tbuckley/cabot-search huggingface dataset:
Development of Lung Adenocarcinomas with Exclusive Dependence on Oncogene Fusions
Authors: Motonobu Saito, Yoko Shimada, Kouya Shiraishi, Hiromi Sakamoto, Koji Tsuta, Hirohiko Totsuka, Suenori Chiku, Hitoshi Ichikawa, Mamoru Kato, Shun-ichi Watanabe, Teruhiko Yoshida, Jun Yokota, Takashi Kohno
Journal: Cancer Research (2015)

This report delivers a comprehensive genetic alteration profile of lung adenocarcinomas (LADC) driven by ALK, RET, and ROS1 oncogene fusions. These tumors are difficult to study because of their rarity. Each drives only a low percentage of LADCs. Whole-exome sequencing and copy-number variation analyses were performed on a Japanese LADC cohort (n = 200) enriched in patients with fusions (n = 31, 15.5%), followed by deep resequencing for validation. The driver fusion cases showed a distinct profile with smaller numbers of nonsynonymous mutations in cancer-related genes or truncating mutations in SWI/SNF chromatin remodeling complex genes than in other LADCs (P < 0.0001). This lower mutation rate was independent of age, gender, smoking status, pathologic stage, and tumor differentiation (P < 0.0001) and was validated in nine fusion-positive cases from a U.S. LADCs cohort (n = 230). In conclusion, our findings indicate that LADCs with ALK, RET, and ROS1 fusions develop exclusively via their dependence on these oncogene fusions. The presence of such few alterations beyond the fusions supports the use of monotherapy with tyrosine kinase inhibitors targeting the fusion products in fusion-positive LADCs.
The human milk oligosaccharide 2′-fucosyllactose modulates CD14 expression in human enterocytes, thereby attenuating LPS-induced inflammation
Authors: YingYing He, ShuBai Liu, David E Kling, Serena Leone, Nathan T Lawlor, Yi Huang, Samuel B Feinberg, David R Hill, David S Newburg
Journal: Gut (2014)

<h3>Background</h3> A major cause of enteric infection, Gram-negative pathogenic bacteria activate mucosal inflammation through lipopolysaccharide (LPS) binding to intestinal toll-like receptor 4 (TLR4). Breast feeding lowers risk of disease, and human milk modulates inflammation. <h3>Objective</h3> This study tested whether human milk oligosaccharides (HMOSs) influence pathogenic <i>Escherichia coli</i>-induced interleukin (IL)-8 release by intestinal epithelial cells (IECs), identified specific proinflammatory signalling molecules modulated by HMOSs, specified the active HMOS and determined its mechanism of action. <h3>Methods</h3> Models of inflammation were IECs invaded by type 1 pili enterotoxigenic <i>E. coli</i> (ETEC) in vitro: T84 modelled mature, and H4 modelled immature IECs. LPS-induced signalling molecules co-varying with IL-8 release in the presence or absence of HMOSs were identified. Knockdown and overexpression verified signalling mediators. The oligosaccharide responsible for altered signalling was identified. <h3>Results</h3> HMOSs attenuated LPS-dependent induction of IL-8 caused by ETEC, uropathogenic <i>E. coli</i>, and adherent-invasive <i>E. coli</i> (AIEC) infection, and suppressed CD14 transcription and translation. CD14 knockdown recapitulated HMOS-induced attenuation. Overexpression of CD14 increased the inflammatory response to ETEC and sensitivity to inhibition by HMOSs. 2′-fucosyllactose (2′-FL), at milk concentrations, displayed equivalent ability as total HMOSs to suppress CD14 expression, and protected AIEC-infected mice. <h3>Conclusions</h3> HMOSs and 2′-FL directly inhibit LPS-mediated inflammation during ETEC invasion of T84 and H4 IECs through attenuation of CD14 induction. CD14 expression mediates LPS-TLR4 stimulation of portions of the 'macrophage migration inhibitory factors' inflammatory pathway via suppressors of cytokine signalling 2/signal transducer and activator of transcription 3/NF-κB. HMOS direct inhibition of inflammation supports its functioning as an innate immune system whereby the mother protects her vulnerable neonate through her milk. 2′-FL, a principal HMOS, quenches inflammatory signalling.
A case of anti-p200 pemphigoid clinically mimicking inflammatory epidermolysis bullosa acquisita
Authors: N. Umemoto, T. Demitsu, S. Toda, T. Noguchi, S.-I. Suzuki, M. Kakurai, T. Yamada, M. Suzuki, H. Nakagawa, A. Komai, T. Hashimoto
Journal: British Journal of Dermatology (2003)

