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The PAS-synthesized sphalerite has a homogeneous sulfur isotopic composition and is suitable to be a matrix-matched reference material for in situ S isotope measurements of sphalerite.

Latino men have been drastically under-represented in research to identify effective behavioral weight-loss interventions. This trial compared 2 interventions for weight loss: (1) a culturally adapted intervention (HOMBRE) and (2) a minimal-intensity intervention.Randomized controlled trial.Latino men with a BMI ≥27 kg/mHOMBRE provided men a choice among 3 options: coach-facilitated group sessions using online video conferencing, coach-facilitated group sessions in person, and prerecorded videos of group sessions available online.The primary outcome was the proportion of participants sustaining clinically significant (≥5% of baseline) weight loss at 18 months. Secondary outcomes included weight loss trajectory over time, 3% and 10% weight loss, cardiometabolic risk factors, health behaviors, and psychosocial well-being at baseline and 18 months. Data were analyzed from October 6, 2020 to January 15, 2022.Participants were predominantly middle aged (47.0 [SD=11.9] years), were married (74.3%), were with at least some college experience (79.7%), and had middle to upper incomes (72.4% with annual family incomes$75,000). Their average BMI was 33.1 kg/mAmong Latino men with overweight and obesity, HOMBRE was not more effective for clinically significant weight loss than a minimal-intensity intervention at 18 months.

The objective of the study was to evaluate the effect of proximal parent artery stenosis on the hemodynamics of aneurysms in the internal carotid artery-posterior communicating artery (ICA-Pcom).A retrospective study of 74 patients with aneurysms in the ICA-Pcom who underwent treatment at the Department of Neurosurgery of Changhai Hospital was conducted between January and June 2018. Patients with proximal parent artery stenosis were included. Case-specific three-dimensional images were reconstructed, and software-based simulations of different stenosis morphologies were performed, focusing on stenosis severity and the distance from the aneurysm to the stenosis. The wall shear stress (WSS) of the aneurysms and blood flow velocity of the aneurysm neck plane were calculated. We performed simulations to evaluate the outcomes of postballoon angioplasty by considering a virtual operation group. To further assess whether WSS after balloon angioplasty increases the risk of aneurysm rupture, a control group of ruptured ICA-Pcom aneurysms without parent artery stenosis was matched with the virtual operation group based on sex, age, history of hypertension, and aneurysm size. Thereafter, the normalized WSS of the 2 groups was calculated.Eight patients with parent artery stenosis were included (2 men and 6 women; average age: 64 ± 15 years). The patients were divided into eccentric and concentric stenosis groups according to the stenotic morphologies, with 4 patients in each group. In both groups, the average WSS of the aneurysm and average blood flow velocity at the neck plane increased with the severity of parent artery stenosis, whereas the WSS did not correlate with distance. In the concentric stenosis group, the average blood flow velocity generally decreased as the distance between stenosis and aneurysm increased; however, no such trend was observed in the eccentric stenosis group. The normalized WSS of aneurysms after virtual balloon angioplasty was higher than that of the ruptured aneurysms (0.599 [0.548, 0.800] vs. 0.367 [0.324, 0.407]; P = 0.007).Intensified severity of proximal stenosis increases the blood flow velocity and aneurysmal WSS, which may lead to the progression of ICA-Pcom aneurysms. Treatment of the stenosis can reduce the WSS of aneurysms; however, its effect on the prognosis of ICA-Pcom aneurysms requires more concrete evidence.

A randomized controlled trial (RCT) is used to study the safety and efficacy of new treatments, by comparing patient outcomes of an intervention group with a control group. Traditionally, RCTs rely on statistical analyses to assess the differences between the treatment and control groups. However, such statistical analyses are generally not designed to assess the impact of the intervention at an individual level. In this paper, we explore machine learning models in conjunction with an RCT for personalized predictions of a depression treatment intervention, where patients were longitudinally monitored with wearable devices. We formulate individual-level predictions in the intervention and control groups from an RCT as a multi-task learning (MTL) problem, and propose a novel MTL model specifically designed for RCTs. Instead of training separate models for the intervention and control groups, the proposed MTL model is trained on both groups, effectively enlarging the training dataset. We develop a hierarchical model architecture to aggregate data from different sources and different longitudinal stages of the trial, which allows the MTL model to exploit the commonalities and capture the differences between the two groups. We evaluated the MTL approach in an RCT involving 106 patients with depression, who were randomized to receive an integrated intervention treatment. Our proposed MTL model outperforms both single-task models and the traditional multi-task model in predictive performance, representing a promising step in utilizing data collected in RCTs to develop predictive models for precision medicine.

