Constructing a Prognostic Model of Uterine Corpus Endometrial Carcinoma and Predicting Drug-Sensitivity Responses Using Programmed Cell Death-Related Pathways.

Background: Uterine Corpus Endometrial Carcinoma (UCEC) is the most common type of cancer that develops in the uterus, specifically originating from the endometrium, the inner lining of the uterus. Programmed cell death (PCD) is a highly regulated process that eliminates damaged, aged, or unwanted cells in the body. Dysregulation of PCD pathways can contribute to the formation and progression of various cancers, including UCEC. Methods: Fourteen PCD pathways (autophagy-dependent cell death, alkaliptosis, apoptosis, cuproptosis, entotic cell death, ferroptosis, immunogenic cell death, lysosome-dependent cell death, MPT-driven necrosis, necroptosis, netotic cell death, oxeiptosis, parthanatos, and pyroptosis) were involved in building a prognostic signature. The model was trained and tested using data from the TCGA-UCEC and validated with the GSE119041 dataset. Results: A 12-gene PCD signature (DRAM1, ELAPOR1, MAPT, TRIM58, UCHL1, CDKN2A, CYFIP2, AKT2, LINC00618, TTPA, TRIM46, and NOS2) was established and validated in an independent dataset. UCEC patients with a high PCD score (PCDS) exhibited worse prognosis. Furthermore, PCDS was found to be associated with immune related cells and key tumor microenvironment components through multiple methods. It was observed that UCEC patients with a high PCD score may not benefit from immunotherapy, but some chemo drugs like Bortezomib may be useful. Conclusion: In conclusion, a novel PCD model was established by comprehensively analyzing diverse cell death patterns. This model accurately predicts the clinical prognosis and drug sensitivity of UCEC. The findings suggest that the PCD signature can serve as a valuable tool in assessing prognosis and guiding treatment decisions for UCEC patients.

Optimization of Mg-Al Layered Double Hydroxide Film Preparation and Corrosion Resistance Study on AZ91D Mg Alloy by Multivariate Polynomial Regression Fitting.

Layered double hydroxide (LDH) films have received extensive attention for their unique physical barrier function and ion exchange properties, which make them promising candidates for corrosion protection of magnesium alloys. In this paper, we used the multiple polynomial regression fitting method to establish a regression equation for the electrochemical corrosion resistance with the reaction temperature (T), pH, and reaction time (t) of the Mg-Al LDH film on the AZ91D magnesium alloy. The goodness of fit, confidence, and residual analyses confirmed the high accuracy of the model equation. According to the calculation using the fmincon function, the best corrosion resistance of the prepared samples could be achieved when the parameters are T = 135 °C, pH = 12.0, and t = 15 h. Then, the experimental results showed that the corrosion current density (Icorr) of the obtained LDH film under the above conditions could be 1.07 × 10-7 A/cm2, approximately 3 orders of magnitude lower than the magnesium alloy substrate, after immersion in a 3.5 wt % NaCl solution for 180 h, the surface structure of the LDH film did not change significantly, and the Icorr was still 2 orders of magnitude higher than that of the magnesium alloy substrate. Hence, a synergistic effect equation for the reaction temperature, pH, and reaction time on the corrosion resistance of the LDH film on a magnesium alloy surface prepared by the hydrothermal method was obtained. Moreover, using this equation, we obtained an LDH film with good corrosion resistance and durability, providing theoretical guidance for optimizing the process of preparing the LDH film by the hydrothermal method in practical applications.

Haploid identification in maize.

Doubled haploid (DH) line production through in vivo maternal haploid induction is widely adopted in maize breeding programs. The established protocol for DH production includes four steps namely in vivo maternal haploid induction, haploid identification, genome doubling of haploid, and self-fertilization of doubled haploids. Since modern haploid inducers still produce relatively small portion of haploids among undesirable hybrid kernels, haploid identification is typically laborious, costly, and time-consuming, making this step the second foremost in the DH technique. This manuscript reviews numerous methods for haploid identification from different approaches including the innate differences in haploids and diploids, biomarkers integrated in haploid inducers, and automated seed sorting. The phenotypic differentiation, genetic basis, advantages, and limitations of each biomarker system are highlighted. Several approaches of automated seed sorting from different research groups are also discussed regarding the platform or instrument used, sorting time, accuracy, advantages, limitations, and challenges before they go through commercialization. The past haploid selection was focusing on finding the distinguishable marker systems with the key to effectiveness. The current haploid selection is adopting multiple reliable biomarker systems with the key to efficiency while seeking the possibility for automation. Fully automated high-throughput haploid sorting would be promising in near future with the key to robustness with retaining the feasible level of accuracy. The system that can meet between three major constraints (time, workforce, and budget) and the sorting scale would be the best option.

