POI-associated EIF4ENIF1 mutations exhibit impaired translation regulation abilities.

Various genetic variants have been found to be associated with the clinical onset of premature ovarian insufficiency (POI). However, when measured in vitro, the functional influence of the variants can be difficult to determine. By whole-exome sequencing (WES) of 93 patients with sporadic POI, we found a missense variant c.623G > A;p.R208H in the EIF4ENIF1 gene. In silico prediction of the variant using different algorithms suggested it might be a damaging variant. We compared the property of EIF4ENIF1 R208H and Q842P, a POI-related mutant that we reported previously, with wildtype (WT) protein using 293FT cells in vitro. Surprisingly, a change in subcellular distribution and granule forming ability (Q842P) and nuclear import capacity (R208H) was not observed, despite domain prediction evidences. Since EIF4ENIF1 was reported to inhibit translation, we employed T&T-seq, a translation-transcription dual-omics sequencing method, to profile gene expression upon overexpression of EIF4ENIF1 WT and mutants. EIF4ENIF1 WT overexpression group exhibited significantly (P < 0.0001) lower translation efficiency (TE) than empty vector or GFP overexpression control group. Surprisingly, EIF4ENIF1 Q842P overexpression failed to repress global translation, showing an overall TE significantly higher than WT group. Overexpression R208H significantly (P < 0.0001) lowered the overall TE, whereas exhibiting a reduced translation inhibitory effect on high-TE genes (TE > 2 in GFP control group). Several fertility-associated genes, such as AMH in Q842P group and SERPINE1 and THBS1 in R208H group, was translationally up-regulated in mutant groups versus WT control, suggesting a potential mechanism of mutated EIF4ENIF1 causing POI via impaired translation repression. It is further proposed that T&T-seq can be a sensitive evaluation tool for the measurement of functional alteration by variants in many other translational regulator genes, not only EIF4ENIF1, helping to eliminate misinterpretation of clinical significance of genetic variants.

Structural modeling of Chinese students' academic achievement identity and basic psychological needs: do academic self-efficacy, and mindfulness play a mediating role?

BACKGROUND: Mindfulness and academic self-efficacy were proposed as mediating variables, with successful academic identity as an exogenous variable. The backdrop for this research centers on the significance of psychological factors in shaping academic identity among first-grade high school students. OBJECTIVES: The primary aim of the research was to investigate the relationship between fundamental psychological needs, mindfulness, academic self-efficacy, and successful academic identity. Specifically, the study explored the direct and indirect impacts of basic psychological needs on successful academic identity mediated by mindfulness and academic self-efficacy. METHOD: The research employed a descriptive method, utilizing correlational studies and structural equation modeling. A sample of 355 undergraduate students at Henan Judicial Police Vocational College, Henan, China, was randomly selected through multistage cluster sampling. Data were collected using established scales, including the Basic Psychological Needs Scale, Baer Mindfulness Scale, Jenkins and Morgan Academic Self-Efficacy Scale, and Vas and Isakson Successful Academic Identity Scale. The data analysis was conducted using AMOS 22 software. FINDINGS: The research findings revealed that fundamental psychological needs directly and indirectly significantly impact successful academic identity. Mindfulness played a mediating role in this relationship. However, academic self-efficacy did not considerably mediate the influence of fundamental psychological needs on successful academic identity (p > 0.05). These results highlight the complex dynamics between psychological needs, mindfulness, academic self-efficacy, and successful academic identity among high school students in the specified academic year. CONCLUSIONS: The findings suggest targeted interventions, such as workshops for families and teachers to address basic needs and psychologist and school counselor interventions to increase mindfulness. Additionally, organizing educational classes is imperative for fostering a supportive environment conducive to successful academic identity among undergraduate students.

TP63 truncating mutation causes increased cell apoptosis and premature ovarian insufficiency by enhanced transcriptional activation of CLCA2.

