tbuckley/cabot-search huggingface dataset:
Regression of K-BALB, CT26 and 4T1 mouse tumors following administration of rSFV replicons expressing IL-12
Authors: Chikkanna C. Gowda, Marina N. Fleeton, Brian J. Sheahan, Gregory J. Atkins
Journal: Cancer Research (2005)

4626  The Semliki Forest Virus vector (pSFV10) is an RNA-based suicide expression vector system that has been used previously for tumour therapy. Recently, a new SFV vector has been developed, pSFVb12a that expresses foreign genes at levels up to ten times higher than the original vector. Interleukin-12, a heterodimeric immunomodulatory cytokine plays a key role in the early induction of T helper1 (Th1) cell-mediated immune responses. This cytokine has been reported to exert strong anti-tumor effects through an antiangiogenic effect mediated by IFNγ. Interleukin 18 (IL-18) is a novel Th1 cytokine that synergizes with IL-12 in the stimulation of IFN-γ production by NK cells and T-cells. In this study, murine IL-12 gene subunits were isolated from mouse splenocytes and cloned into pSFVb12a and pSFV10 vectors. Both the constructs were characterised in vitro for their expression and secretion levels of biologically active IL-12 in BHK-21 and murine K-BALB tumor cells. A tumor treatment study was carried out in Balb/c mice vaccinated with recombinant SFV expressing the antigen β-galactosidase (rSFV-LacZ replicons). The effect of treatment using rSFVb12a-IL-12 (4.5x108iu/injection) alone or in combination with rSFV-LacZ in vaccinated and unvaccinated K-BALB tumor-bearing mice was carried out to investigate the anti-tumor therapeutic efficiency of rSFVb12a-mIL-12. A further in vivo study using rSFV expressing the cytokine IL-18 (rSFVb12a-IL-18) alone or in combination with rSFVb12a-IL-12 on K-BALB and CT26 tumours demonstrated an inhibitory effect of IL-18 on IL-12 treatment. Finally, subcutaneous K-BALB and CT26 tumors were treated using rSFVb12a-mIL-12 replicons (4.5x109i.u/injection) alone, and complete permanent tumour regression was found in comparison to control or rSFV10-IL-12 treated groups. Immunohistochemistry studies of tumors revealed massive tumor necrosis and the antiangiogenic effects of IL-12. A challenge experiment was carried out in IL-12 treated K-BALB regressed mice and significant tumor inhibition was observed for K-BALB cells but not for CT-26 cells, indicating that immunological memory was specific for the tumor model. Another in vivo IL-12 tumor treatment study on a metastasing tumor (4T1) model showed tumor growth inhibition and massive reduction of lung metastasis. These in vivo studies indicate the potential of rSFV replicons expressing IL-12 as an efficient anti-tumor therapeutic agent.
GP leaders ballot profession on mass list closure
Authors: Gareth Iacobucci
Journal: BMJ (2017)

GPs’ representatives in England have begun balloting general practices on the potential mass closure of patient lists in response to the ongoing crisis facing the profession.

The move comes after local medical committees, which represent GPs locally, passed a motion at their annual conference in May. This demanded that the BMA’s General Practitioners Committee ballot GPs on whether they would be willing to collectively close their lists in response to the huge pressures facing general practice and the inadequate response of NHS England’s rescue package.1

In a letter sent to GPs on 10 July, Richard Vautrey, acting chair of the General Practitioners Committee, urged GPs to take part in the ballot …
Abstract 15037: Hyperreninemic Aldosteronism in Caucasian and African-American Patients With Apparent Resistant Hypertension
Authors: Rajat Kalra, Lama Ghazi, David A Calhoun, Suzanne Oparil, Tanja Dudenbostel
Journal: Circulation (2015)

