tbuckley/cabot-search huggingface dataset:
Multiple common variants for celiac disease influencing immune gene expression
Authors: Patrick C A Dubois, Gosia Trynka, Lude Franke, Karen A Hunt, Jihane Romanos, Alessandra Curtotti, Alexandra Zhernakova, Graham A R Heap, Róza Ádány, Arpo Aromaa, Maria Teresa Bardella, Leonard H van den Berg, Nicholas A Bockett, Emilio G de la Concha, Bárbara Dema, Rudolf S N Fehrmann, Miguel Fernández-Arquero, Szilvia Fiatal, Elvira Grandone, Peter M Green, Harry J M Groen, Rhian Gwilliam, Roderick H J Houwen, Sarah E Hunt, Katri Kaukinen, Dermot Kelleher, Ilma Korponay-Szabo, Kalle Kurppa, Padraic MacMathuna, Markku Mäki, Maria Cristina Mazzilli, Owen T McCann, M Luisa Mearin, Charles A Mein, Muddassar M Mirza, Vanisha Mistry, Barbara Mora, Katherine I Morley, Chris J Mulder, Joseph A Murray, Concepción Núñez, Elvira Oosterom, Roel A Ophoff, Isabel Polanco, Leena Peltonen, Mathieu Platteel, Anna Rybak, Veikko Salomaa, Joachim J Schweizer, Maria Pia Sperandeo, Greetje J Tack, Graham Turner, Jan H Veldink, Wieke H M Verbeek, Rinse K Weersma, Victorien M Wolters, Elena Urcelay, Bozena Cukrowska, Luigi Greco, Susan L Neuhausen, Ross McManus, Donatella Barisani, Panos Deloukas, Jeffrey C Barrett, Paivi Saavalainen, Cisca Wijmenga, David A van Heel
Journal: Nature Genetics (2010)
Neoadjuvant Treatment of Regional Stage IIIB Melanoma With High-Dose Interferon Alfa-2b Induces Objective Tumor Regression in Association With Modulation of Tumor Infiltrating Host Cellular Immune Responses
Authors: Stergios J. Moschos, Howard D. Edington, Stephanie R. Land, Uma N. Rao, Drazen Jukic, Janice Shipe-Spotloe, John M. Kirkwood
Journal: Journal of Clinical Oncology (2006)

Purpose Adjuvant high-dose interferon-alfa-2b (HDI) improves disease-free and overall survival in patients with high-risk melanoma. However, its mechanism of action is largely unknown. Therefore, HDI was investigated in the neoadjuvant setting to assess clinical and pathologic responses after 4 weeks of HDI and to perform immunohistochemical evaluation of immune cell subsets and melanoma-associated antigens. Patients and Methods Patients with palpable regional lymph node metastases from melanoma (American Joint Committee on Cancer stage IIIB-C) underwent surgical biopsy at study entry and then received standard intravenous HDI (20 million units/m 2 , 5 days per week) for 4 weeks followed by complete lymphadenectomy and standard maintenance subcutaneous HDI (10 million units/m 2 3 times per week) for 48 weeks. Biopsy samples were obtained before and after intravenous HDI and subjected to immunohistochemical analysis as well as routine pathologic study. Results Twenty patients were enrolled, and biopsy samples were informative for 17. Eleven patients (55%) demonstrated objective clinical response, and 3 patients (15%) had complete pathologic response. At a median follow-up of 18.5 months (range, 7 months to 50 months) 10 patients had no evidence of recurrent disease. Clinical responders had significantly greater increases in endotumoral CD11c + and CD3 + cells and significantly greater decreases in endotumoral CD83 + cells compared with nonresponders. No changes in the expression of melanoma-associated lineage antigens, tumor cell proliferation, angiogenesis, or apoptosis were evident. Conclusion Neoadjuvant HDI is highly effective for the treatment of palpable stage IIIB-C melanoma, and the findings of this study implicate an indirect immunomodulatory mechanism rather than a direct antitumor mechanism.
Socioeconomic status and cancer survival.
Authors: D F Cella, E J Orav, A B Kornblith, J C Holland, P M Silberfarb, K W Lee, R L Comis, M Perry, R Cooper, L H Maurer
Journal: Journal of Clinical Oncology (1991)

