tbuckley/cabot-search huggingface dataset:
Abstract IA03: Medulloblastoma predisposition according to molecular subgroup: The usual suspects and beyond
Authors: Paul A. Northcott
Journal: Cancer Research (2020)

Abstract Cancer genomics has illuminated a wide spectrum of genes and core molecular processes contributing to human malignancy. Still, the genetic and molecular basis of many cancers remains only partially explained. Genetic predisposition accounts for 5-10% of cancer diagnoses, and genetic events cooperating with known somatic driver events are poorly understood. Analyzing established cancer predisposition genes in medulloblastoma (MB), a malignant childhood brain tumor, we recently identified pathogenic germline variants that account for 5-6% of all MB patients. The incidence of genetic predisposition to MB varied according to patient age and molecular subgroup status, with up to 25% of childhood SHH-MB patients predicted to harbor pathogenic germline variation. These estimates only account for known cancer predisposition genes, and ongoing studies designed to investigate unknown pathogenic events in the germline of MB patients have implicated novel MB predisposition genes. This presentation aims to summarize these recent insights into genetic predisposition to MB and contextualize these findings with their associated clinical implications. Citation Format: Paul A. Northcott. Medulloblastoma predisposition according to molecular subgroup: The usual suspects and beyond [abstract]. In: Proceedings of the AACR Special Conference on the Advances in Pediatric Cancer Research; 2019 Sep 17-20; Montreal, QC, Canada. Philadelphia (PA): AACR; Cancer Res 2020;80(14 Suppl):Abstract nr IA03.
Audio Interview: The Impact of Covid-19 on Patients with Other Diseases, with Arnold Epstein
Authors: Eric J. Rubin, Lindsey R. Baden, Arnold Epstein, Stephen Morrissey
Journal: New England Journal of Medicine (2020)

The Impact of Covid-19 on Patients with Other Diseases, with Arnold Epstein In this audio interview conducted on August 5, 2020, the editors are joined by health policy expert Dr. Arnold Epstein to...
GCH1 variants contribute to the risk and earlier age-at-onset of Parkinson’s disease: a two-cohort case-control study
Authors: Hong-xu Pan, Yu-wen Zhao, Jun-pu Mei, Zheng-huan Fang, Yige Wang, Xun Zhou, Yang-jie Zhou, Rui Zhang, Kai-lin Zhang, Li Jiang, Qian Zeng, Yan He, Zheng Wang, Zhen-hua Liu, Qian Xu, Qi-ying Sun, Yang Yang, Ya-cen Hu, Ya-se Chen, Juan Du, Li-fang Lei, Hai-nan Zhang, Chun-yu Wang, Xin-xiang Yan, Lu Shen, Hong Jiang, Jie-qiong Tan, Jin-chen Li, Bei-sha Tang, Ji-feng Guo
Journal: Translational Neurodegeneration (2020)

Abstract Background Common and rare variants of guanosine triphosphate cyclohydrolase 1 ( GCH1 ) gene may play important roles in Parkinson’s disease (PD). However, there is a lack of comprehensive analysis of GCH1 genotypes, especially in non-coding regions. The aim of this study was to explore the genetic characteristics of GCH1 , including rare and common variants in coding and non-coding regions, in a large population of PD patients in Chinese mainland, as well as the phenotypic characteristics of GCH1 variant carriers. Methods In the first cohort of this case-control study, we performed whole-exome sequencing in 1555 patients with early-onset or familial PD and 2234 healthy controls; then in the second cohort, whole-genome sequencing was performed in sporadic late-onset PD samples (1962 patients), as well as 1279 controls. Variants at target GCH1 regions were extracted, and then genetic and detailed phenotypic data were analyzed using regression models and the sequence kernel association test. We also performed a meta-analysis to correlate deleterious GCH1 variants with age at onset (AAO) in PD patients. Results For coding variants, we identified a significant burden of GCH1 deleterious variants in early-onset or familial PD cases compared to controls (1.2% vs 0.1%, P &lt; 0.0001). In the analysis of possible regulatory variants in GCH1 non-coding regions, rs12323905 ( P = 0.001, odds ratio = 1.19, 95%CI 1.07–1.32) was significantly associated with PD, and variant sets in untranslated regions and intron regions, GCH1 brain-specific expression quantitative trait loci, and two possible promoter/enhancer (GH14J054857 and GH14J054880) were suggestively associated with PD. Genotype-phenotype correlation analysis revealed that the carriers of GCH1 deleterious variants manifested younger AAO ( P &lt; 0.0001), and had milder motor symptoms, milder fatigue symptoms and more autonomic nervous dysfunctions. Meta-analysis of six studies demonstrated 6.4-year earlier onset in GCH1 deleterious variant carriers ( P = 0.0009). Conclusions The results highlight the importance of deleterious variants and non-coding variants of GCH1 in PD in Chinese mainland and suggest that GCH1 mutation can influence the PD phenotype, which may help design experimental studies to elucidate the mechanisms of GCH1 in the pathogenesis of PD.
COVID-19 Outbreak Among Employees at a Meat Processing Facility — South Dakota, March–April 2020
Authors: Jonathan Steinberg, Erin D. Kennedy, Colin Basler, Michael P. Grant, Jesica R. Jacobs, Dustin Ortbahn, John Osburn, Sharon Saydah, Suzanne Tomasi, Joshua L. Clayton
Journal: MMWR Morbidity and Mortality Weekly Report (2020)

