Atomic-scale origin of the enantiospecific decomposition of tartaric acid on chiral copper surfaces.

The origin of the enantiospecific decomposition of L- and D-tartaric acid on chiral Cu surfaces is elucidated on a structure-spread domed Cu(110) crystal by spatially resolved XPS and atomic-scale STM imaging. Extensive enantiospecific surface restructuring leads to the formation of surfaces vicinal to Cu(14,17,2) which are responsible for the enantiospecificity.

High-dimensional mapping of human CEACAM1 expression on immune cells and association with melanoma drug resistance.

BACKGROUND: Human carcinoembryonic antigen cell adhesion molecule 1 (CEACAM1) is an inhibitory cell surface protein that functions through homophilic and heterophilic ligand binding. Its expression on immune cells in human tumors is poorly understood. METHODS: An antibody that distinguishes human CEACAM1 from other highly related CEACAM family members was labeled with 159Tb and inserted into a panel of antibodies that included specificity for programmed cell death protein 1 (PD1) and PD-L1, which are targets of immunotherapy, to gain a data-driven immune cell atlas using cytometry by time-of-flight (CyTOF). A detailed inventory of CEACAM1, PD1, and PD-L1 expression on immune cells in metastatic lesions to lymph node or soft tissues and peripheral blood samples from patients with treatment-naive and -resistant melanoma as well as peripheral blood samples from healthy controls was performed. RESULTS: CEACAM1 is absent or at low levels on healthy circulating immune cells but is increased on immune cells in peripheral blood and tumors of melanoma patients. The majority of circulating PD1-positive NK cells, innate T cells, B cells, monocytic cells, dendritic cells, and CD4+ T cells in the peripheral circulation of treatment-resistant disease co-express CEACAM1 and are demonstrable as discrete populations. CEACAM1 is present on distinct types of cells that are unique to the tumor microenvironment and exhibit expression levels that are highest in treatment resistance; this includes tumor-infiltrating CD8+ T cells. CONCLUSIONS: To the best of our knowledge, this work represents the first comprehensive atlas of CEACAM1 expression on immune cells in a human tumor and reveals an important correlation with treatment-resistant disease. These studies suggest that agents targeting CEACAM1 may represent appropriate partners for PD1-related pathway therapies.

Some proteins, such as programmed cell death protein 1 (PD1), can stop the immune system from attacking cancer cells, allowing cancers to grow. Therapies targeting these proteins can be highly effective, but tumors can become resistant. It is important to identify factors involved in this resistance to develop improved cancer therapies. Human carcinoembryonic antigen cell adhesion molecule 1 (CEACAM1) is a protein that inhibits an immune response and its levels have been associated with poor patient outcomes. We applied a method that allows for the detection of proteins on a single cell to uncover CEACAM1 patterns in melanoma. We found that increased CEACAM1 expression levels on multiple different immune cell types was associated with tumors that were resistant to therapy. These findings may help us to understand the role of CEACAM1 in cancer and to develop better cancer therapies.

Disparities based on demographic features in the intensity and treatment of chronic pain in US patients with spinal cord injury.

OBJECTIVE: Informed by Minority Stress Theory, to investigate disparities in pain intensity, interference, and care in patients with spinal cord injuries (SCI) based on demographic features. DESIGN: Cross-sectional survey SETTING: Outpatient SCI clinics in two academic medical centers in the northwestern US. PARTICIPANTS: Sample of 242 SCI clinic patients who endorsed SCI-related pain, were 18-years-of-age or older, English-fluent, not diagnosed with bipolar or psychotic disorders, and able to make their own medical decisions. Participants were 74.8% male, an average of 48.5 years (range 18.1-89.8 years), 76.2% White, 31.9% privately insured, and 64.7% making less than $50,000 per year. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE(S): Exploratory analyses of screening data from a randomized controlled trial for pain treatment. Primary outcomes included pain intensity, pain interference, and the patient report of recommended pain treatments by a medical provider, tried by the patient, or that the patient would be willing to try. RESULTS: More treatments recommended was associated with younger age (ρ=-0.14, 95%CI: -0.01 to -0.27, p=.03) and private insurance ((ρ=-0.15, 95%CI: 0.02 to 0.27, p=.03), while more treatments tried was associated with private insurance alone (ρ=0.20, 95%CI: 0.07 to 0.32, p=.003). Number of treatments willing to be tried was associated with lower income (ρ=-0.15, 95%CI: -0.02 to -0.28, p=.03). SCI Patients of Color (POC) reported higher pain intensity (Cohen's D = 0.41, 95%CI:0.11-0.71) and greater odds of receiving psychotherapy for pain (OR: 7.12, 95%CI: 1.25-40.46) than their White peers. CONCLUSION(S): These exploratory findings indicate differences in SCI-related pain intensity based on identifying as POC, and differences in SCI-related pain treatment modalities based on identifying as POC, age, insurance type, and income. Further work exploring differences in SCI-related pain care based on patient social identities is warranted.

