tbuckley/cabot-search huggingface dataset:
CT and D-dimer testing are overused in patients with suspected pulmonary embolism, US college says
Authors: Michael McCarthy
Journal: BMJ (2015)

Patients with suspected acute pulmonary embolism (PE) should be stratified based on their likelihood of having a PE before having a D-dimer test or computer tomography (CT), guidelines have said. 

New “best practice” guidelines from the clinical guidelines committee of the American College of Physicians were published online on 28 September.1 “With the rising cost of PE evaluations, along with increasing awareness of potential harm and doubts about mortality benefits, a more focused strategy is needed,” the committee said.

CT exposes patients to potentially hazardous radiation and is associated with risk of nephropathy from contrast agents. Although use of CT for the evaluation of PE was increasing, there was no evidence that increased use …
Tumor proliferation in rectal cancer following preoperative irradiation.
Authors: C G Willett, G Warland, M P Hagan, W J Daly, J Coen, P C Shellito, C C Compton
Journal: Journal of Clinical Oncology (1995)

This study examines the effect of preoperative irradiation on tumor proliferation in rectal cancer.One hundred twenty-two patients with locally advanced rectal cancer received 45 to 50 Gy of preoperative irradiation followed by surgery. Pretreatment tumor biopsies and postirradiation surgical specimens were scored for proliferative activity by assaying the extent of Ki-67 and proliferating-cell nuclear antigen (PCNA) immunostaining and the number of mitoses per 10 high-power fields (hpf). Preirradiation and postirradiation proliferative activity was determined and correlated to clinical outcome.There was an overall reduction in the tumor proliferative activity of rectal cancer after irradiation compared with its preirradiation state. Decreases in the activity of all three markers of tumor proliferation (Ki-67 and PCNA immunostaining, and mitotic counts) were observed in irradiated tumors compared with pretreatment biopsies. Postirradiation tumor proliferative activity was associated with pathologic tumor stage. A high level of proliferative activity was observed in tumors downstaged to the rectal wall (T1-2) compared with tumors that retained transmural penetration (T3-4). Multivariate analysis indicated that postirradiation proliferative activity and stage were independently associated with survival following surgery. Patients with tumors that exhibited elevated proliferative activity postirradiation had improved survival compared with patients with tumors that showed less proliferative activity.Moderate- to high-dose preoperative irradiation decreases both the tumor size and proliferative activity of rectal cancers. Elevated postirradiation tumor proliferative activity correlates strongly with improved survival. This may aid in identifying high-risk patients following preoperative irradiation and surgery.
A Review of: “Matthew Albright.<i>Profits Pending: How Life Patents Represent the Biggest Swindle of the 21st Century</i>”
Authors: Sarah E. Roberts-Cady
Journal: The American Journal of Bioethics (2005)

It is hard not to be drawn in by the shocking claim that appears on the back cover of the book, “Somebody owns your genes.” Admittedly, the claim is misleading. As one discovers within the book, th...
In Patients With Cirrhosis, Driving Simulator Performance Is Associated With Real-life Driving
Authors: Mette M. Lauridsen, Leroy R. Thacker, Melanie B. White, Ariel Unser, Richard K. Sterling, Richard T. Stravitz, Scott Matherly, Puneet Puri, Arun J. Sanyal, Edith A. Gavis, Velimir Luketic, Muhammad S. Siddiqui, Douglas M. Heuman, Michael Fuchs, Jasmohan S. Bajaj
Journal: Clinical Gastroenterology and Hepatology (2015)
Structure, Function, and Serology of the T-Cell Antigen Receptor Complex
Authors: J P Allison, L L Lanier
Journal: Annual Review of Immunology (1987)

Exhausted CD8 T (Tex) cells are a distinct cell lineage that arise during chronic infections and cancers in animal models and humans. Tex cells are characterized by progressive loss of effector functions, high and sustained inhibitory receptor expression, ...Read More
Impact of Plant Genetic Engineering on Foods and Nutrition
Authors: Luca Comai
Journal: Annual Review of Nutrition (1993)

