Association Between Cardiovascular Health and Retinopathy in US Adults: From NHANES 2005-2008.

PURPOSE: Investigating the relationship between cardiovascular health (CVH) and retinopathy in the adult population of the United States. DESIGN: The cross-sectional study Methods: The study utilized samples, including the diabetes population, from the National Health and Nutrition Examination Survey (NHANES) conducted between 2005 and 2008 (N= 4,249), to assess cardiovascular health (CVH) using the Life's Essential 8 (LE8) assessment. Retinopathy are determined through imaging assessment by professionals independently grading fundus photographs. Univariable and multivariable weighted logistic regression models, restricted cubic splines (RCS), Subgroup analysis and weighted quantile sum (WQS) regression approaches were employed to assess the association between LE8 score-based CVH status and retinopathy. The mediation analysis was conducted to investigate whether serum albumin levels mediated the relationship between LE8 score and retinopathy. RESULTS: In a fully adjusted logistic regression model, participants in the moderate and high CVH groups had a 39% (odds ratio (OR) 0.61, 95% confidence intervals (CI) 0.43-0.87, P- value = 0.01) and 56% (OR 0.44, 95%CI 0.25-0.77, P- value < 0.001) lower odds of developing retinopathy compared to the low CVH group. The RCS model indicates a significant non-linear relationship between CVH and retinopathy. The WQS regression analysis suggests that blood glucose (47.65%) and blood pressure (19.41%) have the highest weights in relation to retinopathy. Mediation analysis suggests that serum albumin partially mediates the relationship between LE8 scores and retinopathy. CONCLUSION: This study demonstrates a significant negative correlation between overall cardiovascular health measured by LE8 scores and retinopathy. Public health strategies that promote achieving optimal cardiovascular health indicators may help reduce the burden of retinal microvascular diseases.

Serum klotho as a novel biomarker for metabolic syndrome: findings from a large national cohort.

Background: Metabolic syndrome is a cluster of metabolic abnormalities that significantly increase the risk of cardiovascular disease and mortality. The identification of novel biomarkers associated with mortality in patients with metabolic syndrome could facilitate early risk stratification and targeted interventions. Methods: We conducted a large prospective cohort study using data from five cycles (2009-2016) of the National Health and Nutrition Examination Survey (NHANES) database, including a total of 40,439 participants. Logistic regression analysis was used to assess the association between serum klotho protein levels and metabolic syndrome, while Cox regression analysis was employed to examine the correlation between serum klotho levels and all-cause mortality. Mortality data were updated until December 31, 2019. Results: After adjusting for demographic and socioeconomic confounders, the logistic regression model demonstrated that higher serum klotho levels were significantly associated with a decreased prevalence of metabolic syndrome (OR [95% CI] Highest vs. lowest quartile: 0.84 [0.70-0.99], P=0.038). In the Cox regression model, elevated klotho levels were found to significantly reduce the risk of all-cause mortality among individuals with metabolic syndrome (HR [95% CI] Highest vs. lowest quartile: 0.68 [0.51-0.90], P=0.006). Conclusion: Serum klotho levels were found to be inversely associated with the prevalence of metabolic syndrome, independent of potential confounding factors such as demographics, socioeconomic status, and lifestyle factors. Furthermore, higher klotho levels strongly indicated a lower risk of all-cause mortality in individuals with metabolic syndrome.

Revisiting the mechanisms linking blood glucose to cognitive impairment: new evidence for the potential important role of klotho.

