tbuckley/cabot-search huggingface dataset:
Covid-19: Caution urged while lockdown eases in England because of vaccine success
Authors: Zosia Kmietowicz
Journal: BMJ (2021)

Covid-19: Caution urged while lockdown eases in England because of vaccine success Zosia KmietowiczThe effectiveness of covid vaccines in reducing infections, hospital admissions, and deaths means that lockdown restrictions can be eased "very considerably" from next week, the prime minister has announced, although he urged people to "exercise caution and common sense."Pubs and restaurants will be able to serve customers indoors from 17 May, theatres, cinemas, and other indoor venues can open, and up to six people or two households can socialise inside.
Research priorities for exacerbations of COPD
Authors: Jaber S Alqahtani, Julian Aquilina, Mona Bafadhel, Charlotte E Bolton, Teresa Burgoyne, Steve Holmes, Joanne King, John Loots, Joan McCarthy, Jennifer K Quint, Heidi A Ridsdale, Elizabeth Sapey, Sheela Upadhyaya, Tom M A Wilkinson, John R Hurst
Journal: The Lancet Respiratory Medicine (2021)
Author Correction: Robust SARS-CoV-2-specific T cell immunity is maintained at 6 months following primary infection
Authors: Jianmin Zuo, Alexander C. Dowell, Hayden Pearce, Kriti Verma, Heather M. Long, Jusnara Begum, Felicity Aiano, Zahin Amin-Chowdhury, Katja Hoschler, Tim Brooks, Stephen Taylor, Jacqueline Hewson, Bassam Hallis, Lorrain Stapley, Ray Borrow, Ezra Linley, Shazaad Ahmad, Ben Parker, Alex Horsley, Gayatri Amirthalingam, Kevin Brown, Mary E. Ramsay, Shamez Ladhani, Paul Moss
Journal: Nature Immunology (2021)
Abstract 16404: Allergy Associated Myocardial Infarction: A Comprehensive Review of Clinical Presentation, Diagnosis and Management of Kounis Syndrome
Authors: Anastasios Roumeliotis, Periklis Davlouros, Maria Anastasopoulou, Grigorios Tsigkas, Georgios Hahalis, Nicholas G Kounis
Journal: Circulation (2020)

Introduction: Kounis syndrome (KS) is defined as acute coronary syndrome (ACS) in the context of a hypersensitivity reaction. Patients may present with normal coronary arteries (Type I), established coronary artery disease (Type II) or in-stent thrombosis and restenosis (Type III). Hypothesis: We sought to investigate the clinical presentation, underlying pathophysiology, diagnosis and medical management of patients with KS. Methods: We searched PubMed until 1/1/2020 for case reports of KS. Patients with age &lt;18 years, non-coronary vascular manifestations and without an established KS diagnosis were excluded. Information regarding patient demographics, medical history, clinical presentation, allergic reaction trigger, angiographic results as well as management were manually extracted from every report. All data were pulled in a combined data set and descriptive statistics were analyzed. Results: Out of the 269 unique patients with KS, 157 (58.4%) had Type I, 64 (23.8%) Type II and 18 (6.7%) Type III while 30 (11.2%) could not be classified. Their mean age was 54.1 years and 190 (70.6%) were male. The majority presented with a combination of cardiac and allergic symptoms [Panel A] and medication was the most commonly reported trigger [Panel B]. Electrocardiographically, 75.1% of cases had ST segment elevation with only 3.3% demonstrating no abnormalities. Coronary imaging was available in 228 (84.8%) patients showing occlusive lesions (32.5%), vascular spasm (16.2%), or normal coronary arteries (51.3%). Percutaneous coronary intervention or coronary artery bypass grafting was performed in 70 (29.4%) of the 238 patients with available information. Conclusions: Hypersensitivity induced ACS is most frequently triggered by medications, and the majority of patients have patent coronary arteries suggesting microvascular dysfunction. KS should be considered in the differential diagnosis of myocardial infarction with non-obstructive coronary arteries.
Abstract P004: Association Between The Liver Fibrosis-4 Score And Incident Atrial Fibrillation In A General Japanese Population Of Middle-aged To Older Adults
Authors: Yoshihiro Tanaka, Sarah Chuzi, Nagisa Morikawa, Hayato Tada, Kenshi Hayashi, Philip Greenland, Lisa B Vanwagner, Sadiya Khan
Journal: Circulation (2021)

