tbuckley/cabot-search huggingface dataset:
The t(14;18)(q32;q21) Characterizes a Subset of Patients with Diffuse Large-B Cell Lymphoma of Germinal Center Origin with Poor Outcome: Report From the International DLBCL Rituximab-CHOP Consortium Program Study
Authors: Carlo Visco, Alexander Tzankov, Zijun Y. Xu-Monette, Roberto N. Miranda, Emanuele S. G. d'Amore, Santiago Montes-Moreno, Karen Dybkaer, April Chiu, Wayne Tam, Attilio Orazi, Youli Zu, Govind Bhagat, Brad S. Kahl, Jane N. Winter, Huan-You Wang, Cherie H. Dunphy, Eric D. Hsi, Frank X. Zhao, Ronald S. Go, William W. L. Choi, Fan Zhou, Magdalena Czader, Xiaoying Zhao, Joannes H.J.M. Van Krieken, Qin Huang, Weiyun Ai, Joan E. Etzell, Maurilio Ponzoni, Andres J.M. Ferreri, Miguel A. Piris, Michael B. Møller, Carlos E. Bueso-Ramos, L. Jeffrey Medeiros, Ken H. Young
Journal: Blood (2011)
Identification of putative germline mutations in 10,288 patients undergoing circulating tumor DNA testing.
Authors: Thomas Paul Slavin, Kimberly Banks, Darya Chudova, Geoffrey R. Oxnard, Justin I. Odegaard, Rebecca J Nagy, Susan L. Neuhausen, Stacy W. Gray, Massimo Cristofanilli, Angel Augusto Rodriguez, Aditya Bardia, Brian Leyland-Jones, Mike Janicek, Michael B. Lilly, Guru Sonpavde, Christine E. Lee, Richard B. Lanman, Funda Meric-Bernstam, Razelle Kurzrock, Jeffrey N. Weitzel
Journal: Journal of Clinical Oncology (2017)

1514 Background: No studies have yet described incidental detection of germline cancer predisposition mutations using circulating cell-free DNA (cfDNA). Methods: Deidentified cfDNA sequencing data from 10288 advanced cancer patients (pts) undergoing clinical circulating tumor DNA testing (Guardant360, 73 genes) were included in this study. CfDNA was extracted from plasma and quantified. A DNA library was prepared and sequenced to 15,000X average read depth. Using Ingenuity Variant Analysis, point mutations and small indels suspicious for germline origin (allele fraction 40-60%) were classified following American College of Medical Genetics and Genomics guidelines. Results: More than 50 cancer types were studied, including lung (40%), breast (20%), CRC (8%), prostate (6%), and pancreas (3%). Average age was 63.6 years (range:18-95), 42% were male. Of 34,873 putative germline variants identified, 520 (1.5%) were pathogenic or likely pathogenic (PV), 16,939 (49%) were of uncertain significance, and 17,414 (50%) were benign or likely benign. Of the 250 pts (2.4%) with hereditary cancer syndrome gene PVs, 83 were excluded due to high level of somatic tumor burden leaving 167 (1.6%) with putative germline PVs; rates were higher in pts &lt;50 vs &gt;50 overall (3.3% vs 1.4%, p=0.02) and in breast cancer pts (4.3% vs 1.5%, p=0.03). Conclusions: The observed frequency of incidentally identified putative germline PVs is expectedly lower than the true germline rate; however, these findings illustrate that detection from cfDNA is clinically feasible. Importantly, incidental germline findings could impact oncology treatment planning (e.g. PARP inhibitors for BRCA1/2 mutations) and could benefit families via increased surveillance/primary prevention. Further research is needed to explore how to report potential germline results to clinicians using a systems-based approach. [Table: see text]
Histopathologic review of suspected disease progression in patients with recurrent glioblastoma (GBM) receiving nivolumab ± ipilimumab: CheckMate 143.
Authors: Solmaz Sahebjam, Shakti Ramkissoon, Joachim M. Baehring, Paul James Mulholland, Oliver M. Grauer, Timothy Francis Cloughesy, David A. Reardon, Michael Lim, Ricardo F. Zwirtes, Robert Raymond Latek, Lewis C. Strauss, Keith L. Ligon
Journal: Journal of Clinical Oncology (2017)

