tbuckley/cabot-search huggingface dataset:
eLetter: Tabalumab, an anti-BAFF monoclonal antibody, in patients with active rheumatoid arthritis with an inadequate response to TNF inhibitors by M Genovese
Authors: Areti Triantafyllou, Athina Pyrpasopoulou, Panagiota Anyfanti, Ekaterini Balaska, Spyros Aslanidis, Stella Douma
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Aims</h3> We set out to identify risk factors for progression in untreated keratoconus patients from 34 centres across Australia, New Zealand, Spain and Italy. <h3>Methods</h3> Patients were divided into ‘progressors’ and ‘stable’ patients for each clinical parameter: visual acuity (VA), steepest keratometry (maximum keratometry (Max-K)) and thinnest corneal thickness (TCT). Primary outcomes were the proportion of eyes with sustained progression in VA, Max-K or TCT within 3 years. Secondary outcomes included predictors of progression. <h3>Results</h3> There were 3994 untreated eyes from 2283 patients. The proportion of eyes with VA, Max-K and TCT progression at 1 year were 3.2%, 6.6% and 3.1% respectively. Factors associated with VA loss were higher baseline VA (HR 1.15 per logMAR line increase in VA; p&lt;0.001) and steeper baseline Max-K (HR 1.07 per 1D increase; p&lt;0.001). Younger baseline age was associated with Max-K steepening (HR 0.96 per year older; p=0.001). Thicker baseline TCT, steeper baseline Max-K and younger baseline age were associated with TCT thinning: (HR 1.08 per 10 µm increase in TCT; p&lt;0.001), (HR 1.03 per 1D increase; p=0.02) and (HR 0.98 per year younger; p=0.01), respectively. <h3>Conclusions</h3> Steeper Max-K and younger age were the most clinically useful baseline predictors of progression as they were associated with worsening of two clinical parameters. Every 1D steeper Max-K was associated with a 7% and 3% greater risk of worsening VA and thinning TCT, respectively. Each 1 year younger was associated with a 4% and 2% greater risk of steepening Max-K and thinning TCT, respectively.
Randomized, Open-Label, Phase III Study Comparing Patupilone (EPO906) With Pegylated Liposomal Doxorubicin in Platinum-Refractory or -Resistant Patients With Recurrent Epithelial Ovarian, Primary Fallopian Tube, or Primary Peritoneal Cancer
Authors: Nicoletta Colombo, Elzbieta Kutarska, Meletios Dimopoulos, Duk-Soo Bae, Izabella Rzepka-Gorska, Mariusz Bidzinski, Giovanni Scambia, Svend Aage Engelholm, Florence Joly, Dirk Weber, Mona El-Hashimy, Jingjin Li, Farida Souami, Patricia Wing, Silke Engelholm, Aristotelis Bamias, Peter Schwartz
Journal: Journal of Clinical Oncology (2012)

This study compared the efficacy and safety of patupilone with those of pegylated liposomal doxorubicin (PLD) in patients with platinum-refractory or -resistant epithelial ovarian, primary fallopian tube, or primary peritoneal cancer.Patients with three or fewer prior regimens were eligible if they had received first-line taxane/platinum-based combination chemotherapy and were platinum refractory or resistant. Patients were randomly assigned to receive patupilone (10 mg/m(2) intravenously every 3 weeks) or PLD (50 mg/m(2) intravenously every 4 weeks).A total of 829 patients were randomly assigned (patupilone, n = 412; PLD, n = 417). There was no statistically significant difference in overall survival (OS), the primary end point, between the patupilone and PLD arms (P = .195; hazard ratio, 0.93; 95% CI, 0.79 to 1.09), with median OS rates of 13.2 and 12.7 months, respectively. Median progression-free survival was 3.7 months for both arms. The overall response rate (all partial responses) was higher in the patupilone arm than in the PLD arm (15.5% v 7.9%; odds ratio, 2.11; 95% CI, 1.36 to 3.29), although disease control rates were similar (59.5% v 56.3%, respectively). Frequently observed adverse events (AEs) of any grade included diarrhea (85.3%) and peripheral neuropathy (39.3%) in the patupilone arm and mucositis/stomatitis (43%) and hand-foot syndrome (41.8%) in the PLD arm.Patupilone did not demonstrate significant improvement in OS compared with the active control, PLD. No new or unexpected serious AEs were identified.