Background: There is increasing evidence that end-organ liver dysfunction is an important risk factor for atrial fibrillation (AF). Whether a non-invasive, laboratory-based marker of liver fibrosis, the fibrosis-4 score (FIB-4), is associated with incident AF is not known. Aim: To examine the longitudinal association of FIB-4 with incident AF in a general Japanese population with public health insurance. Methods: We used data from the National Japanese Health Check-Up performed in Kanazawa City, which included unemployed or retired participants aged ≥ 40 years. The baseline examination occurred in 2013 and participants were invited for annual routine examinations with follow-up data available through 2018. We excluded participants with pre-existing AF or missing data at baseline or follow-up. Incident AF was based on 12-lead electrocardiogram. We calculated the FIB-4 score (composed of age [years], aspartate and alanine aminotransferase, and platelet levels) for each participant and estimated the cumulative incidence of AF stratified by FIB-4 score quartiles. We also examined the association between quartiles of FIB-4 and incident AF using Cox proportional hazard models adjusted for risk factors with the lowest FIB-4 quartile as referent. Results: Of 37,892 participants, 37% were male and mean age was 72.4±9.6 years. Median (interquartile range [IQR]) of the FIB-4 score was 1.75 (IQR 1.38, 2.27). During a median (IQR) follow-up period of 5.0 years (4.0, 5.0), 707 cases of incident AF were identified. Cumulative incidence in the highest quartile of FIB-4 was 3.9% compared with 1.0% in the lowest quartile (log-rank p&lt;0.001, Figure A ). Higher quartiles of the FIB-4 score had a dose-dependent increased risk of AF with adjusted HR of 1.70 (1.29, 2.23) in the highest quartile compared with the lowest quartile ( Figure B ). Conclusion: FIB-4 was independently associated with incident AF in a general, older Japanese population and may reflect risk of AF, in addition to traditional cardiovascular risk factors.
64P Mammographic density to predict response to neoadjuvant chemotherapy for breast cancer
Authors: S. Di Cosimo, C. Depretto, R. Miceli, P. Baili, M. Sant, G. Pruneri, A. Vingiani, S. Folli, M. Bini, M.C. De Santis, G. Scaperrotta
Journal: Annals of Oncology (2021)
Racial Segregation and Respiratory Outcomes among Urban Black Residents with and at Risk of Chronic Obstructive Pulmonary Disease
Authors: Han Woo, Emily P. Brigham, Kassandra Allbright, Chinedu Ejike, Panagis Galiatsatos, Miranda R. Jones, Gabriela R. Oates, Jerry A. Krishnan, Christopher B. Cooper, Richard E. Kanner, Russell P. Bowler, Eric A. Hoffman, Alejandro P. Comellas, Gerard Criner, R. Graham Barr, Fernando J. Martinez, MeiLan Han, Victor E. Ortega, Trisha M. Parekh, Stephanie Christenson, Daniel Belz, Sarath Raju, Amanda Gassett, Laura M. Paulin, Nirupama Putcha, Joel D. Kaufman, Nadia N. Hansel
Journal: American Journal of Respiratory and Critical Care Medicine (2021)

Rationale: Racial residential segregation has been associated with worse health outcomes, but the link with chronic obstructive pulmonary disease (COPD) morbidity has not been established.Objectives: To investigate whether racial residential segregation is associated with COPD morbidity among urban Black adults with or at risk of COPD.Methods: Racial residential segregation was assessed using isolation index, based on 2010 decennial census and baseline address, for Black former and current smokers in the multicenter SPIROMICS (Subpopulations and Intermediate Outcome Measures in COPD Study), a study of adults with or at risk for COPD. We tested the association between isolation index and respiratory symptoms, physiologic outcomes, imaging parameters, and exacerbation risk among urban Black residents, adjusting for established COPD risk factors, including smoking. Additional mediation analyses were conducted for factors that could lie on the pathway between segregation and COPD outcomes, including individual and neighborhood socioeconomic status, comorbidity burden, depression/anxiety, and ambient pollution.Measurements and Main Results: Among 515 Black participants, those residing in segregated neighborhoods (i.e., isolation index ⩾0.6) had worse COPD Assessment Test score (β = 2.4; 95% confidence interval [CI], 0.7 to 4.0), dyspnea (modified Medical Research Council scale; β = 0.29; 95% CI, 0.10 to 0.47), quality of life (St. George's Respiratory Questionnaire; β = 6.1; 95% CI, 2.3 to 9.9), and cough and sputum (β = 0.8; 95% CI, 0.1 to 1.5); lower FEV1% predicted (β = −7.3; 95% CI, −10.9 to −3.6); higher rate of any and severe exacerbations; and higher percentage emphysema (β = 2.3; 95% CI, 0.7 to 3.9) and air trapping (β = 3.8; 95% CI, 0.6 to 7.1). Adverse associations attenuated with adjustment for potential mediators but remained robust for several outcomes, including dyspnea, FEV1% predicted, percentage emphysema, and air trapping.Conclusions: Racial residential segregation was adversely associated with COPD morbidity among urban Black participants and supports the hypothesis that racial segregation plays a role in explaining health inequities affecting Black communities.
Human skin equivalents: Impaired barrier function in relation to the lipid and protein properties of the stratum corneum
Authors: Joke A. Bouwstra, Richard W.J. Helder, Abdoelwaheb El Ghalbzouri
Journal: Advanced Drug Delivery Reviews (2021)

