tbuckley/cabot-search huggingface dataset:
Human Variation in Short Regions Predisposed to Deep Evolutionary Conservation
Authors: G. G. Loots, I. Ovcharenko
Journal: Molecular Biology and Evolution (2010)

The landscape of the human genome consists of millions of short islands of conservation that are 100% conserved across multiple vertebrate genomes (termed “bricks”), the majority of which are located in noncoding regions. Several hundred thousand bricks are deeply conserved reaching the genomes of amphibians and fish. Deep phylogenetic conservation of noncoding DNA has been reported to be strongly associated with the presence of gene regulatory elements, introducing bricks as a proxy to the functional noncoding landscape of the human genome. Here, we report a significant overrepresentation of bricks in the promoters of transcription factors and developmental genes, where the high level of phylogenetic conservation correlates with an increase in brick overrepresentation. We also found that the presence of a brick dictates a predisposition to evolutionary constraint, with only 0.7% of the amniota brick central nucleotides being diverged within the primate lineage—an 11-fold reduction in the divergence rate compared with random expectation. Human single-nucleotide polymorphism (SNP) data explains only 3% of primate-specific variation in amniota bricks, thus arguing for a widespread fixation of brick mutations within the primate lineage and prior to human radiation. This variation, in turn, might have been utilized as a driving force for primate- and hominoid-specific adaptation. We also discovered a pronounced deviation from the evolutionary predisposition in the human lineage, with over 20-fold increase in the substitution rate at brick SNP sites over expected values. In addition, contrary to typical brick mutations, brick variation commonly encountered in the human population displays limited, if any, signatures of negative selection as measured by the minor allele frequency and population differentiation (F-statistical measure) measures. These observations argue for the plasticity of gene regulatory mechanisms in vertebrates—with evidence of strong purifying selection acting on the gene regulatory landscape of the human genome, where widespread advantageous mutations in putative regulatory elements are likely utilized in functional diversification and adaptation of species.
Educational Epidemiology
Authors: Patricia A. Carney, David W. Nierenberg, Catherine F. Pipas, W. Blair Brooks, Therese A. Stukel, Adam M. Keller
Journal: JAMA (2004)

Conducting educational research in medical schools is challenging partly because interventional controlled research designs are difficult to apply. In addition, strict accreditation requirements and student/faculty concerns about educational inequality reduce the flexibility needed to plan and execute educational experiments. Consequently, there is a paucity of rigorous and generalizable educational research to provide an evidence-guided foundation to support educational effectiveness. "Educational epidemiology," ie, the application across the physician education continuum of observational designs (eg, cross-sectional, longitudinal, cohort, and case-control studies) and randomized experimental designs (eg, randomized controlled trials, randomized crossover designs), could revolutionize the conduct of research in medical education. Furthermore, the creation of a comprehensive national network of educational epidemiologists could enhance collaboration and the development of a strong educational research foundation.
Circulating DNA in systemic lupus erythematosus. Isolation and characterization.
Authors: C R Steinman
Journal: Journal of Clinical Investigation (1984)

Immunoprecipitable double-stranded (dsDNA) was previously shown to persist in the circulation of a clinically recognizable subgroup of patients with systemic lupus erythematosus (SLE). Plasma from 10 such patients was subjected to a DNA isolation procedure that used a combination of proteolysis, phenol extraction, and hydroxylapatite adsorption and elution in the presence of urea. The isolated dsDNA was radiolabeled by nick translation and then characterized by isopyknic ultracentrifugation in CsCl under both neutral and alkaline conditions, as well as after digestion with S1-endonuclease. These experiments demonstrated essential identity in nucleotide base composition between the plasma-derived DNA and human genomic DNA. The presence of specific human base sequences in the plasma DNA was demonstrated by finding that authentic human genomic DNA accelerated the renaturation of plasma DNA when compared with the effect of nonhuman, control DNA. The proportion of such sequences in plasma DNA was estimated by attempting to renature the plasma DNA in the presence of human DNA under conditions shown to result in complete renaturation of human DNA in model experiments. In this way, a minimum of 47% of plasma DNA base sequences could be shown also to be present in human genomic DNA. However, an average of 10-20% of the plasma-derived DNA failed to renature under these conditions, a result that was further confirmed by comparing the renaturation of the tritium-labeled plasma DNA specimens, in double-label experiments, with internal controls consisting of 14C-labeled authentic human DNA. Attempts to drive the reaction to completion with human DNA led to a similar conclusion. The relative nonrenaturability of this fraction of plasma DNA did not appear to be attributable to extensive chain breakage, although adequate analysis of this DNA subfraction was limited by reagent availability. It was therefore concluded that, in this group of SLE patients, persistently circulating DNA consisted largely of base sequences also found in human genomic DNA. The additional presence in plasma of a DNA subfraction that differed in its renaturation behavior from human genomic DNA was recognized, although its significance could not be established with certainty.
Compromised stem cell mobilization following induction therapy with lenalidomide in myeloma
Authors: H Paripati, A K Stewart, S Cabou, A Dueck, V J Zepeda, N Pirooz, C Ehlenbeck, C Reeder, J Slack, J F Leis, J Boesiger, A S Torloni, R Fonseca, P L Bergsagel
Journal: Leukemia (2008)
Acute respiratory failure in intensive care units. FINNALI: a prospective cohort study
Authors: Rita Linko, Marjatta Okkonen, Ville Pettilä, Juha Perttilä, Ilkka Parviainen, Esko Ruokonen, Jyrki Tenhunen, Tero Ala-Kokko, Tero Varpula
Journal: Intensive Care Medicine (2009)
Maryland State Society to Erect Library Building.
Authors: Arthur P. Herring
Journal: JAMA (1907)

