Molecular diagnosis, clinical evaluation and phenotypic spectrum of Townes-Brocks syndrome: insights from a large Chinese hearing loss cohort.

BACKGROUND: Townes-Brocks syndrome (TBS) is a rare genetic disorder characterised by multiple malformations. Due to its phenotypic heterogeneity and rarity, diagnosis and recognition of TBS can be challenging and there has been a lack of investigation of patients with atypical TBS in large cohorts and delineation of their phenotypic characteristics. METHODS: We screened SALL1 and DACT1 variants using next-generation sequencing in the China Deafness Genetics Consortium (CDGC) cohort enrolling 20 666 unrelated hearing loss (HL) cases. Comprehensive clinical evaluations were conducted on seven members from a three-generation TBS family. Combining data from previously reported cases, we also provided a landscape of phenotypes and genotypes of patients with TBS. RESULTS: We identified five novel and two reported pathogenic/likely pathogenic (P/LP) SALL1 variants from seven families. Audiological features in patients differed in severity and binaural asymmetry. Moreover, previously undocumented malformations in the middle and inner ear were detected in one patient. By comprehensive clinical evaluations, we further provide evidence for the causal relationship between SALL1 variation and certain endocrine abnormalities. Penetrance analysis within familial contexts revealed incomplete penetrance among first-generation patients with TBS and a higher disease burden among their affected offspring. CONCLUSION: This study presents the first insight of genetic screening for patients with TBS in a large HL cohort. We broadened the phenotypic-genotypic spectrum of TBS and our results supported an underestimated prevalence of TBS. Due to the rarity and phenotypic heterogeneity of rare diseases, broader spectrum molecular tests, especially whole genome sequencing, can improve the situation of underdiagnosis and provide effective recommendations for clinical management.

A real-world observation on thrombopoietic agents for patients with cancer treatment-induced thrombocytopenia in China: A multicenter, cross-sectional study.

BACKGROUND: Studies on various thrombopoietic agents for cancer treatment-induced thrombocytopenia (CTIT) in China are lacking. This study aimed to provide detailed clinical profiles to understand the outcomes and safety of different CTIT treatment regimens. METHODS: In this retrospective, cross-sectional study, 1664 questionnaires were collected from 33 hospitals between March 1 and July 1, 2021. Patients aged >18 years were enrolled who were diagnosed with CTIT and treated with recombinant interleukin 11 (rhIL-11), recombinant thrombopoietin (rhTPO), or a thrombopoietin receptor agonist (TPO-RA). The outcomes, compliance, and safety of different treatments were analyzed. RESULTS: Among the 1437 analyzable cases, most patients were treated with either rhTPO alone (49.3%) or rhIL-11 alone (27.0%). The most common combination regimen used was rhTPO and rhIL-11 (10.9%). Platelet transfusions were received by 117 cases (8.1%). In multivariate analysis, rhTPO was associated with a significantly lower proportion of platelet recovery, platelet transfusion, and hospitalization due to chemotherapy-induced thrombocytopenia (CIT) than rhIL-11 alone. No significant difference was observed in the time taken to achieve a platelet count of >100 × 109/L and chemotherapy dose reduction due to CIT among the different thrombopoietic agents. The outcomes of thrombocytopenia in 170 patients who received targeted therapy and/or immunotherapy are also summarized. The results show that the proportion of platelet recovery was similar among the different thrombopoietic agents. No new safety signals related to thrombopoietic agents were observed in this study. A higher proportion of physicians preferred to continue treatment with TPO-RA alone than with rhTPO and rhIL-11. CONCLUSIONS: This survey provides an overview of CTIT and the application of various thrombopoietic agents throughout China. Comparison of monotherapy with rhIL-11, rhTPO, and TPO-RA requires further randomized clinical trials. The appropriate application for thrombopoietic agents should depend on the pretreatment of platelets, treatment variables, and risk of bleeding. PLAIN LANGUAGE SUMMARY: To provide an overview of the outcome of cancer treatment-induced thrombocytopenia in China, our cross-sectional study analyzed 1437 cases treated with different thrombopoietic agents. Most of the patients were treated with recombinant interleukin 11 (rhIL-11) and recombinant thrombopoietin (rhTPO). rhTPO was associated with a significantly lower proportion of platelet recovery and platelet transfusion compared with rhIL-11.

