tbuckley/cabot-search huggingface dataset:
Augmentation of Immune Checkpoint Cancer Immunotherapy with IL18
Authors: Zhifeng Ma, Wen Li, Shinichi Yoshiya, Yunfeng Xu, Masaki Hata, Yosif El-Darawish, Tzvetanka Markova, Kyosuke Yamanishi, Hiromichi Yamanishi, Hideaki Tahara, Yoshimasa Tanaka, Haruki Okamura
Journal: Clinical Cancer Research (2016)

Recent clinical trials and animal models demonstrated that immune checkpoint blockade enhanced effector cell responses and tumor rejection; however, further development and improvement of cancer immunotherapy is necessary for more favorable objective responses. In this study, we examined the effect of IL18 on the antitumor effect of immune checkpoint inhibitors.We examined the effect of IL18 on the peritoneal dissemination of CT-26 cells or tail vein injection metastasis of B16/F10 cells using antiprogrammed death-1 ligand-1 (αPD-L1) and/or anti-CTL-associated antigen-4 (αCTLA-4) mAbs.Massive ascites developed after intraperitoneal inoculation of CT-26, resulting in animal death within 30 days. Treatment of mice with αPD-L1 and/or αCTLA-4 significantly prolonged their survival, and a combination of the antibodies and IL18 provided a much greater therapeutic benefit. The combination modality led to the accumulation of precursor of mature natural killer (pre-mNK) cells in the peritoneal cavity together with increased CD8(+) T and decreased CD4(+)CD25(+)Foxp3(+) T cells. Depletion of the pre-mNK cells abrogated the therapeutic effects and increased the number of CD4(+)CD25(+)Foxp3(+) T cells. The combination treatment also suppressed tail vein injection metastasis of B16/F10 cells.The results demonstrated that IL18 enhanced therapeutic effects of immune checkpoint blockade against peritoneal dissemination of carcinoma or tail vein injection metastasis of melanoma through accumulation of pre-mNK cells, memory-type CD8(+) T cells, and suppression of CD4(+)CD25(+)Foxp3(+) T cells. A combination of immune checkpoint inhibitors with IL18 may give a suggestion to the development of next-generation cancer immunotherapy. Clin Cancer Res; 22(12); 2969-80. ©2016 AACR.
Phase II trial of Serratia marcescens extract in recurrent malignant astrocytoma.
Authors: K A Jaeckle, A Mittelman, F H Hill
Journal: Journal of Clinical Oncology (1990)

Nineteen assessable patients with recurrent malignant astrocytomas who had failed standard therapy (surgery, radiation, and/or chemotherapy) were treated on a phase I-II trial with a biologic extract of Serratia marcescens (ImuVert; Cell Technology, Boulder, CO) a new biologic response modifier (BRM). Two complete responses (CRs) were seen, of 63 and 77+ weeks duration. One minor response (MR) occurred, of 6 weeks duration. There were four additional stable (S) patients, with durations of 58+, 39, 12, and 7 weeks. Median time to progression and median survival in the CR plus MR patients were 63 and 129+ weeks, respectively. Overall, median time to progression and median survival were 12 and 19 weeks, respectively. Three patients are alive greater than or equal to 2.5 years from study entry. Common toxicities included transient (less than 72 hours) tenderness, induration, and erythema at the injection sites. Systemic toxicities were less frequent and included fever, chills, nausea/vomiting, headache, arthralgia, and hypotension. The response rate (CR plus MR) to this new BRM is modest (16%). However, the observation of CRs in patients with advanced recurrent malignant astrocytomas, with acceptable overall toxicity, warrants further study of this agent.
Peripheral Blood T Cells Generated After Allogeneic Bone Marrow Transplantation: Lower Levels of Bcl-2 Protein and Enhanced Sensitivity to Spontaneous and CD95-Mediated Apoptosis In Vitro. Abrogation of the Apoptotic Phenotype Coincides With the Recovery of Normal Naive/Primed T-Cell Profiles
Authors: Nadia Chafika Hebib, Olivier Déas, Matthieu Rouleau, Antoine Durrbach, Bernard Charpentier, Françoise Beaujean, Jean-Paul Vernant, Anna Senik
Journal: Blood (1999)
Abstract 13814: Lack of a Beneficial Effect on Neurologic Outcome When Mild Therapeutic Hypothermia is Augmented with the Noble Gas Argon after Cardiac Arrest
Authors: Anne Brucken, Pinar Kurnaz, Christian Bleilevens, Matthias Derwall, Philipp Fohr, Kay Nolte, Joachim Weis, Rolf Rossaint, Michael Fries
Journal: Circulation (2012)

