tbuckley/cabot-search huggingface dataset:
Comorbidities associated with mortality in 31,461 adults with COVID-19 in the United States: A federated electronic medical record analysis
Authors: Stephanie L. Harrison, Elnara Fazio-Eynullayeva, Deirdre A. Lane, Paula Underhill, Gregory Y. H. Lip
Journal: PLoS Medicine (2020)

Background At the beginning of June 2020, there were nearly 7 million reported cases of coronavirus disease 2019 (COVID-19) worldwide and over 400,000 deaths in people with COVID-19. The objective of this study was to determine associations between comorbidities listed in the Charlson comorbidity index and mortality among patients in the United States with COVID-19. Methods and findings A retrospective cohort study of adults with COVID-19 from 24 healthcare organizations in the US was conducted. The study included adults aged 18–90 years with COVID-19 coded in their electronic medical records between January 20, 2020, and May 26, 2020. Results were also stratified by age groups (<50 years, 50–69 years, or 70–90 years). A total of 31,461 patients were included. Median age was 50 years (interquartile range [IQR], 35–63) and 54.5% (n = 17,155) were female. The most common comorbidities listed in the Charlson comorbidity index were chronic pulmonary disease (17.5%, n = 5,513) and diabetes mellitus (15.0%, n = 4,710). Multivariate logistic regression analyses showed older age (odds ratio [OR] per year 1.06; 95% confidence interval [CI] 1.06–1.07; p < 0.001), male sex (OR 1.75; 95% CI 1.55–1.98; p < 0.001), being black or African American compared to white (OR 1.50; 95% CI 1.31–1.71; p < 0.001), myocardial infarction (OR 1.97; 95% CI 1.64–2.35; p < 0.001), congestive heart failure (OR 1.42; 95% CI 1.21–1.67; p < 0.001), dementia (OR 1.29; 95% CI 1.07–1.56; p = 0.008), chronic pulmonary disease (OR 1.24; 95% CI 1.08–1.43; p = 0.003), mild liver disease (OR 1.26; 95% CI 1.00–1.59; p = 0.046), moderate/severe liver disease (OR 2.62; 95% CI 1.53–4.47; p < 0.001), renal disease (OR 2.13; 95% CI 1.84–2.46; p < 0.001), and metastatic solid tumor (OR 1.70; 95% CI 1.19–2.43; p = 0.004) were associated with higher odds of mortality with COVID-19. Older age, male sex, and being black or African American (compared to being white) remained significantly associated with higher odds of death in age-stratified analyses. There were differences in which comorbidities were significantly associated with mortality between age groups. Limitations include that the data were collected from the healthcare organization electronic medical record databases and some comorbidities may be underreported and ethnicity was unknown for 24% of participants. Deaths during an inpatient or outpatient visit at the participating healthcare organizations were recorded; however, deaths occurring outside of the hospital setting are not well captured. Conclusions Identifying patient characteristics and conditions associated with mortality with COVID-19 is important for hypothesis generating for clinical trials and to develop targeted intervention strategies.
D‐dimer in COVID‐19: A Guide With Pitfalls
Authors: Roger E. Schutgens
Journal: HemaSphere (2020)

D-dimers, as degradation products of fibrin, are widely used in the diagnosis (exclusion) of venous thrombosis. In addition, D-dimers have been shown to be of prognostic value in various diseases, including cancer and cardiovascular disease. There is plethora of data on the coagulation disturbances in patients with COVID-19, both clinically and by the use of various laboratory measurements. A high D-dimer at admission was an independent predictor for mortality in COVID-19 patients from Wuhan. Patients with a D-dimer ≥2.0 μg/ml had a much higher mortality incidence than those with levels ≤2.0 μg/ml (HR 51.5),1 where the HR was 18.4 in D-dimers ≥1.0 μg/ml.2 Also, D-dimers were able to distinguish patients with moderate from severe disease in 75 patients from China.3 Even more so, dynamic changes of D-dimer levels during the course of the disease was prognostic of poor outcome in 276 Chinese patients.4 Higher D-dimer levels were associated with a greater probability of pulmonary embolism 3, 6, 9, and 12 days after determining D-dimer levels with an OR of 1.7, 2.0, 2.4, and 2.4, respectively in 21 patients from Spain.5 Similar results were found in 106 French patients, although the D-dimer threshold to exclude PE (2660 μg/L) was much higher than usual.6 A higher threshold was also suggested in 156 COVID-19 patients with asymptomatic deep venous thrombosis.7 Anticoagulation therapy was associated with lower mortality in COVID-19 and this was especially true for patients with high D-dimers.8 As the relationship between D-dimers and the severity of COVID-19 and/or the occurrence of PE is evident and even appears to be dynamic, it is appealing to start an early intervention based on D-dimer levels. Several clinical guideline already advocate the use of different D-dimer cut-off levels to determine the anticoagulation dose. However, as a recent review pointed out very clearly,9 there is a high variety of D-dimer tests with a large variability in the way they report their results. Most importantly, differences in the reported units (either D-Dimer Units [DDU]) or Fibrin Equivalent Units [FEU], the assay cut-off values and the absolute measuring units (mg/L, ng/mL, μ/mL) hamper generalisability of the results and the use of a clear cut-off point for decision making. The authors correctly call out for at least fully reporting the necessary variables to ensure study results can be translated to other clinics. Therefore, although the role of D-dimers in guiding treatment of COVID-19 is attractive, clinicians should be aware of the details of their local D-dimer test before implementing standard cut-offs provided by others.
Prevascularized Scaffolds Bearing Human Dental Pulp Stem Cells for Treating Complete Spinal Cord Injury
Authors: Shaowei Guo, Idan Redenski, Shira Landau, Ariel Szklanny, Uri Merdler, Shulamit Levenberg
Journal: Advanced Healthcare Materials (2020)

