Research on fatigue detection of flight trainees based on face EMF feature model combination with PSO-CNN algorithm.

Even though the capability of aircraft manufacturing has improved, human factors still play a pivotal role in flight accidents. For example, fatigue-related accidents are a common factor in human-led accidents. Hence, pilots' precise fatigue detections could help increase the flight safety of airplanes. The article suggests a model to recognize fatigue by implementing the convolutional neural network (CNN) by implementing flight trainees' face attributions. First, the flight trainees' face attributions are derived by a method called the land-air call process when the flight simulation is run. Then, sixty-eight points of face attributions are detected by employing the Dlib package. Fatigue attribution points were derived based on the face attribution points to construct a model called EMF to detect face fatigue. Finally, the proposed PSO-CNN algorithm is implemented to learn and train the dataset, and the network algorithm achieves a recognition ratio of 93.9% on the test set, which can efficiently pinpoint the flight trainees' fatigue level. Also, the reliability of the proposed algorithm is validated by comparing two machine learning models.

Enabling AI-Generated Content for Gadolinium-Free Contrast-Enhanced Breast Magnetic Resonance Imaging.

BACKGROUND: There is increasing interest in utilizing AI-generated content for gadolinium-free contrast-enhanced breast MRI. PURPOSE: To develop a generative model for gadolinium-free contrast-enhanced breast MRI and evaluate the diagnostic utility of the generated scans. STUDY TYPE: Retrospective. POPULATION: Two hundred seventy-six women with 304 breast MRI examinations (49 ± 13 years, 243/61 for training/testing). FIELD STRENGTH/SEQUENCE: ZOOMit diffusion-weighted imaging (DWI), T1-weighted volumetric interpolated breath-hold examination (T1W VIBE), and axial T2 3D SPACE at 3.0 T. ASSESSMENT: A generative model was developed to generate contrast-enhanced scans using precontrast T1W VIBE and DWI images. The generated and real images were quantitatively compared using the structural similarity index (SSIM), mean absolute error (MAE), and Dice similarity coefficient. Three radiologists with 8, 5, and 5 years of experience independently rated the image quality and lesion visibility on AI-generated and real images within various subgroups using a five-point scale. Four breast radiologists, with 8, 8, 5, and 5 years of experience, independently and blindly interpreted four reading protocols: unenhanced MRI protocol alone and combined with AI-generated scans, abbreviated MRI protocol, and full-MRI protocol. STATISTICAL ANALYSIS: Results were assessed using t-tests and McNemar tests. Using pathology diagnosis as reference standard, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated for each reading protocol. A P value <0.05 was considered significant. RESULTS: In the test set, the generated images showed similarity to the real images (SSIM: 0.935 ± 0.047 [SD], MAE: 0.015 ± 0.012 [SD], and Dice coefficient: 0.726 ± 0.177 [SD]). No significant difference in lesion visibility was observed between real and AI-generated scans of the mass, non-mass, and benign lesion subgroups. Adding AI-generated scans to the unenhanced MRI protocol slightly improved breast cancer detection (sensitivity: 92.86% vs. 85.71%, NPV: 76.92% vs. 70.00%); achieved non-inferior diagnostic utility compared to the AB-MRI protocol and full-protocol (sensitivity: 92.86%, 95.24%; NPV: 75.00%, 81.82%). DATA CONCLUSION: AI-generated gadolinium-free contrast-enhanced breast MRI has potential to improve the sensitivity of unenhanced MRI in detecting breast cancer. EVIDENCE LEVEL: 4 TECHNICAL EFFICACY: Stage 3.

Constructing an interaction in plant polyphenol-modified carbon fiber with amylopectin-based waterborne polyurethane sizing agent via hydrogen bonding to improve the interfacial performance of carbon fiber/nylon 6 composites.

The adhesive strength between the sizing agent and carbon fiber (CF) plays a crucial role in improving the interfacial properties of composites, while such a vital aspect has been consistently disregarded. In this study, a hyperbranched waterborne polyurethane (HWPU) sizing agent was synthesized from biogenetically raw materials including gallic acid, l-Lysine diisocyanate and amylopectin. Concurrently, hydrogen-bonded cross-linked network structures were established utilizing a botanical polyphenol tannin as coupling agent to effectively connect CF with HWPU. This meticulous process yielded CF/nylon 6 composites with improved properties and their mechanical characteristics were systematically investigated. The findings showcased a noteworthy boost in flexural strength and interlaminar shear strength (ILSS), showing enhancements of 54.6 % and 61.4 %, respectively, surpassing those of untreated CF. Furthermore, the interfacial shear strength (IFSS) test indicated a remarkable 70.3 % improvement. This approach presents a highly promising concept aimed at developing sustainable green waterborne polyurethane sizing agent and improving the interfacial performance of CF composite materials.

