tbuckley/cabot-search huggingface dataset:
How medicine is broken, and how we can fix it
Authors: Ben Goldacre, Carl Heneghan
Journal: BMJ (2015)

<h3>Background</h3> HIV is an infectious disease transmitted through blood or body fluids. The main cause of death for patients with HIV are opportunistic infections (OIs), since patients have a weakened immune system, leaving them susceptible to any infectious agent. OIs are becoming less frequent because of better immunity of HIV patients and earlier screening for OIs for treatment and prevention. As per international guidelines, it is recommended that patients with HIV are screened for hepatitis B, hepatitis C, and tuberculosis upon HIV diagnosis because of their frequent co-infection with HIV and similar route of transmission. However, gaps in screening for common co-infections still occur. The aim of this study was to estimate the prevalence of hepatitis B, hepatitis C, and tuberculosis among HIV-positive patients, and to assess the adherence of healthcare workers to the screening guidelines of common HIV co-infections. <h3>Methods</h3> This was a retrospective analysis of all HIV-positive patients diagnosed at KAMC-Riyadh from 2000 to 2018. Data regarding results of infectious diseases were extracted from each patient’s medical file. <h3>Results</h3> A total of 126 patients tested positive for HIV in KAMC-Riyadh during the study period. 53 of these patients were screened for hepatitis B, of whom four were positive; 55 were screened for hepatitis C, of whom four were also positive, and 72 patients were screened for tuberculosis, of whom seven were positive. The remainder of the patients were never screened for any of the diseases. <h3>Conclusion</h3> More than 40% of patients with HIV were not screened for either hepatitis B, hepatitis C, or tuberculosis, which are the most common co-infections with HIV. These diseases may progress quickly and could be managed if discovered early or prevented. These results demonstrate the need for a comprehensive HIV program that involves early screening and protection against all infectious diseases.
The antitussive pentoxyverine (POV) has a low proarrhythmic risk based on an in vitro and in vivo integrated risk assessment
Authors: Thomas Weiser, Brian Guth, Georg Rast, Michael Markert, Holger Fuchs, André Liesener
Journal: European Respiratory Journal (2014)

Our study investigated POV-induced effects in various preclinical models, since potency for blocking hERG channels alone is not sufficient to assess its proarrhythmic potential.  POV inhibited hERG channels with an IC 50  of 13.8 uM using a manual patch clamp assay. Action potential duration (APD) in the guinea pig papillary muscle was prolonged minimally by ∼3% at 1 uM but then was reduced by ∼20% at 10 uM. Thus, the  in vitro  data suggest that concentrations that could cause hERG-mediated APD prolongation are associated with other effects that lead to a substantial APD shortening.  The effect of POV on the QT-interval was investigated in anaesthetized Beagle dogs using intravenous infusion of 1, 3, 10 and finally 30 mg/kg using an escalating dose design. Heart rate (HR), blood pressure (BP), max. value of the first derivative of the left ventricular pressure (LVdP/dtmax), as well as the ECG were measured and related to plasma drug levels.  The step-wise infusions lead to POV plasma concentrations of 0.63, 2.1, 12.2 and 108 uM at the end of each dose step. HR was held constant with pacing. BP was reduced starting at POV concentrations >12.2 uM. Only a slight (∼5%) prolongation of the QT-interval was observed at 12 uM but higher concentrations led to an exposure-dependent and ultimately fatal drop in BP and LVdP/dtmax.  Our data show that POV does not affect the QT interval relevantly up to the highest tolerable concentration in the  in vivo  model used. Based on all available data, both   in vitro  and  in vivo , the proarrhythmic risk based on QT prolongation with therapeutic doses of POV (mean C max  in man @ 30 mg appr. 0.14 uM) is considered very low.
Blow your own trumpet
Authors: Theodore Dalrymple
Journal: BMJ (2009)

Modesty was once considered a virtue, but nowadays it is clearly an impediment to a successful career. We prefer—or perhaps I should say we demand—boastfulness. To judge by job applications, the world is now stuffed full of paragons whose moral commitment to the welfare of humankind is equalled only by the brilliance of their contributions to medical science.

It therefore seems to me that all medical students and young doctors should take a leaf out of Dr Williams’s pamphlet, published in Shrewsbury in 1841, entitled “An Account of Numerous Cases of Extraordinary Cures Effected by Dr Williams.”

