tbuckley/cabot-search huggingface dataset:
Metabolic Reprogramming Regulates the Proliferative and Inflammatory Phenotype of Adventitial Fibroblasts in Pulmonary Hypertension Through the Transcriptional Corepressor C-Terminal Binding Protein-1
Authors: Min Li, Suzette Riddle, Hui Zhang, Angelo D’Alessandro, Amanda Flockton, Natalie J. Serkova, Kirk C. Hansen, Radu Moldovan, B. Alexandre McKeon, Maria Frid, Sushil Kumar, Hong Li, Hongbing Liu, Angela Caánovas, Juan F. Medrano, Milton G. Thomas, Dijana Iloska, Lydie Plecitá-Hlavatá, Petr Ježek, Soni Pullamsetti, Mehdi A. Fini, Karim C. El Kasmi, QingHong Zhang, Kurt R. Stenmark
Journal: Circulation (2016)

Background: Changes in metabolism have been suggested to contribute to the aberrant phenotype of vascular wall cells, including fibroblasts, in pulmonary hypertension (PH). Here, we test the hypothesis that metabolic reprogramming to aerobic glycolysis is a critical adaptation of fibroblasts in the hypertensive vessel wall that drives proliferative and proinflammatory activation through a mechanism involving increased activity of the NADH-sensitive transcriptional corepressor C-terminal binding protein 1 (CtBP1). Methods: RNA sequencing, quantitative polymerase chain reaction, 13 C–nuclear magnetic resonance, fluorescence-lifetime imaging, mass spectrometry–based metabolomics, and tracing experiments with U- 13 C-glucose were used to assess glycolytic reprogramming and to measure the NADH/NAD + ratio in bovine and human adventitial fibroblasts and mouse lung tissues. Immunohistochemistry was used to assess CtBP1 expression in the whole-lung tissues. CtBP1 siRNA and the pharmacological inhibitor 4-methylthio-2-oxobutyric acid (MTOB) were used to abrogate CtBP1 activity in cells and hypoxic mice. Results: We found that adventitial fibroblasts from calves with severe hypoxia-induced PH and humans with idiopathic pulmonary arterial hypertension (PH-Fibs) displayed aerobic glycolysis when cultured under normoxia, accompanied by increased free NADH and NADH/NAD + ratios. Expression of the NADH sensor CtBP1 was increased in vivo and in vitro in fibroblasts within the pulmonary adventitia of humans with idiopathic pulmonary arterial hypertension and animals with PH and cultured PH-Fibs, respectively. Decreasing NADH pharmacologically with MTOB or genetically blocking CtBP1 with siRNA upregulated the cyclin-dependent genes (p15 and p21) and proapoptotic regulators (NOXA and PERP), attenuated proliferation, corrected the glycolytic reprogramming phenotype of PH-Fibs, and augmented transcription of the anti-inflammatory gene HMOX1 . Chromatin immunoprecipitation analysis demonstrated that CtBP1 directly binds the HMOX1 promoter. Treatment of hypoxic mice with MTOB decreased glycolysis and expression of inflammatory genes, attenuated proliferation, and suppressed macrophage numbers and remodeling in the distal pulmonary vasculature. Conclusions: CtBP1 is a critical factor linking changes in cell metabolism to cell phenotype in hypoxic and other forms of PH and a therapeutic target.
Prevalence of interleukin-6 receptor polymorphism in Castleman disease and association with increased soluble interleukin-6 receptor levels.
Authors: K. Stone, E. Woods, S. M. Szmania, O. Stephens, T. K. Garg, A. Moreno-Bost, B. Barlogie, J. D. Shaughnessy, B. Hall, M. P. Reddy, F. Van Rhee
Journal: Journal of Clinical Oncology (2011)

