tbuckley/cabot-search huggingface dataset:
Improving concussion education: consensus from the NCAA-Department of Defense Mind Matters Research &amp; Education Grand Challenge
Authors: Emily Kroshus, Kenneth L Cameron, J Douglas Coatsworth, Christopher D"Lauro, Eungjae Kim, Katherine Lee, Johna K Register-Mihalik, Jeffery J Milroy, E Paul Roetert, Julianne D Schmidt, Ross D Silverman, Dee Warmath, Heidi A Wayment, Brian Hainline
Journal: British Journal of Sports Medicine (2020)

Early disclosure of possible concussive symptoms has the potential to improve concussion-related clinical outcomes. The objective of the present consensus process was to provide useful and feasible recommendations for collegiate athletic departments and military service academy leaders about how to increase concussion symptom disclosure in their setting. Consensus was obtained using a modified Delphi process. Participants in the consensus process were grant awardees from the National Collegiate Athletic Association and Department of Defense Mind Matters Research &amp; Education Grand Challenge and a multidisciplinary group of stakeholders from collegiate athletics and military service academies. The process included a combination of in-person meetings and anonymous online voting on iteratively modified recommendations for approaches to improve concussion symptom disclosure. Recommendations were rated in terms of their utility and feasibility in collegiate athletic and military service academy settings with a priori thresholds for retaining, discarding and revising statements. A total of 17 recommendations met thresholds for utility and feasibility and are grouped for discussion in five domains: (1) content of concussion education for athletes and military service academy cadets, (2) dissemination and implementation of concussion education for athletes and military service academy cadets, (3) other stakeholder concussion education, (4) team and unit-level processes and (5) organisational processes. Collectively, these recommendations provide a path forward for athletics departments and military service academies in terms of the behavioural health supports and institutional processes that are needed to increase early and honest disclosure of concussion symptoms and ultimately to improve clinical care outcomes.
Sample pooling for SARS-CoV-2 RT-PCR screening
Authors: Adolfo de Salazar, Antonio Aguilera, Rocio Trastoy, Ana Fuentes, Juan Carlos Alados, Manuel Causse, Juan Carlos Galán, Antonio Moreno, Matilde Trigo, Mercedes Pérez-Ruiz, Carolina Roldán, Maria José Pena, Samuel Bernal, Esther Serrano-Conde, Gema Barbeito, Eva Torres, Cristina Riazzo, Jose Luis Cortes-Cuevas, Natalia Chueca, Amparo Coira, Juan Manuel Sanchez-Calvo, Eduardo Marfil, Federico Becerra, María José Gude, Ángeles Pallarés, María Luisa Pérez Del Molino, Federico García
Journal: Clinical Microbiology and Infection (2020)
Guidelines for clinical trial protocols for interventions involving artificial intelligence: the SPIRIT-AI extension
Authors: Samantha Cruz Rivera, Xiaoxuan Liu, An-Wen Chan, Alastair K Denniston, Melanie J Calvert, Hutan Ashrafian, Andrew L Beam, Gary S Collins, Ara Darzi, Jonathan J Deeks, M Khair ElZarrad, Cyrus Espinoza, Andre Esteva, Livia Faes, Lavinia Ferrante di Ruffano, John Fletcher, Robert Golub, Hugh Harvey, Charlotte Haug, Christopher Holmes, Adrian Jonas, Pearse A Keane, Christopher J Kelly, Aaron Y Lee, Cecilia S Lee, Elaine Manna, James Matcham, Melissa McCradden, David Moher, Joao Monteiro, Cynthia Mulrow, Luke Oakden-Rayner, Dina Paltoo, Maria Beatrice Panico, Gary Price, Samuel Rowley, Richard Savage, Rupa Sarkar, Sebastian J Vollmer, Christopher Yau
Journal: The Lancet Digital Health (2020)

