Causal associations of cognition, intelligence, education, health and lifestyle factors with cervical spondylosis: a mendelian randomization study.

Background: Education, cognition, and intelligence are phenotypically and genetically related. Education has been shown to have a protective effect on the risk of developing cervical spondylosis. However, it is unclear whether cognition and intelligence have independent causal effects on cervical spondylosis, and whether health and lifestyle factors influence this association. Methods: We first assessed the independent effects of education, cognition, and intelligence on cervical spondylosis by two-sample Mendelian randomization and multivariable Mendelian randomization analysis, and evaluated 26 potential association mediators using two-step Mendelian randomization, and calculated the median proportion. Results: The results showed that only education had an independent causal effect on cervical spondylosis, and had a protective effect on the risk of cervical spondylosis (ß: 0.3395; se: 0.166; p < 0.05; OR:0.71; [95%CI: 0.481-0.943]. Of the 26 potential associated mediators, a factor was identified: SHBG (mediated proportion: 2.5%). Univariable Mendelian randomization results showed that the risk factors for cervical spondylosis were time spent watching TV (OR:1.96; [95%CI: 1.39-2.76]), smoking (OR:2.56; [95%CI: 1.061-1.486]), body mass index (OR:1.26; [95%CI: 1.124-1.418]), percentage of body fat (OR:1.32; [95%CI: 1.097-1.593]), major depression (OR:1.27; [95%CI: 1.017-1.587]) and sitting height (OR:1.15; [95%CI: 1.025-1.291]). Protective factors include computer using (OR:0.65; [95%CI: 0.418-0.995]), sex hormone binding globulin (OR:0.87; [95%CI: 0.7955-0.951]) and high-density lipoprotein (OR:0.90; [95%CI: 0.826-0.990]). Conclusion: Our findings demonstrate the causal and independent effects of education on cervical spondylosis and suggest that lifestyle media may be a priority target for the prevention of cervical spondylosis due to low educational attainment.

Aberrant brain topological organization and granger causality connectivity in Parkinson's disease with impulse control disorders.

Introduction: Impulse control disorders (ICDs) refer to the common neuropsychiatric complication of Parkinson's disease (PD). The white matter (WM) topological organization and its impact on brain networks remain to be established. Methods: A total of 17 PD patients with ICD (PD-ICD), 17 without ICD (PD-NICD), and 18 healthy controls (HCs) were recruited. Graph theoretic analyses and Granger causality analyses were combined to investigate WM topological organization and the directional connection patterns of key regions. Results: Compared to PD-NICD, ICD patients showed abnormal global properties, including decreased shortest path length (Lp) and increased global efficiency (Eg). Locally, the ICD group manifested abnormal nodal topological parameters predominantly in the left middle cingulate gyrus (MCG) and left superior cerebellum. Decreased directional connectivity from the left MCG to the right medial superior frontal gyrus was observed in the PD-ICD group. ICD severity was significantly correlated with Lp and Eg. Discussion: Our findings reflected that ICD patients had excessively optimized WM topological organization, abnormally strengthened nodal structure connections within the reward network, and aberrant causal connectivity in specific cortical- limbic circuits. We hypothesized that the aberrant reward and motor inhibition circuit could play a crucial role in the emergence of ICDs.

Post-marketing safety concerns of sotorasib: A disproportionality analysis based on FDA adverse event reporting system.

