tbuckley/cabot-search huggingface dataset:
Decreased Mortality Associated With the Use of Metformin Compared With Sulfonylurea Monotherapy in Type 2 Diabetes
Authors: Jeffrey A. Johnson, Sumit R. Majumdar, Scot H. Simpson, Ellen L. Toth
Journal: Diabetes Care (2002)

OBJECTIVE—The aim of this study was to examine the relationship between use of metformin and sulfonylurea and mortality in new users of these agents. RESEARCH DESIGN AND METHODS—Saskatchewan Health databases were used to examine population-based mortality rates for new users of oral antidiabetic agents. Individuals with prescriptions for sulfonylurea or metformin in 1991–1996 and no use in the year prior were identified as new users. Prescription records were prospectively followed for 1–9 years; subjects with any insulin use were excluded. Causes of death were identified based on ICD-9 codes in an electronic vital statistics database. Multivariate logistic regression and survival analyses were used to assess the differences in mortality between drug cohorts, after adjusting for potential confounding variables. RESULTS—The total study sample comprised 12,272 new users of oral antidiabetic agents; the average length of follow-up was 5.1 (SD 2.2) years. In subjects with at least 1 year of drug exposure and no insulin use, mortality rates were 750/3,033 (24.7%) for those receiving sulfonylurea monotherapy, 159/1,150 (13.8%) for those receiving metformin monotherapy, and 635/4,683 (13.6%) for those receiving combination therapy over an average 5.1 (SD 2.2) years of follow-up. The adjusted odds ratio (OR) for all-cause mortality for metformin monotherapy was 0.60 (95% CI 0.49–0.74) compared with sulfonylurea monotherapy. Sulfonylurea plus metformin combination therapy was also associated with reduced all-cause mortality (OR 0.66, 95% CI 0.58–0.75). Reduced cardiovascular-related mortality rates were also observed in metformin users compared with sulfonylurea monotherapy users. CONCLUSIONS—Metformin therapy, alone or in combination with sulfonylurea, was associated with reduced all-cause and cardiovascular mortality compared with sulfonylurea monotherapy among new users of these agents.
Adrenocorticotropic Hormone, β-Lipotropin, and Endorphin-Related Peptides in Health and Disease
Authors: Y. Peng Loh, L. Lynn Loriaux
Journal: JAMA (1982)

IT HAS been clear for some time that the secretion of adrenocorticotropic hormone (ACTH) and β-lipotropin (β-LPH) appear to be linked, both being present in high concentrations in patients with disorders of hypersecretion (Cushing's syndrome, Addison's disease) and low in patients with disorders of hyposecretion (secondary adrenal insufficiency). Other molecular species also appear to be associated with ACTH secretion; for example, molecules larger than ACTH but with ACTH immunoreactivity have been found in many cases of "ectopic" ACTH secretion. Recent studies into the biosynthesis of ACTH and β-LPH appear to explain these interrelationships and hold forth the promise of important advances in our understanding of the relationship between the hypothalamus, pituitary, and the adrenal gland in man. Early chemical studies have recognized the existence of several peptides that are structurally related to ACTH in the pituitary gland of many species including man. These include β-LPH, α-melanocyte-stimulating hormone (MSH), and β-MSH.
Serological detection of variable region (Vh) subgroups of Ig heavy chains.
Authors: O Forre, J B Natvig, H G Kunkel
Journal: The Journal of Experimental Medicine (1976)

Serological test systems were established for determining the heavy-chain variable region (Vh) subgroups of immunoglobulin heavy chains. Myeloma proteins with known Vh subgroups based on amino acid sequence were utilized as the primary basis of reference for analysis by hemagglutination and hemagglutination inhibition. Good agreement between the chemical and serological typing was obtained and nonoverlapping systems established for the three major Vh subgroups. In a survey of 167 myeloma proteins, all except two were exclusively positive in one of the three systems. The two exceptions may represent a fourth subgroup. There was an overall incidence ratio of 1:2:3 for VhI:VhII:VhIII subgroups. Some differences in the overall ratios were encountered within the immunoglobulin classes. Certain advantages of the serological typing antisera were discussed with special emphasis on their use for studies of Vh antigens on the membranes of lymphocytes.
Vestibular and visual control on posture and locomotor equilibrium
Authors: R. S. A. Thomas
Journal: British Journal of Sports Medicine (1986)