2001 Background: Patients treated with immunotherapies can have a transient increase in lesion size due to immune cell infiltration that is suggestive of disease progression, but undergo subsequent regression with continued treatment. For patients with GBM, distinguishing progression from immune-related treatment effects using neuroimaging is challenging. Histopathologic examination of tumors could show the activity of immunotherapies in GBM and potentially minimize premature discontinuation of therapy and increase clinical benefit. Neuropathologic data from patients with recurrent GBM treated in CheckMate 143 who underwent biopsy/resection after suspected progression are presented. Methods: Patients received nivolumab 3 mg/kg (nivo 3) Q2W or nivo 3 + ipilimumab 1 mg/kg (ipi 1) Q3W × 4 doses then nivo 3 Q2W. Tissue collected from patients with suspected radiologic progression was submitted for blinded central review by 2 neuropathologists. Potentially significant treatment effect was defined as ≥30% necrosis/reactive changes and ≤50% viable solid tumor by area in posttreatment samples, or significant morphological changes from a prior biopsy if available. Results were compared with those from automated morphometry, pretreatment biopsy, and control pairs from unrelated patients with GBM treated with standard of care. Results: Of patients treated with nivo 3 (n = 20) or nivo 3 + ipi 1 (n = 1), 13 had potential treatment-related effects and 8 had no evidence of treatment effects (consistent with disease progression). Results were sent in real time to the treating physician to help inform treatment decisions; 4/13 patients with potential treatment effects continued therapy. Treatment effects were unrelated to age, MGMT methylation status, or PD-L1 expression (clone 28-8; archival tissue). Results were similar for automated morphometry analyses and showed differences between patients receiving nivo ± ipi and unrelated controls. Conclusions: These results suggest that histopathologic analyses may help better inform decisions on continuing nivo ± ipi in challenging cases, and show that immunotherapies may have intracerebral biological activity. Clinical trial information: NCT02017717.
Potential role for carbon nanoparticles identification and preservation in situ of parathyroid glands during total thyroidectomy and central compartment node dissection.
Authors: Jinbiao Shang, Jialei Gu, Wendong Wang, Xilin Nie, Qianbo Han, Kejing Wang
Journal: Journal of Clinical Oncology (2015)

e17048 Background: Patients undergoing thyroid surgery are at risk for hypoparathyroidism. We hypothesized that carbon nanoparticles identification of parathyroid glands might help maximize parathyroid preservation and reduce postoperative hypoparathyroidism. Methods: Patients with thyroid cancer who underwent total thyroidectomy and central compartment node dissection (CCND) were randomly assigned to receive intraoperative injection of carbon nanoparticles (CN) or not for identifying and preserving normal parathyroid glands. We compared the levels of parathyroid hormone and serum calcium before surgery and at day 1, 3 and 30 after surgery between the 2 groups, as well as postoperative thyroid pathological and lymph node dissection results. Results: A total of 100 patients with thyroid carcinoma were included in the research, 50 in CN group and 50 in control group. There was no significantly difference for preoperative and postoperative PTH levels between the CN and control group (p > 0.05). The levels of AASC before surgery and at day 1and 1 month after surgery did not reach the significant difference between the two groups (p > 0.05). However, the patients in CN group had the higher level of AASC at day 3 after surgery than those in control group (p = 0.044). Transient postoperative hypoparathyroidism occurred in 24(48%) patients in CN group and 28(56%) in control groups, respectively (p = 0.423). The incidence of transient postoperative hypocalcemia was 20% (10/50) in CN group and 24% (12/50) in control groups, respectively (p = 0.629). Conclusions: Carbon nanoparticles can make the thyroid gland and the central lymph node black-stained, but no-stained for parathyroid glands. After rapidly identifying parathyroid and distinguishing it from thyroid and lymph nodes by carbon nanoparticles, complete lymph node dissection and preservation of parathyroid glands become feasible during total thyroidectomy with neck lymph node dissection. After identification, strict adherence to capsular dissection remains essential for safe preservation in situ of the parathyroid glands and their blood supply.
Abstract P351: Statins Prevent Expansive Remodeling in Arterialized Vein Grafts
Authors: Beiping Qiang, Jonathan Toma, Hiroko Fujii, Azriel Osherov, Nafiseh Nili, Paul Fefer, Michelle Samuel, Jagdish Butany, Howard Leong-Poi, Bradley H Strauss
Journal: Circulation Research (2011)

