tbuckley/cabot-search huggingface dataset:
Natural Selection in the Great Apes
Authors: Alexander Cagan, Christoph Theunert, Hafid Laayouni, Gabriel Santpere, Marc Pybus, Ferran Casals, Kay Prüfer, Arcadi Navarro, Tomas Marques-Bonet, Jaume Bertranpetit, Aida M. Andrés
Journal: Molecular Biology and Evolution (2016)

Natural selection is crucial for the adaptation of populations to their environments. Here, we present the first global study of natural selection in the Hominidae (humans and great apes) based on genome-wide information from population samples representing all extant species (including most subspecies). Combining several neutrality tests we create a multi-species map of signatures of natural selection covering all major types of natural selection. We find that the estimated efficiency of both purifying and positive selection varies between species and is significantly correlated with their long-term effective population size. Thus, even the modest differences in population size among the closely related Hominidae lineages have resulted in differences in their ability to remove deleterious alleles and to adapt to changing environments. Most signatures of balancing and positive selection are species-specific, with signatures of balancing selection more often being shared among species. We also identify loci with evidence of positive selection across several lineages. Notably, we detect signatures of positive selection in several genes related to brain function, anatomy, diet and immune processes. Our results contribute to a better understanding of human evolution by putting the evidence of natural selection in humans within its larger evolutionary context. The global map of natural selection in our closest living relatives is available as an interactive browser at http://tinyurl.com/nf8qmzh.
Peripheral Neuropathy Profile of Vincristine Sulfate Liposomes Injection (VSLI, Marqibo®), a Nanoparticle Vincristine Formulation, in Adult Subjects with Relapsed/Refractory Acute Lymphoblastic Leukemia (ALL) and Non-Hodgkin’s Lymphoma (NHL)
Authors: Biao Lu, Anne E Hagey, Feng Zhou, Steven R. Deitcher
Journal: Blood (2008)
Dissecting a Case of Abdominal Pain
Authors: Jonathan Casey, Anand Vaidya, Natasha Frank, Joshua A. Beckman, Amy Miller
Journal: New England Journal of Medicine (2016)

A 43-year-old man with no notable medical history presented to the emergency department within 1 hour after the abrupt onset of abdominal pain. The patient stated that he had been dressing for work when severe, “crampy” abdominal pain occurred in the left upper quadrant. On a scale of 0 to 10, with 0 indicating no pain and 10 the worst imaginable pain, the patient rated the pain at 10. . . .
Hypertension-Linked Pathophysiological Alterations in the Gut
Authors: Monica M. Santisteban, Yanfei Qi, Jasenka Zubcevic, Seungbum Kim, Tao Yang, Vinayak Shenoy, Colleen T. Cole-Jeffrey, Gilberto O. Lobaton, Daniel C. Stewart, Andres Rubiano, Chelsey S. Simmons, Fernando Garcia-Pereira, Richard D. Johnson, Carl J. Pepine, Mohan K. Raizada
Journal: Circulation Research (2016)