User-Friendly Multifunctional Red-Emissive Carbon Dots for Rapid Cell Nucleus Staining via Targeting Nuclear Proteins.

Cytoarchitectural staining is of great importance in disease diagnosis and cell biology research. This study developed user-friendly multifunctional red-emissive carbon dots (R-CDs) for rapid cell nucleus staining via targeting nuclear proteins. R-CDs, simply prepared by electrochemical treatment of 1,2,4-benzenetriamine, exhibit strong emission at 635 nm when excited at 507 nm. The R-CDs can rapidly stain the nucleus of human SH-SY5Y, HepG2, and HUH-7 cells with a high signal-to-noise ratio owing to fluorescence enhancement after entering the nucleus. Compared to conventional cytosolic dyes such as Hoechst and DAPI, R-CDs are cheaper, more highly dispersed in water, and more stable (requiring no stringent storage conditions). The R-CDs show stable optical properties with insignificant photobleaching over 7 days and salt resistance up to 2 M of NaCl. More importantly, R-CDs, possessing a positive charge, allow rapid staining of live cells (3 min) and dead cells (10 s) in saline. According to kinetic variation, R-CDs can distinguish live cells from dead cells. Staining exhibits high efficiency in onion epidermal cells, Aspergillus niger, Caenorhabditis elegans, and human spermatozoa. The mechanism for efficient staining is based on their fast accumulation in the nucleus due to their small size and positive charge and strong interaction with nuclear proteins at amino acid residues of histidine and arginine, resulting in fluorescence enhancement by dozens of times. The developed R-CDs do not bind to DNA and would not cause genetic damage and will find various safe applications in biological and medical fields.

High Accuracy of Clinical Verification of Electrohydrodynamic-Driven Nanobox-on-Mirror Platform for Molecular Identification of Respiratory Viruses.

The molecular detection of multiple respiratory viruses provides evidence for the rational use of drugs and effective health management. Herein, we developed and tested the clinical performance of an electrohydrodynamic-driven nanobox-on-mirror platform (E-NoM) for the parallel, accurate, and sensitive detection of four respiratory viral antigens. The E-NoM platform uses gold-silver alloy nanoboxes as the core material with the deposition of a silver layer as a shell on the core surfaces to amplify and enable a reproducible Raman signal readout that facilitates accurate detection. Additionally, the E-NoM platform employs gold microelectrode arrays as the mirror with electrohydrodynamics to manipulate the fluid flow and enhance molecular interactions for an improved biosensing response. The presence of viral antigens binds the nanobox-based core-shell nanostructure on the gold microelectrode and creates the nanocavity with extremely strong "hot spots" to benefit sensitive analysis. Significantly, in a large clinical cohort with 227 patients, the designed E-NoM platform demonstrates the capability of screening respiratory infection with achieved clinical specificity, sensitivity, and accuracy of 100.0, 96.48, and 96.91%, respectively. It is anticipated that the E-NoM platform can find a position in clinical usage for respiratory disease diagnosis.

Efficacy and safety of anti-PD-1/PD-L1-based dual immunotherapies versus PD-1/PD-L1 inhibitor alone in patients with advanced solid tumor: a systematic review and meta-analysis.

INTRODUCTION: Numerous randomized controlled trials (RCTs) have investigated PD-1/PD-L1 inhibitor-based combination therapies. The debate surrounding the potential additive clinical benefits of combination of two immune-oncology (IO) therapies for cancer patients persists. METHODS: Both published and grey sources of randomized clinical trials that compared anti-PD-1/PD-L1-based immunotherapy combinations with monotherapy in patients with advanced or metastatic solid tumors were encompassed. The primary outcome was progression-free survival (PFS), and secondary outcomes included objective response rate (ORR), overall survival (OS) and treatment-related adverse events (TRAEs). RESULTS: Our analysis encompassed 31 studies comprising 10,341 patients, which covered 12 distinct immune-oncology combination regimens. Across all patients, the immunotherapy combinations exhibited the capability to enhance the ORR (OR = 1.23 [95% CI 1.13-1.34]) and extend PFS (HR = 0.91 [95% CI 0.87-0.95]). However, the observed enhancement in OS (HR = 0.96 [95% CI 0.91-1.01]) was of no significance. Greater benefits in terms of PFS (HR = 0.82 [95% CI 0.72 to 0.93]) and OS (HR = 0.85 [95% CI 0.73 to 0.99]) may be particularly pronounced in cases where PD-L1 expression is negative. Notably, despite a heightened risk of any-grade TRAEs (OR = 1.72 [95% CI 1.40-2.11]) and grade greater than or equal to 3 TRAEs (OR = 2.01 [95% CI 1.67-2.43]), toxicity was generally manageable. CONCLUSIONS: This study suggests that incorporating an additional immunotherapy agent with PD-1/PD-L1 inhibitors can elevate the response rate and reduce the risk of disease progression, all while maintaining manageable toxicity. However, there remains a challenge in translating these primary clinical benefits into extended overall survival.