BACKGROUND: Premature ovarian insufficiency (POI) is a severe disorder leading to female infertility. Genetic mutations are important factors causing POI. TP63-truncating mutation has been reported to cause POI by increasing germ cell apoptosis, however what factors mediate this apoptosis remains unclear. METHODS: Ninety-three patients with POI were recruited from Beijing Obstetrics and Gynecology Hospital, Capital Medical University. Whole-exome sequencing (WES) was performed for each patient. Sanger sequencing was used to confirm potential causative genetic variants. A minigene assay was performed to determine splicing effects of TP63 variants. A TP63-truncating plasmid was constructed. Real-time quantitative PCR, western blot analyses, dual luciferase reporter assays, immunofluorescence staining, and cell apoptosis assays were used to study the underlying mechanism of a TP63-truncating mutation causing POI. RESULTS: By WES of 93 sporadic patients with POI, we found a 14-bp deletion covering the splice site in the TP63 gene. A minigene assay demonstrated that the 14-bp deletion variant led to exon 13 skipping during TP63 mRNA splicing, resulting in the generation of a truncated TP63 protein (TP63-mut). Overexpression of TP63-mut accelerated cell apoptosis. Mechanistically, the TP63-mut protein could bind to the promoter region of CLCA2 and activate the transcription of CLCA2 several times compared to that of the TP63 wild-type protein. Silencing CLCA2 using a specific small interfering RNA (siRNA) or inhibiting the Ataxia Telangiectasia Mutated (ATM) pathway using the KU55933 inhibitor attenuated cell apoptosis caused by TP63-mut protein expression. CONCLUSION: Our findings revealed a crucial role for CLCA2 in mediating apoptosis in POI pathogenesis, and suggested that CLCA2 is a potential therapeutic target for POI.

METTL16 inhibits papillary thyroid cancer tumorigenicity through m6A/YTHDC2/SCD1-regulated lipid metabolism.

Papillary thyroid carcinoma (PTC) stands as the leading cancer type among endocrine malignancies, and there exists a strong correlation between thyroid cancer and obesity. However, the clinical significance and molecular mechanism of lipid metabolism in the development of PTC remain unclear. In this study, it was demonstrated that the downregulation of METTL16 enhanced lipid metabolism and promoted the malignant progression of PTC. METTL16 was expressed at lower levels in PTC tissues because of DNMT1-mediated hypermethylation of its promoter. Loss- and gain-of-function studies clarified the effects of METTL16 on PTC progression. METTL16 overexpression increased the abundance of m6A in SCD1 cells, increasing RNA decay via the m6A reader YTHDC2. The SCD1 inhibitor A939572 inhibited growth and slowed down lipid metabolism in PTC cells. These results confirm the crucial role of METTL16 in restraining PTC progression through SCD1-activated lipid metabolism in cooperation with YTHDC2. This suggests that the combination of METTL16 and anti-SCD1 blockade might constitute an effective therapy for PTC.

Implication of androgen receptor gene dysfunction in human Müllerian duct anomalies.

