tbuckley/cabot-search huggingface dataset:
The LEukemia Artificial Intelligence Program (LEAP) in chronic myeloid leukemia in chronic phase: A model to improve patient outcomes
Authors: Koji Sasaki, Elias J. Jabbour, Farhad Ravandi, Marina Konopleva, Gautam Borthakur, William G. Wierda, Naval Daver, Koichi Takahashi, Kiran Naqvi, Courtney DiNardo, Guillermo Montalban‐Bravo, Rashmi Kanagal‐Shamanna, Ghayas Issa, Preetesh Jain, Jeffrey Skinner, Mary B. Rios, Sherry Pierce, Kelly A. Soltysiak, Junya Sato, Guillermo Garcia‐Manero, Jorge E. Cortes
Journal: American Journal of Hematology (2020)

Abstract Extreme gradient boosting methods outperform conventional machine‐learning models. Here, we have developed the LEukemia Artificial intelligence Program (LEAP) with the extreme gradient boosting decision tree method for the optimal treatment recommendation of tyrosine kinase inhibitors (TKIs) in patients with chronic myeloid leukemia in chronic phase (CML‐CP). A cohort of CML‐CP patients was randomly divided into training/validation (N = 504) and test cohorts (N = 126). The training/validation cohort was used for 3‐fold cross validation to develop the LEAP CML‐CP model using 101 variables at diagnosis. The test cohort was then applied to the LEAP CML‐CP model and an optimum TKI treatment was suggested for each patient. The area under the curve in the test cohort was 0.81899.Backward multivariate analysis identified age at diagnosis, the degree of comorbidities, and TKI recommended therapy by the LEAP CML‐CP model as independent prognostic factors for overall survival. The bootstrapping method internally validated the association of the LEAP CML‐CP recommendation with overall survival as an independent prognostic for overall survival. Selecting treatment according to the LEAP CML‐CP personalized recommendations, in this model, is associated with better survival probability compared to treatment with a LEAP CML‐CP non‐recommended therapy. This approach may pave a way of new era of personalized treatment recommendations for patients with cancer.
SAT0039 Clinical changes in oligoarticular forms of psoriatic arthritis after a course of five years
Authors: MD Lopez-Montilla, A Escudero, M Romero, V Perez, C Castro, J Gonzalez, MC Muñoz-Villanueva, E Collantes
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> One of the most salient features of psoriatic arthritis is the wide variety of clinical manifesta-tions it can exhibit. This facilitates interrelationships among its clinical forms and changes from one to another. <h3>Objectives</h3> To evaluate the clinical manifestations of patients with psoriatic arthritis of initially oligo-articular form after a course of five years. <h3>Methods</h3> An overall 32 patients with psoriatic arthritis of initially oligoarticular form (viz. with fewer than three joints affected in an unsymmetric form) were examined and the specific form prevailing after a course of five years was determined. Simultaneously, clinical activity was studied on the basis of the following criteria: (a) morning stiffness for less than 15 min; (b) absence of fatigue; (c) absence of articular pain; (d) absence of pain in response to pressure or movement; (e) absence of swollen joints; (f) VSG below 30. Those patients fulfilling at least five of the previous six criteria were considered to be in remission. <h3>Results</h3> The following Table 1 classifies the patients according to status and clinical form of the disease. <h3>Conclusion</h3> Our results confirm that oligoarticular forms of psoriatic arthritis are not static, but rather change during the course of the disease.
Abstract 151: Barriers and Opportunities for a Drone-Delivered AED Network in Durham, North Carolina
Authors: Monique A Starks, Jessica Sperling, Amy Cardenas, Audrey L Blewer, Edward Sharpe, Daniel M Buckland, Anjni Joiner, Jessica Zegre-Hemsey, Daniel B Mark
Journal: Circulation (2020)

