tbuckley/cabot-search huggingface dataset:
GENO-27GENOMIC CHARACTERIZATION OF PRIMARY CENTRAL NERVOUS SYSTEM LYMPHOMA REVEALS PREDOMINANT NONSYNONYMOUS SOMATIC MUTATIONS OF MYD88 AND PIM1 GENES
Authors: Motoo Nagane, Kazutaka Fukumura, Toshihide Ueno, Jeunghun Lee, Yukiko Shishido-Hara, Kazuhiko Mishima, Koichi Ichimura, Akitake Mukasa, Yoshitaka Narita, Hiroyuki Aburatani, Ryo Nishikawa, Hiroyuki Mano
Journal: Neuro-Oncology (2015)

Primary central nervous system lymphoma (PCNSL) is a rare malignancy confined to CNS. Despite low tendency of systemic dissemination, its prognosis is poor with median overall survival of 4 years when treated with standard of care high-dose methotrexate-based chemoradiotherapy. Despite majority of PCNSL is diffuse large B-cell lymphoma (DLBCL), its response to therapy and biological behavior differ from the systemic disease, necessitating detailed investigation of its pathogenesis and genetic alterations. Here we performed whole-exome sequencing (WES) on 41 PCNSL and paired normal specimens as well as RNA sequencing. Seven cases were classified as germinal center B-cell-like (GCB) subtype (17%), while 34 cases were non-GCB. Progression-free survival was significantly longer in cases with GCB subtype as in systemic DLBCL (p = 0.027). WES yielded sequencing data with a mean coverage of 158Χ with 98% of the targeted bases covered by ≥20 independent reads. We identified a total of 17,385 somatic mutations, of which 62% were nonsynonymous single nucleotide variations. The predominant nucleotide substitution was a C > T transition (57.8%), especially in the context of the sequence GCG. WES revealed a substantial extent of aberrant somatic hypermutation (aSHM) with a high frequency of nonsynonymous somatic mutations especially in PIM1 (90.2%) and BTG2 (65.9%). Genes mutated other than aSHM include MYD88 (85.4%), most of which being L265P activating mutation. These mutations were not associated with GCB/non-GCB subtypes. Notably, mutations in a number of genes related to the NF-κB signaling pathway were also prominent. Copy number aberration analysis identified gains in chromosomes 1q, 7, 12, and 18q, and a loss of 6q. These results suggest that MYD88 and PIM1 mutations may play an important role in PCNSL development regardless of GCB subtypes, and NF-κB pathway could be the therapeutic targets of this intractable disease.
Abstract IA05: Clinical genomics alters care, informs new science
Authors: Barry S. Taylor
Journal: Clinical Cancer Research (2016)

Abstract Broad-based prospective sequencing has begun to inform the care of individual cancer patients. Such genomically driven cancer medicine is facilitating the use of mechanism-based therapeutic approaches in patients. In addition to the value of such data to inform the treatment of individual patients under active clinical care, over time these accrue as unprecedented datasets of integrated genomic, clinical, and treatment response data that can inform translational cancer research. Here, we present preliminary results of our efforts to combine both large-scale retrospective and prospective sequencing data in cancer to drive translational cancer biology. We will report on our efforts to develop a computational oncology framework to mine these data not only for new treatment hypotheses that can be tested clinically and the preliminary results from those studies, but also how this is driving new approaches to understand so-called long tail mutations both biologically and clinically. These efforts lie at the interface of retrospective and prospective studies to inform precision oncology through new tools that move beyond enumerating individual genetic vulnerabilities toward interpreting their biological and clinical interpretation for the benefit of patients. Citation Format: Barry S. Taylor. Clinical genomics alters care, informs new science. [abstract]. In: Proceedings of the AACR Precision Medicine Series: Integrating Clinical Genomics and Cancer Therapy; Jun 13-16, 2015; Salt Lake City, UT. Philadelphia (PA): AACR; Clin Cancer Res 2016;22(1_Suppl):Abstract nr IA05.
ERCP using a Special Catheter with External Steering
Authors: M. Staritz, U. Baas, K. Ewe, K.-H. Meyer zum Büschenfelde
Journal: Endoscopy (1985)

