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Abstract Background It has been postulated that genetic predisposition may influence the susceptibility to SARS-coronavirus infection and disease outcomes. A recent study has suggested that the deletion allele (D allele) of the angiotensin converting enzyme (ACE) gene is associated with hypoxemia in SARS patients. Moreover, the ACE D allele has been shown to be more prevalent in patients suffering from adult respiratory distress syndrome (ARDS) in a previous study. Thus, we have investigated the association between ACE insertion/deletion (I/D) polymorphism and the progression to ARDS or requirement of intensive care in SARS patients. Method One hundred and forty genetically unrelated Chinese SARS patients and 326 healthy volunteers were recruited. The ACE I/D genotypes were determined by polymerase chain reaction and agarose gel electrophoresis. Results There is no significant difference in the genotypic distributions and the allelic frequencies of the ACE I/D polymorphism between the SARS patients and the healthy control subjects. Moreover, there is also no evidence that ACE I/D polymorphism is associated with the progression to ARDS or the requirement of intensive care in the SARS patients. In multivariate logistic analysis, age is the only factor associated with the development of ARDS while age and male sex are independent factors associated with the requirement of intensive care. Conclusion The ACE I/D polymorphism is not directly related to increased susceptibility to SARS-coronavirus infection and is not associated with poor outcomes after SARS-coronavirus infection.

Background. It is unclear whether pandemic 2009 influenza A (pH1N1) infection caused more significant disease among hospitalized adults than seasonal influenza. Methods. A prospective, observational study was conducted in adults hospitalized with polymerase chain reaction-confirmed pH1N1 infection in 2 acute-care general hospitals from June 2009 to May 2010 (n = 382). Complications and outcomes were described and compared with those in a seasonal influenza cohort (2007-2008, same hospitals; n = 754). Results. Hospitalized patients with pH1N1 influenza were younger than those with seasonal influenza (mean age ± standard deviation, 47 ± 20 vs 70 ± 19 years) and fewer had comorbid conditions (48% vs 64%). The rate of positive immunofluorescence assay results was low (54% vs 84%), and antiviral use was frequent (96% vs 52%). Most patients in both cohorts developed complicated illnesses (67.8% vs 77.1%), but patients with pH1N1 influenza had higher rates of extrapulmonary complications (23% vs 16%; P = .004) and intensive care unit admission and/or death (patient age <35 years, 2.3% vs 0%; 35-65 years, 12.4% vs 3.2%; >65 years, 13.5% vs 8.5%; adjusted odds ratio [OR] 2.13; 95% confidence interval [CI], 1.25-3.62; P = .005). Patients who received antiviral treatment within 96 h after onset had better survival (log-rank test, P < .001). However, without timely treatment, the mortality risk was higher with pH1N1 infection (9.0% vs 5.8% for seasonal influenza; adjusted OR, 6.85; 95% CI, 1.64-28.65; P = .008]. Bacterial superinfection worsened outcomes. Conclusions. Adults hospitalized for pH1N1 influenza had significant complications and mortality despite being younger than patients with seasonal influenza. Antiviral treatment within 96 h may improve survival. [ABSTRACT FROM AUTHOR]

Background: Severe acute respiratory syndrome (SARS) has become a global public health emergency.Objective: To evaluate the characteristics and outcomes of patients with SARS in Hong Kong and to identify predictors of mortality.Design: Retrospective cohort study.Setting: Quarantine hospital for patients with SARS in Hong Kong.Patients: 267 consecutive patients hospitalized from 26 February to 31 March 2003 for probable or confirmed SARS.Measurements: Clinical, laboratory, and radiographic measures; 3-month mortality rate.Results: According to our case definition, there were 227 cases of confirmed SARS and 40 cases of probable SARS. Common presenting symptoms were fever (99% of patients), chills (74%), malaise (63%), and myalgia (50%). Laboratory findings included lymphopenia (73%), thrombocytopenia (50%), hyponatremia (60%), and elevated levels of lactate dehydrogenase (47%) and C-reactive protein (75%). During hospitalization, incidence of diarrhea (53%), anemia (53%), and acute renal failure (6%) increased. Sixty-nine patients (26%) required intensive care because of respiratory failure. The 3-month mortality rate was 12% (95% CI, 8% to 16%). Factors contributing to mortality were respiratory failure, acute renal failure, and nosocomial sepsis. On multivariate Cox regression, age older than 60 years (relative risk, 5.10 [CI, 2.30 to 11.31]; P < 0.001) and lactate dehydrogenase level greater than 3.8 micro kat/L at presentation (relative risk, 2.20 [CI, 1.03 to 4.71]; P = 0.04) were independent predictors of mortality.Conclusion: Because of the longer follow-up period in our cohort, the mortality rate in these patients is higher than rates reported in previous studies. Advanced age and high lactate dehydrogenase level at presentation predict mortality. *For members of the Princess Margaret Hospital SARS Study Group, see the Appendix. [ABSTRACT FROM AUTHOR]

In human in-vitro fertilization (IVF)-embryo transfer, the in-vitro culture environment differs from in-vivo conditions in that the oxygen concentration is higher, and in such conditions the mouse embryos show a higher concentration of reactive oxygen species (ROS) in simple culture media. ROS are believed to cause damage to cell membranes and DNA fragmentation in somatic cells. This study was conducted to ascertain the level of H2O2 concentration within embryos and the morphological features of cell damage induced by H2O2. A total of 62 human oocytes and embryos (31 fragmented, 15 non-fragmented embryos, 16 unfertilized oocytes) was obtained from the IVF-embryo transfer programme. The relative intensity of H2O2 concentrations within embryos was measured using 2',7'-dichlorodihydrofluorescein diacetate by Quanti cell 500 fluorescence imaging and DNA fragmentation was observed with transmission electron microscopy and an in-situ apoptosis detection kit. The H2O2 concentrations were significantly higher in fragmented embryos (72.21 ± 9.62, mean ± SEM) compared to non-fragmented embryos (31.30 ± 3.50, P < 0.05) and unfertilized oocytes (30.75 ± 2.67, P < 0.05). Apoptosis was observed only in fragmented embryos, and was absent in non-fragmented embryos. Electron microscopic findings confirmed apoptotic bodies and cytoplasmic condensation in the fragmented blastomeres. We conclude that there is a direct relationship between increased H2O2 concentration and apoptosis, and that further studies should be undertaken to confirm these findings. [ABSTRACT FROM PUBLISHER]

