tbuckley/cabot-search huggingface dataset:
Prospective evaluation of risk of vertebral fractures using quantitative ultrasound measurements and bone mineral density in a population-based sample of postmenopausal women: results of the Basel Osteoporosis Study
Authors: R Hollaender, F Hartl, M-A Krieg, A Tyndall, C Geuckel, C Buitrago-Tellez, M Manghani, M Kraenzlin, R Theiler, D Hans
Journal: Annals of the Rheumatic Diseases (2008)

Objective: Prospective studies have shown that quantitative ultrasound (QUS) techniques predict the risk of fracture of the proximal femur with similar standardised risk ratios to dual-energy x -ray absorptiometry (DXA). Few studies have investigated these devices for the prediction of vertebral fractures. The Basel Osteoporosis Study (BOS) is a population-based prospective study to assess the performance of QUS devices and DXA in predicting incident vertebral fractures. Methods: 432 women aged 60–80 years were followed-up for 3 years. Incident vertebral fractures were assessed radiologically. Bone measurements using DXA (spine and hip) and QUS measurements (calcaneus and proximal phalanges) were performed. Measurements were assessed for their value in predicting incident vertebral fractures using logistic regression. Results: QUS measurements at the calcaneus and DXA measurements discriminated between women with and without incident vertebral fracture, (20% height reduction). The relative risks (RRs) for vertebral fracture, adjusted for age, were 2.3 for the Stiffness Index (SI) and 2.8 for the Quantitative Ultrasound Index (QUI) at the calcaneus and 2.0 for bone mineral density at the lumbar spine. The predictive value (AUC (95% CI)) of QUS measurements at the calcaneus remained highly significant (0.70 for SI, 0.72 for the QUI, and 0.67 for DXA at the lumbar spine) even after adjustment for other confounding variables. Conclusions: QUS of the calcaneus and bone mineral density measurements were shown to be significant predictors of incident vertebral fracture. The RRs for QUS measurements at the calcaneus are of similar magnitude as for DXA measurements.
BICEPS FEMORIS MUSCLE ARCHITECTURE – THE INFLUENCE OF PREVIOUS INJURY
Authors: R Timmins, K Porter, M Williams, A Shield, D Opar
Journal: British Journal of Sports Medicine (2014)

Background A history of hamstring strain injury (HSI) has been indicated as a primary risk factor for a future injury. It is unknown whether a prior strain influences the architectural characteristics of the hamstring. Objective To determine if alterations occur to the architecture of the long head (BFlh) muscle in those with a history of strain injury to this muscle. Design Reliability and retrospective case-control study design. Setting Clinical setting with recreationally active males and elite Australian Footballers. Participants 31 males (Australian Footballers n=14, recreational males n=17). Of the 31 participants, 18 had a prior unilateral HSI, whereas the other 13 formed an uninjured control group. Risk factor assessment The independent variables were muscle fascicle length (FL), pennation angle (PA) and thickness (MT)). Main outcome measure The BFlh muscle architecture of both limbs was assessed utilising B-mode ultrasound (General Electric Vivid-i) whilst rested in a prone position. The scan site was determined as 50% of the distance between the ischial tuberosity and the lateral knee joint line. The hypothesis prior to recruitment was that a history of injury would result in a reduction of FL and MT and an increase in PA. Reliability was assessed at a second time point within ten days of the initial visit and was determined utilising intra-class correlations (ICC). Results The assessment of the architectural characteristics of the BFlh was shown as reliable whilst in a rested state (FL and PA ICC=0.97, MT=0.96). PA's (P=.001) and FL's (P=.013) were significantly less in the previously injured BFlh then the contralateral uninjured limb. Muscle thickness was not significantly different (p=0.466). Conclusions Ultrasound is a reliable measure of architectural characteristics in the BFlh. A previously injured BFlh displays reductions in FL and increases in PA. These variations may partly explain the high rate of recurrence of HSI's.
Assessing Benefit and Risk in the Prevention of Prostate Cancer: The Prostate Cancer Prevention Trial Revisited
Authors: Eric A. Klein, Catherine M. Tangen, Phyllis J. Goodman, Scott M. Lippman, Ian M. Thompson
Journal: Journal of Clinical Oncology (2005)

