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BACKGROUND Suicide attempts and suicide death disproportionately affect sexual and gender minority emerging adults (ages 18-24). However, suicide prevention strategies tailored for emerging adult sexual and gender minorities (EA-SGM) are not widely available. OBJECTIVE We will pilot test the combination of peer mentoring alongside an app-based intervention (Supporting Transitions to Adulthood and Reducing Suicide; STARS) designed to reduce suicidal ideation and behaviors. STARS will include suicide prevention content and will target positive affect, discrimination, and social support. After an in-person Safety Planning Intervention (SPI) with a clinician, STARS users can access content and activities to increase their intentions to use the SPI and overcome obstacles to its use. METHODS Guided by the RE-AIM framework, we will recruit and enroll a racially/ethnically diverse sample of 60 EA-SGM reporting past-month suicidal ideation. Using a Type 1 Effectiveness-Implementation Hybrid Design, participants will be randomized to receive the SP intervention (Control arm) or to receive the SP intervention alongside STARS (Intervention arm). We will follow participants for six months, with evaluations at 2, 4, and 6 months. Preliminary effectiveness outcomes (suicidal ideation and behavior) and hypothesized mechanisms of change (positive affect, coping with discrimination, and social support) will serve as our primary outcomes. Secondary outcomes include key implementation indicators, including participants’ willingness and adoption of SPI and STARS, and staff’s experiences delivering the program. RESULTS Research activities began in September 2021 and are ongoing. The University of Pennsylvania is the central institutional review board for this study (protocol #849500). Study recruitment began on October 14, 2022. CONCLUSIONS This project will be among the first tailored, mobile-based interventions for EA-SGM at risk for suicide. This project is responsive to documented gaps for this population: 1) approaches that address chosen family; 2) focus on a life-course perspective; 3) online approaches; and 4) focus on health equity and provision of additional services relevant to sexual minority youth. CLINICALTRIAL ClinicalTrials.gov NCT05018143

Objectives: In a national sample of college students, this study aimed to evaluate whether barriers to mental health treatment varied by race and ethnicity. Methods: Data were drawn from a large multicampus study conducted across 26 US colleges and universities. The sample (n = 5841) included students who screened positive for at least one mental health disorder and who were not currently receiving psychotherapy. Results: Black and Hispanic/Latine individuals showed a greater willingness to seek treatment than White individuals. However, Black and Hispanic/Latine individuals faced more financial barriers to treatment, whereas Hispanic/Latine individuals also showed a lower perceived importance of mental health. Asian American individuals preferred to handle their issues on their own or with support from family/friends and had lower readiness, willingness, and intentions to seek help than White individuals, with greater financial barriers as well.Conclusions: Disparities in unmet treatment need may arise from both distinct and common barriers, and point to the potential benefits of tailored intervention approaches to address the unique needs of students of color from varying racial/ethnic backgrounds. Policy implications: Addressing barriers to treatment may require policies that cater to the unique needs of different racial/ethnic groups.Keywords: barriers to treatment, mental health, unmet need, students of color, health disparities

The contrast avoidance model (CAM) proposes that persons with generalized anxiety disorder (GAD) are sensitive to sharp increases in negative emotion or decreases in positive emotion (i.e., negative emotional contrasts; NEC) and use worry to avoid NEC. Sensitivity to and avoidance of NEC could also be a shared feature of major depressive disorder (MDD) and social anxiety disorder (SAD).In a large college sample (N = 1409), we used receiver operating characteristics analysis to examine the accuracy of a measure of emotional contrast avoidance in detecting probable GAD, MDD, and SAD.Participants with probable GAD, MDD, and SAD all reported higher levels of contrast avoidance than participants without the disorder (Cohen's d = 1.32, 1.62 and 1.53, respectively). Area under the curve, a measure of predictive accuracy, was 0.81, 0.87, and 0.83 for predicting probable GAD, MDD, and SAD, respectively. A cutoff score of 48.5 optimized predictive accuracy for probable GAD and SAD, and 50.5 optimized accuracy for probable MDD.A measure of emotional contrast avoidance demonstrated excellent ability to predict probable GAD, MDD, and SAD. Sensitivity to and avoidance of NEC appears to be a transdiagnostic feature of these disorders.

