Deaths with COVID-19 and from all-causes following first-ever SARS-CoV-2 infection in individuals with preexisting mental disorders: A national cohort study from Czechia.

BACKGROUND: Evidence suggests reduced survival rates following Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection in people with preexisting mental disorders, especially psychotic disorders, before the broad introduction of vaccines. It remains unknown whether this elevated mortality risk persisted at later phases of the pandemic and when accounting for the confounding effect of vaccination uptake and clinically recorded physical comorbidities. METHODS AND FINDINGS: We used data from Czech national health registers to identify first-ever serologically confirmed SARS-CoV-2 infections in 5 epochs related to different phases of the pandemic: 1st March 2020 to 30th September 2020, 1st October 2020 to 26th December 2020, 27th December 2020 to 31st March 2021, 1st April 2021 to 31st October 2021, and 1st November 2021 to 29th February 2022. In these people, we ascertained cases of mental disorders using 2 approaches: (1) per the International Classification of Diseases 10th Revision (ICD-10) diagnostic codes for substance use, psychotic, affective, and anxiety disorders; and (2) per ICD-10 diagnostic codes for the above mental disorders coupled with a prescription for anxiolytics/hypnotics/sedatives, antidepressants, antipsychotics, or stimulants per the Anatomical Therapeutic Chemical (ATC) classification codes. We matched individuals with preexisting mental disorders with counterparts who had no recorded mental disorders on age, sex, month and year of infection, vaccination status, and the Charlson Comorbidity Index (CCI). We assessed deaths with Coronavirus Disease 2019 (COVID-19) and from all-causes in the time period of 28 and 60 days following the infection using stratified Cox proportional hazards models, adjusting for matching variables and additional confounders. The number of individuals in matched-cohorts ranged from 1,328 in epoch 1 to 854,079 in epoch 5. The proportion of females ranged from 34.98% in people diagnosed with substance use disorders in epoch 3 to 71.16% in individuals diagnosed and treated with anxiety disorders in epoch 5. The mean age ranged from 40.97 years (standard deviation [SD] = 15.69 years) in individuals with substance use disorders in epoch 5 to 56.04 years (SD = 18.37 years) in people with psychotic disorders in epoch 2. People diagnosed with or diagnosed and treated for psychotic disorders had a consistently elevated risk of dying with COVID-19 in epochs 2, 3, 4, and 5, with adjusted hazard ratios (aHRs) ranging from 1.46 [95% confidence intervals (CIs), 1.18, 1.79] to 1.93 [95% CIs, 1.12, 3.32]. This patient group demonstrated also a consistently elevated risk of all-cause mortality in epochs 2, 3, 4, and 5 (aHR from 1.43 [95% CIs, 1.23, 1.66] to 1.99 [95% CIs, 1.25, 3.16]). The models could not be reliably fit for psychotic disorders in epoch 1. People diagnosed with substance use disorders had an increased risk of all-cause mortality 28 days postinfection in epoch 3, 4, and 5 (aHR from 1.30 [95% CIs, 1.14, 1.47] to 1.59 [95% CIs, 1.19, 2.12]) and 60 days postinfection in epoch 2, 3, 4, and 5 (aHR from 1.22 [95% CIs, 1.08, 1.38] to 1.52 [95% CIs, 1.16, 1.98]). Cases ascertained based on diagnosis of substance use disorders and treatment had increased risk of all-cause mortality in epoch 2, 3, 4, and 5 (aHR from 1.22 [95% CIs, 1.03, 1.43] to 1.91 [95% CIs, 1.25, 2.91]). The models could not be reliably fit for substance use disorders in epoch 1. In contrast to these, people diagnosed with anxiety disorders had a decreased risk of death with COVID-19 in epoch 2, 3, and 5 (aHR from 0.78 [95% CIs, 0.69, 0.88] to 0.89 [95% CIs, 0.81, 0.98]) and all-cause mortality in epoch 2, 3, 4, and 5 (aHR from 0.83 [95% CIs, 0.77, 0.90] to 0.88 [95% CIs, 0.83, 0.93]). People diagnosed and treated for affective disorders had a decreased risk of both death with COVID-19 and from all-causes in epoch 3 (aHR from 0.87 [95% CIs, 0.79, 0.96] to 0.90 [95% CIs, 0.83, 0.99]), but demonstrated broadly null effects in other epochs. Given the unavailability of data on a number of potentially influential confounders, particularly body mass index, tobacco smoking status, and socioeconomic status, part of the detected associations might be due to residual confounding. CONCLUSIONS: People with preexisting psychotic, and, less robustly, substance use disorders demonstrated a persistently elevated risk of death following SARS-CoV-2 infection throughout the pandemic. While it cannot be ruled out that part of the detected associations is due to residual confounding, this excess mortality cannot be fully explained by lower vaccination uptake and more clinically recorded physical comorbidities in these patient groups.

