tbuckley/cabot-search huggingface dataset:
Is Positron Emission Tomography Scanning changing the Management of Upper Gastrointestinal Malignancies?
Authors: M Doyle, C Moran, GP McEntee
Journal: Endoscopy (2004)

Aims: Spiral CT is the current gold standard for staging hepatic, pancreatic and gastric malignancies, with gadolinium MRI also used to determine the resectability of hepatic tumours. As PET has more recently been used to identify patients with stage four disease, we wished to determine it's effect on the surgical management of hepatic, pancreatic and gastric malignancies.
Outcomes in Transplant Eligible Multiple Myeloma African American Patients Appear Similar to Caucasian Patients
Authors: Megan H Jagosky, Kyle L Madden, Myra M Robinson, Blake B Goodbar, Manisha Bhutani, Preeya Patel, Rupali Bose, Jill Eddy, Sarah LeStrange, Candice G Roth, Lynn S Sanders, James T Symanowski, Tammy D Cogdill, Dragos Plesca, Belinda R. Avalos, Edward A. Copelan, Saad Z Usmani
Journal: Blood (2016)
Most London hospitals and clinics exceed air pollution limits
Authors: Pauline Castres, David Dajnak, Melissa Lott, Nick Watts
Journal: BMJ (2017)

More than half of London’s NHS facilities are blanketed in air pollution that is above legal limits, shows new analysis jointly published by King’s College London and the UK Health Alliance on Climate Change. Health professionals are having to care for their patients in environments where air pollution could aggravate existing illnesses. NHS staff are among those exposed to this health risk, but it is patients’ health that is of most concern, especially children’s.

Air pollutants, and in particular fine particles and nitrogen dioxide, damage our health throughout our lifetime, from before birth and well into old age. Robust scientific evidence has linked poor air quality to an increased prevalence of ischaemic heart disease, cerebrovascular accidents, chronic obstructive pulmonary disease, asthma, and lung cancer.1 Emerging evidence indicates a link between exposure to air pollution and type 2 diabetes, obesity, and dementia.2

Toxins and particulates are pumped into the air by our cars and power plants, damaging our health in the short term. In the long term the same activities produce …
Patient Outcomes With STEMI Caused by Aneurysmal Coronary Artery Disease and Treated With Primary PCI
Authors: Gianmarco Iannopollo, Marco Ferlini, Marek Koziński, Maurizio Ferrario Ormezzano, Gabriele Crimi, Ludovico Lanfranchi, Rita Camporotondo, Luigi Oltrona Visconti, Gaetano Maria De Ferrari, Stefano De Servi
Journal: Journal of the American College of Cardiology (2017)
Interpreting Lymphocyte Reconstitution Data From the Pivotal Phase 3 Trials of Alemtuzumab
Authors: David Baker, Samuel S. Herrod, Cesar Alvarez-Gonzalez, Gavin Giovannoni, Klaus Schmierer
Journal: JAMA Neurology (2017)

<h3>Importance</h3> Alemtuzumab, a CD52-depleting monoclonal antibody, effectively inhibits relapsing multiple sclerosis (MS) but is associated with a high incidence of secondary B-cell autoimmunities that limit use. These effects may be avoided through control of B-cell hyperproliferation. <h3>Objective</h3> To investigate whether the data describing the effect of alemtuzumab on lymphocyte subsets collected during the phase 3 trial program reveal mechanisms explaining efficacy and the risk for secondary autoimmunity with treatment of MS. <h3>Design, Setting, and Participants</h3> Lymphocyte reconstitution data from regulatory submissions of the pivotal Comparison of Alemtuzumab and Rebif Efficacy in Multiple Sclerosis I and II (CARE-MS I and II) trials were obtained from the European Medicines Agency via Freedom of Information requests. Data used in this study were reported from June 22 to October 12, 2016. <h3>Main Outcomes and Measures</h3> Tabulated data from T- and B-lymphocyte subset analysis and antidrug antibody responses were extracted from the supplied documents. <h3>Results</h3> Alemtuzumab depleted CD4<sup>+</sup>T cells by more than 95%, including regulatory cells (−80%) and CD8<sup>+</sup>T cells (&gt;80% depletion), which remained well below reference levels throughout the trials. However, although CD19<sup>+</sup>B cells were initially also depleted (&gt;85%), marked (180% increase) hyperrepopulation of immature B cells occurred with conversion to mature B cells over time. These lymphocyte kinetics were associated with rapid development of alemtuzumab-binding and -neutralizing antibodies and subsequent occurrence of secondary B-cell autoimmunity. Hyperrepopulation of B cells masked a marked, long-term depletion of CD19<sup>+</sup>memory B cells that may underpin efficacy in MS. <h3>Conclusions and Relevance</h3> Although blockade of memory T and B cells may limit MS, rapid CD19<sup>+</sup>B-cell subset repopulation in the absence of effective T-cell regulation has implications for the safety and efficacy of alemtuzumab. Controlling B-cell proliferation until T-cell regulation recovers may limit secondary autoimmunity, which does not occur with other B-cell–depleting agents.
A Cluster of Crohn's Disease in Ballybrack – Fact or Fiction?
Authors: D O'Donovan, D Keegan, G McEvoy, H Mulcahy, D O'Donoghue
Journal: Endoscopy (2004)

