tbuckley/cabot-search huggingface dataset:
Blocking antibodies induced by allergen‐specific immunotherapy ameliorate allergic airway disease in a human/mouse chimeric model
Authors: C. Vizzardelli, M. Gindl, S. Roos, C. Möbs, B. Nagl, F. Zimmann, V. Sexl, L. Kenner, A. Neunkirchner, G. J. Zlabinger, W. F. Pickl, W. Pfützner, B. Bohle
Journal: Allergy (2017)

Allergen-specific immunotherapy (AIT) induces specific blocking antibodies (Ab), which are claimed to prevent IgE-mediated reactions to allergens. Additionally, AIT modulates cellular responses to allergens, for example, by desensitizing effector cells, inducing regulatory T and B lymphocytes and immune deviation. It is still enigmatic which of these mechanisms mediate(s) clinical tolerance. We sought to address the role of AIT-induced blocking Ab separately from cellular responses in a chimeric human/mouse model of respiratory allergy.Nonobese diabetic severe combined immunodeficient γc-/- (NSG) mice received intraperitoneally allergen-reactive PBMC from birch pollen-allergic patients together with birch pollen extract and human IL-4. Engraftment was assessed by flow cytometry. Airway hyperresponsiveness (AHR) and bronchial inflammation were analyzed after intranasal challenges with allergen or PBS. Sera collected from patients before and during AIT with birch pollen were added to the allergen prior to intranasal challenge. The IgE-blocking activity of post-AIT sera was assessed in vitro.Human cells were detected in cell suspensions of murine lungs and spleens indicating successful humanization. Humanized mice displayed a more pronounced AHR and bronchial inflammation when challenged with allergen compared to negative controls. Post-AIT sera exerted IgE-blocking activity. In contrast to pre-AIT sera, the presence of heterologous and autologous post-AIT sera significantly reduced the allergic airway inflammation and matched their IgE-blocking activity determined in vitro.Our data demonstrate that post-AIT sera with IgE-blocking activity ameliorate allergic airway inflammation in a human/mouse chimeric model of respiratory allergy independently of AIT-induced cellular changes.
High plasma 25-hydroxyvitamin D and high risk of nonmelanoma skin cancer: a Mendelian randomization study of 97 849 individuals
Authors: U.C. Winsløw, B.G. Nordestgaard, S. Afzal
Journal: British Journal of Dermatology (2017)

High plasma 25‐hydroxyvitamin D [25(OH)D] concentration has been associated observationally with a high risk of nonmelanoma skin cancer (NMSC), whereas many studies suggest that vitamin D could have a protective effect against cancer. The true association between vitamin D and risk of skin cancer remains unclear. To test the hypothesis that genetically high plasma 25(OH)D protects against NMSC. We included 103 084 individuals from the Danish general population, of whom 35 298 had plasma 25(OH)D measured and 97 849 were genotyped for four genetic variants near DHCR7 and CYP2R1 associated with 25(OH)D concentrations. We tested the association between plasma 25(OH)D levels and NMSC observationally and between genetically determined 25(OH)D levels and NMSC, using an instrumental variable approach. Multivariate‐adjusted hazard ratios of NMSC were 3·27 [95% confidence interval (CI) 2·22–4·84] for plasma 25(OH)D ≥ 50 nmol L−1 vs. < 25 nmol L−1. Genetic variants around DHCR7 and CYP2R1 were associated with up to 8·2 nmol L−1 higher 25(OH)D concentrations (F = 314). The odds ratio (OR) for a genetically determined 20 nmol L−1 higher plasma 25(OH)D was 1·11 (95% CI 0·91–1·35) for NMSC, with a corresponding observational multivariable adjusted OR of 1·13 (95% CI 1·10–1·17). Genetically determined high 25(OH)D levels did not appear to protect against NMSC, whereas high plasma 25(OH)D concentrations were associated with an observational high risk of NMSC. Thus, the observational association likely reflects confounding by sun exposure rather than causality.
Handheld Echocardiography
Authors: Mohammed A. Chamsi-Pasha, Partho P. Sengupta, William A. Zoghbi
Journal: Circulation (2017)

