tbuckley/cabot-search huggingface dataset:
Thyroid and Glucocorticoid Hormones Promote Functional T-Tubule Development in Human-Induced Pluripotent Stem Cell–Derived Cardiomyocytes
Authors: Shan S. Parikh, Daniel J. Blackwell, Nieves Gomez-Hurtado, Michael Frisk, Lili Wang, Kyungsoo Kim, Christen P. Dahl, Arnt Fiane, Theis Tønnessen, Dmytro O. Kryshtal, William E. Louch, Bjorn C. Knollmann
Journal: Circulation Research (2017)

Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) are increasingly being used for modeling heart disease and are under development for regeneration of the injured heart. However, incomplete structural and functional maturation of hiPSC-CM, including lack of T-tubules, immature excitation-contraction coupling, and inefficient Ca-induced Ca release remain major limitations.Thyroid and glucocorticoid hormones are critical for heart maturation. We hypothesized that their addition to standard protocols would promote T-tubule development and mature excitation-contraction coupling of hiPSC-CM when cultured on extracellular matrix with physiological stiffness (Matrigel mattress).hiPSC-CM were generated using a standard chemical differentiation method supplemented with T3 (triiodothyronine) and/or Dex (dexamethasone) during days 16 to 30 followed by single-cell culture for 5 days on Matrigel mattress. hiPSC-CM treated with T3+Dex, but not with either T3 or Dex alone, developed an extensive T-tubule network. Notably, Matrigel mattress was necessary for T-tubule formation. Compared with adult human ventricular cardiomyocytes, T-tubules in T3+Dex-treated hiPSC-CM were less organized and had more longitudinal elements. Confocal line scans demonstrated spatially and temporally uniform Ca release that is characteristic of excitation-contraction coupling in the heart ventricle. T3+Dex enhanced elementary Ca release measured by Ca sparks and promoted RyR2 (ryanodine receptor) structural organization. Simultaneous measurements of L-type Ca current and intracellular Ca release confirmed enhanced functional coupling between L-type Ca channels and RyR2 in T3+Dex-treated cells.Our results suggest a permissive role of combined thyroid and glucocorticoid hormones during the cardiac differentiation process, which when coupled with further maturation on Matrigel mattress, is sufficient for T-tubule development, enhanced Ca-induced Ca release, and more ventricular-like excitation-contraction coupling. This new hormone maturation method could advance the use of hiPSC-CM for disease modeling and cell-based therapy.
TRKA expression and NTRK1 gene copy number across solid tumors
Authors: G. Mauri, E. Valtorta, A. Sartore-Bianchi, G. Cerea, A. Amatu, M. Schirru, G. Marrapese, V. Fiorillo, P. Recchimuzzo, I. Stella, S. Veronese, F. Tosi, M. Maiolani, M. Truini, S. Siena
Journal: Annals of Oncology (2017)
Preliminary efficacy and safety of lorlatinib in patients (Pts) with ROS1-positive non-small cell lung cancer (NSCLC)
Authors: B. Besse, A.T. Shaw, B.J. Solomon, T.M. Bauer, R. Chiari, C-C. Lin, M. Satouchi, J.S. Clancy, L.P. James, A. Abbattista, E. Felip Font
Journal: Annals of Oncology (2017)
Heart Failure Within the Federal Prison System
Authors: Ersilia M. DeFilippis
Journal: JAMA Cardiology (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 Cardiology 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 Cardiology journal
Antibody mediated blockade of phosphatidylserine to enhance immune checkpoint blockade by repolarizing immune suppressive mechanisms of the tumor microenvironment.
Authors: Jeff Hutchins, Michael J Gray, Xianming Huang, Jian Gong, Michaela MS Hatch, Van Nguyen, Christopher C.W. Hughes, Rolf A. Brekken, Bruce D Freimark, David E. Gerber
Journal: Journal of Clinical Oncology (2016)

