tbuckley/cabot-search huggingface dataset:
Managing chest drains on medical wards
Authors: F R Millar, T Hillman
Journal: BMJ (2018)

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Evidence of Artemisinin-Resistant <i>Plasmodium falciparum</i> Malaria in Eastern India
Authors: Sabyasachi Das, Bhaskar Saha, Amiya K. Hati, Somenath Roy
Journal: New England Journal of Medicine (2018)

Artemisinin Resistance in India In this study, possible resistance mutations and parasite survival among Plasmodium falciparum isolates obtained from patients in West Bengal, India, were investigat...
Modulating the Tumor Microenvironment via Oncolytic Viruses and CSF-1R Inhibition Synergistically Enhances Anti-PD-1 Immunotherapy
Authors: Gang Shi, Qianmei Yang, Yujing Zhang, Qingyuan Jiang, Yi Lin, Shenshen Yang, Huiling Wang, Lin Cheng, Xin Zhang, Yimin Li, Qingnan Wang, Yi Liu, Qin Wang, Hantao Zhang, Xiaolan Su, Lei Dai, Lei Liu, Shuang Zhang, Jia Li, Zhi Li, Yang Yang, Dechao Yu, Yuquan Wei, Hongxin Deng
Journal: Molecular Therapy (2018)

Immunotherapy based on the immune checkpoint blockade has emerged as the most promising approach for cancer therapy. However, the proportion of colorectal cancer patients who benefit from immunotherapy is small due to the immunosuppressive tumor microenvironment. Hence, combination immunotherapy is an ideal strategy to overcome this limitation. In this study, we developed a novel combination of CSF-1R (colony-stimulating factor 1 receptor) inhibitor (PLX3397), oncolytic viruses, and anti-PD-1 antibody. Our results demonstrated that the triple treatment synergistically conferred significant tumor control and prolonged the survival of mouse models of colon cancer. Approximately 43% and 82% of mice bearing the CT26 and MC38 tumor, respectively, survived long term following the triple treatment. This combination therapy reprogrammed the immunosuppressive tumor microenvironment toward a CD8+ T cell-biased anti-tumor immunity by increasing T cell infiltration in the tumor and augmenting anti-tumor CD8+ T cell function. Our results provide a robust strategy for clinical combination therapy. Immunotherapy based on the immune checkpoint blockade has emerged as the most promising approach for cancer therapy. However, the proportion of colorectal cancer patients who benefit from immunotherapy is small due to the immunosuppressive tumor microenvironment. Hence, combination immunotherapy is an ideal strategy to overcome this limitation. In this study, we developed a novel combination of CSF-1R (colony-stimulating factor 1 receptor) inhibitor (PLX3397), oncolytic viruses, and anti-PD-1 antibody. Our results demonstrated that the triple treatment synergistically conferred significant tumor control and prolonged the survival of mouse models of colon cancer. Approximately 43% and 82% of mice bearing the CT26 and MC38 tumor, respectively, survived long term following the triple treatment. This combination therapy reprogrammed the immunosuppressive tumor microenvironment toward a CD8+ T cell-biased anti-tumor immunity by increasing T cell infiltration in the tumor and augmenting anti-tumor CD8+ T cell function. Our results provide a robust strategy for clinical combination therapy.
Re: Liselotte M.S. Boevé, Maarten C.C.M. Hulshof, André N. Vis, et al. Effect on Survival of Androgen Deprivation Therapy Alone Compared to Androgen Deprivation Therapy Combined with Concurrent Radiation Therapy to the Prostate in Patients with Primary Bone Metastatic Prostate Cancer in a Prospective Randomised Clinical Trial: Data from the HORRAD Trial. Eur Urol 2019;75:410–8
Authors: Herney Andrés García-Perdomo
Journal: European Urology (2018)
A Randomized Phase III Study of Ibrutinib (PCI-32765)-Based Therapy Vs. Standard Fludarabine, Cyclophosphamide, and Rituximab (FCR) Chemoimmunotherapy in Untreated Younger Patients with Chronic Lymphocytic Leukemia (CLL): A Trial of the ECOG-ACRIN Cancer Research Group (E1912)
Authors: Tait D. Shanafelt, Victoria Wang, Neil E. Kay, Curtis A. Hanson, Susan M. O'Brien, Jacqueline C Barrientos, Harry P. Erba, Richard M. Stone, Mark R. Litzow, Martin S. Tallman
Journal: Blood (2018)
AB0552 The clinical and laboratory features of antiphospholipid antibody positive patients with or without systemic lupus erythematosus
Authors: A. Yazici, A. Omma, S. Yilmaz, S. Yavuz, K. Ayar, E. Kasapoglu, B. Kisacik, A. Cefle, D. Erkan