The American Academy of Pediatrics recommends that children be screened for autism at 18 and 24 months. It is unknown whether a positive screen usually represents the first developmental concern or is typically preceded by other developmental and/or medical concerns. This study evaluated the proportions of toddlers (M = 18.69 months) who screened positive for autism for whom caregivers or providers had prior concerns, the nature and timing of prior concerns, and their relationship with family characteristics. The electronic health records of 242 children who screened positive using the Modified Checklist for Autism in Toddlers–Revised with Follow-up during routine well-child visits were reviewed. Among toddlers who screened positive for autism, the majority (79.34%) had a documented prior motor, language, and/or autism concern. The presence of specific concerns was associated with earlier timing and higher Modified Checklist for Autism in Toddlers–Revised with Follow-up scores. Prior medical concerns were common, such as sleep (23.14%) and gastrointestinal (66.12%) problems. A positive autism screen often occurs in the context of pre-existing concerns. Thus, screening can provide providers with an opportunity to contextualize feedback about autism in the context of prior developmental and medical concerns. Lay abstract The American Academy of Pediatrics recommends that all children be screened for autism at their 18- and 24-month well-child visit. For children who screen positive for autism, it is unknown whether this usually represents the first time a developmental concern has been raised or if other developmental concerns typically precede a positive autism screen. Such knowledge could help guide providers in how to appropriately convey feedback regarding autism screening. This study found that, for close to 80% of children with a positive autism screen, caregivers or providers had a prior autism, language, motor, or other developmental concern documented in the electronic health record. Many also had other prior concerns frequently linked to autism, such as sleep and gastrointestinal problems, and received physical or speech therapy. On average, prior to screening children who received a positive Modified-Checklist for Autism in Toddlers had two documented concerns by at 1 year of age and three concerns by 2 years of age. These findings imply that screening for autism as a part of routine pediatric care likely takes place in the context of larger conversations regarding existing developmental concerns, allowing for a less stigmatizing discussion of autism. Framing the presence of prior concerns in the setting of a positive screen in this context may create a reaffirming space for existing caregiver concerns and a lessened emotional burden on caregivers.

The coronavirus disease 2019 (COVID-19) pandemic resulted in significant increases in insomnia, with up to 60% of people reporting increased insomnia. However, it is unclear whether exposure to risk factors for the virus or worries about COVID-19 are more strongly associated with insomnia. Using a three-part survey over the course of the first 6 months of the pandemic, we evaluated associations between COVID-19 exposures, COVID-19 worries, and insomnia. We hypothesised that COVID-19-related worries and exposure to risk of COVID-19 would predict increases in insomnia. Participants (N = 3,560) completed a survey at three time-points indicating their exposures to COVID-19 risk factors, COVID-19-related worries, and insomnia. COVID-19 worry variables were consistently associated with greater insomnia severity, whereas COVID-19 exposure variables were not. COVID-19 worries decreased significantly over time, and there were significant interactions between change in COVID-19 worries and change in insomnia severity over time. Individuals who experienced increases in COVID-19 worries also experienced increases in insomnia severity. Changes in worry during the COVID-19 pandemic were associated with changes in insomnia; worries about COVID-19 were a more consistent predictor of insomnia than COVID-19 exposures. Evidence-based treatments targeting virus-related worries may improve insomnia during this and future calamities.

