Premature Death, Suicide, and Nonlethal Intentional Self-Harm After Psychiatric Discharge.

Importance: There is a need for representative research on serious adverse outcomes following discharge from psychiatric hospitalization. Objective: To compare rates of premature death, suicide, and nonlethal intentional self-harm after psychiatric discharge with rates in the general population and investigate associations of these outcomes with relevant variables associated with the index psychiatric hospitalization. Design, Setting, and Participants: This retrospective cohort study included all residents from Catalonia, Spain (7.6 million population), who had psychiatric hospitalizations between January 1, 2014, and December 31, 2018, and were older than 10 years at the index (first) hospitalization. Follow-up was until December 31, 2019. Statistical analysis was performed from December 1, 2022, through April 11, 2024. Exposures: Socioeconomic status, psychiatric diagnoses, duration of index hospitalization, and number of previous psychiatric hospitalizations. Main Outcomes and Measures: Postdischarge premature death (ie, all-cause death before age 70 years) and suicide (International Statistical Classification of Diseases and Related Health Problems, Tenth Revision [ICD-10] code range X60-X84), identified using mortality data, and postdischarge nonlethal intentional self-harm, identified using electronic health record and self-harm case register data. Standardized mortality ratios (SMRs) compared rates of premature death and suicide between the cohort and the general population. Fully adjusted, multivariable, cause-specific Cox proportional hazards regression models for the 3 outcomes were fitted. Results: A total of 49 108 patients discharged from psychiatric hospitalization were included (25 833 males [52.6%]; mean [SD] age at discharge, 44.2 [18.2] years). During follow-up, 2260 patients (4.6%) died prematurely, 437 (0.9%) died by suicide, and 4752 (9.7%) had an episode of nonlethal intentional self-harm. The overall SMR for premature death was 7.5 (95% CI, 7.2-7.9). For suicide, SMR was 32.9 (95% CI, 29.9-36.0) overall and was especially high among females (47.6 [95% CI, 40.2-54.9]). In fully adjusted sex-stratified hazard models, postdischarge premature death was associated with cognitive disorders (adjusted hazard ratio [AHR], 2.89 [95% CI, 2.24-3.74] for females; 2.59 [95% CI, 2.17-3.08] for males) and alcohol-related disorders (AHR, 1.41 [95% CI, 1.18-1.70] for females; 1.22 [95% CI, 1.09-1.37] for males). Postdischarge suicide was associated with postdischarge intentional self-harm (AHR, 2.83 [95% CI, 1.97-4.05] for females; 3.29 [95% CI, 2.47-4.40] for males), with depressive disorders (AHR, 2.13 [95% CI, 1.52-2.97]) and adjustment disorders (AHR, 1.94 [95% CI, 1.32-2.83]) among males, and with bipolar disorder among females (AHR, 1.94 [95% CI, 1.21-3.09]). Postdischarge intentional self-harm was associated with index admissions for intentional self-harm (AHR, 1.95 [95% CI, 1.73-2.21] for females; 2.62 [95% CI, 2.20-3.13] for males) as well as for adjustment disorders (AHR, 1.48 [95% CI, 1.33-1.65] for females; 1.99 [95% CI, 1.74-2.27] for males), anxiety disorders (AHR, 1.24 [95% CI, 1.10-1.39] for females; 1.36 [95% CI, 1.18-1.58] for males), depressive disorders (AHR, 1.54 [95% CI, 1.40-1.69] for females; 1.80 [95% CI, 1.58-2.04] for males), and personality disorders (AHR, 1.59 [95% CI, 1.46-1.73] for females; 1.43 [95% CI, 1.28-1.60] for males). Conclusions and Relevance: In this cohort study of patients discharged from psychiatric hospitalization, risk for premature death and suicide was significantly higher compared with the general population, suggesting individuals discharged from psychiatric inpatient care are a vulnerable population for premature death and suicidal behavior.

Active immunization with recombinant GnRH6-CRM197 inhibits reproductive function of male rats.