Purpose The Prostate Cancer Prevention Trial demonstrated a 25% reduction in period prevalence of prostate cancer in men randomly assigned to 5 mg/d of finasteride. However, widespread use of finasteride for prevention is inhibited by the observed increased risk of high-grade disease. We present a model of risk and benefit that estimates the potential effects of histologic artifact in the assignment of excess risk for high-grade disease and the possible effect of overdetection bias introduced by finasteride-induced volume reduction. Methods The absolute benefit/absolute risk ratio of finasteride use was estimated by calculating the ratio of absolute risk reduction in the finasteride arm to the absolute risk of excess high-grade cancers. This ratio was recalculated for assumptions that 10%, 25%, or 50% of the excess high-grade cancers were due to histologic artifact, and that there was a 25% overdetection bias in the finasteride arm. Results For all cancers the absolute benefit/absolute risk ratio increased from 4.6:1 to 5.1:1, 6.2:1, and 9.2:1 for assumptions of 10%, 25%, or 50% histologic artifact, respectively. The ratio increased from 4.6:1 to 8.2:1 for the assumption of 25% overdetection bias, and to 9.1:1, 10.9:1, and 16.3:1 for combined assumptions of 25% overdetection bias and 10%, 25%, or 50% histologic artifact, respectively. Conclusion The adoption of a prevention strategy hinges on potential benefits weighed against potential risks. This model demonstrates the magnitude of effect for a hypothesized range of histologic artifact and overdetection bias on the assessment of risk versus benefit for finasteride.
Role of Parental Monitoring in Understanding the Benefits of Parental Acceptance on Adolescent Adherence and Metabolic Control of Type 1 Diabetes
Authors: Cynthia A. Berg, Jorie M. Butler, Peter Osborn, Gary King, Debra L. Palmer, Jonathan Butner, Mary Murray, Rob Lindsay, David Donaldson, Carol Foster, Michael Swinyard, Deborah J. Wiebe
Journal: Diabetes Care (2008)

OBJECTIVE—This study examined 1) whether the benefits of mothers’ and fathers’ accepting relationships with their adolescents regarding diabetes control were due to parental monitoring and 2) how parents together may provide sufficient acceptance and monitoring for diabetes management. RESEARCH DESIGN AND METHODS—Adolescents aged 10–14 years with type 1 diabetes (n = 185) and their mothers (n = 185) and fathers (n = 145) completed assessments of parental acceptance and monitoring of diabetes tasks. Adolescents completed a modified version of the Self-Care Inventory (1) to measure adherence. A1C scores were used as a marker of glycemic control. RESULTS—Mediational analyses revealed that the benefits of adolescents’ reports of fathers’ acceptance on A1C and mothers’ and fathers’ acceptance on better adherence were partially mediated by monitoring. Both mothers’ and fathers’ monitoring and fathers’ acceptance had independent effects in predicting adherence. However, only fathers’ monitoring had an independent effect on A1C. The effect of fathers’ monitoring on A1C occurred as fathers were monitoring at a lower level than mothers. Mothers’ and fathers’ reports of their own acceptance and monitoring were not associated with A1C or adherence. CONCLUSIONS—Results reveal the importance of fathers’ acceptance and monitoring in diabetes management, a role that should be encouraged, despite the little attention it has received.
Docetaxel 100 versus 80 mg/m2 as adjuvant treatments of early breast cancer: an exploratory analysis of a randomised trial
Authors: P. Bono, P.-L. Kellokumpu-Lehtinen, T. Alanko, R. Kokko, R. Asola, T. Turpeenniemi-Hujanen, S. Jyrkkiö, V. Kataja, M. Leinonen, H. Joensuu
Journal: Annals of Oncology (2009)
Early Glycemic Control, Age at Onset, and Development of Microvascular Complications in Childhood-Onset Type 1 Diabetes
Authors: Maria Svensson, Jan W. Eriksson, Gisela Dahlquist
Journal: Diabetes Care (2004)

