tbuckley/cabot-search huggingface dataset:
Abstract 4445: Defining a pipeline to use next generation sequencing for genetic testing in hereditary cancer
Authors: Conxi Lazaro, Adriana López-Doriga, Ester Castellsagué, Jesús del Valle, Eva Tornero, Víctor Moreno, Marta Pineda, Sara González, Lídia Feliubadaló, Gabriel Capellá
Journal: Cancer Research (2012)

Abstract One of the emerging Next Generation Sequencing (NGS) applications is amplicon resequencing, which can be applied to screen for mutations in defined genes with diagnostic value. However, in this scenario, methods and protocols are still poorly developed. To address this need, we have established a study workflow that integrates experimental work and bioinformatics analyses. Our Unit of Genetic Testing for Hereditary Cancer is using kits for Multiplex Amplification of Specific Targets for Resequencing (MASTR) from the Multiplicom Company in order to generate highly homogeneous gene specific libraries for point mutation detection. Currently we have completed a proof of concept for the Breast Cancer Susceptibility kit (BRCA1 and BRCA2). We analysed a training set of 267 variants in 28 samples, and a validation set of 137 variants in 14 samples. Results from the GS Junior were combined with those resulting from the analysis of the homopolymer sequences in each gene. Sanger confirmation was performed in all the identified DNA variants. Low coverage (&amp;lt;=38x; 1.2% of the target) regions were also Sanger sequenced. The bioinformatics analysis combined the Variant Identification Pipeline software (VIP, De Shrijver, JM et al. BMC Bioinformatics 2010) together with a set of in-house designed R scripts in order to obtain both a Coverage Report as well as a Variant Calling Report. The first training set of 28 samples showed a sensitivity and specificity of 97.6% and 100%, respectively. After the improvement of the kit and the analysis pipeline, the validation set of 14 samples demonstrated an excellent specificity and sensitivity of the pipeline (100% both). In conclusion, we showed that a combined algorithm both at the experimental as well as at the bioinformatics level allows the interpretation of NGS results with a good specificity and sensitivity for diagnosis purposes. We are now finishing our proof of concept for genes responsible for Hereditary Colorectal Cancer, results will be presented at the meeting. This work has been supported by Spanish Ministry of Science and Innovation, Carlos III Health Institute ISCIII (RD06/0020/1050; RD06/0020/1051; PI10/01422; CA10/01474); The Government of Catalonia (2009SGR290) and The Spanish Association Against Cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4445. doi:1538-7445.AM2012-4445
Disappointing article, not disappointing biotech
Authors: Fredric J Cohen
Journal: BMJ (2005)

EDITOR—Joppi et al's critique and not biotech itself is disappointing.1

The authors classified most of the biotech drugs (24/61) as “copycat or me too products”—pejorative terms intended to cast prejudicial doubt on a drug's value. I am familiar with one of the drugs on the copycat list, teriparatide (rhPTH1-34, Forteo, Eli Lilly), a treatment for osteoporosis. I helped …
Alterations in the adenosine metabolism and CD39/CD73 adenosinergic machinery cause loss of Treg cell function and autoimmunity in ADA-deficient SCID
Authors: Aisha V. Sauer, Immacolata Brigida, Nicola Carriglio, Raisa Jofra Hernandez, Samantha Scaramuzza, Daniela Clavenna, Francesca Sanvito, Pietro L. Poliani, Nicola Gagliani, Filippo Carlucci, Antonella Tabucchi, Maria Grazia Roncarolo, Elisabetta Traggiai, Anna Villa, Alessandro Aiuti
Journal: Blood (2011)
Sézary syndrome in a young man with severe atopic dermatitis
Authors: None VAN HASELEN, None TOONSTRA, None PREESMAN, None VAN DER PUTTE, None BRUIJNZEEL-KOOMEN, None VAN VLOTEN
Journal: British Journal of Dermatology (1999)

