Enhanced multi-class pathology lesion detection in gastric neoplasms using deep learning-based approach and validation.

This study developed a new convolutional neural network model to detect and classify gastric lesions as malignant, premalignant, and benign. We used 10,181 white-light endoscopy images from 2606 patients in an 8:1:1 ratio. Lesions were categorized as early gastric cancer (EGC), advanced gastric cancer (AGC), gastric dysplasia, benign gastric ulcer (BGU), benign polyp, and benign erosion. We assessed the lesion detection and classification model using six-class, cancer versus non-cancer, and neoplasm versus non-neoplasm categories, as well as T-stage estimation in cancer lesions (T1, T2-T4). The lesion detection rate was 95.22% (219/230 patients) on a per-patient basis: 100% for EGC, 97.22% for AGC, 96.49% for dysplasia, 75.00% for BGU, 97.22% for benign polyps, and 80.49% for benign erosion. The six-class category exhibited an accuracy of 73.43%, sensitivity of 80.90%, specificity of 83.32%, positive predictive value (PPV) of 73.68%, and negative predictive value (NPV) of 88.53%. The sensitivity and NPV were 78.62% and 88.57% for the cancer versus non-cancer category, and 83.26% and 89.80% for the neoplasm versus non-neoplasm category, respectively. The T stage estimation model achieved an accuracy of 85.17%, sensitivity of 88.68%, specificity of 79.81%, PPV of 87.04%, and NPV of 82.18%. The novel CNN-based model remarkably detected and classified malignant, premalignant, and benign gastric lesions and accurately estimated gastric cancer T-stages.

Control of OPC proliferation and repopulation by the intellectual disability gene PAK1 under homeostatic and demyelinating conditions.

Appropriate proliferation and repopulation of oligodendrocyte progenitor cells (OPCs) determine successful (re)myelination in homeostatic and demyelinating brains. Activating mutations in p21-activated kinase 1 (PAK1) cause intellectual disability, neurodevelopmental abnormality, and white matter anomaly in children. It remains unclear if and how PAK1 regulates oligodendroglial development. Here, we report that PAK1 controls proliferation and regeneration of OPCs. Unlike differentiating oligodendrocytes, OPCs display high PAK1 activity which maintains them in a proliferative state by modulating PDGFRa-mediated mitogenic signaling. PAK1-deficient or kinase-inhibited OPCs reduce their proliferation capacity and population expansion. Mice carrying OPC-specific PAK1 deletion or kinase inhibition are populated with fewer OPCs in the homeostatic and demyelinated CNS than control mice. Together, our findings suggest that kinase-activating PAK1 mutations stall OPCs in a progenitor state, impacting timely oligodendroglial differentiation in the CNS of affected children and that PAK1 is a potential molecular target for replenishing OPCs in demyelinating lesions.

Miracle friends and miracle money in California: a mixed-methods experiment of social support and guaranteed income for people experiencing homelessness.

BACKGROUND: This paper describes the protocols for a randomized controlled trial using a parallel-group trial design that includes an intervention designed to address social isolation and loneliness among people experiencing homelessness known as Miracle Friends and an intervention that combines Miracles Friends with an economic poverty-reduction intervention known as Miracle Money. Miracle Friends pairs an unhoused person with a volunteer "phone buddy." Miracle Money provides guaranteed basic income of $750 per month for 1 year to Miracle Friends participants. The study will examine whether either intervention reduces social isolation or homelessness compared to a waitlist control group. METHODS: Unhoused individuals who expressed interest in the Miracle Friends program were randomized to either receive the intervention or be placed on a waitlist for Miracle Friends. Among those randomized to receive the Miracle Friends intervention, randomization also determined whether they would be offered Miracle Money. The possibility of receiving basic income was only disclosed to study participants if they were randomly selected and participated in the Miracle Friends program. All study participants, regardless of assignment, were surveyed every 3 months for 15 months. RESULTS: Of 760 unhoused individuals enrolled in the study, 256 were randomized to receive Miracle Friends, 267 were randomized to receive Miracle Money, and 237 were randomized to the waitlist control group. In the two intervention groups, 360 of 523 unhoused individuals were initially matched to a phone buddy. Of the 191 study participants in the Miracle Money group who had been initially matched to a volunteer phone buddy, 103 were deemed to be participating in the program and began receiving monthly income. DISCUSSION: This randomized controlled trial will determine whether innovative interventions involving volunteer phone support and basic income reduce social isolation and improve housing outcomes for people experiencing homelessness. Although we enrolled unhoused individuals who initially expressed interest in the Miracle Friends program, the study team could not reach approximately 30% of individuals referred to the study. This may reflect the general lack of stability in the lives of people who are unhoused or limitations in the appeal of such a program to some portion of the unhoused population. TRIAL REGISTRATION: ClinicalTrials.gov NCT05408884 (first submitted on May 26, 2022).