Background: Sotorasib has been approved for the treatment of adult patients with KRAS G12C-mutated locally advanced or metastatic non-small cell lung cancer (NSCLC). Due to the limitations of clinical trials, potential adverse events (AEs) and long-term safety issues cannot be detected. The presented study aimed to evaluate sotorasib-associated AEs using the FDA Adverse Event Reporting System (FAERS) database. Methods: Post-marketing AE reports of sotorasib in the database were collected for analysis. Disproportionality analyses, including the reporting odds ratio (ROR), proportional reporting ratio (PRR), information component (IC) and empirical bayes geometric mean (EBGM) algorithms, were performed to mine the signals of sotorasib-associated AEs. The median duration, quartiles and the Weibull shape parameter (WSP) test were used to assess the onset time data. Results: The database contained 1538 cases of sotorasib as primary suspect (PS), with 27 signals detected, scattering in 5 SOCs. The SOC of hepatobiliary disorders (182, ROR 4.48, PRR 4.07, IC 2.02, EBGM 4.07) met the four methodological thresholds. The median onset time of sotorasib-associated AEs was 42 days (interquartile range [IQR] 14-86.75 days). Different SOCs had different types of risk over time. Conclusion: After obtaining marketing authorization, the study identified all potentially relevant adverse event (AE) signals expected to have a reporting frequency higher than anticipated and characterized them during sotorasib treatment.

Cancer-associated fibroblast-derived gene signature discriminates distinct prognoses by integrated single-cell and bulk RNA-seq analyses in breast cancer.

BACKGROUND: Cancer-associated fibroblasts (CAFs) are one of the most predominant cellular subpopulations in the tumor stroma and play an integral role in cancer occurrence and progression. However, the prognostic role of CAFs in breast cancer remains poorly understood. METHODS: We identified a number of CAF-related biomarkers in breast cancer by combining single-cell and bulk RNA-seq analyses. Based on univariate Cox regression as well as Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis, a novel CAF-associated prognostic model was developed. Breast cancer patients were grouped according to the median risk score and further analyzed for outcome, clinical characteristic, pathway activity, genomic feature, immune landscape, and drug sensitivity. RESULTS: A total of 341 CAF-related biomarkers were identified from single-cell and bulk RNA-seq analyses. We eventually screened eight candidate prognostic genes, including CERCAM, EMP1, SDC1, PRKG1, XG, TNN, WLS, and PDLIM4, and constructed the novel CAF-related prognostic model. Grouped by the median risk score, high-risk patients showed a significantly worse prognosis and exhibited distinct pathway activities such as uncontrolled cell cycle progression, angiogenesis, and activation of glycolysis. In addition, the combined risk score and tumor mutation burden significantly improved the ability to predict patient prognosis. Importantly, patients in the high-risk group had a higher infiltration of M2 macrophages and a lower infiltration of CD8+ T cells and activated NK cells. Finally, we calculated the IC50 for a range of anticancer drugs and personalized the treatment regimen for each patient. CONCLUSION: Integrating single-cell and bulk RNA-seq analyses, we identified a list of compositive CAF-associated biomarkers and developed a novel CAF-related prognostic model for breast cancer. This robust CAF-derived gene signature acts as an excellent predictor of patient outcomes and treatment responses in breast cancer.

Methods for implementing integrated step-selection functions with incomplete data.

Integrated step-selection analyses (iSSAs) are versatile and powerful frameworks for studying habitat and movement preferences of tracked animals. iSSAs utilize integrated step-selection functions (iSSFs) to model movements in discrete time, and thus, require animal location data that are regularly spaced in time. However, many real-world datasets are incomplete due to tracking devices failing to locate an individual at one or more scheduled times, leading to slight irregularities in the duration between consecutive animal locations. To address this issue, researchers typically only consider bursts of regular data (i.e., sequences of locations that are equally spaced in time), thereby reducing the number of observations used to model movement and habitat selection. We reassess this practice and explore four alternative approaches that account for temporal irregularity resulting from missing data. Using a simulation study, we compare these alternatives to a baseline approach where temporal irregularity is ignored and demonstrate the potential improvements in model performance that can be gained by leveraging these additional data. We also showcase these benefits using a case study on a spotted hyena (Crocuta crocuta).

Valproic Acid Treatment after Traumatic Brain Injury in Mice Alleviates Neuronal Death and Inflammation in Association with Increased Plasma Lysophosphatidylcholines.

