tbuckley/cabot-search huggingface dataset:
Inequalities in life expectancy in six large Latin American cities from the SALURBAL study: an ecological analysis
Authors: Usama Bilal, Marcio Alazraqui, Waleska T Caiaffa, Nancy Lopez-Olmedo, Kevin Martinez-Folgar, J Jaime Miranda, Daniel A Rodriguez, Alejandra Vives, Ana V Diez-Roux
Journal: The Lancet Planetary Health (2019)

BackgroundLatin America is one of the most unequal regions in the world, but evidence is lacking on the magnitude of health inequalities in urban areas of the region. Our objective was to examine inequalities in life expectancy in six large Latin American cities and its association with a measure of area-level socioeconomic status.MethodsIn this ecological analysis, we used data from the Salud Urbana en America Latina (SALURBAL) study on six large cities in Latin America (Buenos Aires, Argentina; Belo Horizonte, Brazil; Santiago, Chile; San José, Costa Rica; Mexico City, Mexico; and Panama City, Panama), comprising 266 subcity units, for the period 2011–15 (expect for Panama city, which was for 2012–16). We calculated average life expectancy at birth by sex and subcity unit with life tables using age-specific mortality rates estimated from a Bayesian model, and calculated the difference between the ninth and first decile of life expectancy at birth (P90–P10 gap) across subcity units in cities. We also analysed the association between life expectancy at birth and socioeconomic status at the subcity-unit level, using education as a proxy for socioeconomic status, and whether any geographical patterns existed in cities between subcity units.FindingsWe found large spatial differences in average life expectancy at birth in Latin American cities, with the largest P90–P10 gaps observed in Panama City (9·8 years for men and 11·2 years for women), Santiago (8·9 years for men and 17·7 years for women), and Mexico City (10·9 years for men and 9·4 years for women), and the narrowest in Buenos Aires (4·4 years for men and 5·8 years for women), Belo Horizonte (4·0 years for men and 6·5 years for women), and San José (3·9 years for men and 3·0 years for women). Higher area-level socioeconomic status was associated with higher life expectancy, especially in Santiago (change in life expectancy per P90–P10 change unit-level of educational attainment 8·0 years [95% CI 5·8–10·3] for men and 11·8 years [7·1–16·4] for women) and Panama City (8·0 years [4·4–11·6] for men and 10·0 years [4·2–15·8] for women). We saw an increase in life expectancy at birth from east to west in Panama City and from north to south in core Mexico City, and a core-periphery divide in Buenos Aires and Santiago. Whereas for San José the central part of the city had the lowest life expectancy and in Belo Horizonte the central part of the city had the highest life expectancy.InterpretationLarge spatial differences in life expectancy in Latin American cities and their association with social factors highlight the importance of area-based approaches and policies that address social inequalities in improving health in cities of the region.FundingWellcome Trust.
Clinical characteristics of enterovirus A71 neurological disease during an outbreak in children in Colorado, USA, in 2018: an observational cohort study
Authors: Kevin Messacar, Emily Spence-Davizon, Christina Osborne, Craig Press, Teri L Schreiner, Jan Martin, Ricka Messer, John Maloney, Alexis Burakoff, Meghan Barnes, Shannon Rogers, Adriana S Lopez, Janell Routh, Susan I Gerber, M Steven Oberste, W Allan Nix, Mark J Abzug, Kenneth L Tyler, Rachel Herlihy, Samuel R Dominguez
Journal: The Lancet Infectious Diseases (2019)
RyR2 regulates Cx43 hemichannel intracellular Ca2+-dependent activation in cardiomyocytes
Authors: Alessio Lissoni, Paco Hulpiau, Tânia Martins-Marques, Nan Wang, Geert Bultynck, Rainer Schulz, Katja Witschas, Henrique Girao, Maarten De Smet, Luc Leybaert
Journal: Cardiovascular Research (2019)

