Novel decision tree models predict the overall survival of patients with submandibular gland cancer.

BACKGROUND: While the accurate prediction of the overall survival (OS) in patients with submandibular gland cancer (SGC) is paramount for informed therapeutic planning, the development of reliable survival prediction models has been hindered by the rarity of SGC cases. The purpose of this study is to identify key prognostic factors for OS in SGC patients using a large database and construct decision tree models to aid the prediction of survival probabilities in 12, 24, 60 and 120 months. MATERIALS AND METHODS: We performed a retrospective cohort study using the Surveillance, Epidemiology and End Result (SEER) program. Demographic and peri-operative predictor variables were identified. The outcome variables overall survival at 12-, 24-, 60, and 120 months. The C5.0 algorithm was utilized to establish the dichotomous decision tree models, with the depth of tree limited within 4 layers. To evaluate the performances of the novel models, the receiver operator characteristic (ROC) curves were generated, and the metrics such as accuracy rate, and area under ROC curve (AUC) were calculated. RESULTS: A total of 1,705, 1,666, 1,543, and 1,413 SGC patients with a follow up of 12, 24, 60 and 120 months and exact survival status were identified from the SEER database. Predictor variables of age, sex, surgery, radiation, chemotherapy, tumor histology, summary stage, metastasis to distant lymph node, and marital status exerted substantial influence on overall survival. Decision tree models were then developed, incorporating these vital prognostic indicators. Favorable consistency was presented between the predicted and actual survival statuses. For the training dataset, the accuracy rates for the 12-, 24-, 60- and 120-month survival models were 0.866, 0.767, 0.737 and 0.797. Correspondingly, the AUC values were 0.841, 0.756, 0.725, and 0.774 for the same time points. CONCLUSIONS: Based on the most important predictor variables identified using the large, SEER database, decision tree models were established that predict OS of SGC patients. The models offer a more exhaustive evaluation of mortality risk and may lead to more personalized treatment strategies.

One-step formation of polymorphous sperm-like microswimmers by vortex turbulence-assisted microfluidics.

Microswimmers are considered promising candidates for active cargo delivery to benefit a wide spectrum of biomedical applications. Yet, big challenges still remain in designing the microswimmers with effective propelling, desirable loading and adaptive releasing abilities all in one. Inspired by the morphology and biofunction of spermatozoa, we report a one-step formation strategy of polymorphous sperm-like magnetic microswimmers (PSMs) by developing a vortex turbulence-assisted microfluidics (VTAM) platform. The fabricated PSM is biodegradable with a core-shell head and flexible tail, and their morphology can be adjusted by vortex flow rotation speed and calcium chloride solution concentration. Benefiting from the sperm-like design, our PSM exhibits both effective motion ability under remote mag/netic actuation and protective encapsulation ability for material loading. Further, it can also realize the stable sustain release after alginate-chitosan-alginate (ACA) layer coating modification. This research proposes and verifies a new strategy for the sperm-like microswimmer construction, offering an alternative solution for the target delivery of diverse drugs and biologics for future biomedical treatment. Moreover, the proposed VTAM could also be a general method for other sophisticated polymorphous structures fabrication that isn't achievable by conventional laminar flow.

Topical administration of GLP-1 eyedrops improves retinal ganglion cell function by facilitating presynaptic GABA release in early experimental diabetes.

