tbuckley/cabot-search huggingface dataset:
Establishment of reference intervals for osteoarthritis-related soluble biomarkers: the FNIH/OARSI OA Biomarkers Consortium
Authors: Virginia B Kraus, David E Hargrove, David J Hunter, Jordan B Renner, Joanne M Jordan
Journal: Annals of the Rheumatic Diseases (2016)

Objective To establish reference intervals for osteoarthritis (OA)-related biomarkers used in the Foundation for the National Institutes of Health (FNIH) OA Biomarkers Consortium Project. Methods A total of 129 ‘multijoint controls’ were selected from 2722 African-American and Caucasian men and women in the Johnston County Osteoarthritis Project. The majority (79%) of those eligible (with biospecimens and baseline data) also had one or more follow-up evaluations 5–15 years later. Multijoint controls were selected to be free of radiographic hand, hip, knee and lumbar spine osteoarthritis (OA), to have no knee or hip symptoms, and minimal hand and spine symptoms at all available time points. Eighteen biomarkers were evaluated in serum (s) and/or urine (u) by ELISA. Reference intervals and partitioning by gender and race were performed with EP Evaluator software. Results Controls were 64% women, 33% African-Americans, mean age 59 years and mean body mass index 29 kg/m 2 . Three biomarkers were associated with age: sHyaluronan (positively), sN-terminal propeptide of collagen IIA (positively) and sCol2-3/4 C-terminal cleavage product of types I and II collagen (negatively). Exploratory analyses suggested that separate reference intervals may be warranted on the basis of gender for uC-terminal cross-linked telopeptide of type II collagen (uCTXII), sMatrix metalloproteinase-3, uNitrated type II collagen degradation fragment (uCol2-1 NO2) and sHyaluronan, and on the basis of race for uCTXII, sCartilage oligomeric matrix protein, sC-terminal cross-linked telopeptide of type I collagen and uCol2-1 NO2. Conclusions To our knowledge, this represents the best and most stringent control group ever assayed for OA-related biomarkers. These well-phenotyped controls, representing a similar age demographic to that of the OA Initiative-FNIH main study sample, provide a context for interpretation of OA subject biomarker data. The freely available data set also provides a reference for future human studies.
Corruption of dendritic cell antigen presentation during acute GVHD leads to regulatory T-cell failure and chronic GVHD
Authors: Lucie Leveque-El mouttie, Motoko Koyama, Laetitia Le Texier, Kate A. Markey, Melody Cheong, Rachel D. Kuns, Katie E. Lineburg, Bianca E. Teal, Kylie A. Alexander, Andrew D. Clouston, Bruce R. Blazar, Geoffrey R. Hill, Kelli P. A. MacDonald
Journal: Blood (2016)
Abstract 11199: Oxidative Stress in the Heart Correlates With Changes in Cardiac Gene Expression Patterns in Rats Chronically Exposed to Ambient Air Pollutants
Authors: Boris Z Simkhovich, Ruty Mehrian-Shai, Dianne Meacher, Glenn Gookin, Ya-Hsuan Hsu, Simon Lin, Gang Feng, Michael T Kleinman, Robert A Kloner
Journal: Circulation (2010)

Introduction: Recently we reported up-regulated expression in cardiac genes for thioredoxin interacting protein (Txnip) and cytochrome P450 (Cyp2e1) in rats chronically exposed to coarse and ultraf...
E1505: Adjuvant chemotherapy +/- bevacizumab for early stage NSCLC—Outcomes based on chemotherapy subsets.
Authors: Heather A. Wakelee, Suzanne Eleanor Dahlberg, Steven M. Keller, William J. Tester, David R. Gandara, Stephen L. Graziano, Alex A. Adjei, Natasha B. Leighl, Charles Andrew Butts, Seena C. Aisner, Jan M. Rothman, Jyoti D. Patel, Mark D. Sborov, Raymond S. McDermott, Roman Perez-Soler, Anne M. Traynor, Tracey L. Evans, Leora Horn, Suresh S. Ramalingam, Joan H. Schiller
Journal: Journal of Clinical Oncology (2016)

