tbuckley/cabot-search huggingface dataset:
Biosynthesis of Parathyroid Hormone
Authors: Joel F. Habener, John T. Potts
Journal: New England Journal of Medicine (1978)

INVESTIGATORS concerned with the biologic functions of cell-secreted proteins such as hormones, immunoglobulins, enzymes and plasma proteins have become increasingly interested in the details of protein biosynthesis to learn how the control of cellular production of secreted proteins is geared to their functional roles. Studies of the synthesis of secretory proteins over the past few years have uncovered much new information. The synthesis of secretory proteins involves precursor forms, larger than the molecules ultimately secreted, that are processed to the final cellular products by a series of cleavages and translocation steps that take place within specialized . . .
Reply to Patel <i>et al</i>.: Tempering the Clinical Effects of Early Myeloid-derived Suppressor Cell Expansion in Severe Sepsis and Septic Shock
Authors: Fabrice Uhel, Christophe Camus, Arnaud Gacouin, Jean-Marc Tadié, Yves Le Tulzo, Mikael Roussel, Karin Tarte
Journal: American Journal of Respiratory and Critical Care Medicine (2017)
Programmed cell death protein 1 on natural killer cells: fact or fiction?
Authors: Monica M. Cho, Aicha E. Quamine, Mallery R. Olsen, Christian M. Capitini
Journal: Journal of Clinical Investigation (2020)

Programmed cell death protein 1 (PD-1) has become one of the most investigated targets for cancer immunotherapy. Most research has centered on inhibiting PD-1 on T cells, but there is increased interest in understanding the role of PD-1 on NK cells. While the expression of PD-1 on NK cells has been controversial, with papers publishing contradictory results in multiple models, there is increased clinical interest in NK and PD-1 immunotherapy. In this issue of the JCI, Judge et al. comprehensively explore the lack of PD-1 expression on murine, canine, and human NK cells and the clinical implication of these findings.
Immune responses to stroke: mechanisms, modulation, and therapeutic potential
Authors: Costantino Iadecola, Marion S. Buckwalter, Josef Anrather
Journal: Journal of Clinical Investigation (2020)

Stroke is the second leading cause of death worldwide and a leading cause of disability. Most strokes are caused by occlusion of a major cerebral artery, and substantial advances have been made in elucidating how ischemia damages the brain. In particular, increasing evidence points to a double-edged role of the immune system in stroke pathophysiology. In the acute phase, innate immune cells invade brain and meninges and contribute to ischemic damage, but may also be protective. At the same time, danger signals released into the circulation by damaged brain cells lead to activation of systemic immunity, followed by profound immunodepression that promotes life-threatening infections. In the chronic phase, antigen presentation initiates an adaptive immune response targeted to the brain, which may underlie neuropsychiatric sequelae, a considerable cause of poststroke morbidity. Here, we briefly review these pathogenic processes and assess the potential therapeutic value of targeting immunity in human stroke.
Choices for the “New Normal”
Authors: Donald M. Berwick
Journal: JAMA (2020)

Choices for the "New Normal"The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has only 15 genes, compared with 30 000 in the human genome.But it is a stern teacher, indeed.Answers to the questions it has raised may reshape both health care and society as a whole.No one can say with certainty what the consequences of this pandemic will be in 6 months, let alone 6 years or 60.Some "new normal" may emerge, in which novel systems and assumptions will replace many others long taken for granted.But at this early stage, it is more honest to frame the new, post-COVID-19 normal not as predictions, but as a series of choices.Specifically, the pandemic nominates at least 6 properties of care for durable change: tempo, standards, working conditions, proximity, preparedness, and equity.
Differential effects of selective- and pan-PPAR agonists on experimental steatohepatitis and hepatic macrophages☆
Authors: Sander Lefere, Tobias Puengel, Jana Hundertmark, Christian Penners, Anna Katharina Frank, Adrien Guillot, Kevin de Muynck, Felix Heymann, Vanessa Adarbes, Evelyne Defrêne, Céline Estivalet, Anja Geerts, Lindsey Devisscher, Guillaume Wettstein, Frank Tacke
Journal: Journal of Hepatology (2020)
Abstract 15546: Influence of Rate Pressure Product Correction on Reclassification of Myocardial Flow Reserve
Authors: Gaurav Sharma, Albert Deluca, Sabahat Bokhari, Kathleen R Flaherty, Andrew J Einstein
Journal: Circulation (2019)

