tbuckley/cabot-search huggingface dataset:
Molecular allergology and its impact in specific allergy diagnosis and therapy
Authors: Domingo Barber, Araceli Diaz‐Perales, Maria M. Escribese, Jörg Kleine‐Tebbe, Paolo M. Matricardi, Markus Ollert, Alexandra F. Santos, Joaquin Sastre
Journal: Allergy (2021)

Abstract Progressive knowledge of allergenic structures resulted in a broad availability of allergenic molecules for diagnosis. Component‐resolved diagnosis allowed a better understanding of patient sensitization patterns, facilitating allergen immunotherapy decisions. In parallel to the discovery of allergenic molecules, there was a progressive development of a regulation framework that affected both in vitro diagnostics and Allergen Immunotherapy products. With a progressive understanding of underlying mechanisms associated to Allergen immunotherapy and an increasing experience of application of molecular diagnosis in daily life, we focus in analyzing the evidences of the value provided by molecular allergology in daily clinical practice, with a focus on Allergen Immunotherapy decisions.
Outcomes With Surgery vs Functional Bracing for Patients With Closed, Displaced Humeral Shaft Fractures and the Need for Secondary Surgery
Authors: Lasse Rämö, Mika Paavola, Bakir O. Sumrein, Vesa Lepola, Tuomas Lähdeoja, Jonas Ranstam, Teppo L. N. Järvinen, Simo Taimela, Mikko T Salmela, Miia Mäntysaari, Thomas Ibounig, Robert Björkenheim, Eerik Hällfors, Antti P Launonen, Antti Riuttanen, Leena Caravitis, Seija Rautiainen, Pasi Aronen, Antti Malmivaara
Journal: JAMA Surgery (2021)

<h3>Importance</h3> Existing evidence indicates that surgery fails to provide superior functional outcome over nonoperative care in patients with a closed humeral shaft fracture. However, up to one-third of patients treated nonoperatively may require secondary surgery. <h3>Objective</h3> To compare the 2-year outcomes of patients who required secondary surgery with the outcomes of patients with successful initial treatment. <h3>Design, Setting, and Participants</h3> This 2-year follow-up of the Finnish Shaft of the Humerus (FISH) randomized clinical trial comparing surgery with nonoperative treatment (functional brace) was completed in January 2020. Enrollment in the original trial was between November 2012 and January 2018 at 2 university hospital trauma centers in Finland. A total of 321 adult patients with closed, displaced humeral shaft fracture were assessed for eligibility. After excluding patients with cognitive disabilities, multimorbidity, or multiple trauma and those refusing randomization, 82 patients were randomized. <h3>Interventions</h3> Interventions were surgery with plate fixation (n = 38; initial surgery group) or functional bracing (n = 44); the latter group was divided into the successful fracture healing group (n = 30; bracing group) and the secondary surgery group (n = 14) with fracture healing problems. <h3>Main Outcomes and Measures</h3> The primary outcome was Disabilities of Arm, Shoulder and Hand (DASH) score at 2 years (range, 0 to 100 points; 0 denotes no disability, 100 extreme disability; minimal clinically important difference, 10 points). <h3>Results</h3> Of 82 randomized patients, 38 (46%) were female. The mean (SD) age was 48.9 (17.1) years. A total of 74 patients (90%) completed the 2-year follow-up. At 2 years, the mean DASH score was 6.8 (95% CI, 2.3 to 11.4) in the initial surgery group, 6.0 (95% CI, 1.0 to 11.0) in the bracing group, and 17.5 (95% CI, 10.5 to 24.5) in the secondary surgery group. The between-group difference was −10.7 points (95% CI, −19.1 to −2.3;<i>P</i> = .01) between the initial and secondary surgery groups and −11.5 points (95% CI, −20.1 to −2.9;<i>P</i> = .009) between the bracing group and secondary surgery group. <h3>Conclusions and Relevance</h3> Patients contemplating treatment for closed humeral shaft fracture should be informed that two-thirds of patients treated with functional bracing may heal successfully while one-third may experience fracture healing problems that require secondary surgery and lead to inferior functional outcomes 2 years after the injury. <h3>Trial Registration</h3> ClinicalTrials.gov Identifier:NCT01719887
Implant Surface Texture and Breast Cancer Recurrence
Authors: Eveline Bijlard, Marc A. M. Mureau
Journal: JAMA Surgery (2021)

