tbuckley/cabot-search huggingface dataset:
Alterations of Gut Microbiome Accelerate Multiple Myeloma Progression By Increasing the Relative Abundances of Nitrogen Recycling Bacteria
Authors: Xingxing Jian, Yinghong Zhu, Jian Ouyang, Qian Lei, Jiliang Xia, Jingyu Zhang, Jiaojiao Guo, Jinuo Wang, Jingchao Lin, Mingming Su, Yongjun Guan, Guancheng Li, Minghua Wu, Jian Li, Juanjuan Xiang, Lu Xie, Lugui Qiu, Wei Jia, Wen Zhou
Journal: Blood (2019)
Update on pilot study on antitumor efficacy of intravenously applied synergistic combinations of diflunisal, PAS, and aspirin in patients with advanced solid tumors.
Authors: Joachim Drevs, Susanne D'Urso, Martin Dayton, Lukas Martinez, Jonas Mueller-Huebenthal, Izumi Kamijo, Werner Kreutz
Journal: Journal of Clinical Oncology (2013)

e22114 Background: Due to chronic hypoxia cancer cells are growing in a more acidic environment compared to physiological tissue. Recent preclinical in vitro and in vivo data have shown direct pH-sensitive anti-tumor activity by pore formation and apoptosis when synergistically acting combinations of Diflunisal, Paraaminosalicylic acid (PAS) and Aspirin were applied. Therefore, a pilot study was performed to evaluate its clinical relevance and its update is presented. Methods: A total of 65 patients (n=65) with advanced solid tumors and the lack of standard treatments were treated with a protocol consisting of 3-5 weeks with 2 daily i.v. infusions of Diflunisal and Aspirin for 4 days per week after they had signed an informed consent form. Response evaluation was assessed by PET/CT differentiating in metabolic and metric (RECIST) response and tumor marker where available. Results: Out of 65 patients treated 8 patients suffered from colorectal cancer, 17 from breast cancer, 6 from ovarian cancer, 3 from lung cancer, 3 from gastric cancer, 3 from glioblastoma, 3 from CUP, 1 from hemangioendothelioma, 1 from pleuramesothelioma, 1 from non-Hodgkin lymphoma, 2 from pancreatic cancer, 1 from choledochus cancer, 3 from prostate cancer, 5 from sarcomas, 2 from head and neck cancer, 1 from melanoma, 1 from cervical cancer, and 1 from thyroid cancer, respectively. Side effects related to the therapy have been fatigue grade I (30%), nausea grade I (13,3%), tinnitus (25%), hypertension (2,5%), dyspnea (3,3%) and burning sensation in tumor areas (65%). 33 patients were evaluable for metric response, 20 for metabolic and 19 for tumor marker response assessment. For tumor marker follow up 11 % had a CR, 53 % a PR, 26 % a SD of &gt; 3 month and 11 % a PD. For metric follow up 3 % had a CR, 33 % a PR, 39 % a SD of &gt; 3 month and 24 % a PD. For metabolic follow up 10 % had a CR, 35 % a PR, 35 % a SD of &gt; 3 month and 20 % a PD. Conclusions: This continuing pilot study confirms a direct pH-sensitive synergistic anti-tumor activity of intravenous Diflunisal, PAS and Aspirin in patients with advanced solid tumors. Therefore, a further evaluation in a controlled clinical phase II study should be performed.
How do memory modules differentially contribute to familiarity and recollection?
Authors: Olya Hakobyan, Sen Cheng
Journal: Behavioral and Brain Sciences (2019)

Abstract We fully support dissociating the subjective experience from the memory contents in recognition memory, as Bastin et al. posit in the target article. However, having two generic memory modules with qualitatively different functions is not mandatory and is in fact inconsistent with experimental evidence. We propose that quantitative differences in the properties of the memory modules can account for the apparent dissociation of recollection and familiarity along anatomical lines.
SWOG S0533: A pilot trial of cisplatin (C)/etoposide (E)/radiotherapy (RT) followed by consolidation docetaxel (D) and bevacizumab (B) (NSC-704865) in three cohorts of patients (pts) with inoperable locally advanced stage III non-small cell lung cancer (NSCLC).
Authors: Antoinette J. Wozniak, James Moon, Charles R. Thomas, Karen Kelly, Philip C. Mack, Laurie E. Gaspar, David Raben, Kishan J. Pandya, David R. Gandara
Journal: Journal of Clinical Oncology (2012)

