tbuckley/cabot-search huggingface dataset:
Understanding Conflicting Neuropathological Findings
Authors: Kurt A. Jellinger
Journal: JAMA Neurology (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 Neurology 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 Neurology journal
Abstract PR04: Cancer drug response networks built for comparative cancer pharmacogenomics identifies combination therapies for repositioning
Authors: Doug Brubaker, Svenson Elena, Kai Smith, Maya Monroe, Christopher Ryu, Mark R. Chance, Goutham Narla, Gurkan Bebek
Journal: Cancer Research (2015)

Abstract We present an integrative framework for classifying drug response: CAncer Drug Response nEtworks (CADREs). We built CADREs for drugs with differential sensitivity profiles in cancer cell lines by integrating baseline copy number, gene expression, and drug sensitivity data for the cell lines. The nodes in the network are drugs and the edges are weighted according to the number of shared copy number variations, differentially expressed genes, and dysregulated pathways present in sensitive cell lines at baseline. These baseline features were mapped into pathways to generate a Pathway CADRE, and were also integrated into a differential gene expression and copy number Feature CADRE. CADREs were built for breast, ovarian, and endometrial cancers individually and combined to assess shared and unique features of drug sensitivity. Analyzing CADRE clusters associated multiple gene features and pathways with sensitivity to frontline therapies used in combination in these cancers. We identified four clusters of breast cancer drugs whose effectiveness is driven by a shared core of pathways. Compounds that were used in combination in clinical trials tended to not share an edge or are completely disconnected in networks. Specifically, ten such drug pairs in our breast CADREs have been found to work in combination in breast cancer and an additional five have been used in combination in other cancers, representing opportunities for repositioning these combinations in breast cancer. Examining highly interconnected CADRE nodes gave us an understanding for compounds that might work best together. Citation Format: Doug Brubaker, Svenson Elena, Kai Smith, Maya Monroe, Christopher Ryu, Mark R. Chance, Goutham Narla, Gurkan Bebek. Cancer drug response networks built for comparative cancer pharmacogenomics identifies combination therapies for repositioning. [abstract]. In: Proceedings of the AACR Special Conference on Translation of the Cancer Genome; Feb 7-9, 2015; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2015;75(22 Suppl 1):Abstract nr PR04.
Mind, brain, and teaching: Some directions for future research
Authors: Elena Pasquinelli, Tiziana Zalla, Katarina Gvodzic, Cassandra Potier-Watkins, Manuela Piazza
Journal: Behavioral and Brain Sciences (2015)

Abstract In line with Kline's taxonomy, highlighting teaching as an array of behaviors with different cognitive underpinnings, we advocate the expansion of a specific line of research on mind, brain, and teaching. This research program is devoted to the understanding of the neurocognitive mechanisms and the evolutionary determinants of teaching skills, with the ultimate goal of helping teachers improve teaching quality.
Abstract 16605: Aortic Carboxypeptidase-Like Protein Promotes the Fibroblast to Myofibroblast Transition
Authors: Kathleen E Tumelty, Barbara D Smith, Matthew D Layne
Journal: Circulation (2012)