Background: The general public is unfamiliar with the concept of medical drones delivering life-saving technologies. Our research sought to define stakeholder attitudes towards development of drone-based emergency care for out-of-hospital cardiac arrest. Methods: Using qualitative methodology, we explored key stakeholder attitudes about using a drone to deliver automated external defibrillators (AED), challenges and facilitators to early establishment of a drone AED network, implementation considerations, and factors related to long-term sustainability. We identified 22 key individuals as potential respondents based on professional position; 16 respondents participated in data collection. Research participants included leaders in government, healthcare, emergency services, business, community, and the aviation industry (regulation and drone operation). Interview data were recorded and transcribed; data were analyzed using NVivo. A coding schema was developed based on constructs identified in previous literature and inductive consideration of this study’s data, including both thematic and descriptive coding. Results: We found broad support for a drone-delivered AED network. Such a network was perceived as valuable for reduced response times and for enhanced access to hard-to-reach areas. Identified challenges included operationalizing an autonomous drone AED network, privacy and safety concerns, current legal and regulatory requirements, financial liabilities, public buy-in and concern for public actually using an AED, and the need for research on treatment and cost- effectiveness of a drone network. Facilitators of development for a drone AED network included solidifying key partnerships (including integration into current EMS or fire services), identifying viable funding from private and public entities, and learning from existing drone models (e.g. commercial package or medical supply delivery). Conclusion: This study found general and conceptual support for the development of a drone network for AED delivery across key informants from an array of related fields. Such information should be considered in developing a regional drone AED network.
Diabetic ketoacidosis with SGLT2 inhibitors
Authors: Giovanni Musso, Francesca Saba, Maurizio Cassader, Roberto Gambino
Journal: BMJ (2020)

### What you need to know

A 45 year old woman with type 2 diabetes complains of malaise, shortness of breath, and nausea for two days. She has been taking metformin and insulin. She was started on canagliflozin six weeks earlier to improve glycaemic control. Over the previous week she has halved the insulin dose. On examination, she is drowsy. Her respiratory rate is 28 breaths/min with a deep breathing pattern. A random blood glucose test shows 8 mmol/L (144 mg/dL). Blood tests reveal metabolic acidosis with an increased anion gap of 23 mmol/L (reference range 8-12 mmol/L), pH 7.18, and bicarbonate 14 mmol/L. Urine dipstick showed ketones +++. 

Sodium-glucose cotransporter-2 (SGLT2) inhibitors, used in patients with diabetes, can cause diabetic ketoacidosis. This is rare but can be serious and life threatening. The US Food and Drug Administration (FDA) and European Medicines Agency (EMA) warn about possible “atypical” presentation of diabetic ketoacidosis with SGLT2 inhibitors12: instead of having hyperglycaemia, patients may have normal or only mildly elevated blood glucose levels (<13.9 mmol/L, <250 mg/dL). This may delay diagnosis. In 2020, the FDA and EMA updated guidance to interrupt SGLT2 inhibitors and monitor ketosis in patients scheduled for surgery or hospitalised.34

SGLT2 inhibitors, also called gliflozins, lower blood sugars by causing kidneys to remove glucose from the body in urine.5 Figure 1 depicts their actions. They are used as second or third line therapy in …
Amelioration of systemic inflammation in advanced chronic liver disease upon beta-blocker therapy translates into improved clinical outcomes
Authors: Mathias Jachs, Lukas Hartl, Dunja Schaufler, Christopher Desbalmes, Benedikt Simbrunner, Ernst Eigenbauer, David Josef Maria Bauer, Rafael Paternostro, Philipp Schwabl, Bernhard Scheiner, Theresa Bucsics, Albert Friedrich Stättermayer, Matthias Pinter, Michael Trauner, Mattias Mandorfer, Thomas Reiberger
Journal: Gut (2020)