ImportanceAutism detection early in childhood is critical to ensure that autistic children and their families have access to early behavioral support. Early correlates of autism documented in electronic health records (EHRs) during routine care could allow passive, predictive model-based monitoring to improve the accuracy of early detection.ObjectiveTo quantify the predictive value of early autism detection models based on EHR data collected before age 1 year.Design, Setting, and ParticipantsThis retrospective diagnostic study used EHR data from children seen within the Duke University Health System before age 30 days between January 2006 and December 2020. These data were used to train and evaluate L2-regularized Cox proportional hazards models predicting later autism diagnosis based on data collected from birth up to the time of prediction (ages 30-360 days). Statistical analyses were performed between August 1, 2020, and April 1, 2022.Main Outcomes and MeasuresPrediction performance was quantified in terms of sensitivity, specificity, and positive predictive value (PPV) at clinically relevant model operating thresholds.ResultsData from 45 080 children, including 924 (1.5%) meeting autism criteria, were included in this study. Model-based autism detection at age 30 days achieved 45.5% sensitivity and 23.0% PPV at 90.0% specificity. Detection by age 360 days achieved 59.8% sensitivity and 17.6% PPV at 81.5% specificity and 38.8% sensitivity and 31.0% PPV at 94.3% specificity.Conclusions and RelevanceIn this diagnostic study of an autism screening test, EHR-based autism detection achieved clinically meaningful accuracy by age 30 days, improving by age 1 year. This automated approach could be integrated with caregiver surveys to improve the accuracy of early autism screening.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with significant cognitive impairment and increased risk for mental health comorbidities. This study aimed to identify specific associations between cognitive impairment, self-reported disruptions in memory, and psychiatric symptoms including depression, anxiety, posttraumatic stress disorder (PTSD), and perceived sleep concerns.Data collected from all consecutive patients with Post-Acute Sequelae of SARS-CoV-2 infection (PASC) who presented to a dedicated Post-COVID Clinic were used to evaluate whether certain psychiatric symptoms were more strongly associated with cognitive impairment and self-reported memory disturbances.Univariate and multivariable analyses revealed that depression symptom severity was significantly associated with the severity of cognitive impairment among patients with PASC. This association was driven primarily by lower performance on verbal fluency, attention, and delayed recall tasks among patients with higher depression symptoms severity. Perceived sleep concerns were an important predictor of self-reported memory disturbances. Conversely, neither PTSD symptom severity nor anxiety symptom severity were significant predictors of cognitive impairment or self-reported memory disturbances.These findings have important clinical implications for justifying the need for screening patients with PASC for both depression and cognitive impairment.

We studied the work function of cesium deposition and co-deposition with the electronegative element on the plasma grid (PG) using the first-principles calculations. The impurity particles may exist in the background plasma and vacuum chamber wall, and the work function of the PG will be affected. The results indicate that the minimum work functions of pure cesium deposition on Mo (110), W (110), and Mo (112) are reached at a partial monolayer. They are 1.66 eV (σ = 0.56 θ), 1.69 eV (σ = 0.75 θ), and 1.75 eV (σ = 0.88 θ), respectively. An appropriate co-deposition model consisting of cesium with electronegative elements can further decrease the work function. The coverage of cesium and electronegative elements are both 0.34 θ in all the co-deposition models. The F-Cs co-deposition model where the Cs atom and F atom are aligned along the surface normal obtains the lowest work function. They are 1.31 eV for F-Cs on Mo (110), and 1.23 eV for F-Cs on W (110), respectively. The change in work function is linearly related to the change in dipole moment density with a slope of −167.03 VÅ. For pure cesium deposition, two factors control the change in dipole-moment density, one is the electron transfer between adsorbates and the substrate, and another one is the restructuring of surface atoms. There are two additional factors for the co-deposition model. One is the intrinsic dipole moment of the double layer, the other is the angle between the intrinsic dipole moment and the surface. The latter two factors play important roles in increasing the total dipole moment.

Attention avoidance and attention vigilance are two typical attentional biases in individuals with social anxiety disorder (SAD). Attention inhibition is a type of attention control, which may be the key factor affecting attention vigilance and attention avoidance. However, previous studies have not examined the difference between the attention inhibition in individuals with SAD and healthy controls.To further explore this question, the current study used the single anti-saccade task with emotional facial stimuli to assess attention inhibition in 27 individuals with SAD and 22 healthy controls.Regardless of the emotional valence of the facial stimuli, error rates in the social anxiety group were lower than that of the healthy control group, but there was no significant group difference in the saccade latency.This research only examined the attentional inhibition process highly related to attention avoidance and attention vigilance. Future research may benefit from adopting different research paradigms for more robust and generalizable conclusions.Results suggest that individuals with SAD have better attention inhibition abilities than healthy control. Such enhanced attention inhibition may underlie their avoidance of threatening social cues.