e23195 Background: The expression of phosphatidylserine (PS) on cell surfaces drives immunosuppressive mechanisms associated with tolerogenic cell death. In the tumor microenvironment, PS is exposed on tumor cells and tumor vascular endothelial cells and is further exposed with conventional anti-neoplastic therapies. PS signals through multiple immune cell signaling receptors where it drives the expansion of myeloid-derived suppressor cells (MDSCs), regulatory T cells, M2 macrophages, and stimulates the production of immunosuppressive cytokines. PS targeting antibodies have significant anti-tumor effects in multiple preclinical tumor models to re-activate the immune response in the tumor microenvironment. Methods: The combination of PS-targeting antibody ch1N11 with anti-PD-1 or anti-PD-L1 antibodies was compared to single agent therapy in E0771 and EMT-6 mouse syngeneic breast tumor models. Mice were treated IP up to twice per week with ch1N11, anti-PD-1, or anti-PD-L1 as single agents or combinations of antibodies. Tumor and spleen tissue were analyzed by FACS, ELISPOT, immunohistochemistry and RNA expression profiling. Results: In both tumor models examined, the anti-tumor effect of ch1N11 with combination therapy was significantly superior to single agent therapy. Combination therapy of ch1N11 with anti-PD-1 or anti-PD-L1 significantly inhibited tumor growth by over 90% with greater complete tumor regression compared to single agent therapy in E0771 tumors. Furthermore, combination treatment induced greater rejection of tumors upon tumor re-challenge. Analysis of the tumor microenvironment indicated that the combination of antibody-mediated blockade of PS and PD-1 significantly enhanced tumor infiltration by CD8+ T cells, upregulation of immune activation genes and a decrease in tumor promoting genes. Conclusions: These results support the combination of PS-targeting antibodies with anti-PD-1 or anti-PD-L1 antibodies for immunotherapy of cancer, including breast cancer.
Risarcimento del danno e infezione professionale da HIV tra gli operatori sanitari in Germania
Authors: J Jarke
Journal: Eurosurveillance (1999)

Entro il 1997, in tutto il mondo, sono stati notificati 286 casi di trasmissione di HIV in ambito lavorativo (1). Un terzo dei casi (95), in cui la sieroconversione si verificava generalmente dopo una specifica esposizione, sono stati classificati come infezioni di origine professionale accertata. Le infezioni rimanenti (191) sono state classificate come possibilmente contratte sul lavoro. Tre delle 95 accertate (2,3) e 22 delle 191 possibili infezioni da HIV contratte professionalmente hanno coinvolto operatori sanitari tedeschi (1).
Diagnosis and Management of Noncardiac Complications in Adults With Congenital Heart Disease: A Scientific Statement From the American Heart Association
Authors: George K. Lui, Arwa Saidi, Ami B. Bhatt, Luke J. Burchill, Jason F. Deen, Michael G. Earing, Michael Gewitz, Jonathan Ginns, Joseph D. Kay, Yuli Y. Kim, Adrienne H. Kovacs, Eric V. Krieger, Fred M. Wu, Shi-Joon Yoo
Journal: Circulation (2017)

Life expectancy and quality of life for those born with congenital heart disease (CHD) have greatly improved over the past 3 decades. While representing a great advance for these patients, who have been able to move from childhood to successful adult lives in increasing numbers, this development has resulted in an epidemiological shift and a generation of patients who are at risk of developing chronic multisystem disease in adulthood. Noncardiac complications significantly contribute to the morbidity and mortality of adults with CHD. Reduced survival has been documented in patients with CHD with renal dysfunction, restrictive lung disease, anemia, and cirrhosis. Furthermore, as this population ages, atherosclerotic cardiovascular disease and its risk factors are becoming increasingly prevalent. Disorders of psychosocial and cognitive development are key factors affecting the quality of life of these individuals. It is incumbent on physicians who care for patients with CHD to be mindful of the effects that disease of organs other than the heart may have on the well-being of adults with CHD. Further research is needed to understand how these noncardiac complications may affect the long-term outcome in these patients and what modifiable factors can be targeted for preventive intervention.
GW28-e1114 The feasibility analysis of targeting the optimal coronary vein using the three-dimensional electroanatomic mapping during the LV lead implantation in CRT patients
Authors: Haibo Yu, Yanchun Liang, Baige Xu, Gao Yang, Rong Liu, Zulu Wang, Yaling Han, Wang Shuang
Journal: Journal of the American College of Cardiology (2017)
Cetuximab-radiotherapy versus cetuximab-radiotherapy plus concurrent chemotherapy in patients with N0-N2a squamous cell carcinoma of the head and neck (SCCHN): Results of the GORTEC 2007-01 phase III randomized trial.
Authors: Jean Bourhis, xu Shan Sun, Christian Sire, Yungan Tao, Laurent Martin, Cedric Khoury, Philippe Maingon, Etienne Bardet, Michel Lapeyre, Thierry Chatellier, Nathalie Ollivier, Alexandre Cornely, Anne Auperin
Journal: Journal of Clinical Oncology (2016)