On March 24, 2020, the South Dakota Department of Health (SDDOH) was notified of a case of coronavirus disease 2019 (COVID-19) in an employee at a meat processing facility (facility A) and initiated an investigation to isolate the employee and identify and quarantine contacts. On April 2, when 19 cases had been confirmed among facility A employees, enhanced testing for SARS-CoV-2, the virus that causes COVID-19, was implemented, so that any employee with a COVID-19-compatible sign or symptom (e.g., fever, cough, or shortness of breath) could receive a test from a local health care facility. By April 11, 369 COVID-19 cases had been confirmed among facility A employees; on April 12, facility A began a phased closure* and did not reopen during the period of investigation (March 16-April 25, 2020). At the request of SDDOH, a CDC team arrived on April 15 to assist with the investigation. During March 16-April 25, a total of 929 (25.6%) laboratory-confirmed COVID-19 cases were diagnosed among 3,635 facility A employees. At the outbreak's peak, an average of 67 cases per day occurred. An additional 210 (8.7%) cases were identified among 2,403 contacts of employees with diagnosed COVID-19. Overall, 48 COVID-19 patients were hospitalized, including 39 employees and nine contacts. Two employees died; no contacts died. Attack rates were highest among department-groups where employees tended to work in proximity (i.e., <6 feet [2 meters]) to one another on the production line. Cases among employees and their contacts declined to approximately 10 per day within 7 days of facility closure. SARS-CoV-2 can spread rapidly in meat processing facilities because of the close proximity of workstations and prolonged contact between employees (1,2). Facilities can reduce this risk by implementing a robust mitigation program, including engineering and administrative controls, consistent with published guidelines (1).
Biomimetic CoO@AuPt nanozyme responsive to multiple tumor microenvironmental clues for augmenting chemodynamic therapy
Authors: Shiyan Fu, Ruihao Yang, Lei Zhang, Weiwei Liu, Guangyuan Du, Yang Cao, Zhigang Xu, Hongjuan Cui, Yuejun Kang, Peng Xue
Journal: Biomaterials (2020)
Acromegalic Arthropathy Assessed By 3.0 Tesla Magnetic Resonance Imaging (MRI): A Case-Control Study
Authors: K.M.J.A. Claessen, P.W. de Bruin, W. Visser, B.J.E. de Lange-Brokaar, A.M. Pereira, H. Kroon, M. Kloppenburg, N.R. Biermasz
Journal: Endocrine Reviews (2014)
VELOUR trial biomarkers update: Impact of RAS, BRAF, and sidedness on aflibercept activity
Authors: Pratyaksha Wirapati, Valentina Pomella, Ben Vandenbosch, Peter Kerr, Evaristo Maiello, Mark Jeffery Grahame, Razvan-Ovidiu D. Curca, Meinolf Karthaus, John A. Bridgewater, Anca C. Mihailov, Igor Kiss, Sandra Merino, James McKendrick Joseph, Zacharenia Saridaki, Xavier J.A. Sagaert, Sabine Tejpar
Journal: Annals of Oncology (2017)
CytoPAN—Portable cellular analyses for rapid point-of-care cancer diagnosis
Authors: Jouha Min, Lip Ket Chin, Juhyun Oh, Christian Landeros, Claudio Vinegoni, Jeeyeon Lee, Soo Jung Lee, Jee Young Park, Ai-Qun Liu, Cesar M. Castro, Hakho Lee, Hyungsoon Im, Ralph Weissleder
Journal: Science Translational Medicine (2020)

