tbuckley/cabot-search huggingface dataset:
Significant Reduction of Late Toxicities in Patients With Extremity Sarcoma Treated With Image-Guided Radiation Therapy to a Reduced Target Volume: Results of Radiation Therapy Oncology Group RTOG-0630 Trial
Authors: Dian Wang, Qiang Zhang, Burton L. Eisenberg, John M. Kane, X. Allen Li, David Lucas, Ivy A. Petersen, Thomas F. DeLaney, Carolyn R. Freeman, Steven E. Finkelstein, Ying J. Hitchcock, Manpreet Bedi, Anurag K. Singh, George Dundas, David G. Kirsch
Journal: Journal of Clinical Oncology (2015)

We performed a multi-institutional prospective phase II trial to assess late toxicities in patients with extremity soft tissue sarcoma (STS) treated with preoperative image-guided radiation therapy (IGRT) to a reduced target volume.Patients with extremity STS received IGRT with (cohort A) or without (cohort B) chemotherapy followed by limb-sparing resection. Daily pretreatment images were coregistered with digitally reconstructed radiographs so that the patient position could be adjusted before each treatment. All patients received IGRT to reduced tumor volumes according to strict protocol guidelines. Late toxicities were assessed at 2 years.In all, 98 patients were accrued (cohort A, 12; cohort B, 86). Cohort A was closed prematurely because of poor accrual and is not reported. Seventy-nine eligible patients from cohort B form the basis of this report. At a median follow-up of 3.6 years, five patients did not have surgery because of disease progression. There were five local treatment failures, all of which were in field. Of the 57 patients assessed for late toxicities at 2 years, 10.5% experienced at least one grade ≥ 2 toxicity as compared with 37% of patients in the National Cancer Institute of Canada SR2 (CAN-NCIC-SR2: Phase III Randomized Study of Pre- vs Postoperative Radiotherapy in Curable Extremity Soft Tissue Sarcoma) trial receiving preoperative radiation therapy without IGRT (P < .001).The significant reduction of late toxicities in patients with extremity STS who were treated with preoperative IGRT and absence of marginal-field recurrences suggest that the target volumes used in the Radiation Therapy Oncology Group RTOG-0630 (A Phase II Trial of Image-Guided Preoperative Radiotherapy for Primary Soft Tissue Sarcomas of the Extremity) study are appropriate for preoperative IGRT for extremity STS.
Supratentorial hemangioblastoma: clinical features, prognosis, and predictive value of location for von Hippel-Lindau disease
Authors: S. A. Mills, M. C. Oh, M. J. Rutkowski, M. E. Sughrue, I. J. Barani, A. T. Parsa
Journal: Neuro-Oncology (2012)

Supratentorial hemangioblastoma is a rare form of hemangioblastoma; little information is available regarding prognosis, treatment, and clinical characteristics, because the available literature is primarily composed of case reports and small case series.Therefore, we performed a systematic review of the literature to analyze clinical characteristics, disease progression, and surgical outcomes with respect to survival for supratentorial hemangioblastomas.The rate of progression-free survival (PFS) was determined using Kaplan-Meier analysis.Differences in categorical factors, including location of tumor and diagnosis of von Hippel-Lindau (VHL) disease, were analyzed using the Pearson x 2 test.A total of 106 articles met the search criteria, which combined for a total of 132 patients.Of the patients with supratentorial tumors, 60% had VHL disease, and 31 (84%) of 37 patients with tumors in the sellar/suprasellar region had associated VHL (x 2 , P < .001).Five-year PFS for gross-total resection and subtotal resection were 100% and 53%, respectively (Log rank, P < .01).On the basis of our analysis of the literature on published cases of supratentorial hemangioblastoma, gross-total resection appears to be superior to other treatment modalities in extending PFS.Von Hippel -Lindau disease is positively correlated with supratentorial hemangioblastoma when compared with non-supratentorial CNS hemangioblastomas, particularly when present in the sellar/suprasellar region.
ProTh2 function of myeloid dendritic cells in persistent occupational asthma after cessation of exposure
Authors: Antoine Froidure, Vinciane D'Alpaos, Geneviève Evrard, Olivier Vandenplas, Charles Pilette
Journal: European Respiratory Journal (2014)

Introduction 

Asthma resolves in only a minority of patients with occupational asthma (OA) despite complete avoidance of the causal agent. We aimed at exploring whether mDC function contributed to persistent disease after cessation of exposure to occupational allergens.