Sézary syndrome (SS) is a rare cutaneous T-cell lymphoma. SS usually develops de novo. We describe a 23-year-old man with a proven history of severe atopic dermatitis since childhood, who developed SS. This case contributes to the discussion about the possibility of a relationship between inflammatory dermatitis, atopy and subsequent SS. We provide criteria that should be fulfilled to define such an association.
ADAPTIVE ITERATIVE DOSE REDUCTION IS ASSOCIATED WITH SIGNIFICANT REDUCTION IN TOTAL AND COMPUTED TOMOGRAPHY CORONARY ANGIOGRAPHY RADIATION EXPOSURE AND IMPROVED IMAGE QUALITY, COMPARED TO TRADITIONAL FILTERED BACKPROJECTION ON 320-MULTIDETECTOR COMPUTED TOMOGRAPHY
Authors: Anum Aslam, Usman Khokhar, Michael Cortegiano, Michael Poon, Szilard Voros
Journal: Journal of the American College of Cardiology (2013)
Effects of a PAF antagonist, Y-24180, on bronchial hyperresponsiveness in patients with asthma.
Authors: S Hozawa, Y Haruta, S Ishioka, M Yamakido
Journal: American Journal of Respiratory and Critical Care Medicine (1995)

The involvement of platelet-activating factor (PAF) in bronchial hyperresponsiveness (BHR) in bronchial asthma has been controversial. To determine whether PAF is involved in BHR in humans, we carried out a randomized, double-blind, placebo-controlled, two-phase cross-over study on the effects of Y-24180, a potent, specific, orally active PAF receptor antagonist, on BHR to methacholine in patients with asthma. The subjects were 13 patients with extrinsic stable asthma. The provocative concentration of methacholine producing a 20% fall in FEV1 (PC20-FEV1) was measured as an index of BHR. Y-24180 (20 mg twice a day) or a placebo was orally administered for 2 wk, respectively. At the time of cross-over from the first treatment regimen to the second regimen, administration of the test drug was suspended for 2 wk. The methacholine challenge test was performed four times, before and after the first treatment period and before and after the second treatment period. Compared with the placebo, Y-24180 significantly (p = 0.005) improved the PC20-FEV1 value without carryover effect and period effect by analysis of variance. These results suggest that PAF is an important mediator involved in the BHR of bronchial asthma in humans.
RENAL ARTERY PLAQUE COMPOSITION IS ASSOCIATED WITH CHANGE IN RENAL PERFUSION FOLLOWING RENAL ARTERY STENTING
Authors: Anand Prasad, Patrick Hu, Nayab M. Zafar, Anita N. Majabo, Kelly A. Enright, Vachaspathi Palakodeti, Sotirios Tsimikas, Ehtisham Mahmud
Journal: Journal of the American College of Cardiology (2010)
Tumor cell adhesion and migration supported by interaction of a receptor-protease complex with its inhibitor
Authors: Edgar G. Fischer, Matthias Riewald, Hui-Yu Huang, Yohei Miyagi, Yoshinobu Kubota, Barbara M. Mueller, Wolfram Ruf
Journal: Journal of Clinical Investigation (1999)

Tissue factor (TF), the cell-surface receptor for coagulation factor VIIa, supports metastasis. Equally important for this process are (a) interactions of the TF cytoplasmic domain, which binds the mobility-enhancing actin-binding protein 280, and (b) the formation of a proteolytically active TF-VIIa complex on the tumor cell surface. In primary bladder carcinoma cells, we find that this complex localizes to the invasive edge, in proximity to tumor-infiltrating vessels that stain intensely for TF pathway inhibitor (TFPI-1), the major inhibitor of the protease activity of the complex. In culture, binding of VIIa to TF-expressing tumor cells is sufficient to allow cell adhesion, migration, and intracellular signaling on immobilized TFPI-1. Immobilized heparin, a mimic for extracellular matrix–associated proteoglycans, binds physiological concentrations of TFPI-1 in a conformation that supports TF-VIIa–dependent cell adhesion. Consistent with a functional role of TFPI-1 in complex extracellular matrices, we show that TF cooperates with integrin-mediated adhesion and migration on composite matrices that contain ligands for both integrins and the TF-VIIa complex. This study thus provides evidence for a novel mechanism of protease-supported migration that is independent of proteolytic matrix degradation but rather involves protease-dependent bridging of TF's extracellular domain to an ECM-associated inhibitor.
Mild and moderate dyskaryosis: can women be selected for colposcopy on the basis of social criteria?
Authors: D. J. Anderson, G. M. Flannelly, H. C. Kitchener, P. M. Fisher, E. M. Mann, M. K. Campbell, A. Templeton
Journal: BMJ (1992)