Background: Clustering of Crohn's Disease (CD) although uncommon is recognised. The pathogenesis of CD is thought to involve an interaction between genetic and environmental factors; the latter may be important in clustering. Residents of Ballybrack raised the hypothesis that there was an increased prevalence of CD in that area.
The Efficacy of JAK2 Inhibitor in Heavily Pretreated Classical Hodgkin Lymphoma: A Prospective Pilot Study of Ruxolitinib in Relapsed or Refractory Classical Hodgkin Lymphoma and Primary Mediastinal Large B-Cell Lymphoma
Authors: Seok Jin Kim, Hye Jin Kang, Shin Dong-Yeop, Ho Sup Lee, Sung Yong Oh, Ho-Jin Shin, Dok Hyun Yoon, Jung Yong Hong, Jee Hyun Kong, Kana Sakamoto, Young Hyeh Ko, Kengo Takeuchi, Cheolwon Suh, Won Seog Kim
Journal: Blood (2016)
Does leisure time physical activity protect against low back pain? Systematic review and meta-analysis of 36 prospective cohort studies
Authors: Rahman Shiri, Kobra Falah-Hassani
Journal: British Journal of Sports Medicine (2017)

Background There are plausible mechanisms whereby leisure time physical activity may protect against low back pain (LBP) but there have been no quality systematic reviews and meta-analyses of the subject. Objective This review aims to assess the effect of leisure time physical activity on non-specific LBP. Methods Literature searches were conducted in PubMed, Embase, Web of Science, Scopus and Google Scholar databases from their inception through July 2016. Methodological quality of included studies was evaluated. A random-effects meta-analysis was performed, and heterogeneity and publication bias were assessed. Results Thirty-six prospective cohort studies (n=158 475 participants) qualified for meta-analyses. Participation in sport or other leisure physical activity reduced the risk of frequent or chronic LBP, but not LBP for &gt; 1 day in the past month or past 6–12 months. Risk of frequent/chronic LBP was 11% lower (adjusted risk ratio (RR)=0.89, CI 0.82 to 0.97, I 2 =31%, n=48 520) in moderately/highly active individuals, 14% lower (RR=0.86, CI 0.79 to 0.94, I 2 =0%, n=33 032) in moderately active individuals and 16% lower (RR=0.84, CI 0.75 to 0.93, I 2 =0%, n=33 032) in highly active individuals in comparison with individuals without regular physical activity. For LBP in the past 1–12 months, adjusted RR was 0.98 (CI 0.93 to 1.03, I 2 =50%, n=32 654) for moderate/high level of activity, 0.94 (CI 0.84 to 1.05, I 2 =3%, n=8549) for moderate level of activity and 1.06 (CI 0.89 to 1.25, I 2 =53%, n=8554) for high level of activity. Conclusions Leisure time physical activity may reduce the risk of chronic LBP by 11%–16%. The finding, however, should be interpreted cautiously due to limitations of the original studies. If this effect size is proven in future research, the public health implications would be substantial.
Abstract 15003: Spatiotemporal Stability of Public Cardiac Arrests
Authors: Derya Demirtas, Steven C Brooks, Laurie J Morrison, Timothy C Chan
Journal: Circulation (2015)