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> A multicenter antiphospholipid antibody (aPL) clinical database was created in 2016 with the pariticipation of six rheumatology centres around the country. The purpose has been to better define aPL-related clinical manifestations and management strategies; and also to establish a resource for future clinical studies. <h3>Objectives</h3> In this first analysis, we compared the clinical and laboratory features of aPL-positive patients with and without systemic lupus erythematosus (SLE). <h3>Methods</h3> The demographic, clinical, laboratory, treatment characteristics of the aPL-positive patients with/without other systemic autoimmune diseases (SAID) are recorded at enrollment according to a predefined protocol. The inclusion criteria are positive aPL (lupus anticoagulant test [LA], anticardiolipin antibody [aCL], and/or anti β<sub>2</sub>-glycoprotein-I antibody [aβ<sub>2</sub>GPI]) based on the Updated Sapporo Antiphospholipid Syndrome (APS) Classification Criteria at least twice within one year prior to enrolment.<sup>1,2</sup> For the purpose of this analysis, we only included aPL-positive patients without other autoimmune diseases (primary aPL/APS) and aPL-positive SLE patients (SLE aPL/APS). <h3>Results</h3> As of January 2018, 105 aPL-positive patients were recruited (mean age: 42.6±10.1 [min-max: 19–70]; 83 [79%] female; and 67 [64%] with another SAID). Ten patients were excluded from the analysis due to their SAID history other than SLE. Of the remaining 95 patients, 38 (40%) had primary aPL/APS; 57 (60%) fulfilled the ACR SLE Classification Criteria; 42 (44%) had thrombotic APS (TAPS) (8 arterial, 24 venous, and 8 both); 21 (22%) had obstetric APS (OAPS); 22 (23%) had both TAPS and OAPS (7 arterial, 14 venous, and 1 both); and 10 (11%) had no TAPS/OAPS. Fifty percent of the patients had history of at least one non-criteria aPL-manifestation. Demographics, clinical and laboratory manifestations, and medications were similar between primary aPL/APS and SLE aPL/APS patients except increased frequency of autoimmune hemolytic anaemia, aCL IgG, and hydroxychloroquine use in SLE aPL/APS patients (table 1). <h3>Conclusions</h3> The analysis of our multicenter aPL database demonstrates that the frequencies of thrombosis and pregnancy morbidity are similar between aPL-positive patients with or without SLE. Half of the patients in both groups had history of at least one "non-criteria" aPL-manifestation; only autoimmune hemolytic anaemia was more frequent in aPL-positive patients with SLE. <h3>References</h3> [1] Schreiber K, Sciascia S, de Groot PG, Devreese K, Jacobsen S, Ruiz-Irastorza G, et al. Antiphospholipid syndrome. Nat Rev Dis Primers2018;4:17103. [2] Gómez-Puerta JA, Cervera R. Diagnosis and classification of the antiphospholipid syndrome. J Autoimmun2014;48–49:20–5. <h3>Disclosure of Interest</h3> None declared
Abstract 13540: Adherence and Healthcare Utilization Following Initiation of Sacubitril/Valsartan Among Veterans With Heart Failure and Reduced Ejection Fraction
Authors: April Mohanty, Emily B Levitan, John A Dodson, Tao He, Patricia A Russo, Adam P Bress
Journal: Circulation (2017)

Introduction: Sacubitril/Valsartan (S/V) is approved to reduce cardiovascular death and hospitalizations in heart failure with reduced ejection fraction (HFrEF) based on the PARADIGM-HF trial, and compared S/V to Enalapril. Adherence data in community-treated HFrEF patients is limited and may inform clinicians as to whether this new medication is well-tolerated in “real-world” settings. Hypothesis: We hypothesized that medication adherence and healthcare utilization is similar in S/V and angiotensin converting enzyme inhibitor (ACEI)/angiotensin receptor blocker (ARB) users. Methods: Retrospective cohort study using Veterans Affairs data of patients with HFrEF (≥1 left ventricular ejection fraction ≤40% and ≥1 in/outpatient visit for heart failure within 1-year pre-index) treated with S/V or an ACEI/ARB from 7/7/15 to 11/21/16. The index date was the first S/V fill and if none, the first ACEI/ARB fill. In Veterans who switched from ACEI/ARB to S/V or maintained ACEI/ARB and who had a 30-day supply index f...
HDL Cholesterol: A “Pathogen Lipid Sink” for Sepsis?
Authors: Tiffanie K. Jones, Hector R. Wong, Nuala J. Meyer
Journal: American Journal of Respiratory and Critical Care Medicine (2018)