7018 Background: Bevacizumab combined with chemotherapy has improved survival in the treatment of advanced NSCLC. This pilot trial was conducted to determine if bevacizumab could be incorporated into the standard chemotherapy/RT for locally advanced NSCLC. Methods: Pts with unresectable stage III NSCLC, PS 0-1, and adequate organ function were eligible. Pts were accrued in two strata, low and high risk (squamous histology, hemoptysis, tumor with cavitation or near a major vessel). Pts were treated with C 50mg/m 2 (d 1 and 8), E 50mg/m 2 (d 1-5) for 2 cycles concurrent with RT (64.8 Gy at 1.8 Gy/fx for 36 fxs) followed by consolidation D 75mg/m 2 and B 15 mg/kg for 3 cycles (Cohort 1). If safety was established then accrual would continue to Cohort 2 (B, d 15, 36, 57) and then Cohort 3 (B d 1, 22, 43). Results: 29 pts (17 Low, 12 High) were registered, all to Cohort 1. 26 pts (stage IIIB 19 pts, squamous 4 pt, adenosquamous 1 pt) were evaluable. 25 completed chemo/RT. Grade 3/4 toxicities during chemo/RT included: neutropenia 10 pts, thrombocytopenia 2, anemia 2, febrile neutropenia 3, esophagitis 2, pneumonitis 1. 21 were assessed for safety with D/B consolidation. The major adverse events during D/B consolidation were pneumonitis (Gr 3 - 2 pt) and 2 episodes of fatal hemoptysis in the high risk group resulting in closure of this stratum. The low risk stratum subsequently closed because of poor accrual. Median overall survival was 23 mos for low risk pts and 17 mos for the high risk stratum. Conclusions: In this trial, bevacizumab could not be successfully integrated into chemo-radiation for stage III NSCLC, particularly in pts considered at high risk for hemoptysis. The trial suffered from several temporary closures as mandated by CTEP when new bevacizumab-related toxicities were reported, contributing to slow accrual. In lower risk pts the data are insufficient to determine safety or efficacy. Supported in part by the following PHS Cooperative Agreement grant numbers awarded by the National Cancer Institute, DHHS: CA32102 and CA38926.
Ethics and Collateral Findings in Pragmatic Clinical Trials
Authors: Stephanie R. Morain, Kevin Weinfurt, Juli Bollinger, Gail Geller, Debra JH Mathews, Jeremy Sugarman
Journal: The American Journal of Bioethics (2020)

Pragmatic clinical trials (PCTs) offer important benefits, such as generating evidence that is suited to inform real-world health care decisions and increasing research efficiency. However, PCTs also present ethical challenges. One such challenge involves the management of information that emerges in a PCT that is unrelated to the primary research question(s), yet may have implications for the individual patients, clinicians, or health care systems from whom or within which research data were collected. We term these findings as ?pragmatic clinical trial collateral findings,? or ?PCT-CFs?. In this article, we explore the ethical considerations associated with the identification, assessment, and management of PCT-CFs, and how these considerations may vary based upon the attributes of a specific PCT. Our purpose is to map the terrain of PCT-CFs to serve as a foundation for future scholarship as well as policy-making and to facilitate careful deliberation about actual cases as they occur in practice.
Paracetamol for pain in adults
Authors: Bruno T Saragiotto, Christina Abdel Shaheed, Chris G Maher
Journal: BMJ (2019)

### What you need to know

A 65 year old retired engineer has experienced a flare up in the pain he experiences with his osteoarthritic knee. While seeing his general practitioner (GP) about a skin lesion, he mentions the knee problem and asks if he should use paracetamol to manage the pain. The patient is overweight and physically inactive. 

Paracetamol (acetaminophen) is one of the most widely used over-the-counter drugs around the world for the treatment of pain.1 More than 100 different preparations, which contain paracetamol alone or in combination with other substances (eg, non-steroidal anti-inflammatory drugs or NSAIDs, caffeine, and tramadol) are available.2 Current understanding is that paracetamol acts by inhibiting the cyclooxygenase (COX) enzymes through metabolism of the peroxidase function of these isoenzymes. It is less certain if its action is mediated by inhibition of COX-1, COX-2, or COX-3 enzymes.234