The introduction begins: “Dr Williams begs leave to acquaint the …
Live birth rates after IVF are lower with frozen donor eggs, study shows:
Authors: Susan Mayor
Journal: BMJ (2015)

The use of cryopreserved donor oocytes for in vitro fertilisation (IVF) is associated with lower live birth rates than those from fresh donor oocytes, US figures reported in a research letter to JAMA have shown.1

Donated oocytes’ use in IVF has increased dramatically in the United States in the past few years. Donated eggs were traditionally used immediately to create embryos, and any extra embryos left over from implantation were cryopreserved for later use. But some IVF centres have started to establish frozen donor egg banks after the American Society …
Stability and agreement of micro-transducer esophageal catheter and air-filled balloon esophageal catheter: in vitro and in vivo study
Authors: Renan Maloni, Andre Albuqueruue, Carlos Carvalho, Joao Salge, Letícia Cardenas, Jeferson Ferreira, Vinicius Iamonti, Luiz Orlandin, Pedro Caruso
Journal: European Respiratory Journal (2014)

Background : the measurement of esophageal pressure (Pes) is applied in physiopathologic studies and clinical practice. Esophageal catheters with micro-transducers (MTC) promise to facilitate the insertion and use of esophageal catheters. Unfortunately the MCT were scarcely tested and validated.  Aim : to evaluate,  in vitro  and  in vivo , the stability and agreement of esophageal catheters with air-filled balloon (BC) and MTC.  Methods :  in vitro:  catheters had their frequency response and stability evaluated over 6h.  In vivo : 9 volunteers had a BC and MTC simultaneously inserted and located at the same esophageal level. The stability of the baseline Pes, ΔPes and Pes during sniff were evaluated over 3h.  Results :  in vitro : the MTC frequency response was higher than BC (261±26 vs 114±33 Hz, p 2 O (range 5.6).  In vivo : the mean drift of the baseline Pes of the BC was higher than the MTC (1.8±4.9 vs-3.1±6.1 cmH 2 O, p  .  Conclusions : MTC have a higher frequency response associated to a lower pressure drift and coefficient of variation than BC. However, due to the low agreement, MTC shall not be consider as surrogates of BC.
Respiratory symptoms and lung function parameters in workers exposed to wood smoke and cooking oil fumes in Nigeria
Authors: Olanisun O. Adewole, Olufemi Desalu, K.K. Kenneth, Tayo Adewole, Greg Erhabor
Journal: European Respiratory Journal (2012)

Introduction: Exposures to wood smoke and oil fumes occurs in both home and industrial setting and is associated with occurrence of both respiratory and non respiratory diseases.  Mai suya is a common job in most northern Nigeria. Our aim is to study the prevalence and respiratory function parameters among this group.  Method: This is a community, and case controlled study involving mai suya and workers who are not exposed to wood smoke and oil fumes in an occupational setting. Both groups underwent an interviewer administered questionnaire followed by on spot spirometric test. Chi square was used to test for association between respiratory symptoms and the job categories. Odd ratios were determined for the risk of respiratory symptoms and exposure to wood smoke and oil fumes.  Result: Both groups are similar in their demographic characters except in their smoking status. The test group had significantly increased occurrence of respiratory symptoms compared with the control group, p value   Conclusion: Workers exposed to wood smoke and oil fumes have increased risk of respiratory symptoms and altered pulmonary functions.
Montelukast prophylaxis of oxaliplatin hypersensitivity reactions.
Authors: S. P. Hopkins, N. Yarom, T. R. Asmis, J. A. Maroun, D. J. Jonker, M. M.ickers, M. Cripps, R. Goel, H. Marginean
Journal: Journal of Clinical Oncology (2010)

