A National Study Exploring the Association between Fasting Duration and Mortality among the Elderly.

(1) Background: The benefits of weight management are widely recognized, and prolonged fasting duration has become a common method for weight control. The suitability of time-restricted eating (TRE) for elderly individuals remains controversial. This study aims to examine the correlation between fasting duration and mortality within a nationally representative cohort of elderly individuals in the United States. (2) Methods: Data were extracted from a prospective cohort study conducted as part of the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2018. Participants aged over 60 with complete data on dietary intake and mortality follow-up information were included. Fasting duration was assessed using two 24 h dietary recalls. All the participants were categorized into fasting duration quartiles. Mortality outcomes were ascertained through the National Death Index. Cox proportional hazards regression models were utilized to analyze the association between fasting duration and mortality. (3) Results: The final analysis included 10,561 elderly participants (mean age 69.89, 45.58% male). Individuals with the longest fasting duration (over 12.38 h) had a significantly higher risk of CVD mortality compared to those with a normal fasting duration (10.58-12.38 h). This elevated CVD mortality risk was particularly pronounced in males, individuals over 70 years old, and non-shift workers. A non-linear relationship was observed between fasting duration and all-cause mortality and CVD mortality. (4) Conclusions: Prolonged fasting periods are associated with a higher risk of CVD mortality in the elderly population, although this correlation is not evident for all-cause, cancer, or other-cause mortality. A fasting duration of 11.49 h correlates with the lowest mortality risk. Additionally, elderly individuals with the shortest fasting duration exhibit elevated hazard ratios for both cancer and other-cause mortality. As with any health intervention, clinicians should exercise caution when recommending a fasting regimen that is personalized to the health condition of people who are older. Further research through randomized controlled trials should be conducted to comprehensively investigate the impact of TRE on mortality.

Radiomics-Based Quality Control System for Automatic Cardiac Segmentation: A Feasibility Study.

PURPOSE: In the past decade, there has been a rapid increase in the development of automatic cardiac segmentation methods. However, the automatic quality control (QC) of these segmentation methods has received less attention. This study aims to address this gap by developing an automatic pipeline that incorporates DL-based cardiac segmentation and radiomics-based quality control. METHODS: In the DL-based localization and segmentation part, the entire heart was first located and cropped. Then, the cropped images were further utilized for the segmentation of the right ventricle cavity (RVC), myocardium (MYO), and left ventricle cavity (LVC). As for the radiomics-based QC part, a training radiomics dataset was created with segmentation tasks of various quality. This dataset was used for feature extraction, selection, and QC model development. The model performance was then evaluated using both internal and external testing datasets. RESULTS: In the internal testing dataset, the segmentation model demonstrated a great performance with a dice similarity coefficient (DSC) of 0.954 for whole heart segmentations. Images were then appropriately cropped to 160 × 160 pixels. The models also performed well for cardiac substructure segmentations. The DSC values were 0.863, 0.872, and 0.940 for RVC, MYO, and LVC for 2D masks and 0.928, 0.886, and 0.962 for RVC, MYO, and LVC for 3D masks with an attention-UNet. After feature selection with the radiomics dataset, we developed a series of models to predict the automatic segmentation quality and its DSC value for the RVC, MYO, and LVC structures. The mean absolute values for our best prediction models were 0.060, 0.032, and 0.021 for 2D segmentations and 0.027, 0.017, and 0.011 for 3D segmentations, respectively. Additionally, the radiomics-based classification models demonstrated a high negative detection rate of >0.85 in all 2D groups. In the external dataset, models showed similar results. CONCLUSIONS: We developed a pipeline including cardiac substructure segmentation and QC at both the slice (2D) and subject (3D) levels. Our results demonstrate that the radiomics method possesses great potential for the automatic QC of cardiac segmentation.

Construction of spidroin coacervate microdroplets and regulation of their morphology.

In recent years, developing artificial cells of higher complexity has emerged as being key to simulating advanced life behaviors, among which coacervate microdroplets are a promising kind of model artificial cell. Constructing simple coacervate systems in vitro which can subsequently achieve specific responses to environmental stimuli to form coacervate microdroplet communities are fundamental for studying the interactions between liquid-liquid phase separated molecules and the way such interactions determine material properties, composition and phase behavior. Herein, we propose a membrane-free artificial cell based on recombinant spidroin, NT2RepCT, which utilizes the complex structure of spidroin to provide coacervate microdroplets with a unique population morphology in response to environmental stimuli. By changing the environmental conditions such as protein concentration, pH and temperature, the coacervate microdroplets of single-type, regular adhesion-type and irregular adhesion-type were statistically generalized, and it is highlighted that the adhesion-type of coacervate microdroplets depended on the α-helical percentage, complex folding degree of spidroin and internally hydrophobic environment of the coacervate, while it was inversely proportional to the surface hydrophobic environment. Much more interesting, regulation of the non-enzymatic polymerization reaction of oligonucleotides was successfully achieved by adjusting the population morphology of coacervate microdroplets.