Paracetamol is inexpensive in most countries and is generally considered safe. This contributes to its widespread use. Paracetamol is available in immediate release (short acting) and modified release (long acting) preparations. In December 2017, the European Medicines Agency recommended suspending the marketing of modified release paracetamol because of concerns about a rise in overdose events and ensuing complications,5 although the modified release preparations are still widely available in countries such as Australia, New Zealand, and the US. …
Management of Acute and Recurrent Pericarditis
Authors: Juan Guido Chiabrando, Aldo Bonaventura, Alessandra Vecchié, George F Wohlford, Adolfo G Mauro, Jennifer H Jordan, John D Grizzard, Fabrizio Montecucco, Daniel Horacio Berrocal, Antonio Brucato, Massimo Imazio, Antonio Abbate
Journal: Journal of the American College of Cardiology (2020)
Misuse of “Usual Care” in Emergency Care Research: A Call for Adapting Rules Governing Exception from Informed Consent (EFIC) Studies
Authors: Ethan Cowan, Kate Sahan, Mark Sheehan
Journal: The American Journal of Bioethics (2020)

Macklin and Natanson (2020) raise concerns surrounding the misrepresentation of usual care in three critical care studies. Emergency care research also yields examples of studies where claims of us...
Recurrent Blistering in an Infant
Authors: Divya Kamat, Debajyoti Chatterjee, Keshavamurthy Vinay
Journal: JAMA Dermatology (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 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
A novel approach to improve detection of somatic DNA variants in solid tumors by next-generation sequencing from FFPE samples.
Authors: Nitin Udar, Robert Haigis, Thomas Gros, Agda Karina Lucio-Eterovic, Qingxiu Zhang, Maryam Zenali, Mark Ross, Erich Jaeger
Journal: Journal of Clinical Oncology (2013)

e22177 Background: Low frequency variant detection by sequencing is a highly desired goal for therapy selection in cancer especially the detection of actionable targets. The lower limit of detection using Sanger sequening is ~20% minor allele frequency (MAF). Deep sequencing of target genes using next generation sequencing (NGS) is gaining popularity. Formalin Fixed Paraffin Embedded (FFPE) tissue is the most common sample type in solid tumor histopathology. However, because the fixation process fragments DNA and damages it at varying frequencies, downstream processes can potentially misclassify modified bases and generate artifacts. We have developed a protocol that addresses both of these issues in a multiplex assay that involves deep sequencing using NGS of targets implicated in lung, gastric, colon, melanoma and ovarian cancers. Methods: The sample set includes 168 FFPE samples and 82 non FFPE samples. TruSeq Custom Amplicon technology was used to generate libraries for targets across 26 genes. Deep sequencing was done on a NGS platform (Illumina-MiSeq). Results: The DNA quality test, which surveys multiple genomic targets by qPCR, was an accurate determinant of DNA amplifiability and yielded a 99% sample success rate. A sensitivity of &lt;5% MAF was achieved by sequencing at a depth of 1,000X for all targets. In order to differentiate true low frequency variants from fixation and other artifacts, our novel approach investigates each of the two DNA strands independently. The information is bioinformatically combined to distinguish true variants from artifacts. Testing of the FFPE samples with a 5% MAF cut off using the two strand approach reduced the potential false positive rate by ~ 40% when compared to information from only one strand of DNA. A comparative analysis of matched FF and FFPE sample showed that a high percentage of false positive calls were present even in the fresh frozen samples at this high level of sensitivity, if only using information from one strand. Conclusions: This protocol, efficiently and accurately detect low frequency variants by NGS in DNA extracted from FFPE tissues.
Promotion of Myofibroblast Differentiation and Tissue Fibrosis by the Leukotriene B<sub>4</sub>–Leukotriene B<sub>4</sub> Receptor Axis in Systemic Sclerosis
Authors: Minrui Liang, Jiaoyan Lv, Zhixing Jiang, Hang He, Chen Chen, Yinluo Xiong, Xiaoxia Zhu, Yu Xue, Yiyun Yu, Sen Yang, Lingbiao Wang, Wenjing Li, Ming Guan, Weiguo Wan, Rui He, Hejian Zou
Journal: Arthritis & Rheumatology (2019)

