tbuckley/cabot-search huggingface dataset:
Adaptive Divergence of Ancient Gene Duplicates in the Avian MHC Class II 
Authors: R. Burri, N. Salamin, R. A. Studer, A. Roulin, L. Fumagalli
Journal: Molecular Biology and Evolution (2010)

Gene duplication and neofunctionalization are known to be important processes in the evolution of phenotypic complexity. They account for important evolutionary novelties that confer ecological adaptation, such as the major histocompatibility complex (MHC), a multigene family crucial to the vertebrate immune system. In birds, two MHC class II β (MHCIIβ) exon 3 lineages have been recently characterized, and two hypotheses for the evolutionary history of MHCIIβ lineages were proposed. These lineages could have arisen either by 1) an ancient duplication and subsequent divergence of one paralog or by 2) recent parallel duplications followed by functional convergence. Here, we compiled a data set consisting of 63 MHCIIβ exon 3 sequences from six avian orders to distinguish between these hypotheses and to understand the role of selection in the divergent evolution of the two avian MHCIIβ lineages. Based on phylogenetic reconstructions and simulations, we show that a unique duplication event preceding the major avian radiations gave rise to two ancestral MHCIIβ lineages that were each likely lost once later during avian evolution. Maximum likelihood estimation shows that following the ancestral duplication, positive selection drove a radical shift from basic to acidic amino acid composition of a protein domain facing the α-chain in the MHCII α β-heterodimer. Structural analyses of the MHCII α β-heterodimer highlight that three of these residues are potentially involved in direct interactions with the α-chain, suggesting that the shift following duplication may have been accompanied by coevolution of the interacting α- and β-chains. These results provide new insights into the long-term evolutionary relationships among avian MHC genes and open interesting perspectives for comparative and population genomic studies of avian MHC evolution.
Symptoms of persistent allergic rhinitis during a full calendar year in house dust mite‐sensitive subjects
Authors: S. R. Downie, M. Andersson, J. Rimmer, J. D. Leuppi, W. Xuan, A. Akerlund, J. K. Peat, C. M. Salome
Journal: Allergy (2004)

Little is known about the natural course of persistent rhinitis symptoms over a prolonged period.To describe the frequency and severity of nasal symptoms and quality of life (QoL) in house dust mite-sensitive persistent rhinitic subjects and to determine if medication use was related to symptoms.Rhinitics and controls were telephoned fortnightly for 1 year to monitor symptoms. QoL was measured every 3 months.Thirty-seven rhinitics and 19 controls completed the study. Total nasal symptom scores (TNSS) were 'high' for 65% (95% CI +/- 6%) of the year in rhinitic subjects. When TNSS increased by 1, the likelihood of nasal medication use increased by 25% (95% CI: 7-46%). General and specific QoL were worse in rhinitic subjects than controls (P < 0.04 and <0.0001). Rhinitics with pollen allergy (n = 21) had seasonal variation in the frequency of high nasal symptom scores (P = 0.02).Nasal symptom scores were consistently high in rhinitics, and their QoL was worse than controls, even in general QoL. An increase in nasal symptom score increased the likelihood of nasal medication use. These findings help to characterize the course of persistent rhinitis over a previously unstudied period of 1 year.
Tobacco and tobacco branding in films most popular in the UK from 1989 to 2008
Authors: A. Lyons, A. McNeill, Y. Chen, J. Britton
Journal: Thorax (2010)

<h3>Background</h3> Tobacco promotion is now tightly restricted in the UK and many other countries, but tobacco imagery including brand appearances in the media remain potentially powerful drivers of smoking uptake among children and young people. The extent to which tobacco imagery and specific products have appeared in the most popular films viewed in the UK over 20 years has been measured, in relation to year of release, the age certification allocated to the film by the British Board of Film Classification (BBFC), country of origin and other characteristics. <h3>Methods</h3> Occurrence of tobacco intervals (tobacco use, implied use or appearance of smoking paraphernalia) and brand appearances were measured by 5 min interval coding in the 15 most commercially successful films in the UK each year from 1989 to 2008. <h3>Results</h3> Tobacco intervals occurred in 70% of all films. Over half (56%) of those that contained tobacco intervals were rated by the BBFC as suitable for viewing by children aged &lt;15, and 92% for people aged &lt;18. Tobacco interval appearances fell by ∼80% over the study period, but persisted in films in all BBFC categories. Brand appearances were nearly twice as likely to occur in films originating wholly or in part from the UK (UK films). Specific brands, particularly Marlboro and Silk Cut, appeared in 9% of all films, and most brand appearances (39%) were in films with BBFC 15 classification. <h3>Conclusions</h3> Tobacco imagery in the most popular films shown in the UK has declined substantially over the past 20 years but continues to occur, particularly in UK films, and predominantly in films categorised as suitable for viewing by children and young people. Specific brand appearances are now rare but occur repeatedly in some films. The BBFC is not currently protecting children and young people from exposure to tobacco imagery in film.
Large intercostal arteriovenous aneurysm: successful surgical correction.
Authors: M Swank, D Lepley, D C Mullen, R J Flemma, L I Bonchek
Journal: Thorax (1978)