e14046 Background: Oxaliplatin acute hypersensitivity reactions (HSRs) are typically a Type I reaction, occurring in patients (pts) with second or subsequent exposure, with an incidence of 10–20% and predominantly grade 1–2. Our institution tracks and documents all acute adverse drug HSRs using an NCI CTC 2.0 derived grading form including cardiac, dermatologic, constitutional, and pulmonary domains. A retrospective review of oxaliplatin HSRs was undertaken to access severity and outcomes depending treatment of the HSR “traditional” (corticosteroids and antihistamines) versus the LTD4 inhibitor, montelukast. Methods: All oxaliplatin related HSRs reported, since form implementation in 2002, were reviewed to determine cycle number and outcome (stopped oxaliplatin for HSR vs completed therapy to alternate endpoint). Results: 75 pts had 101 oxaliplatin HSRs. Pts were treated for metastatic disease (40 pts) or adjuvantly (35 pts). HSRs were grade 1 (42%), gr 2 (28%), gr 3 (27%) and gr 4 (3%). Dyspnea and hypoxia were the primary grade 3 and 4 symptoms. The first HSR occurred in median cycle 8 (range cycle 1–26). Timing of first HSR was similar for metastatic vs. adjuvant pts. Post-HSR, pts received a mean of 2.1 additional cycles of oxaliplatin. Montelukast-treated pts received 3.6 cycles on average vs. 1.93 cycles with traditional premedication. Of the 35 adjuvant pts, oxaliplatin was discontinued by 15 and completed by 20 (average 4.2 cycles of oxaliplatin post HSR). Of the 40 metastatic pts, 22 pts discontinued oxaliplatin due to HSR, while 18 stopped due to progressive disease or neuropathy. Of five pts receiving montelukast secondary prophylaxis (2 adjuvant, 3 metastatic), none stopped therapy due to further HSRs; both adjuvant pts completed therapy (12 cycles), 2 metastatic pts progressed (2 and 8 cycles later) while a third pt completed 3 more cycles then initiated targeted maintenance therapy. All pts treated with montelukast reported subjective improvement in their symptoms of HSR with subsequent oxaliplatin. None of the pts were retreated with a formal desensitization regimen. Conclusions: Montelukast may prevent early discontinuation of oxaliplatin following HSRs without a desensitization regimen. Further study in secondary prophylaxis is warranted. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Merck, sanofi-aventis sanofi-aventis
Cloning and gene map assignment of the Xiphophorus DNA ligase 1 gene.
Authors: R B Walter, R L Rolig, K A Kozak, B McEntire, D C Morizot, R S Nairn
Journal: Molecular Biology and Evolution (1993)

Fishes represent the stem vertebrate condition and have maintained several gene arrangements common to mammalian genomes throughout the 450 Myr of divergence from a common ancestor. One such syntenic arrangement includes the GPI-PEPD enzyme association on Xiphophorus linkage group IV and human chromosome 19. Previously we assigned the Xiphophorus homologue of the human ERCC2 gene to linkage group U5 in tight association with the CKM locus. CKM is also tightly linked to the ERCC2 locus on human chromosome 19, leading to speculation that human chromosome 19 may have arisen by fusion of two ancestral linkage groups which have been maintained in fishes. To investigate this hypothesis further, we isolated and sequenced Xiphophorus fish genomic regions exhibiting considerable sequence similarity to the human DNA ligase 1 amino acid sequence. Comparison of the fish DNA ligase sequence with those of other species suggests several modes of amino acid conservation in this gene. A 2.2-kb restriction fragment containing part of an X. maculatus DNA ligase 1 exon was used in backcross hybrid mapping with 12 enzyme or RFLP loci. Significant linkage was observed between the nucleoside phosphorylase (NP2) and the DNA ligase (LIG1) loci on Xiphophorus linkage group VI. This assignment suggests that the association of four DNA repair-related genes on human chromosome 19 may be the result of chance chromosomal rearrangements.
Intra-Operative Parathyroid Hormone Assay for Simplified Localization of Parathyroid Adenomas
Authors: M Saharay, A Farooqui, S Farrow, M Fahie-Wilson, A Brown
Journal: Journal of the Royal Society of Medicine (1996)