Connexin-based gap junctions are crucial for electrical communication in the heart; they are each composed of two docked hemichannels (HCs), supplied as unpaired channels via the sarcolemma. When open, an unpaired HC forms a large pore, high-conductance and Ca2+-permeable membrane shunt pathway that may disturb cardiomyocyte function. HCs composed of connexin 43 (Cx43), a major cardiac connexin, can be opened by electrical stimulation but only by very positive membrane potentials. Here, we investigated the activation of Cx43 HCs in murine ventricular cardiomyocytes voltage-clamped at -70 mV.Using whole-cell patch-clamp, co-immunoprecipitation, western blot analysis, immunocytochemistry, proximity ligation assays, and protein docking studies, we found that stimulation of ryanodine receptors (RyRs) triggered unitary currents with a single-channel conductance of ∼220 pS, which were strongly reduced by Cx43 knockdown. Recordings under Ca2+-clamp conditions showed that both RyR activation and intracellular Ca2+ elevation were necessary for HC opening. Proximity ligation studies indicated close Cx43-RyR2 apposition (<40 nm), and both proteins co-immunoprecipitated indicating physical interaction. Molecular modelling suggested a strongly conserved RyR-mimicking peptide sequence (RyRHCIp), which inhibited RyR/Ca2+ HC activation but not voltage-triggered activation. The peptide also slowed down action potential repolarization. Interestingly, alterations in the concerned RyR sequence are known to be associated with primary familial hypertrophic cardiomyopathy.Our results demonstrate that Cx43 HCs are intimately linked to RyRs, allowing them to open at negative diastolic membrane potential in response to RyR activation.
Polymorphisms in fragile histidine triad gene (<i>FHIT</i>) associated with aggressive prostate cancer and cancer specific mortality.
Authors: Yan Ding, Amanda Black, Ann W Hsing, Gerald L. Andriole
Journal: Journal of Clinical Oncology (2012)

4646 Background: FHIT is a 1.5 Mb gene encoding a 16.8 kD triphosphatase known to promote apoptosis responding to DNA damage in epithelial cells. It resides in the most frequently observed fragile site in the human genome, FRA3B, and is frequently deleted in early development of multiple cancer types. More importantly, down regulation of FHIT protein has been associated with clinical features of tumors, such as the presence of extraprostatic extension and Gleason Score &gt; 8 in prostate cancer (CaP), advanced diseases in breast cancer, and shorter survival after platinum-based treatment for advanced non-small cell lung cancer. Previously, a genetic locus for CaP has been reported in FHIT. Here we evaluated association of aggressive CaP and death due to CaP with Single nucleotide polymorphisms (SNPs) in FHIT using cases and controls of European origin nested in the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening trial with 13 years of follow-up. Methods: We analyzed 659 SNPs on FHIT in 1,164 CaP patients (476 with nonaggressive CaP, Gleason &lt; 7 and stage &lt; III; 688 with aggressive CaP, Gleason &gt;= 7 and/or stage III/IV; 63 with death due to CaP) and 1,167 controls using an incidence density sampling strategy. Stratified Cochran-Mantel-Haenszel test and logistic regression were performed to test association. Results: We detected significant association (p &lt; 0.05) of incident CaP to 48 SNPs and aggressive CaP to 52 SNPs. After 50,000 permutations, two SNPs within a 7 kb region, one for incident CaP and the other for aggressive CaP, remained marginally significant (corrected p = 0.053 and 0.093, respectively). The same risk allele for aggressive CaP was also associated with CaP-specific mortality (OR = 1.50, p = 0.027). The association was stronger after adjusting for Gleason, stage, and PSA at diagnosis, treatment options after diagnosis. Test on imputed SNPs within the 7 kb intronic region identified 7 additional SNPs in 2 linkage disequilibrium groups at higher risk to CaP-specific death (OR = 1.98, p = 0.00015 and OR = 2.51, p = 0.0027). Conclusions: Risk SNPs in FHIT were implicated for aggressive disease and CaP specific death. Replication of these SNPs in other populations is warranted.
BrightFocus Alzheimer’s Fast Track 2019
Authors: Keith W. Whitaker, Frank M. LaFerla, Harry W. M. Steinbusch, Cynthia A. Lemere, Diane E. Bovenkamp
Journal: Molecular Neurodegeneration (2019)

Abstract The 3 day workshop “Alzheimer’s Fast Track” is a unique opportunity for graduate students, postdoctoral fellows, or other early-career scientists, focused on Alzheimer’s disease research, to gain new knowledge and become an expert in where this emerging scientific field is moving. In addition, it is not only about receiving a good overview, but also learning to write and defend a successful application for securing funding for Alzheimer’s disease research projects.
Ranitidine: patients taking certain batches should “immediately discontinue use,” says FDA
Authors: Elisabeth Mahase
Journal: BMJ (2019)

Patients who have ranitidine tablets from certain batches, identified through the US’s National Drug Code, should “immediately discontinue use and consult with their physician or healthcare provider about treatment options,” says an alert from Glenmark Pharmaceuticals.1

The alert, published on the US Food and Drug Administration website, said that the company had announced a voluntary recall of all unexpired lots of ranitidine tablets (150 mg and 300 mg), including from patients.

