPSMult to established risk factors increased the C‐statistic for predicting plaque presence from 0.718 to 0.734 (P=0.02). Furthermore, a PRS for low‐density lipoprotein cholesterol was associated with plaque presence with OR of 1.21 (95% CI, 1.01–1.44; P=0.04), and partially calcified plaque with OR of 1.21 (95% CI, 1.01–1.45; P=0.04) per SD. Conclusions Among people with HIV treated with antiretroviral therapy without documented atherosclerotic cardiovascular disease and at low‐to‐moderate calculated risk in REPRIEVE, an externally developed CAD PRS was predictive of subclinical atherosclerosis. PRS for low‐density lipoprotein cholesterol was also associated with subclinical atherosclerosis, supporting a role for low‐density lipoprotein cholesterol in HIV‐associated CAD. Registration URL: https://www.reprievetrial.org; Unique identifier: NCT02344290.

Abstract The present study aimed to investigate the factors associated with the level of rumination about the war among people living in Poland and Ukraine. This cross‐sectional study recruited internet users from advertisements on social media. Levels of rumination, Depression, Anxiety and Stress Scale (DASS), Impact of Event Scale‐Revised (IES‐R), time spent on news of the war, and related demographic variables were collected. The reliability and construct validity of rumination were estimated. Potential factors associated with the level of rumination were identified using univariate linear regression analysis, and further entered into a stepwise multivariate linear regression model to identify independent factors. Due to the non‐normality of distribution, multivariate linear regression with 5000 bootstrap samples was used to verify the results. A total of 1438 participants were included in the analysis, of whom 1053 lived in Poland and 385 lived in Ukraine. The questionnaires on rumination were verified to have satisfactory reliability and validity. After analysis with stepwise and bootstrap regression, older age, female gender, higher DASS and IES‐R scores, and longer time spent on news of the war were significantly associated with higher levels of rumination for both people living in Poland and Ukraine. Lower self‐rated health status, history of chronic medical illness and coronavirus disease 2019 infection were also positively associated with rumination for people living in Poland. We identified several factors associated with the level of rumination about the Russo‐Ukrainian War. Further investigations are warranted to understand how rumination affects individuals’ lives during crises such as war.

Abstract Background Typically, animal models studying gastrointestinal microbiotas compromised in early life have employed either germ-free animals or mice treated with a cocktail of antibiotics. Such studies intend to mimic scenarios of infants born by caesarean section and/or subjected to antibiotic treatment. However, the antibiotics used in these studies are rarely prescribed to infants. Therefore, an early life model was developed in which the murine gastrointestinal microbiota was severely disrupted by clindamycin treatment. Results In this mouse model, we investigated the extent supplementation with a synbiotic mixture of prebiotics, being scGOS/lcFOS with the human milk oligosaccharide 2’-Fucosyllactose (2’-FL), in combination with or without single strain or mix of “infant type” bifidobacteria, can rescue an antibiotic-compromised microbiota. Shotgun metagenomic sequencing showed that the microbiota was severely disrupted by the clindamycin challenge. No recovery was observed 3 weeks post-challenge in the scGOS/lcFOS/2’FL group, while the group that received the synbiotic treatment of scGOS/lcFOS/2’-FL with Bifidobacterium breve NRBB01 showed partial recovery. Strikingly in the scGOS/lcFOS/2’-FL group receiving the mixture of bifidobacteria resulted in a recovery of the microbiota disruption. Histological analyses showed that the clindamycin-treated animals at the end of the experiment still suffered from mild oedema and villi/colonic crypt irregularities which was ameliorated by the synbiotic intervention. Conclusion Our study demonstrates that supplementation of synbiotic mixture of scGOS/lcFOS/2’-FL in combination with a specific mix of infant-type bifidobacterial strains is able to partially revive an antibiotic-perturbed gastrointestinal microbiota. Video Abstract