Gonadotropin-releasing hormone (GnRH) vaccines have been successfully used for the inhibition of gonadal development and function, but current GnRH-based vaccines often present variability in the response. Cross-reactive material 197 (CRM197) has been used as carrier molecules to enhance an immune response to associated antigens. So, the synthetic mammalian tandem-repeated GnRH hexamer (GnRH6) gene was integrated into the expression plasmid pET-21a. Recombinant GnRH6-CRM197 protein was subsequently overexpressed in Escherichia coli strain BL21 and purified through Nickel column affinity chromatography and the antigenicity and biological effects of GnRH6-CRM197 were evaluated in rats. Sixteen 4-month-old adult male rats were randomly divided into two groups: the GnRH6-CRM197 group (n = 8) and the control group (n = 8). The GnRH6-CRM197 group rats were subcutaneously immunized with 100 µg of GnRH6-CRM197, administered thrice at 2-week intervals with GnRH6-CRM197.The control group received only a white oil adjuvant. Following the initial immunization, the weights of animals were recorded, and blood samples were collected from the orbital sinus at 4, 4.5, 5, 5.5, 6, 6.5, and 7 months. Serum antibody titers and testosterone concentrations were quantified using ELISA and CLIA, respectively. Additionally, testicular tissues were collected for morphological examination. The results revealed a significant increase in serum GnRH antibody titers (p < 0.05), but a significant decrease in serum testosterone concentrations (p < 0.05), and the weight, length, width, and girth of the testis, and the number of spermatogonia cells, spermatocytes, and sperm cells in the immunized rats. Furthermore, seminiferous tubules revealed significant atrophy and no sperm were observed in the immunized animals. Thus, GnRH6-CRM197 may be an effective antigen and a potential immunocastration vaccine.

The transcription factor MhZAT10 enhances antioxidant capacity by directly activating the antioxidant genes MhMSD1, MhAPX3a, and MhCAT1 in apple rootstock SH6 (Malus honanensis × M. domestica).

Stress tolerance in apple (Malus domestica) can be improved by grafting to a stress-tolerant rootstock, such as 'SH6' (Malus honanensis × M. domestica 'Ralls Genet'). However, the mechanisms of stress tolerance in this rootstock are unclear. In Arabidopsis (Arabidopsis thaliana), the transcription factor ZINC FINGER OF ARABIDOPSIS THALIANA 10 (ZAT10) is a key component of plant tolerance to multiple abiotic stresses and positively regulates antioxidant enzymes. However, how reactive oxygen species (ROS) are eliminated upon activation of ZAT10 in response to abiotic stress remains elusive. Here, we report that MhZAT10 in the rootstock SH6 directly activates the transcription of three genes encoding the antioxidant enzymes MANGANESE SUPEROXIDE DISMUTASE 1 (MhMSD1), ASCORBATE PEROXIDASE 3A (MhAPX3a), and CATALASE 1 (MhCAT1) by binding to their promoters. Heterologous expression in Arabidopsis protoplasts showed that MhMSD1, MhAPX3a, and MhCAT1 localize in multiple subcellular compartments. Overexpressing MhMSD1, MhAPX3a, or MhCAT1 in SH6 fruit calli resulted in higher superoxide dismutase, ascorbate peroxidase, and catalase enzyme activities in their respective overexpressing calli than in those overexpressing MhZAT10. Notably, the calli overexpressing MhZAT10 exhibited better growth and lower ROS levels under simulated osmotic stress. Apple SH6 plants overexpressing MhZAT10 in their roots via Agrobacterium rhizogenes-mediated transformation also showed enhanced tolerance to osmotic stress, with higher leaf photosynthetic capacity, relative water content in roots, and antioxidant enzyme activity, as well as less ROS accumulation. Overall, our study demonstrates that the transcription factor MhZAT10 synergistically regulates the transcription of multiple antioxidant-related genes and elevates ROS detoxification.

TiN/anatase/rutile phase junction obtained by in-situ thermal transformation for efficient photothermal-assisted photocatalytic hydrogen generation.

Phase junctions exhibit great potential in photocatalytic energy conversion, yet the narrow light response region and inefficient charge transfer limit their photocatalytic performance. Herein, an anatase/rutile phase junction modified by plasmonic TiN and oxygen vacancies (TiN/(A-R-TiO2-Ov)) is prepared through an in-situ thermal transformation from TiN for efficient photothermal-assisted photocatalytic hydrogen production for the first time. The content of TiN, oxygen vacancies, and phase components in TiN/(A-R-TiO2-Ov) hybrids can be well-adjusted by tuning the heating time. The as-prepared photocatalysts display a large specific area and wide light absorption due to the synergistic effect of plasmonic excitation, oxygen vacancies, and bandgap excitations. Meanwhile, the multi-interfaces between TiN, anatase, and rutile provide built-in electric fields for efficient separation of photoinduced carriers and hot electron injection via ohmic contact and type-Ⅱ band arrangement. As a result, the TiN/(A-R-TiO2-Ov) photocatalyst shows an excellent photocatalytic hydrogen generation rate of 15.07 mmol/g/h, which is 20.6 times higher than that of titanium dioxide P25. Moreover, temperature-dependent photocatalytic tests reveal that the excellent photothermal conversion caused by plasmonic heating and crystal lattice vibrations in TiN/(A-R-TiO2-Ov) has about 25 % enhancement in photocatalysis (18.84 mmol/g/h). This work provides new inspiration for developing high-performance photocatalysts by optimizing charge transfer and photothermal conversion.