Background: Public access automated external defibrillator (AED) deployment and community cardiopulmonary resuscitation (CPR) programs should target geographical areas with high risk of out-of-hospital cardiac arrest (OHCA). Although these long-term, location-based interventions implicitly assume that the geographical OHCA risk remains stable over time, there is a paucity of evidence to support this assumption. Objective: To determine whether geographic OHCA risk is stable over time in a Canadian urban setting. Methods: We identified all atraumatic public-location OHCAs in Toronto, Canada from Jan. 2006 – Dec. 2014 and allocated each of them to one of the 140 neighborhoods defined by the City of Toronto. We then calculated the intra-class correlation (ICC) to measure the relative variability of OHCA counts within and between neighbourhoods over time. Results: We identified 2506 atraumatic public OHCAs. The figure shows that the average number of public OHCAs in Toronto was 278.4 (±41.4) per year. The highest-risk neighborhood had an average number of 12.9 OHCAs per year and remained the highest-risk neighborhood during six of the nine years. The four lowest-risk neighborhoods each had a rate of 0.1 OHCA per year. The ICC value was 0.67 [95% CI, 0.61 to 0.73], indicating that there was less year-to-year variation within the same neighborhood (i.e., more temporal stability) and more variation between neighborhoods. Conclusion: The OHCA rate in Toronto is stable at the neighborhood level over time. High-risk neighborhoods tend to remain high-risk, which supports focusing public health resources in those areas to increase the efficiency of these scarce resources and improve long-term impact.
Hospitals and GP surgeries may be targets for terrorists, police warn
Authors: Ingrid Torjesen
Journal: BMJ (2017)

The UK police counterterrorism unit has warned hospitals and general practices that they may be targets for terrorist attacks, in updated guidance on protecting crowded places from a terrorist attack issued on 8 June.1

The release of the updated Crowded Places Guidance by the National Counter Terrorism Security Office came after a series of terrorist attacks on crowded places this year at London Bridge, Westminster Bridge, and a concert at Manchester Arena.

The document, which gives advice on ramping up the security of all crowded settings, has a specific section dedicated to healthcare. It tells health professionals, “It is possible that your hospital or surgery for example could be the target of a terrorist incident. This might include having to deal …
Memory-phenotype CD4 <sup>+</sup> T cells spontaneously generated under steady-state conditions exert innate T <sub>H</sub> 1-like effector function
Authors: Takeshi Kawabe, Dragana Jankovic, Shuko Kawabe, Yuefeng Huang, Ping-Hsien Lee, Hidehiro Yamane, Jinfang Zhu, Alan Sher, Ronald N. Germain, William E. Paul
Journal: Science Immunology (2017)

Conventional CD4+ T cells are composed of naïve, pathogen-specific memory, and pathogen-independent memory-phenotype (MP) cells under steady state. Naïve and pathogen-specific memory cells play key roles in adaptive immunity, whereas the homeostatic mechanisms regulating the generation of MP cells and their biological functions are unclear. We show that MP cells are autonomously generated from peripheral naïve cells in the absence of infectious stimulation in a T cell receptor (TCR)- and CD28-dependent manner. We further demonstrate that MP cells contain a T-bethi subpopulation that is continuously generated by environmental interleukin-12 (IL-12) and rapidly produces interferon-γ (IFN-γ) in response to IL-12 in the absence of pathogen recognition. These cells can provide nonspecific host resistance against Toxoplasma gondii infection while enhancing the adaptive CD4+ T cell responses. Together, these findings reveal that MP cells are continuously generated from naïve precursors and have a previously undescribed innate immune function by which they produce an early, T helper cell type 1 (TH1)-like protective response against pathogens.
Primary Amebic Meningoencephalitis.
Authors: Richard J. Duma
Journal: Annals of Internal Medicine (1970)

Meeting Abstracts1 May 1970Primary Amebic Meningoencephalitis.Richard J. Duma, M.D.Richard J. Duma, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-72-5-798_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptThe protozoological, epidemiological, clinical, and pathological findings in four patients with culturally proven fatal primary amebic meningoencephalitis were studied before and after death. In each patient the responsible pathogen was a free-living ameboflagellate of the genusNaegleria, probablyN. gruberi. Based on histories obtained antemortem, infections were contracted on July 23, 1967, August 4, 1968, and July 3 and 4, 1969; the source of each was traced to one of three fresh-water public swimming lakes located within a radius of 6 miles in Chesterfield County, Virginia. The incubation period was 5 to 6 days. The patients' ages were 14, 15,... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Richmond, Va. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 May 1970Volume 72, Issue 5Page: 798-798KeywordsMeningoencephalitisPathogensSwimming Issue Published: 1 May 1970 PDF downloadLoading ...
Final results of 4-monthly screening in the UK Familial Ovarian Cancer Screening Study (UKFOCSS Phase 2).
Authors: Adam N Rosenthal, Lindsay Fraser, Susan Philpott, Ranjit Manchanda, Philip Badman, Richard Hadwin, D. Gareth Evans, Diana Eccles, Steven James Skates, James Mackay, Usha Menon, Ian Jacobs
Journal: Journal of Clinical Oncology (2013)