The histone deacetylase inhibitor (HDACi) valproic acid (VPA) has neuroprotective and anti-inflammatory effects in experimental traumatic brain injury (TBI), which have been partially attributed to the epigenetic disinhibition of the transcription repressor RE1-Silencing Transcription Factor/Neuron-Restrictive Silencer Factor (REST/NRSF). Additionally, VPA changes post-traumatic brain injury (TBI) brain metabolism to create a neuroprotective environment. To address the interconnection of neuroprotection, metabolism, inflammation and REST/NRSF after TBI, we subjected C57BL/6N mice to experimental TBI and intraperitoneal VPA administration or vehicle solution at 15 min, 1, 2, and 3 days post-injury (dpi). At 7 dpi, TBI-induced an up-regulation of REST/NRSF gene expression and HDACi function of VPA on histone H3 acetylation were confirmed. Neurological deficits, brain lesion size, blood-brain barrier permeability, or astrogliosis were not affected, and REST/NRSF target genes were only marginally influenced by VPA. However, VPA attenuated structural damage in the hippocampus, microgliosis and expression of the pro-inflammatory marker genes. Analyses of plasma lipidomic and polar metabolomic patterns revealed that VPA treatment increased lysophosphatidylcholines (LPCs), which were inversely associated with interleukin 1 beta (Il1b) and tumor necrosis factor (Tnf) gene expression in the brain. The results show that VPA has mild neuroprotective and anti-inflammatory effects likely originating from favorable systemic metabolic changes resulting in increased plasma LPCs that are known to be actively taken up by the brain and function as carriers for neuroprotective polyunsaturated fatty acids.

Lipids as potential mediators linking body mass index to diabetes: evidence from a mediation analysis based on the NAGALA cohort.

BACKGROUND: Body mass index (BMI) and lipid disorders are both known to be strongly associated with the development of diabetes, however, the indirect effect of lipid parameters in the BMI-related diabetes risk is currently unknown. This study aimed to investigate the mediating role of lipid parameters in the association of BMI with diabetes risk. METHODS: We assessed the association of diabetes risk with BMI, as well as lipid parameters including high-density lipoprotein cholesterol(HDL-C), low-density lipoprotein cholesterol(LDL-CF and LDL-CS), triglycerides(TG), total cholesterol(TC), remnant cholesterol(RC), non-HDL-C, and combined indices of lipid parameters with HDL-C (RC/HDL-C ratio, TG/HDL-C ratio, TC/HDL-C ratio, non-HDL/HDL-C ratio, LDL/HDL-C ratio) using data from 15,453 subjects in the NAGALA project. Mediation models were used to explore the mediating role of lipid parameters in the association of BMI with diabetes risk, and mediation percentages were calculated for quantifying the strength of the indirect effects. Finally, receiver operating characteristic curve (ROC) analysis was used to compare the accuracy of BMI and BMI combined with lipid parameters in predicting incident diabetes. RESULTS: Multivariate regression models, adjusted for confounding factors, demonstrated robust associations of lipid parameters, BMI, with diabetes risk, with the exception of TC, LDL-CF, LDL-CS, and non-HDL-C. Mediation analysis showed that lipid parameters except TC, LDL-CF, LDL-CS, and Non-HDL-C were involved in and mediated the association of BMI with diabetes risk, with the largest mediation percentage being the RC/HDL-C ratio, which was as high as 40%; it is worth mentioning that HDL-C and HDL-C-related lipid ratio parameters also play an important mediating role in the association between BMI and diabetes, with the mediator proportion being greater than 30%. Finally, based on the ROC results, we found that the prediction performance of all lipid parameters in the current study except TC was significantly improved when combined with BMI. CONCLUSION: Our fresh findings suggested that lipid parameters partially mediated the association of BMI with diabetes risk; this result indicated that in the context of diabetes risk screening and disease management, it is important to not only monitor BMI but also pay attention to lipid parameters, particularly HDL-C and HDL-C-related lipid ratio parameters.

Assessment of anxiety in children with neurodevelopment disorders: Rasch analysis of the Spence Children's Anxiety Scale.