Introduction: Experimentally, combining xenon and mild therapeutic hypothermia (MTH) after cardiac arrest (CA) confers a degree of protection that is greater than either of the two interventions al...
Diversity of T Cells Restricted by the MHC Class I-Related Molecule MR1 Facilitates Differential Antigen Recognition
Authors: Nicholas A. Gherardin, Andrew N. Keller, Rachel E. Woolley, Jérôme Le Nours, David S. Ritchie, Paul J. Neeson, Richard W. Birkinshaw, Sidonia B.G. Eckle, John N. Waddington, Ligong Liu, David P. Fairlie, Adam P. Uldrich, Daniel G. Pellicci, James McCluskey, Dale I. Godfrey, Jamie Rossjohn
Journal: Immunity (2016)
Quantifying influenza virus diversity and transmission in humans
Authors: Leo L M Poon, Timothy Song, Roni Rosenfeld, Xudong Lin, Matthew B Rogers, Bin Zhou, Robert Sebra, Rebecca A Halpin, Yi Guan, Alan Twaddle, Jay V DePasse, Timothy B Stockwell, David E Wentworth, Edward C Holmes, Benjamin Greenbaum, Joseph S M Peiris, Benjamin J Cowling, Elodie Ghedin
Journal: Nature Genetics (2016)
A reliability assessment of the Psychotherapy Supervisory Inventory
Authors: S B Shanfield, P C Mohl, K Matthews, V Hetherly
Journal: American Journal of Psychiatry (1989)

The authors investigated the reliability of the Psychotherapy Supervisory Inventory scales, which rate behaviors of supervisors on the basis of observation of supervision sessions. The scales assess focus on the therapist and the patient, intellectual and experimental orientation, number of clarifying and interpretive comments, intensity of confrontation, depth of exploration, verbal activity level of the supervisor, dominance of the supervisor and the therapist, comfort and tension levels, and empathy of the supervisor. Intraclass correlation coefficients were significant for all scales, indicating that trained observers can agree in distinguishing supervisory behaviors. These scales can be used in further research and for feedback to supervisors.
Atrial Tachycardia Arising Adjacent to Noncoronary Aortic Sinus
Authors: Xingpeng Liu, Jianzeng Dong, Siew Yen Ho, Ashok Shah, Deyong Long, Ronghui Yu, Ribo Tang, Meleze Hocini, Michel Haissaguerre, Changsheng Ma
Journal: Journal of the American College of Cardiology (2010)
Prospective Pilot Study of Sildenafil for Treatment of Postradiotherapy Erectile Dysfunction in Patients With Prostate Cancer
Authors: Damien C. Weber, Sabine Bieri, John M. Kurtz, Raymond Miralbell
Journal: Journal of Clinical Oncology (1999)