Journal Article A case of anti‐p200 pemphigoid clinically mimicking inflammatory epidermolysis bullosa acquisita Get access N. Umemoto, N. Umemoto Departments of Dermatology and Search for other works by this author on: Oxford Academic Google Scholar T. Demitsu, T. Demitsu Departments of Dermatology and T.Demitsu. E‐mail: demitsu@omiya.jichi.ac.jp Search for other works by this author on: Oxford Academic Google Scholar S. Toda, S. Toda Departments of Dermatology and Search for other works by this author on: Oxford Academic Google Scholar T. Noguchi, T. Noguchi Dentistry and Oral Surgery, Jichi Medical School, Omiya Medical Centre, 1‐847 Amanuma‐machi, Saitama 330–8503 Search for other works by this author on: Oxford Academic Google Scholar S.‐I. Suzuki, S.‐I. Suzuki Division of Surgery, Kameari Central Hospital, Tokyo Search for other works by this author on: Oxford Academic Google Scholar M. Kakurai, M. Kakurai Department of Dermatology, Jichi Medical School, School of Medicine, Tochigi, and Search for other works by this author on: Oxford Academic Google Scholar T. Yamada, T. Yamada Department of Dermatology, Jichi Medical School, School of Medicine, Tochigi, and Search for other works by this author on: Oxford Academic Google Scholar M. Suzuki, M. Suzuki Department of Dermatology, Jichi Medical School, School of Medicine, Tochigi, and Search for other works by this author on: Oxford Academic Google Scholar H. Nakagawa, H. Nakagawa Department of Dermatology, Jichi Medical School, School of Medicine, Tochigi, and Search for other works by this author on: Oxford Academic Google Scholar A. Komai, A. Komai Department of Dermatology, Kurume University, School of Medicine, Kurume, Japan Search for other works by this author on: Oxford Academic Google Scholar ... Show more T. Hashimoto T. Hashimoto Department of Dermatology, Kurume University, School of Medicine, Kurume, Japan Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 148, Issue 5, 1 May 2003, Pages 1058–1060, https://doi.org/10.1046/j.1365-2133.2003.05312.x Published: 01 May 2003
Inside Guidelines
Authors: Jako S. Burgers, Julia V. Bailey, Niek S. Klazinga, Akke K. Van der Bij, Richard Grol, Gene Feder
Journal: Diabetes Care (2002)