BACKGROUND: Müllerian duct anomalies (MDAs) are congenital developmental disorders exhibiting as a variety of malformations of female reproductive tract. The identified etiology of MDAs is limited. The present study aimed to unravel the underlying genetic causes of MDAs. METHODS: Rare variants in androgen receptor (AR) were called from the cohort consists of patients with MDAs and underwent whole exome sequencing (WES) at Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing, China. Sanger sequencing was used to confirm the causative genetic mutations. In silico analysis were used to classify the pathogenicity of each variant. Molecular modeling and simulations were conducted to investigate the conformational changes between the wild-type (WT) and mutant proteins. RESULTS: A total of 3 rare heterozygous variants in AR from the MDAs cohort in our institution were identified, with unknown effects. All variants were missense mutations, including c.173A > T, c.558C > A and c.1208C > T, and were absent or rare in East Asian populations in Genome Aggregation Database and the Exome Aggregation Consortium Database. According to the American College of Medical Genetics and Genomics guidelines, c.1208C > T variant was classified as likely pathogenic, while the other two were variants of uncertain significance. During molecular dynamics simulations, WT and mutant proteins all reached stable status according to root-mean-square variance. Values of radius of gyration showed that Q58L and S186R protein would be more compact than WT, while the structure of A403V became looser. Despite, in comparison with WT, the number of hydrogen bonds increased in Q58L, while decreased in the other two variants. Furthermore, the solvent-accessible surface area diminished in Q58L and A403V while enlarged in S186R proteins, when compared with WT. CONCLUSIONS: To our knowledge, this is the first report regarding the association of AR mutation and MDAs. The identification of these variants, predicted to damage the structure and function of AR protein, not only expanded the mutational spectrum of causative genes of MDAs, but provide novel molecular genetic reference for future studies.

DNMT3B Alleviates Liver Steatosis Induced by Chronic Low-grade LPS via Inhibiting CIDEA Expression.

BACKGROUND & AIMS: Nonalcoholic fatty liver disease is the most prevalent chronic liver disease and threats to human health. Gut dysbiosis caused by lipopolysaccharide (LPS) leakage has been strongly related to nonalcoholic fatty liver disease progression, although the underlying mechanisms remain unclear. METHODS: Previous studies have shown that low-grade LPS administration to mice on a standard, low-fat chow diet is sufficient to induce symptoms of fatty liver. This study confirmed these findings and supported LPS as a lipid metabolism regulator in the liver. RESULTS: Mechanically, LPS induced dysregulated lipid metabolism by inhibiting the expression of DNA methyltransferases 3B (DNMT3B). Genetic overexpression of DNMT3B alleviated LPS-induced lipid accumulation, whereas its knockdown increased steatosis in mice and human hepatocytes. LPS-induced lower expression of DNMT3B led to hypomethylation in promoter region of CIDEA, resulting in increased binding of SREBP-1c to its promoter and activated CIDEA expression. Hepatic interference of CIDEA reversed the effect of LPS on lipogenesis. These effects were independent of a high-fat diet or high fatty acid action. CONCLUSIONS: Overall, these findings sustain the conclusion that LPS is a lipogenic factor and could be involved in hepatic steatosis progression.

Lymphangiogenesis in gastric cancer: function and mechanism.

Increased lymphangiogenesis and lymph node (LN) metastasis are thought to be important steps in cancer metastasis, and are associated with patient's poor prognosis. There is increasing evidence that the lymphatic system may play a crucial role in regulating tumor immune response and limiting tumor metastasis, since tumor lymphangiogenesis is more prominent in tumor metastasis and diffusion. Lymphangiogenesis takes place in embryonic development, wound healing, and a variety of pathological conditions, including tumors. Tumor cells and tumor microenvironment cells generate growth factors (such as lymphangiogenesis factor VEGF-C/D), which can promote lymphangiogenesis, thereby inducing the metastasis and diffusion of tumor cells. Nevertheless, the current research on lymphangiogenesis in gastric cancer is relatively scattered and lacks a comprehensive understanding. Therefore, in this review, we aim to provide a detailed perspective on molecules and signal transduction pathways that regulate gastric cancer lymphogenesis, which may provide new insights for the diagnosis and treatment of cancer.

You are not lab rats at teaching hospitals: A systematic review of resident and fellow participation leads to improved colonoscopy.