ABSTRACT: Diabetic retinopathy is a prominent cause of blindness in adults, with early retinal ganglion cell (RGC) loss contributing to visual dysfunction or blindness. In the brain, defects in y-aminobutyric acid (GABA) synaptic transmission are associated with pathophysiological and neurodegenerative disorders, whereas glucagon-like peptide-1 (GLP-1) has demonstrated neuroprotective effects. However, it is not yet clear whether diabetes causes alterations in inhibitory input to RGCs and whether and how GLP-1 protects against neurodegeneration in the diabetic retina through regulating inhibitory synaptic transmission to RGCs. In the present study, we used the patch-clamp technique to record GABA subtype A receptor-mediated miniature inhibitory postsynaptic currents (mIPSCs) in RGCs from streptozotocin-induced diabetes model rats. We found that early diabetes (4 weeks of hyperglycemia) decreased the frequency of GABAergic mIPSCs in RGCs without altering their amplitude, suggesting a reduction in the spontaneous release of GABA to RGCs. Topical administration of GLP-1 eyedrops over a period of 2 weeks effectively countered the hyperglycemia-induced downregulation of GABAergic mIPSC frequency, subsequently enhancing the survival of RGCs. Concurrently, the protective effects of GLP-1 on RGCs in diabetic rats were eliminated by topical administration of exendin-9-39, a specific GLP-1 receptor antagonist, or SR95531, a specific antagonist of the GABA subtype A receptor. Furthermore, extracellular perfusion of GLP-1 was found to elevate the frequencies of GABAergic mIPSCs in both ON- and OFF-type RGCs. This elevation was shown to be mediated by activation of the phosphatidylinositol-phospholipase C/inositol 1,4,5-trisphosphate receptor/Ca2+/protein kinase C signaling pathway downstream of GLP-1 receptor activation. Moreover, multielectrode array recordings revealed that GLP-1 functionally augmented the photoresponses of ON-type RGCs. Optomotor response tests demonstrated that diabetic rats exhibited reductions in visual acuity and contrast sensitivity that were significantly ameliorated by topical administration of GLP-1. These results suggest that GLP-1 facilitates the release of GABA onto RGCs through the activation of GLP-1 receptor, leading to the de-excitation of RGC circuits and the inhibition of excitotoxic processes associated with diabetic retinopathy. Collectively, our findings indicate that the GABA system has potential as a therapeutic target for mitigating early-stage diabetic retinopathy. Furthermore, the topical administration of GLP-1 eyedrops represents a non-invasive and effective treatment approach for managing early-stage diabetic retinopathy.

Dynamic Microcirculation Characteristics of Plantar Skin Under Metatarsal Head of Human Foot in Response to Life-Like Pressure Stimulus.

OBJECTIVE: Diabetic foot ulcer (DFU) is a severe complication with high mortality. High plantar pressure and poor microcirculation are considered main causes of DFU. The specific aims were to provide a novel technique for real-time measurement of plantar skin blood flow (SBF) under walking-like pressure stimulus and delineate the first plantar metatarsal head dynamic microcirculation characteristics because of life-like loading conditions in healthy individuals. METHODS: Twenty young healthy participants (14 male and 6 female) were recruited. The baseline (i.e., unloaded) SBF of soft tissue under the first metatarsal head were measured using laser Doppler flowmetry (LDF). A custom-made machine was utilized to replicate daily walking pressure exertion for 5 min. The exerted plantar force was adjusted from 10 N (127.3 kPa) to 40 N (509.3 kPa) at an increase of 5 N (63.7 kPa). Real-time SBF was acquired using the LDF. After each pressure exertion, postload SBF was measured for comparative purposes. Statistical analysis was performed using the R software. RESULTS: All levels of immediate-load and postload SBF increased significantly compared with baseline values. As the exerted load increased, the postload and immediate-load SBF tended to increase until the exerted load reached 35 N (445.6 kPa). However, in immediate-load data, the increasing trend tended to level off as the exerted pressure increased from 15 N (191.0 kPa) to 25 N (318.3 kPa). For postload and immediate-load SBF, they both peaked at 35 N (445.6 kPa). However, when the exerted force exceeds 35 N (445.6 kPa), both the immediate-load and postload SBF values started to decrease. CONCLUSIONS: Our study offered a novel real-time plantar soft tissue microcirculation measurement technique under dynamic conditions. For the first metatarsal head of healthy people, 20 N (254.6 kPa)-plantar pressure has a fair microcirculation stimulus compared with higher pressure. There might be a pressure threshold at 35 N (445.6 kPa) for the first metatarsal head, and soft tissue microcirculation may decrease when local pressure exceeds it.

Plant YABBY transcription factors: a review of gene expression, biological functions, and prospects.

Transcription factors often contain several different functional regions, including DNA-binding domains, and play an important regulatory role in plant growth, development, and the response to external stimuli. YABYY transcription factors are plant-specific and contain two special domains (N-terminal C2C2 zinc-finger and C-terminal helix-loop-helix domains) that are indispensable. Specifically, YABBY transcription factors play key roles in maintaining the polarity of the adaxial-abaxial axis of leaves, as well as in regulating: vegetative and reproductive growth, hormone response, stress resistance, and secondary metabolite synthesis in plants. Recently, the identification and functional verification of YABBY transcription factors in different plants has increased. On this basis, we summarize recent advances in the: identification, classification, expression patterns, and functions of the YABBY transcription factor family. The normal expression and function of YABBY transcription factors rely on a regulatory network that is established through the interaction of YABBY family members with other genes. We discuss the interaction network of YABBY transcription factors during leaf polarity establishment and floral organ development. This article provides a reference for research on YABBY function, plant genetic improvement, and molecular breeding.