The recalled 150 mg batches are: NDC 684620-248-60; 684620-248-01; and 684620-248-05 (expiry date range December 2019 to May 2022). The recalled 300 mg batches are: 684620-249-30; 684620-249-01; and 684620-249-20 …
How to identify patients who are less likely to have metachronous neoplasms after a colon cancer: a predictive model
Authors: Leonardo Frazzoni, Liboria Laterza, Alessandro Mussetto, Rocco Maurizio Zagari, Cristina Trovato, Mario De Bellis, Silvia Paggi, Stefania Piccirelli, Luigi Ricciardiello, Paola Cesaro, Cristiano Spada, Giulia Dal Piaz, Marina La Marca, Fabio Fabbian, Laura Petrella, Veronica Smania, Pietro Marone, Fabiana Tatangelo, Franco Bazzoli, Franco Radaelli, Alessandro Repici, Cesare Hassan, Michele Scagliarini, Lorenzo Fuccio
Journal: Endoscopy (2019)

Abstract Background Patients with prior colon cancer have increased risk of metachronous colorectal neoplasms; therefore, endoscopic surveillance is indicated. Current recommendations are not risk-stratified. We investigated predictive factors for colorectal neoplasms to build a model to spare colonoscopies for low-risk patients. Methods This was a multicenter, retrospective study including patients who underwent surgery for colon cancer in 2001 – 2008 (derivation cohort) and 2009 – 2013 (validation cohort). A predictive model for neoplasm occurrence at second surveillance colonoscopy was developed and validated. Results 421 and 203 patients were included in derivation and validation cohort, respectively. At second surveillance colonoscopy, 112 (26.6 %) and 55 (27.1 %) patients had metachronous neoplasms in derivation and validation groups; three cancers were detected in the latter. History of left-sided colon cancer (OR 1.64, 95 %CI 1.02 – 2.64), ≥ 1 advanced adenoma at index colonoscopy (OR 1.90, 95 %CI 1.05 – 3.43), and ≥ 1 adenoma at first surveillance colonoscopy (OR 2.06, 95 %CI 1.29 – 3.27) were independently predictive of metachronous colorectal neoplasms at second surveillance colonoscopy. For patients without such risk factors, diagnostic accuracy parameters were: 89.3 % (95 %CI 82.0 %-94.3 %) and 78.2 % (95 %CI 65.0 %-88.2 %) sensitivity, and 28.5 % (95 %CI 23.5 %-33.9 %) and 33.8 % (95 %CI 26.2 %-42.0 %) specificity in derivation and validation group, respectively. No cancer would be missed. Conclusions Patients with prior left-sided colon cancer or ≥ 1 advanced adenoma at index colonoscopy or ≥ 1 adenoma at first surveillance colonoscopy had a significantly higher risk of neoplasms at second surveillance colonoscopy; patients without such factors had much lower risk and could safely skip the second surveillance colonoscopy. A prospective, multicenter validation study is needed.
Acute hypoxaemic respiratory failure in immunocompromised patients: abandon bronchoscopy or make it better?
Authors: Matt S. Zinter, Guang-Shing Cheng
Journal: European Respiratory Journal (2019)

<b>A discussion of the strengths and limitations of recent data associating bronchoscopy with mortality in immunocompromised adults with acute hypoxaemic respiratory failure</b>http://bit.ly/31mMpGL
Tumor Mutational Load and Germline Polygenic Risk Score Predicts Time-to-First Treatment in Chronic Lymphocytic Leukemia (CLL) and High-Count Monoclonal B Cell Lymphocytosis (MBL)
Authors: Geffen Kleinstern, Daniel R O'Brien, Brian Kabat, Kari G Rabe, Aaron D. Norman, Huihuang Yan, Celine M. Vachon, Shulan Tian, Timothy G. Call, Sameer A. Parikh, Jose F. Leis, Wei Ding, James R. Cerhan, Neil E. Kay, Esteban Braggio, Susan L. Slager
Journal: Blood (2019)
Organic semiconducting polymer amphiphile for near-infrared-II light-triggered phototheranostics
Authors: Chao Yin, Xiaozhen Li, Guohua Wen, Boguang Yang, Yachao Zhang, Xiaoyu Chen, Pengchao Zhao, Shengliang Li, Rui Li, Lidai Wang, Chun-Sing Lee, Liming Bian
Journal: Biomaterials (2019)
Racism should have consequences
Authors: Steven Crane
Journal: BMJ (2019)

Mathew is correct in her assertion that our response to patients’ racism is not always straightforward and that there cannot be a “one size fits all” approach to such incidents.1 I remember being on call for an emergency department many years ago when an abusive, intoxicated man with a head injury was refusing to have a wound sutured by my black staff grade colleague and was demanding …
What’s hot that the other lot got
Authors: Daryl Cheng
Journal: Thorax (2019)