Introduction: SNMMI and ASNC suggest consideration of correction of resting myocardial blood flow (MBF) for rate pressure product (RPP) when interpreting myocardial flow reserve (MFR) in cardiac po...
Expression of CD44 in human hepatocellular carcinoma cell lines*1
Authors: M HARAMAKI
Journal: Hepatology (1995)

CD44 is a glycosylated cell surface adhesion molecule expressed on a diverse range of cells and has several variant forms, some of which are involved in metastasis of cancer cells. Because little is known about CD44 in human hepatocellular carcinoma (HCC), we investigated its expression in tissue specimens from primary lesions (12 cases), in smear specimens from peritoneal effusions (2 cases), and in cell lines (HCC cell lines, KIM-1, KYN-1, KYN-2, KYN-3, HAK-1A, and HAK-1B; combined hepatocholangiocarcinoma cell lines, KMCH-1 and KMCH-2; and bile duct carcinoma cell lines, KMC-1 and KMBC). Immunohistochemical studies using monoclonal antibody recognizing epitope Group 1 of human CD44 molecule showed that HCC cells in all tissue specimens, including the original tumors of one smear specimen and HAK-1A, were negative for CD44; whereas, HCC cells in two-smear specimens, KIM-1, KYN-2, KYN-3, HAK-1A, HAK-1B, KMCH-1, KMC-1, and KMBC, showed positive reactions on the cell membrane. Immunostainpositive cell lines showed a positive cell rate of 51.9% to 99.8% by flow cytometric analysis. Western blotting detected CD44 protein of hemopoietic type in KIM-1, KYN-3, HAK-1A, and HAK-B and epithelial type in KMC1 and KMBC. Southern blotting of complementary DNA amplified after reverse transcriptase-polymerase chain reaction (RT-PCR) detected hemopoietic type and some variant forms with longer insertion in all cell lines but KMCH-2, whereas hemopoietic type and variants with minor insertion were only detectable in tissue specimens. These findings suggest that HCC cells in ascites and in culture often express CD44, but those in tissue do not at protein level.
A prospective study of XELIRI plus bevacizumab as the first-line therapy in Japanese patients with unresectable or recurrent colorectal cancer (KSCC1101).
Authors: Koichi Hanazono, Yasunori Emi, Akihito Tsuji, Fumiaki Kishihara, Eiji Oki, Masahiro Hamanoue, Hideo Baba, Shoji Natsugoe, Yutaka Ogata, Kenji Sakai, Yoshihiko Maehara
Journal: Journal of Clinical Oncology (2015)

752 Background: XELIRI plus bevacizumab (Bev) might be one of the standard therapies for metastatic colorectal cancer (mCRC). However, there was no clinical practice data in Japan. This study was designed to evaluate the efficacy and safety of XELIRI plus Bev in clinical practice in Japanese mCRC patients (pts.). Methods: This was a multicenter, single-arm, open-label prospective study. The major inclusion criteria were previously untreated mCRC; presence of measurable lesions; age ≥20 years; ECOG performance status (PS) of 0–2; and adequate organ function. Pts received Bev 7.5 mg/kg day 1 and XELIRI (irinotecan 200 mg/m 2 day 1 plus capecitabine 800 mg/m 2 bid d1-14) q3w. This schedule was repeated until unacceptable toxicity or disease progression occurred. The primary endpoint was RECIST-confirmed objective response rate (ORR). A sample size of 35 was planned for a threshold ORR of 30% and expected value of 53%, with one-sided alpha of 0.05 and beta of approximately 0.2. Results: A total of 36 pts (male/female, 23/13; median age, 65.0 years (range 44.0-80.0); PS 0/1/2, 31/5/0) were enrolled in this study from July 2011 to September 2012. One patient did not fulfill the eligibility criteria and one withdrew the informed consent before the start of protocol treatment. Thirty-four pts were assessed for response; CR 0, PR 18, SD 9, PD 4, and NE 3. The confirmed ORR was 52.9% (90% CI, 37.7-67.8%). Median PFS was 9.6 months (95% CI, 5.1-11.1 months) and mOS was 23.0 months (95% CI, 11.3-NE months). mTTF was 5.3 months (95% CI, 3.2-8.3 months). The most common grade 3/4 adverse events were neutropenia 31.4%, anemia 20.0%, thrombocytopenia 5.7%, hyponatremia 20.0%, anorexia 20.0%, diarrhea 22.8%, fatigue 0.0%, hypertension 2.9%, hand-foot syndrome 0.0%, and bleeding 0.0%. Conclusions: First-line treatment of XELIRI + Bev showed a promising response rate and an acceptable tolerability profile in the clinical practice in Japanese mCRC pts. Clinical trial information: UMIN000006070.
When Should Clinicians Act on Non–Statistically Significant Results From Clinical Trials?
Authors: Paul J. Young, Christopher P. Nickson, Anders Perner
Journal: JAMA (2020)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Self-expandable metal stent placement as a rescue procedure for lumen-apposing metal stent misdeployment in biliary drainage
Authors: Alessandro Fugazza, Roberto Gabbiadini, Matteo Colombo, Silvia Carrara, Roberta Maselli, Alessandro Repici, Andrea Anderloni
Journal: Endoscopy (2020)

