tbuckley/cabot-search huggingface dataset:
Improving MMR coverage in Birmingham
Authors: A. M. Rouse, J. Chambers, J. Nelson
Journal: BMJ (2011)

<h3>Abstract</h3> Proteome-wide Mendelian randomization (MR) shows value in prioritizing drug targets in Europeans, but limited data has made identification of causal proteins in other ancestries challenging. Here we present a multi-ancestry proteome-wide MR analysis pipeline based on cross-population data from the Global Biobank Meta-analysis Initiative (GBMI). We estimated the causal effects of 1,545 proteins on eight complex diseases in up to 32,658 individuals of African ancestries and 1.22 million individuals of European ancestries. We identified 45 and seven protein-disease pairs with MR and genetic colocalization evidence in the two ancestries respectively. 15 protein-disease pairs showed evidence of differential effects between males and females. A multi-ancestry MR comparison identified two protein-disease pairs with MR evidence of an effect in both ancestries, seven pairs with European-specific effects and seven with African-specific effects. Integrating these MR signals with observational and clinical trial evidence, we were able to evaluate the efficacy of one existing drug, identify seven drug repurposing opportunities and predict seven novel effects of proteins on diseases. Our results highlight the value of proteome-wide MR in informing the generalisability of drug targets across ancestries and illustrate the value of multi-cohort and biobank meta-analysis of genetic data for drug development. <h3>Graphical abstract</h3> Notation: genome-wide association study (GWAS); Mendelian randomization (MR); primary open-angle glaucoma (POAG); idiopathic pulmonary fibrosis (IPF); chronic obstructive pulmonary disease (COPD); heart failure (HF), venous thromboembolism (VTE). European ancestry (EUR); African ancestry (AFR)*For the seven protein-disease associations, one association passed FDR threshold of 0.05 in proteome-wide MR, six additional associations passed FDR of 0.05 in the multi-ancestry comparison analysis. <h3>Highlights</h3> A multi-ancestry proteome-wide Mendelian randomization (MR) analysis of 1,545 proteins on eight diseases in more than 1.26 million individuals from a disease GWAS meta-analysis of 19 biobanks. We find evidence for putative causal effects in 45 protein-disease pairs in European ancestry and seven protein-disease pairs in African ancestry, with 15 pairs showing sex specific effects. We identify evidence of causality for two protein-disease pairs that are common to both African and European ancestries, seven pairs with European-specific effects and seven pairs with African-specific effects. Triangulating with clinical trial and observational evidence prioritizes seven new targets, seven drug repurposing opportunities and one existing drug target that generalise to African ancestry.
Interaction of allergens from house‐dust mite and from cereal flours: <i>Dermatophagoides pteronyssinus</i>α‐amylase (Der p 4) and wheat and rye α‐amylase inhibitors
Authors: R. Sánchez‐Monge, G. García‐Casado, D. Barbe, G. Salcedo
Journal: Allergy (1996)

Major wheat and rye allergens associated with baker's asthma have been identified as specific inhibitors of Dermatophagoides pteronyssinus α‐amylase (Der p 4). The most active inhibitors were the wheat tetrameric one and the rye dimeric RDAI‐1. These data suggest that interaction between mite and cereal allergens (α‐amylase/inhibitor complexes) might occur in house‐dust‐mite‐infected flours. In contrast to the strong inhibition of the D. pteronyssinus enzyme by the wheat and rye inhibitors, the amylases from D. farinae, Lepidoglyphus destructor , and Tyrophagus putrescentiae were much less affected. Moreover, the D. pteronyssinus amylase showed higher pH optimum (6.5 versus 5.0) and activity level (2–6 times/mg of protein in whole‐mite extracts) than those from the three other mite species.
Abstract 2826: Carbohydrate intake, glycemic load, and glycemic index and prostate cancer risk
Authors: Christina D. Williams, Brian Whitley, Cathrine Hoyo, Delores Grant, Jared Iraggi, Kathryn Newman, Leah Gerber, Loretta Taylor, Stephen Freedland
Journal: Cancer Research (2010)