ERCP is the most sensitive procedure for opacification of the bile and pancreatic ducts. The procedure fails, however, in up to 60 % of Billroth II resected patients, and in 5 % of non-gastrectomized patients, often owing to problems of papillary cannulation with the conventional ERC-catheter, or insufficient control in the bile duct. Therefore, we attempted to perform ERCP with a catheter provided with external steering, which can be introduced through the channel of any commercially available endoscope. This catheter permitted successful ERCP in 11 patients in whom conventional ERCP technique had failed. The endoscopic procedure with the catheter described was simple and reduced papillary cannulation problems in patients with juxtapapillary diverticulum and in those with Billroth II resection, and it permitted selective opacification of intrahepatic bile ducts or the cystic duct.
Comparison of Denosumab Vs Zoledronic Acid for Treatment of Bone Disease in Adults with Newly Diagnosed Multiple Myeloma: a Randomized, Double-Blind, Multinational Phase 3 Trial
Authors: E. Terpos, N. Raje, B.G. Durie, R. Garcia-Sanz, K. Shimizu, W. Willenbacher, L. Zhu, A. Braun, R. Jain, A. Palumbo
Journal: Annals of Oncology (2014)
Standards affecting mental health care: a review and commentary
Authors: S H Nelson
Journal: American Journal of Psychiatry (1979)

The author describes the increasing focus on regulation and the standards applied to the field of mental health. He discusses four distinct but overlapping types of standards: 1) clinical, 2) practitioner, 3) program and facility, and 4) payment. He emphasizes the increasing influence of legislation and judicial decisions and points out several trends in standard setting affecting mental health care. Psychiatrists and other mental health practitioners are called on to take a larger role in shaping these standards to ensure that the quality of patient care is not compromised.
Psychoanalytic concepts in psychiatric training
Authors: H Pardes
Journal: American Journal of Psychiatry (1980)

The author describes, categorizes, and appraises psychiatric training programs on the basis of how each handles psychoanalytic concepts. He suggests rationales for including a proper balance of psychoanalytic conceptualizations in each type of program. Some emphasis complementing a balanced curriculum is recommended. He also notes that the psychiatrist is both a physician and a mental health professional who looks at the biologic, psychological, and social aspects of behavior; the synthesis of these several perspectives should be conveyed effectively and without bias to all students entering psychiatry.
Interferon-driven alterations of the host’s amino acid metabolism in the pathogenesis of typhoid fever
Authors: Christoph J. Blohmke, Thomas C. Darton, Claire Jones, Nicolas M. Suarez, Claire S. Waddington, Brian Angus, Liqing Zhou, Jennifer Hill, Simon Clare, Leanne Kane, Subhankar Mukhopadhyay, Fernanda Schreiber, Maria A. Duque-Correa, James C. Wright, Theodoros I. Roumeliotis, Lu Yu, Jyoti S. Choudhary, Asuncion Mejias, Octavio Ramilo, Milensu Shanyinde, Marcelo B. Sztein, Robert A. Kingsley, Stephen Lockhart, Myron M. Levine, David J. Lynn, Gordon Dougan, Andrew J. Pollard
Journal: The Journal of Experimental Medicine (2016)

Enteric fever, caused by Salmonella enterica serovar Typhi, is an important public health problem in resource-limited settings and, despite decades of research, human responses to the infection are poorly understood. In 41 healthy adults experimentally infected with wild-type S. Typhi, we detected significant cytokine responses within 12 h of bacterial ingestion. These early responses did not correlate with subsequent clinical disease outcomes and likely indicate initial host–pathogen interactions in the gut mucosa. In participants developing enteric fever after oral infection, marked transcriptional and cytokine responses during acute disease reflected dominant type I/II interferon signatures, which were significantly associated with bacteremia. Using a murine and macrophage infection model, we validated the pivotal role of this response in the expression of proteins of the host tryptophan metabolism during Salmonella infection. Corresponding alterations in tryptophan catabolites with immunomodulatory properties in serum of participants with typhoid fever confirmed the activity of this pathway, and implicate a central role of host tryptophan metabolism in the pathogenesis of typhoid fever.
Investigation of Migration and Differentiation of Human Mesenchymal Stem Cells on Five‐Layered Collagenous Electrospun Scaffold Mimicking Native Cartilage Structure
Authors: Jenny W. Reboredo, Tobias Weigel, Andre Steinert, Lars Rackwitz, Maximilian Rudert, Heike Walles
Journal: Advanced Healthcare Materials (2016)