Anxiety is common in neurodevelopmental disorders (NDD). The parent version of the Spence Children's Anxiety Scale (SCAS-P) is a widely used measure to assess anxiety across a broad range of childhood populations. However, assessment of the measurement properties of the SCAS-P in NDDs have been limited. The present study aimed to assess the psychometric properties of the SCAS-P in children with attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) using Rasch Measurement Theory. Data from the Province of Ontario Neurodevelopmental Disorders Network Registry were used in the analysis. Children (ages 6-13 years old) with a primary diagnosis of ADHD (n=146) or ASD (n=104) were administered the SCAS-P. Rasch Measurement Theory was used to assess measurement properties of the SCAS-P, including unidimensionality and item-level fit, category ordering, item targeting, person separation index and reliability and differential item functioning. The SCAS-P fit well to the Rasch model in both ADHD and ASD, including unidimensionality, satisfactory category ordering and goodness-of-fit. However, item-person measures showed poor precision at lower levels of anxiety. Some items showed differential item functioning, including items within the obsessive-compulsive, panic/agoraphobia and physical injury fears domains, suggesting that the presentation of anxiety may differ between ADHD and ASD. Overall, the results generally support the use of the SCAS-P to screen and monitor anxiety symptoms in children with ADHD and ASD. Future studies would benefit from examination of more severely anxious NDD cohort, including those with clinically diagnosed anxiety.

Terpinen-4-ol from tea tree oil prevents Aspergillus flavus growth in postharvest wheat grain.

Plant volatile organic compounds (PVOCs) have gained increasing attention for their role in preventing fungal spoilage and insect contamination in postharvest agro-products owing to their effectiveness and sustainability. In this study, the essential oil was extracted from fresh M. alternifolia (tea tree) leaves, and the fumigation vapor of tea tree oil (TTO) completely inhibited the growth of Aspergillus flavus on agar plates at a concentration of 1.714 µL/mL. Terpinen-4-ol was identified as the major component (40.76 %) of TTO volatiles analyzed using headspace gas chromatography-mass spectrometry. Terpinen-4-ol vapor completely inhibited the A. flavus growth on agar plates and 20 % moisture wheat grain at 0.556 and 1.579 µL/mL, respectively, indicating that terpinen-4-ol serves as the main antifungal constituent in TTO volatiles. The minimum inhibitory concentration of terpinen-4-ol in liquid-contact culture was 1.6 µL/mL. Terpinen-4-ol treatment caused depressed, wrinkled, and punctured mycelial morphology and destroyed the plasma membrane integrity of A. flavus. Metabolomics analysis identified significant alterations in 93 metabolites, with 79 upregulated and 14 downregulated in A. flavus mycelia exposed to 1.6 µL/mL terpinen-4-ol for 6 h, involved in multiple cellular processes including cell membrane permeability and integrity, the ABC transport system, pentose phosphate pathway, and the tricarboxylic acid cycle. Biochemical analysis and 2,7-dichlorofluorescein diacetate staining showed that terpinen-4-ol induced oxidative stress and mitochondrial dysfunction in A. flavus mycelia. This study provides new insights into the antifungal effects of the main TTO volatile compounds terpinen-4-ol on the growth of A. flavus.

Predictors of substance use disorder treatment and mutual support group participation among Black women across the criminal legal spectrum: A latent class approach.

BACKGROUND: The purpose of this study includes: 1) identifying classes of substance-related needs among Black women, and 2) examining the effect of substance-related need classes and culturally-relevant factors on Black women's use of substance use disorder (SUD) treatment and mutual support groups. METHODS: As part of a longitudinal cohort study, Black women were recruited in prison nearing release, on probation, and in the community without involvement in the criminal legal system (CLS, n=565) and followed-up at 18-months. We conducted a baseline latent class analysis of substance-related needs among Black women. Logistic regression models adjusted for culturally-relevant factors to predict the use of treatment and frequency of mutual support group participation over 18-months among Black women who use drugs. RESULTS: Four classes by level of needs were found: low, daily marijuana use, high mental health, and high comorbidity. During the 18-month follow-up, women characterized by the high comorbidity need class and with higher scores of religious well-being were more likely to frequently participate in mutual support groups. Non-CLS-involved women were less likely to engage with both treatment and mutual support groups than women from the prison sample at 18-months. CONCLUSIONS: This study highlights four distinct classes of substance-related needs among Black women, highlighting the complex patterns of behavior and within-racial group differences among Black women. Black women with high comorbidity needs were more likely to participate in mutual support groups, but the latent classes did not predict SUD treatment indicating other non-medical and social contextual need factors may be at play.

