tbuckley/cabot-search huggingface dataset:
Glucose Variability Assessed by Low Blood Glucose Index Is Predictive of Hypoglycemic Events in Patients With Type 1 Diabetes Switched to Pump Therapy
Authors: Laurent Crenier, Charlotte Abou-Elias, Bernard Corvilain
Journal: Diabetes Care (2013)

To determine whether subgroups of type 1 diabetic patients with different glucose variability indices respond differently to continuous subcutaneous insulin infusion (CSII) in terms of reduced hypoglycemic events.We studied 50 adults with long-standing type 1 diabetes switched to CSII because of persistently high A1C or frequent hypoglycemia despite well-managed intensive basal-bolus therapy. We compared A1C, hypoglycemic events, and glucose variability from self-monitoring of blood glucose profiles at baseline and after 6 months of CSII. Regression analysis was performed to identify predictors of response.In multivariate analysis, baseline low blood glucose index (LBGI) was the best independent predictor of hypoglycemia outcome on CSII (R(2) = 0.195, P = 0.0013). An ROC curve analysis demonstrated a sensitivity of 70.8% (95% CI 48.9-87.4) and specificity of 73.1% (52.2-88.4) by using the LBGI cutoff of 3.34 as predictor of reduction of hypoglycemia on CSII. By grouping patients by LBGI tertiles, we found a 23.3% reduction in hypoglycemic events (<60 mg/dL [3.3 mmol/L]) in the third tertile (range 4.18-9.34) without change in A1C (P < 0.05). Conversely, the first tertile (range 0.62-2.05) demonstrated the greatest A1C reduction, -0.99% (P = 0.00001), but with increasing hypoglycemia.Baseline LBGI predicts the outcome of type 1 diabetic patients who switch to CSII in terms of hypoglycemia.
A NOTCH3 Transcriptional Module Induces Cell Motility in Neuroblastoma
Authors: Johan van Nes, Alvin Chan, Tim van Groningen, Peter van Sluis, Jan Koster, Rogier Versteeg
Journal: Clinical Cancer Research (2013)

Neuroblastoma is a childhood tumor of the peripheral sympathetic nervous system with an often lethal outcome due to metastatic disease. Migration and epithelial-mesenchymal transitions have been implicated in metastasis but they are hardly investigated in neuroblastoma.Cell migration of 16 neuroblastoma cell lines was quantified in Transwell migration assays. Gene expression profiling was used to derive a migration signature, which was applied to classify samples in a neuroblastoma tumor series. Differential expression of transcription factors was analyzed in the subsets. NOTCH3 was prioritized, and inducible transgene expression studies in cell lines were used to establish whether it functions as a master switch for motility.We identified a 36-gene expression signature that predicts cell migration. This signature was used to analyse expression profiles of 88 neuroblastoma tumors and identified a group with distant metastases and a poor prognosis. This group also expressed a known mesenchymal gene signature established in glioblastoma. Neuroblastomas recognized by the motility and mesenchymal signatures strongly expressed genes of the NOTCH pathway. Inducible expression of a NOTCH intracellular (NOTCH3-IC) transgene conferred a highly motile phenotype to neuroblastoma cells. NOTCH3-IC strongly induced expression of motility- and mesenchymal marker genes. Many of these genes were significantly coexpressed with NOTCH3 in neuroblastoma, as well as colon, kidney, ovary, and breast tumor series.The NOTCH3 transcription factor is a master regulator of motility in neuroblastoma. A subset of neuroblastoma with high expression of NOTCH3 and its downstream-regulated genes has mesenchymal characteristics, increased incidence of metastases, and a poor prognosis.
Wegener's granulomatosis patients show an adequate antibody response to influenza vaccination
Authors: A Holvast, C A Stegeman, C A Benne, A Huckriede, J C Wilschut, A M Palache, C G M Kallenberg, M Bijl
Journal: Annals of the Rheumatic Diseases (2008)