6003 Background: Chemo-radiotherapy (CT/RT) and cetuximab-RT (cetux-RT) were established as standard treatments in non-operated locally advanced (LA) SCCHN. While the addition of cetux to cisplatin/RT offers no benefit as compared to the same CT/RT alone (RTOG 0522 trial), it was not known whether the addition of carboplatin/5FU to cetux-RT would improve outcome, as compared to cetux-RT alone. Methods: The GORTEC 2007-01 trial was restricted to patients (pts) with no or limited nodal spread (N0-N2a) and was run in parallel with GORTEC 2007-02 trial testing induction vs concurrent CT in N2b/c-N3 pts. Inclusion criteria were pts fit for receiving CT, non-metastatic, non-operated stage III-IV SCC of oral cavity, oro/hypopharynx and larynx. The 1:1 randomization between cetux-RT (arm A) and cetux-CT/RT (arm B) was done by minimization on centers, N and T stages. Cetux was given as a loading dose of 400 mg/m2 followed by weekly 250 mg/m2 during RT. RT total dose was 70 Gy (2 Gy/day, 5 days/week). Concurrent CT was 3 cycles of carboplatin 70mg/m²/d + 5FU 600mg/m²/d D1-4 (Calais JNCI 1999). p16 status was available for 89% of oropharyngeal cancers (OPC). Primary endpoint was progression free survival (PFS). To detect a hazard ratio (HR) of 0.64 inclusion of 406 pts was required to achieve 85% power at 2-sided significance level of 0.05. PFS was analyzed using Cox model adjusted for minimization factors. Results: Between Feb 2008 and Feb 2014, 406 pts were randomized, 84% males, median age 57 years, 65% OPC (21% p16+), well balanced between arms. Median FU: 4.4 years. 3-year PFS rate was 52.3% in arm B vs 40.5% in arm A (HR = 0.73; 95%CI 0.57-0.94; p = 0.015). For loco-regional control, the HR was 0.54 (95%CI 0.38-0.76, p = 0.0005) in favor of arm B. The overall survival was not significantly different between both arms (HR = 0.80; 95%CI 0.61-1.05; p = 0.11). Overall, the rate of pts with grade 3-4 acute toxicity was not different between arms but mucositis and leucopenia were significantly more frequent in arm B. Conclusion: The addition of concomitant CT to cetux-RT markedly improved PFS and LRC, with a non-significant gain in survival. Clinical trial information: NCT00609284.
Review of Serodiagnostic Tests for Cancer&lt;xref ref-type="fn" rid="fn1"&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/xref&gt;
Authors: Mary E. Maver
Journal: JNCI Journal of the National Cancer Institute (1944)