Background: The association between blood glucose and cognition is controversial. Klotho is an anti-aging protein with neural protective effects. This study aimed to use a population-based study to disentangle the relationship between blood glucose levels and cognitive function in older adults, and to explore the role of klotho in it. Methods: A total of 1445 eligible participants from National Health and Nutrition Examination Survey (NHANES) 2011-2014 were included in our study. Cognitive function was assessed by Digit Symbol Substitution Test (DSST) and categorized into four quartiles (Q1-Q4). General characteristics and laboratory test results including serum klotho concentration and blood glucose levels were collected. Associations of cognitive function and klotho levels with blood glucose concentrations were explored through multivariate linear regression models. Mediation models were constructed to figure out the mediating role of klotho. Results: All three multivariate linear regression models showed a negative correlation between blood glucose and cognitive function. (Model 1, ß=-0.149, 95%CI: -0.202,-0.096, p=0.001; Model 2, ß=-0.116, 95%CI: -0.167,-0.065, p=0.001; Model 3, ß=-0.007, 95%CI: -0.118,-0.023, p=0.003). Mediation analysis showed that klotho mediated the statistical association between blood glucose level and cognitive function with proportions (%) of 12.5. Conclusion: Higher blood glucose levels are associated with poorer cognitive performance in non-diabetic older adults, partially mediated through lower klotho levels.

Inflammation mediates the relationship between diet quality assessed by healthy eating index-2015 and metabolic syndrome.

Background: Metabolic syndrome is a cluster of metabolic disorders, including obesity, hypertension, hyperglycemia, and abnormal lipid levels. However, researches on the association between overall dietary quality measured by the Healthy Eating Index-2015 (HEI-2015) and the risk of metabolic syndrome is still lacking. Methods: This study utilized data from four cycles (2011-2018) of the National Health and Nutrition Examination Survey (NHANES) database, including 17,582 participants. Logistic regression analysis was employed to explore the correlation between HEI and the risk of metabolic syndrome. Additionally, mediation analysis was conducted to examine the effects of Systemic Immune-Inflammation Index (SII) and serum uric acid as potential mediators between HEI and metabolic syndrome risk. Weighted quantile sum (WQS) regression evaluated the composite exposure impact of the 13 components of the HEI on metabolic syndrome, as well as the proportion of their weights. Results: Higher dietary quality measured by HEI-2015 (at the 75th percentile) was negatively correlated with the risk of metabolic syndrome (OR=0.80, 95%CI=0.72-0.89, P=0.003). Higher SII and serum uric acid levels were identified as risk factors for metabolic syndrome (P for trend<0.001). Approximately 37.5% of the effect of HEI on metabolic syndrome occurrence was mediated by SII (Indirect effect=-0.002, 95%CI (-0.003,-0.001), Direct effect=-0.022, 95%CI (-0.0273,-0.015)). Additionally, 25% of the effect of HEI on metabolic syndrome occurrence was mediated by serum uric acid levels (Indirect effect=-0.006, 95%CI (-0.010,-0.012), Direct effect=-0.024, 95%CI (-0.041,-0.009)). WQS regression analysis revealed the highest weighted proportions for seafood and plant proteins (25.20%) and sodium (17.79%), while the weight for whole fruit was the lowest (0.25%). Conclusion: Better dietary quality measured by HEI-2015 was associated with a lower likelihood of metabolic syndrome. Higher SII and serum uric acid levels were identified as risk factors for metabolic syndrome and potential mediators.

Vitamin B6 Turnover Predicts Long-term Mortality Risk in Patients with Type 2 Diabetes.

