tbuckley/cabot-search huggingface dataset:
Time to abolish QOF
Authors: T. Willis
Journal: BMJ (2009)

Developmental enhancers are essential regulatory elements that drive precise spatio-temporal gene expression patterns. They do so by interacting with the promoter of their target genes, often across large genomic distances, in a highly specific manner. However, it is unclear how such specificity can be achieved. While several studies have suggested that Topologically Associating Domains (TADs)<sup>1–3</sup> facilitate and constrain enhancer-promoter interactions, the role of TAD boundaries in effectively restricting enhancer-promoter interactions is heavily debated. Here we show that enhancers can establish long-range interactions across TAD boundaries and even between different chromosomes. Moreover, some of these interactions are functional <i>in vivo</i>, illustrating their functional importance. Using the <i>twist</i> locus in <i>Drosophila</i> embryos, we systematically relocated one of its enhancers to different regulatory contexts and distances from the <i>twist</i> promoter. We found that the <i>twist</i> promoter can engage in functional enhancer-promoter interactions across a TAD boundary and that distal interactions are sometimes favored over proximal ones. Our results demonstrate that TAD boundaries are not sufficient to constrain enhancer-promoter interactions and that the formation of long-range interactions is not solely driven by distance. These observations suggest that other general mechanisms must exist to establish and maintain specific enhancer-promoter interactions across large distances.
SIDS: genetic and environmental influences may cause arrhythmia in this silent killer
Authors: J. C. Makielski
Journal: Journal of Clinical Investigation (2006)

In this issue of the JCI, Bowers et al. show that the common polymorphism of the cardiac voltage-gated sodium channel, type Vα (SCN5A), designated S1103Y, found in African Americans is associated with an increased risk of sudden infant death syndrome (SIDS). Wild-type and mutant SCN5A channels both functioned typically under normal conditions in vitro, but exposure to acidic intracellular pH levels such as those found in respiratory acidosis — a known risk factor for SIDS — produced abnormal gain-of-function late reopenings of S1103Y channels, behavior that is often associated with cardiac arrhythmias. These pathologic late reopenings were suppressed by low levels of the channel-blocking drug mexiletine. These findings provide an excellent illustration of a causal relationship between the interaction of the environment and genetic background in SIDS and also raise interesting questions about the linkage of a genetic abnormality with a clinical phenotype.
Do inhaled steroids have similar efficacy? A case of bronchial asthma suggesting different efficacy of inhaled glucocorticosteroids
Authors: B. B. Larsen, R. Dahl
Journal: Allergy (1995)

We report a 35‐year‐old woman who had had bronchial asthma for 17 years. Her asthma worsened and became unstable on treatment with beclomethasone dipropionate (BDP), budesonide (BUD), and oral glucocorticosteroids (GC). At the age of 31, she had participated in a clinical trial with fluticasone propionate (FP), and after 2 weeks' treatment her asthma was well controlled. Because of pregnancy, her participation was terminated and treatment continued with available inhaled GC; however, the disease deteriorated and treatment with FP was resumed 2 years ago. Lung function normalized after 3 weeks and she has remained clinically stable since.
THE ORIGIN AND STRUCTURE OF A FIBROUS TISSUE FORMED IN WOUND HEALING
Authors: George A. Baitsell
Journal: The Journal of Experimental Medicine (1916)

1. In experimental wounds, made by removing various sized pieces of skin from the frog, there is a rapid coagulation of the blood plasma and lymph to form a coagulation tissue which fills the wound cavity. 2. The observations on the living animals show that the coagulation a grave intoxication, but a low reading may be observed in some fatal cases and gives no assurance that a fatal intoxication may not supervene. The kidneys in practically all these experiments are normal in all respects. It is possible that protein or tissue destruction rather than impaired eliminative function is responsible for the rise in non-coagulable nitrogen of the blood in these acute intoxications. Transfusions of dextrose solutions often benefit intestinal obstruction, and may depress the level of the non-coagulable nitrogen in the blood. Some cases show no change in non-coagulable nitrogen following transfusions and diuresis, and, as a rule, such cases present the most severe intoxication.
Critical role of transcription factor PU.1 in the expression of CD80 and CD86 on dendritic cells
Authors: Shunsuke Kanada, Chiharu Nishiyama, Nobuhiro Nakano, Ryuyo Suzuki, Keiko Maeda, Mutsuko Hara, Nao Kitamura, Hideoki Ogawa, Ko Okumura
Journal: Blood (2010)
Altered expression of glomerular heat shock protein 27 in experimental nephrotic syndrome.
Authors: W E Smoyer, A Gupta, P Mundel, J D Ballew, M J Welsh
Journal: Journal of Clinical Investigation (1996)