8507 Background: Adjuvant chemotherapy (chemo) for resected early stage NSCLC provides modest survival benefit. E1505 offers the first opportunity to study 4 modern cisplatin-based regimens in the adjuvant setting in the context of a single trial. As previously reported from this trial, the addition of bevacizumab (B) to adjuvant chemo failed to improve the primary endpoint of overall survival (OS HR=0.99; 95% CI: 0.82-1.19, p=0.91) or disease free survival (DFS HR=0.99; 95%CI: 0.85-1.15, p=0.89). Here we explore outcomes by chemo regimen utilized. Methods: Patients (pts) with resected early stage NSCLC, stratified by stage, histology, sex, and chemo option, were randomized 1:1 to chemo alone or chemo with B (15 mg/kg every 3 weeks for up to 1 year). Chemo consisted of a planned 4 cycles of every 3-week cisplatin (75 mg/m2 d1) with investigator's choice of vinorelbine (V) (30 mg/m2 d1,8), docetaxel (D) (75 mg/m2 d1), gemcitabine (G) (1200 mg/m2 d1,8), or pemetrexed (P) (500 mg/m2d1). P was added in 2009 for non-squamous (NSq) pts only. Results: From 7/2007 to 9/2013, 1501 pts were enrolled: V 25%, D 23%, G 19% and P 33%. Arms were well balanced for known prognostic factors; 28% had Sq histology. Median f/up per chemo group is: V 54.3 months (mos); D 60.3 mos; G 57.0 mos; P 40.6 mos. When pts were pooled across +/- B arms and divided into NSq and Sq cohorts (to account for P restriction to NSq pts) there was no significant difference in OS or DFS by chemo regimen with the following logrank p-values: OS NSq, p=0.19; DFS NSq, p=0.67; OS Sq, p=0.96; DFS Sq, p=0.85. Toxicities were consistent with known profiles of the drugs. V was associated with more neutropenia and G with more thrombocytopenia. Sq pts had no differences in total Gr 3-5 toxicity by chemo groups, but NSq pts who received P had significantly less total Gr 3-5 toxicity (p<0.001) than NSq pts receiving other regimens. Conclusions: No differences in OS or DFS were observed between 4 different adjuvant cisplatin-based chemotherapy regimens for surgically resected early stage NSCLC patients. Clinical trial information: NCT00324805.
Durable remissions with brentuximab vedotin (SGN-35): Updated results of a phase II study in patients with relapsed or refractory systemic anaplastic large cell lymphoma (sALCL).
Authors: B. Pro, R. Advani, P. Brice, N. Bartlett, J. D. Rosenblatt, T. Illidge, J. Matous, R. Ramchandren, M. A. Fanale, J. M. Connors, Y. Yang, E. L. Sievers, D. A. Kennedy, A. R. Shustov
Journal: Journal of Clinical Oncology (2011)

8032 Background: sALCL is a CD30-expressing malignancy comprising ~2-3% of all NHL cases. Brentuximab vedotin consists of an anti-CD30 antibody conjugated by a plasma-stable linker to the potent antimicrotubule agent, monomethyl auristatin E (MMAE). Brentuximab vedotin selectively induces apoptotic death of CD30+ cells by binding, internalizing, and releasing MMAE. Methods: A phase II, single-arm, multicenter study evaluated the efficacy and safety of brentuximab vedotin in patients (pts) with relapsed or refractory sALCL. Pts received brentuximab vedotin 1.8 mg/kg q3 weeks (wks) as a 30‐minute outpatient IV infusion for up to 16 cycles. The primary endpoint was the objective response rate (ORR) per an independent review facility (IRF) according to Cheson 2007. Results: 58 pts were enrolled; 57% were male, median age was 52 yrs (range 14–76 yrs). 72% of pts had ALK negative sALCL. Pts had received a median of 2 (range 1–6) prior systemic therapies. 62% of pts had primary refractory disease, 50% were refractory to their most recent prior therapy, and 22% had never responded to any prior therapy. At the time of primary efficacy analysis, ORR per IRF was 86% (50 of 58 pts) with CRs in 53% of pts (31 of 58). Median duration of objective response had not yet been reached; the duration ranged from 0.3 to 45.3 wks. Of 15 pts with malignant cutaneous lesions at baseline, 14 (93%) had resolution of all lesions; median time to resolution was 4.9 wks. After achieving a remission with brentuximab vedotin, 7 pts received an allogeneic stem cell transplant (SCT) and 7 pts had an autologous SCT. Treatment-related adverse events (AEs) of any grade in ≥15% of pts were peripheral sensory neuropathy (36%), nausea (24%), fatigue (22%), diarrhea (19%), and neutropenia (17%). AEs ≥ Grade 3 in ≥10% of patients were neutropenia (21%); thrombocytopenia (14%), and peripheral sensory neuropathy (10%). No treatment-related Grade 5 events were observed. Conclusions: Brentuximab vedotin induced objective responses in 86% of pts with highly refractory sALCL, including a high proportion of CRs, with manageable AEs. Updated response durability and safety will be presented at the meeting.
Association of a Genetic Risk Score With Body Mass Index Across Different Birth Cohorts
Authors: Stefan Walter, Iván Mejía-Guevara, Karol Estrada, Sze Y. Liu, M. Maria Glymour
Journal: JAMA (2016)