Background: Inflammation can increase vitamin B6 uptake and catabolism. Higher vitamin B6 turnover [4-pyridoxic acid (4-PA)/pyridoxal 5'-phosphate (PLP) ratio], was associated with mortality risk in the general population. Objectives: We aimed to investigate the association between 4-PA/PLP and long-term mortality in patients with type 2 diabetes mellitus (T2DM), an inflammatory disease. Methods: In this prospective cohort study from the National Health and Nutrition Examination Survey (NHANES) cycles 2005-2010, the concentrations of 4-PA and PLP in plasma were measured using high-performance liquid chromatography, with mortality data updated to 31 December 2019. We included 2074 patients with T2DM aged between 20 and 85 y at baseline. Results: There were 739 deaths among 2279 patients with T2DM with a median follow-up of 11.83 y. In the age- and sex-adjusted COX model (model 1), 4-PA/PLP was positively associated with mortality in patients with T2DM [hazard ratio (HR) and 95% confidence interval (CI) highest compared with lowest quartiles: 35.55 (18.29, 69.09); P < 0.001], and in model 3, which was adjusted for demographics as well as inflammation, nutrition, and renal function, high 4-PA/PLP concentrations remained an independent risk factor for mortality in patients with T2DM [HR (95% CI) highest compared with lowest quartiles: 5.03 (2.46, 10.30); P < 0.001]. In restricted cubic spline (RCS), the link between 4-PA/PLP and all-cause mortality displays a positive correlation. Patients with died within the previous 2 y were excluded, the sensitivity analysis had no effect on the association between 4-PA/PLP and mortality in patients with T2DM. Finally, comparable results were found in subgroup analyses of specific-cause mortality. Conclusion: Higher vitamin B6 turnover is associated with long-term mortality risk in patients with T2DM. 4-PA/PLP may serve as a convenient prognostic marker in T2DM management.

Associations of micronutrient dietary patterns with sarcopenia among US adults: a population-based study.

Background: Current epidemiological evidence points to an association between micronutrient (MN) intake and sarcopenia, but studies have focused on single MN, and no combined effects on MNs have been reported. The aim of this study was to investigate the relationship between different MN intake patterns and sarcopenia and skeletal muscle mass. Methods: We performed a population-based cross-sectional study, with a total of 5,256 U.S. adults aged 20-59 years, and we collected total daily MN intake and appendicular skeletal muscle mass measured by Dual-Energy X-ray Absorptiometry (DXA). Principal component analysis (PCA) was used to obtain nutrient patterns and principal component scores based on the intake of 14 MNs, and logistic regression analysis was used to assess the effects of single MN and MN intake patterns on sarcopenia and muscle mass. Results: We defined three MN intake patterns by PCA: (1) adherence to VitB-mineral, high intake of vitamin B and minerals; (2) adherence to VitAD-Ca-VB12, high intake of vitamin A, vitamin D, calcium and vitamin B12; and (3) adherence to Antioxidant Vit, high intake of antioxidant vitamins A, C, E, and K. These three nutrient patterns explained 73.26% of the variance of the population. A negative association was observed between most single MN intakes and sarcopenia, and after adjusting for confounders, adherence to the highest tertile of the three nutrient patterns was associated with a lower risk of sarcopenia and relatively higher skeletal muscle mass compared to the lowest adherence. In subgroup analysis, MN intake patterns were significantly correlated with sarcopenia in middle-aged females. Conclusion: Nutritional patterns based on MN intake were significantly related to sarcopenia, indicating that MNs interact with each other while exerting their individual functions, and that MN dietary patterns may provide promising strategies for preventing the loss of muscle mass, with further prospective studies warranted in the future.

The PG-SGA outperforms the NRS 2002 for nutritional risk screening in cancer patients: a retrospective study from China.

Background and aims: As a chronic wasting disease, cancer can lead to metabolic and physiological changes in patients, resulting in severe malnutrition. Therefore, accurate assessment of nutritional status and adoption of scientifically sound nutritional interventions are of great importance for patients with cancer. This study aimed to assess the necessity of implementing the Nutrition Risk Screening 2002 (NRS 2002) tool in conjunction with the Patient-Generated Subjective Global Assessment (PG-SGA) in patients with cancer. Methods: This retrospective study collected the clinical data of cancer patients from November 2011 to December 2018 in the Department of Oncology, Cancer Center, First Hospital of Jilin University. The NRS 2002 and the PG-SGA were used as screening tools for malnutrition. Clinical characteristics and laboratory results were detected. Anthropometric indices including hand-grip strength (HGS), visceral fat area (VFA), calf circumstance (CC), and appendicular skeletal muscle mass index (ASMI) were also collected. The diagnostic results from the NRS 2002 were compared to the malnutrition diagnosis using the PG-SGA. Results: Of the 2,645 patients included in this retrospective study, the nutritional risk was found in 1763 (66.6%) patients based on the PG-SGA, and in 240 (9.1%) patients based on the NRS 2002, respectively. Among the 240 patients evaluated by the NRS 2002 for risk of malnutrition, 230 were also assessed by the PG-SGA as malnourished. There were no significant differences observed in the clinical characteristics and laboratory parameters between the two groups. Conclusion: The PG-SGA is effective and had a higher positive rate in screening malnutrition for patients with cancer. The NRS 2002 is not necessary for patients who are to be assessed with the PG-SGA.

