tbuckley/cabot-search huggingface dataset:
A systematic review of the applications of artificial intelligence and machine learning in autoimmune diseases
Authors: I. S. Stafford, M. Kellermann, E. Mossotto, R. M. Beattie, B. D. MacArthur, S. Ennis
Journal: npj Digital Medicine (2020)

Abstract Autoimmune diseases are chronic, multifactorial conditions. Through machine learning (ML), a branch of the wider field of artificial intelligence, it is possible to extract patterns within patient data, and exploit these patterns to predict patient outcomes for improved clinical management. Here, we surveyed the use of ML methods to address clinical problems in autoimmune disease. A systematic review was conducted using MEDLINE, embase and computers and applied sciences complete databases. Relevant papers included “machine learning” or “artificial intelligence” and the autoimmune diseases search term(s) in their title, abstract or key words. Exclusion criteria: studies not written in English, no real human patient data included, publication prior to 2001, studies that were not peer reviewed, non-autoimmune disease comorbidity research and review papers. 169 (of 702) studies met the criteria for inclusion. Support vector machines and random forests were the most popular ML methods used. ML models using data on multiple sclerosis, rheumatoid arthritis and inflammatory bowel disease were most common. A small proportion of studies (7.7% or 13/169) combined different data types in the modelling process. Cross-validation, combined with a separate testing set for more robust model evaluation occurred in 8.3% of papers (14/169). The field may benefit from adopting a best practice of validation, cross-validation and independent testing of ML models. Many models achieved good predictive results in simple scenarios (e.g. classification of cases and controls). Progression to more complex predictive models may be achievable in future through integration of multiple data types.
Abstract P145: Associations Of Corin Protein And Its Coding Gene Methylation With Hypertension In Chinese Adults: A Mediation Analysis In The Gusu Cohort
Authors: Hao Peng, Jia Yu, Liyun Ren, Yan He, Jing Li, Shengqi Ma, Mingzhi Zhang
Journal: Circulation (2020)

Hypothesis: Corin protein, a physiological activator of the atrial natriuretic peptide, has been associated with hypertension with unclear mechanisms. Its coding gene methylation may be involved in the underlined mechanisms but with no evidence. Objectives: We aimed to examine 1) whether CORIN gene methylation was associated with hypertension and 2) whether this association was mediated by corin protein. Methods: As illustrated in the following picture, peripheral blood DNA methylation of CORIN promoter was quantified by targeted bisulfite sequencing in 2,498 community members (mean aged 53 years, 38% men) as a discovery sample and 1,771 independent participants (mean aged 62 years, 54% men) as a replication sample. We constructed a causal mediation model with DNA methylation as the predictor variable, serum corin as the mediator variable, and blood pressure as the outcome variable, adjusting for age, sex, education level, cigarette smoking, alcohol consumption, obesity, fasting glucose, lipids, and antihypertensive medications. Multiple testing was controlled by adjusting for the total number of CpG loci tested. Results: Of the 9 CpG loci assayed, hyper-methylation methylation of 8 CpGs was significantly associated with lower systolic blood pressure in the discovery sample and 7 associations were also significant in the replication sample (all FDR-adjusted P &lt;0.05). Of the 8 significant CpGs, DNA methylation at only one CpG locus (located at Chr4:47839981) was significantly associated with serum corin (β=-0.003, P =0.038). Serum corin mediated approximately 2.45% (95%CI: 0.05%-7.00%, P =0.046), 7.15% (95%CI: 0.60%-28.00%, P =0.036), and 6.37% (95%CI: 0.10%-42.00%, P =0.048) of the negative associations of hyper-methylation at this CpG site with systolic blood pressure, diastolic blood pressure, and hypertension, respectively. Conclusions: Hyper-methylation at CORIN promoter is associated with hypertension, at least partially through suppressing corin expression or excretion.
Bromodomain Inhibition Is Effective Against Acute Myeloid Leukemia Cells Under Hypoxia and Induces Genome-Dependent Metabolic Perturbations
Authors: Giorgia Simonetti, Samantha Bruno, Carmine Onofrillo, Marco Malferrari, Cristina Papayannidis, Giovanni Marconi, Michele Cavo, Stefania Rapino, Lorenzo Montanaro, Giovanni Martinelli
Journal: Blood (2017)
Evaluation of Association Between Oral and Topical Terbinafine Use in Pregnancy and Risk of Major Malformations and Spontaneous Abortion
Authors: Niklas Worm Andersson, Simon Francis Thomsen, Jon Trærup Andersen
Journal: JAMA Dermatology (2020)