Pericytes in Alzheimer's disease: Key players and therapeutic targets.

Alzheimer's disease (AD) is a devastating neurodegenerative disorder that leads to progressive cognitive decline and neuropathological changes. Pericytes, which are vessel mural cells on the basement membrane of capillaries, play a crucial role in regulating cerebrovascular functions and maintaining neurovascular unit integrity. Emerging research substantiates the involvement of pericytes in AD. This review provides a comprehensive overview of pericytes, including their structure, origin, and markers and various functions within the central nervous system. Emphatically, the review explores the intricate mechanisms through which pericytes contribute to AD, including their interactions with amyloid beta and apolipoprotein E, as well as various signaling pathways. The review also highlights potential for targeted pericyte therapy for AD, with a focus on stem cell therapy and drug treatments. Future research directions include the classification of pericyte subtypes, studies related to aging, and the role of pericytes in exosome-related mechanisms in AD pathology. In conclusion, this review consolidates current knowledge on the pivotal roles of pericytes in AD and their potential as therapeutic targets, providing valuable insights for future research and clinical interventions aimed at addressing the impact of AD on patients' lives.

Prognostic factors and novel prediction models for overall survival of patients with submandibular gland cancer: A population-based retrospective cohort study.

Background: Accurately predicting the survival rate of submandibular gland cancer (SGC) is of significant importance for guiding treatment decision-making and improving patient outcomes. This study was aimed to identify the independent prognostic factors of overall survival (OS) in SGC patients, and develop novel prediction models to aid clinicians in predicting the survival probability. Materials and methods: Patients diagnosed with primary SGC after the year 2010 were extracted from SEER database and then randomly allocated into training and test samples in a 7:3 ratio. Uni- and multi-variable COX analyses were employed using the training sample to ascertain independent prognostic factors for OS. Subsequently, graphic and online dynamic nomograms were established basing on the independent prognostic factors. We utilized C-index, calibration curve, receiver operating characteristic (ROC) curve, and area under ROC curve (AUC) value to evaluate the discrimination capacity and the consistency between predicted and actual survival. Results: A total of 527 SGC patients were included (369 assigned to training group and 158 assigned to test group). The multivariable COX analysis showed that age, sex, marital status, tumor histology, summary stage, metastases to bone, and tumor size were independently associated with OS. Novel graphical and online dynamic (URL: https://yangxg1209.shinyapps.io/overall_survival_submandibular_gland_tumor/) nomograms were established. The C-indices (training: 0.77, 95%CI 0.71-0.84; test: 0.77, 95%CI 0.68-0.85) indicate favorable discrimination ability of the model, and the calibration curves demonstrated favorable consistency between the predicted and actual survival rates. Conclusions: Our study identified the independent prognostic factors influencing OS in patients with SGC, and successfully established and validated novel nomograms, which provide accurate prediction of survival rates and allows for personalized risk assessment.

Reinforcement Learning for Robust Dynamic Event-Driven Constrained Control.

We consider a robust dynamic event-driven control (EDC) problem of nonlinear systems having both unmatched perturbations and unknown styles of constraints. Specifically, the constraints imposed on the nonlinear systems' input could be symmetric or asymmetric. Initially, to tackle such constraints, we construct a novel nonquadratic cost function for the constrained auxiliary system. Then, we propose a dynamic event-triggering mechanism relied on the time-based variable and the system states simultaneously for cutting down the computational load. Meanwhile, we show that the robust dynamic EDC of original nonlinear-constrained systems could be acquired by solving the event-driven optimal control problem of the constrained auxiliary system. After that, we develop the corresponding event-driven Hamilton-Jacobi-Bellman equation, and then solve it through a unique critic neural network (CNN) in the reinforcement learning framework. To relax the persistence of excitation condition in tuning CNN's weights, we incorporate experience replay into the gradient descent method. With the aid of Lyapunov's approach, we prove that the closed-loop auxiliary system and the weight estimation error are uniformly ultimately bounded stable. Finally, two examples, including a nonlinear plant and the pendulum system, are utilized to validate the theoretical claims.