Associations of multiple toxic metal exposures with metabolic dysfunction-associated fatty liver disease: NHANES 2011-2018.

Background: The occurrence of metabolic dysfunction-associated fatty liver disease (MASLD) is driven by multiple factors including obesity, hypertension, dyslipidemia, and insulin resistance. However, epidemiological research investigating the association between metal exposure and MASLD occurrence remains limited. Methods: We conducted a large cross-sectional study with 6,520 participants who were involved in the National Health and Nutrition Examination Survey (NHANES) between 2011 and 2018. Using generalized linear regression, we examined the relationship between five heavy metals (mercury, manganese, lead, selenium, cadmium) and MASLD. Furthermore, restricted cubic spline models and weighted quantile sum (WQS) analysis were employed to characterize the exposure-response relationship between the five metals and MASLD. Results: Higher blood selenium levels were associated with an increased likelihood of MASLD among US adults. Blood lead exposure was also positively correlated with MASLD risk. However, there was no significant association observed between blood cadmium, mercury, manganese levels, and MASLD risk. Among the five metals, blood cadmium exposure accounted for the highest proportion of MASLD risk. Conclusion: Our study indicated the significant association between blood cadmium and lead exposure levels and the occurrence of MASLD in a representative sample of US adults.

FTO-mediated LINC01134 stabilization to promote chemoresistance through miR-140-3p/WNT5A/WNT pathway in PDAC.

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer most frequently detected at an advanced stage that limits treatment options to systemic chemotherapy, which has provided only marginal positive clinical outcomes. Currently, the first-line chemotherapeutic agent for PDAC is gemcitabine (GEM). However, the chemotherapy resistance to GEM is often overlooked in the clinical treatment of PDAC due to the lack of effective biological markers. Therefore, it is crucial to find new prognostic markers and therapeutic targets for patients with PDAC. In this study, we identified a novel regulatory mechanism in the development of resistance to GEM in PDAC. Here, we report that LINC01134 was significantly upregulated in primary tumors from PDAC patients. In vitro and in vivo functional studies revealed that LINC01134 promotes PDAC resistance to GEM through facilitating stem cell features and modulating the cell cycle. Mechanistically, LINC01134 interactes with tumor suppressor miR-497-5p in PDAC cells. Increased LINC01134 downregulates miR-140-3p to promotes the oncogenic WNT5A expression. Moreover, m6A demethylase FTO participated in the upregulation of LINC01134 by maintaining LINC01134 mRNA stability through YTHDF2. Taken together, the present study suggested FTO-mediated LINC01134 stabilization to promote chemotherapy resistance to GEM through miR-140-3p/WNT5A/WNT pathway in PDAC. Our study identified new prognostic markers and new therapeutic targets for patients with PDAC.

Prognostic value of the combined effect of nutritional status and body water component in patients with colorectal cancer.