To describe the distribution of cervical intraepithelial neoplasia grades among women with mild and moderate dyskaryosis after a single cervical smear and to determine whether social criteria could help identify women who are at increased risk of grade II or III disease.Cross sectional analysis within a randomised prospective study. Subjects had a repeat smear, a colposcopic examination, and an excision biopsy of the transformation zone. In addition, women were asked to complete a social questionnaire.Colposcopy clinic, Aberdeen.228 women with a single smear test showing mild or moderate dyskaryosis.Histology, age, sexual and contraceptive history, cigarette smoking.159 (70%) women had cervical intraepithelial neoplasia grades II or III. Among current smokers the prevalence of grade II and III disease was higher in women who smoked greater than or equal to 20 cigarettes a day (84%) than among those who smoked less (66%; p less than 0.04). Women with more than one sexual partner also had a higher prevalence (75%) than women with only one partner (50%; p = 0.0028). Use of oral contraceptives and younger age were not significantly associated. The prevalence of grade II or III disease was up to 66% in the lower risk groups.Because of the high prevalence of cervical intraepithelial neoplasia grades II and III in both the high and the low risk groups social factors are not useful for selecting women with mild or moderate dyskaryosis for either early referral to colposcopy or cytological surveillance.
A cruel practice experienced
Authors: H Keszler
Journal: BMJ (1994)

The year was 1953, the place a small town in Bohemia. It was a beautiful, sunny Sunday in May. Suddenly three shots rang out from the attic of the surgeon's house. The first two in quick succession, the third about five seconds later. In the small county hospital preparations for surgery started only minutes later. By then a second nurse and an orderly were also heading for the hospital on their bicycles. The chief (and only fully qualified) surgeon arrived in his small car soon after the others and immediately proceeded to the surgical ward, where the resident and the general practitioner were already waiting for him. The emergency had not been caused by the shooting. The shots were fired from the attic by the surgeon's wife as a signal for the doctor to return immediately from his favourite pastime, hunting. The general practitioner told the surgeon about the patient's medical history and findings as well as his reasons for sending the patient to the hospital for surgery without delay. The resident added his own observations and basic laboratory …
Development and validation of a prognostic scoring system for patients with chronic myelomonocytic leukemia
Authors: Esperanza Such, Ulrich Germing, Luca Malcovati, José Cervera, Andrea Kuendgen, Matteo G. Della Porta, Benet Nomdedeu, Leonor Arenillas, Elisa Luño, Blanca Xicoy, Mari L. Amigo, David Valcarcel, Kathrin Nachtkamp, Ilaria Ambaglio, Barbara Hildebrandt, Ignacio Lorenzo, Mario Cazzola, Guillermo Sanz
Journal: Blood (2013)
Radiation-Induced Osteosarcoma and Papillary Carcinoma of the Thyroid
Authors: Adam Tonakie, Barry L. Shulkin, James C. Sisson, Gregory A. Yanik, Raymond J. Hutchinson
Journal: Clinical Nuclear Medicine (2005)

Purpose: This article describes a patient with dual radiation-induced malignancies after treatment of neuroblastoma. Materials and Methods: A 12-year-old boy with a history of neuroblastoma was treated with chemotherapy, I-131 MIBG, and radiotherapy at age 4. He was disease-free for 8 years, but then developed left shoulder pain resulting from osteosarcoma. A thyroid malignancy was discovered during the evaluation. Results: The patient was treated with thyroidectomy and then chemotherapy according to a Children's Cancer Group Study protocol. Conclusion: Radiation-induced sarcoma should be suspected whenever a patient who has received radiation several years previously presents with pain or swelling in the irradiated area.
Prevalences of diabetes and cardiovascular disease risk factors in Hindu Indian subcommunities in Tanzania.
Authors: K L Ramaiya, A B Swai, D G McLarty, R S Bhopal, K G Alberti
Journal: BMJ (1991)

