tbuckley/cabot-search huggingface dataset:
Asthma and other pulmonary diseases in former elite athletes.
Authors: U M Kujala, S Sarna, J Kaprio, M Koskenvuo
Journal: Thorax (1996)

BACKGROUND: The prevalence of asthma is rising and there are recent reports of increasing asthma rates among top level skiers and runners in the Nordic countries. METHODS: The lifetime occurrence of pulmonary diseases (asthma, chronic bronchitis, emphysema) and current bronchitis symptoms was compared in former elite male athletes (n = 1282) who represented Finland between 1920 and 1965 at least once in international competitions and controls (n = 777) who, at the age of 20, were classified as healthy and who responded to a questionnaire in 1985. The presence of disease and symptoms was identified from the questionnaire and, in the case of asthma, also from a nationwide reimbursable medication register. The death certificates of the subjects of our original cohort who died between 1936 and 1985 were also investigated to determine the cause of death. RESULTS: The occurrence of the pulmonary diseases was associated with age, smoking habits, occupational group, and a history of exposure to chemicals. After adjusting for these variables, athletes who participated in mixed sports (odds ratio (OR) 0.46, 95% confidence interval (CI) 0.23 to 0.92) and power sports (OR 0.43, 95% CI 0.21 to 0.87) had lower odds ratios for emphysema, and endurance sports athletes had a lower odds ratio for the presence of at least one pulmonary disease (OR 0.53, 95% CI 0.28 to 0.98) when compared with controls. Athletes also tended to have fewer reimbursable medications for asthma and fewer current symptoms for chronic bronchitis. Between 1936 and 1985 two controls but none of the athletes died of asthma. CONCLUSIONS: The lifetime occurrence of asthma or other pulmonary diseases is not increased in former elite athletes, and exercise alone, even in a cold environment, did not appear to increase the prevalence of asthma, at least up to the mid 1980s.
FRMD4A Upregulation in Human Squamous Cell Carcinoma Promotes Tumor Growth and Metastasis and Is Associated with Poor Prognosis
Authors: Stephen J. Goldie, Klaas W. Mulder, David Wei-Min Tan, Scott K. Lyons, Andrew H. Sims, Fiona M. Watt
Journal: Cancer Research (2012)

Abstract New therapeutic strategies are needed to improve treatment of head and neck squamous cell carcinoma (HNSCC), an aggressive tumor with poor survival rates. FRMD4A is a human epidermal stem cell marker implicated previously in epithelial polarity that is upregulated in SCC cells. Here, we report that FRMD4A upregulation occurs in primary human HNSCCs where high expression levels correlate with increased risks of relapse. FRMD4A silencing decreased growth and metastasis of human SCC xenografts in skin and tongue, reduced SCC proliferation and intercellular adhesion, and stimulated caspase-3 activity and expression of terminal differentiation markers. Notably, FRMD4A attenuation caused nuclear accumulation of YAP, suggesting a potential role for FRMD4A in Hippo signaling. Treatment with the HSP90 inhibitor 17-DMAG or ligation of CD44 with hyaluronan caused nuclear depletion of FRMD4A, nuclear accumulation of YAP and reduced SCC growth and metastasis. Together, our findings suggest FRMD4A as a novel candidate therapeutic target in HNSCC based on the key role in metastatic growth we have identified. Cancer Res; 72(13); 3424–36. ©2012 AACR.
Mumps Outbreak in Orthodox Jewish Communities in the United States
Authors: Albert E. Barskey, Cynthia Schulte, Jennifer B. Rosen, Elizabeth F. Handschur, Elizabeth Rausch-Phung, Margaret K. Doll, Kisha P. Cummings, E. Oscar Alleyne, Patricia High, Jacqueline Lawler, Andria Apostolou, Debra Blog, Christopher M. Zimmerman, Barbara Montana, Rafael Harpaz, Carole J. Hickman, Paul A. Rota, Jennifer S. Rota, William J. Bellini, Kathleen M. Gallagher
Journal: New England Journal of Medicine (2012)