Baltimore, Nov. 19, 1907. <h3>To the Editor:</h3> —In the last two issues ofThe Journal, under Medical News from Maryland, have appeared notices concerning the new medical library building which the Medical and Chirurgical Faculty of Maryland contemplates erecting within the next year, and for which it is conducting an active campaign to raise $100,000. The impression has been given that this is to be an Osler memorial building, which is only partially true. The committee in charge of this work deems it advisable to present through your columns the real purpose of this new building. During the winter of 1905, when friends of Dr. Osler learned that he was going to leave this country, they conceived the idea of erecting a building to be known as the "Osler Memorial Building." Funds were collected for this purpose amounting to about $20,000 and then the matter rested for nearly a year.
Hemolytic Phospholipase C Inhibition Protects Lung Function during <i>Pseudomonas aeruginosa</i> Infection
Authors: Matthew J. Wargo, Maegan J. Gross, Sathish Rajamani, Jenna L. Allard, Lennart K. A. Lundblad, Gilman B. Allen, Michael L. Vasil, Laurie W. Leclair, Deborah A. Hogan
Journal: American Journal of Respiratory and Critical Care Medicine (2011)

Rationale: The opportunistic pathogen Pseudomonas aeruginosa causes both acute and chronic lung infections and is particularly problematic in patients with cystic fibrosis and those undergoing mechanical ventilation. Decreased lung function contributes significantly to morbidity and mortality during P. aeruginosa infection, and damage inflicted by P. aeruginosa virulence factors contributes to lung function decline.Objectives: We sought to describe direct contribution of a bacterial phospholipase C/sphingomyelinase, PlcHR, to alteration of host lung physiology and characterize a potential therapeutic for protection of lung function.Methods: We infected C57Bl/6 mice with P. aeruginosa wild-type or isogenic plcHR deletion strains and measured lung function using computer-controlled ventilators. For in vivo testing, miltefosine was delivered intraperitoneally 1 hour after infection. Infection and respiratory endpoints were at 24 hours after infection.Measurements and Main Results: P. aeruginosa wild-type infection caused significant lung function impairment, whereas the effects of a ΔplcHR strain infection were much less severe. Surfactometry analysis of bronchoalveolar lavage fluid indicated that PlcHR decreased pulmonary surfactant function. Miltefosine has structural similarity to the PC and sphingomyelin substrates of PlcHR, and we found that it inhibits the cleavage of these choline-containing lipids in vitro. Miltefosine administration after P. aeruginosa infection limited the negative effects of PlcHR activity on lung function.Conclusions: We have directly linked production of a single virulence factor in P. aeruginosa with effects on lung function, and demonstrated that the inhibitor miltefosine protects lung function from PlcHR-dependent surfactant dysfunction.
Further details of third recorded case of redwater (Babesiosis) in man
Authors: J. E. P. Fitzpatrick, C. C. Kennedy, M. G. McGeown, D. G. Oreopoulos, J. H. Robertson, M. A. Soyannwo
Journal: BMJ (1969)