OBJECTIVE—The aim of this work was to study the impact of glycemic control (HbA1c) early in disease and age at onset on the occurrence of incipient diabetic nephropathy (MA) and background retinopathy (RP) in childhood-onset type 1 diabetes. RESEARCH DESIGN AND METHODS—All children, diagnosed at 0–14 years in a geographically defined area in northern Sweden between 1981 and 1992, were identified using the Swedish Childhood Diabetes Registry. From 1981, a nationwide childhood diabetes care program was implemented recommending intensified insulin treatment. HbA1c and urinary albumin excretion were analyzed, and fundus photography was performed regularly. Retrospective data on all 94 patients were retrieved from medical records and laboratory reports. RESULTS—During the follow-up period, with a mean duration of 12 ± 4 years (range 5–19), 17 patients (18%) developed MA, 45 patients (48%) developed RP, and 52% had either or both complications. A Cox proportional hazard regression, modeling duration to occurrence of MA or RP, showed that glycemic control (reflected by mean HbA1c) during the follow-up was significantly associated with both MA and RP when adjusted for sex, birth weight, age at onset, and tobacco use as potential confounders. Mean HbA1c during the first 5 years of diabetes was a near-significant determinant for development of MA (hazard ratio 1.41, P = 0.083) and a significant determinant of RP (1.32, P = 0.036). The age at onset of diabetes significantly influenced the risk of developing RP (1.11, P = 0.021). Thus, in a Kaplan-Meier analysis, onset of diabetes before the age of 5 years, compared with the age-groups 5–11 and &amp;gt;11 years, showed a longer time to occurrence of RP (P = 0.015), but no clear tendency was seen for MA, perhaps due to lower statistical power. CONCLUSIONS—Despite modern insulin treatment, &amp;gt;50% of patients with childhood-onset type 1 diabetes developed detectable diabetes complications after ∼12 years of diabetes. Inadequate glycemic control, also during the first 5 years of diabetes, seems to accelerate time to occurrence, whereas a young age at onset of diabetes seems to prolong the time to development of microvascular complications.
PET of Brain Amyloid and Tau in Mild Cognitive Impairment
Authors: Gary W. Small, Vladimir Kepe, Linda M. Ercoli, Prabha Siddarth, Susan Y. Bookheimer, Karen J. Miller, Helen Lavretsky, Alison C. Burggren, Greg M. Cole, Harry V. Vinters, Paul M. Thompson, S.-C. Huang, N. Satyamurthy, Michael E. Phelps, Jorge R. Barrio
Journal: New England Journal of Medicine (2006)

Amyloid senile plaques and tau neurofibrillary tangles are neuropathological hallmarks of Alzheimer's disease that accumulate in the cortical regions of the brain in persons with mild cognitive impairment who are at risk for Alzheimer's disease. Noninvasive methods to detect these abnormal proteins are potentially useful in developing surrogate markers for drug discovery and diagnostics.We enrolled 83 volunteers with self-reported memory problems who had undergone neurologic and psychiatric evaluation and positron-emission tomography (PET). On the basis of cognitive testing, 25 volunteers were classified as having Alzheimer's disease, 28 as having mild cognitive impairment, and 30 as having no cognitive impairment (healthy controls). PET was performed after injection of 2-(1-{6-[(2-[F-18]fluoroethyl)(methyl)amino]-2-naphthyl}ethylidene)malononitrile (FDDNP), a molecule that binds to plaques and tangles in vitro. All subjects also underwent 2-deoxy-2-[F-18]fluoro-D-glucose (FDG) PET, and 72 underwent magnetic resonance imaging (MRI).Global values for FDDNP-PET binding (average of the values for the temporal, parietal, posterior cingulate, and frontal regions) were lower in the control group than in the group with mild cognitive impairment (P<0.001), and the values for binding in the group with mild cognitive impairment were lower than in the group with Alzheimer's disease (P<0.001). FDDNP-PET binding differentiated among the diagnostic groups better than did metabolism on FDG-PET or volume on MRI.FDDNP-PET scanning can differentiate persons with mild cognitive impairment from those with Alzheimer's disease and those with no cognitive impairment. This technique is potentially useful as a noninvasive method to determine regional cerebral patterns of amyloid plaques and tau neurofibrillary tangles.
Oregovomab Maintenance Monoimmunotherapy Does Not Improve Outcomes in Advanced Ovarian Cancer
Authors: Jonathan Berek, Peyton Taylor, William McGuire, L. Mary Smith, Birgit Schultes, Christopher F. Nicodemus
Journal: Journal of Clinical Oncology (2008)