Widespread correction of brain pathology in feline alpha-mannosidosis by dose escalation of intracisternal AAV vector injection.

Alpha-mannosidosis is caused by a genetic deficiency of lysosomal alpha-mannosidase, leading to the widespread presence of storage lesions in the brain and other tissues. Enzyme replacement therapy is available but is not approved for treating the CNS, since the enzyme does not penetrate the blood-brain barrier. However, intellectual disability is a major manifestation of the disease; thus, a complimentary treatment is needed. While enzyme replacement therapy into the brain is technically feasible, it requires ports and frequent administration over time that are difficult to manage medically. Infusion of adeno-associated viral vectors into the cerebrospinal fluid is an attractive route for broadly targeting brain cells. We demonstrate here the widespread post-symptomatic correction of the globally distributed storage lesions by infusion of a high dose of AAV1-feline alpha-mannosidase (fMANB) into the CSF via the cisterna magna in the gyrencephalic alpha-mannosidosis cat brain. Significant improvements in clinical parameters occurred, and widespread global correction was documented pre-mortem by non-invasive magnetic resonance imaging. Postmortem analysis demonstrated high levels of MANB activity and reversal of lysosomal storage lesions throughout the brain. Thus, CSF treatment by adeno-associated viral vector gene therapy appears to be a suitable complement to systemic enzyme replacement therapy to potentially treat the whole patient.

Synthetic Roadmap to a Large Library of Colloidal High-Entropy Rare Earth Oxyhalide Nanoparticles Containing up to Thirteen Metals.

Nanoparticles of high-entropy materials that incorporate five or more elements randomized on a crystalline lattice often exhibit synergistic properties that can be influenced by both the identity and number of elements combined. These considerations are especially important for structurally and compositionally complex materials such as multimetal multianion compounds, where cation and anion mixing can influence properties in competitive and contradictory ways. Here, we demonstrate the synthesis of a large library of colloidal high-entropy rare earth oxyhalide (REOX) nanoparticles. We begin with the synthesis of (LaCePrNdSmEuGdDyHoErYbScY)OCl, which homogeneously incorporates 13 distinct rare earth elements. Through time point studies, we find that (LaNdSmGdDy)OCl, a 5-metal analogue, forms through in situ generation of compositionally segregated core@shell@shell intermediates that convert to homogeneously mixed products through apparent core-shell interdiffusion. Assuming that all possible combinations of 5 through 13 rare earth metals are synthetically accessible, we propose the existence of a 7099-member REOCl nanoparticle library, of which we synthesize and characterize 40 distinct members. We experimentally validate the incorporation of a large number of rare earth elements using energy dispersive X-ray spectra, despite closely spaced and overlapping X-ray energy lines, using several fingerprint matching strategies to uniquely correlate experimental and simulated spectra. We confirm homogeneous mixing by analyzing elemental distributions in high-entropy nanoparticles versus physical mixtures of their constituent compounds. Finally, we characterize the band gaps of the 5- and 13-metal REOCl nanoparticles and find a significantly narrowed band gap, relative to the constituent REOCl phases, in (LaCePrNdSmEuGdDyHoErYbScY)OCl but not in (LaNdSmGdDy)OCl.

Gephyrin promotes autonomous assembly and synaptic localization of GABAergic postsynaptic components without presynaptic GABA release.