A large aberrant systemic artery to superior vena cava communication associated with normal lungs and normal pulmonary arteries has never been reported. This lesion, its diagnosis, and successful surgical management are discussed.
Int6 Expression Can Predict Survival in Early-Stage Non–Small Cell Lung Cancer Patients
Authors: Fiamma Buttitta, Carla Martella, Fabio Barassi, Lara Felicioni, Simona Salvatore, Sandra Rosini, Tommaso D'Antuono, Antonio Chella, Felice Mucilli, Rocco Sacco, Andrea Mezzetti, Franco Cuccurullo, Robert Callahan, Antonio Marchetti
Journal: Clinical Cancer Research (2005)

Abstract Purpose: The Int6 gene was originally identified as a common insertion site for the mouse mammary tumor virus in virally induced mouse mammary tumors. Recent studies indicate that Int6 is a multifaceted protein involved in the regulation of protein translation and degradation through binding with three complexes: the eukaryotic translation initiation factor 3, the proteasome regulatory lid, and the constitutive photomorphogenesis 9 signalosome. This study aimed to investigate the prognostic role of Int6 in a large series of stage I non–small cell lung cancers (NSCLC) patients with long-term follow-up. Experimental Design: We determined the methylation status of Int6 DNA by methylation-specific PCR and the steady-state levels of Int6 RNA by quantitative real-time reverse transcription-PCR in 101 NSCLCs and matched normal lung tissues. Results: In 27% of the tumors, Int6 RNA levels were reduced relative to normal tissue. In 85% of the tumors with reduced Int6 expression, the transcription promoter and first exon were hypermethylated, whereas only 4% of the tumors with elevated Int6 RNA levels were hypermethylated (P &amp;lt; 0.000001). Low levels of Int6 RNA were found a significant predictor of overall and disease-free survival (P = 0.0004 and P = 0.0020, respectively). A multivariate analysis confirmed that low Int6 expression was the only independent factor to predict poor prognosis, for both overall (P = 0.0006) and disease-free (P = 0.024) survival. Conclusions: Our results suggest that Int6 expression, evaluated by quantitative real-time PCR, may represent a new prognostic factor in patients with stage I NSCLC.
Magnesium Deficiency in the Cebus Monkey
Authors: JOSEPH J. VITALE, HERNAN VELEZ, CARLOS GUZMAN, PELAYO CORREA
Journal: Circulation Research (1963)

Purified diets containing cholesterol and deficient or adequate in magnesium were fed to young growing Cebus (fatuella) monkeys. Diet-induced magnesium deficiency resulted in weight loss, hyperirritability, and in several monkeys, convulsions. In addition to the expected hypomagnesemia, deficient animals also had decreased serum potassium levels. However, after several weeks on diet, the electrocardiogram of deficient animals showed significant changes consisting primarily of S-T segment depression and peaking of the T wave; changes usually seen in hyperkalemic states. Prior to sacrificing the animals, the tolerance to K-strophanthidin, a cardiac glycoside, was ascertained in both deficient and control animals. The cardiac glycoside was administered slowly by the intravenous route to anesthetized monkeys and the appearance of four consecutive ventricular premature contractions in the electrocardiogram was taken as the end-point. Deficient animals required approximately one-half the dose administered to control monkeys to develop extrasystoles. The histopathology consisted of marked vascular sudanophilic deposits and dense fibrous connective tissue plaques in the ascending and descending aorta of deficient monkeys. Control animals showed little, if any, vascular sudanophilia. The serum cholesterol concentration increased significantly in the deficient group while the rise seen in control monkeys lacked statistical significance.
Continuing medical education across Europe: the role of EBAP and the ERS in facing the challenges of life-long learning
Authors: M. Gaga, T. Séverin, R. Stevenson
Journal: European Respiratory Journal (2010)