Clinical Outcomes of A New Hydrophobic Trifocal Intraocular Lens with Hydroxyethyl Methacrylate in Cataract Surgery: A Prospective Multicenter Study.

Purpose: To investigate the clinical outcomes of new hydrophobic trifocal intraocular lens (IOL) with hydroxyethyl methacrylate (HEMA) in the Korean population. Methods: This prospective, multicenter, and observational study evaluated the clinical outcomes of eighty eyes of 40 patients with age-related cataract underwent cataract surgery using CNWT (Clareon PanOptix). Assessment included monocular and binocular uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), uncorrected intermediate visual acuity (UIVA at 60cm), near visual acuity (UNVA at 40cm and 33cm), uncorrected defocus curves, questionnaires evaluating photic phenomena, spectacle independence and spectacle free satisfaction. Results: At 3-month postoperatively, mean uncorrected binocular visual acuities were 0.04, 0.04, 0.03 logMAR at far, intermediate, and near distances respectively. All patients achieved uncorrected binocular VAs of 0.2 logMAR or better. Monocular and binocular defocus curve indicated a mean VA of 0.2 logMAR or better at the defocus range of +1.0 D to - 3.0D (100 cm to 33 cm) and +1.0 D to - 3.5 D (100 cm to 28 cm). High spectacle independence was observed at all distances, with 37.5% patients reporting photic phenomena. Conclusions: The Clareon PanOptix IOL has shown positive clinical outcomes, providing a viable option for cataract surgery. These lenses effectively address patients' visual needs, especially in intermediate and near distance tasks, reducing dependence on glasses.

Neurotoxic effects of polystyrene nanoplastics on memory and microglial activation: Insights from in vivo and in vitro studies.

Nanoplastics, arising from the fragmentation of plastics into environmental pollutants and specialized commercial applications, such as cosmetics, have elicited concerns due to their potential toxicity. Evidence suggests that the oral ingestion of nanoplastics smaller than 100 nm may penetrate the brain and induce neurotoxicity. However, comprehensive research in this area has been hampered by technical challenges associated with the detection and synthesis of nanoplastics. This study aimed to bridge this research gap by successfully synthesizing fluorescent polystyrene nanoplastics (PSNPs, 30-50 nm) through the incorporation of IR-813 and validating them using various analytical techniques. We administered PSNPs orally (10 and 20 mg/kg/day) to mice and observed that they reached brain tissues and induced cognitive dysfunction, as measured by spatial and fear memory tests, while locomotor and social behaviors remained unaffected. In vitro studies (200 µg/mL) demonstrated a predominant uptake of PSNPs by microglia over astrocytes or neurons, leading to microglial activation, as evidenced by immunostaining of cellular markers and morphological analysis. Transcriptomic analysis indicated that PSNPs altered gene expression in microglia, highlighting neuroinflammatory responses that may contribute to cognitive deficits. To further explore the neurotoxic effects of PSNPs mediated by microglial activation, we measured endogenous neuronal activity using a multi-electrode array in cultured hippocampal neurons. The application of conditioned media from microglia exposed to PSNPs suppressed neuronal activity, which was reversed by inhibitors of microglial activation. Our findings offer detailed insights into the mechanisms by which nanoplastics damage the brain, particularly emphasizing the potential environmental risk factors that contribute to cognitive impairment in neurodegenerative diseases.

Risk Assessment of Metachronous Gastric Neoplasm after Endoscopic Resection for Early Gastric Cancer According to Age at Helicobacter pylori Eradication.