The SPIRIT 2013 statement aims to improve the completeness of clinical trial protocol reporting by providing evidence-based recommendations for the minimum set of items to be addressed. This guidance has been instrumental in promoting transparent evaluation of new interventions. More recently, there has been a growing recognition that interventions involving artificial intelligence (AI) need to undergo rigorous, prospective evaluation to demonstrate their impact on health outcomes. The SPIRIT-AI (Standard Protocol Items: Recommendations for Interventional Trials-Artificial Intelligence) extension is a new reporting guideline for clinical trial protocols evaluating interventions with an AI component. It was developed in parallel with its companion statement for trial reports: CONSORT-AI (Consolidated Standards of Reporting Trials-Artificial Intelligence). Both guidelines were developed through a staged consensus process involving literature review and expert consultation to generate 26 candidate items, which were consulted upon by an international multi-stakeholder group in a two-stage Delphi survey (103 stakeholders), agreed upon in a consensus meeting (31 stakeholders) and refined through a checklist pilot (34 participants). The SPIRIT-AI extension includes 15 new items that were considered sufficiently important for clinical trial protocols of AI interventions. These new items should be routinely reported in addition to the core SPIRIT 2013 items. SPIRIT-AI recommends that investigators provide clear descriptions of the AI intervention, including instructions and skills required for use, the setting in which the AI intervention will be integrated, considerations for the handling of input and output data, the human-AI interaction and analysis of error cases. SPIRIT-AI will help promote transparency and completeness for clinical trial protocols for AI interventions. Its use will assist editors and peer reviewers, as well as the general readership, to understand, interpret, and critically appraise the design and risk of bias for a planned clinical trial.
YAP-Mediated Repression of HRK Regulates Tumor Growth, Therapy Response, and Survival Under Tumor Environmental Stress in Neuroblastoma
Authors: Jenny Shim, Jasmine Y. Lee, Hunter C. Jonus, Amanda Arnold, Robert W. Schnepp, Kaitlyn M. Janssen, Victor Maximov, Kelly C. Goldsmith
Journal: Cancer Research (2020)

Following chemotherapy and relapse, high-risk neuroblastoma tumors harbor more genomic alterations than at diagnosis, including increased transcriptional activity of the Yes-associated protein (YAP), a key downstream component of the Hippo signaling network. Although YAP has been implicated in many cancer types, its functional role in the aggressive pediatric cancer neuroblastoma is not well-characterized. In this study, we performed genetic manipulation of YAP in human-derived neuroblastoma cell lines to investigate YAP function in key aspects of the malignant phenotype, including mesenchymal properties, tumor growth, chemotherapy response, and MEK inhibitor response. Standard cytotoxic therapy induced YAP expression and transcriptional activity in patient-derived xenografts treated in vivo, which may contribute to neuroblastoma recurrence. Moreover, YAP promoted a mesenchymal phenotype in high-risk neuroblastoma that modulated tumor growth and therapy resistance in vivo. Finally, the BH3-only protein, Harakiri (HRK), was identified as a novel target inhibited by YAP, which, when suppressed, prevented apoptosis in response to nutrient deprivation in vitro and promoted tumor aggression, chemotherapy resistance, and MEK inhibitor resistance in vivo. Collectively, these findings suggest that YAP inhibition may improve chemotherapy response in patients with neuroblastoma via its regulation of HRK, thus providing a critical strategic complement to MEK inhibitor therapy. SIGNIFICANCE: This study identifies HRK as a novel tumor suppressor in neuroblastoma and suggests dual MEK and YAP inhibition as a potential therapeutic strategy in RAS-hyperactivated neuroblastomas.
Climate change could shift disease burden from malaria to arboviruses in Africa
Authors: Erin A Mordecai, Sadie J Ryan, Jamie M Caldwell, Melisa M Shah, A Desiree LaBeaud
Journal: The Lancet Planetary Health (2020)