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Isochrony, vocal learning, and the acquisition of rhythm and melody
Authors: Andrea Ravignani
Journal: Behavioral and Brain Sciences (2021)

Abstract A cross-species perspective can extend and provide testable predictions for Savage et al.'s framework. Rhythm and melody, I argue, could bootstrap each other in the evolution of musicality. Isochrony may function as a temporal grid to support rehearsing and learning modulated, pitched vocalizations. Once this melodic plasticity is acquired, focus can shift back to refining rhythm processing and beat induction.
Immune dysregulation and autoreactivity correlate with disease severity in SARS-CoV-2-associated multisystem inflammatory syndrome in children
Authors: Anjali Ramaswamy, Nina N. Brodsky, Tomokazu S. Sumida, Michela Comi, Hiromitsu Asashima, Kenneth B. Hoehn, Ningshan Li, Yunqing Liu, Aagam Shah, Neal G. Ravindra, Jason Bishai, Alamzeb Khan, William Lau, Brian Sellers, Neha Bansal, Pamela Guerrerio, Avraham Unterman, Victoria Habet, Andrew J. Rice, Jason Catanzaro, Harsha Chandnani, Merrick Lopez, Naftali Kaminski, Charles S. Dela Cruz, John S. Tsang, Zuoheng Wang, Xiting Yan, Steven H. Kleinstein, David van Dijk, Richard W. Pierce, David A. Hafler, Carrie L. Lucas
Journal: Immunity (2021)
A call for the standardised reporting of factors affecting the exogenous loading of extracellular vesicles with therapeutic cargos
Authors: Stephanie Rankin-Turner, Pieter Vader, Lorraine O'Driscoll, Bernd Giebel, Liam M. Heaney, Owen G. Davies
Journal: Advanced Drug Delivery Reviews (2021)

Extracellular vesicles (EVs) are complex nanoparticles required for the intercellular transfer of diverse biological cargoes. Unlike synthetic nanoparticles, EVs may provide a natural platform for the enhanced targeting and functional transfer of therapeutics across complex and often impenetrable biological boundaries (e.g. the blood–brain barrier or the matrix of densely organised tumours). Consequently, there is considerable interest in utilising EVs as advanced drug delivery systems for the treatment of a range of challenging pathologies. Within the past decade, efforts have focused on providing standard minimal requirements for conducting basic EV research. However, no standard reporting framework has been established governing the therapeutic loading of EVs for drug delivery applications. The purpose of this review is to critically evaluate progress in the field, providing an initial set of guidelines that can be applied as a benchmark to enhance reproducibility and increase the likelihood of translational outcomes.
High Level of IL-2-Receptor and of TIM-3 in Plasma at Day +18 after Allogeneic Transplantation Can Identify Early Patients at Risk for Treatment Related Mortality
Authors: Giuseppe Milone, Viviana Frontini, Alessandra Cupri, Salvatore Leotta, Annalia DiMarco, Carla Consoli, Luca Scalise, Giuseppe Sapienza, Gaetano Moschetti, Giuseppe Avola, Andrea Spadaro, AnnaElisa Marchese
Journal: Blood (2017)
A Fc engineering approach to define functional humoral correlates of immunity against Ebola virus
Authors: Bronwyn M. Gunn, Richard Lu, Matthew D. Slein, Philipp A. Ilinykh, Kai Huang, Caroline Atyeo, Sharon L. Schendel, Jiyoung Kim, Caitlin Cain, Vicky Roy, Todd J. Suscovich, Ayato Takada, Peter J. Halfmann, Yoshihiro Kawaoka, Matthias G. Pauthner, Mambu Momoh, Augustine Goba, Lansana Kanneh, Kristian G. Andersen, John S. Schieffelin, Donald Grant, Robert F. Garry, Erica Ollmann Saphire, Alexander Bukreyev, Galit Alter
Journal: Immunity (2021)

Protective Ebola virus (EBOV) antibodies have neutralizing activity and induction of antibody constant domain (Fc)-mediated innate immune effector functions. Efforts to enhance Fc effector functionality often focus on maximizing antibody-dependent cellular cytotoxicity, yet distinct combinations of functions could be critical for antibody-mediated protection. As neutralizing antibodies have been cloned from EBOV disease survivors, we sought to identify survivor Fc effector profiles to help guide Fc optimization strategies. Survivors developed a range of functional antibody responses, and we therefore applied a rapid, high-throughput Fc engineering platform to define the most protective profiles. We generated a library of Fc variants with identical antigen-binding fragments (Fabs) from an EBOV neutralizing antibody. Fc variants with antibody-mediated complement deposition and moderate natural killer (NK) cell activity demonstrated complete protective activity in a stringent in vivo mouse model. Our findings highlight the importance of specific effector functions in antibody-mediated protection, and the experimental platform presents a generalizable resource for identifying correlates of immunity to guide therapeutic antibody design.
Covid-19: India looks to import oxygen as cases surge, overwhelming hospitals
Authors: Anoo Bhuyan
Journal: BMJ (2021)

