tbuckley/cabot-search huggingface dataset:
IN-SEASON ARCHITECTURAL ADAPTATIONS OF THE BICEPS FEMORIS LONG HEAD IN ELITE AUSTRALIAN FOOTBALLERS
Authors: Ryan Timmins, Matthew Bourne, Morgan Williams, David Opar
Journal: British Journal of Sports Medicine (2017)

Background Hamstring strain injuries (HSI) are the predominant injury in the elite Australian Football League (AFL). Athletes who possess short biceps femoris long head (BFlh) fascicle lengths have an increased risk of future HSI than those who have longer fascicles. Fascicle length can be altered following interventions, however it is unknown what alterations occur in-season. It is also unknown if this may differ between those with and without a history of HSI. Objective Determine what architectural changes occur during an AFL season. Identify if these changes are different between those with and without a history of HSI. Design Cross-sectional retrospective injury study. Setting Elite Australian Football. Participants Thirty elite AFL players with (n=12) and without (n=18) a unilateral history of HSI. Assessment of Risk Factors BFlh architecture was assessed once a month on six separate occasions during the 2016 AFL season using two-dimensional ultrasound. Main Outcome Measurements BFlh fascicle length. Results Limbs with a history of HSI possess shorter fascicles than previously uninjured limbs at the start and throughout the season. From time point 1 to time point 2, previously injured BFlh fascicle lengths did not significantly change (p=0.247, d= 0.23), whilst the contralateral uninjured BFlh(p=0.009, d =0.56) and athletes with no history of injury (p=0.002, d =0.75), significantly increased BFlh fascicle length. All athletes, independent of injury history, had a significant reduction in fascicle length at time point 6 compared to time point 2. Conclusions Fascicle lengths of BFlh vary across the in-season period in elite AFL players and the extent of these alterations appears to be influenced somewhat by HSI history. However, independent of injury history, there was a gradual decay in fascicle length as the season progresses.
Prognostic biomarkers after colorectal liver metastasis resection: Exploratory study for VEGF, VEGFR and SPARC expression
Authors: Federico Longo Muñoz, Alfonso Cortés Salgado, Pablo Reguera Puertas, Estefania Romio, Constantino Varona, Eva Cristobal, Vanessa Pachón Olmos, Reyes Ferreiro Monteagudo, Mercedes Rodriguez Garrote, Maria Vaz, Maria Gion Cortés, Ainhoa Madariaga Urrutia, Javier Molina Cerrillo, Olga Martínez Saez, Maria Villamayor Delgado, Pedro Lopez-Hervas, Adolfo Lopez-Buenadicha, Roberto Peromingo, Nuria Losa, Javier Nuño, Jose Palacios, Alfredo Carrato
Journal: Annals of Oncology (2017)
Expression of hypoxia-inducible factor-1α and glucose transporter-1 in primary and recurred papillary thyroid cancer
Authors: Kyu Eun Lee, Bo Sung Kim, Kyeong Cheon Jung, Yeo-Kyu Youn
Journal: Clinical Cancer Research (2008)

B24   It is known that the glucose uptake and metabolism is increased in malignant tumors. Glucose transporter-1 (GLUT-1) has been proposed to explain this phenomenon. Hypoxia-inducible factor-1alpha (HIF-1α) is a transcription factor that mediates cellular adaptive responses to hypoxia and is known to control the expression of GLUT-1 in other malignancies. The aim of this study is to evaluate the expression of HIF-1α and GLUT-1 in primary and recurred papillary thyroid cancer (PTC); to compare these with the clinicopathologic parameters; and, to verify the correlation between HIF-1α and GLUT-1 expression. Fifty-nine cases of primary PTC and 40 cases of recurred PTC were selected and tissue microarrays were built. Immunohistochemical analyses of HIF-1α and GLUT-1 were conducted. HIF-1α expression was positive in 36 cases (61.0%) of primary PTC and in 32 cases (80%) of recurred PTC. GLUT-1 expression was positive in 47 cases (79.7%) of primary PTC and in 19 cases (47.5%) of recurred PTC. HIF-1α expression was more frequent in recurred PTC than in primary PTC (P=0.003), but GLUT-1 expression was less frequent in recurred PTC than in primary PTC (P=0.001). The expression of GLUT-1 was correlated with the size of tumor, the presence of extrathyroidal extension, the number of metastatic lymph nodes, and the T stage in primary PTC. There were no correlation between the expression of HIF-1α and GLUT-1. In conclusion, both HIF-1α and GLUT-1 were overexpressed in PTC, and GLUT-1 was correlated with the pathologic parameters. It is suggested that there would be other pathways rather than HIF-1α to regulate the expression of GLUT-1 in PTC because in this study the expression of HIF-1α and GLUT-1 did not show correlation.
Recovery of left ventricular mechanics following transcatheter aortic valve implantation: long-term follow-up in patients with four subtypes of aortic stenosis
Authors: Daniel R Harland, Daniel P O’Hair, Bijoy K Khandheria, Robert Richmond, Tanvir K Bajwa, Amada Kirby, Susan Olet, Renuka Jain
Journal: Circulation (2016)