BACKGROUND: Participation in colonoscopies is an essential aspect of endoscopic training. The purpose of this study was to explore the impact of fellow/trainee participation on colonoscopy outcomes. METHODS: This meta-analysis was registered on the International Prospective Register of Systematic Reviews (PROSPERO). From database inception to July 2022, studies investigating fellow involvement and colonoscopy outcomes were searched across Cochrane library, PubMed, and other databases. The random-effects model was applied to generate more conservative estimates. Sensitive analysis was conducted to explore whether the result would depend on a particular study. Egger's test and Begg's test were used to estimate the potential for publication bias. RESULTS: Seventeen studies including 30,062 participants were included. We found that fellow/trainee involvement enhanced the overall rates of adenoma detection and polyp detection (OR = 1.26, 95% CI = 1.14-1.40, p < 0.001; OR = 1.29, 95% CI = 1.02-1.63, p = 0.020, respectively). The mean number of adenoma/polyps per colonoscopy was also higher with fellow/trainee participation (MD = 0.12, 95% CI = 0.08-0.17, p < 0.001; MD = 0.15, 95% CI = 0.02-0.28, p = 0.020, respectively). CONCLUSION: In addition to its educational purpose, fellow or trainee involvement is associated with beneficial effects on colonoscopy outcomes.

Mechanistic illustration on lipid-metabolism disorders induced by triclosan exposure from the viewpoint of m6A-RNA epigenetic modification.

As a typically anthropogenic contaminant, the toxicity effects of triclosan (TCS) were investigated in-depth from the viewpoint of m6A-pre-miRNAs modification. Based on miRNAs high-throughput sequencing, we unravelled the underlying molecular mechanisms regarding TCS-induced lipid-metabolism functional disorders. TCS exposure caused severe lipid accumulation in 120 hpf zebrafish liver and reduced their locomotor activity. Both bioinformatics analysis and experimental validation verified that TCS targeted miR-27b up-regulation to further trigger lipid-metabolism disorders and developmental malformations, including shortened body length, yolk cysts, curved spine and delayed yolk absorption. TCS exposure and miR-27b upregulation both caused the enhanced levels of triglyceride and total cholesterol. Knockdown and overexpression of miR-27b regulated the expression changes of several functional genes related to downstream lipid metabolism of miR-27b, and most downstream target genes of miR-27b were suppressed and enriched in the AMPK signaling pathway. The experiments of pathway inhibitors and agonists further evidenced that TCS caused lipid-metabolism disorders by suppressing the AMPK signaling pathway. In upstream of miR-27b, TCS decreased total m6A-RNA level by targeting upregulation of demethylase and downregulation of methylase reader ythdf1. Molecular docking and ythdf1 siRNA interference further confirmed that TCS targeted the expression change of ythdf1. Under ythdf1 knockdown in upstream of miR-27b, both abnormal lipid metabolism and miR-27b upregulation highlighted that TCS-induced lipid-metabolism disorders were attributable to the decreasing m6A-RNA methylation levels in vivo. These perspectives provide an innovative idea for prevention and treatment of the lipid metabolism-related diseases and these findings open a novel avene for TCS's risk assessment and early intervention of the contaminant.

Gut microbiota disorder induces liver dysfunction in polycystic ovary syndrome rats' model by regulating metabolite rosmarinic acid.

AIMS: The present study aims to investigate the impact of the gut microbiota and serum metabolites on the regulation of liver dysfunction in PCOS. MATERIALS AND METHODS: PCOS rat models were established by treating Sprague Dawley (SD) rats with DHEA (an androgen, 60 mg/kg) and LET (a nonsteroidal aromatase inhibitor, 1 mg/kg) for 90 days. Hematoxylin and eosin staining (H&E), Western blotting, and radioimmunoassay were employed to test ovarian and liver functions. Gut microbiome and serum metabolites were assessed using 16S rRNA amplicon sequencing and non-targeted metabolomics, respectively. The association between gut microbiota and serum metabolites was examined using Spearman analysis. Finally, using HepG2 cells to investigate the function of the serum metabolite rosmarinic acid (RA). KEY FINDINGS: Both Dehydroepiandrosterone (DHEA) and letrozole (LET) treatments induced a PCOS phenotype and liver dysfunction. However, LET resulted in more severe lipid accumulation and liver cell apoptosis than DHEA. 16S rRNA sequencing and non-targeted metabolomics analysis revealed significant differences in beta diversity and serum metabolite profiles among the three groups. Furthermore, among the significantly changed metabolites, RA was found to have a significant correlation with the levels of serum aspartate transaminase (AST) and lactate dehydrogenase (LDH) and could promote HepG2 cell apoptosis. SIGNIFICANCE: Restoring gut microbiota, altering serum metabolites and/or decreasing RA may provide a new insight to treat this complication.

