Improving cancer immunotherapy in prostate cancer by modulating T cell function through targeting the galectin-1.

Our study aimed to elucidate the role of Galectin-1 (Gal-1) role in the immunosuppressive tumor microenvironment (TME) of prostate cancer (PCa). Our previous findings demonstrated a correlation between elevated Gal-1 expression and advanced PCa stages. In this study, we also observed that Gal-1 is expressed around the tumor stroma and its expression level is associated with PCa progression. We identified that Gal-1 could be secreted by PCa cells, and secreted Gal-1 has the potential to induce T cell apoptosis. Gal-1 knockdown or inhibition of Gal-1 function by LLS30 suppresses T cell apoptosis resulting in increased intratumoral T cell infiltration. Importantly, LLS30 treatment significantly improved the antitumor efficacy of anti-PD-1 in vivo. Mechanistically, LLS30 binds to the carbohydrate recognition domain (CRD) of Gal-1, disrupting its binding to CD45 leading to the suppression of T cell apoptosis. In addition, RNA-seq analysis revealed a novel mechanism of action for LLS30, linking its tumor-intrinsic oncogenic effects to anti-tumor immunity. These findings suggested that tumor-derived Gal-1 contributes to the immunosuppressive TME in PCa by inducing apoptosis in effector T cells. Targeting Gal-1 with LLS30 may offer a strategy to enhance anti-tumor immunity and improve immunotherapy.

Relationship between shift type and sleep quality in rotating-shift nurses with chronotype as a moderator variable.

BACKGROUND: Rotating-shift nurses are susceptible to sleep disorders due to numerous factors, such as their biological clock, emotions, and age. At present, a lack of research exists on whether chronotype and shift type jointly influence the sleep quality of nurses. AIM: To verify whether chronotype is a moderator variable of the relationship between shift type and sleep quality in nurses in order to provide empirical evidence for future mental and physical health improvement. METHOD: Clinical rotating-shift nurses at a medical center in northern Taiwan were recruited as participants between November 1, 2023, and December 13, 2023. All of the nurses were working a monthly rotating shift schedule. Hierarchical multiple regression analysis was employed to investigate whether the influence of shift type on sleep quality in nurses varied with chronotype. The STROBE checklist was used for reporting this study. RESULTS: The participants were 255 rotating-shift nurses in this study. Hierarchical multiple regression results revealed that rotating-shift nurses who were older (B = 0.19, p = 0.029), had greater physical fatigue (B = 0.27, p = 0.016), and had more negative emotions (B = 0.17, p = 0.011) suffered from poorer sleep quality. After controlling the above factors, we further found that chronotype indeed had moderating effects on the influence of shift type on sleep quality (B = -1.83, p = 0.049). CONCLUSIONS: This study demonstrates that early- and intermediate-type nurses are more suitable for working the day and evening shifts, whereas late-type nurses are more suitable for working the night shift. IMPLICATION FOR NURSING AND HEALTH POLICY: Coordinating chronotype with shift type will ensure that shift schedules better match the biological clocks of nurses; such individual considerations could help to improve their sleep quality.

Genetic evidence for a causal link between gut microbiota and arterial embolism and thrombosis: a two-sample Mendelian randomization study.

Background: Previous research has hinted at a crucial link between gut microbiota and arterial embolism and thrombosis, yet the causal relationship remains enigmatic. To gain a deeper understanding, we aimed to comprehensively explore the causal relationship and elucidate the impact of the gut microbiota on the risk through a two-sample Mendelian randomization (MR) study. Methods: Genetic instrumental variables for gut microbiota were identified from a genome-wide association study (GWAS) of 18,340 participants. Summary statistics for IBS were drawn from a GWAS including 1,076 cases and 381,997 controls. We used the inverse-variance weighted (IVW) method as the primary analysis. To test the robustness of our results, we further performed the weighted median method, MR-Egger regression, and MR pleiotropy residual sum and outlier test. Results: We identified three bacterial traits that were associated with the risk of arterial embolism and thrombosis: odds ratio (OR): 1.58, 95% confidence interval (CI): 1.08-2.31, p = 0.017 for genus Catenibacterium; OR: 0.64, 95% CI: 0.42-0.96, p = 0.031 for genus Dialister; and OR: 2.08, 95% CI: 1.25-3.47, p = 0.005 for genus Odoribacter. The results of sensitivity analyses for these bacterial traits were consistent (P<0.05). Conclusion: Our systematic analyses provided evidence to support a potential causal relationship between several gut microbiota taxa and the risk of arterial embolism and thrombosis. More studies are required to show how the gut microbiota affects the development of arterial embolism and thrombosis.