Introduction: Left ventricular mechanics are impaired in patients with severe aortic stenosis (AS). Global longitudinal strain (GLS) may improve after transcatheter aortic valve implantation (TAVI)...
Transplant trials with Tregs: perils and promises
Authors: Qizhi Tang, Flavio Vincenti
Journal: Journal of Clinical Investigation (2017)

Modern immunosuppression regimens effectively control acute rejection and decrease graft loss in the first year after transplantation; however, these regimens do not have a durable effect on long-term graft survival owing to a combination of drug toxicities and the emergence of chronic alloimmune responses. Eliminating drugs and their toxicities while maintaining graft acceptance has been the primary aim of cellular therapies. Tregs suppress both autoimmune and alloimmune responses and are particularly effective in protecting allografts in experimental transplant models. Further, Treg-based therapies are selective, do not require harsh conditioning, and do not have a risk of graft-versus-host disease. Trial designs should consider the distinct immunological features of each transplanted organ, Treg preparations, dose, and frequency, and the ability to detect and quantify Treg effects in a given transplant environment. In this Review, we detail the ongoing clinical trials of Treg therapy in liver and kidney transplantation. Integration of Treg biology gleaned from preclinical models and experiences in human organ transplantation should allow for optimization of trial design that will determine the potential efficacy of a given therapy and provide guidelines for further therapeutic development.
PEGPH20 improves pfs in patients with metastatic pancreatic ductal adenocarcinoma: A randomized phase 2 study in combination with nab-paclitaxel/gemcitabine
Authors: Sunil Hingorani, Andrea Bullock, Tara Seery, Lei Zheng, Darren Sigal, Paul Ritch, Fadi Braiteh, Mark Zalupski, Nathan Bahary, William Harris, Jie Pu, Carrie Aldrich, Sihem Khelifa, Wilson Wu, Joaquina Baranda, Ping Jiang, Andrew Hendifar
Journal: Annals of Oncology (2017)
A clinical and genomic profile of inflammatory myofibroblastic tumors.
Authors: Sugganth Daniel, Laurie M. Gay, Jo-Anne Vergilio, Jeffrey S. Ross
Journal: Journal of Clinical Oncology (2017)