Abstract Background: The typical U.S. diet is characterized by high carbohydrate intake, and dietary carbohydrates can modulate insulin sensitivity depending on their glycemic effect. Glycemic load and glycemic index, which represent the quality and quantity of carbohydrate foods, and prostate cancer risk are poorly characterized. Objective: To examine the association between dietary carbohydrate intake, glycemic load, and glycemic index and risk of prostate cancer, and determine if these associations differ between Whites and Blacks. Methods: We analyzed data from an ongoing case-control study of White (N=109) and Black (N=143) veterans at the Durham VA Medical Center. Cases were 65 men with biopsy-confirmed prostate cancer. There were two groups of controls: biopsy-negative controls (N=89) and healthy (i.e. no biopsy indication) controls (N=98). All men had a PSA test done in the year prior to enrolling in the study. Demographic and lifestyle risk factors were collected using self-administered questionnaires. Diet information was obtained using the Harvard food frequency questionnaire. Odds ratios (OR) and corresponding 95% confidence intervals (95% CI) for prostate cancer risk were obtained using logistic regression analyses adjusted for age, race, and total energy. Results: Mean carbohydrate intake, glycemic load, and glycemic index were similar among cases and both groups of controls (all p-values &amp;gt;0.05). We did not observe any statistically significant risk estimates for high (≥median) carbohydrate intake, glycemic load, or glycemic index. Compared to healthy controls, the ORs for prostate cancer risk associated with high carbohydrate intake, glycemic load, and glycemic index were 0.66 (95% CI 0.34-1.30), 0.57 (95% CI 0.22-1.49), and 1.18 (95% CI 0.61-2.02) respectively. Corresponding ORs when compared to biopsy-negative controls were 0.88 (95% CI 0.46-1.70), 0.69 (95% CI 0.29-1.64), and 0.83 (95% CI 0.43-1.59), respectively. The associations between carbohydrate intake, glycemic load, or glycemic index and risk of low-grade (gleason score &amp;lt;7) as well as high-grade (gleason score ≥7) prostate cancer relative to healthy controls were null for all analyses. There was no evidence of effect modification by race in our analyses. Additional adjustment for fiber intake did not appreciably alter any of the ORs. Conclusion: Our findings in a small case-control study do not suggest that a high carbohydrate intake and/or high glycemic load increase the risk of prostate cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2826.
Erosive duodentis during cimetidine treatment.
Authors: G Fedeli, M Anti, G L Rapaccini
Journal: BMJ (1978)

to belittle Harvey's great contributions to the discovery of the circulation of the blood, but is it not time that we in Britain stopped perpetuating what at least is an oversimplified claim, that it was Harvey and Harvey alone who made this great discovery?It would be most interesting, especially to me, to learn the views of professional medical historians-British, Italian, and Dutch.
Impact Of Dose Reduction Of Bleomycin and Vincristine In Patients With Advanced Hodgkin Lymphoma Treated With Beacopp: A Comprehensive Analysis Of The German Hodgkin Study Group (GHSG) HD12 and HD15 Trials
Authors: Bastian von Tresckow, Heinz Haverkamp, Boris Böll, Dennis A. Eichenauer, Stephanie Sasse, Michael Fuchs, Peter Borchmann, Andreas Engert
Journal: Blood (2013)
Racial Disparities on the Use of Invasive and Noninvasive Staging in Patients with Non-small Cell Lung Cancer
Authors: Jennifer Marie Suga, Danh V. Nguyen, Sandra M. Mohammed, Monica Brown, Royce Calhoun, Ken Yoneda, David R. Gandara, Primo N. Lara
Journal: Journal of Thoracic Oncology (2010)
THE PART PLAYED BY CONCOMITANT INFECTION WITH ANAEROBIC ORGANISMS (OTHER THAN B. TETANI) IN THE CAUSATION OF TETANUS
Authors: W. J. Tulloch
Journal: BMJ (1918)

~A~~l7lfuT , 9flattening of the iliac bones, more marked on the right side.When worked out,' the amount compares favourabl-y with the doctor's direct measurements.
Quantitative liver function tests as surrogate markers for end-points in controlled clinical trials: A retrospective feasibility study
Authors: E Lotterer, J Hogel, W Gaus, W E Fleig, J Bircher
Journal: Hepatology (1997)