The comorbidity mechanism of problematic internet use and depression among Chinese college students: A cross-lagged panel network analysis.

Problematic internet use (PIU) and depression usually co-occur and are common among college students. According to network theory, it may be attributed to the interplay of symptoms that connect these two mental health problems. However, most studies have failed to examine complex and subtle connections at the symptom level and have not clarified how PIU and depression symptoms are intercorrelated, which symptoms serve as the source of comorbidity (i.e., the central symptoms), and whether such a comorbidity mechanism would change with higher grades. To explore these questions, this study examined four contemporaneous networks and three cross-lagged panel networks, visualizing the symptoms as nodes and the connections between symptoms as edges. A total of 2,420 college students (Mage = 18.35, SD = 0.84; 67.98 % girls) completed four annual surveys. Overall, the results of contemporaneous networks and cross-lagged panel networks indicated that (a) PIU and depression symptoms are intercorrelated; (b) the core symptoms responsible for comorbidity mostly belonged to PIU, and (c) the comorbidity mechanism would change with time. These findings explain the dynamic relation between PIU and depression and identify possible primary symptoms that comorbidity programs can mitigate at different stages of the college years.

Mendelian randomization combined with multi-omics explores the relationship between heart failure and cancer.

Background: Whether there is an association between HF (HF) and cancer has not been conclusively established, and it is not clear whether patients with cancer can share similar hospitalization strategies and outcomes with patients with HF. Methods: Genome-wide association summary statistics were performed using a two-sample Mendelian randomization (MR) method for HF patients and cancer patients from the GWAS directory, with co-localization and Summary Data-Based Mendelian Randomization (SMR) analyses to identify HF-associated genes, and transcriptomic analyses to analyze the roles of these genes in the clinical diagnosis and targeted therapies of multiple cancer types. Results: Two-sample MR analysis showed that increased risk of HF was associated with decreased risk of cervical, brain, breast, colorectal, lung, and skin cancers, and co-localization combined with SMR analysis identified ABO and SURF1 as HF-associated genes, and transcriptomic analyses showed that ABO is a risk factor for HF and a protective factor against cancer, whereas SURF1 is a protective factor against HF and a protective factor against cancer. Conclusion: There was no causal relationship between heart failure and cancers (Cervical, brain, breast, colorectal, lung and skin cancers) risk factors, however there was a trend toward a negative causal relationship between heart failure and cancers (Cervical, brain, breast, colorectal, lung and skin cancers) occurrence.

Demand analysis of health care services for community-dwelling breast cancer survivors based on the Kano model: A cross-sectional study.

Objectives: Providing satisfactory healthcare services for breast cancer survivors can effectively reduce their burden and the pressure on medical resources. The aim of this study was to explore health care service demands for community-dwelling breast cancer survivors using the Kano model. Methods: A cross-sectional survey was conducted from January to March 2023 among breast cancer survivors discharged from a tertiary cancer hospital. Participants were asked to fill out a self-designed questionnaire involving the Kano model, which helped to categorize and prioritize the attributes of healthcare services. The questionnaire included 30 health care services. Additionally, their social demographic characteristics were collected during the survey. Results: A total of 296 valid questionnaires were collected, and demand attributes of the 30 health care services were evaluated. The findings revealed that one of 30 services was classified as "must-be attributes" (body image management), 13 as "one-dimensional attributes" (focused on medical security support, health management, and health counseling), 3 as "attractive attributes" (focused on communication needs and telehealth services), and 11 as "indifferent attributes" (mainly in the area of psycho-social services). Conclusions: Breast cancer survivors in the community have different levels of need for various health care services. It's crucial for healthcare providers to identify these needs and devise effective strategies to deliver the appropriate services. Services with must-be and one-dimensional attributes should be given priority, and efforts should be made to provide services with attractive attributes, hence improving the quality of life of breast cancer survivors.