Bifidobacterium adolescentis-derived hypaphorine alleviates acetaminophen hepatotoxicity by promoting hepatic Cry1 expression.

Acetaminophen (APAP)-induced liver injury (AILI) is a pressing public health concern. Although evidence suggests that Bifidobacterium adolescentis (B. adolescentis) can be used to treat liver disease, it is unclear if it can prevent AILI. In this report, we prove that B. adolescentis significantly attenuated AILI in mice, as demonstrated through biochemical analysis, histopathology, and enzyme-linked immunosorbent assays. Based on untargeted metabolomics and in vitro cultures, we found that B. adolescentis generates microbial metabolite hypaphorine. Functionally, hypaphorine inhibits the inflammatory response and hepatic oxidative stress to alleviate AILI in mice. Transcriptomic analysis indicates that Cry1 expression is increased in APAP-treated mice after hypaphorine treatment. Overexpression of Cry1 by its stabilizer KL001 effectively mitigates liver damage arising from oxidative stress in APAP-treated mice. Using the gene expression omnibus (GEO) database, we verified that Cry1 gene expression was also decreased in patients with APAP-induced acute liver failure. In conclusion, this study demonstrates that B. adolescentis inhibits APAP-induced liver injury by generating hypaphorine, which subsequently upregulates Cry1 to decrease inflammation and oxidative stress.

Development and validation of an artificial intelligence-based model for detecting urothelial carcinoma using urine cytology images: a multicentre, diagnostic study with prospective validation.

Background: Urine cytology is an important non-invasive examination for urothelial carcinoma (UC) diagnosis and follow-up. We aimed to explore whether artificial intelligence (AI) can enhance the sensitivity of urine cytology and help avoid unnecessary endoscopy. Methods: In this multicentre diagnostic study, consecutive patients who underwent liquid-based urine cytology examinations at four hospitals in China were included for model development and validation. Patients who declined surgery and lacked associated histopathology results, those diagnosed with rare subtype tumours of the urinary tract, or had low-quality images were excluded from the study. All liquid-based cytology slides were scanned into whole-slide images (WSIs) at 40 × magnification and the WSI-labels were derived from the corresponding histopathology results. The Precision Urine Cytology AI Solution (PUCAS) was composed of three distinct stages (patch extraction, features extraction, and classification diagnosis) and was trained to identify important WSI features associated with UC diagnosis. The diagnostic sensitivity was mainly used to validate the performance of PUCAS in retrospective and prospective validation cohorts. This study is registered with the ChiCTR, ChiCTR2300073192. Findings: Between January 1, 2018 and October 31, 2022, 2641 patients were retrospectively recruited in the training cohort, and 2335 in retrospective validation cohorts; 400 eligible patients were enrolled in the prospective validation cohort between July 7, 2023 and September 15, 2023. The sensitivity of PUCAS ranged from 0.922 (95% CI: 0.811-0.978) to 1.000 (0.782-1.000) in retrospective validation cohorts, and was 0.896 (0.837-0.939) in prospective validation cohort. The PUCAS model also exhibited a good performance in detecting malignancy within atypical urothelial cells cases, with a sensitivity of over 0.84. In the recurrence detection scenario, PUCAS could reduce 57.5% of endoscopy use with a negative predictive value of 96.4%. Interpretation: PUCAS may help to improve the sensitivity of urine cytology, reduce misdiagnoses of UC, avoid unnecessary endoscopy, and reduce the clinical burden in resource-limited areas. The further validation in other countries is needed. Funding: National Natural Science Foundation of China; Key Program of the National Natural Science Foundation of China; the National Science Foundation for Distinguished Young Scholars; the Science and Technology Planning Project of Guangdong Province; the National Key Research and Development Programme of China; Guangdong Provincial Clinical Research Centre for Urological Diseases.

Integrative proteomic and transcriptomic analysis in the female goat ovary to explore the onset of puberty.