Teaching Masked Autoencoder With Strong Augmentations.

Masked autoencoder (MAE) has been regarded as a capable self-supervised learner for various downstream tasks. Nevertheless, the model still lacks high-level discriminability, which results in poor linear probing performance. In view of the fact that strong augmentation plays an essential role in contrastive learning, can we capitalize on strong augmentation in MAE? The difficulty originates from the pixel uncertainty caused by strong augmentation that may affect the reconstruction, and thus, directly introducing strong augmentation into MAE often hurts the performance. In this article, we delve into the potential of strong augmented views to enhance MAE while maintaining MAE's advantages. To this end, we propose a simple yet effective masked Siamese autoencoder (MSA) model, which consists of a student branch and a teacher branch. The student branch derives MAE's advanced architecture, and the teacher branch treats the unmasked strong view as an exemplary teacher to impose high-level discrimination onto the student branch. We demonstrate that our MSA can improve the model's spatial perception capability and, therefore, globally favors interimage discrimination. Empirical evidence shows that the model pretrained by MSA provides superior performances across different downstream tasks. Notably, linear probing performance on frozen features extracted from MSA leads to 6.1% gains over MAE on ImageNet-1k. Fine-tuning (FT) the network on VQAv2 task finally achieves 67.4% accuracy, outperforming 1.6% of the supervised method DeiT and 1.2% of MAE. Codes and models are available at https://github.com/KimSoybean/MSA.

Cardiac autonomic regulation following a 246-km mountain ultra-marathon: An observational study.

Physical exercise requires integrated autonomic and cardiovascular adjustments to maintain homeostasis. We aimed to observe acute posture-related changes in blood pressure, and apply a portable noninvasive monitor to measure the heart index for detecting arrhythmia among elite participants of a 246-km mountain ultra-marathon. Nine experienced ultra-marathoners (8 males and 1 female) participating in the Run Across Taiwan Ultra-marathon in 2018 were enrolled. The runners' Heart Spectrum Blood Pressure Monitor measurements were obtained in the standing and supine positions before and immediately after the race. Their high-sensitivity troponin T and N-terminal proB-type natriuretic peptide levels were analyzed 1 week before and immediately after the event. Heart rate was differed significantly in the immediate postrace assessment compared to the prerace assessment, in both the standing (P = .011; d = 1.19) and supine positions (P = .008; d = 1.35). Postural hypotension occurred in 4 (44.4%) individuals immediately postrace. In 3 out of 9 (33.3%) recruited finishers, the occurrence of premature ventricular complex signals in the standing position was detected; premature ventricular complex signal effect was observed in the supine position postrace in only 1 participant (11.1%). Premature ventricular complex signal was positively correlated with running speed (P = .037). Of the 6 individuals who completed the biochemical tests postrace, 2 (33.3%) had high-sensitivity troponin T and 6 (100%) had N-terminal proB-type natriuretic peptide values above the reference interval. A statistically significant increase was observed in both the high-sensitivity troponin T (P = .028; d = 1.97), and N-terminal proB-type natriuretic peptide (P = .028; d = 2.91) levels postrace compared to prerace. In conclusion, significant alterations in blood pressure and heart rate were observed in the standing position, and postexercise (postural) hypotension occurred among ultra-marathoners. The incidence of premature ventricular complexes was higher after the race than before.

The Significant Associations between Epigenetic Clocks and Bladder Cancer Risks.