Psychotherapy is a standard depression treatment; however, determining a patient's prognosis with therapy relies on clinical judgment that is subject to trial-and-error and provider variability.To develop machine learning (ML) algorithms to predict depression remission for patients undergoing 6 months of problem-solving therapy (PST).Using data from the treatment arm of 2 randomized trials, ML models were trained and validated on ENGAGE-2 (ClinicalTrials.gov, #NCT03841682) and tested on RAINBOW (ClinicalTrials.gov, #NCT02246413) for predictions at baseline and at 2-months. Primary outcome was depression remission using the Depression Symptom Checklist (SCL-20) score 0.5 at 6 months. Predictor variables included baseline characteristics (sociodemographic, behavioral, clinical, psychosocial) and intervention engagement through 2-months.Of the 26 candidate variables, 8 for baseline and 11 for 2-months were predictive of depression remission, and used to train the models. The best-performing model predicted remission with an accuracy significantly greater than chance in internal validation using the ENGAGE-2 cohort, at baseline [72.6% (SD = 3.6%), p 0.0001] and at 2-months [72.3% (5.1%), p 0.0001], and in external validation with the RAINBOW cohort at baseline [58.3% (0%), p 0.0001] and at 2-months [62.3% (0%), p 0.0001]. Model-agnostic explanations highlighted key predictors of depression remission at the cohort and patient levels, including female sex, lower self-reported sleep disturbance, lower sleep-related impairment, and lower negative problem orientation.ML models using clinical and patient-reported data can predict depression remission for patients undergoing PST, affording opportunities for prospective identification of likely responders, and for developing personalized early treatment optimization along the patient care trajectory.

Consumer-based voice assistants have the ability to deliver evidence-based treatment, but their therapeutic potential is largely unknown. In a pilot trial of a virtual voice-based coach, Lumen, delivering problem-solving treatment, adults with mild-to-moderate depression and/or anxiety were randomized to the Lumen intervention (n = 42) or waitlist control (n = 21). The main outcomes included changes in neural measures of emotional reactivity and cognitive control, and Hospital Anxiety and Depression Scale [HADS] symptom scores over 16 weeks. Participants were 37.8 years (SD = 12.4), 68% women, 25% Black, 24% Latino, and 11% Asian. Activation of the right dlPFC (neural region of interest in cognitive control) decreased in the intervention group but increased in the control group, with an effect size meeting the prespecified threshold for a meaningful effect (Cohen’s d = 0.3). Between-group differences in the change in activation of the left dlPFC and bilateral amygdala were observed, but were of smaller magnitude (d = 0.2). Change in right dlPFC activation was also meaningfully associated (r ≥ 0.4) with changes in self-reported problem-solving ability and avoidance in the intervention. Lumen intervention also led to decreased HADS depression, anxiety, and overall psychological distress scores, with medium effect sizes (Cohen’s d = 0.49, 0.51, and 0.55, respectively), compared with the waitlist control group. This pilot trial showed promising effects of a novel digital mental health intervention on cognitive control using neuroimaging and depression and anxiety symptoms, providing foundational evidence for a future confirmatory study.