8077 Background: Castleman Disease (CD) comprises a clinically and histologically heterogeneous group of rare lymphoproliferative disorders and presents either with localized (unicentric, UCD) or generalized (multicentric, MCD) lymphadenopathy. MCD has protean clinical manifestations largely driven by overproduction of interleukin-6 (IL6), which results in an acute phase reaction. Others have shown that single nucleotide polymorphisms (SNPs) in the IL6 receptor (IL6R) lead to increased levels of the soluble form of IL6R (sIL6R). We hypothesized that CD patients may express the minor allele of IL6R SNPs at higher frequencies than the general population, and sIL6R levels may be increased in individuals possessing one or more copies of the minor allele of these SNPs. Methods: Two well-studied IL6R SNPs were chosen for analysis: rs4537545(C/T) and rs2228145(A/C). Peripheral blood mononuclear cells and serum were obtained from 48 CD patients and 45 healthy donors. These cohorts comprised similar racial/ethnic profiles in order to exclude such influences on allele frequencies. Results: We found these IL6R SNPs to be in linkage disequilibrium (D’ = 0.973, r2 = 0.772). A significant difference in the frequency of the minor T allele of IL6R SNP rs4537545 was observed between CD patients and controls (0.49 and 0.32, respectively; p < 0.019). Similarly, the minor C allele of IL6R SNP rs2228145 was overexpressed in CD patients versus controls (0.43 vs. 0.29, p < 0.05). sIL6R levels were measured in the serum of CD patients and controls by ELISA. Individuals possessing at least one copy of the minor T allele of the IL6R SNP rs4537545, on average, expressed higher levels of sIL6R than those homozygous for the major C allele (51,544 pg/mL and 32,869 pg/mL, respectively; p = 8.9 x 10-13). Furthermore, individuals possessing one or more copies of the minor C allele of IL6R SNP rs2228145 also produced significantly higher mean levels of sIL6R (52,324 pg/mL vs. 34,248 pg/mL, p = 3.9 x 10-11). Conclusions: These data suggest that IL6R polymorphism may be a contributing factor in CD, and further research is warranted. Clinical data pertaining to correlation with polymorphism will be presented.
Ramifications of New Terminology for Encapsulated Follicular Variant of Papillary Thyroid Carcinoma
Authors: P.V. Pradeep
Journal: JAMA Oncology (2016)

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 Oncology 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 Oncology journal
Lag Time to Benefit for Preventive Therapies
Authors: Holly M. Holmes, Lillian Min, Cynthia Boyd
Journal: JAMA (2014)

To the Editor Dr Lee and colleagues1 discussed using lag time to benefit along with magnitude of benefit when considering preventive therapies in older adults. However, using time-to-benefit information from randomized clinical trials (RCTs) entails a number of challenges that warrant discussion.
Dissection of CD20 regulation in lymphoma using RNAi
Authors: M Słabicki, K S Lee, A Jethwa, L Sellner, F Sacco, T Walther, J Hüllein, S Dietrich, B Wu, D B Lipka, C C Oakes, S Mamidi, B Pyrzyńska, M Winiarska, M Oleś, M Seifert, C Plass, M Kirschfink, M Boettcher, J Gołąb, W Huber, S Fröhling, T Zenz
Journal: Leukemia (2016)
Invasive coronary strategy improves survival after MI, shows UK study
Authors: Susan Mayor
Journal: BMJ (2016)

An invasive coronary strategy, including procedures such as coronary angiography, improves survival in patients with non-ST segment elevation myocardial infarction (NSTEMI) much more than decreases in baseline clinical risk or the greater use of drugs, a large study in England and Wales has found.

International studies have previously reported declines in mortality after NSTEMI, but it is unknown whether these were due to changes in people’s clinical risk factors or the increased use of investigations and treatments.

The new …
Iron Uptake via DMT1 Integrates Cell Cycle with JAK-STAT3 Signaling to Promote Colorectal Tumorigenesis
Authors: Xiang Xue, Sadeesh K. Ramakrishnan, Kevin Weisz, Daniel Triner, Liwei Xie, Durga Attili, Asha Pant, Balázs Győrffy, Mingkun Zhan, Christin Carter-Su, Karin M. Hardiman, Thomas D. Wang, Michael K. Dame, James Varani, Dean Brenner, Eric R. Fearon, Yatrik M. Shah
Journal: Cell Metabolism (2016)
Strike cannot be justified and could harm patients, GMC warns
Authors: Abi Rimmer
Journal: BMJ (2016)

Planned strike action by junior doctors in England cannot be justified and could harm patients, the General Medical Council has warned.

The BMA announced last week that junior doctors in England will stage four rounds of industrial action from September until December. Each round will comprise full withdrawal of labour between the hours of 8 am and 5 pm for five consecutive weekdays.1

Terence Stephenson, chair of the GMC, said that the BMA’s announcement marked a “substantial escalation” on previous industrial action because it involved the removal of emergency care, a rolling …
Reassessing ACOs and Health Care Reform
Authors: Kevin A. Schulman, Barak D. Richman
Journal: JAMA (2016)

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 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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
Sexual Activity and Function in the Year After an Acute Myocardial Infarction Among Younger Women and Men in the United States and Spain
Authors: Stacy Tessler Lindau, Emily Abramsohn, Hector Bueno, Gail D’Onofrio, Judith H. Lichtman, Nancy P. Lorenze, Rupa Mehta Sanghani, Erica S. Spatz, John A. Spertus, Kelly M. Strait, Kristen Wroblewski, Shengfan Zhou, Harlan M. Krumholz
Journal: JAMA Cardiology (2016)