A Universal Molecular Clock of Protein Folds and Its Power in Tracing the Early History of Aerobic Metabolism and Planet Oxygenation
Authors: Minglei Wang, Ying-Ying Jiang, Kyung Mo Kim, Ge Qu, Hong-Fang Ji, Jay E. Mittenthal, Hong-Yu Zhang, Gustavo Caetano-Anollés
Journal: Molecular Biology and Evolution (2010)

The standard molecular clock describes a constant rate of molecular evolution and provides a powerful framework for evolutionary timescales. Here, we describe the existence and implications of a molecular clock of folds, a universal recurrence in the discovery of new structures in the world of proteins. Using a phylogenomic structural census in hundreds of proteomes, we build phylogenies and time lines of domains at fold and fold superfamily levels of structural complexity. These time lines correlate approximately linearly with geological timescales and were here used to date two crucial events in life history, planet oxygenation and organism diversification. We first dissected the structures and functions of enzymes in simulated metabolic networks. The placement of anaerobic and aerobic enzymes in the time line revealed that aerobic metabolism emerged about 2.9 billion years (giga-annum; Ga) ago and expanded during a period of about 400 My, reaching what is known as the Great Oxidation Event. During this period, enzymes recruited old and new folds for oxygen-mediated enzymatic activities. Remarkably, the first fold lost by a superkingdom disappeared in Archaea 2.6 Ga ago, within the span of oxygen rise, suggesting that oxygen also triggered diversification of life. The implications of a molecular clock of folds are many and important for the neutral theory of molecular evolution and for understanding the growth and diversity of the protein world. The clock also extends the standard concept that was specific to molecules and their timescales and turns it into a universal timescale-generating tool.
Frequency and significance of anemia in non-Hodgkin’s lymphoma patients
Authors: I. Moullet, G. Salles, N. Ketterer, C. Dumontet, F. Bouafia, E.-M. Neidhart-Berard, C. Thieblemont, P. Felman, B. Coiffier
Journal: Annals of Oncology (1998)

Retrospective evaluation of anemia frequency and its prognostic value in patients with different subtypes of non-Hodgkin's lymphoma and comparison with other clinical characteristics.Anemia was defined as a hemoglobin value less than or equal to 12 g/dl for all men and women over 50 years of age, and less than or equal to 11 g/dl for women under 50 years of age. The study included 1077 adult lymphoma patients treated between 1980 and 1995 with the following histologic subtypes: 127 patients with small lymphocytic or lymphoplasmacytoid, 62 with marginal zone, 50 with mantle-cell, 208 with follicular, 104 with T-cell lymphoma, 426 with diffuse large-cell and, finally, 73 patients with other high-grade lymphomas.Anemia was present in 341 patients (32%). It was an adverse prognostic factor (P < 0.0001) for overall survival (OS) and progression-free survival (PFS) but not for relapse-free survival (RFS). When patients with and those without bone marrow involvement were considered separately, anemia remained an adverse factor. Anemia was significantly associated with shorter PFS in small lymphocytic or lymphoplasmacytoid, mantle cell, diffuse large cell and high-grade lymphomas and with shorter OS in all histologic subgroups except marginal zone lymphoma. In multivariate analysis, anemia was a significant prognostic factor for OS and PFS for the population as a whole (P = 0.0001 and P = 0.0048, respectively) and in patients with bone marrow involvement (P = 0.007 and P = 0.005, respectively) but not in patients without bone marrow involvement. Finally, the addition of anemia to the International Prognostic Index led to an improvement for OS (P = 0.0004) and PFS (P = 0.0004).Anemia is an important adverse prognostic factor for the outcome of lymphoma patients, particularly in some histologic subgroups and in patients with bone marrow involvement.