Preoperative neutrophil-to-lymphocyte ratio predicts symptomatic anastomotic leakage in elderly colon cancer patients: Multicenter propensity score-matched analysis.

BACKGROUND: The neutrophil-to-lymphocyte ratio (NLR), a composite inflammatory biomarker, is associated with the prognosis in patients with colorectal tumors. However, whether the NLR can be used as a predictor of symptomatic postoperative anastomotic leakage (AL) in elderly patients with colon cancer is unclear. AIM: To assess the role of the NLR in predicting the occurrence of symptomatic AL after surgery in elderly patients with colon cancer. METHODS: Data from elderly colon cancer patients who underwent elective radical colectomy with anastomosis at three centers between 2018 and 2022 were retrospectively analyzed. Receiver operating characteristic curve analysis was performed to determine the best predictive cutoff value for the NLR. Twenty-two covariates were matched using a 1:1 propensity score matching method, and univariate and multivariate logistic regression analyses were used to determine risk factors for the development of postoperative AL. RESULTS: Of the 577 patients included, 36 (6.2%) had symptomatic AL. The optimal cutoff value of the NLR for predicting AL was 2.66. After propensity score matching, the incidence of AL was significantly greater in the ≥ 2.66 NLR subgroup than in the < 2.66 NLR subgroup (11.5% vs 2.5%; P = 0.012). Univariate logistic regression analysis revealed statistically significant correlations between blood transfusion intraoperatively and within 2 d postoperatively, preoperative albumin concentration, preoperative prognostic nutritional index, and preoperative NLR and AL occurrence (P < 0.05); multivariate logistic regression analysis revealed that an NLR ≥ 2.66 [odds ratio (OR) = 5.51; 95% confidence interval (CI): 1.50-20.26; P = 0.010] and blood transfusion intraoperatively and within 2 d postoperatively (OR = 2.52; 95%CI: 0.88-7.25; P = 0.049) were risk factors for the occurrence of symptomatic AL. CONCLUSION: A preoperative NLR ≥ 2.66 and blood transfusion intraoperatively and within 2 d postoperatively are associated with a higher incidence of postoperative symptomatic AL in elderly patients with colon cancer. The preoperative NLR has predictive value for postoperative symptomatic AL after elective surgery in elderly patients with colon cancer.

Genomic basis of the distinct biosynthesis of ß-glucogallin, a biochemical marker for hydrolyzable tannin production, in three oak species.

Hydrolyzable tannins (HTs), predominant polyphenols in oaks, are widely used in grape wine aging, feed additives, and human healthcare. However, the limited availability of a high-quality reference genome of oaks greatly hampered the recognition of the mechanism of HT biosynthesis. Here, high-quality reference genomes of three Asian oak species (Quercus variabilis, Quercus aliena, and Quercus dentata) that have different HT contents were generated. Multi-omics studies were carried out to identify key genes regulating HT biosynthesis. In vitro enzyme activity assay was also conducted. Dual-luciferase and yeast one-hybrid assays were used to reveal the transcriptional regulation. Our results revealed that ß-glucogallin was a biochemical marker for HT production in the cupules of the three Asian oaks. UGT84A13 was confirmed as the key enzyme for ß-glucogallin biosynthesis. The differential expression of UGT84A13, rather than enzyme activity, was the main reason for different ß-glucogallin and HT accumulation. Notably, sequence variations in UGT84A13 promoters led to different trans-activating activities of WRKY32/59, explaining the different expression patterns of UGT84A13 among the three species. Our findings provide three high-quality new reference genomes for oak trees and give new insights into different transcriptional regulation for understanding ß-glucogallin and HT biosynthesis in closely related oak species.

The prevalence of obesity and relationship between obesity indicators and chronic diseases in Northern Shaanxi, China.