Echocardiography is the primary imaging modality for diagnosing cardiac conditions. Over the past 2 decades, technological advancements have resulted in the emergence of miniaturized handheld ultrasound equipment that is compact and battery operated, and handheld echocardiography can be readily performed at the point of care with reasonable image quality. The simplicity of use, availability at the patient’s bedside, easy transportability, and relatively low cost have encouraged physicians to use these devices for prompt medical decision making. As a consequence, the use of handheld echocardiography is on the rise even among nonechocardiographers (intensivists, emergency care physicians, internists, and medical students). One of the real utilities of ultrasound-augmented clinical diagnosis is in evaluating patients efficiently and selecting patients for appropriate downstream diagnostic testing including comprehensive echocardiography. Although clinical evidence supports the use of handheld devices in various clinical settings and by different users, proficiency in point-of-care ultrasound requires dedicated training in both performance and interpretation. This review summarizes the existing literature on the use of handheld echocardiography in conducting focused cardiac examinations: its training requirements, challenges, opportunities, and future perspectives in the care of the cardiovascular patient.
The efficacy and onset risk of interstitial lung disease of nivolumab in elderly (75 years old or older) patients with non-small cell lung cancer
Authors: A. Tamiya, M. Tamiya, K. Nakahama, Y. Taniguchi, T. Shiroyama, S-I Isa, T. Inoue, K. Okishio, K. Nishino, T. Kumagai, H. Suzuki, T. Hirashima, F. Imamura, S. Atagi
Journal: Annals of Oncology (2017)
P2.03b-030 Retrospective Review Clinical Use of a cfDNA Blood Test for Identification of Targetable Molecular Alterations in Patients with Lung Cancer
Authors: Hai Tran, Jianjun Zhang, Marya Vasquez, Frank Fossella, George Simon, Anne Tsao, Don Lynn Gibbons, Yasir Elamin, Kimberly Banks, Richard Lanman, Vassiliki Papadimitrakopoulou, John Heymach
Journal: Journal of Thoracic Oncology (2017)
Abstract 21289: The Presence of Warning Labels on AEDs Decreases the Odds of Device Use by Lay Rescuers
Authors: Elliot Carhart, Aaron Murray
Journal: Circulation (2017)

Background: Significant resources have been invested in public access defibrillation programs; however, the true rate of lay rescuer AED use remains unknown. Even in circumstances where the device location is known, numerous potential barriers to lay rescuer use remain. Among these is the presence of warning labels (e.g. “Trained Responders Only”), which may induce anxiety and reinforce a state of low self-efficacy. The purpose of this study was to determine if the presence of warning labels on or near public access defibrillators influences lay rescuer self-reported willingness to utilize such devices in an emergency scenario. Methodology: This prospective cross-sectional survey study utilized a simple random sample of adults age 18-65. Healthcare providers were excluded. Participants were asked a series of questions regarding their past experiences with CPR/AED training and were then shown a static picture of an AED. Two versions of the picture were alternated between participants in a random fashion with half of participants seeing a warning label on the device. Participants were asked about their willingness to utilize the device if faced with a victim of cardiac arrest. Comparisons were made between participants in the two groups to determine the potential influence of warning labels on self-reported willingness to render aid. Reported experience and demographics (e.g. age, gender, income, education, etc.) were used for control purposes. Results: Most participants (71%, N=500) indicated a willingness to assist, but fewer participants were willing to assist when presented with a warning label (65%) then when no such label was present (75%). The odds of lay rescuer AED use was significantly decreased in the presence of a warning label (OR=0.51, 95% CI=0.34, 0.75). Conclusion: The presence of warning labels on an AED decreased the odds of device use by lay rescuers, but it is unknown if actual human performance would be consistent with such responses in the face of an actual emergency.
Malattia dei legionari associata al viaggio in Europa: 1997 e 1998
Authors: E Slaymaker, C Joseph, C L R Bartlett
Journal: Eurosurveillance (1999)