1538 Background: Inflammatory Myofibroblastic Tumors (IMT) are tumors that morphologically traverse the neoplastic and inflammatory realms. With a predilection for children and young adults, many patients present with systemic symptoms and the tumors demonstrate local invasiveness and even metastasis. IMTs are composed of fascicles of myofibroblastic spindle cells with a marked lymphoplasmacytic infiltrate. Methods: Integrated genomic profiling of DNA and RNA from IMTs in 30 patients was performed using a hybrid capture, paired-end NGS sequencing method and customized pipeline analysis. Results: 23 patients were children or young adults ( &lt; 30y), overall the age ranged from 7 months to 72 years. The tumor was clinically aggressive in 10 patients; 3 metastatic, 5 multifocal and 2 locally invasive. Epithelioid morphology was documented in 2 cases, one demonstrated the ALK-RANBP2 fusion. ALK rearrangements were detected in 13 patients, with 7 different fusion partners. ALK IHC or FISH was performed in 23 patients and were all concordant with the genomic results. 22 gene fusions were detected in 21 patients, 4 tumors had ROS1-TFG fusions, 2 had NTRK3-ETV6 fusions. 3 had novel fusions in JAK1-PML, PDGFRB-NOTCH1 and MUTYH-TESK2 respectively. Intact tyrosine kinase domains (TKD) in JAK1 are transposed to the promoter coiled-coil motif in PML, in the rearrangement. While the TKDs are preserved in the PDGRB and TESK2 rearrangements, the functional roles of their partners are yet to be elucidated. The prevalence of rearrangements was higher in patients below 30 years of age (20/23) compared to that above 30y (3/7). All 10 aggressive tumors were detected to have rearrangements. Conclusions: IMTs are seen predominantly in younger age groups. Gene rearrangements are seen more frequently in patients with younger age and also in more aggressive tumors, in a statistically significant manner. Alterations in genes associated with hematopoietic neoplasms such as JAK1 among others, are interesting, given the hematologic component of the lesion, and the presence of novel tyrosine kinase rearrangements warrant further investigations to elucidate mechanistic models.
A striking annular rash in a young man
Authors: Sze Ting Ivy Ngu, David Bilsland
Journal: BMJ (2017)

A 34 year old man in Scotland described an expanding itchy rash on the right flank (fig 1⇓) over a period of three months, despite using topical steroids, oral antifungals, and oral antihistamines. Borrelia serology performed four weeks after the start of the rash had been negative. He did not recall a history of an insect bite or foreign travel, but visits the Scottish highlands regularly. What is the most likely diagnosis?



Fig 1  Large annular rash on the right flank covering the posterior and lateral aspects, with an erythematous raised border and …
Increased expression of renal neutral endopeptidase (EC 3.4.24.11) in rats with CCl4-induced cirrhosis with ascites: acute effects of its pharmacological inhibiton with i.v. Candoxatrilat.
Authors: G Sansoé, M Aragno, R Mastrocola, F Restivo, S Silvano, G Mengozzi, A Smedile, F Rosina, O Danni, M. Rizzetto
Journal: Journal of Hepatology (2004)
Analysis of GATA1 Mutations in Down Syndrome Infants with Transient Abnormal Myelopoiesis and Clinical Impacts of GATA1 Mutation Types: A Report from the JPLSG TAM-10 Study
Authors: Kiminori Terui, Tsutomu Toki, Asahito Hama, Hideki Muramatsu, Daisuke Hasegawa, Myoung-Ja Park, Shotaro Iwamoto, Takashi Taga, Ryu Yanagisawa, Katsuyoshi Koh, Akiko M. Saito, Keizo Horibe, Yasuhide Hayashi, Souichi Adachi, Shuki Mizutani, Kenichiro Watanabe, Etsuro Ito
Journal: Blood (2016)
Confirmatory analysis to determine associations between platinum-sensitivity, molecular signature of combined tumor suppressor defects and aggressive variant prostate carcinomas (AVPC).
Authors: Paul Gettys Corn, Elsa Li Ning Tapia, Lianchun Xiao, Elisabeth I. Heath, Haidee Chancoco, Anh Hoang, Eleni Efstathiou, Timothy C. Thompson, Patricia Troncoso, Christopher Logothetis, Ana Aparicio
Journal: Journal of Clinical Oncology (2016)