Introduction: While primary aldosteronism (PA) is a recognized and relatively well-defined cause of resistant hypertension (RHTN), there is a relative paucity of data defining patients with hyperreninemic aldosteronism (HA) and RHTN. Hypothesis: We sought to identify characteristics of patients with HA and compare them to patients with and without PA within a large cohort of patients with RHTN. Methods: We analyzed 1236 RHTN patients who were referred to our Hypertension Clinic with and underwent complete biochemical work-up including plasma aldosterone concentration, plasma renin activity, and 24-hour urinary aldosterone. Demographics, antihypertensive drug regimen, comorbidities, biochemical parameters and evaluation for secondary RHTN, where indicated, were evaluated. Hyperreninemic aldosteronism was defined as plasma renin activity &gt;1 ng/mL*hr, aldosterone-renin-ratio of ≈ 8 or more, and 24-hour urinary aldosterone &gt;12 mcg/24h. Results: In 128 eligible patients with resistant hypertension and HA, the mean age was 52.9±12.1 years with 56% being males (Table). Systolic and diastolic blood pressures were 149.2±22.0 and 87.9±15.5 mm Hg, respectively. Significant numbers of HA patients had co-morbid obesity (63.3%) and obstructive sleep apnea (44.9%). Compared to patients with PA, patients with HA had statistically significant lower proportions of patients with African-American race and systolic blood pressure. Compared to all RHTN patients, HA patients had lower mean age and systolic blood pressure, but were more likely to be male and have obstructive sleep apnea. Conclusions: Resistant hypertension due to hyperreninemic aldosteronism appears to predominantly affect obese, middle-aged males. Patients with HA causing RHTN have distinct differences from PA patients with RHTN. More investigation is required to identify appropriate treatment protocols for this poorly defined subset of patients with RHTN.
Angiosarcoma treated successfully with anti-PD-1 therapy - a case report
Authors: Simran Sindhu, Lana H. Gimber, Lee Cranmer, Ali McBride, Andrew S. Kraft
Journal: Journal for ImmunoTherapy of Cancer (2017)

<h3>Background</h3> Angiosarcomas are tumors of malignant endothelial origin that have a poor prognosis with a five-year survival of less than 40%. These tumors can be found in all age groups, but are more common in older patients; with the cutaneous form most common in older white men. Combined modality therapy including surgery and radiation appears to have a better outcome than each modality alone. When metastatic, agents such as liposomal doxorubicin, paclitaxel and ifosfamide have activity but it is short-lived and not curative. Immunotherapy targeting either the PD-1 receptor or PD-L1 ligand has recently been shown to have activity in multiple cancers including melanoma, renal, and non-small lung cancer. Although these agents have been used in sarcoma therapy, their ability to treat angiosarcoma has not been reported. <h3>Case presentation</h3> Here we describe the case of a 63-year-old man who presented initially with angiosarcoma of the nose and received surgery for the primary. Over 4&nbsp;years he had recurrent disease in the face and liver and was treated with nab-paclitaxel, surgery, and radioembolization, but continued to have progressive disease. His tumor was found to express PD-L1 and he received off-label pembrolizumab 2&nbsp;mg/kg every 21&nbsp;days for 13&nbsp;cycles with marked shrinkage of his liver disease and no new facial lesions. Secondary to this therapy he developed hepatitis and has been treated with decreasing doses of prednisone. During the 8&nbsp;months off therapy he has developed no new or progressive lesions. <h3>Conclusions</h3> Although occasional responses to immunotherapy have been reported for sarcomas, this case report demonstrates that angiosarcoma can express PD-L1 and have a sustained response to PD-1 directed therapy.
Rapid Expansion of Gene-Marked Lymphocytes in X-SCID Dogs after AMD3100+G-CSF-Based Hematopoietic Stem/Progenitor Cell Mobilization and Intravenous Injection of a Common γ-Chain Expressing Foamy Viral Vector
Authors: Frieda Chan, Olivier Humbert, Troy Torgerson, Nicholas Hubbard, Patricia O'Donnell, Daniel R Humphrys, Jennifer E Adair, Peter Felsburg, Grant D. Trobridge, Andrew M. Scharenberg, David J. Rawlings, Hans-Peter Kiem
Journal: Blood (2016)
International recruitment scheme brings 38 GPs to NHS
Authors: Abi Rimmer
Journal: BMJ (2017)

An international recruitment programme that aims to appoint 500 GPs from overseas has so far recruited only 38 doctors, NHS England has said.

In April 2016 NHS England published the General Practice Forward View , which included plans to “create an extra 5000 additional doctors working in general practice by 2021.”1

As part of this ambition NHS England said that it would create a “major new international recruitment campaign” to attract as many as 500 extra GPs from …
The ethics of research using human fetal tissue: (II)
Authors: D. E. Redmond, D. Spencer, F. Naftolin, R. H. Roth, B. S. Bunney, C. Leranth, Richard J. Robbins, L. Kier, T. Vollmer, R. J. Levine, M. Genel, H. Zonana
Journal: New England Journal of Medicine (1989)
Antinuclear Antibody and Subserology Testing in the Evaluation of Fibromyalgia
Authors: Nivedita Arora, Arjun Gupta, Swathi B. Reddy
Journal: JAMA Internal Medicine (2017)