The editors, Makoto Igarashi and F. Owen Black, are most respected workers in the field and the papers of many distinguished scientists are presented.Perhaps the most interesting area of discussion was the importance of postural control in a space environment.This is certainly not a book for the casual reader, but those involved in research into locomotion, posture and the sensory control of both and those interested in vestibular abnormalities will find much food for thought.It is certainly a reference book that is more suited to the library, than to the bookshelf of the ordinary practitioner in the field of sports medicine and rehabilitation.
Selection of hepatitis B surface “escape” mutants during passive immune prophylaxis following liver transplantation: potential impact of genetic changes on polymerase protein function
Authors: P L Shields, A Owsianka, W F Carman, E Boxall, S G Hubscher, J Shaw, K O’Donnell, E Elias, D J Mutimer
Journal: Gut (1999)

A patient is described who developed hepatitis B virus (HBV) reinfection five months following liver transplantation. Failure of hepatitis B immunoglobulin prophylaxis was associated with the emergence of mutations. HBV gene sequencing identified nucleotide substitutions associated with amino acid changes, one within the major hydrophilic region (MHR) of the HBV surface antigen at amino acid position 144 and one outside the MHR. Because of the overlapping reading frames of surface and polymerase genes, the latter surface antigen change was associated with an amino acid change in the polymerase protein. The patient developed significant allograft hepatitis and was treated with lamivudine (3TC) 100 mg daily. Rapid decline of serum HBV DNA was observed with loss of HBV e antigen and HBV surface antigen from serum. There was normalisation of liver biochemistry, and liver immunohistochemistry showed a reduction in HBV core and disappearance of HBs antigen staining.Surface antigen encoding gene mutations associated with HBIg escape may be associated with alteration of the polymerase protein. The polymerase changes may affect sensitivity to antiviral treatment. Selection pressure on one HBV reading frame (for example, HBIg pressure on HBsAg, or nucleoside analogue pressure on polymerase protein) may alter the gene product of the overlapping frame. Such interactions are relevant to strategies employing passive immune prophylaxis and antiviral treatment.
Cranial factors in neocortical evolution
Authors: Geoffrey O'Shea
Journal: Behavioral and Brain Sciences (2003)

Our understanding of paleoneurology can benefit through considerations of how ontogenetic patterns of skull suture ossification can limit the phylogenetic expansion of underlying brain tissue to specific regions. Additionally, the influence of biochemical, rather than biomechanical, mechanisms on skull suture morphogenesis enable a reconceptualization of the skull as an independent evolutionary system from the brain.
Enhanced renal prostaglandin production in the dog. The effect of sodium arachidonate in nonfiltering kidney.
Authors: J G Gerber, J L Data, A S Nies
Journal: Circulation Research (1978)

Sodium arachidonate, 10(-5) g/kg per minute, was infused into the renal artery of a nonfiltering canine kidney in situ in order to determine the effects of enhanced prostaglandin synthesis on renal blood flow and its distribution in circumstances where prostaglandins produced in the medulla could not gain access to the cortex via tubular fluid. The contralateral normal kidney was also infused with sodium arachidonate and served as control. Radioactive microspheres were used to calculate the hemodynamic effects. In the nonfiltering kidney, the total renal blood flow increased after sodium arachidonate from a mean of 105 ml/min per 100 g to 146 ml/min per 100 g (P less than 0.01). This increase was completely abolished by prior treatment with indomethacin, 8 mg/kg, intravenously. The normal kidney responded qualitatively the same as the nonfiltering side. In both kidneys, blood flow increased significantly to all cortical zones except the outermost (zone 1), but the fractional distribution of renal blood flow was significantly increased only in the innermost cortex (zone 4). Since the kidneys were nonfiltering, the increase of renal blood flow during infusion of arachidonic acid cannot be explained by prostaglandins being transported from renal medulla to the cortex through renal tubules. Most likely prostaglandins are produced locally in the cortex and have only local effects.
OrthoClust: an orthology-based network framework for clustering data across multiple species
Authors: Koon-Kiu Yan, Daifeng Wang, Joel Rozowsky, Henry Zheng, Chao Cheng, Mark Gerstein
Journal: Genome biology (2014)

Abstract Increasingly, high-dimensional genomics data are becoming available for many organisms.Here, we develop OrthoClust for simultaneously clustering data across multiple species. OrthoClust is a computational framework that integrates the co-association networks of individual species by utilizing the orthology relationships of genes between species. It outputs optimized modules that are fundamentally cross-species, which can either be conserved or species-specific. We demonstrate the application of OrthoClust using the RNA-Seq expression profiles of Caenorhabditis elegans and Drosophila melanogaster from the modENCODE consortium. A potential application of cross-species modules is to infer putative analogous functions of uncharacterized elements like non-coding RNAs based on guilt-by-association.
Increased Waking Salivary Cortisol Levels in Young People at Familial Risk of Depression
Authors: Zola N. Mannie, Catherine J. Harmer, Philip J. Cowen
Journal: American Journal of Psychiatry (2007)