In medicine, good professional training and education are pivotal, and these include initial medical studies and, even more importantly, continuing medical education (CME). Learning on the job is an important and indisputable part of continuing medical education but, in itself, it is not enough. Attending meetings, reading journals and books, seeking expert advice and, in recent years, getting information from web-based sources are the usual ways by which doctors learn and keep up to date. However, because CME is not only necessary for the physician but is also associated with better patient care, it should be done in a structured and validated way. This concept is currently being incorporated in the legislation governing medical practice in many countries. From this has stemmed the need for CME credits and associated accreditation processes. Initially, CME accreditation required only attendance at meetings but, in recent years, CME journals and books, as well as various other forms of accessible and interactive e-learning activities, have been added. All these now come under the heading of CME, which has been defined by the Accreditation Council for Continuing Medical Education in the USA as “educational activities that serve to maintain, develop or increase the knowledge, skills and professional performance and relationships a physician uses to provide services for patients, the public or the profession”.

On a European level, the European Accreditation Council for Continuing Medical Education (EACCME) was set up in 1999 by the European Union of Medical Specialties (UEMS). Initially, European CME was accredited jointly …
Public views on healthcare performance indicators and patient choice
Authors: H. Magee, L.-J. Davis, A. Coulter
Journal: Journal of the Royal Society of Medicine (2003)

Patients on certain waiting lists in the UK National Health Service (NHS) are now offered the choice of persevering with their home hospital or switching to another hospital where they will be treated on a guaranteed date. Such decisions require knowledge of performance. We used facilitated focus groups to investigate the views of patients and members of the public on publication of information about the performance of healthcare providers. Six groups with a total of 50 participants met in six different locations in England. Participants felt that independent monitoring of healthcare performance is necessary, but they were ambivalent about the value of performance indicators and hospital rankings. They tended to distrust government information and preferred the presentational style of 'Dr Foster', a commercial information provider, because it gave more detailed locally relevant information. Many participants felt the NHS did not offer much scope for choice of provider. If public access to performance information is to succeed in informing referral decisions and raising quality standards, the public and general practitioners will need education on how to interpret and use the data.
Construction of peptides encompassing multideterminant clusters of human immunodeficiency virus envelope to induce in vitro T cell responses in mice and humans of multiple MHC types.
Authors: J A Berzofsky, C D Pendleton, M Clerici, J Ahlers, D R Lucey, S D Putney, G M Shearer
Journal: Journal of Clinical Investigation (1991)

To make synthetic peptide vaccines effective in a broad population of outbred humans, one would have to incorporate enough antigenic determinants to elicit recognition by T cells of most HLA types. We have previously defined multideterminant regions of the human immunodeficiency virus (HIV) envelope that include overlapping determinants seen by proliferating T cells of three or four haplotypes of mice. We have now tested the hypothesis that synthetic peptides encompassing such multideterminant regions will be recognized by T cells of multiple murine MHC types as well as by human T cells representing multiple HLA types. Six such peptides of 20-33 residues in length were prepared, and tested for their ability to stimulate T cells from mice of four distinct MHC types immunized with recombinant envelope protein rgp 160, as well as from 42 HIV-infected humans of different HLA types. Results identify several such peptides that are broadly recognized by mice of four H-2 types and by 52-73% of infected humans who still retain IL-2 productive responses to control recall antigens such as influenza A virus or tetanus toxoid. 86% of such infected donors tested against at least three peptides respond to at least one of the six peptides, and 77% of an additional group of seropositives respond to a mixture of the peptides. Moreover, the peptides can be used to immunize mice to elicit T cells reactive with the intact HIV envelope protein. These peptides therefore may be useful for both vaccine development in the broad human population, and diagnostic or prognostic use.
SURVIVAL OF POLIOMYELITIC VIRUS IN THE BRAIN OF THE RABBIT
Authors: Harold L. Amoss
Journal: The Journal of Experimental Medicine (1918)