[Research progress on regulation of N6-adenylate methylation modification in lipid metabolism disorders].

Lipid metabolism is a complex physiological process, which is closely related to nutrient regulation, hormone balance and endocrine function. It involves the interactions of multiple factors and signal transduction pathways. Lipid metabolism disorder is one of the main mechanisms to induce a variety of diseases, such as obesity, diabetes, non-alcoholic fatty liver disease, hepatitis, hepatocellular carcinoma and their complications. At present, more and more studies have found that the "dynamic modification" of N6-adenylate methylation (m6A) on RNA represents a new "post-transcriptional" regulation mode. m6A methylation modification can occur in mRNA, tRNA, ncRNA, etc. Its abnormal modification can regulate gene expression changes and alternative splicing events. Many latest references have reported that m6A RNA modification is involved in the epigenetic regulation of lipid metabolism disorder. Based on the major diseases induced by lipid metabolism disorders, we reviewed the regulatory roles of m6A modification in the occurrence and development of those diseases. These overall findings inform further in-depth investigations of the underlying molecular mechanisms regarding the pathogenesis of lipid metabolism disorders from the perspective of epigenetics, and provide reference for health prevention, molecular diagnosis and treatment of related diseases.

A New Online Dynamic Nomogram: Construction and Validation of a Predictive Model for Distant Metastasis Risk and Prognosis in Patients with Gastrointestinal Stromal Tumors.

BACKGROUND: Gastrointestinal stromal tumor (GIST) is the most common sarcoma of the digestive tract, among which patients with distant metastases tend to have a poor prognosis. This study aimed to develop a model for predicting distant metastasis in GIST patients and to develop two models for monitoring overall survival (OS) and cancer-specific survival (CSS) in GIST patients with metastasis. This would allow us to develop an optimal, individualized treatment strategy. METHODS: We reviewed demographic and clinicopathological characteristics data from 2010 to 2017 of patients diagnosed with GIST in the Surveillance, Epidemiology, and End Results (SEER) database. The data of the external validation group was reviewed from the Forth Hospital of Hebei Medical University. Univariate and multivariate logistic regression analyses were used to confirm the independent risk factors for distant metastasis in the GIST patients, and univariate and multivariate Cox regression analyses were performed to identify the independent prognostic factors for OS and CSS in the GIST patients with distant metastasis. Subsequently, three web-based novel nomograms were developed, which were evaluated by the receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA). RESULTS: Of the 3639 patients who met the inclusion criteria, 418 (11.4%) had distant metastases. The risk factors for distant metastasis in GIST patients included sex, primary site, grade, N stage, tumor size, and mitotic count. For OS, the independent prognosis factors for GIST patients with metastasis included age, race, marital, primary site, chemotherapy, mitotic count, and metastasis at the lung, and for CSS, age, race, marital, primary site, and metastasis at the lung were the independent prognosis factors. Three web-based nomograms were constructed based on these independent factors, respectively. The ROC curves, calibration curves, and DCA were performed in the training, testing, and validation sets which confirmed the high accuracy and strong clinical practice power for the nomograms. CONCLUSION: Population-based nomograms can help clinicians predict the occurrence and prognosis of distant metastases in patients with GIST, which may be helpful for clinicians to formulate clinical management and appropriate treatment strategies.

Modeling the effect of loving pedagogy dispositions and teacher self-efficacy on teacher burnout.