INTRODUCTION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 191 THE TECHNOLOGIES OF PLANT GENETIC ENGINEERING . . . . . . . . . . . . . 192 Plant Transformation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 192 Gene Expression . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 194 Gene Inactivation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 195
Intrahepatic hepatitis B virus replication and liver histology in subjects with occult hepatitis B infection
Authors: D.K.-H. Wong, J. Fung, C.-K. Lee, W.-K. Seto, J. Leung, F.-Y. Huang, C.-K. Lin, C.-L. Lai, M.-F. Yuen
Journal: Clinical Microbiology and Infection (2015)
Marine Pharmacology: Bioactive Molecules from the Sea
Authors: P N Kaul, P Daftari
Journal: The Annual Review of Pharmacology and Toxicology (1986)

Mankind has known for at least several thousand years that marine organisms contain substances capable of potent biological activity (1). Undoubtedly we are aware that most of the currently available therapeutic agents stem either directly or indirectly from naturally occurring organic molecules derived from terrestrial plants and/or animals. However, the abundant floras and faunas inhabiting the 70% of the Earth's surface covered by the ocean waters remain relatively unexplored. It is only in the past three decades that a significant research activity has suggested that the sea offers an enormous biomedical potential yet to be harnessed by man. Attention to pharmacologically active substances in the sea in recent decades was first drawn by Emerson & Taft (2). Several subsequent reviews and monographs have dealt mostly with the pharmacology and toxicity of crude and semipurified extracts of marine organisms (3-13). More recent reviews, however, describe the pharmacology of some of the pure compounds of marine origin (14-17). This review focuses on pharmacological activities of pure compounds iso­ lated from marine organisms, as well as the pharmacologic activities of some highly potent substances broadly given the notorious name of marine toxins. Note that we take the same view of toxicity as Paracelsus-that at a given dosage level all compounds are toxic but that the right dose via the right route can make all the difference. Digitalis and tetrodotoxin (18) are but two ex­ amples among many that support this view.
Levels of TGFβ and IL10 in Mother's Breast Milk and Child's Risk of Sensitization to Egg, Milk, or Peanut in a Birth Cohort
Authors: Christine L.M. Joseph, Suzanne Havstad, Kevin Bobbitt, Kimberley J. Woodcroft, Christian G. Nageotte, Rana T. Misiak, Jerel M. Ezell, Edward M. Zoratti, Ganesa Wegienka, Dennis Ownby, Christine Cole Johnson
Journal: Journal of Allergy and Clinical Immunology (2013)
A Type 1 Diabetes Genetic Risk Score Can Aid Discrimination Between Type 1 and Type 2 Diabetes in Young Adults
Authors: Richard A. Oram, Kashyap Patel, Anita Hill, Beverley Shields, Timothy J. McDonald, Angus Jones, Andrew T. Hattersley, Michael N. Weedon
Journal: Diabetes Care (2015)

With rising obesity, it is becoming increasingly difficult to distinguish between type 1 diabetes (T1D) and type 2 diabetes (T2D) in young adults. There has been substantial recent progress in identifying the contribution of common genetic variants to T1D and T2D. We aimed to determine whether a score generated from common genetic variants could be used to discriminate between T1D and T2D and also to predict severe insulin deficiency in young adults with diabetes.We developed genetic risk scores (GRSs) from published T1D- and T2D-associated variants. We first tested whether the scores could distinguish clinically defined T1D and T2D from the Wellcome Trust Case Control Consortium (WTCCC) (n = 3,887). We then assessed whether the T1D GRS correctly classified young adults (diagnosed at 20-40 years of age, the age-group with the most diagnostic difficulty in clinical practice; n = 223) who progressed to severe insulin deficiency <3 years from diagnosis.In the WTCCC, the T1D GRS, based on 30 T1D-associated risk variants, was highly discriminative of T1D and T2D (area under the curve [AUC] 0.88 [95% CI 0.87-0.89]; P < 0.0001), and the T2D GRS added little discrimination (AUC 0.89). A T1D GRS >0.280 (>50th centile in those with T1D) is indicative of T1D (50% sensitivity, 95% specificity). A low T1D GRS (<0.234, <5th centile T1D) is indicative of T2D (53% sensitivity, 95% specificity). Most discriminative ability was obtained from just nine single nucleotide polymorphisms (AUC 0.87). In young adults with diabetes, T1D GRS alone predicted progression to insulin deficiency (AUC 0.87 [95% CI 0.82-0.92]; P < 0.0001). T1D GRS, autoantibody status, and clinical features were independent and additive predictors of severe insulin deficiency (combined AUC 0.96 [95% CI 0.94-0.99]; P < 0.0001).A T1D GRS can accurately identify young adults with diabetes who will require insulin treatment. This will be an important addition to correctly classifying individuals with diabetes when clinical features and autoimmune markers are equivocal.
Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China: a microbiological and molecular biological study
Authors: Yi-Yun Liu, Yang Wang, Timothy R Walsh, Ling-Xian Yi, Rong Zhang, James Spencer, Yohei Doi, Guobao Tian, Baolei Dong, Xianhui Huang, Lin-Feng Yu, Danxia Gu, Hongwei Ren, Xiaojie Chen, Luchao Lv, Dandan He, Hongwei Zhou, Zisen Liang, Jian-Hua Liu, Jianzhong Shen
Journal: The Lancet Infectious Diseases (2015)
Association of maternal thyroid function during early pregnancy with offspring IQ and brain morphology in childhood: a population-based prospective cohort study
Authors: Tim I M Korevaar, Ryan Muetzel, Marco Medici, Layal Chaker, Vincent W V Jaddoe, Yolanda B de Rijke, Eric A P Steegers, Theo J Visser, Tonya White, Henning Tiemeier, Robin P Peeters
Journal: The Lancet Diabetes & Endocrinology (2015)
Immobilis in mobili: performing arts, BCI, and locked-in syndrome
Authors: Andrés Aparicio
Journal: Brain-Computer Interfaces (2015)