By 2005, vaccination had reduced the annual incidence of mumps in the United States by more than 99%, with few outbreaks reported. However, in 2006, a large outbreak occurred among highly vaccinated populations in the United States, and similar outbreaks have been reported worldwide. The outbreak described in this report occurred among U.S. Orthodox Jewish communities during 2009 and 2010.Cases of salivary-gland swelling and other symptoms clinically compatible with mumps were investigated, and demographic, clinical, laboratory, and vaccination data were evaluated.From June 28, 2009, through June 27, 2010, a total of 3502 outbreak-related cases of mumps were reported in New York City, two upstate New York counties, and one New Jersey county. Of the 1648 cases for which clinical specimens were available, 50% were laboratory-confirmed. Orthodox Jewish persons accounted for 97% of case patients. Adolescents 13 to 17 years of age (27% of all patients) and males (78% of patients in that age group) were disproportionately affected. Among case patients 13 to 17 years of age with documented vaccination status, 89% had previously received two doses of a mumps-containing vaccine, and 8% had received one dose. Transmission was focused within Jewish schools for boys, where students spend many hours daily in intense, face-to-face interaction. Orchitis was the most common complication (120 cases, 7% of male patients ≥12 years of age), with rates significantly higher among unvaccinated persons than among persons who had received two doses of vaccine.The epidemiologic features of this outbreak suggest that intense exposures, particularly among boys in schools, facilitated transmission and overcame vaccine-induced protection in these patients. High rates of two-dose coverage reduced the severity of the disease and the transmission to persons in settings of less intense exposure.
Prevalence of Depression Among U.S. Adults With Diabetes
Authors: Chaoyang Li, Earl S. Ford, Tara W. Strine, Ali H. Mokdad
Journal: Diabetes Care (2007)

To estimate the prevalence rate of depression among adults with diabetes using a large population-based sample in the U.S.Data from the 2006 Behavioral Risk Factor Surveillance System, a standardized telephone survey among U.S. adults aged >or=18 years, were analyzed (n = 18,814). The Patient Health Questionnaire diagnostic algorithm was used to identify major depression.The age-adjusted prevalence rate of major depression was 8.3% (95% CI 7.3-9.3), ranging from a low of 2.0% in Connecticut to a high of 28.8% in Alaska. There were 25-fold differences in the rate among racial/ethnic subgroups (lowest, 1.1% among Asians; highest, 27.8% among American Indians/Alaska Natives). People with type 2 diabetes who were currently using insulin had a higher rate than people with type 1 diabetes (P = 0.0009) and those with type 2 diabetes who were currently not using insulin (P = 0.01).Major depression was highly prevalent among people with diabetes; the prevalence rate varied greatly by demographic characteristics and diabetes types.
Use of Ultrasound‐Guided Small Joint Biopsy to Evaluate the Histopathologic Response to Rheumatoid Arthritis Therapy: Recommendations for Application to Clinical Trials
Authors: Frances Humby, Stephen Kelly, Rebecca Hands, Vidalba Rocher, Maria DiCicco, Nora Ng, Lu Zou, Serena Bugatti, Antonio Manzo, Roberto Caporali, Carlomaurizio Montecucco, Michele Bombardieri, Costantino Pitzalis
Journal: Arthritis & Rheumatology (2015)

To examine in a cohort of rheumatoid arthritis (RA) patients undergoing serial ultrasound (US)-guided biopsies of small joints in the context of clinical trials whether sufficient synovial tissue could be obtained at both baseline and second biopsy to: 1) accurately evaluate the synovial immune phenotype, 2) permit adequate RNA extraction to determine molecular signatures, and 3) sensitively detect change in the number of synovial sublining macrophages (CD68+) following effective therapy.Synovial samples from RA patients undergoing US-guided biopsy of small joints as part of 2 clinical trials (Barts Early Arthritis Cohort [n = 18] and the Clinical and Pathological Response to Certolizumab Pegol (CLIP-Cert) study [n = 17]) were examined, and the quality and quantity of histologic samples and RNA extracted per joint were determined and compared to synovial thickness and power Doppler scores determined by US before biopsy. Modulation of the number of CD68+ sublining macrophages was correlated with clinical response to treatment.Good quality synovial tissue that accurately reflected the synovial immune phenotype of the total joint was obtained in 80% of US-guided procedures when synovial thickness (higher than grade 2) was documented before biopsy. In 100% of the procedures, sufficient RNA was extracted to permit molecular analysis. There was a significant correlation between change in CD68+ sublining macrophage number and clinical response to treatment.This study provides minimum standards for sample retrieval for small joint biopsy. Furthermore, our findings confirm the clinical utility of the procedure in the largest reported cohort of US-guided small joint biopsies. The demonstration that small joint synovial tissue can be readily accessed by a technically simple, minimally invasive procedure is likely to facilitate critical advancements in the knowledge of RA pathobiology and personalized health care.
Grounding the meaning of non-prototypical smiles on motor behavior
Authors: Timothy A. Mann, Yoonsuck Choe
Journal: Behavioral and Brain Sciences (2010)