We present the case of an 85-year-old man with jaundice due to cephalopancreatic cancer and a previous failed endoscopic retrograde cholangiopancreatography (ERCP) due to infiltration of the papilla ([Fig. 1]). Endoscopic ultrasound-guided biliary drainage (EUS-BD) with a transbulbar approach was scheduled.
MORTALITY-RATES AFTER MULTIFACTORIAL PRIMARY PREVENTION OF CARDIOVASCULAR-DISEASES
Authors: V A Naukkarinen, Timo Strandberg, Hannu T Vanhanen, V V Salomaa, S J Sarna, Tatu Miettinen
Journal: Annals of Internal Medicine (1989)

Eleven-year mortality rates were studied in middle aged men who had participated in a randomised 5-year multifactorial primary prevention trial on cardiovascular diseases during 1974-1980. The men were given health education advice before the study. The 5-year trial markedly improved the risk factor status in the men in the intervention group (n = 612), but their 5-year incidence of total coronary events tended to be higher than in the randomised non-treated control group (n = 610) and significantly higher than in an non-randomised, non-treated low risk group (n = 593). During the six years following the discontinuation of the trial, 11 deaths from cardiovascular disease occurred both in the intervention and in the control groups and three in the non-randomised low risk group. Thus, the cumulative eleven-year cardiovascular mortality rates and their 95% confidence intervals (Cl95) were 2.45% (Cl95: 1.38, 3.67) in the intervention group and 1.97% (Cl95: 1.01, 3.34) in the randomised high risk control group. In the non-randomised low risk group the mortality rate was 0.51 (Cl95: 0.01, 1.46). Multiple logistic regression analysis showed that overweight and hypercholesterolaemia, and smoking in the high risk controls, were the initial risk factors associated with the 11-year cardiovascular mortality. The latter was not accumulated in any treatment measure during the prevention period. Furthermore, despite the unfavourable effect of beta-blocking agents on total cardiac events during the intervention, beta-blockers were not associated with cardiac deaths in the 11-year follow up.(ABSTRACT TRUNCATED AT 250 WORDS)
NON-FAMILIAL HYPERTROPHIC CARDIOMYOPATHY: PREVALENCE, NATURAL HISTORY AND CLINICAL IMPLICATIONS
Authors: Jodie Ingles, Charlotte Burns, Richard Bagnall, Lien Lam, Laura Yeates, Tanya Sarina, Raj Puranik, Tom Briffa, John Atherton, Tim Driscoll, Christopher Semsarian
Journal: Journal of the American College of Cardiology (2017)
Trying for a BRAF Slam Dunk
Authors: Antoni Ribas, Roger S. Lo
Journal: Cancer Discovery (2020)

Abstract Summary: The first basket clinical trial testing the BRAF inhibitor vemurafenib resulted in evidence of activity in 13 unique cancer types with BRAFV600 mutations, but the response rates were variable. Therefore, different cancer histologies with the same driver oncogene display different degrees of oncogenic pathway addiction. See related article by Subbiah et al., p. 657.
Children with Covid-19 in Pediatric Emergency Departments in Italy
Authors: Niccolò Parri, Matteo Lenge, Danilo Buonsenso
Journal: New England Journal of Medicine (2020)

Children with Covid-19 in Italy This letter describes a cohort of 100 children younger than 18 years of age with RT-PCR–confirmed Covid-19 who were assessed in 17 pediatric emergency departments in...
Respiratory syncytial virus infection exacerbates pneumococcal pneumonia via Gas6/Axl-mediated macrophage polarization
Authors: Takehiko Shibata, Airi Makino, Ruiko Ogata, Shigeki Nakamura, Toshihiro Ito, Kisaburo Nagata, Yoshihiko Terauchi, Taku Oishi, Mikiya Fujieda, Yoshimasa Takahashi, Manabu Ato
Journal: Journal of Clinical Investigation (2020)

