tbuckley/cabot-search huggingface dataset:
The Risk of Melanoma in Airline Pilots and Cabin Crew
Authors: Martina Sanlorenzo, Mackenzie R. Wehner, Eleni Linos, John Kornak, Wolfgang Kainz, Christian Posch, Igor Vujic, Katia Johnston, Deborah Gho, Gabriela Monico, James T. McGrath, Simona Osella-Abate, Pietro Quaglino, James E. Cleaver, Susana Ortiz-Urda
Journal: JAMA Dermatology (2014)

Airline pilots and cabin crew are occupationally exposed to higher levels of cosmic and UV radiation than the general population, but their risk of developing melanoma is not yet established.To assess the risk of melanoma in pilots and airline crew.PubMed (1966 to October 30, 2013), Web of Science (1898 to January 27, 2014), and Scopus (1823 to January 27, 2014).All studies were included that reported a standardized incidence ratio (SIR), standardized mortality ratio (SMR), or data on expected and observed cases of melanoma or death caused by melanoma that could be used to calculate an SIR or SMR in any flight-based occupation.Primary random-effect meta-analyses were used to summarize SIR and SMR for melanoma in any flight-based occupation. Heterogeneity was assessed using the χ2 test and I2 statistic. To assess the potential bias of small studies, we used funnel plots, the Begg rank correlation test, and the Egger weighted linear regression test.Summary SIR and SMR of melanoma in pilots and cabin crew.Of the 3527 citations retrieved, 19 studies were included, with more than 266 431 participants. The overall summary SIR of participants in any flight-based occupation was 2.21 (95% CI, 1.76-2.77; P < .001; 14 records). The summary SIR for pilots was 2.22 (95% CI, 1.67-2.93; P = .001; 12 records). The summary SIR for cabin crew was 2.09 (95% CI, 1.67-2.62; P = .45; 2 records). The overall summary SMR of participants in any flight-based occupation was 1.42 (95% CI, 0.89-2.26; P = .002; 6 records). The summary SMR for pilots was 1.83 (95% CI, 1.27-2.63, P = .33; 4 records). The summary SMR for cabin crew was 0.90 (95% CI, 0.80-1.01; P = .97; 2 records).Pilots and cabin crew have approximately twice the incidence of melanoma compared with the general population. Further research on mechanisms and optimal occupational protection is needed.
Effects of oxygen on acute myocardial infarction: a thermographic study in the dog
Authors: A. MALM, M. ARBORELIUS, S. BORNMYR, B. LILJA, R. L. GILL
Journal: Cardiovascular Research (1977)

An acute myocardial infarction was created in a series of dogs by ligation of a branch from the left anterior descending coronary artery. The effects on the infarction with 100% oxygen were studied by thermography in 23 animals. The changes in the infarction size were registered on polaroid photographs. In 10 dogs the infarction showed a uniform cool area, permitting accurate measurement by cutting out and weighing the black, infarcted area from the photographs. During oxygen administration 2 dogs showed a considerable increase in the cool area and 6 other dogs a moderate but significant increase. The remaining 2 dogs in this group showed non-significant change in the infarcted area. In the other 13 animals the cool area was not sufficiently uniform to allow accurate measurement. However, all the dogs in this group, except one, presented a visable increase of the cool area of varying degree. High oxygen supply does not seem to have a favourable effect on an experimentally induced acute myocardial infarction. It is known to promote a lowering of the coronary artery perfusion pressure. In addition to this, it may somehow decrease the arterial supply from the vascular bed round the ischaemic area.
Resolving the Gatekeeper Conundrum
Authors: Kevin Grumbach, Joe V. Selby, Cheryl Damberg, Andrew B. Bindman, Charles Quesenberry, Jr, Alison Truman, Connie Uratsu
Journal: JAMA (1999)