Review of Serodiagnostic Tests for Cancer Get access Mary E. Maver Mary E. Maver senior biochemist National Cancer Institute, National Institute of Health, United States Public Health Service Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 4, Issue 6, June 1944, Pages 571–578, https://doi.org/10.1093/jnci/4.6.571 Published: 01 June 1944
Phase I clinical trial on pomalidomide and dexamethasone in treating patients with relapsed/refractory primary central nervous system lymphoma (PCNSL) or primary vitreoretinal lymphoma (PVRL).
Authors: Han W. Tun, Patrick B. Johnston, Christian Grommes, Craig B. Reeder, Antonio Marcilio Padula Omuro, David M Menke, John A. Copland, Lisa Marie DeAngelis, Thomas E. Witzig
Journal: Journal of Clinical Oncology (2017)

7516 Background: PCNSL is a diffuse large B cell lymphoma confined to the CNS. Pomalidomide (POM) is a novel immunomodulatory agent with excellent CNS penetration (~40%) based on CNS PK analysis in rats and pre-clinical therapeutic activity against CNS lymphoma. Methods: A Phase I clinical trial was undertaken to determine the maximal tolerated dose (MTD) of POM, safety profile and overall response rate (ORR). Treatment consists of POM daily for 21 days every 28 days in combination with dexamethasone 40 mg PO weekly for two cycles followed by POM alone in subsequent cycles until progression or intolerance. 4 dose escalation levels of POM (3mg, 5mg, 7mg, and 10 mg) were planned. Thromboprophylaxis with oral anticoagulant or aspirin was required. MTD determination has been completed and expansion of the MTD cohort is ongoing. Therapeutic responses were evaluated per the international PCNSL collaborative group (IPCG) criteria after 2 cycles of treatment. The trial is registered with ClinicalTrials.gov (#NCT01722305). Results: 21 of 25 patients accrued were eligible for assessment. The MTD was determined to be 5 mg qd for 21 days every 28 days. Two DLTs were seen at dose level 3 (Grade 3 dyspnea and grade 4 thrombocytopenia). One DLT was seen in the expanded MTD cohort (Grade 4 neutropenia and lymphocytopenia). ORR for the study (9/21) was 43% (95% CI- 22%, 66%) with 4 CR, 1 CRu and 4 PR. 3 responders completed 2, 4, and 6 cycles before progression. 6 responders have completed 4, 5, 6, 10, 12, and 32 cycles and remain on treatment. ORR for the MTD dose level was (5/12) 42% (95% CI- 15%, 72%) with 3 CR and 2 PR. 2 patients had stable disease (SD). Pseudo-progression was seen in 1 patient. Overall, grade 3/4 toxicity was hematologic (neutropenia, anemia, and thrombocytopenia) in 38.1% and non-hematologic in 33.3% (fatigue, pneumonia, sepsis, syncope, dyspnea, hypoxia, respiratory failure and maculo-papular rash). Percent CSF/blood ratio of POM was determined to be 19% in 1 patient. Conclusions: Pomalidomide treatment is feasible with therapeutic activity against relapsed/refractory PCNSL and should be further developed. Clinical trial information: NCT01722305.
Pharmacological treatment optimisation for stable COPD: an endless story?
Authors: Maeva Zysman, François Chabot, Bruno Housset, Capucine Morelot Panzini, Philippe Devillier, Nicolas Roche
Journal: European Respiratory Journal (2017)

In recent years, several global and local guidelines, recommendations and proposals on chronic obstructive pulmonary disease (COPD) management have been published [1–14]. They illustrate the great interest in this disease that, although no cure exists, is no longer considered untreatable. They also reflect its major and growing burden from both public health and individual perspectives. Finally, they parallel the increasing knowledge of its pathophysiology, clinical characteristics and natural history, as well as of treatment effects, with the goal of personalising care as much as possible. Here, we aim to present recent proposals of the French-Language Respiratory Society (Société de Pneumologie de Langue Française (SPLF)) and put them in perspective with the similarly recent Global Initiative for Chronic Obstructive Lung Disease (GOLD) document, which represents a major revision of GOLD proposals. It is also crucial to take this opportunity to emphasise here that the story of a guideline does not end with its production: the implementation phase is even more important and truly never ends until the next guideline, resulting in an endless cycle. Local adaptations of global recommendations on COPD may be necessary to facilitate appropriation and implementation <http://ow.ly/wgNE30eONaG>
Comparison of injection-site reactions between the etanercept biosimilar SB4 and the reference etanercept in patients with rheumatoid arthritis from a phase III study
Authors: G. Girolomoni, S.R. Feldman, P. Emery, J. Ghil, J.W. Keum, S.Y. Cheong, E. Hong
Journal: British Journal of Dermatology (2017)