PURPOSE: Erectile dysfunction is a common late complication patients may experience after external-beam radiotherapy for prostate cancer. The efficacy and safety of oral sildenafil to correct sexual dysfunction caused by external-beam radiotherapy was studied in patients participating in our prospective trial. PATIENTS AND METHODS: Thirty-five assessable patients participated in this prospective pilot study. Using a 25-point scale based on the International Index of Sexual Function, erectile dysfunction was assessed weekly, during which time patients received sildenafil 100 mg orally once a week for 6 consecutive weeks. Response was defined as a score of 18 or more, corresponding to at least one successful attempt at sexual intercourse per week. RESULTS: Thirty patients (86%) completed the 6-week study. Seventy-seven percent of these patients had significantly improved erectile function, allowing recovery of full capacity for sexual intercourse. Of 27 patients not receiving concomitant hormone treatment, failure to respond was observed in only four patients (15%) compared with four (50%) of eight patients receiving hormonal treatment during the study. The time course of response was gradual, with 40%, 57%, 66%, 69%, and 74% responding at weeks 1 through 5, respectively. Therapy was generally well tolerated. The most frequently reported side effects in patients were flushing (37%), transient headache (17%), and dyspepsia (9%). No patient reported priapism, and no cardiovascular event or death was observed. After response, 12 patients (34%) reported the ability to achieve and maintain an erection sufficient for intercourse in the absence of sildenafil (ie, 24 hours to 6 days after taking the medication). CONCLUSION: This study suggests that oral sildenafil is well tolerated and can reverse erectile dysfunction after radiotherapy in a substantial proportion of prostate cancer patients.
Marginal kidneys for transplantation
Authors: Jeremy R Chapman
Journal: BMJ (2015)

Smarter allocation to the right recipients improves outcomes

Transplant waiting lists are growing in most developed countries, along with the need to increase the supply of organs donated after death. Increasing the age of eligible donors and thus reducing the “quality” criteria for donated kidneys may be one answer to the mismatch between supply and demand, opening up the possibility of donation for older donors with significant comorbidities. In a population based cohort study (doi:10.1136/bmj.h3557), Olivier and colleagues used data from four renal transplant programmes in France to examine the long term outcomes of transplantation using kidneys from expanded criteria donors (ECD).1

The authors classify expanded criteria organs as coming from donors older than 60 years or older than 50 years with associated vascular comorbidities.2 In the United States, ECD represent fewer than 20% of donors, from whom 40% of retrieved kidneys are not even transplanted; but in France, these donors provide 47% of kidney transplants. It is clear that kidneys from expanded criteria donors are associated with worse outcomes than are kidneys from standard criteria donors (SCD), including reduced graft and patient survival.3 The fairness of allocation principles for …
Polycomb Repressive Complex 2 Is a Barrier to KRAS-Driven Inflammation and Epithelial-Mesenchymal Transition in Non-Small-Cell Lung Cancer
Authors: Michela Serresi, Gaetano Gargiulo, Natalie Proost, Bjorn Siteur, Matteo Cesaroni, Martijn Koppens, Huafeng Xie, Kate D. Sutherland, Danielle Hulsman, Elisabetta Citterio, Stuart Orkin, Anton Berns, Maarten van Lohuizen
Journal: Cancer Cell (2016)
First US case of Zika virus infection is identified in Texas
Authors: Michael McCarthy
Journal: BMJ (2016)

Thank you for your interest in spreading the word about The BMJ.NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address. Username * Your Email * Send To * You are going to email the following First US case of Zika virus infection is identified in Texas Your Personal Message CAPTCHA This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
A Randomized Trial of Progesterone in Women with Recurrent Miscarriages
Authors: Arri Coomarasamy, Helen Williams, Ewa Truchanowicz, Paul T. Seed, Rachel Small, Siobhan Quenby, Pratima Gupta, Feroza Dawood, Yvonne E.M. Koot, Ruth Bender Atik, Kitty W.M. Bloemenkamp, Rebecca Brady, Annette L. Briley, Rebecca Cavallaro, Ying C. Cheong, Justin J. Chu, Abey Eapen, Ayman Ewies, Annemieke Hoek, Eugenie M. Kaaijk, Carolien A.M. Koks, Tin-Chiu Li, Marjory MacLean, Ben W. Mol, Judith Moore, Jackie A. Ross, Lisa Sharpe, Jane Stewart, Nirmala Vaithilingam, Roy G. Farquharson, Mark D. Kilby, Yacoub Khalaf, Mariette Goddijn, Lesley Regan, Rajendra Rai
Journal: New England Journal of Medicine (2015)

Progesterone is essential for the maintenance of pregnancy. However, whether progesterone supplementation in the first trimester of pregnancy would increase the rate of live births among women with a history of unexplained recurrent miscarriages is uncertain.
Abstract 158: Ultrasound-Induced Inhibition and Modulation of Neonatal Ventricular Cardiomyocyte Depolarization
Authors: Natasha Mehta, J Yasha Kresh, Steven P Kutalek, Peter A Lewin, Andrew R Kohut
Journal: Circulation Research (2014)