Background/Aims: Helicobacter pylori eradication can reduce the incidence of metachronous gastric neoplasm (MGN) after endoscopic submucosal dissection (ESD) for early gastric cancer (EGC). This study evaluated the risk of developing MGN after ESD for EGC based on age at H. pylori eradication. Methods: Data of patients who underwent curative ESD for EGC with H. pylori infection between 2005 and 2018 were retrospectively analyzed. The patients were allocated to four groups according to age at H. pylori eradication: group 1 (<50 years), group 2 (50-59 years), group 3 (60-69 years), and group 4 (≥70 years). Results: All patients were followed up for at least 5 years after ESD. The 5-year cumulative incidence of MGN was 2.1%, 7.0%, 8.7%, and 16.7% in groups 1, 2, 3, and 4, respectively (p<0.001), and groups 3 and 4 showed a significant increase in the risk of MGN (hazard ratio [HR], 4.66; 95% confidence interval [CI], 1.09 to 19.92 and HR, 10.75; 95% CI, 2.45 to 47.12). After adjustments for moderate to severe intestinal metaplasia based on the updated Sydney system, groups 3 and 4 remained significantly associated with MGN (HR, 4.40; 95% CI, 1.03 to 18.84 and HR, 10.14; 95% CI, 2.31 to 44.57). Conclusions: The incidence of MGN after ESD for EGC increased with age at H. pylori eradication. Age at H. pylori eradication ≥60 years was an independent risk factor for MGN, even after adjusting for the presence of advanced intestinal metaplasia.

Safety assessment and gastrointestinal retention of orally administered cerium oxide nanoparticles in rats.

Cerium oxide nanoparticles (CeO2 NPs, NM-212) are well-known for their catalytic properties and antioxidant potential, and have many applications in various industries, drug delivery, and cosmetic formulations. CeO2 NPs exhibit strong antimicrobial activity and can be used to efficiently remove pathogens from different environments. However, knowledge of the toxicological evaluation of CeO2 NPs is too limited to support their safe use. In this study, CeO2 NPs were orally administered to Sprague Dawley rats for 13 weeks at the doses of 0, 10, 100, and 1000 mg/kg bw/day, followed by a four week recovery period. The hematology values for the absolute and relative reticulocyte counts in male rats treated with 1000 mg/kg bw/day CeO2 NPs were lower than those in control rats. The clinical chemistry values for sodium and chloride in the treated male rat groups (100 and 1000 mg/kg/day) and total protein and calcium in the treated female rat groups (100 mg/kg/day) were higher than those in the control groups. However, these changes were not consistent in both sexes, and no abnormalities were found in the corresponding pathological findings. The results showed no adverse effects on any of the parameters assessed. CeO2 NPs accumulated in the jejunum, colon, and stomach wall of rats administered 1000 mg/kg CeO2 NPs for 90 days. However, these changes were not abnormal in the corresponding histopathological and immunohistochemical examinations. Therefore, 1000 mg/kg bw/day may be considered the "no observed adverse effect level" of CeO2 NPs (NM-212) in male and female SD rats under the present experimental conditions.

Associations of Broader Parental Factors with Children's Happiness and Weight Status through Child Food Intake, Physical Activity, and Screen Time: A Longitudinal Modeling Analysis of South Korean Families.

This study investigated how broader parental factors including parental happiness, parental play engagement, and parenting stress are related to Korean children's happiness and weight status across three years via indirect pathways through the children's energy-related behaviors of healthy and unhealthy food intake, physical activity, and screen time. Data from 1551 Korean parent pairs and 7-year-old children in the Panel Study on Korean Children were analyzed. A path analysis and gender-based multi-group analysis were conducted. Maternal happiness was negatively related to child screen time. Maternal play engagement showed positive concurrent associations with child healthy food intake and physical activity and negative associations with screen time. Maternal parenting stress was negatively related to child healthy eating. There was one significant finding related to fathers' role on children's energy-related behaviors, happiness, and weight status: the positive association between parental happiness and boys' unhealthy food intake. Child screen time was positively related to child weight status and negatively to child happiness at each age. Broader maternal parenting factors can serve as a protective factor for childhood happiness and weight status in 7-to-9-year-olds through being associated with a reduction in child screen time.

CYB5R3 functions as a tumor suppressor by inducing ER stress-mediated apoptosis in lung cancer cells via the PERK-ATF4 and IRE1α-JNK pathways.