To advance drug development representative reliable skin models are indispensable. Animal skin as test model for human skin delivery is restricted as their properties greatly differ from human skin. In vitro 3D-human skin equivalents (HSEs) are valuable tools as they recapitulate important aspects of the human skin. However, HSEs still lack the full barrier functionality as observed in native human skin, resulting in suboptimal screening outcome. In this review we provide an overview of established in-house and commercially available HSEs and discuss in more detail to what extent their skin barrier biology is mimicked in vitro focusing on the lipid properties and cornified envelope. Further, we will illustrate how underlying factors, such as culture medium improvements and environmental factors affect the barrier lipids. Lastly, potential improvements in skin barrier function will be proposed aiming at a new generation of HSEs that may replace animal skin delivery studies fully.
Tezepelumab in Adults and Adolescents with Severe, Uncontrolled Asthma
Authors: Andrew Menzies-Gow, Jonathan Corren, Arnaud Bourdin, Geoffrey Chupp, Elliot Israel, Michael Wechsler, Christopher Brightling, Janet Griffiths, Åsa Hellqvist, Karin Bowen, Primal Kaur, Gun Almqvist, Sandhia Ponnarambil, Gene Colice
Journal: New England Journal of Medicine (2021)

Tezepelumab is a human monoclonal antibody that blocks thymic stromal lymphopoietin, an epithelial-cell–derived cytokine implicated in the pathogenesis of asthma. The efficacy and safety of tezepelumab in patients with severe, uncontrolled asthma require further assessment.
Abstract 15658: Anatomical Characteristics of the Cavotricuspid Isthmus and Their Correlation With Obstructive Sleep Apnea
Authors: Carola Gianni, Yalçin Gökoglan, Javier E Sanchez, CHINTAN TRIVEDI, Sanghamitra Mohanty, Domenico G Della Rocca, Amin Al-ahmad, Mohamed A Bassiouny, J D Burkhardt, G J Gallinghouse, Rodney P Horton, Patrick M Hranitzky, Luigi Di Biase, Andrea Natale
Journal: Circulation (2020)

Introduction: Macro-reentrant arrhythmias involving the cavo-tricuspid isthmus (CTI) are common in patients with atrial fibrillation (AF). Bidirectional CTI block is the ablation strategy of choice, but it can be surprisingly difficult to obtain at times. Objective: Aim of this study was to systematically assess the characteristics of the CTI to determine its most common anatomical variants to be anticipated for ablation. Methods: This is a prospective observational study in which intracardiac echocardiography (ICE) was used to visualize the CTI of patients undergoing AF ablation. The presence of anatomical variants was recorded, and length was measured along the central CTI in atrial systole. CTI systolic shortening measured in sinus rhythm and defined as: [(diastolic length - systolic length)/(diastolic length)]x100. Results: 180 patients (65±9 years old, 31% female, 37% paroxysmal AF) are included in the study. Mean CTI length was 31±9 mm, with a systolic shortening of 25±13%. A prominent Eustachian ridge was present in 32%, a Chiari network in 11%, and at least one pouch-like recess in 35%, with a mean depth of 5.3±2.5 mm (Figure). A longer CTI was observed in patients with non-PAF compared with patients with PAF (33 vs. 27 mm, P&lt;0.0001) and in patients with known obstructive sleep apnea (OSA; 37 vs. 32 mm, P=0.0077). Of note, after excluding patients with heart failure, ROC analysis showed that a CTI length ≥ 33 mm was predictive of the presence of OSA (67 % sensitivity and specificity, AUC = 0.71). Less CTI systolic shortening was observed in patients with non-PAF compared those with PAF (22 vs. 32%; P&lt;0.0001). Conclusion: Anatomical variants of the CTI are common and should be anticipated in case of a challenging CTI ablation. A long CTI is associated with OSA and might warrant further clinical screening to identify this common AF comorbidity. CTI systolic shortening correlates with the type of AF and could represent a measure of right atrial contractility.
Age Is Not a Predictive Marker in Molecularly Annotated Elderly Patients with Myelofibrosis Treated with Ruxolitinib: a Multicenter Study on 277 Patients.
Authors: Francesca Palandri, Maria Rosaria Sapienza, Giuseppe A Palumbo, Massimiliano Bonifacio, Giulia Benevolo, Elisabetta Abruzzese, Bruno Martino, Roberto Latagliata, Nicola Polverelli, Roberto Massimo Lemoli, Mario Tiribelli, Massimo Breccia, Francesco Cavazzini, Gianni Binotto, Alessia Tieghi, Ambra Di Veroli, Nicola Sgherza, Alessandro Isidori, Adalberto Ibatici, Monica Crugnola, Costanza Bosi, Malgorzata Monika Trawinska, Daniela Bartoletti, Luigi Scaffidi, Elena Sabattini, Giovanni Martinelli, Michele Cavo, Nicola Vianelli, Lucia Catani, Florian H. Heidel
Journal: Blood (2017)
John I Harper
Authors: Peter H Hoeger, Veronica A Kinsler
Journal: BMJ (2021)

