tbuckley/cabot-search huggingface dataset:
The devil in the details
Authors: Thomas Wynn
Journal: Behavioral and Brain Sciences (2002)

Despite challenges on minimum necessary competence, intentionality, reliability, and context, the example of cognitive archaeology presented in the target article holds up well. The commentaries also present perspectives on cognition and symmetry that suggest an alternative to the target article's characterization of the cognitive abilities of early Homo erectus. However, the major conclusion of the initial argument – that the human ability to coordinate shape recognition and spatial cognition evolved hundreds of thousands of year ago in conditions unlike those of the modern world – remains intact.
Changes in joint position sense after surgically treated chronic lateral ankle instability
Authors: T Halasi, Á Kynsburg, A Tállay, I Berkes
Journal: British Journal of Sports Medicine (2005)

A search of the literature shows that the effect of surgery on ankle proprioception has been hardly investigated.To examine the effect of anatomical reconstruction of the anterolateral capsuloligamentous complex on ankle joint position sense.A prospective study using the "slope box" test. Ten consecutive patients were included in the study, and 10 healthy athletes represented the control group.Similar test-retest reliability rates (overall reliability 0.92; p = 0.0013) were obtained to those of the original designers of the method. There were no significant differences with respect to side dominance (p = 0.9216). Investigation of the characteristics of mean absolute estimate errors showed that the controls tested became error prone in the range of slope altitudes 7.5-25 degrees in every direction, compared with the range 0-5 degrees (range of p values 0.00003-0.00072). The results of the intervention group showed that, for the two main directions of interest (anterior and lateral), preoperative differences in mean absolute estimate errors between injured (anterior 3.91 (2.81) degrees ; lateral 4.06 (2.85) degrees ) and healthy (anterior 2.94 (2.21) degrees , lateral 3.19 (2.64) degrees ) sides (anterior, p = 0.0124; lateral, p = 0.0250) had disappeared (postoperative differences: anterior, p = 0.6906; lateral, p = 0.4491). The afflicted ankle had improved significantly after surgery in both important directions (anterior, p<0.0001; lateral, p = 0.0023).The study shows that differences in joint position sense between healthy and injured ankles disappeared as the result of surgery. Preoperative data show that proprioceptive malfunction is a cause of functional instability. If treatment is by means of surgery, the retensioning of the original anterolateral structures is inevitable, even if other grafting or surgical techniques are used.
The clinical response to infliximab in rheumatoid arthritis is in part dependent on pretreatment tumour necrosis factor expression in the synovium
Authors: C A Wijbrandts, M G W Dijkgraaf, M C Kraan, M Vinkenoog, T J Smeets, H Dinant, K Vos, W F Lems, G J Wolbink, D Sijpkens, B A C Dijkmans, P P Tak
Journal: Annals of the Rheumatic Diseases (2007)

<h3>Objective:</h3> To determine whether the heterogeneous clinical response to tumour necrosis factor (TNF)α blocking therapy in rheumatoid arthritis (RA) can be predicted by TNFα expression in the synovium before initiation of treatment. <h3>Methods:</h3> Prior to initiation of infliximab treatment, arthroscopic synovial tissue biopsies were obtained from 143 patients with active RA. At week 16, clinical response was evaluated using the 28-joint Disease Activity Score (DAS28). Immunohistochemistry was used to analyse the cell infiltrate as well as the expression of various cytokines, adhesion molecules and growth factors. Stained sections were evaluated by digital image analysis. Student t tests were used to compare responders (decrease in DAS28 ⩾1.2) with non-responders (decrease in DAS28 &lt;1.2) and multivariable regression was used to identify the independent predictors of clinical response. <h3>Results:</h3> Synovial tissue analysis confirmed our hypothesis that the baseline level of TNFα expression is a significant predictor of response to TNFα blocking therapy. TNFα expression in the intimal lining layer and synovial sublining were significantly higher in responders than in non-responders (p = 0.047 and p = 0.008, respectively). The numbers of macrophages, macrophage subsets and T cells (all able to produce TNFα) were also significantly higher in responders than in non-responders. The expression of interleukin (IL)1β, IL6, IL18, IL10, E-selectin, intercellular adhesion molecule (ICAM)-1, vascular cell adhesion molecule (VCAM)-1, vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) was not associated with response to anti-TNFα treatment. <h3>Conclusion:</h3> The effects of TNFα blockade are in part dependent on synovial TNFα expression and infiltration by TNFα producing inflammatory cells. Clinical response cannot be predicted completely, indicating involvement of other as yet unknown mechanisms.
Ia antigens in rat kidney, with special reference to their expression in tubular epithelium.
Authors: G Mayrhofer, M A Schon-Hegrad
Journal: The Journal of Experimental Medicine (1983)