Objective: Cortisol hypersecretion is one of the most reliable biological abnormalities in major depression, but it is uncertain if it represents an illness marker or a trait vulnerability to mood disorder. The present study sought to answer this question by measuring waking salivary cortisol levels in young people at familial risk of depression but with no personal history of mood disorder. Method: The authors studied 49 young people who had not been depressed themselves but who had a parent with a history of major depression (FH+) and a comparison group of 55 participants who had no personal history of depression and no reported depression in a first-degree relative. The authors measured the amount of cortisol secreted in saliva during the first 30 minutes after awakening on a workday and on a nonworkday. Results: The amount of cortisol secreted by the FH+ subjects was greater than that of the comparison subjects on both workdays (mean=698 nmol×minutes/liter, SD=243, versus mean=550, SD=225) and nonworkdays (mean=633 nmol×minutes/liter, SD=216, versus mean=492, SD=166). The increase in cortisol secretion was not accounted for by differences in parental attachment, life events, personality, or current mental state. Conclusions: Hypersecretion of cortisol can be detected in asymptomatic individuals at genetic risk of depression and may represent an illness endophenotype. Further studies will be needed to find out if increased waking salivary cortisol levels can predict individual risk of illness and whether the increased cortisol secretion has implications for general health and cognitive function.
Identifying CpG Sites Associated with Eczema Via Random Forest Screening of Epigenome-Wide DNA Methylation
Authors: Bilal M. Quraishi, Hongmei Zhang, Todd M. Everson, Gabrielle A. Lockett, Meredith Ray, John W. Holloway, Syed H. Arshad, Wilfried Karmaus
Journal: Journal of Allergy and Clinical Immunology (2015)
Gas Gangrene and Vascularization of Muscles
Authors: R. W. Power
Journal: BMJ (1945)

Additional Points on Cases 1.It is notable that most R.A.F.crew members who have been involved in a flying accident seem to remember the trau- matic experience -viv1dly and in detail.This is contrary to Kardiner's observation; but his cases were of 'much longer standing-years, instead of weeks or months, having elapsed since the event.It is probable that hysterical processes entered far more often into the psychodynamics of his group.2. There is, in a considerable proportion of the cases coming under my observation, retrospective evidence that there was conscious fear at the time of the occurrence." Delayed inhibition" in the Pavlovian sense does not seem to have been the process responsible in them for the subsequent psycho- neurosis.3. It is possible that some stupors are essentially states of extreme preoccupation with the frightening experiences (cf.Hoch's (1921) Benign Stupors and the preoccupation with death).4. Other stupors are presumably hysterical (avoidance) methods of dealing with the same kind of experience.5. The long persistence of conditioned responses after traurna, up to two years ln some R.A.F.cases, and probably indefinitely longer, has its parallel (Anderson and Parmenter, 1941) in sheep with experimental neuroses.6. Some phobias, not of war origin, have probably the same kind of basis, extended to other si Lations recall:ng the orignal traumat:c one in some way.
Efficacy of nafarelin in assisted reproductive technology: a meta-analysis
Authors: J. M. Wong
Journal: Human Reproduction Update (2001)

A systematic review identified nine randomized, controlled trials (both published and unpublished) which assessed the efficacy of nafarelin during IVF compared with other gonadotrophin-releasing hormone (GnRH) agonists. The trials included 1,014 women (nafarelin n = 597) in protocols employing three different dosage regimens, long and short stimulation protocols, and three comparative GnRH agonists (buserelin n = 348; triptorelin n = 14, and leuprolide n = 55). The meta-analysis of the data showed that pregnancy rates per embryo transfer with nafarelin were equivalent to those obtained with other GnRH agonists. Nafarelin and other agonists were also comparable in terms of several intermediate IVF outcomes, including fertilization rates, number of oocytes retrieved, peak oestradiol concentrations, and cycle cancellations. Women treated with nafarelin required fewer ampoules of human menopausal gonadotrophin (HMG)/FSH for ovarian stimulation and fewer days of stimulation. Safety results from both the meta-analysis and a qualitative analysis of 12 additional reports suggested that adverse effects were within the accepted tolerance range; the most frequent adverse effects were hypo-oestrogenic symptoms. In conclusion, the overall efficacy of nafarelin was equivalent to that of other GnRH agonists. The possibility that the reduced gonadotrophin requirements in women taking nafarelin will translate into cost savings per IVF treatment cycle requires further study.
Glutamine deprivation facilitates tumour necrosis factor induced bacterial translocation in Caco-2 cells by depletion of enterocyte fuel substrate
Authors: E C Clark
Journal: Gut (2003)