Papillary-Muscle-Derived Radiomic Features for Hypertrophic Cardiomyopathy versus Hypertensive Heart Disease Classification.

Purpose: This study aimed to assess the value of radiomic features derived from the myocardium (MYO) and papillary muscle (PM) for left ventricular hypertrophy (LVH) detection and hypertrophic cardiomyopathy (HCM) versus hypertensive heart disease (HHD) differentiation. Methods: There were 345 subjects who underwent cardiovascular magnetic resonance (CMR) examinations that were analyzed. After quality control and manual segmentation, the 3D radiomic features were extracted from the MYO and PM. The data were randomly split into training (70%) and testing (30%) datasets. Feature selection was performed on the training dataset. Five machine learning models were evaluated using the MYO, PM, and MYO+PM features in the detection and differentiation tasks. The optimal differentiation model was further evaluated using CMR parameters and combined features. Results: Six features were selected for the MYO, PM, and MYO+PM groups. The support vector machine models performed best in both the detection and differentiation tasks. For LVH detection, the highest area under the curve (AUC) was 0.966 in the MYO group. For HCM vs. HHD differentiation, the best AUC was 0.935 in the MYO+PM group. Comparing the radiomics models to the CMR parameter models for the differentiation tasks, the radiomics models achieved significantly improved the performance (p = 0.002). Conclusions: The radiomics model with the MYO+PM features showed similar performance to the models developed from the MYO features in the detection task, but outperformed the models developed from the MYO or PM features in the differentiation task. In addition, the radiomic models performed better than the CMR parameters' models.

Fast Detection of Heavy Metal Content in Fritillaria thunbergii by Laser-Induced Breakdown Spectroscopy with PSO-BP and SSA-BP Analysis.

Fast detection of heavy metals is important to ensure the quality and safety of herbal medicines. In this study, laser-induced breakdown spectroscopy (LIBS) was applied to detect the heavy metal content (Cd, Cu, and Pb) in Fritillaria thunbergii. Quantitative prediction models were established using a back-propagation neural network (BPNN) optimized using the particle swarm optimization (PSO) algorithm and sparrow search algorithm (SSA), called PSO-BP and SSA-BP, respectively. The results revealed that the BPNN models optimized by PSO and SSA had better accuracy than the BPNN model without optimization. The performance evaluation metrics of the PSO-BP and SSA-BP models were similar. However, the SSA-BP model had two advantages: it was faster and had higher prediction accuracy at low concentrations. For the three heavy metals Cd, Cu and Pb, the prediction correlation coefficient (Rp2) values for the SSA-BP model were 0.972, 0.991 and 0.956; the prediction root mean square error (RMSEP) values were 5.553, 7.810 and 12.906 mg/kg; and the prediction relative percent deviation (RPD) values were 6.04, 10.34 and 4.94, respectively. Therefore, LIBS could be considered a constructive tool for the quantification of Cd, Cu and Pb contents in Fritillaria thunbergii.

Myocardial Tissue-Level Characteristics of Adults With Metabolically Healthy Obesity.