Adipose tissue-derived metabolite risk scores and risk for type 2 diabetes in South Asians.

BACKGROUND: South Asians are at higher risk for type 2 diabetes (T2D) than many other race/ethnic groups. Ectopic adiposity, specifically hepatic steatosis and visceral fat may partially explain this. Our objective was to derive metabolite risk scores for ectopic adiposity and assess associations with incident T2D in South Asians. METHODS: We examined 550 participants in the Mediators of Atherosclerosis in South Asians Living in America (MASALA) cohort study aged 40-84 years without known cardiovascular disease or T2D and with metabolomic data. Computed tomography scans at baseline assessed hepatic attenuation and visceral fat area, and fasting serum specimens at baseline and after 5 years assessed T2D. LC-MS-based untargeted metabolomic analysis was performed followed by targeted integration and reporting of known signals. Elastic net regularized linear regression analyses was used to derive risk scores for hepatic steatosis and visceral fat using weighted coefficients. Logistic regression models associated metabolite risk score and incident T2D, adjusting for age, gender, study site, BMI, physical activity, diet quality, energy intake and use of cholesterol-lowering medication. RESULTS: Average age of participants was 55 years, 36% women with an average body mass index (BMI) of 25 kg/m2 and 6% prevalence of hepatic steatosis, with 47 cases of incident T2D at 5 years. There were 445 metabolites of known identity. Of these, 313 metabolites were included in the MET-Visc score and 267 in the MET-Liver score. In most fully adjusted models, MET-Liver (OR 2.04 [95% CI 1.38, 3.03]) and MET-Visc (OR 2.80 [1.75, 4.46]) were associated with higher odds of T2D. These associations remained significant after adjustment for measured adiposity. CONCLUSIONS: Metabolite risk scores for intrahepatic fat and visceral fat were strongly related to incident T2D independent of measured adiposity. Use of these biomarkers to target risk stratification may help capture pre-clinical metabolic abnormalities.

Integrating data distribution prior via Langevin dynamics for end-to-end MR reconstruction.

PURPOSE: To develop a novel deep learning-based method inheriting the advantages of data distribution prior and end-to-end training for accelerating MRI. METHODS: Langevin dynamics is used to formulate image reconstruction with data distribution before facilitate image reconstruction. The data distribution prior is learned implicitly through the end-to-end adversarial training to mitigate the hyper-parameter selection and shorten the testing time compared to traditional probabilistic reconstruction. By seamlessly integrating the deep equilibrium model, the iteration of Langevin dynamics culminates in convergence to a fix-point, ensuring the stability of the learned distribution. RESULTS: The feasibility of the proposed method is evaluated on the brain and knee datasets. Retrospective results with uniform and random masks show that the proposed method demonstrates superior performance both quantitatively and qualitatively than the state-of-the-art. CONCLUSION: The proposed method incorporating Langevin dynamics with end-to-end adversarial training facilitates efficient and robust reconstruction for MRI. Empirical evaluations conducted on brain and knee datasets compellingly demonstrate the superior performance of the proposed method in terms of artifact removing and detail preserving.

Combinatorial metabolic engineering of Bacillus subtilis for de novo production of polymyxin B.