Quantitative liver function tests such as the determination of galactose elimination capacity (GEC) or the aminopyrine breath test (ABT) may have the potential to serve as refined entry criteria and surrogate markers for end-points in controlled clinical trials. The magnitude of a statistically detectable difference in test results and the period of observation required to document such a difference must be known to properly design such trials. Therefore, we explored retrospectively the time course of changes in GEC and ABT and their reproducibility from a cohort of patients with alcoholic cirrhosis followed for 12 to 42 months, with a median of 34 months. In 15 patients who stopped drinking, GEC improved significantly by 0.64 mg/min/kg within 1 year (mean; 95% confidence interval [CI]: 0.42; 0.86). In contrast, it deteriorated by 0.53 mg/min/kg within 1 year (95% CI: 0.32; 0.74) in another 17 patients who continued to drink (P < .01). The residual standard deviation of the changes in GEC with respect to the patients' initial values was 0.43 mg/min/kg (95% CI: 0.32; 0.52). In addition, ABT improved significantly by 0.14% dose x kg/mmol CO2 (95% CI: 0.09; 0.18) in the abstinent group, and deteriorated by 0.09% dose x kg/mmol CO2 (95% CI: 0.06; 0.13) in the nonabstinent group (P < .01). The residual standard deviation in the above sense for ABT was 0.08% dose x kg/mmol CO2 (95% CI: 0.06; 0.10). These data indicate that clinical trials with a sample size of n = 20 in each group must achieve absolute differences (ADs) in GEC of 0.6 mg/min/kg and of 0.7 mg/min/kg to reach statistical significance at the 5% and 1% level, respectively. In the present study, a period of 11 and 12 months was necessary to observe such differences. The corresponding results for the ABT are 0.11% dose x kg/mmol CO2 (9 months of follow-up; 5% level) and 0.13% dose x kg/mmol CO2 (11 months of observation; 1% level), respectively. Provided that patients with liver diseases treated with drugs are similar to the abstinent and nonabstinent patients with alcoholic liver disease investigated in this study, such numbers could serve for the planning of controlled clinical trials, in which the control group is likely to deteriorate and the treated group is expected to improve. Trials based on GEC or ABT would require only 37 or 30 patient years of observation compared with a median of 444 patient years (range, 50-2,100 patient years) reported for various published controlled clinical trials using survival analysis.
Cover story: Meg Campbell's "Mother and Child"
Authors: T. Delamothe
Journal: BMJ (1994)

Given its subject matter, Simon Knowles's description of the pregnancy loss roadshow (p 1705) seemed an obvious choice for Christmas. Its visual references — to photographs, hand and foot prints, and identity bracelets — suggested that it might also provide the basis for this year's cover.

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I saw Meg Campbell's etchings at an exhibition called “Reclaiming the Madonna: Artists as Mothers.” They came out of a joint residency at the Princess Anne Maternity Hospital, Southampton, with poet Fiona Sampson.

In the catalogue, Ms Campbell moved from a description of a caesarean section to her …

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Population and Pedigree Studies Reveal a Lack of Association Between the Dopamine D2 Receptor Gene and Alcoholism
Authors: Annabel M. Bolos
Journal: JAMA (1990)

Using the dopamine D<sub>2</sub>receptor clone λhD2G1, Blum et al recently found that the D<sub>2</sub>/<i>Taq</i>I allele (A1) was present in 69% of 35 deceased alcoholics but in only 20% of an equal number of controls. To assess this association further, we evaluated the D<sub>2</sub>/Taq I polymorphism and a single-strand conformation polymorphism detected by polymerase chain reaction and nondenaturing gel electrophoresis (PCR-SSCP) of the 3' noncoding region of the D<sub>2</sub>receptor gene. We studied 40 unrelated white alcoholics, 127 racially matched controls, and two white pedigrees. The Schedule for Affective Disorders and Schizophrenia—Lifetime Version (SADS-L) clinical diagnostic interviews were rated blindly by two clinicians. The SADS-L interviews and other data were then used to ascertain diagnoses according to the<i>Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition (DSM-III-R)</i>criteria. Alcoholics were subtyped according to age of onset, severity, presence of antisocial personality, and family history. No significant differences in either D<sub>2</sub>/<i>Taq</i>I or PCR-SSCP allele frequencies were observed between alcoholics, subpopulations of alcoholics, or controls. The PCR-SSCP polymorphism provided independent information against linkage at the D<sub>2</sub>receptor locus. Several recombinants between the D<sub>2</sub>/<i>Taq</i>I locus and alcoholism were observed in two white families with an alcoholic parent who possessed the A1 allele. This study does not support a widespread or consistent association between the D<sub>2</sub>receptor gene and alcoholism. (<i>JAMA</i>. 1990;264:3156-3160)
CTLA-4–Ig Activates Forkhead Transcription Factors and Protects Dendritic Cells from Oxidative Stress in Nonobese Diabetic Mice
Authors: Francesca Fallarino, Roberta Bianchi, Ciriana Orabona, Carmine Vacca, Maria L. Belladonna, Maria C. Fioretti, David V. Serreze, Ursula Grohmann, Paolo Puccetti
Journal: The Journal of Experimental Medicine (2004)

