tbuckley/cabot-search huggingface dataset:
Concern Over Family Planning Clinics
Authors: Jeff Lyon
Journal: JAMA (2017)

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TCTAP C-067 Kissing Balloon Technique with Drug-coated Balloons Is Effective for Repeated In-stent Restenosis at the Bifurcation of Left Anterior Descending Artery and Left Circumflex Artery
Authors: Mayumi Saso, Yuya Tanaka, Yoko Kurumatani, Kazuyoshi Ohata
Journal: Journal of the American College of Cardiology (2017)
Pharmacogenomic modeling of pancreatic cancer (PDAC) for prediction of chemotherapy response and resistance in second-line treatment setting.
Authors: Kenneth H. Yu, Vineet Sangar, Mark Ricigliano, Manuel Hidalgo, Eileen Mary O'Reilly, Ghassan K. Abou-Alfa, Maeve Aine Lowery, Joseph F. Crotty, Kristen Gary, Brandon Cooper, Rena G. Lapidus, Mariola Sadowska
Journal: Journal of Clinical Oncology (2014)

4130 Background: PDAC is a leading and rising cause of cancer mortality. Despite this, modern cytotoxics (C) can induce tumor responses and extend life. Xenograft models have shown that pharmacogenomic (PGx) modeling of C can predict efficacy. We previously presented results supporting PGx profiling of circulating tumor and invasive cells (CTICs) to predict effective C in the 1st line setting. We now present results in the second-line setting. Methods: PGx models for five common PDAC C regimens were created from the GI50 data obtained from the NCI-60 cell lines. These PGx models were validated in a prospective study of 50 patients with unresectable PDAC. 10 mL of peripheral blood was collected prior to C and at disease progression. CTICs were isolated, total RNA extracted and gene-expression analysis performed. Gene and pathway analyses were performed comparing patients with short v long TTP and for an individual patient at baseline v at time of progression. Results: CTICs were isolated, and gene expression profiles were obtained in all 50 patients prior to initiating C and in 25 patients at first-line disease progression. In the 1st line setting, we previously presented that CTIC PGx profiling predicted effective versus ineffective C treatment. In the 2nd line setting, 15 patients were evaluable for C response. Clinical benefit was again seen for patients treated with C predicted to be effective versus ineffective (PFS 5.7 mo v 2.5 mo, p=0.027, HR 0.15; OS 8.6 mo v 3.4 mo, p=0.020, HR 0.14). Changes in PGx profiles at disease progression reflected resistance to first-line C treatment. Widespread dysregulation in 32 gene pathways was found in CTICs at disease progression. CTIC SMAD4, ATM and XPO1 expression levels correlated with TTP in the first-line setting. Conclusions: PGx profiling of CTICs from patients with unresectable PDAC can predict effective C, both in the first- and second-line setting. Repeat PGx profiling identifies key gene pathways associated with treatment resistance. Clinical trial information: NCT01474564. Treatment response, PGx prediction Sensitive Resistant First Line (n=35) PFS (mo) 10.4 3.6 p = 0.0001, HR 0.14 OS (mo) 17.2 8.3 p = 0.0249, HR 0.29 Second Line (n=15) PFS (mo) 5.7 2.5 p = 0.027, HR 0.15 OS (mo) 8.6 3.4 p = 0.020, HR 0.14
Marginal zone B cells control the response of follicular helper T cells to a high-cholesterol diet
Authors: Meritxell Nus, Andrew P Sage, Yuning Lu, Leanne Masters, Brian Y H Lam, Stephen Newland, Sandra Weller, Dimitrios Tsiantoulas, Juliette Raffort, Damiënne Marcus, Alison Finigan, Lauren Kitt, Nichola Figg, Reinhold Schirmbeck, Manfred Kneilling, Giles S H Yeo, Christoph J Binder, José Luis de la Pompa, Ziad Mallat
Journal: Nature Medicine (2017)
Protease‐activated receptor‐2 suppresses interleukin (<scp>IL</scp>)‐10 expression in B cells via upregulating Bcl2L12 in patients with allergic rhinitis
Authors: J.‐M. Xue, L.‐T. Yang, G. Yang, X.‐R. Geng, Z.‐Q. Liu, S. Wang, H.‐L. Zhao, Z.‐G. Liu, C.‐Q. Zhao, P.‐C. Yang
Journal: Allergy (2017)