Abstract Living in high expressed emotion (EE) environments tends to increase the relapse rate in schizophrenia (SZ). At present, the neural substrates responsible for high EE in SZ remain poorly understood. Functional near-infrared spectroscopy (fNIRS) may be of great use to quantitatively assess cortical hemodynamics and elucidate the pathophysiology of psychiatric disorders. In this study, we designed novel low- (positivity and warmth) and high-EE (criticism, negative emotion, and hostility) stimulations, in the form of audio, to investigate cortical hemodynamics. We used fNIRS to measure hemodynamic signals while participants listened to the recorded audio. Healthy controls (HCs, $$n=42$$ n = 42 ) showed increased hemodynamic activation in the major language centers across EE stimulations, with stronger activation in Wernicke’s area during the processing of negative emotional language. Compared to HCs, people with SZ ( $$n=41$$ n = 41 ) exhibited smaller hemodynamic activation in the major language centers across EE stimulations. In addition, people with SZ showed weaker or insignificant hemodynamic deactivation in the medial prefrontal cortex. Notably, hemodynamic activation in SZ was found to be negatively correlated with the negative syndrome scale score at high EE. Our findings suggest that the neural mechanisms in SZ are altered and disrupted, especially during negative emotional language processing. This supports the feasibility of using the designed EE stimulations to assess people who are vulnerable to high-EE environments, such as SZ. Furthermore, our findings provide preliminary evidence for future research on functional neuroimaging biomarkers for people with psychiatric disorders.

Abstract The goal of this study was to reproduce and evaluate the reliability of the network meta-analysis performed in the article “The best drug supplement for obesity treatment: A systematic review and network meta-analysis” by Salari et al. In recent years, it has become more common to employ network meta-analysis to assess the relative efficacy of treatments often used in clinical practice. To duplicate Salari et al.‘s research, we pulled data directly from the original trials and used Cohen’s D to determine the effect size for each treatment. We reanalyzed the data since we discovered significant differences between the data we retrieved and the data given by Salari et al. We present new effect size estimates for each therapy and conclude that the prior findings were somewhat erroneous. Our findings highlight the importance of ensuring the accuracy of network meta-analyses to determine the quality and strength of existing evidence.

Abstract Outcomes for patients with melanoma have improved over the past decade with the clinical development and approval of immunotherapies targeting immune checkpoint receptors such as programmed death-1 (PD-1), programmed death ligand 1 (PD-L1) or cytotoxic T lymphocyte antigen-4 (CTLA-4). Combinations of these checkpoint therapies with other agents are now being explored to improve outcomes and enhance benefit-risk profiles of treatment. Alternative inhibitory receptors have been identified that may be targeted for anti-tumor immune therapy, such as lymphocyte-activation gene-3 (LAG-3), as have several potential target oncogenes for molecularly targeted therapy, such as tyrosine kinase inhibitors. Unfortunately, many patients still progress and acquire resistance to immunotherapy and molecularly targeted therapies. To bypass resistance, combination treatment with immunotherapies and single or multiple TKIs have been shown to improve prognosis compared to monotherapy. The number of new combinations treatment under development for melanoma provides options for the number of patients to achieve a therapeutic benefit. Many diagnostic and prognostic assays have begun to show clinical applicability providing additional tools to optimize and individualize treatments. However, the question on the optimal algorithm of first- and later-line therapies and the search for biomarkers to guide these decisions are still under investigation. This year, the Melanoma Bridge Congress (Dec 1st–3rd, 2022, Naples, Italy) addressed the latest advances in melanoma research, focusing on themes of paramount importance for melanoma prevention, diagnosis and treatment. This included sessions dedicated to systems biology on immunotherapy, immunogenicity and gene expression profiling, biomarkers, and combination treatment strategies.

Background It is unclear how metabolic syndrome (MetS) and diabetes affect Gal‐3 (galectin 3) levels and the resulting implications for heart failure (HF) risk. We assessed relationships of MetS and diabetes with Gal‐3, and their joint associations with incident HF. Methods and Results We included 8445 participants without HF (mean age, 63 years; 59% men; 16% Black race) at ARIC (Atherosclerosis Risk in Communities) study visit 4 (1996–1999). We categorized participants as having MetS only, MetS with diabetes, or neither, and by quartiles of MetS severity Z score. We assessed cross‐sectional associations of metabolic risk categories with high Gal‐3 level (≥75th percentile) using logistic regression. We used Cox regression to evaluate combined associations of metabolic risk categories and Gal‐3 quartiles with HF. In cross‐sectional analyses, compared with no MetS and no diabetes, MetS only (odds ratio [OR], 1.24 [95% CI, 1.10–1.41]) and MetS with diabetes (OR, 1.59 [95% CI, 1.32–1.92]) were associated with elevated Gal‐3. Over a median follow‐up of 20.5 years, there were 1749 HF events. Compared with individuals with neither diabetes nor MetS and with Gal‐3 in the lowest quartile, the combination of MetS with diabetes and Gal‐3 ≥75th percentile was associated with a 4‐fold higher HF risk (hazard ratio, 4.35 [95% CI, 3.30–5.73]). Gal‐3 provided HF prognostic information above and beyond MetS, NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide), high‐sensitivity cardiac troponin T, and CRP (C‐reactive protein) (ΔC statistic for models with versus without Gal‐3: 0.003; P=0.004). Conclusions MetS and diabetes are associated with elevated Gal‐3. The HF risk significantly increased with the combination of greater metabolic risk and higher Gal‐3.