Although nephrotic syndrome is a very common kidney disease, little is known about the molecular changes occurring within glomerular capillary loops during development of disease. The characteristic histologic change is retraction (effacement) of the distal "foot" processes of glomerular epithelial cells (GEC) which surround the capillary loops. The GEC foot processes are an essential part of the kidney's filtration barrier, and their structure is regulated primarily by actin microfilaments, cytoskeletal proteins present in high concentrations in foot processes. Actin polymerization has been reported to be regulated via phosphorylation of the low molecular weight heat shock protein, hsp27. We localized hsp27 within normal rat GECs using immunofluorescence and immunoelectron microscopy. Induction of nephrotic syndrome and GEC foot process effacement using the puromycin aminonucleoside rat model resulted in significant increases in: (a) renal cortical hsp27 mRNA expression (826 +/- 233%, x +/- SEM, P < 0.01 vs. control); (b) glomerular hsp27 protein expression (87 +/- 2%, P < 0.001 vs. control); and (c) glomerular hsp27 phosphorylation (101 +/- 32%, P < 0.05 vs. control). These findings support the hypothesis that hsp27, by regulating GEC foot process actin polymerization, may be important in maintaining normal foot process structure, and regulating pathophysiologic GEC cytoskeletal changes during development of nephrotic syndrome.
PTPRD (protein tyrosine phosphatase receptor type delta) is associated with restless legs syndrome
Authors: Barbara Schormair, David Kemlink, Darina Roeske, Gertrud Eckstein, Lan Xiong, Peter Lichtner, Stephan Ripke, Claudia Trenkwalder, Alexander Zimprich, Karin Stiasny-Kolster, Wolfgang Oertel, Cornelius G Bachmann, Walter Paulus, Birgit Högl, Birgit Frauscher, Viola Gschliesser, Werner Poewe, Ines Peglau, Pavel Vodicka, Jana Vávrová, Karel Sonka, Sona Nevsimalova, Jacques Montplaisir, Gustavo Turecki, Guy Rouleau, Christian Gieger, Thomas Illig, H-Erich Wichmann, Florian Holsboer, Bertram Müller-Myhsok, Thomas Meitinger, Juliane Winkelmann
Journal: Nature Genetics (2008)
SPECKLE TRACKING STRAIN ECHOCARDIOGRAPHY FOR RISK ASSESSMENT OF VENTRICULAR ARRHYTHMIAS AFTER LEFT VENTRICULAR ASSIST DEVICE PLACEMENT
Authors: Ehimare Akhabue, Chan Seok Park, Sean Pinney, Ani Anyanwu, Farooq Chaudhry, Jagat Narula, Ajith Nair, Partho Sengupta
Journal: Journal of the American College of Cardiology (2014)
Trial of strategy for reducing the use of laboratory tests.
Authors: F G Fowkes, R Hall, J H Jones, M F Scanlon, G H Elder, D R Hobbs, A Jacobs, I A Cavill, S Kay
Journal: BMJ (1986)

Clinical guidelines and a weekly review of medical records were introduced into a medical unit in a teaching hospital to promote a more discriminating use of laboratory tests. This strategy resulted in an immediate reduction in the average number of requests each week from 74 to 27 haematological tests (64%) and 158 to 58 biochemical tests (64%). During a period of 10 weeks after the strategy was introduced (the intervention period) the mean number of haematological tests for each person decreased from 2.0 during the baseline period to 1.1 (45% reduction; p less than 0.01) and the mean number of biochemical tests decreased from 4.4 to 2.7 (39%; p less than 0.0001). The decrease in the number of repeat requests was greater than that for new requests and accounted for half the reduction in use. There was no significant change in the number of tests requested from an adjacent medical unit that was not exposed to the interventions. This strategy is worthy of trial in other specialties and hospitals, but attention will have to be paid to possible difficulties in sustaining reductions in use over long periods of time.
Cardiac output and arterial CO2 response during intermittent positive pressure breathing with oxygen: A comparison of patients with chronic airflow obstruction and controls
Authors: P. P. Tulou
Journal: Thorax (1971)