Polymyxin is a lipopeptide antibiotic that is effective against multidrug-resistant Gram-negative bacteria. However, its clinical development is limited due to low titer and the presence of homologs. To address this, the polymyxin gene cluster was integrated into Bacillus subtilis, and sfp from Paenibacillus polymyxa was expressed heterologously, enabling recombinant B. subtilis to synthesize polymyxin B. Regulating NRPS domain inhibited formation of polymyxin B2 and B3. The production of polymyxin B increased to 329.7 mg/L by replacing the native promoters of pmxA, pmxB, and pmxE with PfusA, C2up, and PfusA, respectively. Further enhancement in this production, up to 616.1 mg/L, was achieved by improving the synthesis ability of 6-methyloctanoic acid compared to the original strain expressing polymyxin heterologously. Additionally, incorporating an anikasin-derived domain into the hybrid nonribosomal peptide synthase of polymyxin increased the B1 ratio in polymyxin B from 57.5% to 62.2%. Through optimization of peptone supply in the fermentation medium and fermentation in a 5.0-L bioreactor, the final polymyxin B titer reached 962.1 mg/L, with a yield of 19.24 mg/g maltodextrin and a productivity of 10.02 mg/(L·h). This study demonstrates a successful approach for enhancing polymyxin B production and increasing the B1 ratio through combinatorial metabolic engineering.

Dexamethasone attenuates neuropathic pain through spinal microglial expression of dynorphin A via the cAMP/PKA/p38 MAPK/CREB signaling pathway.

This study aimed to elucidate the opioid mechanisms underlying dexamethasone-induced pain antihypersensitive effects in neuropathic rats. Dexamethasone (subcutaneous and intrathecal) and membrane-impermeable Dex-BSA (intrathecal) administration dose-dependently inhibited mechanical allodynia and thermal hyperalgesia in neuropathic rats. Dexamethasone and Dex-BSA treatments increased expression of dynorphin A in the spinal cords and primary cultured microglia. Dexamethasone specifically enhanced dynorphin A expression in microglia but not astrocytes or neurons. Intrathecal injection of the microglial metabolic inhibitor minocycline blocked dexamethasone-stimulated spinal dynorphin A expression; intrathecal minocycline, the glucocorticoid receptor antagonist Dex-21-mesylate, dynorphin A antiserum, and κ-opioid receptor antagonist GNTI completely blocked dexamethasone-induced mechanical antiallodynia and thermal antihyperalgesia. Additionally, dexamethasone elevated spinal intracellular cAMP levels, leading to enhanced phosphorylation of PKA, p38 MAPK and CREB. The specific adenylate cyclase inhibitor DDA, PKA inhibitor H89, p38 MAPK inhibitor SB203580 and CREB inhibitor KG-501 completely blocked dexamethasone-induced anti-neuropathic pain and increased microglial dynorphin A exprression. In conclusion, this study reveal that dexamethasone mitigateds neuropathic pain through upregulation of dynorphin A in spinal microglia, likely involving the membrane glucocorticoid receptor/cAMP/PKA/p38 MAPK/CREB signaling pathway.

Enhancing thalassemia gene carrier identification in non-anemic populations using artificial intelligence erythrocyte morphology analysis and machine learning.

BACKGROUND: Non-anemic thalassemia trait (TT) accounted for a high proportion of TT cases in South China. OBJECTIVE: To use artificial intelligence (AI) analysis of erythrocyte morphology and machine learning (ML) to identify TT gene carriers in a non-anemic population. METHODS: Digital morphological data from 76 TT gene carriers and 97 controls were collected. The AI technology-based Mindray MC-100i was used to quantitatively analyze the percentage of abnormal erythrocytes. Further, ML was used to construct a prediction model. RESULTS: Non-anemic TT carriers accounted for over 60% of the TT cases. Random Forest was selected as the prediction model and named TT@Normal. The TT@Normal algorithm showed outstanding performance in the training, validation, and external validation sets and could efficiently identify TT carriers in the non-anemic population. The top three weights in the TT@Normal model were the target cells, microcytes, and teardrop cells. Elevated percentages of abnormal erythrocytes should raise a strong suspicion of being a TT gene carrier. TT@Normal could be promoted and used as a visualization and sharing tool. It is accessible through a URL link and can be used by medical staff online to predict the possibility of TT gene carriage in a non-anemic population. CONCLUSIONS: The ML-based model TT@Normal could efficiently identify TT carriers in non-anemic people. Elevated percentages of target cells, microcytes, and teardrop cells should raise a strong suspicion of being a TT gene carrier.

The Ceiling Effects of EQ-5D-3L and 5L in General Population Health Surveys: A Systematic Review and Meta-Analysis.