BACKGROUND: It remains unclear whether adults with metabolically healthy obesity (MHO) have altered myocardial tissue-level characteristics. OBJECTIVES: This study aims to assess the subclinical myocardial tissue-level characteristics of adults with MHO. METHODS: The EARLY-MYO-OBESITY (EARLY Assessment of MYOcardial Tissue Characteristics in OBESITY; NCT05277779) registry was a prospective, 3-center, cardiac imaging study of obese nondiabetic individuals without cardiac symptoms who underwent cardiac magnetic resonance. Myocardial tissue-level characteristics, including extracellular volume fraction (ECV) and native T2 values, were measured as indicators of myocardial fibrosis and edema. Global longitudinal peak systolic strain and early diastolic longitudinal strain rate were assessed by tissue tracking analysis to detect subclinical systolic and diastolic dysfunction. RESULTS: A total of 120 participants were included: MHO (n = 32; mean age, 38 years; 41% men), metabolically healthy controls without obesity (n = 32; mean age: 37 years; 41% men), and metabolically unhealthy obesity (MUHO) (n = 56; mean age: 37 years; 55% men). The MHO group had higher ECV and native T2 values than healthy controls (both P < 0.001); furthermore, the ECV was higher in the MUHO group than in the MHO group (P = 0.002). The prevalence of myocardial fibrosis was 44% (14 of 32) in the MHO group and 71% (40 of 56) in the MUHO group. Although there was no intergroup difference in left ventricular ejection fraction, the MHO group had reduced global longitudinal peak systolic and early diastolic longitudinal strain rates, indicating subclinical systolic and diastolic dysfunction. Multivariate regression analysis identified increased body mass index to be an independent risk factor for myocardial fibrosis (OR: 6.28 [95% CI: 3.17-12.47]; P < 0.001). CONCLUSIONS: This study provides the first evidence of subclinical myocardial tissue-level remodeling in adults with obesity, regardless of metabolic health. Early identification of cardiac impairment may facilitate preventive strategies against heart failure in the MHO population. (EARLY Assessment of MYOcardial Tissue Characteristics in OBESITY [EARLY-MYO-OBESITY]; NCT05277779).

Protocol for pyrotinib cardiac safety in patients with HER2-positive early or locally advanced breast cancer-The EARLY-MYO-BC study.

Background and aim: Cardiotoxicity has become the most common cause of non-cancer death among breast cancer patients. Pyrotinib, a tyrosine kinase inhibitor targeting HER2, has been successfully used to treat breast cancer patients but has also resulted in less well-understood cardiotoxicity. This prospective, controlled, open-label, observational trial was designed to characterize pyrotinib's cardiac impacts in the neoadjuvant setting for patients with HER2-positive early or locally advanced breast cancer. Patients and methods: The EARLY-MYO-BC study will prospectively enroll HER2-positive breast cancer patients who are scheduled to receive four cycles of neoadjuvant therapy with pyrotinib or pertuzumab added to trastuzumab before radical breast cancer surgery. Patients will undergo comprehensive cardiac assessment before and after neoadjuvant therapy, including laboratory measures, electrocardiography, transthoracic echocardiography, cardiopulmonary exercise testing (CPET), and cardiac magnetic resonance (CMR). To test the non-inferiority of pyrotinib plus trastuzumab therapy to pertuzumab plus trastuzumab therapy in terms of cardiac safety, the primary endpoint will be assessed by the relative change in global longitudinal strain from baseline to completion of neoadjuvant therapy by echocardiography. The secondary endpoints include myocardial diffuse fibrosis (by T1-derived extracellular volume), myocardial edema (by T2 mapping), cardiac volumetric assessment by CMR, diastolic function (by left ventricular volume, left atrial volume, E/A, and E/E') by echocardiography, and exercise capacity by CPET. Discussion: This study will comprehensively assess the impacts of pyrotinib on myocardial structural, function, and tissue characteristics, and, furthermore, will determine whether pyrotinib plus trastuzumab is a reasonable dual HER2 blockade regimen with regard to cardiac safety. Results may provide information in selecting an appropriate anti-HER2 treatment for HER2-positive breast cancer. Clinical trial registration: https://clinicaltrials.gov/, identifier NCT04510532.

Biochemical and biophysical properties of an unreported T96R mutation causing transthyretin cardiac amyloidosis.

OBJECTIVES: We presented an unreported T96R mutation induced transthyretin cardiac amyloidosis (ATTR). The biochemical and biophysical properties were explored to support its pathogenicity. BACKGROUND: Understanding the biochemical and biophysical nature of genetically mutated transthyretin (TTR) proteins is key to provide precise medical cares for ATTR patients. RESULTS: Genetic testing showed heterozygosity for the T96R pathogenic variant c.347C > G (ATTR p.T116R) after myocardial biopsy confirmed amyloid deposition. Biochemical characterizations revealed slight perturbation of its thermodynamic stability (Cm=3.7 M for T96R, 3.4 M for WT and 2.3 M for L55P (commonly studied TTR mutant)) and kinetic stability (t1/2=39.8 h for T96R, 42 h for WT and 4.4 h in L55P). Crosslinking experiment demonstrated heterozygous subunit exchange between wild-type and TTR T96R protein destabilized the tetramer. Inhibitory effect of tafamidis and diflunisal on TTR T96R fibril formation was slightly less effective compared to WT and L55P. CONCLUSIONS: A novel T96R mutation was identified for TTR protein. Biochemical and biophysical analyses revealed slightly destabilized kinetic stability. T96R mutation destabilized heterozygous protein but not proteolytic degradation, explaining its pathogenicity. Inhibitory effect of small molecule drugs on T96R mutation was different, suggesting personalized treatment may be required.