Cartilage degeneration is the major cause of chronic pain, lost mobility, and reduced quality of life for over estimated 150 million osteoarthritis sufferers worldwide. Despite intensive research, none of the available therapies can restore the hyaline cartilage surface beyond just fibrous repair. To overcome these limitations, numerous cell-based approaches for cartilage repair are being explored that aim to provide an appropriate microenvironment for chondrocyte maintenance and differentiation of multipotent mesenchymal stem cells (MSCs) toward the chondrogenic lineage. Articular cartilage is composed of highly organized collagen network that entails the tissue into four distinct zones and each zone into three different regions based on differences in matrix morphology and biochemistry. Current cartilage implants cannot establish the hierarchical tissue organization that seems critical for normal cartilage function. Therefore, in this study, a structured, multilayered collagen scaffold designed for the replacement of damaged cartilage is presented that allows repopulation by host cells and synthesis of a new natural matrix. By using the electrospinning method, the potential to engineer a scaffold consisting of two different collagen types is obtained. With the developed collagen scaffold, a five-layered biomaterial is created that has the potency to induce the differentiation of human bone marrow derived MSCs toward the chondrogenic lineage.
Making evidence based medicine work for individual patients
Authors: Margaret McCartney, Julian Treadwell, Neal Maskrey, Richard Lehman
Journal: BMJ (2016)

Margaret McCartney and colleagues argue that new models of evidence synthesis and shared decision making are needed to accelerate a move from guideline driven care to individualised care A Google Scholar search using the term "evidence based medicine" identifies more than 1.8 million papers. Over more than two decades, evidence based medicine has rightfully become part of the fabric of modern clinical practice and has contributed to many advances in healthcare. But many clinicians and patients have expressed dissatisfaction with the way evidence based medicine has been applied to individuals, especially in primary care.1 There is concern that guidelines intended to reduce variation and improve the quality of care have instead resulted in medicine becoming authoritarian and bureaucratic.2 Evidence generated from large populations has been distilled into large numbers of lengthy and technically complex guidelines. Guidelines in turn have been used to create financial incentive schemes such as the UK's Quality and Outcomes Framework, whereby a substantial proportion of general practice income depends on achieving thresholds for drug therapy or surrogate outcomes in accordance with National Institute for Health and Care Excellence guidelines. Not only do these thresholds exceed the limits of the evidence for many people but they also encourage clinicians to ignore the need to elicit and respect the preferences and goals of patients. Guidelines grew out of a need to communicate best current evidence to clinicians, but their limitations are often not explicitly stated (box 1). For example, some guidelines on heart failure adopt an entirely disease oriented approach, ignoring patients' views about the quality of their remaining life and the need to incorporate their goals in decision making.3 Depression guidelines often fail to acknowledge individual patient circumstances, especially how adverse life events or social support influences symptoms and responses to treatment.4 #### Box 1: Problems with applying population based evidence to individuals
Chemotherapy delivery in patients with hereditary angioedema
Authors: C. Morelli, V. Formica, M.D. Guarino, V. Cereda, E. Krasniqui, L. Martano, A. Menghi, A.M. Morelli, S. Pellicori, R. Perricone, M. Roselli
Journal: Annals of Oncology (2015)
Influenza vaccination coverage in elderly people, Campania (Italy), 1999
Authors: P D'Argenio, B Adamo, R Coluccio, A D'Apice, M. A. Ferrara, F Giugliano, R Parrella, F Peluso, V Romeo, C Ronga, A Simonetti, A Citarella
Journal: Eurosurveillance (2001)

A study on the coverage of influenza vaccination among elderly people was carried out. Fity-six per cent of those interviewed had been vaccinated (weighted coverage 50%), compared with the target of 75%, but higher rates were reported in those older than 74 years and those with chronic diseases.
Symposium: Characterization of Oncornaviruses and Related Viruses-A Report
Authors: Albert J. Dalton, Ursula I. Heine, J. L. Melnick
Journal: JNCI Journal of the National Cancer Institute (1975)

