Citations

AbstractObjective:The aim of the study was to determine the association between self-reported vasomotor symptoms (VMS) and obstructive sleep apnea (OSA) risk.Methods:The STOP-BANG to evaluate OSA and Menopause Rating Scale (MRS) were administered to 2,935 women seen in the Women's Health Clinic at Mayo Clinic in Rochester, MN, between May 2015 and December 2016. Of these, 1,691 women were included in the analysis. Total MRS and VMS ratings were compared using logistic regression, with age, smoking, and body mass index (BMI) included as covariates between women at intermediate/high risk versus low risk for OSA.Results:Total MRS scores were significantly higher in women with intermediate/high-risk OSA scores versus those with low-risk scores [mean (SD): 16.8 (8.0) vs 12.9 (7.0),P < 0.001]. Women at intermediate/high OSA risk were older, had more education, self-reported hypertension, BMI >35 kg/m2, and were less likely to be married or employed. Self-reported severe/very severe VMS were significantly associated with intermediate/high risk versus low risk for OSA (26.6% vs 15.0%;P < 0.001). After adjusting for age, BMI, smoking status, and self-reported hypertension, the odds of having intermediate/high risk for OSA were 1.87 times higher for those with severe/very severe VMS compared with those with none/mild/moderate VMS (95% CI, 1.29-2.71,P < 0.001). This association persisted upon subgroup analysis based on BMI <25 kg/m2(odds ratio 2.15; 95% CI, 1.12-4.16,P= 0.022).Conclusions:Self-reported severe/very severe VMS were associated with intermediate/high risk for OSA in midlife women, even in women with BMI <25 kg/m2. Given the limitations of the STOP-BANG tool, OSA risk may, however, have been overestimated.

Objective Determinants of the increased risk of diffuse large B-cell lymphoma (DLBCL) in SLE are unclear. Using data from a recent lymphoma genome-wide association study (GWAS), we assessed whether certain lupus-related single nucleotide polymorphisms (SNPs) were also associated with DLBCL. Methods GWAS data on European Caucasians from the International Lymphoma Epidemiology Consortium (InterLymph) provided a total of 3857 DLBCL cases and 7666 general-population controls. Data were pooled in a random-effects meta-analysis. Results Among the 28 SLE-related SNPs investigated, the two most convincingly associated with risk of DLBCL included the CD40 SLE risk allele rs4810485 on chromosome 20q13 (OR per risk allele=1.09, 95% CI 1.02 to 1.16, p=0.0134), and the HLA SLE risk allele rs1270942 on chromosome 6p21.33 (OR per risk allele=1.17, 95% CI 1.01 to 1.36, p=0.0362). Of additional possible interest were rs2205960 and rs12537284. The rs2205960 SNP, related to a cytokine of the tumour necrosis factor superfamily TNFSF4, was associated with an OR per risk allele of 1.07, 95% CI 1.00 to 1.16, p=0.0549. The OR for the rs12537284 (chromosome 7q32, IRF5 gene) risk allele was 1.08, 95% CI 0.99 to 1.18, p=0.0765. Conclusions These data suggest several plausible genetic links between DLBCL and SLE.

ABSTRACTX‐chromosome inactivation (XCI) epigenetically silences transcription of an X chromosome in females; patterns of XCI are thought to be aberrant in women's cancers, but are understudied due to statistical challenges. We develop a two‐stage statistical framework to assess skewed XCI and evaluate gene‐level patterns of XCI for an individual sample by integration of RNA sequence, copy number alteration, and genotype data. Our method relies on allele‐specific expression (ASE) to directly measure XCI and does not rely on male samples or paired normal tissue for comparison. We model ASE using a two‐component mixture of beta distributions, allowing estimation for a given sample of the degree of skewness (based on a composite likelihood ratio test) and the posterior probability that a given gene escapes XCI (using a Bayesian beta‐binomial mixture model). To illustrate the utility of our approach, we applied these methods to data from tumors of ovarian cancer patients. Among 99 patients, 45 tumors were informative for analysis and showed evidence of XCI skewed toward a particular parental chromosome. For 397 X‐linked genes, we observed tumor XCI patterns largely consistent with previously identified consensus states based on multiple normal tissue types. However, 37 genes differed in XCI state between ovarian tumors and the consensus state; 17 genes aberrantly escaped XCI in ovarian tumors (including many oncogenes), whereas 20 genes were unexpectedly inactivated in ovarian tumors (including many tumor suppressor genes). These results provide evidence of the importance of XCI in ovarian cancer and demonstrate the utility of our two‐stage analysis.