Terbinafine is a commonly used antifungal agent, but safety data of its use in pregnancy are limited.To examine the association between oral and topical terbinafine exposure in pregnancy and the risk of major malformations and spontaneous abortion.A nationwide, registry-based cohort study was conducted in Denmark from January 1, 1997, to December 31, 2016, in a cohort of 1 650 649 pregnancies. Data analysis was performed from July 11 to October 20, 2019. Pregnancies were matched on propensity scores comparing oral terbinafine exposed vs unexposed (1:10 ratio), topical terbinafine exposed vs unexposed (1:10), and oral vs topical terbinafine exposed (1:1).Filled prescriptions for oral or topical terbinafine.Logistic regression was used to compute prevalence odds ratios for the primary outcome of major malformations and Cox proportional hazards regression was used to compute hazard ratios for the secondary outcome of spontaneous abortion.Based on a cohort of 1 650 649 pregnancies, oral terbinafine-exposed (n = 891 pregnancies; mean [SD] age, 30.4 [6] years) and topical terbinafine-exposed (n = 3174; mean [SD] age, 29.5 [5.4] years) pregnancies were identified; up to a total of 40 650 unexposed pregnancies were included for the matched outcome analyses. In propensity-matched comparisons of the risk of major malformations, the prevalence odds ratios were 1.01 (95% CI, 0.63-1.62) for oral terbinafine-exposed vs unexposed pregnancies (absolute risk difference [ARD], 0.04%; 95% CI, -1.69% to 1.76%), 1.08 (95% CI, 0.81-1.44) for topical terbinafine-exposed vs unexposed pregnancies (ARD, 0.26%; 95% CI, -0.73% to 1.26%), and 1.18 (95% CI, 0.61-2.29) for oral vs topical terbinafine-exposed pregnancies (ARD, 0.59%; 95% CI, -1.71% to 2.88%). For the risk of spontaneous abortion, the hazard ratios were 1.06 (95% CI, 0.86-1.32) for oral terbinafine-exposed vs unexposed pregnancies (ARD, 0.13%; 95% CI, -1.97% to 2.24%), 1.04 (95% CI, 0.88-1.21) for topical terbinafine-exposed vs unexposed pregnancies (ARD, 0.17%; 95% CI, -0.64% to 0.98%), and 1.19 (95% CI, 0.84-1.70) for oral vs topical terbinafine-exposed (ARD, 1.13%; 95% CI, -2.23% to 4.50%) pregnancies.Among pregnancies exposed to oral or topical terbinafine, no increased risk of major malformations or spontaneous abortion was identified.
Computationally Derived Image Signature of Stromal Morphology Is Prognostic of Prostate Cancer Recurrence Following Prostatectomy in African American Patients
Authors: Hersh K. Bhargava, Patrick Leo, Robin Elliott, Andrew Janowczyk, Jon Whitney, Sanjay Gupta, Pingfu Fu, Kosj Yamoah, Francesca Khani, Brian D. Robinson, Timothy R. Rebbeck, Michael Feldman, Priti Lal, Anant Madabhushi
Journal: Clinical Cancer Research (2020)

Abstract Purpose: Between 30%–40% of patients with prostate cancer experience disease recurrence following radical prostatectomy. Existing clinical models for recurrence risk prediction do not account for population-based variation in the tumor phenotype, despite recent evidence suggesting the presence of a unique, more aggressive prostate cancer phenotype in African American (AA) patients. We investigated the capacity of digitally measured, population-specific phenotypes of the intratumoral stroma to create improved models for prediction of recurrence following radical prostatectomy. Experimental Design: This study included 334 radical prostatectomy patients subdivided into training (VT, n = 127), validation 1 (V1, n = 62), and validation 2 (V2, n = 145). Hematoxylin and eosin–stained slides from resected prostates were digitized, and 242 quantitative descriptors of the intratumoral stroma were calculated using a computational algorithm. Machine learning and elastic net Cox regression models were constructed using VT to predict biochemical recurrence-free survival based on these features. Performance of these models was assessed using V1 and V2, both overall and in population-specific cohorts. Results: An AA-specific, automated stromal signature, AAstro, was prognostic of recurrence risk in both independent validation datasets [V1,AA: AUC = 0.87, HR = 4.71 (95% confidence interval (CI), 1.65–13.4), P = 0.003; V2,AA: AUC = 0.77, HR = 5.7 (95% CI, 1.48–21.90), P = 0.01]. AAstro outperformed clinical standard Kattan and CAPRA-S nomograms, and the underlying stromal descriptors were strongly associated with IHC measurements of specific tumor biomarker expression levels. Conclusions: Our results suggest that considering population-specific information and stromal morphology has the potential to substantially improve accuracy of prognosis and risk stratification in AA patients with prostate cancer.
A Needle‐Type Microrobot for Targeted Drug Delivery by Affixing to a Microtissue
Authors: Seungmin Lee, Jin‐young Kim, Junyoung Kim, Ali Kafash Hoshiar, Jongeon Park, Sunkey Lee, Jonghyun Kim, Salvador Pané, Bradley J. Nelson, Hongsoo Choi
Journal: Advanced Healthcare Materials (2020)

