tbuckley/cabot-search huggingface dataset:
Quality of Life (QOL) among Renal Cell Carcinoma (RCC) Patients in A Randomized Double Blind Cross-Over Patient Preference Study of Pazopanib (P) Versus Sunitinib (S)
Authors: D. Cella, K. Kaiser, J. Beaumont, J. Diaz, L. McCann, F. Mehmud, S. Lata, P. Bono, C. Porta, B. Escudier
Journal: Annals of Oncology (2012)
Real-world fusion landscape in advanced Chinese pancreatic cancer using next generation sequecing: A multicenter study
Authors: Y. Shen, S. Fang, X. Cai, Y. Fang, R. Lin, Y. Zhang, J. Li, X. Liang, L. Wang, L. Lin, L. Zhang, H. Feng, S. Lan, X. Cai, C. Xu, W. Wang, M. Fang, J. Zhang
Journal: Annals of Oncology (2019)
Abstract NT-099: NOVEL ANTIBODY DRUG CONJUGATE (ADC) AND COMPANION DIAGNOSTICS AGAINST CD248+ CANCER
Authors: Yi Guo, Yujue Wang, Xiaohui Peng, George Coukos, Chunsheng Li
Journal: Clinical Cancer Research (2019)

Abstract Antibodies recognizing specific tumor targets can be used to deliver therapeutic payloads with high degree of specificity. The simultaneous use of antibody against same target for imaging and for therapy, an approach named “theranostics”, offers unique opportunities for precision medicine and rapidly assessing therapeutic response at molecular level. The first example of such antibody-based theranotics is Herceptin in HER2-positive breast cancer: Herceptin is used as companion diagnostic imaging tool as well as the targeted therapy. To develop effective anti-tumor therapeutics, one needs a robust biomarker, AND a good antibody that can specifically bind to the target. We and others have found one for EOC: CD248/TEM1. It is present at high level in tumor and its microenvironment in EOC and almost absent in normal organs. Importantly, CD248 is expressed by &amp;gt;90% EOC patients on the tumor or tumor vasculature, and its high expression correlates with poor survival. This means that if we can target it, we may destroy tumor but leave normal tissues intact. We also have developed robust antibody against CD248 (78Fc panel, US Patent 61/639,325). We showed that our patented antibodies can find the biomarker and upon binding deliver a payload, for PET imaging, near-infrared optical imaging or therapeutic, to CD248-expressing cells. Different toxin payload, such as auristatin and MD117, were conjugated to the antibody, and such ADCs were tested in vitro and in vivo in mice models. Surprisingly, we found such immunotherapies only directly kill, but also induce significant lymphocyte infiltration into tumors. In addition, tumor rejection was observed upon re-challenging in preclinical models. Such immune activation we observed could in turn sensitizing previously “cold tumor” EOC, to checkpoint inhibitors such as PD-1/CDLA4. The long term goal is to develop companion diagnostics and antibody-immunotherapy: screening methods (such as antibody-based immunoPET and serum ELISA) to identify patients with EOC that can be treated with anti-CD248 drugs; and develop drugs that are linked to the antibody (such as antibody-drug conjugate) so it can be delivered to the tumor directly to kill. In addition, combined with PD-1 blockade, ADC therapies may exert antitumor immune response to sensitize “cold” tumors that previously resistant to PD-1 therapy. Citation Format: Yi Guo, Yujue Wang, Xiaohui Peng, George Coukos, Chunsheng Li. NOVEL ANTIBODY DRUG CONJUGATE (ADC) AND COMPANION DIAGNOSTICS AGAINST CD248+ CANCER [abstract]. In: Proceedings of the 12th Biennial Ovarian Cancer Research Symposium; Sep 13-15, 2018; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2019;25(22 Suppl):Abstract nr NT-099.
Randomized Phase II Trial of S-1 versus S-1 Plus Oxaliplatin (SOX) in Patients with Gemcitabine Refractory Pancreatic Cancer
Authors: T. Okusaka, S. Ohkawa, H. Isayama, A. Fukutomi, K. Yamaguchi, M. Ikeda, A. Funakoshi, M. Nagase, S. Nakamori, Y. Hamamoto
Journal: Annals of Oncology (2012)
Epidural Catheter Use and Further Issues in Patients With Atrial Fibrillation Receiving a Direct Oral Anticoagulant
Authors: Loredana Tomassini, Patrizia Della Valle, Armando D’Angelo
Journal: JAMA Internal Medicine (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 Internal Medicine 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 Internal Medicine journal
Airway mucus accumulation in COPD: the cholinergic paradox!
Authors: Pierre-Régis Burgel
Journal: European Respiratory Journal (2020)