The aim of this study was to explore the impact of Geriatric Nutritional Risk Index (GNRI) and body water component (BWC) on the survival of colorectal cancer (CRC) patients and whether the combined effect had a potential prognostic and predictive efficacy. We evaluated the accuracy of GNRI for malnutrition and estimated the predictive capacity of BWC for survival. Kaplan-Meier survival curves and cox regression analyses were used to examine the prognostic effects. A nutrition-water score (NWS) model was developed and evaluated the survival predictive power. GNRI and extracellular water-to-intracellular water ratio (ECW/ICW) were integrated, with the cut-off values of 103.5 and 63.7%. Lower GNRI and higher ECW/ICW were independent risk factors for poor prognosis in CRC patients. The combination of the two into the NWS model demonstrated a higher risk of death for patients with NWS ≥ 1 compared to those with NWS of 0. NWS showed a better predictive capability compared to GNRI and ECW/ICW, with the concordance index of 0.681. Our study demonstrates GNRI and ECW/ICW's prognostic utility in CRC, with their combination improving survival prediction to help guide patient-centered treatment.

Remarkable response to PD-1 inhibitor in a patient with extensive-stage small cell lung cancer: a case report and literature review.

We report a case of a 59-year-old male diagnosed with extensive-stage small cell lung cancer (SCLC). He received first-line platinum doublet chemotherapy and second-line topotecan-based regimen, but experienced disease progression after each line of therapy. He was then treated with Sintilimab, a PD-1 inhibitor, in combination with nab-paclitaxel in the third-line setting, which resulted in significant tumor shrinkage. Restaging scans showed a partial response per RECIST criteria with 62% reduction in tumor burden. This case highlights the application and efficacy of immune checkpoint inhibitors in extensive-stage SCLC.

Potential causal association between aspirin use and the reduced risk of hayfever or allergic rhinitis: a Mendelian randomization study.

Background: The evidence from observational studies on the association between the use of aspirin and the risk of hayfever or allergic rhinitis is conflicting, with a dearth of high-quality randomized controlled trials. Objective: This study aims to investigate the causal relationship between aspirin use and the risk of hayfever or allergic rhinitis. Methods: We conducted a two-sample Mendelian randomization (MR) analysis using the inverse-variance weighted (IVW), weighted median, and MR-Egger regression methods. We utilized publicly available summary statistics datasets from genome-wide association studies (GWAS) meta-analyses on aspirin use in individuals of European descent (n = 337,159) as the exposure variable, and a GWAS on doctor-diagnosed hayfever or allergic rhinitis in individuals from the UK Biobank (n = 83,529) as the outcome variable. Results: We identified 7 single nucleotide polymorphisms (SNPs) at genome-wide significance from the GWASs associated with aspirin use as instrumental variables (P<5×10-8; linkage disequilibrium r2 <0.1). The IVW method provided evidence supporting a causal association between aspirin use and reduced risk of hayfever or allergic rhinitis (ß = -0.349, SE = 0.1356, P = 0.01008). MR-Egger regression indicated no causal association between aspirin use and hayfever or allergic rhinitis (ß = -0.3742, SE = 0.3809, P = 0.371), but the weighted median approach yielded evidence of a causal association (ß = -0.4155, SE = 0.1657, P = 0.01216). Cochran's Q test and the funnel plot indicated no evidence of heterogeneity and asymmetry, indicating no directional pleiotropy. Conclusion: The findings of the MR analysis support a potential causal relationship between aspirin use and the reduced risk of hayfever or allergic rhinitis.

The efficacy of fat-free mass index and appendicular skeletal muscle mass index in cancer malnutrition: a propensity score match analysis.