Lack of success in parathyroid surgery is usually due to failure to identify the abnormal parathyroid gland correctly at operation. The surgeon may be helped by rapid parathyroid hormone (PTH) assay in peripheral blood after removal of a suspected adenoma, and by frozen section histology, but these are not true localization techniques. We have adapted a non-isotopic immunoassay for rapid measurement of PTH in samples from the upper, middle and lower thyroid veins taken at operation, before exploration begins. Fifteen patients with primary hyperparathyroidism were operated on. In 10 the parathyroid adenoma was located easily, and was associated with high local venous PTH levels. In four patients the abnormal parathyroid was not immediately apparent but the assay indicated its location, which was confirmed after further exploration. In one patient there was no difference in PTH levels in the six venous samples. An ectopic adenomatous gland was successfully identified behind the thymus. The operation was successful in all patients as shown by a fall in the plasma calcium to the normal range. We conclude that intra-operative selective venous sampling and rapid PTH assay facilitates operative localization of parathyroid adenomas.
Circadian Rhythm of Intestinal Sucrase Activity in Rats
Authors: Mark A. Kaufman, Helen A. Korsmo, Ward A. Olsen
Journal: Journal of Clinical Investigation (1980)

Past investigation has revealed that the circadian rhythm of intestinal sucrase activity in rats is primarily cued by the time of feeding. We examined the mechanism of the circadian rhythm by methods involving quantitative immunoprecipitation of sucrase-isomaltase protein and study of decay of radioactively labeled protein. Rats were placed on a controlled feeding regimen (1000-1500 h) and then sacrificed at 3-h intervals over a 24-h period. Immunotitration experiments indicated that the circadian rhythm was the result of changes in the absolute amount of sucrase-isomaltase protein present and not of changes in the enzyme's catalytic efficiency.
Concept and design of a genome-wide association genotyping array tailored for transplantation-specific studies
Authors: Yun R. Li, Jessica van Setten, Shefali S. Verma, Yontao Lu, Michael V. Holmes, Hui Gao, Monkol Lek, Nikhil Nair, Hareesh Chandrupatla, Baoli Chang, Konrad J. Karczewski, Chanel Wong, Maede Mohebnasab, Eyas Mukhtar, Randy Phillips, Vinicius Tragante, Cuiping Hou, Laura Steel, Takesha Lee, James Garifallou, Toumy Guettouche, Hongzhi Cao, Weihua Guan, Aubree Himes, Jacob van Houten, Andrew Pasquier, Reina Yu, Elena Carrigan, Michael B. Miller, David Schladt, Abdullah Akdere, Ana Gonzalez, Kelsey M. Llyod, Daniel McGinn, Abhinav Gangasani, Zach Michaud, Abigail Colasacco, James Snyder, Kelly Thomas, Tiancheng Wang, Baolin Wu, Alhusain J. Alzahrani, Amein K. Al-Ali, Fahad A. Al-Muhanna, Abdullah M. Al-Rubaish, Samir Al-Mueilo, Dimitri S. Monos, Barbara Murphy, Kim M. Olthoff, Cisca Wijmenga, Teresa Webster, Malek Kamoun, Suganthi Balasubramanian, Matthew B. Lanktree, William S. Oetting, Pablo Garcia-Pavia, Daniel G. MacArthur, Paul I W de Bakker, Hakon Hakonarson, Kelly A. Birdwell, Pamala A. Jacobson, Marylyn D. Ritchie, Folkert W. Asselbergs, Ajay K. Israni, Abraham Shaked, Brendan J. Keating
Journal: Genome Medicine (2015)

In addition to HLA genetic incompatibility, non-HLA difference between donor and recipients of transplantation leading to allograft rejection are now becoming evident. We aimed to create a unique genome-wide platform to facilitate genomic research studies in transplant-related studies. We designed a genome-wide genotyping tool based on the most recent human genomic reference datasets, and included customization for known and potentially relevant metabolic and pharmacological loci relevant to transplantation. We describe here the design and implementation of a customized genome-wide genotyping array, the 'TxArray', comprising approximately 782,000 markers with tailored content for deeper capture of variants across HLA, KIR, pharmacogenomic, and metabolic loci important in transplantation. To test concordance and genotyping quality, we genotyped 85 HapMap samples on the array, including eight trios. We show low Mendelian error rates and high concordance rates for HapMap samples (average parent-parent-child heritability of 0.997, and concordance of 0.996). We performed genotype imputation across autosomal regions, masking directly genotyped SNPs to assess imputation accuracy and report an accuracy of >0.962 for directly genotyped SNPs. We demonstrate much higher capture of the natural killer cell immunoglobulin-like receptor (KIR) region versus comparable platforms. Overall, we show that the genotyping quality and coverage of the TxArray is very high when compared to reference samples and to other genome-wide genotyping platforms. We have designed a comprehensive genome-wide genotyping tool which enables accurate association testing and imputation of ungenotyped SNPs, facilitating powerful and cost-effective large-scale genotyping of transplant-related studies.
Effect of Low-Dose-Rate Irradiation on the Division Potential of Cells In Vitro. V. Human Skin Fibroblasts From Donors With a High Risk of Cancer&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;
Authors: C Diatloff, A Macieira-Coelho
Journal: JNCI Journal of the National Cancer Institute (1979)