Mucus accumulation, related to excess mucus production and secretion in proximal and distal airways, is an established characteristic in the airways of patients with COPD. Chronic bronchitis, a consequence of cigarette smoking that can be found in smokers with or without COPD, is a disabling symptom and has been associated with increased rates of exacerbations and hospitalisations in patients with COPD [1] and in subjects with normal spirometry [2]. Chronic bronchitis is usually ascribed to inflammation and airway mucus hypersecretion by airway epithelium and submucosal glands in proximal airways [3]. Cholinergic stimulation increases mucociliary clearance but long-acting anti-muscarinic treatment remains one of the major therapies for patients with COPD <http://bit.ly/2RlXAwl>
Thyroid disease assessment and management: summary of NICE guidance
Authors: Melina Vasileiou, James Gilbert, Sarah Fishburn, Kristien Boelaert
Journal: BMJ (2020)

### What you need to know

Thyroid disease, comprising thyroid dysfunction and enlargement, is common and often identified in primary care. Conditions causing thyroid dysfunction can be broadly divided into those that result in thyroid gland underactivity (overt and subclinical hypothyroidism) or overactivity (thyrotoxicosis). Hypothyroidism is usually managed by general practitioners. This article summarises some of the most recent recommendations from the NICE guideline “Thyroid disease: assessment and management.”1

NICE recommendations are based on systematic reviews of best available clinical evidence and explicit consideration of cost effectiveness. When minimal evidence is available, recommendations are based on the Guideline Committee’s experience and opinion of what constitutes good practice. The levels of evidence supporting the recommendations is given in italics in square brackets.

The type of evidence underpinning the recommendations in the guideline varied. Most recommendations were based on randomised controlled trials (RCTs) and Guideline Committee consensus. Conducting RCTs can be challenging in some aspects of thyroid disease management, with ethical and practical challenges of …
The Origin of Our Modern Concept of Depression—The History of Melancholia From 1780-1880
Authors: Kenneth S. Kendler
Journal: JAMA Psychiatry (2020)

The modern concept of depression arose from earlier diagnostic formulations of melancholia over the hundred years from the 1780s to the 1880s. In this historical sketch, this evolution is traced from the writings of 12 authors outlining the central roles played by the concepts of faculty psychology and understandability. Five of the authors, writing from 1780 through the 1830s, including Cullen, Pinel, and Esquirol, defined melancholia as a disorder of intellect or judgment, a "partial insanity" often, but not always, associated with sadness. Two texts from the 1850s by Guislain, and Bucknill and Tuke were at the transition between paradigms. Both emphasized a neglected disorder-melancholia without delusions-arguing that it reflected a primary disorder of mood-not of intellect. In the final phase in the 1860s to 1880s, 5 authors (Griesinger, Sankey, Maudsley, Krafft-Ebing, and Kraepelin) all confronted the problem of the cause of delusional melancholia. Each author concluded that melancholia was a primary mood disorder and argued that the delusions emerged understandably from the abnormal mood. In this 100-year period, the explanation of delusional melancholia in faculty psychology terms reversed itself from an intellect to mood to a mood to intellect model. The great nosologists of the 19th century are often seen as creating our psychiatric disorders using a simple inductive process, clustering the symptoms, signs, and later the course of the patients. This history suggests 2 complexities to this narrative. First, in addition to bottom-up clinical studies, these nosologists were working top-down from theories of faculty psychology proposed by 18th century philosophers. Second, for patient groups experiencing disorders of multiple faculties, the nosologists used judgments about understandability to assign primary causal roles. This historical model suggests that the pathway from patient observation to the nosologic categories-the conceptual birth of our diagnostic categories-has been more complex than is often realized.
Sharing data–taming the beast: barriers to meta-analyses of individual patient data (IPD) and solutions
Authors: Marienke van Middelkoop, Stefan Lohmander, Sita M A Bierma-Zeinstra
Journal: British Journal of Sports Medicine (2020)