OBJECTIVES: This review aims to examine the ceiling effects of EQ-5D-3L (3L) and EQ-5D-5L (5L) in general adult populations and identify the factors influencing these effects. METHODS: We searched 8 databases for observational studies published in English from inception to 24 July 2023. Ceiling effects were calculated by dividing the number of participants reporting full health at dimension or profile level by the total sample size. Subgroup analysis and meta-regression using the metafor package in R software were performed. RESULTS: We identified 94 studies from 70 articles, including 4 543 647 adults across 37 countries. The global pooled proportion of individuals reporting full health ("11111") was 56% (95% CI 51%-62%) for 3L and 49% (95% CI 44%-54%) for 5L. The self-care dimension showed the highest ceiling effects (3L: 97%; 5L: 94%), whereas pain/discomfort had the lowest (3L: 69%; 5L: 60%). The ceiling effects in East/South-East Asia were higher than in Europe by 25% (95% CI 18%-32%) in 3L and 9% (95% CI -2%-20%) in 5L. Adjusting for mean age and proportion of males, significant regional differences persisted in the overall profile level of 3L, in all 3L dimensions (except for self-care), and 5L dimensions (except for pain/discomfort and anxiety/depression). CONCLUSIONS: This review highlights significant ceiling effects in the EQ-5D, especially in Asian populations. The 5L version exhibited fewer ceiling effects than the 3L, indicating its superiority for general population surveys. Further research is crucial to understand the disparities in self-reported health outcomes between Asians and other populations.

Comparison of the effects of imputation methods for missing data in predictive modelling of cohort study datasets.

BACKGROUND: Missing data is frequently an inevitable issue in cohort studies and it can adversely affect the study's findings. We assess the effectiveness of eight frequently utilized statistical and machine learning (ML) imputation methods for dealing with missing data in predictive modelling of cohort study datasets. This evaluation is based on real data and predictive models for cardiovascular disease (CVD) risk. METHODS: The data is from a real-world cohort study in Xinjiang, China. It includes personal information, physical examination data, questionnaires, and laboratory biochemical results from 10,164 subjects with a total of 37 variables. Simple imputation (Simple), regression imputation (Regression), expectation-maximization(EM), multiple imputation (MICE) , K nearest neighbor classification (KNN), clustering imputation (Cluster), random forest (RF), and decision tree (Cart) were the chosen imputation methods. Root Mean Square Error (RMSE) and Mean Absolute Error (MAE) are utilised to assess the performance of different methods for missing data imputation at a missing rate of 20%. The datasets processed with different missing data imputation methods were employed to construct a CVD risk prediction model utilizing the support vector machine (SVM). The predictive performance was then compared using the area under the curve (AUC). RESULTS: The most effective imputation results were attained by KNN (MAE: 0.2032, RMSE: 0.7438, AUC: 0.730, CI: 0.719-0.741) and RF (MAE: 0.3944, RMSE: 1.4866, AUC: 0.777, CI: 0.769-0.785). The subsequent best performances were achieved by EM, Cart, and MICE, while Simple, Regression, and Cluster attained the worst performances. The CVD risk prediction model was constructed using the complete data (AUC:0.804, CI:0.796-0.812) in comparison with all other models with p<0.05. CONCLUSION: KNN and RF exhibit superior performance and are more adept at imputing missing data in predictive modelling of cohort study datasets.

Early blood pressure lowering therapy is associated with good functional outcome in patients with intracerebral hemorrhage.

BACKGROUND: The implementation of a care bundle might improve functional outcome for patients with intracerebral hemorrhage (ICH). However, the impact of anti-hypertensive treatment on ICH outcomes remains uncertain. Our objective is to examine whether early blood pressure (BP) lowering therapy within first 12 h is associated with good outcome in ICH patients. METHODS: We included acute ICH patients who had baseline computed tomography (CT) scans within 6 h after onset of symptoms between October 2013 and December 2021. Early BP reduction was defined as use of anti-hypertensive agents within 12 h after onset of symptom. The clinical characteristics were compared between patients who received early BP lowering therapy and those without. The associations between early BP lowering and good outcome and functional independence at 3 months were assessed by using multivariable logistic regression analyses. RESULTS: A total of 377 patients were finally included in this study for outcome analysis. Of those, 212 patients received early BP reduction within 12 h after ICH. A total of 251 (66.6%) patients had good outcome. After adjustment for age, admission systolic BP, admission GCS score, baseline hematoma volume, hematoma expansion, and presence of intraventricular hemorrhage, early BP lowering therapy was associated with functional independence (adjusted odd ratio:1.72, 95% confidence interval:1.03-2.87; P = 0.039) and good outcome (adjusted odd ratio: 2.02, 95% confidence interval:1.08-3.76; P = 0.027). CONCLUSIONS: In ICH patients presenting within 6 h after symptom onset, early BP reduction within first 12 h is associated with good outcome and functional independence when compared to those who do not undergo such early intervention. Implementation of quality measures to ensure early BP reduction is crucial for management of ICH.