Prostate cancer adeno-to-neuroendocrine lineage transition has emerged as a mechanism of targeted therapeutic resistance. Identifying the direct molecular drivers and developing pharmacological strategies using clinical-grade inhibitors to overcome lineage transition-induced therapeutic resistance are imperative. Here, using single-cell multiomics analyses, we investigate the dynamics of cellular heterogeneity, transcriptome regulation, and microenvironmental factors in 107,201 cells from genetically engineered mouse prostate cancer samples with complete time series of tumor evolution seen in patients. We identify that FOXA2 orchestrates prostate cancer adeno-to-neuroendocrine lineage transition and that Foxa2 expression is significantly induced by androgen deprivation. Moreover, Foxa2 knockdown induces the reversal of adeno-to-neuroendocrine transition. The KIT pathway is directly regulated by FOXA2 and specifically activated in neuroendocrine prostate cancer (NEPC). Pharmacologic inhibition of KIT pathway significantly suppresses mouse and human NEPC tumor growth. These findings reveal that FOXA2 drives adeno-to-neuroendocrine lineage plasticity in prostate cancer and provides a potential pharmacological strategy for castration-resistant NEPC.

SummaryCholecystokinin receptors, CCKAR and CCKBR, are important neuro-intestinal peptide hormone receptors and play a vital role in food intake and appetite regulation. Here we report three crystal structures of the human CCKAR in complex with different ligands, including one peptide agonist and two small-molecule antagonists, as well as two cryo-electron microscopy structures of CCKBR–gastrin in complex with Gi2 and Gq, respectively. These structures reveal the recognition pattern of different ligand types and the molecular basis of peptide selectivity in the cholecystokinin receptor family. By comparing receptor structures in different conformational states, a stepwise activation process of cholecystokinin receptors is proposed. Combined with pharmacological data, our results provide atomic details for differential ligand recognition and receptor activation mechanisms. These insights will facilitate the discovery of potential therapeutics targeting cholecystokinin receptors.

Chromatin accessibility plays an essential role in controlling cellular identity and the therapeutic response of human cancers. However, the chromatin accessibility landscape and gene regulatory network of pancreatic cancer are largely uncharacterized. Here, we integrate the chromatin accessibility profiles of 84 pancreatic cancer organoid lines with whole-genome sequencing data, transcriptomic sequencing data and the results of drug sensitivity analysis of 283 epigenetic-related chemicals and 5 chemotherapeutic drugs. We identify distinct transcription factors that distinguish molecular subtypes of pancreatic cancer, predict numerous chromatin accessibility peaks associated with gene regulatory networks, discover regulatory noncoding mutations with potential as cancer drivers, and reveal the chromatin accessibility signatures associated with drug sensitivity. These results not only provide the chromatin accessibility atlas of pancreatic cancer but also suggest a systematic approach to comprehensively understand the gene regulatory network of pancreatic cancer in order to advance diagnosis and potential personalized medicine applications.

The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has rapidly become a global public health threat. The efficacy of several repurposed drugs has been evaluated in clinical trials. Among these drugs, a second-generation antiandrogen agent, enzalutamide, was proposed because it reduces the expression of transmembrane serine protease 2 (TMPRSS2), a key component mediating SARS-CoV-2-driven entry, in prostate cancer cells. However, definitive evidence for the therapeutic efficacy of enzalutamide in COVID-19 is lacking. Here, we evaluated the antiviral efficacy of enzalutamide in prostate cancer cells, lung cancer cells, human lung organoids and Ad-ACE2-transduced mice. Tmprss2 knockout significantly inhibited SARS-CoV-2 infection in vivo. Enzalutamide effectively inhibited SARS-CoV-2 infection in human prostate cells, however, such antiviral efficacy was lacking in human lung cells and organoids. Accordingly, enzalutamide showed no antiviral activity due to the AR-independent TMPRSS2 expression in mouse and human lung epithelial cells. Moreover, we observed distinct AR binding patterns between prostate cells and lung cells and a lack of direct binding of AR to TMPRSS2 regulatory locus in human lung cells. Thus, our findings do not support the postulated protective role of enzalutamide in treating COVID-19 through reducing TMPRSS2 expression in lung cells., Enzalutamide, an approved drug for prostate cancer, acts on TMPRSS2 expression, a key mediator for SARS-CoV-2 infection. Here, the authors characterize the anti-SARS-CoV-2 effects of Enzalutamide in prostate cancer cells, lung cancer cells, human lung organoids and in hACE2-transduced Tmprss2 knockout mice and show lack antiviral action in human lung cells and human lung organoids, likely due to the AR-independent TMPRSS2 expression in mouse and human lung epithelial cells.

