tbuckley/cabot-search huggingface dataset:
Plasma Concentrations of Afamin Are Associated With Prevalent and Incident Type 2 Diabetes: A Pooled Analysis in More Than 20,000 Individuals
Authors: Barbara Kollerits, Claudia Lamina, Cornelia Huth, Pedro Marques-Vidal, Stefan Kiechl, Ilkka Seppälä, Jackie Cooper, Steven C. Hunt, Christa Meisinger, Christian Herder, Ludmilla Kedenko, Johann Willeit, Barbara Thorand, Doreen Dähnhardt, Doris Stöckl, Karin Willeit, Michael Roden, Wolfgang Rathmann, Bernhard Paulweber, Annette Peters, Mika Kähönen, Terho Lehtimäki, Olli T. Raitakari, Steve E. Humphries, Peter Vollenweider, Hans Dieplinger, Florian Kronenberg
Journal: Diabetes Care (2017)

The human vitamin E-binding glycoprotein afamin is primarily expressed in the liver and has been associated with prevalent and incident metabolic syndrome. These data were in line with observations in transgenic mice. We thus investigated whether afamin concentrations are associated with prediabetes, type 2 diabetes, and insulin resistance (IR).Individual-level baseline (n = 20,136) and follow-up data (n = 14,017) of eight prospective cohort studies were investigated. Study-level data were combined using random-effects meta-analyses. Main outcomes were prevalent and incident type 2 diabetes, prediabetes, and IR. Discrimination and reclassification of participants was analyzed for incident type 2 diabetes.Mean afamin concentrations between studies ranged from 61 to 73 mg/L. The eight studies included 1,398 prevalent and 585 incident cases of type 2 diabetes. Each increase of afamin by 10 mg/L was associated with prevalent type 2 diabetes (odds ratio [OR] 1.19 [95% CI 1.12-1.26], P = 5.96 × 10-8). Afamin was positively associated with IR assessed by HOMA-IR (β 0.110 [95% CI 0.089-0.132], P = 1.37 × 10-23). Most importantly, afamin measured at baseline was an independent predictor for 585 incident cases of type 2 diabetes (OR 1.30 [95% CI 1.23-1.38], P = 3.53 × 10-19) and showed a significant and valuable gain in risk classification accuracy when added to this extended adjustment model.This pooled analysis in >20,000 individuals showed that afamin is strongly associated with IR, prevalence, and incidence of type 2 diabetes independent of major metabolic risk factors or parameters. Afamin might be a promising novel marker for the identification of individuals at high risk for the development of type 2 diabetes.
Recurrent Tumor Cell–Intrinsic and –Extrinsic Alterations during MAPKi-Induced Melanoma Regression and Early Adaptation
Authors: Chunying Song, Marco Piva, Lu Sun, Aayoung Hong, Gatien Moriceau, Xiangju Kong, Hong Zhang, Shirley Lomeli, Jin Qian, Clarissa C. Yu, Robert Damoiseaux, Mark C. Kelley, Kimberley B. Dahlman, Philip O. Scumpia, Jeffrey A. Sosman, Douglas B. Johnson, Antoni Ribas, Willy Hugo, Roger S. Lo
Journal: Cancer Discovery (2017)