There are actors who cannot move. The question is, can they act? The traditional conception of performing arts would demand an answer in the negative. However, technology provides a way to go beyond the traditional definition and present people with locked-in syndrome or other severe motor impairments with the opportunity to claim a place in the performing arts. BCIs in particular represent an interesting venue for reaching this goal as they aim to provide an efficient mechanism of control of external systems and these external systems might, in turn, be defined, designed, and built with artistic expression purposes in mind. This paper proposes three conceptual models to guide the design of such systems.
Randomized phase II study of axitinib versus placebo plus best supportive care in second-line treatment of advanced hepatocellular carcinoma
Authors: Y.-K. Kang, T. Yau, J.-W. Park, H.Y. Lim, T.-Y. Lee, S. Obi, S.L. Chan, S.K. Qin, R.D. Kim, M. Casey, C. Chen, H. Bhattacharyya, J.A. Williams, O. Valota, D. Chakrabarti, M. Kudo
Journal: Annals of Oncology (2015)
Radiotherapy Combined with Novel STING-Targeting Oligonucleotides Results in Regression of Established Tumors
Authors: Jason R. Baird, David Friedman, Benjamin Cottam, Thomas W. Dubensky, David B. Kanne, Shelly Bambina, Keith Bahjat, Marka R. Crittenden, Michael J. Gough
Journal: Cancer Research (2015)

Cytotoxic therapies prime adaptive immune responses to cancer by stimulating the release of tumor-associated antigens. However, the tumor microenvironment into which these antigens are released is typically immunosuppressed, blunting the ability to initiate immune responses. Recently, activation of the DNA sensor molecule STING by cyclic dinucleotides was shown to stimulate infection-related inflammatory pathways in tumors. In this study, we report that the inflammatory pathways activated by STING ligands generate a powerful adjuvant activity for enhancing adaptive immune responses to tumor antigens released by radiotherapy. In a murine model of pancreatic cancer, we showed that combining CT-guided radiotherapy with a novel ligand of murine and human STING could synergize to control local and distant tumors. Mechanistic investigations revealed T-cell-independent and TNFα-dependent hemorrhagic necrosis at early times, followed by later CD8 T-cell-dependent control of residual disease. Clinically, STING was found to be expressed extensively in human pancreatic tumor and stromal cells. Our findings suggest that this novel STING ligand could offer a potent adjuvant for leveraging radiotherapeutic management of pancreatic cancer.
Clinical and prognostic significance of bone marrow involvement in patients with diffuse aggressive B-cell lymphoma.
Authors: Y Yan, W C Chan, D D Weisenburger, J R Anderson, M A Bast, J M Vose, P J Bierman, J O Armitage
Journal: Journal of Clinical Oncology (1995)