circMTO1/miR-30c-5p/SOCS3 axis alleviates oral submucous fibrosis through inhibiting fibroblast-myofibroblast transition.

BACKGROUND: circRNAs have been shown to participate in diverse diseases; however, their role in oral submucous fibrosis (OSF), a potentially malignant disorder, remains obscure. Our preliminary experiments detected the expression of circRNA mitochondrial translation optimization 1 homologue (circMTO1) in OSF tissues (n = 20) and normal mucosa tissues (n = 20) collected from Hunan Xiangya Stomatological Hospital, and a significant decrease of circMTO1 expression was showed in OSF tissues. Therefore, we further explored circMTO1 expression in OSF. METHODS: Target molecule expression was detected using RT-qPCR and western blotting. The migration and invasion of buccal mucosal fibroblasts (BMFs) were assessed using wound healing and Transwell assays. The interaction between miR-30c-5p, circMTO1, and SOCS3 was evaluated using dual luciferase, RNA immunoprecipitation (RIP), and RNA pull-down assays. The colocalisation of circMTO1 and miR-30c-5p was observed using fluorescence in situ hybridisation (FISH). RESULTS: circMTO1 and SOCS3 expression decreased, whereas miR-30c-5p expression increased in patients with OSF and arecoline-stimulated BMFs. Overexpression of circMTO1 effectively restrained the fibroblast-myofibroblast transition (FMT), as evidenced by the increase in expression of Coll I, α-SMA, Vimentin, and the weakened migration and invasion functions in BMFs. Mechanistic studies have shown that circMTO1 suppresses FMT by enhancing SOCS3 expression by sponging miR-30c-5p and subsequently inactivating the FAK/PI3K/AKT pathway. FMT induced by SOCS3 silencing was reversed by the FAK inhibitor TAE226 or the PI3K inhibitor LY294002. CONCLUSION: circMTO1/miR-30c-5p/SOCS3 axis regulates FMT in arecoline-treated BMFs via the FAK/PI3K/AKT pathway. Expanding the sample size and in vivo validation could further elucidate their potential as therapeutic targets for OSF.

An Engineered Microbial Consortium Provides Precursors for Fengycin Production by Bacillus subtilis.

Fengycin has great potential for applications in biological control because of its biosafety and degradability. In this study, the addition of exogenous precursors increased fengycin production by Bacillus subtilis. Corynebacterium glutamicum was engineered to produce high levels of precursors (Thr, Pro, Val, and Ile) to promote the biosynthesis of fengycin. Furthermore, recombinant C. glutamicum and Yarrowia lipolytica providing amino acid and fatty acid precursors were co-cultured to improve fengycin production by B. subtilis in a three-strain artificial consortium, in which fengycin production was 2100 mg·L-1. In addition, fengycin production by the consortium in a 5 L bioreactor reached 3290 mg·L-1. Fengycin had a significant antifungal effect on Rhizoctonia solani, which illustrates its potential as a food preservative. Taken together, this work provides a new strategy for improving fengycin production by a microbial consortium and metabolic engineering.

The effectiveness of digital psychosocial interventions on psychological distress, depression, anxiety, and health-related quality of life in patients with gynaecological cancer: a systematic review and meta-analysis.

