tbuckley/cabot-search huggingface dataset:
Abstract 19360: Abnormal Cerebral Circulation in Patients With Fontan Circulation
Authors: Clara Kurishima, Seiko Kuwata, Yoichi Iwamoto, Hirofumi Saiki, Hirotaka Ishido, Satoshi Masutani, Hideaki Senzaki
Journal: Circulation (2016)

Background: Impairment of higher brain function often occurs in patients who have undergone Fontan surgery. Apart from the surgery being conducted immediately after birth, abnormalities of the cere...
Hydrogen bonds autonomously powered gelatin methacrylate hydrogels with super-elasticity, self-heal and underwater self-adhesion for sutureless skin and stomach surgery and E-skin
Authors: Bingcheng Liu, Ying Wang, Yong Miao, Xinyu Zhang, Zhexiang Fan, Gurankit Singh, Xingying Zhang, Kaige Xu, Bingyun Li, Zhiqi Hu, Malcolm Xing
Journal: Biomaterials (2018)
Abstract #LB-18: The Arf GTPase-activating protein AGAP2 regulates focal adhesion kinase activity and focal adhesion remodeling
Authors: Yunjuan Zhu, Yuanjun Wu, Jae Kim, Zhimin Wang, Yehia Daaka, zhongzhen Nie
Journal: Cancer Research (2009)

Focal adhesions are specialized sites of cell attachment to the extracellular matrix where integrin receptors link extracellular matrix to the actin cytoskeleton, and focal adhesions are constantly remodeled during cell migration. Focal adhesion kinase (FAK) is, among others, an important regulator of focal adhesion remodeling. AGAP2 is an Arf GTPase-activating protein that is overexpressed in different human cancers. We examined the regulation of FAK activity and remodeling of focal adhesions by AGAP2. Our results show that AGAP2 forms a complex with FAK through the pleckstrin homology domain of AGAP2, and the binding of AGAP2 to FAK is independent of the activation status of EGF receptors. Overexpression of AGAP2 augments the activity of FAK, and, concordantly, the knockdown of AGAP2 with RNAi inhibits the FAK activity following stimulation of EGF or PDGF receptors. AGAP2 is present in focal adhesions and colocalizes with markers of focal adhesions, including paxillin and vinculin. Overexpression of AGAP2 disrupts focal adhesions, and overexpressed AGAP2 colocalizes with paxillin and vinculin in punctate structures in cells with dissolution of focal adhesions. The AGAP2-induced dissolution of focal adhesions is independent of its GAP activity, while the N-terminal G protein-like domain of AGAP2 contributes to its effect on the focal adhesions. Knockdown of AGAP2 stabilizes focal adhesions and slows cell migration. Our results support the idea that AGAP2 binds to and regulates the activity of FAK to increase focal adhesion disassembly and cell migration.  Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr LB-18.
Do not throw the baby out with the bathwater; screening can identify meaningful risk factors for sports injuries
Authors: Evert Verhagen, Nicol van Dyk, Nicholas Clark, Ian Shrier
Journal: British Journal of Sports Medicine (2018)

Norway’s Professor Roald Bahr recently highlighted that screening does not predict which athlete will sustain an injury.1 Some interpreted this to mean screening is useless for injury prevention. However, screening remains essential in our efforts to protect athletes’ health. To extend what has been a robust discussion, we argue how screening can be important for an individual athlete , and offer potential reasons why and how individual screening tests still lack clinical utility.

Previous injury is a well-established injury risk factor. Figure 1 shows data on ACL (re)injuries from Krosshaug et al .2 Applying a traditional (predictive) diagnostic test on these data yields unimpressive results; a positive predictive value of only 29%, with most injuries occurring in previously uninjured athletes. If effective interventions target only previously injured athletes, it would be withheld from the majority of athletes who could benefit. Consequently, we agree with Bahr,1 that all athletes receive effective interventions.



Figure 1 
The relationship between unilateral ACL injuries and ACL reinjuries in a multiseason prospective cohort study in female football and handball players. (Based on original data from Krosshaug et al .2 



But consider another perspective on the same risk factor ‘previous injury’. Regardless of the low predictive value, previous injury is …
Single hepatocellular carcinoma (HCC) ineligible for surgical resection (SR): High tumor control rate with conformal radiotherapy + transarterial chemoembolization (CRT + TACE).
Authors: Philippe Merle, Agnes Rode, Anne-Frederique Manichon, Nadim Fares, Celia Prevost, Christian Ducerf, Mickael Lesurtel, Jean-Yves Mabrut, Francoise Mornex
Journal: Journal of Clinical Oncology (2018)