Long-Term Follow-Up Analysis of HD9601 Trial Comparing ABVD Versus Stanford V Versus MOPP/EBV/CAD in Patients With Newly Diagnosed Advanced-Stage Hodgkin's Lymphoma: A Study From the Intergruppo Italiano Linfomi
Authors: Teodoro Chisesi, Monica Bellei, Stefano Luminari, Antonella Montanini, Luigi Marcheselli, Alessandro Levis, Paolo Gobbi, Umberto Vitolo, Caterina Stelitano, Vincenzo Pavone, Francesco Merli, Marina Liberati, Luca Baldini, Roberto Bordonaro, Emanuela Anna Pesce, Massimo Federico
Journal: Journal of Clinical Oncology (2011)

The Intergruppo Italiano Linfomi HD9601 trial compared doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) versus doxorubicin, vinblastine, mechloretamine, vincristine, bleomycin, etoposide, and prednisone (Stanford V [StV]) versus the combination of mechlorethamine, vincristine, procarbazine, prednisone (MOPP) with epidoxorubicin, bleomycin, vinblastine (EBV), lomustine, doxorubicin, and vindesine (CAD) (MOPP/EBV/CAD [MEC]) for the initial treatment of advanced-stage Hodgkin's lymphoma to select which regimen would best support a reduced radiotherapy program (limited to two or fewer sites of either previous bulky or partially remitting disease). Superiority of ABVD and MEC to StV was demonstrated. We report analysis of long-term outcome and toxicity.Patients with stage IIB, III, or IV were randomly assigned among six cycles of ABVD, three cycles of StV, and six cycles of MEC; radiotherapy was administered in 76, 71, and 50 patients in the three arms, respectively.Currently, the median follow-up is 86 months; in the prolonged observation period, eight additional failures, including two relapses, both in the StV arm, and six additional deaths in complete response were recorded. The 10-year overall survival rates were 87%, 80%, and 78% for ABVD, MEC, and StV, respectively (P = .4). The 10-year failure-free survival was 75%, 74%, and 49% in the ABVD, MEC, and StV arms, respectively (P < .001). The 10-year disease-free survival of patients treated or not with radiotherapy (RT) showed no difference for ABVD or MEC (85% v 80% and 93% v 68%), and a statistically significant difference for StV (76% v 33%; P = .004). No significant long-term toxicity was recorded.The long-term analysis confirmed ABVD and MEC superiority to StV. The use of RT after StV was established as mandatory. ABVD is still to be considered as the standard treatment with a good balance between efficacy and toxicity.