PURPOSE We studied the effect of morphology and extent of bone marrow (BM) infiltrate on the survival of patients with diffuse aggressive B-cell non-Hodgkin's lymphoma (NHL), along with clinical features. PATIENTS AND METHODS Sixty adult patients with diffuse aggressive B-cell NHL and BM involvement at the time of presentation were studied. All patients were uniformly staged and treated with a curative high-dose chemotherapy regimen. BM involvement was assessed according to the cytology, pattern of infiltration, and extent of involvement, and was correlated with overall survival (OS) and failure-free survival (FFS). RESULTS Patients with BM involvement that consisted of &gt; or = 50% large cells or BM involvement of &gt; or = 70% had a poorer OS (P = .065 and P = .055, respectively). Those who presented with an infiltrate of less than 50% large cells and an international prognostic index (IPI) of &lt; or = 3 had a significantly longer postrelapse survival time (P = .003). A diffuse or interstitial pattern of BM involvement was predictive of both poor OS and FFS (P = .008 and .009, respectively). Multivariate analysis indicated that only IPI (P = .0005) and pattern of BM infiltration (P = .009) were independent predictors of OS, and only the former was predictive of FFS (P = .03). CONCLUSION The IPI is predictive of OS and FFS, while BM involvement with a diffuse or interstitial pattern is associated with significantly poorer OS. Patients with BM infiltration that involved &gt; or = 70% of the marrow or contained &gt; or = 50% large cells had poor OS, but more patients need to be studied to determine the significance. Two parameters, IPI &lt; or = 3 and BM large cells less than 50%, identify a group of patients with long-term survival after relapse.
Use of seven-valent pneumococcal conjugate vaccine (PCV7) in Europe, 2001-2007
Authors: H De Carvalho Gomes, M Muscat, D L Monnet, J Giesecke, P L Lopalco
Journal: Eurosurveillance (2009)

The first pneumococcal vaccine targeting the youngest age groups, a seven-valent conjugate vaccine (PCV7), was licensed in Europe in 2001. Since then several European countries have introduced PCV7 in their childhood vaccination schedules. Still, information on vaccination schemes, vaccine uptake and impact of vaccine introduction is scarce in Europe. The following article summarises the characteristics of national pneumococcal vaccination programmes for children in 32 European countries and provides an estimate of vaccine use based on sales data for 22 countries between 2001 and 2007. There were wide variations in the recommended PCV7 vaccination schemes and in PCV7 use. High vaccine uptake was not always related to the presence of a national vaccination programme.
Letter by Savas and Kalay Regarding Article, “Invasive Evaluation of Patients With Angina in the Absence of Obstructive Coronary Artery Disease”
Authors: Goktug Savas, Nihat Kalay
Journal: Circulation (2015)

We read with great interest the report by Lee et al 1 in a previous issue of Circulation.The authors reported that invasive assessment of patients with angina in the absence of obstructive coronary artery disease (CAD) may provide important diagnostic information.The investigators found that 77% of patients had occult coronary abnormalities, diagnosed with endothelial function tests and intravascular ultrasound.Although these are important findings, some issues should be considered in the interpretation of the study results.It is well known that increased myocardial wall tension and reduced coronary flow reserve cause angina in the hypertensive population. 2 In a previous study, Iriarte et al 3 stated that typical angina in hypertensive patients was common (30%) and that 61% of these patients had normal coronary arteries.Current guidelines recommend that blood pressure should be lowered to <140/90 mm Hg in patients with CAD to control anginal symptoms.However, in the present study, the authors did not mention the classification of blood pressure.In our opinion, the high rate of coronary abnormalities in patients with nonobstructive CAD may be the result of neglecting hypertension.Blood pressure values should be evaluated in patients with angina.On the other hand, a previous study showed that the prevalence of depression is considerably high (63%) among patients with chest pain in the absence of obstructive CAD. 4 Therefore, screening for depression in patients with CAD is now recommended by the American Heart Association.This is an important issue because depression is a predictor of treatment success.Anginal symptoms may regress if patients are treated with an antidepressant.In addition, Chen et al 5 stated that depression and stress were associated with impaired endothelial function parameters.Accordingly, depression and stress may have changed the hemodynamic parameters in the present study.Therefore, depression should be considered in evaluating patients with angina.In this way, comprehensive invasive assessment of patients with angina may not be necessary.
Effective therapy for poor-prognosis non-Hodgkin's lymphoma with 8 weeks of high-dose-intensity combination chemotherapy.
Authors: T M Waits, F A Greco, J P Greer, D H Johnson, S N Wolff, R S Stein, M L McMaster, J D Hainsworth
Journal: Journal of Clinical Oncology (1993)