433 Background: SR is a curative therapy of single HCC. CRT is efficient for small HCC (≤ 5 cm), whereas its combination to TACE (CRT+TACE) is needed for large ( &gt; 5 cm) HCC. However, SR remains the gold-standard in guidelines for large HCC. This work aims to compare these approaches. Methods: Retrospective analysis of prospectively collected data, on patients (pts) included at Lyon North Hepatobiliary Centre, Child-Pugh-A, single HCC. CRT+TACE was decided at the HCC board by ineligibility for SR, radiofrequency or liver transplantation. Outcome of pts was compared between CRT+TACE and SR. Continuous variables were assessed by the t-Student test, and survival analysis by the Cox proportional-hazards regression. Results: 178 pts (68 CRT+TACE, 110 SR), males 78%, cirrhosis 52%, etiology (alcohol 46%, HCV 17%, HBV 13%, NASH 30%), 103 small, 75 large HCC, median age 66 ys, tumor size 50 mm, AFP 8 ng/mL, albuminemia (ALB) 39 g/L, platelets (PLAT) 166 Giga/L, follow-up 33 months. CRT+TACE complete response rate: 92% small / 80% large HCC. Small HCC comparison: CRT+TACE vs SR: age (67 vs 64, P= NS), cirrhosis (94% vs 47%, P&lt; 0.0001), ALB (36 vs 40, P= 0.0001), PLAT (150 vs 201, P= 0.02), AFP (381 vs 300, P= NS). CRT-TACE was a poor outcome factor in univariate analysis for overall survival (OS) (HR 2.32; P= 0.01), progression-free survival (PFS) (HR 1.90; P= 0.007), but did not remain independent in multivariate analysis due to combined factors: age &gt; 70, cirrhosis, ALB &lt; 35, PLAT &lt; 100. Large HCC comparison: CRT+TACE vs SR: age (73 vs 62, P= 0.0008), cirrhosis (70% vs 25%, P= 0.0004), ALB (38 vs 39, P= NS), PLAT (173 vs 240, P= 0.01), AFP (5616 vs 3456, P= NS). CRT-TACE was a poor outcome factor only for OS (HR 3.01; P= 0.0007) in univariate analysis. After adjustment to other factors (age &gt; 70, cirrhosis, PLAT &lt; 100), CRT-TACE was not independent in multivariate analysis for OS ( P= 0.19). Conclusions: CRT+TACE induced an encouraging tumor control rate in a population of older pts, more deteriorated chronic hepatopathy than pts treated by SR. Especially for large HCC, SR was not better than CRT+TACE on the outcome. Prospective randomized trials are warranted to confirm these data.
Polymer physics predicts the effects of structural variants on chromatin architecture
Authors: Simona Bianco, Darío G. Lupiáñez, Andrea M. Chiariello, Carlo Annunziatella, Katerina Kraft, Robert Schöpflin, Lars Wittler, Guillaume Andrey, Martin Vingron, Ana Pombo, Stefan Mundlos, Mario Nicodemi
Journal: Nature Genetics (2018)
An analysis of the efficacy and safety of direct oral anticoagulants (DOACs) in gastrointestinal cancer-associated venous thromboembolism (GI-CAVTE).
Authors: Alejandro Recio Boiles, Hani M. Babiker, Aaron James Scott, Steve Malangone, Ali McBride, Emad Elquza
Journal: Journal of Clinical Oncology (2018)