INTRODUCTION: Obesity not only affects human health but also is an important risk factor for a variety of chronic diseases. Therefore, it is particularly important to analyse the epidemic trend of obesity and actively carry out the prevention and control of obesity in the population. MATERIAL AND METHODS: A total of 4565 adults were selected by multi-stage stratified random sampling in Shenmu, Shaanxi Province, China. Univariate analysis was used to explore the epidemic characteristics of obesity in this region. Multivariate logistic regression was used to analyse the relationship between obesity and chronic diseases. Finally, the prediction efficiency of different obesity indexes was analysed by drawing receiver operator characteristic curves (ROC). All statistical analysis was completed by SPSS 26.0 software. RESULTS: The prevalence rates of overweight, obesity, and central obesity were 39.9%, 18.2%, and 48.0%, respectively. After adjusting for other confounding factors, multivariate logistic regression analysis showed that overweight and obesity were risk factors for hypertension, dyslipidaemia, and hyperuricaemia. Central obesity is a risk factor for dyslipidaemia and hyperuricaemia. High level of waist-to-height ratio (WHtR) was a risk factor for dyslipidaemia and hyperuricaemia (p < 0.05). Obesity-related indicators: body mass index (BMI), waist circumference (WC), and WHtR, are strongly correlated with the increased risk of chronic diseases in northern Shaanxi, China. The optimal BMI cut-off values for predicting hypertension, dyslipidaemia, and hyperuricaemia were 24.27, 24.04, and 25.54, respectively. The optimal WC cut-off values for predicting dyslipidaemia and hyperuricaemia were 84.5 and 90.5, and WHtR cut-off values were 0.52 and 0.54, respectively. CONCLUSION: The problem of overweight, obesity, and central obesity in adults is serious in northern Shaanxi, China. Obesity of all types will increase the risk of chronic diseases. Therefore, a variety of preventive and therapeutic measures should be adopted to curb obesity and reduce the incidence of related chronic diseases.

Combined Remediation Effects of Sewage Sludge and Phosphate Fertilizer on Pb-Polluted Soil from a Pb-Acid Battery Plant.

Pb soil pollution poses a serious health risk to both the environment and humans. Immobilization is the most common strategy for remediation of heavy metal polluted soil. In this study, municipal sewage sludge was used as an amendment for rehabilitation of Pb-contaminated soils, for agricultural use, near a lead-acid battery factory. The passivation effect was further improved by the addition of phosphate fertilizer. It was found that the leachable Pb content in soils was decreased from 49.6 mg kg-1 to 16.1-36.6 mg kg-1 after remediation of sludge for 45 d at applied dosage of municipal sewage sludge of 4-16 wt%, and further decreased to 14.3-34.3 mg kg-1 upon extension of the remediation period to 180 d. The addition of phosphate fertilizer greatly enhanced the Pb immobilization, with leachable Pb content decreased to 2.0-23.6 mg kg-1 with increasing dosage of phosphate fertilizer in range of 0.8-16 wt% after 180 d remediation. Plant assays showed that the bioavailability of Pb was significantly reduced by the soil remediation, with the content of absorbed Pb in mung bean roots decreased by as much as 87.0%. The decrease in mobility and biotoxicity of the soil Pb is mainly attributed to the speciation transformation of carbonate, Fe-Mn oxides and organic matter bound Pb to residue Pb under the synergism of reduction effect of sludge and acid dissolution and precipitation effect of phosphate fertilizer. This study suggests a new method for remediation of Pb-contaminated soil and utilization of municipal sewage sludge resources.

TBC1D5 reverses the capability of HIF-2α in tumor progression and lipid metabolism in clear cell renal cell carcinoma by regulating the autophagy.

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is known for abnormal lipid metabolism and widespread activation of HIF-2α. Recently, the importance of autophagy in ccRCC has been focused, and it has potential connections with HIF-2α and lipid metabolism. However, the specific regulatory mechanism between HIF-2α, autophagy, and lipid metabolism in ccRCC is still unclear. METHODS: In this study, Bioinformatics Analysis and Sequencing of the whole transcriptome were used to screen our target. The expression of TBC1D5 in renal clear cell carcinoma was confirmed by database analysis, immunohistochemistry, PCR and Western blot. The effects of TBC1D5 on tumor cell growth, migration, invasion and lipid metabolism were examined by CCK8, Transwell and oil red staining, and the mechanism of TBC1D5 on autophagy was investigated by Western blot, fluorescence microscopy and electron microscopy. Chloroquine and rapamycin were used to verified the key role of autophagy in effects of TBC1D5 on tumor cell. The regulatory mechanism of TBC1D5 in renal clear cell carcinoma (RCC) was investigated by shhif-2α, shTBC1D5, mimic, inhibitor, ChIP and Luciferase experiments. The animal model of ccRCC was used to evaluate the biological function of TBC1D5 in vivo. RESULTS: In this study, TBC1D5 was found to be an important bridge between autophagy and HIF-2α. Specifically, TBC1D5 is significantly underexpressed in ccRCC, serving as a tumor suppressor which inhibits tumor progression and lipid accumulation, and is negatively regulated by HIF-2α. Further research has found that TBC1D5 regulates the autophagy pathway to reverse the biological function of HIF-2α in ccRCC. Mechanism studies have shown that HIF-2α regulates TBC1D5 through hsa-miR-7-5p in ccRCC, thereby affecting tumor progression and lipid metabolism through autophagy. CONCLUSIONS: Our research reveals a completely new pathway, HIF-2α/hsa-miR-7-5p/TBC1D5 pathway affects ccRCC progression and lipid metabolism by regulating autophagy.