This Teachable Moment highlights that clinical judgement is sufficient to diagnose fibromyalgia, and antinuclear antibody and subserology testing is not essential to rule out autoimmune conditions in the absence of suggestive signs and symptoms.
Association of Coffee Consumption With Total and Cause-Specific Mortality Among Nonwhite Populations
Authors: Song-Yi Park, Neal D. Freedman, Christopher A. Haiman, Loïc Le Marchand, Lynne R. Wilkens, Veronica Wendy Setiawan
Journal: Annals of Internal Medicine (2017)

Coffee consumption has been associated with reduced risk for death in prospective cohort studies; however, data in nonwhites are sparse.
Concordant bone marrow involvement of diffuse large B-cell lymphoma represents a distinct clinical and biological entity in the era of immunotherapy
Authors: Z Yao, L Deng, Z Y Xu-Monette, G C Manyam, P Jain, A Tzankov, C Visco, G Bhagat, J Wang, K Dybkaer, W Tam, E D Hsi, J H van Krieken, M Ponzoni, A J M Ferreri, M B Møller, J N Winter, M A Piris, L Fayad, Y Liu, Y Song, R Z Orlowski, H Kantarjian, L J Medeiros, Y Li, J Cortes, K H Young
Journal: Leukemia (2017)
GlucoCEST magnetic resonance imaging in vivo may be diagnostic of acute renal allograft rejection
Authors: Dominik Kentrup, Philipp Bovenkamp, Annika Busch, Katharina Schuette-Nuetgen, Helga Pawelski, Hermann Pavenstädt, Eberhard Schlatter, Karl-Heinz Herrmann, Jürgen R. Reichenbach, Bettina Löffler, Barbara Heitplatz, Veerle Van Marck, Nirbhay N. Yadav, Guanshu Liu, Peter C.M. van Zijl, Stefan Reuter, Verena Hoerr
Journal: Kidney International (2017)
Novel mechanisms of PIEZO1 dysfunction in hereditary xerocytosis
Authors: Edyta Glogowska, Eve R. Schneider, Yelena Maksimova, Vincent P. Schulz, Kimberly Lezon-Geyda, John Wu, Kottayam Radhakrishnan, Siobán B. Keel, Donald Mahoney, Alison M. Freidmann, Rachel A. Altura, Elena O. Gracheva, Sviatoslav N. Bagriantsev, Theodosia A. Kalfa, Patrick G. Gallagher
Journal: Blood (2017)
p62-ZZ Domain Signaling Inhibition Rescues MM-Induced Epigenetic Repression at the Runx2 promoter and Allows Osteoblast Differentiation of MM Patient Pre-Osteoblasts In Vitro
Authors: Rebecca Silbermann, Juraj Adamik, Dan Zhou, Xiang-Qun Xie, Noriyoshi Kurihara, G. David Roodman, Deborah Lynn Galson
Journal: Blood (2016)
2017 AHA/ACC Key Data Elements and Definitions for Ambulatory Electronic Health Records in Pediatric and Congenital Cardiology
Authors: Jeffrey R. Boris, Marie J. Béland, Lisa J. Bergensen, Steven D. Colan, Joanna Dangel, Curtis J. Daniels, Christopher Davis, Allen D. Everett, Rodney Franklin, J. William Gaynor, Darryl T. Gray, Jennifer C. Hirsch-Romano, Jeffrey P. Jacobs, Marshall Jacobs, Howard Jeffries, Otto Nils Krogmann, Edwin A. Lomotan, Leo Lopez, Ariane Marelli, Gerard R. Martin, G. Paul Matherne, Constantine Mavroudis, Ken McCardle, Gail D. Pearson, Geoffrey Rosenthal, John S. Scott, Gerald A. Serwer, Stephen S. Seslar, Robert Shaddy, Timothy Slesnick, David F. Vener, Henry L. Walters, Paul M. Weinberg
Journal: Journal of the American College of Cardiology (2017)
The Clinical and Economic Effect of Vascular Access Selection in Patients Initiating Hemodialysis with a Catheter
Authors: Alian Al-Balas, Timmy Lee, Carlton J. Young, Jeffrey A. Kepes, Jill Barker-Finkel, Michael Allon
Journal: Journal of the American Society of Nephrology (2017)