5507^ Background: Annual transvaginal ultrasound (TVS) and serum CA125 screening for women at high-risk of Ovarian/Fallopian tube cancer (OC/FTC) in Phase 1 of UKFOCSS lacked sensitivity for early stage disease but downstaged disease volume and may have improved optimal debulking rates. More frequent screening might provide greater benefits. Here we report the final results of 4-monthly screening in one of the largest such trials worldwide. Methods: Between 14/06/2007 and 29/03/2012, 4,531 women at an estimated ≥10% lifetime risk of OC/FTC were recruited and screened by 42 UK centres for 14,263 women screen years. Screening comprised 4-monthly CA125 tests analysed by a risk of ovarian cancer algorithm, adjusted for menopausal status. TVS was annual in those with normal algorithm results, but was triggered sooner if results were non-normal. Women with suspicious scan and/or algorithm results were referred for consideration of surgical intervention. Participants were followed prospectively by centres, questionnaire and national cancer registries. Data was censored 365 days after final screen, withdrawal or death. Clinical trial information: 32794457.
Association of plasma exosomal mRNA changes with long-term durable response to ipilimumab (IPI) in metastatic melanoma (MM) patients.
Authors: Christine M. Coticchia, Ryan J. Sullivan, James D. Hurley, Lan Hu, Donald P. Lawrence, Keith Flaherty, Shauna M. Blackmon, Graham Brock, Vincent J. O'Neill, Johan Skog
Journal: Journal of Clinical Oncology (2016)

3037 Background: Identifying MM patients who will achieve long-term benefit from immunotherapy is an unmet need. We investigated using exosomal RNA (exoRNA) as a liquid biopsy approach to monitor response and aid in selecting therapy. Exosomes are released from cells, including tumor cells and can be extracted from biofliuds enabling non-invasive monitoring of a patient’s tumor status in real-time. However, the response signature must be identified against a background of exosomes from normal processes, such as exosomes released during maturation of reticulocytes. We have developed the ExosomeDx Depletion/Enrichment (EDDE) platform to remove non-relevant exosomes from plasma. Using EDDE, we identified a plasma exoRNA signature associated with durable response to IPI. Methods: Plasma was obtained from 16 MM patients before IPI (baseline) and during the first 2-4 weeks of treatment (week 2/4). Response to therapy was determined by RECIST. Patients with > 12 months PFS from start of IPI were classified as durable responders (DR) and compared to all other patients (non-DR). Matched patient plasma samples at baseline and week 2/4 were processed both with a total exoRNA extraction method as well as with the EDDE platform to evaluate the strength of the signatures after enrichment. The exoRNA was analyzed by TaqMan qPCR on the OpenArray platform, examining the expression level of 607 mRNAs in each sample. Results: To date, we have evaluated a signature of IPI treated patients (n = 16). Of the 607 genes examined, the EDDE platform revealed 8 genes significantly increased at week 2/4 in most ( ≥ 3/5) of DR patients and decreased in the majority of non-DR patients. The signature includes immune-related and inflammatory signaling ligands and receptors such as BDKRB1, BMP8B, CNTFR and TNFSF11. In contrast, using the same gene selection criteria, total exoRNA revealed no significantly dysregulated genes. Conclusions: The EDDE platform depletes normal exosomes from plasma increasing the power to discriminate early exoRNA changes associated with DR to IPI. Our ongoing experiments are identifying exoRNA signatures associated with long-term PFS of MM patients treated with anti-PD-1 therapy.
The contribution of rare variants to risk of schizophrenia in individuals with and without intellectual disability
Authors: Tarjinder Singh, James T R Walters, Mandy Johnstone, David Curtis, Jaana Suvisaari, Minna Torniainen, Elliott Rees, Conrad Iyegbe, Douglas Blackwood, Andrew M McIntosh, Georg Kirov, Daniel Geschwind, Robin M Murray, Marta Di Forti, Elvira Bramon, Michael Gandal, Christina M Hultman, Pamela Sklar, Aarno Palotie, Patrick F Sullivan, Michael C O'Donovan, Michael J Owen, Jeffrey C Barrett
Journal: Nature Genetics (2017)
Evaluation of radiomic features on baseline CT scan to predict clinical benefit for pemetrexed based chemotherapy in metastatic lung adenocarcinoma.
Authors: Sagar Rakshit, Mahdi Orooji, Niha Beig, Mehdi Alilou, Nathan A. Pennell, James Stevenson, Marc A. Shapiro, Anant Madabhushi, Vamsidhar Velcheti
Journal: Journal of Clinical Oncology (2016)