Images captured in a dark environment may suffer from low visibility, which may degrade the visual aesthetics of images and the performance of vision-based systems. Extensive studies have focused on the low-light image enhancement (LIE) problem. However, we observe that even though the state-of-the-art LIE methods may oversharpen the low-light image and introduce visual artifacts. To reduce the overshoot effects of LIE, this paper proposes an illumination-aware image quality assessment, called LIE-IQA, for the enhanced low-light images. Since directly using the IQA of degraded image may fail to perform well, the proposed LIE-IQA is an illumination-aware and learnable metric. At first, the reflectance and shading components of both the enhanced low-light image and reference image are extracted by intrinsic image decomposition. Then, we use the weighted similarity between the VGG-based feature of enhanced low-light image and reference image to obtain LIE-IQA, where the weight of the measurement can be learned from pairs of data on benchmark dataset. Qualitative and quantitative experiments illustrate the superiority of the LIE-IQA to measure the image quality of LIE on different datasets, including a new IQA dataset built for LIE. We also use the LIE-IQA as a regularization of a loss function to optimize an end-to-end LIE method, and the results indicate the potential of the optimization framework with LIE-IQA to reduce the overshoot effects of low-light enhancement.

We present MMOCR-an open-source toolbox which provides a comprehensive pipeline for text detection and recognition, as well as their downstream tasks such as named entity recognition and key information extraction. MMOCR implements 14 state-of-the-art algorithms, which is significantly more than all the existing open-source OCR projects we are aware of to date. To facilitate future research and industrial applications of text recognition-related problems, we also provide a large number of trained models and detailed benchmarks to give insights into the performance of text detection, recognition and understanding. MMOCR is publicly released at https://github.com/open-mmlab/mmocr., Comment: Accepted to ACM MM (Open Source Competition Track)

Although cancer is commonly perceived as a disease of dedifferentiation, the hallmark of early-stage prostate cancer is paradoxically the loss of more plastic basal cells and the abnormal proliferation of more differentiated secretory luminal cells. However, the mechanism of prostate cancer proluminal differentiation is largely unknown. Through integrating analysis of the transcription factors (TFs) from 806 human prostate cancers, we found that ERG was highly correlated with prostate cancer luminal subtyping. ERG overexpression in luminal epithelial cells inhibited those cells' normal plasticity to transdifferentiate into a basal lineage, and ERG superseded PTEN loss, which favored basal differentiation. ERG KO disrupted prostate cell luminal differentiation, whereas AR KO had no such effects. Trp63 is a known master regulator of the prostate basal lineage. Through analysis of 3D chromatin architecture, we found that ERG bound and inhibited the enhancer activity and chromatin looping of a Trp63 distal enhancer, thereby silencing its gene expression. Specific deletion of the distal ERG binding site resulted in the loss of ERG-mediated inhibition of basal differentiation. Thus, ERG, in its fundamental role in lineage differentiation in prostate cancer initiation, orchestrated chromatin interactions and regulated prostate cell lineage toward a proluminal program.