Sympathetic nervous system control of inflammation plays a central role in hypertension. The gut receives significant sympathetic innervation, is densely populated with a diverse microbial ecosystem, and contains immune cells that greatly impact overall inflammatory homeostasis. Despite this uniqueness, little is known about the involvement of the gut in hypertension.Test the hypothesis that increased sympathetic drive to the gut is associated with increased gut wall permeability, increased inflammatory status, and microbial dysbiosis and that these gut pathological changes are linked to hypertension.Gut epithelial integrity and wall pathology were examined in spontaneously hypertensive rat and chronic angiotensin II infusion rat models. The increase in blood pressure in spontaneously hypertensive rat was associated with gut pathology that included increased intestinal permeability and decreased tight junction proteins. These changes in gut pathology in hypertension were associated with alterations in microbial communities relevant in blood pressure control. We also observed enhanced gut-neuronal communication in hypertension originating from paraventricular nucleus of the hypothalamus and presenting as increased sympathetic drive to the gut. Finally, angiotensin-converting enzyme inhibition (captopril) normalized blood pressure and was associated with reversal of gut pathology.A dysfunctional sympathetic-gut communication is associated with gut pathology, dysbiosis, and inflammation and plays a key role in hypertension. Thus, targeting of gut microbiota by innovative probiotics, antibiotics, and fecal transplant, in combination with the current pharmacotherapy, may be a novel strategy for hypertension treatment.
UNR/CSDE1 Drives a Post-transcriptional Program to Promote Melanoma Invasion and Metastasis
Authors: Laurence Wurth, Panagiotis Papasaikas, David Olmeda, Nadine Bley, Guadalupe T. Calvo, Santiago Guerrero, Daniela Cerezo-Wallis, Javier Martinez-Useros, María García-Fernández, Stefan Hüttelmaier, Maria S. Soengas, Fátima Gebauer
Journal: Cancer Cell (2016)
SÍNDROME DE POLIPOSIS SERRADA. PRESENTACIÓN DE 3 CASOS CLÍNICOS
Authors: J Suárez Teran, P Gonçalves Da Cunha, O Díaz-Canel Fernandez, LE Yip Baldeón, M Blasi Puig, E Jauregui Juárez, Á Méndez Bocanegra, X Ribot Molinet, R Durán Bermejo, J Merlo Mas
Journal: Endoscopy (2016)

Introduccion: Un tercio de los casos de CCR se originan de una vía serrada, caracterizada por hipermetilación de numerosos genes donde la lesión precursora es el pólipo serrado. El SPS es todavía una entidad desconocida, con factores que la determinan como hereditaria y un alto riesgo de CCR.
TCT-777 Safety and Performance of the Shockwave Medical Lithoplasty® System in treating calcified peripheral vascular lesions: 6-Month Results from the two-phase DISRUPT PAD Study
Authors: Todd Brinton, Marianne Brodmann, Martin Werner, Gunnar Tepe, Andrew Holden, Dierk Scheinert, Florian Wolf, Giovanni Torsello, Alexandra Lansky, Michael Jaff, Thomas Zeller
Journal: Journal of the American College of Cardiology (2016)
Membrane-Associated Proteinase 3 On Granulocytes and Myeloid Leukemia Mediates Reversible Inhibition of T Cell Proliferation Associated with Altered ZAP70 and ERK Signaling
Authors: Tian-Hui Yang, Karen Clise-Dwyer, S Lisa, St. John, Gheath Alatrash, Kathryn Ruisaard, Sijie Lu, Jeffrey J. Molldrem
Journal: Blood (2012)
Popular measure in California ballot targets drug prices
Authors: Michael McCarthy
Journal: BMJ (2016)

Despite a $100m (£82m; €92m) opposition campaign largely funded by drug companies, polls indicate that Californians strongly favor a measure in the state’s upcoming 8 November ballot mandating that the state should negotiate steep discounts on drugs purchased through its health programs.