Clinical details and laboratory and postmortem findings of a human case of redwater (piroplasmosis or babesiosis) caused by Babesia divergens. This is the third proved case in man. All three patients had had splenectomies.
TCT-365 Pregnancy-Induced Disorders Identify High-Risk Women who Benefit from Cardiovascular Screening: Results from the Women's Heart Health Initiative, an OB/GYN Screening Pilot Program
Authors: Jennifer Yu, Jerri Johnson, Kleanthis Theodoropoulos, Sudhir Mungee, Michele Couri, Beth Malasky, Robert Wild, David Dobies, Auroa Badin, Raj Vadde, Samantha Sartori, Nilusha Gukathasan, Ziad Sergie, Usman Baber, Roxana Mehran
Journal: Journal of the American College of Cardiology (2012)
The role of apolipoprotein E and glucose intolerance in gallstone disease in middle aged subjects
Authors: M Niemi, K Kervinen, A Rantala, H Kauma, M Päivänsalo, M J Savolainen, M Lilja, Y A Kesäniemi
Journal: Gut (1999)

BACKGROUND The polymorphism of apolipoprotein E has been suggested to be associated with the cholesterol content of gallstones, the crystallisation rate of gall bladder bile, and the prevalence of gallstone disease (GSD). AIMS To investigate whether apolipoprotein E polymorphism modulates the susceptibility to GSD at the population level and to study the possible associations between impaired glucose tolerance, diabetes, and GSD. METHODS Apolipoprotein E phenotypes were determined in a middle aged cohort of 261 randomly selected hypertensive men, 259 control men, 257 hypertensive women, and 267 control women. All subjects without a documented history of diabetes were submitted to a two hour oral glucose tolerance test (OGTT). GSD was verified by ultrasonography. RESULTS In women with apolipoprotein E2 (phenotypes E2/2, 2/3, and 2/4) compared with women without E2 (E3/3, 4/3, and 4/4), the odds ratio for GSD was 0.28 (95% confidence interval 0.08–0.92). There was no protective effect in men. The relative risk for GSD was 1.2 (0.8–1.7) for hypertensive women and 1.8 (1.0–2.7) for hypertensive men. In a stepwise multiple logistic regression model, E2 protected against GSD in women, whereas two hour blood glucose in the OGTT, serum insulin, and plasma triglycerides were risk factors. Elevated blood glucose during the OGTT was also a significant risk factor for GSD in men. CONCLUSIONS The data suggest that apolipoprotein E2 is a genetic factor providing protection against GSD in women. In contrast, impaired glucose tolerance and frank diabetes are associated with the risk of GSD.
TCT-525 Wound depth assessed by Texas grade affect wound healing in critical limb ischemia after endovascular therapy
Authors: Norihiro Kobayashi, Keisuke Hirano, Masatsugu Nakano, Toshiya Muramatsu, Reiko Tsukahara, Yoshiaki Ito, Hiroshi Ishimori
Journal: Journal of the American College of Cardiology (2014)
The Real Doctor Guillotin
Authors: Dora B. Weiner
Journal: JAMA (1972)

The guillotine, the beheading mechanism widely used in the French Revolution, is familiar to everyone. Yet historians hardly know the real Dr. Guillotin. A recent popular biography is a sensationalist travesty; journals in many languages contain short pieces on the guillotine irrelevant to Dr. Guillotin's life. A scholarly article might be technical and discuss the shape of the deadly blade—it evolved from crescentshaped to diagonal—because the surgeon Antoine Louis demonstrated on sheep that diagonal instruments make neater incisions. Elsewhere an author might discuss whether "life" lingered in the severed head or body, and adduce contemporary evidence that a head managed a prearranged wink at the audience. Or again a writer might explore the reasons why the name "guillotine" stuck to a machine that Guillotin neither invented nor christened. The famous doctor himself has left us no books or articles that might reveal his personality. This may be one reason why
Decreased serum osmolality promotes ductus arteriosus constriction
Authors: Rika Aoki, Utako Yokoyama, Yasuhiro Ichikawa, Masataka Taguri, Shun Kumagaya, Ryo Ishiwata, Chiharu Yanai, Shujiro Fujita, Masanari Umemura, Takayuki Fujita, Satoshi Okumura, Motohiko Sato, Susumu Minamisawa, Toshihide Asou, Munetaka Masuda, Shiho Iwasaki, Shigeru Nishimaki, Kazuo Seki, Shumpei Yokota, Yoshihiro Ishikawa
Journal: Cardiovascular Research (2014)