5020 Background: Clinically defined AVPC is associated with platinum-sensitivity and a molecular profile of combined (≥2) alterations in PTEN, Tp53 and/or RB1 (Aparicio et al. Clin Cancer Res 2013;19 and Clin Cancer Res 2015;1). Based on these findings we conducted a validation study of cabazitaxel (CAB) plus or minus carboplatin (CARB) in men with CRPC stratified for the presence or absence of AVPC criteria (Corn et al. ASCO 2015; Funding: Sanofi). Methods: Clinical data were updated and available specimens were assembled for analysis. Immunohistochemistry was performed for AR, Ki67, RB1 and PTEN. DNA was extracted from remaining tumor cells and subject to next-generation sequencing to include Tp53. Results: At a median follow up of 21.6 months (mo), median progression free survival (mPFS) is 4.6 mo (95%CI 3.5-5.8) with CAB vs 7.4 mo (95% CI 5.6-8.3) with CAB/CARB (p = 0.004). In men meeting AVPC criteria, mPFS is 3.8 mo (95% CI 2.8-5.7) with CAB vs 5.6 mo (95% CI 4.4-8.0) with CAB/CARB (p = 0.012). After 86 deaths, median overall survival (mOS) is 17.4 mo (95% CI 12.6-25.9) with CAB vs 19.2 (95% CI 17.0-29.3) with CAB/CARB (p=0.489). 53% (42/79) of CAB patients and 23% (19/81) of CAB/CARB patients received additional salvage platinum-based therapy after progression. We identified 124 samples from 92 patients, of which 95 contained sufficient tumor for analysis. Of 54 analyzed to date, 38 belonged to men receiving CAB/CARB (30 AVPC) and 16 to men receiving CAB (10 AVPC). ≤10% of cells stained for AR, RB1 and PTEN in 6 (15%), 17 (42.5%) and 5 (12.5%) of 40 AVPC tumors and 0 (0%), 5 (35.7%) and 2 (14.3%) of non-AVPC tumors respectively. Tp53 sequencing is ongoing. Conclusions: Adding CARB to CAB is safe and significantly improves mPFS and response rates in men with mCRPC with a trend towards improved mOS. Men meeting AVPC clinical criteria benefit most from the CAB/CARB combination. We observed a high frequency of tumor suppressor defects in the characterized samples. Further analysis of the rate of their combination, association with AVPC criteria and benefit from CARB will be informative. Clinical trial information: NCT01505868.
Weight loss for overweight and obese individuals with gout: a systematic review of longitudinal studies
Authors: Sabrina M Nielsen, Else M Bartels, Marius Henriksen, Eva E Wæhrens, Henrik Gudbergsen, Henning Bliddal, Arne Astrup, Filip K Knop, Loreto Carmona, William J Taylor, Jasvinder A Singh, Fernando Perez-Ruiz, Lars E Kristensen, Robin Christensen
Journal: Annals of the Rheumatic Diseases (2017)

Weight loss is commonly recommended for gout, but the magnitude of the effect has not been evaluated in a systematic review. The aim of this systematic review was to determine benefits and harms associated with weight loss in overweight and obese patients with gout.
Error in Figures 2, 3, and 4
Authors: David Brent, Giovanna Porta
Journal: JAMA Psychiatry (2019)

Tania Da Silva, MSc; Sina Hafizi, MD; Jeremy J. Watts, BSc; Cynthia Shannon Weickert, PhD; Jeffrey H. Meyer, MD, PhD; Sylvain Houle, MD, PhD; Pablo Rusjan, PhD; Romina Mizrahi, MD, PhD
Abstract 17973: Clinical Markers Associated With Subclinical Atherosclerosis in Otherwise Apparently Healthy Young Adults
Authors: Stephanie LeBlanc, Karine Bibeau, Élianne De Larochellière, Philippe Pibarot, Jean-Pierre Després, Eric Larose
Journal: Circulation (2015)