Abstract Background and aims The function of interleukin ( IL )‐10‐producing B cells (B10 cell) is compromised in patients with allergic diseases. Protease‐activated receptor ( PAR )‐2 has immunoregulatory functions. This study aimed to elucidate the role of PAR 2 in the suppression of IL ‐10 expression in peripheral B cells. Methods Peripheral blood B cells were collected from patients with allergic rhinitis ( AR ). A correlation between the expression of Bcl2‐like protein 12 (Bcl2L12) and IL ‐10 in the B cells was analyzed. An AR mouse model was developed. Results We observed that the expression of IL ‐10 was lower in the peripheral B cells from patients with airway allergy. A negative correlation was identified between the expression of IL ‐10 and PAR 2 in B cells. Activation of PAR 2 of B cells increased the expression of Bcl2L12 and suppression of LPS ‐induced IL ‐10 expression, which were inhibited by knocking down the Bcl2L12 gene. Treating B cells from AR patients with Bcl2L12‐sh RNA ‐carrying liposomes reversed the capability of IL ‐10 expression and the immunosuppressive function. Administration of Bcl2L12 sh RNA ‐carrying liposomes attenuated experimental AR in mice. Conclusions Activation of PAR 2 inhibits the expression of IL ‐10 in B cells, which can be reversed by treating B cells with Bcl2L12 sh RNA ‐carrying liposomes. The data suggest that regulation of Bcl2L12 may be a novel approach in the treatment for AR .
Chemotherapy-Resistant Human Acute Myeloid Leukemia Cells Are Not Enriched for Leukemic Stem Cells but Require Oxidative Metabolism
Authors: Thomas Farge, Estelle Saland, Fabienne de Toni, Nesrine Aroua, Mohsen Hosseini, Robin Perry, Claudie Bosc, Mayumi Sugita, Lucille Stuani, Marine Fraisse, Sarah Scotland, Clément Larrue, Héléna Boutzen, Virginie Féliu, Marie-Laure Nicolau-Travers, Stéphanie Cassant-Sourdy, Nicolas Broin, Marion David, Nizar Serhan, Audrey Sarry, Suzanne Tavitian, Tony Kaoma, Laurent Vallar, Jason Iacovoni, Laetitia K. Linares, Camille Montersino, Rémy Castellano, Emmanuel Griessinger, Yves Collette, Olivier Duchamp, Yara Barreira, Pierre Hirsch, Tony Palama, Lara Gales, François Delhommeau, Barbara H. Garmy-Susini, Jean-Charles Portais, François Vergez, Mary Selak, Gwenn Danet-Desnoyers, Martin Carroll, Christian Récher, Jean-Emmanuel Sarry
Journal: Cancer Discovery (2017)

Abstract Chemotherapy-resistant human acute myeloid leukemia (AML) cells are thought to be enriched in quiescent immature leukemic stem cells (LSC). To validate this hypothesis in vivo, we developed a clinically relevant chemotherapeutic approach treating patient-derived xenografts (PDX) with cytarabine (AraC). AraC residual AML cells are enriched in neither immature, quiescent cells nor LSCs. Strikingly, AraC-resistant preexisting and persisting cells displayed high levels of reactive oxygen species, showed increased mitochondrial mass, and retained active polarized mitochondria, consistent with a high oxidative phosphorylation (OXPHOS) status. AraC residual cells exhibited increased fatty-acid oxidation, upregulated CD36 expression, and a high OXPHOS gene signature predictive for treatment response in PDX and patients with AML. High OXPHOS but not low OXPHOS human AML cell lines were chemoresistant in vivo. Targeting mitochondrial protein synthesis, electron transfer, or fatty-acid oxidation induced an energetic shift toward low OXPHOS and markedly enhanced antileukemic effects of AraC. Together, this study demonstrates that essential mitochondrial functions contribute to AraC resistance in AML and are a robust hallmark of AraC sensitivity and a promising therapeutic avenue to treat AML residual disease. Significance: AraC-resistant AML cells exhibit metabolic features and gene signatures consistent with a high OXPHOS status. In these cells, targeting mitochondrial metabolism through the CD36–FAO–OXPHOS axis induces an energetic shift toward low OXPHOS and strongly enhanced antileukemic effects of AraC, offering a promising avenue to design new therapeutic strategies and fight AraC resistance in AML. Cancer Discov; 7(7); 716–35. ©2017 AACR. See related commentary by Schimmer, p. 670. This article is highlighted in the In This Issue feature, p. 653
Abstract 11: Associations of Gluten Intake With Type 2 Diabetes Risk and Weight Gain in Three Large Prospective Cohort Studies of US Men and Women
Authors: Geng Zong, Benjamin Lebwohl, Frank Hu, Laura Sampson, Lauren Dougherty, Walter Willett, Andrew Chan, Qi Sun
Journal: Circulation (2017)