Background: An improved understanding of pathways to alcohol use disorder (AUD) among service members may inform efforts to reduce the substantial impact of AUD on this population. This study examined whether the relationship between a service-related risk factor (combat exposure) and later AUD varied based on individual differences in genetic liability to AUD., Methods: The sample consisted of 1203 US Army soldiers of genetically determined European ancestry who provided survey and genomic data in the Army STARRS Pre/Post Deployment Study (PPDS; 2012-2014) and follow-up survey data in wave 1 of the STARRS Longitudinal Study (2016-2018). Logistic regression was used to estimate the conditional effect of combat exposure level (self-reported in PPDS) on odds of probable AUD diagnosis at follow-up, as a function of a soldier's polygenic risk score (PRS) for AUD., Results: The direct effect of combat exposure on AUD risk was non-significant (AOR=1.12, 95 % CI=1.00-1.26, p=.051); however, a significant combat exposure x PRS interaction was observed (AOR=1.60, 95 % CI=1.03-2.46, p=.033). Higher combat exposure was more strongly associated with elevated AUD risk among soldiers with heightened genetic liability to AUD., Conclusions: The effect of combat exposure on AUD risk appeared to vary based on a service member's level of genetic risk for AUD. Continued investigation is warranted to determine whether PRS can help stratify AUD risk within stress-exposed groups such as combat-deployed soldiers. Such efforts might reveal opportunities to focus prevention efforts on smaller subgroups at the intersection of having both environmental exposures and genetic vulnerability to AUD., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Robert J. Ursano reports financial support was provided by National Institute of Mental Health. Robert J. Ursano reports financial support was provided by US Department of Defense. Karmel Choi reports financial support was provided by National Institute of Mental Health. Karmel Choi reports financial support was provided by Brain and Behavior Research Foundation. In the past 3 years, Dr. Kessler was a consultant for Cambridge Health Alliance, Canandaigua VA Medical Center, Child Mind Institute, Holmusk, Massachusetts General Hospital, Partners Healthcare, Inc., RallyPoint Networks, Inc., Sage Therapeutics, and University of North Carolina. He has stock options in Cerebral Inc., Mirah, PYM (Prepare Your Mind), Roga Sciences, and Verisense Health. In the past 3 years, Dr. Stein received consulting income from Aptinyx, atai Life Sciences, BigHealth, Biogen, Bionomics, Boehringer Ingelheim, Delix Therapeutics, EmpowerPharm, Engrail Therapeutics, Janssen, Jazz Pharmaceuticals, Karuna Therapeutics, NeuroTrauma Sciences, Otsuka US, PureTech Health, Sage Therapeutics, and Roche/Genentech. Dr. Stein has stock options in Oxeia Biopharmaceuticals and EpiVario. He has been paid for his editorial work on Depression and Anxiety (Editor-in-Chief), Biological Psychiatry (Deputy Editor), and UpToDate (Co-Editor-in-Chief for Psychiatry). He has also received research support from NIH, the Department of Veterans Affairs, and the Department of Defense. He is on the scientific advisory board of the Brain and Behavior Research Foundation and the Anxiety and Depression Association of America. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Importance: Leveraging real-world clinical biobanks to investigate the associations between genetic and environmental risk factors for mental illness may help direct clinical screening efforts and evaluate the portability of polygenic scores across environmental contexts., Objective: To examine the associations between sexual trauma, polygenic liability to mental health outcomes, and clinical diagnoses of schizophrenia, bipolar disorder, and major depressive disorder in a clinical biobank setting., Design, Setting, and Participants: This genetic association study was conducted using clinical and genotyping data from 96 002 participants across hospital-linked biobanks located at Vanderbilt University Medical Center (VUMC), Nashville, Tennessee (including 58 262 individuals with high genetic similarity to the 1000 Genomes Project [1KG] Northern European from Utah reference population [1KG-EU-clustered] and 11 047 with high genetic similarity to the 1KG African-ancestry reference population of Yoruba in Ibadan, Nigeria [1KG-YRI-clustered]), and Mass General Brigham (MGB), Boston, Massachusetts (26 693 individuals with high genetic similarity to the combined European-ancestry superpopulation [1KG-EU-clustered]). Clinical data analyzed included diagnostic billing codes and clinical notes spanning from 1976 to 2023. Data analysis was performed from 2022 to 2024., Exposures: Clinically documented sexual trauma disclosures and polygenic scores for schizophrenia, bipolar disorder, and major depressive disorder., Main Outcomes and Measures: Diagnoses of schizophrenia, bipolar disorder, and major depressive disorder, determined by aggregating related diagnostic billing codes, were the dependent variables in logistic regression models including sexual trauma disclosure status, polygenic scores, and their interactions as the independent variables., Results: Across the VUMC and MGB biobanks, 96 002 individuals were included in analyses (VUMC 1KG-EU-clustered: 33 011 [56.7%] female; median [range] age, 56.8 [10.0 to >89] years; MGB 1KG-EU-clustered: 14 647 [54.9%] female; median [range] age, 58.0 [10.0 to >89] years; VUMC 1KG-YRI-clustered: 6961 [63.0%] female; median [range] age, 44.6 [10.1 to >89] years). Sexual trauma history was associated with all mental health conditions across institutions (ORs ranged from 8.83 [95% CI, 5.50-14.18] for schizophrenia in the VUMC 1KG-YRI-clustered cohort to 17.65 [95% CI, 12.77-24.40] for schizophrenia in the VUMC 1KG-EU-clustered cohort). Sexual trauma history and polygenic scores jointly explained 3.8% to 8.8% of mental health phenotypic variance. Schizophrenia and bipolar disorder polygenic scores had greater associations with mental health outcomes in individuals with no documented disclosures of sexual trauma (schizophrenia interaction: OR, 0.70 [95% CI, 0.56-0.88]; bipolar disorder interaction: OR, 0.83 [95% CI, 0.74-0.94])., Conclusions and Relevance: Sexual trauma and mental health polygenic scores, while correlated with one another, were independent and joint risk factors for severe mental illness in a large, diverse hospital biobank population. Furthermore, associations of schizophrenia and bipolar disorder polygenic scores with respective diagnoses were greater in those without disclosures, suggesting that genetic predisposition to mental illness as measured by polygenic scores may be less impactful in the presence of this severe environmental risk factor.

Major depressive disorder (MDD) is highly prevalent in youth and generally characterized by psychiatric comorbidities. Secular trends in co-occurring diagnoses remain unclear, especially in healthcare settings. Using large-scale electronic health records data from a major U.S. healthcare system, we examined the prevalence of MDD diagnoses and co-occurring psychiatric conditions during adolescence (12-18 years; N = 133,753) across four generations (birth years spanning 1985 to 2002) and by sex. Then using a phenome-wide association analysis, we explored which of 67 psychiatric conditions were associated with adolescent MDD diagnosis in earlier versus recent generations. Adolescent MDD diagnosis prevalence increased (8.9 to 11.4%) over time. Over 60% with an MDD diagnosis had co-occurring psychiatric diagnoses, especially neurodevelopmental and anxiety disorders. Co-occurring diagnoses generally increased over time, especially for anxiety disorders (14 to 50%) and suicidal behaviors (6 to 23%), across both sexes. Eight comorbidities interacted with generation, showing stronger associations with MDD diagnosis in earlier (e.g., conduct disorder) versus more recent (e.g., suicidal ideation and behaviors) generations. The findings underscore the importance of assessing psychiatric complexity in adolescents diagnosed with MDD, applying transdiagnostic approaches to address co-occurring presentations, and further investigating potential causes for generational increases., Competing Interests: JWS is a member of the Leon Levy Foundation Neuroscience Advisory Board, the Scientific Advisory Board of Sensorium Therapeutics (with equity), and has received grant support from Biogen, Inc. He is PI of a collaborative study of the genetics of depression and bipolar disorder sponsored by 23andMe for which 23andMe provides analysis time as in-kind support but no payments.

Background: Major depressive disorder (MDD) is the leading cause of disability globally, with moderate heritability and well-established socio-environmental risk factors. Genetic studies have been mostly restricted to European settings, with polygenic scores (PGS) demonstrating low portability across diverse global populations., Methods: This study examines genetic architecture, polygenic prediction, and socio-environmental correlates of MDD in a family-based sample of 10 032 individuals from Nepal with array genotyping data. We used genome-based restricted maximum likelihood to estimate heritability, applied S-LDXR to estimate the cross-ancestry genetic correlation between Nepalese and European samples, and modeled PGS trained on a GWAS meta-analysis of European and East Asian ancestry samples., Results: We estimated the narrow-sense heritability of lifetime MDD in Nepal to be 0.26 (95% CI 0.18-0.34, p = 8.5 × 10 -6 ). Our analysis was underpowered to estimate the cross-ancestry genetic correlation (rg = 0.26, 95% CI -0.29 to 0.81). MDD risk was associated with higher age (beta = 0.071, 95% CI 0.06-0.08), female sex (beta = 0.160, 95% CI 0.15-0.17), and childhood exposure to potentially traumatic events (beta = 0.050, 95% CI 0.03-0.07), while neither the depression PGS (beta = 0.004, 95% CI -0.004 to 0.01) or its interaction with childhood trauma (beta = 0.007, 95% CI -0.01 to 0.03) were strongly associated with MDD., Conclusions: Estimates of lifetime MDD heritability in this Nepalese sample were similar to previous European ancestry samples, but PGS trained on European data did not predict MDD in this sample. This may be due to differences in ancestry-linked causal variants, differences in depression phenotyping between the training and target data, or setting-specific environmental factors that modulate genetic effects. Additional research among under-represented global populations will ensure equitable translation of genomic findings.

Objective: Prior work suggests that psychological resilience to trauma may protect not only mental but also physical health. This study examined the relationship of prepandemic psychological resilience to lifetime trauma with self-reported COVID-19 infection and symptoms during the early years of the COVID-19 pandemic., Methods: Data are from 18,670 longitudinal cohort participants in the Nurses' Health Study II. Based on prior evidence that trauma and subsequent distress can increase infection risk and severity, and that psychological assets may offset this risk, we hypothesized higher versus lower psychological resilience to prior trauma would be associated with lower risk for COVID-19 infection. Prepandemic resilience was assessed via self-report between 2017 and 2019 based on self-reported lifetime trauma exposure and psychological health. COVID-19 infection and symptoms were self-reported on seven questionnaires administered between May 2020 and October 2021, from which we derived a composite outcome measure of probable COVID-19 infection, defined as having 3+ COVID-19 symptoms (out of 9) and/or a positive COVID-19 test result at any single assessment., Results: Multivariable regression revealed significant associations between higher prepandemic resilience scores and lower risk for probable COVID-19 infection, adjusting for sociodemographic and COVID-19-related risk factors (risk ratio [RR] = 0.90 [95% confidence interval {CI}, 0.87-0.93]). Considering subcomponents of the composite COVID-19 infection measure separately, prepandemic resilience was significantly associated with lower risk of reported symptoms (RR = 0.83 [95% CI, 0.79-0.88]), but not with a positive test result alone (RR = 0.96 [95% CI, 0.91-1.01])., Conclusion: Identifying protective factors for infection risk may help inform psychosocial interventions to improve health outcomes., (Copyright © 2024 by the American Psychosomatic Society.)