Skin fibroblasts from normal donors, donors with ataxia-telangiectasia or Fanconi's anemia, and from 1 cancer patient were treated with repeated gamma-radiation at about 16 rads per hour. The remaining division potential of all fibroblasts, except for the Fanconi's anemia cells, was reduced to different extents by radiation. The growth potential of Fanconi's anemia cells was increased in all the irradiated cultures. The increase was 54% in the group that survived the longest. These results were identical to those obtained with fibroblasts from certain species that have a high probability of transformation.
A likelihood approach for comparing synonymous and nonsynonymous nucleotide substitution rates, with application to the chloroplast genome.
Authors: S V Muse, B S Gaut
Journal: Molecular Biology and Evolution (1994)

A model of DNA sequence evolution applicable to coding regions is presented. This represents the first evolutionary model that accounts for dependencies among nucleotides within a codon. The model uses the codon, as opposed to the nucleotide, as the unit of evolution, and is parameterized in terms of synonymous and nonsynonymous nucleotide substitution rates. One of the model's advantages over those used in methods for estimating synonymous and nonsynonymous substitution rates is that it completely corrects for multiple hits at a codon, rather than taking a parsimony approach and considering only pathways of minimum change between homologous codons. Likelihood-ratio versions of the relative-rate test are constructed and applied to data from the complete chloroplast DNA sequences of Oryza sativa, Nicotiana tabacum, and Marchantia polymorpha. Results of these tests confirm previous findings that substitution rates in the chloroplast genome are subject to both lineage-specific and locus-specific effects. Additionally, the new tests suggest tha the rate heterogeneity is due primarily to differences in nonsynonymous substitution rates. Simulations help confirm previous suggestions that silent sites are saturated, leaving no evidence of heterogeneity in synonymous substitution rates.
Acute effects of water-pipe smoking on pulmonary function and cardio-pulmonary exercise capacity in healthy subjects
Authors: Feras Hawari, Hiba Ayub, Nour Obeidat, Iyad Ghonimat, Sahar Dawahrah, Thomas Eissenberg
Journal: European Respiratory Journal (2011)

Background: Waterpipe tobacco smoking (WTS) has gained popularity, but the physiologic effects of WTS have not been extensively studied. Studies that have evaluated the impact of WTS have focused on its chronic effects or have only evaluated limited parameters. In a pilot study, we evaluated the acute effects of WTS on lung function and exercise capacity in water-pipe users. We hypothesized that acute exposure to WTS alters pulmonary function and cardio-pulmonary exercise test (CPET) responses.

Methods: We recruited 15 healthy WTS male subjects (S). We used a single-group pre-test (having abstained from WTS for at least 48 hours before testing) post-test (within half an hour of 45-minute WTS session in a cafe design). We performed spirometry and CPET (cycloergometer; 2-min 20-Watt warm-up and 25-Watt increase every 2-min for 10 min).

Results: Mean age was 21.2 years; average carbon monoxide pre-test was 4.6 ppm and 27.5 ppm post-test; forced expiratory volume in one second (FEV1) decreased in 7/15 S by 0.48 L/sec (9%), forced expiratory flow from 25% to 75% of vital capacity (FEF25-75%) decreased in 11/15 S by 0.65 L/sec (12%). Breathing reserve decreased in 10/15 S by 10.2%; oxygen pulse decreased in 9/15 S by 2.4 mL/beat (19%); 8/15 S could not complete the CPET after WTS (8.29 min average), vs. 6/15 S pre-WTS (8.33 min average); 9/15 S reported greater degree of shortness of breath at mid/peak exercise using Borg scale; among those completing exercise time pre and post (6/15 S), maximum oxygen consumption (VO2max) dropped in 5/6 S.

Conclusion: Acute WTS causes impairment in pulmonary function and CPET ventilatory and cardiovascular responses.