Background: Gluten-free diets have grown in popularity, but evidence is lacking regarding gluten intake and long-term health. Methods: In Nurses’ Health Study (NHS, n=69,276), NHSII (n=88,610), and the Health Professionals Follow-Up Study (HPFS, n=41,908), we estimated gluten intake using a validated food-frequency questionnaire collected every 2-4 years. Incident T2D was defined as physician diagnosed diabetes and confirmed with supplementary information. Results: Gluten intake (mean ± standard deviation) was 5.83±2.23, 6.77±2.50, and 7.06±2.76 grams/day in NHS, NHSII, and HPFS, respectively, and strongly correlated with intakes of carbohydrate sources, especially refined grains, starch, and cereal fiber (Spearman correlation coefficients &gt; 0.6). During 4.24 million years of follow-up, 15,947 T2D cases were confirmed. An inverse association between gluten intake and T2D risk was observed in all three cohorts after multivariate adjustment (table), and hazard ratio (HR, 95% confidence intervals [95%CI]) comparing extreme quintiles was 0.80(0.76, 0.84; P&lt;0.001). The associations were slightly attenuated after further adjusting for cereal fiber (HR[95%CI]= 0.87[0.81, 0.93]), but not other carbohydrate components. Among participants without major chronic diseases and aged &lt;65 years, changes in gluten intake were not significantly associated with weight gain in multivariate adjusted model: 4-year weight change (95%CI, lb) was 0.08(-0.06, 0.22; P=0.25) in NHS, -0.05(-0.18, 0.08; P=0.43) in NHSII, and 0.36(-0.24, 0.96; P=0.24) HPFS for each 5 grams increase in gluten intake. Conclusions: Our findings suggest that gluten intake may not exert significant adverse effects on the incidence of T2D or excess weight gain. Limiting gluten from diet is thus unlikely to facilitate T2D prevention and may lead to reduced consumption of cereal fiber or whole grains that help reduce diabetes risk.
TCTAP C-213 Successful Endovascular Treatment of Chronic Total Superficial Femoral Artery Occlusion Using a Side-hole Sheath and Re-entry Catheter
Authors: Reiko Shiomura, Yasuhiro Takahashi, Erito Furuse, Junya Matsuda, Taisuke Sato, Wataru Shimizu
Journal: Journal of the American College of Cardiology (2017)
Lodamin (PEG-PLA-TNP-470), a novel formulation for oral administration of TNP-470 as a potent antiangiogenic and anti-cancer drug.
Authors: Ofra Benny, Ofer Fainaru, Lauren Bazinet, Samir Koirala, Gabriel Corfas, Judah Folkman
Journal: Cancer Research (2008)