Il sistema europeo per la sorveglianza sulla malattia dei legionari associata ai viaggi (European Surveillance Scheme for Travel Associated Legionnaires Disease) e stato creato, nel 1987, dall'European Working Group on Legionella Infections (EWGLI), allo scopo di identificare i casi di infezione da legionella nei viaggiatori di ritorno e per rilevare focolai epidemici e cluster della malattia dei legionari. Il programma e stato inizialmente coordinato dallo Swedish Institute for Infectious Disease Control (SIIDC) di Stoccolma, dove e stata finanziato dall'Organizzazione Mondiale per la Sanita (OMS). Nel 1993, si e spostato nella sistemazione attuale, presso il Public Health Laboratory Service (PHLS) Communicable Disease Surveillance Centre (CDSC) di Londra, spostamento che e coinciso con l'inizio del finanziamento da parte della Direzione Generale V della Commissione Europea.
P2.05-007 Sterotactic-Body-Radiotherapy for Early-Lung Cancer: Is FDG-PET/TC a Predictor of Outcome?
Authors: N. Farré, M.D.V. Camacho, A. Fernández, J. Balart, G. Sancho, K. Majercakova, E. Acosta, P. Carrasco, M. Majem, A. Giménez, E. Martínez, J.C. Trujillo, A. Torrego, V. Pajares, J. Craven-Bartle
Journal: Journal of Thoracic Oncology (2017)
Liver fibrosis is associated with cutaneous inflammation in the imiquimod-induced murine model of psoriasiform dermatitis
Authors: P. Vasseur, M. Pohin, J.F. Jégou, L. Favot, N. Venisse, J. Mcheik, F. Morel, J.C. Lecron, C. Silvain
Journal: British Journal of Dermatology (2017)

Psoriasis exhibits several extracutaneous manifestations. Little is known about hepatic parameters specifically associated with psoriasis. To study whether psoriasiform dermatitis is associated with liver injury. We studied liver parameters of inflammation and fibrosis in a murine model of psoriasiform dermatitis induced by topical application of imiquimod for 9 weeks. Topical treatment with imiquimod induced a form of psoriasiform dermatitis reminiscent of the human disorder, characterized by thickened and scaly skin, psoriasiform epidermal hyperplasia, altered keratinocyte differentiation and cutaneous overexpression of interleukin‐17A. Mice with dermatitis displayed hepatitis, as shown by elevation of plasma transaminase levels, as well as portal and periportal hepatitis, characterized by T‐lymphocyte (CD3ε+) and polymorphonuclear cell (Gr1+) infiltrates. The hepatitis progressed towards liver fibrogenesis, as shown by excessive Sirius red staining, which is consistent with the expression of α‐smooth muscle actin by hepatic stellate cells. These results indicate that liver inflammation and fibrosis are associated with experimental psoriasiform dermatitis. Our results suggest that psoriatic inflammation may be associated with specific liver injury.
Intergenerational capital flows are central to fitness dynamics and adaptive evolution in humans
Authors: Ian J. Rickard
Journal: Behavioral and Brain Sciences (2017)

Abstract Human fitness dynamics are uniquely and profoundly governed by the flow of capital to subsequent generations. Low socioeconomic status individuals may possess limited capacity to direct capital to descendants and may respond to such constraints adaptively or maladaptively. Mitigation of capital constraints may provide practicable routes to alleviation of the behavioural constellation of deprivation.
Nurses’ roles and responsibilities in the provision of early palliative care: A grounded theory study.
Authors: Shan Darrel Mohammed, Pamela Savage, Camilla Zimmermann
Journal: Journal of Clinical Oncology (2017)