Puberty is considered a prerequisite for affecting reproductive performance and productivity. Little was known about molecular changes in pubertal goat ovaries. Therefore, we measured and performed a correlation analysis of the mRNA and proteins changes in the pre-pubertal and pubertal goat ovaries. The results showed that only six differentially expressed genes and differentially abundant proteins out of 18,139 genes and 7550 proteins quantified had significant correlations. CNTN2 and THBS1, discovered in the mRNA-mRNA interaction network, probably participated in pubertal and reproductive regulation by influencing GnRH receptor signals, follicular development, and ovulation. The predicted core transcription factors may either promote or inhibit the expression of reproductive genes and act synergistically to maintain normal reproductive function in animals. The interaction between PKM and TIMP3 with other proteins may impact animal puberty through energy metabolism and ovarian hormone secretion. Pathway enrichment analyses revealed that the co-associated key pathways between ovarian genes and proteins at puberty included calcium signalling pathway and olfactory transduction. These pathways were associated with gonadotropin-releasing hormone synthesis and secretion, signal transmission, and cell proliferation. In summary, these results enriched the potential molecules and signalling pathways that affect puberty and provided new insights for regulating and promoting the onset of puberty. SIGNIFICANCE: This study conducted the first transcriptomic and proteomic correlation analysis of pre-pubertal and pubertal goat ovaries and identified six significantly correlated molecules at both the gene and protein levels. Meanwhile, we were drawn to several molecules and signalling pathways that may play a regulatory role in the onset of puberty and reproduction by influencing reproductive-related gene expression, GnRH receptor signals, energy metabolism, ovarian hormone secretion, follicular development, and ovulation. This information contributed to identify potential biomarkers in pubertal goat ovaries, which was vital for predicting the onset of puberty and improving livestock performance.

Developing a clinical decision support system software prototype that assists in the management of patients with self-harm in the emergency department: protocol of the PERMANENS project.

BACKGROUND: Self-harm presents a significant public health challenge. Emergency departments (EDs) are crucial healthcare settings in managing self-harm, but clinician uncertainty in risk assessment may contribute to ineffective care. Clinical Decision Support Systems (CDSSs) show promise in enhancing care processes, but their effective implementation in self-harm management remains unexplored. METHODS: PERMANENS comprises a combination of methodologies and study designs aimed at developing a CDSS prototype that assists clinicians in the personalized assessment and management of ED patients presenting with self-harm. Ensemble prediction models will be constructed by applying machine learning techniques on electronic registry data from four sites, i.e., Catalonia (Spain), Ireland, Norway, and Sweden. These models will predict key adverse outcomes including self-harm repetition, suicide, premature death, and lack of post-discharge care. Available registry data include routinely collected electronic health record data, mortality data, and administrative data, and will be harmonized using the OMOP Common Data Model, ensuring consistency in terminologies, vocabularies and coding schemes. A clinical knowledge base of effective suicide prevention interventions will be developed rooted in a systematic review of clinical practice guidelines, including quality assessment of guidelines using the AGREE II tool. The CDSS software prototype will include a backend that integrates the prediction models and the clinical knowledge base to enable accurate patient risk stratification and subsequent intervention allocation. The CDSS frontend will enable personalized risk assessment and will provide tailored treatment plans, following a tiered evidence-based approach. Implementation research will ensure the CDSS' practical functionality and feasibility, and will include periodic meetings with user-advisory groups, mixed-methods research to identify currently unmet needs in self-harm risk assessment, and small-scale usability testing of the CDSS prototype software. DISCUSSION: Through the development of the proposed CDSS software prototype, PERMANENS aims to standardize care, enhance clinician confidence, improve patient satisfaction, and increase treatment compliance. The routine integration of CDSS for self-harm risk assessment within healthcare systems holds significant potential in effectively reducing suicide mortality rates by facilitating personalized and timely delivery of effective interventions on a large scale for individuals at risk of suicide.

Vitamin E biofortification: enhancement of seed tocopherol concentrations by altered chlorophyll metabolism.

Homogentisate Phytyltransferase (HPT) catalyzes condensation of homogentisate (HGA) and phytyl diphosphate (PDP) to produce tocopherols, but can also synthesize tocotrienols using geranylgeranyl diphosphate (GGDP) in plants engineered for deregulated HGA synthesis. In contrast to prior tocotrienol biofortification efforts, engineering enhanced tocopherol concentrations in green oilseeds has proven more challenging due to the integral role of chlorophyll metabolism in supplying the PDP substrate. This study show that RNAi suppression of CHLSYN coupled with HPT overexpression increases tocopherol concentrations by >two-fold in Arabidopsis seeds. We obtained additional increases in seed tocopherol concentrations by engineering increased HGA production via overexpression of bacterial TyrA that encodes chorismate mutase/prephenate dehydrogenase activities. In overexpression lines, seed tocopherol concentrations increased nearly three-fold, and resulted in modest tocotrienol accumulation. We further increased total tocochromanol concentrations by enhancing production of HGA and GGDP by overexpression of the gene for hydroxyphenylpyruvate dioxygenase (HPPD). This shifted metabolism towards increased amounts of tocotrienols relative to tocopherols, which was reflected in corresponding increases in ratios of GGDP/PDP in these seeds. Overall, our results provide a theoretical basis for genetic improvement of total tocopherol concentrations in green oilseeds (e.g., rapeseed, soybean) through strategies that include seed-suppression of CHLSYN coupled with increased HGA production.

