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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/28088842/unbiased-split-variable-selection-for-random-survival-forests-using-maximally-selected-rank-statistics
#2
Marvin N Wright, Theresa Dankowski, Andreas Ziegler
The most popular approach for analyzing survival data is the Cox regression model. The Cox model may, however, be misspecified, and its proportionality assumption may not always be fulfilled. An alternative approach for survival prediction is random forests for survival outcomes. The standard split criterion for random survival forests is the log-rank test statistic, which favors splitting variables with many possible split points. Conditional inference forests avoid this split variable selection bias. However, linear rank statistics are utilized by default in conditional inference forests to select the optimal splitting variable, which cannot detect non-linear effects in the independent variables...
January 15, 2017: Statistics in Medicine
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/28088808/shunt-surgery-in-idiopathic-intracranial-hypertension-aided-by-electromagnetic-navigation
#4
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
#5
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
#6
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
#7
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/28088801/natural-history-of-untreated-hemifacial-spasm-a-study-of-104-consecutive-patients-over-5-years
#8
Jeong-A Lee, Kyung-Hee Kim, Kwan Park
BACKGROUND: The natural history without treatment of a large series of hemifacial spasm (HFS) patients has not been well-documented. OBJECTIVE: The purpose of this study was to characterize the natural history and clinical outcome in patients with HFS. METHODS: The initial visits of all 2,155 patients and the diagnosis of HFS took place between 2001 and 2010. In 1,775 of the patients, compressing vessels were identified on magnetic resonance imaging...
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
#9
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
#10
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/28088794/the-lack-of-association-between-fcn2-gene-promoter-region-polymorphisms-and-dental-caries-in-polish-children
#11
T Olszowski, M Milona, J Janiszewska-Olszowska, K Safranow, K Skonieczna-Żydecka, A Walczak, M Sikora, D Chlubek, A Madlani, G Adler
The aim of this study was to examine the association of single-nucleotide polymorphisms (SNPs) in the gene encoding ficolin-2 protein (FCN2 gene) at positions -986 (rs17514136), -602 (rs3124953), and -4 (rs3124952) with dental caries in Polish children. Two hundred and sixty Polish Caucasian children aged 15 years were enrolled in this study: 82 with "higher" caries experience (DMFT >5) and 178 with "lower" caries experience (DMFT ≤5). In addition, subjects with caries experience (DMFT ≥1) and caries-free subjects (DMFT = 0) were compared...
January 14, 2017: Caries Research
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/28088790/intraperitoneal-immunotherapy-with-t-cells-stably-and-transiently-expressing-anti-epcam-car-in-xenograft-models-of-peritoneal-carcinomatosis
#15
Wei Xia Ang, Zhendong Li, Zhixia Chi, Shou-Hui Du, Can Chen, Johan C K Tay, Han Chong Toh, John E Connolly, Xue Hu Xu, Shu Wang
The epithelial cell adhesion molecule (EpCAM) is overexpressed in a wide variety of tumor types, including peritoneal carcinomatosis (PC) from gastrointestinal and gynecological malignancies. To develop a chimeric antigen receptor T (CART) cell therapy approach to treat patients with end-stage PC, we constructed third generation CARs specific to EpCAM using the 4D5MOC-B single chain variable fragment. CART cells were generated with lentiviral transduction and exhibited specific in vitro killing activity against EpCAM-positive human ovarian and colorectal cancer cells...
January 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28088789/gprc5a-knockout-mouse-lung-epithelial-cells-predicts-ceruloplasmin-lipocalin-2-and-periostin-as-potential-biomarkers-at-early-stages-of-lung-tumorigenesis
#16
Beibei Sun, Wenzheng Guo, Song Hu, Feng Yao, Keke Yu, Jie Xing, Ronghua Wang, Hongyong Song, Yueling Liao, Tong Wang, Pengfei Jiang, Baohui Han, Jiong Deng
Lung cancer is the leading cause of cancer death. As most of lung cancer patients were diagnosed with the advanced stage, early detection is considered as the most effective strategy to reduce high mortality. Thus, it is desirable to identify specific biomarkers at early stages of lung tumorigenesis. GPRC5A is a lung tumor suppressor gene. GPRC5A deficiency is linked to lung cancer development. We hyposthesized that, dysregulated gene expression that results from Gprc5a deficiency may provide potential biomarkers at early stages of lung tumorigenesis...