Background: Ultrasound can interact with tissue through either thermal or non-thermal physical mechanisms. Radiation force has been shown to stimulate cardiac and neural tissue in vivo. Ultrasound might hold clinical potential as a noninvasive therapeutic tool via specific bioeffects on cardiomyocytes. This study aims to assess the effect of ultrasound on cardiomyocyte depolarization in a tissue culture model. Methods: Cardiomyocytes were isolated from neonatal rat ventricular tissue and plated directly on microelectrode arrays to record depolarization patterns. A custom 2.5 MHz unfocused ultrasound transducer was directed at the cardiomyocytes in a tissue culture model. A function generator, with an amplified signal +50 dB, delivered acoustic energy at variable settings of 0.1, 0.3, 0.5 and 1.0 Vpp, pulse durations of 2, 5 and 10 ms, and burst periods of 100, 250 and 300 ms. Five trials were conducted at each setting (36 total trials) with 30s of continuous ultrasound exposure followed by an off interval of 1 minute. Results: The R-R interval durations (ID) were measured throughout the recording period. Prior to ultrasound delivery, the IDs were highly irregular, ID range = 0.3-2.7 s. As ultrasound was delivered in an asynchronous manner, using 0.1 and 0.3 Vpp and PD = 2 and 5 ms, there was suppression/inhibition of cellular depolarization for the first 5-10 s. Then 10-15 s after the start of ultrasound delivery, the depolarization rate increased and demonstrated less R-R interval variability (ID=0.88-1.03 s, P value&lt;0.05), even after the ultrasound exposure. Conclusion: Ultrasound can inhibit and modify the frequency of spontaneous electrical depolarizations of neonatal ventricular cardiomyocytes in a tissue culture model. Our observations could be due to conditioning via stretch and compression-mediated mechanosensitive pathways, by modifying intracellular calcium handling or altering cell signaling.
Alternative Strategies to Achieve Cardiovascular Mortality Goals in China and India
Authors: Sanjay Basu, John S. Yudkin, Jeremy B. Sussman, Christopher Millett, Rodney A. Hayward
Journal: Circulation (2016)

Background— The World Health Organization aims to reduce mortality from chronic diseases including cardiovascular disease (CVD) by 25% by 2025. High blood pressure is a leading CVD risk factor. We sought to compare 3 strategies for treating blood pressure in China and India: a treat-to-target (TTT) strategy emphasizing lowering blood pressure to a target, a benefit-based tailored treatment (BTT) strategy emphasizing lowering CVD risk, or a hybrid strategy currently recommended by the World Health Organization. Methods and Results— We developed a microsimulation model of adults aged 30 to 70 years in China and in India to compare the 2 treatment approaches across a 10-year policy-planning horizon. In the model, a BTT strategy treating adults with a 10-year CVD event risk of ≥10% used similar financial resources but averted ≈5 million more disability-adjusted life-years in both China and India than a TTT approach based on current US guidelines. The hybrid strategy in the current World Health Organization guidelines produced no substantial benefits over TTT. BTT was more cost-effective at $205 to $272/disability-adjusted life-year averted, which was $142 to $182 less per disability-adjusted life-year than TTT or hybrid strategies. The comparative effectiveness of BTT was robust to uncertainties in CVD risk estimation and to variations in the age range analyzed, the BTT treatment threshold, or rates of treatment access, adherence, or concurrent statin therapy. Conclusions— In model-based analyses, a simple BTT strategy was more effective and cost-effective than TTT or hybrid strategies in reducing mortality.
India is at high risk from surge in cases of melioidosis, warn researchers
Authors: Sophie Cousins
Journal: BMJ (2016)