Bladder cancer is an age-related disease, with over three-quarters of cases occurring in individuals aged 65 years and older. Accelerated biological aging has been linked to elevated cancer risks. Epigenetic clocks serve as excellent predictors of biological age, yet it remains unclear whether they are associated with bladder cancer risk. In this large case-control study, we assessed the associations between four well-established epigenetic clocks-HannumAge, HorvathAge, GrimAge, and PhenoAge-and bladder cancer risk. Utilizing single nucleotide polymorphisms (SNPs), which were identified in a genome-wide association study (GWAS), linked to these clocks as instruments, we constructed a weighted genetic risk score (GRS) for each clock. We discovered that higher HannumAge and HorvathAge GRS were significantly associated with increased bladder cancer risk (OR = 1.69 per SD increase, 95% CI, 1.44-1.98, p = 1.56 × 10-10 and OR = 1.09 per SD increase, 95% CI, 1.00-1.19, p = 0.04, respectively). Employing a summary statistics-based Mendelian randomization (MR) method, inverse-variance weighting (IVW), we found consistent risk estimates for bladder cancer with both HannumAge and HorvathAge. Sensitivity analyses using weighted median analysis and MR-Egger regression further supported the validity of the IVW method. However, GrimAge and PhenoAge were not associated with bladder cancer risk. In conclusion, our data provide the first evidence that accelerated biological aging is associated with elevated bladder cancer risk.

Systemic interindividual DNA methylation variants in cattle share major hallmarks with those in humans.

BACKGROUND: We recently identified ~ 10,000 correlated regions of systemic interindividual epigenetic variation (CoRSIVs) in the human genome. These methylation variants are amenable to population studies, as DNA methylation measurements in blood provide information on epigenetic regulation throughout the body. Moreover, establishment of DNA methylation at human CoRSIVs is labile to periconceptional influences such as nutrition. Here, we analyze publicly available whole-genome bisulfite sequencing data on multiple tissues of each of two Holstein cows to determine whether CoRSIVs exist in cattle. RESULTS: Focusing on genomic blocks with ≥ 5 CpGs and a systemic interindividual variation index of at least 20, our approach identifies 217 cattle CoRSIVs, a subset of which we independently validate by bisulfite pyrosequencing. Similar to human CoRSIVs, those in cattle are strongly associated with genetic variation. Also as in humans, we show that establishment of DNA methylation at cattle CoRSIVs is particularly sensitive to early embryonic environment, in the context of embryo culture during assisted reproduction. CONCLUSIONS: Our data indicate that CoRSIVs exist in cattle, as in humans, suggesting these systemic epigenetic variants may be common to mammals in general. To the extent that individual epigenetic variation at cattle CoRSIVs affects phenotypic outcomes, assessment of CoRSIV methylation at birth may become an important tool for optimizing agriculturally important traits. Moreover, adjusting embryo culture conditions during assisted reproduction may provide opportunities to tailor agricultural outcomes by engineering CoRSIV methylation profiles.

Nonsignaling extracellular spacer regulates tumor antigen selectivity of CAR T cells.

Advancing chimeric antigen receptor (CAR)-engineered T cells for the treatment of solid tumors is a major focus in the field of cellular immunotherapy. Several hurdles have hindered similar CAR T cell clinical responses in solid tumors as seen in hematological malignancies. These challenges include on-target off-tumor toxicities, which have inspired efforts to optimize CARs for improved tumor antigen selectivity and overall safety. We recently developed a CAR T cell therapy targeting prostate stem cell antigen (PSCA) for prostate and pancreatic cancers, showing improved preclinical antitumor activity and T cell persistence by optimizing the intracellular co-stimulatory domain. Similar studies were undertaken to optimize HER2-directed CAR T cells with modifications to the intracellular co-stimulatory domain for selective targeting of breast cancer brain metastasis. In the present study, we evaluate various nonsignaling extracellular spacers in these CARs to further improve tumor antigen selectivity. Our findings suggest that length and structure of the extracellular spacer can dictate the ability of CARs to selectively target tumor cells with high antigen density, while sparing cells with low antigen density. This study contributes to CAR construct design considerations and expands our knowledge of tuning solid tumor CAR T cell therapies for improved safety and efficacy.

A Lactobacillus Combination Ameliorates Lung Inflammation in an Elastase/LPS-induced Mouse Model of Chronic Obstructive Pulmonary Disease.