Vein grafts (VG) account for more than 70% of conduits used in aortocoronary bypass surgery, but have high failure rates by 10 years. We have previously shown in an experimental model that VG undergo marked expansion by 4 weeks, which was followed by increased total LDL retention at 12 weeks. The objective of this study was to determine whether statin therapy would prevent these expansive remodelling changes. Methods and Results Reversed jugular vein-to-common carotid artery interposition graft were constructed in 24 cholesterol-fed (0.5%) rabbits. Rabbits were randomized to either control or atorvastatin (5 mg/kg/day) groups, starting two weeks prior to vein graft implantation and continuing until sacrifice at 1 or 12 weeks post-surgery. Ultrasound measurements of arterial luminal cross-sectional area (LCSA) were done at day 3 and at 4, 8 and 12 weeks post-surgery. Histomorphometric measurements were performed following sacrifice at 12 weeks. Atorvastatin treatment significantly decreased total plasma cholesterol levels at 12 weeks (6.70±4.19mmol/L vs placebo 38.65±10.55mmol/L, p&lt;0.001). Atorvastatin significantly reduced expansive remodelling at all time points, including at 12 weeks (44.6±6.62mm 2 vs placebo 77.6±10.68mm 2 , p&lt;0.001). Intimal CSA by histomorphometry was significantly reduced by atorvastatin at 12 weeks (5.59±2.19mm 2 vs placebo 9.57±2.43mm 2 , p&lt;0.05). At 1 week, macrophage infiltration was significantly reduced (Ram11 positive intimal staining 0.018±0.019 vs 0.189±0.049, p&lt;0.05). Atorvastatin treated samples at 1 week showed reduction in both MMP 2 activity (gelatin zymography) and metalloelastase activity (casein zymography). Conclusion: Atorvastatin prevents expansive remodelling in arterialized VG, likely through inhibition of macrophage infiltration and reduction of tissue proteolytic activity. This may be an important mechanism preventing VG atherosclerosis and late VG failure.
Characteristics of paediatricpediatric concussion patients utilisingutilizing emergency department services prior to initial concussion clinic evaluation
Authors: Valerie De Maio, Johna Register-Mihalik, Mackenzie Herzog, Janna Fonseca, Kristen Phillips, O Josh Bloom
Journal: British Journal of Sports Medicine (2017)

Objective To evaluate characteristics of paediatric concussion patients utilising the emergency department (ED) prior to initial concussion clinic evaluation. Design Prospective cohort. Setting Clinics of an American urban/suburban family practice (12/2014–04/2015). Subjects Consented concussion patients 8–18 years presenting to clinic within 3 days of injury (n=195; age=14.3, SD=2.1 years; female=42.3%). Intervention Participants completed a systematic evaluation at initial clinic visit and survey at 4-6 weeks (73.8% follow-up). Criterion variables included demographics, prior head injury, time of injury (TOI) factors, total symptom severity, Immediate Postconcussion Assessment and Cognitive Test (ImPACT) composites, one-month persistent symptoms, one-month Paediatric Quality of Life (PedsQL). Outcome measures ED visit before clinic evaluation (yes/no) served as the dependent variable. Results ED visits were reported for 12.8% (n=25) of participants. Amnesia (36.0% vs. 10.1%; p&lt;0.001), loss of consciousness (LOC) (20.8% vs. 6.7%; p=0.021), confusion (40.0% vs. 20.0%; p&lt;0.0255), difficulty remembering (52.0% vs. 26.5%; p&lt;0.0091), paresthesias (16.0% vs. 4.7%; p&lt;0.0282), and CT imaging (60.0% vs. 0.6%; p&lt;0.0001) were greater for the ED group. Initial symptom severity and ImPACT composite scores, and one-month outcomes of persistent symptoms and PedsQL, were no different for the ED group. Conclusions Paediatric patients presenting to concussion clinic with 72 hours of injury who first visited an ED, have more dramatic symptoms at the TOI, yet do not appear to have any worse initial symptom severity, ImPACT scores, or one-month persistent symptoms or PedsQL than those who presented first to clinic. Future study should evaluate these relationships in larger samples. Competing interests The current study is funded in part by the National Operating Committee on Standards for Athletic Equipment. Ms. Fonseca is employed at the study setting. Ms. Phillips is employed at the study setting. Dr. Bloom is employed at the study setting.
Abstract P319: Protein Modulation in Mouse Heart Under Acute and Chronic Hypoxia
Authors: Cecilia Gelfi, Agnese Viganò, Michele Vasso, Daniele Capitanio, Roberta Leone, Anna Caretti, Michele Samaja
Journal: Circulation Research (2011)