Abstract We address how the motor system can contribute to the “meaning” component of smile perception. A smile perceiver can ground the meaning of non-prototypical smiles by interacting with the presenter to maintain the presenter's type of smile. In this case, the meaning of that smile is congruent with the motor behavior that elicits that smile (such as a funny gesture).
FLI1 monoallelic expression combined with its hemizygous loss underlies Paris-Trousseau/Jacobsen thrombopenia
Authors: Hana Raslova, Emiko Komura, Jean Pierre Le Couédic, Frederic Larbret, Najet Debili, Jean Feunteun, Olivier Danos, Olivier Albagli, William Vainchenker, Rémi Favier
Journal: Journal of Clinical Investigation (2004)

Paris-Trousseau syndrome (PTS; also known as Jacobsen syndrome) is characterized by several congenital anomalies including a dysmegakaryopoiesis with two morphologically distinct populations of megakaryocytes (MKs). PTS patients harbor deletions on the long arm of chromosome 11, including the FLI1 gene, which encodes a transcription factor essential for megakaryopoiesis. We show here that lentivirus-mediated overexpression of FLI1 in patient CD34(+) cells restores the megakaryopoiesis in vitro, indicating that FLI1 hemizygous deletion contributes to the PTS hematopoietic defects. FISH analysis on pre-mRNA and single-cell RT-PCR revealed that FLI1 expression is mainly monoallelic in CD41(+)CD42(-) progenitors, while it is predominantly biallelic in the other stages of megakaryopoiesis. In PTS cells, the hemizygous deletion of FLI1 generates a subpopulation of CD41(+)CD42(-) cells completely lacking FLI1 transcription. We propose that the absence of FLI1 expression in these CD41(+)CD42(-) cells might prevent their differentiation, which could explain the segregation of the PTS MKs into two subpopulations: one normal and one composed of small immature MKs undergoing a massive lysis, presumably originating from either FLI1(+) or FLI1(-) CD41(+)CD42(-) cells, respectively. Thus, we point to the role of transient monoallelic expression of a gene essential for differentiation in the genesis of human haploinsufficiency-associated disease and suggest that such a mechanism may be involved in the pathogenesis of other congenital or acquired genetic diseases.
Effect of preventive and curative interventions on hepatitis C virus transmission in Egypt (ANRS 1211): a modelling study
Authors: Romulus Breban, Naglaa Arafa, Sandrine Leroy, Aya Mostafa, Iman Bakr, Laura Tondeur, Mohamed Abdel-Hamid, Wahid Doss, Gamal Esmat, Mostafa K Mohamed, Arnaud Fontanet
Journal: The Lancet Global Health (2014)

Most hepatitis C virus (HCV) transmission in Egypt is related to medical injections and procedures. To control the spread of HCV, the Egyptian Ministry of Health initiated awareness and education campaigns, strengthened infection control in health-care facilities, and subsidised anti-HCV treatment. We aimed to investigate the effect of these interventions on the spread of HCV by mathematical modelling.We developed a mathematical model of HCV transmission in Zawyat Razin, a typical rural community. Our model assumes that each individual has two distinct types of medical procedures: injections and more invasive medical procedures. To quantify the severity of the spread of HCV, we used the notion of the basic reproduction number R0, a standard threshold parameter signalling whether transmission of an infectious disease is self-sustained and maintains an epidemic. If R0 is greater than 1, HCV is self-sustained; if R0 is 1 or less, HCV transmission is not self-sustained. We investigated whether heterogeneity in the rate of injection or invasive medical procedures is the determinant factor for HCV transmission and whether most iatrogenic transmission is caused by a small group of individuals who receive health-care interventions frequently. We then assessed whether interventions targeted at this group could reduce the spread of HCV.The R0 of the spread of HCV without treatment was 3·54 (95% CI 1·28-6·18), suggesting a self-sustained spread. Furthermore, the present national treatment programme only decreased R0 from 3·54 to 3·03 (95% CI 1·10-5·25). Individuals with high rates of medical injections seem to be responsible for the spread of HCV in Egypt; the R0 of the spread of HCV without treatment would be 0·64 (95% CI 0·41-0·93) if everybody followed the average behaviour. The effect of treatment on HCV transmission is greatly enhanced if treatment is provided a mean of 2·5 years (95% CI 0·1-9·2) after chronic infection and with drug regimens with more than 80% efficacy. With these treatment parameters, preventive and curative interventions targeting individuals with high rates of medical injections might decrease R0 below 1 for treatment coverage lower than 5%.Targeting preventive and curative interventions to individuals with high rates of medical injections in Egypt would result in a greater reduction the spread of HCV than would untargeted allocation. Such an approach might prove beneficial in other resource-limited countries with health-care-driven epidemics.Agence Nationale de Recherche sur le SIDA et les Hépatites Virales (ANRS 1211), ANR grant Labex Integrative Biology of Emerging Infectious Diseases.
Cytotoxic T Lymphocyte Antigen 4 (Ctla-4) Engagement Delivers an Inhibitory Signal through the Membrane-Proximal Region in the Absence of the Tyrosine Motif in the Cytoplasmic Tail
Authors: Chiaki Nakaseko, Shoichiro Miyatake, Tomohiko Iida, Satoru Hara, Ryo Abe, Hiroshi Ohno, Takashi Saito
Journal: The Journal of Experimental Medicine (1999)