The measure comes at a time when 63% of the US public said in a recent poll that government action to lower prescription drug prices was a top priority. US consumers face the highest drug prices in the world, spending $858 per capita in 2013—more than twice the $400 average in 19 other industrialized nations.1 …
TCT-6 Simultaneous Impact of Thrombotic and Bleeding Risks on Use of Novel P2Y12 inhibitors in Contemporary PCI: Results from a Large Single-Center Registry
Authors: Usman Baber, Roxana Mehran, Serdar Farhan, Melissa Aquino, Jason Kovacic, Joseph Sweeny, Pedro Moreno, Srushti Shah, Pooja Vijay, George Dangas, Nitin Barman, Annapoorna Kini, Samin Sharma
Journal: Journal of the American College of Cardiology (2016)
Secondary or Concomitant Neoplasms among Adults Diagnosed with Acute Lymphoblastic Leukemia (ALL) and Treated According to the LALA-87 and LALA-94 Trials.
Authors: Emmanuelle Tavernier, Stephane de Botton, Nathalie Dhedin, Claude-Eric Bulabois, Oumedaly Reman, Norbert Vey, Frederic Garban, Jean-Michel Boiron, Claude Gardin, Nathalie Fegueux, Francis Witz, Bruno Lioure, Nicole Gratecos, Francoise Isnard, Andre Delannoy, Jean-Paul Vernant, Herve Dombret, Veronique Lheritier, Denis Fiere, Xavier Thomas
Journal: Blood (2005)
TCT-418 Procedural and mid-term outcomes of Bioresorbable scaffOlds versus drug-elutiNg stents In chronic Total Occlusions: the BONITO Registry
Authors: Lorenzo Azzalini, Gennaro Giustino, Soledad Ojeda, Antonio Serra, Alessio La Manna, Hung Ly, Barbara Bellini, Susanna Benincasa, Jorge Chavarria Viquez, Livia L. Gheorghe, Giovanni Longo, Eligio Miccichè, Guido D'Agosta, Fabien Picard, Manuel Pan, Corrado Tamburino, Azeem Latib, Mauro Carlino, Alaide Chieffo, Antonio Colombo
Journal: Journal of the American College of Cardiology (2016)
ZW38, a bispecific CD3 x CD19 azymetric antibody to deplete human leukemic B cells by the “controlled” activation of T cells.
Authors: Gordon Ng, Nina Weisser, Grant Wickman, Thomas Spreter von Kreudenstein
Journal: Journal of Clinical Oncology (2015)

e14019 Background: Redirected T cell cytotoxicity (RTCC) has emerged as a promising mechanism for cancer treatments and relies on the co-engagement of tumor antigens and T cells, which can be achieved by the use of bi-specific antibodies. While efficacious, drug classes (like bi-specific T-cell engagers) that redirect the immune system are associated with severe cytokine release syndrome and neurological toxicities. ZW38 is an efficacious bi-specific CD3 x CD19 antibody engineered to confer T cell cytotoxicity with controlled T cell activation for maximal B cell depletion while retaining favorable antibody-like PK and CMC properties. Methods: A bi-specific CD3 x CD19 T cell engager, ZW38, was engineered based on our proprietary Azymetric IgG1-based antibody scaffold. ZW38 was evaluated for its ability to deplete B cells, stimulate T cell proliferation, and promote cytokine release. Results: ZW38 binds to CD3+ and CD19+ cells with nM affinity, and efficiently forms cytolytic immune synapses between human T and B cells. ZW38 effectively depletes human CD19+ lymphoma cells and autologous B cells from ex vivo PBMC and human whole blood cultures and robustly depletes autologous B cells in CLL, MCL, and NHL patient-derived whole blood. In vivo activity of ZW38 was assessed in NSG mice engrafted with IL-2 activated human PBMC and human B-ALL cells. ZW38 induced near complete depletion of leukemic ALL B cells in peripheral blood and secondary lymphoid organs. ZW38’s activity is strictly target dependent as it has been demonstrated to spare CD19- erythroleukemia cells even in the presence of IL-2 stimulated T cells. Furthermore, low levels of T cell proliferation and cytokine release accompanied ZW38-mediated killing, which may translate into an improved therapeutic index. ZW38’s Fc domain has been engineered to knockout Fc-mediated effector functions while retaining binding to FcRn to maintain antibody-like serum half-life and a favorable dosing schedule. Conclusions: ZW38’s efficacy, toxicity profile, PK characteristics, and manufacturability position it as a promising potential therapeutic to treat CD19+ B cell malignancies.
TCT-478 Within a High-Bleeding Risk population which factors drive Stent Choice the most?
Authors: Sang Yeub Lee, Rebecca Torguson, Hector M. Garcia-Garcia, Arie Steinvil, Toby Rogers, Sarkis Kiramijyan, Edward Koifman, Michael Gaglia, Lowell Satler, Augusto Pichard, Ron Waksman
Journal: Journal of the American College of Cardiology (2016)
Randomized Phase II Trial of Seribantumab in Combination With Paclitaxel in Patients With Advanced Platinum-Resistant or -Refractory Ovarian Cancer
Authors: Joyce F. Liu, Isabelle Ray-Coquard, Frederic Selle, Andrés M. Poveda, David Cibula, Hal Hirte, Felix Hilpert, Francesco Raspagliesi, Laurence Gladieff, Philipp Harter, Salvatore Siena, Josep Maria del Campo, Isabelle Tabah-Fisch, Joseph Pearlberg, Victor Moyo, Kaveh Riahi, Rachel Nering, William Kubasek, Bambang Adiwijaya, Akos Czibere, R. Wendel Naumann, Robert L. Coleman, Ignace Vergote, Gavin MacBeath, Eric Pujade-Lauraine
Journal: Journal of Clinical Oncology (2016)