OBJECTIVE—To compare guidelines on diabetes from different countries in order to examine whether differences in recommendations could be explained by use of different research evidence. RESEARCH DESIGN AND METHODS—We analyzed 15 clinical guidelines on type 2 diabetes from 13 countries using qualitative methods to compare the recommendations and bibliometric methods to measure the extent of overlap in citations used by different guidelines. A further qualitative analysis of recommendations and cited evidence for two specific issues in diabetes care explored the apparent discrepancy between recommendations and evidence. RESULTS—The recommendations made in the guidelines were in agreement about the general management of type 2 diabetes, with some important differences in treatment details. There was little overlap in evidence cited by the guidelines, with 18% (185/1,033) of citations shared with any other guideline, and only 10 studies (1%) appearing in six or more guidelines. The measurable overlap in evidence between guidelines increases if multiple publications from the same study and the use of reviews are taken into account. Research originating from the U.S. predominated (40% of citations); however, nearly all (11/12) guidelines were significantly more likely to cite evidence originating from their own countries. CONCLUSIONS—Despite the variation in cited evidence and preferential citation of evidence from a guideline’s country of origin, we found a high degree of international consensus in recommendations made for the clinical care of type 2 diabetes. The influence of professional bodies such as the American Diabetes Association may be an important factor in explaining international consensus. Globalization of recommended management of diabetes is not a simple consequence of the globalization of research evidence.
Use of Ga-67 Imaging in Diagnosis and Follow-Up After Steroid Treatment of Retroperitoneal Fibrosis
Authors: SANJAY J. TALATI, REZA ABGHARI, JAMES J. KOCHKODAN, SHARON R. HELMER
Journal: Clinical Nuclear Medicine (1995)

Retroperitoneal fibrosis is an entity with an unknown cause. It is characterized by symptoms associated with the gradual compression of the retroperitoneal structures. This case report demonstrates the use of Ga-67 imaging in the early noninvasive diagnostic work-up and follow-up evaluation of poststeroid therapy.
Efficacy of a 24-week course of PEG-interferon α-2b monotherapy in patients with acute hepatitis C after failure of spontaneous clearance
Authors: Teresa Santantonio, Massimo Fasano, Emanuele Sinisi, Angela Guastadisegni, Caterina Casalino, Michele Mazzola, Ruggiero Francavilla, Giuseppe Pastore
Journal: Journal of Hepatology (2004)
Arrhythmias following Cardiac Valve Replacement
Authors: ROGER SMITH, WILLIAM GROSSMAN, LEWIS JOHNSON, HERMAN SEGAL, JOHN COLLINS, JAMES DALEN
Journal: Circulation (1972)

A prospective study of 50 consecutive patients undergoing cardiac valve replacement was designed to determine the incidence, types, and predisposing factors to postoperative arrhythmias. Patients were monitored continuously for the first 7 days following surgery. Thirty-seven patients (74%) experienced a total of 66 episodes of arrhythmia. Supra-ventricualr arrhythmias were the most common (43 of 66; 65%). The most frequent specific arrhythmia was atrial fibrillation (21 of 66; 32%). Arrhythmias occurred 77% of the time within the first 48 hours of surgery. Of 25 factors evaluated preoperatively in each patient, only two were found to predispose to postoperative arrhythmias. These were: (1) previous cardiac surgery; and (2) elevated blood urea nitrogen. There were four hospital deaths, representinig a hospital mortality of 8%. No deaths were due to a primary arrhythmia. It is concluded that whereas arrhythmias are a very common complication of cardiac valve replacement, early detection and treatment has lessened their significance as a cause of postoperative mortality and morbidity.
Managing delayed or altered puberty in boys
Authors: N. Pitteloud
Journal: BMJ (2012)

Early identification and treatment, both medical and psychological, is key 

Two linked patient journeys describe the experience of male puberty gone awry (doi:10.1136/bmj.e6938, doi:10.1136/bmj.e6971). Puberty is a period of substantial physical development that culminates in reproductive capacity, and it is marked by major psychological changes. The normal timing of puberty is influenced by several factors, including those that are familial, ethnic, and environmental. It is estimated that genetic factors account for 50-80% of the variance in the onset of puberty.1 Accumulating evidence suggests a secular trend towards decreasing age of onset of puberty, which could be related, in part, to obesity.1 2 Failure to initiate spontaneous puberty, which represents the extreme end of the pubertal spectrum, could trigger presentation to medical services for a number of adolescents. For the clinician faced with an adolescent male patient who is not developing signs of starting puberty, differentiating normal variation from pathology is not always straightforward. However, as the linked patient stories clearly show, failure to deal with clinical concerns in a timely fashion for such patients can have longlasting psychological and emotional effects.