Chronic obstructive pulmonary disease (COPD) is the world's leading lung disease and lacks effective and specific clinical strategies. Probiotics are increasingly used to support the improvement of the course of inflammatory diseases. In this study, we evaluated the potential of a lactic acid bacteria (LAB) combination containing Limosilactobacillus reuteri GMNL-89 and Lacticaseibacillus paracasei GMNL-133 to decrease lung inflammation and emphysema in a COPD mouse model. This model was induced by intranasal stimulation with elastase and LPS for 4 weeks, followed by 2 weeks of oral LAB administration. The results showed that the LAB combination decreased lung emphysema and reduced inflammatory cytokines (IL-1ß, IL-6, TNF-α) in the lung tissue of COPD mice. Microbiome analysis revealed that Bifidobacterium and Akkermansia muciniphila, reduced in the gut of COPD mice, could be restored after LAB treatment. Microbial α-diversity in the lungs decreased in COPD mice but was reversed after LAB administration, which also increased the relative abundance of Candidatus arthromitus in the gut and decreased Burkholderia in the lungs. Furthermore, LAB-treated COPD mice exhibited increased levels of short-chain fatty acids, specifically acetic acid and propionic acid, in the cecum. Additionally, pulmonary emphysema and inflammation negatively correlated with C. arthromitus and Adlercreutzia levels. In conclusion, the combination of L. reuteri GMNL-89 and L. paracasei GMNL-133 demonstrates beneficial effects on pulmonary emphysema and inflammation in experimental COPD mice, correlating with changes in gut and lung microbiota, and providing a potential strategy for future adjuvant therapy.

Impact of Vitamin D Receptor Genotypes on Taiwan Hallux Valgus.

BACKGROUND/AIM: Hallux valgus (HV) is the most prevalent deformity affecting the forefoot; however, its genetic etiology remains unclear. In the literature, vitamin D receptor (VDR) genotypes have been reported to be associated with the risk of skeletal malformations accompanied by inflammation. This study aimed to examine the hypothesis that VDR genotypes are associated with the risk of HV. MATERIALS AND METHODS: The VDR rs731236, rs1544410, rs2228570 and rs7975232 genotypes of 150 HV patients and 600 non-HV subjects were determined using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methodology and examined regarding their associations with HV risk. RESULTS: The results showed that none of the genetic frequency distributions of VDR rs731236, rs1544410, rs2228570, or rs7975232 were significant between the HV cases and non-HV controls (p for trend=0.4055, 0.2170, 0.7220, 0.5509, respectively). Additionally, allelic frequency analysis showed that none of the allelic frequencies of VDR rs731236, rs1544410, rs2228570, or rs7975232 were significantly distributed (p=0.2285, 0.1572, 0.9278, and 0.5547, respectively). Furthermore, stratified analysis showed that no correlation was observed between VDR rs731236 and different age groups (either younger or older than 51) or sex (p=0.3953 and p=0.9576). Moreover, no correlation was found between VDR rs731236 genotype and the risk of HV in individuals within subgroups of height, weight, or body mass index (BMI) (p=0.8317, 0.5346, and p=0.8783, respectively). CONCLUSION: VDR rs731236, rs1544410, rs2228570, and rs7975232 may not serve as indicators for a higher risk of HV.

Association of Matrix Metalloproteinase-9 Genotypes With Nasopharyngeal Carcinoma Risk.

BACKGROUND/AIM: The up-regulation of matrix metalloproteinase-9 (MMP-9) expression is a characteristic feature observed across various malignancies, including nasopharyngeal carcinoma (NPC). Nevertheless, the influence of MMP-9 genotype in the context of NPC remains underexplored. This study examined the implications of MMP-9 promoter rs3918242 genotypes on the susceptibility to NPC in Taiwan. MATERIALS AND METHODS: In a cohort comprising 208 NPC cases and 416 healthy controls, genotyping of MMP-9 rs3918242 was conducted utilizing polymerase chain reaction-restriction fragment length polymorphism methodology. RESULTS: Individuals harbouring the variant CT or TT genotype of MMP-9 rs3918242 did not demonstrate a discernible alteration in NPC risk when compared to wild-type CC carriers [odds ratio (OR)=0.83 and 0.79, with 95% confidence intervals (95%CI)=0.56-1.24 and 0.27-2.29; p=0.4205 and 0.8675, respectively]. Moreover, the presence of the variant T allele did not confer a modified risk of NPC (OR=0.84, 95%CI=0.60-1.19, p=0.3761). Intriguingly, a protective effect associated with the MMP-9 rs3918242 CT genotype against NPC risk was discerned among individuals abstaining from betel quid chewing behaviour (OR=0.51, 95%CI=0.30-0.87, p=0.0166). Notably, no significant association was established between the MMP-9 rs3918242 CT or TT genotype and NPC risk among individuals with or without smoking or alcohol consumption habits. CONCLUSION: Presence of the variant CT or TT genotype at MMP-9 rs3918242 did not appear to substantially contribute to an elevated risk of NPC. Notably, a protective effect against NPC risk was observed in individuals carrying the CT genotype, particularly in those abstaining from betel quid chewing.