What's hot that the other lot got Daryl chengWhich patients With bronchiectasis benefit from long-term antibiotics?Current bronchiectasis guidelines recommend that long-term macrolide antibiotics should be given to patients with frequent exacerbations and those without Pseudomonas aeruginosa infection.This study attempts to address the calls from the European Respiratory Society and the Cochrane Collaboration for further work in identifying the subgroups of patients with bronchiectasis who will benefit most from macrolide treatment (Chalmers et al, Lancet Respir Med 2019;7;845).This systematic review and meta-analysis addresses this using individual patient data from three randomised controlled trials providing data on 173 subjects on macrolide therapy and 168 on placebo.Consistent with the individual trials, the analysis found that macrolide therapy was associated with a significant reduction in the frequency of exacerbations over 6-12 months (adjusted incidence rate ratio 0.49, 95% CI 0.36 to 0.66; p<0.0001).The authors examined prespecified subgroups and found no significant interaction effects of these subgroups except for the cause of bronchiectasis (p interaction =0.034).Notably, there was similar efficacy of therapy in patients with and without P. aeruginosa in baseline sputum culture (incident rate ratio (IRR) 0.36, 95% CI 0.18 to 0.72, p=0.004, and IRR 0.53, 95% CI 0.38 to 0.74, p<0.0001, respectively; p inter-
Late Recurrences After Estrogen Receptor–Positive Breast Cancer
Authors: Steven A. Narod, Vasily Giannakeas, Victoria Sopik
Journal: JAMA Oncology (2019)

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GP who is cleared of sexual assault says he “lost everything” after conviction
Authors: Clare Dyer
Journal: BMJ (2019)

A GP who was wrongly jailed for sexually assaulting a patient has had his conviction overturned by the Court of Appeal after new evidence emerged showing the patient had lied on oath.

Rajeshkumar Mehta, 65, was charged with touching the patient’s breast during a walk-in consultation at The Hill General Practice in Sparkhill, Birmingham. He was convicted …
Abstract B56: Endogenous retrovirus transcript levels are associated with immunogenic signatures in multiple metastatic cancer types
Authors: James T. Topham, Emma Titmuss, Erin Pleasance, Laura M. Williamson, Joanna M. Karasinska, Luka Culibrk, Michael K.C. Lee, Steve E. Kalloger, Shehara Mendis, Richard A. Moore, Andrew J. Mungall, Janessa Laskin, Jonathan M. Loree, Dixie L. Mager, Marco A. Marra, Steven J.M. Jones, David F. Schaeffer, Daniel J. Renouf
Journal: Cancer Research (2019)

Abstract Variability in the immunogenic landscape of metastatic cancer lesions has revealed insight into detection of potential immunotherapy-responsive patients, though underlying mechanisms driving such variation are not fully understood. Endogenous retrovirus (ERV)-containing transcripts have recently emerged as a potential source of tumor-associated antigen that are orthogonal to somatic mutation-derived neoantigens. To characterize the intersection between ERV levels and predicted immunogenicity in metastatic cancer, we comprehensively profiled the transcript abundance of 702,533 ERV loci in 199 metastatic tumors from breast, colorectal, and pancreatic cancer patients. In all three cancer types, overall ERV transcript load was associated with upregulation of genes involved in innate antiviral response pathways as well as genes involved in both adaptive and innate immune signaling. In colorectal and pancreatic tumors, samples with concomitant increases in ERV load and antiviral response gene expression, termed viral mimicry tumors, showed high expression of the DNA demethylation gene TET2, a gene previously described to promote transcription of ERV-containing transcripts. Collectively, these data are compatible with the notion that an increased level of ERV-containing transcripts may account for increased immunogenicity in a subset of metastatic tumors and support the relationship between DNA demethylation and ERV load in colorectal and pancreatic tumors. Citation Format: James T. Topham, Emma Titmuss, Erin Pleasance, Laura M. Williamson, Joanna M. Karasinska, Luka Culibrk, Michael K.C. Lee, Steve E. Kalloger, Shehara Mendis, Richard A. Moore, Andrew J. Mungall, Janessa Laskin, Jonathan M. Loree, Dixie L. Mager, Marco A. Marra, Steven J.M. Jones, David F. Schaeffer, Daniel J. Renouf. Endogenous retrovirus transcript levels are associated with immunogenic signatures in multiple metastatic cancer types [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; 2019 Sept 6-9; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2019;79(24 Suppl):Abstract nr B56.
Development of the Angioedema Control Test—A patient‐reported outcome measure that assesses disease control in patients with recurrent angioedema
Authors: Karsten Weller, Tamara Donoso, Markus Magerl, Emel Aygören‐Pürsün, Petra Staubach, Inmaculada Martinez‐Saguer, Tomasz Hawro, Sabine Altrichter, Karoline Krause, Frank Siebenhaar, Martin Metz, Torsten Zuberbier, Denise Freier, Marcus Maurer
Journal: Allergy (2019)