To examine the association between COVID-19 impact and clinical outcomes of an integrated collaborative care intervention for adults with obesity and comorbid depression.Latent class analysis identified clusters of self-reported COVID-19 impact. Cluster characteristics were examined using Fishers' least significant difference method and canonical discriminant analysis. Intervention vs. usual care effects on primary (body mass index [BMI], depressive symptoms) and secondary (anxiety symptoms and other psychosocial) outcomes stratified by cluster were examined using linear mixed models.Three clusters were identified: mental health and sleep impact (cluster 1, n = 37), economic impact (cluster 2, n = 18), and less overall impact (cluster 3, n = 20). Clusters differed in age, income, diet, and baseline coping skills. The intervention led to improvements across several health outcomes compared with usual care, with medium to large effects on functional impairments (standardized mean difference, -0.7 [95% CI: -1.3, -0.1]) in cluster 1, depressive symptoms (-1.1 [95% CI: -2.0, -0.1]) and obesity-related problems (-1.6 [95% CI: -2.8, -0.4]) in cluster 2, and anxiety (-1.1 [95% CI: -1.9, -0.3]) in cluster 3.People with obesity and comorbid depression may have varied intervention responses based on COVID-19 impact. Interventions tailored to specific COVID-19 impact clusters may restore post-pandemic health.

The complex mechanism of immune-system damage in HIV infection is incompletely understood. HIV-infected “rapid progressors” (RPs) have severe damage to the immune system early in HIV infection, which provides a “magnified” opportunity to study the interaction between HIV and the immune system. In this study, forty-four early HIV-infected patients (documented HIV acquisition within the previous 6 months) were enrolled. By study the plasma of 23 RPs (CD4+ T-cell count < 350 cells/µl within 1 year of infection) and 21 “normal progressors” (NPs; CD4+ T-cell count > 500 cells/μl after 1 year of infection), eleven lipid metabolites were identified that could distinguish most of the RPs from NPs using an unsupervised clustering method. Among them, the long chain fatty acid eicosenoate significantly inhibited the proliferation and secretion of cytokines and induced TIM-3 expression in CD4+ and CD8+ T cells. Eicosenoate also increased levels of reactive oxygen species (ROS) and decreased oxygen consumption rate (OCR) and mitochondrial mass in T cells, indicating impairment in mitochondrial function. In addition, we found that eicosenoate induced p53 expression in T cells, and inhibition of p53 effectively decreased mitochondrial ROS in T cells. More importantly, treatment of T cells with the mitochondrial-targeting antioxidant mito-TEMPO restored eicosenoate-induced T-cell functional impairment. These data suggest that the lipid metabolite eicosenoate inhibits immune T-cell function by increasing mitochondrial ROS by inducing p53 transcription. Our results provide a new mechanism of metabolite regulation of effector T-cell function and provides a potential therapeutic target for restoring T-cell function during HIV infection.

The clinical adverse reaction monitoring data of Human subtilisin converting enzyme 9 gene (proprotein converting enzyme subtilisin/kexin type 9, PCSK9) inhibitors showed that there were neurocognitive adverse events. In order to early warning of the potential danger of PCSK9 inhibitors to cognitive impairment in the process of regulating lipid homeostasis, this study aimed to explore the microscopic effects of plasma exosomes. MicroRNA-222 (miR-222) as an early warning marker for shRNA-PCSK9-induced cognitive impairment. The hypercholesterolemia mouse model (high-fat diet, HFD-model group) was prepared by feeding with high-fat diet. The HFD-models were then divided into shRNA control group (HFD-shRNA-control group) and shRNA PCSK9 group (HFD-shRNA-PCSK9 group). The shRNA-PCSK9 was constructed, injected intravenously into the body, and the expression of PCSK9 mRNA was detected by real-time PCR (RT-PCR) and immunohistochemistry (IHC). Tau protein and phosphorylation in brain tissue were observed by IHC. Western blot(WB)was used to detect Tau protein and P-Tau protein. Serum amyloid Aβ1-42Ab levels were determined by enzyme-linked immunosorbent assay (ELISA). The kits extract plasma exosomes step by step, identify the exosome morphology by negative staining electron microscopy, and determine the size of exosomes by NTA technology. RT-PCR technique was used to detect the expression level of miR-222 carried in plasma exosomes. The HFD-model model was prepared by feeding a high-fat diet for 13 weeks, and the serum total cholesterol (TC) and low-density lipoprotein (LDL-C) contents were significantly increased. At the same time, the expression of PCSK9 mRNA in the brain tissue of HFD-model mice was significantly increased. After shRNA-PCSK9 lentivirus interference, PCSK9 mRNA expression was inhibited, and IHC observed that shRNA-PCSK9 induced abnormal expression and hyperphosphorylation of Tau protein in brain tissue, indicating that the pathological changes of neurofibrillary tangles have occurred. However, at this time, serum Aβ1-42Ab has not been significantly increased, and it has not yet been of significance for the diagnosis of cognitive impairment. The microRNA in plasma exosomes was extracted, and RT-PCR results showed that the expression of miR-222 carried in the exosomes of the HFD-shRNA-PCSK9 group was significantly lower than that of the HFD-shRNA-control group. At the same time, MiR-222 levels in plasma-derived exosomes were inversely correlated with Aβ1-42Ab in serum. MiR-222 carried by plasma-derived exosomes provides an early warning marker for shRNA-PCSK9-induced cognitive impairment.

