tbuckley/cabot-search huggingface dataset:
CLIMB-COVID: continuous integration supporting decentralised sequencing for SARS-CoV-2 genomic surveillance
Authors: Samuel M. Nicholls, Radoslaw Poplawski, Matthew J. Bull, Anthony Underwood, Michael Chapman, Khalil Abu-Dahab, Ben Taylor, Rachel M. Colquhoun, Will P. M. Rowe, Ben Jackson, Verity Hill, Áine O’Toole, Sara Rey, Joel Southgate, Roberto Amato, Rich Livett, Sónia Gonçalves, Ewan M. Harrison, Sharon J. Peacock, David M. Aanensen, Andrew Rambaut, Thomas R. Connor, Nicholas J. Loman
Journal: Genome biology (2021)

Abstract In response to the ongoing SARS-CoV-2 pandemic in the UK, the COVID-19 Genomics UK (COG-UK) consortium was formed to rapidly sequence SARS-CoV-2 genomes as part of a national-scale genomic surveillance strategy. The network consists of universities, academic institutes, regional sequencing centres and the four UK Public Health Agencies. We describe the development and deployment of CLIMB-COVID, an encompassing digital infrastructure to address the challenge of collecting and integrating both genomic sequencing data and sample-associated metadata produced across the COG-UK network.
Risk Factor Control and Cardiovascular Event Risk in People With Type 2 Diabetes in Primary and Secondary Prevention Settings
Authors: Alison K. Wright, Milton Fabian Suarez-Ortegon, Stephanie H. Read, Evangelos Kontopantelis, Iain Buchan, Richard Emsley, Naveed Sattar, Darren M. Ashcroft, Sarah H. Wild, Martin K. Rutter
Journal: Circulation (2020)

To examine the association between the degree of risk factor control and cardiovascular disease (CVD) risk in type 2 diabetes and to assess if the presence of cardio-renal disease modifies these relationships.A retrospective cohort study using data from English practices from CPRD GOLD (Clinical Practice Research Datalink) and the SCI-Diabetes dataset (Scottish Care Information-Diabetes), with linkage to hospital and mortality data. We identified 101 749 with type 2 diabetes (T2D) in CPRD matched with 378 938 controls without diabetes and 330 892 with type 2 diabetes in SCI-Diabetes between 2006 and 2015. The main exposure was number of optimized risk factors: nonsmoker, total cholesterol ≤4 mmol/L, triglycerides ≤1.7 mmol/L, glycated haemoglobin (HbA1c) ≤53 mmol/mol (≤7.0%), systolic blood pressure <140mm Hg, or <130 mm Hg if high risk. Cox models were used to assess cardiovascular risk associated with levels of risk factor control.In CPRD, the mean baseline age in T2D was 63 years and 28% had cardio-renal disease (SCI-Diabetes: 62 years; 35% cardio-renal disease). Over 3 years follow-up (SCI-Diabetes: 6 years), CVD events occurred among 27 900 (27%) CPRD-T2D, 101 362 (31%) SCI-Diabetes-T2D, and 75 520 (19%) CPRD-controls. In CPRD, compared with controls, T2D participants with optimal risk factor control (all risk factors controlled) had a higher risk of CVD events (adjusted hazard ratio, 1.21; 95% confidence interval, 1.12-1.29). In T2D participants from CPRD and SCI-Diabetes, pooled hazard ratios for CVD associated with 5 risk factors being elevated versus optimal risk factor control were 1.09 (95% confidence interval, 1.01-1.17) in people with cardio-renal disease but 1.96 (95% confidence interval, 1.82-2.12) in people without cardio-renal disease. People without cardio-renal disease were younger and more likely to have likely to have suboptimal risk factor control but had fewer prescriptions for risk factor modifying medications than those with cardio-renal disease.Optimally managed people with T2D have a 21% higher CVD risk when compared with controls. People with T2D without cardio-renal disease would be predicted to benefit greatly from CVD risk factor intervention.
Treatment sequence, hospital practice patterns, and completion of multimodality therapy for locally advanced gastric cancer.
Authors: Jorge Ignacio Portuondo, Hop Sanderson Tran Cao, Nader Nabile Massarweh
Journal: Journal of Clinical Oncology (2020)