<h3>Importance</h3> Many genetic variants are associated with body mass index (BMI). Associations may have changed with the 20th century obesity epidemic and may differ for black vs white individuals. <h3>Objective</h3> Using birth cohort as an indicator for exposure to obesogenic environment, to evaluate whether genetic predisposition to higher BMI has a larger magnitude of association among adults from more recent birth cohorts, who were exposed to the obesity epidemic at younger ages. <h3>Design, Setting, and Participants</h3> Observational study of 8788 adults in the US national Health and Retirement Study who were aged 50 years and older, born between 1900 and 1958, with as many as 12 BMI assessments from 1992 to 2014. <h3>Exposures</h3> A multilocus genetic risk score for BMI (GRS-BMI), calculated as the weighted sum of alleles of 29 single nucleotide polymorphisms associated with BMI, with weights equal to the published per-allele effects. The GRS-BMI represents how much each person’s BMI is expected to differ, based on genetic background (with respect to these 29 loci), from the BMI of a sample member with median genetic risk. The median-centered GRS-BMI ranged from −1.68 to 2.01. <h3>Main Outcomes and Measures</h3> BMI based on self-reported height and weight. <h3>Results</h3> GRS-BMI was significantly associated with BMI among white participants (n = 7482; mean age at first assessment, 59 years; 3373 [45%] were men;<i>P</i>&lt;.001) and among black participants (n = 1306; mean age at first assessment, 57 years; 505 [39%] were men;<i>P</i>&lt;.001) but accounted for 0.99% of variation in BMI among white participants and 1.37% among black participants. In multilevel models accounting for age, the magnitude of associations of GRS-BMI with BMI were larger for more recent birth cohorts. For example, among white participants, each unit higher GRS-BMI was associated with a difference in BMI of 1.37 (95% CI, 0.93 to 1.80) if born after 1943, and 0.17 (95% CI, −0.55 to 0.89) if born before 1924 (<i>P</i> = .006). For black participants, each unit higher GRS-BMI was associated with a difference in BMI of 3.70 (95% CI, 2.42 to 4.97) if born after 1943, and 1.44 (95% CI, −1.40 to 4.29) if born before 1924. <h3>Conclusions and Relevance</h3> For participants born between 1900 and 1958, the magnitude of association between BMI and a genetic risk score for BMI was larger among persons born in later cohorts. This suggests that associations of known genetic variants with BMI may be modified by obesogenic environments.
Inhibition of Leukocyte Migration by Tumor-Associated Antigens in Soluble Extracts of Human Malignant Melanoma2
Authors: J. L. McCoy, L. F. Jerome, J. H. Dean, E. Perlin, R. H. Oldham, D. H. Char, M. H. Cohen, E. L. Felix, R. B. Herberman
Journal: JNCI Journal of the National Cancer Institute (1975)

Direct leukocyte migration inhibition (LMI) assays were performed to investigate whether cell-mediated immune reactions could be detected in response to tumor-associated antigens of human melanoma. The antigens were 3 M KCI-soluble extracts of different fresh melanomas, other cancers, and benign nevus tissue. A total of 48 of the 79 (61 %) blood samples from melanoma patients (64 patients) reacted with extracts of melanoma tissue. Since the subjects were usually tested with two or three extracts, 57/134 (42%) tests with melanoma patients' leukocytes were inhibited by KCI extracts of melanoma tissue, whereas only 3/50 (6%) tests with leukocytes of normal donors and 4/27 (15%) with patients having other cancers gave positive results. No positive reactions were obtained when 13 melanoma patients were tested with a 3 M KCI extract of benign nevus tissue. Likewise, only 2/26 (8%) positive tests were obtained from melanoma patients tested with extracts of other cancers. Individuals in all stages of disease had similar incidences of positive reactions to the soluble melanoma extracts, except for patients with stage-1 disease who exhibited a somewhat higher incidence of reactivity. The highest incidence of reactivity was observed in patients before surgical resection of the tumor, and somewhat decreased reactivity was seen 0–14 days post surgery. The results indicate that the direct LMI assay may be used to measure cell immune reactivity against melanoma-associated antigens. Since many of the positive results were obtained with allogeneic extracts, the results also indicate that different melanomas possess common antigens.
Rabies – a recurrent danger to European countries from dogs introduced from endemic countries
Authors: I Steffens, K Ekdahl
Journal: Eurosurveillance (2008)