Introduction:  Organ fibrosis is characterized by the overgrowth, hardening, and scarring of tissues and impacts both cardiovascular and pulmonary systems. Fibrosis is exacerbated by extracellular matrix (ECM) remodeling and accumulation of active transforming growth factor β (TGFβ) which promote the production of smooth muscle alpha actin (SMA)-positive myofibroblasts and collagen secretion. Aortic Carboxypeptidase-Like Protein (ACLP) is an ECM protein secreted by vascular smooth muscle cells and myofibroblasts. ACLP knockout mice are protected from bleomycin-induced fibrosis and have decreased accumulation of myofibroblasts. However, the mechanism of ACLP action is currently unknown. Hypothesis: Because of ACLP’s expression in the fibrotic ECM and the accumulation of TGFβ in organ fibrosis, we hypothesize that ACLP stimulates the fibroblast to myofibroblast transition by promoting SMA and collagen expression, in part, by activating TGFβ signaling.   Methods:  We used gain of function and loss of function studies in primary mouse lung fibroblasts and cultured human lung fibroblasts with recombinant protein, co-culture, and siRNA-mediated knockdown.   Results  and   Conclusions:  As primary lung fibroblasts differentiate into myofibroblasts, ACLP protein expression precedes SMA and collagen protein expression. Recombinant ACLP (rACLP) induces SMA and collagen protein and gene expression in both primary mouse lung fibroblasts and cultured human lung fibroblasts. Knockdown of ACLP slows and reverts the fibroblast to myofibroblast transition. Treatment of fibroblasts with rACLP induces phosphorylation of Smad3 and Smad1, and both this phosphorylation and induction of SMA expression is dependent on TGFβ receptor kinase activity. In conclusion, these data suggest that ACLP stimulates the fibroblast to myofibroblast transition via the TGFβ receptors. This project has unveiled both novel signaling events that occur in early stages of disease progression and molecules that could serve as targets of drugs designed to slow the progression of organ fibrosis.
Pharmacokinetics, safety and efficacy of a full dose sofosbuvir-based regimen given daily in hemodialysis patients with chronic hepatitis C
Authors: Aude Desnoyer, Dan Pospai, Minh Patrick Lê, Anne Gervais, Alexandra Heurgué-Berlot, Achour Laradi, Stanislas Harent, Adriana Pinto, Dominique Salmon, Sophie Hillaire, Hélène Fontaine, David Zucman, Anne-Marie Simonpoli, Patrice Muret, Lucile Larrouy, Brigitte Bernard Chabert, Diane Descamps, Yazdan Yazdanpanah, Gilles Peytavin
Journal: Journal of Hepatology (2016)
P-309 PROSPECT-R: A PROSPECTive translational study investigating molecular predictors of resistance and response to Regorafenib (REG) monotherapy in RAS mutant (mt) metastatic colorectal cancer (CRC)
Authors: K. Khan, I. Chau, M. Gerlinger, N. Valeri, D.-M. Koh, N. Starling, D. Watkins, S. Rao, N. Tunariu, N. Fotiadis, R. Begum, C. Saffery, D. Cunningham
Journal: Annals of Oncology (2015)
Comparative Effects of Steroids on Skin Maintained in Organ Culture. I. Adrenal Steroids&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: R. W. Gillette, D. Goulian, Jr., H. Conway
Journal: JNCI Journal of the National Cancer Institute (1965)

Full-thickness, auricular skin from adult mice was maintained for 1 - to 4-week periods in vitro. The effects of either deoxycorticosterone acetate (DOCA), cortisone acetate (CA), or a combination of these steroids incorporated in the culture medium were studied. The ability of skin to function as an autograft after treatment with these compounds was compared. The gross and microscopic changes produced by the steroids were studied. Wet and dry weights were compared for control and treated cultures of skin maintained for different lengths of time. Gross and microscopic effects of several compounds related to either DOCA or CA were compared to those of the parent compounds. Skin treated with CA functioned as autografts after 3 to 4 weeks in vitro, while untreated skin lost its ability to function as a graft after 10 days to 2 weeks in vitro. DOCA maintained the structural integrity of skin better than CA and for longer periods in vitro, but the skin lost its ability to function as an autograft after 1 week in vitro. When a combination of DOCA and CA was used, the effects of DOCA predominated. This particular dichotomy of structural integrity and functional ability is discussed.
Hodgkin lymphoma post‐transplant lymphoproliferative disorder: A comparative analysis of clinical characteristics, prognosis, and survival
Authors: Aaron S. Rosenberg, Andreas K. Klein, Robin Ruthazer, Andrew M. Evens
Journal: American Journal of Hematology (2016)

Hodgkin lymphoma post-transplant lymphoproliferative disorder (HL-PTLD) is an uncommon PTLD with unclear prognosis and differences between HL-PTLD and immunocompetent HL are not well defined. Patient characteristics were compared among 192 patients with HL-PTLD from the Scientific Registry of Transplant Recipients and 13,847 HL patients in SEER (HL-SEER). Overall survival (OS) and disease-specific survival (DSS) were compared after exact matching. Additionally, multivariable analyses were used to identify prognostic markers of survival and associations between treatment and survival. Median time from transplant to HL-PTLD diagnosis was 88 months. When compared with HL-SEER, patients with HL-PTLD were older (median age, 52 vs. 36 years, P = 0.001), more likely male (73% vs. 54%, P < 0.001), Caucasian (81% vs. 70%, P = 0.02), and had extranodal disease (42% vs. 3%, P < 0.001). Five-year OS for patients with HL-PTLD was 57% versus 80% for HL-SEER (P < 0.001); DSS was also inferior (P < 0.001). For patients with HL-PTLD, the use of any chemotherapy was associated with decreased hazard of death (HR = 0.36, P < 0.001). Furthermore, patients who received no chemotherapy or nontraditional HL regimens had increased hazard of death (aHR = 2.94, P = 0.001 and 2.01, P = 0.04) versus HL-specific chemotherapy regimens. In multivariable analysis, advanced age and elevated creatinine were associated with inferior OS (aHR = 1.26/decade P < 0.001 and 1.64/0.1 mg/dL increase P = 0.02). A prognostic score based on the number of these adverse factors (0, 1, 2) was associated with 10-year OS rates of 79%, 53%, and 11%, respectively (P < 0.001). Altogether, HL-PTLD patients have inferior survival when compared with HL-SEER. Furthermore, treatment with HL-specific chemotherapy was associated with improved OS, whereas age and creatinine identified patients with markedly divergent survival. Am. J. Hematol. 91:560-565, 2016. © 2016 Wiley Periodicals, Inc.
Cardiac surgeons at Birmingham hospital must submit weekly mortality data after higher than expected deaths
Authors: Nigel Hawkes
Journal: BMJ (2016)

Queen Elizabeth Hospital Birmingham has been told to submit weekly returns on its cardiac surgery mortality after more patients died there than would have been expected.