Objective To investigate the role of the inflammatory lipid mediator leukotriene B 4 ( LTB 4 ) and its receptor, BLT1, in the development and progression of systemic sclerosis ( SS c). Methods Serum levels of LTB 4 were compared in 64 patients with SS c and 80 healthy controls. Skin and lung tissue sections from patients with SS c and healthy donors were immunostained for leukotriene A 4 hydrolase ( LTA 4 H), the critical enzyme for LTB 4 synthesis, and BLT1, in combination with different cell markers. In mouse models of SS c using bleomycin or angiotensin II challenge or immunization with the DNA topoisomerase I, genetic or pharmacologic interruption of the LTB 4 – BLT1 axis in mice was carried out to assess its effects on systemic disease features and myofibroblast markers. Immunoblotting was performed to examine the signaling pathway in fibroblasts and endothelial cells following stimulation with LTB 4 or with serum from SSc patients. Results Serum LTB 4 levels were 44.93% higher in patients with SS c than in matched healthy controls (mean ± SD 220.3 ± 74.75 pg/ml versus 152.0 ± 68.05 pg/ml; P &lt; 0.0001), and this was associated with the patient subsets of SS c‐associated interstitial lung disease and diffuse cutaneous SS c. Levels of LTA 4 H and BLT1 were increased in lesional areas of the skin and lungs of SS c patients, and both were abundant in myofibroblasts and endothelial cells. Interruption of the LTB 4 – BLT1 axis in mouse models of SS c significantly mitigated dermal and pulmonary fibrosis, with 54.00% and 52.65% fewer α‐smooth muscle actin–positive myofibroblasts accumulating in the skin and lungs of mice, respectively, after bleomycin challenge. Immunoblotting of cultures with recombinant LTB 4 –stimulated fibroblasts and endothelial cells or with serum from SS c patients showed that fibroblast–myofibroblast and endothelial–mesenchymal transitions were promoted via BLT1, and that this was dependent on activation of the phosphatidylinositol 3‐kinase ( PI 3K)/Akt/mechanistic target of rapamycin ( mTOR ) pathway but independent of the release of transforming growth factor β ( TGF β) by fibroblasts or endothelial cells. Conclusion The LTB 4 – BLT1 axis may contribute to fibrosis in SS c by directly promoting myofibroblast differentiation via the PI 3K/Akt/ mTOR pathway, and this appears to operate independently of autocrine secretion of TGF β.
N-Acetylcysteine: A Natural Antidote for Alzheimer's Disease
Authors: Martínez-Banaclocha Marcos
Journal: Alzheimers Disease & Dementia (2016)

Alzheimer's disease (AD) is the most devastating age-related dementia, which has no effective treatment. Since the pathological hallmarks of AD brains are Aβ plaques and intra-neuronal tau-containing neurofibrillary tangles, most therapeutic approaches, including immunotherapy, are based on the concept that the accumulation of these proteins produces neuronal damage and death. Alternatively, it has been proposed that reactive species can cause oxidative damage including mitochondrial disruption, contributing to AD initiation and progression. Can these cellular dysfunctions be linked by a common pathogenic mechanism susceptible to therapy with the natural compound N-acetylcysteine? A cellular cysteine network (CYSTEINET) has been proposed as a functional and structural matrix of interconnected sensitive cysteine-containing proteins (SCCPs) that in conjunction with reactive species and the cysteine/glutathione cycles can regulate the bioenergetic metabolism, the redox homeostasis, and the cellular survival through different pathways that bear the same regulatory thiol radical. The present paper proposes that cysteinet is impaired in Alzheimer's disease resulting in a functional and structural deregulation of the matrix of interconnected cysteine-containing proteins that result in misfolding, aggregation and accumulation of specific toxic proteins. In this context, the role of N-acetylcysteine to prevent and restore cysteinet deregulation in AD development and progression is discussed.
Randomized Phase III Study of Continuation Maintenance Bevacizumab With or Without Pemetrexed in Advanced Nonsquamous Non–Small-Cell Lung Cancer: COMPASS (WJOG5610L)
Authors: Takashi Seto, Koichi Azuma, Takeharu Yamanaka, Shunichi Sugawara, Hiroshige Yoshioka, Kazushige Wakuda, Shinji Atagi, Yasuo Iwamoto, Hidetoshi Hayashi, Isamu Okamoto, Hideo Saka, Shigeki Mitsuoka, Daichi Fujimoto, Kazumi Nishino, Atsushi Horiike, Haruko Daga, Takashi Sone, Nobuyuki Yamamoto, Kazuhiko Nakagawa, Yoichi Nakanishi
Journal: Journal of Clinical Oncology (2019)

