tbuckley/cabot-search huggingface dataset:
Points: Emergencies at sea
Authors: A. G Jones
Journal: BMJ (1985)

<h3>ABSTRACT</h3> We have developed and used high-time-resolution, single-molecule field-effect transistors (smFETs) to characterize the conformational free-energy landscape of RNA stem-loops. Stem-loops are some of the most common RNA structural motifs and serve as building blocks for the formation of more complex RNA structures. Given their prevalence and integral role in RNA folding, the kinetics of stem-loop (un)folding has been extensively characterized using both experimental and computational approaches. Interestingly, these studies have reported vastly disparate timescales of (un)folding, which has been recently interpreted as evidence that (un)folding of even simple stem-loops occurs on a highly rugged conformational energy landscape. Because smFETs do not rely on fluorophore reporters of conformation or on the application of mechanical (un)folding forces, they provide a unique and complementary approach that has allowed us to directly monitor tens of thousands of (un)folding events of individual stem-loops at a 200 μs time resolution. Our results show that under our experimental conditions, stem-loops fold and unfold over a 1-200 ms timescale during which they transition between ensembles of unfolded and folded conformations, the latter of which is composed of at least two sub-populations. The 1-200 ms timescale of (un)folding we observe here indicates that smFETs report on complete (un)folding trajectories in which relatively extended unfolded conformations of the RNA spend long periods of time wandering the free-energy landscape before sampling one of several misfolded conformations or, alternatively, the natively folded conformation. Our findings demonstrate how the combination of single-molecule sensitivity and high time resolution makes smFETs unique and powerful tools for characterizing the conformational free-energy landscape of RNA and highlight the extremely rugged landscape on which even the simplest RNA structural elements fold.
223. Proteomic Analysis of the Striatum of Wild Type and HPRT-Deficient Mouse
Authors: Ling T. Guo, Charles C. King, Shaochun Song, Theodore Friedmann
Journal: Molecular Therapy (2006)

The enzyme hypoxanthine-guanine phosphoribosyltransferase (HPRT) catalyzes the conversion of hypoxanthine and guanine to ionosine monophosphate and guanosine monophosphate in the purine salvage pathway. Mutations in HPRT gene cause Lesch-Nyhan disease (LND) in human, a central nervous system (CNS) disorder characterized by hyperuricemia, mental retardation, a severe movement disorder and compulsive self-mutilatory behavior. On a molecular level, LND is characterized by severe deficiency of the neurotransmitter dopamine in the basal ganglia.
Incidence and duration of neck pain among patients injured in car accidents.
Authors: G T Deans, J N McGalliard, W H Rutherford
Journal: BMJ (1986)

Resultats d'un questionnaire envoye a toutes les victimes d'accidents hospitalises dans un centre en 1982-83. Les douleurs cervicales sont frequentes apres les traumatismes de toutes orientations, et plus frequentes apres collision. La frequence des douleurs cervicales est augmentee depuis l'obligation legale de la ceinture de securite. L'appuie-tete en haut du dossier peut reduire les degâts par choc d'avant en arriere, pas ceux par choc d'arriere en avant
A PLEA FOR CONSERVATIVE OPERATIONS ON THE OVARIESFROM A NEUROTIC STANDPOINT, WITH REPORT OF CASES.
Authors: JAMES W. COKENOWER
Journal: JAMA (1904)

The subject of ovarian neurosis is one of the most difficult the gynecologist has to deal with to-day, because of his inability to fix a standard from which to determine the beginning of surgical treatment. Hence the question is of diagnosis rather than of surgery, and the thing to decide is whether the woman's symptoms arise directly or indirectly from pelvic disease. This decided, the treatment is simplified, but should the pelvic disease not enter into the case further than one of many other factors, then it is not a surgical case, and should be treated accordingly; and it is this very factor which complicates the subject and has given discredit to legitimate surgery and brought to view the shining light of the operator, while the conscientious surgeon prevents damage to the patient and injury to his profession. It is my purpose to emphasize the importance of a better knowledge
How Squirrels Become Eunuchs.
Authors: C. E. Marlette
Journal: JAMA (1898)