1118  Targeting angiogenesis, the formation of new blood vessels, is becoming an important strategy for cancer therapy. TNP-470, an analog of fumagillin, is among the most potent inhibitors of angiogenesis. This drug has broader antiangiogenic activity than most known drugs, as demonstrated in numerous animal tumor models.  In clinical trials, TNP-470 showed significant inhibition of tumors, including durable complete regression (Kudelka AP et al. N Engl J Med 338, 991-2, 1998). The clinical efficacy of TNP-470 was limited by neurotoxicity that was solved by the development of Caplostatin, an HPMA polymer conjugate of TNP-470 (formulation for injection) (Satchi-Fainaro et al., Nature Medicine 10, 255-261, 2004, Satchi-Fainaro et al., Cancer Cell 7, 251-61, 2005).  However, a major clinical limitation still remains: The TNP-470 has a poor oral availability and short plasma half-life (minutes), necessitating frequent continuous parenteral administration as an infusion of 1-4 hr a few times a week.  We have now addressed these issues, and report here for the first time a formulation for oral administration of TNP-470, named Lodamin. TNP-470 is conjugated to a copolymer: poly(ethylene-glycol)-poly(lactic)acid (PEG-PLA). The conjugation is then self-assembled into polymeric-micelles, where TNP-470 is located in the core, and protected from the acidic environment of the stomach, thus enabling oral availability.  Lodamin has a spherical morphology as shown by transmission electron microscopy (10-100 nm). The release kinetics of TNP-470 from Lodamin was determined in-vitro at pH 1.2 and 7.4 and revealed a slow release for up to 28 days.  In-vitro, Lodamin was rapidly taken up by endothelial cells as demonstrated by confocal microscopy and flow cytometry, and significantly inhibited cell proliferation.  Lodamin was effectively absorbed in the intestineand remained active. A corneal micropocket assay, in which the angiogenic response was measured 6 days after implantation of VEGF pellets, showed that oral Lodamin inhibited VEGF-induced vessel growth by 40%. In tumor-bearing mice, Lodamin effectively inhibited tumor growth of both subcutaneous Lewis Lung Carcinoma (~87%) and B16/F10 melanoma (~77%), while oral free TNP-470 did not affect tumor growth. Histological sections of the tumors showed that oral Lodamin decreased angiogenesis and proliferation of tumor cells.  Biodistribution experiments showed Lodamin to be concentrated in tumors without penetration into the brain. Furthermore, unlike free TNP-470, oral Lodamin did not cause TNP-470-related neurological impairment, as tested by the ability of mice to walk on a narrow-beam without losing their balance.  Therefore, we report Lodamin as a first in its class compound of oral antiangiogenic, non-toxic, anti-cancer drugs that can be chronically administered for cancer therapy or for prevention of tumor recurrence.
Donor type, in addition to transplantation in chronic phase and myeloablative conditioning, influence transplant survival for patients with advanced chronic myeloid leukemia in the era of tyrosine kinase inhibitors
Authors: P Kongtim, K Adekola, D R Milton, R Ramlal, A Jimenez, J Chen, G Rondon, S Ahmed, P Kebriaei, O Betul, C M Hosing, U Popat, I Khouri, E Jabbour, J E Cortes, H M Kantarjian, R E Champlin, S O Ciurea
Journal: Leukemia (2017)
FUNCTIONAL MOVEMENT SCREEN AND LOWER LIMB STRENGTH ASYMMETRY IN PROFESSIONAL SOCCER PLAYERS
Authors: Italo Sannicandro, Giacomo Cofano, Anna Rosa Rosa, Paolo Traficante, Andrea Piccinno
Journal: British Journal of Sports Medicine (2017)

Background The Functional Movement Screen (FMS) protocol consists of 7 tests (Cook &amp; Burton, 2014). At higher values mean higher quality of movement execution. Lower limb functional asymmetry (FA) is monitored to control the athlete's injury risk (Sannicandro et al ., 2011). Objective To examine the correlation between the FMS score and strength asymmetry in professional soccer players (PSP). Design Descriptive study (correlation study investigating the relationship between variables). Setting Professional soccer. Participants n=30 professional soccer players (age: 22.2±4.6; weight: 74.3±10,1 kg; height: 176.1±8.7 cm), 4 players were excluded due to joint or muscle injury within the last 18 months. Assessment of Risk Factors The FMS protocol identifies athletes as being at risk of injury when the total score is ≤14. The Hop Test (HT), Side Hop (SH) and Hop Crossover (CH) test are considered to represent a valid assessment of the single lower limb FA. The counter movement jump (CMJ) test indirectly evaluates explosive strength capacity (jump height). Main Outcome Measurements The sample was evaluated using the 7 FMS test and CMJ, HT, SH and CH tests for strength capacity. FA was calculated between the two limbs as follows: (jump dominant limb–jump non-dominant limb)/jump dominant-limb*100 (Yamamoto, 1993). Results We observed a significant inverse correlation between FMS score and the SH asymmetry percentage (r=−0.678, p&lt;0.01) and the CH asymmetry percentage (r=−0.572,p&lt;0.01). We also observed a significant positive correlation between the FMS score and CMJ values (r=0.531, p&lt;0.01). No significant correlation was found between FMS and the HT asymmetry percentage (r=−0.245). Conclusions The best quality movement in FMS test was correlated with high performance in CMJ and with low percentage of lower limb FA, respectively.
Emotional Modulation of Learning and Memory: Pharmacological Implications
Authors: Ryan T. LaLumiere, James L. McGaugh, Christa K. McIntyre
Journal: Pharmacological Reviews (2017)