A protocol for a multidisciplinary early intervention during chemotherapy to improve dietary management behavior in breast cancer patients: a two-arm, single-center randomized controlled trial.

BACKGROUND: Adverse reactions are prone to occur in the early stage of chemotherapy and can negatively affect the dietary intake and nutritional status of breast cancer (BC) patients. Consequently, they need to participate in health self-management and lifestyle promotion programs. Early multidisciplinary interventions aim to enhance dietary management behavior and quality of life in chemotherapy-treated BC patients. METHODS: This single-blinded, single-center, randomized controlled trial will include 88 females who have not yet started the early or middle stage of the chemotherapy cycle. A random number table will be used randomly assign females to the intervention group or usual group at a 1:1 ratio. The intervention elements are based on the theoretical guidance of the Integrated Theory of Health Behavior Change (ITHBC). A multidisciplinary team (MDT) comprising oncologists, dietitians, nurses, traditional Chinese medicine (TCM) practitioners, and psychologists will provide the intervention. Intervention sessions will be conducted once a week for 8 weeks, beginning in the early or middle stage of the chemotherapy cycle and continuing through admission and a home-based interval chemotherapy period. The intervention includes face-to-face discussions, online meetings, WeChat messaging, and telephone calls. The themes target adverse reactions, dietary information and habits, self-care self-efficacy, treatment self-regulation, dietary supplement and TCM use, social support, weight management, and outcome expectations. The primary outcome is dietary management behavior measured by the Dietary Management Behavior Questionnaire (DMBQ). Secondary outcomes are self-care self-efficacy assessed by the Strategies Used by People to Promote Health (SUPPH); quality of life measured by the Functional Assessment of Cancer Therapy-Breast (FACT-B); and body mass index (BMI) measured by an electronic meter. All participants will be assessed at baseline and immediately, 1 month, 3 months, 6 months, and 12 months after the intervention. DISCUSSION: Early dietary intervention is needed, as diet is one of the most common health self-management behaviors influenced by chemotherapy. Early multidisciplinary interventions may provide a foundation for dietary self-management and improve nutritional status in the survival period. TRIAL REGISTRATION: This intervention protocol was registered with the Chinese Clinical Trials Registry (ChiCTR2300076503, October 10, 2023).

Comparing clinical outcomes of patients with severe lower limb trauma undergoing orthoplastic and orthopedic surgeries: A long-term study protocol.

This long-term study protocol aims to compare the clinical outcomes of patients with severe lower limb trauma undergoing orthoplastic and orthopedic surgeries, focusing on their physical and psychological status. Patients with lower limb injuries and open fractures have been recruited since October 2019 and will be followed up until October 2024. The patients will be divided into two groups: (1) Orthoplastic group, where single-stage debridement, fixation, and soft tissue repair will be performed, and (2) Orthopedic group, where soft tissue repair will be done in a delayed-stage. The follow-up period will be one year, during which clinical data, limb function recovery, psychological scores, and health-related quality of life (HRQOL) will be evaluated to assess postoperative recovery and clinical outcomes. Additional clinical data, such as socio-demographic information, baseline features, Enneking score, Visual Analogue Scale (VAS) score, two-point discrimination score, and blood test parameters will also be collected. The 36-Item Short Form Health Survey (SF-36) will be used to evaluate HRQOL, while the Post-traumatic Stress Disorder Checklist (PCL) will assess the severity of self-reported post-traumatic stress disorder. The results of this study will provide valuable insights into prognostically relevant targets and contribute to improving the management and outcomes of patients with lower limb injuries and open fractures, who often face challenges related to limb disability and potential amputation postoperatively, significantly impacting their psychological and physical well-being.

A novel dual-signal output strategy for POCT of CEA based on a smartphone electrochemical aptasensing platform.