Introduction: Foreign language teaching is a demanding and challenging profession, and teacher burnout is a common issue in this field. There is a growing research interest in exploring the factors that can protect teachers from burnout and promote their well-being, as well as their effectiveness in the classroom. One such factor might be loving pedagogy, which refers to a teacher's positive and compassionate attitudes and behaviors toward their students. This study aimed to examine the association between Dispositions toward Loving Pedagogy (DTLP), teacher self-efficacy, and teacher burnout among a sample of Chinese English as a foreign language (EFL) teachers. Methods: The participants included 428 English teachers from various parts of China. Data on the three constructs were gathered using an electronic survey which comprised three valid questionnaires for these variables. Structural equation modeling (SEM) was used to test the hypothesized relations among the latent constructs. Results: The results indicated that loving pedagogy dispositions negatively affected teacher burnout and that teacher self-efficacy mediated the effect of loving pedagogy on burnout. More precisely, higher levels of loving pedagogy were associated with greater levels of teacher self-efficacy, which is in turn negatively affected teacher burnout. Discussion: These outcomes shed more light on the importance of loving pedagogy dispositions for teachers' mental health and well-being. The findings have implications for theory and practice, as they suggest that fostering loving pedagogy dispositions among teachers can help prevent burnout and promote their well-being. Teacher training programs could integrate this construct into their curricula to support teachers in developing these attitudes and behaviors. Additionally, future research could explore ways to enhance loving pedagogy and self-efficacy among teachers and assess their impact on teacher well-being and effectiveness.

Association between Antibiotic Exposure and the Risk of Rash in Children with Infectious Mononucleosis: a Multicenter, Retrospective Cohort Study.

Present evidence suggests that the administration of antibiotics, particularly aminopenicillins, may increase the risk of rash in children with infectious mononucleosis (IM). This retrospective, multicenter cohort study of children with IM was conducted to explore the association between antibiotic exposure in IM children and the risk of rash. A robust error generalized linear regression was performed to address the potential cluster effect, as well as confounding factors such as age and sex. A total of 767 children (aged from 0 to 18 years) with IM from 14 hospitals in Guizhou Province were included in the final analysis. The regression analysis implied that exposure to antibiotics was associated with a significantly increased incidence of overall rash in IM children (adjusted odds ratio [AOR], 1.47; 95% confidence interval [CI], ~1.04 to 2.08; P = 0.029). Of 92 overall rash cases, 43 were probably related to antibiotic exposure: two cases (4.08%) in the amoxicillin-treated group and 41 (8.15%) in the group treated with other antibiotics. Regression analysis indicated that the risk of rash induced by amoxicillin in IM children was similar to that induced by other penicillins (AOR, 1.12; 95% CI, ~0.13 to 9.67), cephalosporins (AOR, 2.45; 95% CI, ~0.43 to 14.02), or macrolides (AOR, 0.91; 95% CI, ~0.15 to 5.43). Antibiotic exposure may be associated with an increased risk of overall rash in IM children, but amoxicillin was not found to be associated with any increased risk of rash during IM compared to other antibiotics. We suggest that clinicians be vigilant against the occurrence of rash in IM children receiving antibiotic therapy, rather than indiscriminately avoiding prescribing amoxicillin.

Moderation of parental socioeconomic status on the relationship between birth health and developmental coordination disorder at early years.