Background: Prior studies have incompletely assessed whether the development of cardiometabolic risk factors (CVDRF) (hypertension, hyperlipidemia, and diabetes mellitus) mediates the association between anxiety and depression (anxiety/depression) and cardiovascular disease (CVD)., Objectives: The authors aimed to evaluate the following: 1) the association between anxiety/depression and incident CVDRFs and whether this association mediates the increased CVD risk; and 2) whether neuro-immune mechanisms and age and sex effects may be involved., Methods: Using a retrospective cohort design, Mass General Brigham Biobank subjects were followed for 10 years. Presence and timing of anxiety/depression, CVDRFs, and CVD were determined using ICD codes. Stress-related neural activity, chronic inflammation, and autonomic function were measured by the assessment of amygdalar-to-cortical activity ratio, high-sensitivity CRP, and heart rate variability. Multivariable regression and mediation analyses were employed., Results: Among 71,214 subjects (median age 49.6 years; 55.3% female), 27,048 (38.0%) developed CVDRFs during follow-up. Pre-existing anxiety/depression associated with increased risk of incident CVDRF (OR: 1.71 [95% CI: 1.59-1.83], P  < 0.001) and with a shorter time to their development (β = -0.486 [95% CI: -0.62 to -0.35], P  < 0.001). The development of CVDRFs mediated the association between anxiety/depression and CVD events (log-odds: 0.044 [95% CI: 0.034-0.055], P  < 0.05). Neuro-immune pathways contributed to the development of CVDRFs ( P  < 0.05 each) and significant age and sex effects were noted: younger women experienced the greatest acceleration in the development of CVDRFs after anxiety/depression., Conclusions: Anxiety/depression accelerate the development of CVDRFs. This association appears to be most notable among younger women and may be mediated by stress-related neuro-immune pathways. Evaluations of tailored preventive measures for individuals with anxiety/depression are needed to reduce CVD risk., Competing Interests: Dr Osborne has received consulting fees from WCG Clinical for unrelated work; and is supported in part by NIH K23HL151909 and AHA 23SCISA1143491. Dr Tawakol’s institution has received grant support from Lung Biotechnologies for unrelated work. Dr Seligowski is supported in part by NIH MH125920. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.PerspectivesCOMPETENCY IN MEDICAL KNOWLEDGE: Important neuroimmune pathways underlie the association between anxiety, depression, and cardiovascular risk. Specific treatment of these pathways may reduce the cardiovascular risk associated with anxiety and depression. COMPETENCY IN PATIENT CARE: A close screening of cardiovascular risk factors should be performed in subjects with anxiety and depression. Younger female, although generally being at low risk of developing cardiovascular risk factors, are particularly susceptible to the cardiometabolic effects of anxiety and depression,, (© 2024 The Authors.)

The fields of coping and emotion regulation have mostly evolved separately over decades, although considerable overlap exists. Despite increasing efforts to unite them from a conceptual standpoint, it remains unclear whether conceptual similarities translate into their measurement. The main objective of this review was to summarize and compare self-reported measures of coping and emotion regulation strategies. The secondary objective was to examine whether other psychological measures (e.g., resilience) indirectly reflect regulatory strategies' effectiveness, thus representing additionally informative approaches. Results indicated substantial overlap between coping and emotion regulation measures. In both frameworks, two to eight individual strategies were usually captured, but only a third included ≤20 items. Most commonly evaluated strategies were reappraisal/reinterpretation, active coping/problem-solving, acceptance, avoidance, and suppression. Evidence also suggested psychological distress and well-being measures, especially in certain contexts like natural stress experiments, and resilience measures are possible indirect assessments of these regulatory strategies' effectiveness. These results are interpreted in the light of a broader, integrative affect regulation framework and a conceptual model connecting coping, emotion regulation, resilience, psychological well-being and psychological distress is introduced. We further discussed the importance of alignment between individuals, contexts, and strategies used, and provide directions for future research. Altogether, coping and emotion regulation measures meaningfully overlap. Joint consideration of both frameworks in future research would widen the repertoire of available measures and orient their selection based on other aspects like length or strategies covered, rather than the framework only., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to report.

The major anxiety disorders (ANX; including generalized anxiety disorder, panic disorder, and phobias) are highly prevalent, often onset early, persist throughout life, and cause substantial global disability. Although distinct in their clinical presentations, they likely represent differential expressions of a dysregulated threat-response system. Here we present a genome-wide association meta-analysis comprising 122,341 European ancestry ANX cases and 729,881 controls. We identified 58 independent genome-wide significant ANX risk variants and 66 genes with robust biological support. In an independent sample of 1,175,012 self-report ANX cases and 1,956,379 controls, 51 of the 58 associated variants were replicated. As predicted by twin studies, we found substantial genetic correlation between ANX and depression, neuroticism, and other internalizing phenotypes. Follow-up analyses demonstrated enrichment in all major brain regions and highlighted GABAergic signaling as one potential mechanism underlying ANX genetic risk. These results advance our understanding of the genetic architecture of ANX and prioritize genes for functional follow-up studies., Competing Interests: Per Hoffmann receives Salary from the Life & Brain GmbH, Bonn, Germany. James L. Kennedy is a member of the Scientific Advisory Board for Myriad Neuroscience Inc. Ian B. Hickie was an inaugural Commissioner on Australia’s National Mental Health Commission (2012-18). He is the Co-Director, Health and Policy at the Brain and Mind Centre (BMC) University of Sydney. The BMC operates an early-intervention youth services at Camperdown under contract to headspace. He is the Chief Scientific Advisor to, and a 5% equity shareholder in, InnoWell Pty Ltd. InnoWell was formed by the University of Sydney (45% equity) and PwC (Australia; 45% equity) to deliver the $30 M Australian Government-funded Project Synergy (2017-20; a three-year program for the transformation of mental health services) and to lead transformation of mental health services internationally through the use of innovative technologies. Andrew M. Mcintosh has received research support from Eli Lilly, Janssen, and The Sackler Trust. AMM has also received speaker fees from Illumina and Janssen. Murray B. Stein has in the past 3 years received consulting income from Acadia Pharmaceuticals, Aptinyx, atai Life Sciences, Boehringer Ingelheim, Bionomics, BioXcel Therapeutics, Clexio, Eisai, EmpowerPharm, Engrail Therapeutics, Janssen, Jazz Pharmaceuticals, and Roche/Genentech. Dr. Stein has stock options in Oxeia Biopharmaceuticals and EpiVario. He is paid for his editorial work on Depression and Anxiety (Editor-in-Chief), Biological Psychiatry (Deputy Editor), and UpToDate (Co-Editor-in-Chief for Psychiatry). He has also received research support from NIH, Department of Veterans Affairs, and the Department of Defense. He is on the scientific advisory board for the Brain and Behavior Research Foundation and the Anxiety and Depression Association of America. Joel Gelernter is named as an inventor on PCT patent application #15/878,640 entitled: “Genotype-guided dosing of opioid agonists,” filed January 24, 2018 and issued on January 26, 2021 as U.S. Patent No. 10,900,082; and is paid for editorial work for the journal “Complex Psychiatry.” Iiris Hovatta received speaker’s honoraria from Lundbeck. Ole A. Andreassen received speaker’s honorarium from Lundbeck and Sunovion, consultant for Cortechs.ai and Precision Health AS. Katharina Domschke has been a member of the Steering Committee Neurosciences, Janssen, Inc. until 2022 and is currently a member of the Board of the German National Society of Psychiatry (DGPPN) and the Neurotorium Editorial Board of the Lundbeck Foundation. Jordan W. Smoller is a member of the Scientific Advisory Board of Sensorium Therapeutics (with equity) and has received an honorarium for an internal seminar Tempus Labs. He is PI of a collaborative study of the genetics of depression and bipolar disorder sponsored by 23andMe for which 23andMe provides analysis time as in-kind support but no payments. Eduard Maron has received research support and has also received speaker fees from Lundbeck. Hans J. Grabe has received travel grants and speakers honoraria from Indorsia, Neuraxpharm, Servier and Janssen Cilag. Henrik Larsson has served as a speaker for Evolan Pharma, Medici and Shire/Takeda and has received research grants from Shire/Takeda; all outside the submitted work. Gerome Breen is an advisory board member for Compass Pathways. Jürgen Deckert is a member of the board of the German Society of Biological Psychiatry and is on the scientific advisory boards of non-profit organizations and foundations. Volker Arolt worked as an advisor for Sanofi-Adventis Germany. Zach Fuller and Xin Wang are employees of 23andMe and hold stock or stock options in 23andMe. All other authors have no competing interests to declare.

What distinguishes vulnerability and resilience to posttraumatic stress disorder (PTSD) remains unclear. Levering traumatic experiences reporting, genetic data, and electronic health records (EHR), we investigated and predicted the clinical comorbidities (co-phenome) of PTSD vulnerability and resilience in the UK Biobank (UKB) and All of Us Research Program (AoU), respectively. In 60,354 trauma-exposed UKB participants, we defined PTSD vulnerability and resilience considering PTSD symptoms, trauma burden, and polygenic risk scores. EHR-based phenome-wide association studies (PheWAS) were conducted to dissect the co-phenomes of PTSD vulnerability and resilience. Significant diagnostic endpoints were applied as weights, yielding a phenotypic risk score (PheRS) to conduct PheWAS of PTSD vulnerability and resilience PheRS in up to 95,761 AoU participants. EHR-based PheWAS revealed three significant phenotypes positively associated with PTSD vulnerability (top association "Sleep disorders") and five outcomes inversely associated with PTSD resilience (top association "Irritable Bowel Syndrome"). In the AoU cohort, PheRS analysis showed a partial inverse relationship between vulnerability and resilience with distinct comorbid associations. While PheRS vulnerability associations were linked to multiple phenotypes, PheRS resilience showed inverse relationships with eye conditions. Our study unveils phenotypic differences in PTSD vulnerability and resilience, highlighting that these concepts are not simply the absence and presence of PTSD., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Polimanti received a research grant from Alkermes for the present study. Drs. Polimanti and Gelernter received honorariums for editorial work in the journal Complex Psychiatry. The other authors have no conflicts of interest to declare., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

This paper proposed a fine dust detection system using time-interleaved counters in which surface acoustic wave (SAW) sensors changed the resonance point characteristic. When fine dust was applied to the SAW sensor, the resonance point decreased. The SAW oscillator made of the SAW sensor and radio frequency (RF) amplifier generated an oscillation frequency that was the same as the resonance frequency. The oscillation frequency was transferred to digital data by a 20-bit asynchronous counter. This system has two channels: a sensing channel and a reference channel. Each channel has a SAW oscillator and a 20-bit asynchronous counter. The difference of the two channel counter results is the frequency difference. Through this, it is possible to know whether fine dust adheres to the SAW sensor. The proposed circuit achieved 0.95 ppm frequency resolution when it was operated at a frequency of 460 MHz. This circuit was implemented in a TSMC 130 nm CMOS process.