PURPOSE Patients with non–small-cell lung cancer (NSCLC) have been shown to benefit from maintenance therapy. COMPASS evaluated the efficacy and safety of bevacizumab with or without pemetrexed as continuation maintenance therapy after carboplatin, pemetrexed, and bevacizumab induction therapy. PATIENTS AND METHODS Patients with untreated advanced nonsquamous NSCLC without confirmed EGFR 19 deletion or L858R mutation received first-line therapy with carboplatin area under the curve 6, pemetrexed 500 mg/m 2 , and bevacizumab 15 mg/kg once every 3 weeks for 4 cycles. Patients without disease progression during the induction therapy were randomly assigned 1:1 for maintenance therapy with pemetrexed 500 mg/m 2 plus bevacizumab 15 mg/kg or bevacizumab 15 mg/kg once every 3 weeks until disease progression or unacceptable toxicity. The primary end point was overall survival (OS) after random assignment. RESULTS Between September 2010 and September 2015, 907 patients received induction therapy. Of those, 599 were randomly assigned: 298 received pemetrexed plus bevacizumab, and 301 received bevacizumab. The median OS was 23.3 v 19.6 months (hazard ratio [HR], 0.87; 95% CI, 0.73 to 1.05; 1-sided stratified log-rank P = .069). In the wild-type EGFR subset, the OS HR was 0.82 (95% CI, 0.68 to 0.99; 1-sided unstratified log-rank P = .020). The median progression-free survival (PFS) was 5.7 v 4.0 months (HR, 0.67; 95% CI, 0.57 to 0.79; 2-sided log-rank P &lt; .001). The safety data were consistent with previous reports of treatment regimens. CONCLUSION In terms of the primary end point of OS, no statistically significant benefit was observed; however, PFS in the total patient population and OS in patients with wild-type EGFR was prolonged with the addition of pemetrexed to bevacizumab maintenance therapy.
Near real-time intraoperative brain tumor diagnosis using stimulated Raman histology and deep neural networks
Authors: Todd C. Hollon, Balaji Pandian, Arjun R. Adapa, Esteban Urias, Akshay V. Save, Siri Sahib S. Khalsa, Daniel G. Eichberg, Randy S. D’Amico, Zia U. Farooq, Spencer Lewis, Petros D. Petridis, Tamara Marie, Ashish H. Shah, Hugh J. L. Garton, Cormac O. Maher, Jason A. Heth, Erin L. McKean, Stephen E. Sullivan, Shawn L. Hervey-Jumper, Parag G. Patil, B. Gregory Thompson, Oren Sagher, Guy M. McKhann, Ricardo J. Komotar, Michael E. Ivan, Matija Snuderl, Marc L. Otten, Timothy D. Johnson, Michael B. Sisti, Jeffrey N. Bruce, Karin M. Muraszko, Jay Trautman, Christian W. Freudiger, Peter Canoll, Honglak Lee, Sandra Camelo-Piragua, Daniel A. Orringer
Journal: Nature Medicine (2020)
HIF2-Induced Long Noncoding RNA RAB11B-AS1 Promotes Hypoxia-Mediated Angiogenesis and Breast Cancer Metastasis
Authors: Yanling Niu, Lei Bao, Yan Chen, Chenliang Wang, Maowu Luo, Bo Zhang, Mi Zhou, Jennifer E. Wang, Yisheng V. Fang, Ashwani Kumar, Chao Xing, Yingfei Wang, Weibo Luo
Journal: Cancer Research (2020)

Hypoxia induces a vast array of long noncoding RNAs (lncRNA) in breast cancer cells, but their biological functions remain largely unknown. Here, we identified a hitherto uncharacterized hypoxia-induced lncRNA RAB11B-AS1 in breast cancer cells. RAB11B-AS1 is a natural lncRNA upregulated in human breast cancer and its expression is induced by hypoxia-inducible factor 2 (HIF2), but not HIF1, in response to hypoxia. RAB11B-AS1 enhanced the expression of angiogenic factors including VEGFA and ANGPTL4 in hypoxic breast cancer cells by increasing recruitment of RNA polymerase II. In line with increased angiogenic factors, conditioned media from RAB11B-AS1-overexpressing breast cancer cells promoted tube formation of human umbilical vein endothelial cells in vitro. Gain- and loss-of-function studies revealed that RAB11B-AS1 increased breast cancer cell migration and invasion in vitro and promoted tumor angiogenesis and breast cancer distant metastasis without affecting primary tumor growth in mice. Taken together, these findings uncover a fundamental mechanism of hypoxia-induced tumor angiogenesis and breast cancer metastasis. SIGNIFICANCE: This study reveals the molecular mechanism by which the lncRNA RAB11B-AS1 regulates hypoxia-induced angiogenesis and breast cancer metastasis, and provides new insights into the functional interaction between a lncRNA and tumor microenvironment. GRAPHICAL ABSTRACT: http://cancerres.aacrjournals.org/content/canres/80/5/964/F1.large.jpg.