Prediabetes and diabetes in nonobese diabetic (NOD) mice have been targeted by a variety of immunotherapies, including the use of a soluble form of cytotoxic T lymphocyte antigen 4 (CTLA-4) and interferon (IFN)-gamma. The cytokine, however, fails to activate tolerogenic properties in dendritic cells (DCs) from highly susceptible female mice early in prediabetes. The defect is characterized by impaired induction of immunosuppressive tryptophan catabolism, is related to transient blockade of the signal transducer and activator of transcription (STAT)1 pathway of intracellular signaling by IFN-gamma, and is caused by peroxynitrite production. Here, we show that soluble CTLA-4 imparts suppressive properties to DCs from early prediabetic NOD female mice through mechanisms that rely on autocrine signaling by IFN-gamma. Although phosphorylation of STAT1 in response to IFN-gamma is compromised in those mice, CTLA-4 obviates the defect. IFN-gamma-driven expression of tryptophan catabolism by CTLA-4-immunoglobulin is made possible through the concomitant activation of the Forkhead Box class O (FOXO) transcription factor FOXO3a, induction of the superoxide dismutase gene, and prevention of peroxynitrite formation.
Failure of coconut oil to accelerate psoriasis clearance in narrow-band UVB phototherapy or photochemotherapy
Authors: S.A. GEORGE, D.J. BILSLAND, N.J. WAINWRIGHT, J. FERGUSON
Journal: British Journal of Dermatology (1993)

Journal Article Failure of coconut oil to accelerate psoriasis clearance in narrow‐band UVB phototherapy or photochemotherapy Get access S.A. GEORGE, S.A. GEORGE Photobiology Unit, Ninewells Hospital and Medical School, Dundee DD1 9SY, Scotland, U.K. Dr S.A. George, Photobiology unit, Ninewells Hospital and Medical School, Dundee, Scotland DD1 9SY, U.K Search for other works by this author on: Oxford Academic Google Scholar D.J. BILSLAND, D.J. BILSLAND Photobiology Unit, Ninewells Hospital and Medical School, Dundee DD1 9SY, Scotland, U.K. Search for other works by this author on: Oxford Academic Google Scholar N.J. WAINWRIGHT, N.J. WAINWRIGHT Photobiology Unit, Ninewells Hospital and Medical School, Dundee DD1 9SY, Scotland, U.K. Search for other works by this author on: Oxford Academic Google Scholar J. FERGUSON J. FERGUSON Photobiology Unit, Ninewells Hospital and Medical School, Dundee DD1 9SY, Scotland, U.K. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 128, Issue 3, 1 March 1993, Pages 301–305, https://doi.org/10.1111/j.1365-2133.1993.tb00175.x Published: 01 March 1993 Article history Accepted: 29 September 1992 Published: 01 March 1993
THE CULTIVATION OF LENS EPITHELIUM IN VITRO
Authors: Daniel B. Kirby
Journal: The Journal of Experimental Medicine (1927)

1. Differentiation of the posterior cells of the lens vesicle into lens cortex has been observed in vitro. 2. It is possible to dissect out the lens of the 5 day embryo chick in such a manner as to free it from all extraneous cells. 3. Lens epithelium even at a very early stage is contained within a cuticula. 4. Lens epithelium under proper conditions will live, migrate, divide, and multiply in vitro in primary explants. 5. An unmixed strain of lens epithelium can be propagated from a primary explant by successive subcultures. This strain can be utilized for controlled experiments on the nutrition of the cells of the lens.
Silo-Filler's Disease: Nitrogen Dioxide-Induced Lung Injury
Authors: J. RAMlREZ-R.
Journal: Annals of Internal Medicine (1971)

A patient has been followed for 7 years after exposure to silage gas. His chest film showed diffuse reticular and fine nodular infiltrates. Except for mild hypoventilation and hypoxemia his pulmonary function has remained normal. Persistent lung malfunction after exposure to silage gas is uncommon in those patients who recover from the initial toxic pulmonary edema. Reported cases of chronic lung disability after silage gas inhalation were probably due to other causes, such as chronic bronchitis.
Case 10-1980
Authors: Richard C. Cabot, Robert E. Scully, James J. Galdabini, Betty U. McNeely, Christopher Longcope, Stanley J. Robboy
Journal: New England Journal of Medicine (1980)

Presentation of CaseA 29-year-old woman was admitted to the hospital because of hirsutism and amenorrhea.Menarche occurred at the age of 12 years, with regular menses preceded by one day of mild cramps; she frequently experienced mittelschmerz. At the age of 21 years a pregnancy was terminated, and she began to use an oral contraceptive medication. Six months later ankle edema appeared, and the medication was discontinued. Four years before admission she resumed the use of oral contraceptive agents, and during the year and a half before admission she used norgestrel and ethinyl estradiol (Ovral). While taking that agent . . .
Hepatitis C Virus Infections From a Contaminated Radiopharmaceutical Used in Myocardial Perfusion Studies
Authors: Priti R. Patel, A. Kirsten Larson, Amanda D. Castel, Lilia M. Ganova-Raeva, Robert A. Myers, Brenda J. Roup, Katherine P. Farrell, Leslie Edwards, Omana Nainan, John P. Krick, David Blythe, Anthony E. Fiore, Jeffrey C. Roche
Journal: JAMA (2006)