Few data are available regarding how patients view the role of primary care physicians as "gatekeepers" in managed care systems.To determine the extent to which patients value the role of their primary care physicians as first-contact care providers and coordinators of referrals, whether patients perceive that their primary care physicians impede access to specialists, and whether problems in gaining access to specialists are associated with a reduction in patients' trust and confidence in their primary care physicians.Cross-sectional survey mailed in the fall of 1997 to 12707 adult patients who were members of managed care plans and received care from 10 large physician groups in California. The response rate among eligible patients was 71%. A total of 7718 patients (mean age, 66.7 years; 32 % female) were eligible for analysis.Questionnaire items addressed 3 main topics: (1) patient attitudes toward the first-contact and coordinating role of their primary care physicians, (2) patients' ratings of their primary care physicians (trust and confidence in and satisfaction with), and (3) patient perceptions of barriers to specialty referrals. Referral barriers were analyzed as predictors of patients' ratings of their physicians.Almost all patients valued the role of a primary care physician as a source of first-contact care (94%) and coordinator of referrals (89%). Depending on the specific medical problem, 75% to 91% of patients preferred to seek care initially from their primary care physicians rather than specialists. Twenty-three percent reported that their primary care physicians or medical groups interfered with their ability to see specialists. Patients who had difficulty obtaining referrals were more likely to report low trust (adjusted odds ratio [OR], 2.7; 95% confidence interval [CI], 2.1-3.5), low confidence (OR, 2.2; 95% CI, 1.6-2.9), and low satisfaction (OR, 3.3; 95% CI, 2.6-4.2) with their primary care physicians.Patients value the first-contact and coordinating role of primary care physicians. However, managed care policies that emphasize primary care physicians as gatekeepers impeding access to specialists undermine patients' trust and confidence in their primary care physicians.
β<sub>2</sub>-Adrenergic Receptor Gene Polymorphism Is Associated with Mortality in Septic Shock
Authors: Taka-aki Nakada, James A. Russell, John H. Boyd, Rosalia Aguirre-Hernandez, Katherine R. Thain, Simone A. Thair, Emiri Nakada, Melissa McConechy, Keith R. Walley
Journal: American Journal of Respiratory and Critical Care Medicine (2009)

Rationale: The CysGlyGln haplotype of the β2-adrenergic receptor gene (ADRB2) is functional and associated with altered responses to adrenergic agonists in patients with asthma. Whether this functional haplotype alters outcome in patients receiving adrenergic agonists in septic shock is unknown.Objectives: To determine whether genetic variation of ADRB2 influences outcome in septic shock.Methods: Two cohorts of patients with septic shock were studied: a single center (St. Paul's Hospital [SPH]) cohort (n = 589) and the Vasopressin and Septic Shock Trial (VASST) cohort (n = 616). The A allele of the rs1042717 G/A polymorphism is in complete linkage disequilibrium with the CysGlyGln haplotype of ADRB2; therefore, rs1042717 was genotyped. Modulation by norepinephrine and salbutamol of IL-6 production by stimulated in vitro lymphoblastoid cells was measured by genotype.Measurements and Main Results: Patients who had the AA genotype of rs1042717 displayed increased 28-day mortality in SPH (adjusted hazard ratio, 2.23; 95% confidence interval, 1.33–3.72; P = 0.0022), and this result was replicated in VASST (adjusted hazard ratio 2.82; 95% confidence interval, 1.56–5.09; P = 0.0006). This genotypic effect was eliminated in patients treated with acute low-dose corticosteroids. In all patients, the AA genotype was associated with more organ dysfunction. Patients with the AA genotype had a higher heart rate (SPH; P < 0.05; VASST; P < 0.05) and required a higher norepinephrine dose over Days 1 through 3 (VASST; P < 0.05). The AA genotype was associated with decreased norepinephrine and salbutamol inhibition of IL-6 production by stimulated lymphoblastoid cells in vitro (P < 0.05).Conclusions: The AA genotype of ADRB2 rs1042717, identifying homozygotes for the CysGlyGln haplotype, was associated with increased mortality and more organ dysfunction in septic shock.
THE INCIDENCE OF PERI-STENT CONTRAST STAINING AFTER PACLITAXEL-COATED BALLOON DILATATION FOR IN-STENT RESTENOSIS LESIONS: A COMPARISON WITH DRUG-ELUTING STENT
Authors: Takeshi Tada, Kazushige Kadota, Seiji Habara, Hiroyuki Tanaka, Tsuyoshi Goto, Kazuaki Mitsudo
Journal: Journal of the American College of Cardiology (2014)
CONVULSIONS IN CHILDHOOD
Authors: M. G. PETERMAN
Journal: JAMA (1934)