Treatment of advanced
AB0864 Sensitivity and specificity of sonographic detection of urate crystal deposits in hyaline cartilage in patients with gout in yearly stage
Authors: A Petrov, V Fursova, A Petrov
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> In some cases differential diagnosis between yearly gouty arthritis and other types of arthritis is very difficult. In 2015 the sonographic detection of urate crystal deposits in hyaline cartilage as a new criterion was included in set of classification criteria of gout [1]. But diagnostic value of that ultrasound marker in first month of disease is underinvestigated. <h3>Objectives</h3> To investigate sensitivity and specificity of sonographic detection of gouty hyperechoic deposits in hyaline cartilage in patients with gout in comparison with other signs of gout in debut of arthritis. <h3>Methods</h3> The 104 patients with yearly arthritis (duration of symptoms less than 6 month) was examined by clinical, laboratory, X-Ray and ultrasonography. After investigation the following diagnoses were made: Gout in 32 patients, Osteoarthritis in 28 patients, Rheumatoid arthritis in 28 patients, Psoriatic arthritis in 16 patients. Ultrasound investigation of affected joints was performed in all subjects by linear probe 18 MHz. Urate crystal deposits were seen on the surface of the hyaline cartilage as a hyperechoic thin line or dots on the cartilage, wich sometimes imitate double contour of bones [2, 3]. Sensitivity and specificity of ultrasound sign were compared with subcutaneous tophi, bone cysts (X-Ray sign) and hyperuricemia. <h3>Results</h3> The urate crystal deposits in gyalinic cartilage of at least one of affected joints were revealed in 28 of 32 (87,5%) patients with Gout, in 3 of 28 (10,7%) patients with Osteoarthritis and 1of 16 (6,3%) patients with Psoriatic arthritis. Comparative data of sensitivity and specificity of crystal deposits, bone cysts, subcutaneous tophi and hyperuricemia are represented in table below. <h3>Conclusions</h3> Ultrasound detection of urate crystal deposits in hyaline cartilage in patients with gout in yearly stage has a high sensitivity and comparable level of specificity with other diagnostic markers of Gout. <h3>References</h3> Neogi T et al. Gout classification criteria: an American College of Rheumatology European League Against Rheumatism collaborative initiative. Ann Rheum Dis. 2015;74(10):1789–1798. Filippucci E., Di Geso L, Grassi W. Tips and tricks to recognize microcrystalline arthritis. Rheumatology 2012;51(7):18–21. Naredo E et al. Ultrasound-detected musculoskeletal urate crystal deposition: which joints and what findings should be assessed for diagnosing gout? Ann Rheum Dis. 2014;73(10):1522–1528. <h3>Disclosure of Interest</h3> None declared
Medical Malpractice Lawsuits Involving Surgical Residents
Authors: Cornelius A. Thiels, Asad J. Choudhry, Mohamed D. Ray-Zack, Rachel A. Lindor, John R. Bergquist, Elizabeth B. Habermann, Martin D. Zielinski
Journal: JAMA Surgery (2017)

Medical malpractice litigation against surgical residents is rarely discussed owing to assumed legal doctrine of respondeat superior, or "let the master answer."To better understand lawsuits targeting surgical trainees to prevent future litigation.Westlaw, an online legal research database containing legal records from across the United States, was retrospectively reviewed for malpractice cases involving surgical interns, residents, or fellows from January 1, 2005, to January 1, 2015. Infant-related obstetric and ophthalmologic procedures were excluded.Involvement in a medical malpractice case.Data were collected on patient demographics, case characteristics, and outcomes and were analyzed using descriptive statistics.During a 10-year period, 87 malpractice cases involving surgical trainees were identified. A total of 50 patients were female (57%), and 79 were 18 years of age or older (91%), with a median patient age of 44.5 years (interquartile range, 45-56 years). A total of 67 cases (77%) resulted in death or permanent disability. Most cases involved elective surgery (61 [70%]) and named a junior resident as a defendant (24 of 35 [69%]). Cases more often questioned the perioperative medical knowledge, decision making errors, and injuries (53 [61%]: preoperative, 19 of 53 [36%]) and postoperative, 34 of 53 [64%]) than intraoperative errors and injuries (43 [49%]). Junior residents were involved primarily with lawsuits related to medical decision making (21 of 24 [87%]). Residents' failure to evaluate the patient was cited in 10 cases (12%) and lack of direct supervision by attending physicians was cited in 48 cases (55%). A total of 42 cases (48%) resulted in a jury verdict or settlement in favor of the plaintiff, with a median payout of $900 000 (range, $1852 to $32 million).This review of malpractice cases involving surgical residents highlights the importance of perioperative management, particularly among junior residents, and the importance of appropriate supervision by attending physicians as targets for education on litigation prevention.
An end-to-end precision medicine approach for matching cancer patients to clinical trials.
Authors: Alexei Protopopov, Jia Xu, Claudia S. Huettner, Meaghan Russell, Scott Schell, Stephen Lyle
Journal: Journal of Clinical Oncology (2015)