Suicide attempt risk predicts inconsistent self-reported suicide attempts: A machine learning approach using longitudinal data.

INTRODUCTION: Inconsistent self-reports of lifetime suicide attempts (LSAs) are a major obstacle for accurate assessment of suicidal behavior. This study is the first to posit that adolescents at higher risk report LSAs more consistently than those at lower risk, revealing a link between suicide attempt risk and consistent reporting. METHODS: A machine learning model was trained with 70 % of the baseline assessment data of a longitudinal sample of Norwegian adolescents (n = 10,739). The model was used to estimate the LSA risk score for the remaining 30 % of the testing dataset. The relationship between these baseline risk scores and the consistency of reporting LSAs was assessed using a 2-year follow-up reassessment of the testing dataset. RESULTS: Internalizing problems, optimism about the future, conduct problems, substance use, and disordered eating were important factors associated with suicide attempt risk. Of the participants, 63.41 % had inconsistent self-reports at the two-year follow-up. Adolescents who consistently reported LSAs had significantly higher scores of suicide attempt risk at baseline. Two logistic regression analyses confirmed an association between suicide attempt risk and inconsistent self-reported LSAs and showed that sex (being male), and lower levels of depression and conduct problems significantly predicted such inconsistencies. Those who inconsistently reported LSAs were more likely than the others to be classified by the model as false negatives at the baseline risk assessment due to their lower estimated risk scores. LIMITATIONS: Suicide attempts were measured with a single item in this study. CONCLUSION: These risk factors support the theory of adolescent suicidality (TAS) and could improve suicide attempt risk assessment. Inconsistent self-reported LSAs signal lower suicide attempt risk.

Grid1 regulates the onset of puberty in female rats.

The study aimed to investigate the effect of Grid1, encoding the glutamate ionotropic receptor delta type subunit 1 (GluD1), on puberty onset in female rats. Grid1 mRNA and protein expression was detected in the hypothalamus of female rats at prepuberty and puberty. The levels of Grid1 mRNA in the hypothalamus, the fluorescence intensity in the arcuate nucleus and paraventricular nucleus of the prepubertal rats was significantly lower than pubertal. Additionally, the expression of Grid1 was suppressed in primary hypothalamus cells and prepubertal rat. Finally, investigated the effect of Grid1 knockdown on puberty onset and reproductive performance. Treatment of hypothalamic neurons with LV-Grid1 decreased the level of Grid1 and Rfrp-3 (encoding RFamide-related peptide 3) mRNA expression, but increased the Gnrh (encoding gonadotropin-releasing hormone) mRNA levels. After an ICV injection, the time for the rat vaginal opening occurred earlier. Moreover, Gnrh mRNA expression was increased, whereas Rfrp-3 mRNA expression was decreased in the hypothalamus. The concentration of progesterone (P4) in the serum was significantly decreased compare with control group. Ovary hematoxylin-eosin staining revealed that the LV-Grid1 group mainly contained primary and secondary follicles. The reproductive performance of the rats was not affected by the Grid1 knockdown. Therefore, Grid1 may affect the onset of puberty in female rats by regulating the levels of Gnrh, and Rfrp-3 in the hypothalamus, as well as the concentrations of P4, but not reproduction performance.

Interpersonal violent injury and subsequent risk of suicide and deliberate self-harm: a register-based national cohort study from Norway, 2010-2018.

Background: Interpersonal violence is a leading cause of morbidity, with potentially severe adverse consequences for the mental health of the injured persons. The extent to which violent injury is associated with subsequent suicidal behavior, however, remains unclear. This study aimed to examine how violent injury was associated with subsequent deliberate self-harm and death by suicide. Methods: This retrospective cohort study used nationwide longitudinal registry data from Norway to identify all individuals presenting to emergency services in 2010-2018 with a violence-related injury, along with sex- and age-matched control individuals from the general population. The primary outcomes were any emergency visit for deliberate self-harm (DSH) and suicide death, observed through 31 December 2018. Rates of each outcome were compared between violence-injured patients and comparison individuals using stratified multivariable Cox regression models, controlling for sociodemographic characteristics as well as history of psychiatric treatment and DSH. Secondary analyses tested for moderation by sex, age, and prior psychiatric treatment. Findings: Violence-injured patients (n = 28,276) had substantially higher rates of DSH (946.7 per 100,000 person-years) and suicide death (74.5 per 100,000) when compared to controls (n = 282,760; 90.0 and 15.2 per 100,000, respectively). The hazard ratios (HRs) remained significantly higher even after accounting for covariates (HRadj for DSH: 5.11; 95% CI: 4.62, 5.66; HRadj for suicide: 2.40; 95% CI: 1.78, 3.24). Sex differences in this association were negligible, but the association between violence injury and DSH increased with age. Violence-injured patients with prior psychiatric treatment had the highest risk of suicidal behavior. Interpretation: Violence-injured patients experience significantly excess rates of suicidal behavior, a finding with potential to inform both clinical intervention and population-level suicide prevention strategies. Funding: Fulbright Norway Scholarship.