Prevalence and characteristics of somatic symptom disorder in the elderly in a community-based population: a large-scale cross-sectional study in China.

INTRODUCTION AND OBJECTIVES: The aging population is expected to reach 2 billion by 2050, but the impact of somatic symptom disorder (SSD) on the elderly has been insufficiently addressed. We aimed to clarify the prevalence of SSD in China and to identify physical and psychological differences between the elderly and non-elderly. METHODS: In this prospective multi-center study, 9020 participants aged (2206 non-elderly adults and 6814 elderly adults) from 105 communities of Shanghai were included (Assessment of Somatic Symptom in Chinese Community-Dwelling People, clinical trial number NCT04815863, registered on 06/12/2020). The Somatic Symptom Scale-China (SSS-CN) questionnaire was used to measure SSD. Depressive and anxiety disorders were assessed by the Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder-7 (GAD-7), respectively. RESULTS: The prevalence of SSD in the elderly was higher than that in the non-elderly (63.2% vs. 45.3%). The elderly suffered more severe SSD (20.4% moderate and severe in elderly vs. 12.0% in non-elderly) and are 1.560 times more likely to have the disorder (95%CI: 1.399-1.739; p < .001) than the non-elderly. Comorbidity of depressive or anxiety disorders was 3.7 times higher than would be expected in the general population. Additionally, the results of adjusted multivariate analyses identified older age, female sex, and comorbid physical diseases as predictive risk factors of SSD in the elderly group. CONCLUSIONS: With higher prevalence of common physical problems (including hypertension, diabetes mellitus and cardio/cerebrovascular disease), the elderly in Shanghai are more vulnerable to have SSD and are more likely to suffer from comorbid depressive and anxiety disorders. SSD screening should be given more attention in the elderly, especially among older females with several comorbid physical diseases.

A hitchhiking approach to reconstruct the finger pulp and the subsequent 1st toe hemi-pulp donor site defect.

BACKGROUND: The free 1st toe hemi-pulp transfer for finger pulp reconstruction was acknowledged as the optimal one. However, the treatment of the 1st toe donor defect, owning to the impossibility of primary closure, was frequently oversimplified. This study presented a "hitchhiking" approach to resurface finger pulp and the subsequent 1st toe donor site defect in a one-stage procedure. METHODS: From 2014 to 2019, finger pulp amputations (13 digits in 12 patients) were reconstructed with free 1st toe pulp flaps, and the donor site was resurfaced by the 2nd toe pedicled flap with the 2nd toe's primary closure. Therapeutic evaluation of repaired fingers and toes was based on cold intolerance, two-point discrimination (2PD), and gait disturbance. RESULTS: All finger and toe pulp flaps survived uneventfully. The average size of free 1st toe and pedicled 2nd toe flap was 3.1 cm × 2.0 cm (3.5 cm × 1.4 cm to 4.2 cm × 2.5 cm) and 3.0 cm × 1.1 cm (2.0 cm × 0.9 cm to 3.8 cm × 1.5 cm), respectively. The regained average static 2PD on the finger and 1st toe pulps was 6 mm (ranged 5-10 mm) and 4 mm (ranged 2-6 mm), respectively. All reconstructed 1st toe pulps were qualified for normal gait. One patient complained the mild cold intolerance, and hammer-toe deformities were involved in two cases. CONCLUSION: To fulfill donor site care and cost-effective rule, the toe-to-finger pulp reconstruction can't underestimate the morbidity on 1st toe donor site due to inappropriate intervention. Equally importantly, the hitchhiking pedicled 2nd toe flap should be recruited in the reconstructive scheme.

Construction of coacervates in proteinosome hybrid microcompartments with enhanced cascade enzymatic reactions.

A spatially segregative coacervate-in-proteinosome hybrid microcompartment is constructed by co-encapsulation of either positively or negatively charged polyelectrolytes within proteinosomes with enhanced cascade enzymatic reactions, providing a step towards the development of artificial eukaryotic cell like microcompartments.