PURPOSE: Patients with gynaecological cancer often experience psychological issues due to multiple stressors. Psychological disturbances have debilitating effects on patients with gynaecological cancer. In recent decades, digital psychosocial interventions have rapidly advanced and been incorporated into mental health interventions. Digital psychosocial interventions could provide patients with several benefits over traditional in-person interventions, including convenience, anonymity, flexible scheduling, and geographic mobility. The aim of this systematic review was to synthesize the effectiveness of digital psychosocial intervention in reducing psychological distress, depression, and anxiety and improving health-related quality of life in patients with gynaecological cancer. METHODS: Three-step extensive search was performed on 22 December 2022 from nine bibliographic databases, trial registries and grey literature. Experimental studies involving patients with gynaecological cancer utilizing digital psychosocial interventions for the improvement of mental health outcomes were included. Meta-analysis was conducted using RevMan 5.4 software. Heterogeneity was analysed by Cochran's Q test and I2. Subgroup analyses were attempted to evaluate relative effect sizes of subgroup features. RESULTS: Meta-analysis of nine studies revealed small effect size in reduction of depression post-intervention (d = 0.24, 95% CI - 0.46 to - 0.02) and medium effect size in reduction of psychological distress post-intervention (d = 0.51, 95% CI - 0.81 to - 0.21) and follow-up (d = 0.65, 95% CI - 1.25 to - 0.05) compared to the control group. The effects of digital psychosocial interventions on anxiety and health-related quality of life were not statistically significant. CONCLUSIONS: Digital psychosocial interventions probably reduced psychological distress and slightly reduced depression amongst patients with gynaecological cancer compared to the control group, which can be integrated into clinical practice. Additional trials with rigorous methodology and bigger sample sizes are needed to validate findings. TRIAL REGISTRATION: PROSPERO (CRD42023389502).

Short-term outcomes of the study of refeeding to optimize inpatient gains for patients with atypical anorexia nervosa.

OBJECTIVE: The StRONG trial demonstrated the safety and efficacy of higher calorie refeeding (HCR) in hospitalized adolescents and young adults with malnutrition secondary to restrictive eating disorders. Here we compare refeeding outcomes in patients with atypical anorexia nervosa (atypical AN) versus anorexia nervosa (AN) and examine the impact of caloric dose. METHOD: Patients were enrolled upon admission and randomized to meal-based HCR, beginning 2000 kcal/day and advancing 200 kcal/day, or lower calorie refeeding (LCR), beginning 1400 kcal/day and advancing 200 kcal every other day. Atypical AN was defined as %median BMI (mBMI) > 85. Independent t-tests compared groups; multivariable linear and logistic regressions examined caloric dose (kcal/kg body weight). RESULTS: Among n = 111, mean ± SD age was 16.5 ± 2.5 yrs; 43% had atypical AN. Compared to AN, atypical AN had slower heart rate restoration (8.7 ± 4.0 days vs. 6.5 ± 3.9 days, p = .008, Cohen's d = -.56), less weight gain (3.1 ± 5.9%mBMI vs. 5.4 ± 2.9%mBMI, p < .001, Cohen's d = .51) and greater hypomagnesemia (29% vs. 11%, p = .03, OR = 3.29). These suboptimal outcomes were predicted by insufficient caloric dose (32.4 ± 6.9 kcal/kg in atypical AN vs. 43.4 ± 9.8 kcal/kg in AN, p < .001, Cohen's d = 1.27). For every 10 kcal/kg increase, heart rate was restored 1.7 days (1.0, 2.5) faster (p < .001), weight gain was 1.6%mBMI (.8, 2.4) greater (p < .001), and hypomagnesemia odds were 70% (12, 128) lower (p = .02). DISCUSSION: Although HCR is more efficacious than LCR for refeeding in AN, it contributes to underfeeding in atypical AN by providing an insufficient caloric dose relative to the greater body weight in this diagnostic group. PUBLIC SIGNIFICANCE: The StRONG trial previously demonstrated the efficacy and safety of higher calorie refeeding in patients with malnutrition due to restrictive eating disorders. Here we show that higher calorie refeeding contributes to underfeeding in patients with atypical anorexia nervosa, including poor weight gain and longer time to restore medical stability. These findings indicate these patients need more calories to support nutritional rehabilitation in hospital.

Accuracy of edentulous full-arch implant impression: An in vitro comparison between conventional impression, intraoral scan with and without splinting, and photogrammetry.