Journal Article Symposium: Characterization of Oncornaviruses and Related Viruses-A Report Get access Albert J. Dalton, Ph.D., Albert J. Dalton, Ph.D. Search for other works by this author on: Oxford Academic PubMed Google Scholar Ursula I. Heine, Ph.D., Ursula I. Heine, Ph.D. Search for other works by this author on: Oxford Academic PubMed Google Scholar J. L. Melnick, M.D. J. L. Melnick, M.D. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 55, Issue 4, October 1975, Pages 941–943, https://doi.org/10.1093/jnci/55.4.941 Published: 01 October 1975 Article history Received: 10 March 1975 Accepted: 09 June 1975 Published: 01 October 1975
Diffuse 18F-FDG Muscle Uptake in Trichinella spiralis Infection
Authors: Christophe M Deroose, Donatienne Van Weehaeghe, Thomas Tousseyn, Anne-Sophie Van Rompuy, Steven Vanderschueren, Daniel Blockmans, Olivier Gheysens
Journal: Clinical Nuclear Medicine (2015)

Two patients were referred to our emergency department with myalgia, fever, general malaise, eosinophilia, and elevated serum levels of creatine kinase and troponin T. 18F-FDG PET/CT scan was performed showing a diffuse and homogenous moderately elevated glucose uptake in all muscle groups. Trichinella spiralis infection was confirmed by a muscle biopsy and detection of trichinella antibodies. The muscle biopsy was taken in the left quadriceps because of equal involvement of the skeletal muscles. The differential diagnosis of diffuse 18F-FDG muscle uptake should include trichinella infection, in particular, in the presence of infectious symptoms, eosinophilia, and biochemical signs of muscle damage.
Adolescent BMI and risk of diabetes versus coronary disease.
Authors: Jose Mario F de Oliveira, Luciano B Lisboa
Journal: New England Journal of Medicine (2011)

n engl j med 364;26 nejm.org june 30, 2011 2558 toms among patients receiving omalizumab was clinically irrelevant, since a relative improvement of 24.5% in the symptom domain is clinically important and paralleled significant reductions in hospitalizations (74.6%), exacerbations (37.9%), and the daily dose of an inhaled glucocorticoid that was needed to maintain disease control (a reduction of 109 μg per day, or 14.1%). Most important, the seasonal peaks in asthma exacerbations were virtually eliminated. Therefore, in our opinion, the value of the clinical effect of this treatment should be assessed in relationship to the multiple domains of asthma morbidity.
Use of a long, stiff, overtube placed by a colonoscope to facilitate the POEM procedure for a 36-year history of achalasia with 13-cm esophageal dilation
Authors: Keoseyla Unn, Piseth Chhorn, Jérome Rivory, Sabine Roman, Jean-Christophe Saurin, Thierry Ponchon, Mathieu Pioche
Journal: Endoscopy (2016)

Achalasia has an insidious onset, and disease progression is gradual. Patients typically experience symptoms for years prior to seeking medical attention, with a mean duration of symptoms of 4.7 years [1]. The delay in diagnosis is mainly due to misinterpretation of typical clinical features rather than atypical findings, and many patients are treated for other disorders, such as reflux, before diagnosis [2].
Patient Education Materials in Dermatology
Authors: Arpan V. Prabhu, Raghav Gupta, Christopher Kim, Ahmed Kashkoush, David R. Hansberry, Nitin Agarwal, Ellen Koch
Journal: JAMA Dermatology (2016)

The lack of consistent oversight of online content can result in inappropriately technical patient education resources. 6 Given that a majority of the patient education sources from the 20 dermatology organizations were written above the National Institutes of Health-recommended reading level, these existing resources should be revised to reach a broader patient audience.A limitation to this study is the lack of patient feedback in assessing the quality of online health care resources.Using quality assessment metrics to subjectively evaluate the online user experience may capture criticisms missed by our quantitative approach.Participants could reflect on the quality of nontextual components such as graphics, website design, interactivity, and user friendliness.A greater emphasis must be placed on developing simpler online dermatologic education resources, given the influence these materials can have on patient decision making in the clinical setting.
Possible mechanisms for lactate's induction of panic
Authors: M R Liebowitz, J M Gorman, A Fyer, D Dillon, M Levitt, D F Klein
Journal: American Journal of Psychiatry (1986)