Increased late-onset glaucoma risk following vitrectomy for macular pucker or hole.

OBJECTIVES: The long-term risk of developing glaucoma after vitrectomy remains uncertain. This retrospective population-based cohort study aimed to explore this risk following vitrectomy for macular pucker or hole. METHODS: Utilizing Taiwan's National Health Insurance Research Database (NHIRD), we included patients who were older than 18 years and had undergone vitrectomy surgery between 2011 and 2019. Exclusions were made for patients with prior diagnoses of glaucoma, congenital or secondary glaucoma, as well as those who had received previous vitreoretinal treatments or had undergone multiple vitrectomies. RESULTS: After an average follow-up period of 51 and 53 months respectively for the vitrectomized and non-vitrectomized group, our results showed a relative risk of 1.71 for glaucoma development in the vitrectomized group. Higher adjusted hazard ratios were also observed for open-angle glaucoma and normal tension glaucoma. Increased risks were associated with male sex, obstructive sleep apnoea, and migraine. In the subgroup analysis, phakic eyes at baseline and those who had undergone cataract surgery post-vitrectomy were associated with a lower risk of glaucoma development during follow-up. Among all glaucoma events, pseudophakic status at baseline had the shortest interval to glaucoma development following vitrectomy. CONCLUSIONS: These findings underscore the potential relationship between vitrectomy and glaucoma onset, emphasizing the need for vigilant monitoring and early detection of glaucoma in post-vitrectomy patients.

Short-Term Disruption of TGFß Signaling in Adult Mice Renders the Aorta Vulnerable to Hypertension-Induced Dissection.

Hypertension and transient increases in blood pressure from extreme exertion are risk factors for aortic dissection in patients with age-related vascular degeneration or inherited connective tissue disorders. Yet, the common experimental model of angiotensin II-induced aortopathy in mice appears independent of high blood pressure as lesions do not occur in response to an alternative vasoconstrictor, norepinephrine, and are not prevented by co-treatment with a vasodilator, hydralazine. We investigated vasoconstrictor administration to adult mice 1 week after disruption of TGFß signaling in smooth muscle cells. Norepinephrine increased blood pressure and induced aortic dissection by 7 days and even within 30 minutes that was rescued by hydralazine; results were similar with angiotensin II. Changes in regulatory contractile molecule expression were not of pathological significance. Rather, reduced synthesis of extracellular matrix yielded a vulnerable aortic phenotype by decreasing medial collagen, most dynamically type XVIII, and impairing cell-matrix adhesion. We conclude that transient and sustained increases in blood pressure cause dissection in aortas rendered vulnerable by inhibition of TGFß-driven extracellular matrix production by smooth muscle cells. A corollary is that medial fibrosis, a frequent feature of medial degeneration, may afford some protection against aortic dissection.

The effects of BDNF rs6265 and FGF21 rs11665896 polymorphisms on alcohol use disorder-related impulsivity in Han Chinese adults.

Introduction: Patients with alcohol use disorder (AUD) often experience repeated withdrawal. Impulsivity is the most relevant factor influencing successful withdrawal. Brain-derived neurotrophic factor (BNDF) and fibroblast growth factor 21 (FGF21) are associated with impulsivity. Previous studies on the differential effects of BDNF or FGF21 on impulsivity have focused on single-gene effects and have inconsistent results. We aim to investigate the effects of BDNF rs6265 and FGF21 rs11665896, individually and together, on impulsivity during alcohol withdrawal in patients with AUD. Methods: We recruited 482 adult Han Chinese males with AUD and assessed their impulsivity using the Barratt Impulsivity Scale. Genomic DNA was extracted and genotyped from peripheral blood samples. Statistical analysis was conducted on the data. Results: The T-test and 2 × 2 analysis of variance were used to investigate the effects of the genes on impulsivity. There was a significant BDNF × FGF21 interaction on no-planning impulsiveness (F = 9.15, p = 0.003, η2p = 0.03). Simple main effects analyses and planned comparisons showed that BDNF rs6265 A allele × FGF21 rs11665896 T allele was associated with higher no-planning impulsiveness. Finally, hierarchical regression analyses revealed that only the interaction of BDNF and FGF21 accounted for a significant portion of the variance in no-planning impulsiveness. Conclusion and significance: The combination of BDNF rs6265 A allele and FGF21 rs11665896 T allele may increase impulsivity and discourage alcohol withdrawal. Our study provides a possible genetic explanation for the effects of associated impulsivity in patients with AUD from the perspective of gene-gene interactions.