ObjectiveBreast cancer was the most prevalent type of cancer and had the highest incidence rate among women worldwide. The wide use of adjuvant chemotherapy might have a detrimental effect on the human brain and result in chemotherapy-related cognitive impairment (CICI) among breast cancer patients. Furthermore, prior to chemotherapy, patients reported cancer-related cognitive impairment (CRCI), which might be due to physiological factors or mood symptoms. The present longitudinal study aimed to investigate microstructural and macroscale white matter alterations by generalized q-sampling imaging (GQI).MethodsThe participants were categorized into a pre-chemotherapy group (BB) if they were diagnosed with primary breast cancer and an age-matched noncancer control group (HC). Some participants returned for follow-up assessment. In the present follow up study, 28 matched pairs of BB/BBF (follow up after chemotherapy) individuals and 28 matched pairs of HC/HCF (follow up) individuals were included. We then used GQI and graph theoretical analysis (GTA) to detect microstructural alterations in the whole brain. In addition, we evaluated the relationship between longitudinal changes in GQI indices and neuropsychological tests as well as psychiatric comorbidity.FindingsThe results showed that disruption of white matter integrity occurred in the default mode network (DMN) of patients after chemotherapy, such as in the corpus callosum (CC) and middle frontal gyrus (MFG). Furthermore, weaker connections between brain regions and lower segregation ability were observed in the post-chemotherapy group. Significant correlations were observed between neuropsychological tests and white matter tracts of the CC, MFG, posterior limb of the internal capsule (PLIC) and superior longitudinal fasciculus (SLF).ConclusionThe results provided evidence of white matter alterations in breast cancer patients, and they may serve as potential imaging markers of cognitive changes. In the future, the study may be beneficial to create and evaluate strategies designed to maintain or improve cognitive function in breast cancer patients undergoing chemotherapy.

Abstract One of the primary challenges in realizing large-scale quantum processors is the realization of qubit couplings that balance interaction strength, connectivity, and mode confinement. Moreover, it is very desirable for the device elements to be detachable, allowing components to be built, tested, and replaced independently. In this work, we present a microwave quantum state router, centered on parametrically driven, Josephson-junction based three-wave mixing, that realizes all-to-all couplings among four detachable quantum modules. We demonstrate coherent exchange among all four communication modes, with an average full-iSWAP time of 764 ns and average inferred inter-module exchange fidelity of 0.969, limited by mode coherence. We also demonstrate photon transfer and pairwise entanglement between module qubits, and parallel operation of simultaneous iSWAP exchange across the router. Our router-module architecture serves as a prototype of modular quantum computer that has great potential for enabling flexible, demountable, large-scale quantum networks of superconducting qubits and cavities.