Synapses containing γ-aminobutyric acid (GABA) constitute the primary centers for inhibitory neurotransmission in our nervous system. It is unclear how these synaptic structures form and align their postsynaptic machineries with presynaptic terminals. Here, we monitored the cellular distribution of several GABAergic postsynaptic proteins in a purely glutamatergic neuronal culture derived from human stem cells, which virtually lacks any vesicular GABA release. We found that several GABAA receptor (GABAAR) subunits, postsynaptic scaffolds, and major cell-adhesion molecules can reliably coaggregate and colocalize at even GABA-deficient subsynaptic domains, but remain physically segregated from glutamatergic counterparts. Genetic deletions of both Gephyrin and a Gephyrin-associated guanosine di- or triphosphate (GDP/GTP) exchange factor Collybistin severely disrupted the coassembly of these postsynaptic compositions and their proper apposition with presynaptic inputs. Gephyrin-GABAAR clusters, developed in the absence of GABA transmission, could be subsequently activated and even potentiated by delayed supply of vesicular GABA. Thus, molecular organization of GABAergic postsynapses can initiate via a GABA-independent but Gephyrin-dependent intrinsic mechanism.

Decoding Early Psychoses: Unraveling Stable Microstructural Features Associated with Psychopathology Across Independent Cohorts.

BACKGROUND: Early Psychosis patients (EP, within 3 years after psychosis onset) show significant variability, making outcome predictions challenging. Currently, little evidence exists for stable relationships between neural microstructural properties and symptom profiles across EP diagnoses, limiting the development of early interventions. METHODS: A data-driven approach, Partial Least Squares (PLS) correlation, was used across two independent datasets to examine multivariate relationships between white matter (WM) properties and symptomatology, to identify stable and generalizable signatures in EP. The primary cohort included EP patients from the Human Connectome Project-Early Psychosis (n=124). The replication cohort included EP patients from the Feinstein Institute for Medical Research (n=78). Both samples included individuals with schizophrenia, schizoaffective disorder, and psychotic mood disorders. RESULTS: In both cohorts, a significant latent component (LC) corresponded to a symptom profile combining negative symptoms, primarily diminished expression, with specific somatic symptoms. Both LCs captured comprehensive features of WM disruption, primarily a combination of subcortical and frontal association fibers. Strikingly, the PLS model trained on the primary cohort accurately predicted microstructural features and symptoms in the replication cohort. Findings were not driven by diagnosis, medication, or substance use. CONCLUSIONS: This data-driven transdiagnostic approach revealed a stable and replicable neurobiological signature of microstructural WM alterations in EP, across diagnoses and datasets, showing a strong covariance of these alterations with a unique profile of negative and somatic symptoms. This finding suggests the clinical utility of applying data-driven approaches to reveal symptom domains that share neurobiological underpinnings.

Electronic Vapor Products: Alarming Trends in United States Adolescents.

Background: The use of electronic vapor products (EVPs) increases the risks of nicotine addiction, drug-seeking behavior, mood disorders, and avoidable premature morbidities and mortality. We explored temporal trends in EVP use among US adolescents. Methods: We used data from the Youth Risk Behavior Survey for school grades 9 through 12 from 2015 (earliest available data) to 2021 (the most recently available data) from the US Centers for Disease Control and Prevention (n=57,006). Results: Daily use of EVPs increased from 2.0% in 2015 to 7.2% in 2019, a greater than 3.5-fold increase. Although the percentage decreased to 5.0% in 2021, it was still a >2.5-fold increase since 2015. In 2015, the percentage of EVP use was significantly higher in boys (2.8%) than girls (1.1%). By 2021, the percentage of EVP use was higher in girls (5.6%) than boys (4.5%), a 1.24-fold increase. In addition, the percentage of EVP use in 2021 was higher in White youth (6.5%) vs Black (3.1%), Asian (1.2%), and Hispanic/Latino (3.4%) youth compared to 2015, but White and Black adolescents had the highest increases of approximately 3.0-fold between 2015 and 2021. Adolescents in grade 12 had the highest percentages of EVP use at all periods. Conclusion: These data show alarming statistically significant and clinically important increases in EVP use in US adolescents in school grades 9 through 12. The magnitude of the increases may have been blunted by coronavirus disease 2019, a hypothesis that requires direct testing in analytic studies. These trends create clinical and public health challenges that require targeted interventions such as mass media campaigns and peer interventions to combat the influences of social norms that promote the adoption of risky health behaviors during adolescence.

Predictors of Physical Activity One Year After Moderate to Severe Traumatic Brain Injury.