Purpose This phase III study tested the hypothesis that the CA-125–specific murine monoclonal antibody, oregovomab, administered as a monoimmunotherapy after front-line therapy in a selected ovarian cancer population would prolong time to relapse (TTR) and, ultimately, survival. Patients and Methods Patients with stage III to IV ovarian cancer with preoperatively elevated CA-125 and objectively defined characteristics were randomly assigned 4 to 12 weeks after front-line carboplatin and paclitaxel chemotherapy to maintenance monoimmunotherapy in a fully blinded protocol. Two mg of oregovomab or placebo was infused over 20 minutes at weeks 0, 4, and 8 and then 12 weeks until recurrence or up to year 5. Patients were evaluated with serial imaging and clinical evaluation for evidence of recurrence at quarterly visits. TTR was the primary end point. Results Three hundred seventy-three patients were accrued at more than 60 centers; 251 patients were assigned to oregovomab and 120 patients were assigned to placebo. The treatment arms were well balanced. There were no differences in the clinical outcomes between treatment groups. Median TTR measured from randomization after completion of chemotherapy for the integrated study was 10.3 months (95% CI, 9.7 to 13.0 months) for oregovomab and 12.9 months (95% CI, 10.1 to 17.4 months) for placebo (P = .29, log-rank test). The treatment was well tolerated. Grade 3 to 4 toxicity was reported in 24.6% of patients in the placebo group and 20.1% of patients in the oregovomab group, respectively. Conclusion Although oregovomab has demonstrated bioactivity, the strategy of monoimmunotherapy is not effective as maintenance therapy after front-line treatment of a favorable subset of patients with advanced ovarian cancer. Future studies of this or other tumor-antigen specific immunization strategies should seek ways to further augment induced immunity.
Phylogenetic Analyses of Two “Archaeal” Genes in Thermotoga maritima Reveal Multiple Transfers Between Archaea and Bacteria
Authors: Camilla L. Nesbo, Stéphane L'Haridon, Karl O. Stetter, W. Ford Doolittle
Journal: Molecular Biology and Evolution (2001)

The genome sequence of Thermotoga maritima revealed that 24% of its open reading frames (ORFs) showed the highest similarity scores to archaeal genes in BLAST analyses. Here we screened 16 strains from the genus Thermotoga and other related Thermotogales for the occurrence of two of these "archaeal" genes: the gene encoding the large subunit of glutamate synthase (gltB) and the myo-inositol 1P synthase gene (ino1). Both genes were restricted to the Thermotoga species within the Thermotogales. The distribution of the two genes, along with results from phylogenetic analyses, showed that they were acquired from Archaea during the divergence of the Thermotogales. Database searches revealed that three other bacteria—Dehalococcoides ethenogenes, Sinorhizobium meliloti, and Clostridium difficile—possess archaeal-type gltBs, and the phylogenetic analyses confirmed at least two lateral gene transfer (LGT) events between Bacteria and Archaea. These LGT events were also strongly supported by gene structure data, as the three domains in bacterial-type gltB are homologous to three independent ORFs in Archaea and Bacteria with archaeal-type gltBs. The ino1 gene has a scattered distribution among Bacteria, and apart from the Thermotoga strains it is found only in Aquifex aeolicus, D. ethenogenes, and some high-G+C Gram-positive bacteria. Phylogenetic analysis of the ino1 sequences revealed three highly supported prokaryotic clades, all containing a mixture of archaeal and bacterial sequences, and suggested that all bacterial ino1 genes had been recruited from archaeal donors. The Thermotoga strains and A. aeolicus acquired this gene independently from different archaeal species. Although transfer of genes from hyperthermophilic Archaea may have facilitated the evolution of bacterial hyperthermophily, between-domain transfers also affect mesophilic species. For hyperthermophiles, we hypothesize that LGT may be as much a consequence as the cause of adaptation to hyperthermophily.
THE NATURE OF THE ANTIGENIC DETERMINANT IN A GENETIC CONTROL OF THE ANTIBODY RESPONSE
Authors: Edna Mozes, Hugh O. McDevitt, Jean-Claude Jaton, Michael Sela
Journal: The Journal of Experimental Medicine (1969)