It is with great sadness that we announce the death of John I Harper, who died suddenly on 5 April 2021. Those who had the good fortune to know him will forever miss his sense of humour and humanity, the unmistakably gentle approach to patients and their families, and his stimulating art of linking clinical and scientific medicine.

John was brought up in Southend on Sea, Essex. He studied at St Mary’s Hospital Medical School, University of London. He had his first taste of paediatrics at St` Charles Hospital, London, where he was inspired by David Harvey. He went on to work in dermatology at Addenbrooke's Hospital, Cambridge, under Drs Rook, Champion, and Roberts, and then, at Wycombe General Hospital, under Darrell Wilkinson.

In 1980, John moved to Westminster Hospital, where he joined the dermatology department under Drs Copeman and …
The potential for vaccination-induced herd immunity against the SARS-CoV-2 B.1.1.7 variant
Authors: David Hodgson, Stefan Flasche, Mark Jit, Adam J Kucharski
Journal: Eurosurveillance (2021)

We assess the feasibility of reaching the herd immunity threshold against SARS-CoV-2 through vaccination, considering vaccine effectiveness (VE), transmissibility of the virus and the level of pre-existing immunity in populations, as well as their age structure. If highly transmissible variants of concern become dominant in areas with low levels of naturally-acquired immunity and/or in populations with large proportions of < 15 year-olds, control of infection without non-pharmaceutical interventions may only be possible with a VE ≥ 80%, and coverage extended to children.
Pitfalls of rubella serology while on the brink of elimination: evaluation of national data, Belgium, 2017
Authors: Sofie Colman, Kris Vernelen, Bernard China, Dorien Van den Bossche, Laura Cornelissen, Marie-Luce Delforge, Marijke Reynders, Mario Berth, Melissa Depypere, Natasja Van Gasse, Sara Vijgen, Jos Van Acker, An Boel, Elizaveta Padalko
Journal: Eurosurveillance (2021)

BackgroundIn Belgium, rubella serology is frequently requested in women of childbearing age, despite high vaccination coverage and a near-absence of congenital rubella cases. Different test kits are available and should be standardised by an international standard preparation.AimTo analyse and compare rubella serology practices in Belgian laboratories.MethodsAs part of the mandatory External Quality Assessment programme for rubella serology in Belgium, the national public health institute, Sciensano, sent a voluntary questionnaire concerning anti-rubella IgM/IgG analyses in women aged 15 to 45 years in 2017 to 130 laboratories.ResultsThe questionnaire response rate was 83.8% (109/130). The majority of 169,494 IgG analyses were performed on Roche (55%), Abbott (17%) and Diasorin (13%) analysers. Not all laboratories used the proposed international cut-off of 10 IU/mL. Assumed median seroprevalence ranged from 76.3% with Liaison (Diasorin) to 96.3% with Modular (Roche). Despite very low rubella incidence in Belgium, 93 laboratories performed 85,957 IgM analyses, with 748 positive and 394 grey zone results. The National Reference Centre for Measles, Mumps and Rubella virus and the National Reference Centre for Congenital infections did not confirm any positive rubella cases in 2017.ConclusionThis retrospective analysis shows that rubella serology results may differ considerably according to the assay used. It is therefore important to use the same test when comparing results or performing follow-up testing. The number of anti-rubella IgM analyses was very high. Incorrect use of IgM for screening women of childbearing age can lead to unwarranted anxiety and overuse of confirmation tests.
Abstract 15640: Long Term Moderate, but Not Intense, Exercise Improves Cognitive Brain Health. Study in a Rat Model
Authors: Gemma Sanguesa, Montserrat Batlle, Emma Munoz Moreno, Guadalupe Soria, Anna Alcarraz, Cira Rubies, Sergio Amaro, Sara Llufriu, Lluis Mont, Eduard Guasch
Journal: Circulation (2020)