Objective: The 1940 Census is a valuable resource for understanding various aspects of historical populations in the United States. Recently, the National Social Life, Health and Aging Project (NSHAP) integrated 1940 Census data into its extensive dataset, providing researchers with an opportunity to explore new avenues of life course investigation. We leverage the newly-introduced measures of childhood residential environment and evaluate their potential predictive utility in older adult cognitive functioning net of childhood and adulthood characteristics known to be key risk factors for poor cognition., Method: We analyzed 777 respondents who were children in 1940 (age<17) that have been linked to the 1940 U.S. Census. We used childhood geographic location, homeownership status, household composition, and parental nativity as predictors. Cognitive function was measured using the Montreal Cognitive Assessment., Results: Regression analysis showed that growing up in an urban area was associated with better cognitive function, while being born in the South was linked to poorer cognitive function, even after controlling for childhood health, parental education, educational attainment, stroke, and smoking status. Additionally, childhood multigenerational household was associated with better cognitive function, and childhood family size was associated with poorer cognitive function. However, these associations became statistically insignificant with the inclusion of educational attainment. We did not find homeownership and parental nativity to be associated with cognitive function., Discussion: The findings may shed light on the potential long-term effects of childhood circumstances on cognitive aging processes. Implications for current literature and directions for future research are discussed., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

How did mental healthcare utilization change during the COVID-19 pandemic period among individuals with pre-existing mental disorder? Understanding utilization patterns of these at-risk individuals and identifying those most likely to exhibit increased utilization could improve patient stratification and efficient delivery of mental health services. This study leveraged large-scale electronic health record (EHR) data to describe mental healthcare utilization patterns among individuals with pre-existing mental disorder before and during the COVID-19 pandemic and identify correlates of high mental healthcare utilization. Using EHR data from a large healthcare system in Massachusetts, we identified three "pre-existing mental disorder" groups (PMD) based on having a documented mental disorder diagnosis within the 6 months prior to the March 2020 lockdown, related to: (1) stress-related disorders (e.g., depression, anxiety) (N = 115,849), (2) serious mental illness (e.g., schizophrenia, bipolar disorders) (N = 11,530), or (3) compulsive behavior disorders (e.g., eating disorder, OCD) (N = 5,893). We also identified a "historical comparison" group (HC) for each PMD (N = 113,604, 11,758, and 5,387, respectively) from the previous year (2019). We assessed the monthly number of mental healthcare visits from March 13 to December 31 for PMDs in 2020 and HCs in 2019. Phenome-wide association analyses (PheWAS) were used to identify clinical correlates of high mental healthcare utilization. We found the overall number of mental healthcare visits per patient during the pandemic period in 2020 was 10-12% higher than in 2019. The majority of increased visits was driven by a subset of high mental healthcare utilizers (top decile). PheWAS results indicated that correlates of high utilization (prior mental disorders, chronic pain, insomnia, viral hepatitis C, etc.) were largely similar before and during the pandemic, though several conditions (e.g., back pain) were associated with high utilization only during the pandemic. Limitations included that we were not able to examine other risk factors previously shown to influence mental health during the pandemic (e.g., social support, discrimination) due to lack of social determinants of health information in EHR data. Mental healthcare utilization among patients with pre-existing mental disorder increased overall during the pandemic, likely due to expanded access to telemedicine. Given that clinical correlates of high mental healthcare utilization in a major hospital system were largely similar before and during the COVID-19 pandemic, resource stratification based on known risk factor profiles may aid hospitals in responding to heightened mental healthcare needs during a pandemic., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: JWS is a member of the Scientific Advisory Board of Sensorium Therapeutics (with equity), and has received grant support from Biogen, Inc. He is PI of a collaborative study of the genetics of depression and bipolar disorder sponsored by 23andMe for which 23andMe provides analysis time as in-kind support but no payments., (Copyright: © 2024 Lee et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Previous epidemiological research has linked posttraumatic stress disorder (PTSD) with specific physical health problems, but the comprehensive landscape of medical conditions associated with PTSD remains uncharacterized. Electronic health records provide an opportunity to overcome clinical knowledge gaps and uncover associations with biological relevance that potentially vary by sex., Methods: PTSD was defined among biobank participants ( N  = 145,959) in 3 major healthcare systems using 2 ICD code-based definitions: broad (≥1 PTSD or acute stress codes vs. 0; n cases  = 16,706) and narrow (≥2 PTSD codes vs. 0; n cases  = 3325). Using a phenome-wide association study design, we tested associations between each PTSD definition and all prevalent disease umbrella categories, i.e., phecodes. We also conducted sex-stratified phenome-wide association study analyses including a sex × diagnosis interaction term in each logistic regression., Results: A substantial number of phecodes were significantly associated with PTSD Narrow (61%) and PTSD Broad (83%). While the strongest associations were shared between the 2 definitions, PTSD Broad captured 334 additional phecodes not significantly associated with PTSD Narrow and exhibited a wider range of significantly associated phecodes across various categories, including respiratory, genitourinary, and circulatory conditions. Sex differences were observed in that PTSD Broad was more strongly associated with osteoporosis, respiratory failure, hemorrhage, and pulmonary heart disease among male patients and with urinary tract infection, acute pharyngitis, respiratory infections, and overweight among female patients., Conclusions: This study provides valuable insights into a diverse range of comorbidities associated with PTSD, including both known and novel associations, while highlighting the influence of sex differences and the impact of defining PTSD using electronic health records., (© 2024 The Authors.)

Background: Major depressive disorder (MDD) is a prevalent and debilitating disorder that has been associated with a range of risk factors and outcomes. Causal pathways between MDD and other traits can be studied using genetic variants as instrumental variables., Methods: A literature review was conducted to identify 201 MDD-associated traits. For 115 traits, there were well-powered genome-wide association study (GWAS) results available that could be used to assess the genetic correlation with MDD. Of these, there were 89 meeting criteria for investigating causal associations in both directions using two-sample Mendelian randomization (TSMR). Of the traits that were not captured by GWAS, 43 could be included as outcomes of MDD using one-sample MR (OSMR). A range of methods and sensitivity tests was applied to gauge robustness of results, together with statistical power analyses to aid interpretation., Outcomes: Moderate to strong genetic overlap was found between MDD and most traits. Support for causal effects of MDD liability were found for circadian, cognitive, diet, medical disease, endocrine, functional, inflammatory, metabolic, mortality, physical activity, reproduction, risk behavior, social, socioeconomic, and suicide outcomes. Most associations were bidirectional, although there was less evidence for diet, disease, and endocrine traits causing MDD risk. Results were robust across sensitivity analyses., Interpretation: This study provides a systematic overview of traits putatively causally related to MDD, confirming previous findings as well as identifying new associations. Our results highlight the importance of MDD as a risk factor cross-cutting across medical, functional, and psychosocial domains and emphasize the need for concerted efforts at reducing this highly prevalent disorder., Competing Interests: Conflict of interest PFS is consultant and shareholder at Neumora Therapeutics. No other authors report potential conflicts of interest.