Delayed puberty is defined as the absence of testicular enlargement in boys 2 to 2.5 …
The risk of deep venous thrombosis and pulmonary embolism in giant cell arteritis: a general population-based study
Authors: J Antonio Aviña-Zubieta, Vidula M Bhole, Neda Amiri, Eric C Sayre, Hyon K Choi
Journal: Annals of the Rheumatic Diseases (2014)

Patients with giant cell arteritis (GCA) may have an increased risk of pulmonary embolism (PE), similar to other systemic vasculitidies; however, no relevant population data are available to date.To evaluate the future risk and time trends of new venous thromboembolism (VTE) in individuals with incident GCA at the general population level.Observational cohort study.General population of British Columbia.909 patients with incident GCA and 9288 age-matched, sex-matched and entry-time-matched control patients without a history of VTE.We calculated incidence rate ratios (IRR) overall, and stratified by GCA duration. We calculated HR of PE and deep vein thrombosis (DVT), adjusting for potential VTE risk factors.Among 909 individuals with GCA (mean age 76 years, 73% women), 18 developed PE and 20 developed DVT. Incidence rates (IR) of VTE, PE and DVT were 13.3, 7.7 and 8.5 per 1000 person-years (PY) in GCA cohort, versus 3.7, 1.9 and 2.2 per 1000 PY in the comparison cohort. The corresponding IRRs (95% CI) for VTE, PE and DVT were 3.58 (2.33 to 5.34), 3.98 (2.22 to 6.81) and 3.82 (2.21 to 6.34) with the highest IRR observed in the first year of GCA diagnosis (7.03, 7.23 and 7.85, respectively). Corresponding fully adjusted HRs (95% CI) were 2.49 (1.45 to 4.30), 2.71 (1.32 to 5.56) and 2.78 (1.39 to 5.54).These findings provide general population-based evidence that patients with GCA have an increased risk of VTE, calling for increased vigilance in preventing this serious, but preventable complication, especially within months after GCA diagnosis.
Educational messages on laboratory results improved diastolic BP but not systolic BP, HbA1c, or cholesterol in diabetes
Authors: Steven A. Smith
Journal: Annals of Internal Medicine (2012)

ACP Journal Club15 May 2012Educational messages on laboratory results improved diastolic BP but not systolic BP, HbA1c, or cholesterol in diabetesSteven A. Smith, MDSteven A. Smith, MDMayo Clinic Rochester, Rochester, Minnesota, USA (S.A.S.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-156-10-201205150-02012 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Source CitationFoy R, Eccles MP, Hrisos S, et al. A cluster randomised trial of educational messages to improve the primary care of diabetes. Implement Sci. 2011;6:129. https://pubmed.ncbi.nlm.nih.gov/22177466Clinical Impact RatingsGIM/FP/GP: References1 O’Connor PJ, Sperl-Hillen J, Johnson PE, Rush WA, Crain AL. Customized feedback to patients and providers failed to improve safety or quality of diabetes care: a randomized trial. Diabetes Care. 2009;32:1158-63. [PMID: 19366977] Google Scholar2 Centers for Medicare & Medicaid Services. CMS EHR meaningful use overview. www.cms.gov/EHRIncentivePrograms/30_Meaningful_Use.asp (accessed 28 Mar 12). Google Scholar3 Montori VM, Breslin M, Maleska M, Weymiller AJ. Creating a conversation: insights from the development of a decision aid. PLoS Med. 2007;4:e233. [PMID: 17683195] Google Scholar4 Glenton C, Santesso N, Rosenbaum S, et al. Presenting the results of Cochrane Systematic Reviews to a consumer audience: a qualitative study. Med Decis Making. 2010;30:566-77. [PMID: 20643912] Google Scholar5 Barry MJ, Edgman-Levitan S. Shared decision making—pinnacle of patient-centered care. N Engl J Med. 2012;366:780-1. [PMID: 22375967] Google Scholar Author, Article, and Disclosure InformationAuthors: Steven A. Smith, MDAffiliations: Mayo Clinic Rochester, Rochester, Minnesota, USA (S.A.S.)This article was published at Annals.org on 1 May 2012. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 15 May 2012Volume 156, Issue 10Page: JC5-12KeywordsBlood pressureCholesterolDiabetes mellitusElectronic medical recordsHbA1cHealth care providersHemoglobinLaboratory testsPatientsResearch laboratories ePublished: 15 May 2012 Issue Published: 15 May 2012 Copyright & PermissionsCopyright © 2012 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
CHANGES IN LIVER GLYCOGEN STUDIED BY THE NEEDLE ASPIRATION TECHNIC IN PATIENTS WITH DIABETIC KETOSIS. WITH A METHOD FOR THE ESTIMATION OF GLYCOGEN FROM HISTOLOGIC PREPARATIONS 1
Authors: Philip K. Bondy, Walter H. Sheldon, Lillian D. Evans
Journal: Journal of Clinical Investigation (1949)