PURPOSE Despite substantial advances in the treatment of aggressive non-Hodgkin's lymphoma, therapeutic results with conventional regimens remain poor in some subsets of patients. In an attempt to improve the prognosis of such patients we used an 8-week, multidrug chemotherapy regimen of high dose-intensity. PATIENTS AND METHODS Between April 1986 and April 1991, 70 patients with advanced intermediate- or high-grade non-Hodgkin's lymphoma were treated. The median age was 41 years (range, 18 to 69). Fifty-one patients (73%) had stage IV disease; 37 (53%) were Shipp's category 3; 17 (24%) had small noncleaved-cell lymphoma; 35 (50%) had Eastern Cooperative Oncology Group (ECOG) performance status &gt; or = 2; 24 (34%) had two or more extranodal sites involved; and 17 (24%) had bone marrow involvement. The 8-week regimen included cyclophosphamide, etoposide, doxorubicin, vincristine, bleomycin, methotrexate with leucovorin rescue, and prednisone. RESULTS Sixty-two of 70 patients completed the regimen as planned. Fifty-seven patients (81%) obtained a complete response (CR) and the actuarial 5-year failure-free survival rate is 52%. Thirty-seven patients remain alive and disease-free a median of 35 months (range, 7 to 68) after therapy. Adverse prognostic factors included age more than 50 years, bone marrow involvement, and serum lactic dehydrogenase (LDH) more than 500 IU/L (normal range, 125 to 250). Myelosuppression was responsible for most of the treatment-related toxicity. Severe leukopenia (&lt; 1,000/microL) occurred in all patients and lasted a median of 9 days. Seven patients (10%) died of myelosuppression-related complications; five of these patients were older than 60 years. CONCLUSION This brief but intensive therapy was effective in treating poor-prognosis patients with non-Hodgkin's lymphoma. With this therapy, patients with small noncleaved-cell lymphoma or Shipp's category 3 disease had treatment outcome similar to the group as a whole. This therapy was not well tolerated by patients older than 60 years, and should not be given to this subgroup. Verification of these results in a randomized trial setting is indicated.
Laboratory diagnosis, clinical management and infection control of the infections caused by extensively drug-resistant Gram-negative bacilli: a Chinese consensus statement
Authors: X. Guan, L. He, B. Hu, J. Hu, X. Huang, G. Lai, Y. Li, Y. Liu, Y. Ni, H. Qiu, Z. Shao, Y. Shi, M. Wang, R. Wang, D. Wu, C. Xie, Y. Xu, F. Yang, K. Yu, Y. Yu, J. Zhang, C. Zhuo
Journal: Clinical Microbiology and Infection (2015)

Extensively drug-resistant (XDR) Gram-negative bacilli (GNB) are defined as bacterial isolates susceptible to two or fewer antimicrobial categories. XDR-GNB mainly occur in Enterobacteriaceae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Stenotrophomonas maltophilia. The prevalence of XDR-GNB is on the rise in China and in other countries, and it poses a major public health threat as a result of the lack of adequate therapeutic options. A group of Chinese clinical experts, microbiologists and pharmacologists came together to discuss and draft a consensus on the laboratory diagnosis, clinical management and infection control of XDR-GNB infections. Lists of antimicrobial categories proposed for antimicrobial susceptibility testing were created according to documents from the Clinical Laboratory Standards Institute (CLSI), the European Committee on Antimicrobial Susceptibility Testing (EUCAST) and the United States Food and Drug Administration (FDA). Multiple risk factors of XDR-GNB infections are analyzed, with long-term exposure to extended-spectrum antimicrobials being the most important one. Combination therapeutic regimens are summarized for treatment of XDR-GNB infections caused by different bacteria based on limited clinical studies and/or laboratory data. Most frequently used antimicrobials used for the combination therapies include aminoglycosides, carbapenems, colistin, fosfomycin and tigecycline. Strict infection control measures including hand hygiene, contact isolation, active screening, environmental surface disinfections, decolonization and restrictive antibiotic stewardship are recommended to curb the XDR-GNB spread.