Survival data from eight Cancer and Leukemia Group B (CALGB) protocols were examined for patients with lung cancer (N = 961), multiple myeloma (N = 577), gastric cancer (N = 231), pancreatic cancer (N = 174), breast cancer (N = 87), and Hodgkin's disease (N = 58). After accounting for differences in survival rate attributable to type of cancer, initial performance status, age, and 14 other protocol-specific prognostic indicators, the additional predictive value of socioeconomic status (SES) was evaluated. Race (white v non-white) was not a significant predictor of survival time, but income and education were. People with lower annual incomes (below $5,000 per year in the years 1977 to 1981) and those with lower educational level (grade school only) showed survival times significantly shorter than those with higher income or education, respectively. These survival differences were associated with, but could not be fully explained by, severity of disease at initial presentation. SES continued to exert a small but significant impact on cancer survival, even after controlling for all known prognostic variables. Economically and educationally disadvantaged cancer patients may require treatment programs that include education about treatment and compliance, even after an initial diagnosis is made and treatment is initiated. Because SES is related to survival independent of all known prognostic variables, it should be included in the data bases of clinical trial groups to provide a more accurate test of the effectiveness of new therapies.
(2) Rothmund-Thomson syndrome
Authors: J.A. Cotterill
Journal: British Journal of Dermatology (1987)

Journal Article (2) Rothmund‐Thomson syndrome Get access J.A. Cotterill J.A. Cotterill The General Infirmary at Leeds Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 117, Issue s32, 1 June 1987, Pages 46–47, https://doi.org/10.1111/j.1365-2133.1987.tb12043.x Published: 01 June 1987
Computational Methods in Drug Discovery
Authors: Gregory Sliwoski, Sandeepkumar Kothiwale, Jens Meiler, Edward W. Lowe
Journal: Pharmacological Reviews (2013)

Computer-aided drug discovery/design methods have played a major role in the development of therapeutically important small molecules for over three decades. These methods are broadly classified as either structure-based or ligand-based methods. Structure-based methods are in principle analogous to high-throughput screening in that both target and ligand structure information is imperative. Structure-based approaches include ligand docking, pharmacophore, and ligand design methods. The article discusses theory behind the most important methods and recent successful applications. Ligand-based methods use only ligand information for predicting activity depending on its similarity/dissimilarity to previously known active ligands. We review widely used ligand-based methods such as ligand-based pharmacophores, molecular descriptors, and quantitative structure-activity relationships. In addition, important tools such as target/ligand data bases, homology modeling, ligand fingerprint methods, etc., necessary for successful implementation of various computer-aided drug discovery/design methods in a drug discovery campaign are discussed. Finally, computational methods for toxicity prediction and optimization for favorable physiologic properties are discussed with successful examples from literature.
Clinical Observations on the Subcutaneous Ligature of Varix and Varicocele
Authors: J. Duncan
Journal: BMJ (1881)

iFNTLEM'hl-I show you to-day a case of varix, which may serve as a text for some remarks on subcutaneous ligature.Whe n the patient was admitted to the infirmary, his leg was much swollen, the veins stood out like large tortuous knotted cords, and an ulcer lay above the ankle.There remain now only a scar and its surrounding pigmentationThe treatment has been rest, with the leg elevated, appropriate dressing to the ulcer, and subcutaneous ligature of the veins.To thc last I desire to draw your attention.Some years ago I pointed out a mode of applying Dittel's elastic ligature to the treatmcnt of nievus.It consists in the passage of the ligature round the n.evus subcu- taneously.With the aid of whipcord this can be easily accomplished, and it has the effect of cutting off the tumour from all blood-supply, except that which may reach it through the skin.I have since em- ployed this method occasionally in ,suitable cases ; not often, because other forms of treatment are usually more appropriate.Thus, when a scar is unseemly, electrolysis is safe and certain; when the cicatrix is of little moment, external ligature and excision are speedy and effectual.But in very large nzevi in very young children, subcutaneous ligature is less tedious than electrolysis, less dangerous and disfiguring than other operations.To appreciate the advantages of subcutaneous surgery, it is only necessary to compare a bruise with a bruised wound, a simple fracture with a compound.Antiseptics have done much to minimise the ,difference, but they are themselves irritants, and their use is subject to manipulative errors.The result, therefore, must be more perfect if, by operating through a wound, small and speedily healed, we can at once avoid the contact of antiseptics with a rawv surface, and prevent the -admission of septic influences.Mly experience with the elastic ligature is in this respect instructive.The ends of the India-rubber thread must be left out that it may be tightened as required, and withdrawn when it has cut its way through.The operation is not, therefore, truly subcutaneous, because there is a persistent possibility of the entrance of putrefactive influences to the injured tissue.In some cases, pretty severe suppuration occurred; and although this inflammatory action is undoubtedly beneficial in ob- literating the noevus, it contains an element of danger, especially in connection with the imperfect drainage, which, under the circumstances, cannot be avoided.In later operations, I employed the usual antiseptic precautions with marked advantage.If, then, the ligature be entirely
Acute phase response in familial Mediterranean fever
Authors: C Korkmaz
Journal: Annals of the Rheumatic Diseases (2002)