Comparison of injection-site reactions between the etanercept biosimilar SB4 and the reference etanercept in patients with rheumatoid arthritis from a phase III study
Abstract 14699: Patterns of Postoperative Transprosthesis Aortic Valve Gradients Predict Bioprosthetic Structural Valve Deterioration
Authors: Tamer Attia, Edward Soltesz, Jeevanantham Rajeswaran, Eric Roselli, Nicholas G Smedira, Joseph F Sabik III, Lars Svensson, Eugene H Blackstone, Douglas R Johnston
Journal: Circulation (2015)

Objectives: To identify 1) patient, procedure, and postoperative variables associated with the development of structural valve deterioration (SVD) in bioprosthetic aortic valves (AV), and 2) the relation between the initial and increasing postoperative gradients requiring explant for SVD Methods: From 1982 to 2011, 5,006 patients underwent aortic valve replacement (AVR) with a pericardial PERIMOUNT bioprosthesis and had at least 2 postoperative echocardiograms available for analysis. Mean size of the implanted prosthesis was 23±2.3 mm. Joint modeling of longitudinal AV mean gradient and time to explant for SVD was performed to assess the effect of pattern parameters on risk of explant for SVD. Results: Mean initial AV gradient was 14±3.0 mmHg. Mean increase in gradient was 0.51±0.74 mmHg/year. One hundred eighteen patients underwent prosthesis explant for SVD. The majority of patients had no to minimal gradient increase over 15 years. A small percentage had progressive gradient increase. Rate of mean gradient increase correlated with risk of explant (P&lt;.0001; Figure). This effect was evident at a rate of increase above 1.5 mmHg/year. A sharper increase was associated with younger age, isolated AV replacement, smaller prosthesis size, and lower creatinine. Conclusion: After AVR with PERIMOUNT bioprosthesis, most patients have very stable gradients out to 15 years. A rate of AV gradient increase of ≥1.5 mmHg/year is predictive of SVD and need for early future reintervention. In contrast to current guidelines, early frequent echocardiographic surveillance is warranted. Figure legend: Effect of rate of change of aortic valve (AV) mean gradient (MnGrad) for different starting gradients on the risk of explant for structural valve deterioration (SVD).
First-in-human phase I study of PF-06747775, a third-generation mutant selective EGFR tyrosine kinase inhibitor (TKI) in metastatic EGFR mutant NSCLC after progression on a first-line EGFR TKI
Authors: H. Husain, R.G. Martins, S.B. Goldberg, P. Senico, W. Ma, J. Masters, N. Pathan, D-W. Kim, M.A. Socinski, Z. Goldberg, B.C. Cho
Journal: Annals of Oncology (2017)
Experimental Gastric Carcinoma: A Critical Review with Comments on the Criteria of Induced Malignancy<xref ref-type="fn" rid="fn1"><sup>a</sup></xref><xref ref-type="fn" rid="fn2"><sup>b</sup></xref><xref ref-type="fn" rid="fn3"><sup>c</sup></xref>
Journal: JNCI Journal of the National Cancer Institute (1941)
Il carico socioeconomico delle infezioni ospedaliere
Authors: R Plowman
Journal: Eurosurveillance (2000)