India’s government has announced that it needs to import 50 000 tonnes of medical oxygen as cases of covid-19 increase across the country and hospitals turn away patients in need of oxygen support or ventilators.

The government has asked diplomats around the world to identify vendors from whom it can purchase oxygen to meet the need. It has also invited vendors to make bids to supply 100 000 oxygen cylinders.

India is currently experiencing its second wave of the covid-19 pandemic, which has eclipsed its first wave. The country has been reporting more than 100 000 cases a day since 4 April, then 200 000 a day since 15 April. Previously the peak had been 97 860 cases on a single day …
Corticosteroids in COVID-19 and non-COVID-19 ARDS: a systematic review and meta-analysis
Authors: Dipayan Chaudhuri, Kiyoka Sasaki, Aram Karkar, Sameer Sharif, Kimberly Lewis, Manoj J. Mammen, Paul Alexander, Zhikang Ye, Luis Enrique Colunga Lozano, Marie Warrer Munch, Anders Perner, Bin Du, Lawrence Mbuagbaw, Waleed Alhazzani, Stephen M. Pastores, John Marshall, François Lamontagne, Djillali Annane, Gianfranco Umberto Meduri, Bram Rochwerg
Journal: Intensive Care Medicine (2021)

Corticosteroids are now recommended for patients with severe COVID-19 including those with COVID-related ARDS. This has generated renewed interest regarding whether corticosteroids should be used in non-COVID ARDS as well. The objective of this study was to summarize all RCTs examining the use of corticosteroids in ARDS. The protocol of this study was pre-registered on PROSPERO (CRD42020200659). We searched online databases including MEDLINE, EMBASE, CDC library of COVID research, CINAHL, and COCHRANE. We included RCTs that compared the effect of corticosteroids to placebo or usual care in adult patients with ARDS, including patients with COVID-19. Three reviewers abstracted data independently and in duplicate using a pre-specified standardized form. We assessed individual study risk of bias using the revised Cochrane ROB-2 tool and rated certainty in outcomes using GRADE methodology. We pooled data using a random effects model. The main outcome for this review was 28-day-mortality. We included 18 RCTs enrolling 2826 patients. The use of corticosteroids probably reduced mortality in patients with ARDS of any etiology (2740 patients in 16 trials, RR 0.82, 95% CI 0.72–0.95, ARR 8.0%, 95% CI 2.2–12.5%, moderate certainty). Patients who received a longer course of corticosteroids (over 7 days) had higher rates of survival compared to a shorter course. The use of corticosteroids probably reduces mortality in patients with ARDS. This effect was consistent between patients with COVID-19 and non-COVID-19 ARDS, corticosteroid types, and dosage.
Para sport translation of the IOC consensus on recording and reporting of data for injury and illness in sport
Authors: Wayne Derman, Marelise Badenhorst, Cheri Blauwet, Carolyn A Emery, Kristina Fagher, Young-Hee Lee, James Kissick, Jan Lexell, Ian Stuart Miller, Babette M Pluim, Martin Schwellnus, Kathrin Steffen, Peter Van de Vliet, Nick Webborn, Richard Weiler
Journal: British Journal of Sports Medicine (2021)

In 2020, the IOC proposed a universal methodology for the recording and reporting of data for injury and illness in sport. Para sport is played by individuals with impairment, and they have a unique set of considerations not captured by these recommendations. Therefore, the aim of this addendum to IOC consensus statement was to guide the Para sport researcher through the complexities and nuances that should be taken into consideration when collecting, registering, reporting and interpreting data regarding Para athlete health. To develop this translation, experts in the field of Para sports medicine and epidemiology conducted a formal consensus development process, which began in March 2020 with the formation of a consensus group that worked over eight phases, incorporating three virtual consensus meetings to finalise the translation. This translation is consistent with the IOC consensus statement, yet provides more detailed Para athlete specific definitions and recommendations on study population, specifically, diagnostic and eligible impairment categorisation and recording of adaptive equipment, and defining and classifying health problems in the context of Para sport. Additionally, recommendations and Para athlete specific examples are described with regards to injury mechanism, mode of onset, injury and illness classification, duration, capturing and reporting exposure and risk. Finally, methods and considerations are provided to cater to the varied needs of athletes with impairment with respect to data collection tools. This harmonisation will allow the science to develop and facilitate a more accurate understanding of injury and illness patterns for tailoring evidence-informed prevention programmes and enabling better planning of medical services for Para sport events.
Vitamin K and osteoarthritis: is there a link?
Authors: Richard F Loeser, Francis Berenbaum, Margreet Kloppenburg
Journal: Annals of the Rheumatic Diseases (2021)