Systematic reviews aim to collate all empirical evidence that fits prespecified eligibility criteria to answer a specific research question.Some systematic reviews undertake a meta-analysis to statistically combine study results and provide a more precise estimate of treatment effects.These meta-analyses are commonly based on aggregate data, extracted from publications or obtained from the original authors of these papers 1 but aggregating data limits the options for in depth analysis.
Phase I trial of donor-derived modified immune cell infusion in kidney transplantation
Authors: Christian Morath, Anita Schmitt, Christian Kleist, Volker Daniel, Gerhard Opelz, Caner Süsal, Eman Ibrahim, Florian Kälble, Claudius Speer, Christian Nusshag, Luiza Pego da Silva, Claudia Sommerer, Lei Wang, Ming Ni, Angela Hückelhoven-Krauss, David Czock, Uta Merle, Arianeb Mehrabi, Anja Sander, Matthes Hackbusch, Christoph Eckert, Rüdiger Waldherr, Paul Schnitzler, Carsten Müller-Tidow, Jörg D. Hoheisel, Shakhawan A. Mustafa, Mohamed S.S. Alhamdani, Andrea S. Bauer, Jochen Reiser, Martin Zeier, Michael Schmitt, Matthias Schaier, Peter Terness
Journal: Journal of Clinical Investigation (2020)

BACKGROUNDPreclinical experiments have shown that donor blood cells, modified in vitro by an alkylating agent (modified immune cells [MICs]), induced long-term specific immunosuppression against the allogeneic donor.METHODSIn this phase I trial, patients received either 1.5 × 106 MICs per kg BW on day -2 (n = 3, group A), or 1.5 × 108 MICs per kg BW on day -2 (n = 3, group B) or day -7 (n = 4, group C) before living donor kidney transplantation in addition to post-transplantation immunosuppression. The primary outcome measure was the frequency of adverse events (AEs) until day 30 (study phase) with follow-up out to day 360.RESULTSMIC infusions were extremely well tolerated. During the study phase, 10 treated patients experienced a total of 69 AEs that were unlikely to be related or not related to MIC infusion. No donor-specific human leukocyte antigen Abs or rejection episodes were noted, even though the patients received up to 1.3 × 1010 donor mononuclear cells before transplantation. Group C patients with low immunosuppression during follow-up showed no in vitro reactivity against stimulatory donor blood cells on day 360, whereas reactivity against third-party cells was still preserved. Frequencies of CD19+CD24hiCD38hi transitional B lymphocytes (Bregs) increased from a median of 6% before MIC infusion to 20% on day 180, which was 19- and 68-fold higher, respectively, than in 2 independent cohorts of transplanted controls. The majority of Bregs produced the immunosuppressive cytokine IL-10. MIC-treated patients showed the Immune Tolerance Network operational tolerance signature.CONCLUSIONMIC administration was safe and could be a future tool for the targeted induction of tolerogenic Bregs.TRIAL REGISTRATIONEudraCT number: 2014-002086-30; ClinicalTrials.gov identifier: NCT02560220.FUNDINGFederal Ministry for Economic Affairs and Technology, Berlin, Germany, and TolerogenixX GmbH, Heidelberg, Germany.
Dapagliflozin Cut Risk of Worsening Heart Failure
Authors: Anita Slomski
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 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
Validity and Reliability of the Pediatric Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events
Authors: Bryce B Reeve, Molly McFatrich, Jennifer W Mack, Scott H Maurer, Shana S Jacobs, David R Freyer, Janice S Withycombe, Justin N Baker, Sharon M Castellino, Li Lin, Nicole R Lucas, Pamela S Hinds
Journal: JNCI Journal of the National Cancer Institute (2020)