January 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28088788/dual-syk-jak-inhibition-overcomes-ibrutinib-resistance-in-chronic-lymphocytic-leukemia-cerdulatinib-but-not-ibrutinib-induces-apoptosis-of-tumor-cells-protected-by-the-microenvironment
#17
Ailin Guo, Pin Lu, Greg Coffey, Pamela Conley, Anjali Pandey, Y Lynn Wang
Ibrutinib (BTK inhibitor) has generated remarkable responses in CLL. However, the drug, to a large extent, does not cause cell death directly and does not eradicate CLL malignant clones. Inability to eradicate CLL has fostered resistance generation. Once patients become resistant, they do poorly with a median survival of 3-4 months. Novel therapeutic strategies are needed to prevent resistance, improve treatment outcome and ultimately cure the disease. Herein, we explore dual targeting of the BCR and JAK-STAT pathways with a novel single agent, cerdulatinib, which selectively inhibits both SYK (a BCR component) and JAK kinases...
January 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28088787/hint2-downregulation-promotes-colorectal-carcinoma-migration-and-metastasis
#18
Weihua Li, Shaoxin Cai, Le Wang, Changshun Yang, Biaohuan Zhou, Huan Wang
Histidine triad nucleotide-binding 2 (HINT2), a member of the histidine triad proteins family, sensitizes cells to apoptosis in hepatocellular carcinoma. Here, we showed that HINT2 expression is lower in primary colorectal cancer (CRC) and metastasis tissues than in normal colorectal tissues, and that HINT2 abundance is inversely correlated with CRC tumor stage. Treating CRC cells with 5-aza-2'-deoxycytidine, a demethylating agent, upregulated HINT2, suggesting HINT2 downregulation is caused by methylation of the gene promoter...
January 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28088786/ezh2-inhibition-suppresses-endometrial-cancer-progression-via-mir-361-twist-axis
#19
Kei Ihira, Peixin Dong, Ying Xiong, Hidemichi Watari, Yosuke Konno, Sharon Jb Hanley, Masayuki Noguchi, Noriyuki Hirata, Futoshi Suizu, Takahiro Yamada, Masataka Kudo, Noriaki Sakuragi
EZH2 inhibition and reactivation of tumor suppressor microRNAs (miRNAs) represent attractive anti-cancer therapeutic strategies. We found that EZH2-suppressed let 7b and miR-361, two likely tumor suppressors, inhibited endometrial cancer (EC) cell proliferation and invasion, and abrogated cancer stem cell-like properties. In EC cells, EZH2 induced and functioned together with YY1 to epigenetically suppress miR-361, which upregulated Twist, a direct target of miR-361. Treating EC cells with GSK343, a specific EZH2 inhibitor, mimicked the effects of siRNA-mediated EZH2 knockdown, upregulating miR-361 and downregulating Twist expression...
January 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28088785/the-igh-locus-3-cis-regulatory-super-enhancer-co-opts-aid-for-allelic-transvection
#20
Sandrine Le Noir, Brice Laffleur, Claire Carrion, Armand Garot, Sandrine Lecardeur, Eric Pinaud, Yves Denizot, Jane Skok, Michel Cogné
Immunoglobulin heavy chain (IgH) alleles have ambivalent relationships: they feature both allelic exclusion, ensuring monoallelic expression of a single immunoglobulin (Ig) allele, and frequent inter-allelic class-switch recombination (CSR) reassembling genes from both alleles. The IgH locus 3' regulatory region (3'RR) includes several transcriptional cis-enhancers promoting activation-induced cytidine deaminase (AID)-dependent somatic hypermutation (SHM) and CSR, and altogether behaves as a strong super-enhancer...
January 10, 2017: Oncotarget
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