Systemic inflammation promotes the development of clinical events in patients with advanced chronic liver disease (ACLD). We assessed whether (1) non-selective beta blocker (NSBB) treatment initiation impacts biomarkers of systemic inflammation and (2) whether these changes in systemic inflammation predict complications and mortality.Biomarkers of systemic inflammation, that is, white blood cell count (WBC), C reactive protein (CRP), interleukin-6 (IL-6) and procalcitonin (PCT) were determined at sequential hepatic venous pressure gradient (HVPG) measurements without NSBB and under stable NSBB intake. The influence of NSBB-related changes in systemic inflammation on the risk of decompensation and liver-related death was analysed using competing risk regression.Our study comprised 307 stable patients with ACLD (Child-A: 77 (25.1%), Child-B: 161 (52.4%), Child-C: 69 (22.5%), median HVPG: 20 (IQR 17-24) mm Hg) including 231 (75.2%) with decompensated disease.WBC significantly decreased upon NSBB therapy initiation (median: -2 (IQR -19;+13)%, p=0.011) in the overall cohort. NSBB-related reductions of WBC (Child-C: -16 (-30;+3)% vs Child-B: -2 (-16;+16)% vs Child-A: +3 (-7;+13)%, p<0.001) and of CRP (Child-C: -26 (-56,+8)% vs Child-B: -16 (-46;+13)% vs Child-A: ±0 (-33;+33)%, p<0.001) were more pronounced in advanced stages of cirrhosis. The NSBB-associated changes in WBC correlated with changes in CRP (Spearman's ρ=0.228, p<0.001), PCT (ρ=0.470, p=0.002) and IL-6 (ρ=0.501, p=0.001), but not with changes in HVPG (ρ=0.097, p=0.088).An NSBB-related decrease in systemic inflammation (ie, WBC reduction ≥15%) was achieved by n=91 (29.6%) patients and was found to be an independent protective factor of further decompensation (subdistribution HR, sHR: 0.694 (0.49-0.98), p=0.038) in decompensated patients and of liver-related mortality in the overall patient cohort (sHR: 0.561 (0.356-0.883), p=0.013).NSBB therapy seems to exert systemic anti-inflammatory activity as evidenced by reductions of WBC and CRP levels. Interestingly, this effect was most pronounced in Child-C and independent of HVPG response. An NSBB-related WBC reduction by ≥15% was associated with a decreased risk of further decompensation and death.
Massive gene presence-absence variation shapes an open pan-genome in the Mediterranean mussel
Authors: Marco Gerdol, Rebeca Moreira, Fernando Cruz, Jessica Gómez-Garrido, Anna Vlasova, Umberto Rosani, Paola Venier, Miguel A. Naranjo-Ortiz, Maria Murgarella, Samuele Greco, Pablo Balseiro, André Corvelo, Leonor Frias, Marta Gut, Toni Gabaldón, Alberto Pallavicini, Carlos Canchaya, Beatriz Novoa, Tyler S. Alioto, David Posada, Antonio Figueras
Journal: Genome biology (2020)

Abstract Background The Mediterranean mussel Mytilus galloprovincialis is an ecologically and economically relevant edible marine bivalve, highly invasive and resilient to biotic and abiotic stressors causing recurrent massive mortalities in other bivalves. Although these traits have been recently linked with the maintenance of a high genetic variation within natural populations, the factors underlying the evolutionary success of this species remain unclear. Results Here, after the assembly of a 1.28-Gb reference genome and the resequencing of 14 individuals from two independent populations, we reveal a complex pan-genomic architecture in M. galloprovincialis , with a core set of 45,000 genes plus a strikingly high number of dispensable genes (20,000) subject to presence-absence variation, which may be entirely missing in several individuals. We show that dispensable genes are associated with hemizygous genomic regions affected by structural variants, which overall account for nearly 580 Mb of DNA sequence not included in the reference genome assembly. As such, this is the first study to report the widespread occurrence of gene presence-absence variation at a whole-genome scale in the animal kingdom. Conclusions Dispensable genes usually belong to young and recently expanded gene families enriched in survival functions, which might be the key to explain the resilience and invasiveness of this species. This unique pan-genome architecture is characterized by dispensable genes in accessory genomic regions that exceed by orders of magnitude those observed in other metazoans, including humans, and closely mirror the open pan-genomes found in prokaryotes and in a few non-metazoan eukaryotes.
Abstract 13904: Ex vivo Biomechanical Analysis of Elastic Artificial Chordae Implantation for Beating-heart Transapical Mitral Valve Repair
Authors: Annabel M Imbrie-moore, Yuanjia Zhu, Matthew Park, Michael J Paulsen, Hanjay Wang, Y Joseph Y Woo
Journal: Circulation (2020)