Data published on the website of the Society for Cardiothoracic Surgery show that in the period 2011 to 2014 a total of 1713 heart operations were conducted at the hospital, with a survival rate of 95.45%, after adjustment for the difficulty of each operation. This is significantly worse than the average rate for all units in England, by …
The Future of US Health Care Policy
Authors: Howard Bauchner, Phil B. Fontanarosa
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 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
Does chemotherapy fulfill its expectations in cancer treatment?
Authors: G. Bonadonna
Journal: Annals of Oncology (1990)

In 1949, Cornelius P. Rhoads, director of the Memorial Sloan-Kettering Cancer Center, made his famous report on the practical value of nitrogen mustard before the Committee on Growth of the National Research Council, a quasi-governmental agency which had accepted the responsibility for the clinical trial of this drug at the end of the war. Doctor Rhoads assigned to David A. Karnofsky the job of receiving reports from individual physicians and analyzing the results in each type of cancer. The conclusions, based on 2500 case reports, indicated that nitrogen mustard did not cure any form of cancer, but it was temporarily useful in chronic leukemias, Hodgkin's disease, malignant lymphomas, and lung cancer. The most valuable outcome of this report was the beginning of massive and direct attack on cancer in humans. Since that time, in fact, there was enthusiasm and interest in studying cancer; physicians have been educated, interested and motivated to treat the disease; investigators became engaged in the search of new growth-inhibiting compounds and research clinicians in the formulation of new treatment strategies. The result was a progressively growing list of tumors responding to drug treatment with increased complete remission, prolonged disease free and even total survival rates particularly in the early stages of given malignancies; patient care, the most important achievement in cancer medicine, has been drastically improved. Clinical chemotherapy of cancer has a long history of controversies. Though never advocated as panacea, this form of treatment has continuously fluctuated between excessive optimism and detraction. Recently, harsh criticism has pointed to the magnitude of the overall results achieved in terms of decreased national mortality statistics for the various malignancies. An impatient group of clinicians, biostatisticians and epidemiologists began to question whether medical oncology has reached a plateau in its control of cancer or whether the entire treatment strategy for the control of cancer is wrong. Since sweeping generalization cannot be supported for the results of treatment in each tumor subset require separate analysis, let us review the biological principles of cancer treatment, the main strategies utilized, and the results achieved in the major groups of malignancies. The paper will also outline the contributions of chemotherapy to the medical sciences and to the care of the patients with cancer during the last 40 years.
A dominant gain-of-function mutation in universal tyrosine kinase <i>SRC</i> causes thrombocytopenia, myelofibrosis, bleeding, and bone pathologies
Authors: Ernest Turro, Daniel Greene, Anouck Wijgaerts, Chantal Thys, Claire Lentaigne, Tadbir K. Bariana, Sarah K. Westbury, Anne M. Kelly, Dominik Selleslag, Jonathan C. Stephens, Sofia Papadia, Ilenia Simeoni, Christopher J. Penkett, Sofie Ashford, Antony Attwood, Steve Austin, Tamam Bakchoul, Peter Collins, Sri V. V. Deevi, Rémi Favier, Myrto Kostadima, Michele P. Lambert, Mary Mathias, Carolyn M. Millar, Kathelijne Peerlinck, David J. Perry, Sol Schulman, Deborah Whitehorn, Christine Wittevrongel, Marc De Maeyer, Augusto Rendon, Keith Gomez, Wendy N. Erber, Andrew D. Mumford, Paquita Nurden, Kathleen Stirrups, John R. Bradley, F. Lucy Raymond, Michael A. Laffan, Chris Van Geet, Sylvia Richardson, Kathleen Freson, Willem H. Ouwehand
Journal: Science Translational Medicine (2016)

E527K hyperactive SRC results in megakaryocytes with increased podosome formation, thrombocytopenia, myelofibrosis, bleeding, and bone pathologies.
Accuracy of diagnostic testing in primary ciliary dyskinesia: are we there yet?
Authors: Eric G. Haarman, Miriam Schmidts
Journal: European Respiratory Journal (2016)