Comparison of modified Furlow palatoplasty using small double-opposing Z-plasty and conventional Furlow palatoplasty: A long-term outcome study.

BACKGROUND: The aim of palatoplasty is to create a functional palate to achieve normal speech, while minimizing post-operative complications. This study aimed to compare the long-term outcomes of modified Furlow palatoplasty using small double-opposing Z-plasty (small-DOZ) and conventional Furlow palatoplasty (conventional-DOZ) performed in a single center. METHODS: A retrospective review of consecutive patients who underwent Furlow palatoplasty between May 2007 and March 2014 was executed. Non-syndromic patients subjected to palatoplasty prior to 24 months of age and followed-up until at least 9 years of age were included. RESULTS: A total of 196 small-DOZ and 280 conventional-DOZ palatoplasty patients were included in this study. Overall, 14 patients (2.9%) developed oronasal fistula, and 40 patients (8.4%) received velopharyngeal insufficiency (VPI) surgery. In comparisons, oronasal fistula rate was significantly higher in conventional-DOZ (0.5% vs. 4.6%, p = 0.01), and the VPI prevalence was not significantly different (9.2% vs. 7.9%, p = 0.62). Patients who developed fistula had a significantly higher likelihood of developing VPI than patients without oronasal fistula (50.0% vs. 7.1%, respectively; p < 0.01), with an odds ratio of 13.0. CONCLUSION: Both modalities of palatoplasty yielded commendable velopharyngeal function in the long-term follow-up. The small-DOZ with reduced tension lowered the risk of oronasal fistula.

Prevalence, proportions of elevated liver enzyme levels, and long-term cardiometabolic mortality of patients with metabolic dysfunction-associated steatotic liver disease.

BACKGROUND AND AIM: This study estimated the prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) according to cardiometabolic risk factors. The long-term impacts of MASLD on all-cause and cardiometabolic-specific mortality were evaluated. METHODS: We enrolled 343 816 adults aged ≥30 years who participated in a health screening program from 1997 through 2013. MASLD was identified on the basis of abdominal ultrasonography and metabolic profiles. The participants were further categorized by liver enzyme elevation. Baseline cardiometabolic comorbidities were classified on the basis of self-reported medication use and clinical seromarkers. All-cause and cardiometabolic-specific deaths were determined through computerized data linkage with nationwide death certifications until December 31, 2020. RESULTS: The overall prevalence of MASLD was 36.4%. Among patients with MASLD, 35.9% had abnormal liver enzyme levels. Compared with patients without MASLD, abnormal liver enzymes were positively associated with cardiometabolic comorbidities in patients with MASLD (Pfor trend < 0.001). After follow-up, patients with MASLD had a 9%-29% higher risk of all-cause, cardiovascular-related, or diabetes-related mortality. In the groups with MASLD and elevated and normal liver enzyme levels, the multivariate-adjusted hazard ratios for cardiovascular deaths were 1.14 (1.05-1.25) and 1.10 (1.03-1.17), respectively, and those for diabetes deaths were 1.42 (1.05-1.93) and 1.24 (0.98-1.57), respectively, compared with those in the non-MASLD group (Pfor trend < 0.001). DISCUSSION: Individuals with MASLD and elevated liver enzyme levels exhibited significantly higher risks of all-cause and cardiometabolic deaths and should be monitored and given consultation on cardiometabolic modifications.

A Wearable Thin-Film Hydrogel Laser for Functional Sensing on Skin.

Flexible photonics offers the possibility of realizing wearable sensors by bridging the advantages of flexible materials and photonic sensing elements. Recently, optical resonators have emerged as a tool to improve their oversensitivity by integrating with flexible photonic sensors. However, direct monitoring of multiple psychological information on human skin remains challenging due to the subtle biological signals and complex tissue interface. To tackle the current challenges, here, we developed a functional thin film laser formed by encapsulating liquid crystal droplet lasers in a flexible hydrogel for monitoring metabolites in human sweat (lactate, glucose, and urea). The three-dimensional cross-linked hydrophilic polymer serves as the adhesive layer to allow small molecules to penetrate from human tissue to generate strong light--matter interactions on the interface of whispering gallery modes resonators. Both the hydrogel and cholesteric liquid crystal microdroplets were modified specifically to achieve high sensitivity and selectivity. As a proof of concept, wavelength-multiplexed sensing and a prototype were demonstrated on human skin to detect human metabolites from perspiration. These results present a significant advance in the fabrication and potential guidance for wearable and functional microlasers in healthcare.

Synthetic minority over-sampling technique-enhanced machine learning models for predicting recurrence of postoperative chronic subdural hematoma.