Introduction: Beating-heart transapical mitral valve repair represents a significant advancement in the minimally invasive treatment of mitral regurgitation. However, current techniques require increased artificial chordae length and altered anchoring position, which may increase the stresses on the suture. We hypothesized that artificial chordae manufactured with increased elasticity will dampen sharp increases in force, thus theoretically increasing durability. Methods: Porcine mitral valves (n=3) were mounted in a heart simulator and isolated mitral regurgitation was induced by cutting posterior primary chordae. Each valve was first repaired with standard CV-5 polytetrafluoroethylene (PTFE) suture affixed to a 3D-printed anchor with an embedded high-resolution Fiber Bragg Grating sensor to measure forces (Fig A). The repair was then repeated with an elastic suture manufactured using a biocompatible silicone and designed with a cross-sectional area of 0.56mm 2 , a geometry calculated to result in a desired 10-15% strain at relevant forces (Fig B). Results: Both materials allowed for successful repairs: mitral leakage volume was reduced from 28.29±4.83ml to 1.26±0.99ml ( p =0.009) with PTFE suture, and to 1.78±0.88ml ( p =0.008) with the elastic suture, with no significant difference between the repairs. Normalized force tracings (Fig C, standard deviation is shaded) revealed that the elastic suture resulted in a significantly lower peak systolic force when compared to PTFE suture (0.23±0.04N vs 0.32±0.03N, p =0.007). Conclusions: Artificial chordae with increased elasticity compared to traditional PTFE suture can dampen sharp peaks in force, thus offering a promising advancement in improving transapical repair durability. This proposal has the potential to apply to open-heart artificial chordae implantation as well. Future work to optimize suture material and manufacturability will help translate this development into clinical use.
Abstract 14775: Barriers to Anticoagulation Treatment in Atrial Fibrillation: A Survey of Providers in a Large Rural Healthcare System
Authors: Macaela N Rudeck, Catherine P Benziger
Journal: Circulation (2020)

Introduction: Atrial fibrillation (AF) is common and oral anticoagulants are recommended to reduce risk of thromboembolism for patients with elevated risk. Barriers to anticoagulation are not well described. Objectives: We aim to evaluate gaps in provider knowledge and barriers to anticoagulation management in AF. Methods: A REDCap survey was sent to providers at Essentia Health (N=894), a large rural healthcare system in MN, WI, and ND. Providers were grouped into 3 categories: cardiology, primary care, and other. Providers were asked how they would manage a hypothetical patient with AF: 67-year-old female with hypertension, recurrent episodes of paroxysmal AF, no other medical history. Answer options included aspirin, warfarin, or novel oral anticoagulant (NOAC). Demographic data were obtained along with answers to questions assessing barriers to anticoagulation use and patient education. Providers who reported they do not see AF patients were excluded (N=23). Results: A total of 220 providers started the survey (75.5% completion rate). Of 157 providers who completed the case study, 74.5% correctly recommended treatment with a NOAC. Providers in cardiology were more likely than those in primary care and other specialties to select NOAC (96.4% vs. 68.5% vs. 76.2%, respectively; p=0.01). Most (92%) providers stated they personally discuss the need for anticoagulation with their patients. Providers noted the primary barrier to educating patients about their increased risk of stroke was: “They have trouble understanding what I am trying to explain to them” (24%), “They think that once their symptoms are being treated, the risk of AF-related stroke goes away” (17%), and “They don't really believe their condition is serious” (13%). Providers cited the top barrier to patient compliance with anticoagulation was patients concern of cost with no difference between specialty (cardiology 40.7% vs. primary care 46.7% vs. other 34.8%; p=0.53). Conclusion: Cardiology providers are more likely to correctly recommend a NOAC, compared to primary care or other specialties, for AF. Primary barriers to patient education and compliance include inadequate patient understanding and medication cost.
Antibiotic Sensitivity Testing
Authors: D. C. Turk
Journal: BMJ (1971)