Although vaccine-preventable, rabies remains a worldwide-occurring disease of major public health concern. Globally, rabies is responsible for about 55,000 human deaths per year, mainly in Asia and Africa, and 30-50% of the cases are in children, most often following an infection transmitted through the bite of a rabid dog.
Abstract 298: Development of a Novel Heart Valve Tissue Engineering Scaffold with Incorporated Cytokine Delivery
Authors: Meghan E Smith, Yakov Elgudin, Olivier Arnoult, Nicholas Greco, Mary Laughlin, Steven Emancipator, Brian Cmolik, Gary Wnek
Journal: Circulation (2008)

Background : Through the use of nano- and microfiber constructs created by electrostatic processing, heart valve tissue engineering scaffolding with higher degrees of functionality can be achieved. Described herein is the development of a novel heart valve tissue engineering construct capable of serving as a delivery vehicle for cytokines, to aid in the direction of cell behavior and differentiation. The purpose of this study was to investigate the incorporation and release of various proteins, including immunoglobulin G (IGG), serving as a model protein system, and vascular endothelial growth factor (VEGF), from biodegradable polymer scaffolds, to assess delivery kinetics, mechanical properties and the impact on the activity of bioactive compounds. Methods and Results: Scaffold production was carried out by electrospinning a suspension of aqueous solution of IGG or VEGF in a solution of poly(ϵ-caprolactone) (PCL) dissolved in chloroform to obtain nonwoven fibrous polymer mats. Fluorescent labeling of the proteins and microscopy was used to locate the proteins within the fibers, and it was found that the proteins were fully isolated within the core of the polymer fiber. Mats were characterized via scanning electron microscopy for fiber diameters and porosity, with fiber diameters ranging from 4um to less then 1 um, and pore throat diameters in the range of 0.5 to 2 um. Using dynamic mechanical analysis, the elastic modulus and tensile strength of the scaffolds were found to be comparable to those of a decellularized porcine leaflet stabilized with a diepoxide, tested under identical conditions. ELISA demonstrated that protein release occurred over several weeks time, with limited burst release, and that activity of the protein was maintained. Conclusions: It was found that scaffolds with either an IGG model protein system of VEGF could be readily produced via electrospinning. Initial mechanical evaluation indicates similar properties to biological leaflets. Delivery of the encapsulated protein in an active state was also achieved, demonstrating that these tissue engineering constructs may be employed to create scaffolds serving both for mechanical cellular supports and to selectively control the cells biochemical environment.
Spontaneous Liver Tumors in Laboratory Rats
Authors: M Pollard
Journal: JNCI Journal of the National Cancer Institute (1982)

Journal Article Spontaneous Liver Tumors in Laboratory Rats Get access JNCI: Journal of the National Cancer Institute, Volume 68, Issue 6, June 1982, Page 884, https://doi.org/10.1093/jnci/68.6.884 Published: 01 June 1982
Denosumab, cortical bone and bone erosions in rheumatoid arthritis
Authors: Maurizio Rossini, Giovanni Adami, Ombretta Viapiana, Luca Idolazzi, Davide Gatti
Journal: Annals of the Rheumatic Diseases (2016)

Takeuchi et al 1 demonstrate an additional inhibitory effect on the progression of bone erosions in rheumatoid arthritis (RA) with the addition to methotrexate of an anti-receptor activator of nuclear factor kappa-B ligand (RANKL) antibody, denosumab, confirming results already reported 8 years ago by Cohen and colleagues.2 Insufficient inhibition of structural joint damage by disease-modifying antirheumatic drugs (DMARDs) was reported despite clinical improvement,3–5 and recently two meta-analysis6 , …
Incidence of viral markers and evaluation of the estimated risk in the Swiss blood donor population from 1996 to 2003
Authors: C Niederhauser, P Schneider, M Fopp, A Ruefer, G Lévy
Journal: Eurosurveillance (2005)