The spike glycoprotein on the surface of the SARS-CoV-2 envelope plays an important role in its invasion into host cells. The binding of the spike glycoprotein RBD to the angiotensin-converting enzyme 2 (ACE2) receptor as a critical step in the spread of the virus has been explored intensively since the outbreak of COVID-19, but the high transmissibility of the virus such as the Delta variant is still not fully understood. Here, molecular simulations on the binding interactions of the wild-type spike protein and its four variants (Beta, Kappa, Delta, and Mu) with ACE2 and the antibody were performed, and the present results reveal that the residue mutations will not strengthen the binding affinity of the variant for ACE2, but remarkably influences the spatial orientation of the spike protein. Only the up-right conformational receptor binding domain (RBD) can bind ACE2, which is stabilized by the nearby RBDs in the down state, revealing that the RBD bears dual functional characteristics. The present results provide new insights into plausible mechanisms for high infectivity of the virus variants and their immune escape.

This study presents a practical method for high-precision Fe isotope determination without column chromatography purification for iron-dominated mineral samples using multi-collector inductively coupled plasma-mass spectrometry (MC-ICP-MS).

BACKGROUND: Depression hinders obesity treatment; elucidating mechanisms may enable treatment enhancements. OBJECTIVES: The aim was to investigate whether changes in neural targets in the negative affect circuit following psychotherapy mediate subsequent changes in weight and behaviors. METHODS: Adults (n = 108) with obesity and depression were randomly assigned to usual care or an intervention that delivered problem-solving therapy (PST) for depression over 2 mo. fMRI for brain imaging was performed at baseline and 2 mo. BMI, physical activity, and diet were measured at baseline and 12 mo. Mediation analysis assessed between-group differences in neural target changes using t test and correlations between neural target changes and outcome changes (simple and interaction effect) using ordinary least-squares regression. RESULTS: Compared with usual care, PST led to reductions in left amygdala activation (−0.75; 95% CI: −1.49, −0.01) and global scores of the negative affect circuit (−0.43; −0.81, −0.06), engaged by threat stimuli. Increases in amygdala activation and global circuit scores at 2 mo correlated with decreases in physical activity outcomes at 12 mo in the usual-care group; these relations were altered by PST. In relation to change in leisure-time physical activity, standardized β-coefficients were −0.67 in usual care and −0.01 in the intervention (between-group difference: 0.66; 0.02, 1.30) for change in left amygdala activation and −2.02 in usual care and −0.11 in the intervention (difference: 1.92; 0.64, 3.20) for change in global circuit scores. In relation to change in total energy expenditure, standardized β-coefficients were −0.65 in usual care and 0.08 in the intervention (difference: 0.73; 0.29, 1.16) for change in left amygdala activation and −1.65 in usual care and 0.08 in the intervention (difference: 1.74; 0.85, 2.63) for change in global circuit scores. Results were null for BMI and diet. CONCLUSIONS: Short-term changes in the negative affect circuit engaged by threat stimuli following PST for depression mediated longer-term changes in physical activity. This trial was registered at www.clinicaltrials.gov as NCT02246413 (https://clinicaltrials.gov/ct2/show/NCT02246413).