The distribution of Ia antigens in rat kidneys has been investigated by an immunoperoxidase technique, using monoclonal antibodies directed at framework determinants on molecules equivalent to gene products of the I-A and I-E/C regions of the mouse major histocompatibility complex (MHC). Antigens mapping to both loci were detected in proximal convoluted tubule epithelium and on scattered dendritic cells in the interstitial connective tissues, glomeruli, and mucosa of the renal pelvis. All other structures were negative. Genetic studies indicate that the levels of expression of Ia molecules from both genetic loci are controlled by non-MHC genes in epithelium, but not on lymphocytes. The subcellular distribution of Ia molecules has been investigated in tubular epithelium and is discussed in relation to their possible functions in epithelia.
Nateglinide Improves Early Insulin Secretion and Controls Postprandial Glucose Excursions in a Prediabetic Population
Authors: Carola Saloranta, Christiane Guitard, Eckhard Pecher, Pedro de Pablos-Velasco, Kaj Lahti, Patrick Brunel, Leif Groop
Journal: Diabetes Care (2002)

OBJECTIVE—The purpose of this study was to evaluate the metabolic effectiveness, safety, and tolerability of nateglinide in subjects with impaired glucose tolerance (IGT) and to identify a dose appropriate for use in a diabetes prevention study. RESEARCH DESIGN AND METHODS—This multicenter, double-blind, randomized, parallel-group, fixed-dose study of 8 weeks’ duration was performed in a total of 288 subjects with IGT using a 2:2:2:1 randomization. Subjects received nateglinide (30, 60, and 120 mg) or placebo before each main meal. Metabolic effectiveness was assessed during a standardized meal challenge performed before and after the 8-week treatment. All adverse events (AEs) were recorded, and confirmed hypoglycemia was defined as symptoms accompanied by a self-monitoring of blood glucose measurement ≤3.3 mmol/l (plasma glucose ≤3.7 mmol/l). RESULTS—Nateglinide elicited a dose-related increase of insulin and a decrease of glucose during standardized meal challenges, with the predominant effect on early insulin release, leading to a substantial reduction in peak plasma glucose levels. Nateglinide was well tolerated, and symptoms of hypoglycemia were the only treatment-emergent AEs. Confirmed hypoglycemia occurred in 28 subjects receiving nateglinide (30 mg, 0 [0%]; 60 mg, 5 [6.6%]; 120 mg, 23 [26.7%]) and in 1 (2.3%) subject receiving placebo. CONCLUSIONS—Nateglinide was safe and effective in reducing postprandial hyperglycemia in subjects with IGT. Preprandial doses of 30 or 60 mg nateglinide would be appropriate to use for longer-term studies to determine whether a rapid-onset, rapidly reversible, insulinotropic agent can delay or prevent the development of type 2 diabetes.
Effects of Matrix Metalloproteinase Inhibition on Ventricular Remodeling Due to Volume Overload
Authors: Amanda L. Chancey, Gregory L. Brower, J. Thomas Peterson, Joseph S. Janicki
Journal: Circulation (2002)