e22138 Background: Precise matching of a patient’s tumor genomic profile with appropriate targeted agents is the goal of precision medicine, and the salutary benefits of these targeted therapies upon survival has been well documented in the literature. Using a novel, 413 cancer-related actionable gene, NGS sequencing panel (KEW CancerPlex v2), we analyzed a variety of solid tumors to identify mutations associated with predicted response to approved and investigational targeted therapy agents. Methods: Tumor profiling was conducted in a CLIA-certified laboratory (KEW Group Inc., Cambridge, MA). DNA was extracted from FFPE tissue sections, slides, cell blocks from FNAs or effusions, or cell pellets, followed by hybrid-capture of target exons. Rapid sequencing runs were employed to generate at least 600 MB data per sample, and mutational analysis performed using the KEW Clinical Genomics Analytical pipeline, linked to the GATK/MuTect tool kit for variant discovery. Variant characterization and annotation was conducted, genotype-based personalized metabolic modeling performed to characterize tumors, and response or resistance to FDA-approved drugs predicted. Matches were identified by screening approximately 260,000 clinical trials, including 59,937 active or recruiting studies. Results: 200 cases, representing a variety of tumor types were analyzed using CancerPlex v2. Mean sequencing depth for > 90% whole exons was 250X (range: 88-333X) and SNPs detection sensitivity was > 98% (10% allele frequency). Tumors averaged 6.65 somatic variants (range: 1-18), of which 2.48 variants (range: 0-9) were deemed clinically actionable (93%). Tumor response, or resistance, markers were identified for FDA-approved therapies (mean: 1.2; range: 0-5) and clinical trials (mean: 7.98 range: 0-24). Mean turnaround time for sample preparation, sequencing, analysis, and reporting was 7 business days. Conclusions: The CancerPlex large scale NGS panel provides a robust, sensitive, and rapid clinical assay yielding clinically actionable findings in 93% of patient tumor samples.
変異アルデヒドデヒドロゲナーゼ2(ALDH2*2)遺伝子型に関連した冠動脈攣縮は日本人の心筋梗塞の重要な病因である
Authors: Mizuno Yuji, Harada Eisaku, Morita Sumio, Morikawa Yoshinobu, Nakagawa Hitoshi, Kashiwagi Yuusuke, Shono Makoto, Yoshimura Michihiro, Yasue Hirofumi
Journal: Circulation (2016)
A phase Ib study combining the second-generation DNA hypomethylating agent (DHA) guadecitabine (SGI-110) and ipilimumab in patients with metastatic melanoma: The NIBIT-M4 study.
Authors: Anna Maria Di Giacomo, Alessia Covre, Pietro Taverna, Sandra Coral, Giovanni Amato, Harold N. Keer, James N. Lowder, Diana Giannarelli, Mohammad Azab, Michele Maio
Journal: Journal of Clinical Oncology (2016)

TPS9595 Background: Epigenetic alterations affect virtually all cellular pathways associated with tumorigenesis and cancer progression. Importantly, the multifaceted immunomodulatory activity of DHA has been shown to improve the immunogenicity and immune recognition of neoplastic cells; thus, we predicted DHA could be part of new and potentially more effective immunotherapeutic combinations in cancer (Maio et al., Clin Can Res, 2015). Targeting immune check-point(s) with immunomodulatory monoclonal antibodies (mAb) is a novel and rapidly evolving strategy to treat cancer. The prototype approach of this therapeutic modality relies on the inhibition of negative signals delivered by CTLA-4 expressed on activated T lymphocytes. CTLA-4 blockade has changed the therapeutic landscape of metastatic melanoma (MM) by significantly improving the long-term survival of mm patients; however, objective clinical responses are limited, thus opening the path to combination regimens to improve its efficacy. Based on the immunomodulatory activity of the second-generation DHA guadecitabine (Covre et al., Semin Oncol, 2015) we designed the NIBIT-M4 study. This trial will sequence guadecitabine and ipilimumab in mm patients to provide proof-of-concept to the immunologic and clinical efficacy of DHA combined with CTLA-4 blockade. Methods: This is a Phase 1b, dose-escalation study in treatment naïve or pretreated unresectable Stage III or Stage IV melanoma patients, amenable to serial tumor biopsies. Primary objective will assess MTD and safety of guadecitabine combined with ipilimumab. Secondary objectives will include immune-related (ir) -DCR, -ORR, -PFS, median OS, and survival rate at 1 and 2-years. Immune-biologic correlates will be exploratory objectives. The dose escalation of guadecitabine will follow a 3+3 design. Cohorts of 3-6 patients will receive ipilimumab i.v. 3 mg/kg on W1, 4, 7 and 10 day 1 q21d and guadecitabine s.c. on W0, 3, 6, 9, days 1-5 q21d at the one of following doses: Dose Level (DL) -1: 15 mg/m2 day; DL 0: 30 mg/m2 day; DL +1: 45 mg/m2 day. Sample size will range from 6 to 19 patients. Four patients have been enrolled to date. Clinical trial information: NCT02608437.
Tezepelumab in Adults with Uncontrolled Asthma
Authors: Jonathan Corren, Jane R. Parnes, Liangwei Wang, May Mo, Stephanie L. Roseti, Janet M. Griffiths, René van der Merwe
Journal: New England Journal of Medicine (2017)