Exploring cellular mechanisms underlying beneficial adaptive processes and detrimental responses to hypoxia represents the object of the present study. Signaling molecules controlling adaptation to hypoxia (HIF-1α), energy balance (AMPK), mitochondrial biogenesis, (PGC-1α) and the regulation of autophagic/apoptotic processes, combined with proteomic dysregulation were assessed. Responses to normobaric acute (48 hrs FiO 2 = 0.08) and chronic (10 days FiO 2 = 0.08) hypoxia in mouse heart proteome were detected applying 2-D DIGE, mass spectrometry and antigen antibody reactions. Both in acute (AH) and chronic (CH) hypoxia, results indicated a deregulation of proteins related to sarcomere stabilization and muscle contraction. Neither in AH nor in CH HIF-1α stabilization was detected. In AH, the metabolic adaptation to oxygen lack is controlled by AMPK activation and sustained by the massive up-regulation of adenosylhomocysteinase and of acetyl coenzyme A synthetase. AH is also characterized by an up-regulation of Bnip 3 which is known to induce mitophagy and decreasing oxidative damage. PGC-1α, a master regulator of mitochondrial biogenesis, was down- regulated. CH was characterized by up-regulation of enzymes involved in antioxidant defense, in aldehyde bio-product detoxification and in misfolded protein degradation. In addition, a massive down-regulation of enzymes controlling anaerobic metabolism was observed. After 10 days of hypoxia, cardioprotective molecules were substantially decreased whereas pro-apoptotic signals were correlated with the increment of apoptotic program and sustained by the down-regulation of specific target proteins. In conclusion, differential analysis provided new insight into target molecules sensing lack of oxygen in vivo and could open new possibilities for protection from damages induced by long term hypoxia exposure.
SALL4 Is a Key Factor in HDAC Inhibitor Mediated Ex Vivo Expansion of Human Peripheral Blood Mobilized Stem/Progenitor CD34+CD90+ Cells
Authors: Hiro Tatetsu, Fei Wang, Chong Gao, Shikiko Ueno, Xi Tian, Myriam Armant, Alex Federation, Jun Qi, James E. Bradner, Daniel G. Tenen, Li Chai
Journal: Blood (2014)
Traditional anti-inflammatory and COXIB use in patients admitted urgently with gastrointestinal haemorrhage
Authors: R Naidoo, T Gilbert, J Woo, C Halling, M Cannon, A Gleeson, C Smyth, FE Murray
Journal: Endoscopy (2006)

Introduction: Non-steroidal anti-inflammatory drugs (NSAIDs) cause peptic ulceration and ulcer complications. Their pattern of use has changed in recent years.
Weekly paclitaxel plus bevacizumab versus docetaxel as second or third-line treatment in advanced non-squamous non-small cell lung cancer (NSCLC): Results from the phase III study IFCT-1103 ULTIMATE.
Authors: Alexis B. Cortot, Clarisse Audigier-Valette, Olivier Molinier, Sylvestre Le Moulec, Fabrice Barlesi, Gerard Zalcman, Patrick Dumont, Damien Pouessel, Claire Poulet, Pierre Jean Souquet, Sandrine Hiret, Adrien Dixmier, Patrick-Aldo Renault, Alexandra Langlais, Marie Paule Lebitasy, Franck Morin, Denis Moro-Sibilot, Benjamin Besse
Journal: Journal of Clinical Oncology (2016)