OBJECTIVES--To seek differences in the prevalence of diabetes mellitus and other coronary heart disease risk factors, and to identify factors associated with these differences within a Hindu Indian community. DESIGN--Population based cross sectional survey. SETTING--Dar-es-Salaam, Tanzania. SUBJECTS--Of 20 Hindu subcommunities categorised by caste in Dar-es-Salaam, seven were randomly selected. 1147 (76.7%) of 1495 subjects aged 15 or over participated. MAIN OUTCOME MEASURES--Blood glucose concentrations (fasting and two hours after oral glucose loading), serum total cholesterol and serum triglyceride concentrations, blood pressure, and height and weight. RESULTS--The subcommunities differed substantially in socioeconomic characteristics and lifestyle. Overall, 9.8% of subjects (109/1113) had diabetes, 17.0% (189/1113) impaired glucose tolerance, 14.5% (166/1143) hypertension, and 13.3% (151/1138) were obese. The mean fasting blood glucose concentration was 4.9 mmol/l, the blood glucose concentration two hours after oral loading (75 g) 6.0 mmol/l, the total cholesterol concentration 4.9 mmol/l, the serum triglyceride concentration 1.4 mmol/l, and body mass index (weight/height: kg/m2) 24.3. Systolic and diastolic blood pressures were 121 and 77 mm Hg respectively. There were important intercommunity differences even after standardisation for age, sex, and body mass index--for example, in mean fasting blood glucose concentration (range 4.5 (Jains) to 5.9 mmol/l (Patels)), serum total cholesterol concentration (range 4.5 (Jains) to 6.2 mmol/l (Suthars)), systolic blood pressure (range 110 (Limbachias) to 127 mm Hg (Bhatias)), and prevalences of diabetes (range 3.4% (3/87 Limbachias) to 18% (20/111 Navnats)) and hypertension (range 5.7% (5/87 Limbachias) to 19.4% (43/222 Bhatias). Variables which showed significant linear correlation with subcommunity variations were entered into a multiple regression model. Intercommunity variations persisted. The Limbachia and Jain communities had the lowest prevalence of and mean values for coronary heart disease risk factors and the Bhatia and Patel communities had the highest. CONCLUSIONS--In this series intercommunity variations in disease and risk factors might have been related to genetic, dietary, socioeconomic, and lifestyle differences but could not be explained by the characteristics studied. Studies of Indian subcommunities are warranted to confirm and extend these descriptive findings and explore the genetic basis of diabetes. Communities of Indian origin should not be perceived as homogeneous.
ALOPECIA AND POLIOSIS OF THE EYELIDS
Authors: WILLIAM CAMPBELL POSEY
Journal: JAMA (1923)

A married woman, aged 37, a brunette, consulted me, Dec. 27, 1922, on account of a falling out of the eyelashes from the left upper lid. This process had not been accompanied by any inflammatory condition of the lid itself or by any loss of hair elsewhere on the body; its duration had been rather rapid, all the lashes disappearing in about four months, with the exception of those growing from the nasal quadrant, which remained several weeks longer than the rest. The patient's physician, Dr. Morris Flexner of Louisville, Ky., attributed the condition to a general asthenia following a miscarriage, three or four months preceding the loss of lashes. An examination of the blood made at the time showed hemoglobin, 85 per cent.; red blood cells, 4,040,000; leukocytes, 11,200; polymorphonuclear neutrophils, 87 per cent.; eosinophils, 3 per cent., and lymphocytes, 10 per cent. Urine examination and the Wassermann test
Treatment of acute mountain sickness by simulated descent: a randomised controlled trial.
Authors: P Bartsch, B Merki, D Hofstetter, M Maggiorini, B Kayser, O Oelz
Journal: BMJ (1993)

OBJECTIVE--To evaluate the therapeutic efficacy of a portable hyperbaric chamber for treatment of acute mountain sickness. DESIGN--Controlled randomised trial over two mountaineering seasons. SETTING--High altitude research laboratory at 4559 m above sea level. SUBJECTS--64 climbers with acute mountain sickness randomly allocated to different treatments. INTERVENTIONS--One hour of treatment in the hyperbaric chamber at a pressure of 193 mbar or 20 mbar as control or bed rest. MAIN OUTCOME MEASURES--Symptoms of acute mountain sickness before, immediately after, and 12 hours after treatment. Permitted intake of analgesic and antiemetic drugs in the follow up period. RESULTS--Treatment with 193 mbar caused greater relief of symptoms than did control treatment or bed rest. During the 12 hour follow up period intake of analgesics was similar (58-80% of subjects in each group). Symptom scores had improved in all subjects after 12 hours with no significant differences between groups. CONCLUSIONS--One hour of treatment with 193 mbar in a portable hyperbaric chamber, corresponding to a descent of 2250 m, leads to a short term improvement in symptoms of acute mountain sickness but has no beneficial long term effects attributable to pressurisation.
The threat of biological weapons--prophylaxis and mitigation
Authors: A. Flanagin
Journal: JAMA (1996)