A needle-type microrobot (MR) for targeted drug delivery is developed to stably deliver drugs to a target microtissue (MT) for a given period time without the need for an external force after affixing. The MRs are fabricatedby 3D laser lithography and nickel (Ni)/titanium oxide (TiO2 ) layers are coated by physical vapor deposition. The translational velocity of the MR is 714 µm s-1 at 20 mT and affixed to the target MT under the control of a rotating magnetic field. The manipulability of the MR is shown by using both manual and automatic controls. Finally, drug release from the paclitaxel-loaded MR is characterized to determine the efficiency of targeted drug delivery. This study demonstrates the utility of the proposed needle-type MR for targeted drug delivery to MT with various flow rates in vitro physiological fluidic environments.
Ethnic diversity: NHS chief pledges to improve representation across England
Authors: Abi Rimmer
Journal: BMJ (2020)

By 2025 ethnic minority staff will make up 19% of every level of the workforce in NHS England and NHS Improvement, matching the ethnic makeup of the wider NHS, the head of the service has vowed.

Currently, people from ethnic minority groups make up 17% of the staff of NHS England and NHS Improvement, but the proportion is much lower at …
Technology exchange for cancer health network
Authors: F. Yunus, W. Teresa, M. Jahanzeb, F. Karen, S. Minhaus, R. Yunus, P. Sydow, M. Merkel, R. Kersey, S. Gray
Journal: Journal of Clinical Oncology (2007)

19598 Background: The Technology Exchange for Cancer Health Network (TECH-Net) is a collaborative, multi-state effort to implement a systematic care program to improve cancer management in the rural communities of west Tennessee, north Mississippi and east Arkansas. This Health Information Technology (HIT) project uses a two-pronged approach to total clinical decision support: (1) provide access to oncology, hematology, and other specialists through the dedicated telehealth network of the University of Tennessee's Health Science Center in conjunction with the University of Tennessee Cancer Institute; and (2) rely on a distributed electronic health record (EHR) with integrated decision support systems for online management of cancer protocols, electronic orders, and medication management. Methods: Patients with a cancer diagnosis requiring treatment for at least one year are eligible to participate. The ultimate goal for this project is to enroll 250 patients (125 rural, 125 urban) and compare quality, safety, and cost outcomes for patients receiving rural Telehealth care versus “routine” urban care. Telehealth patients see their oncologist in person at the rural sites for initial care, and see their physician via telemedicine for approximately one-half of their subsequent visits. This approach allows the clinician to make in-person clinical assessments on a regular basis while still taking advantage of the time savings associated with telemedicine. Results: 163 patients have been enrolled in the study (127 rural, 36 urban) over 18 months. Patient satisfaction has been high - 95 % of patients indicated their telemedicine visit was as good as or better than an in-person office visit. Cost analysis comparing cost savings (physician travel time) with telemedicine costs (equipment, high speed lines) indicates that the cost-benefit depends critically on distance to the rural facility and number of physician trips avoided. Initial cost data indicate that telemedicine must save at least 5 hours of physician travel time per month to break even. Conclusions: Telemedicine offers a feasible method for increasing access to oncology care in rural areas that is well-accepted by both patients and clinicians. No significant financial relationships to disclose.
Systematic Establishment of Robustness and Standards in Patient-Derived Xenograft Experiments and Analysis
Authors: Yvonne A. Evrard, Anuj Srivastava, Jelena Randjelovic, James H. Doroshow, Dennis A. Dean, Jeffrey S. Morris, Jeffrey H. Chuang
Journal: Cancer Research (2020)