14 Background: Optimal oncologic care for patients with locally advanced gastric cancer includes multimodality therapy (MMT). While both perioperative chemotherapy and postoperative chemoradiotherapy are recommended, it is unclear whether one approach is more effective for ensuring patients complete MMT. Methods: National cohort study of 5,450 patients with locally advanced gastric cancer (i.e.: ≥cT2 and/or cN+) treated at 983 hospitals within the National Cancer Data Base (2006-15). Patients were categorized as having surgery first or chemotherapy first (patients not undergoing resection after chemotherapy or not receiving adjuvant after surgery were included based on intent-to-treat). MMT was defined as surgical resection with either neoadjuvant chemotherapy or adjuvant chemoradiotherapy. Hospitals were categorized into terciles based on utilization of chemotherapy first: 1.) predominantly chemotherapy first; 2.) mixed pattern; 2.) predominantly surgery first. The association between patient-level treatment, hospital practice pattern, and MMT completion was evaluated using multivariable hierarchical regression and the association with overall risk of death using multivariable Cox shared frailty modeling. Results: Overall, 55.5% of surgery first and 64.8% of chemotherapy first patients completed MMT (p&lt;0.001) and five-year survival for those completing MMT was 45.5% and 46.6%, respectively (log-rank, p=0.91). At the patient-level, chemotherapy first was significantly associated with MMT completion (Odds Ratio [OR] 1.61 [1.39– 1.86]). By comparison, relative to mixed hospitals, care at surgery first hospitals was associated with MMT completion (OR 1.32 [1.08 – 1.59]), which was due to differences in case-mix and the proportion of patients not receiving resection after chemotherapy (surgery first hospitals—4.1%; mixed hospitals—19.0%; chemotherapy first hospitals—29.4%, p&lt;0.001). MMT by either approach was associated with lower risk of death (ref—surgery only; chemotherapy first – Hazard Ratio [HR] 0.77 [0.68 – 0.86]; surgery first – HR 0.77 [0.68 – 0.87]) while hospital practice pattern was not. Conclusions: The type of MMT strategy is less important than ensuring patients complete MMT. After accounting for treatment drop-outs (which are substantial with either strategy), chemotherapy first appears more effective in the general community for ensuring patients complete MMT. National guidelines should be modified to emphasize neoadjuvant over surgery first MMT strategies.
Performance comparison of fiveextraction kits for SARS-CoV-2 RNA extraction
Authors: I. M. Lungu, A. De Luca, J. Li, J. Bayani, M. Spears, T. J. Pugh, J. M. S. Bartlett
Journal: Clinical Cancer Research (2020)

A new type of coronavirus, SARS-CoV-2, was identified in January 2020  Its associated disease, COVID-19, wasannounced as a pandemic by the World Health Organization in March 2020  The Ontario Institute for CancerResearch quickly engaged to support viral sequencing, not only in frontline health care workers but in cancerpatients  A key deliverable was the selection of an extraction methodology that would not impact the supply ofapproved diagnostic testing reagents  This consideration was in response to reports of possible shortages predictedearly in the pandemic and as indicated by the Public Health Agency of Canada (PHAC), through their call forreagents in April 2020  Five commercially available kits for automated nucleic acid extraction were compared  TheKingFisher Flex Purification System (ThermoFisher, 5400610) was used for nucleic acid extraction  Four kits wereselected based on availability, system compatibility, and exclusion from PHAC's call for COVID-19 testing reagents The MagMAX CORE Nucleic Acid Purification Kit (CORE;ThermoFisher, A32702), MagMAX Total Nucleic AcidIsolation Kit (Total NA;ThermoFisher, AM1840), MagMAX Total RNA Isolation Kit (Total RNA;ThermoFisher, AM1830), and Mag-Bind Viral DNA/RNA 96 Kit (Omega;Omega BioTek, M6246-03) were evaluated  The MagMAXViral/Pathogen Kit (MVP;ThermoFisher, A42352), approved by the Food and Drug Administration of Canada fordiagnostic testing, was used as a benchmark  Test samples were prepared using Universal Human RNA (Agilent,740000), lambda DNA solution (Sigma Aldrich, ERMAD442K), SARS-CoV-2 RNA (ATCC, VR1986D) and heat-inactivated virus (ATCC, VR-1986HK)  Extractions were performed by two operators on replicate samples  Protocols were assessed on reproducibility, yield, reagent availability, run time, and ease of use  The top two kits were validated with nasopharyngeal swab samples from SARS-CoV-2-positive patients  Four of five kits demonstratedreproducible yields, while yields from the Total RNA kit were inconsistent  The CORE and Omega kits possessedthe best overall extraction efficiencies (both 70%)  The MVP kit and Total NA kit were 59% and 44% efficient inrecovery, respectively  The CORE and Omega kits ranked best after overall assessment  Patient samples weresubsequently extracted using both kits and successfully sequenced  Extraction kits do not all perform to the samespecification  In our hands, we found the MVP kit did not perform as well as others, despite being approved fordiagnostic use, and the Total RNA kit showed inconsistent results  Many reagents are commercially available andshould be explored as alternatives to the approved SARS-CoV-2 diagnostic reagents, particularly during a globalcrisis  Interestingly, following our validation testing, supply of the CORE kit became limited with unknown futureavailability  This illustrated the need to validate multiple methods during uncertain times in order to maintain criticaltesting
Spatiotemporal Heterogeneity in Multiparametric Physiologic MRI Is Associated with Patient Outcomes in IDH-Wildtype Glioblastoma
Authors: Ji Eun Park, Ho Sung Kim, NakYoung Kim, Seo Young Park, Young-Hoon Kim, Jeong Hoon Kim
Journal: Clinical Cancer Research (2020)