Previous attempts to estimate the glycogen content of the human liver were based on deter- minations performed on material obtained by op- erative biopsy or from postmortem specimens.Observations on animals have shown that these procedures may introduce an important error through the effect of the commonly used anesthetic agents, or of trauma, before the specimen is ob- tained.The development of a technic for the re- moval of small specimens of liver by aspiration biopsy is well adapted to the study of glycogen metabolism, for it avoids the uncertain effects of premedication, general anesthesia and the trauma of operation.By this method serial biopsies of the liver have been obtained in a study of patients under treatment for diabetic acidosis. METHODSLiver tissue was obtained by needle biopsy, using the Vim-Silverman needle, under local procaine infiltration.With practice, it was possible to obtain an adequate specimen in less than three seconds from the time of insertion of the needle into the substance of the liver.Speed was desirable, since patients in severe acidosis were unable to hold their breath.The specimens were immediately fixed in iced absolute alcohol or Rossman's fixative.Plasma carbon dioxide combining powers were deter- mined by the method of Van Slyke and Neill (1).The Folin-Wu method was used for the determination of blood glucose (2). THE TECHNIC FOR THE ESTIMATION OF HEPATIC GLYCOGENAt first, the glycogen concentration was determined by the chemical method of Good, Kramer and Somogyi (3).This technic was unsatisfactory, however, since without histologic examination it was impossible to be
Medical Lessons from Malpractice Cases
Authors: Don Harper Mills
Journal: JAMA (1963)

One-thousand current malpractice cases covering the entire field of medicine were critically reviewed to determine the presence and type, if any, of medical and surgical problems which may add to the burdens of a successful defense. This retrospective analysis parallels courtroom evaluation, since both are colored by the prejudice of hindsight. Therefore, for the benefit of doctor and patient, it is hoped that the conclusions presented will engender increased foresight and awareness of potential pitfalls in practice. Of particular interest is the observation concerning complications of therapy: The fact that such complications occurred was often of less importance than their identification and treatment by the attending physicians.
Instruments, illustrations, information, and animals
Authors: Charles Marwick
Journal: JAMA (1984)