To test the hypothesis that not all acute phase reactants respond in the same way during attacks of familial Mediterranean fever (FMF) and that there is a subclinical acute phase response (APR) in a proportion of patients during the interval between attacks.Blood and urine samples were obtained from 49 patients with FMF during an attack and the attack-free period that followed, to test for erythrocyte sedimentation rate, C reactive protein (CRP), fibrinogen, white blood cell count, platelet count, factor VIII related antigen, haptoglobin, protein electrophoresis, ferritin, proteinuria, and haematuria. Control groups comprised 29 patients with juvenile idiopathic arthritis, 10 patients with various infectious diseases, and 19 healthy subjects.A marked APR was seen during the FMF attacks which was comparable with that obtained in the diseased control groups. CRP was the only acute phase protein that was raised during all attacks. Neither thrombocytosis nor an increase in ferritin levels (except one) was noted in any attack. Serum albumin levels remained unchanged. In two thirds of the patients with FMF a continuing APR was seen in between the attacks.Platelet, ferritin, and albumin responses are not part of the significant APR seen during short lived attacks of FMF, and inflammation continues in about two thirds of the patients during an attack-free period.
Addition of sorafenib versus placebo to standard therapy in patients aged 60 years or younger with newly diagnosed acute myeloid leukaemia (SORAML): a multicentre, phase 2, randomised controlled trial
Authors: Christoph Röllig, Hubert Serve, Andreas Hüttmann, Richard Noppeney, Carsten Müller-Tidow, Utz Krug, Claudia D Baldus, Christian H Brandts, Volker Kunzmann, Hermann Einsele, Alwin Krämer, Kerstin Schäfer-Eckart, Andreas Neubauer, Andreas Burchert, Aristoteles Giagounidis, Stefan W Krause, Andreas Mackensen, Walter Aulitzky, Regina Herbst, Mathias Hänel, Alexander Kiani, Norbert Frickhofen, Johannes Kullmer, Ulrich Kaiser, Hartmut Link, Thomas Geer, Albert Reichle, Christian Junghanß, Roland Repp, Frank Heits, Heinz Dürk, Jana Hase, Ina-Maria Klut, Thomas Illmer, Martin Bornhäuser, Markus Schaich, Stefani Parmentier, Martin Görner, Christian Thiede, Malte von Bonin, Johannes Schetelig, Michael Kramer, Wolfgang E Berdel, Gerhard Ehninger
Journal: The Lancet Oncology (2015)
Treatment of Relapsed Wilms’ Tumor With High-Dose Therapy and Autologous Hematopoietic Stem-Cell Rescue: The Experience at Children’s Memorial Hospital
Authors: Andrew D. Campbell, Susan L. Cohn, Marleta Reynolds, Roopa Seshadri, Elaine Morgan, Grant Geissler, Alfred Rademaker, Maryann Marymount, John Kalapurakal, Paul R. Haut, Reggie Duerst, Morris Kletzel
Journal: Journal of Clinical Oncology (2004)

To investigate whether high-dose therapy with hematopoietic stem-cell rescue (HSCR) will improve survival for patients with relapsed Wilms' tumor.Thirteen children with relapsed Wilms' tumor were treated with one or two cycles of high-dose chemotherapy (HDT) followed by autologous HSCR. Twelve of 13 patients received reinduction chemotherapy before HDT and HSCR. The median age at diagnosis was 4.8 years, and the median time to relapse was 12 months. The histology was favorable in 12 of 13 patients. The ablative regimens included: (1) thiotepa (TT)/cyclophosphamide (CTX)/carboplatin (CP; n = 2); (2) TT/CTX (n = 5); (3) TT/etoposide (ETP; n = 1); and (4) CP/ETP/CTX (n = 1). Four patients received two cycles of HDT and HSCR. Cycle 1 consisted of CP/ETP/CTX, and melphalan/CTX were used in cycle 2.Seven of 13 patients are alive without evidence of disease, with a median follow-up of 30 months. The 4-year estimated event-free survival (EFS) rate is 60% (95% CI, 0.40 to 6.88), and the overall survival (OS) at 4 years is 73% (95% CI, 0.40 to 6.86). There was no transplant-related mortality. All patients engrafted to an absolute neutrophil count 500/microL at a median of 13 days (range, 8 to 62 days) and had an unsustained platelet count > 20.0 micro at a median of 16 days (range, 10 to 202 days).Our results suggest that HDT with HSCR is an effective treatment for patients with Wilms' tumor who experience relapse.
Multiple Polycyclic Brownish to Reddish Macules on the Skin in an Infant
Authors: Despoina Papathemeli, Klaus Mohnike, Andreas Ambach
Journal: JAMA Dermatology (2015)