Malaria is a long-standing public health problem in sub-Saharan Africa, whereas arthropod-borne viruses (arboviruses) such as dengue and chikungunya cause an under-recognised burden of disease. Many human and environmental drivers affect the dynamics of vector-borne diseases. In this Personal View, we argue that the direct effects of warming temperatures are likely to promote greater environmental suitability for dengue and other arbovirus transmission by Aedes aegypti and reduce suitability for malaria transmission by Anopheles gambiae. Environmentally driven changes in disease dynamics will be complex and multifaceted, but given that current public efforts are targeted to malaria control, we highlight Ae aegypti and dengue, chikungunya, and other arboviruses as potential emerging public health threats in sub-Saharan Africa.
慢性骨髄性白血病の管理に関する欧州白血病ネット(European LeukemiaNet)の推奨事項: 2013年
Authors: Baccarani Michele, W Deininger Michael, Rosti Gianantonio, Hochhaus Andreas, Soverini Simona, F Apperley Jane, Cervantes Francisco, E Clark Richard, E Cortes Jorge, Guilhot Francois, Hjorth-Hansen Henrik, P Hughes Timothy, M Kantarjian Hagop, Kim Dong-Wook, A Larson Richard, H Lipton Jeffrey, Mahon Francois-Xavier, Martinelli Giovanni, Mayer Jiri, C Mueller Martin, Niederwieser Dietger, Pane Fabrizio, P Radich Jerald, Rousselot Philippe, Saglio Giuseppe, Saussele Susanne, Schiffer Charles, Silver Richard, Simonsson Bengt, Steegmann Juan-Luis, M Goldman John, Hehlmann Ruediger
Journal: Blood (2013)
Development of a pathogenesis‐based therapy for peeling skin syndrome type 1*
Authors: F. Valentin, H. Wiegmann, T. Tarinski, H. Nikolenko, H. Traupe, E. Liebau, M. Dathe, V. Oji
Journal: British Journal of Dermatology (2020)

Peeling skin syndrome type 1 (PSS1) is a rare and severe autosomal recessive form of congenital ichthyosis. Patients are affected by pronounced erythroderma accompanied by pruritus and superficial generalized peeling of the skin. The disease is caused by nonsense mutations or complete deletion of the CDSN gene encoding for corneodesmosin (CDSN). PSS1 severely impairs quality of life and therapeutic approaches are totally unsatisfactory.The objective of this study was to develop the first steps towards a specific protein replacement therapy for CDSN deficiency. Using this approach, we aimed to restore the lack of CDSN and improve cell-cell cohesion in the transition area of the stratum granulosum (SG) to the stratum corneum.Human CDSN was recombinantly expressed in Escherichia coli. A liposome-based carrier system, prepared with a cationic lipopeptide to mediate the transport to the outer membrane of keratinocytes, was developed. This formulation was chosen for CDSN delivery into the skin. The liposomal carrier system was characterized with respect to size, stability and toxicity. Furthermore, the interaction with primary keratinocytes and human epidermal equivalents was investigated.The liposomes showed an accumulation at the membranes of keratinocytes. CDSN-deficient epidermal equivalents that were treated with liposomal encapsulated CDSN demonstrated presence of CDSN in the SG. Finally, the penetration assay and histological examinations revealed an improved epidermal integrity for CDSN-deficient epidermal equivalents, if they were treated with liposomal encapsulated CDSN.This study presents the first preclinical in vitro experiments for a future specific protein replacement therapy for patients affected by PSS1.
Complement and coagulation: key triggers of COVID-19–induced multiorgan pathology
Authors: Berhane Ghebrehiwet, Ellinor I. Peerschke
Journal: Journal of Clinical Investigation (2020)

In a stunningly short period of time, the unexpected coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS–CoV-2), has turned the unprepared world topsy-turvy. Although the rapidity with which the virus struck was indeed overwhelming, scientists throughout the world have been up to the task of deciphering the mechanisms by which SARS–CoV-2 induces the multisystem and multiorgan inflammatory responses that, collectively, contribute to the high mortality rate in affected individuals. In this issue of the JCI, Skendros and Mitsios et al. is one such team who report that the complement system plays a substantial role in creating the hyperinflammation and thrombotic microangiopathy that appear to contribute to the severity of COVID-19. In support of the hypothesis that the complement system along with neutrophils and platelets contributes to COVID-19, the authors present empirical evidence showing that treatment with the complement inhibitor compstatin Cp40 inhibited the expression of tissue factor in neutrophils. These results confirm that the complement axis plays a critical role and suggest that targeted therapy using complement inhibitors is a potential therapeutic option to treat COVID-19–induced inflammation.
Endoscopic removal of two duodenal stents that had migrated into the colon, using the invagination method
Authors: Takashi Sasaki, Tsuyoshi Takeda, Chihiro Yasue, Junki Tokura, Daisuke Ide, Shoichi Saito, Naoki Sasahira
Journal: Endoscopy (2020)