Most younger adults who experience an acute myocardial infarction (AMI) are sexually active before the AMI, but little is known about sexual activity or sexual function after the event.
Prostate-specific membrane antigen antibody drug conjugate (PSMA ADC): A phase I trial in taxane-refractory prostate cancer.
Authors: D. P. Petrylak, P. W. Kantoff, Y. Rotshteyn, R. J. Israel, W. C. Olson, T. Ramakrishna, S. Morris
Journal: Journal of Clinical Oncology (2011)

158 Background: The unique expression of PSMA type II transmembrane glycoprotein on prostate cancer cells provides a potentially attractive target for antibody therapy. PSMA ADC, a fully humanized antibody to PSMA linked to the potent antitubulin agent monomethyl auristatin E (MMAE), binds PSMA and is internalized within the prostate cancer cell where cleavage and release of free MMAE occur, causing cell cycle arrest and apoptosis. We report results from an ongoing phase I dose escalation study of PSMA ADC in patients (pts) with taxane refractory metastatic prostate cancer (metCRPC). Methods: Eligibility requirements included pts ≥18 years with metCRPC after failure of a taxane- containing regimen and ECOG status of 0 or 1. PSMA ADC is administered by IV infusion Q3W for up to 4 cycles. Adverse events, PK, PSA, circulating tumor cells, clinical disease progression and immunogenic response to PSMA ADC continue to be assessed. Serum concentrations of PSMA ADC and total antibody are measured by an enzyme-linked immunosorbent assay (ELISA) method, and free MMAE is measured by liquid chromatography/mass spectrometry/mass spectrometry (LC/MS/MS) method. Dosing cohorts ranged from 0.4 mg/kg to 1.8 mg/kg. Results: The demographics of 15 subjects enrolled in the four dosing cohorts (0.4, 0.7, 1.1 and 1.8 mg/kg) were similar. Treatment has to date been generally well tolerated and the most common laboratory abnormalities were reversible changes in liver and hematological parameters. Exposure to PSMA ADC and serum half life (t 1/2 ) increased in a dose-proportional manner. Similar PK metrics were observed after the first and third doses. Exposure to free MMAE was also dose proportional and approximately &lt;0.1% of PSMA ADC. Conclusions: In this first-in-human evaluation, PSMA ADC appears to exhibit dose-proportional PK and limited release of free MMAE. Ongoing enrollment allows for assessment of potential clinical utility of this unique potential treatment of metCRPC. [Table: see text]
Peripheral blood blast clearance is an independent prognostic factor for survival and response to acute myeloid leukemia induction chemotherapy
Authors: Nicholas J. Short, Christopher B. Benton, Hsiang‐Chun Chen, Peng Qiu, Lisa Gu, Sherry Pierce, Mark Brandt, Abhishek Maiti, Taejin L. Min, Kiran Naqvi, Alfonso Quintas‐Cardama, Marina Konopleva, Tapan Kadia, Jorge Cortes, Guillermo Garcia‐Manero, Farhad Ravandi, Elias Jabbour, Hagop Kantarjian, Michael Andreeff
Journal: American Journal of Hematology (2016)

In patients with acute myeloid leukemia (AML), rapid reduction of circulating blasts with induction chemotherapy may serve as an in vivo marker of chemosensitivity. We performed a retrospective analysis of 363 patients with untreated AML who received induction chemotherapy in order to determine the relationship between day of blast disappearance (DOBD) and complete remission (CR) rates, event‐free survival (EFS), and overall survival (OS). DOBD ≤ 5 vs. &gt;5 was identified as the most discriminating cutoff for OS. DOBD &gt; 5 was observed in 35 patients (9.6%). The CR rate for patients with DOBD ≤ 5 vs. &gt;5 was 74.0 and 28.6%, median EFS was 9.4 and 1.8 months, and median OS was 17.1 and 5.8 months, respectively ( P &lt; 0.001 for all). DOBD &gt; 5 was independently associated with a lower CR rate and shorter EFS and OS ( P &lt; 0.001 for all). DOBD &gt; 5 retained prognostic significance for EFS and OS when patients were stratified by cytogenetic risk group, de novo vs. secondary or therapy‐related AML, European LeukemiaNet‐based risk groups, and whether CR was achieved. We propose DOBD &gt; 5 as a simple and early marker of disease resistance that identifies patients with poor prognosis who otherwise may not be identified with existing risk stratification systems. Am. J. Hematol. 91:1221–1226, 2016. © 2016 Wiley Periodicals, Inc.
Malpractice, Patient Satisfaction, and Physician-Patient Communication-Reply
Authors: Gerald B. Hickson
Journal: JAMA (1995)