A 6-month-old daughter of nonconsanguineous parents was seen with multiple polycyclic dark to less dark brown, partly livid shimmeringmacules, which covered large areas of the back, neck, buttocks, and lower extremities (Figure, A). According to hermother, new lesions had appeared during the past weeks on the shoulders. Physical examination revealed coarse facial features, hepatomegaly (7 cm below the costal arch), distinctive lumbarkyphosis, andmuscularhypotoniacomparedwithher twinbrother.Dermoscopyshowed faint clouds of nonhomogeneously distributed light brown pigment. Clinical picture A
Long-term intake of dietary fat and risk of ulcerative colitis and Crohn's disease
Authors: Ashwin N Ananthakrishnan, Hamed Khalili, Gauree G Konijeti, Leslie M Higuchi, Punyanganie de Silva, Charles S Fuchs, Walter C Willett, James M Richter, Andrew T Chan
Journal: Gut (2013)

<h3>Introduction</h3> Dietary fats influence intestinal inflammation and regulate mucosal immunity. Data on the association between dietary fat and risk of Crohn9s disease (CD) and ulcerative colitis (UC) are limited and conflicting. <h3>Methods</h3> We conducted a prospective study of women enrolled in the Nurses' Health Study cohorts. Diet was prospectively ascertained every 4 years using a validated semi-quantitative food frequency questionnaire. Self-reported CD and UC were confirmed through medical record review. We examined the effect of energy-adjusted cumulative average total fat intake and specific types of fat and fatty acids on the risk of CD and UC using Cox proportional hazards models adjusting for potential confounders. <h3>Results</h3> Among 170 805 women, we confirmed 269 incident cases of CD (incidence 8/100 000 person-years) and 338 incident cases of UC (incidence 10/100 000 person-years) over 26 years and 3 317 338 person-years of follow-up. Cumulative energy-adjusted intake of total fat, saturated fats, unsaturated fats, n-6 and n-3 polyunsaturated fatty acids (PUFAs) were not associated with risk of CD or UC. However, greater intake of long-chain n-3 PUFAs was associated with a trend towards lower risk of UC (HR 0.72, 95% CI 0.51 to 1.01). In contrast, high long-term intake of trans-unsaturated fatty acids was associated with a trend towards an increased incidence of UC (HR 1.34, 95% CI 0.94 to 1.92). <h3>Conclusions</h3> A high intake of dietary long-chain n-3 PUFAs may be associated with a reduced risk of UC. In contrast, high intake of trans-unsaturated fats may be associated with an increased risk of UC.
Ulcers on an Infant’s Sacrum
Authors: Melissa M. Mauskar, Dominique C. Pichard, Scott A. Norton
Journal: JAMA Pediatrics (2015)

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Pulmonary Langerhans' Cell Granulomatosis (Histiocytosis X)
Authors: P Soler, M Kambouchner, D Valeyre, A J Hance
Journal: Annual Review of Medicine (1992)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), emerged in China in December 2019 and quickly spread around the globe, killing more than 4 million people and causing a severe economic crisis. ...Read More
Trogocytic intercellular membrane exchanges among hematological tumors
Authors: Joel LeMaoult, Julien Caumartin, Marina Daouya, Magdalena Switala, Vera Rebmann, Bertrand Arnulf, Edgardo D Carosella
Journal: Journal of Hematology & Oncology (2015)