Among the well known transfusion-associated risks, the transmission of pathogenic viruses is regarded as one of the most serious. Over the past two decades, a series of overlapping safety procedures have been successively implemented to minimise this risk. It is now generally considered that the risk of transmitting viral infections via blood products is very low in developed countries. The present study analyses the incidence of the key infectious diseases HIV, hepatitis B virus (HBV) and hepatitis C virus (HCV) between 1996 and 2003 from 99% of voluntary repeat blood donors visiting the blood transfusion service of the Swiss Red Cross. Furthermore the estimated risk of these viral markers was calculated. From 1996 to 2003 the incidence rate for HCV decreased continuously, whereas no significant decrease in the incidence rate of HIV and HBV was observed. From 2001 to 2003, the last calculated period, the residual risk was estimated to be 1 in 1 900 000 for HIV, 1 in 2 200 0000 for HCV and 1 in 115 000 for HBV, respectively. This agrees with international studies, which have been shown that the estimated residual risk for HBV between 1996 and 2003 is higher than that of HCV and HIV.
The Diagnosis, Treatment and End Results of Tuberculous Disease of the Hip Joint.
Journal: JAMA (1926)

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Cross-study comparisons of self-reported alcohol consumption in four clinical groups
Authors: K M Adams, I Grant, A S Carlin, R Reed
Journal: American Journal of Psychiatry (1981)

Clinical research on the chronic effects of alcohol has been difficult to evaluate and compare because of the failure by investigators to quantify self-reported alcohol consumption. The authors describe four diverse groups of patients who were treated for alcohol and/or drug abuse. After devising a procedure for comparing the data from these studies, they found that patient self-reports of alcohol consumption may be less distorted than commonly assumed. The present findings are consistent with current research indicating that self-reports of alcohol use are reliable and clinically consistent. The authors also discuss the relationship between neuropsychological impairment and measures of alcohol and drug abuse.
The Chemokine Receptor Profile As Distinctive Criterion Between Normal B-Cell Subsets and As Potential Discriminative Marker to Identify the Cell of Origin in Patients with Chronic Lymphocytic Leukemia and Richter Syndrome
Authors: Katharina Troppan, Kerstin Wenzl, Peter Neumeister, Christine Beham-Schmid, Martina Przekopowitz, Hildegard T. Greinix, Helmut Schaider, Alexander JA Deutsch
Journal: Blood (2015)
Readmission in COPD patients: should we consider it a marker of quality of care or a marker of a more severe disease with a worse prognosis?
Authors: Sylvia Hartl, Jose Luis Lopez-Campos
Journal: European Respiratory Journal (2016)

We thank Ernesto Crisafulli, Mónica Guerrero, Alfredo Chetta and Antoni Torres for their differentiated perspective on the topic of hospital readmission of chronic obstructive pulmonary disease (COPD). It is high time for a holistic approach to COPD exacerbation including each suitable intervention to the risk profile <http://ow.ly/iUok300hb8V>
Gestion actuelle des patients atteints de fièvres hémorragiques virales au Royaume-Uni
Authors: N Crowcroft, D W Brown, R Gopal
Journal: Eurosurveillance (2002)

Au Royaume-Uni, les cas suspects et confirmes de fievre hemorragique virale sont actuellement geres d’apres les recommandations emises en 1996 par le Comite consultatif sur les pathogenes dangereux (Advisory Committee on Dangerous Pathogens), qui decrit une approche pour evaluer les risques des cas suspects. Ce comite fournit egalement des conseils en matiere de prise en charge des patients, dont leurs transferts, les examens biologiques, la lutte contre l’infection, et la surveillance des personnes exposees d’apres l’evaluation des risques. Les cas confirmes sont places dans des chambres d’isolement ( unites Trexler ), dont deux sont situees au sein des departements de haute securite traitant des maladies infectieuses au Royaume-Uni. Ces recommandations sont en cours de revision et pourraient etre modifiees. En effet, des experiences recentes ont montre que communiquer, et rassurer les personnels soignants et le public etaient des tâches importantes dans la gestion de ces cas.
<i>The BMJ</i>appoints two new ethics committee members
Authors: Anne Gulland
Journal: BMJ (2016)

The BMJ has appointed two new members of its ethics committee, Andy Petros and Graham Cole.

Petros, a consultant paediatric intensivist at Great Ormond Street Hospital, London, has published widely on medical ethics, is a member of the Camden and King’s Cross research ethics committee, and has provided expert opinion on several complex High Court cases involving treatment options for …