Patient-reported outcome (PRO) measurements linked to Common Terminology Criteria for Adverse Events (CTCAE) grading may improve symptom adverse event (AE) reporting in pediatric oncology trials. We evaluated construct validity, responsiveness, and test-retest reliability of the Ped-PRO-CTCAE measurement system for children and adolescents undergoing cancer care.A total of 482 children and adolescents (7-18 years, 41.5% not non-Hispanic white) newly diagnosed with cancer and their caregivers participated from nine pediatric oncology hospitals. Surveys were completed at 72 hours preceding treatment initiation (T1) and at follow-up (T2) approximately 7-17 days later for chemotherapy, and 4+ weeks for radiation. Psychometric analyses examined the relationship of Ped-PRO-CTCAE items (assessing 62 symptom AEs) with Patient-Reported Outcomes Measurement Information System, Memorial Symptom Assessment Scale, Lansky Play-Performance Scale, and medication use. A separate test-retest study included 46 children.Ped-PRO-CTCAE and Memorial Symptom Assessment Scale were strongly correlated across age groups at T2: 7-12 years (r = 0.62-0.80), 13-15 years (r = 0.44-0.94), and 16-18 years (r = 0.65-0.98); and over time. The Ped-PRO-CTCAE was strongly correlated with Patient-Reported Outcomes Measurement Information System Pediatric measures at T2; for example, pain interference (r = 0.70, 95% confidence interval [CI] = 0.64 to 0.76), fatigue severity (r = 0.63, 95% CI = 0.56 to 0.69), and depression severity (r = 0.76, 95% CI = 0.71 to 0.81). Ped-PRO-CTCAE items differentiated children by Lansky Play-Performance Scale and by medication use. Test-retest agreement ranged from 54.3% to 93.5%.This longitudinal study provided evidence for the construct validity and reliability of the core Ped-PRO-CTCAE symptom AE items relative to several established measures. Additional responsiveness data with clinical anchors are recommended. Incorporation of Ped-PRO-CTCAE in trials may lead to a better understanding of the cancer treatment experience.
Iron increases busulfan toxicity in vivo and in vitro
Authors: Jerome Bouligand, Nicolas Simmonard, Fabienne Munier, Paule Opolon, Angelo Paci, Gilles Vassal
Journal: Cancer Research (2007)