Cardiac output and arterial blood gases were studied before, during, and after intermittent positive pressure breathing, using 40% oxygen (IPPB/O<sub>2</sub>). The subjects of this study were eight patients with lung disease, seven of them with chronic airflow obstruction and eight control subjects without respiratory symptoms. During IPPB/O<sub>2</sub>, cardiac output was definitely lowered without a significant decrease in arterial Pco<sub>2</sub> in the patients with airflow obstruction. Conversely, the control subjects during IPPB/O<sub>2</sub> had a large decrease in arterial Pco<sub>2</sub> with a moderate reduction in cardiac output. Considering this response of the lung with airflow obstruction, the more frequent use of cardiac output and arterial gas measurements in patients receiving IPPB/O<sub>2</sub> treatments appears desirable. Individual cases are presented.
Statistics in Medical Research
Authors: Harold M. Schoolman
Journal: New England Journal of Medicine (1969)

Not long ago medical research was mainly concerned with effects that were so large that statistics were of little relevance. In some cases this is still true, but more and more we are attempting to detect relatively small effects. When it is important to know whether small differences are real we must do an inordinate amount of work, run a high risk of failing to demonstrate an effect or markedly increase the efficiency of our operation.The last 50 years has seen the development of statistics as a powerful tool to increase the efficiency with which we adjudicate the confusion . . .
Risk of breast cancer increases with number of years' smoking
Authors: R. Dobson
Journal: BMJ (2002)

Women who smoke for many years may increase their risk of developing breast cancer. New research shows that for women who had smoked for 40 years or longer, the risk of breast cancer was 60% higher than that of women who had never smoked.

Among those who smoked 20 cigarettes or more a day for 40 years, the increased risk rose to 83%.

“Our findings suggest that smoking of very long duration and high intensity may be associated with increased risk of …
A Maximum Likelihood Method for Analyzing Pseudogene Evolution: Implications for Silent Site Evolution in Humans and Rodents
Authors: Carlos D. Bustamante, Rasmus Nielsen, Daniel L. Hartl
Journal: Molecular Biology and Evolution (2002)

We present a new likelihood method for detecting constrained evolution at synonymous sites and other forms of nonneutral evolution in putative pseudogenes. The model is applicable whenever the DNA sequence is available from a protein-coding functional gene, a pseudogene derived from the protein-coding gene, and an orthologous functional copy of the gene. Two nested likelihood ratio tests are developed to test the hypotheses that (1) the putative pseudogene has equal rates of silent and replacement substitutions; and (2) the rate of synonymous substitution in the functional gene equals the rate of substitution in the pseudogene. The method is applied to a data set containing 74 human processed-pseudogene loci, 25 mouse processed-pseudogene loci, and 22 rat processed-pseudogene loci. Using the informatics resources of the Human Genome Project, we localized 67 of the human-pseudogene pairs in the genome and estimated the GC content of a large surrounding genomic region for each. We find that, for pseudogenes deposited in GC regions similar to those of their paralogs, the assumption of equal rates of silent and replacement site evolution in the pseudogene is upheld; in these cases, the rate of silent site evolution in the functional genes is ∼70% the rate of evolution in the pseudogene. On the other hand, for pseudogenes located in genomic regions of much lower GC than their functional gene, we see a sharp increase in the rate of silent site substitutions, leading to a large rate of rejection for the pseudogene equality likelihood ratio test.
Doctor who acted as witness outside his competence was punished too severely, court rules
Authors: C. Dyer
Journal: BMJ (2014)

A decision to suspend a psychiatrist from the UK medical register for three months for acting outside his competence as an expert witness was “flawed and disproportionate,” the High Court has ruled.

Richard Pool lacked the right qualifications and experience and should not have accepted instructions as an expert witness for the Health Professions Council in deciding whether a paramedic was fit to …
Assessment of central blook volume in cirrhosis by radionusclide angiography: What does it really mean?
Authors: Jens H. Henriksen, Søren Møller, Flemming Bendtsen, Helmer Ring-Larsen, Heine K. Stokholm, Jens Møgelvang, Thorkild I. A. Sørensen, Alexander L. Gerbes, Florence Wong, Peter Liu, Laurence Blendis
Journal: Hepatology (1994)
THE MECHANISM OF ACTION OF 17-HYDROXY-11-DEHYDROCORTICOSTERONE (COMPOUND E) AND OF THE ADRENOCORTICOTROPIC HORMONE IN EXPERIMENTAL HYPERSENSITIVITY IN RABBITS
Authors: Frederick G. Germuth, Jiro Oyama, Barbara Ottinger
Journal: The Journal of Experimental Medicine (1951)

