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https://www.readbyqxmd.com/read/28088843/evaluating-surrogate-marker-information-using-censored-data
#1
Layla Parast, Tianxi Cai, Lu Tian
Given the long follow-up periods that are often required for treatment or intervention studies, the potential to use surrogate markers to decrease the required follow-up time is a very attractive goal. However, previous studies have shown that using inadequate markers or making inappropriate assumptions about the relationship between the primary outcome and surrogate marker can lead to inaccurate conclusions regarding the treatment effect. Currently available methods for identifying and validating surrogate markers tend to rely on restrictive model assumptions and/or focus on uncensored outcomes...
January 15, 2017: Statistics in Medicine
https://www.readbyqxmd.com/read/28088839/pharmacokinetic-pharmacodynamic-modeling-of-the-pde4-inhibitor-tak-648-in-type-2-diabetes-early-translational-approaches-for-human-dose-prediction
#2
N Plock, S Vollert, M Mayer, G Hanauer, G Lahu
TAK-648 is a PDE4 inhibitor with demonstrated preclinical antidiabetic properties. Our objective was to develop a translational pharmacokinetic/pharmacodynamic (PK/PD) model for human type 2 diabetes (T2D) dose prediction using HbA1c results from a db/db mouse study. Estimated parameters in combination with tPDE4i values calculated for the clinical roflumilast dose of 500 μg were used to translate preclinical effects of TAK-648 to required exposure in humans. A first-in-human study with single TAK-648 doses of 0...
January 15, 2017: Clinical and Translational Science
https://www.readbyqxmd.com/read/28088837/disease-severity-classification-using-quantitative-magnetic-resonance-imaging-data-of-cartilage-in-femoroacetabular-impingement
#3
Lisa L Henn, John Hughes, Eleena Iisakka, Jutta Ellermann, Shabnam Mortazavi, Connor Ziegler, Mikko J Nissi, Patrick Morgan
Femoroacetabular impingement (FAI) is a condition in which subtle deformities of the femoral head and acetabulum (hip socket) result in pathological abutment during hip motion. FAI is a common cause of hip pain and can lead to acetabular cartilage damage and osteoarthritis. For some patients with FAI, surgical intervention is indicated, and it can improve quality of life and potentially delay the onset of osteoarthritis. For other patients, however, surgery is contraindicated because significant cartilage damage has already occurred...
January 15, 2017: Statistics in Medicine
https://www.readbyqxmd.com/read/28088836/upregulation-of-long-noncoding-rna-tug1-promotes-cervical-cancer-cell-proliferation-and-migration
#4
Yingying Hu, Xiangwei Sun, Chenchen Mao, Gangqiang Guo, Sisi Ye, Jianfeng Xu, Ruanmin Zou, Jun Chen, Ledan Wang, Ping Duan, Xiangyang Xue
Long noncoding RNAs (lncRNAs), a novel class of transcripts that have critical roles in carcinogenesis and progression, have emerged as important gene expression modulators. Recent evidence indicates that lncRNA taurine-upregulated gene 1 (TUG1) functions as an oncogene in numerous types of human cancers. However, its function in the development of cervical cancer remains unknown. The aim of this research was to investigate the clinical significance and biological functions of TUG1 in cervical cancer. TUG1 was found to be significantly upregulated in cervical cancer tissues and four cervical cancer cell lines by quantitative real-time polymerase chain reaction (qRT-PCR)...
January 15, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28088808/shunt-surgery-in-idiopathic-intracranial-hypertension-aided-by-electromagnetic-navigation
#5
Elvis J Hermann, Manolis Polemikos, Hans E Heissler, Joachim K Krauss
BACKGROUND: Idiopathic intracranial hypertension (IIH) is characterized by increased cerebrospinal fluid (CSF) pressure and normal or slit ventricles. Lumboperitoneal shunting had been favored by many investigators for CSF diversion in IIH for decades; however, it has been associated with various side effects. Because of the small ventricular size adequate positioning of a ventricular catheter is challenging. OBJECTIVES: Here, we investigated the usefulness of electromagnetic (EM)-guided ventricular catheter placement for ventriculoperitoneal shunting in IIH...