In some patients with moderate-to-severe asthma, particularly those with noneosinophilic inflammation, the disease remains uncontrolled. This trial evaluated the efficacy and safety of tezepelumab (AMG 157/MEDI9929), a human monoclonal antibody specific for the epithelial-cell–derived cytokine thymic stromal lymphopoietin (TSLP), in patients whose asthma remained uncontrolled despite treatment with long-acting beta-agonists and medium-to-high doses of inhaled glucocorticoids.
Infections and respiratory tract disease as risk factors for idiopathic inflammatory myopathies: a population-based case<b>–</b>control study
Authors: John Svensson, Marie Holmqvist, Ingrid E Lundberg, Elizabeth V Arkema
Journal: Annals of the Rheumatic Diseases (2017)

To investigate the association between infection or respiratory tract disease and future risk of developing idiopathic inflammatory myopathy (IIM).A case-control study was performed using Swedish nationwide registers. Adults with newly diagnosed IIM were identified (2002-2011) from the National Patient Register (NPR) and the Swedish Rheumatology Register (n=957). Controls were matched by age, sex and place of residence (n=9476). Outpatient visits and hospitalisations preceding IIM diagnosis indicating infection or respiratory disease were identified from NPR. Conditional logistic regression models were used to calculate OR and 95% CI. Sensitivity analyses were performed by varying the exposure definition, adjusting for previous healthcare consumption and excluding individuals with connective tissue disease, IIM lung phenotype or IIM-associated cancer.Preceding infections were more common in IIM cases compared with controls (13% vs 9%) and were associated with an increased risk of IIM (OR 1.5, 95% CI 1.2 to 1.9). Gastrointestinal and respiratory tract infections were associated with an increased risk of IIM while cutaneous infections were not.Preceding respiratory tract disease was present in 10% of IIM cases and 4% of controls (OR 2.3, 95% CI 1.8 to 3.0). Both upper and lower respiratory tract diseases were associated with an increased risk of IIM.Variations in exposure and outcome definitions did not greatly affect the results.Infections and respiratory tract diseases are associated with an increased risk of IIM which suggests that the triggering of the immune system may take place outside the skeletal muscle.
がん治療:c‐FOSおよびDUSP1のターゲッティングはBCR‐ABL白血病でチロシンキナーゼ阻害剤に対する内因性耐性を消失させる
Authors: Kesarwani Meenu, Kincaid Zachary, Gomaa Ahmed, Huber Erika, Rohrabaugh Sara, Siddiqui Zain, Bouso Muhammad F, Komurov Kakajan, Mulloy James C, Cancelas Jose A, Grimes H Leighton, Azam Mohammad, Latif Tahir, Xu Ming
Journal: Nature Medicine (2017)
Different glucosamine sulfate products generate different outcomes on osteoarthritis symptoms
Authors: Jean-Yves L Reginster, Olivier Bruyere, Cyrus Cooper
Journal: Annals of the Rheumatic Diseases (2017)

Runhaar and colleagues1 produced an elegant meta-analysis of various glucosamine-containing products in knee and hip osteoarthritis (OA), based on individual patient data (IPD). Although they were able to access and analyse only 5 out 21 eligible studies, their results are in agreement with most glucosamine meta-analyses in OA: glucosamine products other than prescription crystalline glucosamine sulfate are not effective in hip or knee OA pain and function.