Background and Objective: This study examined the potential influence of pre-pandemic psychological resilience on use of approach or avoidant coping styles and strategies to manage stress during the COVID-19 pandemic. We hypothesized that higher resilience would be associated with more approach coping and less avoidant coping., Design and Methods: Longitudinal cohort data were from the Nurses' Health Study II, including 13,143 female current and former healthcare professionals with pre-pandemic lifetime trauma. Pre-pandemic resilience was assessed between 2018-2019 and current coping during the outbreak of the pandemic in the United States (May-August 2020). Multiple linear regression model results identified associations between continuous pre-pandemic resilience scores and use of approach and avoidant coping styles, as well as individual coping strategies, adjusting for relevant covariates., Results: Greater resilience was associated with higher use of approach coping (ß = 0.06, 95% CI 0.05, 0.08) and lower use of avoidant coping styles (ß = -0.39, 95% CI -0.41, -0.38). Higher pre-pandemic resilience was also associated with use of eight (distraction [ß = -0.18, 95% CI -0.20, -0.16], substance use [ß = -0.15, 95% CI -0.17, -0.13], behavioral disengagement [ß = -0.29, 95% CI -0.30, -0.27], self-blame [ß = -0.44, 95% CI -0.45, -0.42], emotional support (ß = 0.03, 95% CI 0.01, 0.05), positive reframing [ß = 0.13, 95% CI 0.12, 0.15], humor [ß = 0.03, 95% CI 0.01, 0.05] and religion [ß = 0.06, 95% CI 0.04, 0.08]) of the nine coping strategies in expected directions., Conclusion: Findings have important implications for intervention or even prevention efforts to support vulnerable groups, such as women with prior trauma histories, during this and other immensely stressful times. Supporting or building psychological resilience following trauma may promote effective coping in times of future stress., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Scoglio et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Post-traumatic stress disorder (PTSD) genetics are characterized by lower discoverability than most other psychiatric disorders. The contribution to biological understanding from previous genetic studies has thus been limited. We performed a multi-ancestry meta-analysis of genome-wide association studies across 1,222,882 individuals of European ancestry (137,136 cases) and 58,051 admixed individuals with African and Native American ancestry (13,624 cases). We identified 95 genome-wide significant loci (80 new). Convergent multi-omic approaches identified 43 potential causal genes, broadly classified as neurotransmitter and ion channel synaptic modulators (for example, GRIA1, GRM8 and CACNA1E), developmental, axon guidance and transcription factors (for example, FOXP2, EFNA5 and DCC), synaptic structure and function genes (for example, PCLO, NCAM1 and PDE4B) and endocrine or immune regulators (for example, ESR1, TRAF3 and TANK). Additional top genes influence stress, immune, fear and threat-related processes, previously hypothesized to underlie PTSD neurobiology. These findings strengthen our understanding of neurobiological systems relevant to PTSD pathophysiology, while also opening new areas for investigation., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

The children's mental health landscape is rapidly changing, and youth with mental health conditions (MHCs) are overrepresented in the child welfare system. Mental health is the largest unmet health need in child welfare, so MHCs may affect the likelihood of system reentry. Concerns regarding mental health contribute to calls for expanded supports, yet systems contact can also generate risk of continued child welfare involvement via surveillance. Still, we know little about how expanded supports at the state-level shape child welfare outcomes. Using the Adoption and Foster Care Analysis Reporting System (AFCARS), we examine the association between MHCs and system reentry within 36 months among youth who reunified with their families in 2016 (N = 41,860). We further examine whether this association varies across states and White, Black, and Latinx racial and ethnic groups via two- and three-way interactions. Results from multilevel models show that, net of individual and state-level factors, MHCs are associated with higher odds of reentry. This relationship is stronger for youth in states that expanded Medicaid by 2016 and with higher Medicaid/CHIP child participation rates. The results also show evidence of the moderating role of state-level factors, specifically student-to-school counselor ratio, diverging across racial and ethnic groups. Our results suggest a need for systems of care to better support youth mental health and counteract potential surveillance., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

With the escalating global awareness of air quality management, the need for continuous and reliable monitoring of toxic gases by using low-power operating systems has become increasingly important. One of which, semiconductor metal oxide gas sensors have received great attention due to their high/fast response and simple working mechanism. More specifically, self-heating metal oxide gas sensors, wherein direct thermal activation in the sensing material, have been sought for their low power-consuming characteristics. However, previous works have neglected to address the temperature distribution within the sensing material, resulting in inefficient gas response and prolonged response/recovery times, particularly due to the low-temperature regions. Here, we present a unique metal/metal oxide/metal (MMOM) nanowire architecture that conductively confines heat to the sensing material, achieving high uniformity in the temperature distribution. The proposed structure enables uniform thermal activation within the sensing material, allowing the sensor to efficiently react with the toxic gas. As a result, the proposed MMOM gas sensor showed significantly enhanced gas response (from 6.7 to 20.1% at 30 ppm), response time (from 195 to 17 s at 30 ppm), and limit of detection (∼1 ppm) when compared to those of conventional single-material structures upon exposure to carbon monoxide. Furthermore, the proposed work demonstrated low power consumption (2.36 mW) and high thermal durability (1500 on/off cycles), demonstrating its potential for practical applications in reliable and low-power operating gas sensor systems. These results propose a new paradigm for power-efficient and robust self-heating metal oxide gas sensors with potential implications for other fields requiring thermal engineering.

Background: The mechanisms underlying the psychological and cardiovascular disease (CVD) benefits of physical activity (PA) are not fully understood., Objectives: This study tested whether PA: 1) attenuates stress-related neural activity, which is known to potentiate CVD and for its role in anxiety/depression; 2) decreases CVD in part through this neural effect; and 3) has a greater impact on CVD risk among individuals with depression., Methods: Participants from the Mass General Brigham Biobank who completed a PA survey were studied. A subset underwent 18 F-fluorodeoxyglucose positron emission tomography/computed tomographic imaging. Stress-related neural activity was measured as the ratio of resting amygdalar-to-cortical activity (AmygA C ). CVD events were ascertained from electronic health records., Results: A total of 50,359 adults were included (median age 60 years [Q1-Q3: 45-70 years]; 40.1% male). Greater PA was associated with both lower AmygA C (standardized β: -0.245; 95% CI: -0.444 to -0.046; P = 0.016) and CVD events (HR: 0.802; 95% CI: 0.719-0.896; P < 0.001) in multivariable models. AmygA C reductions partially mediated PA's CVD benefit (OR: 0.96; 95% CI: 0.92-0.99; P < 0.05). Moreover, PA's benefit on incident CVD events was greater among those with (vs without) preexisting depression (HR: 0.860; 95% CI: 0.810-0.915; vs HR: 0.929; 95% CI: 0.910-0.949; P interaction = 0.011). Additionally, PA above guideline recommendations further reduced CVD events, but only among those with preexisting depression (P interaction = 0.023)., Conclusions: PA appears to reduce CVD risk in part by acting through the brain's stress-related activity; this may explain the novel observation that PA reduces CVD risk to a greater extent among individuals with depression., Competing Interests: Funding Support and Author Disclosures This study is in part funded by National Institutes of Health (NIH) grants R56AR077187-01 and P01HL131478-05. This study was in part supported by NIH grants 1R01AR077187 (Dr Tawakol), P01HL131478 (Drs Tawakol and Fayad), K23HL151909 (Dr Osborne). Dr Osborne has received consulting fees from WCG Intrinsic Imaging, LLC, for unrelated work. Dr Choi has received support in part by funding from the National Institute of Mental Health (K08MH127413) and a NARSAD Brain and Behavior Foundation Young Investigator Award. Dr Smoller has received support for work outside the submitted research; is a member of the Scientific Advisory Board of Sensorium Therapeutics (with equity); has received an honorarium for an internal seminar at Tempus Labs and Biogen, Inc; and is PI of a study sponsored by 23andMe. Dr Tawakol has received grants from the National Institutes of Health, International Atomic Energy Agency, Osler/Harvard, and Lung Biotechnologies for work outside the submitted research. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Suicide is a leading cause of death worldwide. Whereas some studies have suggested that a direct measure of common genetic liability for suicide attempts (SA), captured by a polygenic risk score for SA (SA-PRS), explains risk independent of parental history, further confirmation would be useful. Even more unsettled is the extent to which SA-PRS is associated with lifetime non-suicidal self-injury (NSSI)., Methods: We used summary statistics from the largest available GWAS study of SA to generate SA-PRS for two non-overlapping cohorts of soldiers of European ancestry. These were tested in multivariable models that included parental major depressive disorder (MDD) and parental SA., Results: In the first cohort, 417 (6.3 %) of 6573 soldiers reported lifetime SA and 1195 (18.2 %) reported lifetime NSSI. In a multivariable model that included parental history of MDD and parental history of SA, SA-PRS remained significantly associated with lifetime SA [aOR = 1.26, 95%CI:1.13-1.39, p < 0.001] per standardized unit SA-PRS]. In the second cohort, 204 (4.2 %) of 4900 soldiers reported lifetime SA, and 299 (6.1 %) reported lifetime NSSI. In a multivariable model that included parental history of MDD and parental history of SA, SA-PRS remained significantly associated with lifetime SA [aOR = 1.20, 95%CI:1.04-1.38, p = 0.014]. A combined analysis of both cohorts yielded similar results. In neither cohort or in the combined analysis was SA-PRS significantly associated with NSSI., Conclusions: PRS for SA conveys information about likelihood of lifetime SA (but not NSSI, demonstrating specificity), independent of self-reported parental history of MDD and parental history of SA., Limitations: At present, the magnitude of effects is small and would not be immediately useful for clinical decision-making or risk-stratified prevention initiatives, but this may be expected to improve with further iterations. Also critical will be the extension of these findings to more diverse populations., Competing Interests: Declaration of competing interest Dr. Kessler has in the past three years received support for his epidemiological studies from Sanofi Aventis; and was a consultant for Datastat, Inc., Sage Pharmaceuticals, and Takeda. Dr. Stein has in the past three years been a paid consultant for Aptinyx, BigHealth, Biogen, Bionomics, Boehringer-Ingelheim, Cerevel Therapeutics, EmpowerPharm, Engrail Therapeutics, Genentech/Roche, GW Pharma, Janssen, Jazz Pharmaceuticals, Otsuka, Oxeia Biopharmaceuticals, PureTech Health, and Sage Therapeutics. Dr. Smoller is a member of the Scientific Advisory Board of Sensorium Therapeutics (with equity), and has received grant support from Biogen, Inc., is PI of a collaborative study of the genetics of depression and bipolar disorder sponsored by 23andMe for which 23andMe provides analysis time as in-kind support but no payments. The remaining authors have no disclosures., (Published by Elsevier B.V.)