At birth, dynamic changes occur in serum components and haemodynamics, such as closure of the ductus arteriosus (DA). A previous study demonstrated that, in full-term human neonates, serum osmolality decreased transiently after birth, but recovered over the next few days. However, the significance of this transient decrease in osmolality has never been addressed. The objective of the present study was to examine the role of changes in serum osmolality after birth in DA closure. We found that rats exhibited a similar transient hypoosmolality after birth. Hypotonic stimulation induced constriction of DA rings and increased Ca2+ transient in DA smooth muscle cells, but not in the aorta. The hypoosmotic sensor transient receptor potential melastatin 3 (TRPM3) was highly expressed in the rat DA, and TRPM3 silencing abolished the Ca2+ response to hypoosmolality. Pregnenolone sulfate stimulation of TRPM3 induced rat DA constriction ex vivo and in vivo. Furthermore, hypertonic fluid injection impaired rat DA closure. In humans, neonatal serum hypoosmolality was observed in relatively mature preterm infants (≥28 weeks). In extremely preterm infants (<28 weeks), however, this hypoosmolality was absent. Instead, a rapid increase in osmolality occurred thereafter. Such an increase was greater, in particular, among patent DA (PDA) patients. A transient decrease in serum osmolality may promote DA closure during the first few days of life. Adjusting serum osmolality to proper levels might help to prevent the onset of PDA, improving the therapeutic outcome in extremely preterm infants.
On the Diagnosis of Chronic Ovarian Tumours
Authors: E. J. Tilt
Journal: BMJ (1852)

CHRONIC OVARIAN TUMOURS.555 ,unu iL nave just alluded.As the patient improves, the vapour-bath must be used, and the iodide of iron given.There may be many other syphilitic symptoms present, with the pustular disease of the skin and its consequences.Pustules are commonly complicated with tubercles, tophi, and almost always in advanced forms, with pains or diseases in the bones.Such states, of course, require modifications in the treatment suited to the exigencies of each particular case.
Challenges of Making Music: What Causes Musician’s Dystonia?
Authors: Alexander Schmidt, Hans-Christian Jabusch, Eckart Altenmüller, Meike Kasten, Christine Klein
Journal: JAMA Neurology (2013)

Musician's dystonia, a task-specific movement disorder, affects 1% to 2% of professional musicians and is thought to be environmentally acquired, related to years of practice. 1,2Indeed, professional musicians will have spent more than 10 000 hours on the instrument by the age of 20 years. 3 Recently, a clustering of different types of dystonia was reported in the families of patients with musician's dystonia, suggesting also a genetic contribution to the disease. 4 However, the underlying molecular genetic factors are currently unknown.We here investigated in a case-control design whether intensive practice or other environmental factors are associated with musician's dystonia in combination with genetic susceptibility.Increased practice, No. (%) [95% CI] 33 (30) [22-39] 73 (74) [64-81] 16 (26) [17-39] Abbreviations: HFM, healthy family member (of patients with musician's dystonia); IMMM, Institute of Music Physiology and Musicians' Medicine; MHD, musician's hand dystonia; NA, not applicable.a 2-sided χ 2 test, P = .004.b 2-sided χ 2 test, P < .001.c For the 9 musicians.d 2-sided t test, P < .001.
Mercurialism
Authors: Cesar A. Cáceres, John C. Stauffer
Journal: New England Journal of Medicine (1955)

THE many years of clinical experience with mercurial diuretics have established these drugs as effective and relatively nontoxic.Although the literature contains many reports of toxicity from parenteral administration of mercurial medication there are few reports of toxicity resulting from the use of mercurial diuretics given by mouth. Batterman, DeGraff and Shorr1 described early mercurialism in 3 patients using mercurophylline (Mercupurin) § by mouth. This was manifested by gastrointestinal symptoms and increasing albuminuria. One of these patients had severe gingivitis and an elevation of blood nonprotein nitrogen to 52 mg. per 100 cc. A fourth patient showed an elevation of nonprotein . . .
Pulmonary Mycobacterium kansasii infection: comparison of the clinical features, treatment and outcome with pulmonary tuberculosis.
Authors: S. A. Evans, A. Colville, A. J. Evans, A. J. Crisp, I. D. Johnston
Journal: Thorax (1996)