Abstract Purpose: Heterogeneity in glioblastomas is associated with poorer outcomes, and physiologic heterogeneity can be quantified with noninvasive imaging. We developed spatial habitats based on multiparametric physiologic MRI and evaluated associations between temporal changes in these habitats and progression-free survival (PFS) after concurrent chemoradiotherapy (CCRT) in patients with glioblastoma. Experimental Design: Ninety-seven patients with isocitrate dehydrogenase (IDH)-wildtype glioblastoma were enrolled and two serial MRI examinations after CCRT were analyzed. Cerebral blood volumes and apparent diffusion coefficients were grouped using k-means clustering into three spatial habitats. Associations between temporal changes in spatial habitats and PFS were investigated using Cox proportional hazard modeling. The performance of significant predictors for PFS and overall survival (OS) was measured using a discrete increase of habitat (habitat risk score) in a temporal validation set from a prospective registry (n = 53, ClinicalTrials.gov NCT02619890). The site of progression was matched with the spatiotemporal habitats. Results: Three spatial habitats of hypervascular cellular, hypovascular cellular, and nonviable tissue were identified. A short-term increase in the hypervascular cellular habitat (HR, 40.0; P = 0.001) and hypovascular cellular habitat was significantly associated with shorter PFS (HR, 3.78; P &amp;lt; 0.001) after CCRT. Combined with clinical predictors, the habitat risk score showed a C-index of 0.79 for PFS and 0.74 for OS and stratified patients with short, intermediate, and long PFS (P = 0.016). An increase in the hypovascular cellular habitat predicted tumor progression sites. Conclusions: Hypovascular cellular habitats derived from multiparametric physiologic MRIs may be useful predictors of clinical outcomes in patients with posttreatment glioblastoma.
Outcome of older cancer patients infected with Covid19 at Gustave Roussy Cancer Center
Authors: Mathilde Hauchecorne, Capucine Baldini, Stephanie Foulon, Arnaud Bayle, Bertrand Gachot, Fanny Pommeret, Helene Vincent, Tina Lamy, Celine Nagera, Christophe Willekens, Franck Griscelli, Florence Netzer, Corinne Balleyguier, Samy Ammari, Fabrice Andre, Florian Scotte, Benjamin Besse, Jean-Charles Soria, Fabrice Barlesi, Laurence Albiges
Journal: Clinical Cancer Research (2020)