PAX2 is regulated by estrogen/progesterone through promoter methylation in endometrioid adenocarcinoma and has an important role in carcinogenesis via the AKT/mTOR signaling pathway.

Endometrioid adenocarcinoma (EEC) is one of the most common cancers of the female reproductive system. In recent years, much emphasis has been placed on early diagnosis and treatment. PAX2 (Paired box 2) inactivation is reportedly an important biomarker for endometrioid intraepithelial neoplasia (EIN) and EEC. However, the role of PAX2 in EEC carcinogenesis remains unclear. PAX2 expression and associated clinical characteristics were analyzed via The Cancer Genome Atlas, Gene Expression Omnibus, and Cancer Cell Line Encyclopedia databases and clinical paired EIN/EEC tissue samples. Bioinformatic analysis was conducted to identify the putative molecular function and mechanism of PAX2. Cell proliferation, colony formation, cell migration, and invasion assays in vitro, and mouse xenograft models were utilized to study the biological functions of PAX2 in vivo. Pyrosequencing and the demethylating drug 5-Aza-dc were used to verify promoter methylation in clinical tissues and cell lines, respectively. The mechanism underlying the regulatory effect of estrogen (E2) and progesterone (P4) on PAX2 expression was investigated by receptor block assay and double luciferase reporter assay. PAX2 expression was found to be significantly downregulated in EIN and EEC tissues, its overexpression inhibited EEC cell malignant behaviors in vivo and in vitro and inhibited the AKT/mTOR signaling pathway. PAX2 inactivation in EEC was related to promoter methylation, and its expression was regulated by E2 and P4 through their receptors via promoter methylation. Our findings elucidated the expression and function of PAX2 in EEC and have provided hitherto undocumented evidence of the underlying molecular mechanisms. PAX2 expression is suppressed by estrogen prompting its methylation through estrogen receptor. Furthermore, PAX2 regulates the AKT/mTOR signaling pathway to influence EEC progression. © 2024 The Pathological Society of Great Britain and Ireland.

Unveiling Adolescent Suicidality: Holistic Analysis of Protective and Risk Factors Using Multiple Machine Learning Algorithms.

Adolescent suicide attempts are on the rise, presenting a significant public health concern. Recent research aimed at improving risk assessment for adolescent suicide attempts has turned to machine learning. But no studies to date have examined the performance of stacked ensemble algorithms, which are more suitable for low-prevalence conditions. The existing machine learning-based research also lacks population-representative samples, overlooks protective factors and their interplay with risk factors, and neglects established theories on suicidal behavior in favor of purely algorithmic risk estimation. The present study overcomes these shortcomings by comparing the performance of a stacked ensemble algorithm with a diverse set of algorithms, performing a holistic item analysis to identify both risk and protective factors on a comprehensive data, and addressing the compatibility of these factors with two competing theories of suicide, namely, The Interpersonal Theory of Suicide and The Strain Theory of Suicide. A population-representative dataset of 173,664 Norwegian adolescents aged 13 to 18 years (mean = 15.14, SD = 1.58, 50.5% female) with a 4.65% rate of reported suicide attempt during the past 12 months was analyzed. Five machine learning algorithms were trained for suicide attempt risk assessment. The stacked ensemble model significantly outperformed other algorithms, achieving equal sensitivity and a specificity of 90.1%, AUC of 96.4%, and AUCPR of 67.5%. All algorithms found recent self-harm to be the most important indicator of adolescent suicide attempt. Exploratory factor analysis suggested five additional risk domains, which we labeled internalizing problems, sleep disturbance, disordered eating, lack of optimism regarding future education and career, and victimization. The identified factors provided stronger support for The Interpersonal Theory of Suicide than for The Strain Theory of Suicide. An enhancement to The Interpersonal Theory based on the risk and protective factors identified by holistic item analysis is presented.

Anti-Ulcerative Colitis Effects and Active Ingredients in Ethyl Acetate Extract from Decoction of Sargentodoxa cuneata.