The current analytical methods of stable antimony isotopes are cumbersome and not suitable for rock samples with low antimony content (1 μg/g). In this study, we propose a new protocol for antimony isotopic analysis with a single column of AG50W-X8 resin and antimony standard doping. This method separates antimony effectively from matrices and then mixes it with the Sb standard. As Te does not affect the accuracy of antimony measurement when the Te/Sb ratio is low, we can obtain an accurate Sb isotope composition of the mixture. Then, we can calculate the antimony isotope composition of natural samples. The error propagation of the mixing and calculation processes was evaluated by the Monte Carlo method, and no significant error was found. The antimony isotope compositions were measured using a Thermo Fisher Scientific Neptune Plus multicollector-inductively coupled-mass spectrometry instrument. The instrumental mass bias of Sb isotopes was corrected with a standard-sample bracketing combined with a Sn internal normalization technique. Using the standard doping method, the measured δ

Background Developmental delay (DD) and intellectual disability (ID) represent one of the biggest medical and social challenges in our society with a prevalence of 1 ~ 3% worldwide. Currently, at least 50% of DD/ID cases remained unexplained. Mental retardation, autosomal dominant 21 (MRD21), caused by mutations in CTCF, is a rare DD/ID-related disease. The clinical phenotypes of MRD21 are highly variable but are not considered sufficiently distinct to be clinically recognizable. To date, only 37 pathogenic/likely pathogenic mutations in CTCF associated with MRD21 have been identified, and the pathogenesis of CTCF remains largely unknown. Methods Whole exon sequencing (WES) and bioinformatics analysis were used to identify the mutation as being responsible for an 18-month-old girl with unexplained DD, abnormality of the face and congenital heart disease. The origin of the mutation was analyzed by Sanger sequencing. The pathogenicity of the missense mutation was mainly analyzed by western blot (WB) and molecular dynamics (MD) simulations. Results We identified a novel missense mutation in CTCF (c.1115C > T, p. Ser372Phe) using WES, and Sanger sequencing indicated that the mutation was de novo. The expression levels of CTCF in 293T cells were unaltered by the missense mutation. However, MD simulations supported the pathogenicity of the p. Ser372Phe mutation, which resulted a decrease in the binding affinity of CTCF with DNA. Conclusions Our study broadens the mutational spectrum of CTCF and provides a better understanding of the pathogenicity of missense mutations in CTCF. This is the first time that MD simulations have been applied to evaluate the pathogenicity of missense mutations in CTCF.

To better understand the variation in mountainous discharge (MD) in the future, a basin case study was conducted in the upstream Taolai River Basin (UTRB) in arid northwestern China. The Blaney-Criddle (B-C) equation, Budyko framework, and water balance method were coupled for MD calculations. The outputs of 10 global climate models (GCMs) are synthesized to confirm the future changes in air temperature and precipitation under 3 selected Representative Concentration Pathway (RCP) scenarios. The climate elasticity (CE) method was used to determine the variation in MD, and the influence of climate factors on that was quantitatively analyzed. The results reveal that the coupling framework of the three methods is suitable for MD determination in the UTRB. The weight-based synthesis of the 10 GCM outputs shows overall increases in temperature (T) and precipitation (P) under the 3 scenarios during most of the time until 2099. The above climate change leads to an increase in MD. According to CE analysis, the positive effectiveness of precipitation is greater than the negative effectiveness of temperature on MD variation, and the increase in precipitation would induce more MD in the UTRB. Uncertainty analysis reveals that GCM outputs dominate in predicting precipitation, while the RCP scenarios influence temperature more. Overall, under the background of climate change, the risk of extreme floods during wet years might increase, and a water deficit will still occur during normal and dry years. The study provides a case example for better understanding MD responses to climate change in the upper reaches of inland river basins. Findings are helpful for reasonable water resource development and utilization in the middle and lower reaches of these basins in the future. As in the Taolai River Basin, considering the future water demand across the whole basin, the development of water-saving technologies and reasonable industrial structures is crucial for a sustainable future.

Fabrication of flexible piezoelectric sensing nanomaterials is essential for the development of wearable and microscopic electronic devices. However, existing piezoelectric sensing materials usuall...

Aqueous ammonium-ion storage has been considered a promising energy storage competitor to meet the requirements of safety, affordability, and sustainability. However, ammonium-ion storage is still in its infancy in the absence of reliable electrode materials. Here, defective VO