Cytotoxic T lymphocyte antigen 4 (CTLA-4) is a T cell costimulation receptor that delivers inhibitory signals upon activation. Although the tyrosine-based motif (165YVKM) within its cytoplasmic tail has been shown to associate in vitro with Src homology 2 domain–containing tyrosine phosphatase (SHP-2) and phosphatidylinositol 3 kinase upon phosphorylation, the mechanism of negative signaling remains unclear. Here, we report a new mechanism of negative signaling based on the analysis of murine T cell clones transfected with various mutants of CTLA-4. Upon T cell activation by cross-linking with anti-CD3 and anti-CD28 antibodies, CTLA-4 engagement inhibited both proliferation and interleukin 2 production in tyrosine mutants as well as in wild-type CTLA-4 transfectants. Furthermore, the mutant CTLA-4 lacking most of the cytoplasmic region strongly suppressed interleukin 2 production as well. These data suggest that negative signals by CTLA-4 could be mediated through the membrane-proximal region of CTLA-4 but not through the YVKM motif and that the association of CTLA-4 with SHP-2 is not required for CTLA-4–mediated suppression of T cell activation.
Safety and Tolerability of Atopaxar in the Treatment of Patients With Acute Coronary Syndromes
Authors: Michelle L. O'Donoghue, Deepak L. Bhatt, Stephen D. Wiviott, Shaun G. Goodman, Desmond J. Fitzgerald, Dominick J. Angiolillo, Shinya Goto, Gilles Montalescot, Uwe Zeymer, Philip E. Aylward, Victor Guetta, Dariusz Dudek, Rafal Ziecina, Charles F. Contant, Marcus D. Flather
Journal: Circulation (2011)

Atopaxar (E5555) is a reversible protease-activated receptor-1 thrombin receptor antagonist that interferes with platelet signaling. The primary objective of the Lessons From Antagonizing the Cellular Effects of Thrombin-Acute Coronary Syndromes (LANCELOT—ACS) trial was to evaluate the safety and tolerability of atopaxar in patients with ACS.Six hundred and three subjects were randomized within 72 hours of non-ST-elevation ACS to 1 of 3 doses of atopaxar (400-mg loading dose followed by 50, 100, or 200 mg daily) or matching placebo. The incidence of Clopidogrel in Unstable Angina to Prevent Recurrent Events (CURE) major or minor bleeding did not differ significantly between the combined atopaxar and placebo groups (3.08% versus 2.17%, respectively; P=0.63), and there was no dose-related trend (P=0.80). The incidence of CURE major bleeding was numerically higher in the atopaxar group compared with the placebo group (1.8% versus 0%; P=0.12). The incidence of cardiovascular death, myocardial infarction, stroke, or recurrent ischemia was similar between the atopaxar and placebo arms (8.03% versus 7.75%; P=0.93). The incidence of CV death, MI, or stroke was 5.63% in the placebo group and 3.25% in the combined atopaxar group (P=0.20). Dose-dependent trends for efficacy were not seen. Atopaxar significantly reduced ischemia on continuous ECG monitoring (Holter) at 48 hours compared with placebo (relative risk, 0.67; P=0.02). Transient dose-dependent transaminase elevation and relative QTc prolongation were observed with the highest doses of atopaxar.In patients after ACS, atopaxar significantly reduced early ischemia on Holter monitoring without a significant increase in major or minor bleeding. Larger trials are required to fully establish the efficacy and safety of atopaxar.URL: http://www.ClinicalTrials.gov. Unique identifier: NCT00548587.
Tularaemia in a brown hare (Lepus europaeus) in 2013: first case in the Netherlands in 60 years
Authors: J M Rijks, M Kik, M G Koene, M Y Engelsma, P van Tulden, M G Montizaan, T Oomen, M A Spierenburg, J IJzer, J  W van der Giessen, A Gröne, H J Roest
Journal: Eurosurveillance (2013)

