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Insulin-like growth factor 1 receptor (IGF1R) is an attractive drug target for cancer therapy and research on IGF1R inhibitors has had success in clinical trials. A particular challenge in the development of specific IGF1R inhibitors is interference from insulin receptor (IR), which has a nearly identical sequence. A few potent inhibitors that are selective for IGF1R have been discovered experimentally with the aid of computational methods. However, studies on the rapid identification of IGF1R-selective inhibitors using virtual screening and confidence-level inspections of ligands that show different interactions with IGF1R and IR in docking analysis are rare. In this study, we established virtual screening and binding-mode prediction workflows based on benchmark results of IGF1R and several kinase receptors with IGF1R-like structures. We used comprehensive analysis of the known complexes of IGF1R and IR with their binding ligands to screen specific IGF1R inhibitors. Using these workflows, 17 of 139,735 compounds in the NCI (National Cancer Institute) database were identified as potential specific inhibitors of IGF1R. Calculations of the potential of mean force (PMF) with GROMACS were further conducted for three of the identified compounds to assess their binding affinity differences towards IGF1R and IR. [ABSTRACT FROM AUTHOR]

The article evaluates the clinical effectiveness and safety of the treatment of patients with fludarabine refractory chronic lymphocytic leukemia by supplying fresh frozen plasma (FFP) to rituximab. The characteristics of chronic lymphocytic leukemia, which is a progressive accumulation of monoclonal B-lymphocytes in the bone marrow, lymphatic organs and blood is discussed. Rituximab is a chemeric monoclonal antibody that is approved by the U.S. Food and Drug Administration for the treatment of low-grade B-cell non-Hodgkin's lymphoma.

Stigma and spikelet characteristics play an essential role in hybrid seed production. A mini-core of 90 accessions developed from USDA rice core collection was phenotyped in field grown for nine traits of stigma and spikelet and genotyped with 109 DNA markers, 108 SSRs plus an indel. Three major clusters were built upon Rogers’ genetic distance, indicative of indicas, and temperate and tropical japonicas. A mixed linear model combining PC-matrix and K-matrix was adapted for mapping marker-trait associations. Resulting associations were adjusted using false discovery rate technique. We identified 34 marker-trait associations involving 22 SSR markers for eight traits. Four markers were associated with single stigma exsertion (SStgE), six with dual exsertion (DStgE) and five with total exsertion. RM5_Chr1 played major role indicative of high regression with not only DStgE but also SStgE. Four markers were associated with spikelet length, three with width and seven with L/W ratio. Numerous markers were co-associated with multiple traits that were phenotypically correlated, i.e. RM12521_Chr2 associated with all three correlated spikelet traits. The co-association should improve breeding efficiency because single marker could be used to assist breeding for multiple traits. Indica entry 1032 (cultivar 50638) and japonica entry 671 (cultivar Linia 84 Icar) with 80.65 and 75.17% of TStgE, respectively are recommended to breeder for improving stigma exsertion. [ABSTRACT FROM AUTHOR]

Prostate cancer remains the most common malignancy among men in United States, and there is no remedy currently available for the advanced stage hormone-refractory cancer. This is partly due to the incomplete understanding of androgen-regulated proteins and their encoded functions. Whole-cell proteomes of androgen-starved and androgen-treated LNCaP cells were analyzed by semi-quantitative MudPIT ESI- ion trap MS/MS and quantitative iTRAQ MALDI- TOF MS/MS platforms, with identification of more than 1300 high-confidence proteins. An enrichment-based pathway mapping of the androgen-regulated proteomic data sets revealed a significant dysregulation of aminoacyl tRNA synthetases, indicating an increase in protein biosynthesis- a hallmark during prostate cancer progression. This observation is supported by immunoblot and transcript data from LNCaP cells, and prostate cancer tissue. Thus, data derived from multiple proteomics platforms and transcript data coupled with informatics analysis provides a deeper insight into the functional consequences of androgen action in prostate cancer. [ABSTRACT FROM AUTHOR]

Hemodialysis patients may obtain clinical benefit from supplementing the fish oil-derived long chain n-3 PUFA, EPA (20:5n3) and DHA (22:6n3), particularly given our previous observations that this population consumes inadequate fish and has suboptimal red blood cell (RBC) n-3 PUFA levels. We tested the hypothesis that supplementing these patients over 12 wks with modest fish oil doses (∼ 1 g fish oil daily AHA) would be efficacious in boosting RBC n-3 levels by performing a randomized, placebo-controlled, double-blind study in an urban American hemodialysis population. 12 subjects were randomized to 1.3 g fish oil or placebo (corn/soybean oil) in a ratio of 2:1 (i.e. 8:4). 75% of subjects consumed one or less fish servings a week. Baseline EPA and DHA RBC levels were relatively low at 0.29 ± 0.24 and 3.2 ± 2.2 (mean ± SD), respectively. Post-supplementation EPA and DHA RBC levels were dramatically increased in the fish oil group [% EPA change (fish oil vs placebo): +395 vs -27, p = 0.004; % DHA change: +160 vs -27, p = 0.008]. Four subjects in the fish oil group noted minor side effects (primarily gastrointestinal). Plasma levels of n-3 PUFA were consistent with the RBC data. Our finding suggests that supplementation of these patients with fish oil boosts tissue n-3 PUFA levels and is generally well-tolerated. These findings must be examined in a larger population on clinical outcomes. [ABSTRACT FROM AUTHOR]

The article discusses research which examined the health-related social needs of older adults enrolled in the Medicare Advantage health insurance plan in the U.S. Topics explored include the prevalence of social needs cited such as food insecurity, poor housing quality, and social isolation, the logistic regression models developed based on individual social needs, and the link between these needs and the characteristics of Medicare Advantage respondents.

Population-based payment in Medicare Advantage (MA) can foster innovation in care delivery by giving risk-bearing providers flexibility and strong incentives to enhance care and engage patients. This may particularly benefit historically underserved groups for whom payments often exceed costs. In this study, using data from Humana MA plans, we examined "senior-focused" primary care organizations that are supported predominantly by population-based payments in contracts with MA plans. We explored whether such organizations supported by such payment are associated with better care and improved equity compared with other primary care organizations receiving other forms of payment in MA. Analyses of data from 462,872 MA beneficiaries in 2021 showed that senior-focused primary care organizations served more Black and dually eligible beneficiaries than other primary care organizations serving MA beneficiaries, and regression-adjusted analysis showed that senior-focused primary care patients received 17 percent more primary care visits. Differences were largest among Black and dual-eligible beneficiaries. These findings suggest that risk-bearing organizations in MA are responding to current payment dynamics and providing enhanced care and access to patients, particularly historically underserved populations.