Abstract Patient-derived tumor xenograft (PDX) mouse models have emerged as an important oncology research platform to study tumor evolution, mechanisms of drug response and resistance, and tailoring chemotherapeutic approaches for individual patients. The lack of robust standards for reporting on PDX models has hampered the ability of researchers to find relevant PDX models and associated data. Here we present the PDX models minimal information standard (PDX-MI) for reporting on the generation, quality assurance, and use of PDX models. PDX-MI defines the minimal information for describing the clinical attributes of a patient's tumor, the processes of implantation and passaging of tumors in a host mouse strain, quality assurance methods, and the use of PDX models in cancer research. Adherence to PDX-MI standards will facilitate accurate search results for oncology models and their associated data across distributed repository databases and promote reproducibility in research studies using these models. Cancer Res; 77(21); e62–66. ©2017 AACR.

AbstractIntroductionWe sought to assess the individual and combined contribution of limbic and neocortical α‐synuclein, tau, and amyloid β (Aβ) to duration of illness in dementia with Lewy bodies (DLB).MethodsQuantitative digital pathology of limbic and neocortical α‐synuclein, tau, and Aβ was assessed in 49 patients with clinically probable DLB. Regression modeling examined the unique and shared contribution of each pathology to the variance of illness duration.ResultsPatients with diffuse Lewy body disease had more severe pathology of each type and a shorter duration of illness than individuals with transitional Lewy body disease. The three pathologies accounted for 25% of the total variance of duration of illness, with 19% accounted for by α‐synuclein alone or in combination with tau and Aβ. When the diffuse Lewy body disease group was examined separately, α‐synuclein deposition significantly exceeded that of tau and Aβ. In this model, 20% of 24% total variance in the model for duration of illness was accounted for independently by α‐synuclein.DiscussionIn DLB, α‐synuclein is an important predictor of disease duration, both independently and synergistically with tau and Aβ.

The patellofemoral joint is an articulation between the patella and the femoral trochlea, which serves to increase the lever arm of the extensor mechanism. The stability of the patella within the trochlear groove is supported statically by the bony confines of the groove itself, as well as the medial patellofemoral ligament, and dynamically by the vastus musculature. Pathologic changes seen on magnetic resonance imaging (MRI) are frequently well correlated with findings found by arthroscopy at the time of surgery. Degenerative changes to the articular cartilage, osteochondral lesions and loose bodies, tears in the retinaculum, and the medial patellofemoral ligament can be seen in MRI and are well correlated with arthroscopy. In addition, other findings that may predispose an individual to injury or degenerative changes over time, such as patella alta and trochlear dysplasia, can also be assessed by MRI and observed arthroscopically.

Abstract Introduction Comparative transcriptome analyses in Alzheimer's disease (AD) and other neurodegenerative proteinopathies can uncover both shared and distinct disease pathways. Methods We analyzed 940 brain transcriptomes including patients with AD, progressive supranuclear palsy (PSP; a primary tauopathy), and control subjects. Results We identified transcriptional coexpression networks implicated in myelination, which were lower in PSP temporal cortex (TCX) compared with AD. Some of these associations were retained even after adjustments for brain cell population changes. These TCX myelination network structures were preserved in cerebellum but they were not differentially expressed in cerebellum between AD and PSP. Myelination networks were downregulated in both AD and PSP, when compared with control TCX samples. Discussion Downregulation of myelination networks may underlie both PSP and AD pathophysiology, but may be more pronounced in PSP. These data also highlight conservation of transcriptional networks across brain regions and the influence of cell type changes on these networks.