Abstract Patient-derived xenografts (PDX) are tumor-in-mouse models for cancer. PDX collections, such as the NCI PDXNet, are powerful resources for preclinical therapeutic testing. However, variations in experimental and analysis procedures have limited interpretability. To determine the robustness of PDX studies, the PDXNet tested temozolomide drug response for three prevalidated PDX models (sensitive, resistant, and intermediate) across four blinded PDX Development and Trial Centers using independently selected standard operating procedures. Each PDTC was able to correctly identify the sensitive, resistant, and intermediate models, and statistical evaluations were concordant across all groups. We also developed and benchmarked optimized PDX informatics pipelines, and these yielded robust assessments across xenograft biological replicates. These studies show that PDX drug responses and sequence results are reproducible across diverse experimental protocols. In addition, we share the range of experimental procedures that maintained robustness, as well as standardized cloud-based workflows for PDX exome-sequencing and RNA-sequencing analyses and for evaluating growth. Significance: The PDXNet Consortium shows that PDX drug responses and sequencing results are reproducible across diverse experimental protocols, establishing the potential for multisite preclinical studies to translate into clinical trials.
Towards a European health research and innovation cloud (HRIC)
Authors: F. M. Aarestrup, A. Albeyatti, W. J. Armitage, C. Auffray, L. Augello, R. Balling, N. Benhabiles, G. Bertolini, J. G. Bjaalie, M. Black, N. Blomberg, P. Bogaert, M. Bubak, B. Claerhout, L. Clarke, B. De Meulder, G. D’Errico, A. Di Meglio, N. Forgo, C. Gans-Combe, A. E. Gray, I. Gut, A. Gyllenberg, G. Hemmrich-Stanisak, L. Hjorth, Y. Ioannidis, S. Jarmalaite, A. Kel, F. Kherif, J. O. Korbel, C. Larue, M. Laszlo, A. Maas, L. Magalhaes, I. Manneh-Vangramberen, E. Morley-Fletcher, C. Ohmann, P. Oksvold, N. P. Oxtoby, I. Perseil, V. Pezoulas, O. Riess, H. Riper, J. Roca, P. Rosenstiel, P. Sabatier, F. Sanz, M. Tayeb, G. Thomassen, J. Van Bussel, M. Van den Bulcke, H. Van Oyen
Journal: Genome Medicine (2020)

Abstract The European Union (EU) initiative on the Digital Transformation of Health and Care (Digicare) aims to provide the conditions necessary for building a secure, flexible, and decentralized digital health infrastructure. Creating a European Health Research and Innovation Cloud (HRIC) within this environment should enable data sharing and analysis for health research across the EU, in compliance with data protection legislation while preserving the full trust of the participants. Such a HRIC should learn from and build on existing data infrastructures, integrate best practices, and focus on the concrete needs of the community in terms of technologies, governance, management, regulation, and ethics requirements. Here, we describe the vision and expected benefits of digital data sharing in health research activities and present a roadmap that fosters the opportunities while answering the challenges of implementing a HRIC. For this, we put forward five specific recommendations and action points to ensure that a European HRIC: i) is built on established standards and guidelines, providing cloud technologies through an open and decentralized infrastructure; ii) is developed and certified to the highest standards of interoperability and data security that can be trusted by all stakeholders; iii) is supported by a robust ethical and legal framework that is compliant with the EU General Data Protection Regulation (GDPR); iv) establishes a proper environment for the training of new generations of data and medical scientists; and v) stimulates research and innovation in transnational collaborations through public and private initiatives and partnerships funded by the EU through Horizon 2020 and Horizon Europe.
Abstract P452: Urinary Metal Levels After Repeated Chelation With Edetate Disodium: Additional Evidence in Support of Metals as Cardiovascular Risk Factors
Authors: Ana Navas-Acien, Zenith Alam, Arce Domingo-Relloso, Francisco Ujueta, Gervasio A LAMAS
Journal: Circulation (2020)

Background: Epidemiologic evidence supports lead and cadmium as CVD risk factors. In the Trial to Assess Chelation Therapy (TACT), edetate disodium infusions lowered CVD risk in patients with a prior myocardial infarction. The impact of repeated chelation on established biomarkers of metal body burden, post-chelation lead and pre-chelation urine cadmium, is unknown. Objective: To assess metals in urine samples collected at the first and at 10 or more infusions with edetate disodium. We hypothesized that post-chelation urine lead and pre-chelation urine cadmium would be lower after 10 infusions compared to the first infusion. Other metals were exploratory. Methods: 13 patients with coronary artery disease (CAD) received a median of 3 g of edetate disodium over 3h per infusion and a median of 51 infusions (range 22-61). We collected pre and post-chelation urine samples at infusions 1 and ≥10. Metals were analyzed with ICPMS and controlled for urine dilution. Pre and post-chelation geometric means (GM) of urine metals at the ≥10 vs. first infusion were compared using paired T-tests. Results: Mean (SD) age was 75 (11) years, 77% participants were men, 46% were past smokers, 92% had diabetes, and 92% had peripheral artery disease. Comparing infusions ≥10 to 1 (Table), the GM (μg/g creatinine) dropped from 0.45 to 0.03 (94% reduction; p=0.005) for pre-chelation lead and from 14.80 to 2.91 (80% reduction; p=0.04) for post-chelation lead. For pre and post-chelation cadmium, the corresponding figures were 0.34 to 0.12 (64% reduction; p=0.17) and 2.81 to 2.35 (16% reduction; p=0.48), respectively. Conclusions: TACT treatment may decrease total body burden of lead, further supporting lead is a modifiable CVD risk factor. Data are insufficient to inform on changes in the burden of cadmium or other metals. Ongoing, larger studies will assess the effect of repeated chelation on toxic metal burden and incident cardiovascular disease.
Covid-19: UK could delay non-urgent care and call doctors back from leave and retirement
Authors: Elisabeth Mahase
Journal: BMJ (2020)