January 14, 2017: Stereotactic and Functional Neurosurgery
https://www.readbyqxmd.com/read/28088807/posterior-versus-anterior-circulation-stroke-in-young-adults-a-comparative-study-of-stroke-aetiologies-and-risk-factors-in-stroke-among-young-fabry-patients-sifap1
#6
Bettina von Sarnowski, Ulf Schminke, Ulrike Grittner, Christian Tanislav, Tobias Böttcher, Michael G Hennerici, Turgut Tatlisumak, Jukka Putaala, Manfred Kaps, Franz Fazekas, Christian Enzinger, Arndt Rolfs, Christof Kessler
BACKGROUND: Although 20-30% of all strokes occur in the posterior circulation, few studies have explored the characteristics of patients with strokes in the posterior compared to the anterior circulation so far. Especially data on young patients is missing. METHODS: In this secondary analysis of data of the prospective multi-centre European sifap1 study that investigated stroke and transient ischemic attack (TIA) patients aged 18-55 years, we compared vascular risk factors, stroke aetiology, presence of white matter hyperintensities (WMH) and cerebral microbleeds (CMB) between patients with ischaemic posterior circulation stroke (PCS) and those having suffered from anterior circulation stroke (ACS) based on cerebral MRI...
January 14, 2017: Cerebrovascular Diseases
https://www.readbyqxmd.com/read/28088806/effects-of-aloe-sterol-supplementation-on-skin-elasticity-hydration-and-collagen-score-a-12-week-double-blind-randomized-controlled-trial
#7
Miyuki Tanaka, Yuki Yamamoto, Eriko Misawa, Kazumi Nabeshima, Marie Saito, Koji Yamauchi, Fumiaki Abe, Fukumi Furukawa
BACKGROUND/AIMS: Our previous study confirmed that Aloe sterol stimulates collagen and hyaluronic acid production in human dermal fibroblasts. This study aims to investigate whether Aloe sterol intake affects skin conditions. METHODS: We performed a 12-week, randomized, double-blind, placebo-controlled study to evaluate the effects of oral Aloe sterol supplementation on skin elasticity, hydration, and the collagen score in 64 healthy women (age range 30-59 years; average 44...
January 14, 2017: Skin Pharmacology and Physiology
https://www.readbyqxmd.com/read/28088803/small-versus-large-ruptured-intracranial-aneurysm-concerns-with-the-site-of-aneurysm
#8
Bum Joon Kim, Hyun Goo Kang, Byeong-Duk Kwun, Jae-Sung Ahn, Jisung Lee, Sung Ho Lee, Dong-Wha Kang, Jong S Kim, Sun U Kwon
BACKGROUND: Although size is one of the strongest predictors, small aneurysms often rupture. We compared the characteristics of small and large ruptured intracranial aneurysms (RIAs) according to their location to find the factors associated with small RIAs in each location. METHODS: Patients with subarachnoid hemorrhage due to saccular RIAs were consecutively enrolled. The sizes were dichotomized as small (<5 mm) or large, and the location was classified as paraclinoid-distal internal carotid artery, sidewalls of anterior or middle cerebral artery (MCA; sidewall), MCA-bifurcation, anterior or posterior communicating artery (Acom or Pcom, respectively), and posterior circulation RIAs...
January 14, 2017: Cerebrovascular Diseases
https://www.readbyqxmd.com/read/28088802/interplay-between-cortical-spreading-depolarization-and-seizures
#9
Daniel R Kramer, Tatsuhiro Fujii, Ifije Ohiorhenuan, Charles Y Liu
Cortical spreading depolarization (CSD) is an electrophysiologic phenomenon found mostly in the setting of neurologic injury resulting in the disturbance of ion homeostasis and leading to changes in the local vascular response. The bioelectric etiology of CSD shares similarities to those in epileptic disorders, yet the relationship between seizures and CSD is unclear, with several studies observing cortical depression before, during, and after seizure activity, thus obscuring our understanding of whether CSD activity potentiates or limits seizures and vice versa...
January 14, 2017: Stereotactic and Functional Neurosurgery
https://www.readbyqxmd.com/read/28088798/the-intracranial-b2leed3s-score-and-the-risk-of-intracranial-hemorrhage-in-ischemic-stroke-patients-under-antiplatelet-treatment
#10
Pierre Amarenco, Leila Sissani, Julien Labreuche, Eric Vicaut, Marie Germaine Bousser, Angel Chamorro, Marc Fisher, Ian Ford, Kim M Fox, Michael G Hennerici, Heinrich Mattle, Peter M Rothwell, Philippe Gabriel Steg, Hans-Christoph Diener, Ralph L Sacco, Jacoba P Greving, Ale Algra
BACKGROUND: Chronic antiplatelet therapy in the post-acute phase of non-cardioembolic ischemic stroke is limited by the risk of intracranial hemorrhage (ICH) complications. METHODS: We developed an ICH risk score based on the PERFORM trial cohort (n = 19,100), which included patients with a non-cardioembolic ischemic stroke or transient ischemic attack, and externally validated this score in one contemporary trial of very similar size and inclusion criteria, the PRoFESS trial (n = 20,332 patients)...