Background — Left ventricular (LV) hypertrophy and dilatation are important compensatory responses to chronic volume overload. Although LV function is initially preserved by these responses, the continued structural remodeling of the myocardium ultimately becomes maladaptive, leading to the development of heart failure. We have shown previously that increased myocardial matrix metalloproteinase (MMP) activity precedes LV dilatation induced by a chronic volume overload. Accordingly, this study focused on the effects of MMP inhibition therapy (PD 166793, 1 mg · kg −1 · d −1 ) on LV size and function in a rat model of volume overload–induced heart failure. Methods and Results — Rats were divided into the following groups: treated and untreated infrarenal abdominal aortocaval fistula and treated and untreated sham-operated (control). LV weights of both fistula groups were increased above that of the control group (868±79 mg; P ≤0.001); LV weights in the treated fistula group, however, were lower than in the untreated fistula group at 8 weeks (1447±186 versus 1715±279 mg, respectively; P ≤0.012). The marked ventricular dilatation seen in the untreated fistula group was significantly diminished in the treated fistula group, although the increase in LV compliance was similar in both treated and untreated fistula hearts. Conclusions — MMP inhibition significantly attenuates the myocardial remodeling associated with chronic volume overload, as evidenced by prevention of dilatation, a marked reduction in LV hypertrophy, and preservation of ventricular function.
Immunoreactivity of bullous pemphigoid (BP) autoantibodies against the NC16A and C-terminal domains of the 180 kDa BP antigen (BP180): immunoblot analysis and enzyme-linked immunosorbent assay using BP180 recombinant proteins
Authors: None Nakatani, None Muramatsu, None Shirai
Journal: British Journal of Dermatology (1998)

The 180 kDa bullous pemphigoid (BP) antigen (BP180) is known to be recognized by sera from patients with BP, herpes gestationis (HG) and cicatricial pemphigoid (CP). A series of previous studies using BP180 recombinant proteins has shown that most sera from patients with BP and HG react with the NC16A domain of BP180, an extracellular non-collagenous region just adjacent to the plasma membrane. In contrast, the C-terminal region of BP180 has been reported to be one of the epitopes of CP. In the present study, we examined the immunoreactivity of 110 BP sera against the NC16A and C-terminal domains of BP180 using immunoblot analysis and enzyme-linked immunosorbent assay (ELISA). Immunoblot analysis revealed that 100 (91%) and 26 (23.5%) of the 110 BP sera recognized the NC16A and C-terminal domains, respectively. The results of the ELISA were correlated with those of immunoblotting. There were no specific or significant clinical features such as severe involvement of mucous membranes and scarring in BP patients whose sera reacted with the C-terminal region. These findings suggest that some BP sera react with the C-terminal region of BP180 without any association with the characteristic clinical features of CP.
Etiological Approach to Characterization of Diabetes Type
Authors: Dana Dabelea, Catherine Pihoker, Jennifer W. Talton, Ralph B. D’Agostino, Wilfred Fujimoto, Georgeanna J. Klingensmith, Jean M. Lawrence, Barbara Linder, Santica M. Marcovina, Elizabeth J. Mayer-Davis, Giuseppina Imperatore, Lawrence M. Dolan
Journal: Diabetes Care (2011)

To describe an etiologic approach to classification of diabetes types in youth based on the 1997 American Diabetes Association (ADA) framework, using data from the SEARCH for Diabetes in Youth Study.SEARCH conducted a comprehensive assessment of 2,291 subjects aged <20 years with recently diagnosed diabetes. Using autoimmunity (at least one of two diabetes autoantibodies) and insulin sensitivity (equation validated against hyperinsulinemic-euglycemic clamps) as the main etiologic markers, we described four categories along a bidimensional spectrum: autoimmune plus insulin-sensitive (IS), autoimmune plus insulin-resistant (IR), nonautoimmune plus IS, and nonautoimmune plus IR. We then explored how characteristics, including genetic susceptibility to autoimmunity (HLA genotypes), insulin deficiency, and clinical factors varied across these four categories.Most subjects fell into either the autoimmune plus IS (54.5%) or nonautoimmune plus IR categories (15.9%) and had characteristics that align with traditional descriptions of type 1 or type 2 diabetes. The group classified as autoimmune plus IR (19.5%) had similar prevalence and titers of diabetes autoantibodies and similar distribution of HLA risk genotypes to those in the autoimmune plus IS group, suggesting that it includes individuals with type 1 diabetes who are obese. The group classified as nonautoimmune plus IS (10.1%) likely includes individuals with undetected autoimmunity but may also include those with monogenic diabetes and thus requires further testing.The SEARCH study offers researchers and clinicians a practical application for the etiologic classification of diabetes type and at the same time identifies a group of youths who would benefit from further testing.
Anaphylaxis in America: The prevalence and characteristics of anaphylaxis in the United States
Authors: Robert A. Wood, Carlos A. Camargo, Philip Lieberman, Hugh A. Sampson, Lawrence B. Schwartz, Myron Zitt, Charlotte Collins, Michael Tringale, Marilyn Wilkinson, John Boyle, F. Estelle R. Simons
Journal: Journal of Allergy and Clinical Immunology (2013)
Multidimensional approach to non-cystic fibrosis bronchiectasis: the FACED score
Authors: Miguel Á. Martínez-García, Javier de Gracia, Monserrat Vendrell Relat, Rosa-Maria Girón, Luis Máiz Carro, David de la Rosa Carrillo, Casilda Olveira
Journal: European Respiratory Journal (2013)