In May 1932 I<sup>1</sup>reported the results of a study of convulsions in children. A new classification was presented with the hope of offering some assistance in the understanding and in the diagnosis of the convulsive states. At the suggestion of Lennox, a further study was made of the case histories reported, particularly in regard to the age at the time of the first convulsion. The information obtained together with the data on eighty-one additional cases necessitates a revision of my classification. This revised classification is presented on the basis of 500 cases in children who were brought to the hospital or to the office in the past nine and one-half years because of convulsive seizures. As stated in the previous report, only those cases are included in which a complete study was made. This includes a careful physical examination, usually a period of observation, a neurologic examination, a
Auditory object processing and primate biological evolution
Authors: Barry Horwitz, Fatima T. Husain, Frank H. Guenther
Journal: Behavioral and Brain Sciences (2005)

This commentary focuses on the importance of auditory object processing for producing and comprehending human language, the relative lack of development of this capability in nonhuman primates, and the consequent need for hominid neurobiological evolution to enhance this capability in making the transition from protosign to protospeech to language.
The Reported Training and Experience of Editors in Chief of Specialist Clinical Medical Journals
Authors: John Garrow
Journal: JAMA (1998)

The majority of the peer-reviewed clinical literature is edited by editors whose training in editorial matters may be limited or nonexistent. We suspect that editors are selected for their clinical or academic rather than editorial ability.To test the hypothesis that editors of medical specialist clinical journals were recruited from active clinicians rather than those with evident ability or training as editors.Anonymous mail survey to editors of the 262 peer-reviewed clinical journals that had received at least 1000 citations in the 1994 Science Citation Index.Training and editorial practices of editors.Replies were received from 191 editors (73%): in 1994 the journals they edited had 6060 (27300/1000 [maximum/minimum]) citations, 234 (740/31) source items, and an impact factor of 2.10 (18.3/0.2); nonresponders' journals had similar characteristics. Of the responding editors, 181 (95%) were part-time, 132 (69%) treated patients, and 164 (86%) were recruited by one of the following methods: election by a scientific society (49 [30%]), nomination by the previous editor (41 [25%]), or response to an advertisement (29 [18%]). There was no strong association between method of recruitment or formal editorial training and the status of the journal. Only 9% of editors in the United States send at least half of the papers to reviewers outside their own country, compared with 41% of editors in the United Kingdom and 73% in other countries, and 69% do not feel bound to follow the advice they receive concerning acceptance of papers.Clinical journals are usually edited by practicing clinicians who are self-taught part-time editors, but willing to accept further training. They usually consult 2 reviewers, but exercise independent judgment on the acceptability of papers.
S54 The Role of Pre-Receptor Glucocorticoid Metabolism in Regulating the Severity and Persistence of Murine Lung Injury
Authors: S Lax, MR Wilson, M Takata, P Stewart, D Thickett
Journal: Thorax (2012)

<h3>Introduction</h3> Acute lung injury (ALI) is a major cause of respiratory failure in the critically ill patient. With a mortality rate of 40–60%, 50% of survivors left with pulmonary impairment and no current licenced treatment there is a need for novel therapies. Our current research suggests that local steroid metabolism by alveolar macrophages is defective in ALI patients. As the predominant function of these cells is phagocytosis of apoptotic neutrophils during resolution of inflammation, we sort to investigate the effect of pre-receptor glucocorticoid metabolism in a murine model of ALI <h3>Methods</h3> Using intra-tracheal instillations of LPS (50µg), we analysed the inflammatory response in wild type (WT) mice compared to those deficient in 11β-hydroxysteroid dehydrogenase-1 (HSD-1 KO). These mice specifically lack the enzyme which converts inactive cortisone to active cortisol. Cell infiltrates and expression of several inflammatory markers within bronchial lavage fluid (BALF), as well as tissue permeability and mouse oximetry were examined to evaluate the immune response and lung damage. <h3>Results</h3> Intra-tracheal LPS challenge in WT mice induced a significant increase in lung permeability (p=0.0153), infiltrating neutrophils (p=0.0121) and recruitment of CD11c+CD11b+ monocytes (p&lt;0.0001), which was associated with significant hypoxia (p&lt;0.0001) compared to PBS-treated controls 48hrs post-instillation. The severity of acute neutrophilic inflammation and epithelial barrier defects as measured by lung permeability index were similar in WT and HSD-1 KO mice. In contrast, during resolution of LPS-induced injury (72 hrs post-instillation), HSD-1 KO mice had a significant accumulation of apoptotic neutrophils (p=0.02) and a significant increase in CD11c<sup>+</sup>CD11b<sup>+</sup> monocytes (p=0.0007) recruited into the lung compared to WT controls. Moreover, Luminex arrays revealed a significant increase in BALF levels of IL-1β (p=0.003) and dysregulation of IL-6, TNFα and CXCL1/KC during the time course. <h3>Conclusion</h3> Our data indicate that insufficient alveolar glucocorticoid metabolism augments the duration but not initial severity of lung injury, possibly via a dysregulation of apoptotic neutrophil clearance and suggests that therapies targeting defective macrophage HSD-1 expression may have value in promoting the resolution of ALI.
Is infant male circumcision an abuse of the rights of the child? Yes
Authors: Geoff Hinchley
Journal: BMJ (2007)