A prospective study of vasculitis patients collected in a five year period: evaluation of the Chapel Hill nomenclature
Authors: S. F. Sorensen
Journal: Annals of the Rheumatic Diseases (2000)

<h3>OBJECTIVE</h3> To test the usefulness of the Chapel Hill nomenclature, supplemented with surrogate parameters, as diagnostic criteria for primary vasculitides. <h3>METHODS</h3> To prospectively evaluate vasculitis patients according to a standardised clinical and para-clinical programme. In accordance with the Chapel Hill publication surrogate parameters were used: proteinuria, haematuria and red blood cell casts (glomerulonephritis), angiographic or ultrasonic demonstration of aneurysms or stenoses (arteritis), radiological lung infiltrates or cavitations of more than one month9s duration (granuloma in the lungs), bloody nasal discharge or crusts, chronic sinusitis, otitis and/or mastoiditis, bone and/or cartilage destruction, and acute hearing loss (granuloma in upper airways). <h3>RESULTS</h3> The following entities were diagnosed: giant cell arteritis (n=14), Takayasu arteritis (n=1), polyarteritis nodosa (n=2), Wegener9s granulomatosis (n=27), Churg-Strauss syndrome (n=2), microscopic polyangiitis (n=12), Henoch-Schönlein purpura (n=2), cutaneous leucocytoclastic angiitis (n=37), and secondary vasculitis (n=21). Giant cell arteritis and cutaneous leucocytoclastic angiitis were in all cases diagnosed by biopsy. Using the Chapel Hill nomenclature supplemented with surrogate parameters, only 8 of 27 patients were diagnosed with Wegener9s granulomatosis, and 3 of 12 cases with microscopic polyangiitis. The number of patients in the remaining diagnostic entities were considered to few to evaluate. <h3>CONCLUSIONS</h3> The Chapel Hill nomenclature, supplemented with surrogate parameters, failed to act as diagnostic criteria in Wegener9s granulomatosis and microscopic polyangiitis. The following diagnostic criteria are proposed for Wegener9s granulomatosis: (1) Biopsy or surrogate parameter for granulomatous inflammation in the respiratory system and (2) Biopsy verified necrotising vasculitis in small to medium sized vessels or biopsy/surrogate parameter for glomerulonephritis or positive PR3-ANCA test and (3) Lack of eosinophilia in blood and biopsy samples. The following diagnostic criteria are proposed for microscopic polyangiitis: (1) Biopsy verified necrotising vasculitis in small vessels and/or glomerulonephritis with few or no immune deposits and (2) Involvement of more than one organ system as indicated by biopsy verified vasculitis in small to medium sized vessels or surrogate parameter for glomerulonephritis and (3) Lack of biopsy and surrogate parameter for granulomatous inflammation in the respiratory system. Using these criteria all Wegener9s patients and 9 of 12 patients with microscopic polyangiitis could be diagnosed.
Intravenous ceftriaxone, followed by 12 or three months of oral treatment with trimethoprim-sulfamethoxazole in Whipple's disease
Authors: Gerhard E. Feurle, Verena Moos, Hendrik Blker, Christoph Loddenkemper, Annette Moter, Andrea Stroux, Thomas Marth, Thomas Schneider
Journal: Journal of Infection (2013)
Heart dimensions may influence the occurrence of the heart rate deflection point in highly trained cyclists.
Authors: A Lucía, A Carvajal, A Boraita, L Serratosa, J Hoyos, J L Chicharro
Journal: British Journal of Sports Medicine (1999)

OBJECTIVES: To determine whether the heart rate (HR) response to exercise in 21 highly trained cyclists (mean (SD) age 25 (3) years) was related to their heart dimensions. METHODS: Before performing an incremental exercise test involving a ramp protocol with workload increases of 25 W/min, each subject underwent echocardiographic evaluation of the following variables: left ventricular end diastolic internal diameter (LVIDd), left ventricular posterior wall thickness at end diastole (LVPWTd), interventricular septal wall thickness at end diastole (IVSTd), left ventricular mass index (LVMI), left atrial dimension (LAD), longitudinal left atrial (LLAD) and right atrial (LRAD) dimensions, and the ratio of early to late (E/A) diastolic flow velocity. RESULTS: The HR response showed a deflection point (HRd) at about 85% VO2MAX in 66.7% of subjects (D group; n = 14) and was linear in 33.3% (NoD group; n = 7). Several echocardiographic variables (LVMI, LAD, LLAD, LRAD) indicative of heart dimensions were similar in each group. However, mean LPWTd (p&lt;0.01) and IVSTd (p&lt;0.05) values were significantly higher in the D group. Finally, no significant difference between groups was found with respect to the E/A. CONCLUSIONS: The HR response is curvilinear during incremental exercise in a considerable number of highly trained endurance athletes-that is, top level cyclists. The departure of HR increase from linearity may predominantly occur in athletes with thicker heart walls.