January 14, 2017: Cerebrovascular Diseases
https://www.readbyqxmd.com/read/28088797/automated-interpretation-of-pulmonary-function-tests-in-adults-with-respiratory-complaints
#11
Marko Topalovic, Stefan Laval, Jean-Marie Aerts, Thierry Troosters, Marc Decramer, Wim Janssens
BACKGROUND: The use of pulmonary function tests is primarily based on expert opinion and international guidelines. Current interpretation strategies are using predefined cutoffs for the description of a typical pattern. OBJECTIVES: We aimed to explore the predicted disease outcome based on the American Thoracic Society/European Respiratory Society (ATS/ERS) interpreting strategy. Subsequently, we investigated whether an unbiased machine learning framework integrating lung function with clinical variables may provide alternative decision trees resulting in a more accurate diagnosis...
January 12, 2017: Respiration; International Review of Thoracic Diseases
https://www.readbyqxmd.com/read/28088793/hnrnp-l-mediates-bladder-cancer-progression-by-inhibiting-apoptotic-signaling-and-enhancing-mapk-signaling-pathways
#12
Daojun Lv, Huayan Wu, Rongwei Xing, Fangpeng Shu, Bin Lei, Chengyong Lei, Xumin Zhou, Bo Wan, Yu Yang, Liren Zhong, Xiangming Mao, Yaguang Zou
Heterogeneous nuclear ribonucleoprotein L (hnRNP-L) is a promoter of various kinds of cancers, but its actions in bladder cancer (BC) are unclear. In this study, we investigated the function and the underlying mechanism of hnRNP-L in bladder carcinogenesis. Our results demonstrated that enhanced hnRNP-L expression in BC tissues was associated with poor overall survival of BC patients. Depletion of hnRNP-L significantly suppressed cell proliferation in vitro and inhibited xenograft tumor growth in vivo. Furthermore, downregulation of hnRNP-L resulted in G1-phase cell cycle arrest and enhanced apoptosis accompanied by inhibition of EMT and cell migration...
January 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28088792/impact-of-nudt15-polymorphisms-on-thiopurines-induced-myelotoxicity-and-thiopurines-tolerance-dose
#13
Dandan Yin, Xuyang Xia, Junlong Zhang, Shouyue Zhang, Fei Liao, Ge Zhang, Yan Zhang, Qianqian Hou, Xue Yang, Hong Wang, Zhigui Ma, Heyao Wang, Yiping Zhu, Wei Zhang, Yuelan Wang, Bo Liu, Lanlan Wang, Heng Xu, Yang Shu
Thiopurines are widely used as anticancer and immunosuppressive agents. However, life-threatening myelotoxicity has been noticed and largely explained by genetic variations, including NUDT15 polymorphisms (e.g., rs116855232). In this study, we conduct a meta-analysis to investigate the impact of rs116855232 on thiopurines-induced myelotoxicity susceptibility (1752 patients from 7 independent cohorts), as well as on thiopurines intolerance dose (2745 patients from 13 cohorts). Variant allele of rs116855232 contributes 7...
January 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28088791/sinomenine-hydrochloride-inhibits-breast-cancer-metastasis-by-attenuating-inflammation-related-epithelial-mesenchymal-transition-and-cancer-stemness
#14
Xiao Li, Pingping Li, Chao Liu, Yu Ren, Xiaojiang Tang, Ke Wang, Jianjun He
Sinomenine hydrochloride (SH) has been investigated for its anti-tumor growth effect. We have previously reported that SH inhibited breast cancer cell proliferation via MAPKs signaling. However, whether SH could inhibit tumor metastasis has not been fully explored. In this study, we found that SH suppressed the metastasis potential of breast cancer cells. The wound healing and transwell assays showed that SH inhibited the migration and invasion ability of both 4T1 and MDA-MB-231 breast cancer cells. The orthotopic mouse model of 4T1 and the experimental mouse model of MDA-MB-231-luc (MDA-MB-231 cell line expressing firefly luciferase) demonstrated that SH treatment inhibited breast cancer metastasis by inhibiting epithelial-mesenchymal transition (EMT) and cancer stem cell (CSC) properties without obvious hepatotoxicity and renal toxicity...