<h3>Background</h3> Glypican-3 (GPC3), a cell surface glycoprotein that is pathologically highly expressed in hepatocellular carcinoma (HCC), is an attractive target for immunotherapies, including chimeric antigen receptor (CAR) T cells. The serum GPC3 is frequently elevated in HCC patients due to the shedding effect of cell surface GPC3. The shed GPC3 (sGPC3) is reported to block the function of cell-surface GPC3 as a negative regulator. Therefore, it would be worth investigating the potential influence of antigen shedding in anti-GPC3 CAR-T therapy for HCC. <h3>Methods</h3> In this study, we constructed two types of CAR-T cells targeting distinct epitopes of GPC3 to examine how sGPC3 influences the activation and cytotoxicity of CAR-T cells in vitro and in vivo by introducing sGPC3 positive patient serum or recombinant sGPC3 proteins into HCC cells or by using sGPC3-overexpressing HCC cell lines. <h3>Results</h3> Both humanized YP7 CAR-T cells and 32A9 CAR-T cells showed GPC3-specific antitumor functions in vitro and in vivo. The existence of sGPC3 significantly inhibited the release of cytokines and the cytotoxicity of anti-GPC3 CAR-T cells in vitro. In animal models, mice carrying Hep3B xenograft tumors expressing sGPC3 exhibited a worse response to the treatment with CAR-T cells under both a low and high tumor burden. sGPC3 bound to CAR-T cells but failed to induce the effective activation of CAR-T cells. Therefore, sGPC3 acted as dominant negative regulators when competed with cell surface GPC3 to bind anti-GPC3 CAR-T cells, leading to an inhibitory effect on CAR-T cells in HCC. <h3>Conclusions</h3> We provide a proof-of-concept study demonstrating that GPC3 shedding might cause worse response to CAR-T cell treatment by competing with cell surface GPC3 for CAR-T cell binding, which revealed a new mechanism of tumor immune escape in HCC, providing a novel biomarker for patient enrolment in future clinical trials and/or treatments with GPC3-targeted CAR-T cells.
Chronic urticaria, arthralgia, raised erythrocyte sedimentation rate and IgG paraproteinaemia: a variant of Schnitzler's syndrome?
Authors: D. NASHAN, C. SUNDERKÖTTER, G. BONSMANN, T. LUGER, S. GOERDT
Journal: British Journal of Dermatology (2006)

Schnitzler's syndrome is a distinct disease entity characterized by the association of chronic urticaria, intermittent fever, arthralgia, elevated erythrocyte sedimentation rate and IgM macroglobulin‐aemia. We report a patient with the same symptoms, but a monoclonal IgG instead of IgM gammopathy. Histological examination of the urticarial lesions showed signs of mild leucocyto‐clastic vasculitis. Except for the different class of the monoclonal immunoglobulin, the clinical symptoms, laboratory findings and histology in this patient were identical with those in classical Schnitzler's syndrome. IgG and IgM paraproteins may be equivalent with regard to the putative pathophysiology of the disease process in Schnitzler's syndrome. We therefore suggest that the spectrum of Schnitzler's syndrome is expanded to include patients with chronic urticaria and monoclonal IgG gammopathy, as a closely related variant.
Abstract 1067: SPROUTY-2 represses E-cadherin expression and vitamin D action in colorectal cancer
Authors: Antonio Barbachano, Paloma Ordonez-Moran, Fabio Pereira, Agustin Sanchez, Jose Maria Rojas, Alberto Munoz
Journal: Cancer Research (2011)