An automated image cytometry system was developed to enable rapid cancer profiling of scant cellular specimens obtained by fine needle aspiration.
Mouse model of SARS-CoV-2 reveals inflammatory role of type I interferon signaling
Authors: Benjamin Israelow, Eric Song, Tianyang Mao, Peiwen Lu, Amit Meir, Feimei Liu, Mia Madel Alfajaro, Jin Wei, Huiping Dong, Robert J. Homer, Aaron Ring, Craig B. Wilen, Akiko Iwasaki
Journal: The Journal of Experimental Medicine (2020)

Severe acute respiratory syndrome–coronavirus 2 (SARS-Cov-2) has caused over 13,000,000 cases of coronavirus disease (COVID-19) with a significant fatality rate. Laboratory mice have been the stalwart of therapeutic and vaccine development; however, they do not support infection by SARS-CoV-2 due to the virus’s inability to use the mouse orthologue of its human entry receptor angiotensin-converting enzyme 2 (hACE2). While hACE2 transgenic mice support infection and pathogenesis, these mice are currently limited in availability and are restricted to a single genetic background. Here we report the development of a mouse model of SARS-CoV-2 based on adeno-associated virus (AAV)–mediated expression of hACE2. These mice support viral replication and exhibit pathological findings found in COVID-19 patients. Moreover, we show that type I interferons do not control SARS-CoV-2 replication in vivo but are significant drivers of pathological responses. Thus, the AAV-hACE2 mouse model enables rapid deployment for in-depth analysis following robust SARS-CoV-2 infection with authentic patient-derived virus in mice of diverse genetic backgrounds.
Assessment of statistical methods from single cell, bulk RNA-seq, and metagenomics applied to microbiome data
Authors: Matteo Calgaro, Chiara Romualdi, Levi Waldron, Davide Risso, Nicola Vitulo
Journal: Genome biology (2020)

Abstract Background The correct identification of differentially abundant microbial taxa between experimental conditions is a methodological and computational challenge. Recent work has produced methods to deal with the high sparsity and compositionality characteristic of microbiome data, but independent benchmarks comparing these to alternatives developed for RNA-seq data analysis are lacking. Results We compare methods developed for single-cell and bulk RNA-seq, and specifically for microbiome data, in terms of suitability of distributional assumptions, ability to control false discoveries, concordance, power, and correct identification of differentially abundant genera. We benchmark these methods using 100 manually curated datasets from 16S and whole metagenome shotgun sequencing. Conclusions The multivariate and compositional methods developed specifically for microbiome analysis did not outperform univariate methods developed for differential expression analysis of RNA-seq data. We recommend a careful exploratory data analysis prior to application of any inferential model and we present a framework to help scientists make an informed choice of analysis methods in a dataset-specific manner.
COVID-19 outcomes in patients with systemic autoimmune diseases treated with immunomodulatory drugs
Authors: Khalil Ansarin, Ali Taghizadieh, Saeid Safiri, Aida Malek Mahdavi, Shirin Ranjbar, Soheil Teymouri, Masoud Ahangari Maleki, Alireza Khabbazi
Journal: Annals of the Rheumatic Diseases (2020)

We read with great interest the paper published by Gianfrancesco and colleagues in Annals of the Rheumatic Diseases in 2020.1 They examined demographic and clinical factors associated with COVID-19 hospitalisation status in people with rheumatic disease using 600 cases from 40 countries. In their multivariable model, it was found that prednisone dose ≥10 mg/day (OR: 2.05, 95% CI 1.06 to 3.96) and anti-tumour necrosis factor inhibitor use (OR: 0.40, 95% CI 0.19 to 0.81) were associated with odds of hospitalisation.1