Cytochrome b5 reductase 3 (CYB5R3) is involved in various cellular metabolic processes, including fatty acid synthesis and drug metabolism. However, the role of CYB5R3 in cancer development remains poorly understood. Here, we show that CYB5R3 expression is downregulated in human lung cancer cell lines and tissues. Adenoviral overexpression of CYB5R3 suppresses lung cancer cell growth in vitro and in vivo. However, CYB5R3 deficiency promotes tumorigenesis and metastasis in mouse models. Transcriptome analysis revealed that apoptosis- and endoplasmic reticulum (ER) stress-related genes are upregulated in CYB5R3-overexpressing lung cancer cells. Metabolomic analysis revealed that CYB5R3 overexpression increased the production of nicotinamide adenine dinucleotide (NAD+) and oxidized glutathione (GSSG). Ectopic CYB5R3 is mainly localized in the ER, where CYB5R3-dependent ER stress signaling is induced via activation of protein kinase RNA-like ER kinase (PERK) and inositol-requiring enzyme 1 alpha (IRE1α). Moreover, NAD+ activates poly (ADP-ribose) polymerase16 (PARP16), an ER-resident protein, to promote ADP-ribosylation of PERK and IRE1α and induce ER stress. In addition, CYB5R3 induces the generation of reactive oxygen species and caspase-9-dependent intrinsic cell death. Our findings highlight the importance of CYB5R3 as a tumor suppressor for the development of CYB5R3-based therapeutics for lung cancer.

Cumulative exposure to impaired fasting glucose and gastrointestinal cancer risk: A nationwide cohort study.

BACKGROUND: Impaired fasting glucose (IFG) is associated with the risk of various cancers, but the cumulative effect of IFG on gastrointestinal cancer risk remains unclear. This study evaluated the association between the cumulative exposure to IFG and gastrointestinal cancer risk. METHODS: The authors extracted data from the Korean National Health Insurance Service and health examination data sets. Among individuals ≥40 years old who were free of diabetes or cancer, 1,430,054 who underwent national health examinations over 4 consecutive years from 2009 to 2012 were selected and followed up until gastrointestinal cancer diagnosis, death, or December 31, 2019. The IFG exposure score (range, 0-4) was based on the number of IFG diagnoses over 4 years. RESULTS: The median follow-up duration was 6.4 years. Consistent normoglycemia for 4 years was found in 44.3% of the population, whereas 5.0% had persistent IFG and 50.7% had intermittent IFG. Compared to the group with an IFG exposure score of 0, groups with IFG exposure scores of 1, 2, 3, and 4 had a 5%, 8%, 9%, and 12% increased risk of gastrointestinal cancer, respectively (score 1: adjusted hazard ratio [aHR], 1.05; 95% confidence interval [CI], 1.01-1.08; score 2: aHR, 1.08; 95% CI, 1.04-1.12; score 3: aHR, 1.09; 95% CI, 1.05-1.14; score 4: aHR, 1.12; 95% CI, 1.06-1.19). Persistent IFG exposure was also associated with higher risks of individual cancer types (colorectum, stomach, pancreas, biliary tract, and esophagus). CONCLUSIONS: Cumulative exposure to IFG is associated with an increased risk of developing gastrointestinal cancer, in a dose-dependent manner. PLAIN LANGUAGE SUMMARY: Hyperglycemia, including both diabetes and prediabetes, has been associated with an increased risk of various cancers. However, the cumulative effect of impaired fasting glucose on the risk of developing gastrointestinal cancer remains unclear. A frequent diagnosis of impaired fasting glucose was dose-dependently associated with a higher risk of developing overall gastrointestinal cancer. Furthermore, risks of individual cancer types increased with persistent impaired fasting glucose. Early detection of hyperglycemia and strict glycemic control can lower the risk of gastrointestinal cancer by reducing hyperglycemic burden. Additionally, for some individuals, lifestyle changes such as managing metabolic syndrome or abstaining from alcohol may also be helpful.

Barrier Abnormalities in Type 1 Diabetes Mellitus: The Roles of Inflammation and Ceramide Metabolism.