Vitamin K is best known for its role in blood coagulation. The reduced form of vitamin K is a necessary cofactor for the γ-carboxylase enzyme that converts specific glutamic acid residues to γ-carboxyglutamic acid (Gla) in the coagulation factors II, XII, IX, X and protein C and protein S.1 Proteins containing one or more Gla residues are often referred to as vitamin K-dependent proteins. The presence of calcium-binding Gla residues is critical to the structure and function of the vitamin K-dependent coagulation proteins. The anticoagulant drugs warfarin and acenocoumarol interfere with the reduction of vitamin K to its active form by inhibiting vitamin K epoxide reductase complex 1 (VKORC1) and so are known as vitamin K antagonists (VKAs).1 These drugs are widely used clinically to treat patients with blood clots or at high risk of blood clots, although newer anticoagulants are available that do not act by inhibiting vitamin K function. These are often referred to as direct oral anticoagulants (DOACs) or non-vitamin K oral anticoagulants (NOACs).

The vitamin K-dependent coagulation proteins are produced primarily in the liver and function within the systemic circulation and vasculature. However, there are a number of vitamin K-dependent proteins not involved in blood coagulation, including several found in joint tissues.2–5 The latter include matrix Gla protein (MGP), Gla-rich protein (GRP) and growth arrest specific gene 6 (Gas6) found in cartilage, the bone proteins bone Gla protein (osteocalcin) and transforming growth factor β (TGFβ)-induced protein, and periostin found in cartilage and the periosteum.5–10 Periostin and TGFβ-induced protein may not be γ-carboxylated in all tissues,11 and their γ-carboxylation status has not been determined in the joint. Although the precise function of the vitamin K-dependent proteins in the joint is not known, MGP and GRP have been shown to inhibit mineralisation, Gas6 …
A 3D personalized cardiac myocyte aggregate orientation model using MRI data-driven low-rank basis functions
Authors: Johanna Stimm, Stefano Buoso, Ezgi Berberoğlu, Sebastian Kozerke, Martin Genet, Christian T. Stoeck
Journal: Medical Image Analysis (2021)

Cardiac myocyte aggregate orientation has a strong impact on cardiac electrophysiology and mechanics. Studying the link between structural characteristics, strain, and stresses over the cardiac cycle and cardiac function requires a full volumetric representation of the microstructure. In this work, we exploit the structural similarity across hearts to extract a low-rank representation of predominant myocyte orientation in the left ventricle from high-resolution magnetic resonance ex-vivo cardiac diffusion tensor imaging (cDTI) in porcine hearts. We compared two reduction methods, Proper Generalized Decomposition combined with Singular Value Decomposition and Proper Orthogonal Decomposition. We demonstrate the existence of a general set of basis functions of aggregated myocyte orientation which defines a data-driven, personalizable, parametric model featuring higher flexibility than existing atlas and rule-based approaches. A more detailed representation of microstructure matching the available patient data can improve the accuracy of personalized computational models. Additionally, we approximate the myocyte orientation of one ex-vivo human heart and demonstrate the feasibility of transferring the basis functions to humans.
Covid-19: India authorises Sputnik V vaccine as cases soar to more than 180 000 a day
Authors: Patralekha Chatterjee
Journal: BMJ (2021)