<h3>Objectives:</h3> Wegener's granulomatosis (WG) is a systemic vasculitis characterised by relapsing and remitting disease activity. Immunosuppressive drugs are used to control disease, but increase susceptibility to infection. Therefore, influenza vaccination should be considered in WG patients. This study was performed to assess the immunogenicity of influenza vaccination in WG patients. <h3>Methods:</h3> A randomised, controlled trial was performed in WG patients with quiescent disease, defined as a Birmingham vasculitis activity score (BVAS) less than 2. Patients were randomly assigned to receive influenza vaccination (n = 49) or to participate as controls (n = 23). In addition, healthy controls (n = 49) were vaccinated. At entry and at 1 and 3–4 months after entry, antibody responses to vaccination were determined. Furthermore, disease activity was measured (BVAS), adverse effects were recorded and antineutrophil cytoplasmic autoantibody (ANCA) titres were determined. <h3>Results:</h3> WG patients achieved high seroprotection rates to all three influenza strains, comparable with healthy controls. Only the A/H1N1 strain patients had a lower seroconversion rate (p = 0.002) and geometric mean titre (p = 0.037) than controls. After 1 month, one control and one vaccinated WG patient had developed active disease. At 3–4 months, two additional control patients had developed active disease compared with none of the vaccinated patients (p = 0.099). Vaccination did not influence ANCA titres. Adverse effects did not differ between patients and healthy controls. <h3>Conclusions:</h3> Influenza vaccination in WG patients with quiescent disease induced a sufficient antibody response. <h3>Trial registration number:</h3> NTR1130.
Accelerated Evolution of Innate Immunity Proteins in Social Insects: Adaptive Evolution or Relaxed Constraint?
Authors: Brock A. Harpur, Amro Zayed
Journal: Molecular Biology and Evolution (2013)

The genomes of eusocial insects have a reduced complement of immune genes—an unusual finding considering that sociality provides ideal conditions for disease transmission. The following three hypotheses have been invoked to explain this finding: 1) social insects are attacked by fewer pathogens, 2) social insects have effective behavioral or 3) novel molecular mechanisms for combating pathogens. At the molecular level, these hypotheses predict that canonical innate immune pathways experience a relaxation of selective constraint. A recent study of several innate immune genes in ants and bees showed a pattern of accelerated amino acid evolution, which is consistent with either positive selection or a relaxation of constraint. We studied the population genetics of innate immune genes in the honey bee Apis mellifera by partially sequencing 13 genes from the bee's Toll pathway (∼10.5 kb) and 20 randomly chosen genes (∼16.5 kb) sequenced in 43 diploid workers. Relative to the random gene set, Toll pathway genes had significantly higher levels of amino acid replacement mutations segregating within A. mellifera and fixed between A. mellifera and A. cerana. However, levels of diversity and divergence at synonymous sites did not differ between the two gene sets. Although we detect strong signs of balancing selection on the pathogen recognition gene pgrp-sa, many of the genes in the Toll pathway show signatures of relaxed selective constraint. These results are consistent with the reduced complement of innate immune genes found in social insects and support the hypothesis that some aspect of eusociality renders canonical innate immunity superfluous.
Intraperitoneal Chemotherapy: Long-Term Outcomes Revive a Long-Running Debate
Authors: Michael A. Bookman, Mark F. Brady
Journal: Journal of Clinical Oncology (2015)

The best clinical trials are thoughtfully designed to address highpriority questions that will improve clinical outcomes for our patients. However, many years can elapse between initial concept, protocol approval, funding, execution, analysis, and presentation. During that time, new targets and predictive markers can emerge, standards may evolve, toxicities are obviated, and scientific-clinical hypotheses become reframed. “Definitive” phase III trials are seldom that, and there are many trials that meet their original primary objective but are not then used to obtain regulatory approval of new interventions or change our standards of care. Defining the role of intraperitoneal (IP) chemotherapy remains one of the longest-running controversies in gynecologic oncology. The article by Tewari et al has given us the benefit of a retrospective aggregated analysis of data from two phase III trials that incorporated IP therapy. The authors offer three primary conclusions: demonstration of an advantage in overall survival (OS) beyond 10 years, the suggestion that IP therapy might also be effective in patients with macroscopic (gross) residual disease no greater than 1 cm, and description of a causative relationship between OS and the number of IP cycles delivered. In brief, we have rated these conclusions “true,” “of interest,” and “subject to overinterpretation,” respectively.
Posttranscriptional Regulation of <i>PER1</i> Underlies the Oncogenic Function of IREα
Authors: Olivier Pluquet, Nicolas Dejeans, Marion Bouchecareilh, Stephanie Lhomond, Raphael Pineau, Arisa Higa, Maylis Delugin, Chantal Combe, Sandrine Loriot, Gaelle Cubel, Nathalie Dugot-Senant, Anne Vital, Hugues Loiseau, Sara J.C. Gosline, Said Taouji, Michael Hallett, Jann N. Sarkaria, Keith Anderson, Wenting Wu, Fausto J. Rodriguez, Jean Rosenbaum, Frédéric Saltel, Martin E. Fernandez-Zapico, Eric Chevet
Journal: Cancer Research (2013)