A smartphone-based electrochemical aptasensing platform was developed for the point-of-care testing (POCT) of carcinoembryonic antigen (CEA) based on the ferrocene (Fc) and PdPt@PCN-224 dual-signal labeled strategy. The prepared PdPt@PCN-224 nanocomposite showed a strong catalytic property for the reduction of H2O2. Phosphate group-labeled aptamer could capture PdPt@PCN-224 by Zr-O-P bonds to form PdPt@PCN-224-P-Apt. Therefore, a dual signal labeled probe was formed by the hybridization between Fc-DNA and PdPt@PCN-224-P-Apt. The presence of CEA forced PdPt@PCN-224-P-Apt to leave the electrode surface due to the specific affinity, leading to the decrease of the reduction current of H2O2. At the same time, the Fc-DNA strand changed to hairpin structure, which made Fc closer to the electrode and resulted in the increase of the oxidation current of Fc. Thus, CEA can be accurately determined through both signals: the decrease of H2O2 reduction current and the increase of Fc oxidation current, which could avoid the false positive signal. Under the optimal conditions, the prepared aptasensor exhibited a wide linear range from 1 pg·mL-1 to 100 ng·mL-1 and low detection limits of 0.98 pg·mL-1 and 0.27 pg·mL-1 with Fc and PdPt@PCN-224 as signal labels, respectively. The aptasensor developed in this study has successfully demonstrated its capability to detect CEA in real human serum samples. These findings suggest that the proposed sensing platform will hold great potential for clinical tumor diagnosis and monitoring.

Assessing attitudes towards biostatistics education among medical students: adaptation and preliminary evaluation of the Chinese version survey of attitudes towards statistics (SATS-36).

BACKGROUND: Despite the numerous advantages of mastering biostatistics, medical students generally perceive biostatistics as a difficult and challenging subject and even experience anxiety during the courses. Evidence for the correlation between students' academic achievements and their attitudes, indicating that attitudes at the beginning of the biostatistics course may affect cognitive competence at the end of the course and subsequently influence student academic performance. However, there are current disagreements regarding the measurement and evaluation of attitudes related to statistics. Thus, there is a need for standard instruments to assess them. This study was conducted to develop a Chinese version of the Survey of Attitudes Toward Statistics (SATS-36) in order to acquire a valid instrument to measure medical students' attitudes toward biostatistics under Chinese medical educational background. METHODS: The Chinese version SATS-36 was developed through translation and back-translation of the original scale, with subsequent revisions based on expert advice to ensure the most appropriate item content. The local adaption was performed with a cohort of 1709 Chinese-speaking medical undergraduate and graduate students enrolled in biostatistics courses. And then, the reliability, validity and discrimination of the questionnaires were evaluated through correlation coefficient calculation, factor analysis, parallel analysis and other methods. RESULTS: The Chinese version SATS-36 consisted of 36 items and loaded a five-factor structure by factor analysis, which offered an alternative similar but not equal to that original six-factor structure. The cumulative variance contribution rate was 62.20%, the Cronbach's α coefficient was 0.908, the Guttman split-half reliability coefficient was 0.905 and the test-retest reliability coefficient was 0.752. Discriminant analysis revealed small to large significant differences in the five attitude subscales. CONCLUSIONS: The Chinese version SATS-36 with good validity and reliability in this study can be used to evaluate the learning framework of Chinese medical students.

Translation, Cross-Cultural Adaptation and Validation of the Chinese Version of the High Activity Arthroplasty Score.

Background: The High Activity Arthroplasty Score (HAAS) is a validated score that assesses functional outcomes after lower limb arthroplasty, with fewer ceiling effects than other scores. The aim is to translate and cross-culturally adapt the HAAS into a Chinese version (HAAS-C) and to evaluate the psychometric properties of HAAS-C in patients after primary total knee arthroplasty (TKA). Methods: A total of 104 patients diagnosed with knee osteoarthritis who had undergone TKA at least 12 months prior were recruited. A forward and backward translation procedure was performed for developing a culturally acceptable HAAS-C. Internal consistency was assessed using Cronbach's α, and test-retest reliability was measured using the intraclass correlation coefficient (ICC) within a 10-day interval. Construct validity was assessed by examining the correlations between HAAS-C and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), EuroQoL Group's five-dimension questionnaire (EQ-5D-5L), and Oxford knee score (OKS). Results: HAAS-C demonstrated adequate Internal consistency reliability, as indicated by Cronbach's α coefficient of 0.75. Test-retest reliability yielded excellent results, with an ICC value of 0.98. Content validity indices were high, with a scale-level validity index of 0.9 and item-level validity indices greater than or equal to 0.8. HAAS-C showed a strong correlation with WOMAC (r = 0.69), a moderate correlation with EQ-5D-5L (r = 0.43), and OKS (r = 0.53) while exhibiting no floor or ceiling effects. Conclusion: The validated HAAS-C questionnaire is a valid instrument for assessing patients undergoing TKA in mainland China.