OBJECTIVE: To identify predictors of moderate to vigorous physical activity (MVPA) at 12-months post-moderate-severe traumatic brain injury (TBI). Setting: Four inpatient rehabilitation centers. PARTICIPANTS: Individuals enrolled in the TBI Model Systems with moderate to severe TBI, admitted to inpatient rehabilitation, and able to ambulate without physical assistance from another person. DESIGN: Prospective longitudinal cohort study. MVPA was measured by having participants wear an ActiGraph GT3X on their wrist for 7 consecutive days. MAIN ANALYSES: We used multivariate regression to predict minutes per week of MVPA at 12 months after TBI. Three classes of predictors were entered hierarchically-demographic and clinical variables (age, sex, body mass index, education, TBI severity, neighborhood walkability score, and self-reported preinjury physical activity [PA] level), baseline TBI-related comorbid conditions (eg, measures of sleep, pain, mood, fatigue, and cognition), and intention to exercise and exercise self-efficacy assessed approximately 1 week after discharge from inpatient rehabilitation. RESULTS: 180 participants (ages 17.7-90.3 years) were enrolled, and 102 provided at least 5 days of valid accelerometer data at 12 months. At 12 months, participants recorded an average of 703 (587) minutes per week of MVPA. In univariate and multivariate analyses, age was the only significant predictor of 12-month MVPA (r = -0.52). A sharp decline in MVPA was observed in the tertile of participants who were over the age of 61. CONCLUSIONS: Older adults with TBI are at elevated risk of being physically inactive. Assuming PA may enhance health after TBI, older adults are a logical target for prevention or early intervention studies. Studies with longer outcomes are needed to understand the trajectory of PA levels after TBI.

The HIV Environmental Riskscape: The Roles of HIV Sexual Risk and Resilience Factors among Black Men Who Have Sex with Men: Findings from the Real Talk Project.

Black and African American men who have sex with men (Black MSM) experience the greatest proportion of new HIV infections in the United States. To address this challenge, a better understanding of the HIV environment riskscape including both risk and resilience factors is warranted among Black MSM. Research indicates that stress is associated with increased HIV sexual risk behaviors. Further, behavioral factors such as serosorting and community level factors including social support and community connection are resilience factors that protect against risk behaviors. The present study examines whether everyday stress is associated with HIV sexual risk behavior, as well as the role of risk and resilience factors among 125 Black MSM recruited in the Real Talk study. The Real Talk project examined the relationships between resilience, HIV risk behaviors, and HIV prevention strategy among a sample of Black MSM. Using generalized estimating equations, our results indicate a positive association between everyday stress and engaging in condomless anal intercourse only after adjusting for risk, resilience, and correlate variables. Similarly, having multiple sex partners and using substances during sex also show positive associations with condomless anal intercourse. Resilience factors of engaging in serosorting and being connected to both the Black and gay communities were negatively associated with condomless anal intercourse. Future prevention research and programming should focus on both risk and resilience factors to mitigate new HIV infections among Black MSM.

Unequal distributions of crowdsourced weather data in England and Wales.

Personal weather stations (PWS) can provide useful data on urban climates by densifying the number of weather measurements across major cities. They do so at a lower cost than official weather stations by national meteorological services. Despite the increasing use of PWS data, little attention has yet been paid to the underlying socio-economic and environmental inequalities in PWS coverage. Using social deprivation, demographic, and environmental indicators in England and Wales, we characterize existing inequalities in the current coverage of PWS. We find that there are fewer PWS in more deprived areas which also observe higher proportions of ethnic minorities, lower vegetation coverage, higher building height and building surface fraction, and lower proportions of inhabitants under 65 years old. This implies that data on urban climate may be less reliable or more uncertain in particular areas, which may limit the potential for climate adaptation and empowerment in those communities.

AI Efficacy as a Function of Trainee Interpreter Proficiency: Lessons from a Randomized Controlled Trial.