Hayneville, Ala., Feb. 10, 1898. <h3>To the Editor:</h3> —In theJournal(Feb. 5,1898) I read a communication from Dr. Eugene S. Talbot on the subject "Do Adult Squirrels Castrate Each Other?" Castrated Squirrels are frequently killed in this country, and the supposition is almost universal that the operation is done through motives of jealousy in desperate combats. This is one of the zoölogical fictions belonging in the same category with the horsehair snake. The missing testicles have been destroyed by a parasitic worm peculiar to those organs of the<i>sciuri</i>family. Yours,
Implications of Methadone Maintenance for Theories of Narcotic Addiction
Authors: Vincent P. Dole
Journal: JAMA (1988)

Clinical success in rehabilitation of heroin addicts with maintenance treatment requires stability of the blood level in a pharmacologically effective range (optimally, 150 to 600 ng/mL)-a phenomenon that emphasizes the central importance of narcotic receptor occupation. It is postulated that the high rate of relapse of addicts after detoxification from heroin use is due to persistent derangement of the endogenous ligand-narcotic receptor system and that methadone in an adequate daily dose compensates for this defect. Some patients with long histories of heroin use and subsequent rehabilitation on a maintenance program do well when the treatment is terminated. The majority, unfortunately, experience a return of symptoms after maintenance is stopped. The treatment, therefore, is corrective but not curative for severely addicted persons. A major challenge for future research is to identify the specific defect in receptor function and to repair it. Meanwhile, methadone maintenance provides a safe and effective way to normalize the function of otherwise intractable narcotic addicts.
Taxing Private Hospitals.
Authors: J. E. Tuckerman
Journal: JAMA (1907)

Cleveland, Ohio, Aug. 15, 1907. <h3>To the Editor:</h3> —InThe Journal, July 27, 1907, the matter of taxing private charitable institutions is discussed. The view there taken is a mistaken one. Public support given private institutions, no matter for what purpose organized, whether religious, charitable or otherwise, is unsafe, as it tends to foster the unjust taxation systems under which we labor. Exactly as I am glad to see half rates withdrawn from ministers of the gospel, so I would be happy to find all land or monopoly values (they amount in last essence to the same thing) taxed on their actual social value and that regardless of what use put to (except in the case of state institutions, where the reason for not taxing is self-evident, clear cut and incapable of misapplication). Human nature being such that men will support the system which is easy on them, i. e.,
Caffeine for Preemies
Authors: Joan Stephenson
Journal: JAMA (2007)

Caffeine therapy for apnea due to prematurity improves the survival rate of infants with very low birth weight without adverse effects on their neurodevelopment, according to findings by researchers from Canada, Australia, and England (Schmidt B et al. N Engl J Med. 2007;357[19]:1832-1902).
Laser Action at the Cellular Level
Authors: Leon Goldman
Journal: JAMA (1966)

During the past six years the new and exciting form of light energy which is generated by the laser has undergone preliminary studies as a potential tool of the physician, biologist, and biophysicist. As occurred in the early investigations of the biological uses of x-radiation and nuclear radiation, a multidisciplined approach was required, and consequently the cooperative efforts of biologists, physicians, physicists, and research engineers have been required in the evaluation of biological applications of the laser beam. It was initially evident that the unique properties of the laser beam, namely its high degree of coherence and monochromaticity, would permit the light energy to be delivered into areas which were in the order of a few microns in diameter. This interesting possibility encouraged the coupling of such standard optical devices as the microscope with the laser for the investigation of laser reactions at the cellular level. The laser systems that
Selecting medical students
Authors: Celia A Brown, Richard J Lilford
Journal: BMJ (2008)

Tests of cognitive ability are probably the best method at present

The selection of the doctors of tomorrow is a subject of constant interest because it raises questions about ensuring equity, predicting human behaviour, and defining the characteristics of a good doctor. In the United Kingdom, it costs about £200 000 (€260 000; $400 000) to train each medical student, but the cost of getting the selection wrong is much greater.

Selection takes place under considerable time pressure—in the UK around 19 000 applicants must be screened for some 8000 places in less than six months, and each applicant may apply to four medical schools. The selection ratio in the United States is remarkably similar—around 42% of 42 000 applicants were successful in 2007, although each student made an average of 13 applications. 