Growing evidence supports a role for the unfolded protein response (UPR) in carcinogenesis; however, the precise molecular mechanisms underlying this phenomenon remain elusive. Herein, we identified the circadian clock PER1 mRNA as a novel substrate of the endoribonuclease activity of the UPR sensor IRE1α. Analysis of the mechanism shows that IRE1α endoribonuclease activity decreased PER1 mRNA in tumor cells without affecting PER1 gene transcription. Inhibition of IRE1α signaling using either siRNA-mediated silencing or a dominant-negative strategy prevented PER1 mRNA decay, reduced tumorigenesis, and increased survival, features that were reversed upon PER1 silencing. Clinically, patients showing reduced survival have lower levels of PER1 mRNA expression and increased splicing of XBP1, a known IRE-α substrate, thereby pointing toward an increased IRE1α activity in these patients. Hence, we describe a novel mechanism connecting the UPR and circadian clock components in tumor cells, thereby highlighting the importance of this interplay in tumor development.
Effects of pHi on isometric force and [Ca2+]i in porcine coronary artery smooth muscle.
Authors: R Nagesetty, R J Paul
Journal: Circulation Research (1994)

During ischemia or hypoxia, alterations in pHi may play a significant role in alteration of vessel wall function. We studied the effects of altering pHi on isometric force and [Ca2+]i in porcine coronary artery. pHi was altered at constant pHo by use of NH4Cl and measured with the fluorescent dye BCECF. [Ca2+]i was monitored with fura 2 and ratiometric fluorescence measurements. Addition of NH4Cl elicited a concentration-dependent (2 to 30 mmol/L) sustained increase in isometric force in unstimulated tissues. In tissues stimulated with KCl (29 mmol/L) or U46619 (1 mumol/L), addition of NH4Cl elicited a rapid but transient decrease followed by a sustained increase in force above the initial stimulated levels. Removal of NH4Cl was associated with a transient decrease and increase followed by a prolonged depression of force and slow recovery to initial levels. Addition of NH4Cl elicited a rapid monotonic increase in pHi and then a slow recovery toward initial levels; washout of NH4Cl led to a rapid acidification followed by recovery. In contrast to the steady state effects of NH4Cl on force, its effects on [Ca2+i were in the opposite direction. During the sustained increase in force elicited by NH4Cl alkalinization, [Ca2+]i was substantially decreased, whereas when force was depressed during the acidification elicited by NH4Cl washout, [Ca2+i was increased to values observed before addition of NH4Cl. The initial transients in force elicited by NH4Cl addition or washout were also associated with opposite changes in [Ca2+]i. Thus, the effects on force of the NH4Cl-induced changes in pHi are associated with changes in the Ca2+ sensitivity of the contractile apparatus rather than mediated through changes in [Ca2+]i.
Associations of CTX-II with biochemical markers of bone turnover raise questions about its tissue origin: data from CHECK, a cohort study of early osteoarthritis
Authors: Harry Sprot
Journal: Annals of the Rheumatic Diseases (2013)

I read with interest this paper by van Spil et al 1 examining further the osteoarthritis biomarker CTX-II (C-terminal telopeptide of type II collagen) and note the suspicions of the authors that this marker might be linked to bone metabolism. High correlation with biomarkers of bone and CTX-II were noted and also a characteristic increase around the time of the menopause. However, it has been …
Metformin Decreases the Dose of Chemotherapy for Prolonging Tumor Remission in Mouse Xenografts Involving Multiple Cancer Cell Types
Authors: Dimitrios Iliopoulos, Heather A. Hirsch, Kevin Struhl
Journal: Cancer Research (2011)