The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has rapidly become a global public health threat due to the lack of effective drugs or vaccines against SARS-CoV-2. The efficacy of several repurposed drugs has been evaluated in clinical trials. Among these drugs, a relatively new antiandrogen agent, enzalutamide, was proposed because it reduces the expression of transmembrane serine protease 2 (TMPRSS2), a key component mediating SARS-CoV-2-driven entry into host cells, in prostate cancer cells. However, definitive evidence for the therapeutic efficacy of enzalutamide in COVID-19 is lacking. Here, we evaluated the antiviral efficacy of enzalutamide in prostate cancer cells, lung cancer cells, human lung organoids and SARS-CoV-2-infected Ad-ACE2-transduced Tmprss2 knockout (Tmprss2-KO) and wild-type (WT) mice. TMPRSS2 knockout significantly inhibited SARS-CoV-2 infection in vivo. Enzalutamide effectively inhibited SARS-CoV-2 infection in human prostate cancer cells (LNCaP) but not in human lung cancer cells or patient-derived lung organoids. Although Tmprss2 knockout effectively blocked SARS-CoV-2 infection in ACE2-transduced mice, enzalutamide showed no antiviral activity due to the AR independence of TMPRSS2 expression in mouse and human lung epithelial cells. Moreover, we observed distinct AR binding patterns between prostate cells and lung cells and a lack of direct binding of AR to TMPRSS2 in human lung cells. Thus, our findings do not support the postulated protective role of enzalutamide in treating COVID-19.

While cancer is commonly perceived as a disease of dedifferentiation, the hallmark of early stage prostate cancer is paradoxically the loss of more plastic basal cells and the abnormal proliferation of more differentiated secretory luminal cells. However, the mechanism of prostate cancer pro-luminal differentiation is largely unknown. Through integrating analysis of the transcription factors (TFs) from 806 human prostate cancers, we have identified that ERG highly correlated with prostate cancer luminal subtyping. ERG overexpression in luminal epithelial cells inhibits its normal plasticity to transdifferentiate into basal lineage and ERG supersedes PTEN-loss which favors basal differentiation. ERG knock-out disrupted prostate cell luminal differentiation, whereas AR knock-out had no such effects. Trp63 is a known master regulator of prostate basal lineage. Through analysis of 3D chromatin architecture, we found that ERG binds and inhibits the enhancer activity and chromatin looping of a Trp63 distal enhancer, thereby silencing its gene expression. Specific deletion of the distal ERG binding site resulted in the loss of ERG-mediated inhibition of basal differentiation. Thus, ERG orchestrates chromatin interactions and regulates prostate cell lineage toward pro-luminal program, as its fundamental role on lineage differentiation in prostate cancer initiation.

Ca2Si5N8:Eu2+ phosphors have been synthesised in a facile one-step route using raw materials including α-Si3N4, CaCO3, Ca(CH3COO)2 and Eu2O3. Compared with the prevailing conventional methods, an inexpensive and simple method under atmospheric pressure with a relative short reaction time is achieved. The reaction process is optimised to obtain Ca2Si5N8:Eu2+ phosphors with high crystallinity and purity. The phosphors exhibit a red emission peaking at 592 nm under a blue light radiation and show a broad excitation band between 250 and 550 nm. The characteristics of broad excitation band and red emission imply a promising application in blue light-based red light-emitting diode and white light-emitting diode (LED). These results indicate a promising prospect for the efficient and economic route in preparing Ca2Si5N8:Eu2+ phosphors for LED applications.

The lattice structure, mechanical properties, electronic structure and thermodynamic properties of W1−xVx alloys (x = 0, 0.0625, 0.125, 0.25, 0.3125, 0.5 and 1) were calculated and simulated by first-principles method based on DFT. The mechanical properties including Poisson’s ratio, elastic moduli and B/G ratio were analysed via V concentration. The simulated results showed the ductility of alloys getting improved while the strength decreased with the addition of vanadium. And we calculated the anisotropy of Young’s modules and ideal tensile strength. The projected density of states is calculated to analyse the electronic structure. Furthermore, thermodynamic properties like Debye temperature and low temperature heat capacity were also calculated in this work. All the results can provide reference for selecting plasma facing materials in fusion reactor design.