Suspensions of the central nervous tissues of monkeys, containing the active filterable virus of poliomyelitis, may be injected into the brain of rabbits without setting up symptoms, provided the volume of injection does not cause dangerous increased intracranial pressure. Aside from the pressure effects which develop quickly, no other symptoms or pathological lesions are produced by the suspensions. The active virus of poliomyelitis survives in the brain of rabbits for 4 days, as determined by tests in the monkey, into which the excised site of injection in the rabbit brain is reinoculated. It cannot be detected by this test after the expiration of 7 days. The virus of poliomyelitis is unadapted to the rabbit, and neither induces lesions nor survives long in the central nervous organs of that animal. In this respect it differs from certain streptococci cultivated from poliomyelitic tissues. A monkey immunized to streptococcus cultivated from human poliomyelitic nervous tissues yielded a serum which agglutinated the streptococcus in high dilution, but was without neutralizing action on the filtered virus; and the streptococcus-immune monkey was not protected against the effects of an intracerebral inoculation of the filtered virus. The experiments recorded provide additional reasons for concluding that the streptococcus cultivated from cases of poliomyelitis differs essentially from the filterable virus and is not the microbic cause of epidemic poliomyelitis.
The Molecular Basis of Goodpasture and Alport Syndromes
Authors: Billy G Hudson
Journal: Journal of the American Society of Nephrology (2004)

<h3>Objective</h3> To provide new insights into the <i>FOXG1-</i>related clinical and imaging phenotypes and refine the phenotype-genotype correlation in <i>FOXG1</i> syndrome. <h3>Methods</h3> We analyzed the clinical and imaging phenotypes of a cohort of 45 patients with a pathogenic or likely pathogenic <i>FOXG1</i> variant and performed phenotype-genotype correlations. <h3>Results</h3> A total of 37 <i>FOXG1</i> different heterozygous mutations were identified, of which 18 are novel. We described a broad spectrum of neurodevelopmental phenotypes, characterized by severe postnatal microcephaly and developmental delay accompanied by a hyperkinetic movement disorder, stereotypes and sleep disorders, and epileptic seizures. Our data highlighted 3 patterns of gyration, including frontal pachygyria in younger patients (26.7%), moderate simplified gyration (24.4%) and mildly simplified or normal gyration (48.9%), corpus callosum hypogenesis mostly in its frontal part, combined with moderate-to-severe myelination delay that improved and normalized with age. Frameshift and nonsense mutations in the N-terminus of <i>FOXG1</i>, which are the most common mutation types, show the most severe clinical features and MRI anomalies. However, patients with recurrent frameshift mutations c.460dupG and c.256dupC had variable clinical and imaging presentations. <h3>Conclusions</h3> These findings have implications for genetic counseling, providing evidence that N-terminal mutations and large deletions lead to more severe <i>FOXG1</i> syndrome, although genotype-phenotype correlations are not necessarily straightforward in recurrent mutations. Together, these analyses support the view that <i>FOXG1</i> syndrome is a specific disorder characterized by frontal pachygyria and delayed myelination in its most severe form and hypogenetic corpus callosum in its milder form.
Detection of a rare CDKN2A intronic mutation in a Hungarian melanoma-prone family and its role in splicing regulation
Authors: K. Balogh, M. Széll, H. Polyánka, F. Pagani, E. Bussani, L. Kemény, J. Oláh
Journal: British Journal of Dermatology (2012)

The major locus for melanoma predisposition is the cell cycle regulatory CDKN2A gene on chromosome 9p21. However, the frequency of germline coding mutations of the CDKN2A gene is lower than expected in melanoma-prone families linked to chromosome 9p21.To investigate whether the rare IVS1+37 G/C intronic mutation of the CDKN2A gene, recently identified in a Hungarian melanoma-prone family, influences mRNA splicing regulation.CDKN2A minigenes containing the wild-type and the mutant intronic sequence were created and transfected into HeLa cells with the aim of studying the mRNA transcripts.The results revealed the emergence of a differential splicing pattern from the wild-type and the mutant minigene, suggesting that this mutation may alter the splicing of CDKN2A primary mRNA and therefore might have a pathogenetic role in familial melanoma.We believe that these results confirm the importance of the identification and characterization of CDKN2A intronic mutations with a view to improving our understanding of the pathogenesis, and explain why the frequency of germline coding mutations of the CDKN2A gene is lower than expected in melanoma-prone families linked to chromosome 9p21.
Surviving the unsurvivable
Authors: Kamran Abbasi
Journal: Journal of the Royal Society of Medicine (2015)