98 Background: The benefits of providing early palliative care (EPC) are well researched. Few studies have explored the knowledge and skill used by nurses to help patients and families transition to and receive palliative care. In this study, we examine the roles and responsibilities of nurses in the provision of EPC and explore some of the barriers and facilitators they encounter as part of this complicated work. Methods: We drew on constructivist grounded theory to guide our methods and analysis. Nurses were recruited from several ambulatory care clinics in a comprehensive cancer center in Ontario, Canada. Nurses who participated in the study completed semi-structured interviews seeking to examine the roles, responsibilities, knowledge, and skills they utilized to provide EPC. Results: Ten nurse practitioners, six staff nurses, and four advanced practice nurses completed interviews for a total of 20 participants. Participants practiced in a variety of settings such as head and neck, breast, pancreatic, and hematology. The core category Brokering Palliative Care includes three subcategories: (1) Moving backwards and forward – stepping back to assess patients’ willingness to hear about EPC and then proceeding by selling the benefits of palliative to improving everyday function; (2) Addressing misconceptions and stigma – dealing with patients’ assumptions about palliative care as diminishing hope and accelerating the end of life; and (3) Advocating with the interprofessional team – bringing patient concerns forward to the team, managing interprofessional dynamics, and seeding the process of referral to EPC. Conclusions: Oncology nurses play a central role by brokering EPC for patients with serious cancers and their families. They draw on their proximity to patients, relational and communication capabilities, care coordination skills, and advocacy abilities. Brokering palliative care is conditional on nurses’ comfort level, experience, workload, and relationships with other healthcare professionals, especially oncologists. Moreover, the brokering work of nurses must be enacted within the boundaries of the nursing role and their relative position within the healthcare system.
Mutant-IDH1-dependent chromatin state reprogramming, reversibility, and persistence
Authors: Sevin Turcan, Vladimir Makarov, Julian Taranda, Yuxiang Wang, Armida W. M. Fabius, Wei Wu, Yupeng Zheng, Nour El-Amine, Sara Haddock, Gouri Nanjangud, H. Carl LeKaye, Cameron Brennan, Justin Cross, Jason T. Huse, Neil L. Kelleher, Pavel Osten, Craig B. Thompson, Timothy A. Chan
Journal: Nature Genetics (2017)
Oesophageal Cancer Surgery
Authors: C C McGuigan
Journal: Journal of the Royal Society of Medicine (2001)

Mr Britton presents a plausible option for the reorganization of oesophageal cancer services (October 2001 JRSM, pp. 500-501). However, the final sentence undermines the overall plan particularly with respect to the single-handed or low-volume specialist. The proposed scheme, he says, ‘does not represent a threat to any specialist in the field provided his or her results withstand local and national review’.

A corollary of low caseload volume is that results will be unlikely to be amenable to meaningful statistical review. A large number of years of data will be needed, ensuring a long delay to closure of the audit loop. The way ahead is surely to review operators' processes rather than outcomes of care. Thus, participation in effective prospective audit and multidisciplinary discussion of cases are surely clinical governance issues as valid as, and more timeous than, outcome.

Regular multidisciplinary team discussion has the further advantage of facilitating peer review of management decisions before they are acted on, and thus might effectively form ‘pre-prospective audit’. The benefit to both operator and patient is clear: sanctioning of treatment decisions by a responsible body of peers, based on regional as well as local experience.
Outcomes of Children and Adolescents with Advanced Hereditary Medullary Thyroid Carcinoma Treated with Vandetanib
Authors: Ira L. Kraft, Srivandana Akshintala, Yuelin Zhu, Haiyan Lei, Claudia Derse-Anthony, Eva Dombi, Seth M. Steinberg, Maya Lodish, Steven G. Waguespack, Oxana Kapustina, Elizabeth Fox, Frank M. Balis, Maria J. Merino, Paul S. Meltzer, John W. Glod, Jack F. Shern, Brigitte C. Widemann
Journal: Clinical Cancer Research (2017)