Obesity, abdominal obesity, metabolic obesity phenotypes, and Helicobacter pylori infection: results from NHANES 1999-2000.

BACKGROUND: Recent studies on the association between Helicobacter pylori (H. pylori) infection and obesity have reported conflicting results. Therefore, the purpose of our study was to investigate the association of obesity, abdominal obesity, and metabolic obesity phenotypes with H. pylori infection. METHODS: A cross-sectional study of 1568 participants aged 20 to 85 was conducted using the National Health and Nutrition Examination Survey (NHANES) cycle 1999-2000. Logistic regression models were employed to evaluate the association of general obesity as defined by body mass index (BMI), abdominal obesity as defined by waist circumference (WC) and waist-height ratio (WHtR), and metabolic obesity phenotypes with H. pylori seropositivity. Subgroup analyses stratified by age were conducted to explore age-specific differences in this association. RESULTS: After grouping individuals according to their WHtR, the prevalence rate of WHtR ≥ 0.5 in H. pylori-seropositive participants was significantly higher than that in H. pylori-seronegative participants (79.75 vs. 68.39, P < 0.001). The prevalence of H. pylori seropositivity in non-abdominal obesity and abdominal obesity defined by WHtR was 24.97% and 31.80%, respectively (P < 0.001). In the subgroup analysis, the adjusted association between abdominal obesity, as defined by the WHtR, and H. pylori seropositivity was significant in subjects aged < 50 years (OR = 2.23; 95% CI, 1.24-4.01; P = 0.01) but not in subjects aged ≥ 50 years (OR = 0.84; 95% CI, 0.35-1.99; P = 0.66). Subjects older than 50 years old had an OR (95% CI) for metabolically healthy obesity of 0.04 (0.01-0.35) compared with the control group. H. pylori seropositivity was consistently not associated with obesity as defined by BMI. CONCLUSIONS: Abdominal obesity, as defined by the WHtR, was associated with H. pylori infection in subjects aged ≤ 50 years.

Modulating social learning-induced evaluation updating during human sleep.

People often change their evaluations upon learning about their peers' evaluations, i.e., social learning. Given sleep's vital role in consolidating daytime experiences, sleep may facilitate social learning, thereby further changing people's evaluations. Combining a social learning task and the sleep-based targeted memory reactivation technique, we asked whether social learning-induced evaluation updating can be modulated during sleep. After participants had indicated their initial evaluation of snacks, they learned about their peers' evaluations while hearing the snacks' spoken names. During the post-learning non-rapid-eye-movement sleep, we re-played half of the snack names (i.e., cued snack) to reactivate the associated peers' evaluations. Upon waking up, we found that the social learning-induced evaluation updating further enlarged for both cued and uncued snacks. Examining sleep electroencephalogram (EEG) activity revealed that cue-elicited delta-theta EEG power and the overnight N2 sleep spindle density predicted post-sleep evaluation updating for cued but not for uncued snacks. These findings underscore the role of sleep-mediated memory reactivation and the associated neural activity in supporting social learning-induced evaluation updating.

Observing the suppression of individual aversive memories from conscious awareness.

When reminded of an unpleasant experience, people often try to exclude the unwanted memory from awareness, a process known as retrieval suppression. Here we used multivariate decoding (MVPA) and representational similarity analyses on EEG data to track how suppression unfolds in time and to reveal its impact on item-specific cortical patterns. We presented reminders to aversive scenes and asked people to either suppress or to retrieve the scene. During suppression, mid-frontal theta power within the first 500 ms distinguished suppression from passive viewing of the reminder, indicating that suppression rapidly recruited control. During retrieval, we could discern EEG cortical patterns relating to individual memories-initially, based on theta-driven visual perception of the reminders (0 to 500 ms) and later, based on alpha-driven reinstatement of the aversive scene (500 to 3000 ms). Critically, suppressing retrieval weakened (during 360 to 600 ms) and eventually abolished item-specific cortical patterns, a robust effect that persisted until the reminder disappeared (780 to 3000 ms). Representational similarity analyses provided converging evidence that retrieval suppression weakened the representation of target scenes during the 500 to 3000 ms reinstatement window. Together, rapid top-down control during retrieval suppression abolished cortical patterns of individual memories, and precipitated later forgetting. These findings reveal a precise chronometry on the voluntary suppression of individual memories.