505 Background: Two major trials and meta-analysis of patients (pts) with active cancer and VTE suggests that apixaban (A) and rivaroxaban (R) showed similar efficacy to enoxaparin and warfarin while having less associated major bleeding. GICA is associated with a higher incidence of VTE compared to other tumors. Moreover, bleeding complications of DOACs are not well defined in GICA pts. We compared the efficacy and safety of DOACs in pts with active GICA and VTE at the University of Arizona Cancer Center (UACC). Methods: A retrospective chart review of pts receiving DOACs with GICA and VTE treated at UACC was performed (11/2013-02/2017). GICA subgroup extracted from clinical trial delineations followed: active cancer, defined as cancer diagnosed at any stage +/- 6 months of VTE diagnosis. Efficacy outcomes were recurrent DVT, nonfatal pulmonary embolism (PE), or fatal PE. Safety outcomes for major bleeding were Hg drop of ≥2 g/dL, transfusion of ≥2 units of PRBC, bleeding in a critical site, or bleeding contributing to death. Fisher exact test is used for testing the difference in categorical variables for p-value &lt; 0.05. Results: Our review included pts on A (n = 28) and R (n = 34). Pts had similar baseline characteristics compared to AMPLIFY (n = 81) and pooled-EINSTEIN (n = 71). Recurrent VTE at 6 months were 7.1% and 2.9% for pts on A and R, respectively. VTE historical comparison to AMPLIFY (3.7%) and EINSTEIN (2.8%) showed no significant difference. Major bleeding at 6 months were 7.1% and 14.7% for A and R, respectively, compared to 2.3% AMPLIFY / 2.8% EINSTEIN. R had the one recurrent non-fatal PE event and a significantly worse safety profile with 2 fatal bleeds (hemopericardium and upper GI bleed) and 2 critical bleeding sites (subarachnoid hemorrhage and retroperitoneal) [p = 0.0348], whereas A had non-significant of the before stated. Conclusions: To our knowledge, this is the first retrospective analysis to present long-term outcome data of DOACs in pts with GICA and VTE, which showed a similar risk of recurrent VTE and worse safety profile with R versus A. This data warrants further prospective clinical analysis of the efficacy and safety of DOACs in pts with GICA and VTE.
188P Treatment switching–adjusted overall survival (OS) in KEYNOTE-024: First-line pembrolizumab versus chemotherapy in patients with advanced non-small cell lung cancer (NSCLC)
Authors: M. Reck, D. Rodríguez-Abreu, A.G. Robinson, R. Hui, T. Csőszi, K. Vandormael, W. Malbecq, M.C. Pietanza, J. Brahmer
Journal: Journal of Thoracic Oncology (2018)
SAT0165 The effect of alendronate on age-specific incidence of key osteoporotic fractures
Authors: M Hochberg, D Thompson, D Black, S Quandt, J Cauley, P Geusens
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> <h3>Objectives</h3> To describe the behaviour of the relative risk (RR), absolute risk reduction (ARR), and number needed to treat (NNT) by attained age for the hip, spine or forearm for alendronate treatment in women with osteoporosis. <h3>Methods</h3> 3658 women with osteoporosis from the Fracture Intervention Trial were followed for 3 to 4.5 years and treated with alendronate (ALN) at 5 mg/day for 2 years followed by 10 mg/day for the remainder of the trial. The age groups used in the analysis were: 55–65, 65–70, 70–75 and 75–85. All fractures were confirmed by x-rays. <h3>Results</h3> Risk reduction of hip, spine and forearm fractures were 53% (RR = 0.47, p &lt; 0.01), 45% (RR = 0.55, P &lt; 0.01) and 30% (RR = 0.70, p = 0.038) respectively. The reductions did not depend on age. The ARR increased with age for each of the fracture sites. For the hip, the ARR increased from 0.13 women per 100 patient-years at risk (PYR) for the 55 to 65 group to 0.53 women per 100 PYR for the 75 to 85 group. The corresponding increases in ARR for the spine were 0.14 and 0.86. The NNTs for 5 years for the hip were 157 for the 55–65 year old and 45 for the 75 to 85 year old women. The corresponding numbers for the spine were 140 and 23. For the composite endpoint, the NNTs (for 5 years) were 38, 25, 17 and 13 for the age groups 55–65, 65–70, 70–75 and 75–85 respectively. <h3>Conclusion</h3> Alendronate is very effective in reducing the risk of osteoporotic fractures, regardless of age.
Efficacy of MaZiRenWan, a Chinese Herbal Medicine, in Patients With Functional Constipation in a Randomized Controlled Trial
Authors: Linda L.D. Zhong, Chung-wah Cheng, Wai Kun, Liang Dai, Dong-dong Hu, Zi-wan Ning, Hai-tao Xiao, Cheng-yuan Lin, Ling Zhao, Tao Huang, Ke Tian, King-hong Chan, Ting-wa Lam, Xiao-rui Chen, Chi-tak Wong, Min Li, Ai-ping Lu, Justin C.Y. Wu, Zhao-xiang Bian
Journal: Clinical Gastroenterology and Hepatology (2018)
Mechanisms of Oncogene-Induced Replication Stress: Jigsaw Falling into Place
Authors: Panagiotis Kotsantis, Eva Petermann, Simon J. Boulton
Journal: Cancer Discovery (2018)