Background: The SARS-CoV-2 outbreak in Paris's region significantly affected Gustave Roussy Cancer Center Previous analyses showed that mortality rate increases with age in the general population  Here, we report theGustave Roussy experience on older patients (OP) with cancer during the SARS-CoV-2 outbreak  Methods: Cancer pts with suspected SARS-CoV-2 infection were admitted at Gustave Roussy starting March 12th Screening indications have been adapted over the time  All the COVID19 pts positively tested and managed atGustave Roussy between March 14th (1st positive case) and April 15th have been included in a REDCap database Pts and underlying oncologic and COVID19 diseases characteristics have been collected  Cancer and COVID-19managements and outcomes have been assessed  The primary endpoint of this analysis was the clinicaldeterioration, defined as the need for O2 supplementation of 6l/min, or death of any cause  Results: Among the first 137 cancer pts diagnosed with SARS-CoV-2, 36 patients were aged 70 years (26%)  Mostof them were female (61%) with a median age of 75 5 years old  Most frequent underlying cancers were solidtumors (92%) including GI (19%), lung (17%), GYN (14%), and head and neck (14%)  Most OP (36%) were ECOGperformance status 2 versus 24% in younger patients (YP)  The diagnosis of SARS-CoV-2 infection was made byRT-PCR or thoracic CT scan alone in 97% and 3% of the cases, respectively, in OP and in 92% and 8% in YP  MostOP experienced symptoms prior to testing (92%) compared to YP (80%)  Symptoms differed according to age withmore cough with sputum production in OP (14% versus 5%), dyspnea (39% versus 31%), diarrhea (17% versus9%), shivers (8% versus 0%), sore throat (8% versus 4%), and no anosmia or agueusia  The majority of OP werehospitalized (81%) compared to 72% of YP and treated with HCQ/AZI (15;52%) with inclusion in the ONCOVID trial(EudraCT: 2020-01250-21) compared to 25 (35%) YP  They did not receive any IL-6 inhibitor  Only one OP wasadmitted in the ICU (3%)  Clinical deterioration occurred in 10 OP (29%)  There was no impact of age on clinicalworsening (HR=1 157;95%CI 0 55-2 42;p=0 7)  However, age was associated with worse overall survival (OS)(HR=2 45 95%CI 1 02-5 92 ;p=0 0463)  Results will be updated at the meeting  Conclusions: OP with cancer had a different disease presentation, same rate of clinical worsening, but worse OSin SARS-CoV-2 infection
PAIP 2019: Liver cancer segmentation challenge
Authors: Yoo Jung Kim, Hyungjoon Jang, Kyoungbun Lee, Seongkeun Park, Sung-Gyu Min, Choyeon Hong, Jeong Hwan Park, Kanggeun Lee, Jisoo Kim, Wonjae Hong, Hyun Jung, Yanling Liu, Haran Rajkumar, Mahendra Khened, Ganapathy Krishnamurthi, Sen Yang, Xiyue Wang, Chang Hee Han, Jin Tae Kwak, Jianqiang Ma, Zhe Tang, Bahram Marami, Jack Zeineh, Zixu Zhao, Pheng-Ann Heng, Rüdiger Schmitz, Frederic Madesta, Thomas Rösch, Rene Werner, Jie Tian, Elodie Puybareau, Matteo Bovio, Xiufeng Zhang, Yifeng Zhu, Se Young Chun, Won-Ki Jeong, Peom Park, Jinwook Choi
Journal: Medical Image Analysis (2020)

Pathology Artificial Intelligence Platform (PAIP) is a free research platform in support of pathological artificial intelligence (AI). The main goal of the platform is to construct a high-quality pathology learning data set that will allow greater accessibility. The PAIP Liver Cancer Segmentation Challenge, organized in conjunction with the Medical Image Computing and Computer Assisted Intervention Society (MICCAI 2019), is the first image analysis challenge to apply PAIP datasets. The goal of the challenge was to evaluate new and existing algorithms for automated detection of liver cancer in whole-slide images (WSIs). Additionally, the PAIP of this year attempted to address potential future problems of AI applicability in clinical settings. In the challenge, participants were asked to use analytical data and statistical metrics to evaluate the performance of automated algorithms in two different tasks. The participants were given the two different tasks: Task 1 involved investigating Liver Cancer Segmentation and Task 2 involved investigating Viable Tumor Burden Estimation. There was a strong correlation between high performance of teams on both tasks, in which teams that performed well on Task 1 also performed well on Task 2. After evaluation, we summarized the top 11 team's algorithms. We then gave pathological implications on the easily predicted images for cancer segmentation and the challenging images for viable tumor burden estimation. Out of the 231 participants of the PAIP challenge datasets, a total of 64 were submitted from 28 team participants. The submitted algorithms predicted the automatic segmentation on the liver cancer with WSIs to an accuracy of a score estimation of 0.78. The PAIP challenge was created in an effort to combat the lack of research that has been done to address Liver cancer using digital pathology. It remains unclear of how the applicability of AI algorithms created during the challenge can affect clinical diagnoses. However, the results of this dataset and evaluation metric provided has the potential to aid the development and benchmarking of cancer diagnosis and segmentation.
Relation between cartilage loss and pain in knee osteoarthritis
Authors: Xiang-Dong Wu, Di Wu, Wei Huang, Gui-Xing Qiu
Journal: Annals of the Rheumatic Diseases (2020)