OBJECTIVES: The purpose of this in vitro study was to compare the trueness and precision of complete arch implant impressions using conventional impression, intraoral scanning with and without splinting, and stereophotogrammetry. MATERIALS AND METHODS: An edentulous model with six implants was used in this study. Four implant impression techniques were compared: the conventional impression (CI), intraoral scanning (IOS) without splinting, intraoral scanning with splinting (MIOS), and stereophotogrammetry (SPG). An industrial blue light scanner was used to generate the baseline scan from the model. The CI was captured with a laboratory scanner. The reference best-fit method was then applied in the computer-aided design (CAD) software to compute the three-dimensional, angular, and linear discrepancies among the four impression techniques. The root mean square (RMS) 3D discrepancies in trueness and precision between the four impression groups were analyzed with a Kruskal-Wallis test. Trueness and precision between single analogs were assessed using generalized estimating equations. RESULTS: Significant differences in the overall trueness (p = .017) and precision (p < .001) were observed across four impression groups. The SPG group exhibited significantly smaller RMS 3D deviations than the CI, IOS, and MIOS groups (p < .05), with no significant difference detected among the latter three groups (p > .05). CONCLUSIONS: Stereophotogrammetry showed superior trueness and precision, meeting misfit thresholds for implant-supported complete arch prostheses. Intraoral scanning, while accurate like conventional impressions, exhibited cross-arch angular and linear deviations. Adding a splint to the scan body did not improve intraoral scanning accuracy.

Social support, psychological capital, multidimensional job burnout, and turnover intention of primary medical staff: a path analysis drawing on conservation of resources theory.

BACKGROUND: Job burnout is a prevalent and emerging challenge in the primary medical system, causing mass turnover, especially of primary medical staff. Little attention has been paid to the different dimensions of job burnout (emotional exhaustion, personality disintegration, and reduced sense of achievement), which may hinder efforts to tackle high turnover intention among primary medical staff. From the perspective of conservation of resources theory, social support and psychological capital are basic resources with potential to diminish job burnout and thus lower turnover intention. However, there is insufficient research evidence on the relationships between social support, psychological capital, and the three dimensions of job burnout within the primary medical system. OBJECTIVES: Focusing on primary medical staff, this study conducts a path analysis to examine the correlations between two types of resources (social support and psychological capital) and the three dimensions of job burnout, and to test the impact of the latter on turnover intention. Based on the results, effective management strategies to improve the work stability of primary medical staff are proposed. METHODS: Multi-stage cluster random sampling was used to select participants in Anhui Province, China. Data were collected using a self-administered questionnaire containing measures of the main variables and demographic questions. In total, 1132 valid questionnaires were returned by primary medical staff. Structural equation modeling was used for path analysis of the data. RESULTS: Social support was negatively associated with emotional exhaustion (ß = - 0.088, P = 0.020), personality disintegration (ß = - 0.235, P < 0.001), and reduced sense of achievement (ß = - 0.075, P = 0.040). Moreover, psychological capital was negatively associated with emotional exhaustion (ß = - 0.079, P = 0.030), personality disintegration (ß = - 0.156, P < 0.001), and reduced sense of achievement (ß = - 0.432, P < 0.001). All three dimensions of job burnout positively affected turnover intention (emotional exhaustion: ß = 0.246, P < 0.001; personality disintegration: ß = 0.076, P = 0.040; reduced sense of achievement: ß = 0.119, P = 0.001). CONCLUSIONS: The results highlight the importance of social support and psychological capital for diminishing the three dimensions of job burnout for primary medical staff and, in turn, lowering their turnover intention. Accordingly, to alleviate job burnout and improve staff retention, material and psychological supports from leaders, colleagues, family, relatives, and friends are essential, as are measures to improve the psychological energy of primary medical staff.

The effect of T cell aging on the change of human tissue structure.

The trend of aging of the global population is becoming more and more significant, and the incidence of age-related diseases continues to rise.This phenomenon makes the problem of aging gradually attracted wide attention of the society, and gradually developed into an independent research field.As a vital defense mechanism of the human body, the immune system changes significantly during the aging process.Age-induced changes in the body's immune system are considered harmful and are commonly referred to as immune aging, which may represent the beginning of systemic aging.Immune cells, especially T cells, are the biggest influencers and participants in age-related deterioration of immune function, making older people more susceptible to different age-related diseases.More and more evidence shows that T cells play an important role in the change of human tissue structure after aging, which fundamentally affects the health and survival of the elderly.In this review, we discuss the general characteristics of age-related T cell immune alterations and the possible effects of aging T cells in various tissue structures in the human body.