Forty-three patients with panic disorder or agoraphobia with panic attacks and 20 control subjects received 0.5 M racemic sodium lactate intravenous infusions, single-blind as to duration and sequence. During the procedure, pulse; blood pressure; blood L-lactate and pyruvate; plasma ionized calcium, phosphate, prolactin, epinephrine, norepinephrine, and cortisol levels; and venous PCO2, pH, and bicarbonate were measured in an attempt to clarify the mechanism of lactate-induced panic attacks. During the infusion, 72% of the patients but none of the control subjects had panic attacks. The laboratory findings suggest that peripheral catecholamine surge is not the mechanism by which lactate causes panic, although elevated epinephrine may be a predisposing factor. Heightened central noradrenergic activity was present in many but not all of the attacks. Contrary to previous hypotheses, neither depression of ionized calcium nor induction of metabolic alkalosis appears sufficient to cause panic during lactate infusion.
High academic achievement in psychotic students
Authors: Z Defries, L Grothe
Journal: American Journal of Psychiatry (1978)

The authors studied 21 schizophrenic and borderline college students who achieved B+ or higher grade averages and underwent psychotherapy while in college. High academic achievement was found to provide relief from feelings of worthlessness and ineffectuality resulting from poor relationships with parents, siblings, and peers. Psychotherapy and the permissive yet supportive college atmosphere reinforced the students' self-esteem.
“Collaborative care” is preferable to “patient centred care”
Authors: JK Aronson
Journal: BMJ (2016)

Healthcare isn’t centralised but a complex network, with interdependent components

Some ideas seem so obviously right that any harmful or counterproductive consequences are unthinkable. When such consequences do occur they are unanticipated, as the US sociologist RK Merton called them; unintended, as we now say.1 One such idea is patient centred care.2

The US Institute of Medicine defines patient centred care as “providing care that is respectful of and responsive to individual patient preferences, needs, and values, and ensuring that patient values guide all clinical decisions.”3 The UK Royal College of General Practitioners defines it as “care that is holistic, empowering and that tailors support according to the individual’s priorities and needs.”4

Patients’ welfare (needs, values, priorities, and preferences) should be a focus of attention. But it’s wrong to …
Chronic Conditions Causing Activity Limitation. United States—July 1963-June 1965.
Authors: A G Dingfelder
Journal: Annals of Internal Medicine (1969)

This is the third report from the Health Interview Survey dealing with the causes of activity limitation. Previous reports on this subject are "Chronic Conditions and Activity Limitation, United States, July 1961-June 1963" (Vital and Health Statistics, Series 10, No. 17) and "Chronic Conditions Causing Limiation of Activities, United States, July 1959-June 1961" (Health Statistics, Series B, No. 36). Some of the statistics in the earlier reports have been updated in the present publication. For example, the distribution of selected causes of limitation among chronically limited persons according to the degree of severity of limitation is shown in each of these reports, and the chronological sequence of these distributions forms a source of data for valid trend comparisons. Comparability has been ensured by the absence of major alterations of questionnaire items related to this subject and by the use of the same chronic condition list for each report.
Diagnosis of Tuberculosis in Three Zoo Elephants and a Human Contact — Oregon, 2013
Authors: Amy Zlot, Jennifer Vines, Laura Nystrom, Lindsey Lane, Heidi Behm, Justin Denny, Mitch Finnegan, Trevor Hostetler, Gloria Matthews, Tim Storms, Emilio DeBess
Journal: MMWR Morbidity and Mortality Weekly Report (2016)

In 2013, public health officials in Multnomah County, Oregon, started an investigation of a tuberculosis (TB) outbreak among elephants and humans at a local zoo. The investigation ultimately identified three bull elephants with active TB and 118 human contacts of the elephants. Ninety-six (81%) contacts were evaluated, and seven close contacts were found to have latent TB infection. The three bulls were isolated and treated (elephants with TB typically are not euthanized) to prevent infection of other animals and humans, and persons with latent infection were offered treatment. Improved TB screening methods for elephants are needed to prevent exposure of human contacts.
Case 15-1976
Authors: Richard C. Cabot, Robert E. Scully, James J. Galdabini, Betty U. McNeely, Kurt J. Block, Robert T. McCluskey
Journal: New England Journal of Medicine (1976)

Presentation of Case First admission. A 53-year-old woman was admitted to the hospital because of proteinuria.She was well until three years previously, when hypertension was discovered; alpha-methyldopa was given for the next 19 months. Seventeen months before entry proteinuria was found. Further studies disclosed that the serum protein was 6.2 g (the albumin 2.8 g, and the globulin 3.4 g) per 100 ml. Agarose-gel electrophoresis (Fig. 1) disclosed an abnormal pattern, with an M component migrating in the alpha2 globulin region; a moderate decrease in the gamma globulin was observed. Serum immunoelectrophoresis showed an M component that . . .