<h3>In Reply.</h3> —The Fallon Clinic's experience is encouraging and suggests that it is possible to enhance patient perceptions of the interpersonal skills of physicians, perhaps even those with high malpractice claims experience. One possible explanation is that the process of obtaining feedback from peers led the clinicians to appreciate the problems so that they could address them. Another is that the training program actually imparted new skill. Understanding the relative importance of peer-provided feedback and providing physicians education concerning the skill to correct identified problems is needed in order to design education strategies that sustain behavioral changes over time. Dr Weyrauch's hypotheses are important, and we would argue that all the interpersonal skills in the world will not heal a physician-patient relationship marred by bias and condescension. Nonetheless, to the extent we looked, we did not find evidence that patients were more likely to see the high-frequency physicians as biased
The effect of diabetes control status on treatment response in pulmonary tuberculosis: a prospective study
Authors: Young Soon Yoon, Jae-Woo Jung, Eun Ju Jeon, Haesook Seo, Yon Ju Ryu, Jae-Joon Yim, Yee Hyung Kim, Byoung-Hoon Lee, Yong Bum Park, Byoung Jun Lee, Hyun Kang, Jae Chol Choi
Journal: Thorax (2016)

<h3>Background</h3> Uncontrolled diabetes, unlike controlled diabetes, is associated with an impaired immune response. However, little is known about the impact of the status of diabetes control on clinical features and treatment outcomes in patients with pulmonary TB (PTB). We conducted this study to evaluate whether the status of diabetes control influences clinical manifestations and treatment responses in PTB. <h3>Methods</h3> A multicentre prospective study was performed between September 2012 and September 2014. The patients were categorised into three groups according to the glycated haemoglobin (HbA1C) level: PTB without diabetes mellitus (non-DM), PTB with controlled diabetes (controlled-DM) and PTB with uncontrolled diabetes (uncontrolled-DM). The primary outcome was the sputum culture conversion rate after 2 months of intensive treatment. <h3>Results</h3> Among 661 patients with PTB, 157 (23.8%) had diabetes and 108 (68.8%) had uncontrolled diabetes (HbA1C≥7.0%). The uncontrolled-DM group exhibited more symptoms, positive sputum smears (p&lt;0.001) and presence of cavities (p&lt;0.001) than the non-DM group. Regarding treatment responses, patients with uncontrolled-DM were more likely to have a positive culture after 2 months (p=0.009) and either treatment failure (p=0.015) or death (p=0.027) compared with the non-DM group. In contrast, those with controlled-DM showed similar treatment responses to the non-DM group. In multivariable analysis, uncontrolled diabetes was an independent risk factor for a positive sputum culture after 2 months of treatment (adjusted OR, 2.11; p=0.042) and either treatment failure or death (adjusted OR, 4.11; p=0.022). <h3>Conclusions</h3> Uncontrolled diabetes is an independent risk factor for poor treatment response in PTB.
Abstract 11666: Targeted Delivery of Rat iPS-Endothelial Cells Overexpressing Neutrophil IL8-RA/RB or Macrophage CCR2/CCR5 Receptors Inhibits Neointima Formation in Balloon Injured Rat Carotid Artery
Authors: Samantha Giordano, Dongqi Xing, Fadi G Hage, Tim M Townes, Chiao-Wang Sun, Li-Chen Wu, Suzanne Oparil, Yiu-Fai Chen
Journal: Circulation (2015)