Purpose Seribantumab is a fully human immunoglobulin G2 monoclonal antibody that binds to human epidermal growth factor receptor (HER) 3 (ErbB3), blocking heregulin (HRG) –mediated ErbB3 signaling and inducing ErbB3 receptor downregulation. This open-label randomized phase II study evaluated progression-free survival (PFS) with seribantumab in combination with once-per-week paclitaxel compared with paclitaxel alone in patients with platinum-resistant or -refractory ovarian cancer. A key secondary objective was to determine if any of five prespecified biomarkers predicted benefit from seribantumab. Patients and Methods Patients with platinum-resistant or -refractory epithelial ovarian, fallopian tube, or primary peritoneal cancer were randomly assigned at a ratio of two to one to receive seribantumab plus paclitaxel or paclitaxel alone. Patients underwent pretreatment core needle biopsy; archival tumor samples were also obtained to support biomarker analyses. Results A total of 223 patients were randomly assigned (seribantumab plus paclitaxel, n = 140; paclitaxel alone, n = 83). Median PFS in the unselected intent-to-treat population was 3.75 months with seribantumab plus paclitaxel compared with 3.68 months with paclitaxel alone (hazard ratio [HR], 1.027; 95% CI, 0.741 to 1.425; P = .864). Among patients whose tumors had detectable HRG mRNA and low HER2 (n = 57 [38%] of 151 with available biomarker data), increased treatment benefit was observed in those receiving seribantumab plus paclitaxel compared with paclitaxel alone (PFS HR, 0.37; 95% CI, 0.18 to 0.76; P = .007). The HR in patients not meeting these criteria was 1.80 (95% CI, 1.08 to 2.98; P = .023). Conclusion The addition of seribantumab to paclitaxel did not result in improved PFS in unselected patients. Exploratory analyses suggest that detectable HRG and low HER2, biomarkers that link directly to the mechanism of action of seribantumab, identified patients who might benefit from this combination. Future clinical trials are needed to validate this finding and should preselect for HRG expression and focus on cancers with low HER2 levels.
TCT-523 Instantaneous Hyperemic Diastolic Velocity Pressure Slope for comprehensive physiological evaluation of epicardial and microvascular status
Authors: Nina van der Hoeven, Alicia Quirós, Guus de Waard, Christopher Broyd, Sukhjinder Nijjer, Tim van de Hoef, Ricardo Petraco, Roel Driessen, Hernán Mejía-Rentería, Martijn van Lavieren, Martijn Meuwissen, Ibrahim Danad, Paul Knaapen, Jan Piek, Justin Davies, Niels van Royen, Javier Escaned
Journal: Journal of the American College of Cardiology (2016)
Immunoregulation of Dendritic Cell Subsets by Inhibitory Receptors in Urothelial Cancer
Authors: Mathieu F. Chevalier, Perrine Bohner, Claire Pieraerts, Benoit Lhermitte, Jolanta Gourmaud, Antoine Nobile, Samuel Rotman, Valerie Cesson, Virginie Martin, Anne-Sophie Legris, Florence Dartiguenave, Dalila Gharbi, Laurence De Leval, Daniel E. Speiser, Denise Nardelli-Haefliger, Patrice Jichlinski, Laurent Derré
Journal: European Urology (2016)
Predictive modeling of the outcomes of chemotherapy-induced (febrile) neutropenia prophylaxis with biosimilar filgrastim (MONITOR-GCSF study)
Authors: M. Aapro, H. Ludwig, C. Bokemeyer, P. Gascón, M. Boccadoro, K. Denhaerynck, A. Krendyukov, M. Gorray, K. MacDonald, I. Abraham
Journal: Annals of Oncology (2016)