Decay and Termite Resistance of Wood Modified by High-Temperature Vapour-Phase Acetylation (HTVPA), a Simultaneous Acetylation and Heat Treatment Modification Process.

High-temperature vapour-phase acetylation (HTVPA) is a simultaneous acetylation and heat treatment process for wood modification. This study was the first investigation into the impact of HTVPA treatment on the resistance of wood to biological degradation. In the termite resistance test, untreated wood exhibited a mass loss (MLt) of 20.3%, while HTVPA-modified wood showed a reduced MLt of 6.6-3.2%, which decreased with an increase in weight percent gain (WPG), and the termite mortality reached 95-100%. Furthermore, after a 12-week decay resistance test against brown-rot fungi (Laetiporus sulfureus and Fomitopsis pinicola), untreated wood exhibited mass loss (MLd) values of 39.6% and 54.5%, respectively, while HTVPA-modified wood exhibited MLd values of 0.2-0.9% and -0.2-0.3%, respectively, with no significant influence from WPG. Similar results were observed in decay resistance tests against white-rot fungi (Lenzites betulina and Trametes versicolor). The results of this study demonstrated that HTVPA treatment not only effectively enhanced the decay resistance of wood but also offered superior enhancement relative to separate heat treatment or acetylation processes. In addition, all the HTVPA-modified wood specimens prepared in this study met the requirements of the CNS 6717 wood preservative standard, with an MLd of less than 3% for decay-resistant materials.

Transcriptomic Insights and the Development of Microsatellite Markers to Assess Genetic Diversity in the Broodstock Management of Litopenaeus stylirostris.

The Pacific blue shrimp (Litopenaeus stylirostris) is a premium product in the international seafood market. However, intensified farming has increased disease incidence and reduced genetic diversity. In this study, we developed a transcriptome database for L. stylirostris and mined microsatellite markers to analyze their genetic diversity. Using the Illumina HiSeq 4000 platform, we identified 53,263 unigenes from muscle, hepatopancreas, the intestine, and lymphoid tissues. Microsatellite analysis identified 36,415 markers from 18,657 unigenes, predominantly dinucleotide repeats. Functional annotation highlighted key disease resistance pathways and enriched categories. The screening and PCR testing of 42 transcriptome-based and 58 literature-based markers identified 40 with successful amplification. The genotyping of 200 broodstock samples revealed that Na, Ho, He, PIC, and FIS values were 3, 0.54 ± 0.05, 0.43 ± 0.09, 0.41 ± 0.22, and 0.17 ± 0.27, respectively, indicating moderate genetic variability and significant inbreeding. Four universal microsatellite markers (CL1472.Contig13, CL517.Contig2, Unigene5692, and Unigene7147) were identified for precise diversity analysis in Pacific blue, Pacific white (Litopenaeus vannamei), and black tiger shrimps (Penaeus monodon). The transcriptome database supports the development of markers and functional gene analysis for selective breeding programs. Our findings underscore the need for an appropriate genetic management system to mitigate inbreeding depression, reduce disease susceptibility, and preserve genetic diversity in farmed shrimp populations.

Contribution of Matrix Metalloproteinase-7 Genotypes to Endometriosis Risk in Taiwan.