Xerosis is a common sign of both type 1 and type 2 diabetes mellitus (DM), and patients with DM and mouse models for DM show a compromised epidermal permeability barrier. Barrier defects then allow the entry of foreign substances into the skin, triggering inflammation, infection, and worsening skin symptoms. Characterizing how barrier abnormalities develop in DM could suggest treatments for xerosis and other skin disease traits. Because the proper ratio, as well as proper bulk amounts, of heterogeneous ceramide species are keys to forming a competent barrier, we investigated how ceramide metabolism is affected in type 1 DM using a mouse model (induced by streptozotocin). Chronic inflammation, evident in the skin of mice with DM, leads to (i) decreased de novo ceramide production through serine racemase activation-mediated attenuation of serine palmitoyl transferase activity by D-serine; (ii) changes in ceramide synthase activities and expression that modify the ratio of ceramide molecular species; and (iii) increased ceramide-1-phosphate, a proinflammatory lipid mediator, that stimulates inflammatory cytokine expression (TNFα and IFN-γ). Together, chronic inflammation affects ceramide metabolism, which attenuates epidermal permeability barrier formation, and ceramide-1-phosphate could amplify this inflammation. Alleviation of chronic inflammation is a credible approach for normalizing barrier function and ameliorating diverse skin abnormalities in DM.

Risk of gastric cancer in relation with serum cholesterol profiles: A nationwide population-based cohort study.

Obesity is a known risk factor for gastric cancer. However, the relationship between serum lipids and gastric cancer risk has not been fully established. We investigated the relationship between serum cholesterol levels and gastric cancer risk using a nationwide population cohort. Adults who received health care screening in 2009 from the Korean National Health Insurance Service were enrolled. Gastric cancer risk in relation to quartiles of high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and total cholesterol (TC) were compared according to sex, using adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs). Among 9690,168 subjects enrolled, 92,403 gastric cancer cases were diagnosed. Higher HDL-C levels were associated with lower gastric cancer risk in the total population, men, and women (aHR [for the highest quartile] = 0.98 [0.96-0.99, P < .0001], aHR = 0.98 [0.96-1.004, P = .0004], and aHR = 0.91 [0.88-0.94, P < .0001], respectively). HDL-C showed consistent trends regardless of age or statin use. Higher LDL-C levels were also associated with lower gastric cancer risk in the total population (aHR = 0.92 [0.91-0.94], P < .0001) and men (aHR = 0.94 [0.91-0.96], P < .0001), but not in women (P = .4073). A subgroup analysis of LDL-C showed significant interactions with age and statin use (Pinteraction < .0001 and Pinteraction = .0497, respectively). The risk of gastric cancer was higher in subjects with elevated LDL-C levels in the younger group (age < 55, HR [for the highest quartile] = 1.02 [0.99-1.04] in the total population; HR = 1.03 [1.003-1.06] in men), the risk was lower in subjects with elevated LDL-C in the elderly (age ≥ 55, HR = 0.93 [0.91-0.95] in the total population; HR = 0.94 [0.92-0.96] in men). Elevated TC was associated with lower gastric cancer risk in the total population (aHR = 0.95 [0.94-0.97], P < .0001), but not in each sex separately (P = .3922 in men; P = .1046 in women). Overall, higher HDL-C levels may play a protective role in gastric cancer pathogenesis. The association between LDL-C/TC and gastric cancer seems to vary according to sex, age, and statin use. Especially in young males under age 55, high LDL-C and TC levels were associated with higher risk of gastric cancer.

Thyroxine metabolite-derived 3-iodothyronamine (T1AM) and synthetic analogs as efficient suppressors of transthyretin amyloidosis.

Aggregation and fibrillization of transthyretin (TTR) is a fatal pathogenic process that can cause cardiomyopathic and polyneuropathic diseases in humans. Although several therapeutic strategies have been designed to prevent and treat related pathological events, there is still an urgent need to develop better strategies to improve potency and wider applicability. Here, we present our study demonstrating that 3-iodothyronamine (T1AM) and selected thyronamine-like compounds can effectively prevent TTR aggregation. T1AM is one of the thyroid hormone (TH) metabolites, and T1AM and its analogs, such as SG2, SG6, and SG12, are notable molecules for their beneficial activities against metabolic disorders and neurodegeneration. Using nuclear magnetic resonance (NMR) spectroscopy and biochemical analysis, we confirmed that T1AM analogs could bind to and suppress acid-induced aggregation of TTR. In addition, we employed computational approaches to further understand the detailed mechanisms of the interaction between T1AM analogs and TTR. This study demonstrates that T1AM analogs, whose beneficial effects against several pathological processes have already been proven, may have additional benefits against TTR aggregation and fibrillization. Moreover, we believe that our work provides invaluable insights to enhance the pleiotropic activity of T1AM and structurally related analogs, relevant for their therapeutic potential, with particular reference to the ability to prevent TTR aggregation.