Different specialties have different requirements, but from our reading of the literature we distil three broad attributes that doctors should have—cognitive ability (including linguistic and mathematical intelligence, problem solving capacity and memory); humanity (kindness, empathy, emotional intelligence, bedside manner and …
Identification of pathways directly regulated by SHORT VEGETATIVE PHASE during vegetative and reproductive development in Arabidopsis
Authors: Veronica Gregis, Fernando Andrés, Alice Sessa, Rosalinda F Guerra, Sara Simonini, Julieta L Mateos, Stefano Torti, Federico Zambelli, Gian Marco Prazzoli, Katrine N Bjerkan, Paul E Grini, Giulio Pavesi, Lucia Colombo, George Coupland, Martin M Kater
Journal: Genome biology (2013)

Abstract Background MADS-domain transcription factors play important roles during plant development. The Arabidopsis MADS-box gene SHORT VEGETATIVE PHASE ( SVP ) is a key regulator of two developmental phases. It functions as a repressor of the floral transition during the vegetative phase and later it contributes to the specification of floral meristems. How these distinct activities are conferred by a single transcription factor is unclear, but interactions with other MADS domain proteins which specify binding to different genomic regions is likely one mechanism. Results To compare the genome-wide DNA binding profile of SVP during vegetative and reproductive development we performed ChIP-seq analyses. These ChIP-seq data were combined with tiling array expression analysis, induction experiments and qRT-PCR to identify biologically relevant binding sites. In addition, we compared genome-wide target genes of SVP with those published for the MADS domain transcription factors FLC and AP1, which interact with SVP during the vegetative and reproductive phases, respectively. Conclusions Our analyses resulted in the identification of pathways that are regulated by SVP including those controlling meristem development during vegetative growth and flower development whereas floral transition pathways and hormonal signaling were regulated predominantly during the vegetative phase. Thus, SVP regulates many developmental pathways, some of which are common to both of its developmental roles whereas others are specific to only one of them.
Hypocalcemia in Rhabdomyolysis-Reply
Authors: Bart Chernow
Journal: JAMA (1987)

<h3>In Reply.—</h3> We thank Dr Davis for his letter related to hypocalcemia and rhabdomyolysis. Our review of hypocalcemia in critical illness did not specifically discuss rhabdomyolysis. Hypocalcemia is common during the early phase of rhabdomyolysis, especially when renal failure occurs. Early hypocalcemia is frequently followed by transient hypercalcemia during the diuretic phase of rhabdomyolysis-induced acute renal failure.<sup>1-3</sup> Early observations in soldiers with massive injury and rhabdomyolysis suggested that hypocalcemia varied with both hyperphosphatemia and the extent of tissue injury. Subsequent studies by Meroney et al<sup>4</sup>showed that calcium salts could be deposited in traumatized muscle at rates sufficient to cause hypocalcemia. The hypocalcemia that occurs in patients with rhabdomyolysis appears to result from multiple factors. Calcium binding or accumulation in damaged muscle is known to occur. However, whether this process alone can account for the hypocalcemia remains unclear. The body is capable of mobilizing calcium from tissue stores
Discovery of New Membrane-Associated Proteins Overexpressed in Small-Cell Lung Cancer
Authors: Sebahat Ocak, David B. Friedman, Heidi Chen, Jamie A. Ausborn, Mohamed Hassanein, Bruno Detry, Birgit Weynand, Frank Aboubakar, Charles Pilette, Yves Sibille, Pierre P. Massion
Journal: Journal of Thoracic Oncology (2014)
A REPORT OF A CASE OF THROMBOSIS OF THE INFERIOR VENA CAVA
Authors: THOMAS WILLETT
Journal: JAMA (1913)

The report of the following single case seems warranted on account of the infrequency of ante-mortem diagnosis, and because of the favorable outcome through the establishment of collateral circulation. We claim no credit whatever for the recovery course, and very little for the diagnosis, which we realize was the result of unusually favorable circumstances:  Patient.  —A woman, American-born, aged 30, weighing about 125 pounds, and presenting a somewhat under-nourished and anemic appearnce. Family history good.  History.  —No infectious or chronic diseases are reported, and no vaginal discharge, swelling of legs, or ascites up to the last pregnancy. Menses began at 14 and are of the regular twenty-eight-day type. Patient has four living children, the youngest born Dec. 20, 1912, and has had two miscarriages; one a pregnancy of a month's duration, between the second and third child, the other of three months' duration, between the third and the last.
Beckwith-Wiedemann syndrome: imprinting in clusters revisited
Authors: Eamonn R. Maher, Wolf Reik
Journal: Journal of Clinical Investigation (2000)