Distinguishable Magnetic Reporter Coordination with Buoyancy-Magnetism Separation for Immobilization-Free Dual-Target Electrochemical Immunosensing.

Simultaneous sensitive and precise determination of multibiomarkers is of great significance for improving detection efficiency, reducing diagnosis and treatment expenses, and elevating survival rates. However, the development of simple and portable biosensors for simultaneous determination of multiplexed targets in biological fluids still faces challenges. Herein, a unique and versatile immobilization-free dual-target electrochemical biosensing platform, which combines distinguishable magnetic signal reporters with buoyancy-magnetism separation, was designed and constructed for simultaneous detection of carcinoembryonic (CEA) and α-fetoprotein (AFP) in intricate biological fluids. To construct such distinguishable magnetic signal reporters with signal transduction, amplification, and output, secondary antibodies of CEA and AFP were respectively functionalized on methylene blue (MB) and 6-(ferrocenyl)hexanethiol (FeC) modified Fe3O4@Au magnetic nanocomposites. Meanwhile, a multifunctional flotation probe with dual target recognition, capture, and isolation capability was prepared by conjugating primary antibodies (Ab1-CEA, Ab1-AFP) to hollow buoyant microspheres. The target antigens of CEA and AFP can trigger a flotation-mediated sandwich-type immunoreaction and capture a certain amount of the distinguishable magnetic signal reporter, which enables the conversion of the target CEA and AFP quantities to the signal of the potential-resolved MB and FeC. Thus, the MB and FeC currents of magnetically adsorbed distinguishable magnetic reporters can be used to determine the CEA and AFP targets simultaneously and precisely. Accordingly, the proposed strategy exhibited a delightful linear response for CEA and AFP in the range of 100 fg·mL-1-100 ng·mL-1 with detection limits of 33.34 and 17.02 fg·mL-1 (S/N = 3), respectively. Meanwhile, no significant nonspecific adsorption and cross-talk were observed. The biosensing platform has shown satisfactory performance in the determination of real clinical samples. More importantly, the proposed approach can be conveniently extended to universal detection just by simply substituting biorecognition events. Thus, this work opens up a new promising perspective for dual and even multiple targets and offers promising potential applications in clinical diagnosis.

The intake of solid fat and cheese may be associated with a reduced risk of Helicobacter pylori infection status: a cross-sectional study based on NHANES 1999-2000.

BACKGROUND: Diet plays an important role in Helicobacter pylori (HP) infection, and our objective was to investigate potential connections between dietary patterns, specific food groups, and HP infection status in U.S. adults. METHODS: The data for this study was obtained from the NHANES (National Health and Nutrition Survey) database for the year 1999-2000. This cross-sectional study involved the selection of adults aged 20 years and older who had undergone dietary surveys and HP testing. Factor analysis was employed to identify dietary patterns, and logistic regression models were utilized to assess the association between these dietary patterns and specific food groups with HP infection status. RESULT: Based on the inclusion and exclusion criteria, our final analysis included 2,952 individuals. The median age of participants was 51.0 years, and 48.7% were male. In the study population, the overall prevalence of HP infection was 44.9%. Factor analysis revealed three distinct dietary patterns: High-fat and high-sugar pattern (including solid fats, refined grains, cheese, and added sugars); Vegetarian pattern (comprising fruits, juices, and whole grains); Healthy pattern (encompassing vegetables, nuts and seeds, and oils). Adjusted results showed that the high-fat and high-sugar pattern (OR = 0.689, 95% CI: 0.688-0.690), vegetarian pattern (OR = 0.802, 95% CI: 0.801-0.803), and healthy pattern (OR = 0.717, 95% CI: 0.716-0.718) were all linked to a lower likelihood of HP infection. Further analysis of the high-fat and high-sugar pattern revealed that solid fats (OR = 0.717, 95% CI: 0.716-0.718) and cheese (OR = 0.863, 95% CI: 0.862-0.864) were protective factors against HP infection, while refined grains (OR = 1.045, 95% CI: 1.044-1.046) and added sugars (OR = 1.014, 95% CI: 1.013-1.015) were identified as risk factors for HP infection. CONCLUSION: Both the Vegetarian pattern and the Healthy pattern are associated with a reduced risk of HP infection. Interestingly, the High-fat and High-sugar pattern, which is initially considered a risk factor for HP infection when the score is low, becomes a protective factor as the intake increases. Within this pattern, animal foods like solid fats and cheese play a protective role, while the consumption of refined grains and added sugars increases the likelihood of HP infection.