Patients in the United States frequently initiate hemodialysis with a central venous catheter (CVC) and subsequently undergo placement of a new arteriovenous fistula (AVF) or arteriovenous graft (AVG). Little is known about the clinical and economic effects of initial vascular access choice. We identified 479 patients starting hemodialysis with a CVC at a large medical center (during 2004–2012) who subsequently had an AVF ( n =295) or AVG ( n =105) placed or no arteriovenous access (CVC group, n =71). Compared with patients receiving an AVG, those receiving an AVF had more frequent surgical access procedures per year (1.01 [95% confidence interval, 0.95 to 1.08] versus 0.62 [95% confidence interval, 0.55 to 0.70]; P &lt;0.001) but a similar frequency of percutaneous access procedures per year. Patients receiving an AVF had a higher median annual cost (interquartile range) of surgical access procedures than those receiving an AVG ($4857 [$2523–$8835] versus $2819 [$1411–$4274]; P &lt;0.001), whereas the annual cost of percutaneous access procedures was similar in both groups. The AVF group had a higher median overall annual access-related cost than the AVG group ($10,642 [$5406–$19,878] versus $6810 [$3718–$13,651]; P =0.001) after controlling for patient age, sex, race, and diabetes. The CVC group had the highest median annual overall access-related cost ($28,709 [$11,793–$66,917]; P &lt;0.001), largely attributable to the high frequency of hospitalizations due to catheter-related bacteremia. In conclusion, among patients initiating hemodialysis with a CVC, the annual cost of access-related procedures and complications is higher in patients who initially receive an AVF versus an AVG.
Infection After Pancreatic Surgery
Authors: Jeffrey B. Matthews
Journal: JAMA Surgery (2017)

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 Surgery HomeNew OnlineCurrent IssueFor Authors Podcast 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 Surgery journal
Phase 2 biomarker-driven study of ipilimumab plus nivolumab (Ipi/Nivo) for ARV7-positive metastatic castrate-resistant prostate cancer (mCRPC).
Authors: Karim Boudadi, Daniel L. Suzman, Brandon Luber, Hao Wang, John Silberstein, Rana Sullivan, Donna Dowling, Rana Harb, Thomas Nirschl, Ryan Vance Dittamore, Michael Anthony Carducci, Mario A. Eisenberger, Michael Haffner, Alan Meeker, James R. Eshleman, Jun Luo, Charles G. Drake, Emmanuel S. Antonarakis
Journal: Journal of Clinical Oncology (2017)

5035 Background: ARV7+ mCRPC is an aggressive phenotype with a median PFS of 3-4 mo and OS of 7-9 mo. We hypothesized that ARV7+ tumors would be enriched for DNA repair mutations, rendering them more responsive to combined immune checkpoint blockade. Methods: We enrolled 15 mCRPC pts with ARV7+ CTCs (using a CLIA-certified assay) into a single arm phase 2 study. Pts received Nivo 3 mg/kg plus Ipi 1 mg/kg every 3 wk x 4 doses, then maintenance Nivo 3 mg/kg every 2 wk. Targeted sequencing for DNA repair defects was performed on pretreatment tumor biopsies (n=11) or cell-free DNA (n=4). Primary endpoint: PSA 50 response rate. Secondary endpoints: objective response rate (ORR) in pts with measurable disease, durable PFS (lack of progression ≥24 wk), PSA‐PFS, radiographic (r)PFS, overall survival (OS), and frequency/intensity of AEs. Results: 15 ARV7+ men were enrolled, with median f/u 8.4 (range 1.9–10.5) mo. Median age was 65, 47% had ECOG ≥1, median PSA was 115 ng/mL, 67% had visceral/nodal mets, all had bone mets, and 60% had ≥4 prior regimens for mCRPC. Mean ARV7/AR ratio was 23% (range 3–75%). 6/15 men (40%) had pathogenic DNA repair gene mutations ( BRCA2, ATM, MSH6, FANCM, FANCA, POLH). Overall, the PSA 50 rate was 1/15 (7%), ORR was 2/8 (25%), durable PFS rate was 3/15 (20%), PSA-PFS was 3.0 (95%CI 2.1–4.9) mo, rPFS was 3.9 (95%CI 2.8–5.5) mo, and OS was 9.5 (95%CI 7.2–NA) mo. Outcomes appeared better in DNA repair deficient (DRD+) tumors vs. DNA repair proficient (DRD–) tumors (TABLE). 15 grade 3-4 treatment-related AEs occurred in 7/15 (46%) men (including 2 hepatitis, 2 colitis, 1 pneumonitis); there were no treatment-related deaths. Conclusions: In this first study targeting ARV7+ mCRPC, treatment with Ipi/Nivo had acceptable safety and encouraging efficacy, particularly in men with DRD+ tumors. DNA repair mutations may be enriched in ARV7+ prostate cancer. Clinical trial information: NCT02601014. [Table: see text]
Tivadar Kosztka Csontváry’s <i>The Old Fisherman</i>—A Remarkable Example of Photodamaged Skin in Art
Authors: Halil Tekiner, Marianna Karamanou
Journal: JAMA Dermatology (2017)