A 77-year-old woman with advanced pancreatic cancer presented with combined biliary and duodenal malignant obstruction. An uncovered self-expandable metal stent (SEMS) (Nexent Duodenal/Pyloric stent, 22 mm × 12 cm; Next Biomedical, Korea) and a partially covered SEMS (Niti-S ComVi stent, 20 mm × 12 cm; Century Medical, Korea) were deployed for the duodenal obstruction ([Fig. 1]). After three cycles of chemotherapy, the two duodenal SEMSs had migrated to the transverse colon ([Fig. 2]). We decided to remove the SEMSs to avoid perforation. A short-type single-balloon enteroscope (SIF-H290S; Olympus Medical, Japan) was inserted with the overtube ([Video 1]). The SEMSs were identified at the bending part of the colon. We first tried to grasp the distal end with a rat-tooth forceps, but the SEMSs were tightly embedded in the wall. Therefore, the enteroscope was inserted across the SEMSs and the proximal end of the partially covered SEMS was grasped by the forceps and removed using the invagination method. The SEMSs and the enteroscope were pulled into the overtube so as not to injure the intestinal wall. Both SEMSs were successfully removed without any complications ([Fig. 3, ] [Fig. 4, ] [Fig. 5]; [Video 1]).
Preparation and characterization of an injectable dexamethasone-cyclodextrin complexes-loaded gellan gum hydrogel for cartilage tissue engineering
Authors: Joo Hee Choi, Ain Park, Wonchan Lee, Jina Youn, Min A. Rim, Wooyoup Kim, Namyeong Kim, Jeong Eun Song, Gilson Khang
Journal: Journal of Controlled Release (2020)
Clinical and genomic characterisation of mismatch repair deficient pancreatic adenocarcinoma
Authors: Robert C Grant, Robert Denroche, Gun Ho Jang, Klaudia M Nowak, Amy Zhang, Ayelet Borgida, Spring Holter, James T Topham, Julie Wilson, Anna Dodd, Raymond Jang, Rebecca Prince, Joanna M Karasinska, David F Schaeffer, Yifan Wang, George Zogopoulos, Scott Berry, Diane Simeone, Daniel J Renouf, Faiyaz Notta, Grainne O'Kane, Jennifer Knox, Sandra Fischer, Steven Gallinger
Journal: Gut (2020)

To describe the clinical, pathological and genomic characteristics of pancreatic cancer with DNA mismatch repair deficiency (MMRD) and proficiency (MMRP).We identified patients with MMRD and MMRP pancreatic cancer in a clinical cohort (N=1213, 519 with genetic testing, 53 with immunohistochemistry (IHC)) and a genomic cohort (N=288 with whole-genome sequencing (WGS)).12 out of 1213 (1.0%) in the clinical cohort were MMRD by IHC or WGS. Of the 14 patients with Lynch syndrome, 3 (21.4%) had an MMRP pancreatic cancer by IHC, and 4 (28.6%) were excluded because tissue was unavailable for testing. MMRD cancers had longer overall survival after surgery (weighted HR after coarsened exact matching 0.11, 95% CI 0.02 to 0.78, p=0.001). One patient with an unresectable MMRD cancer has an ongoing partial response 3 years after starting treatment with PD-L1/CTLA-4 inhibition. This tumour showed none of the classical histopathological features of MMRD. 9 out of 288 (3.1%) tumours with WGS were MMRD. Despite markedly higher tumour mutational burden and neoantigen loads, MMRD cancers were significantly less likely to have mutations in usual pancreatic cancer driver genes like KRAS and SMAD4, but more likely to have mutations in genes that drive cancers with microsatellite instability like ACV2RA and JAK1. MMRD tumours were significantly more likely to have a basal-like transcriptional programme and elevated transcriptional markers of immunogenicity.MMRD pancreatic cancers have distinct clinical, pathological and genomic profiles. Patients with MMRD pancreatic cancer should be considered for basket trials targeting enhanced immunogenicity or the unique genomic drivers in these malignancies.
Thiopurine monotherapy has a limited place in treatment of patients with mild-to-moderate Crohn’s disease
Authors: Bram Verstockt, Liesbeth Boets, João Sabino, Séverine Vermeire, Marc Ferrante
Journal: Gut (2020)