heterogeneity in its definition.Longitudinal data would be informative with regard to whether sensitization has a role in bronchiectasis pathogenesis or the bronchiectasis state predisposes the host to atopy.The study is notable on several levels.The international collaboration is, again, remarkable.The study moves the field of bronchiectasis forward in two significant ways: first, it describes atopy and sensitization in bronchiectasis on a large, multicenter scale that has not been done before.Second, it identifies sensitization as an "endophenotype" of bronchiectasis.The need for endophenotypes in bronchiectasis was born out of failed trials that sent a painful but clear message that non-CF bronchiectasis not only is not CF but also will not behave like CF in response to therapies with proven efficacy in CF.These data may in part explain the baffling failures of large-scale therapeutic trials to demonstrate improvement in exacerbation frequency from inhaled antibiotics despite a decrease in bacterial burden.With further study, the sensitization patterns and immune profiles identified in this work will mature as guides to categorization and therapy.No doubt Mac Aogáin and colleagues have gotten off to a productive start.
Addressing Health-Related Misinformation on Social Media
Authors: Wen-Ying Sylvia Chou, April Oh, William M. P. Klein
Journal: JAMA (2018)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Abstract 15000: VEGFR2 is Activated by High-Density Lipoproteins and Plays a Key Role in the Pro-Angiogenic Action of HDL in Ischemia
Authors: Carla M. Cannizzo, Aaron A. Adonopulos, Anisyah Ridiandries, Laura Z. Vanags, Sui Ching G. Yuen, Tania Tsatralis, Rodney Henriquez, Stacy Robertson, Martin K. C. Ng, Yuen Ting Lam, Christina A. Bursill, Joanne T. M. Tan
Journal: Circulation (2017)

Introduction: High-density lipoproteins (HDL) are implicated in the augmentation of hypoxia-induced angiogenesis. We have previously shown that reconstituted HDL (rHDL) induces the key angiogenic g...
Abstract 13: PRMT1 as a therapeutic target in diffuse large B-cell lymphoma
Authors: Aarthi Goverdhan, Heng-Huan Lee, Ondrej Havranek, Richard Eric Davis, Mien-Chie Hung
Journal: Clinical Cancer Research (2017)

Abstract Diffuse large B-cell lymphomas (DLBCL) harbor recurrent abnormalities in epigenetic regulators, such as loss-of-function mutations in EP300 and CREBBP. These include gain-of-function mutations in EZH2, largely restricted to the germinal center B-Cell (GCB) subtype. An EZH2 inhibitor EPZ-6438 showed efficacy as a single agent in phase I clinical trials in relapsed/refractory GCB-DLBCL. We examined the effect of EZH2 inhibition in GCB-DLBCL cell lines, and found an increase in histone arginine methylation in surviving cells, which was attributable to increased Type I PRMT activity. Specifically, we discovered that EZH2 inhibitors activated PRMT1, which mediated protective effects through transcriptional changes at survival genes such as BCL2, and through modulation of B-cell receptor signaling. This exciting observation suggested an opportunity for combination therapy with PRMT1 inhibitors. Since PRMT1 is poorly studied in DLBCL, we performed single-agent studies in lymphoma cell lines and discovered that inhibition of PRMT1 elicited remarkable suppression of lymphoma cell growth and viability. Analysis of gene expression data from patients indicates that PRMT1 is overexpressed in untreated DLBCL tumor samples, compared to normal B-lymphocytes. Additionally, survival analysis revealed that patients with high PRMT1 expression showed poor overall survival. These observations support the potential for combinatorial treatment with EZH2 and PRMT1 inhibitors in patients. To summarize, our studies uncover a novel epigenetic target in DLBCL, and offer avenues for improving the antitumor efficacy of EZH2 inhibitors. Citation Format: Aarthi Goverdhan, Heng-Huan Lee, Ondrej Havranek, Richard Eric Davis, Mien-Chie Hung. PRMT1 as a therapeutic target in diffuse large B-cell lymphoma [abstract]. In: Proceedings of the Second AACR Conference on Hematologic Malignancies: Translating Discoveries to Novel Therapies; May 6-9, 2017; Boston, MA. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(24_Suppl):Abstract nr 13.
Association of MTHFR gene polymorphisms with glioma and meningioma patients in Indian population
Authors: R. Kumawat, S.H. Gowda, E. Debnath, S. Rashid, R. Niwas, A. Suri, C. Sarkar, S. Sinha, K. Chosdol
Journal: Annals of Oncology (2018)
Preclinical Efficacy of Endoglin-Targeting Antibody–Drug Conjugates for the Treatment of Ewing Sarcoma
Authors: Pilar Puerto-Camacho, Ana Teresa Amaral, Salah-Eddine Lamhamedi-Cherradi, Brian A. Menegaz, Helena Castillo-Ecija, José Luis Ordóñez, Saioa Domínguez, Carmen Jordan-Perez, Juan Diaz-Martin, Laura Romero-Pérez, Maria Lopez-Alvarez, Gema Civantos-Jubera, María José Robles-Frías, Michele Biscuola, Cristina Ferrer, Jaume Mora, Branko Cuglievan, Keri Schadler, Oliver Seifert, Roland Kontermann, Klaus Pfizenmaier, Laureano Simón, Myriam Fabre, Ángel M. Carcaboso, Joseph A. Ludwig, Enrique de Álava
Journal: Clinical Cancer Research (2018)