Abstract Introduction: Colorectal cancer (CRC) is one of the highest in prevalence and mortality worldwide. Epidemiological and preclinical studies indicate that 1alpha,25-dihydroxyvitamin D3 (1,25(OH)2D3), the most active metabolite of vitamin D, and several analogs have protective effects against CRC. Previously we have reported that 1,25(OH)2D3 inhibits the proliferation and promotes the differentiation of human colon cancer cells at least in part by the induction of the adhesion molecule E-cadherin and the antagonism of the Wnt/β-catenin pathway (Pálmer et al., J. Cell Biol., 2001; Aguilera et al., Carcinogenesis, 2007). A transcriptomic analysis revealed a decrease in the RNA level of SPROUTY-2 (SPRY2), a gene that modulates signaling mediated by several tyrosine kinase receptors following treatment of human SW480-ADH cells with 1,25(OH)2D3 (5.6-fold at 4 h post-treatment; Pálmer et al., Cancer Res., 2003). Methods: Protein expression in cell lines were done by Western blot analysis. RNA expression were performed by quantitative RT-PCR. To knock-down gene expression, cells were infected with lentiviral particles containing a U6 promoter driving an shRNA targeting the respective RNA. Protein expression in human colon tumors were performed by immunofluorescence. Cell proliferation was measure by MTT assay. Results: In this study, we show that the expression of SPRY2 is inhibited by 1,25(OH)2D3 in colon cancer cells by E-cadherin-dependent and -independent mechanisms. In turn, ectopic expression of SPRY2 in SW480-ADH cells inhibits both basal and 1,25(OH)2D3-induced E-cadherin expression. SPRY2 induces ZEB-1 RNA and protein, a transcriptional repressor of CDH1/E-cadherin, and prevents the induction of an adhesive phenotype by 1,25(OH)2D3. A study of the mutual repression between SPRY2 and E-cadherin proteins revealed that their expression levels are inversely correlated in colon cancer cell lines and in xenografted tumors. In colon cancer patients, SPRY2 expression correlates also inversely with that of E-cadherin and is upregulated in invasive areas and high grade tumors. In addition, the ectopic expression of SPRY2 precludes other 1,25(OH)2D3 actions such as the antagonism of Wnt/beta-catenin signaling and the inhibition of cell proliferation. Conclusions: Our data indicate that SPRY2 is a negative regulator of E-cadherin and 1,25(OH)2D3 action and has a putative tumorigenic action in colorectal cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1067. doi:10.1158/1538-7445.AM2011-1067
Increased risk of hepatocellular carcinoma development in patients with cirrhosis and with high hepatocellular proliferation
Authors: Giorgio Ballardini, Paolo Groff, Marco Zoli, GianPaolo Bianchi, Fabrizio Giostra, Raffaella Francesconi, Marco Lenzi, Daniela Zauli, Fabio Cassani, Francesco Bianchi
Journal: Journal of Hepatology (1994)
Acute Bleeding from a Gastric Ulcer in an Infant Evaluated by Technetium-99m RBC Imaging
Authors: CARL-JOHAN EDELING, POVL B??CHLER FREDERIKSEN, ERIK ??STERGAARD, SVEND A. PEDERSEN
Journal: Clinical Nuclear Medicine (1988)

A 4-year-old boy was admitted to the hospital because of melanotic stools and abdominal pain. Anterior Tc-99m RBC imaging showed abnormal accumulation in the epigastrium. Gastroduodenoscopy showed a large stomach ulcer. The patient was treated with cimetidine and remained well until nine months later, when he was readmitted because of the same symptoms. Tc-99m RBC imaging was normal. Tc-99m pertechnetate images showed a focus of increased activity of the superior margin of the bladder. A Meckel's diverticulum was surgically located and resected.
Rate-Controlled Drug Delivery
Authors: Jan Koch-Weser, Peter Goldman
Journal: New England Journal of Medicine (1982)

THE goal of pharmaceutical research is to find drugs with desirable therapeutic properties and low risks of undesirable side effects. Drugs with such high therapeutic ratios are usually sought as new chemical entities — molecules designed to produce the desirable effects without the undesirable ones. However, another method of achieving the goal of pharmaceutical research is through the development of drug-delivery systems that achieve pharmacologic selectivity not solely on the basis of chemical structure but also on the basis of pharmacokinetic principles. Drug products achieving controlled rates of delivery offer one such approach. A few of these are already available . . .