Such results, as acknowledged by the Authors, had already been demonstrated in several previous and more comprehensive meta-analyses, including a dedicated Cochrane Review2 and a recent effort by Eriksen et al 3 specifically investigating possible differences in efficacy among glucosamine products. Indeed, glucosamine exists in different forms for pharmaceutical use, as extensively reviewed by Altman.4 Among these, glucosamine hydrochloride (used in three out of …
Abstract #2436: Microarray analysis of the expression levels of molecular components of relevant signaling pathways in response to FUra/IFN-gamma treatment protocols in human colon carcinoma cell lines
Authors: Mohammad Aziz, J DeVecchio, T Jani, K Peters, T Mazumdar, A Sarkar, J Houghton
Journal: Cancer Research (2009)

Colon carcinoma is the third largest cause of death in United States. 5-Fluorouracil (FUra)-based chemotherapy has contributed significantly in improving the prognosis of this disease. Earlier studies performed in our laboratories have established the significant advantage of using FUra/ Leucovorin (LV) + IFN-gamma in obtaining selective and synergistic therapeutic action. In the current study, five different colon carcinoma cell lines (RKO, HT29, GC3, HCT8 and HCT116) were treated with different combinations of FUra/LV and IFN-gamma. A folate-based thymidylate synthase inhibitor (BGC9331) was also utilized in HCT116 cells that induced DNA damage in contrast to FUra/LV, which induced RNA mediated damage. All cell lines were treated for 24 hr and total RNA was isolated after harvesting the cells. All reactions were carried out in triplicate. Total RNA isolated from treated and control cell lines was used for carrying out Illumina cDNA microarray analysis (RF-8). The results obtained were analyzed using Beadstudio software available from Illumina (Gene Expression Analysis module). The data obtained were initially analyzed using Cluster analysis dendrograms to confirm the groups and subgroups of cell lines with different treatment designs. The data were validated using all four clustering metrics: Correlation, Absolute Correlation, Manhattan and Euclidian. Any outlier groups were eliminated from further analysis. Scatter analysis was used to determine genes that were significantly altered in their expression levels in response to a particular drug treatment or in combination. Bar plot analysis was conducted to visualize the change in expression level of a particular gene in response to different treatments in different cell lines. Of specific interest was that a significant reduction in levels of the thymidylate synthase gene expression was detected in response to IFN-gamma. The difference was most pronounced in RKO cells. Similarly other genes of interest are currently being studied individually including those known to be involved in the synergistic interaction between FUra, LV and IFN-gamma. We are also elucidating the differential expression of sets of genes known to be involved in important signaling pathways including Fas, Wnt and Hedgehog as well as elucidating gene signature(s) that will differentiate DNA damage (toxic to colon cancer cells) from RNA damage (that initiates GI toxicity). It is anticipated that these studies will improve our understanding of molecular targets for FUra-based therapy in colon cancer and will aid in elucidating novel drug targets that will be more effective and selective for colon cancer therapy. Supported by NCI awards CA32613 and CA108929   Citation Information:  In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 2436.
Enhancing diversity in the hematology biomedical research workforce: A mentoring program to improve the odds of career success for early stage investigators
Authors: Betty S. Pace, Levi H. Makala, Rita Sarkar, Li Liu, Mayuko Takezaki, Narla Mohandas, Glorias Dixon, Ellen M. Werner, Donna B. Jeffe, Treva K. Rice, Nita J. Maihle, Juan González
Journal: American Journal of Hematology (2017)
Medical informatics
Authors: J. Sims
Journal: BMJ (1998)

If you have not yet heard of medical informatics then expect to do so repeatedly in the future. As medical knowledge continues to expand rapidly, as the demands for more efficient coordination of patient data become paramount, and as the pressures for improved practice and application of evidence based medicine increase, medical informatics will have increasing influence in our working lives as clinicians. Recent white papers have highlighted the need for improved organisation and communication of health information and have offered solutions.(1)(2) Medical informatics is at the centre of the overall objectives, linking such areas as knowledge management, guidance on best practice, education of professionals and the public, and the use of new communication and computer technologies. The growing emphasis on the development, collation, and delivery of information in health care means increasing opportunities for clinicians from all specialties to become involved. ### Role models for the budding informatician
Analysis of the prophages carried by human infecting isolates provides new insight into the evolution of Group B Streptococcus species
Authors: N. van der Mee-Marquet, S.M. Diene, L. Barbera, L. Courtier-Martinez, L. Lafont, A. Ouachée, A.-S. Valentin, S. Dos Santos, R. Quentin, P. François
Journal: Clinical Microbiology and Infection (2017)