Background: Reduced muscle mass (RMM) is a phenotypic criterion for malnutrition; the appendicular skeletal muscle mass index (ASMI) and fat-free mass index (FFMI) are both applicable indicators in the global leadership initiative on malnutrition (GLIM) guideline. However, their sensitivity and prognostic effect remain unclear. Methods: Clinical data of 2,477 patients with malignant tumors were collected. Multi-frequency bioelectrical impedance analysis was used to obtain ASMI and FFMI. RMM was confirmed by ASMI (< 7.0 kg/m2 for men and < 5.7 kg/m2 for women) or FFMI (< 17 kg/m2 for men and < 15 kg/m2 for women). Propensity score match analysis and logistic regression analysis were used to evaluate the efficacy of FFMI and ASMI in diagnosing severe malnutrition and multivariate Cox regression analysis to determine the efficacy of RMM in predicting survival. Results: In total, 546 (22.0%) and 659 (26.6%) participants were diagnosed with RMM by ASMI (RMM.ASMI group) and FFMI (RMM.FFMI group); 375 cases overlapped. Body mass index (BMI), midarm circumference, triceps skinfold thickness, and maximum calf circumference were all significantly larger in the RMM.FFMI group for both sexes (P < 0.05). A 1:1 matched dataset constructed by propensity score match contained 810 cases. RMM.FFMI was an influential factor of severe malnutrition with HR = 3.033 (95% CI 2.068-4.449, P < 0.001), and RMM.ASMI was a predictive factor of overall survival (HR = 1.318, 95% CI 1.060-1.639, P = 0.013 in the RMM.ASMI subgroup, HR = 1.315, 95% CI 1.077-1.607, P = 0.007 in the RMM.FFMI subgroup). Conclusion: In general, RMM indicates negative clinical outcomes; when defined by FFMI, it predicts nutritional status, and when defined by ASMI, it is related to poor survival in cancer patients.

Association Between Visceral Fat Area and Cancer Prognosis: A Population-Based Multicenter Prospective Study.

BACKGROUND: Diverse indicators have been used to represent adipose tissue, while the relationship between body adipose mass and the prognosis of patients with cancer remains controversial. OBJECTIVE: This study aimed to explore the indicators of optimal body composition that represent body fat mass to predict risk of cancer-related mortality. METHODS: We conducted a population-based multicenter prospective cohort study of patients with initial cancer between February 2012 and September 2020. Clinical information, body composition indicators, hematologic test results, and follow-up data were collected. Body composition indicators were analyzed using principal component analysis to select the most representative indicators, and the cutoff value was set according to the optimal stratification method. The hazard ratio (HR) for mortality was calculated using Cox proportional hazards regression models. RESULTS: Among 14,018 patients with complete body composition data, visceral fat area (VFA) is a more optimal indicator for body fat content (principal component index: 0.961) than body mass index (principal component index: 0.850). The cutoff points for VFA in terms of time to mortality were 66 cm2 and 102 cm2 for gastric/esophageal cancer and other cancers, respectively. Among the 2788 patients treated systemically, multivariate analyses demonstrated that a lower VFA was associated with a higher risk of death in patients with cancer of diverse types (HR: 1.33; 95% CI: 1.08, 1.64; P = 0.007), especially gastric cancer (HR: 2.13; 95% CI: 1.3, 3.49; P = 0.003), colorectal cancer HR: 1.81; 95% CI: 1.06, 3.08; P = 0.030) and nonsmall-cell lung cancer (HR: 1.27; 95% CI: 1.01, 1.59; P = 0.040). CONCLUSION: VFA is an independent prognostic indicator of muscle mass in patients with diverse types of cancer, particularly gastric, colorectal, and nonsmall-cell lung cancers. TRIAL REGISTRATION NUMBER: ChiCTR1800020329.

Association of Neutrophil-to-Lymphocyte Ratio with Nutrition in Patients with Various Types of Malignant Tumors: A Multicenter Cross-Sectional Study.