<h3>Background</h3> Early childhood diagnosis of HIV is a challenge in many developing countries, including Mozambique. Approximately 50% of exposed children and HIV-positive are lost to follow-up, i.e. during Postpartum Consultation (CPP), at-risk child consultation (CCR) or ART consultation in the country. The objective was to carry out an intervention to reduce the loss to follow-up of children exposed to and positive for HIV in Manica and Sofala provinces. <h3>Methods</h3> Intervention study in HIV-positive women and their children in CPP and CCR in six health facilities in 2016. Stepped-wedge design with 3 cohorts for 3 months of two health facilities randomly selected. Interventions included activist allocation, telephone calls to contact the mothers, guide the mothers with exposed child from CPP to CCR, active outreach to missed mothers, and initiation of ART in the CCR for 3 months. Data were collected from the health facilities and study books. Analysis was binomial logistic regression model with mixed effects. <h3>Results</h3> Of the aggregated data, PCR +was 7.7%, and proportion of HIV-positive women in CPP 17.4%. In the control group only 24% of the mothers had more than 2 visits with us, compared with 60% in the intervention group [OR=2.05 (95% CI: 1.60, 2.62)]. In the intervention group, more children were transferred to CCR 52% vs 32% in the control [OR=1.7 (CI: 1.3–2.41)], 65% of the mothers in intervention group reached at CCR vs 57% of the mothers in the control group [OR=1.69 CI: 1.27–2.41)] and returned to receive the PCR result of their child, 6.7% in the control vs 8.2% in intervention [OR=2.3 (CI: 1.36, 3.87)]. <h3>Conclusion</h3> The intervention had a greater impact on the number of visits to CPP, the transfer of mothers from CPP to CCR, and the reception of PCR results in CCR by the companion.
Feasibility Of Pegylated-Asparaginase (PEG-ASP) During Induction In Adults With Acute Lymphoblastic Leukaemia (ALL): Results From The UK Phase 3 Multicentre Trial UKALL 14
Authors: Bella Patel, A Kirkwood, Aditi Dey, Clare Rowntree, Andrew McMillan, David Marks, Tobias Menne, Paul Smith, Simon Purnell, Lynda Micklewright, Adele K Fielding
Journal: Blood (2013)
A CD1d-dependent lipid antagonist to NKT cells ameliorates atherosclerosis in ApoE<sup>−/−</sup>mice by reducing lesion necrosis and inflammation
Authors: Yi Li, Peter Kanellakis, Hamid Hosseini, Anh Cao, Virginie Deswaerte, Peter Tipping, Ban-Hock Toh, Alex Bobik, Tin Kyaw
Journal: Cardiovascular Research (2015)

Atherosclerosis-related deaths from heart attacks and strokes remain leading causes of global mortality, despite the use of lipid-lowering statins. Thus, there is an urgent need to develop additional therapies. Reports that NKT cells promote atherosclerosis and an NKT cell CD1d-dependent lipid antagonist (DPPE-PEG350, 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine-N[methoxy(polyethyleneglycol)-350]) reduces allergen-induced inflammation led us to investigate its therapeutic potential in preventing the development and progression of experimental atherosclerosis. DPPE-PEG350 was administered to hyperlipidaemic ApoE−/− mice with/without established atherosclerosis. Atherosclerosis and immune cells were assessed in the aortic sinus lesions. Lesion expression of monocyte chemoattractant protein-1 (MCP-1) and vascular cell adhesion protein-1 (VCAM-1) responsible for inflammatory immune cell recruitment as well as mRNA expression of IFNγ and its plasma levels were investigated. Necrotic cores and lesion smooth muscle and collagen contents important in plaque stability were determined as were plasma lipid levels. DPPE-PEG350 reduced atherosclerosis development and delayed progression of established atherosclerosis without affecting plasma lipids. CD4 and CD8 T cells and B cells in atherosclerotic lesions were decreased in DPPE-PEG350-treated mice. Lesion MCP-1 and VCAM-1 protein expression and necrotic core size were reduced without affecting lesion smooth muscle and collagen content. IFNγ and lymphocytes were unaffected by the treatment. The attenuation of progression of established atherosclerosis together with reduced development of atherosclerosis in hyperlipidaemic mice by the NKT antagonist, without affecting NKT cell or other lymphocyte numbers, suggests that targeting lesion inflammation via CD1d-dependent activation of NKT cells using DPPE-PEG350 has a therapeutic potential in treating atherosclerosis.
Phase 2 study of the bispecific T-cell engager (BiTE) antibody blinatumomab in relapsed/refractory diffuse large B-cell lymphoma
Authors: Andreas Viardot, Marie-Elisabeth Goebeler, Georg Hess, Svenja Neumann, Michael Pfreundschuh, Nicole Adrian, Florian Zettl, Martin Libicher, Cyrus Sayehli, Julia Stieglmaier, Alicia Zhang, Dirk Nagorsen, Ralf C. Bargou
Journal: Blood (2016)
Abstract 10678: Pharmacokinetic and Pharmacodynamic Effects of Prasugrel and Clopidogrel According to CYP2C19 Genotype in Very Elderly and Non-Elderly Patients With Coronary Artery Disease
Authors: Paul A Gurbel, Dominick J Angiolillo, Jurrien M Ten Berg, Stefan James, Tomas L Lindahl, Peter Svensson, Joseph A Jakubowski, Patricia B Brown, Suman Duvvuru, Scott Sundseth, Joseph R Walker, David S Small, Brian A Moser, Kenneth J Winters, David Erlinge
Journal: Circulation (2012)