Oncogenic intercellular signaling is regulated by extracellular vesicles (EVs), but the underlying mechanisms remain mostly unclear. Since TCTP (translationally controlled tumor protein) is an EV component, we investigated whether it has a role in genotoxic stress signaling and malignant transformation. By generating a Tctp-inducible knockout mouse model (Tctp -/f- ), we report that Tctp is required for genotoxic stress-induced apoptosis signaling via small EVs (sEVs). Human breast cancer cells knocked-down for TCTP show impaired spontaneous EV secretion, thereby reducing sEV-dependent malignant growth. Since Trp53 -/- mice are prone to tumor formation, we derived tumor cells from Trp53 -/- ;Tctp -/f- double mutant mice and describe a drastic decrease in tumori-genicity with concomitant decrease in sEV secretion and content. Remarkably, Trp53 -/- ;Tctp -/f- mice show highly prolonged survival. Treatment of Trp53 -/- mice with sertraline, which inhibits TCTP function, increases their survival. Mechanistically, TCTP binds DDX3, recruiting RNAs, including miRNAs, to sEVs. Our findings establish TCTP as an essential protagonist in the regulation of sEV-signaling in the context of apoptosis and tumorigenicity., (© 2024. The Author(s).)

Context: Rotator cuff tear is one of the most common causes of shoulder pain and has become a prominent disease most frequently treated by surgery., Objectives: To investigate the long-term therapeutic effect of integrative Korean medicine (KM) as a conservative treatment in treating rotator cuff tears., Design: A multicenter observational study., Settings: The settings involve four regional network KM hospitals., Patients: The study participants are 288 patients aged 19-70 with rotator cuff tear identified by radiologist based on magnetic resonance imaging who received integrative KM treatment for the chief complaint of shoulder pain between 1 January 2015 and 31 March 2020., Intervention: None., Main Outcomes: The primary outcome was the pain score in the affected shoulder, measured by the numeric rating scale (NRS). The secondary outcomes were Shoulder Pain and Disability Index (SPADI), 5-Level Quality of life: EuroQol 5-Dimension (EQ-5D-5L), Patient Global Impression of Change (PGIC), and range of motion (ROM) scores., Results: Eligible patients for MCID achievement analysis for minimally clinical important change were 167, and 109 completed the follow-up survey. The mean NRS pain score in the affected shoulder was 5.80 ± 1.27 at admission, 3.50 ± 1.32 at discharge, and 3.83 ± 2.04 at follow-up.The mean SPADI score was 51.48 ± 20.18 at admission, 37.76 ± 19.23 at discharge, and 24.26 ± 21.80 at follow-up. The improvement at discharge (P-value < 0.001) and follow-up (P-value < 0.001) compared to those at admission was statistically significant. The results also presented a significant improvement in ROM for all motions at discharge after treatment (P-value < 0.001). The number of patients who achieved minimal clinically important difference in NRS was 116 (69.5%) at discharge and 71 (65.1%) at follow-up, and in SPADI was 82 (50.9%) at discharge and 77 (70.6%) at follow-up., Conclusion: The results of this study suggested that integrative KM treatment can help improve pain, functional impairment, QoL, and ROM in patients with a rotator cuff tear TRIAL REGISTRATION: NCT04566939., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Patients with schizophrenia have substantial comorbidity that contributes to reduced life expectancy of 10 to 20 years. Identifying modifiable comorbidities could improve rates of premature mortality. Conditions that frequently co-occur but lack shared genetic risk with schizophrenia are more likely to be products of treatment, behavior, or environmental factors and therefore are enriched for potentially modifiable associations., Methods: Phenome-wide comorbidity was calculated from electronic health records of 250,000 patients across 2 independent health care institutions (Vanderbilt University Medical Center and Mass General Brigham); associations with schizophrenia polygenic risk scores were calculated across the same phenotypes in linked biobanks., Results: Schizophrenia comorbidity was significantly correlated across institutions ( r  = 0.85), and the 77 identified comorbidities were consistent with prior literature. Overall, comorbidity and polygenic risk score associations were significantly correlated ( r  = 0.55, p  = 1.29 × 10 -118 ). However, directly testing for the absence of genetic effects identified 36 comorbidities that had significantly equivalent schizophrenia polygenic risk score distributions between cases and controls. This set included phenotypes known to be consequences of antipsychotic medications (e.g., movement disorders) or of the disease such as reduced hygiene (e.g., diseases of the nail), thereby validating the approach. It also highlighted phenotypes with less clear causal relationships and minimal genetic effects such as tobacco use disorder and diabetes., Conclusions: This work demonstrates the consistency and robustness of electronic health record-based schizophrenia comorbidities across independent institutions and with the existing literature. It identifies known and novel comorbidities with an absence of shared genetic risk, indicating other causes that may be modifiable and where further study of causal pathways could improve outcomes for patients., (© 2024 The Authors.)

Bipolar disorder is a leading contributor to disability, premature mortality, and suicide. Early identification of risk for bipolar disorder using generalizable predictive models trained on diverse cohorts around the United States could improve targeted assessment of high risk individuals, reduce misdiagnosis, and improve the allocation of limited mental health resources. This observational case-control study intended to develop and validate generalizable predictive models of bipolar disorder as part of the multisite, multinational PsycheMERGE Network across diverse and large biobanks with linked electronic health records (EHRs) from three academic medical centers: in the Northeast (Massachusetts General Brigham), the Mid-Atlantic (Geisinger) and the Mid-South (Vanderbilt University Medical Center). Predictive models were developed and valid with multiple algorithms at each study site: random forests, gradient boosting machines, penalized regression, including stacked ensemble learning algorithms combining them. Predictors were limited to widely available EHR-based features agnostic to a common data model including demographics, diagnostic codes, and medications. The main study outcome was bipolar disorder diagnosis as defined by the International Cohort Collection for Bipolar Disorder, 2015. In total, the study included records for 3,529,569 patients including 12,533 cases (0.3%) of bipolar disorder. After internal and external validation, algorithms demonstrated optimal performance in their respective development sites. The stacked ensemble achieved the best combination of overall discrimination (AUC = 0.82-0.87) and calibration performance with positive predictive values above 5% in the highest risk quantiles at all three study sites. In conclusion, generalizable predictive models of risk for bipolar disorder can be feasibly developed across diverse sites to enable precision medicine. Comparison of a range of machine learning methods indicated that an ensemble approach provides the best performance overall but required local retraining. These models will be disseminated via the PsycheMERGE Network website., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Toxic gases have surreptitiously influenced the health and environment of contemporary society with their odorless/colorless characteristics. As a result, a pressing need for reliable and portable gas-sensing devices has continuously increased. However, with their negligence to efficiently microstructure their bulky supportive layer on which the sensing and heating materials are located, previous semiconductor metal-oxide gas sensors have been unable to fully enhance their power efficiency, a critical factor in power-stringent portable devices. Herein, an ultrathin insulation layer with a unique serpentine architecture is proposed for the development of a power-efficient gas sensor, consuming only 2.3 mW with an operating temperature of 300 °C (≈6% of the leading commercial product). Utilizing a mechanically robust serpentine design, this work presents a fully suspended standalone device with a supportive layer thickness of only ≈50 nm. The developed gas sensor shows excellent mechanical durability, operating over 10 000 on/off cycles and ≈2 years of life expectancy under continuous operation. The gas sensor detected carbon monoxide concentrations from 30 to 1 ppm with an average response time of ≈15 s and distinguishable sensitivity to 1 ppm (ΔR/R0 = 5%). The mass-producible fabrication and heating efficiency presented here provide an exemplary platform for diverse power-efficient-related devices., (© 2023 Wiley-VCH GmbH.)