BackgroundRisk models of chemotherapy-induced (CIN) and febrile neutropenia (FN) have to date focused on determinants measured at the start of chemotherapy. We extended this static approach with a dynamic approach of CIN/FN risk modeling at the start of each cycle.DesignWe applied predictive modeling using multivariate logistic regression to identify determinants of CIN/FN episodes and related hospitalizations and chemotherapy disturbances (CIN/FN consequences) in analyses at the patient ('ever' during the whole period of chemotherapy) and cycle-level (during a given chemotherapy cycle). Statistical dependence of cycle data being 'nested' under patients was managed using generalized estimation equations. Predictive performance of each model was evaluated using bootstrapped c concordance statistics.ResultsStatic patient-level risk models of 'ever' experiencing CIN/FN adverse events and consequences during a planned chemotherapy regimen included predictors related to history, risk factors, and prophylaxis initiation and intensity. Dynamic cycle-level risk models of experiencing CIN/FN adverse events and consequences in an upcoming cycle included predictors related to history, risk factors, and prophylaxis initiation and intensity; as well as prophylaxis duration, CIN/FN in prior cycle, and treatment center characteristics.Conclusion(s)These 'real-world evidence' models provide clinicians with the ability to anticipate CIN/FN adverse events and their consequences at the start of a chemotherapy line (static models); and, innovatively, to assess risk of CIN/FN adverse events and their consequences at the start of each cycle (dynamic models). This enables individualized patient treatment and is consistent with the EORTC recommendation to re-appraise CIN/FN risk at the start of each cycle. Prophylaxis intensity (under-, correctly-, or over-prophylacted relative to current EORTC guidelines) is a major determinant. Under-prophylaxis is clinically unsafe. Over-prophylaxis of patients administered chemotherapy with intermediate or low myelotoxicity levels may be beneficial, both in patients with and without risk factors, and must be validated in future studies.
TCT-165 Hyperemic microvascular resistance is a predictor of clinical outcome after revascularization for acute myocardial infarction: A patient-level pooled analysis
Authors: Guus de Waard, Gregor Fahrni, Douwe de Wit, Hironori Kitabata, Rupert Williams, Niket Patel, Paul Teunissen, Paul Knaapen, Divaka Perera, Takashi Akasaka, Murat Sezer, Rajesh Kharbanda, Niels van Royen
Journal: Journal of the American College of Cardiology (2016)
TGF-β inhibitor LY2157299 (galunisertib) in combination with standard chemotherapy and inhibition of signaling to pSmad and EMT and suppression of tumor growth in gastric cancer.
Authors: Sawako Miyoshi, Masahisa Kudo, Kohei Shitara, Mayumi Yamauchi, Toshihiko Doi, Yasuhiro Matsumura
Journal: Journal of Clinical Oncology (2016)