Deficient cytokine response of human allergen-specific T lymphocytes from humanized SCID mice and reconstitution by professional antigen-presenting cells
Authors: Elizabeth R. Jarman, Kathrin Perschke, Evelyn Montermann, Udo Herz, Harald Renz, Jürgen Knop, Angelika B. Reske-Kunz
Journal: Journal of Allergy and Clinical Immunology (2000)
Randomised controlled trial comparing cost effectiveness of general practitioners and nurse practitioners in primary care
Authors: P Venning, A Durie, M Roland, C Roberts, B Leese
Journal: BMJ (2000)

<h3>Abstract</h3> <b>Objective:</b> To compare the cost effectiveness of general practitioners and nurse practitioners as first point of contact in primary care. <b>Design:</b> Multicentre randomised controlled trial of patients requesting an appointment the same day. <b>Setting:</b> 20 general practices in England and Wales. <b>Participants:</b> 1716 patients were eligible for randomisation, of whom 1316 agreed to randomisation and 1303 subsequently attended the clinic. Data were available for analysis on 1292 patients (651 general practitioner consultations and 641 nurse practitioner consultations). <b>Main outcome measures:</b> Consultation process (length of consultation, examinations, prescriptions, referrals), patient satisfaction, health status, return clinic visits over two weeks, and costs. <b>Results:</b> Nurse practitioner consultations were significantly longer than those of the general practitioners (11.57 <i>v</i> 7.28 min; adjusted difference 4.20, 95% confidence interval 2.98 to 5.41), and nurses carried out more tests (8.7% <i>v</i> 5.6% of patients; odds ratio 1.66, 95% confidence interval 1.04 to 2.66) and asked patients to return more often (37.2% <i>v</i> 24.8%; 1.93, 1.36 to 2.73). There was no significant difference in patterns of prescribing or health status outcome for the two groups. Patients were more satisfied with nurse practitioner consultations (mean score 4.40 <i>v</i> 4.24 for general practitioners; adjusted difference 0.18, 0.092 to 0.257). This difference remained after consultation length was controlled for. There was no significant difference in health service costs (nurse practitioner £18.11 <i>v</i> general practitioner £20.70; adjusted difference £2.33, −£1.62 to £6.28). <b>Conclusions:</b> The clinical care and health service costs of nurse practitioners and general practitioners were similar. If nurse practitioners were able to maintain the benefits while reducing their return consultation rate or shortening consultation times, they could be more cost effective than general practitioners.
Pleiotropic Associations of Risk Variants Identified for Other Cancers With Lung Cancer Risk: The PAGE and TRICL Consortia
Authors: S. Lani Park, Megan D. Fesinmeyer, Maria Timofeeva, Christian P. Caberto, Jonathan M. Kocarnik, Younghun Han, Shelly-Ann Love, Alicia Young, Logan Dumitrescu, Yi Lin, Robert Goodloe, Lynne R. Wilkens, Lucia Hindorff, Jay H. Fowke, Cara Carty, Steven Buyske, Frederick R. Schumacher, Anne Butler, Holli Dilks, Ewa Deelman, Michele L. Cote, Wei Chen, Mala Pande, David C. Christiani, John K. Field, Heike Bickebӧller, Angela Risch, Joachim Heinrich, Paul Brennan, Yufei Wang, Timothy Eisen, Richard S. Houlston, Michael Thun, Demetrius Albanes, Neil Caporaso, Ulrike Peters, Kari E. North, Gerardo Heiss, Dana C. Crawford, William S. Bush, Christopher A. Haiman, Maria Teresa Landi, Rayjean J. Hung, Charles Kooperberg, Christopher I. Amos, Loïc Le Marchand, Iona Cheng
Journal: JNCI Journal of the National Cancer Institute (2014)