Receptor-specific contributions of caveolae, PKC, and Src tyrosine kinase to serotonergic and adrenergic regulation of Kv channels and vasoconstriction.

AIMS: Caveolae are invaginated, Ω-shaped membrane structures. They are now recognized as portals for signal transduction of multiple chemical and mechanical stimuli. Notably, the contribution of caveolae has been reported to be receptor-specific. However, details of how they differentially contribute to receptor signaling remain unclear. MAIN METHODS: Using isometric tension measurements, patch-clamping, and western blotting, we examined the contribution of caveolae and their related signaling pathways to serotonergic (5-HT2A receptor-mediated) and adrenergic (α1-adrenoceptor-mediated) signaling in rat mesenteric arteries. KEY FINDINGS: Disruption of caveolae by methyl-ß-cyclodextrin effectively blocked vasoconstriction mediated by the 5-HT2A receptor (5-HT2AR), but not by the α1-adrenoceptor. Caveolar disruption selectively impaired 5-HT2AR-mediated voltage-dependent K+ channel (Kv) inhibition, but not α1-adrenoceptor-mediated Kv inhibition. In contrast, both serotonergic and α1-adrenergic effects on vasoconstriction, as well as Kv currents, were similarly blocked by the Src tyrosine kinase inhibitor PP2. However, inhibition of protein kinase C (PKC) by either GO6976 or chelerythrine selectively attenuated the effects mediated by the α1-adrenoceptor, but not by 5-HT2AR. Disruption of caveolae decreased 5-HT2AR-mediated Src phosphorylation, but not α1-adrenoceptor-mediated Src phosphorylation. Finally, the PKC inhibitor GO6976 blocked Src phosphorylation by the α1-adrenoceptor, but not by 5-HT2AR. SIGNIFICANCE: 5-HT2AR-mediated Kv inhibition and vasoconstriction are dependent on caveolar integrity and Src tyrosine kinase, but not on PKC. In contrast, α1-adrenoceptor-mediated Kv inhibition and vasoconstriction are not dependent on caveolar integrity, but rather on PKC and Src tyrosine kinase. Caveolae-independent PKC is upstream of Src activation for α1-adrenoceptor-mediated Kv inhibition and vasoconstriction.

Implantable Multi-Cross-Linked Membrane-Ionogel Assembly for Reversible Non-Faradaic Neurostimulation.

Neural interfaces play a major role in modulating neural signals for therapeutic purposes. To meet the demand of conformable neural interfaces for developing bioelectronic medicine, recent studies have focused on the performance of electrical neurostimulators employing soft conductors such as conducting polymers and electronic or ionic conductive hydrogels. However, faradaic charge injection at the interface of the electrode and nerve tissue causes irreversible gas evolution, oxidation of electrodes, and reduction of biological ions, thus causing undesired tissue damage and electrode degradation. Here we report a conformable neural interface engineering based on multicross-linked membrane-ionogel assembly (termed McMiA), which enables nonfaradaic neurostimulation without irreversible charge transfer reaction. The McMiA consists of a genipin-cross-linked biopolymeric ionogel coupled with a dopamine-cross-linked graphene oxide membrane to prevent ion exchange between biological and synthetic McMiA ions and to function as a bioadhesive forming covalent bonds with the target tissues. In addition, the demonstration of bioelectronic medicine via the McMiA-based neurostimulation of sciatic nerves shows the enhanced clinical utility in treating the overactive bladder syndrome. As the McMiA-based neural interface is soft, robust for bioadhesion, and stable in a physiological environment, it can offer significant advancement in biocompatibility and long-term operability for neural interface engineering.

ATF6 is a critical regulator of cadmium-mediated apoptosis in spermatocytes.