Patients with respiratory syncytial virus (RSV) infection exhibit enhanced susceptibility to subsequent pneumococcal infections. However, the underlying mechanisms involved in this increased susceptibility remain unclear. Here, we identified potentially novel cellular and molecular cascades triggered by RSV infection to exacerbate secondary pneumococcal pneumonia. RSV infection stimulated the local production of growth arrest-specific 6 (Gas6). The Gas6 receptor Axl was crucial for attenuating pneumococcal immunity in that the Gas6/Axl blockade fully restored antibacterial immunity. Mechanistically, Gas6/Axl interaction regulated the conversion of alveolar macrophages from an antibacterial phenotype to an M2-like phenotype that did not exhibit antibacterial activity, and the attenuation of caspase-1 activation and IL-18 production in response to pneumococcal infection. The attenuated IL-18 production failed to drive both NK cell-mediated IFN-γ production and local NO and TNF-α production, which impair the control of bacterial infection. Hence, the RSV-mediated Gas6/Axl activity attenuates the macrophage-mediated protection against pneumococcal infection. The Gas6/Axl axis could be a potentially novel therapeutic target for RSV-associated secondary bacterial infection.
Outpatient Inhaled Nitric Oxide in a Patient with Vasoreactive Idiopathic Pulmonary Arterial Hypertension and COVID-19 Infection
Authors: Roham T. Zamanian, Charles V. Pollack, Michael A. Gentile, Moira Rashid, John Christian Fox, Kenneth W. Mahaffey, Vinicio de Jesus Perez
Journal: American Journal of Respiratory and Critical Care Medicine (2020)

Author(s): Zamanian, Roham T; Pollack, Charles V; Gentile, Michael A; Rashid, Moira; Fox, John Christian; Mahaffey, Kenneth W; de Jesus Perez, Vinicio
The Use of Random Forests to Identify Brain Regions on Amyloid and FDG PET Associated With MoCA Score
Authors: Katherine Zukotynski, Vincent Gaudet, Phillip H. Kuo, Sabrina Adamo, Maged Goubran, Christopher J.M. Scott, Christian Bocti, Michael Borrie, Howard Chertkow, Richard Frayne, Robin Hsiung, Robert Laforce, Michael D. Noseworthy, Frank S. Prato, Demetrios J. Sahlas, Eric E. Smith, Vesna Sossi, Alexander Thiel, Jean-Paul Soucy, Jean-Claude Tardif, Sandra E. Black
Journal: Clinical Nuclear Medicine (2020)

Purpose The aim of this study was to evaluate random forests (RFs) to identify ROIs on 18 F-florbetapir and 18 F-FDG PET associated with Montreal Cognitive Assessment (MoCA) score. Materials and Methods Fifty-seven subjects with significant white matter disease presenting with either transient ischemic attack/lacunar stroke or mild cognitive impairment from early Alzheimer disease, enrolled in a multicenter prospective observational trial, had MoCA and 18 F-florbetapir PET; 55 had 18 F-FDG PET. Scans were processed using the MINC toolkit to generate SUV ratios, normalized to cerebellar gray matter ( 18 F-florbetapir PET), or pons ( 18 F-FDG PET). SUV ratio data and MoCA score were used for supervised training of RFs programmed in MATLAB. Results 18 F-Florbetapir PETs were randomly divided into 40 training and 17 testing scans; 100 RFs of 1000 trees, constructed from a random subset of 16 training scans and 20 ROIs, identified ROIs associated with MoCA score: right posterior cingulate gyrus, right anterior cingulate gyrus, left precuneus, left posterior cingulate gyrus, and right precuneus. Amyloid increased with decreasing MoCA score. 18 F-FDG PETs were randomly divided into 40 training and 15 testing scans; 100 RFs of 1000 trees, each tree constructed from a random subset of 16 training scans and 20 ROIs, identified ROIs associated with MoCA score: left fusiform gyrus, left precuneus, left posterior cingulate gyrus, right precuneus, and left middle orbitofrontal gyrus. 18 F-FDG decreased with decreasing MoCA score. Conclusions Random forests help pinpoint clinically relevant ROIs associated with MoCA score; amyloid increased and 18 F-FDG decreased with decreasing MoCA score, most significantly in the posterior cingulate gyrus.
Air Pollution and Mortality in the Medicare Population—Reply
Authors: Joel D. Schwartz
Journal: JAMA (2018)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
A phase I study of concurrent chemotherapy (paclitaxel and carboplatin) and thoracic radiotherapy with swallowed manganese superoxide dismutase (MnSOD) plasmid liposome (PL) protection in patients with locally advanced stage III non-small cell lung cancer.
Authors: R. E. Schillo, A. A. Tarhini, C. P. Belani, J. D. Luketich, A. Argiris, S. S. Ramalingam, D. Liggitt, T. Championsmith, M. W. Epperly, J. S. Greenberger
Journal: Journal of Clinical Oncology (2010)