Analysis of risk factors and development of a nomogram-based prediction model for defective bony non-union.

Objective: To explore risk factors for defective non-union of bone and develop a nomogram-based prediction model for such an outcome. Methods: This retrospective study analysed the case data of patients with defective bony non-unions who were treated at the authors' hospital between January 2010 and December 2020. Patients were divided into the union and non-union groups according to their Radiographic Union Score for Tibia scores 1 year after surgery. Univariate analysis was performed to assess factors related to demographic characteristics, laboratory investigations, surgery, and trauma in both groups. Subsequently, statistically significant factors were included in the multivariate logistic regression analysis to identify independent risk factors. A nomogram-based prediction model was established using statistically significant variables in the multivariate analysis. The accuracy and stability of the model were evaluated using receiver operating characteristic (ROC) and calibration curves. The clinical applicability of the nomogram model was evaluated using decision curve analysis. Results: In total, 204 patients (171 male, 33 female; mean [±SD] age, 39.75 ± 13.00 years) were included. The mean body mass index was 22.95 ± 3.64 kg/m2. Among the included patients, 29 were smokers, 18 were alcohol drinkers, and 21 had a previous comorbid systemic disease (PCSD). Univariate analysis revealed that age, occupation, PCSD, smoking, drinking, interleukin-6, C-reactive protein (CRP), procalcitonin, alkaline phosphatase, glucose, and uric acid levels; blood calcium ion concentration; and bone defect size (BDS) were correlated with defective bone union (all P < 0.05). Multivariate logistic regression analysis revealed that PCSD, smoking, interleukin-6, CRP, and glucose levels; and BDS were associated with defective bone union (all P < 0.05), and the variables in the multivariate analysis were included in the nomogram-based prediction model. The value of the area under the ROC curve for the predictive model for bone defects was 0.95. Conclusion: PCSD, smoking, interleukin-6, CRP, and glucose levels; and BDS were independent risk factors for defective bony non-union, and the incidence of such non-union was predicted using the nomogram. These findings are important for clinical interventions and decision-making.

Early-life exercise induces immunometabolic epigenetic modification enhancing anti-inflammatory immunity in middle-aged male mice.

Exercise is usually regarded to have short-term beneficial effects on immune health. Here we show that early-life regular exercise exerts long-term beneficial effects on inflammatory immunity. Swimming training for 3 months in male mice starting from 1-month-old curbs cytokine response and mitigates sepsis when exposed to lipopolysaccharide challenge, even after an 11-month interval of detraining. Metabolomics analysis of serum and liver identifies pipecolic acid, a non-encoded amino acid, as a pivotal metabolite responding to early-life regular exercise. Importantly, pipecolic acid reduces inflammatory cytokines in bone marrow-derived macrophages and alleviates sepsis via inhibiting mTOR complex 1 signaling. Moreover, early-life exercise increases histone 3 lysine 4 trimethylation at the promoter of Crym in the liver, an enzyme responsible for catalyzing pipecolic acid production. Liver-specific knockdown of Crym in adult mice abolishes this early exercise-induced protective effects. Our findings demonstrate that early-life regular exercise enhances anti-inflammatory immunity during middle-aged phase in male mice via epigenetic immunometabolic modulation, in which hepatic pipecolic acid production has a pivotal function.

Dual-potential ratiometric electrochemiluminescence based on single emitter and single coreactant for the sensitive detection of carcinoembryonic antigen.

Dual-potential ratiometric electrochemiluminescence (ECL) is in favor of resistance to environmental interference. However, two kinds of emitters or coreactants, and a wide scan potential range (>2 V) are mandatory. This work developed a new dual-potential ratiometric ECL sensor for detection of carcinoembryonic antigen (CEA) using single emitter (luminol) and single coreactant (H2O2) with a mild potential range from -0.1 to 0.6 V. Luminol could produce a strong cathodic ECL (Ec) induced by hydroxyl radicals (HO‧) from the reduction of H2O2, and a relatively weak anodic ECL (Ea). After the ferrocene modified CEA aptamer (Apt-Fc) was attached, Fc could promote Ea by catalyzing the oxidation of H2O2, and reduce Ec by consuming HO‧. With the cycling amplification of the exonuclease I, CEA could substantially reduce the amount of Apt-Fc, resulting in the decrease of Ea and the rise of Ec. So, the ratio of Ec to Ea (Ec/Ea) was used as the detection signal, realizing the sensitive determination of CEA from 0.1 pg mL-1 to 10 ng mL-1 with a LOD of 41.85 fg mL-1 (S/N = 3). The developed sensor demonstrated excellent specificity, stability and reproducibility, with satisfactory results in practical detection.