In this study, we examined the mechanisms of cadmium exposure-induced endoplasmic reticulum (ER) stress response and apoptosis in spermatocytes. Responses to cadmium toxicity were investigated using spermatocytes overexpressing p50ATF6, ATF4, and spliced XBP1s, belonging to the 3 unfolded protein response pathways. The ER stress and apoptosis response to cadmium were most strongly stimulated through the activating transcription factor 6 (ATF6) pathway; in contrast, siRNA-induced inhibition of protein expression could reduce apoptosis under stressful conditions. An in vivo experiment using mice confirmed that upregulation of p50ATF6 in the testis increased apoptosis in response to cadmium exposure. Further, when confirming the correlation between ER stress and MAPK in cadmium toxicity, p38 MAPK phosphorylation was strongly regulated by p50ATF6; p-p38 also mediated the activity of p50ATF6. Overall, these findings suggest that modulating the activity of p38 MAPK and p50ATF6 in cadmium exposure-induced toxicity can be considered a potential strategy to treat infertility.

Lower risk of depression after smoking cessation and alcohol abstinence in patients with gastric cancer who underwent gastrectomy: A population-based, nationwide cohort study.

BACKGROUND: Although depression is associated with poor treatment outcomes in patients with cancer, little is known about whether lifestyle modifications could help prevent depression. The authors aimed to identify the effect of lifestyle modifications, including smoking cessation, alcohol abstinence, and starting regular physical activity, on new-onset depression in patients with gastric cancer who underwent surgery. METHODS: By using the Korean National Health Insurance Service database, patients with gastric cancer who underwent surgery between 2010 and 2017 were identified. Self-reported lifestyle behaviors within 2 years before and after surgery were analyzed using the health examination database. Patients were classified according to changes in lifestyle behaviors, and their risk of new-onset depression was compared. RESULTS: Among 18,902 patients, 2302 (12.19%) developed depression (26.00 per 1000 person-years). Smoking cessation (hazard ratio [HR], 0.77; 95% confidence interval [CI], 0.66-0.91) and alcohol abstinence (HR, 0.79; 95% CI, 0.69-0.90) were associated with reduced risk of depression development compared with persistent smoking and persistent drinking, respectively. Starting regular physical activity was not associated with risk of depression. When lifestyle behaviors after gastrectomy were scored from 0 to 3 points (1 point each for not smoking, not drinking, and being physically active), the risk of depression tended to decrease as lifestyle scores increased from 0 points (reference) to 1 point (HR, 0.69; 95% CI, 0.55-0.83), 2 points (HR, 0.60; 95% CI, 0.50-0.76), and 3 points (HR, 0.55; 95% CI, 0.45-0.68). CONCLUSIONS: Smoking cessation and alcohol abstinence are associated with reduced risk of developing depression in patients with gastric cancer who undergo surgery.

Universal School-Based Social and Emotional Learning (SEL) for Diverse Student Subgroups: Implications for Enhancing Equity Through SEL.

School-based, universal social and emotional learning (SEL) has been widely practiced and promoted as a promising approach to prevent youth mental, emotional, and behavioral problems. Although prior research has accumulated robust evidence of the average effects of universal SEL, it remains unclear whether it works similarly or differentially across diverse sociocultural subgroups of students. Investigating subgroup effects has implications for understanding the impact of universal SEL on possible subgroup disparities in student social-emotional competence (SEC). This study examined whether the effects of a universal SEL program on student SEC development differed across diverse student subgroups classified by gender, race, ethnicity, socioeconomic status, disability status, and English learner status. Data came from student SEC progress monitoring collected during a 1-year quasi-experimental study of a universal SEL program (N = 1592; Grades K-2). The results of multigroup latent growth modeling suggest that (a) the intervention effects were slightly larger for Black students, compared to White or other racial-ethnic subgroups, and (b) the effects were not different across other examined subgroups. This study also found that in the comparison condition, the SEC disparities between Black and White students tended to widen throughout the year, whereas in the intervention condition, Black students showed a similar rate of growth as their White peers. Findings suggest that universal SEL may be similarly beneficial across many diverse student subgroups, while it may yield larger benefits among some racially marginalized subgroups, preventing racial disparities from further widening. Yet the benefits of SEL may not be sufficient to reduce existing subgroup disparities. These findings suggest a need for more studies to examine differential effects of universal preventive programs by diverse subgroups to better inform practices that enhance equity in youth outcomes.