Material and methods 

We recruited 32 patients with OA to flour or latex ascertained by specific inhalation challenge who were no longer exposed to the causal allergen. At follow-up, cure was defined by the absence of asthma symptoms, use of asthma medication, and nonspecific bronchial hyperresponsiveness to histamine (PC20>8 mg/mL). A buffy coat was obtained from each patient to isolate and characterize mDCs, and their functionality was studied in co-culture with CD4+ T cells from control subjects.

Results 

When compared to cure (n=11), asthma persistence (n=21) was associated with higher expression of thymic stromal lymphopoietin receptor (TSLPR) (58.8 ± 16.9% vs 28.4 ± 8.4 %, P<0.001) and lower expression of ICOS-ligand (13.9 ± 9.4% vs 25.9 ± 14.8 %, P=0.011) on mDCs.

Upon allergen pulsing in vitro , mDCs from patients with persistent asthma upregulated the production of IL-5 (from 0.48 ± 0.4 ng/mL to 1.16 ± 0.5 ng/mL, vs from 0.41 ± 0.5 ng/mL to 0.5 ± 0.6 ng/mL, P=0.02) and IL-13 (from 0.23 ± 0.1 ng/mL to 0.59 ± 0.3 ng/mL vs from 0.17 ± 0.1 ng/mL to 0.31 ± 0.2 ng/mL, P=0.02) by co-cultured CD4+ T cells. Unlike mDCs from cured patients, they also upregulated programmed death-ligand 2 (35.04 ± 6.3 % vs 27.2 ± 11.8 % P=0.04).

Conclusions 

These data show that in patients with occupational asthma, pro-allergic functionality of mDCs correlates with disease activity after cessation of exposure to the causal allergen.
Mammalian Nonsynonymous Sites Are Not Overdispersed: Comparative Genomic Analysis of Index of Dispersion of Mammalian Proteins
Authors: S.-H. Kim, S. V. Yi
Journal: Molecular Biology and Evolution (2007)

It is often stated that patterns of nonsynonymous rate variation among mammalian lineages are more irregular than expected or overdispersed under the neutral model, whereas synonymous sites conform to the neutral model. Here we reexamined genome-wide patterns of the variance to mean ratio, or index of dispersion (R), of substitutions in proteins from human, mouse, and dog. Contrary to the prevailing notion, we found that the mean index of dispersion for nonsynonymous sites of mammalian proteins is not significantly different from 1. We propose that earlier analyses were biased because the data included disproportionately more protein hormones, which tend to be more dispersed than genes in other functional categories. Synonymous sites exhibit greater degree of dispersion than nonsynonymous sites, although similar to earlier estimates and potentially due to errors associated with correction for multiple hits. Overall, our analysis identifies strong genome-wide generation-time effect and natural selection as important determinants of among-lineage variation of protein evolutionary rates. Furthermore, patterns of lineage-specific selective constraint are consistent with the nearly neutral model of molecular evolution.
Disparities Between Aortic and Peripheral Pulse Pressures Induced by Upright Exercise and Vasomotor Changes in Man
Authors: LORING B. ROWELL, GEORGE L. BRENGELMANN, JOHN R. BLACKMON, ROBERT A. BRUGE, JOHN A. MURRAY
Journal: Circulation (1968)

Blood pressures were recorded simultaneously from the aortic arch and radial artery using two manometric systems with identical static and dynamic sensitivities. Measurements were made in four normal young men at rest and upright exercise requiring 29, 49, 78, and 100% of maximal oxygen uptake. Average radial arterial pressure rose from 133/66 mm Hg at rest to 236/58 mm Hg at maximal exercise. At the same time, average aortic pressures were 112/68 and 154/70 mm Hg, respectively. From rest to maximal exercise, pulse pressures at central and peripheral sites increased by factors of 1.95 and 2.60, respectively. Inducing reactive hyperemia in the arm abolished peripheral amplification. This amplification also diminished with time during prolonged heavy exercise. Mean pressures were nearly identical at the two sites at any oxygen uptake; mean pressures rose from 87 to 104 mm Hg from mild to maximal exercise. We conclude that estimates of stress on aortic and cerebral vessel walls and central baroreceptors would be grossly overestimated by use of peripheral pulse pressures.
Cash incentives might help to change behaviour, MPs told
Authors: Adrian O’Dowd
Journal: BMJ (2008)

Cash incentives to encourage people to change their behaviour may help to end health inequalities in the United Kingdom, MPs have been told.

Cash incentives will be considered by the clinical watchdog the National Institute for Health and Clinical Excellence (NICE), the parliamentary health select committee was told last week as part of its inquiry into health inequalities.

MPs asked whether cash incentives should be considered to encourage people to change their behaviour to improve health.