Performance and micro-pacing in sprint cross-country skiing: A comparison of individual time-trial and head-to-head race formats.

This study compared performance strategies and sub-technique selection in cross-country skate skiing sprint races, specifically individual time-trial (ITT) and head-to-head (H2H) formats. Fourteen male cross-country skiers from the Chinese national team participated in the FIS-sanctioned sprint race day. GNSS and heart rate sensors recorded positioning, skiing speeds, heart rate, sub-technique usage, and skiing kinematics. Statistical parametric mapping (SPM) was used to determine the course positions (clusters) where instantaneous skiing speed was significantly associated with section time. One-way analyses of variance were used to examine differences between the ITT and H2H. H2H race speeds were 2.4 ± 0.2% faster than the ITT race (p < 0.05).Variations in sub-technique and skiing kinematics were observed between race formats, indicating different strategies and tactics employed by athletes. SPM identified specific clusters (primarily uphill) where the fastest athlete gained significant time over the slowest. The greatest time gains were associated with higher G3 sub-technique usage and longer G3 cycle length on steep uphill terrain (9-13% gradients). Integrating SPM analyses and sub-technique assessments can help optimise performance and tactics in sprint races. This study enhances our understanding of cross-country skiing dynamics and performance variations among elite competitors.

Differential contributions of G protein- or arrestin subtype-mediated signalling underlie urocortin 3-induced somatostatin secretion in pancreatic δ cells.

BACKGROUND AND PURPOSE: Pancreatic islets are modulated by cross-talk among different cell types and paracrine signalling plays important roles in maintaining glucose homeostasis. Urocortin 3 (UCN3) secreted by pancreatic ß cells activates the CRF2 receptor (CRF2R) and downstream pathways mediated by different G protein or arrestin subtypes in δ cells to cause somatostatin (SST) secretion, and constitutes an important feedback circuit for glucose homeostasis. EXPERIMENTAL APPROACH: Here, we used Arrb1-/-, Arrb2-/-, Gsfl/fl and Gqfl/fl knockout mice, the G11-shRNA-GFPfl/fl lentivirus, as well as functional assays and pharmacological characterization to study how the coupling of Gs, G11 and ß-arrestin1 to CRF2R contributed to UCN3-induced SST secretion in pancreatic δ cells. KEY RESULTS: Our study showed that CRF2R coupled to a panel of G protein and arrestin subtypes in response to UCN3 engagement. While RyR3 phosphorylation by PKA at the S156, S2706 and S4697 sites may underlie the Gs-mediated UCN3- CRF2R axis for SST secretion, the interaction of SYT1 with ß-arrestin1 is also essential for efficient SST secretion downstream of CRF2R. The specific expression of the transcription factor Stat6 may contribute to G11 expression in pancreatic δ cells. Furthermore, we found that different UCN3 concentrations may have distinct effects on glucose homeostasis, and these effects may depend on different CRF2R downstream effectors. CONCLUSIONS AND IMPLICATIONS: Collectively, our results provide a landscape view of signalling mediated by different G protein or arrestin subtypes downstream of paracrine UCN3- CRF2R signalling in pancreatic ß-δ-cell circuits, which may facilitate the understanding of fine-tuned glucose homeostasis networks.

Empagliflozin in children with glycogen storage disease-associated inflammatory bowel disease: a prospective, single-arm, open-label clinical trial.

Glycogen storage disease type Ib (GSD-Ib) is a rare inborn error of glycogen metabolism caused by mutations in SLC37A4. Patients with GSD-Ib are at high risk of developing inflammatory bowel disease (IBD). We evaluated the efficacy of empagliflozin, a renal sodium‒glucose cotransporter protein 2 (SGLT2) inhibitor, on colonic mucosal healing in patients with GSD-associated IBD. A prospective, single-arm, open-label clinical trial enrolled eight patients with GSD-associated IBD from Guangdong Provincial People's Hospital in China from July 1, 2022 through December 31, 2023. Eight patients were enrolled with a mean age of 10.34 ± 2.61 years. Four male and four female. The endoscopic features included deep and large circular ulcers, inflammatory hyperplasia, obstruction and stenosis. The SES-CD score significantly decreased at week 48 compared with before empagliflozin. Six patients completed 48 weeks of empagliflozin therapy and endoscopy showed significant improvement or healing of mucosal ulcers, inflammatory hyperplasia, stenosis, and obstruction. One patient had severe sweating that required rehydration and developed a urinary tract infection. No serious or life-threatening adverse events. This study suggested that empagliflozin may promote colonic mucosal healing and reduce hyperplasia, stenosis, and obstruction in children with GSD-associated IBD.