Endoglin (ENG; CD105) is a coreceptor of the TGFβ family that is highly expressed in proliferating endothelial cells. Often coopted by cancer cells, ENG can lead to neo-angiogenesis and vasculogenic mimicry in aggressive malignancies. It exists both as a transmembrane cell surface protein, where it primarily interacts with TGFβ, and as a soluble matricellular protein (sENG) when cleaved by matrix metalloproteinase 14 (MMP14). High ENG expression has been associated with poor prognosis in Ewing sarcoma, an aggressive bone cancer that primarily occurs in adolescents and young adults. However, the therapeutic value of ENG targeting has not been fully explored in this disease.We characterized the expression pattern of transmembrane ENG, sENG, and MMP14 in preclinical and clinical samples. Subsequently, the antineoplastic potential of two novel ENG-targeting monoclonal antibody-drug conjugates (ADC), OMTX503 and OMTX703, which differed only by their drug payload (nigrin-b A chain and cytolysin, respectively), was assessed in cell lines and preclinical animal models of Ewing sarcoma.Both ADCs suppressed cell proliferation in proportion to the endogenous levels of ENG observed in vitro. Moreover, the ADCs significantly delayed tumor growth in Ewing sarcoma cell line-derived xenografts and patient-derived xenografts in a dose-dependent manner.Taken together, these studies demonstrate potent preclinical activity of first-in-class anti-ENG ADCs as a nascent strategy to eradicate Ewing sarcoma.
Myocardial and Systemic Inflammation in Acute Stress-Induced (Takotsubo) Cardiomyopathy
Authors: Caroline Scally, Hassan Abbas, Trevor Ahearn, Janaki Srinivasan, Alice Mezincescu, Amelia Rudd, Nicholas Spath, Alim Yucel-Finn, Raif Yuecel, Keith Oldroyd, Ciprian Dospinescu, Graham Horgan, Paul Broadhurst, Anke Henning, David E. Newby, Scott Semple, Heather M. Wilson, Dana K. Dawson
Journal: Circulation (2019)