The concurrent administration of compound E at a daily dosage of 2 mg. per kg. to rabbits receiving daily intracutaneous injections of crystalline egg albumin markedly inhibited the development of anaphylactic hypersensitivity of the Arthus type. ACTH, when given at a similar dosage, produced a much less marked effect. Both hormones suppressed circulating antibody and as with the Arthus reaction, the suppression produced by compound E was much greater than that obtained with ACTH. When treatment with compound E was started following sensitization, there was a rapid decline in circulating antibody and, if the pretreatment serum antibody was low, there was also a progressive decrease in skin reactivity, becoming negative after 5 days of treatment. When the pretreatment serum antibody concentration was great, so that by the termination of treatment the antibody concentration was still above the level ordinarily sufficient for a maximal skin response, the Arthus reaction was unaffected by treatment. These considerations as well as the failure of compound E to inhibit the systemic passive Arthus reaction suggest that the inhibitory effect of compound E and ACTH on the development of experimental hypersensitivity results from the hormonal reduction of circulating antibody. Treatment with compound E had no effect on the rate of disappearance of circulating antibody in the passively immunized rabbit. This finding suggests that ACTH and compound E reduce circulating antibody by inhibiting antibody formation rather than by promoting antibody destruction. The question is raised as to whether the marked lymphoid atrophy produced by these hormones may be related to the interference with antibody production.
A cross-species perspective on the selfishness axiom
Authors: Sarah F. Brosnan, Frans B. M. de Waal
Journal: Behavioral and Brain Sciences (2005)

Henrich et al. describe an innovative research program investigating cross-cultural differences in the selfishness axiom (in economic games) in humans, yet humans are not the only species to show such variation. Chimpanzees and capuchin monkeys show signs of deviating from the standard self-interest paradigm in experimental settings by refusing to take foods that are less valuable than those earned by conspecifics, indicating that they, too, may pay attention to relative gains. However, it is less clear whether these species also show the other-regarding preferences seen in humans.
A Method of Sterilising Soft Catheters
Authors: H. T. Herring
Journal: BMJ (1901)

usually found that the smallest boys' urethrae would admit a .6 to 8 lithotrite and a No. 7 cannula.But for a stone over 30 grs. this was slow work.I always tried to pass a full-sized No. 8 lithotrite, and this instrument crushed nearly all the larger stones in boys.In boys over 14 a full-sized lithotrite would generally pass.To be efficient, a lithotrite should have -a large eye in the female blade.In female patients there was no difficulty except that the bladder sometimes refused to retain fluid.A raised pelvis and a finger pressing the meatus upwards helped to obviate -this, and of course greater care was necessary to avoid nipping the vesical wall.LITHOTOMY.I only performed lithotomy when the crushing operation was impossible or inadvisable.Naturally the mortality was higher in proportion-3 out of 36 cases as against 3 out of i6i ecases of lithotrity.Very many of our cases were unfavour- -able from debility, cystitis, malaria, etc.Two of the 6 deaths were only fatal indirectly.One old man contracted bronch- itis, and died a fortnight after lateral lithotomy had been performed for prostatic calculi; and another old man died from diarrhcea some days after I had easily crushed a I5 drachm stone.He also probably caught a chill.The four deaths more directly attributable to the operation were ,chiefly from exhaustion.In fact, all were nearly hopeless before the operation.But I consider the removal of a stone imperative where there is any hope of recovery, and especially in boys.In bad cases we always insist on a period of pre- liminary treatment and rest.Thus many very bad cases are saved.The first of the four was an old man of 70, who succumbed on the third day after lithotrity for a stone weighing 9 drachms.The second was a boy aged 7, with kidney disease.His urine was loaded with albumen, and its specific gravity was only 1007.He died the third day after I removed, by lateral lithotomy, a stone weighing half an ounce.The third was also a case of lithotomy in a small wizened child of 3.He was unfit for operation, but his friends had brought khim a long way, and implored me to operate.The stone was small, but he died next morning from shock.The last case was the lithotrity case in a boy of 31, already mentioned.
Incidence of Breast Cancer With Distant Involvement Among Women in the United States, 1976 to 2009
Authors: Rebecca H. Johnson, Franklin L. Chien, Archie Bleyer
Journal: JAMA (2013)