Objective: Chronic subdural hematoma (CSDH) is a neurological condition with high recurrence rates, primarily observed in the elderly population. Although several risk factors have been identified, predicting CSDH recurrence remains a challenge. Given the potential of machine learning (ML) to extract meaningful insights from complex data sets, our study aims to develop and validate ML models capable of accurately predicting postoperative CSDH recurrence. Methods: Data from 447 CSDH patients treated with consecutive burr-hole irrigations at Wenzhou Medical University's First Affiliated Hospital (December 2014-April 2019) were studied. 312 patients formed the development cohort, while 135 comprised the test cohort. The Least Absolute Shrinkage and Selection Operator (LASSO) method was employed to select crucial features associated with recurrence. Eight machine learning algorithms were used to construct prediction models for hematoma recurrence, using demographic, laboratory, and radiological features. The Border-line Synthetic Minority Over-sampling Technique (SMOTE) was applied to address data imbalance, and Shapley Additive Explanation (SHAP) analysis was utilized to improve model visualization and interpretability. Model performance was assessed using metrics such as AUROC, sensitivity, specificity, F1 score, calibration plots, and decision curve analysis (DCA). Results: Our optimized ML models exhibited prediction accuracies ranging from 61.0% to 86.2% for hematoma recurrence in the validation set. Notably, the Random Forest (RF) model surpassed other algorithms, achieving an accuracy of 86.2%. SHAP analysis confirmed these results, highlighting key clinical predictors for CSDH recurrence risk, including age, alanine aminotransferase level, fibrinogen level, thrombin time, and maximum hematoma diameter. The RF model yielded an accuracy of 92.6% with an AUC value of 0.834 in the test dataset. Conclusion: Our findings underscore the efficacy of machine learning algorithms, notably the integration of the RF model with SMOTE, in forecasting the recurrence of postoperative chronic subdural hematoma. Leveraging the RF model, we devised an online calculator that may serve as a pivotal instrument in tailoring therapeutic strategies and implementing timely preventive interventions for high-risk patients.

MyTrack+: Human-centered design of an mHealth app to support long-term weight loss maintenance.

A growing body of research has focused on the utility of adaptive intervention models for promoting long-term weight loss maintenance; however, evaluation of these interventions often requires customized smartphone applications. Building such an app from scratch can be resource-intensive. To support a novel clinical trial of an adaptive intervention for weight loss maintenance, we developed a companion app, MyTrack+, to pair with a main commercial app, FatSecret (FS), leveraging a user-centered design process for rapid prototyping and reducing software engineering efforts. MyTrack+ seamlessly integrates data from FS and the BodyTrace smart scale, enabling participants to log and self-monitor their health data, while also incorporating customized questionnaires and timestamps to enhance data collection for the trial. We iteratively refined the app by first developing initial mockups and incorporating feedback from a usability study with 17 university students. We further improved the app based on an in-the-wild pilot study with 33 participants in the target population, emphasizing acceptance, simplicity, customization options, and dual app usage. Our work highlights the potential of using an iterative human-centered design process to build a companion app that complements a commercial app for rapid prototyping, reducing costs, and enabling efficient research progress.

Proteomics reveals the mechanism of protein degradation and its relationship to sensorial and texture characteristics in dry-cured squid during processing.

Proteolysis in dry-cured squid contributes to the development of sensory and textural attributes. In this study, label-free quantitative proteomics was conducted to study the mechanism of proteolysis and its correlation with quality changes. The results showed that the protein profile of dry-cured squid changed markedly during processing, which was confirmed by the quantification of myofibrillar protein, amino nitrogen and total free acids, and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis. Thirty-two key differentially abundant proteins were found to be correlated with sensory and texture characteristics, including myofibrillar protein, tubulin beta chain, collagens, heat shock proteins and cytochrome c. The correlation analysis indicated that myosin regulatory light chain and tubulin beta chain played the most important role in the development of texture and sensory attributes in squid samples during the dry-curing process. The results offered novel insights into proteolysis in dry-cured squid and its relationship to quality changes.

Achieve fairness without demographics for dermatological disease diagnosis.