Ulcerative colitis (UC) is an intractable disease prevalent worldwide. While ethyl acetate extract from decoction of Sargentodoxa cuneata (EAdSc) has potential anti-inflammatory activity, its effects on UC remain unknown. In this study, the constituent compounds discussed in the literature and identified by gas chromatography and mass spectrometry (GC-MS) were collected, and the blood-soluble components of EAdSc were identified by liquid chromatography-mass spectrometry. The network pharmacology analysis and molecular docking analysis were performed to explore the potential underlying mechanism and active ingredients of EAdSc against UC. Furthermore, mice with dextran sulfate sodium (DSS)-induced UC were used to study the therapeutic effects and validate the mechanism of EAdSc against UC. A total of 53 compounds from EAdSc were identified in the literature and by GC-MS, and 22 blood-soluble EAdSc components were recognized. Network pharmacology analysis revealed that multiple inflammatory signaling pathways are involved in EAdSc's anti-UC activity. Furthermore, molecular docking analysis showed that the eleutheroside A, liriodendrin, epicatechin, 2-methoxy-4-vinylphenol, catechin, androsin, coumaroyltyramine, and catechol may be active against UC through the TLR4/NF-κB/NLRP3 pathway. EAdSc reduced the disease activity, macroscopic colon damage, and histological damage indices, as well as inhibiting DSS-induced spleen enlargement and colon shortening. In addition, EAdSc decreased the levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-1ß, IL-6, and IL-17, as well as the expression of TLR4, NF-κB p65, NLRP3, and Caspase-1 mRNA in colon tissues. These results provide insights into the anti-UC effects and underlying mechanisms of EAdSc and help elucidate the active ingredients of EAdSc in the treatment of UC.

Significant Enhancement of Circular Polarization in Light Emission through Controlling Helical Pitches of Semiconductor Nanohelices.

Circularly polarized light emission (CPLE) can be potentially applied to three-dimensional displays, information storage, and biometry. However, these applications are practically limited by a low purity of circular polarization, i.e., the small optical dissymmetry factor gCPLE. Herein, glancing angle deposition (GLAD) is performed to produce inorganic nanohelices (NHs) to generate CPLE with large gCPLE values. CdSe NHs emit red CPLE with gCPLE = 0.15 at a helical pitch (P) ≈ 570 nm, having a 40-fold amplification of gCPLE compared to that at P ≈ 160 nm. Ceria NHs emit ultraviolet-blue CPLE with gCPLE ≈ 0.06 at P ≈ 830 nm, with a 103-fold amplification compared to that at P ≈ 110 nm. Both the photoluminescence and scattering among the close-packed NHs complicatedly account for the large gCPLE values, as revealed by the numerical simulations. The GLAD-based NH-fabrication platform is devised to generate CPLE with engineerable color and large gCPLE = 10-2-10-1, shedding light on the commercialization of CPLE devices.

Integrative proteomic and phosphoproteomic analysis in the female goat hypothalamus to study the onset of puberty.

BACKGROUND: Puberty marks the end of childhood and achieve sexual maturation and fertility. The role of hypothalamic proteins in regulating puberty onset is unclear. We performed a comprehensive differential proteomics and phosphoproteomics analysis in prepubertal and pubertal goats to determine the roles of hypothalamic proteins and phosphoproteins during the onset of puberty. RESULTS: We used peptide and posttranslational modifications peptide quantification and statistical analyses, and identified 69 differentially expressed proteins from 5,057 proteins and 576 differentially expressed phosphopeptides from 1574 phosphorylated proteins. Combined proteomic and phosphoproteomics, 759 correlated proteins were identified, of which 5 were differentially expressed only at the protein level, and 201 were only differentially expressed at the phosphoprotein level. Pathway enrichment analyses revealed that the majority of correlated proteins were associated with glycolysis/gluconeogenesis, Fc gamma R-mediated phagocytosis, focal adhesion, GABAergic synapse, and Rap1 signaling pathway. These pathways are related to cell proliferation, neurocyte migration, and promoting the release of gonadotropin-releasing hormone in the hypothalamus. CTNNB1 occupied important locations in the protein-protein interaction network and is involved in focal adhesion. CONCLUSION: The results demonstrate that the proteins differentially expression only at the protein level or only differentially expressed at the phosphoprotein level and their related signalling pathways are crucial in regulating puberty in goats. These differentially expressed proteins and phosphorylated proteins may constitute the proteomic backgrounds between the two different stages.

Situation Analysis of Suicide and Self-Harm in the WHO Eastern Mediterranean Region.