Mike Kelly, director of NICE’s centre for public health excellence, said, “We’ve got that in the pipeline as something that NICE is going to …
Regression of Glomerulosclerosis with High-Dose Angiotensin Inhibition Is Linked to Decreased Plasminogen Activator Inhibitor-1
Authors: Li-Jun Ma, Shinya Nakamura, Jean Claude Aldigier, Michele Rossini, Haichun Yang, Xiubin Liang, Ikuko Nakamura, Carmelita Marcantoni, Agnes B. Fogo
Journal: Journal of the American Society of Nephrology (2005)

The potential and possible mechanisms for regression of existing glomerulosclerosis by angiotensin II type 1 receptor antagonist (AT1RA) and/or angiotensin I converting enzyme inhibitor (ACEI) were investigated. Adult male Sprague Dawley rats underwent 5/6 nephrectomy (Nx). Glomerulosclerosis was assessed by renal biopsy 8 wk later, and rats were divided into groups with equal biopsy sclerosis and treated for the next 4 wk until they were killed at 12 wk as follows: Control with no further treatment (CONT), high-dose AT1RA, high-dose ACEI, and varying AT1RA+ACEI combinations. Hypertension and proteinuria induced by 5/6 Nx were significantly decreased by all treatments, except high-dose ACEI, which showed persistent proteinuria. High-dose AT1RA and ACEI markedly decreased progression of sclerosis, with -2.3% average decrease in sclerosis from biopsy to autopsy in AT1RA versus 194% increase in CONT (P < 0.0001). Glomerulosclerosis regressed, with less severe lesions at the time when the rats were killed than at biopsy in 62% of AT1RA-treated and 57% of ACEI-treated rats. In contrast, only 17 to 33% of rats in combination groups had regression. Alternatively, these data might be viewed as reflecting halting of progression, as some groups had higher BP and proteinuria. However, this potential confounding effect does not negate the effects to achieve regression of sclerosis in these rats. Regression was not explained by changes in mRNA of TGF-beta1 and matrix metalloproteinase-2 and -9 but was linked to decreased tissue inhibitor of metalloproteinase-1 and plasminogen activator inhibitor-1. It is concluded that angiotensin inhibition mediates regression in part by effects on matrix modulation.
Familial Aggregation of Blood Lipid Response to Exercise Training in the Health, Risk Factors, Exercise Training, and Genetics (HERITAGE) Family Study
Authors: Treva Rice, Jean-Pierre Després, Louis Pérusse, Yuling Hong, Michael A. Province, Jean Bergeron, Jacques Gagnon, Arthur S. Leon, James S. Skinner, Jack H. Wilmore, Claude Bouchard, D.C. Rao
Journal: Circulation (2002)

Background — Fasting levels of plasma lipids and lipoproteins are reported to improve with regular exercise training. However, little is known on whether the training responses are influenced by heritable factors. Methods and Results — The lipid profile was assessed in 115 black (224 individuals) and 99 white families (469 individuals), who participated in the HERITAGE Family Study, while in a sedentary state (baseline visit) and after exercise training for 20 weeks (post visit). Variables included total cholesterol, triglyceride, low-density lipoprotein cholesterol (LDL-C), apolipoprotein B (ApoB), high-density lipoprotein cholesterol (HDL-C), apolipoprotein A-I, and HDL-C subfractions 2 (HDL 2 -C) and 3 (HDL 3 -C). Familial correlations for the training responses (Δ=post−baseline) were significant for most variables, and the percent variance accounted for by familial factors (ie, maximal heritabilities) ranged from 25% to 38%. Exceptions were for higher heritabilities near 60% for ΔApoB in blacks and ΔHDL 2 -C in whites and a lower estimate of zero for ΔLDL-C in blacks. Conclusions — Heritable factors in part determine lipid profile responses to regular exercise. Maximal heritabilities were similar across ethnic groups and variables, except for ΔLDL-C, ΔApoB, and ΔHDL 2 -C. Molecular studies to identify the markers and genes associated with these influences are currently underway.
Computers in the Clinical Laboratory
Authors: Arthur F. Krieg
Journal: JAMA (1981)