Bronchiectasis is a multidimensional disease and, therefore, its severity or prognosis cannot be adequately quantified by analysing one single variable. The objective of the present study was to develop a multidimensional score that classifies the severity of bronchiectasis according to its prognosis. This is an observational multicentre study including 819 patients diagnosed with non-cystic fibrosis bronchiectasis using high-resolution computed tomography. 397 subjects were selected at random to construct the score while the remaining 422 were used for its validation. The outcome was 5-year all-cause mortality after radiological diagnosis. A logistic regression analysis was used to select the variables included in the final score. The final seven-point score incorporated five dichotomised variables: forced expiratory volume in 1 s % predicted (F, cut-off 50%, maximum value 2 points); age (A, cut-off 70 years, maximum value 2 points); presence of chronic colonisation by Pseudomonas aeruginosa (C, dichotomic, maximum value 1 point); radiological extension (E, number of lobes affected, cut-off two lobes, maximum value 1 point); and dyspnoea (D, cut-off grade II on the Medical Research Council scale, maximum value 1 point) to construct the FACED score. The validation cohort confirmed the score’s validity. We conclude that this easy-to-use multidimensional grading system proved capable of accurately classifying the severity of bronchiectasis according to its prognosis.
Long-acting β-agonist prescribing in people with asthma in primary care: Table 1
Authors: Daniel R Morales, Cathy Jackson, Shona Fielding, Bruce Guthrie
Journal: Thorax (2012)

Long-acting β2-agonist (LABA) monotherapy is contraindicated in asthma following reports of serious adverse events. Anonymised Scottish health data were used to determine the prevalence of LABA prescribing and LABA monotherapy (sustained and episodic) in asthma during 2006. Of 73 486 asthma patients identified, 5592 (7.6%; 95% CI 7.4% to 7.8%) were prescribed LABAs as a separate inhaler of which 991 patients had LABA monotherapy (17.7% (95% CI 16.7% to 18.7%) of patients at risk). Asthma reviews were associated with reductions in sustained (OR 0.44; 95% CI 0.32 to 0.61) but not episodic monotherapy (OR 1.16; 95% CI 0.85 to 1.57). These findings support recent changes in UK asthma guidelines recommending LABAs in fixed-dose combination inhalers.
Use of Metformin in the Setting of Mild-to-Moderate Renal Insufficiency
Authors: Kasia J. Lipska, Clifford J. Bailey, Silvio E. Inzucchi
Journal: Diabetes Care (2011)

A common clinical conundrum faces all U.S. practitioners treating patients with type 2 diabetes. Today’s U.S. Food and Drug Administration prescribing guidelines for metformin contraindicate its use in men and women with serum creatinine concentrations ≥1.5 and ≥1.4 mg/dL (≥132 and ≥123 µmol/L), respectively. In a patient tolerating and controlled with this medication, should it automatically be discontinued as the creatinine rises beyond these cut points over time? Stopping metformin often results in poorly controlled glycemia and/or the need for other agents with their own adverse-effect profiles. Moreover, is the now widespread use of estimated glomerular filtration rate (eGFR) in lieu of serum creatinine levels creating even more confusion, especially in those with abnormalities in one but not the other indirect measure of renal function? Indeed, more than a decade and a half after metformin became available in the U.S., debate continues over the best approach in these settings (1–3). How many patients are unable to receive this medication on the basis of guidelines which, although well intentioned, are somewhat arbitrary and outdated based on modern assessments of renal status?