Aim: Neutrophil-to-lymphocyte ratio (NLR) is an index of systemic inflammation. This study is to clarify the role of NLR in body functional status, nutritional risk and nutritional status in the course of tumor. Methods: A multi-center cross-sectional study of patients with various types of malignant tumors was accrued from the whole country. There were 21,457 patients with completed clinical data, biochemical indicators, physical examination, the Patient-Generated Subjective Global Assessment (PG-SGA) and Nutrition Risk Screening 2002 (NRS2002) survey. Logistic regression analysis was used to figure out the influencing factors of NLR, and four models were established to evaluate the influence of NLR on body functions, nutritional risks and nutritional status. Results: Male patients, TNM stage IV, total bilirubin, hypertension and coronary atherosclerotic heart disease (CAHD) were independent predictors of NLR >2.5. BMI, digestive systemic tumors and triglyceride negatively affect NLR in multivariable logistic regression. NLR was an independent predictor of Karnofsky Performance Scale (KPS), fat store deficit in all degrees, moderate and severe muscle deficit, mild fluid retention and PG-SGA grade. Conclusion: Male patients and those with hypertension and CAHD are prone to systemic inflammation. Systemic inflammation significantly degrades body function status and nutritional status, increases nutritional risk and influences fat and muscle metabolism in patients with malignant tumor. Improving the intervenable indicators such as elevating albumin and pre-albumin, decreasing total bilirubin and enhancing nutrition support are imperative. Obesity and triglyceride behave like anti-systemic inflammation, which is misleading due to reverse causation in the course of malignancy.

The Interactive Effects of Deficit Irrigation and Bacillus pumilus Inoculation on Growth and Physiology of Tomato Plant.

The effects of inoculating plant growth promoting rhizobacteria (PGPR) and soil water deficits on crop growth and physiology remain largely unknown. Here, the responses of leaf gas exchange, growth, and water use efficiency (WUE) of tomato plants to Bacillus pumilus (B.p.) inoculation under four irrigation strategies (I1-I4) were investigated in a greenhouse. Results showed that soil water deficits, especially at I4 (20%, v/v), significantly decreased leaf stomatal conductance (gs), transpiration rate (Tr), and photosynthetic rate (An), and the decrease of gs and Tr were more pronounced than An. Reduced irrigation regimes significantly lowered dry matter and plant water use both in the non-B.p. control and the B.p. plants, while reduced irrigation significantly increased plant WUE, and B.p. inoculation had little effect on this parameter. Synergistic effects of PGPR and deficit irrigation on leaf gas exchange, leaf abscisic acid content, and stomatal density were found in this study, and specifically, B.p. treated plants at I4 possessed the highest WUE at stomatal and leaf scales, suggesting that B.p. inoculation could optimize water use and partly alleviate the negative effects of soil water deficit. These findings provide useful information for effective irrigation management and the application of PGPR in agriculture in the future.

A whole-joint histopathologic grading system for murine knee osteoarthritis.

This study aims to develop a comprehensive and easily executable histopathologic grading scheme for murine knee osteoarthritis (OA) using specific scoring criteria for both cartilage and periarticular changes, which may overcome important limitations of the existing grading systems. The new grading scheme was developed based on mouse knee OA models with observation periods up to 24 months of age (spontaneous OA) or 24-week post-injury (posttraumatic OA). Semi-quantitative assessments of the histopathologic OA changes were applied to all four quadrants per femorotibial joint for 50 joints (200 quadrants) using specific scoring criteria rather than mild to severe grades. Scoring elements per quadrant were as follows: cartilage lesion (0-7), osteophyte (0-3), subchondral bone change (0-3), synovitis (0-3), and ectopic periarticular soft-tissue chondrogenesis and ossification (0-3). The new histopathologic grading scheme had high intra- and interobserver reproducibility (correlation coefficients r > 0.95) across experienced and novice observers. Sensitivity and reliability analyses confirmed the ability of the new scheme to detect minimal but significant OA progression (p < 0.01) within a 2-week interval and to accurately identify tissue- and quadrant-specific OA severity within the joints. In conclusion, this study presents the first whole-joint histopathologic grading scheme for murine knee OA that covers all-stage osteoarthritic changes in all major joint tissues, including periarticular soft-tissue ossification that is not included in any of the existing OA grading systems. This reproducible scheme is easy to execute and sensitive to minimal OA progression without using computer software, suitable for quick OA severity assessments of the entire femorotibial joint.