BACKGROUND/AIM: The activity and expression of matrix metalloproteinase-7 (MMP7) have been found to be upregulated in the late stages of endometriosis. However, the contribution of MMP7 genotype to endometriosis has seldom been examined. This study aimed to investigate the role of MMP7 promoter A-181G (rs11568818) and C-153T (rs11568819) genotypes in determining personal susceptibility to endometriosis in a Taiwanese cohort. PATIENTS AND METHODS: In this hospital-based case-control study, MMP7 genotypes were analyzed in 153 endometriosis and 636 individuals without endometriosis using typical polymerase chain reaction-restriction fragment length polymorphism methodology. RESULTS: The statistical analysis revealed that MMP7 rs11568818 genotypes were differentially distributed between the endometriosis and control groups (p for trend=0.0048). Specifically, the MMP7 rs11568818 homozygous variant GG was associated with endometriosis risk compared to the wild-type AA genotype (OR=4.59, 95% CI=1.46-14.48, p=0.0136). However, the MMP7 rs11568818 heterozygous variant AG was not associated with endometriosis risk (OR=1.57, 95% CI=0.97-2.53, p=0.0854). The frequency of than variant allele G of MMP7 rs11568818 was 12.7% in the endometriosis group, significantly higher than the 7.2% observed in the control group (OR=1.90, 95% CI=1.27-2.82, p=0.0021). CONCLUSION: MMP7 rs11568818 GG genotype was found to be a novel marker for endometriosis risk in Taiwanese.

Ocular inflammation in tsutsugamushi disease - a case report.

A 64-year-old male, working at a mountain site in Taitung County, suffered from primary open angle glaucoma (POAG) post trabeculectomy with well-controlled intraocular pressure (IOP) in both eyes (OU). He presented with headache accompanied by red eyes (OU) for 10 days. Physical examination revealed fever up to 38.2°C, neck stiffness, one eschar at the left forearm and another at the left ankle. Abnormal laboratory data indicated bacterial infection with central nervous system involvement. Ophthalmic examination showed elevated IOP, moderate conjunctival congestion, subconjunctival hemorrhage, anterior uveitis, cotton-wool spots on the retina and multiple white dots on the temporal retina (OU). Under the impression of uveitis in tsutsugamushi disease with atypical meningitis, oral doxycycline, anti-glaucoma and anti-inflammation eye drugs were prescribed. IOP returned to 12 mmHg and anterior uveitis subsided. The lesions of cotton-wool spots on the retina disappeared within 2 weeks, but multiple white dots remained persistently on the temporal retina.

Neuromorphic Computing with Emerging Antiferromagnetic Ordering in Spin-Orbit Torque Devices.

Field-free switching (FFS) and spin-orbit torque (SOT)-based neuromorphic characteristics were realized in a W/Pt/Co/NiO/Pt heterostructure with a perpendicular exchange bias (HEB) for brain-inspired neuromorphic computing (NC). Experimental results using NiO-based SOT devices guided the development of fully spin-based artificial synapses and sigmoidal neurons for implementation in a three-layer artificial neural network. This system achieved impressive accuracies of 91-96% when applied to the Modified National Institute of Standards and Technology (MNIST) image data set and 78.85-81.25% when applied to Fashion MNIST images, due presumably to the emergence of robust NiO antiferromagnetic (AFM) ordering. The emergence of AFM ordering favored the FFS with an enhanced HEB, which suppressed the memristivity and reduced the recognition accuracy. This indicates a trade-off between the requirements for solid-state memory and those required for brain-inspired NC devices. Nonetheless, our findings revealed opportunities by which the two technologies could be aligned via controllable exchange coupling.

Longitudinal study on all-cause and suicide mortality among individuals with attention deficit hyperactivity disorder.

BACKGROUND: Previous research has linked attention deficit hyperactivity disorder (ADHD) with an increased risk of all-cause mortality, primarily owing to unnatural causes such as accidents and suicides. This increase may be attributable to the co-occurrence of major psychiatric disorders, including schizophrenia (SCZ), bipolar disorder (BD), major depressive disorder (MDD), autism spectrum disorder (ASD), anxiety disorders, substance use disorders (SUDs), and personality disorders (PDs). This study examined the all-cause and specific-cause mortality rates in individuals with ADHD and the influence of psychiatric comorbidities. METHODS: Between 2003 and 2017, 1.17 million individuals were enrolled in the study, of which 233,886 received a diagnosis of ADHD from the Taiwan's National Health Insurance Research Database. A 1:4 sex- and birth year-matched control group without ADHD was also included. Hazard ratios (HRs) for mortality rates were estimated between groups after adjusting for demographic data. RESULTS: During the follow-up period, 781 individuals with ADHD died. The HR for all-cause mortality was 1.45 (95% confidence interval [CI]: 1.30-1.61), largely owing to unnatural causes, particularly suicide. Suicide rates were particularly high in individuals with ADHD and psychiatric comorbidities: the HRs for suicide were 47.06 in ADHD with SUDs (95% CI: 6.12-361.99), 32.02 in ADHD with SCZ (7.99-128.29), 23.60 in ADHD with PDs (7.27-76.66), 10.11 in ADHD with anxiety disorders (5.74-17.82), 9.30 in ADHD with BD (4.48-19.33), 8.36 in ADHD with MDD (5.66-12.35), and 6.42 in ADHD with ASD (1.83-22.53) relative to ADHD only. DISCUSSION: ADHD was associated with increased mortality rates, primarily owing to suicide. The presence of major psychiatric comorbidities was associated with a further increase in suicide mortality risk.