Statins as a risk factor for diabetic retinopathy: a Mendelian randomization and cross-sectional observational study.

BACKGROUND: Diabetic retinopathy (DR) is the foremost cause of vision loss among the global working-age population, and statins are among the most frequently prescribed drugs for lipid management in patients with DR. The exact relationship between statins and DR has not been determined. This study sought to validate the causal association between statins usage and diabetic retinopathy. METHODS: The summary-data-based Mendelian randomization (SMR) method and inverse-variance-weighted Mendelian randomization (IVW-MR) were used to identify the causal relationship between statins and DR via the use of expression quantitative trait loci (eQTL) data for 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) (31,684 blood samples), low density lipoprotein cholesterol-related GWAS data (sample size: 440,546), and DR-related GWAS data (14,584 cases and 176,010 controls). Additionally, a cross-sectional observational study based on the data from the National Health and Nutrition Examination Survey (NHANES) was conducted to supplement the association between DR and statins (sample size: 106,911). The odds ratios (ORs) with corresponding 95% confidence intervals (CIs) was employed to evaluate the results. RESULTS: Based on the results of the MR analysis, HMGCR inhibitors were causally connected with a noticeably greater incidence of DR (IVW: OR = 0.54, 95% CI [0.42, 0.69], p = 0.000002; SMR: OR = 0.66, 95% CI [0.52, 0.84], p = 0.00073). Subgroup analysis revealed that the results were not affected by the severity of DR. The sensitivity analysis revealed the stability and reliability of the MR analysis results. The results from the cross-sectional study based on NHANES also support the association between not taking statins and a decreased risk of DR (OR = 0.54, 95% CI [0.37, 0.79], p = 0.001). CONCLUSIONS: This study revealed that a significant increase in DR risk was causally related to statins use, providing novel insights into the role of statins in DR. However, further investigations are needed to verify these findings.

Ultrasound-guided fine needle aspiration thyroglobulin in the diagnosis of lymph node metastasis of differentiated papillary thyroid carcinoma and its influencing factors.

Background: Ultrasound-guided fine needle aspiration thyroglobulin (FNA-Tg) is recommended for the diagnosis of lymph node metastasis (LNM) in differentiated thyroid cancer (DTC), but its optimal cutoff value remains controversial, and the effect of potential influencing factors on FNA-Tg levels is unclear. Method: In this study, a retrospective analysis was conducted on 281 patients diagnosed with DTC, encompassing 333 lymph nodes. We analyze the optimal cutoff value and diagnostic efficacy of FNA-Tg, while also evaluating the potential influence of various factors on FNA-Tg. Results: For FNA-Tg, the optimal cutoff value was 16.1 ng/mL (area under the curve (AUC)= 0.942). The optimal cutoff value for FNA-Tg/sTg was 1.42 (AUC = 0.933). The AUC for FNA combined with FNA-Tg yielded the highest value compared to other combined diagnostic methods (AUC = 0.955). It has been found that serum thyroglobulin (sTg) is positively correlated with FNA-Tg (Rs = 0.318), while serum thyroglobulin antibodies (sTgAb) is negatively correlated with FNA-Tg (Rs = -0.147). In cases where the TNM stage indicated N1b, the presence of large or high volume lymph node metastasis(HVLNM), lymph node lateralization/suspicion (L/S) ratio ≤ 2, ultrasound findings indicating lymph node liquefaction, calcification, and increased blood flow, patients with coexisting Hashimoto's thyroiditis (HT), a tumor size ≥10 mm, and postoperative pathology confirming invasion of the thyroid capsule, higher levels of FNA-Tg were observed. However, the subgroup classification of DTC and the presence or absence of thyroid tissue did not demonstrate any significant impact on the levels of FNA-Tg. Conclusion: The findings of this study indicate that the utilization of FNA in conjunction with FNA-Tg is a crucial approach for detecting LNM in DTC. TNM stage indicated N1b, the presence of HVLNM, the presence of HT, lymph node L/S ratio, liquefaction, calcification, tumor diameter, sTg and sTgAb are factors that can impact FNA-Tg levels.In the context of clinical application, it is imperative to individualize the use of FNA-Tg.