The Role of Large Language Models in Transforming Emergency Medicine: Scoping Review.

BACKGROUND: Artificial intelligence (AI), more specifically large language models (LLMs), holds significant potential in revolutionizing emergency care delivery by optimizing clinical workflows and enhancing the quality of decision-making. Although enthusiasm for integrating LLMs into emergency medicine (EM) is growing, the existing literature is characterized by a disparate collection of individual studies, conceptual analyses, and preliminary implementations. Given these complexities and gaps in understanding, a cohesive framework is needed to comprehend the existing body of knowledge on the application of LLMs in EM. OBJECTIVE: Given the absence of a comprehensive framework for exploring the roles of LLMs in EM, this scoping review aims to systematically map the existing literature on LLMs' potential applications within EM and identify directions for future research. Addressing this gap will allow for informed advancements in the field. METHODS: Using PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews) criteria, we searched Ovid MEDLINE, Embase, Web of Science, and Google Scholar for papers published between January 2018 and August 2023 that discussed LLMs' use in EM. We excluded other forms of AI. A total of 1994 unique titles and abstracts were screened, and each full-text paper was independently reviewed by 2 authors. Data were abstracted independently, and 5 authors performed a collaborative quantitative and qualitative synthesis of the data. RESULTS: A total of 43 papers were included. Studies were predominantly from 2022 to 2023 and conducted in the United States and China. We uncovered four major themes: (1) clinical decision-making and support was highlighted as a pivotal area, with LLMs playing a substantial role in enhancing patient care, notably through their application in real-time triage, allowing early recognition of patient urgency; (2) efficiency, workflow, and information management demonstrated the capacity of LLMs to significantly boost operational efficiency, particularly through the automation of patient record synthesis, which could reduce administrative burden and enhance patient-centric care; (3) risks, ethics, and transparency were identified as areas of concern, especially regarding the reliability of LLMs' outputs, and specific studies highlighted the challenges of ensuring unbiased decision-making amidst potentially flawed training data sets, stressing the importance of thorough validation and ethical oversight; and (4) education and communication possibilities included LLMs' capacity to enrich medical training, such as through using simulated patient interactions that enhance communication skills. CONCLUSIONS: LLMs have the potential to fundamentally transform EM, enhancing clinical decision-making, optimizing workflows, and improving patient outcomes. This review sets the stage for future advancements by identifying key research areas: prospective validation of LLM applications, establishing standards for responsible use, understanding provider and patient perceptions, and improving physicians' AI literacy. Effective integration of LLMs into EM will require collaborative efforts and thorough evaluation to ensure these technologies can be safely and effectively applied.

Emulation of randomized trials of direct oral anticoagulants with claims data and implications for new Factor XI inhibitors.

Direct oral anticoagulants (DOACs) revolutionized the management of thromboembolic disorders. Clinical care may be further improved as Factor XIs undergo large-scale outcome trials. What role can non-randomized database studies play in expediting understanding of these drugs in clinical practice? The RCT-DUPLICATIVE Initiative emulated the design of eight DOAC randomized clinical trials (RCT) using non-randomized claims database studies. RCT study design parameters and measurements were closely emulated by the database studies and produced highly concordant results. The results of the single database study that did not meet all agreement metrics with the specific RCT it was emulating were aligned with a meta-analysis of six trials studying similar questions, suggesting the trial result was an outlier. Well-designed database studies using fit-for-purpose data came to the same conclusions as DOAC trials, illustrating how database studies could complement RCTs for Factor XI inhibitors-by accelerating insights in underrepresented populations, demonstrating effectiveness and safety in clinical practice, and testing broader indications.