The Division of Research Services has four main areas of responsibility through which it serves the 8,000 staff members of the intramural programs at the NIH. It provides and maintains animals for research; designs and constructs instruments for medical research and clinical application; produces illustrative material such as graphs, charts, and photographs in its medical arts branch; and supplies library facilities, independent from but complementary to those rendered by the much larger National Library of Medicine. The division's annual budget of around $28 million is met largely by charging the institutes for these services. The division was established in 1956. Its present director, Joe R. Held, DVM, has held the position since July 1972. He is leaving at the beginning of next month to become director of the Pan-American Health Organization's Zoonoses Center in Buenos Aires. In terms of budget, the largest of the division's four branches is the Veterinary
Mutations in<i>SYNGAP1</i>in Autosomal Nonsyndromic Mental Retardation
Authors: Fadi F. Hamdan, Julie Gauthier, Dan Spiegelman, Anne Noreau, Yan Yang, Stéphanie Pellerin, Sylvia Dobrzeniecka, Mélanie Côté, Elizabeth Perreau-Linck, Lionel Carmant, Guy D'Anjou, Éric Fombonne, Anjene M. Addington, Judith L. Rapoport, Lynn E. Delisi, Marie-Odile Krebs, Faycal Mouaffak, Ridha Joober, Laurent Mottron, Pierre Drapeau, Claude Marineau, Ronald G. Lafrenière, Jean Claude Lacaille, Guy A. Rouleau, Jacques L. Michaud
Journal: New England Journal of Medicine (2009)

Although autosomal forms of nonsyndromic mental retardation account for the majority of cases of mental retardation, the genes that are involved remain largely unknown. We sequenced the autosomal gene SYNGAP1, which encodes a ras GTPase-activating protein that is critical for cognition and synapse function, in 94 patients with nonsyndromic mental retardation. We identified de novo truncating mutations (K138X, R579X, and L813RfsX22) in three of these patients. In contrast, we observed no de novo or truncating mutations in SYNGAP1 in samples from 142 subjects with autism spectrum disorders, 143 subjects with schizophrenia, and 190 control subjects. These results indicate that SYNGAP1 disruption is a cause of autosomal dominant nonsyndromic mental retardation.
Management of intrahepatic stones: The role of subcutaneous hepaticojejunal access loop. A prospective cohort study
Authors: Mohamed I. Kassem, Magdy A. Sorour, Abdel-Hamid A. Ghazal, Hany M. El-Haddad, Mohamed T. El-Riwini, Hassan A. El-Bahrawy
Journal: International Journal of Surgery (2014)
Absence of Herpesvirus in AIDS-Associated Smooth-Muscle Tumors
Authors: Hal B. Jenson, Charles T. Leach, Eduardo A. Montalvo, Jung-Chung Lin, Sharon B. Murphy
Journal: New England Journal of Medicine (1996)

To the Editor: Tibbles and Edelsberg (June 20 issue) 1 present a complete and cogent summary of the therapeutic usefulness of hyperbaric-oxygen therapy.However, their review contains a recommendation that is not supported by evidence.In the section on the treatment of carbon monoxide poisoning, the authors present a balanced discussion of studies demonstrating conflicting results.The available evidence does not guide us one way or the other as to the effectiveness of hyperbaric-oxygen therapy in this setting.Yet in a seeming non sequitur the authors state, we think that patients with severe carbon monoxide poisoning should receive at least one treatment with hyperbaric oxygen at 2.5 to 3.0 atmospheres; additional treatments may produce greater improvement in neuropsychological deficits.For patients with lesser degrees of poisoning, we advise consultation with a toxicologist to determine whether the administration of 100 percent normobaric oxygen for four to six hours, or until symptoms abate, would be adequate therapy.We find this recommendation incomplete at best, and misleading at worst.In a recent review, Tibbles and Perrotta stated that "no randomized, controlled, blinded clinical trial demonstrated a clear advantage of HBO [hyperbaric-oxygen therapy] over NBO [normobaric-oxygen therapy] in reducing morbidity and mortality in carbon monoxide poisoning." 2 An accompanying article in the same journal concluded that "the standard of care for pa-tients exposed to CO [carbon monoxide] is yet to be determined." 3We believe readers need to be reminded of these facts.
The elevated NF-kB activity and MCP-1 expression in endothelial-injured arteries from hypercholesterolemic rabbits are prevented by quinapril
Authors: Miguel H. Presa, Carmen Bustos, Mónica Ortego, José Tuñón, Marta Ruiz-Ortega, Julio G. Puente, Jesús Egido
Journal: Journal of the American College of Cardiology (1996)