Metformin, the first-line drug for treating diabetes, selectively kills the chemotherapy resistant subpopulation of cancer stem cells (CSC) in genetically distinct types of breast cancer cell lines. In mouse xenografts, injection of metformin and the chemotherapeutic drug doxorubicin near the tumor is more effective than either drug alone in blocking tumor growth and preventing relapse. Here, we show that metformin is equally effective when given orally together with paclitaxel, carboplatin, and doxorubicin, indicating that metformin works together with a variety of standard chemotherapeutic agents. In addition, metformin has comparable effects on tumor regression and preventing relapse when combined with a four-fold reduced dose of doxorubicin that is not effective as a monotherapy. Finally, the combination of metformin and doxorubicin prevents relapse in xenografts generated with prostate and lung cancer cell lines. These observations provide further evidence for the CSC hypothesis for cancer relapse, an experimental rationale for using metformin as part of combinatorial therapy in a variety of clinical settings, and for reducing the chemotherapy dose in cancer patients.
Points from letters: Doctors' wives and the Sex Discrimination Act
Authors: M. B. Gilmore
Journal: BMJ (1976)

indicates that consultants in teaching hospitals are on average of higher quality than those in peripheral hospitals and that similar considerations apply respectively to those working in the South and the North of England and also to physicians and surgeons as opposed to geriatricians and psychiatrists.If Drs Bruggen and Bourne do not believe this they should say why.There are, of course, people who believe that merit should not be financially rewarded as the work involved is cleaner and more interesting than unskilled work.There are also people who believe that it is impossible to assess merit and it would appear from the Points from LettersClinical or administrative postal addresses ?
A phase I dose escalation study of Ad GV.EGR.TNF.11D (TNFerade™ Biologic) with concurrent chemoradiotherapy in patients with recurrent head and neck cancer undergoing reirradiation
Authors: T.Y. Seiwert, T. Darga, D. Haraf, E.A. Blair, K. Stenson, E.E.W. Cohen, J.K. Salama, V. Villaflor, M.E. Witt, M.W. Lingen, R.R. Weichselbaum, E.E. Vokes
Journal: Annals of Oncology (2012)
Screening for Risk of Persistent Posttraumatic Stress in Injured Children and Their Parents
Authors: Flaura K. Winston
Journal: JAMA (2003)

Injury, a leading health threat to children, is also a common cause of posttraumatic stress disorder (PTSD) in childhood. Most injured children with PTSD are not diagnosed or treated.To develop a stand-alone screening tool for use by clinicians during acute trauma care to identify injured children and their parents who are at risk of significant, persistent posttraumatic stress symptoms.The Screening Tool for Early Predictors of PTSD (STEPP) was derived from a 50-item risk factor survey administered within 1 month of injury as part of a prospective cohort study of posttraumatic stress in injured children and their parents. Symptoms of PTSD were assessed at least 3 months after injury.Urban, pediatric level I trauma center.A sample of 269 children aged 8 to 17 years admitted for treatment of traffic-related injuries between July 1999 and October 2001, and one parent per child, completed a risk factor survey assessing potential predictors of PTSD outcome. One hundred seventy-one families (63%) completed a follow-up assessment.The Clinician-Administered PTSD Scale for Children and Adolescents and the PTSD Checklist served as criterion standards for child and parent outcomes, respectively. Positive cases were defined as those meeting criteria for at least subsyndromal PTSD with continuing impairment ("persistent traumatic stress").The STEPP contains 4 dichotomous questions asked of the child, 4 asked of one parent, and 4 items obtained easily from the emergency medical record. STEPP sensitivity in predicting posttraumatic stress was 0.88 for children and 0.96 for parents, with negative predictive values of 0.95 for children and 0.99 for parents. The odds ratio for prediction of persistent traumatic stress was 6.5 (95% confidence interval [CI], 1.8-22.8) in children and 26.6 (95% CI, 3.5-202.1) in parents.The STEPP represents a new method to guide clinicians in making evidence-based decisions for the allocation of scarce mental health resources for traumatic stress. Its brevity and simple scoring rule suggest that it can be easily administered in the acute care setting.
Non-cirrhotic portal fibrosis.
Authors: S K Sarin
Journal: Gut (1989)