Abstract Background Major depressive disorder (MDD) is a recurrent psychiatric condition that presents challenges in responding to treatment and achieving long-term remission. To improve outcomes, a shared decision-making treatment approach with patient and healthcare practitioner (HCP) engagement is vital. PatientsLikeMe (PLM), a peer community of patients, provides information on MDD, symptoms, and treatment through forums and resources, helping patients stay engaged in their treatment journey. Data on PLM can be harnessed to gain insights into patient perspectives on MDD symptom management, medication switches, and treatment goals and measures. Methods This ongoing, decentralized, longitudinal, observational, prospective study is being conducted using the PLM platform in two parts, enrolling up to 500 patients with MDD in the United States aged ≥ 18 years to compare vortioxetine with other monotherapy antidepressants. The first qualitative component consists of a webinar and discussion forum with PLM community members with MDD, followed by a pilot for functionality testing to improve the study flow and questions in the quantitative survey. The quantitative component follows on the PLM platform, utilizing patient-reported assessments, over a 24-week period. Three surveys will be conducted at baseline and weeks 12 and 24 to collect data on patient global impression of improvement, depression severity, cognitive function, quality of life (QoL) and well-being, medication satisfaction, emotional blunting, symptoms of anhedonia and resilience, as well as goal attainment. Quantitative results will be compared between groups. The qualitative component is complete; patient recruitment is underway for the quantitative component, with results expected in late 2023. Discussion These results will help HCPs understand patient perspectives on the effectiveness of vortioxetine versus other monotherapy antidepressants in alleviating symptoms of MDD and improvements in QoL. Data from the PLM platform will support a patient goal-based treatment approach, as results can be shared by patients with their HCPs, providing them with insights on patient-centric goals, treatment management and adherence, as well as allowing them to observe changes in patient-related outcomes scores. Findings from the study will also help to optimize the PLM platform to build scalable solutions and connectivity within the community to better serve patients with MDD.

Abstract Ukraine has been embroiled in an increasing war since February 2022. In addition to Ukrainians, the Russo-Ukraine war has affected Poles due to the refugee crisis and the Taiwanese, who are facing a potential crisis with China. We examined the mental health status and associated factors in Ukraine, Poland, and Taiwan. The data will be used for future reference as the war is still ongoing. From March 8 to April 26, 2022, we conducted an online survey using snowball sampling techniques in Ukraine, Poland, and Taiwan. Depression, anxiety, and stress were measured using the Depression, Anxiety, and Stress (DASS)-21 item scale; post-traumatic stress symptoms by the Impact of Event Scale-Revised (IES-R) and coping strategies by the Coping Orientation to Problems Experienced Inventory (Brief-COPE). We used multivariate linear regression to identify factors significantly associated with DASS-21 and IES-R scores. There were 1626 participants (Poland: 1053; Ukraine: 385; Taiwan: 188) in this study. Ukrainian participants reported significantly higher DASS-21 (p

Abstract Background Depression among adolescents is a seriously disabling public health problem with an extremely high prevalence. Identifying risk factors of depression at an early stage is important to reduce the disease burden. Childhood maltreatment (CM) is one of the major risk factors for depression. The key mediating processes that how CM affects the development of depression, however, still need further clarification. The present study tested the mediating effect of self-esteem, internalizing problems, and externalizing problems between CM and depressive symptoms. Potential sex differences in the foregoing associations were also explored. Methods A three-wave longitudinal study was carried out among 1,957 middle and high school students from 69 classes in 10 public schools in the Guangdong province of China. Data collection started when students were in grades 7 and 10 (median age: 13.0, range: 11–18) between January and April 2019, and the students were followed up once a year thereafter. Self-reported CM, depressive symptoms, self-esteem, internalizing and externalizing problems, and other demographics were collected. The multiple serial mediation analysis was conducted. Results We found that CM was positively related to subsequent internalizing and externalizing problems, as well as depressive symptoms, while self-esteem was negatively related to depressive symptoms. Serial mediation analysis indicated that self-esteem (mediator 1) and internalizing problems (mediator 2) sequentially mediated the path from CM to depressive symptoms in the overall and male population. Moreover, with externalizing problems as mediator 2, self-esteem (mediator 1) acted as a partial mediator in the association between CM and depressive symptoms in males, whereas externalizing problems played a complete mediating role in females. Conclusion Findings revealed that self-esteem and internalizing problems sequentially mediated the influence of CM on depressive symptoms whereas externalizing problems played an independent mediating role. In addition, sex differences need to be taken into consideration when designing prevention and intervention strategies, given the different psychosocial processes between boys and girls.