Comparative Study for Propranolol Adsorption on the Biochars from Different Agricultural Solid Wastes.

Currently, large amounts of agricultural solid wastes have caused serious environmental problems. Agricultural solid waste is made into biochar by pyrolysis, which is an effective means of its disposal. As the prepared biochar has a good adsorption capacity, it is often used to treat pollutants in water, such as heavy metals and pharmaceuticals. PRO is an emerging contaminant in the environment today. However, there are limited studies on the interaction between biochars with PRO. Thus, in this study, we investigate the adsorption of PRO onto the biochars derived from three different feedstocks. The order of adsorption capacity was corn stalk biochar (CS, 10.97 mg/g) > apple wood biochar (AW, 10.09 mg/g) > rice husk biochar (RH, 8.78 mg/g). When 2 < pH < 9, the adsorption capacity of all the biochars increased as the pH increased, while the adsorption decreased when pH > 9, 10 and 10.33 for AW, CS and RH, respectively. The adsorption of PRO on biochars was reduced with increasing Na+ and Ca2+ concentrations from 0 to 200 mg·L-1. The effects of pH and coexisting ions illustrated that there exist electrostatic interaction and cation exchange in the process. In addition, when HA concentration was less than 20 mg/L, it promoted the adsorption of PRO on the biochars; however, when the concentration was more than 20 mg/L, its promoting effect was weakened and gradually changed into an inhibitory effect. The adsorption isotherm data of PRO by biochars were best fitted with the Freundlich model, indicating that the adsorption process is heterogeneous adsorption. The adsorption kinetics were fitted well with the pseudo-second-order model. All the results can provide new information into the adsorption behavior of PRO and the biochars in the aquatic environment and a theoretical basis for the large-scale application of biochar from agricultural solid wastes.

ASG-YOLOv5: Improved YOLOv5 unmanned aerial vehicle remote sensing aerial images scenario for small object detection based on attention and spatial gating.

With the accelerated development of the technological power of society, aerial images of drones gradually penetrated various industries. Due to the variable speed of drones, the captured images are shadowed, blurred, and obscured. Second, drones fly at varying altitudes, leading to changing target scales and making it difficult to detect and identify small targets. In order to solve the above problems, an improved ASG-YOLOv5 model is proposed in this paper. Firstly, this research proposes a dynamic contextual attention module, which uses feature scores to dynamically assign feature weights and output feature information through channel dimensions to improve the model's attention to small target feature information and increase the network's ability to extract contextual information; secondly, this research designs a spatial gating filtering multi-directional weighted fusion module, which uses spatial filtering and weighted bidirectional fusion in the multi-scale fusion stage to improve the characterization of weak targets, reduce the interference of redundant information, and better adapt to the detection of weak targets in images under unmanned aerial vehicle remote sensing aerial photography; meanwhile, using Normalized Wasserstein Distance and CIoU regression loss function, the similarity metric value of the regression frame is obtained by modeling the Gaussian distribution of the regression frame, which increases the smoothing of the positional difference of the small targets and solves the problem that the positional deviation of the small targets is very sensitive, so that the model's detection accuracy of the small targets is effectively improved. This paper trains and tests the model on the VisDrone2021 and AI-TOD datasets. This study used the NWPU-RESISC dataset for visual detection validation. The experimental results show that ASG-YOLOv5 has a better detection effect in unmanned aerial vehicle remote sensing aerial images, and the frames per second (FPS) reaches 86, which meets the requirement of real-time small target detection, and it can be better adapted to the detection of the weak and small targets in the aerial image dataset, and ASG-YOLOv5 outperforms many existing target detection methods, and its detection accuracy reaches 21.1% mAP value. The mAP values are improved by 2.9% and 1.4%, respectively, compared with the YOLOv5 model. The project is available at https://github.com/woaini-shw/asg-yolov5.git.

Active metabolomics identify potential functional metabolites for preeclampsia prevention.