Objective: This study investigated whether parental SES moderates the effect of birth health on Developmental Coordination Disorder (DCD) in preschool children. Methods: One hundred and twenty-two children aged 4 to 6 years were enrolled in the study. The Movement Assessment Battery for Children --2nd Edition (MABC-2) test was used to assess the motor coordination of children. They were preliminarily categorized into either the DCD (<=16th percentile, n = 23) or typically developing (TD) group (>16th percentile, n = 99) based on the testing results. All children in the DCD group were further confirmed to meet other diagnostic criteria of the DSM-V using the intellectual test and parental questionnaires. Moderation analysis was conducted using the PROCESS macro for SPSS, and 95% confidence intervals with a bootstrap procedure were calculated to identify the significant moderating effect. Results: Maternal education (unstandardized coefficient = 0.6805, SE = 0.3371, p < 0.05) and maternal employment status (unstandardized coefficient = 0.6100, SE = 0.3059, p < 0.05) were found to moderate the relationship between birth length and the probability of having DCD. Moreover, the relationship between birth weight and the probability of having DCD was moderated by the annual household income (unstandardized coefficient = -0.0043, SE = 0.0022, p < 0.05). Conclusion: The lower maternal education level and maternal unemployment strengthened the negative relationship between birth length and the probability of having DCD. Additionally, the negative relationship between birth weight and the probability of having DCD was statistically significant in high annual household salaries.

Clinical Analysis and Prognostic Prediction Model for Patients with Uterine Leiomyosarcoma at FIGO Stage I.

Purpose: To reveal the clinical status and construct a predictive prognostic model for patients with uterine leiomyosarcoma (uLMS) at International Federation of Gynecology and Obstetrics (FIGO) stage I. Patients and Methods: The medical records of patients with stage I uLMS during the study period were retrospectively reviewed. Multiple imputation, Martingale residuals and restricted cubic spline were used for data processing. Univariate and multivariate analyses were used to determine independent prognostic factors. The Schoenfeld individual test was used to verify the proportional hazards (PH) assumption. The predictive ability of the nomogram was validated internally. Results: Ultimately, 102 patients were included. The median age at diagnosis was 51 years old. During the medium follow-up time of 68 months, 55 (53.9%) patients developed recurrence. The median recurrence interval was 32 months. The most common metastatic site was the lung (27 cases). Eventually, 38 (37.3%) patients died of uLMS. The 3-year and 5-year overall survival rates were 66.0% and 52.0%, respectively. Age at diagnosis >49 years, larger tumor size, MI>10/10HPF, presence of LVSI and Ki-67 labeling index (LI) >25% (P=0.0467, 0.0077, 0.0475, 0.0294, and 0.0427, respectively) were independent prognostic factors. The PH assumption remained inviolate. The concordance index was 0.847, the area under the time-dependent receiver operating characteristic curve surpassed 0.7, and the calibration curve showed gratifying consistency. Conclusion: Age at diagnosis, tumor size, MI, LVSI, and Ki-67 LI were identified as independent prognostic factors for stage I uLMS. This prognostic nomogram would provide personalized assessment with superior predictive performance.

Action Research on Applying Compound Stimulus Approach to Improve Empathetic Communication: The Case of Physical Therapy Students.

(1) Background: Empathetic communicative skills are the first step in establishing a good therapeutic relationship. The purpose of this study is to understand the effectiveness of improving the empathetic communicative skills applied to obtain accurate and precise information from patients via compound stimulus-drama in education. (2) Methods: A cross-sectional, one-group, pre- and post-test design was used for this study. In the two-day workshop, four clinical physiotherapists acted as tutors for the "Compound Stimulus-Drama in Education" module and assessed students' performances. The Standard Patient Rating Scale (SPRS), Objective Structured Clinical Examination Scale (OSCES), Professional and Communication Self-Assessment Scale (PCSS), Patients' Information (PI), and the Jefferson Scale of Empathy (JSE) were used to assess the students' empathy scores and communication skills, before and after the course. (3) Results: Fifty-seven students participated in this study. The results showed that there were significant improvements in the SPRS, OSCES, PCSS, PI, and JSE (p < 0.05). Both the quantitative data and the participants' reflection feedback suggest that this novel module was more helpful than traditional clinical practice courses for improving clinical empathy communication skills. (4) Conclusions: This study provided an innovative teaching model and assessment tools for learning clinic empathetic communicative skills in future education training.

A deep belief network-based clinical decision system for patients with osteosarcoma.