Introduction: A U-shaped relationship between exercise load and cardiovascular risk has been demonstrated. In the brain, moderate exercise improves cognitive performance but the consequences of intense exercise remain unknown. We aimed to describe the effects of moderate and intensive exercise load on brain structure and function. Methods: Male Wistar rats were subjected to moderate (MOD, 35 cm/s for 45 min, n=8) or intense (INT, 60 cm/s for 60 min, n=8) exercise for 16 weeks, 5 days/week; sedentary rats (SED, n=10) were used as controls. At 16 weeks, learning and motivation tests, and brain magnetic resonance (MR) were obtained. In MR, structural brain networks were analyzed using fractional anisotropy normalized connectomes, and cerebral blood flow (CBF) was assessed using pulsed arterial spin labelling. BDNF levels were analysed in plasma, hippocampus and frontal cortex samples with ELISA. Results: MOD rats showed a greater motivation than SED rats and enhanced learning capacity than INT rats. In the MR, only moderate exercise increased global and local efficiency and average clustering coefficient. Global CBF was increased by moderate but not intensive exercise (Fig A). CBF was subsequently assessed at specific brain regions. In comparison to SED, MOD rats presented a higher CBF in the right and left cortex, and in the left hippocampus; in INT rats, CBF was higher only in the left cortex compared to SED (Fig B). MOD training induced a significant decrease in BDNF protein levels in the hippocampus compared to both SED and INT groups. No significant differences were found on BDNF levels in plasma and frontal cortex samples among groups. Conclusions: In a rat model, moderate exercise induces brain structural and functional improvements that are not perpetuated with intensive exercise, supporting the existence of a U-shaped relationship between exercise load and brain function.
Multiple sclerosis: doubling down on MHC
Authors: Roland Martin, Mireia Sospedra, Thomas Eiermann, Tomas Olsson
Journal: Trends in Genetics (2021)

Genes of the human leukocyte antigen (HLA)-DR15 haplotype show a strong association with disease risk for multiple sclerosis (MS).Current genotyping tools failed to pinpoint the second HLA-DR allele, DRB5*01:01, besides the well-known DRB1*15:01 gene, despite their close to 100% linkage disequilibrium (LD).Functional studies illustrate the complex mechanisms of how both DR15 alleles shape a CD4+ T cell repertoire that is selected and maintained by peptides from the HLA-DR molecules but reacts more strongly to peptides from both MS-associated infectious organisms and autoantigens.The multiple roles of disease-associated HLA-DR molecules include serving as antigen-presenting structure and as a source of antigen.The cooperativity between two HLA-DR alleles of the same haplotype likely applies to other HLA-disease associations as well and should be examined. Human leukocyte antigen (HLA)-encoded surface molecules present antigenic peptides to T lymphocytes and play a key role in adaptive immune responses. Besides their physiological role of defending the host against infectious pathogens, specific alleles serve as genetic risk factors for autoimmune diseases. For multiple sclerosis (MS), an autoimmune disease that affects the brain and spinal cord, an association with the HLA-DR15 haplotype was described in the early 1970s. This short opinion piece discusses the difficulties of disentangling the details of this association and recent observations about the functional involvement of not only one, but also the second gene of the HLA-DR15 haplotype. This information is not only important for understanding the pathomechanism of MS, but also for antigen-specific therapies. Human leukocyte antigen (HLA)-encoded surface molecules present antigenic peptides to T lymphocytes and play a key role in adaptive immune responses. Besides their physiological role of defending the host against infectious pathogens, specific alleles serve as genetic risk factors for autoimmune diseases. For multiple sclerosis (MS), an autoimmune disease that affects the brain and spinal cord, an association with the HLA-DR15 haplotype was described in the early 1970s. This short opinion piece discusses the difficulties of disentangling the details of this association and recent observations about the functional involvement of not only one, but also the second gene of the HLA-DR15 haplotype. This information is not only important for understanding the pathomechanism of MS, but also for antigen-specific therapies.