Background: In non-elderly (NE) (≥45 to <65 yrs) patients, CYP2C19 genotype has been reported to influence the response to clopidogrel (Clop) but not prasugrel (Pras). A Pras 5 mg/d dose in very el...
Extracellular Circulating DNA in Lymphoma Patients: Biological Correlates and Prognostic Impact
Authors: Dino Dujmovic, Vedrana Skaro, Sandra Basic-Kinda, Dora Markulin, Ivana Samarzija, Pavle Roncevic, Ivo Radman, Danijela Kolenc, Klara Dubravcic, Gordan Lauc, Igor Aurer
Journal: Blood (2014)
Proteinase-activated receptor 2 modulates OA-related pain, cartilage and bone pathology
Authors: Carmen Huesa, Ana C Ortiz, Lynette Dunning, Laura McGavin, Louise Bennett, Kathryn McIntosh, Anne Crilly, Mariola Kurowska-Stolarska, Robin Plevin, Rob J van 't Hof, Andrew D Rowan, Iain B McInnes, Carl S Goodyear, John C Lockhart, William R Ferrell
Journal: Annals of the Rheumatic Diseases (2015)

Proteinase-activated receptor 2 (PAR2) deficiency protects against cartilage degradation in experimental osteoarthritis (OA). The wider impact of this pathway upon OA-associated pathologies such as osteophyte formation and pain is unknown. Herein, we investigated early temporal bone and cartilage changes in experimental OA in order to further elucidate the role of PAR2 in OA pathogenesis. OA was induced in wild-type (WT) and PAR2-deficient (PAR2-/-) mice by destabilisation of the medial meniscus (DMM). Inflammation, cartilage degradation and bone changes were monitored using histology and microCT. In gene rescue experiments, PAR2-/- mice were intra-articularly injected with human PAR2 (hPAR2)-expressing adenovirus. Dynamic weight bearing was used as a surrogate of OA-related pain. Osteophytes formed within 7 days post-DMM in WT mice but osteosclerosis was only evident from 14 days post induction. Importantly, PAR2 was expressed in the proliferative/hypertrophic chondrocytes present within osteophytes. In PAR2-/- mice, osteophytes developed significantly less frequently but, when present, were smaller and of greater density; no osteosclerosis was observed in these mice up to day 28. The pattern of weight bearing was altered in PAR2-/- mice, suggesting reduced pain perception. The expression of hPAR2 in PAR2-/- mice recapitulated osteophyte formation and cartilage damage similar to that observed in WT mice. However, osteosclerosis was absent, consistent with lack of hPAR2 expression in subchondral bone. This study clearly demonstrates PAR2 plays a critical role, via chondrocytes, in osteophyte development and subchondral bone changes, which occur prior to PAR2-mediated cartilage damage. The latter likely occurs independently of OA-related bone changes.