Development of a telomere vector-based approach to overcome limitations caused by lethal phenotypes in the study of essential genes in Magnaporthe oryzae.

Reverse genetic approaches are common tools in genomics for elucidating gene functions, involving techniques such as gene deletion followed by screening for aberrant phenotypes. If the generation of gene deletion mutants fails, the question arises whether the failure stems from technical issues or because the gene of interest (GOI) is essential, meaning that the deletion causes lethality. In this report, we introduce a novel method for assessing gene essentiality using the phytopathogenic ascomycete Magnaporthe oryzae. The method is based on the observation that telomere vectors are lost in transformants during cultivation without selection pressure. We tested the hypothesis that essential genes can be identified in deletion mutants co-transformed with a telomere vector. The M. oryzae gene MoPKC, described in literature as essential, was chosen as GOI. Using CRISPR/Cas9 technology transformants with deleted GOI were generated and backed up by a telomere vector carrying a copy of the GOI and conferring fenhexamid resistance. Transformants in which the GOI deletion in the genome was not successful lost the telomere vector on media without fenhexamid. In contrast, transformants with confirmed GOI deletion retained the telomere vector even in absence of fenhexamid selection. In the latter case, the maintenance of the telomere indicates that the GOI is essential for the surveillance of the fungi, as it would have been lost otherwise. The method presented here allows to test for essentiality of genes when no mutants can be obtained from gene deletion approaches, thereby expanding the toolbox for studying gene function in ascomycetes.

Comparative genomic analyses provide insight into the pathogenicity of three Pseudomonas syringae pv. actinidiae strains from Anhui Province, China.

BACKGROUND: Pseudomonas syringae pv. actinidiae (Psa) is an important bacterial plant pathogen that causes severe damage to the kiwifruit industry worldwide. Three Psa strains were recently obtained from different kiwifruit orchards in Anhui Province, China. The present study mainly focused on the variations in virulence and genome characteristics of these strains based on the pathogenicity assays and comparative genomic analyses. RESULTS: Three strains were identified as biovar 3 (Psa3), along with strain QSY6 showing higher virulence than JZY2 and YXH1 in pathogenicity assays. The whole genome assembly revealed that each of the three strains had a circular chromosome and a complete plasmid. The chromosome sizes ranged from 6.5 to 6.6 Mb with a GC content of approximately 58.39 to 58.46%, and a predicted number of protein-coding sequences ranging from 5,884 to 6,019. The three strains clustered tightly with 8 Psa3 reference strains in terms of average nucleotide identity (ANI), whole-genome-based phylogenetic analysis, and pangenome analysis, while they were evolutionarily distinct from other biovars (Psa1 and Psa5). Variations were observed in the repertoire of effectors of the type III secretion system among all 15 strains. Moreover, synteny analysis of the three sequenced strains revealed eight genomic regions containing 308 genes exclusively present in the highly virulent strain QSY6. Further investigation of these genes showed that 16 virulence-related genes highlight several key factors, such as effector delivery systems (type III secretion systems) and adherence (type IV pilus), which might be crucial for the virulence of QSY6. CONCLUSION: Three Psa strains were identified and showed variant virulence in kiwifruit plant. Complete genome sequences and comparative genomic analyses further provided a theoretical basis for the potential pathogenic factors responsible for kiwifruit bacterial canker.

Lived experiences of adolescents with major depressive disorder during the COVID pandemic: A qualitative study from a tertiary care center.