Abstract Oncogene activation disturbs cellular processes and accommodates a complex landscape of changes in the genome that contribute to genomic instability, which accelerates mutation rates and promotes tumorigenesis. Part of this cellular turmoil involves deregulation of physiologic DNA replication, widely described as replication stress. Oncogene-induced replication stress is an early driver of genomic instability and is attributed to a plethora of factors, most notably aberrant origin firing, replication–transcription collisions, reactive oxygen species, and defective nucleotide metabolism. Significance: Replication stress is a fundamental step and an early driver of tumorigenesis and has been associated with many activated oncogenes. Deciphering the mechanisms that contribute to the replication stress response may provide new avenues for targeted cancer treatment. In this review, we discuss the latest findings on the DNA replication stress response and examine the various mechanisms through which activated oncogenes induce replication stress. Cancer Discov; 8(5); 537–55. ©2018 AACR.
Pathological Response in a Triple-Negative Breast Cancer Cohort Treated with Neoadjuvant Carboplatin and Docetaxel According to Lehmann's Refined Classification
Authors: Isabel Echavarria, Sara López-Tarruella, Antoni Picornell, Jose Ángel García-Saenz, Yolanda Jerez, Katherine Hoadley, Henry L. Gómez, Fernando Moreno, María Del Monte-Millan, Iván Márquez-Rodas, Enrique Alvarez, Rocío Ramos-Medina, Javier Gayarre, Tatiana Massarrah, Inmaculada Ocaña, María Cebollero, Hugo Fuentes, Agusti Barnadas, Ana Isabel Ballesteros, Uriel Bohn, Charles M. Perou, Miguel Martin
Journal: Clinical Cancer Research (2018)

Abstract Purpose: Triple-negative breast cancer (TNBC) requires the iden- tification of reliable predictors of response to neoadjuvant chemotherapy (NACT). For this purpose, we aimed to evaluate the performance of the TNBCtype-4 classifier in a cohort of patients with TNBC treated with neoadjuvant carboplatin and docetaxel (TCb). Methods: Patients with TNBC were accrued in a nonrandomized trial of neoadjuvant carboplatin AUC 6 and docetaxel 75 mg/m2 for six cycles. Response was evaluated in terms of pathologic complete response (pCR, ypT0/is ypN0) and residual cancer burden by Symmans and colleagues. Lehmann's subtyping was performed using the TNBCtype online tool from RNAseq data, and germline sequencing of a panel of seven DNA damage repair genes was conducted. Results: Ninety-four out of the 121 patients enrolled in the trial had RNAseq available. The overall pCR rate was 44.7%. Lehmann subtype distribution was 34.0% BL1, 20.2% BL2, 23.4% M, 14.9% LAR, and 7.4% were classified as ER+. Response to NACT with TCb was significantly associated with Lehmann subtype (P = 0.027), even in multivariate analysis including tumor size and nodal involvement, with BL1 patients achieving the highest pCR rate (65.6%), followed by BL2 (47.4%), M (36.4%), and LAR (21.4%). BL1 was associated with a significant younger age at diagnosis and higher ki67 values. Among our 10 germline mutation carriers, 30% were BL1, 40% were BL2, and 30% were M. Conclusions: TNBCtype-4 is associated with significantly different pCR rates for the different subtypes, with BL1 and LAR displaying the best and worse responses to NACT, respectively. Clin Cancer Res; 24(8); 1845–52. ©2018 AACR.
The difference in prognostic value of tumour-infiltrating T cells according to adjuvant chemotherapy in radiochemonaïve gastroesophageal cancer.
Authors: Maria Christina Svensson, Jonna Berntsson, Charlotta Hedner, David Borg, Bjorn Nodin, Karin Leandersson, Agnieszka Krzyzanowska, Anders Bjartell, Jakob Eberhard, Karin Jirstrom
Journal: Journal of Clinical Oncology (2017)