e17501 Background: Esophageal toxicity has been accepted reluctantly, as a necessary side effect of the benefits of chemoradiotherapy for lung cancer. MnSOD is a genetically engineered therapeutic DNA/liposome containing the human MnSOD transgene. Preclincial studies in mouse models have demonstrated that the expression of the human MnSOD transgene confers protection of normal tissues from ionizing irradiation damage. Methods: Chemotherapy (carboplatin AUC=2 and paclitaxel 45 mg/m2 intravenously) was given weekly (for 7 weeks), concurrently with radiation therapy for pts with locally advanced NSCLC. MnSOD PL was swallowed twice a week (total 14 doses), at 3 dose levels: 0.3, 3, and 30 mg. Dose escalation followed a standard phase I design. Esophagoscopy was done at baseline, day 4 and 6 weeks after radiation with biopsies of the squamous lining cells. DNA was extracted and analyzed by PCR for the detection of the MnSOD transgene DNA. Results: Nine patients with stage IIIA (2) and IIIB (7) completed the course of therapy per study protocol. Five had squamous histology, 2 adenocarcinoma, and 2 not specified. These patients were treated in 3 different cohorts at 3 dose levels of MnSOD PL: 0.3, 3, and 30 mg. The median dose of radiation was 77.7Gy (range 63-79.10Gy). Overall response rate for the standard chemo-radiation regimen was 67% (n=9). Grade 2 dyspepsia and a grade 1 rash in one patient was considered possibly related to MnSOD PL. None of the other reported toxicities were considered possibly, probably, or definitely related to MnSOD PL. There were no dose-limiting toxicities reported in all 3 dosing tiers. MnSOD PCR product was not detected in the esophageal samples. Conclusions: The oral administration of MnSOD PL is feasible and safe. The phase II recommended dose is 30 mg. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Valentis, Inc.
JMJD2B-induced amino acid alterations enhance the survival of colorectal cancer cells under glucose-deprivation via autophagy
Authors: Juan Tan, Hao-Lian Wang, Jie Yang, Qian-Qian Liu, Chun-Min Li, Yun-Qian Wang, Lin-Na Fu, Qin-Yan Gao, Ying-Xuan Chen, Jing-Yuan Fang
Journal: Theranostics (2020)

: Post-translational modifications have emerged as vital players in alterations to tumor metabolism, including amino acid metabolic reprogramming. Jumonji domain-containing protein 2B (JMJD2B) enhances colorectal cancer (CRC) cell survival upon glucose deficiency. In the present study, we hypothesized that JMJD2B affects tumor cell amino acid metabolism in CRC and consequently promotes survival of CRC cells upon glucose deprivation.
Inhibitors of the Renin–Angiotensin–Aldosterone System and Covid-19
Authors: John A Jarcho, Julie R Ingelfinger, Mary Beth Hamel, Ralph B D'Agostino, David P Harrington
Journal: New England Journal of Medicine (2020)

RAAS Inhibitors and Covid-19 The editors comment on three Journal articles that provide observational data about whether ACE inhibitors and ARBs are harmful in the context of the Covid-19 epidemic....
Making simple things complicated using anti-inflammatory reliever therapy
Authors: Brian Lipworth, Chris RuiWen Kuo, Rory Chan
Journal: European Respiratory Journal (2020)

We appreciated reading the eloquent editorial from Beasley et al . [1], who make a cogent evidence-based case for using budesonide/formoterol (BUD/FM) on demand ( p.r.n .) as the preferred asthma reliever, in keeping with the latest GINA guidelines. They proffer what appears at first sight to be a pragmatic stepwise treatment algorithm and associated action plan for using BUD/FM p.r.n . as anti-inflammatory reliever (AIR)±maintenance therapy across Global Initiative for Asthma steps 1 to 3. Use more budesonide/formoterol when you need it, and less when you don't <http://bit.ly/2PKsCOH>