1565  Busulfan is an alkylating agent widely used in combination high-dose chemotherapy regimens followed by allogeneic or autologous haematopoietic stem cell transplantation (HSCT). The effect of iron on busulfan toxicity was investigated since we proposed that iron-generated pro-oxidant state may explain busulfan toxicity during HSCT.  Toxicology and metabolism of busulfan (16.5 mg/kg bid over four days) combined with melphalan (20 mg/kg) and syngeneic bone marrow transplantation (BMT) were investigated in iron overloaded mice (C57Bl6 male). Mice were supplemented during one month with a special diet with Renutryl® in which were added high concentrations of FeSO4 (almost 500 fold the content in the control diet). Iron overload was evidenced by histology in the liver of supplemented mice compared to control animals. Liver accumulation was associated with a significant increase in plasma concentrations from 19 ± 4 µM to 39 ± 4 µM. No difference was observed in busulfan plasma clearance in between control animals and supplemented animals. However in both cases, a significant induction of clearance through the glutathione pathway during repeated injections was observed. In spite of equivalent busulfan exposure, we observed a dramatic increase of the toxicity after a combined treatment with busulfan and melphalan in iron supplemented mice with a median survival of 2 days after BMT. We have shown previously that busulfan metabolism through the glutathione pathway induces an increase of cysteine liver content in order to sustain glutathione levels. Consequently iron may be reduced from the ferric to the ferrous form. This latter is known to be responsible of the pro-oxidant state through the Fenton reaction.  This hypothesis was investigated in vitro. Prior cell cycle analyses have shown the time-dependent toxicity of busulfan. These investigations allowed to define optimal conditions to investigate busulfan toxicity in vitro against two cell lines; IGR-N91, a cell line derived from a neuroblastoma and HepG2, a cell line derived from an hepatocarcinoma. Busulfan was combined with iron and cysteine and the cytotoxicity was investigated after one week of treatment with the MTT assay. In vitro experiments have shown that iron enhanced significantly the cytotoxicity of busulfan. This enhancement of busulfan cytoxicity was maximal when iron (1 mM) was combined with cysteine (2 mM) to favour the pro-oxidant ferrous state. In these conditions, the CI50 of busulfan decreased from 15.5 ± 4.2 µM to 4.8 ± 1.1 µM in IGR-N91 and from 21.7 ± 7.2 µM to 13.0 ± 0.9 µM in Hep-G2.  In conclusion, iron increases busulfan toxicity. Mechanisms need to be elucidated, especially through the investigation of the metabolism of busulfan by the glutathione/glutathione S-transferase pathway.
The Canary in the Coal Mine: Biomaterial Implants to Monitor Cancer Recurrence
Authors: Matthew T. Wolf, Jennifer H. Elisseeff
Journal: Cancer Research (2020)

Abstract Synthetic biomaterials implanted in the body induce a foreign body reaction characterized by chronic inflammation and fibrosis. In this issue of Cancer Research, Oakes and colleagues used biomaterial implants and their associated immunologic activity to develop a “metastasis sensor” for detection of tumor burden at distal sites. A scoring system was developed from computational analysis of gene expression patterns from implant biopsies that could predict the presence of tumor. This unexpected use of biomaterials for early detection of cancer provides a more accurate systemic sampling compared with blood or liquid biopsies and alleviates the need for inefficient imaging and biopsy sampling from potential metastatic target tissues. See related article by Oakes et al., p. 602
Abstract 12175: Higher Anxiety and More Depressive Symptoms Are Associated With Low Vitamin C Intake in Patients With Heart Failure
Authors: Jia Rong Wu, Terry A Lennie, Debra K Moser
Journal: Circulation (2018)

Background: Psychological distress (anxiety and depressive symptoms) is associated with oxidative stress. Patients with heart failure (HF), who already have high oxidative stress, may be particular...
Tumor pH-responsive metastable-phase manganese sulfide nanotheranostics for traceable hydrogen sulfide gas therapy primed chemodynamic therapy
Authors: Ting He, Xialing Qin, Chao Jiang, Dawei Jiang, Shan Lei, Jing Lin, Wei-Guo Zhu, Junle Qu, Peng Huang
Journal: Theranostics (2020)

Manganese-based nanomaterials have piqued great interest in cancer nanotheranostics, owing to their excellent physicochemical properties.Here we report a facile wet-chemical synthesis of size-controllable, biodegradable, and metastable γ-phase manganese sulfide nanotheranostics, which is employed for tumor pH-responsive traceable gas therapy primed chemodynamic therapy (CDT), using bovine serum albumin (BSA) as a biological template (The final product was denoted as MnS@BSA).The as-prepared MnS@BSA can be degraded in response to the mildly acidic tumor microenvironment, releasing hydrogen sulfide (H 2 S) for gas therapy and manganese ions for magnetic resonance imaging (MRI) and CDT.In vitro experiments validated the pH-responsiveness of MnS@BSA at pH 6.8 and both H 2 S gas and •OH radicals were detected during its degradation.In vivo experiments showed efficiently tumor turn-on T 1 -weighted MRI, significantly suppressed tumor growth and greatly prolonged survival of tumor-bearing mice following intravenous administration of MnS@BSA.Our findings indicated that MnS@BSA nanotheranostics hold great potential for traceable H 2 S gas therapy primed CDT of cancer.