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 Dermatology HomeNew OnlineCurrent IssueFor Authors Podcast 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 Dermatology journal
Brain disorders? Not really: Why network structures block reductionism in psychopathology research
Authors: Denny Borsboom, Angélique O. J. Cramer, Annemarie Kalis
Journal: Behavioral and Brain Sciences (2018)

Abstract In the past decades, reductionism has dominated both research directions and funding policies in clinical psychology and psychiatry. The intense search for the biological basis of mental disorders, however, has not resulted in conclusive reductionist explanations of psychopathology. Recently, network models have been proposed as an alternative framework for the analysis of mental disorders, in which mental disorders arise from the causal interplay between symptoms. In this target article, we show that this conceptualization can help explain why reductionist approaches in psychiatry and clinical psychology are on the wrong track. First, symptom networks preclude the identification of a common cause of symptomatology with a neurobiological condition; in symptom networks, there is no such common cause. Second, symptom network relations depend on the content of mental states and, as such, feature intentionality. Third, the strength of network relations is highly likely to depend partially on cultural and historical contexts as well as external mechanisms in the environment. Taken together, these properties suggest that, if mental disorders are indeed networks of causally related symptoms, reductionist accounts cannot achieve the level of success associated with reductionist disease models in modern medicine. As an alternative strategy, we propose to interpret network structures in terms of D. C. Dennett's (1987) notion of real patterns , and suggest that, instead of being reducible to a biological basis, mental disorders feature biological and psychological factors that are deeply intertwined in feedback loops. This suggests that neither psychological nor biological levels can claim causal or explanatory priority, and that a holistic research strategy is necessary for progress in the study of mental disorders.
Reply to Jae Heon Kim, Bora Lee, and Benjamin I. Chung's Letter to the Editor re: Philipp Mandel, Felix Preisser, Markus Graefen, et al. High Chance of Late Recovery of Urinary and Erectile Function Beyond 12 Months After Radical Prostatectomy. Eur Urol 2017;71:848–50
Authors: Philipp Mandel, Derya Tilki
Journal: European Urology (2017)
Inferior Access to Allogeneic Transplant in Disadvantaged Populations: A CIBMTR Analysis
Authors: Kristjan Paulson, Ruta Brazauskas, Naya He, David Szwajcer, Matthew D. Seftel, Yoshiko Atsuta, Jignesh D Dalal, Theresa Hahn, Carmem Bonfim, Nandita Khera, Linda J. Burns, Lih-Wen Mau, Navneet S. Majhail, Wael Saber
Journal: Blood (2016)
Breaching peripheral tolerance promotes the production of HIV-1–neutralizing antibodies
Authors: Kristin M.S. Schroeder, Amanda Agazio, Pamela J. Strauch, Sean T. Jones, Scott B. Thompson, Michael S. Harper, Roberta Pelanda, Mario L. Santiago, Raul M. Torres
Journal: The Journal of Experimental Medicine (2017)

A subset of characterized HIV-1 broadly neutralizing antibodies (bnAbs) are polyreactive with additional specificities for self-antigens and it has been proposed immunological tolerance may present a barrier to their participation in protective humoral immunity. We address this hypothesis by immunizing autoimmune-prone mice with HIV-1 Envelope (Env) and characterizing the primary antibody response for HIV-1 neutralization. We find autoimmune mice generate neutralizing antibody responses to tier 2 HIV-1 strains with alum treatment alone in the absence of Env. Importantly, experimentally breaching immunological tolerance in wild-type mice also leads to the production of tier 2 HIV-1–neutralizing antibodies, which increase in breadth and potency following Env immunization. In both genetically prone and experimentally induced mouse models of autoimmunity, increased serum levels of IgM anti-histone H2A autoantibodies significantly correlated with tier 2 HIV-1 neutralization, and anti-H2A antibody clones were found to neutralize HIV-1. These data demonstrate that breaching peripheral tolerance permits a cross-reactive HIV-1 autoantibody response able to neutralize HIV-1.