Abstract Purpose: Vandetanib is well-tolerated in patients with advanced medullary thyroid carcinoma (MTC). Long-term outcomes and mechanisms of MTC progression have not been reported previously. Experimental Design: We monitored toxicities and disease status in patients taking vandetanib for hereditary, advanced MTC. Tumor samples were analyzed for molecular mechanisms of disease progression. Results: Seventeen patients [8 male, age 13 (9–17)* years] enrolled; 16 had a RET p.Met918Thr germline mutation. The duration of vandetanib therapy was 6.1 (0.1–9.7+)* years with treatment ongoing in 9 patients. Best response was partial response in 10, stable disease in 6, and progressive disease in one patient. Duration of response was 7.4 (0.6–8.7+)* and 4.9 (0.6–7.8+)* years in patients with PR and SD, respectively. Six patients died 2.0 (0.4–5.7)* years after progression. Median progression-free survival (PFS) was 6.7 years [95% confidence interval (CI): 2.3 years–undefined] and 5-year overall survival (OS) was 88.2% (95% CI: 60.6%–96.9%). Of 16 patients with a RET p.Met918Thr mutation, progression-free survival was 6.7 years (95% CI: 3.1–undefined) and 5-year overall survival was 93.8% (95% CI: 63.2%–99.1%). No patients terminated treatment because of toxicity. DNA sequencing of tissue samples (n = 11) identified an increase in copy number alterations across the genome as a potential mechanism of drug resistance [*median (range)]. Conclusions: This study demonstrates that vandetanib is safe and results in sustained responses in children and adolescents with hereditary MTC. Our preliminary molecular data suggest that an increase in copy number abnormalities may be associated with tumor progression in hereditary MTC patients treated with vandetanib. Clin Cancer Res; 24(4); 753–65. ©2017 AACR.
Abstract 21108: Early Evidence That the Female Genome Does Matter for Acute Coronary Syndrome Risk
Authors: Jennifer R Dungan, Xuejun Qin, Abanish Singh, William E Kraus, Elizabeth Hauser
Journal: Circulation (2017)

Introduction: Women of all ethnicities have the highest rates of Acute Coronary Syndrome (ACS) misdiagnosis, delayed treatment, and ACS-related near-term mortality. Known physiologic differences and traditional risk factors have failed to fully explain these ACS disparities among women. Our knowledge gap of genomic variation underlying women’s unique ACS phenotypes means that there is no female-derived ACS risk biomarker that reflects female-specific biology and phenotype features. Among 510 women, we previously identified 122 SNPs within 14 genomic regions that significantly predicted ‘survivorship in CAD’ (all-cause mortality among coronary artery disease cases; p&lt;10-5); none of which were significant in males or controls. Given the recent recognition of sex as a biological variable, our purpose was to identify female-specific genomic markers that predict ACS case status. Methods: We performed secondary case-control analysis for 1,382 females (796 ACS cases/586 non-ACS controls) of the Duke Catheterization Genetics (CATHGEN) Study (Illumina Human Infinium 1.0 platform). ACS was defined as having no previous MI history plus either documented unstable angina pain type or incident myocardial infarction. We employed logistic regression models of ACS case status for each SNP separately, assuming additive genetic models, and controlling for age and 3 PCAs of ethnicity. Results: Twenty-three SNPs among 3 biologically relevant candidates ( LPAGT1 , SLC9A9 , &amp; RAP1GAP2 ) significantly predicted women’s ACS (range p=7.43x10 -5 - 0.05) with positive and negative odds ratios observed. LPGAT1 is involved in cardiolipin synthesis; SLC9A9 is involved in endosome recycling; and, RAP1GAP2 regulates secretion of dense granules from platelets at endothelial damage sites. Additionally, 74 SNPs within the 11 novel survivorship with CAD candidates significantly predicted ACS (p&lt;0.05). Conclusions: We demonstrate proof of principal for unique , female-specific genomic effects on ACS case status; and, shared genomic variation with ACS and survivorship in CAD among women. Validation of this work is required. Future research is needed to identify female-derived genomic markers that may uniquely characterize women’s ACS and coronary disease expression.
Medical Specialty Board Finances
Authors: Lois Margaret Nora
Journal: JAMA (2017)

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