<h3>The Physician-Laboratory-Physician Communication Loop</h3> During the past few years, we have seen steady progress toward improved accuracy and precision in the clinical laboratory. New methods, new instruments, and new quality-control systems have decreased the frequency of laboratory error due to improper analysis. Improved analytic performance means that an increasing percentage of laboratory problems are now related to communication and interpretation of results.<sup>1-3</sup>Some common problems include (1) requests that never reach the laboratory; (2) reports that never reach the patient chart; (3) unreasonable delays in the cycle of request-analysis-report; and (4) "data overload"—as the volume of laboratory data increases, interpretation becomes increasingly difficult. In some settings, more than 10% of requests never reach the laboratory; more than 10% of reports never reach the patient chart; more than 10% of results do not reach the attending physician while still relevant; and other results have little or no value in terms
The forkhead transcription factor Foxo1 (Fkhr) confers insulin sensitivity onto glucose-6-phosphatase expression
Authors: Jun Nakae, Tadahiro Kitamura, David L. Silver, Domenico Accili
Journal: Journal of Clinical Investigation (2001)

Type 2 diabetes is characterized by the inability of insulin to suppress glucose production in the liver and kidney. Insulin inhibits glucose production by indirect and direct mechanisms. The latter result in transcriptional suppression of key gluconeogenetic and glycogenolytic enzymes, phosphoenolpyruvate carboxykinase (Pepck) and glucose-6-phosphatase (G6p). The transcription factors required for this effect are incompletely characterized. We report that in glucogenetic kidney epithelial cells, Pepck and G6p expression are induced by dexamethasone (dex) and cAMP, but fail to be inhibited by insulin. The inability to respond to insulin is associated with reduced expression of the forkhead transcription factor Foxo1, a substrate of the Akt kinase that is inhibited by insulin through phosphorylation. Transduction of kidney cells with recombinant adenovirus encoding Foxo1 results in insulin inhibition of dex/cAMP–induced G6p expression. Moreover, expression of dominant negative Foxo1 mutant results in partial inhibition of dex/cAMP–induced G6p and Pepck expression in primary cultures of mouse hepatocyes and kidney LLC-PK1-FBPase+ cells. These findings are consistent with the possibility that Foxo1 is involved in insulin regulation of glucose production by mediating the ability of insulin to decrease the glucocorticoid/cAMP response of G6p.
Churg-Strauss syndrome
Authors: B D W HARRISON
Journal: Thorax (2001)

seem to be specific to PCH, demonstrating the usefulness of HRCT scanning for diagnosis of this disease.Other previously reported CT findings of the disease include increased soft tissue density of the mediastinum 1 2 and mediastinal and hilar lymph adenopathies, 7 but such findings were absent in our case.Possible explanations for the stable condition of our case over a long period are either that it was a chance discovery of an early phase of the disease by HRCT scanning or that PCH has separate subtypes with diVering speeds of progression.Wider use of HRCT scanning and more extensive understanding of PCH would resolve this issue in the future.
Prospective comparative study of the influence of postoperative bile reflux on gastric mucosal histology and Campylobacter pylori infection.
Authors: G J Offerhaus, P N Rieu, J B Jansen, H J Joosten, C B Lamers
Journal: Gut (1989)

Biopsies of 17 peptic ulcer patients, randomly treated by partial gastrectomy with either Billroth-II (n = 9) or Roux-en-Y (n = 8) anastomosis were studied before and six months after surgery to determine the role of bile reflux in the early postoperative histological alterations of the gastric mucosa. After BII-gastrectomy bile acid reflux (median 16.1 mumol/h) was significantly higher (p less than 0.0001) than after RY-gastrectomy (0.1 mumol/h). Campylobacter pylori was present in the preoperative biopsies of all 17 patients. After RY-gastrectomy biopsies of all eight patients were positive for Campylobacter pylori, but was detected in only five of the nine patients with BII-gastrectomy. Preoperative scores of gastritis grading were similar in both groups and no significant differences were found postoperatively. Gastritis scores of the anastomotic mucosa in patients with BII-gastrectomy were significantly higher (p less than 0.02) than in the RY-gastrectomy group. Moreover, the reflux gastritis score in the four BII-gastrectomy patients cleared from Campylobacter pylori was significantly higher (p less than 0.02) than in the postgastrectomy patients harbouring Campylobacter pylori. The results suggest that reflux gastritis and Campylobacter pylori related gastritis are distinct microscopic entities and that bile reflux may play a role in the eradication of Campylobacter pylori after gastrectomy.
Pharmacodynamic Markers of Perifosine Efficacy
Authors: Bryan T. Hennessy, Yiling Lu, Enrique Poradosu, Qianghua Yu, Shuangxing Yu, Hassan Hall, Mark S. Carey, Murali Ravoori, Ana Maria Gonzalez-Angulo, Robert Birch, I. Craig Henderson, Vikas Kundra, Gordon B. Mills
Journal: Clinical Cancer Research (2007)