The study of domestic accidents, which includes accidents in and around the home and in institutions, is of increasing importance. The mortality statistics are shown in Table 1. In 1974, 18,335 people died from accidents in the UK (RoSPA, 1974) equivalent to the population of a reasonably sized town. Accidents form one of the four main causes of death in this country and have become relatively more common in recent years. Analysis of the causes of home accidents make it possible to plan ways of preventing them. General practitioners and their colleagues in the primary health care team have the principal responsibility.
Abstract 13198: Immunohematologic Failure Identifies Fibrotic Phenotype in Heart Failure With Preserved Ejection Fraction
Authors: Mariam N Rana, Graham Bevan, Zainab Albar, David A Zidar, Sadeer Al-Kindi
Journal: Circulation (2020)

Background: We have shown that immunohematologic failure (IHF: lymphopenia (absolute lymphocyte count (ALC)&lt;1.5 x10 3 /μL) and anisocytosis (red cell distribution width, RDW &gt; 14.5%)) is associated with risk of heart failure. Lymphopenic patients have elevated numbers of regulatory T cells with profibrotic phenotype. Hypothesis: We hypothesized that IHF is associated with fibrosis in HFpEF. Methods: We investigated the association between ALC, RDW, and IHF with markers of fibrosis (galectin-3 and Corboxy-Terminal Telopeptide of Collagen Type I [CITP]) in patients enrolled in RELAX trial of HFpEF (Clinicaltrials.gov NCT00763867) using linear regression, and adjusting for age, sex, race, eGFR, BMI and diabetes status. Results: A total of 122 patients with both ALC and RDW were included. There was a modest correlation between ALC and RDW (Spearman’s rho=-0.22, P=0.017). Both ALC and RDW were significantly associated with galectin 3 and CITP (figure). A total of 33 (27%) patients had IHF. Patients with IHF had lower GFR (62±25 vs 53 ± 21 ml/min/1.73 m 2 , P&lt;0.001), lower peak VO2 (12.5±2.8 vs 11.0 ± 3.0 ml/kg/min, P=0.007), lower exercise capacity (78 ± 26 vs 64 ± 35 watts, P=0.018), higher NT-proBNP (900±1152 vs 1615 ± 1247 pg/mL, P=0.004), galectin-3 (13.3 ± 4.1 vs 17.7 ± 5.8, P&lt;0.001 ng/mL) and CITP (6.1 ± 3.5 vs 11.0 ± 5.7 μg/L, P&lt;0.001) but no difference in age, sex, race, CRP or diabetes status. After multiple adjustments, IHF was associated with higher galectin-3 levels (P=0.01) and CITP (P&lt;0.001). Conclusions: Immunohematologic failure is common in HFpEF and is associated with fibrotic phenotype. The mechanisms linking IHF and fibrosis need to be elucidated in future studies.
SARS‐CoV‐2‐mediated immune system activation and potential application in immunotherapy
Authors: Yuan Tan, Faqin Tang
Journal: Medicinal Research Reviews (2020)