This study examines the relationship between individual-level social capital and compliance attitudes toward health protective measures in the context of COVID-19. We drew on secondary population-based data fielded during the pandemic's initial phase (April - June of 2020). The analytic sample consists of 9124 older American adults (ages 55 and over) across 18 U.S. States and Metropolitan Statistical Areas. We estimated mixed-effects models with random intercepts and slopes. People who are better socially connected are more willing to comply with anti-pandemic government intervention. This relationship is stronger among those who are more psychologically distressed. Its magnitude also increases in more densely populated areas and places with higher numbers of coronavirus infection. Older Americans' anti-coronavirus compliance attitudes is significantly driven by preexisting interpersonal connectedness and civic engagement. The role of social capital is also contingent on the existing levels of risk factor (threat and vulnerability)., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Importance: Posttraumatic stress disorder (PTSD) has been reported to be a risk factor for several physical and somatic symptoms. However, the genetics of PTSD and its potential association with medical outcomes remain unclear., Objective: To examine disease categories and laboratory tests from electronic health records (EHRs) that are associated with PTSD polygenic scores., Design, Setting, and Participants: This genetic association study was conducted from July 15, 2021, to January 24, 2023, using EHR data from participants across 4 biobanks. The polygenic scores of PTSD symptom severity (PGS-PTSD) were tested with all available phecodes in Vanderbilt University Medical Center's biobank (BioVU), Mass General Brigham (MGB), Michigan Genomics Initiative (MGI), and UK Biobank (UKBB). The significant medical outcomes were tested for overrepresented disease categories and subsequently tested for genetic correlation and 2-sample mendelian randomization (MR) to determine genetically informed associations. Multivariable MR was conducted to assess whether PTSD associations with health outcomes were independent of the genetic effect of body mass index and tobacco smoking., Exposures: Polygenic score of PTSD symptom severity., Main Outcomes and Measures: A total of 1680 phecodes (ie, International Classification of Diseases, Ninth Revision- and Tenth Revision-based phenotypic definitions of health outcomes) across 4 biobanks and 490 laboratory tests across 2 biobanks (BioVU and MGB)., Results: In this study including a total of 496 317 individuals (mean [SD] age, 56.8 [8.0] years; 263 048 female [53%]) across the 4 EHR sites, meta-analyzing associations of PGS-PTSD with 1680 phecodes from 496 317 individuals showed significant associations to be overrepresented from mental health disorders (fold enrichment = 3.15; P = 5.81 × 10-6), circulatory system (fold enrichment = 3.32; P = 6.39 × 10-12), digestive (fold enrichment = 2.42; P = 2.16 × 10-7), and respiratory outcomes (fold enrichment = 2.51; P = 8.28 × 10-5). The laboratory measures scan with PGS-PTSD in BioVU and MGB biobanks revealed top associations in metabolic and immune domains. MR identified genetic liability to PTSD symptom severity as an associated risk factor for 12 health outcomes, including alcoholism (β = 0.023; P = 1.49 × 10-4), tachycardia (β = 0.045; P = 8.30 × 10-5), cardiac dysrhythmias (β = 0.016, P = 3.09 × 10-5), and acute pancreatitis (β = 0.049, P = 4.48 × 10-4). Several of these associations were robust to genetic effects of body mass index and smoking. We observed a bidirectional association between PTSD symptoms and nonspecific chest pain and C-reactive protein., Conclusions and Relevance: Results of this study suggest the broad health repercussions associated with the genetic liability to PTSD across 4 biobanks. The circulatory and respiratory systems association was observed to be overrepresented in all 4 biobanks.

The high explosiveness of hydrogen gas in the air necessitates prompt detection in settings where hydrogen is used. For this reason, hydrogen sensors are required to offer rapid detection and possess superior sensing characteristics in terms of measurement range, linearity, selectivity, lifetime, and environment insensitivity according to the publicized protocol. However, previous approaches have only partially achieved the standardized requirements and have been limited in their capability to develop reliable materials for spatially accessible systems. Here, an electrical hydrogen sensor with an ultrafast response (∼0.6 s) satisfying all demands for hydrogen detection is demonstrated. Tailoring structural engineering based on the reaction kinetics of hydrogen and palladium, an optimized heating architecture that thermally activates fully suspended palladium (Pd) nanowires at a uniform temperature is designed. The developed Pd nanostructure, at a designated temperature distribution, rapidly reacts with hydrogen, enabling a hysteresis-free response from 0.1% to 10% and durable characteristics in mechanical shock and repetitive operation (>10,000 cycles). Moreover, the device selectively detects hydrogen without performance degradation in humid or carbon-based interfering gas circumstances. Finally, to verify spatial accessibility, the wireless hydrogen detection system has been demonstrated, detecting and reporting hydrogen leakage in real-time within just 1 s.

Objective: We evaluated the efficacy of the newly developed optimized in vitro culture (OIVC) dish for cultivating preimplantation mouse embryos. This dish minimizes the need for mineral oil and incorporates microwells, providing a stable culture environment and enabling independent monitoring of individual embryos., Methods: Mouse pronuclear (PN) zygotes and two-cell-stage embryos were collected at 18 and 46 hours after human chorionic gonadotropin injection, respectively. These were cultured for 120 hours using potassium simplex optimized medium (KSOM) to reach the blastocyst stage. The embryos were randomly allocated into three groups, each cultured in one of three dishes: a 60-mm culture dish, a microdrop dish, and an OIVC dish that we developed., Results: The OIVC dish effectively maintained the osmolarity of the KSOM culture medium over a 5-day period using only 2 mL of mineral oil. This contrasts with the significant osmolarity increase observed in the 60-mm culture dish. Additionally, the OIVC dish exhibited higher blastulation rates from two-cell embryos (100%) relative to the other dish types. Moreover, blastocysts derived from both PN zygotes and two-cell embryos in the OIVC dish group demonstrated significantly elevated mean cell numbers., Conclusion: Use of the OIVC dish markedly increased the number of cells in blastocysts derived from the in vitro culture of preimplantation mouse embryos. The capacity of this dish to maintain medium osmolarity with minimal mineral oil usage represents a breakthrough that may advance embryo culture techniques for various mammals, including human in vitro fertilization and embryo transfer programs.

Objective: Postpartum depression (PPD) is a common subtype of major depressive disorder (MDD) that is more heritable, yet is understudied in psychiatric genetics. The authors conducted meta-analyses of genome-wide association studies (GWASs) to investigate the genetic architecture of PPD., Method: Meta-analyses were conducted on 18 cohorts of European ancestry (17,339 PPD cases and 53,426 controls), one cohort of East Asian ancestry (975 cases and 3,780 controls), and one cohort of African ancestry (456 cases and 1,255 controls), totaling 18,770 PPD cases and 58,461 controls. Post-GWAS analyses included 1) single-nucleotide polymorphism (SNP)-based heritability ([Formula: see text]), 2) genetic correlations between PPD and other phenotypes, and 3) enrichment of the PPD GWAS findings in 27 human tissues and 265 cell types from the mouse central and peripheral nervous system., Results: No SNP achieved genome-wide significance in the European or the trans-ancestry meta-analyses. The [Formula: see text] of PPD was 0.14 (SE=0.02). Significant genetic correlations were estimated for PPD with MDD, bipolar disorder, anxiety disorders, posttraumatic stress disorder, insomnia, age at menarche, and polycystic ovary syndrome. Cell-type enrichment analyses implicate inhibitory neurons in the thalamus and cholinergic neurons within septal nuclei of the hypothalamus, a pattern that differs from MDD., Conclusions: While more samples are needed to reach genome-wide levels of significance, the results presented confirm PPD as a polygenic and heritable phenotype. There is also evidence that despite a high correlation with MDD, PPD may have unique genetic components. Cell enrichment results suggest GABAergic neurons, which converge on a common mechanism with the only medication approved by the U.S. Food and Drug Administration for PPD (brexanolone)., Competing Interests: Dr. Choi has received an honorarium from Depression and Anxiety for service as Deputy Editor. Dr. Raffield has served as a consultant for the TOPMed Administrative Coordinating Center (through Westat). Dr. Andreassen has received speaking honoraria from Janssen, Lundbeck, and Sunovion, and he has served as a consultant for Cortechs.ai and HealthLytix. Dr. Frey has received research support from MediPharm and Janssen. Dr. Grigoriadis has received royalties from the Canadian Pharmacists Association, Norton, and UpToDate. Dr. Jones has received grant funding from Takeda and Akrivia health. Dr. Kennedy has served as a scientific advisory board member for Myriad Neuroscience. Dr. McIntosh has served as a speaker for Illumina and Janssen. Dr. Munk-Olsen has served as a speaker for Lundbeck. Dr. Rubinow has received research funding from the Buszucki Foundation, NIH, and Sage Therapeutics; he serves on scientific advisory boards for the Foundation of Hope, Sage Therapeutics, and Sensorium Therapeutics and on clinical advisory boards for EmbarkNeuro and Felicity Pharma; he has served as a consultant for Aldeyra Therapeutics, Arrivo Bioventures, Brii Biosciences, and GH Research–Ireland; and he has stock options from Sage Therapeutics and Sensorium Therapeutics. Dr. Skalkidou has served as a consultant for Biogen; she receives compensation for lectures and organization of courses in reproductive endocrinology; and she is a shareholder and serves on the board of Svensk Telepsykiatri. Dr. Smoller has served on a scientific advisory board for Sensorium Therapeutics; he has received grant support from Biogen; and he is principal investigator of a collaborative study of the genetics of depression and bipolar disorder sponsored by 23andMe, for which 23andMe provides analysis time as in-kind support but no payments. Dr. Stein has received personal fees from Discovery Vitality, Johnson & Johnson, Kanna, L'Oreal, Lundbeck, Orion, Sanofi, Servier, Takeda, and Vistagen. Dr. Stowe has served on scientific advisory boards for Sage Therapeutics and Reunion Neuroscience. Dr. Taylor has given a lecture for AbbVie. Dr. Vigod has received royalties from UpToDate. Dr. Zar has received funding from the Bill and Melinda Gates Foundation. Dr. Meltzer-Brody has received sponsored research grant funding from Sage Therapeutics; she has served as a consultant for EmbarkNeuro and the Neuroscience Education Institute; and she serves as a professional corporation owner for Modern Health. Dr. Sullivan has served as an adviser for, and is a shareholder in, Neumora Therapeutics. The other authors report no financial relationships with commercial interests.