Healthcare staff on leave and those who have retired could be called “back to duty,” and non-urgent care could be delayed, as doctors are forced to prioritise dealing with covid-19, the UK government’s action plan lays out.

The government will also implement a “distribution strategy for the UK’s stockpiles of key medicines and equipment (e.g. protective clothing),” the document said.

However, the plan did not include details of how or when these measures would be put in place.

Speaking at a press briefing at 10 Downing Street …
Relationship between persistent neurotoxicity and long-term platinum exposure after treatment with cisplatin
Authors: E. E. Brouwers, A. D. Huitema, W. Boogerd, J. H. Beijnen, J. H. Schellens
Journal: Journal of Clinical Oncology (2007)

2546 Background: We aimed to assess relationships between the severity of persistent neuropathy and long-term platinum exposure in patients previously treated with cisplatin. Methods: Twenty patients, treated with a cisplatin containing regimen 18 to 75 months before participating in this study, were included. Sensory nerve function in hands and feet was evaluated using vibration threshold (VT) determination. Platinum levels in plasma and plasma ultrafiltrate were assessed using inductively coupled plasma mass spectrometry (ICP- MS). Possible factors affecting sensory nerve function or platinum retention were collected, including cumulative dose, follow-up time, route of administration, renal function, glutathione S-transferase (GST) genotypes, co-administration of sodium thiosulfate (STS with intra-arterial (i.a.) cisplatin), and co-morbidity (alcoholism and diabetes). Results were evaluated using non linear mixed effects modelling. Results: Patients (9 testis, 8 head-neck, 1 NSCLC, 1 SCLC, and 1 yolk sac) were treated with a cumulative dose of 300–600 mg·m -2 . Five patients received STS. Platinum plasma concentrations ranged between 142.4–1154 ng·L -1 of which on average14.8% was recovered in ultrafiltrate. Platinum levels decreased with a half-life of 21.7 months and were related to the cumulative dose. Platinum levels were reduced by 60% with i.a. cisplatin and co-administration of STS (p=0.002). The hand-VT decreased with time (t 1/2 =19.9 months) and was related to cumulative dose and to alcohol use (p=0.06). Moreover, the half-life of recovery of the hand-VT was related to the elimination half-life of platinum, albeit non-significant. In contrast, the feet-VT did not improve over time and did not show an association with cumulative dose or any of the other factors. GST genotypes and renal function were not related to VT and platinum levels. Conclusions: Our data suggest that plasma platinum levels are related to follow-up time, cumulative dose, and STS use. The data show that neuropathy in the feet might be irreversible in contrast to the hand-VT, which was also related to cumulative dose and alcohol use. Whether recovery of neuropathy was related to platinum elimination remains to be established. No significant financial relationships to disclose.
Abstract 16286: Myocardial Oxygenation is Reduced in End-Stage Renal Failure: A Novel Blood Oxygen Level Dependant (BOLD)-Cardiac MRI Study
Authors: Susie F Parnham, Suchi Grover, Carmine De Pasquale, Darryl Leong, Jonathan M Gleadle, Joseph Selvanayagam
Journal: Circulation (2013)

Background: Cardiovascular disease is the leading cause of mortality in end-stage renal failure (ESRF), mostly from coronary artery disease (CAD). Majority is asymptomatic and current cardiac stres...
Cardiovascular adverse events in patients with non-Hodgkin lymphoma treated with first-line cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or CHOP with rituximab (R-CHOP): a systematic review and meta-analysis
Authors: Marijke Linschoten, Janine A M Kamphuis, Anna van Rhenen, Laurens P Bosman, Maarten J Cramer, Pieter A Doevendans, Arco J Teske, Folkert W Asselbergs
Journal: The Lancet Haematology (2020)