Non-cirrhotic portal hypertension (NCPH) comprises of diseases having an increase in portal pressure (PP) due to intraheptic or prehepatic lesions, in the absence of cirrhosis. The lesions are generally vascular, either in the portal vein, its branches or in the perisinusoidal area. Because the wedged hepatic venous pressure (WHVP) is near normal, measurement of intravariceal or intrasplenic pressure is needed to assess portal pressure. The majority of the diseases included in the category of NCPH are well characterized disease entities where portal hypertension (PHT) is a late manifestation and hence, these are not discussed. Two diseases which present only with features of PHT and are common in developing countries are NCPF and extra-hepatic portal vein obstruction (EHPVO). Non-cirrhotic portal fibrosis is a syndrome of obscure etiology, characterized by 'Obliterative portovenopathy' leading to PHT, massive splenomegaly, repeated well tolerated episodes of variceal bleeding and anemia in young adults from low socio-economic strata of life. The hepatic parenchymal functions are nearly normal. Jaundice, ascites and hepatic encephalopathy are rare. Management of variceal bleeding remains the main concern as nearly 85% of patients with NCPF present with variceal bleeding. Endoscopic variceal ligation or sclerotherapy are equally effective in about 90-95% of the patients. Gastric varices are seen in about 25% patients and a bleed from them can be managed with cyanoacrylate glue injection or surgery. Other indications for surgery include failure of endoscopic therapy to control acute bleed and symptomatic hypersplenism. The prognosis of patients with NCPF is good and 5-years survival rates in patients in whom variceal bleeding can be controlled is about > 95%.
Contribution of the beating ventricles in closed-chest left-ventricular bypass in the dog
Authors: L. A. GEDDES, P. CABLER, A. G. MOORE, R. STEINBERG
Journal: Cardiovascular Research (1972)

Journal Article Contribution of the beating ventricles in closed-chest left-ventricular bypass in the dog Get access L. A. GEDDES, L. A. GEDDES From the Division of Biomedical Engineering and the Department of Physiology, Baylor College of Medicine, Houston, Texas, U.S.A. Search for other works by this author on: Oxford Academic PubMed Google Scholar P. CABLER, P. CABLER From the Division of Biomedical Engineering and the Department of Physiology, Baylor College of Medicine, Houston, Texas, U.S.A. Search for other works by this author on: Oxford Academic PubMed Google Scholar A. G. MOORE, A. G. MOORE From the Division of Biomedical Engineering and the Department of Physiology, Baylor College of Medicine, Houston, Texas, U.S.A. Search for other works by this author on: Oxford Academic PubMed Google Scholar R. STEINBERG R. STEINBERG From the Division of Biomedical Engineering and the Department of Physiology, Baylor College of Medicine, Houston, Texas, U.S.A. Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 6, Issue 5, September 1972, Pages 541–548, https://doi.org/10.1093/cvr/6.5.541 Published: 01 September 1972
Cardiovascular Disease and Risk Factors in Asia
Authors: Hirotsugu Ueshima, Akira Sekikawa, Katsuyuki Miura, Tanvir Chowdhury Turin, Naoyuki Takashima, Yoshikuni Kita, Makoto Watanabe, Aya Kadota, Nagako Okuda, Takashi Kadowaki, Yasuyuki Nakamura, Tomonori Okamura
Journal: Circulation (2008)
Accelerated Maturation and Abnormal Morphology in the Preterm Neonatal Kidney
Authors: Megan R. Sutherland, Lina Gubhaju, Lynette Moore, Alison L. Kent, Jane E. Dahlstrom, Rosemary S. C. Horne, Wendy E. Hoy, John F. Bertram, M. Jane Black
Journal: Journal of the American Society of Nephrology (2011)

Nephrogenesis is ongoing at the time of birth for the majority of preterm infants, but whether postnatal renal development follows a similar trajectory to normal in utero growth is unknown. Here, we examined tissue collected at autopsy from 28 kidneys from preterm neonates, whose postnatal survival ranged from 2 to 68 days, including 6 that had restricted intrauterine growth. In addition, we examined kidneys from 32 still-born gestational controls. We assessed the width of the nephrogenic zone, number of glomerular generations, cross-sectional area of the renal corpuscle, and glomerular maturity and morphology. Renal maturation accelerated after preterm birth, with an increased number of glomerular generations and a decreased width of the nephrogenic zone in the kidneys of preterm neonates. Of particular concern, compared with gestational controls, preterm kidneys had a greater percentage of morphologically abnormal glomeruli and a significantly larger cross-sectional area of the renal corpuscle, suggestive of renal hyperfiltration. These observations suggest that the preterm kidney may have fewer functional nephrons, thereby increasing vulnerability to impaired renal function in both the early postnatal period and later in life.