Introduction: Interleukin 8 Receptors A and B (IL8RA and IL8RB) and C-C chemokine receptors 2 and 5 (CCR2 and CCR5) found on neutrophil and macrophage membranes respectively, modulate leukocyte chemotaxis after vascular injury. We have generated targeted cell therapy using adenoviral vectors that contain full length IL8RA, IL8RB, CCR2 and CCR5 cDNAs and green fluorescent protein. Transduced endothelial cells differentiated from rat induced pluripotent stem cells (RiPS-ECs) overexpressing these receptors provides support for autologous targeted cell therapy. We hypothesize that transfusion of RiPS-EC overexpressing IL8RA/B (RiPS-IL8RA/B-ECs), CCR2/5 (RiPS-CCR2/5-ECs) or both IL8RA/B and CCR2/5 (RiPS-IL8RA/B+CCR2/5-EC) into rats with balloon injury of the carotid artery will target to the area of injury, decrease the inflammatory response, and inhibit neointima formation. We will further determine the individual contribution of neutrophils and macrophage in the acute vascular injury response. Methods: 12 wk old male Sprague-Dawley rats received balloon injury of the right carotid artery and were immediately administered i.v. transfusion of 1) saline vehicle, 2)1.5x106 RiPS-Null-ECs; 3)1.5x106 RiPS-IL8RA/B-ECs, 4) 1.5x106 RiPS-CCR2/5-ECs, 6)1.5x106 RiPS-IL8RA/B+CCR2/5-ECs. One group of rats was sacrificed 24 hr post injury and cell transfusion and infiltration of neutrophils and monocytes/macrophages and pro-inflammatory cytokine levels were measured. A second group of rats was sacrificed 2 wks post injury for measurement of neointima formation. Results: RiPS-ECs equipped with the IL8RA/B or CCR2/5 homing device mimic the behavior of leukocytes and target to the injured arteries and inhibited neointima formation after endoluminal injury. Conclusions: These findings indicate a novel treatment for vascular injury using targeted cell therapy against both neutrophils and macrophages.
Contact Lens–Related Corneal Infections — United States, 2005–2015
Authors: Jennifer R. Cope, Sarah A. Collier, Krithika Srinivasan, Erkinay Abliz, Ann Myers, Courtney J. Millin, Andrew Miller, Michelle E. Tarver
Journal: MMWR Morbidity and Mortality Weekly Report (2016)

August 22-26, 2016, marks the third annual Contact Lens Health Week.In collaboration with partners from clinical, public health, industry, and regulatory sectors, CDC is promoting healthy contact lens wear and care practices to reduce the risk for eye infections among the approximately 41 million persons in the United States who wear contact lenses.Research after outbreaks of rare but serious eye infections in the United States have indicated that these infections occur most often in contact lens wearers who do not take proper care of their contact lenses, indicating a need to promote safer wear and care (1,2).A report in this issue of MMWR analyzed 1,075 contact lens-related eye infections reported to the Food and Drug Administration's Medical Device Report database.Nearly 20% of the reports described a patient who had eye damage, and approximately 25% of the reports described potentially modifiable factors that might have put patients at risk for a contact lens-related corneal infection, such as sleeping in lenses or wearing lenses for longer periods than prescribed.Although most contact lens wearers receive the benefits of vision correction, contact lenses can pose an infection risk, especially if they are not worn and cared for properly.Practicing proper contact lens hygiene and regularly visiting an eye care provider are important actions for keeping contact lens wearers' eyes healthy.Additional information on Contact Lens Health Week and the proper wear and care of contact lenses is available at http://www.cdc.gov/contactlenses.
Safety and Response of Incorporating CD19 Chimeric Antigen Receptor T Cell Therapy in Typical Salvage Regimens for Children and Young Adults with Acute Lymphoblastic Leukemia
Authors: Daniel W. Lee, Maryalice Stetler-Stevenson, Constance M. Yuan, Terry J. Fry, Nirali N Shah, Cindy Delbrook, Bonnie Yates, Hua Zhang, Ling Zhang, James N. Kochenderfer, Steven A. Rosenberg, David Stroncek, Crystal L. Mackall
Journal: Blood (2015)
Dual Transgenesis of T Cells with a Novel CD44v6-Specific Chimeric Antigen Receptor and a Suicide Gene for Safe and Effective Targeting of Chemoresistance in Hematopoietic Tumors
Authors: Monica Casucci, Laura Falcone, Benedetta Nicolis di Robilant, Barbara Camisa, Pietro Genovese, Bernhard Gentner, Luigi Naldini, Barbara Savoldo, Fabio Ciceri, Claudio Bordignon, Gianpietro Dotti, Chiara Bonini, Attilio Bondanza
Journal: Blood (2011)
Autologous Stem Cell Transplantation after FLAG-IDA Chemotherapy for High-Risk Myelodysplastic Syndromes (MDS) and Acute Myeloid Leukemias Secondary to MDS (sAML) Does Not Improve Outcome: A PETHEMA Experience in 103 Patients.
Authors: Guillermo F. Sanz, Armando V. Mena-Duran, Jose M. Ribera, Teresa Bernal, Luis Palomera, Maria C. del Cañizo, Mar Tormo, Maria J. Sayas, Raimundo García-Boyero, Javier de la Serna, Manuel Pérez-Encinas, Montserrat Pérez-Sánchez, María J. Arilla, Juan J. Moneva, Maria L. Amigo, Luis Benlloch, Montserrat Batlle, Consuelo Rayon
Journal: Blood (2005)