Computed Tomography-Based Body Composition Is Not Consistently Associated with Outcome in Older Patients with Colorectal Cancer

Background: Current literature is inconsistent in the associations between computed tomography (CT)-based body composition measures and adverse outcomes in older patients with colorectal cancer (CRC). Moreover, the associations with consecutive treatment modalities have not been studied. This study compared the associations of CT-based body composition measures with surgery- and chemotherapy-related complications and survival in older patients with CRC. Materials and Methods: A retrospective single-center cohort study was conducted in patients with CRC aged ≥65 years who underwent elective surgery between 2010 and 2014. Gender-specific standardized scores of preoperative CT-based skeletal muscle (SM), muscle density, intermuscular adipose tissue (IMAT), visceral adipose tissue (VAT), subcutaneous adipose tissue, IMAT percentage, SM/VAT, and body mass index (BMI) were tested for their associations with severe postoperative complications, prolonged length of stay (LOS), readmission, and dose-limiting toxicity using logistic regression and 1-year and long-term survival (range 3.7–6.6 years) using Cox regression. Bonferroni correction was applied to account for multiple testing. Results: The study population consisted of 378 patients with CRC with a median age of 73.4 (interquartile range 69.5–78.4) years. Severe postoperative complications occurred in 13.0%, and 39.4% of patients died during follow-up. Dose-limiting toxicity occurred in 77.4% of patients receiving chemotherapy (n = 53). SM, muscle density, VAT, SM/VAT, and BMI were associated with surgery-related complications, and muscle density, IMAT, IMAT percentage, and SM/VAT were associated with long-term survival. After Bonferroni correction, no CT-based body composition measure was significantly associated with adverse outcomes. Higher BMI was associated with prolonged LOS. Conclusion: The associations between CT-based body composition measures and adverse outcomes of consecutive treatment modalities in older patients with CRC were not consistent or statistically significant. Implications for Practice: Computed tomography (CT)-based body composition, including muscle mass, muscle density, and intermuscular, visceral, and subcutaneous adipose tissue, showed inconsistent and nonsignificant associations with surgery-related complications, dose-limiting toxicity, and overall survival in older adults with colorectal cancer. This study underscores the need to verify whether CT-based body composition measures are worth implementing in clinical practice

Determinants of medication adherence to antihypertensive medications among a Chinese population using Morisky medication adherence scale

<b>Background and objectives</b> Poor adherence to medications is one of the major public health challenges. Only one-third of the population reported successful control of blood pressure, mostly caused by poor drug adherence. However, there are relatively few reports studying the adherence levels and their associated factors among Chinese patients. This study aimed to study the adherence profiles and the factors associated with antihypertensive drug adherence among Chinese patients.<p></p> <b>Methods</b> A cross-sectional study was conducted in an outpatient clinic located in the New Territories Region of Hong Kong. Adult patients who were currently taking at least one antihypertensive drug were invited to complete a self-administered questionnaire, consisting of basic socio-demographic profile, self-perceived health status, and self-reported medication adherence. The outcome measure was the Morisky Medication Adherence Scale (MMAS-8). Good adherence was defined as MMAS scores greater than 6 points (out of a total score of 8 points).<p></p> <b>Results</b> From 1114 patients, 725 (65.1%) had good adherence to antihypertensive agents. Binary logistic regression analysis was conducted. Younger age, shorter duration of antihypertensive agents used, job status being employed, and poor or very poor self-perceived health status were negatively associated with drug adherence.<p></p> <b>Conclusion</b> This study reported a high proportion of poor medication adherence among hypertensive subjects. Patients with factors associated with poor adherence should be more closely monitored to optimize their drug taking behavior

A simple spreadsheet-based, MIAME-supportive format for microarray data: MAGE-TAB

BACKGROUND: Sharing of microarray data within the research community has been greatly facilitated by the development of the disclosure and communication standards MIAME and MAGE-ML by the MGED Society. However, the complexity of the MAGE-ML format has made its use impractical for laboratories lacking dedicated bioinformatics support. RESULTS: We propose a simple tab-delimited, spreadsheet-based format, MAGE-TAB, which will become a part of the MAGE microarray data standard and can be used for annotating and communicating microarray data in a MIAME compliant fashion. CONCLUSION: MAGE-TAB will enable laboratories without bioinformatics experience or support to manage, exchange and submit well-annotated microarray data in a standard format using a spreadsheet. The MAGE-TAB format is self-contained, and does not require an understanding of MAGE-ML or XML

Combining specificity determining and conserved residues improves functional site prediction

<p>Abstract</p> <p>Background</p> <p>Predicting the location of functionally important sites from protein sequence and/or structure is a long-standing problem in computational biology. Most current approaches make use of sequence conservation, assuming that amino acid residues conserved within a protein family are most likely to be functionally important. Most often these approaches do not consider many residues that act to define specific sub-functions within a family, or they make no distinction between residues important for function and those more relevant for maintaining structure (e.g. in the hydrophobic core). Many protein families bind and/or act on a variety of ligands, meaning that conserved residues often only bind a common ligand sub-structure or perform general catalytic activities.</p> <p>Results</p> <p>Here we present a novel method for functional site prediction based on identification of conserved positions, as well as those responsible for determining ligand specificity. We define Specificity-Determining Positions (SDPs), as those occupied by conserved residues within sub-groups of proteins in a family having a common specificity, but differ between groups, and are thus likely to account for specific recognition events. We benchmark the approach on enzyme families of known 3D structure with bound substrates, and find that in nearly all families residues predicted by SDPsite are in contact with the bound substrate, and that the addition of SDPs significantly improves functional site prediction accuracy. We apply SDPsite to various families of proteins containing known three-dimensional structures, but lacking clear functional annotations, and discusse several illustrative examples.</p> <p>Conclusion</p> <p>The results suggest a better means to predict functional details for the thousands of protein structures determined prior to a clear understanding of molecular function.</p