11582 Background: Many patients receiving standard of care pemetrexed based platinum doublet followed by maintenance pemetrexed for lung adenocarcinoma do not receive clinical benefit. Currently there are no clinically validated biomarkers to identify patients who benefit from these treatments. We conducted a retrospective proof-of concept study to identify predictive computer extracted image features from pre-treatment computed tomographic (CT) scans. Methods: Pre-chemotherapy CT scans were obtained for 105 lung adenocarcinoma patients treated with pemetrexed based chemotherapy at the Cleveland Clinic from 2004-2010. Clinical benefit was defined as patients with an objective response or more than 12 cycles of pemetrexed therapy. We identified and annotated CT images in 2 groups- 46 with clinical benefit and 59 without clinical benefit. After adjusting for image quality and CT filters, 32 and 33 patients remained for final analysis in the 2 groups respectively. A total of 1108 radiomic features including both textural and shape features of the lung nodule as well as the peritumoral region were investigated. The features were evaluated and ranked in their ability to discriminate between the 2 groups in conjunction with a linear discriminant classifier, both in terms of univariate and multivariate analysis. Results: Two of the top 3 ranked features were from within the nodule and the third was from within the peritumoral area. Mean of Sum Average, a co-occurrence based texture measure within the nodule was the most discriminating feature. Combination of features within and around the nodule yielded even higher AUC values (See Table for combination of best features). Conclusions: Texture and shape features extracted from within and around the lung nodule on CT images could identify patients who could potentially benefit from pemetrexed based chemotherapy. Further validation in a larger retrospective, multi-institutional cohort is needed. Feature Vector Area Under ROC Curve ± Standard Deviation Mean of Intratumoral Sum Average(1) 69.5% ± 3.0% 1+Minimum of Intratumoral Law L5xE5(2) 75.2% ± 3.2% 1+2+Mean of Peritumoral Law S5xW5(3) 77.6% ± 1.9%
Vaccination alone will not halt the next global pandemic
Authors: Allen G Ross
Journal: BMJ (2017)

A US$1-billion initiative was launched in January 2017 with the aim of having vaccines ready in order to prevent the next global pandemic.2][3] Moreover, CEPI has selected 3 pathogens on which to focus their initial vaccination efforts. 1-3However, the vaccines for these pathogens are in the very early stages of development (preclinical stage) and may take decades before they are ready for use in an epidemic. 2Despite Bill Gates' claim that DNA/RNA vaccines (third-generation vaccines) can serve as a 'vaccine pipeline' to accelerate vaccine development against other pathogens, there is no licensed DNA or RNA vaccine approved by the US Food and Drug Administration for human use. 4 There is no Th1adjuvant in existence which may prove to be a vital component of a future viral vaccine.Furthermore, a vaccine, once developed, cannot be tested in a Phase II or III Clinical Trial as there are few or no cases outside an epidemic for most of the potential pathogens.I believe CEPI's focus solely on vaccination is a mistake.CEPI needs to carefully consider other innovations (passive immune therapy, antiviral drug discovery, adjuvant discovery, highthroughput viral genome sequencing) and capacity building initiatives (diagnostics, real-time reporting, zoonotic surveillance in animal reservoirs, mathematical modelling, GIS risk mapping) that will compliment vaccination.
Veit Stoss’s High Altar of St Mary's Church—A 15th Century Altar Depicting Skin Lesions
Authors: Andrzej Wincewicz
Journal: JAMA Dermatology (2017)

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