Genomic imprinting, a process that causes genes to be expressed according to their parental origin, affects a minority of human genes, probably less than 1,000. Nevertheless, this class of epigenetic modification acts on many genes with critical roles in growth and development, and disordered imprinting is implicated in genetic disease and in many cancers. Various theories have been proposed to explain the evolution of imprinting in mammals. The most popular is the Haig parental conflict model, which holds that imprinting evolved as a result of opposing interests of the maternal and paternal genomes. Thus, in polygamous species, paternally derived genes will favor fetal growth at the expense of depleting maternal resources and disadvantaging further offspring. In contrast, the maternal genes will oppose the paternal effect and conserve resources to ensure the fitness of the mother and future offspring. This model predicts that although paternally expressed imprinted genes should promote growth, maternally expressed genes should have opposite effects. Many, but not all, imprinted genes identified to date conform to these predictions (1).

The mechanisms by which imprinting is established and maintained are the subject of intense investigation (2). The process must involve a reversible epigenetic marking, and a number of features of imprinted genes have been described. Thus, differential methylation of maternal and paternal alleles is a major characteristic of imprinted genes, and defects in methylation processes (e.g., methyltransferase deficiency) disrupt normal genomic imprinting. Parental allele-specific alterations in the chromosome environment of imprinted genes are revealed by the presence of asynchronous DNA replication and differences in chromatin structure and modification (e.g., histone acetylation).

A striking feature of imprinted genes in mammals is their tendency to cluster in the genome. The arrangement of coordinately or oppositely imprinted genes within a cluster offers insights into the mechanisms by which cells establish and maintain appropriate imprints on functionally related genes. Here, we discuss the organization and function of a major imprinted gene cluster, occurring on human chromosome 11p15.5, that has been implicated in the imprinting disorder Beckwith-Wiedemann syndrome (BWS) and in a variety of human cancers including Wilms’ tumor (3, 4). Because the regulation of imprinted genes in the homologous region in the mouse (distal region of chromosome 7) is broadly conserved between mice and humans, experiments in mice have complemented molecular analyses of BWS pathology and have contributed greatly to our current knowledge of mammalian genomic imprinting mechanisms. In this review, we consider the mechanisms and role of genomic imprinting in human development and in BWS pathogenesis, drawing on research on the human and the mouse clusters of imprinted genes.
Multifocal Extra-Adrenal Paraganglioma Evaluated With Different PET Tracers
Authors: Giorgio Treglia, Giuseppe Cardillo, Antonella Stefanelli, Davide Di Franco, Gerard Ngome Enang, Alessandro Giordano, Vittoria Rufini
Journal: Clinical Nuclear Medicine (2013)

A 40-year-old female patient with suspected multifocal extra-adrenal paraganglioma, on the basis of biochemical, genetic, and conventional imaging data, underwent 18F-FDG, 18F-DOPA and 68Ga DOTANOC PET/CT. FDOPA- and FDG-PET/CT detected a multifocal mediastinal and cervical paraganglioma. 68Ga-DOTANOC PET/CT detected 2 additional lesions compared to the other PET/CT methods. In our case, somatostatin receptor PET/CT with 68Ga-DOTANOC correctly assessed the extent of the disease in a patient with multifocal paraganglioma.
Laceration of the lung following blunt trauma
Authors: K. Moghissi
Journal: Thorax (1971)

Laceration of the lung was found in 4·4% of cases of chest injury caused by blunt trauma admitted to two thoracic centres. Criteria for accurate diagnosis are presented. It is suggested that thoracotomy should be considered and carried out as soon as possible when the diagnosis is made. It was found that cases treated with early thoracotomy did not require any pulmonary resection. In others, lack of prompt diagnosis and a conservative approach led eventually to loss of lung parenchyma.
Experts Hold Hope for Obesity Treatments Targeted to Specific Regulatory Miscues
Authors: Chris Anne Raymond
Journal: JAMA (1986)

"THE TREATMENT of obesity remains a puzzling challenge," says Bernard Guy-Grand, MD, of the Hôtel-Dieu de Paris (hospital), France. Furthermore, physicians "must expect failure" when they administer treatments "without understanding the [specific defect in] physiology underlying the problem." Guy-Grand's comments reflect some of the frustration felt by clinicians who try to help their patients lose weight, only to see anywhere from 75% to 95% of them regain the lost pounds (see Bray GA (ed):<i>Obesity in America</i>. US Dept of Health, Education and Welfare, 1979.) They also suggest a feeling among obesity specialists that perhaps some new approaches to treatment are in order. William Bennett, MD, editor of the<i>Harvard Medical School Health Letter</i>, Boston, thinks that "we ought to abandon a cure model for obesity in favor of a rehabilitation model. [This would focus] not on improving weight, but on the composition of the diet, changing lipid levels, etc."
Repeated Hyperventilation Causes Peripheral Airways Inflammation, Hyperreactivity, and Impaired Bronchodilation in Dogs
Authors: MICHAEL S. DAVIS, ARTHUR N. FREED
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