41 Background: Several studies have demonstrated a beneficial prognostic impact of tumour-infiltrating lymphocytes (TILs) in oesophageal and gastric adenocarcinoma, but whether this association differs according to adjuvant chemotherapy has not been reported. Herein, we examined the prognostic impact of different TIL subsets according to adjuvant chemotherapy in these cancer types. Methods: Immunohistochemistry was applied to assess the density of T cells (CD3+, CD8+, FoxP3+) and natural killer (NK)/T cells (CD56+) in radiochemonaïve tumors from a consecutive cohort of 174 patients with resected oesophageal or gastric adenocarcinoma. Cox proportional hazard’s modelling was applied to examine the impact of the investigated markers on time to recurrence (TTR) and overall survival (OS). Results: Dense infiltration of CD3+, CD8+, and FoxP3+ cells were all associated with a significantly prolonged TTR in univariable Cox regression analysis (hazard ratio[HR] = 0.57; 95% confidence interval [CI] 0.37-0.89; HR = 0.31, 95% CI 0.13-0.77, and HR = 0.44, 95% CI 0.28-0.68). This association remained significant for CD8+ and FoxP3+ cells in multivariable analysis, adjusted for age, tumour location, TNM stage, differentiation grade, resection margin and adjuvant chemotherapy ( HR = 0.30, 95% CI 0.11-0.77, and HR = 0.52, 95% CI 0.32-0.84), and borderline significant for CD3+ cells (HR = 0.63, 95% CI 0.39-1.02). Similar associations were observed for all markers in relation to OS. Notably, analysis in strata according to adjuvant chemotherapy revealed that none of the investigated lymphocyte subsets carried prognostic information in patients having received treatment (n = 13; 7.5%), with a significant treatment interaction between CD3+ and CD8+ cells and adjuvant chemotherapy (p interaction 0.035 and 0.021). Conclusions: These results confirm the prognostic value of a high density of TILs in gastroesophageal adenocarcinoma, but also indicate that adjuvant chemotherapy is only beneficial in patients with tumors displaying a low density of TILs. These results are of potential clinical relevance and need to be confirmed in additional, preferentially randomized, studies.
A Randomized, Controlled Trial of Methylprednisolone or Naloxone in the Treatment of Acute Spinal-Cord Injury
Authors: M B Bracken, M J Shepard, W F Collins, T R Holford, W Young, D S Baskin, H M Eisenberg, E Flamm, L Leo-Summers, J Maroon
Journal: New England Journal of Medicine (1990)

Studies in animals indicate that methylprednisolone and naloxone are both potentially beneficial in acute spinal-cord injury, but whether any treatment is clinically effective remains uncertain.
Variability in the use of cut-off points with different commercial and lab-developed assays for PD-L1 expression testing in the NSCLC clinical setting in the United States.
Authors: Pieter De Richter
Journal: Journal of Clinical Oncology (2017)

46 Background: Following the recent approval of several companion diagnostic and complementary diagnostic assays for PD-L1 expression testing, as well as the availability of multiple antibodies for use in laboratory testing, pathologists have a range of tools at their disposal for measuring expression levels of this predictive biomarker. While specific cut-off points for positivity are specified by the assay manufacturer and/or recommended based on trial data, clinicians can choose different cut-off points to define positivity. In this study, we explore the variety of test brands and cut-off points that are being used in clinical practice in the US by examining real-world usage data. Methods: Between June and August 2016, a panel of pathologists (n = 27) in the US were asked to report on their practices relating to PD-L1 expression testing for NSCLC patients, through the submission of online de-identified record forms (n = 167 PD-L1-tested samples). Results: Of the 167 samples, 112 (67%) were tested with the Dako 22C3 pharmDx assay, 37 (22%) with the Dako 28-8 pharmDx assay and 16 (10%) with a lab-developed test (LDT). When using 22C3 pharmDx, 72% of samples were tested with the recommended 50% cut-off point, with the remaining 28% using lower cut-off points, ranging from 1% to 25%. For 28-8 pharmDx, both the 1% cut-off point (in 54% of cases) and the 5% cut-off point (in 35% of cases) were frequently used (1% recommended; 5% being investigated in clinical trials e.g. CHEKMATE-026). LDTs were mostly (88%) employed with a cut-off of 1% across antibodies. Conclusions: The use of PD-L1 expression testing to determine eligibility for PD-(L)1 inhibitors in the clinical setting shows significant fragmentation in the US, with multiple different assays being employed. Furthermore, there is a lack of standardization in terms of the cut-off points that are used when testing with each of those assays. This lack of consistency adds a level of complexity to oncologists treatment decisions when choosing whether or not to treat with a PD-(L)1 inhibitor, and which brand to choose.
DAMBE7: New and Improved Tools for Data Analysis in Molecular Biology and Evolution
Authors: Xuhua Xia
Journal: Molecular Biology and Evolution (2018)

DAMBE is a comprehensive software package for genomic and phylogenetic data analysis on Windows, Linux, and Macintosh computers. New functions include imputing missing distances and phylogeny simultaneously (paving the way to build large phage and transposon trees), new bootstrapping/jackknifing methods for PhyPA (phylogenetics from pairwise alignments), and an improved function for fast and accurate estimation of the shape parameter of the gamma distribution for fitting rate heterogeneity over sites. Previous method corrects multiple hits for each site independently. DAMBE's new method uses all sites simultaneously for correction. DAMBE, featuring a user-friendly graphic interface, is freely available from http://dambe.bio.uottawa.ca (last accessed, April 17, 2018).