<b>Background and aims:</b> Factors that induce luminal bacteria to cross the intestinal epithelium following injury remain poorly defined. The aim of this study was to investigate the interaction between glutamine metabolism, energy supply, and inflammatory mediators in determining the translocation of non-pathogenic bacteria across cultured enterocytes. <b>Methods:</b> The effect of tumour necrosis factor α (TNF-α) on translocation of <i>Escherichia coli</i> C25 across Caco-2 epithelial monolayers was studied in the presence of products and inhibitors of glutamine metabolism. Simultaneous measurements of transepithelial electrical resistance (TEER) and flux of lucifer yellow were used to assess effects on the paracellular pathway. Lactate dehydrogenase release was used to monitor enterocyte integrity. Imaging of monolayers in these experimental conditions was undertaken with transmission electron microscopy. <b>Results:</b> Exposure to basolateral TNF-α (20 ng/ml) for six hours induced translocation of <i>E coli</i> across Caco-2 but only if accompanied by simultaneous glutamine depletion (p&lt;0.01). Translocation was inhibited by addition of glutamine for two hours (p&lt;0.01) but not by an isonitrogenous mixture of non-glutamine containing amino acids. Inhibition of glutamine conversion to α-ketoglutarate, but not blockade of glutathione or polyamine synthesis, also induced translocation in the presence of TNF-α. Manipulations that induced bacterial translocation were associated with a marked reduction in enterocyte ATP levels. No effect of these treatments on paracellular permeability or lactate dehydrogenase release was observed. Conditions in which translocation occurred were associated with the presence of bacteria within enterocyte vacuoles but not the paracellular space. <b>Conclusions:</b> In inflammatory conditions, the availability of glutamine as an enterocyte fuel substrate is essential for the preservation of a functional barrier to microorganisms. In conditions of acute glutamine depletion, cytokine mediated bacterial translocation appears to be primarily a transcellular process.
A Genome-Wide Association Study of Myasthenia Gravis
Authors: Alan E. Renton, Hannah A. Pliner, Carlo Provenzano, Amelia Evoli, Roberta Ricciardi, Michael A. Nalls, Giuseppe Marangi, Yevgeniya Abramzon, Sampath Arepalli, Sean Chong, Dena G. Hernandez, Janel O. Johnson, Emanuela Bartoccioni, Flavia Scuderi, Michelangelo Maestri, J. Raphael Gibbs, Edoardo Errichiello, Adriano Chiò, Gabriella Restagno, Mario Sabatelli, Mark Macek, Sonja W. Scholz, Andrea Corse, Vinay Chaudhry, Michael Benatar, Richard J. Barohn, April McVey, Mamatha Pasnoor, Mazen M. Dimachkie, Julie Rowin, John Kissel, Miriam Freimer, Henry J. Kaminski, Donald B. Sanders, Bernadette Lipscomb, Janice M. Massey, Manisha Chopra, James F. Howard, Wilma J. Koopman, Michael W. Nicolle, Robert M. Pascuzzi, Alan Pestronk, Charlie Wulf, Julaine Florence, Derrick Blackmore, Aimee Soloway, Zaeem Siddiqi, Srikanth Muppidi, Gil Wolfe, David Richman, Michelle M. Mezei, Theresa Jiwa, Joel Oger, Daniel B. Drachman, Bryan J. Traynor
Journal: JAMA Neurology (2015)