It may be difficult to see the benefit in conflict. Preventing war is akin to preventing disease, but medicine’s role in conflict is as old as war itself. Doctors and other health professionals play a brave and commendable part in healing or providing palliation to casualties. The nature of conflict is such that any medical intervention is urgent, rapid, and often overwhelmed. Conflict takes human behaviour to an extreme and the medical response is tested to its limits. In this high-pressure environment, innovation has flourished. So has comedy, in the guise of MASH,
Statin use is associated with reduced incidence and progression of knee osteoarthritis in the Rotterdam study
Authors: S Clockaerts, G J V M Van Osch, Y M Bastiaansen-Jenniskens, J A N Verhaar, F Van Glabbeek, J B Van Meurs, H J M Kerkhof, A Hofman, B H Ch Stricker, S M Bierma-Zeinstra
Journal: Annals of the Rheumatic Diseases (2011)

Background Osteoarthritis is the most frequent chronic joint disease causing pain and disability. Besides biomechanical mechanisms, the pathogenesis of osteoarthritis may involve inflammation, vascular alterations and dysregulation of lipid metabolism. As statins are able to modulate many of these processes, this study examines whether statin use is associated with a decreased incidence and/or progression of osteoarthritis. Methods Participants in a prospective population-based cohort study aged 55 years and older (n=2921) were included. x-Rays of the knee/hip were obtained at baseline and after on average 6.5 years, and scored using the Kellgren and Lawrence score for osteoarthritis. Any increase in score was defined as overall progression (incidence and progression). Data on covariables were collected at baseline. Information on statin use during follow-up was obtained from computerised pharmacy databases. The overall progression of osteoarthritis was compared between users and non-users of statins. Using a multivariate logistic regression model with generalised estimating equation, OR and 95% CI were calculated after adjusting for confounding variables. Results Overall progression of knee and hip osteoarthritis occurred in 6.9% and 4.7% of cases, respectively. The adjusted OR for overall progression of knee osteoarthritis in statin users was 0.43 (95% CI 0.25 to 0.77, p=0.01). The use of statins was not associated with overall progression of hip osteoarthritis. Conclusions Statin use is associated with more than a 50% reduction in overall progression of osteoarthritis of the knee, but not of the hip.
The role of magnetic resonance imaging in staging of NSCLC
Authors: Aleksey Reshetov, Nikolai Mitrifanov, Vasily Klimenko, Olga Kakisheva, Aleksey Elkin
Journal: European Respiratory Journal (2013)

Objective: MRI is used to T and N staging of non small cell lung cancer (NSCLC) as a non invasive tool. The role of the MRI in staging of NSCLC is not clear. We wanted to determine effect of the MRI in the T and N staging of NSCLC vs. CT.  Methods: Between 2010 and 2013, 157 patients underwent operations for NSCLC. Mediastinoscopy was performed in 98 cases. MRI was carried out to 51 patients with NSCLC. We compared data received through MRI with data received in a group of NSCLC (n=106) patients, which we used only CT. In all cases the data received in pre-operative investigation was compared with data received during operation and morphological research of removed organs. During this comparison, local invasion of hilus and mediastinum (T-staging), and lymfatic metastases (N-staging) were payed special attention.  Results: For T-staging sensitivity, spesificity, false positivity, false negativity rates and accuracy of the MRT were calculated as 98%, 96%, 2%, 4%, 98% respectively. Whereas sensitivity spesificity, false positivity, false negativity and accuracy rates of the CT for T-staging were 71%, 58%, 25%, 10%, 75% respectively. For N-staging spesificity, false positivity, false negativity rates and accuracy of the CT and MRT were 64%, 53%, 35%, 14%, 55% and 75%, 64%, 40%, 26%, 63% respectively. Both of this methods were worse for N-staging then mediastinoscopy which sensitivity, spesificity, false positivity, false negativity rates and accuracy were 85%, 98%, 26%, 0%, 62%.  Conclusion: MRI is the method of choice for T-staging NSCLC. For N-staging MRI and CT yields to the invasive methods such as mediastinoscopy.