The response of inbred mouse strains to two polypeptides derived from multichain polyprolines, (T,G)-Pro--L and (Phe,G)-Pro--L, is different from the response of the same mouse strains to a similar series of polymers built on multi-poly-D,L-alanyl--poly-L-lysine, although the same short sequences of amino acids are attached to the side chains of the polypeptides in the two series. These results indicate that a portion of the side chain (e.g. polyalanine or polyproline) participates in the antigenic determinant. This was confirmed by studying the response of different mouse strains to two kinds of polypeptides: (T,G)-Pro-A--L 717 and 718 and (T,G)-A-Pro--L 719 and 721. Antibody assay of antisera to (Phe,G)-Pro--L with the cross-reacting antigens (T,G)-Pro--L and (Phe,G)-A-L indicates that different inbred mouse strains make antibodies specific for different parts of the same polypeptide. Thus, antibody from DBA/1 mice reacts almost exclusively with the (Phe,G) sequence, while SJL antisera bind only (T,G)-Pro--L and fail to bind (Phe,G)-A-L. The immune responses to the same amino acids on two different polypeptides (i.e. A--L and Pro--L) appear to be under separate genetic control.
Treatment Quality and Outcomes of African American Versus White Breast Cancer Patients: Retrospective Analysis of Southwest Oncology Studies S8814/S8897
Authors: Dawn L. Hershman, Joseph M. Unger, William E. Barlow, Laura F. Hutchins, Silvana Martino, C. Kent Osborne, Robert B. Livingston, Kathy S. Albain
Journal: Journal of Clinical Oncology (2009)

Women of African ancestry (AA) have lower WBC counts and are more likely to have treatment delays and discontinue adjuvant breast cancer therapy early compared with white women. We assessed the association between race and treatment discontinuation/delay, WBC counts, and survival in women enrolled onto breast cancer clinical trials.AA and white women from Southwest Oncology Group adjuvant breast cancer trials (S8814/S8897) were matched by age and protocol. Only the treatment arms in which patients were scheduled to receive six cycles of chemotherapy were analyzed.A total of 317 pairs of patients (n = 634) were analyzed. At baseline, AA women had higher body-surface area (P < .0001) and lower WBC (P = .0009). AA women were more likely to have tumors that were > or = 2 cm (P = .01) and hormone receptor negative (P < .0001). AA women, versus white women, were marginally more likely to discontinue treatment early (11% v 7%, respectively; P = .07) or have one or more treatment delays (85% v 79%, respectively; P = .07) and were significantly more likely to experience the combined end point (discontinuation/delay; 87% v 81%, respectively; P = .04). The mean relative dose-intensity (RDI) was similar for both groups (87% in AA women v 86% in white women); however, overall, 43% had an RDI of less than 85%. After adjusting for baseline WBC and prognostic factors in a multivariate model, AA women had worse disease-free survival (hazard ratio [HR] = 1.56; 95% CI, 1.15 to 2.11; P = .005) and overall survival (HR = 1.95; 95% CI, 1.36 to 2.78; P = .0002). The inclusion of RDI and treatment delivery/quality in the regression had little impact on the results.On cooperative group breast cancer trials, AA and white women had similar RDIs, but AA women were more likely to experience early discontinuation or treatment delay. Despite correcting for these factors and known predictors of outcome, AA women still had worse survival.
Mutations of P450c21 (steroid 21-hydroxylase) at Cys428, Val281, and Ser268 result in complete, partial, or no loss of enzymatic activity, respectively.
Authors: D A Wu, B C Chung
Journal: Journal of Clinical Investigation (1991)

Steroid 21-hydroxylase deficiency is the major cause of congenital adrenal hyperplasia (CAH), a common genetic disease. To define the relationship between gene mutations and enzyme deficiency, we generated missense mutations of the 21-hydroxylase cDNA at three different sites and characterized the mutant proteins after expressing them in cultured mammalian and yeast cells. Among them, Ser268 and Val281 have been found to be mutated in CAH patients, whereas Cys428 has been implicated as the heme ligand. Our results show mutations at these sites result in complete, partial, or no loss of the enzymatic activity. All the Cys428 mutants had neither enzymatic activity nor P450 absorption, thus supporting the notion that Cys428 is the heme ligand. All the 268-mutants exhibited the same activity as normal 21-hydroxylase, demonstrating that the clinically observed Ser268----Thr change represents a polymorphism rather than the cause of the enzyme deficiency. The 281-mutants had normal Km but greatly reduced Vmax values that also paralleled the reduction in the heme content, in the order Val281 (normal, 100%) greater than Ile281 (50%) greater than Leu281 (20%) greater than Thr281 (10%). Our findings suggest that the methyl group at the beta-carbon of Val281 is required for heme incorporation and consequently enzymatic activity.