Multi-omic profiling of clear cell renal cell carcinoma identifies metabolic reprogramming associated with disease progression.

Clear cell renal cell carcinoma (ccRCC) is a complex disease with remarkable immune and metabolic heterogeneity. Here we perform genomic, transcriptomic, proteomic, metabolomic and spatial transcriptomic and metabolomic analyses on 100 patients with ccRCC from the Tongji Hospital RCC (TJ-RCC) cohort. Our analysis identifies four ccRCC subtypes including De-clear cell differentiated (DCCD)-ccRCC, a subtype with distinctive metabolic features. DCCD cancer cells are characterized by fewer lipid droplets, reduced metabolic activity, enhanced nutrient uptake capability and a high proliferation rate, leading to poor prognosis. Using single-cell and spatial trajectory analysis, we demonstrate that DCCD is a common mode of ccRCC progression. Even among stage I patients, DCCD is associated with worse outcomes and higher recurrence rate, suggesting that it cannot be cured by nephrectomy alone. Our study also suggests a treatment strategy based on subtype-specific immune cell infiltration that could guide the clinical management of ccRCC.

Enhanced d-π overlap in a graphene supported Ni/PtNi heterojunction for efficient seawater hydrogen evolution.

d-π overlap, which represents overlap between metal-d and graphene-π orbitals to facilitate electron transfer, has rarely been reported. Ni/PtNi-G2 exhibits exceptional performance in seawater hydrogen evolution due to the electron-rich surface on Pt resulting from enhanced d-π overlap and subsequent electron transfer from graphene and Ni to Pt.

Learning From Human Educational Wisdom: A Student-Centered Knowledge Distillation Method.

Existing studies on knowledge distillation typically focus on teacher-centered methods, in which the teacher network is trained according to its own standards before transferring the learned knowledge to a student one. However, due to differences in network structure between the teacher and the student, the knowledge learned by the former may not be desired by the latter. Inspired by human educational wisdom, this paper proposes a Student-Centered Distillation (SCD) method that enables the teacher network to adjust its knowledge transfer according to the student network's needs. We implemented SCD based on various human educational wisdom, e.g., the teacher network identified and learned the knowledge desired by the student network on the validation set, and then transferred it to the latter through the training set. To address the problems of current deficiency knowledge, hard sample learning and knowledge forgetting faced by a student network in the learning process, we introduce and improve Proportional-Integral-Derivative (PID) algorithms from automation fields to make them effective in identifying the current knowledge required by the student network. Furthermore, we propose a curriculum learning-based fuzzy strategy and apply it to the proposed PID control algorithm, such that the student network in SCD can actively pay attention to the learning of challenging samples after with certain knowledge. The overall performance of SCD is verified in multiple tasks by comparing it with state-of-the-art ones. Experimental results show that our student-centered distillation method outperforms existing teacher-centered ones.

Lack of incremental value of three-dimensional measurement in assessing invasiveness for lung cancer.

OBJECTIVES: The aim of this study was to evaluate the performance of consolidation-to-tumour ratio (CTR) and the radiomic models in two- and three-dimensional modalities for assessing radiological invasiveness in early-stage lung adenocarcinoma. METHODS: A retrospective analysis was conducted on patients with early-stage lung adenocarcinoma from Guangdong Provincial People's Hospital and Shenzhen People's Hospital. Manual delineation of pulmonary nodules along the boundary was performed on cross-sectional images to extract radiomic features. Clinicopathological characteristics and radiomic signatures were identified in both cohorts. CTR and radiomic score for every patient were calculated. The performance of CTR and radiomic models were tested and validated in the respective cohorts. RESULTS: A total of 818 patients from Guangdong Provincial People's Hospital were included in the primary cohort, while 474 patients from Shenzhen People's Hospital constituted an independent validation cohort. Both CTR and radiomic score were identified as independent factors for predicting pathological invasiveness. CTR in two- and three-dimensional modalities exhibited comparable results with areas under the receiver operating characteristic curves and were demonstrated in the validation cohort (area under the curve: 0.807 vs 0.826, P = 0.059) Furthermore, both CTR in two- and three-dimensional modalities was able to stratify patients with significant relapse-free survival (P < 0.000 vs P < 0.000) and overall survival (P = 0.003 vs P = 0.001). The radiomic models in two- and three-dimensional modalities demonstrated favourable discrimination and calibration in independent cohorts (P = 0.189). CONCLUSIONS: Three-dimensional measurement provides no additional clinical benefit compared to two-dimensional.