Trogocytosis is the transfer of plasma membrane fragments and the molecules they contain between one donor and one acceptor/acquirer cell. Through trogocytosis, acceptor cells temporarily display and use cell-surface molecules they do not express themselves, but borrow from other cells. Here, we investigated whether liquid tumors possessed a trogocytic capability, if immune escape molecules could be acquired by tumor cells, transferred between cells of the same tumor, and if this could benefit the tumor as a whole.For this, we investigated trogocytosis in hematological cell lines and freshly isolated hematological tumor cells. We demonstrate that hematological tumor lines possess a trogocytic capability that allows them to capture membranes that contain the immune-inhibitory molecule HLA-G from allogeneic as well as from autologous sources. We further show that freshly isolated hematological tumor cells also possess these capabilities. This work reports for the first time the trogocytic capabilities of liquid tumor cells and introduces the notion of immune escape strategy sharing among tumor cells through trogocytosis of membrane-bound immune-inhibitory molecules.
Pembrolizumab for Treatment of Patients with Advanced or Unresectable Melanoma
Authors: Ryan J. Sullivan, Keith T. Flaherty
Journal: Clinical Cancer Research (2015)

From Coley's toxin to combination immune checkpoint inhibition, strategies to activate the immune system and generate anticancer immunity have been ongoing for well over a century. Over the past decade, the so-called immune checkpoint inhibitors, generally monoclonal antibodies that target key regulators of T-cell activation, emerged as the most effective immune-targeted agents. Pembrolizumab is the first anti-programmed death 1 (PD-1) antibody approved by the FDA for the treatment of metastatic melanoma. With responses seen in 25% to 40% of patients, depending on dose and setting (i.e., before or after ipilimumab), pembrolizumab specifically and anti-PD-1 antibodies generally are revolutionizing the treatment of melanoma. However, in the setting of other recent advances in the field, a number of practical issues are emerging that need to be addressed to optimize the care of patients with melanoma. First, the optimal sequencing of therapy (first-line immunotherapy over molecular targeted therapy, ipilimumab versus pembrolizumab as initial immune checkpoint inhibitor) is unknown and must be evaluated through randomized trials. Second, there is a strong rationale to combine immune checkpoint inhibitors (i.e., anti-PD-1 with ipilimumab) and to combine immune therapies with targeted therapy agents, so determining whether combination therapy is better than direct sequencing is another critical issue that needs to be addressed in carefully carried out studies.
Molecular diagnostics of psoriasis, atopic dermatitis, allergic contact dermatitis and irritant contact dermatitis
Authors: M. Kamsteeg, P.A.M. Jansen, I.M.J.J. Van Vlijmen-Willems, P.E.J. Van Erp, D. Rodijk-Olthuis, P.G. Van Der Valk, T. Feuth, P.L.J.M. Zeeuwen, J. Schalkwijk
Journal: British Journal of Dermatology (2009)

Journal Article Molecular diagnostics of psoriasis, atopic dermatitis, allergic contact dermatitis and irritant contact dermatitis Get access M. Kamsteeg, M. Kamsteeg Department of Dermatology, Search for other works by this author on: Oxford Academic Google Scholar P.A.M. Jansen, P.A.M. Jansen Department of Dermatology,Nijmegen Centre for Molecular Life Sciences, and Search for other works by this author on: Oxford Academic Google Scholar I.M.J.J. Van Vlijmen‐Willems, I.M.J.J. Van Vlijmen‐Willems Department of Dermatology, Search for other works by this author on: Oxford Academic Google Scholar P.E.J. Van Erp, P.E.J. Van Erp Department of Dermatology, Search for other works by this author on: Oxford Academic Google Scholar D. Rodijk‐Olthuis, D. Rodijk‐Olthuis Department of Dermatology, Search for other works by this author on: Oxford Academic Google Scholar P.G. Van Der Valk, P.G. Van Der Valk Department of Dermatology, Search for other works by this author on: Oxford Academic Google Scholar T. Feuth, T. Feuth Department of Epidemiology, Biostatistics and Health Technology Assessment, Radboud University Nijmegen Medical Centre, PO Box 9101, 6500 HB Nijmegen, the Netherlands Search for other works by this author on: Oxford Academic Google Scholar P.L.J.M. Zeeuwen, P.L.J.M. Zeeuwen Department of Dermatology,Nijmegen Centre for Molecular Life Sciences, and Search for other works by this author on: Oxford Academic Google Scholar J. Schalkwijk J. Schalkwijk Department of Dermatology,Nijmegen Centre for Molecular Life Sciences, and Joost Schalkwijk. E‐mail: j.schalkwijk@ncmls.ru.nl Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 162, Issue 3, 1 March 2010, Pages 568–578, https://doi.org/10.1111/j.1365-2133.2009.09547.x Published: 01 March 2010