BACKGROUND: Preeclampsia (PE) is a leading cause of maternal and fetal morbidity and mortality, with limited effective clinical treatment options. Active metabolomics offers a promising approach to uncover metabolic changes in PE and identify potential biomarkers or therapeutic targets. This study performed untargeted metabolomics using LC-MS to compare serum samples from preeclampsia and normal pregnancies. METHODS: We performed untargeted metabolomics using liquid chromatography-mass spectrometry (LC-MS) to compare serum samples from PE patients and normal pregnancies. We analyzed the alterations in metabolites and conducted functional experiments to assess the effects of LysoPE(16:0) on trophoblast cell invasion and migration. Mechanistic studies were performed to explore the potential targeting of GSK-3ß by LysoPE(16:0). RESULTS: Our metabolomics analysis revealed significant alterations in several metabolites, including lysophosphatidylcholines and organic acids. Notably, LysoPE(16:0) was found to be downregulated in the serum of PE patients. Functional experiments demonstrated that LysoPE(16:0) could promote trophoblast cell invasion and migration. Mechanistic studies suggest that the protective effect of LysoPE(16:0) against PE might be mediated through the modulation of the GSK-3ß/ß-Catenin pathway, with LysoPE(16:0) potentially targeting the GSK-3ß protein. CONCLUSIONS: Our findings highlight the potential role of LysoPE(16:0) in the pathophysiology of PE and its ability to modulate the GSK-3ß/ß-Catenin pathway. These results provide new insights into the metabolic changes associated with PE and suggest that LysoPE(16:0) could serve as a promising biomarker or therapeutic target for the prevention and treatment of PE.

Interaction between mental disorders and social disconnectedness on mortality: a population-based cohort study.

BACKGROUND: Despite the recognised importance of mental disorders and social disconnectedness for mortality, few studies have examined their co-occurrence. AIMS: To examine the interaction between mental disorders and three distinct aspects of social disconnectedness on mortality, while taking into account sex, age and characteristics of the mental disorder. METHOD: This cohort study included participants from the Danish National Health Survey in 2013 and 2017 who were followed until 2021. Survey data on social disconnectedness (loneliness, social isolation and low social support) were linked with register data on hospital-diagnosed mental disorders and mortality. Poisson regression was applied to estimate independent and joint associations with mortality, interaction contrasts and attributable proportions. RESULTS: A total of 162 497 individuals were followed for 886 614 person-years, and 9047 individuals (5.6%) died during follow-up. Among men, interaction between mental disorders and loneliness, social isolation and low social support, respectively, accounted for 47% (95% CI: 21-74%), 24% (95% CI: -15 to 63%) and 61% (95% CI: 35-86%) of the excess mortality after adjustment for demographics, country of birth, somatic morbidity, educational level, income and wealth. In contrast, among women, no excess mortality could be attributed to interaction. No clear trends were identified according to age or characteristics of the mental disorder. CONCLUSIONS: Mortality among men, but not women, with a co-occurring mental disorder and social disconnectedness was substantially elevated compared with what was expected. Awareness of elevated mortality rates among socially disconnected men with mental disorders could be of importance to qualify and guide prevention efforts in psychiatric services.

Co-transcriptional R-loops-mediated epigenetic regulation drives growth retardation and docetaxel chemosensitivity enhancement in advanced prostate cancer.

R-loops are prevalent three-stranded nucleic acid structures, comprising a DNA-RNA hybrid and a displaced single-stranded DNA, that frequently form during transcription and may be attributed to genomic stability and gene expression regulation. It was recently discovered that RNA modification contributes to maintain the stability of R-loops such as N6-methyladenosine (m6A). Yet, m6A-modified R-loops in regulating gene transcription remains poorly understood. Here, we demonstrated that insulin-like growth factor 2 mRNA-binding proteins (IGF2BPs) recognize R-loops in an m6A-dependent way. Consequently, IGF2BPs overexpression leads to increased overall R-loop levels, cell migration inhibition, and cell growth retardation in prostate cancer (PCa) via precluding the binding of DNA methyltransferase 1(DNMT1) to semaphorin 3 F (SEMA3F) promoters. Moreover, the K homology (KH) domains of IGF2BPs are required for their recognition of m6A-containing R-loops and are required for tumor suppressor functions. Overexpression of SEMA3F markedly enhanced docetaxel chemosensitivity in prostate cancer via regulating Hippo pathway. Our findings point to a distinct R-loop resolution pathway mediated by IGF2BPs, emphasizing the functional importance of IGF2BPs as epigenetic R-loop readers in transcriptional genetic regulation and cancer biology.The manuscript summarizes the new role of N6-methyladenosine in epigenetic regulation, we introduce the distinct R-loop resolution mediated by IGF2BP proteins in an m6A-dependent way, which probably lead to the growth retardation and docetaxel chemotherapy resistance in prostate cancer. Moreover, our findings first emphasized the functional importance of IGF2BPs as epigenetic R-loop readers in transcriptional genetic regulation and cancer biology. In addition, our research provides a novel RBM15/IGF2BPs/DNMT1 trans-omics regulation m6A axis, indicating the new crosstalk between RNA m6A methylation and DNA methylation in prostate cancer.