BACKGROUND: In the United Kingdom Mycobacterium kansasii is the most common pulmonary non-tuberculous mycobacteria to cause disease in the non-HIV positive population. METHODS: The clinical features, treatment, and outcome of 47 patients (13 women) of mean (SD) age 58 (17) years with culture positive pulmonary M kansasii infection were compared with those of 87 patients (23 women) of mean (SD) age 57 (16) years with culture positive pulmonary M tuberculosis infection by review of their clinical and laboratory records. Each patient with M kansasii infection was matched for age, sex, race and, where possible, year of diagnosis with two patients with M tuberculosis infection. RESULTS: All those with M kansasii infection were of white race. Haemoptysis was more common in patients infected with M kansasii but they were less likely to present as a result of an incidental chest radiograph or symptoms other than those due to mycobacterial infection. Patients with M kansasii were also less likely to have a history of diabetes, but the frequency of previous chest disease and tuberculosis was similar. An alcohol intake of &gt; 14 units/week was less frequent in those with M kansasii, but there were no significant differences in drug history, past and present smoking habit, occupational exposures, social class, or marital status. Patients with M kansasii received a longer total course of antimycobacterial therapy and, in particular, extended treatment with ethambutol and rifampicin was given. There was no significant difference in outcome between pulmonary M kansasii or M tuberculosis infection. CONCLUSIONS: There are group differences between the clinical features of the two infections but, with the possible exception of diabetes and alcohol intake, these features are unlikely to be diagnostically helpful. Treatment of M kansasii infection with ethambutol, isoniazid, and rifampicin in these patients was as effective as standard regimens given to patients infected with M tuberculosis.
Transmission of Tuberculosis in a Jail
Authors: Timothy F. Jones, Allen S. Craig, Sarah E. Valway, Charles L. Woodley, William Schaffner
Journal: Annals of Internal Medicine (1999)

Outbreaks of tuberculosis are uncommonly recognized in jails. In 1996, an increase in active tuberculosis cases was noted among inmates of a large urban jail.To determine the source and extent of a tuberculosis outbreak in an urban jail and to recommend control measures.Retrospective cohort study.Urban jail.Inmates and guards with tuberculosis.Outbreak evaluation and control.Medical records of inmates and guards with tuberculosis were reviewed, and inmates were interviewed. DNA fingerprinting was performed on Mycobacterium tuberculosis isolates.From 1 January 1995 through 31 December 1997, active tuberculosis was diagnosed in 38 inmates and 5 guards from the jail. Nineteen (79%) of the 24 culture-positive inmates had isolates with DNA fingerprints matching those of other inmates. Isolates from both culture-positive guards matched the predominant inmate strain; only 6 (14%) of 43 isolates from infected persons in the community had this pattern. The median length of incarceration of all inmates in the jail was 1 day; the median length of continuous incarceration before diagnosis of tuberculosis in inmates was 138 days. Inmates with tuberculosis had been incarcerated a median of 15 times. Forty-three percent of persons in this city with tuberculosis diagnosed from January 1995 through July 1997 had been incarcerated in the jail at some time before diagnosis.Traditional and molecular epidemiologic investigations suggest that tuberculosis was transmitted among inmates and guards in an urban jail. Aggressive measures to screen for active tuberculosis upon incarceration are important for preventing spread of disease in jails and to the surrounding community.
First secondary case of Ebola outside Africa: epidemiological characteristics and contact monitoring, Spain, September to November 2014
Authors: M A Lópaz, C Amela, M Ordobas, M F Domínguez-Berjón, C Álvarez, M Martínez, M J Sierra, F Simon, J M Jansá, D Plachouras, J Astray, Collective Working group of Ebola outbreak investigation team of Madrid
Journal: Eurosurveillance (2015)

On 6 October 2014, a case of Ebola virus disease (EVD) acquired outside Africa was detected in Madrid in a healthcare worker who had attended to a repatriated Spanish missionary and used proper personal protective equipment. The patient presented with fever <38.6 °C without other EVD-compatible symptoms in the days before diagnosis. No case of EVD was identified in the 232 contacts investigated. The experience has led to the modification of national protocols.
Germany passes law to attract doctors to rural areas
Authors: A. Tuffs
Journal: BMJ (2011)

The German coalition government has enacted legislation to incentivise young doctors to take over general practices and specialist clinics in rural areas, where the doctor to patient ratio has been steadily falling, while the numbers of elderly people have been rising.

But the opposition parties and health insurance companies claim that the incentive scheme will never work as long as there are no financial disincentives for taking over practices in urban areas where the number of doctors is already high.

The new law allows doctors practising in rural areas to be given a per patient financial incentive …