It is critical to develop methods to quantify the early pharmacodynamic effects of targeted therapeutics in vivo to make drug development more efficient and ensure biologically relevant dosing. Furthermore, an ability to identify patients likely to respond to targeted therapeutics would decrease the size, duration, and cost of clinical trials, resulting in more efficient translation to improved patient outcomes. Recent studies suggest that perifosine inhibits the phosphatidylinositol-3'-kinase (PI3K) pathway by preventing cell membrane recruitment of the AKT pleckstrin homology domain.A novel functional proteomics technology, reverse phase protein array, was used to establish and quantify pharmacodynamic markers of perifosine efficacy.Perifosine selectively prevents AKT recruitment to the membrane and blocks activation of downstream effectors. Perifosine inhibited breast, ovarian, and prostate cancer models. Growth inhibition was associated with apoptosis. Activation of AKT as a consequence of genomic aberrations predicted perifosine efficacy. In cell lines and xenografts, there was a highly statistically significant correlation between the degree of antitumor efficacy of different perifosine doses and quantified down-regulation of phosphorylation of AKT and of its downstream targets, particularly S6.Because of a strong correlation between proportional modulation of PI3K pathway biomarkers and quantified perifosine efficacy, it is likely that early measurement of such pharmacodynamic biomarkers with reverse phase protein array will optimize selection of responding patients and guide perifosine dosing. Furthermore, PI3K pathway activation status may allow baseline selection of patients most likely to respond to perifosine alone or in combination with other therapies.
Development of Personalized Tumor Biomarkers Using Massively Parallel Sequencing
Authors: Rebecca J. Leary, Isaac Kinde, Frank Diehl, Kerstin Schmidt, Chris Clouser, Cisilya Duncan, Alena Antipova, Clarence Lee, Kevin McKernan, Francisco M. De La Vega, Kenneth W. Kinzler, Bert Vogelstein, Luis A. Diaz, Victor E. Velculescu
Journal: Science Translational Medicine (2010)

Rapid detection of specific aberrant rearrangements in tumors from individuals yields a well-poised technological advance toward personalized oncology.
Graft-Versus-Host Disease in Children Who Have Received a Cord-Blood or Bone Marrow Transplant from an HLA-Identical Sibling
Authors: Vanderson Rocha, John E. Wagner, Kathleen A. Sobocinski, John P. Klein, Mei Jie Zhang, Mary M. Horowitz, Eliane Gluckman
Journal: New England Journal of Medicine (2000)

Umbilical-cord blood as an alternative to bone marrow for hematopoietic stem-cell transplantation may lower the risk of graft-versus-host disease (GVHD).
Regional contributions of six preventable risk factors to achieving the 25 × 25 non-communicable disease mortality reduction target: a modelling study
Authors: Vasilis Kontis, Colin D Mathers, Ruth Bonita, Gretchen A Stevens, Jürgen Rehm, Kevin D Shield, Leanne M Riley, Vladimir Poznyak, Samer Jabbour, Renu Madanlal Garg, Anselm Hennis, Heba M Fouad, Robert Beaglehole, Majid Ezzati
Journal: The Lancet Global Health (2015)
What's hot today? Current topics in sports and exercise medicine
Authors: David J Berkoff
Journal: British Journal of Sports Medicine (2012)

This American Medical Society for Sports Medicine (AMSSM)-shaped issue of BJSM highlights ‘hot topics’ in sports medicine. The Merriam-Webster's dictionary defines ‘hot’ as: of intense and immediate interest. I used this simple definition to guide AMSSM's selection of articles for this issue. This issue's selections are clearly ‘hot topics’ but to whom are they considered ‘hot?’

What defines a sport and exercise medicine practitioner? Is it the team physician who cares for the professional or elite athlete? Is it the paediatrician who encourages the obese adolescent to put down the Wii controller and get outside? Or is it the cardiologist who dedicates herself to getting a heart failure patient back to tolerating light exercise? How does someone best describe what we do for our patients? We as ‘sports and exercise medicine’ providers have a unique role that encompasses multiple specialties, age groups and patient populations. We are tasked with prescreening athletes prior to activity, preventing and treating all manners of sporting injury. We care for the elderly, the young and those with chronic illness. We follow patients after injuries and are often the experts consulted with difficult and challenging medical cases that are both medical and sports related. We are a diverse group and we meet a wide range of needs. Thus, choosing what is ‘hot’ and relevant to everyone reading this AMSSM-shaped issue was challenging.

So how did we select these articles? There are hundreds of topics of interest to the sports and exercise medicine practitioner, but which of these are of interest to our …