There is some evidence that early treatment with metformin is associated with reduced cardiovascular morbidity and total mortality in newly diagnosed type 2 diabetic patients (4). However, the data come from a small subgroup of a much larger trial. In contrast, despite multiple trials of intensive glucose control using a variety of glucose-lowering strategies, there is a paucity of data to support specific advantages with other agents on cardiovascular outcomes (5–7).

In the original UK Prospective Diabetes Study (UKPDS), 342 overweight patients with newly diagnosed diabetes were randomly assigned to metformin therapy (8). After a median period of 10 years, this subgroup experienced a 39% ( P = 0.010) risk reduction for myocardial infarction and a …
Radiologists' Interpretations: The Problem of Context Bias-Reply
Authors: Thomas Egglin
Journal: JAMA (1997)

In Reply.  —The availability of a clinical history certainly affects the interpretations of radiologists. We agree with Dr Vermont that informing the radiologists in our study that patients belonged to either high-risk or low-risk groups might have had a significant impact on their diagnoses. We believe, however, that his proposed scenario would simply replicate the effect of adding the history. Our results showed that, even when such influences are avoided, radiologists' diagnoses are not based solely on each set of films. Context bias demonstrates the effect of particular sequences or combinations of films. These influences of history, risk, and context complicate the objective assessment of radiologic tests, although their relation to the outcomes of patient care remains unexplored.
Human tumour xenografts growing in immunodeficient mice: a useful model for assessing chemotherapeutic agents in bronchial carcinoma.
Authors: R J Fergusson, J Carmichael, J F Smyth
Journal: Thorax (1986)

Xenografts from eight human bronchial carcinomas have been established in CBA/Lac mice rendered immunodeficient by neonatal thymectomy followed three weeks later by whole body irradiation (7.35 Gy (735 rads)) after a priming dose of cytosine arabinoside. Growth rates of individual tumour lines remain constant and the histological and chromosomal characteristics of the original tumour are maintained through multiple serial passages over many months. With specific growth delay as the principal end point this system may be used to assess the response of histologically different lung tumours to chemotherapeutic agents.
Differential Changes in Cardiac Phospholamban and Sarcoplasmic Reticular Ca <sup>2+</sup> -ATPase Protein Levels
Authors: Eva Kiss, Nancy A. Ball, Evangelia G. Kranias, Richard A. Walsh
Journal: Circulation Research (1995)

The objective of this study was to elucidate the role of the sarcoplasmic reticulum (SR) in the transition from compensated pressure-overload hypertrophy (increased left ventricular [LV] mass, normal LV function, and no pulmonary congestion) to congestive heart failure (increased LV mass, depressed LV function, and pulmonary congestion). To address this issue, the descending thoracic aorta was banded for 4 and 8 weeks in adult guinea pigs, and the changes in isovolumic LV mechanics, SR Ca2+ transport, and SR protein levels were determined and compared with age-matched sham-operated control animals. A subgroup of the 8-week banded animals manifested the congestive heart failure phenotype with diminished developed LV pressure normalized by LV mass, reduced rates of LV pressure development and relaxation, and markedly increased lung weight-to-body weight ratios. The cardiac mechanical and morphometric changes were associated with depressed protein levels of the SR Ca(2+)-ATPase (85% of the control) and phospholamban (65% of the control) assessed by quantitative immunoblotting. Resultant rates of SR Ca2+ uptake (Vmax) and the affinity of SR Ca(2+)-ATPase for Ca2+ (EC50) were significantly depressed [32 +/- 6 nmol Ca2+.min-1.mg-1 and 0.59 +/- 0.12 (mumol/L)/L, respectively] compared with the 8-week sham-operated control animals [40 +/- 1 nmol Ca2+.min-1.mg-1 and 0.40 +/- 0.05 (mumol/L)/L, respectively]. We conclude that this model of pressure overload-induced cardiac failure is associated with (1) diminished LV force development, rates of pressure development, and decay; (2) depressed protein expression of the Ca(2+)-cycling proteins SR Ca(2+)-ATPase and phospholamban; and (3) decreased Vmax and affinity of the SR Ca(2+)-ATPase for Ca2+.(ABSTRACT TRUNCATED AT 250 WORDS)