Columbianadin suppresses glioblastoma progression by inhibiting the PI3K-Akt signaling pathway.

Glioblastoma (GBM) is the most common malignant glioma among brain tumors with low survival rate and high recurrence rate. Columbianadin (CBN) has pharmacological properties such as anti-inflammatory, analgesic, thrombogenesis-inhibiting and anti-tumor effects. However, it remains unknown that the effect of CBN on GBM cells and its underlying molecular mechanisms. In the present study, we found that CBN inhibited the growth and proliferation of GBM cells in a dose-dependent manner. Subsequently, we found that CBN arrested the cell cycle in G0/G1 phase and induced the apoptosis of GBM cells. In addition, CBN also inhibited the migration and invasion of GBM cells. Mechanistically, we chose network pharmacology approach by screening intersecting genes through targets of CBN in anti-GBM, performing PPI network construction followed by GO analysis and KEGG analysis to screen potential candidate signaling pathway, and found that phosphatidylinositol 3-kinase/Protein Kinase-B (PI3K/Akt) signaling pathway was a potential target signaling pathway of CBN in anti-GBM. As expected, CBN treatment indeed inhibited the PI3K/Akt signaling pathway in GBM cells. Furthermore, YS-49, an agonist of PI3K/Akt signaling, partially restored the anti-GBM effect of CBN. Finally, we found that CBN inhibited GBM growth in an orthotopic mouse model of GBM through inhibiting PI3K/Akt signaling pathway. Together, these results suggest that CBN has an anti-GBM effect by suppressing PI3K/Akt signaling pathway, and is a promising drug for treating GBM effectively.

Study on the correlation between serum indole-3-propionic acid levels and the progression and prognosis of acute ischemic stroke.

OBJECTIVE: This study aimed to explore the correlation between the serum level of indole-3-propionic acid (IPA) and the progression and prognosis of acute cerebral infarction (ACI). METHODS: This study enrolled 197 patients with ACI, and 53 participants from a community-based stroke screening program during the same period were included as the control group. The patients with ACI were divided into quartiles of serum IPA. A logistic regression model was used for comparison. Receiver operating characteristic (ROC) curves were drawn to evaluate the predictive value of the IPA. RESULTS: Compared with the healthy control group, the ACI group had lower serum IPA (P < 0.05). The serum IPA was an independent factor for acute ischemic stroke (OR=0.992, 95% CI: 0.984-0.999, P=0.035). The serum IPA was lower in patients with progressive stroke or poor prognosis than in patients with stable stroke or good prognosis (P < 0.05). Patients with ACI with low serum IPA are prone to progression and poor prognosis. The best cutoff value for predicting progression was 193.62 pg/mL (sensitivity, 67.5%; specificity 83.7%), and that for poor prognosis was 193.77 pg/mL (sensitivity, 71.1%; specificity, 72.5%). CONCLUSION: The serum level of IPA was an independent predictor of ACI and had certain clinical value for predicting stroke progression and prognosis in patients with ACI.

Guanine nucleotide exchange factor RABGEF1 facilitates TNF-induced necroptosis by targeting cIAP1.