Objectives: Depression is a leading cause of global disease burden and morbidity among adolescents. Studies have reported higher rates of depression and anxiety secondary to the COVID pandemic and the psychosocial impact of social distancing measures. There is a paucity of literature on the subjective experiences of depressed adolescents in such pandemic circumstances. The objective of this study was to explore the lived experiences of adolescents with major depressive disorder (MDD) during the COVID pandemic, and the impact of the pandemic, and pandemic-related circumstances on adolescents' mental health and coping. Materials and Methods: In-depth interviews with eight adolescents diagnosed with MDD were analyzed using interpretative phenomenological analysis. Results: The analysis revealed three major themes; "The pandemic was arduous," "Negativity in family interactions," and "Effects on depression." Most adolescents coped using excessive screen time as a distraction, and their families perceived them as indolent. Conclusion: The study found that adolescents' experience of depression during the pandemic was extremely overwhelming because, on the one hand, they had to deal with immediate COVID infection-related worries and were not able to adjust to the new routine, not able to concentrate during online classes while also dealing with greater interpersonal discord with their parents and limited social resources for coping. The findings expand the clinical understanding of adolescents' experience of depression during pandemic circumstances and would aid in better management planning.

Effectiveness of nurse-led fever, sugar-hyperglycemia, and swallowing bundle care on clinical outcome of patients with stroke at a tertiary care center: A randomized controlled trial.

Objectives: Stroke is a medical emergency, the leading cause of death, and a significant cause of disability in developing countries. The primary goals of stroke management focus on reducing disability, which needs prompt treatment in time. Fever, sugar-hyperglycemia, and swallowing (FeSS) bundle are a promising nurse-led composite for reducing disability and death. The present study aims to assess the effect of FeSS bundle care on disability, functional dependency, and death among acute stroke patients. Materials and Methods: A randomized controlled trial was conducted among 104 acute stroke patients, who were admitted within the first 48 h of stroke symptoms and had no previous neurological deficits. Randomization was stratified based on gender and type of stroke. The intervention group received FeSS bundle care, which included nurse-led fever and sugar management for the first 72 h, and a swallowing assessment done within the first 24 h or before the first oral meal. A follow-up assessment was done after 90 days to assess the disability, functional dependency, and mortality status using a modified Rankin scale and Barthel index. Results: No significant difference was noted in the 90-day disability and functional dependency between the groups. A reduction in mortality was noted in the intervention group. The risk ratio for mortality between groups was 2.143 (95% confidence interval: 0.953-4.820). Conclusion: Although no significant reduction in disability, there was a reduction in mortality in the intervention group. Hence, the study suggested the promotion of nurse-led intervention using the FeSS bundle in stroke units.

Evidence quality assessment of acupuncture intervention for stroke hemiplegia: an overview of systematic reviews and meta-analyses.

Objective: Summarize the conclusions of the systematic review/meta-analysis of the clinical efficacy of acupuncture for stroke hemiplegia, and evaluate its methodological quality and the quality of evidence. Methods: Two researchers searched and extracted 8 databases for systematic reviews (SRs)/meta-analyses (MAs), and independently assessed the methodological quality, risk of bias, reporting quality, and quality of evidence of SRs/MAs included in randomized controlled trials (RCTs). Tools used included the Assessment of Multiple Systematic Reviews 2 (AMSTAR-2), the Risk of Bias in Systematic (ROBIS) scale, the list of Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA), and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. The search time is from database building to July 2023. Results: A total of 11 SRs/MAs were included, including 2 English literature and 9 Chinese literature, with all study sites in China. AMSTAR-2 evaluation results showed that the methodological quality of 11 articles was rated as very low quality; Based on the ROBIS evaluation results, the SRs/MAs was assessed as a high risk of bias; According to the results of the PRISMA checklist evaluation, most of the SRs/MAs reports are relatively complete; according to GRADE system, 42 outcomes were extracted from the included SRs/MAs for evaluation, of which 1 was rated as high-quality evidence, 14 as moderate-quality evidence, 14 as low-quality evidence, and 13 as very low-quality evidence. Conclusion: The available evidence indicates that acupuncture has certain clinical efficacy in the treatment of stroke hemiplegia. However, there are still some limitations to this study, such as the lower quality of SRs/MAs methodologies and evidence included, and more high-quality studies are needed to verify them.