Genome-wide association studies have identified hundreds of genetic variants associated with specific cancers. A few of these risk regions have been associated with more than one cancer site; however, a systematic evaluation of the associations between risk variants for other cancers and lung cancer risk has yet to be performed. We included 18023 patients with lung cancer and 60543 control subjects from two consortia, Population Architecture using Genomics and Epidemiology (PAGE) and Transdisciplinary Research in Cancer of the Lung (TRICL). We examined 165 single-nucleotide polymorphisms (SNPs) that were previously associated with at least one of 16 non–lung cancer sites. Study-specific logistic regression results underwent meta-analysis, and associations were also examined by race/ethnicity, histological cell type, sex, and smoking status. A Bonferroni-corrected P value of 2.5×10 –5 was used to assign statistical significance. The breast cancer SNP LSP1 rs3817198 was associated with an increased risk of lung cancer (odds ratio [OR] = 1.10; 95% confidence interval [CI] = 1.05 to 1.14; P = 2.8×10 –6 ). This association was strongest for women with adenocarcinoma ( P = 1.2×10 –4 ) and not statistically significant in men ( P = .14) with this cell type ( Phet by sex = .10). Two glioma risk variants, TERT rs2853676 and CDKN2BAS1 rs4977756, which are located in regions previously associated with lung cancer, were associated with increased risk of adenocarcinoma (OR = 1.16; 95% CI = 1.10 to 1.22; P = 1.1×10 –8 ) and squamous cell carcinoma (OR = 1.13; CI = 1.07 to 1.19; P = 2.5×10 –5 ), respectively. Our findings demonstrate a novel pleiotropic association between the breast cancer LSP1 risk region marked by variant rs3817198 and lung cancer risk.
Issues at the interface between primary and secondary care in the management of common respiratory disease bullet 6: Do hospital physicians have a role in reducing antibiotic prescribing in the community?
Authors: J. Macfarlane
Journal: Thorax (2000)

Recent reports from the Audit Commission 1 and the House of Lords Select Committee 2 on resistance to antibiotics have both been critical of general practitioner (GP) prescribing for the excessive use of antibiotics in respiratory illness, the increasing antibiotic resistance of respiratory pathogens, and excessive drug costs in the community.Such criticism of GPs is not new and appears to have little eVect on prescribing habits.Why do all doctors prescribe antibiotics so often, is this behaviour amenable to change, and what does it have to do with hospital physicians?If changes in prescribing in the community are to be achieved, there probably needs to be a better appreciation of the issues which drive it.This understanding is important, not only for those working in primary care, but also for those in hospital practice.Respiratory physicians and microbiologists teach and influence GPs, medical students, and junior doctors.Their advice and example is important but is less influential, especially in primary care, if it does not also reflect and address the diYculties experienced by doctors who have to treat patients whose attitudes and expectations may diVer significantly from their own.This review highlights some of the issues behind dependence on antibiotic prescribing, particularly for respiratory disease.It focuses on managing the commonest presentation of acute respiratory illness: a previously well adult consulting with a new episode of cough and other lower respiratory tract symptoms.This is often called "acute bronchitis", an imperfect diagnostic label. 3For most of these patients the doctor is uncertain whether antibiotics are indicated, but still prescribes them.
Does the hand reflect implicit knowledge? Yes and no
Authors: Susan Goldin-Meadow, Martha Wagner Alibali
Journal: Behavioral and Brain Sciences (1999)

Gesture does not have a fixed position in the Dienes &amp; Perner framework. Its status depends on the way knowledge is expressed. Knowledge reflected in gesture can be fully implicit (neither factuality nor predication is explicit) if the goal is simply to move a pointing hand to a target. Knowledge reflected in gesture can be explicit (both factuality and predication are explicit) if the goal is to indicate an object. However, gesture is not restricted to these two extreme positions. When gestures are unconscious accompaniments to speech and represent information that is distinct from speech, the knowledge they convey is factuality-implicit but predication-explicit.