IMPORTANCE-Myasthenia gravis is a chronic, autoimmune, neuromuscular disease characterized by fluctuating weakness of voluntary muscle groups.Although genetic factors are known to play a role in this neuroimmunological condition, the genetic etiology underlying myasthenia gravis is not well understood.OBJECTIVE-To identify genetic variants that alter susceptibility to myasthenia gravis, we performed a genome-wide association study.DESIGN, SETTING, AND PARTICIPANTS-DNA was obtained from 1032 white individuals from North America diagnosed as having acetylcholine receptor antibody-positive myasthenia gravis and 1998 race/ethnicity-matched control individuals from January 2010 to January 2011.These samples were genotyped on Illumina OmniExpress single-nucleotide polymorphism arrays.An independent cohort of 423 Italian cases and 467 Italian control individuals were used for replication. MAIN OUTCOMES AND MEASURES-We calculated P values for association between8114394 genotyped and imputed variants across the genome and risk for developing myasthenia gravis using logistic regression modeling.A threshold P value of 5.0 × 10 -8 was set for genomewide significance after Bonferroni correction for multiple testing. RESULTS-In the over all case-control cohort, we identified association signals at CTLA4 (rs231770; P = 3.98 × 10 -8 ; odds ratio, 1.37; 95% CI, 1.25-1.49),HLA-DQA1 (rs9271871; P = 1.08 × 10 -8 ; odds ratio, 2.31; 95% CI, 2.02 -2.60), and TNFRSF11A (rs4263037; P = 1.60 × 10 -9 ; odds ratio, 1.41; 95% CI, 1.29-1.53).These findings replicated for CTLA4 and HLA-DQA1 in an independent cohort of Italian cases and control individuals.Further analysis revealed distinct,
Disease activity as a risk factor for myocardial infarction in rheumatoid arthritis
Authors: B J Radovits, D A Popa-Diaconu, C Popa, A Eijsbouts, R F J M Laan, P L C M van Riel, J Fransen
Journal: Annals of the Rheumatic Diseases (2008)

Objective: Patients with rheumatoid arthritis (RA) are at greater risk of developing coronary heart disease than the general population. Systemic inflammation may contribute to this risk. This study investigated whether the level of disease activity is associated with the risk of developing myocardial infarction (MI) in patients with RA. Methods: A case-control study was performed within a large prospective cohort of patients with RA. Cases were patients who developed their first MI after the diagnosis of RA, controls were patients with RA without MI. Cases and controls had similar RA disease duration. Traditional and disease-specific risk factors for MI were collected and a time-averaged disease activity score (DAS28) was calculated. The data were analysed using conditional logistic regression analysis. Results: Cases of MI were significantly older, were more often male, with higher body mass index (BMI) and total cholesterol and lower high-density lipoprotein (HDL) serum levels than controls. Time-averaged disease activity was similar for cases and controls. The raw odds ratio for MI in patients with a "high" (>4.0) versus a "low" (⩽4.0) average DAS28 was 1.2 (95% CI 0.61 to 2.36). The odds ratio corrected for age, gender, BMI, baseline Health Assessment Questionnaire and baseline HDL was 0.91 (95% CI 0.39 to 2.12). Conclusion: Patients with RA who developed MI had more classical risk factors but not higher disease activity over time than control patients with RA. Low levels of inflammation may be sufficient for accelerated atherogenesis and an excess risk of cardiovascular disease in RA.
Outcomes for births booked under an independent midwife and births in NHS maternity units: matched comparison study
Authors: A. Symon, C. Winter, M. Inkster, P. T Donnan
Journal: BMJ (2009)

<h3>Background</h3> Stimulation of 4-1BB with agonistic antibodies is a promising strategy for improving the therapeutic efficacy of immune checkpoint inhibitors (ICIs) or for overcoming resistance to ICIs. However, dose-dependent hepatotoxicity was observed in clinical trials with monoclonal anti-4-1BB agonistic antibodies due to the activation of 4-1BB signaling in liver resident Kupffer cells. <h3>Methods</h3> To avoid this on-target liver toxicity, we developed a novel bispecific antibody (4-1BB×PD-L1 bispecific antibody, termed “ABL503”) uniquely designed to activate 4-1BB signaling only in the context of PD-L1, while also blocking PD-1/PD-L1 signaling. <h3>Results</h3> Functional evaluation using effector cells expressing both 4-1BB and PD-1 revealed superior biological activity of ABL503 compared with the combination of each monoclonal antibody. ABL503 also augmented T-cell activation in in vitro assays and further enhanced the anti-PD-L1-mediated reinvigoration of tumor-infiltrating CD8<sup>+</sup> T cells from patients with cancer. Furthermore, in humanized PD-L1/4-1BB transgenic mice challenged with huPD-L1-expressing tumor cells, ABL503 induced superior anti-tumor activity and maintained an anti-tumor response against tumor rechallenge. ABL503 was well tolerated, with normal liver function in monkeys. <h3>Conclusion</h3> The novel anti-4-1BB×PD-L1 bispecific antibody may exert a strong anti-tumor therapeutic efficacy with a low risk of liver toxicity through the restriction of 4-1BB stimulation in tumors.