We read with interest the multicentre UK study by Stournaras et al on the long-term effectiveness of thiopurine monotherapy for the treatment of patients with IBD.1 Through a similar retrospective, single-centre design at the tertiary IBD referral centre of the University Hospitals Leuven (Leuven, Belgium), we evaluated the outcome of patients with active Crohn’s disease (CD) who initiated thiopurine monotherapy between 1988 and 2016. Response was defined as continuation of thiopurine monotherapy for at least 1 year,2 with minimal corticosteroids use (<2 corticosteroids courses/year) and without additional treatment (surgery, biological agents). Patients had to be exposed to thiopurines for at least 4 months before response could be evaluated, as thiopurines are not recommended for induction of response.3 In total, 823 CD patients (99.9% azathioprine) with a median follow-up of 13.0 (IQR 7.7–18.0) years were screened (figure 1).



Figure 1 
Flowchart summarising the main findings of the current observational study on thiopurine monotherapy in Crohn’s disease.



Similar to the discontinuation rates linked to intolerance reported in the UK study,1 229 patients (29.4%) discontinued thiopurine therapy after a median of 31.0 (IQR 13.0–74.7) days, mainly because of leucopenia (n=13), liver function abnormalities (n=26), pancreatitis (n=62) or GI intolerance (n=59). On the long term, three patients were diagnosed with …
In older patients with NSTE-ACS, clopidogrel safely reduced bleeding compared with ticagrelor at 1 year
Authors: Michelle D. Kelsey, L. Kristin Newby
Journal: Annals of Internal Medicine (2020)

Source Citation Gimbel M, Qaderdan K, Willemsen L, et al. Clopidogrel versus ticagrelor or prasugrel in patients aged 70 years or older with non-ST-elevation acute coronary syndrome (POPular AGE): the randomised, open-label, non-inferiority trial. Lancet. 2020;395:1374-81. 32334703
RNA Drugs and RNA Targets for Small Molecules: Principles, Progress, and Challenges
Authors: Ai-Ming Yu, Young Hee Choi, Mei-Juan Tu
Journal: Pharmacological Reviews (2020)

RNA-based therapies, including RNA molecules as drugs and RNA-targeted small molecules, offer unique opportunities to expand the range of therapeutic targets. Various forms of RNAs may be used to selectively act on proteins, transcripts, and genes that cannot be targeted by conventional small molecules or proteins. Although development of RNA drugs faces unparalleled challenges, many strategies have been developed to improve RNA metabolic stability and intracellular delivery. A number of RNA drugs have been approved for medical use, including aptamers (e.g., pegaptanib) that mechanistically act on protein target and small interfering RNAs (e.g., patisiran and givosiran) and antisense oligonucleotides (e.g., inotersen and golodirsen) that directly interfere with RNA targets. Furthermore, guide RNAs are essential components of novel gene editing modalities, and mRNA therapeutics are under development for protein replacement therapy or vaccination, including those against unprecedented severe acute respiratory syndrome coronavirus pandemic. Moreover, functional RNAs or RNA motifs are highly structured to form binding pockets or clefts that are accessible by small molecules. Many natural, semisynthetic, or synthetic antibiotics (e.g., aminoglycosides, tetracyclines, macrolides, oxazolidinones, and phenicols) can directly bind to ribosomal RNAs to achieve the inhibition of bacterial infections. Therefore, there is growing interest in developing RNA-targeted small-molecule drugs amenable to oral administration, and some (e.g., risdiplam and branaplam) have entered clinical trials. Here, we review the pharmacology of novel RNA drugs and RNA-targeted small-molecule medications, with a focus on recent progresses and strategies. Challenges in the development of novel druggable RNA entities and identification of viable RNA targets and selective small-molecule binders are discussed. <h3>Significance Statement</h3> With the understanding of RNA functions and critical roles in diseases, as well as the development of RNA-related technologies, there is growing interest in developing novel RNA-based therapeutics. This comprehensive review presents pharmacology of both RNA drugs and RNA-targeted small-molecule medications, focusing on novel mechanisms of action, the most recent progress, and existing challenges.
Convalescent plasma for covid-19
Authors: Lise J Estcourt, David J Roberts
Journal: BMJ (2020)