Necroptosis is a form of regulated cell death that depends on the receptor-interacting serine-threonine kinase 3 (RIPK3) and mixed lineage kinase domain-like (MLKL). The molecular mechanisms underlying distinct instances of necroptosis have only recently begun to emerge. In the present study, we characterized RABGEF1 as a positive regulator of RIPK1/RIPK3 activation in vitro. Based on the overexpression and knockdown experiments, we determined that RABGEF1 accelerated the phosphorylation of RIPK1 and promoted necrosome formation in L929 cells. The pro-necrotic effect of RABGEF1 is associated with its E3 ubiquitin ligase activity and guanine nucleotide exchange factor (GEF) activity. We further confirmed that RABGEF1 interacts with cIAP1 protein by inhibiting its function and plays a regulatory role in necroptosis, which can be abolished by treatment with the antagonist Smac mimetic (SM)-164. In conclusion, our study highlights a potential and novel role of RABGEF1 in promoting TNF-induced cell necrosis.

Discovery of tricyclic PARP7 inhibitors with high potency, selectivity, and oral bioavailability.

PARP7 has been recently identified as an effective drug target due to its specific role in tumor generation and immune function recovery. Herin, we report the discovery of compound 8, which contained a tricyclic fused ring, as a highly selective PARP7 inhibitor against other PARPs. In particular, compound 8 strongly inhibits PARP7 with an IC50 of 0.11 nM, and suppresses the proliferation of NCI-H1373 lung cancer cells with an IC50 of 2.5 nM. Compound 8 exhibits a favorable pharmacokinetic profile with a bioavailability of 104 % in mice, and 78 % in dogs. Importantly, daily treatment of 30 mg/kg of 8 induced 81.6 % tumor suppression in NCI-H1373 lung xenograft mice tumor models, which is significantly better than the clinical candidate, RBN-2397. These intriguing features highlight the promising advantages of 8 as an antitumor agent.

Chemotherapeutic drug elemene induces pain and anxiety-like behaviors by activating GABAergic neurons in the lateral septum of mice.

Most chemotherapeutic drugs are potent and have a very narrow range of dose safety and efficacy, most of which can cause many side effects. Chemotherapy-induced peripheral neuropathy (CIPN) is the most common and serious side effect of chemotherapy for cancer treatment. However, its mechanism of action is yet to be fully elucidated. In the present study, we found that the treatment of the chemotherapy drug elemene induced hyperalgesia accompanied by anxiety-like emotions in mice based on several pain behavioral assays, such as mechanical allodynia and thermal hyperalgesia tests. Second, immunostaining for c-fos (a marker of activated neurons) further showed that elemene treatment activated several brain regions, including the lateral septum (LS), cingulate cortex (ACC), paraventricular nucleus of the thalamus (PVT), and dorsomedial hypothalamic nucleus (DMH), most notably in the GABAergic neurons of the lateral septum (LS). Finally, we found that both chemogenetic inhibition and apoptosis of LS neurons significantly reduced pain- and anxiety-like behaviors in mice treated with elemene. Taken together, these findings suggest that LS is involved in the regulation of elemene-induced chemotherapy pain and anxiety-like behaviors, providing a new target for the treatment of chemotherapy pain induced by elemene.

The Role of Socioeconomic Position in the Association Between Mental Disorders and Mortality: A Systematic Review and Meta-Analysis.

Importance: Studies are lacking summarizing how the association between mental disorders and mortality varies by socioeconomic position (SEP), particularly considering different aspects of SEP, specific types of mental disorders, and causes of death. Objective: To investigate the role of SEP in the association between mental disorders and mortality and the association between SEP and mortality among people with mental disorders. Data Sources: MEDLINE, Embase, PsycINFO, and Web of Science were searched from January 1, 1980, through April 3, 2023, and a snowball search of reference and citation lists was conducted. Study Selection: Inclusion criteria were observational studies estimating the associations between different types of mental disorders and mortality, stratified by SEP and between SEP and mortality in people with mental disorders. Data Extraction and Synthesis: Pairs of reviewers independently extracted data using a predefined data extraction form and assessed the risk of bias using the adapted Newcastle-Ottawa scale. Graphical analyses of the dose-response associations and random-effects meta-analyses were performed. Heterogeneity was explored through meta-regressions and sensitivity analyses. Main Outcomes and Measures: All-cause and cause-specific mortality. Results: Of 28 274 articles screened, 71 including more than 4 million people with mental disorders met the inclusion criteria (most of which were conducted in high-income countries). The relative associations between mental disorders and mortality were similar across SEP levels. Among people with mental disorders, belonging to the highest rather than the lowest SEP group was associated with lower all-cause mortality (pooled relative risk [RR], 0.79; 95% CI, 0.73-0.86) and mortality from natural causes (RR, 0.73; 95% CI, 0.62-0.85) and higher mortality from external causes (RR, 1.18; 95% CI, 0.99-1.41). Heterogeneity was high (I2 = 83% to 99%). Results from subgroup, sensitivity, and meta-regression analyses were consistent with those from the main analyses. Evidence on absolute scales, specific diagnoses, and specific causes of death was scarce. Conclusion and Relevance: This study did not find a sufficient body of evidence that SEP moderated the relative association between mental disorders and mortality, but the underlying mortality rates may differ by SEP group, despite having scarcely been reported. This information gap, together with our findings related to SEP and a possible differential risk between natural and external causes of death in individuals with specific types of mental disorders, warrants further research.