January 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28088772/thrombospondin-immune-regulation-and-the-kidney
#15
Claudio Ponticelli, Hans-Joachim Anders
Most therapeutic attempts to prevent the progression of kidney diseases have been based on interventions to inhibit the production of transforming growth factor-β (TGF-β). Thrombospondins (TSPs) play an important role in activating TGF-β. In the healthy kidney, two TSPs are expressed, TSP1 and TSP2, which exert contrasting effects. While TSP1 is a major activator of TGF-β in renal cells and exerts pro-inflammatory effects both in vitro and in vivo, TSP2 lacks the ability for TGF-β activation but regulates matrix remodeling and inflammation in experimental kidney disease...
January 14, 2017: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/28088771/do-we-still-need-cross-sectional-studies-in-nephrology-yes-we-do
#16
Giovanni Tripepi, Graziella D'Arrigo, Kitty J Jager, Vianda S Stel, Friedo W Dekker, Carmine Zoccali
Cross-sectional studies represent the second line of evidence (after case reports) in the ladder of evidence aimed at defining disease aetiology. This study design is used to generate hypotheses about the determinants of a given disease but also to investigate the accuracy of diagnostic tests and to assess the burden of a given disease in a population. The intrinsic limitation of cross-sectional studies, when applied to generate aetiological hypotheses, is that both the exposure under investigation and the disease of interest are measured at the same point in time...
January 14, 2017: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/28088747/decreased-s100b-serum-levels-after-treatment-in-bipolar-patients-in-a-manic-phase
#17
Meng-Chang Tsai, Tiao-Lai Huang
BACKGROUND: Previous studies have suggested that patients with bipolar disorder might have brain damage. The aim of this study was to investigate the serum levels of brain injury biomarkers and S100A10 in bipolar patients in a manic phase, and evaluate the changes in S100B, neuron specific enolase (NSE), heat shock protein 70 (HSP70) and S100A10 after treatment. METHOD: We consecutively enrolled 17 bipolar inpatients in a manic phase and 30 healthy subjects. Serum brain injury biomarkers and S100A10 were measured with assay kits...
January 3, 2017: Comprehensive Psychiatry
https://www.readbyqxmd.com/read/28088742/patterns-of-drug-use-and-hiv-infection-among-adults-in-a-nationally-representative-sample
#18
Stephanie Shiau, Stephen M Arpadi, Michael T Yin, Silvia S Martins
BACKGROUND: Little is known about drug use patterns among people living with HIV in comparison to an uninfected group in the general population. The aim of this study was to investigate the association between legal and illegal drug use and HIV infection in a nationally representative sample of adults in the United States. METHODS: Public use data files (2005-2014) from the National Survey on Drug Use and Health (NSDUH) were used. Respondents were asked whether a medical professional had ever told them that they had HIV/AIDS...
January 7, 2017: Addictive Behaviors
https://www.readbyqxmd.com/read/28088740/associations-between-adverse-childhood-experiences-student-teacher-relationships-and-non-medical-use-of-prescription-medications-among-adolescents
#19
Myriam Forster, Amy L Gower, Iris W Borowsky, Barbara J McMorris
OBJECTIVE: Few studies have investigated associations between adverse childhood experiences (ACE) and nonmedical use of prescription medication (NMUPM) in population-based samples of adolescents, and even fewer have examined whether promotive factors might buffer these effects. The present study assesses the direct effects of ACE and positive student-teacher relationships on NUMPD and whether positive student-teacher relationships moderate this association. DESIGN: Data were from the 2013 Minnesota Student Survey (MSS), an in-school survey administered every three years to students throughout Minnesota...
January 6, 2017: Addictive Behaviors
https://www.readbyqxmd.com/read/28088738/piperine-modulates-isoproterenol-induced-myocardial-ischemia-through-antioxidant-and-anti-dyslipidemic-effect-in-male-wistar-rats
#20
Velumani Dhivya, Lohanathan Bharathi Priya, Hilda T Chirayil, Swamiappan Sathiskumar, Chih-Yang Huang, Viswanadha Vijaya Padma
Myocardial infarction due to ischemia accounts for majority of deaths among cardiovascular disorders. Isoproterenol (ISO) induced myocardial infarction and the protection offered by piperine was investigated in the present report. Lipid profile analysis by determining the levels of cholesterol, phospholipids, triglycerides and lipoproteins in serum and heart tissues showed anti-dyslipidemic action of piperine against ISO induced myocardial injury by modulating the ISO induced altered lipid profiles, maintaining to near control values...
January 12, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
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