Tularaemia has not been reported in Dutch wildlife since 1953. To enhance detection, as of July 2011, brown hares (Lepus europaeus) submitted for post-mortem examination in the context of non-targeted wildlife disease surveillance, were routinely tested for tularaemia by polymerase chain reaction (PCR). Francisella tularensis subspecies holarctica infection was confirmed in a hare submitted in May 2013. The case occurred in Limburg, near the site of the 1953 case. Further surveillance should clarify the significance of this finding.
Palliative care needs of minorities
Authors: A R. Gatrad
Journal: BMJ (2003)

Understanding their needs is the key 

The opportunity to die with dignity is recognised by health professionals the world over as one of the most fundamental of all human rights. What is often forgotten is that notions of a good death vary considerably between cultures (and individuals within a culture), raising the risk of misunderstanding and cultural insensitivity.1 This need not be the case, as our experiences show. Even in ethnically and religiously diverse modern Britain, receiving high quality care at the end of life is possible and may, we hope, soon be probable for all.2 3 Realising this aspiration will need fundamental changes on at least three fronts: tackling institutional discrimination in the provision of palliative care, progress in incorporating transcultural medicine into medical and nursing curriculums, and a greater willingness on the part of healthcare providers to embrace complexity and …
Morphological studies of bronchial mucosal biopsies from asthmatics before and after ten years of treatment with inhaled steroids
Authors: R Lundgren, M Soderberg, P Horstedt, R Stenling
Journal: European Respiratory Journal (1988)

To examine the influence of inhaled steroids on the bronchial mucosa, biopsies from six patients with severe bronchial asthma were studied before and after ten years of daily treatment with inhaled steroids. Biopsies from six healthy subjects were also examined. In the biopsies taken from the asthmatic patients before treatment there was a significant increase in inflammatory cell numbers compared with the biopsies from the control subjects. In all patients scanning electron microscopy showed a reduced coverage by cilia. Squamous cell metaplasia was seen in two patients. After ten years of treatment the number of inflammatory cells was significantly reduced compared to that before treatment and was not different from the control biopsies. Most of the epithelial cells showed a ciliated surface. Small focal areas with non-ciliated cells could still be seen in four patients. In the two patients with squamous cell metaplasia before treatment, small areas of metaplasia could still be seen. Despite the absence of inflammation and reduced epithelial damage during treatment all patients still had bronchial hyperresponsiveness.
MEASUREMENT OF CHANGING PSYCHOPATHOLOGY WITH THE MINNESOTA MULTIPHASIC PERSONALITY INVENTORY
Authors: LOUIS J. WEST
Journal: American Journal of Psychiatry (1953)

The MMPI is widely accepted as the best of the questionnaire-type personality tests. It is simple to administer and score, conservative of the clinician's time, well accepted by patients, and provides an extensive anamnesis and a graphic indication of psychopathological status that is easy to interpret. It Should not be used as a substitute for the physician's history-taking (which is so important in the early development of a therapeutic relationship), nor should it be used alone to "make" a diagnosis. With experience in the use of the MMPI, characteristic profiles can be recognized as indicative of personality structure and disturbance that are not limited to diagnostic categories of any particular school. Examples have been selected to demonstrate how the MMPI can be used in measurement of changing psychopathology, thus indicating its value in analysis of clinical progress and results of treatment.
Orthocyanosis: a sign of pulmonary arteriovenous malformation.
Authors: V H Hoeppner
Journal: Thorax (1982)

Normally the arterial oxygen tension (Pao,) remains the same or rises with the change from the supine to the upright position.'Several patients showing the opposite phenomenon (orthodeoxia) have been reported, some with a pulmonary arteriovenous malformation.While cyanosis is a recognised feature of pulmonary arteriovenous malformation,3 4 our patient is of interest because she had cyanosis when she was upright but not when she was supine (orthocyanosis).Case report 'AV.,\C