Abstract Although novel severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2)‐mediated pulmonary inflammation has recently attracted great attention, its pathology and pathogenesis are not clear. Notably, due to both its high infective and pathogenicity, SARS‐CoV‐2 infection may cause a severe sometimes fatal respiratory disease. A specific vaccine, which relies on the analysis of SARS‐CoV‐2 structural protein‐derived antigenic peptides, is indispensable for restraining the spread and reducing the mortality of SARS‐CoV‐2. SARS‐CoV‐2 infections activate cytototxic, myeloid‐derived suppressor cells, dendritic cells, macrophages, as well as natural killer, B, helper T, and regulatory T cells, thus further stimulating innate and antigen‐specific immune responses. Nevertheless, many immune effector cells cause hyperinflammation and pulmonary immunopathology by releasing proinflammatory cytokines and chemokines, including interferon (IFN)‐α, IFN‐β, IFN‐γ, monocyte chemoattractant protein‐1, macrophage inflammatory protein (MIP)‐1A, MIP1B, interleukin (IL)‐1, IL‐2, IL‐4, IL‐6, IL‐7, IL‐8, IL‐9, IL‐12, IL‐17, and IL‐18, platelet‐derived growth factor, fibroblast growth factor, tumor necrosis factor‐α, and induced protein 10. Interestingly, related products derived from SARS‐CoV‐2 are likely to trigger immune evasion. Therefore, investigating SARS‐CoV‐2‐specific vaccines, blocking immunopathology, and prohibiting immune evasion are urgently required for treating SARS‐CoV‐2 infection. In this review, we emphatically illuminated the development of a SARS‐CoV‐2‐specific vaccine based on the analysis of epitopes, also expounding the molecular mechanisms of SARS‐CoV‐2‐mediated cytokine release syndrome. Furthermore, we comprehensively discussed SARS‐CoV‐2‐associated immune evasion and lung immunopathology. Lastly, potential therapeutic strategies against SARS‐CoV‐2 were explored.
Abstract 13655: Chronic Kidney Disease Progression and Prediction of Clinical Cardiovascular Disease and Total Mortality: The Coronary Artery Risk Development in Young Adults (cardia) Study
Authors: Daniel A Duprez, Yuni Choi, Gautam R Shroff, Haitao Chu, Holly J Kramer, David R Jacobs
Journal: Circulation (2020)

Introduction: The Kidney Disease Improving Global Outcomes (KDIGO)Guidelines proposed a chronic kidney disease (CKD) risk assessment matrix based on estimated glomerular filtration (eGFR) together with albuminuria categories (urine albumin-to-creatinine (ACR)). This classification system tends to focus on nuances at the severe CKD end of the spectrum among middle-aged and older adults. We expanded the KDIGO risk categories to include less severe manifestations of CKD, applicable to a generally healthy population in young adulthood. Hypothesis: CKD progression in its less severe range is common and predicts CVD and total mortality starting in generally healthy young adults. Methods: In a community-based sample of black and white men and women, both eGFR (creatinine) and spot urine ACR were assayed at study year 10 (age 27-41y) and every 5 y for 20 y through year 30. We expanded the 4 KDIGO risk categories by adding 2 less severe categories (see Figure). We estimated CKD stage prevalence at each exam and transition probabilities, including 4389 participants by year 30. We used proportional hazards regression with time-varying CKD stage, age, sex, and race as predictors of the endpoints any incident CVD or total death. Results: As expected, extreme risk was seen in 131 people (3% prevalence) who reached stages 4-6 (See Figure). Important increases in risk (hazard ratios 1.55 to 3.11) occurred in 1601 people (36% prevalence) who reached stages 2-3. Transition to higher stage (mostly by 1 stage) occurred in 5-10% per 5 years (~30% in 20 years). Conclusions: These data suggest that clinically important changes occur in CKD risk staging throughout middle age, though most of these changes are currently regarded as minor occurrences. Research should explore whether more aggressive, low risk treatment options, which currently exist, would be beneficial in people with small changes in CKD stage, starting in young adulthood.