9005 Background: Adding bevacizumab to weekly paclitaxel (wPB) has shown synergistic effect and increased activity in various tumor types. The ULTIMATE study evaluated wPB vs. docetaxel (DOC) as 2nd or 3rd-line treatment in patients with advanced non-squamous NSCLC. Methods: Patients with non-squamous NSCLC progressing after 1 or 2 lines of treatment including platinum-based chemotherapy were randomized 2:1 (stratified by PS, previous lines, prior exposure to bevacizumab) to wPB (paclitaxel 90 mg/m² D1, 8, 15 and bevacizumab 10 mg/kg D1, 15, q28d) or DOC (75 mg/m² q21d) until progression. Patients were allowed to cross-over to the other arm following progression. The primary endpoint was progression-free survival (PFS). Results: From 05/2013 to 08/2014, 166 patients were randomized (wPB: 111, DOC: 55). Clinical characteristics were balanced between both arms. 31% had received previous bevacizumab and 69% had received 1 previous line of treatment. Median follow-up was 28.9 months. The adjusted hazard ratio (HR) for PFS was 0.62 (IC95%: 0.44-0.86, p=0.005). Median PFS was 5.4 months for wPB vs. 3.9 months for DOC. Efficacy was observed regardless of number of previous lines (1 line: HR 0.56, IC95% [0.39-0.89], p=0.01; 2 lines: HR 0.56, IC95% [0.30-1.04], p=0.07). ORR was 22.5% with wPB and 5.5% with DOC (p=0.006). 21 out of 55 pts treated with DOC crossed over to wPB. No difference in OS was observed (median wPB 9.9 months, DOC 10.8 months, adjusted HR 1.15, p=0.49). Grade 3-4 adverse events (AE) occurring during the first sequence of treatment were comparable between wPB and DOC (45.9% and 54.5%) and included neutropenia (19.3% vs. 45.4%), asthenia (8.3% vs 5.5%), neuropathy (8.3% vs. 0.0%) and hypertension (7.3% vs. 0.0%). Grade 3-4 bleeding AEs upon wPB occurred in 0.9% of patients. 3 patients had grade 5 drug-related AEs (1.8% in each arm). Conclusions: ULTIMATE trial mets its primary endpoint. wPB significantly improved PFS and ORR vs. DOC in advanced non-squamous NSCLC patients as second or third-line treatment, with a manageable safety profile. wPB should be considered as a treatment option in this setting. Clinical trial information: NCT01763671.
The Metabolodiuretic Promise of Sodium-Dependent Glucose Cotransporter 2 Inhibition
Authors: Subodh Verma, John J. V. McMurray, David Z. I. Cherney
Journal: JAMA Cardiology (2017)

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The association between body size and susceptibility to breast cancer in Chinese Han women.
Authors: Xin Wang, Liang Li, Jiaqi Liu, Mingming Guo, Wenyan Wang, Jie Wang, Zeyu Xing, Jidong Gao, Zhigang Yu, Xiang Wang
Journal: Journal of Clinical Oncology (2016)

e13089 Background: Even obesity has been accused to predispose to breast cancer worldwide, there are still some inconsistencies regarding the association between obesity and breast cancer. As BMI (body mass index) is mostly used to assess the extent of obesity, other body size characteristics, such as waist and hip circumference, are still needed to be better assessed by the susceptibility to breast cancer in Chinese Han women. Methods: Female patients were recruited from 21 hospitals in northern and eastern China from April 2012 to April 2013. The significant differences of factors related to body size between the breast-cancer case and control groups were determined by Student’s t-tests and Chi-Square tests. We also conducted univariate and multivariate conditional logistic regression to assess the association between different body size characteristics with the risk for breast cancer in different menopausal status. Results: We conducted a case-control study of 2800 Chinese Han female participants in this study. Premenopausal women with breast cancer manifested higher BMI, longer waist and hip circumference (p = 2×10-4, < 1×10-6 and 2×10-5, respectively). However, these body size factors were identified not associated with postmenopausal breast cancer (p = 0.45, 0.32 and 0.12, respectively). High level BMI (BMI between 28.0-30.0kg/m2 or > 32.0kg/m2) were identified related to breast cancer among both overall and premenopausal individuals, but not in postmenopausal group. In multivariate conditional logistic regression, we found that factors that were independently associated with breast cancer are waist circumference (p = 0.04). However, BMI and hip circumference didn’t perform significantly associated with female breast cancer in Chinese Han individuals (p = 0.85 and 0.83, respectively). Conclusions: In summary, obesity is significantly associated with breast cancer in Chinese Han premenopausal women and abdominal obesity, so as to larger waist circumference, is a more sensitive body size factor than BMI. Thus it is important to realize that the body weight control, especially avoiding abdominal obesity, should be considered as one of the most effective methods to reduce the breast cancer susceptibility.
Indian government’s advice to pregnant women to shun meat and sex criticised by doctors
Authors: Sumi S Dutta
Journal: BMJ (2017)

A booklet issued by the Indian government to pregnant women, asking them to shun “meat, eggs, and lustful thoughts,” in order to have healthy babies, has angered doctors who say the advice is based on religion rather than scientific evidence.

The booklet, Mother and Child Care , was distributed widely by the Central Council for Research in Yoga and Naturopathy, an arm of the Indian ministry that promotes traditional and alternative medicine, ahead of the 3rd International Yoga Day on 21June.

The booklet says that eggs and meat of all kinds should be avoided during pregnancy, and adds that pregnant women “should detach themselves from desire, anger, attachment, hatred, and lustful thoughts,” advice which is …