ContextNuclear pharmacies prepare radiopharmaceutical products for use in common diagnostic procedures, including myocardial perfusion studies. Hepatitis C virus (HCV) transmission has not been reported previously in the setting of nuclear imaging studies.ObjectiveTo investigate an outbreak of acute HCV infection identified among patients who underwent myocardial perfusion studies on October 15, 2004, using an injected radiopharmaceutical.Design, Setting, and PatientsOutbreak investigation including molecular epidemiology and pharmacy site investigation at outpatient cardiology clinics and a nuclear pharmacy in Maryland. Ninety patients who received injections drawn from select radiopharmaceutical vials prepared on October 14-15, 2004, at a single nuclear pharmacy were offered testing for bloodborne pathogens. Pharmacy procedures were reviewed and HCV quasi species analysis was performed.Main Outcome MeasuresHepatitis C virus infection and quasispecies sequence similarity.ResultsSixteen patients with acute HCV infection were identified from 3 separate clinics. All patients received radiopharmaceutical injections drawn from a single pharmacy vial (vial 1). None of the 59 tested patients who received doses from 6 other vials had acute HCV infection. Blood from a potential source patient with HCV and human immunodeficiency virus (HIV) infection was processed for a radiolabeled white blood cell study in the pharmacy 12 hours before vial 1 was prepared. The HCV quasispecies sequences from this potential source patient were nearly identical to those from cases (97.8%-98.5% similarity). No acute HIV infections were identified. Pharmacy practices that could have led to blood cross-contamination included reuse of needles and syringes during dilutions and use of common flow hoods for some steps in the preparation of sterile and blood-derived products.ConclusionsSixteen persons acquired HCV infection from a blood-contaminated radiopharmaceutical. The source and practices that could have facilitated breaks in aseptic technique were identified at the pharmacy. Nuclear pharmacies that handle biological products should follow appropriate aseptic technique to prevent contamination of sterile radiopharmaceuticals.
Treatment of Severe Decompression Sickness in Aviators
Authors: P. Cannon, T. R. Gould
Journal: BMJ (1964)

exclusion of those transferred successfully to oral therapy leads to a reduction of the ultimate overall success rate from 42% to 37 %, and even this value may be too high, since there may have been others controllable, but untried, with tablets.On the other hand, it should be observed that with I.Z.S., even after continuous administration for more than five years, a large number of patients still maintained good control.This was observed particularly in those with maturity onset (51%), those requiring less than 40 units of insulin (54%), and those who gave a history of former obesity (55%).From the results presented it is apparent that more and more patients lapse from I.Z.S. control the longer it is continued.It might be thought that this was due simply to the diabetic state becoming more difficult to control.Good control can, however, be regained in some cases by a change from I.Z.S. to another insulin, whereas it cannot be achieved by increasing the dose of I.Z.S. itself.We suggest that part at least of the explanation of failing control with I.Z.S. is attributable to failure of its crystalline component to exert its desired effect, since its other component, I.Z.S. amorphous, often continues to be of great value. SummaryA review was made of 211 non-obese diabetic patients who began taking insulin zinc suspension (" lente " insulin) between 1953 and 1957.Control was better in patients who received I.Z.S. as the first insulin than in those who were transferred from other insulin regimes.It was most readily maintained in patients with maturity-onset diabetes, in those requiring less than 40 units of insulin daily, and in those who gave a history of previous obesity.A sulphonylurea drug was substituted for I.Z.S. in 39 cases, and patients who had been overweight in the prediabetic years showed a strikingly better response than those who had never been obese.Initially 67% of all cases were well controlled by I.Z.S. but there was a decrease year by year in the proportion of those who maintained good control.This seemed to be related to the duration of treatment, and after five years only 42% of cases were satisfactory.Attempts to obtain better control by other regimes were often successful in those who had failed on I.Z.S., and eventually 70.6 % of all patients achieved good control.The most successful of these methods was two daily doses of insulin.For this purpose I.Z.S. amorphous (" semilente ") often proved useful, and it is accordingly suggested that the poor results with I.Z.S. might be attributable to failure of the I.Z.S. crystalline (" ultralente ") component.