BACKGROUND AND PURPOSE: Recently, AI tools have been deployed with increasing speed in educational and clinical settings. However, the use of AI by trainees across different levels of experience has not been well studied. This study investigates the impact of AI assistance on diagnostic accuracy for intracranial hemorrhage (ICH) and large vessel occlusion (LVO) by medical students (MS) and resident trainees (RT). MATERIALS AND METHODS: This prospective study was conducted between March 2023 and October 2023. MS and RT were asked to identify ICH and LVO in 100 non-contrast head CTs and 100 head CTAs, respectively. One group received diagnostic aid simulating AI for ICH only (n = 26), the other for LVO only (n = 28). Primary outcomes included accuracy, sensitivity, and specificity for ICH / LVO detection without and with aid. Study interpretation time was a secondary outcome. Individual responses were pooled and analyzed with chi-square; differences in continuous variables were assessed with ANOVA. RESULTS: 48 participants completed the study, generating 10,779 ICH or LVO interpretations. With diagnostic aid, MS accuracy improved 11.0 points (P < .001) and RT accuracy showed no significant change. ICH interpretation time increased with diagnostic aid for both groups (P < .001) while LVO interpretation time decreased for MS (P < .001). Despite worse performance in detection of the smallest vs. the largest hemorrhages at baseline, MS were not more likely to accept a true positive AI result for these more difficult tasks. Both groups were considerably less accurate when disagreeing with the AI or when supplied with an incorrect AI result. CONCLUSIONS: This study demonstrated greater improvement in diagnostic accuracy with AI for MS compared to RT. However, MS were less likely than RT to overrule incorrect AI interpretations and were less accurate, even with diagnostic aid, than the AI was by itself. ABBREVIATIONS: ICH = intracranial hemorrhage; LVO = large vessel occlusion; MS = medical students; RT = resident trainees.

Disease progression modelling reveals heterogeneity in trajectories of Lewy-type α-synuclein pathology.

Lewy body (LB) diseases, characterized by the aggregation of misfolded α-synuclein proteins, exhibit notable clinical heterogeneity. This may be due to variations in accumulation patterns of LB neuropathology. Here we apply a data-driven disease progression model to regional neuropathological LB density scores from 814 brain donors with Lewy pathology. We describe three inferred trajectories of LB pathology that are characterized by differing clinicopathological presentation and longitudinal antemortem clinical progression. Most donors (81.9%) show earliest pathology in the olfactory bulb, followed by accumulation in either limbic (60.8%) or brainstem (21.1%) regions. The remaining donors (18.1%) initially exhibit abnormalities in brainstem regions. Early limbic pathology is associated with Alzheimer's disease-associated characteristics while early brainstem pathology is associated with progressive motor impairment and substantial LB pathology outside of the brain. Our data provides evidence for heterogeneity in the temporal spread of LB pathology, possibly explaining some of the clinical disparities observed in Lewy body disease.

An alternative to the igneous crust fluid + sediment melt paradigm for arc lava geochemistry.

A long-standing paradigm of arc geochemistry is that the trace element compositions of arc lavas arise from two compositionally distinct slab components: an aqueous dehydration fluid from the subducting igneous ocean crust that transports "fluid-mobile" elements, such as barium (Ba), and a sediment melt that supplies thorium (Th) and the light rare earth elements. This two-component framework has been widely called upon to explain global geochemical trends as well as geochemical variations within individual arcs, such as the Marianas. Here, we show that this paradigm is inconsistent with mass balance, due to the low Ba contents of igneous ocean crust, and with experimental data, which show that aqueous fluids from the igneous oceanic crust would be too dilute to substantially affect arc compositions. Observations previously attributed to the sediment melt/igneous-crust-fluid hypothesis are better explained by diverse subducting sediment compositions coupled with ambient mantle wedge heterogeneity, both globally and for the Marianas.

Electroconvulsive Therapy Changes Immunological Markers in Patients With Major Depressive Disorder: A Scoping Review.

ABSTRACT: Major depressive disorder (MDD) is a highly prevalent and disabling condition. As such, understanding the causes of and treatment options for MDD is critical. Electroconvulsive therapy (ECT) remains the gold standard depression treatment, but the molecular mechanisms that underlie its effects are still largely unknown. One such explanation hinges on the immuno-inflammatory correlates of ECT treatment, given mounting evidence supporting the inflammatory hypothesis of depression. This review aims to provide an overview of the suggested immunomodulatory effects of ECT and the predictive value of immune biomarkers in relation to treatment outcomes and side effects. We conducted a preregistered, systematic literature search utilizing MEDLINE (PubMed), Embase (Elsevier), and PsycINFO (EBSCO) databases. We employed keywords related to MDD, ECT, gut microbiome, and the immune system. We only included human subjects research published between 1985 and January 13, 2021. Twenty-six unique studies were included in our analyses. Findings indicate a proinflammatory profile associated with MDD, with immune biomarkers exhibiting acute and chronic changes following ECT. Consistently, lower baseline interleukin 6 levels and higher C-reactive protein levels are correlated with a greater reduction in depressive symptoms following ECT. Furthermore, included studies emphasize the predictive value of peripheral immune changes, specifically interleukin 6 and tumor necrosis factor α, on cognitive outcomes following ECT. Given these results, further exploration of the potential roles of immunomodulatory effects on ECT treatment outcomes, as well as adverse cognitive side effects, is indicated.