Introduction: Traditional risk factors are poor predictors of cardiovascular events in younger adults. Considering the long silent evolution of atherosclerosis beginning in younger adulthood before the appearance of clinical events at a more advanced age, a simple tool to predict early atherosclerosis in young adults would be desirable to guide primordial prevention. An altered cardiometabolic profile is associated with increased cardiovascular disease in older adults independent from traditional risk factors, but the value of this profile in an otherwise healthy young adult population is unknown. Hypothesis: Cardiometabolic risk markers would be associated with early atherosclerosis in young adults despite the absence of traditional risk factors. Methods: Healthy young adults (18-35 years) devoid of cardiovascular risk factors (diabetes, smoking, hypertension, dyslipidemia) and obesity were prospectively enrolled. Anthropometric measurements, ECG, lipid profile, fasting blood glucose, blood pressure and high-resolution carotid artery MRI were realized. Results: Although the 240 participants (25.8 years, SEM=0.29, 48% women) were at low risk for atherosclerosis, we identified atherosclerosis in 72.6% of men and 64.7% of women (p=0.19). Males had greater atherosclerosis burden vs. females (carotid wall volume [CWV]: 1817 mm3/48mm, SEM=29.7 vs. 1579 mm3/48mm, SEM=21.2; p&lt;0.0001). By multivariate analysis, atherosclerosis burden was associated with fasting blood glucose (p=0.01), BMI (p=0.01), and waist circumference (p&lt;0.001), the latter having the strongest correlation with atherosclerosis burden (r=0.41, p&lt;0.0001). ROC analyses established cutoffs for waist circumference identifying greater atherosclerosis burden in apparently healthy young adults. Conclusion: A simple low-cost office-based tool, waist circumference measurement improves prediction of early atherosclerosis in otherwise apparently healthy young adults.
Patient and Carer Satisfaction about Current Support Service from Upper Gastrointestinal Team in a Tertiary Referral Centre – A Survey
Authors: PC Munipalle, NS Laking, H Wescott, S McKinney, PA Davis, YKS Viswanath
Journal: Endoscopy (2006)

Aims: Major upper GI resections for cancer have significant morbidity hence the patient and family need support from the attending health care team in the perioperative period for optimum results from treatment. We feel there is no adequate reporting on feedback from the patients and their families about the current support service.
Abstract 13097: Novel Interaction of Antioxidant-1 With NADPH Oxidase p47phox and TRAF4: Role in TNFα-Induced Inflammation and Atherosclerosis
Authors: Archita Das, Sudhahar Varadarajan, Gin-Fu Chen, Bayasgalan Surenkhuu, Jun Tian, Masuko Ushio-Fukai, Tohru Fukai
Journal: Circulation (2015)

Tumor necrosis factor-TNFα plays a key role in atherosclerosis via NADPH oxidase-derived reactive oxygen species (ROS) and its downstream redox-sensitive inflammatory responses. Copper (Cu) has been implicated in atherosclerosis and inflammation with unknown mechanism. Bioavailability of Cu is controlled by transport-proteins including Cu-chaperone Atox1 which obtains Cu via Cu-importer CTR1 localized at plasma membrane. We recently found that Atox1 also functions as a Cu-dependent transcription factor for NADPH oxidase p47phox. However, role of Atox1 in atherosclerosis is unknown. Here we show that ApoE-/-Atox1-/- mice with 16 weeks high-fat-diet (HFD) showed decreased atherosclerotic lesion (40%, Oil-O-red staining). inflammatory cell recruitment (50% decrease, Mac3+) and extracellular matrix deposition (Masson’s Trichrome) compared to ApoE-/-HFD. Mechanistically, in cultured endothelial cells (ECs), Atox1 knockdown with siRNA, or Cu-chelator BCS inhibited TNFα-induced ROS production (70%) at later phase (16hrs) and its downstream VCAM1/ICAM1 expression and monocyte adhesion by reducing transcription of p47phox. Unexpectedly, TNFα stimulation rapidly promoted Atox1/p47phox binding in a PKCδ-dependent and Cu-“independent” manner, which is required for p47phox membrane translocation involved in early phase of (5min) ROS production and subsequent Cys oxidation of Cu-importer CTR1 detected by a biotin-labeled Cys-OH trapping reagent. This was followed by CTR1/Cu-dependent Atox1 binding to TNFα receptor associated factor (TRAF)4, which promoted Atox1 nuclear translocation to increase p47phox expression leading to late-phase of ROS production, facilitating further monocyte adhesion to ECs. In summary, Atox1 plays an important role in activating p47phox-based NADPH oxidase and inflammatory responses in ECs by binding to p47phox that induces early phase of ROS to promote CTR1 oxidation in Cu-independent manner. This is followed by Cu-dependent Atox1/TRAF4 binding required for Atox1 nuclear translocation to function as a transcription factor for p47phox, leading to late-phase of ROS production, which contributes to acceleration of atherosclerosis in vivo.
FDG PET and FES PET Predict PFS on Endocrine Therapy—Letter
Authors: David Groheux, François Bénard
Journal: Clinical Cancer Research (2017)