50 Background: TGF-β signaling is known to promote epithelial-mesenchymal transition (EMT) of tumor cells, thus producing tumor progression, invasion, and metastasis. Therefore, this signaling has been expected to be a new target of cancer therapy. In this study, we evaluated the antitumor effect of LY2157299, a TGF-βR1 kinase inhibitor, alone and in combination with 5-fluorouracil (5-FU) or paclitaxel (PTX), key agents in the treatment of gastric cancer (GC). Methods: TGF-β inhibition impedes phosphorylation of Smad2 and induces the expression of vimentin, an EMT marker. Vimentin expression was examined +/- LY2157299 by western blot. The phenotypic change of human GC cell, 44As3-Luc after TGF-β and LY2157299 treatment was assessed by Matrigel migration/invasion assay. The in vitro cytocidal effect and in vivo antitumor effect of LY2157299 alone or with either 5-FU or PTX were evaluated by water soluble tetrazolium-1 (WST-1) assay and by xenograft mouse model, respectively. Results: The phosphorylation of Smad2, the expression of vimentin and the optical mesenchymal transformation in 44As3-Luc induced by TGF-β were successfully suppressed by LY2157299. Accordingly, the activity of migration and invasion evoked by TGF-β was suppressed significantly by co-administration of LY2157299 with TGF-β. Although LY2157299 monotherapy did not show a tumor suppressive effect and LY2157299 did not potentiate the cell toxicity of 5-FU and PTX in vitro, LY2157299 reduced tumor volume (TV) of 44As3-Luc xenografts by 64% of control (p &lt; 0.05). 5-FU + LY2157299 treatment reduced TV of 5-FU alone by 52% (p &lt; 0.05) and PTX + LY2157299 treatment also reduced TV of PTX alone by 52% (p &lt; 0.05). These results suggest that LY2157299 suppresses tumor growth possibly through some effect of LY2157299 in tumor-stroma environment. Conclusions: LY2157299 inhibited migration and invasion of GC cell line. Moreover, the monotherapy of LY2157299 and the combination therapy of LY2157299 with 5-FU or PTX significantly suppressed tumor growth. These findings warrant clinical evaluation of LY2157299 in patients with GC.
Patterns of use and outcomes with irinotecan and oxaliplatin in the treatment of 5-fluorouracil (5-FU) refractory metastatic colorectal cancer: An Australian population based analysis
Authors: D. Damianovich, M. Adena, N. Tebbutt
Journal: Journal of Clinical Oncology (2006)

3630 Background: Randomised clinical trials have established an important role for oxaliplatin (O) and irinotecan (I) in the management of advanced colorectal cancer (CRC). However, patients (pts) enrolled in clinical studies represent a restricted population and little is known about the use of O and I in the general population and the subsequent outcomes outside clinical studies. We used the Australian Health Insurance Commission (HIC) database to describe prescribing patterns of O and I and their impact on survival in all patients with 5-FU refractory CRC in Australia in 2002 and 2003. Methods: The Australian HIC database was searched to identify all patients with 5-FU refractory CRC who received initial treatment with either O or I in 2002 and 2003. Survival of patients was determined based on subsequent receipt of any other prescriptions for other medication identified in the HIC database. Results: 2999 patients received initial treatment with O or I in Australia in 2002 and 2003. 62% of pts were male and 23% and 2% were aged ≥70 years and ≥80 years respectively. There was a marked increase in initial treatment with O rather than I; 48% of pts received O first in 2002 versus 66% in 2003 (p&lt;0.001). Overall 40–45% of pts received both O and I, however younger pts were more likely to receive both drugs (p&lt;0.001). After 5-FU failure and treatment with O or I, estimated 6-month and 12-month survival was 0.67 (95% CI 0.66–0.69) and 0.42 (95% CI 0.40–0.44) respectively. Six and twelve month survival was superior for pts who received both O and I, however the sequence of O and I had no impact on survival. Survival of older pts (≥70 years) was inferior to younger pts no matter whether O or I was used as initial treatment. Conclusions: Analysis of the Australian HIC database provides a valuable means of assessing patterns of use and outcomes of new therapies. This type of analysis could also be used to evaluate other new agents. [Table: see text]
TCT-94 Impact of Thin-Cap Fibroatheromas on Unanticipated Ischemic Events in Medically Treated Patients With Diabetes Mellitus: Insights From the PROSPECT Study
Authors: Elvin Kedhi, Mark Kennedy, Akiko Maehara, Alexandra Lansky, Thomas McAndrew, Steven Marso, Bernard De Bruyne, Patrick Serruys, Gregg Stone
Journal: Journal of the American College of Cardiology (2016)
TCT-262 Clinical Outcomes of Deferred Revascularisation Using Fractional Flow Reserve in Patients With and Without Diabetes Mellitus
Authors: Mark Kennedy, Eliza Kaplan, Rik Hermanides, Enrico Fabris, Veemal Hemradj, Petra Koopmans, Jan-Henk Dambrink, Marcel Gosselink, Arnoud van't Hof, Jan Paul Ottervanger, Vincent Roolvink, Wouter Remkes, Aize van der Sluis, Harry Suryapranata, Elvin Kedhi
Journal: Journal of the American College of Cardiology (2016)