Triceps skinfold-albumin index significantly predicts the prognosis of cancer cachexia: A multicentre cohort study.

BACKGROUND: The fat mass and nutritional status play important roles in the onset and progression of cancer cachexia. The present study evaluated the joint prognostic value of the fat mass, as indicated by the triceps skinfold thickness (TSF), and the serum albumin level, for mortality in patients with cancer cachexia. METHODS: We performed a multicentre cohort study including 5134 patients with cancer cachexia from January 2013 to April 2019. The sum of the TSF (mm) and serum albumin (g/L) was defined as the triceps skinfold-albumin index (TA). Harrell's C index, a time-dependent receiver operating characteristic (ROC) curve analysis and the area under the curve (AUC) were used to evaluate the prognostic performance of the TA and other indices. Optimal stratification was used to identify the thresholds to define a low TA, and the association of the TA with all-cause mortality was evaluated using Kaplan-Meier analysis and Cox proportional hazard regression models. RESULTS: The study enrolled 2408 women and 2726 men with a median age of 58.6 years and a median follow-up of 44 months. A total of 607 women (TA < 49.9) and 817 men (TA < 45.6) were classified as having a low TA. The TA showed better discrimination performance (C index = 0.621, 95% confidence interval [CI] = 0.607-0.636) to predict mortality in patients with cancer cachexia than the handgrip strength, the nutritional risk index, the prognostic nutritional index, the controlling nutritional status index, the systemic immune-inflammation index, the modified Glasgow prognostic score, and the TSF or albumin alone in the study population (all P < 0.05). The 1-, 3- and 5-year time-dependent ROC analyses (AUC = 0.647, 0.625 and 0.630, respectively) showed that the TA had the highest prognostic value among all indices investigated (all P < 0.05). Univariate analysis showed that a lower TA was associated with an increased death hazard (hazard ratio [HR] = 1.859, 95% CI = 1.677-2.062), regardless of the sex and cancer type. Multivariable survival analysis showed that a lower TA was independently associated with an increased death hazard (HR = 1.381, 95% CI = 1.223-1.560). This association was significantly strengthened in patients who did not receive curative chemotherapy (HR = 1.491, 95% CI = 1.298-1.713), those who had higher serum total protein levels (HR = 1.469, 95% CI = 1.284-1.681) and those with better physical performance (HR = 1.453, 95% CI = 1.271-1.662). CONCLUSIONS: This study defined and evaluated a new prognostic index, the TA, which may improve the selection of intervention strategies to optimize the survival of patients with cancer cachexia.

Knowledge Sharing for Pulmonary Nodule Detection in Medical Cyber-Physical Systems.

With the rapid development of edge intelligence (EI) and machine learning (ML), the applications of Cyber-Physical Systems (CPS) have been discovered in all aspects of the life world. As one of its most essential branches, Medical CPS (MCPS) determines human health and medical treatment in the Internet of Everything (IOE) era. Knowledge sharing is the critical point of MCPS and has also been humanity's best dream through the ages. This paper explores a novel knowledge-sharing model in MCPS and takes a pulmonary nodule detection task as a significant case for building an Unet-based mask generator. A Classification-guided Module (CGM)-based discriminator with knowledge from EMRs is set against a generator to offer a promising result for each mask from the inexperienced participant of federated ML. After an iterative communication between the federated server and its clients for knowledge sharing, the segmented sub-image owns a coincident attribute distribution with that of the EMRs from the experts. Besides, the adversarial network augment the data to normalize the data distribution for all the clients as a remission for none independent identically distributed (non-IID) data problem. We implement a detection framework on the simulated EI environment following an existing adaptive synchronization strategy based on data sharing and median loss function. On 1304 scans of the merged dataset, our proposed framework can help boost the detection performance for most of the existing methods of pulmonary nodule detection.