We read with interest the recent work in Annals of the Rheumatic Diseases by Bacon and colleagues regarding the relationship between cartilage loss and pain in patients with knee osteoarthritis (OA).1 The authors included 600 participants within the Osteoarthritis Initiative and found that cartilage loss was significantly associated with a small degree of worsening in pain over 24 months. The relation between cartilage thickness loss and pain was partially mediated by synovitis change, rather than by changes in bone marrow lesions. This finding prompted us to reconsider the relation between cartilage loss and pain, and the clinical efficacy of the chondroprotective application in the treatment of knee OA. Their excellent and important work adds to our knowledge base, but …
Equitable application of pancreatic cancer treatment guidelines to mitigate racial and insurance disparities at a comprehensive cancer center.
Authors: Andrea M. Schiefelbein, Amy K Taylor, John K. Krebsbach, Jienian Zhang, Yana Puckett, Xiao Zhang, John M. Hampton, Amy Trentham-Dietz, Sharon M. Weber, Melissa C. Skala, John M. Eason, Noelle K. LoConte
Journal: Journal of Clinical Oncology (2020)

119 Background: Race and ethnicity-based treatment and survival disparities are documented for pancreatic cancer. Studies cite patient genetic, biological, and social factors and differences across treatment centers and geographical areas that may contribute to disparities. We investigated treatment and survival disparities for a cohort of 1,569 pancreatic cancer (PC) patients at the local level within a National Cancer Institute-designated comprehensive cancer center. Methods: Data from 1,569 PC patients aged over 18 diagnosed with adenocarcinoma, NOS or infiltrating duct carcinoma, NOS from 2004 to 2016 who received some or all of their care at the University of Wisconsin Carbone Cancer Center were included in the study. Sequential models of adjusted Cox proportional hazard regression were performed to describe the association between race/ethnicity and overall survival. Model I included age, sex and race/ethnicity; model II added BMI, Charlson Comorbidity Index and stage; model III added rurality, treatment course and payer. Treatment course, defined as the receipt of chemoradiation, surgery with/without chemoradiation, or no treatment, rurality, and insurance status were factors of interest. Results: 38.6% of patients were diagnosed with metastatic disease. Overall survival was 11.6 months. Non-Hispanic black (NHB) patients experienced an 88% increased risk of death (95% CI: 23%-188%) and patients categorized as other race/ethnicity experienced a 32% (10%-60%) increased risk of death compared to NH white (NHW) patients in model II. After adding treatment course and insurance status, the hazard ratio for NHB patients decreased to 1.41 (0.92-2.17) and other race/ethnicity patients decreased to 1.27 (1.05-1.53) compared to NHW Patients. Medicaid patients had an adjusted hazard ratio of 1.41 (1.01-1.95) and unknown/uninsured patients had an adjusted hazard ratio of 1.62 (1.71-4.02) compared to managed care patients. Incarcerated patients had an adjusted hazard ratio of 1.28 (0.98-1.67) compared to managed care patients. Conclusions: To reduce disparities across race/ethnicity and insurance status, organizations should invest in financial support programs for patients in need and monitor treatment courses for people of color, underinsured or uninsured patients to verify access to treatment, equitable treatment, and adherence to treatment guidelines. Future studies should investigate the contribution of clinician and healthcare system bias to race and ethnicity-based cancer disparities.
Aspirin in the Prevention of Colorectal Neoplasia
Authors: David A. Drew, Andrew T. Chan
Journal: Annual Review of Medicine (2020)

High-quality evidence indicates that regular use of aspirin is effective in reducing the risk for precancerous colorectal neoplasia and colorectal cancer (CRC). This has led to US and international guidelines recommending aspirin for the primary prevention of CRC in specific populations. In this review, we summarize key questions that require addressing prior to broader adoption of aspirin-based chemoprevention, review recent evidence related to the benefits and harms of aspirin use among specific populations, and offer a rationale for precision prevention approaches. We specifically consider the mechanistic implications of evidence showing differences in aspirin's effects according to age, the potential role of modifiable mechanistic biomarkers for personalizing prevention, and emerging evidence that the gut microbiota may offer novel aspirin-associated preventive targets to reduce high-risk neoplasia.
Single-Cell Study of Two Rat Models of Pulmonary Arterial Hypertension Reveals Connections to Human Pathobiology and Drug Repositioning
Authors: Jason Hong, Douglas Arneson, Soban Umar, Gregoire Ruffenach, Christine M. Cunningham, In Sook Ahn, Graciel Diamante, May Bhetraratana, John F. Park, Emma Said, Caroline Huynh, Trixie Le, Lejla Medzikovic, Marc Humbert, Florent Soubrier, David Montani, Barbara Girerd, David-Alexandre Trégouët, Richard Channick, Rajan Saggar, Mansoureh Eghbali, Xia Yang
Journal: American Journal of Respiratory and Critical Care Medicine (2020)

The cellular and molecular landscape and translational value of commonly used models of pulmonary arterial hypertension (PAH) are poorly understood. Single-cell transcriptomics can enhance molecular understanding of preclinical models and facilitate their rational use and interpretation.