Secondo uno studio pubblicato di recente (1), pazienti adulti ricoverati nei comuni reparti ospedalieri, che sviluppano un’infezione ospedaliera (IO), rimangono in ospedale 2,5 volte piu a lungo, vanno incontro a costi ospedalieri almeno tre volte piu alti, e, dopo la dimissione, a costi per medico di base, assistenza infermieristica di distretto e ospedale, maggiori di quelli dei pazienti non infettati. Questo studio, condotto dal Public Health Laboratory Service e dalla London School of Hygiene and Tropical Medicine per conto del Department of Health del Regno Unito (UK), ha anche riscontrato che i pazienti infettati hanno sostenuto costi personali piu alti e sono tornati alle lore attivita quotidiane e/o al lavoro piu tardi dei pazienti non infettati.
The proto-oncogene tyrosine protein kinase Src is essential for macrophage-myofibroblast transition during renal scarring
Authors: Patrick Ming-Kuen Tang, Shuang Zhou, Chun-Jie Li, Jinyue Liao, Jun Xiao, Qing-Ming Wang, Guang-Yu Lian, Jinhong Li, Xiao-Ru Huang, Ka-Fai To, Chi-Fai NG, Charing Ching-Ning Chong, Ronald Ching-Wa Ma, Tin-Lap Lee, Hui-Yao Lan
Journal: Kidney International (2017)
Predictive factors for early progression during induction chemotherapy (IC) and chemotherapy-free interval (CFI): Analysis from PRODIGE 9 trial
Authors: T. Aparicio, J. Bennouna, K. Le Malicot, V. Boige, J. Taieb, O. Bouche, E. Francois, J-M. Phelip, C. Borel, R. Faroux, L. Dahan, J-B. Bachet, J. Egreteau, M-C. Kaminsky-Forrett, J-M. Gornet, O. Cojocarasu, M. Gasmi, V. Guerin-Meyer, F. Ghiringhelli, C. Lepage
Journal: Annals of Oncology (2017)
Open-label randomized study of individualized pharmacokinetically (PK)-guided dosing versus body surface area (BSA) dosing of paclitaxel (PTX) in advanced Non-Small Cell Lung Cancer (NSCLC) NCT02058433
Authors: S.J. Salamone, J. Zhang, H. Qi, H. Ni, Y. Li, J.B. Courtney, C. Zhou
Journal: Annals of Oncology (2017)
Identification of an RNF43 mutated gastric cancer patient population with potential sensitivity to porcupine inhibitor RXC004 and development of a complimentary ctDNA liquid biopsy assay for patient screening
Authors: M. Bingham, I. Bhamra, R. Armer, B. Thompson, S. Woodcock, A. Thomason, C. Phillips, H. McKeever, J. Bradford, B. Chaffey, L. Little, G. Clack
Journal: Annals of Oncology (2017)
Les prisons: des risques sanitaires mais aussi une occasion d’agir pour la santé
Authors: C Weilandt, D Radun
Journal: Eurosurveillance (2007)

“Les prisons figurent parmi les lieux les plus dangereux dans nos societes. En prison, les gens ne sont pas seulement prives de liberte mais ils sont egalement exposes a des menaces telles que la violence, la drogue et les maladies infectieuses, alors que parallelement, leur capacite a gerer ces risques est severement reduite » [1].
Growth Rate and Development of Tumors Induced with Ultraviolet Radiation
Authors: Harold F. Blum
Journal: JNCI Journal of the National Cancer Institute (1944)

Journal Article Growth Rate and Development of Tumors Induced with Ultraviolet Radiation Get access Harold F. Blum Harold F. Blum formerly senior pharmacologist National Cancer Institute, National Institute of Health, United States Public Health Service Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 4, Issue 6, June 1944, Pages 559–569, https://doi.org/10.1093/jnci/4.6.559 Published: 01 June 1944
Father loses appeal for £1m damages against IVF clinic to raise daughter
Authors: Clare Dyer
Journal: BMJ (2017)

A man who became an unwilling father to a daughter after his former partner forged his signature on an in vitro fertilisation clinic form has lost a £1m (€1.1m; $1.3m) damages claim against the clinic for the cost of bringing her up.1

The clinic, Hammersmith IVF Limited, had already helped the couple, whose identities are protected by a court order, to have a son, now aged 8. But after they split up the woman, referred to in court as R, wanted to use their frozen embryos to have another baby. …