<h3>Background</h3> The third international consensus definition for sepsis recommended use of a new prognostic tool, the quick Sequential Organ Failure Assessment (qSOFA), based on its ability to predict inhospital mortality and prolonged intensive care unit (ICU) stay in patients with suspected infection. While several studies have compared the prognostic accuracy of qSOFA to the Systemic Inflammatory Response Syndrome (SIRS) criteria in suspected sepsis, few have compared qSOFA and SIRS to the widely used National Early Warning Score (NEWS). <h3>Methods</h3> This was a retrospective cohort study carried out in a UK tertiary centre. The study population comprised emergency admissions in whom sepsis was suspected and treated. The accuracy for predicting inhospital mortality and ICU admission was calculated and compared for qSOFA, SIRS and NEWS. <h3>Results</h3> Among 1818 patients, 53 were admitted to ICU (3%) and 265 died in hospital (15%). For predicting inhospital mortality, the area under the receiver operating characteristics curve for NEWS (0.65, 95% CI 0.61 to 0.68) was similar to qSOFA (0.62, 95% CI 0.59 to 0.66) (test for difference, P=0.18) and superior to SIRS (P&lt;0.001), which was not predictive. The sensitivity of NEWS≥5 (74%, 95% CI 68% to 79%) was similar to SIRS≥2 (80%, 95% CI 74% to 84%) and higher than qSOFA≥2 (37%, 95% CI 31% to 43%). The specificity of NEWS≥5 (43%, 95% CI 41% to 46%) was higher than SIRS≥2 (21%, 95% CI 19% to 23%) and lower than qSOFA≥2 (79%, 95% CI 77% to 81%). The negative predictive value was 88% (86%–90%) for qSOFA, 86% (82%–89%) for SIRS and 91% (88%–93%) for NEWS. Results were similar for the secondary outcome of ICU admission. <h3>Conclusion</h3> NEWS has equivalent or superior value for most test characteristics relative to SIRS and qSOFA, calling into question the rationale of adopting qSOFA in institutions where NEWS is already in use.
The WHO Global Diabetes Compact: a new initiative to support people living with diabetes
Authors: Daniel Hunt, Bianca Hemmingsen, Alena Matzke, Cherian Varghese, Asmus Hammerich, Silvana Luciani, Anselm Hennis, Francesco Branca, Fiona Bull, Nino Berdzuli, Jean-Marie Dangou, Razia Pendse, Angela Pratt, Bente Mikkelsen
Journal: The Lancet Diabetes & Endocrinology (2021)
Abstract 13719: Molecular Chaperones Facilitate the Pre-Secretory Degradation of Apolipoprotein B, the Major Proteinaceous Component in Chylomicrons and Very Low Density Lipoprotein Particles
Authors: Deepa Kumari, Jeffrey L Brodsky
Journal: Circulation (2019)

Coronary artery disease (CAD) kills 17.3 million people every year, and elevated levels of apolipoprotein B (ApoB) are a major risk factor for CAD. ApoB is the primary component of atherogenic lipo...
Pathologic Antibodies to Platelet Factor 4 after ChAdOx1 nCoV-19 Vaccination
Authors: Marie Scully, Deepak Singh, Robert Lown, Anthony Poles, Tom Solomon, Marcel Levi, David Goldblatt, Pavel Kotoucek, William Thomas, William Lester
Journal: New England Journal of Medicine (2021)

The mainstay of control of the coronavirus disease 2019 (Covid-19) pandemic is vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Within a year, several vaccines have been developed and millions of doses delivered. Reporting of adverse events is a critical postmarketing activity.We report findings in 23 patients who presented with thrombosis and thrombocytopenia 6 to 24 days after receiving the first dose of the ChAdOx1 nCoV-19 vaccine (AstraZeneca). On the basis of their clinical and laboratory features, we identify a novel underlying mechanism and address the therapeutic implications.In the absence of previous prothrombotic medical conditions, 22 patients presented with acute thrombocytopenia and thrombosis, primarily cerebral venous thrombosis, and 1 patient presented with isolated thrombocytopenia and a hemorrhagic phenotype. All the patients had low or normal fibrinogen levels and elevated d-dimer levels at presentation. No evidence of thrombophilia or causative precipitants was identified. Testing for antibodies to platelet factor 4 (PF4) was positive in 22 patients (with 1 equivocal result) and negative in 1 patient. On the basis of the pathophysiological features observed in these patients, we recommend that treatment with platelet transfusions be avoided because of the risk of progression in thrombotic symptoms and that the administration of a nonheparin anticoagulant agent and intravenous immune globulin be considered for the first occurrence of these symptoms.Vaccination against SARS-CoV-2 remains critical for control of the Covid-19 pandemic. A pathogenic PF4-dependent syndrome, unrelated to the use of heparin therapy, can occur after the administration of the ChAdOx1 nCoV-19 vaccine. Rapid identification of this rare syndrome is important because of the therapeutic implications.