<h3>Importance</h3>Evidence from the US National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) database suggests that the incidence of advanced breast cancer in young women is increasing.<h3>Objective</h3>To quantify this trend and analyze it as a function of stage at diagnosis, race/ethnicity, residence, and hormone receptor status.<h3>Design, Setting, and Patients</h3>Breast cancer incidence, incidence trends, and survival rates as a function of age and extent of disease at diagnosis were obtained from 3 SEER registries that provide data spanning 1973-2009, 1992-2009, and 2000-2009. SEER defines localized as disease confined to the breast, regional to contiguous and adjacent organ spread (eg, lymph nodes, chest wall), and distant disease to remote metastases (bone, brain, lung, etc).<h3>Main Outcome Measure</h3>Breast cancer incidence trends in the United States.<h3>Results</h3>In the United States, the incidence of breast cancer with distant involvement at diagnosis increased in 25- to 39-year-old women from 1.53 (95% CI, 1.01 to 2.21) per 100 000 in 1976 to 2.90 (95% CI, 2.31 to 3.59) per 100 000 in 2009. This is an absolute difference of 1.37 per 100 000, representing an average compounded increase of 2.07% per year (95% CI, 1.57% to 2.58%; P &lt; .001) over the 34-year interval. No other age group or extent-of-disease subgroup of the same age range had a similar increase. For 25- to 39-year-olds, there was an increased incidence in distant disease among all races and ethnicities evaluated, especially non-Hispanic white and African American, and this occurred in both metropolitan and nonmetropolitan areas. Incidence for women with estrogen receptor–positive subtypes increased more than for women with estrogen receptor–negative subtypes.<h3>Conclusion and Relevance</h3>Based on SEER data, there was a small but statistically significant increase in the incidence of breast cancer with distant involvement in the United States between 1976 and 2009 for women aged 25 to 39 years, without a corresponding increase in older women.
AB0532 Oxidative stress and its related factors in patients with ankylosing spondylitis
Authors: D. Solmaz, D. Kozacı, I. Sari, N. Güney, A. Taylan, F. Onen, N. Akkoc, S. Akar
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Ankylosing spondylitis (AS) is chronic inflammatory disease of the spine and sacroiliac joints with an unknown etiology. In recent years some researchers revealed an increased oxidative stress, which is thought to play an important role in the pathogenesis of some diseases, in AS. However, data regarding this subject is limited and additional studies are required. <h3>Objectives</h3> The primary aim of this study was to investigate oxidative stress and related factors in AS. <h3>Methods</h3> 85 AS patients, diagnosed according to the Modified New York criteria(mean age (36±10 years; 39M/17F) and 56 healthy subjects (36±10 years; 39M/17F) with no known CV risk factors including hypertension (HT), diabetes mellitus (DM), hyperlipidemia, and smoking were included in the study. Serum total oxidant status (TOS) and total anti-oxidant status (TAS) were studied. BASFI, BASDAI and BASMI were calculated. Disease duration and medications were noted. Logistic regression model was used to identify the independent risk factors for TOS. <h3>Results</h3> There were no differences with respect to the age, sex distribution, waist circumferences, glucose, lipid and TAS concentrations between the patient and control groups. On the other hand, serum TOS levels were significantly higher in AS group than the controls (p=0.03). Comparison of active (BASDAI≥4) and inactive AS patients revealed that TOS were significantly higher in the active group (Table). Subgroup analysis of patients with respect to the treatment revealed that TOS and TAS concentrations were not different between patients treated with biologics and conventional agents. Correlation analysis yielded significant correlations between TOS, TAS, BASMI, BASFI, BASDAI, ESR, CRP (p&lt;0.05; r=0.291, r=0.451, r=0.271, r=0.363, r=0.456 and 0.437 respectively) and a positive correlation between TAS and BASMI (p&lt;0.05; r=0.344).). In regression analysis, only BASMI and CRP were independently predicted the TOS levels (P&lt;0.05). <h3>Conclusions</h3> (1) There is an increased oxidative stress in AS patients compared with healthy subjects; (2) Patients with active disease had significantly higher oxidative stress compared with inactive patients and healthy controls; (3) Treatment status seems no effect on TOS; and (4) BASMI and CRP are the independent variables associated with TOS. <h3>Disclosure of Interest</h3> None Declared