The influence of diabetes and age-related degeneration on body balance control during static standing: a study based on plantar center-of-pressure trajectories and principal component analysis.

BACKGROUND: Aging and diabetes can impair the balance function of the elderly and diabetic patients and increase their fall risk. This study aimed to assess the shaking amplitude of the center-of-pressure (CoP) during static standing, to analyze the effects of aging and diabetes on the balance control. MATERIALS AND METHODS: This cross-sectional observational study, compared the balance performance of 20 healthy younger adults (27.65 ± 5.60 years), 16 healthy older adults (58.88 ± 3.54 years) and 15 diabetic patients (58.33 ± 5.33 years) in four static standing conditions on a force plate: horizontal, anteroposterior (AP), left and right slope planes (5° angles on AP, left and right directions, respectively). The trajectory coordinates of the CoP over time were recorded and analyzed by principal components analysis to obtain the 95% confidence ellipse and its parameters: angle, major and minor axes lengths, and area. The balance indicators were compared among the three groups using one-way analysis of variance (ANOVA), Brown-Forsythe test or Kruskal-Wallis H test, depending on the normality and homogeneity of variance assumptions. RESULTS: The diabetic group had a significantly larger confidence ellipse area than the healthy younger adults on the horizontal plane (P = 0.032) and than the healthy older adults on the horizontal (P = 0.036), AP slope (P = 0.023), and right ML slope (P = 0.037) planes. There were no significant differences in the major axis length of the confidence ellipse among the three groups. The diabetic group had a significantly longer minor axis length than the healthy younger adults on the AP slope (P = 0.039), left ML slope (P = 0.045) and right ML slope (P = 0.016) planes and than the healthy older adults on the AP slope (P = 0.007), left ML slope (P = 0.035) and right ML slope (P = 0.012) planes. CONCLUSIONS: The balance control of diabetic patients is decreased compared with healthy younger and older people, and the body swing amplitude increases mainly in the direction of minor axis of confidence ellipse during static standing, while the swing amplitude in the direction of the major axis has no significant change. Evaluating the balance function of diabetic patients can help clinicians identify people with fall risk early and intervene early, thereby reducing the occurrence of fall events in this population.

Exendin-4 promotes retinal ganglion cell survival and function by inhibiting calcium channels in experimental diabetes.

Progressive damage of retinal ganglion cells (RGCs) is observed in early diabetic retinopathy. Intracellular Ca2+ overload mediated by Ca2+ influx through voltage-gated Ca2+ channels (VGCCs) is involved in neurodegeneration, whereas glucagon-like peptide-1 (GLP-1) provides neuroprotection. However, whether GLP-1 plays a neuroprotective role in diabetic retinas by modulating VGCCs remains unknown. We found that eye drops of exendin-4, a long-acting GLP-1 receptor (GLP-1R) agonist, prevented the increase of L-type Ca2+ current (ILCa) densities of RGCs induced by 4-week hyperglycemia and promoted RGC survival by suppressing L-type VGCC (L-VGCC) activity in streptozotocin-induced diabetic rats. Moreover, exendin-4-induced suppression of ILCa in RGCs may be mediated by a GLP-1R/Gs/cAMP-PKA/ryanodine/Ca2+/calmodulin/calcineurin/PP1 signaling pathway. Furthermore, exendin-4 functionally improved the light-evoked spiking ability of diabetic RGCs. These results suggest that GLP-1R activation enhances cAMP to PP1 signaling and that PP1 inactivates L-VGCCs by dephosphorylating them, thereby reducing Ca2+ influx, which could protect RGCs against excitotoxic Ca2+ overload.