Accuracy of Phantomless Calibration of Routine Computed Tomography Scans for Opportunistic Osteoporosis Screening in the Spine Clinic.

STUDY DESIGN: Diagnostic accuracy study. OBJECTIVE: To establish a simple method of phantomless bone mineral density (BMD) measurement by using preoperative lumbar Computed Tomography (CT) scans, and compare the accuracy of reference tissue combinations to diagnose low BMD against uncalibrated Hounsfield units (HUs). SUMMARY OF BACKGROUND DATA: HUs are used as a measure of BMD; however, associations between HU and T-scores vary widely. Quantitative CT (qCT) scans are more accurate, but they require density calibration with an object of known density (phantom), which limits feasibility. As an emerging technique, phantomless (internal) calibration of routine CT scans may provide a good opportunity for screening. METHODS: Patients who were scheduled to undergo lumbar surgery, with a preoperative CT scan, and a dual-energy x-ray absorptiometry (DXA) scan within six months were included. Four tissues were selected for calibration: subcutaneous adipose (A), erector spinae (ES), psoas (P) and aortic blood (AB). The HUs of these tissues were used in linear regression against ground-truth values. Calibrations were performed by using two different internal tissues at a time to maintain simplicity and in-office applicability.Volumetric bone mineral densities (vBMD) derived from internally calibrated CT scans were analyzed for new threshold values for low bone density. Areas under the curve (AUC) were calculated with 95% confidence intervals (CI). RESULTS: 45 patients were included (M/F=10/35, mean age:63.3). Calibrated vBMDs had stronger correlations with DXA T-scores when compared with HUs, with L2 exhibiting the highest coefficients. Calibration by using A and ES with the threshold of 162 mg/cm3 had a sensitivity of 90% in detecting low BMD (AUC=0.671). CONCLUSIONS: This novel method allows simple, in-office calibration of routine preoperative CT scans without the use of a phantom. Calibration using adipose and erector spinae with a threshold of 162 mg/cm3 is proposed for low bone density screening with high sensitivity (90%). LEVEL OF EVIDENCE: Level III.

Decoding Early Psychoses: Unraveling Stable Microstructural Features Associated with Psychopathology Across Independent Cohorts.

Background: Early Psychosis patients (EP, within 3 years after psychosis onset) show significant variability, making outcome predictions challenging. Currently, little evidence exists for stable relationships between neural microstructural properties and symptom profiles across EP diagnoses, limiting the development of early interventions. Methods: A data-driven approach, Partial Least Squares (PLS) correlation, was used across two independent datasets to examine multivariate relationships between white matter (WM) properties and symptomatology, to identify stable and generalizable signatures in EP. The primary cohort included EP patients from the Human Connectome Project-Early Psychosis (n=124). The replication cohort included EP patients from the Feinstein Institute for Medical Research (n=78). Both samples included individuals with schizophrenia, schizoaffective disorder, and psychotic mood disorders. Results: In both cohorts, a significant latent component (LC) corresponded to a symptom profile combining negative symptoms, primarily diminished expression, with specific somatic symptoms. Both LCs captured comprehensive features of WM disruption, primarily a combination of subcortical and frontal association fibers. Strikingly, the PLS model trained on the primary cohort accurately predicted microstructural features and symptoms in the replication cohort. Findings were not driven by diagnosis, medication, or substance use. Conclusions: This data-driven transdiagnostic approach revealed a stable and replicable neurobiological signature of microstructural WM alterations in EP, across diagnoses and datasets, showing a strong covariance of these alterations with a unique profile of negative and somatic symptoms. This finding suggests the clinical utility of applying data-driven approaches to reveal symptom domains that share neurobiological underpinnings.