Memory consolidation involves the process by which newly acquired information becomes stored in a long-lasting fashion. Evidence acquired over the past several decades, especially from studies using post-training drug administration, indicates that emotional arousal during the consolidation period influences and enhances the strength of the memory and that multiple different chemical signaling systems participate in this process. The mechanisms underlying the emotional influences on memory involve the release of stress hormones and activation of the basolateral amygdala, which work together to modulate memory consolidation. Moreover, work suggests that this amygdala-based memory modulation occurs with numerous types of learning and involves interactions with many different brain regions to alter consolidation. Additionally, studies suggest that emotional arousal and amygdala activity in particular influence synaptic plasticity and associated proteins in downstream brain regions. This review considers the historical understanding for memory modulation and cellular consolidation processes and examines several research areas currently using this foundational knowledge to develop therapeutic treatments.
Lenalidomide Maintenance Compared With Placebo in Responding Elderly Patients With Diffuse Large B-Cell Lymphoma Treated With First-Line Rituximab Plus Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone
Authors: Catherine Thieblemont, Hervé Tilly, Maria Gomes da Silva, Rene-Olivier Casasnovas, Christophe Fruchart, Franck Morschhauser, Corinne Haioun, Julien Lazarovici, Anida Grosicka, Aurore Perrot, Judith Trotman, Catherine Sebban, Dolores Caballero, Richard Greil, Koen van Eygen, Amos M. Cohen, Hugo Gonzalez, Reda Bouabdallah, Lucie Oberic, Bernadette Corront, Bachra Choufi, Armando Lopez-Guillermo, John Catalano, Achiel Van Hoof, Josette Briere, Jose Cabeçadas, Gilles Salles, Philippe Gaulard, Andre Bosly, Bertrand Coiffier
Journal: Journal of Clinical Oncology (2017)

Purpose The standard treatment of patients with diffuse large B-cell lymphoma (DLBCL) is rituximab in combination with cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). Lenalidomide, an immunomodulatory agent, has shown activity in DLBCL. This randomized phase III trial compared lenalidomide as maintenance therapy with placebo in elderly patients with DLBCL who achieved a complete response (CR) or partial response (PR) to R-CHOP induction. Methods Patients with previously untreated DLBCL or other aggressive B-cell lymphoma were 60 to 80 years old, had CR or PR after six or eight cycles of R-CHOP, and were randomly assigned to lenalidomide maintenance 25 mg/d or placebo for 21 days of every 28-day cycle for 24 months. The primary end point was progression-free survival (PFS). Results A total of 650 patients were randomly assigned. At the time of the primary analysis (December 2015), with a median follow-up of 39 months from random assignment, median PFS was not reached for lenalidomide maintenance versus 58.9 months for placebo (hazard ratio, 0.708; 95% CI, 0.537 to 0.933; P = .01). The result was consistent among analyzed subgroups (eg, male v female, age-adjusted International Prognostic Index 0 or 1 v 2 or 3, age younger than 70 v ≥ 70 years), response (PR v CR) after R-CHOP, and positron emission tomography status at assignment (negative v positive). With longer median follow-up of 52 months (October 2016), overall survival was similar between arms (hazard ratio, 1.218; 95% CI, 0.861 to 1.721; P = .26). Most common grade 3 or 4 adverse events associated with lenalidomide versus placebo maintenance were neutropenia (56% v 22%) and cutaneous reactions (5% v 1%), respectively. Conclusion Lenalidomide maintenance for 24 months after obtaining a CR or PR to R-CHOP significantly prolonged PFS in elderly patients with DLBCL.
Invariant natural killer T cells ameliorate murine chronic GVHD by expanding donor regulatory T cells
Authors: Jing Du, Katelyn Paz, Govindarajan Thangavelu, Dominik Schneidawind, Jeanette Baker, Ryan Flynn, Omar Duramad, Colby Feser, Angela Panoskaltsis-Mortari, Robert S. Negrin, Bruce R. Blazar
Journal: Blood (2017)
Clinical decision tools are needed to identify HIV-positive patients at high risk for poor outcomes after initiation of antiretroviral therapy
Authors: Margaret L. McNairy, Elaine J. Abrams, Miriam Rabkin, Wafaa M. El-Sadr
Journal: PLoS Medicine (2017)

Margaret McNairy and colleagues highlight the need for clinical decision tools to help identify HIV patients who would benefit from tailored services to avoid poor outcomes such as death and loss to follow-up.