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Recognizing that palliative care improves the care quality and reduces the healthcare costs for individuals in their end of life, health plan providers strive to better enroll the appropriate target population for palliative care. Current research has not adequately addressed challenges related to proactively select potential palliative care beneficiaries from a population health perspective. This study presents a Generalized Machine Learning Pipeline (GMLP) to predict palliative needs in patients using administrative claims data. The GMLP has five steps data cohort creation, feature engineering, predictive modeling, scoring beneficiaries, and model maintenance. It encapsulates principles of population health management, business domain knowledge, and machine learning (ML) process knowledge with an innovative data pull strategy. The GMLP was applied in a regional health plan using a data cohort of 17,197 patients. Multiple ML models were turned and evaluated against a custom performance metric based on the business requirement. The best model was an AdaBoost model with a precision of 71.43% and a recall of 67.98%. The post-implementation evaluation of the GMLP showed that it increased the recall of high mortality risk patients, improved their quality of life, and reduced the overall cost. The GMLP is a novel approach that can be applied agnostically to the data and specific ML algorithms. To the best of our knowledge, it is the first attempt to continuously score palliative care beneficiaries using administrative data. The GMLP and its use case example presented in the paper can serve as a methodological guide for different health plans and healthcare policymakers to apply ML in solving real-world clinical challenges, such as palliative care management and other similar risk-stratified care management workflows.

Recent studies have shown increased all-cause mortality among workers following disabling workplace injury. These studies did not account for two potentially important confounders, smoking and obesity. We estimated injury-related mortality accounting for these factors.

We followed workers receiving New Mexico workers' compensation benefits (1994-2000) through 2013. Using data from the Panel Study of Income Dynamics, we derived the joint distribution of smoking status and obesity for workers with and without lost-time injuries. We conducted a quantitative bias analysis (QBA) to determine the adjusted relationship of injury and mortality.

We observed hazard ratios after adjusting for smoking and obesity of 1.13 for women (95% simulation interval (SI) 0.97 to 1.31) and 1.12 for men (95% SI 1.00 to 1.27). The estimated fully adjusted excess hazard was about half the estimates not adjusted for these factors.

Using QBA to adjust for smoking and obesity reduced the estimated mortality hazard from lost-time injuries and widened the simulation interval. The adjusted estimate still showed more than a 10 percent increase for both women and men, although the 95% SI for women included 1.0. The change in estimates reveals the importance of accounting for these confounders. Of course, the results depend on the methods and assumptions used.