We read with interest the study by Kurland and colleagues (1) that was recently published in Clinical Cancer Research. They evaluated the ability of 18F-fluorodeoxyglucose (FDG) PET and 18F-fluoroestradiol (FES) PET to predict progression-free survival (PFS) in 84 patients treated by salvage endocrine therapy for luminal metastatic breast cancer (MBC).Previous studies suggested that FES PET imaging performed at a single time point before beginning a novel line of endocrine therapy could be helpful to predict response in patients with pretreated luminal MBC (2, 3). In those studies, a defined cutoff [value of 1.5 (2) or 2 (3)] for the standardized uptake values (SUV) was applied to separate tumors sensitive to the treatment (high SUV values) from those who are resistant (low SUV values).Unfortunately, in the study from Kurland and colleagues, none of the qualitative or quantitative parameters measured on FES PET imaging performed before beginning the hormonal therapy was predictive of PFS. On the opposite, FDG uptake was a good indicator of patient's outcome with shorter PFS in the case of metastases with high FDG uptake. Similarly, in the case of patients with luminal tumors without pretreatment, FDG uptake measured at a single time point before neoadjuvant chemotherapy (4) or before initial surgery (5) has been associated with patient's survival. These results suggest that FDG PET is more likely to predict outcome than the FES PET does.However, in the study from Kurland and colleagues, although FES PET was not predictive of patient's survival in the whole population, this imaging was of interest to better stratify the patients having high FDG uptake. Finally, three subgroups were identified: those with a good prognosis (in the case of tumors with low FDG uptake), those with a bad prognosis (tumor with high FDG uptake and low FES uptake), and those with an intermediate prognosis (tumor with high FDG uptake and high FES uptake).In conclusion, although previous studies showed that FES PET was a good indicator of response to endocrine therapy, the study from Kurland suggests that FES imaging has limited value in terms of prognosis. FDG imaging seems more helpful than FES PET to predict patient outcome. Nevertheless, FES imaging could be of interest in addition to FDG PET. The predictive and prognostic value of the two PET imaging and their additional role need to be investigated in a multicenter prospective study with a larger cohort of patients.See the Response, p. 3475No potential conflicts of interest were disclosed.
Prolonged enteral nutrition after total gastrectomy due to cancer: Phase III study
Authors: Tomasz Olesinski, Andrzej Cichocki, Piotr Saramak, Marek Szpakowski, Andrzej Rutkowski, Leszek Zajac, Łukasz Zyskowski, Adam Dmitruk, Paulina Wieszczy, Magdalena Jodkiewicz, Lucjan Wyrwicz, Jaroslaw Regula
Journal: Annals of Oncology (2017)
Inhibiting p53 Acetylation Reduces Cancer Chemotoxicity
Authors: Shunsheng Zheng, Xin Yu Koh, Hui Chin Goh, Siti Aishah B. Rahmat, Le-Ann Hwang, David P. Lane
Journal: Cancer Research (2017)

Abstract Chemotoxicity due to unwanted p53 activation in the bone marrow remains an unmet clinical challenge. Doxorubicin, a first-line chemotherapy drug, often causes myelosuppression in patients, thus limiting its effectiveness. In this study, we discovered that C646, a reversible p300 inhibitor, downregulates p53 transcription and selectively protects noncancerous cells from p53-dependent apoptosis. C646 treatment blocked acetylation of specific lysine residues that regulate p53 activity. Exploitation of differential p53 genetic backgrounds between human hematopoietic and colorectal cancer cells improved the therapeutic index of doxorubicin with C646 cotreatment. C646 administration in mice afflicted with p53-mutant tumors protected them from doxorubicin-induced neutropenia and anemia while retaining antitumor efficacy. We deduce that temporary and reversible inhibition of p53 acetylation in cancer subjects, especially those with p53-mutant tumors, may protect them from severe chemotoxicity while allowing treatment regimens to effectively proceed. Cancer Res; 77(16); 4342–54. ©2017 AACR.