Objectives: We examine the relationship between social isolation, poor health behaviors, and the perceived worsening of older adults' health behaviors following the coronavirus outbreak. We assess the extent to which psychological pathways mediate the relationship between social isolation and worsening health behaviors., Methods: Drawing on data from the National Social Life Health and Aging Project Round 3 (2015) and its coronavirus immune disease 2019 (COVID-19) substudy (2020; N = 2,549), we use generalized linear models to explore how indicators of social isolation during the COVID-19 pandemic-infrequent in-person contact with friends and family in 2020 and decreased in-person contact with friends and family since COVID-19 started-are associated with (1) poor health behaviors (low physical activity, drinks per week, smoking, and poor sleep) in 2020 and (2) perceived worsening of health behaviors (reports of decreased physical activity, increased drinking and smoking, and feeling less rested) since the pandemic started., Results: Infrequent in-person contact was not associated with poor health behaviors. Decreases in in-person contact, on the other hand, were associated with worsening health behaviors. Older adults who reported decreases in in-person contact were more likely to perceive a decrease in physical activity, an increase in drinking, and feeling less rested. Emotional well-being, particularly loneliness compared to anxiety or depressive feelings, partially mediated the relationship between perceived worsening of health behaviors and a decrease in in-person contact with friends, and to a lesser extent, with family., Discussion: Our study suggests that in-person contact may play a distinct role in shaping older adults' well-being during the pandemic., (© The Author(s) 2023. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Many servicemembers experience difficulties transitioning from military to civilian life. We examined whether changes in mental health observed during active duty were associated with indices of post-military adjustment., Methods: Survey data from the multi-wave Army STARRS Pre/Post Deployment Study (PPDS; conducted 2012-2014) were linked to follow-up data from wave 1 of the STARRS Longitudinal Study (STARRS-LS1; conducted 2016-2018). Empirical Bayes estimates of intercepts and slopes of posttraumatic stress, problematic anger, and depressive symptoms during the PPDS were extracted from mixed-effects growth models and evaluated as predictors of life stress among 1080 participants who had separated or retired from the Army at STARRS-LS1; and of job satisfaction among 586 veterans who were employed at STARRS-LS1., Results: Higher average levels and larger increases in posttraumatic stress, anger, and depression over the deployment period were each associated with increased stress and (in the case of anger and depression) reduced job satisfaction. Posttraumatic stress and anger slopes were associated with overall stress (b = 5.60, p < 0.01 and b = 15.64, p = 0.04, respectively) and relationship stress (b = 5.50, p = 0.01 and b = 22.86, p = 0.01, respectively) beyond the average levels of those symptoms., Limitations: Some transition-related difficulties may have resolved before outcome assessment; some measures were not previously validated., Conclusions: Larger increases in posttraumatic stress and anger over a deployment period were associated with increased stress after leaving the Army, even after controlling for average symptom levels during the same period. Monitoring changes in mental health during active duty may help identify personnel who need additional support to facilitate the military-to-civilian transition., Competing Interests: Declaration of competing interest In the past 3 years, Dr. Kessler was a consultant for Cambridge Health Alliance, Canandaigua VA Medical Center, Holmusk, Partners Healthcare, Inc., RallyPoint Networks, Inc., and Sage Therapeutics. He has stock options in Cerebral Inc., Mirah, PYM, and Roga Sciences. In the past 3 years, Dr. Stein has received consulting income from Acadia Pharmaceuticals, Aptinyx, atai Life Sciences, BigHealth, Bionomics, BioXcel Therapeutics, Boehringer Ingelheim, Clexio, Eisai, EmpowerPharm, Engrail Therapeutics, Janssen, Jazz Pharmaceuticals, NeuroTrauma Sciences, PureTech Health, Sumitomo Pharma, and Roche/Genentech. Dr. Stein has stock options in Oxeia Biopharmaceuticals and EpiVario. He has been paid for his editorial work on Depression and Anxiety (Editor-in-Chief), Biological Psychiatry (Deputy Editor), and UpToDate (Co-Editor-in-Chief for Psychiatry). He has also received research support from NIH, Department of Veterans Affairs, and the Department of Defense. He is on the scientific advisory board for the Brain and Behavior Research Foundation and the Anxiety and Depression Association of America. The other authors have no known conflicts of interest to declare., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Importance: Children's exposure to screen time has been associated with poor mental health outcomes, yet the role of genetic factors remains largely unknown., Objective: To assess the extent of genetic confounding in the associations between screen time and attention problems or internalizing problems in preadolescent children., Design, Setting, and Participants: This cohort study analyzed data obtained between 2016 and 2019 from the Adolescent Brain Cognitive Development Study at 21 sites in the US. The sample included children aged 9 to 11 years of genetically assigned European ancestry with self-reported screen time. Data were analyzed between November 2021 and September 2023., Exposure: Child-reported daily screen time (in hours) was ascertained from questionnaires completed by the children at baseline., Main Outcomes and Measures: Child psychiatric problems, specifically attention and internalizing problems, were measured with the parent-completed Achenbach Child Behavior Checklist at the 1-year follow-up. Genetic sensitivity analyses model (Gsens) was used, which incorporated polygenic risk scores (PRSs) of both exposure and outcomes as well as either single-nucleotide variant (SNV; formerly single-nucleotide polymorphism)-based heritability or twin-based heritability to estimate genetic confounding., Results: The 4262 children in the sample included 2269 males (53.2%) with a mean (SD) age of 9.9 (0.6) years. Child screen time was associated with attention problems (β = 0.10 SD; 95% CI, 0.07-0.13 SD) and internalizing problems (β = 0.03 SD; 95% CI, 0.003-0.06 SD). The television time PRS was associated with child screen time (β = 0.18 SD; 95% CI, 0.14-0.23 SD), the attention-deficit/hyperactivity disorder PRS was associated with attention problems (β = 0.13 SD; 95% CI, 0.10-0.16 SD), and the depression PRS was associated with internalizing problems (β = 0.10 SD; 95% CI, 0.07-0.13 SD). These PRSs were associated with cross-traits, suggesting genetic confounding. Estimates using PRSs and SNV-based heritability showed that genetic confounding accounted for most of the association between child screen time and attention problems and for 42.7% of the association between child screen time and internalizing problems. When PRSs and twin-based heritability estimates were used, genetic confounding fully explained both associations., Conclusions and Relevance: Results of this study suggest that genetic confounding may explain a substantial part of the associations between child screen time and psychiatric problems. Genetic confounding should be considered in sociobehavioral studies of modifiable factors for youth mental health.

Background: Depression and anxiety are common and highly comorbid, and their comorbidity is associated with poorer outcomes posing clinical and public health concerns. We evaluated the polygenic contribution to comorbid depression and anxiety, and to each in isolation., Methods: Diagnostic codes were extracted from electronic health records for four biobanks [ N = 177 865 including 138 632 European (77.9%), 25 612 African (14.4%), and 13 621 Hispanic (7.7%) ancestry participants]. The outcome was a four-level variable representing the depression/anxiety diagnosis group: neither, depression-only, anxiety-only, and comorbid. Multinomial regression was used to test for association of depression and anxiety polygenic risk scores (PRSs) with the outcome while adjusting for principal components of ancestry., Results: In total, 132 960 patients had neither diagnosis (74.8%), 16 092 depression-only (9.0%), 13 098 anxiety-only (7.4%), and 16 584 comorbid (9.3%). In the European meta-analysis across biobanks, both PRSs were higher in each diagnosis group compared to controls. Notably, depression-PRS (OR 1.20 per s.d. increase in PRS; 95% CI 1.18-1.23) and anxiety-PRS (OR 1.07; 95% CI 1.05-1.09) had the largest effect when the comorbid group was compared with controls. Furthermore, the depression-PRS was significantly higher in the comorbid group than the depression-only group (OR 1.09; 95% CI 1.06-1.12) and the anxiety-only group (OR 1.15; 95% CI 1.11-1.19) and was significantly higher in the depression-only group than the anxiety-only group (OR 1.06; 95% CI 1.02-1.09), showing a genetic risk gradient across the conditions and the comorbidity., Conclusions: This study suggests that depression and anxiety have partially independent genetic liabilities and the genetic vulnerabilities to depression and anxiety make distinct contributions to comorbid depression and anxiety.

In this paper, we propose a novel transformer-based classification algorithm for the brain computer interface (BCI) using a motor imagery (MI) electroencephalogram (EEG) signal. To design the MI classification algorithm, we apply an up-to-date deep learning model, the transformer, that has revolutionized the natural language processing (NLP) and successfully widened its application to many other domains such as the computer vision. Within a long MI trial spanning a few seconds, the classification algorithm should give more attention to the time periods during which the intended motor task is imagined by the subject without any artifact. To achieve this goal, we propose a hierarchical transformer architecture that consists of a high-level transformer (HLT) and a low-level transformer (LLT). We break down a long MI trial into a number of short-term intervals. The LLT extracts a feature from each short-term interval, and the HLT pays more attention to the features from more relevant short-term intervals by using the self-attention mechanism of the transformer. We have done extensive tests of the proposed scheme on four open MI datasets, and shown that the proposed hierarchical transformer excels in both the subject-dependent and subject-independent tests.