OBJECTIVE: An estimated 41,000 lives are lost to suicide each year in World Health Organization Eastern Mediterranean Region Office (WHO EMRO) countries. The objective of this study was to conduct a situation analysis for suicide and self-harm in the WHO EMRO region. METHODS: Data on suicide were obtained from the WHO Global Health Estimates for the years 2000-2019. Information on risk groups efforts to prevent self-harm and suicide in the EMRO region were retrieved through scientific studies, grey literature, and public websites. RESULTS: During 2000-2019, the age-standardized suicide rate was 6.7 per 100,000 inhabitants, albeit there are concerns regarding data quality. Self-harm and suicide remain criminal acts in more than half of the countries. Few countries have a national plan for prevention of suicide. Toxic agents, such as pesticides and black henna, are easily available and frequently used for suicide in some areas, as are firearms and self-immolation. Successful prevention measures include means restriction and psychosocial interventions after self-harm. CONCLUSION: Many WHO EMRO countries remain underserved in terms of mental health care. Decriminalization of suicide and means restriction might be further promoted. Online-based tools for mental health literacy and psychosocial therapy are other options to explore.

Suicidal behavior remains a criminal act in more than half of the WHO EMRO countries.Easily available toxic agents, such as pesticides and black henna, and firearms are common methods used for suicidal behavior in the WHO EMRO countries.Access to mental health care is limited in many of the WHO EMRO countries.Online-based psychoeducation and psychosocial intervention programs might be further explored as preventive efforts.

Psychiatric disorders among adult deliberate self-harm patients and subsequent risk of dying by suicide, mental and behavioural disorders and other external causes.

INTRODUCTION: Deliberate self-harm (DSH) treated in general hospital is a well-established risk factor for suicide and other cause mortality. However, few studies have used population data to investigate the differential impact of specific psychiatric disorders on the risk of subsequent suicide, by sex and age of the patient in the context of previous DSH episodes. METHOD: All patients aged 18 and older treated for DSH in general hospitals during the period 2008-2018 were identified through national registers. Cox proportional hazards regression was used to ascertain the associated risk of death by suicide, mental and behavioural disorder and other external causes. RESULTS: The cohort consisted of 39 479 patients of which 878 died by suicide, 461 by mental and behavioural disorders and 1037 by other external causes. Overall, schizophrenia spectrum disorders, affective disorders and personality disorders increased the risk of suicide. Large gender and age differences were identified in the risk of suicide associated with personality disorders and affective disorders. Alcohol use disorders and dementia increased the risk of dying by mental and behavioural disorders and alcohol use disorders and other substance use disorders increased the risk of death by external causes. CONCLUSION: Schizophrenia spectrum disorders, affective disorders and personality disorders increased the risk of suicide among DSH patients, but the effect varied by gender, age and history of previous DSH. Psychiatric evaluation of all DSH patients and treatment tailored to the patient's specific needs is essential to reduce the risk of premature death.

Prognostic Predicting Model of Pancreatic Body Tail Carcinoma Using Clinical and CT Radiomic Data.

Objective: To collect the clinical, pathological, and computed tomography (CT) data of 143 accepted surgical cases of pancreatic body tail cancer (PBTC) and to model and predict its prognosis. Methods: The clinical, pathological, and CT data of 143 PBTC patients who underwent surgical resection or endoscopic ultrasound biopsy and were pathologically diagnosed in Xiangyang No.1 People's Hospital Hospital from December 2012 to December 2022 were retrospectively analyzed. The Kaplan-Meier method was adopted to make survival curves based on the 1 to 5 years' follow-up data, and then the log-rank was employed to analyze the survival. According to the median survival of 6 months, the PBTC patients were divided into a group with a good prognosis (survival time ≥ 6 months) and a group with a poor prognosis (survival time < 6 months), and further the training set and test set were set at a ratio of 7/3. Then logistic regression was conducted to find independent risk factors, establish predictive models, and further the models were validated. Results: The Kaplan-Meier analysis showed that age, diabetes, tumor, node, and metastasis stage, CT enhancement mode, peripancreatic lymph node swelling, nerve invasion, surgery in a top hospital, tumor size, carbohydrate antigen 19-9, carcinoembryonic antigen, Radscore 1/2/3 were the influencing factors of PBTC recurrence. The overall average survival was 7.4 months in this study. The multivariate logistic analysis confirmed that nerve invasion, surgery in top hospital, dilation of the main pancreatic duct, and Radscore 2 were independent factors affecting the mortality of PBTC (P < .05). In the test set, the combined model achieved the best predictive performance [AUC 0.944, 95% CI (0.826-0.991)], significantly superior to the clinicopathological model [AUC 0.770, 95% CI (0.615-0.886), P = .0145], and the CT radiomics model [AUC 0.883, 95% CI (0.746-0.961), P = .1311], with a good clinical net benefit confirmed by decision curve. The same results were subsequently validated on the test set. Conclusion: The diagnosis and treatment of PBTC are challenging, and survival is poor. Nevertheless, the combined model benefits the clinical management and prognosis of PBTC.