Development and validation of serological dynamic risk score to predict outcome in gastric cancer with adjuvant chemotherapy: a multicentre, longitudinal, cohort study.

Background: Baseline serological biomarkers have the potential to predict the benefits of adjuvant chemotherapy in patients with gastric cancer. However, the fluctuating nature of postoperative recurrence risk makes precise treatment challenging. We aimed to develop a risk score in real-time predicting outcomes for postoperative GC patients using blood chemistry tests. Materials and methods: This was a retrospective, multicentre, longitudinal cohort study from three cancer centres in China, with a total of 2737 GC patients in the pTNM stage Ib to III. Among them, 1651 patients with at least two serological records were assigned to the training cohort. Model validation was carried out using separate testing data with area under curve (AUC). The least absolute shrinkage and selection operator (LASSO) and random forest-recursive feature elimination (RF-RFE) algorithm were used to select the parameters. Results: The Cox regression model derived six risk factors to construct a composite score (low-risk: 0-2 score; high risk: 3-6 score), including CEA, CA125, CA199, haemoglobin, albumin, and neutrophil to lymphocyte ratio. The risk score accurately predicted mortality in 1000-time bootstrap (AUROCs:0.658; 95% CI: 0.645, 0.670), with the highest AUROC (0.767; 95% CI: 0.743, 0.791) after 1 year since the gastrectomy. In validation dataset, the risk score had an AUROC of 0.586 (95% CI 0.544, 0.628). Furthermore, patients with high risk at 1 month derived significant clinical benefits from adjuvant chemotherapy (P for interaction <0.0001). Compared with the low-low-low risk group, the low-low-high risk group of the long-term state chain (risk state at baseline, 6 months, 1 year) had the worse OS (HR, 6.91; 95%CI: 4.27, 11.19) and DFS (HR, 7.27; 95%CI: 4.55, 11.63). Conclusion: The dynamic risk score is an accurate and user-friendly serological risk assessment tool for predicting outcomes and assisting clinical decisions after gastrectomy.

Association of survival with adjuvant chemotherapy in patients with stage IB gastric cancer: a multicentre, observational, cohort study.

Background: Recurrence following radical resection in patients with stage IB gastric cancer (GC) is not uncommon. However, whether postoperative adjuvant chemotherapy could reduce the risk of recurrence in stage IB GC remains contentious. Methods: We collected data on 2110 consecutive patients with pathologic stage IB (T1N1M0 or T2N0M0) GC who were admitted to 8 hospitals in China from 2009 to 2018. The survival of patients who received adjuvant chemotherapy was compared with that of postoperative observation patients using propensity score matching (PSM). Two survival prediction models were constructed to estimate the predicted net survival gain attributable to adjuvant chemotherapy. Findings: Of the 2110 patients, 1344 received adjuvant chemotherapy and 766 received postoperative observation. Following the 1-to-1 matching, PSM yielded 637 matched pairs. Among matched pairs, adjuvant chemotherapy was not associated with improved survival compared with postoperative observation (OS: hazard ratio [HR], 0.72; 95% CI, 0.52-1.00; DFS: HR, 0.91; 95% CI, 0.64-1.29). Interestingly, in the subgroup analysis, reduced mortality after adjuvant chemotherapy was observed in the subgroups with elevated serum CA19-9 (HR, 0.22; 95% CI, 0.08-0.57; P = 0.001 for multiplicative interaction), positive lymphovascular invasion (HR, 0.32; 95% CI, 0.17-0.62; P < 0.001 for multiplicative interaction), or positive lymph nodes (HR, 0.17; 95% CI, 0.07-0.38; P < 0.001 for multiplicative interaction). The survival prediction models mainly based on variables associated with chemotherapy benefits in the subgroup analysis demonstrated good calibration and discrimination, with relatively high C-indexes. The C-indexes for OS were 0.74 for patients treated with adjuvant chemotherapy and 0.70 for patients treated with postoperative observation. Two nomograms were built from the models that can calculate individualized estimates of expected net survival gain attributable to adjuvant chemotherapy. Interpretation: In this cohort study, pathologic stage IB alone was not associated with survival benefits from adjuvant chemotherapy compared with postoperative observation in patients with early-stage GC. High-risk clinicopathologic features should be considered simultaneously when evaluating patients with stage IB GC for adjuvant chemotherapy. Funding: National Natural Science Foundation of China; the National Key R&D Program of China.