Recent advances in molecular biology have important implications for human welfare. On the one hand, they help man to a deeper understanding of his own evolution and functioning as the most complex of life forms on earth . . . . On the other hand, molecular biology might be exploited for military purposes and result in a biological weapons race whose aim could well become the most efficient means for removing man from the planet. . . . My gravest concern is that similar scientific breakthroughs of a rather predictable kind will be made and their potential military significance exploited, so as to result in a transformation of current doctrine about unreliable biological weapons.’
Drug companies sue South African government over generics
Authors: P. Sidley
Journal: BMJ (2001)

More than 40 pharmaceutical companies, many of them the world's largest and most powerful companies, will be taking the South African government to court to try to stop it enacting legislation aimed at reducing the price of medicines for South Africans.

The Medicines and Related Substances Act of 1997 was fought strenuously by the multinational drug companies during its passage through parliament. As it was passed, the industry gave notice of its intention to have the law overturned, and in so doing effectively prevented the act coming into force.

Although the law also seeks to regulate the marketing and distribution of medicines in South Africa, it is seen largely as a test case, with international implications, for the use of parallel importing of cheaper drugs and generic substitution for brand name drugs.

The South African government is currently exploring changes to its Patents Act as a vehicle …
3D TEE During Catheter-Based Interventions
Authors: Francesco Fulvio Faletra, Giovanni Pedrazzini, Elena Pasotti, Stefano Muzzarelli, Maria Cristina Dequarti, Romina Murzilli, Susanne Anna Schlossbauer, Iveta Petrova Slater, Tiziano Moccetti
Journal: JACC. Cardiovascular imaging (2014)
Vancomycin-sensitive and vancomycin-resistant enterococcal infections in the ICU: attributable costs and outcomes
Authors: Robert K. Pelz, Pamela A. Lipsett, Sandra M. Swoboda, Marie Diener-West, Neil R. Powe, Roy G. Brower, Trish M. Perl, Janet M. Hammond, Craig W. Hendrix
Journal: Intensive Care Medicine (2002)
The United States Cover-up of Japanese Wartime Medical Atrocities: Complicity Committed in the National Interest and Two Proposals for Contemporary Action
Authors: Jing-Bao Nie
Journal: The American Journal of Bioethics (2006)

To monopolize the scientific data gained by Japanese physicians and researchers from vivisections and other barbarous experiments performed on living humans in biological warfare programs such as Unit 731, immediately after the war the United States (US) government secretly granted those involved immunity from war crimes prosecution, withdrew vital information from the International Military Tribunal for the Far East, and publicly denounced otherwise irrefutable evidence from other sources such as the Russian Khabarovsk trial. Acting in "the national interest" and for the security of the US, authorities in the US tramped justice and morality, and engaged in what the English common law tradition clearly defines as "complicity after the fact." To repair this historical injustice, the US government should issue an official apology and offer appropriate compensation for having covered up Japanese medical war crimes for six decades. To help prevent similar acts of aiding principal offender(s) in the future, international declarations or codes of human rights and medical ethics should include a clause banning any kind of complicity in any unethical medicine-whether before or after the fact-by any state or group for whatever reasons.
Alexander Pope (1688-1744): his spinal deformity and his doctors
Authors: J.M. Shneerson
Journal: European Respiratory Journal (2000)

s interesting account of Alexander Pope's spinal deformity [1] comments on the doctors who attended him, but, despite their eminence, none of them appears to have contributed any ideas or practical advice about how to assess or treat his condition.They may however have been aware of the remarkably modern views of a French physician, PETIT [2], who published a Thesis in France in 1723 which was translated into English in 1726.In this account he attributes breathlessness to the distortion of the spine which alters the disposition of the ribs and respiratory muscles, and to the smallness of the lungs.PETIT [2] also commented that the force of the heart was increased and that there was an obstruction in the capillary vessels of the substance of the lungs.This corresponds to the modern idea that it is the restriction of the pulmonary microcirculation, due to the reduction in lung volume and to hypoxic vasoconstriction, that contributes to right heart failure.PETIT [2] also mentioned the "heaviness and ill quality" of the blood that has its equivalents in the polycythaemia that arises because of increased erythropietin production in response to hypoxia.The physiological explanations of the cardiorespiratory consequences of scoliosis by PETIT [2] were remarkably in advance of others who attempted to explain the effects of spinal deformity [3] and gave Alexander Pope''s doctors the basis on which they could have formulated an approach to the treatment of his problems.