Educational institutions are transitioning their learning modalities to flexible learning from remote education; educators and staff continuously encounter ambiguous work demands that negatively affect their well-being. Literature indicates the influence of autonomy support, psychological capital, work engagement, and economic factors (i.e., financial preparedness and job insecurity) on well-being. We propose that social, psychological, work, and economic factors influence the well-being of university educators and staff. 315 employees voluntarily completed the autonomy support, work engagement, hope, self-efficacy, job insecurity, and financial preparedness scales. We used IBM SPSS Amos for the confirmatory factor analysis and structural equation modeling. Five separate models were conducted to test the research objective. Results indicate good to excellent model fit indices for the research scales and structural model. We also found that self-efficacy, work engagement, hope, and financial preparedness during emergencies positively predict well-being, while job insecurity is detrimental. Our findings could serve as a basis for mental health programs to address the mental issues of educators and staff.

Abstract Cognitive load reduces both empathy and prosocial behaviour. However, studies demonstrating these effects have induced cognitive load in a temporally limited, artificial manner that fails to capture real-world cognitive load. Drawing from cognitive load theory, we investigated whether naturally occurring cognitive load from the ongoing COVID-19 pandemic moderated the relationship between empathy and prosocial behaviour (operationalised as support for public health measures). This large study in an Australian sample (N = 600) identified negative relationships between pandemic fatigue, empathy for people vulnerable to COVID-19, and prosocial behaviour, and a positive relationship between empathy and prosocial behaviour. Additionally, we found that the negative effect of the pandemic on prosocial behaviour depended on empathy for vulnerable others, with pandemic fatigue’s effects lowest for those with the highest empathy. These findings highlight the interrelationships of cognitive load and empathy, and the potential value of eliciting empathy to ease the impact of real-world cognitive load on prosocial behaviour.

Background: The 2022 War in Ukraine has significantly affected the psychological well-being and daily lives of people in many countries. Objective: Two aims of this transnational study were (1) to compare psychological distress and coping strategies among people living in Ukraine, Poland, and Taiwan, (2) to examine whether the associations between various coping strategies (ie. problem-focused coping, emotion-focused coping, and avoidance) and psychological distress (ie. depression, anxiety, stress, posttraumatic stress disorder symptoms, and hopelessness about the ongoing war) differed among people of various countries during the initial stage of the 2022 War in Ukraine. Method: In total, 1,598 participants (362 from Ukraine, 1,051 from Poland, and 185 from Taiwan) were recruited using an online advertisement to complete online survey questionnaires, including the Brief Coping Orientation to Problems Experienced inventory; the 21-item Depression, Anxiety and Stress Scale; the Impact of Event Scale-Revised; and a questionnaire devised to assess the level of hopelessness about the ongoing war. Results: Psychological distress and adoption of coping strategies differed across people of various countries. Among Taiwanese and Polish respondents, avoidant coping strategies were most strongly associated with all categories of psychological distress compared with problem- and emotion-focused coping strategies. However, the associations of various coping strategies with psychological distress differed to a less extent among Ukrainian respondents. In addition, problem- and emotion-focused coping strategies had comparable associations with psychological distress among the people of Ukraine, Poland, and Taiwan. Conclusions: The 2022 War in Ukraine has affected the psychological well-being of people, especially the Ukrainians. Because of the strong association between the adoption of avoidance coping strategies and psychological distress, despite a less extent among Ukrainian respondents, adaptive coping strategies such as (problem- and emotion-focused) are suggested to help people during times of war.

Stressful life events (SLEs) and suicidal ideation (SI) are prevalent in persons with major depression disorder (MDD). Less is known about the underlying role of insomnia symptoms in the association between SLEs and SI. This three-wave prospective cohort study sought to investigate the longitudinal association among SLEs, insomnia symptoms, and SI in persons with MDD. The study population included 511 persons with MDD (mean [SD] age, 28.7 [6.7] years; 67.1% were females). Generalized estimated equations (GEEs) were utilized to explore prospective association among exposure of SLEs, insomnia symptoms, and SI. Additionally, a structural equation model (SEM) was employed to estimate the longitudinal mediating effect of insomnia symptoms in the relationship between SLEs and SI. Our study demonstrated that cumulative SLEs were determined to be longitudinally associated with SI in persons with MDD. We further observed that the association between SLEs and SI was significantly mediated by insomnia symptoms. Clinicians assessing persons with MDD, especially those with the history of SLE, could carefully evaluate and promptly treat insomnia symptoms as part of personalized assessment of their depressive illness, thereby achieving early prevention and intervention for suicidal behaviors in persons with MDD.