Patients with autoimmune diseases (AD) are at an increased risk of infectious diseases due to the effects of the disease on the immune system function, much comorbidity caused by various comorbidities such as kidney and lung damage, diabetes mellitus and hypertension, as well as the chronic use of immunomodulatory drugs.2 3 Patients treated with immunomodulatory drugs are vulnerable to viral infections,3 4 and worse prognosis of COVID-19 is probable in patients with ADs5 that need to be studied. Here, we would like to share our study results that were conducted on patients with …
[18F]-Florbetaben PET/CT for Differential Diagnosis Among Cardiac Immunoglobulin Light Chain, Transthyretin Amyloidosis, and Mimicking Conditions
Authors: Dario Genovesi, Giuseppe Vergaro, Assuero Giorgetti, Paolo Marzullo, Michele Scipioni, Maria Filomena Santarelli, Angela Pucci, Gabriele Buda, Elisabetta Volpi, Michele Emdin
Journal: JACC. Cardiovascular imaging (2020)
Chromosome 1q12 Instability Drives Both 1q21 Amplification and Arm-Length Deletions in Multiple Myeloma
Authors: Jeffery R. Sawyer, Erming Tian, Brian A Walker, Charles M. Swanson, Janet L Lukacs, Gael M. Sammartino, Clyde Bailey, Sharmilan Thanendrarajan, Carolina D. Schinke, Maurizio Zangari, Frits van Rhee, Faith E. Davies, Gareth J. Morgan
Journal: Blood (2017)
ILC2-driven innate immune checkpoint mechanism antagonizes NK cell antimetastatic function in the lung
Authors: Martijn J. Schuijs, Shaun Png, Arianne C. Richard, Anastasia Tsyben, Gregory Hamm, Julie Stockis, Celine Garcia, Silvain Pinaud, Ashley Nicholls, Xavier Romero Ros, Jing Su, Matthew D. Eldridge, Angela Riedel, Eva M. Serrao, Hans-Reimer Rodewald, Matthias Mack, Jacqueline D. Shields, E. Suzanne Cohen, Andrew N. J. McKenzie, Richard J. A. Goodwin, Kevin M. Brindle, John C. Marioni, Timotheus Y. F. Halim
Journal: Nature Immunology (2020)
Assessment of Disparities in Digital Access Among Medicare Beneficiaries and Implications for Telemedicine
Authors: Eric T. Roberts, Ateev Mehrotra
Journal: JAMA Internal Medicine (2020)

quine from retail pharmacies, including an approximate additional 93 000 patients who received both hydroxychloroquine and azithromycin.First, evidence of efficacy in preventing or treating COVID-19 is limited.Treatment guidelines found insufficient clinical data to recommend for or against hydroxychloroquine or chloroquine use and recommend against combining either with azithromycin, except in clinical trials. 1 Second, because of reports of cardiac and other adverse events, the US Food and Drug Administration has cautioned against using hydroxychloroquine or chloroquine for COVID-19 outside of hospitalized settings or clinical trials. 5 If azithromycin is used with hydroxychloroquine or chloroquine, correcting electrolyte levels, completing electrocardiographic monitoring, and avoiding other QTc interval-prolonging drugs are recommended. 6 Third, sudden increases in demand for hydroxychloroquine and chloroquine limit availability for FDAapproved uses for rheumatoid arthritis, lupus, and malaria. 5 While some of the largest increases in hydroxychloroquine and chloroquine dispensing occurred in states with high COVID-19 case rates (eg, New Jersey, New York), other states with large increases in dispensing had moderate (eg, Florida) or low (eg, Hawaii) case rates.These data do not include prescribing indication, so not all increased dispensing may be for COVID-19.It is unknown if patients immediately used or saved these medications.Finally, data were collected prior to release of many treatment guidelines and as state board of pharmacy dispensing regulations for hydroxychloroquine and chloroquine were evolving. 2 As COVID-19 continues to spread, ongoing assessment of the use of potential therapies will be essential to inform safe and appropriate treatment, along with prompt adverse event reporting to FDA's MedWatch safety reporting program (https:// www.fda.gov/safety/medwatch
Correspondence on: ‘Paediatric multisystem inflammatory syndrome temporally associated with SARS-CoV-2 mimicking Kawasaki disease (Kawa-COVID-19): a multicentre cohort’ by Pouletty<i>et al</i>
Authors: Rosa Pino, Ana Carolina Izurieta, María Ríos-Barnés, Sílvia Ricart, Mariona F De Sevilla, Laura Monfort, Cristian Launes, Iván Cano, Laura Lecina, Judith Sánchez Manubens, Juan Manuel Mosquera, Iolanda Jordan, Joan Sánchez de Toledo, Manuel Monsonís, Cristina Esteva, Carmen Muñoz-Almagro, Victòria Fumadó, Clàudia Fortuny, Juan José Garcia Garcia, Antoni Noguera-Julian, Jordi Anton
Journal: Annals of the Rheumatic Diseases (2020)

We read with interest the article by Pouletty et al ,1 in which the authors describe a multicentre compilation of patients with Kawasaki disease (KD) in France, associated with the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Other colleagues in Europe and USA have recently reported similar experiences.2–5

We report a prospective case series of paediatric patients that fulfilled clinical diagnostic criteria of KD during the SARS-CoV-2 pandemic in a paediatric referral centre in Barcelona, Spain. KD was defined according to the 2017 criteria of the American Heart Association.6 Assessment of SARS-CoV-2 infection was made by means of quantitative real-time PCR assay (GeneFinder COVID-19 Plus, Elitech; Puteaux, France) in nasopharyngeal samples; stools were tested in patients with diarrhoea. SARS-CoV-2 IgG qualitative determination (SARS-CoV-2 IgG chemiluminescent microparticle immunoassay; Abbot, Chicago, Illinois) was performed during admission. Statistical analyses were performed using SPSS V.25 (IBM). Informed consent was obtained from parents or legal guardians, as was informed assent in patients aged >12 years.