Authorisation in the US was premature, and a missed opportunity Plasma from people recovering from infection, particularly after severe illness, may contain high levels of polyclonal, pathogen specific antibodies. These antibodies may confer passive immunity to recipients, and in viral diseases are thought to act mainly by neutralising viral particles.1 Convalescent plasma, or purified antibodies from the plasma (hyperimmune globulin), was often used in clinical practice before the advent of vaccines, including during the influenza pandemic of 1918.2 Hyperimmune globulin is still used for post-exposure prophylaxis against various viral infections, including hepatitis B, varicella zoster, and rabies. The use of convalescent plasma to treat patients with covid-19 has understandably attracted a lot of attention, but definitive evidence of efficacy has been elusive. Nevertheless, on 23 August the US Food and Drugs Administration authorised its emergency use for hospital patients with covid-19. At the time, only two small underpowered trials had been published.34 Until this authorisation the large scale clinical administration of convalescent plasma in the US was regulated under the FDA’s expanded access treatment protocol, which required individual patient authorisation and collection of data on clinical outcomes and side effects. Over five months, from 1 …
The Lancet NCDI Poverty Commission: bridging a gap in universal health coverage for the poorest billion
Authors: Gene Bukhman, Ana O Mocumbi, Rifat Atun, Anne E Becker, Zulfiqar Bhutta, Agnes Binagwaho, Chelsea Clinton, Matthew M Coates, Katie Dain, Majid Ezzati, Gary Gottlieb, Indrani Gupta, Neil Gupta, Adnan A Hyder, Yogesh Jain, Margaret E Kruk, Julie Makani, Andrew Marx, J Jaime Miranda, Ole F Norheim, Rachel Nugent, Nobhojit Roy, Cristina Stefan, Lee Wallis, Bongani Mayosi, Kafui Adjaye-Gbewonyo, Alma Adler, Fred Amegashie, Mary Kigasia Amuyunzu-Nyamongo, Said Habib Arwal, Nicole Bassoff, Jason A. Beste, Chantelle Boudreaux, Peter Byass, Jean Roland Cadet, Wubaye Walelgne Dagnaw, Arielle Wilder Eagan, Andrea Feigl, Gladwell Gathecha, Annie Haakenstad, Abraham Mitike Haileamlak, Kjell Arne Johansson, Mamusu Kamanda, Biraj Karmacharya, Noel Kasomekera, Alex Kintu, Bhagawan Koirala, Gene F. Kwan, Nancy Charles Larco, Sarah Maongezi, Jones Masiye, Mary Mayige, Amy McLaughlin, Solomon Tessema Memirie, Humberto Nelson Muquingue, Kibachio Joseph Muiruri Mwangi, Gilles Francois Ndayisaba, Christopher A. Noble, Bashir Noormal, Maia Olsen, Paul Park, Gisela Robles Aguilar, Osman A. Sankoh, Akshar Saxena, Leah N. Schwartz, Dan K. Schwarz, Jonathan D. Shaffer, Andrew P. Sumner, Zoe Taylor Doe, Senendra Raj Upreti, Stéphane Verguet, David Watkins, Emily B. Wroe
Journal: The Lancet (2020)