Impact of background music listening on anxiety in cancer patients undergoing initial radiation therapy: a randomized clinical trial.

BACKGROUND: Patients undergoing radiation therapy (RT) often experience anxiety, which may jeopardize the treatment success. The efficacy of music interventions in reducing anxiety remains contentious. This randomized trial aimed to evaluate the impact of music listening on anxiety symptoms in patients undergoing initial RT. METHODS: First-time RT patients were randomly allocated to experimental and control groups. The Brief Symptom Rating Scale (BSRS-5), Distress Thermometer (DT), and Beck Anxiety Inventory (BAI-C) were administered pre- and post-RT. Changes in physiological anxiety symptoms were monitored over 10 consecutive days starting from the first day of RT. The experimental group received music during RT; the control group did not. The generalized linear mixed model was used to estimate the pre-post difference in the BSRS-5, DT, and BAI-C scores between the music intervention and control group. RESULTS: This study included 50 patients each in the experimental and control groups. BSRS-5 and DT scores were significantly reduced in the experimental group post-RT (p = 0.0114 and p = 0.0023, respectively). When music listening was discontinued, these scores rebounded. While the posttest BAI-C score was significantly lower in the experimental group (p < 0.0001), the pre-post difference between the two groups was not significant (p = 0.0619). On cessation of music listening, the BAI-C score also rebounded. CONCLUSIONS: For cancer patients undergoing initial RT, music listening intervention significantly reduced anxiety symptoms measured using the BSRS-5, DT, and BAI-C scores after two weeks. Our results demonstrate the effectiveness of music listening intervention in reducing anxiety symptoms, thereby potentially improving the quality of life of cancer patients undergoing RT.

Fungal metabolite altersolanol a exhibits potent cytotoxicity against human placental trophoblasts in vitro via mitochondria-mediated apoptosis.

Altersolanol A, a fungus-derived tetrahydroanthraquinone, has shown cytotoxic effects on multiple cancer cells. However, its reproductive toxicity in humans has not been well-addressed. The present study was aimed at investigating the cytotoxicity of altersolanol A on human placental trophoblasts including choriocarcinoma cell line JEG-3 and normal trophoblast cell line HTR-8/SVneo in vitro. The results showed that altersolanol A inhibited proliferation and colony formation of human trophoblasts, and the choriocarcinoma cells were more sensitive to the compound than the normal trophoblasts. Altersolanol A induced cell cycle arrest at G2/M phase in JEG-3 cells and S phase in HTR-8/SVneo cells, downregulated the expression of cell cycle-related checkpoint proteins, and upregulated the p21 level. Altersolanol A also promoted apoptosis in human trophoblasts via elevating the Bax/Bcl-2 ratio and decreasing both caspase-3 and caspase-9 levels. Meanwhile, altersolanol A suppressed the mitochondrial membrane potential and induced ROS production and cytochrome c release, which activated the mitochondria-mediated intrinsic apoptosis. Moreover, migration and invasion were inhibited upon altersolanol A exposure with downregulation of matrix metalloproteinase (MMP)-2 in JEG-3 cells and MMP-9 in HTR-8/SVneo cells. Mechanically, altersolanol A supplement decreased the phosphorylation of JNK, ERK, and p38, manifesting the inactivation of MAPK signaling pathway in the human trophoblasts. In conclusion, altersolanol A exhibited potential reproductive cytotoxicity against human trophoblasts via promoting mitochondrial-mediated apoptosis and inhibiting the MAPK signaling pathway.