Using QBA to adjust for smoking and obesity reduced the estimated mortality hazard from lost-time injuries and widened the simulation interval. The adjusted estimate still showed more than a 10 percent increase for both women and men, although the 95% SI for women included 1.0. The change in estimates reveals the importance of accounting for these confounders. Of course, the results depend on the methods and assumptions used.The purpose of this study was to characterize the bacteria isolated from rockfish intestines and to investigate the effects of feed supplementation in rockfish aquaculture. Bacillus sp. KRF-7 isolated from the intestine of rockfish (Sebastes schlegelii) was demonstrated to be safe based on in vitro tests confirming the absence of hemolysis, cytotoxicity, and genes with toxigenic potential. In a feeding trial, providing a supplemental diet of 1 × 108 CFU g-1Bacillus sp. KRF-7 was observed to positively alter the weight gain, specific growth rate, feed conversion ratio, and protein efficiency ratio of juvenile rockfish. KRF-7 supplementation showed positive regulation of nonspecific immune parameters, such as superoxide dismutase, lysozyme activity, and myeloperoxidase activity. This analysis also revealed a change in the composition of the intestinal microbiota at the phylum level from Proteobacteria to Firmicutes. In both the kidney and spleen, the expression levels of IL-10, NF-κB, and B cell activating factors in the KRF-7-supplemented group were significantly increased compared to those in the control group. Therefore, this study verified the safety of KRF-7 isolated from the intestine of rockfish and suggests that dietary supplementation with KRF-7 enhances the growth performance of rockfish and has beneficial effects on the regulation of the intestinal microbiota and immune response.Hybridization is an artificial breeding strategy for generating potentially desirable offspring. L-Kynurenine concentration Recently, a novel Hulong grouper hybrid (Epinephelus fuscogutatus × Epinephelus lanceolatus) yielded significant growth superiority over its parent. Improved innate immunity is considered as another desirable feature during hybridization. However, whether this Hulong grouper achieved disease resistance has not yet been revealed. In this study, we first examine the infection intensity of C. irritans in the Hulong grouper, and found that the Hulong grouper is less susceptible to C. irritans primary infection. A higher immobilization titer was found in the infected Hulong grouper at Day 2 when compared with the control grouper. Furthermore, severe hyperplasia was observed in the orange-spotted grouper, but not in the Hulong grouper's skin epidermis. To further understand the innate immune mechanism against C. irritans, we conducted a comparative transcriptome analysis of the Hulong grouper during the infection. There are 6464 differentially expressed genes (DEGs) identified in the skin between the control and infected Hulong grouper. This indicates that the innate immune components, such as the complement system, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, Interleukin 17 (IL-17) signaling pathway, and Toll-like receptor (TLR) signaling pathway were up-regulated during the infection. These results show that the C. irritans infection can induce a remarkable inflammatory response in the Hulong grouper. Moreover, a total of 75 pairs of orthologs with the ratio of nonsynonymous (Ka) to synonymous (Ks) substitutions >1, considered rapidly evolving genes (REGs), was identified between the Hulong and orange-spotted grouper. More critically, most REGs were enriched in the immune system, suggesting that rapid evolution of the immune system might occur in the Hulong grouper. These results provide a more comprehensive understanding of the innate immunity mechanism of the hybrid Hulong grouper.Seven immune factors, lysozyme, hepcidin, heat-shock protein (HSP) 70, HSP90, immunoglobulin M, C-type lectin, and Lily-type lectin, were measured by PCR in the livers, spleens, and head kidneys of turbot infected with Vibrio anguillarum. Additive main effects and multiplicative interaction (AMMI) and genotype main effects and genotype × environment interaction (GGE) biplot analysis were used to analyze genotype × tissue interactions for immunological factors. The AMMI analysis revealed that immune factor expression was significantly affected by genotype, tissue, and genotype × tissue interactions. Genotype (65.85%) was the major contributor to the total variation in immune factor expression in comparison to tissue effects (7.54%) and genotype × tissue interactions (12.52%). GGE biplot analysis revealed differences in the ranking of the seven immune factors in the three tissues; head kidney possessed the strongest ability to distinguish the seven immune factors. The test tissue locations were divided into liver-spleen and head kidneys regions; HSP70 was expressed the highest in the liver-spleen regions, and lysozyme had the highest expression in the head kidney region. Overall, HSP70 and HSP90 had the best expression and stability in the three tissues.Nonalcoholic fatty liver disease (NAFLD) is common in farmed fish fed a high-fat diet (HFD), which disrupts lipid metabolism, inhibits growth performance, and poses a serious threat to sustainable aquaculture. This study explored the anti-NAFLD effect and hepatoprotective mechanism of YZW-A, a water-soluble heteroglycan extracted from the pomelo fruitlet (Citrus maxima), in hybrid grouper (Epinephelus lanceolatus♂ × Epinephelus fuscoguttatus♀). Hybrid grouper were fed an HFD, with 15% lipid, supplemented with YZW-A for 56 days. In vivo, addition of YZW-A resulted in improved growth performance and feed utilization, while it reduced whole body and muscle lipid content, viscerosomatic and hepatosomatic indexes, and lipid deposition in the hepatocytes. Lipogenesis-related genes were downregulated while lipolysis-related genes were upregulated in grouper supplemented with YZW-A. Additionally, destructive morphological changes in the liver tissue cells detected in HFD-fed grouper were normalized after treatment with YZW-A. In vitro, YZW-A improved lipid emulsion-induced hepatic steatosis by modulating key factors of lipid metabolism, achieved by triggering the AMP-activated protein kinase (AMPK) pathway in the hepatocytes and activating the AMPK/Nrf2/ARE axis. These results demonstrated the therapeutic effect of YZW-A on diet-induced NAFLD in hybrid grouper and elucidated a possible mechanism underlying NAFLD prevention and suppression of further deterioration by YZW-A.Idiopathic pulmonary fibrosis (IPF) induces significant morbidity and mortality, for which there are limited therapeutic options available. Here, we found that tetraethylthiuram disulphide (disulfiram, DSF), a derivative of thiuram, used in the treatment of alcohol abuse, has an inhibitory effect on bleomycin (BLM)-induced pulmonary fibrosis via the attenuation of the fibroblast-to-myofibroblast transition, migration, and proliferation of fibroblasts. Furthermore, DSF inhibited the activation of primary pulmonary fibroblasts and fibroblast cell line under transforming growth factor-β 1 (TGF-β1) challenge. Mechanistically, the anti-fibrotic effect of DSF on fibroblasts depends on the inhibition of TGF-β signalling. We further determined that DSF interrupts the interaction between SMAD3 and TGF-β receptor Ι (TBR Ι), and identified that DSF directly binds with SMAD3, in which Trp326, Thr330, and Cys332 of SMAD3 are critical binding sites for DSF. Collectively, our results reveal a powerful anti-fibrotic function of DSF in pulmonary fibrosis through the inhibition of TGF-β/SMAD signalling in pulmonary fibroblasts, indicating that DSF is a promising therapeutic candidate for IPF.Pulmonary fibrosis is a devastating lung disease with multifactorial etiology characterized by alveolar injury, fibroblast proliferation and excessive deposition of extracellular matrix proteins, which progressively results in respiratory failure and death. Accumulating evidence from experimental and clinical studies supports a central role of the renin angiotensin aldosterone system (RAAS) in the pathogenesis and progression of idiopathic pulmonary fibrosis. Angiotensin II (Ang II), a key vasoactive peptide of the RAAS mediates pro-inflammatory and pro-fibrotic effects on the lungs, adversely affecting organ function. Recent years have witnessed seminal discoveries in the field of RAAS. Identification of new enzymes, peptides and receptors has led to the development of several novel concepts. Of particular interest is the establishment of a protective axis of the RAAS comprising of Angiotensin converting enzyme 2 (ACE2), Angiotensin-(1-7) [Ang-(1-7)], and the Mas receptor (the ACE2/Ang-(1-7)/Mas axis), and the discovery of a functional role for the Angiotensin type 2 (AT2) receptor.

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