Acute stress-induced (takotsubo) cardiomyopathy can result in a heart failure phenotype with a prognosis comparable with that of myocardial infarction. In this study, we hypothesized that inflammation is central to the pathophysiology and natural history of takotsubo cardiomyopathy.In a multicenter study, we prospectively recruited 55 patients with takotsubo cardiomyopathy and 51 age-, sex-, and comorbidity-matched control subjects. During the index event and at the 5-month follow-up, patients with takotsubo cardiomyopathy underwent multiparametric cardiac magnetic resonance imaging, including ultrasmall superparamagnetic particles of iron oxide (USPIO) enhancement for detection of inflammatory macrophages in the myocardium. Blood monocyte subpopulations and serum cytokines were assessed as measures of systemic inflammation. Matched control subjects underwent investigation at a single time point.Subjects were predominantly middle-aged (64±14 years) women (90%). Compared with control subjects, patients with takotsubo cardiomyopathy had greater USPIO enhancement (expressed as the difference between pre-USPIO and post-USPIO T2*) in both ballooning (14.3±0.6 milliseconds versus 10.5±0.9 milliseconds; P<0.001) and nonballooning (12.9±0.6 milliseconds versus 10.5±0.9 milliseconds; P=0.02) left ventricular myocardial segments. Serum interleukin-6 (23.1±4.5 pg/mL versus 6.5±5.8 pg/mL; P<0.001) and chemokine (C-X-C motif) ligand 1 (1903±168 pg/mL versus 1272±177 pg/mL; P=0.01) concentrations and classic CD14++CD16- monocytes (90±0.5% versus 87±0.9%; P=0.01) were also increased whereas intermediate CD14++CD16+ (5.4±0.3% versus 6.9±0.6%; P=0.01) and nonclassic CD14+CD16++ (2.7±0.3% versus 4.2±0.5%; P=0.006) monocytes were reduced in patients with takotsubo cardiomyopathy. At 5 months, USPIO enhancement was no longer detectable in the left ventricular myocardium, although persistent elevations in serum interleukin-6 concentrations ( P=0.009) and reductions in intermediate CD14++CD16+ monocytes (5.6±0.4% versus 6.9±0.6%; P=0.01) remained.We demonstrate for the first time that takotsubo cardiomyopathy is characterized by a myocardial macrophage inflammatory infiltrate, changes in the distribution of monocyte subsets, and an increase in systemic proinflammatory cytokines. Many of these changes persisted for at least 5 months, suggesting a low-grade chronic inflammatory state.URL: https://www.clinicaltrials.gov . Unique identifier: NCT02897739.
PI3K p110δ inactivation antagonizes chronic lymphocytic leukemia and reverses T cell immune suppression
Authors: Shuai Dong, Bonnie K. Harrington, Eileen Y. Hu, Joseph T. Greene, Amy M. Lehman, Minh Tran, Ronni L. Wasmuth, Meixiao Long, Natarajan Muthusamy, Jennifer R. Brown, Amy J. Johnson, John C. Byrd
Journal: Journal of Clinical Investigation (2018)

Targeted therapy with small molecules directed at essential survival pathways in leukemia represents a major advance, including the phosphatidylinositol-3′-kinase (PI3K) p110δ inhibitor idelalisib. Here, we found that genetic inactivation of p110δ (p110δD910A/D910A) in the Eμ-TCL1 murine chronic lymphocytic leukemia (CLL) model impaired B cell receptor signaling and B cell migration, and significantly delayed leukemia pathogenesis. Regardless of TCL1 expression, p110δ inactivation led to rectal prolapse in mice resembling autoimmune colitis in patients receiving idelalisib. Moreover, we showed that p110δ inactivation in the microenvironment protected against CLL and acute myeloid leukemia. After receiving higher numbers of TCL1 leukemia cells, half of p110δD910A/D910A mice spontaneously recovered from high disease burden and resisted leukemia rechallenge. Despite disease resistance, p110δD910A/D910A mice exhibited compromised CD4+ and CD8+ T cell response, and depletion of CD4+ or CD8+ T cells restored leukemia. Interestingly, p110δD910A/D910A mice showed significantly impaired Treg expansion that associated with disease clearance. Reconstitution of p110δD910A/D910A mice with p110δWT/WT Tregs reversed leukemia resistance. Our findings suggest that p110δ inhibitors may have direct antileukemic and indirect immune-activating effects, further supporting that p110δ blockade may have a broader immune-modulatory role in types of leukemia that are not sensitive to p110δ inhibition.
Neuron-Subtype-Specific Expression, Interaction Affinities, and Specificity Determinants of DIP/Dpr Cell Recognition Proteins
Authors: Filip Cosmanescu, Phinikoula S. Katsamba, Alina P. Sergeeva, Goran Ahlsen, Saurabh D. Patel, Joshua J. Brewer, Liming Tan, Shuwa Xu, Qi Xiao, Sonal Nagarkar-Jaiswal, Aljoscha Nern, Hugo J. Bellen, S. Lawrence Zipursky, Barry Honig, Lawrence Shapiro
Journal: Neuron (2018)