Abstract Background Recurrent angioedema (AE) is an important clinical problem in the context of chronic urticaria (mast cell mediator–induced), ACE‐inhibitor intake and hereditary angioedema (both bradykinin‐mediated). To help patients obtain control of their recurrent AE is a major treatment goal. However, a tool to assess control of recurrent AE is not yet available. This prompted us to develop such a tool, the Angioedema Control Test (AECT). Methods After a conceptional framework was developed for the AECT, a list of potential AECT items was generated by a combined approach of patient interviews, literature review and expert input. Subsequent item reduction was based on impact analysis, inter‐item correlation, additional predefined criteria for item performance, and a review of the item selection process for content validity. Finally, an instruction section was generated, and an US‐American‐English version was developed by a structured translation process. Results A 4‐item AECT with recall periods of 4 weeks and 3 months was developed based on 106 potential items tested in 97 patients with mast cell mediator‐induced (n = 49) or bradykinin‐mediated recurrent AE (n = 48). Eighty‐four items were excluded based on impact analysis. The remaining 22 items could be further reduced by a method‐mix of inter‐item correlation, additional predefined criteria for item performance and review for content validity. Conclusions The AECT is the first tool to assess disease control in recurrent AE patients. Its retrospective approach, its brevity and its simple scoring make the AECT ideally suited for clinical practice and trials. Its validity and reliability need to be determined in future independent studies.
Publisher Correction: Common brain disorders are associated with heritable patterns of apparent aging of the brain
Authors: Tobias Kaufmann, Dennis van der Meer, Nhat Trung Doan, Emanuel Schwarz, Martina J Lund, Ingrid Agartz, Dag Alnæs, Deanna M Barch, Ramona Baur-Streubel, Alessandro Bertolino, Francesco Bettella, Mona K Beyer, Erlend Bøen, Stefan Borgwardt, Christine L Brandt, Jan Buitelaar, Elisabeth G Celius, Simon Cervenka, Annette Conzelmann, Aldo Córdova-Palomera, Anders M Dale, Dominique J F de Quervain, Pasquale Di Carlo, Srdjan Djurovic, Erlend S Dørum, Sarah Eisenacher, Torbjørn Elvsåshagen, Thomas Espeseth, Helena Fatouros-Bergman, Lena Flyckt, Barbara Franke, Oleksandr Frei, Beathe Haatveit, Asta K Håberg, Hanne F Harbo, Catharina A Hartman, Dirk Heslenfeld, Pieter J Hoekstra, Einar A Høgestøl, Terry L Jernigan, Rune Jonassen, Erik G Jönsson, Peter Kirsch, Iwona Kłoszewska, Knut K Kolskår, Nils Inge Landrø, Stephanie Le Hellard, Klaus-Peter Lesch, Simon Lovestone, Arvid Lundervold, Astri J Lundervold, Luigi A Maglanoc, Ulrik F Malt, Patrizia Mecocci, Ingrid Melle, Andreas Meyer-Lindenberg, Torgeir Moberget, Linn B Norbom, Jan Egil Nordvik, Lars Nyberg, Jaap Oosterlaan, Marco Papalino, Andreas Papassotiropoulos, Paul Pauli, Giulio Pergola, Karin Persson, Geneviève Richard, Jaroslav Rokicki, Anne-Marthe Sanders, Geir Selbæk, Alexey A Shadrin, Olav B Smeland, Hilkka Soininen, Piotr Sowa, Vidar M Steen, Magda Tsolaki, Kristine M Ulrichsen, Bruno Vellas, Lei Wang, Eric Westman, Georg C Ziegler, Mathias Zink, Ole A Andreassen, Lars T Westlye
Journal: Nature Neuroscience (2019)
Phase 2 Study of Efgartigimod, a Novel FcRn Antagonist, in Adult Patients with Primary Immune Thrombocytopenia
Authors: Adrian C. Newland, Blanca Sánchez-González, László Rejtő, Miklos Egyed, Nataliya Romanyuk, Marie Godar, Katrien Verschueren, Domenica Gandini, Peter Ulrichts, Jon Beauchamp, Torsten Dreier, E. Sally Ward, Marc Michel, Howard A. Liebman, Hans De Haard, Nicolas Leupin, David J. Kuter
Journal: Blood (2019)