The clinical risk stratification of diffuse large B-cell lymphoma (DLBCL) relies on the International Prognostic Index (IPI) for the identification of high-risk disease. Recent studies suggest that the immune microenvironment plays a role in treatment response prediction and survival in DLBCL. This study developed a risk prediction model and evaluated the model’s biological implications in association with the estimated profiles of immune infiltration. Gene-expression profiling of 718 patients with DLBCL was done, for which RNA sequencing data and clinical covariates were obtained from Reddy et al. (2017). Using unsupervised and supervised machine learning methods to identify survival-associated gene signatures, a multivariable model of survival was constructed. Tumor-infiltrating immune cell compositions were enumerated using CIBERSORT deconvolution analysis. A four gene-signature-based score was developed that separated patients into high- and low-risk groups. The combination of the gene-expression-based score with the IPI improved the discrimination on the validation and complete sets. The gene signatures were successfully validated with the deconvolution output. Correlating the deconvolution findings with the gene signatures and risk score, CD8+ T-cells and naïve CD4+ T-cells were associated with favorable prognosis. By analyzing the gene-expression data with a systematic approach, a risk prediction model that outperforms the existing risk assessment methods was developed and validated.

Objective. A cross-cultural comparative study was developed that surveyed university students in Atlanta (United States), New Delhi (India), and Newcastle upon Tyne (United Kingdom) to understand the prevalence and perspectives of CAM in three urban societies with different healthcare systems. Design. Surveys were sent to students in the three aforementioned cities. Survey distribution occurred over 6 months from May to November 2015. A total of 314 surveys were received. Results. Dietary and vitamin supplements had the highest prevalence collectively (n = 203), followed by meditation, yoga, and massage. Commentary analysis showed the importance of science and evidence in justifying CAM practice. Conclusions. Matching the most prevalent practices with their designated NCCAM categories suggested that the students were attracted to biologically based, body-based, and mind-body practices as the central themes of attraction. Selected and prevalent CAM practices suggested the students' desire to maintain physical and mental fitness. Access to healthcare may have influence on the prevalence of CAM. Indian students were more likely to view CAM as a viable alternative to conventional medicine.

Retinoic acid‐related drugs have shown promising pre‐clinical activity in Adult T‐cell Leukemia/Lymphoma, but RORC signaling has not been explored. Therefore, we investigated transcriptome‐wide interactions of the RORC pathway in HTLV‐1 and ATL, using our own and publicly available gene expression data for ATL and other leukemias. Gene expression data from ATL patients were analyzed using WGCNA to determine gene modules and their correlation to clinical and molecular data. Both PBMCs and CD4 + T‐Cells exhibited decreased RORC expression in four different ATL cohorts. A small subset of RORC hi ATL patients was identified with significantly lower pathognomonic CADM1 and HBZ levels but similar levels of other ATL markers (CD4/CD25/CCR4), hinting at a less aggressive ATL subtype. An age‐dependent decrease in RORC expression was found in HTLV‐1‐infected individuals, but not in healthy controls, suggesting an early molecular event predisposing to leukemogenesis. Genes upstream of RORC signaling were members of a proliferative gene module (containing proliferation markers PCNA/Ki67), whereas downstream members clustered in an anti‐proliferative gene module. IL17C transcripts showed the strongest negative correlation to PCNA in both ATL cohorts, which was replicated in two large cohorts of T‐ and B‐cell acute lymphoid leukemia (ALL). Finally, IL17C expression in purified CD4 + CCR4 + CD26‐CD7‐ “ATL‐like” cells from HTLV‐1‐infected individuals and ATL patients was negatively correlated with clonality, underscoring a possible antileukemic/antiproliferative role. In conclusion, decreased RORC expression and downstream signaling might represent an early event in ATL pathogenesis. An antiproliferative IL17C/PCNA link is shared between ATL, T‐ALL and B‐ALL, suggesting (immuno)therapeutic benefit of boosting RORC/IL17 signaling.

No abstract

Theoretically, identifying prediabetics would reduce the diabetic burden on the American healthcare system. As we expect the prevalence rate of prediabetes to continue increasing, we wonder if there is a better way of managing prediabetics and reducing the economic cost on the healthcare system. To do so, understanding the demographics and behavioral factors of known prediabetics was important. For this purpose, responses of prediabetic/borderline diabetes patients from the most recent publicly available 2015 Behavioral Risk Factor Surveillance System (BRFSS) survey were analyzed. The findings showed that there was a correlation between household income, geographic residence in the US, and risk for developing diabetes mellitus type 2, aside from the accepted risk factors such as high BMI. In conclusion, implementation of the National Diabetes Prevention Program is a rational way of reducing the burden of DM on the healthcare system both economically and by prevalence. However, difficulties arise in ensuring patient compliance to the program and providing access to all regions and communities of the United States. Technology incorporation in the NDPP program would maintain a low-cost implementation by the healthcare system, be affordable and accessible for all participants, and decrease economic burden attributed to diabetes mellitus.

Young male Zucker rats with a leptin receptor mutation are obese, have a non-insulin-dependent diabetes mellitus (NIDDM), and other endocrinopathies. Tibial branches of the sciatic nerve reveal a progressive demyelination that progresses out of the Schwann cells (SCs) where electron-contrast deposits are accumulated while the minor lines or intermembranous SC contacts display exaggerated spacings. Cajal bands contain diversely contrasted vesicles adjacent to the abaxonal myelin layer with blemishes; they appear dispatched centripetally out of many narrow electron densities, regularly spaced around the myelin annulus. These anomalies widen and yield into sectors across the stacked myelin layers. Throughout the worse degradations, the adaxonal membrane remains along the axonal neuroplasm. This peripheral neuropathy with irresponsive leptin cannot modulate hypothalamic-pituitaryadrenal axis and SC neurosteroids, thus exacerbates NIDDM condition. Additionally, the ultrastructure of the progressive myelin alterations may have unraveled a peculiar, centripetal mode of trafficking maintenance of the peripheral nervous system myelin, while some adhesive glycoproteins remain between myelin layers, somewhat hindering the axon mutilation. Heading title: Peripheral neuropathy and myelin ARTICLE HISTORY

No abstract

Myocardial perfusion single photon emission computed tomography provides functional information of the anatomical lesions and MSCT provides anatomical information. Both are two different diagnostic modalities. The MSCT has high NPV in patients with less likelihood for CAD. When compared with CAG, the correlation with MSCT was good and is useful where the calcium score is low.