Although primary ciliary dyskinesia (PCD) is a rare disease, symptoms like recurrent upper and lower respiratory tract infections are extremely common, especially in the paediatric population. Therefore, an important but complicated task for clinicians is to identify patients suffering from this autosomal-recessive condition among the large cohort of individuals with recurrent respiratory symptoms. However, diagnosing PCD is difficult, as there is no single gold standard and it relies on a combination of complex techniques, only available in few specialised centres worldwide [1–4]. There are no evidence-based guidelines and consequently, diagnostic algorithms vary among centres depending on local expertise. Diagnostic testing in PCD: an appraisal of current and future diagnostic techniques <http://ow.ly/VBZKr>
Adjuvant Chemotherapy for Adult Soft Tissue Sarcoma: Is There a Standard of Care?
Authors: Vivien H.C. Bramwell
Journal: Journal of Clinical Oncology (2001)

Article Tools EDITORIAL Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2001.19.5.1235 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 11230463 Adjuvant Chemotherapy for Adult Soft Tissue Sarcoma: Is There a Standard of Care? Vivien H.C. BramwellxVivien H.C. BramwellSearch for articles by this author Show More University of Western Ontario, London Regional Cancer Centre, London, Ontario, Canada https://doi.org/10.1200/JCO.2001.19.5.1235 First Page Full Text PDF Figures and Tables © 2001 by American Society of Clinical Oncology
David Oliver: The real world for NHS doctors
Authors: David Oliver
Journal: BMJ (2016)

in geriatrics and acute general medicine Berkshire Doctors' working lives, terms, and conditions aren't generally newsworthy.Most go through their careers miles from the media spotlight or industrial relations.Yet in England, recent stand-offs with the government over proposed new contracts have brought unaccustomed attention.We've seen much public support, especially for the junior doctors' cause-but, among the reportage and the comments below articles, many have called for "these doctors" or "these NHS workers" to join "the real world."This makes me wonder: in which "real world" don't we live?We work with people at their most vulnerable, who are ill, injured, or dying.We have many difficult conversations, including breaking bad news and trying to support and counsel patients' families.We meet people from every social stratum, including those facing deprivation, addiction, homelessness, or serious mental health problems.Most professions don't do this.So it can't be that.
Detection of Occult Micrometastases in Patients With Clinical Stage I Non–Small-Cell Lung Cancer: A Prospective Analysis of Mature Results of CALGB 9761 (Alliance)
Authors: Linda W. Martin, Jonathan D’Cunha, Xiaofei Wang, Debra Herzan, Lin Gu, Naif Abraham, Todd L. Demmy, Frank C. Detterbeck, Shawn S. Groth, David H. Harpole, Mark J. Krasna, Kemp Kernstine, Leslie J. Kohman, G. Alexander Patterson, David J. Sugarbaker, Robin T. Vollmer, Michael A. Maddaus, Robert A. Kratzke
Journal: Journal of Clinical Oncology (2016)

Outcomes after resection of stage I non-small-cell lung cancer (NSCLC) are variable, potentially due to undetected occult micrometastases (OM). Cancer and Leukemia Group B 9761 was a prospectively designed study aimed at determining the prognostic significance of OM.Between 1997 and 2002, 502 patients with suspected clinical stage I (T1-2N0M0) NSCLC were prospectively enrolled at 11 institutions. Primary tumor and lymph nodes (LNs) were collected and sent to a central site for molecular analysis. Both were assayed for OM using immunohistochemistry (IHC) for cytokeratin (AE1/AE3) and real-time reverse transcriptase polymerase chain reaction (RT-PCR) for carcinoembryonic antigen.Four hundred eighty-nine of the 502 enrolled patients underwent complete surgical staging. Three hundred four patients (61%) had pathologic stage I NSCLC (T1, 58%; T2, 42%) and were included in the final analysis. Fifty-six percent had adenocarcinomas, 34% had squamous cell carcinomas, and 10% had another histology. LNs from 298 patients were analyzed by IHC; 41 (14%) were IHC-positive (42% in N1 position, 58% in N2 position). Neither overall survival (OS) nor disease-free survival was associated with IHC positivity; however, patients who had IHC-positive N2 LNs had statistically significantly worse survival rates (hazard ratio, 2.04, P = .017). LNs from 256 patients were analyzed by RT-PCR; 176 (69%) were PCR-positive (52% in N1 position, 48% in N2 position). Neither OS nor disease-free survival was associated with PCR positivity.NSCLC tumor markers can be detected in histologically negative LNs by AE1/AE3 IHC and carcinoembryonic antigen RT-PCR. In this prospective, multi-institutional trial, the presence of OM by IHC staining in N2 LNs of patients with NSCLC correlated with decreased OS. The clinical significance of this warrants further investigation.