From March 23 to May 14, twelve previously healthy patients with KD were admitted to our institution (table 1). The yearly number of patients with KD diagnosed in our centre is around 10–12. Prior to diagnosis, several patients reported gastrointestinal symptoms (10/12, 83.3%; vomiting, diarrhoea and abdominal pain) and neurological symptoms (5/12, 41.6%; irritability, headache, decreased consciousness and febrile seizures). Only patient 10 was referred with respiratory symptoms …
Universal test-and-treat in Zambian and South African correctional facilities: a multisite prospective cohort study
Authors: Michael E Herce, Christopher J Hoffmann, Katherine Fielding, Stephanie M Topp, Harry Hausler, Lucy Chimoyi, Helene J Smith, Candice M Chetty-Makkan, Rachel Mukora, Mpho Tlali, Abraham J Olivier, Monde Muyoyeta, Stewart E Reid, Salome Charalambous
Journal: The Lancet HIV (2020)
Hydroxychloroquine ineffective for COVID-19 prophylaxis in lupus and rheumatoid arthritis
Authors: Mendel E Singer, David C Kaelber, Maria J Antonelli
Journal: Annals of the Rheumatic Diseases (2020)

Table 1 Proportion of patients taking hydroxychloroquine: COVID-19 vs two control groups COVID-19 Influenza/ pneumonia/LRI CI for difference (COVID-19 vs I/P/LRI) Any outpatient visit CI for difference (COVID-19 vs OP) Age 18 and over No of patients, N 16 869 198 114 3 970 695 Lupus or RA on an immunosuppressant, N 159 2609 32 599 Hydroxychloroquine, % (N) 34.6% (55) 31.4% (819) (-4.4% to 10.8%) p=0.4290 32.7% (10 645) (-5.5% to 9.4%) p=0.6115Age 18-64 No of patients, N 13 327 128 280 2 715 365 Lupus or RA on an immunosuppressant, N 121 1477 20 256 Hydroxychloroquine, % (N) 37.2% (45) 37.0% (547) (-8.8% to 9.1%) p=1.0000 36.9% (7473) (-8.3% to 8.9%) p=1.0000
Incidence of osteoporosis and fragility fractures in asthma: a UK population-based matched cohort study
Authors: Christos V. Chalitsios, Tricia M. McKeever, Dominick E. Shaw
Journal: European Respiratory Journal (2020)

Introduction Osteoporosis and fragility fractures are associated with corticosteroids which are the mainstay treatment for asthma; however, these bone comorbidities within asthma need to be better described. Methods A matched cohort study was conducted using the UK Clinical Practice Research Database (CPRD). Adults with an incident asthma code were identified and matched, with up to four randomly selected people without asthma, by age, sex and practice. Osteoporosis and fragility fracture incidence rates were calculated, and Cox regression was performed comparing hazard rates to the general population. We report the impact of age, sex, glucocorticoids and the risk of specific fractures. Results Patients with asthma had a higher risk of osteoporosis (adjusted hazard ratio (aHR) 1.18, 95% CI 1.13–1.23) and were 12% (aHR 1.12, 95% CI 1.07–1.16) more likely to sustain fragility fractures than the general population. Age modified the effect of asthma on osteoporosis and fragility fractures, such that the effect was stronger in younger people (p interaction &lt;0.0001). The vertebra (aHR 1.40, 95% CI 1.33–1.48) and forearm/wrist (aHR 1.27, 95% CI 1.22–1.32) were the sites linked with a larger incidence. A dose–response relationship between oral corticosteroids (OCS) and osteoporosis was observed, whereas the risk of fragility fractures increased in those with six or more OCS courses per year. Regular use of inhaled corticosteroids (ICS) increased the risk of both bone conditions. Conclusions Patients with asthma are more likely to develop osteoporosis or sustain fragility fractures than the general population, with a particular concern in younger people and those more frequently using OCS and ICS.