Hypusine biosynthesis in β cells links polyamine metabolism to facultative cellular proliferation to maintain glucose homeostasis

Deoxyhypusine synthase (DHPS) utilizes the polyamine spermidine to catalyze the hypusine modification of the mRNA translation factor eIF5A and promotes oncogenesis through poorly-defined mechanisms. Because germline deletion of Dhps is embryonically lethal, its role in normal postnatal cellular function in vivo remains unknown. We generated a mouse model that enabled the inducible, postnatal deletion of Dhps specifically in postnatal islet β cells, which function to maintain glucose homeostasis. Removal of Dhps did not have an effect under normal physiologic conditions. However, upon development of insulin resistance, which induces β-cell proliferation, Dhps deletion caused alterations in proteins required for mRNA translation and protein secretion, reduced production of the cell cycle molecule cyclin D2, impaired β-cell proliferation, and induced overt diabetes. We found that hypusine biosynthesis was downstream of protein kinase C-ζ and was required for c-Myc-induced proliferation. Our studies reveal a requirement for DHPS in β cells to link polyamines to mRNA translation to effect facultative cellular proliferation and glucose homeostasis

Variants at multiple loci implicated in both innate and adaptive immune responses are associated with Sjögren’s syndrome

Sjögren’s syndrome is a common autoimmune disease (~0.7% of European Americans) typically presenting as keratoconjunctivitis sicca and xerostomia. In addition to strong association within the HLA region at 6p21 (Pmeta=7.65×10−114), we establish associations with IRF5-TNPO3 (Pmeta=2.73×10−19), STAT4 (Pmeta=6.80×10−15), IL12A (Pmeta =1.17×10−10), FAM167A-BLK (Pmeta=4.97×10−10), DDX6-CXCR5 (Pmeta=1.10×10−8), and TNIP1 (Pmeta=3.30×10−8). Suggestive associations with Pmeta<5×10−5 were observed with 29 regions including TNFAIP3, PTTG1, PRDM1, DGKQ, FCGR2A, IRAK1BP1, ITSN2, and PHIP amongst others. These results highlight the importance of genes involved in both innate and adaptive immunity in Sjögren’s syndrome

New high statistics measurement of Ke4K_{e4} decay form factors and ππ\pi\pi scattering phase shifts

We report results from a new measurement of the $K_{e4}$ decay $K^{\pm} \rightarrow \pi^{+}\pi^{-}e^{\pm}\nu$ by the NA48/2 collaboration at the CERN SPS, based on a partial sample of more than 670000 $K_{e4}$ decays in both charged modes collected in 2003. The form factors of the hadronic current (F, G, H) and $\pi\pi$ phase difference ($\delta=\delta_{s}-\delta_{p}$) have been measured in ten independent bins of the $\pi\pi$ mass spectrum to investigate the variation. A sizeable acceptance at large $\pi\pi$ mass, a low background and a very good resolution contribute to an improved experimental accuracy, a factor two better than in the previous measurement, when extracting the $\pi\pi$ scattering lengths $a^{0}_{0}$ and $a^{2}_{0}$. Under the assumption of isospin symmetry and using numerical solutions of the Roy equations, the following values are obtained in the plane ($a^{0}_{0}, a^{2}_{0}): a^{0}_{0}=0.233 \pm 0.016_{stat} \pm 0.007_{syst}, a^{2}_{0}=-0.0471 \pm 0.011_{stat} \pm 0.004_{syst}$. The presence of potentially large isospin effects is also considered and will allow comparison with precise predictions from Chiral Perturbation Theory

Search for direct CP violating charge asymmetries in K±→π±π+π−K^\pm\to\pi^\pm\pi^+\pi^- and K±→π±π0π0K^\pm\to\pi^\pm\pi^0\pi^0 decays

A measurement of the direct CP violating charge asymmetries of the Dalitz plot linear slopes $A_g=(g^+-g^-)/(g^++g^-)$ in $K^\pm\to\pi^\pm\pi^+\pi^-$ and $K^\pm\to\pi^\pm\pi^0\pi^0$ decays by the NA48/2 experiment at CERN SPS is presented. A new technique of asymmetry measurement involving simultaneous $K^+$ and $K^-$ beams and a large data sample collected allowed a result of an unprecedented precision. The charge asymmetries were measured to be $A^c_g=(-1.5\pm2.2)\times10^{-4}$ with $3.11\times 10^9$ $K^{\pm}\to\pi^\pm\pi^+\pi^-$ decays, and $A^n_g=(1.8\pm1.8)\times10^{-4}$ with $9.13\times 10^7$ $K^{\pm}\to\pi^\pm\pi^0\pi^0$ decays. The precision of the results is limited mainly by the size of the data sample.Comment: 29 pages, 9 figures. An updated version accepted by the EPJ

Observation of Charge-Dependent Azimuthal Correlations in p-Pb Collisions and Its Implication for the Search for the Chiral Magnetic Effect

Peer reviewe