In medical image diagnosis, fairness has become increasingly crucial. Without bias mitigation, deploying unfair AI would harm the interests of the underprivileged population and potentially tear society apart. Recent research addresses prediction biases in deep learning models concerning demographic groups (e.g., gender, age, and race) by utilizing demographic (sensitive attribute) information during training. However, many sensitive attributes naturally exist in dermatological disease images. If the trained model only targets fairness for a specific attribute, it remains unfair for other attributes. Moreover, training a model that can accommodate multiple sensitive attributes is impractical due to privacy concerns. To overcome this, we propose a method enabling fair predictions for sensitive attributes during the testing phase without using such information during training. Inspired by prior work highlighting the impact of feature entanglement on fairness, we enhance the model features by capturing the features related to the sensitive and target attributes and regularizing the feature entanglement between corresponding classes. This ensures that the model can only classify based on the features related to the target attribute without relying on features associated with sensitive attributes, thereby improving fairness and accuracy. Additionally, we use disease masks from the Segment Anything Model (SAM) to enhance the quality of the learned feature. Experimental results demonstrate that the proposed method can improve fairness in classification compared to state-of-the-art methods in two dermatological disease datasets.

Microstructure and Perfusion Alterations of Globus Pallidus in Neonates with Hyperbilirubinemia.

BACKGROUND: Previous studies have indicated the abnormality of the globus pallidus in neonates with hyperbilirubinemia. OBJECTIVE: This study aims to explore the microstructure and cerebral perfusion of globus pallidus in neonatal hyperbilirubinemia by using Diffusion Tensor Imaging (DTI) and Arterial Spin Labeling (ASL) approaches. METHODS: Thirty-seven neonates were enrolled in this study, which were classified into Bilirubin-Induced Neurologic Dysfunction (BIND) group (hyperbilirubinemia with BIND, n=12), non-BIND group (hyperbilirubinemia without BIND, n=15), and healthy controls (HC) group (n=10). The quantitative values of globus pallidus were calculated from DTI, including the Apparent Diffusion Coefficient (ADC), the Fractional Anisotropy (FA), and Volume Ratio (VR) values. Additionally, the relative Cerebral Blood Flow (rCBF) values were obtained from ASL. RESULTS: It was observed that the mean DTI signal of globus pallidus was significantly different among the three groups (p < 0.05). However, there were no significant differences in the rCBF of globus pallidus among the three groups (p > 0.05). A positive correlation was also observed between the fractional anisotropy (FA) value and serum bilirubin level (r = 0.561, p = 0.002), while the VR value showed a negative correlation with serum bilirubin level (r=-0.484, p=0.011). The area under the curve (AUC) of FA, VR, and FA and VR combined was 0.897, 0.858, and 0.933, respectively. CONCLUSION: The alterations of microstructure in globus pallidus, especially FA and VR value, may be valuable and sensitive at the early stage of hyperbilirubinemia encephalopathy, suggesting that early hyperbilirubinemia may lead to cytotoxic edema and decreased permeability of the cell membrane.

An iridium(iii)-based photosensitizer disrupting the mitochondrial respiratory chain induces ferritinophagy-mediated immunogenic cell death.

Cancer cells have a strategically optimized metabolism and tumor microenvironment for rapid proliferation and growth. Increasing research efforts have been focused on developing therapeutic agents that specifically target the metabolism of cancer cells. In this work, we prepared 1-methyl-4-phenylpyridinium-functionalized Ir(iii) complexes that selectively localize in the mitochondria and generate singlet oxygen and superoxide anion radicals upon two-photon irradiation. The generation of this oxidative stress leads to the disruption of the mitochondrial respiratory chain and therefore the disturbance of mitochondrial oxidative phosphorylation and glycolysis metabolisms, triggering cell death by combining immunogenic cell death and ferritinophagy. To the best of our knowledge, this latter is reported for the first time in the context of photodynamic therapy (PDT). To provide cancer selectivity, the best compound of this work was encapsulated within exosomes to form tumor-targeted nanoparticles. Treatment of the primary tumor of mice with two-photon irradiation (720 nm) 24 h after injection of the nanoparticles in the tail vein stops the primary tumor progression and almost completely inhibits the growth of distant tumors that were not irradiated. Our compound is a promising photosensitizer that efficiently disrupts the mitochondrial respiratory chain and induces ferritinophagy-mediated long-term immunotherapy.

Separability Transitions in Topological States Induced by Local Decoherence.

We study states with intrinsic topological order subjected to local decoherence from the perspective of separability, i.e., whether a decohered mixed state can be expressed as an ensemble of short-range entangled pure states. We focus on toric codes and the X-cube fracton state and provide evidence for the existence of decoherence-induced separability transitions that precisely coincide with the threshold for the feasibility of active error correction. A key insight is that local decoherence acting on the "parent" cluster states of these models results in a Gibbs state. As an example, for the 2D (3D) toric code subjected to bit-flip errors, we show that the decohered density matrix can be written as a convex sum of short-range entangled states for p>p_{c}, where p_{c} is related to the paramagnetic-ferromagnetic transition in the 2D (3D) random bond Ising model along the Nishimori line.