Item-specific neural representations during human sleep support long-term memory.

Understanding how individual memories are reactivated during sleep is essential in theorizing memory consolidation. Here, we employed the targeted memory reactivation (TMR) paradigm to unobtrusively replaying auditory memory cues during human participants' slow-wave sleep (SWS). Using representational similarity analysis (RSA) on cue-elicited electroencephalogram (EEG), we found temporally segregated and functionally distinct item-specific neural representations: the early post-cue EEG activity (within 0 to 2,000 ms) contained comparable item-specific representations for memory cues and control cues, signifying effective processing of auditory cues. Critically, the later EEG activity (2,500 to 2,960 ms) showed greater item-specific representations for post-sleep remembered items than for forgotten and control cues, indicating memory reprocessing. Moreover, these later item-specific neural representations were supported by concurrently increased spindles, particularly for items that had not been tested prior to sleep. These findings elucidated how external memory cues triggered item-specific neural representations during SWS and how such representations were linked to successful long-term memory. These results will benefit future research aiming to perturb specific memory episodes during sleep.

Colonic de novo Clear Cell Adenocarcinoma of Intestinal-Type: A Case Report and Review of the Literature.

Colorectal clear cell adenocarcinomas are rare tumors. They can be divided into two types: intestinal- and Müllerian-type. Most intestinal-type clear cell adenocarcinomas show a composite morphology, and most early-stage (T1) intestinal-type clear cell adenocarcinomas have an adenoma component. We report an additional early-stage (T1) colonic clear cell adenocarcinoma that was a de novo adenocarcinoma without any adenoma component. It had a pure morphology and the smallest size (0.6 cm) ever reported. Immunohistochemical results demonstrated an intestinal phenotype (KRT20+, KRT7-, CEA+, and CDX2+). Periodic acid-schiff and alcian blue stains were both negative, which demonstrated decrease in mucin expression in the clear tumor cells. Enteroblastic differentiation was observed in a few colorectal clear cell adenocarcinomas in the literature, while it had not been observed in the present tumor. The tumor did not have deep submucosal invasion and cancer embolus, endoscopic submucosal dissection with regular follow-up was an appropriate treatment for the patient. Due to the rarity and diversity of primary colorectal clear cell adenocarcinomas, the cause of clear cytoplasm change and the impact on patient prognosis remain unknown. Accumulating evidence indicates that clear cell adenocarcinomas of intestinal-type is a histological variant of colorectal adenocarcinoma.

Enhanced rich club connectivity in mild or moderate depression after nonpharmacological treatment: A preliminary study.

INTRODUCTION: It has been suggested that the rich club organization in major depressive disorder (MDD) was altered. However, it remained unclear whether the rich club organization could be served as a biomarker that predicted the improvement of clinical symptoms in MDD. METHODS: The current study included 29 mild or moderate patients with MDD, who were grouped into a treatment group (receiving cognitive behavioral therapy or real-time fMRI feedback treatment) and a no-treatment group. Resting-state MRI scans were obtained for all participants. Graph theory was employed to investigate the treatment-related changes in network properties and rich club organization. RESULTS: We found that patients in the treatment group had decreased depressive symptom scores and enhanced rich club connectivity following the nonpharmacological treatment. Moreover, the changes in rich club connectivity were significantly correlated with the changes in depressive symptom scores. In addition, the nonpharmacological treatment on patients with MDD increased functional connectivity mainly among the salience network, default mode network, frontoparietal network, and subcortical network. Patients in the no-treatment group did not show significant changes in depressive symptom scores and rich club organization. CONCLUSIONS: Those results suggested that the remission of depressive symptoms after nonpharmacological treatment in MDD patients was associated with the increased efficiency of global information processing.