Osteosarcoma was the most frequent type of malignant primary bone tumor with a poor survival rate mainly occurring in children and adolescents. For precision treatment, an accurate individualized prognosis for Osteosarcoma patients is highly desired. In recent years, many machine learning-based approaches have been used to predict distant metastasis and overall survival based on available individual information. In this study, we compared the performance of the deep belief networks (DBN) algorithm with six other machine learning algorithms, including Random Forest, XGBoost, Decision Tree, Gradient Boosting Machine, Logistic Regression, and Naive Bayes Classifier, to predict lung metastasis for Osteosarcoma patients. Therefore the DBN-based lung metastasis prediction model was integrated as a parameter into the Cox proportional hazards model to predict the overall survival of Osteosarcoma patients. The accuracy, precision, recall, and F1 score of the DBN algorithm were 0.917/0.888, 0.896/0.643, 0.956/0.900, and 0.925/0.750 in the training/validation sets, respectively, which were better than the other six machine-learning algorithms. For the performance of the DBN survival Cox model, the areas under the curve (AUCs) for the 1-, 3- and 5-year survival in the training set were 0.851, 0.806 and 0.793, respectively, indicating good discrimination, and the calibration curves showed good agreement between the prediction and actual observations. The DBN survival Cox model also demonstrated promising performance in the validation set. In addition, a nomogram integrating the DBN output was designed as a tool to aid clinical decision-making.

Impact of skeletal muscle loss during conversion therapy on clinical outcomes in lavage cytology positive patients with gastric cancer.

Background: The relationship between sarcopenia and clinical outcomes during conversion therapy in patients with lavage cytology positive gastric cancer (GC-CY1) remains unclear. This study aimed to investigate the impact of sarcopenia and skeletal muscle loss on the efficacy of conversion therapy, tumour response and survival in GC-CY1 patients. Methods: Retrospective analysis of data from a prospective trial of conversion therapy conducted between April 2018 and August 2019 in patients with GC-CY1 (NCT03718624). Skeletal muscle index (SMI) was measured at the level of the third lumbar (L3) vertebra and the sarcopenia was defined using published cut-off points in all patients. We defined ΔSMI (%)/50 days above 9.53% for men and ΔSMI (%)/50 days above 8.81% for women as significant muscle loss (SML) and analysed the changes in skeletal muscle during conversion therapy in relation to treatment efficacy, survival and tumour response. Results: Of the 36 patients, 7 patients (19.44%) developed sarcopenia before conversion therapy, 6 (16.67%) developed new sarcopenia after conversion therapy, and 8 (22.22%) developed SML during treatment. Multivariate analysis showed that sarcopenia before treatment [Odds Ratio (OR) =8.923, 95%CI: 1.341-25.321, p=0.002] and SML during treatment (OR=7.803, 95%CI: 1.106-16.189, p=0.001) had a negative impact on the success rate of conversion therapy. Cox multifactorial analysis found that pre-treatment sarcopenia [overall survival (OS): Hazard Ratio (HR) =6.341, 95%CI: 1.269-18.943, p=0.001; progression-free survival (PFS): HR=8.212, 95%CI: 1.569-36.582, p=0.001], newly developed sarcopenia after conversion therapy (OS: HR=3.189, 95%CI: 1.023-9.811, p=0.012; PFS: HR=3.084, 95%CI: 1.042-14.236, p=0.013) and the presence of SML during treatment (OS: HR=10.234, 95%CI: 2.532-54.231, p=0.002; PFS: HR=9.562, 95%CI: 2.341-38.092, p=0.002) were independent risk factor for OS and PFS in GC-CY1 patients. Conclusion: Pre-treatment sarcopenia and the presence of SML during treatment are strongly correlated with the immediate and long-term outcomes of GC-CY1 patients and can be used as imaging markers to predict the treatment efficacy and prognosis of patients in clinical practice.