Winter athletes have an increased incidence of asthma, suggesting that repetitive hyperventilation with cold air may predispose individuals to airways disease. We used a canine model of exercise-induced hyperpnea to examine the effects of repeated hyperventilation with cool, dry air (i.e., dry air challenge [DAC]) on peripheral airway resistance (Rp), reactivity, and inflammation. Specific bronchi were exposed to a single DAC on five consecutive days. Rp and Δ Rp to aerosolized histamine, intravenous histamine, or hypocapnia were measured daily. Bronchoalveolar lavage fluid (BALF) was obtained on the fifth day. Rp increased from 0.70 ± 0.08 to 1.13 ± 0.22 cm H2O/ml/s (n = 25) 24 h after the first DAC, rose to 1.49 ± 0.24 cm H2O/ml/s by Day 3, and remained elevated throughout the remainder of the protocol. Repeated DAC increased reactivity to hypocapnia and intravenous histamine. Intravenous salbutamol failed to reduce Rp as effectively in challenged airways (111% of Day 1 baseline) as in naive airways (54% of baseline). Repeated DAC caused increased BALF neutrophils, eosinophils, and sulfidopeptide leukotrienes. We conclude that repeated DAC causes peripheral airways inflammation, obstruction, hyperreactivity, and impaired β -agonist-induced relaxation. This suggests that other mechanisms in addition to increased smooth muscle tone may contribute to the development of repetitive hyperventilation–induced bronchial obstruction and hyperreactivity.Keywords: asthma; β-agonist; bronchoconstriction; hyperreactivity; airway resistance
Impaired chronotropic response to exercise in patients with congestive heart failure. Role of postsynaptic beta-adrenergic desensitization.
Authors: W S Colucci, J P Ribeiro, M B Rocco, R J Quigg, M A Creager, J D Marsh, D F Gauthier, L H Hartley
Journal: Circulation (1989)

The mechanism responsible for the attenuated heart rate (HR) response to exercise in patients with congestive heart failure (CHF) was investigated in 46 normal subjects and 59 patients with CHF stratified by peak exercise oxygen consumption (VO2). The peak exercise HR and the increment in HR from rest to peak exercise were decreased in CHF patients, and both correlated strongly with peak VO2 (r = 0.810, p less than 0.0001; r = 0.863, p less than 0.0001, respectively). Peak exercise norepinephrine level (NE) and the increment in NE from rest to peak exercise were not attenuated in CHF patients. Resting NE was elevated in CHF patients and correlated inversely with peak VO2 (r = -0.595, p less than 0.001). However, no significant correlation occurred between peak VO2 and either peak exercise NE or the exercise increment in NE. The ratio of the exercise increments in HR and NE, and indirect index of sinoatrial node sympathetic responsiveness, was markedly reduced in CHF patients and was inversely related to the severity of exercise impairment. Likewise, the HR response to a graded isoproterenol infusion was markedly reduced in CHF patients. Age-matching of normal subjects and CHF patients did not affect the foregoing observations. Infusion of CHF patients with the phosphodiesterase inhibitor milrinone caused a significant increase in the ratio of the exercise increments in HR and NE. These data strongly suggest that the attenuated HR response to exercise in CHF patients is due, at least in part, to postsynaptic desensitization of the beta-adrenergic receptor pathway.
Management of Traction Wire Fracture Complicating Mechanical Basket Lithotripsy
Authors: R. E. Hintze, A. Adler, W. Veltzke, N. V. Ramani, H. Abou-Rebyeh
Journal: Endoscopy (1997)

Background and Study Aims: The application of basket catheters has become the main method of removing calculi from the biliary and pancreatic duct. However, larger or impacted stones have to be crushed and fragmented by mechanical lithotriptors before removal is possible. Sometimes, fracture of the traction wire occurrs as a severe and fraught complication. We describe a precautionary measure which helps to manage this complication.