The regeneration of injured spinal cord is hampered by the lack of vascular supply and neurotrophic support. Transplanting tissue-engineered constructs with developed vascular networks and neurotrophic factors, and further understanding the pattern of vessel growth in the remodeled spinal cord tissue are greatly desired. To this end, highly vascularized scaffolds embedded with human dental pulp stem cells (DPSCs) are fabricated, which possess paracrine-mediated angiogenic and neuroregenerative potentials. The potent pro-angiogenic effect of the prevascularized scaffolds is first demonstrated in a rat femoral bundle model, showing robust vessel growth and blood perfusion induced within these scaffolds postimplantation, as evidenced by laser speckle contrast imaging and 3D microCT dual imaging modalities. More importantly, in a rat complete spinal cord transection model, the implantation of these scaffolds to the injured spinal cords can also promote revascularization, as well as axon regeneration, myelin deposition, and sensory recovery. Furthermore, 3D microCT imaging and novel morphometric analysis on the remodeled spinal cord tissue demonstrate substantial regenerated vessels, more significantly in the sensory tract regions, which correlates with behavioral recovery following prevascularization treatment. Taken together, prevascularized DPSC-embedded constructs bear angiogenic and neurotrophic potentials, capable of augmenting and modulating SCI repair.
Diagnosis of Chronic Hepatitis B Pericomplication: Risk factors and Trends Over Time
Authors: Lauren Lapointe‐Shaw, Hannah Chung, Laura Holder, Jeffrey C. Kwong, Beate Sander, Peter C. Austin, Harry L.A. Janssen, Jordan J. Feld
Journal: Hepatology (2020)

Background and Aims Hepatitis B virus (HBV) is a major cause of chronic liver disease, which can progress to cirrhosis, hepatocellular carcinoma, and death. A timely diagnosis allows for antiviral treatment, which can prevent liver‐related complications. Conversely, a late diagnosis signals a missed opportunity for earlier care and treatment. Our objective was to measure the proportion of chronic HBV diagnoses that are made within 6 months of presentation with a liver disease–related complication and examine associated factors and trends over time. Approach and Results We used provincial laboratory data to identify patients with chronic HBV diagnosed from 2003 to 2014. We measured the proportion who experienced a liver disease complication (decompensated cirrhosis, hepatocellular carcinoma, or liver transplant) within ±6 months of their HBV diagnosis date. A multivariable logistic regression model was used to identify factors associated with HBV diagnosis pericomplication. Of 18,434 patients with chronic HBV, 1,279 (6.9%) developed an HBV‐related complication during the follow‐up period. Among these, 570 (44.6%) had a first diagnosis pericomplication. HBV diagnosis pericomplication did not decrease over time and was independently associated with older age at HBV diagnosis, rural residence, alcohol use, and moderate to high levels of comorbidity. Female patients, immigrants, and those with more outpatient physician visits were less likely to have an HBV diagnosis pericomplication. Conclusions A high proportion of patients with HBV‐related complications are first diagnosed with HBV pericomplication. These signal missed opportunities for earlier detection and treatment. Our findings support expansion of HBV screening.
AB0002 One of susceptibility loci for rheumatoid arthritis is lying inside 14q11.1–11.2 bands suggested by a linkage study
Authors: MY Krylov, SA Finigenova, MA Moshnina, EY Samarkina, VA Maykotkin
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Rheumatoid arthritis (RA) is a complex disorder with genetic component that has been suggested by familial aggregation, twin studies, and segregation analysis. Early we show that the type of the inheritance of RA corresponded to a single autosomal two-alleles locus model with incomplete penetrance. This model was used in our study for parametric linkage analysis candidate genes: HLA, T-cell receptors (TCRA, TCRB, TCRD), Col1A2, Col<sup>2</sup>A1. Lod scores were negative (less than – 2.0) for HLA, TCRB, Col1A2 and Col<sup>2</sup>A1 loci. <h3>Objectives</h3> To identify a new RA susceptibility genes to lying inside 14 q11.1–11.2 chromosomal segment. <h3>Methods</h3> We conducted a study in 25 multiplex RA families, 10–15 of them were informative for linkage analysis. The polymorphism of TCRD and TCRA genes, D14S261 and D14S283 microsatellites were investigated by single-strand conformation polymorphism. The TCRD point variation (TCRDpv) was confirmed by restriction fragment length polymorphism. <h3>Results</h3> Lod scores (LS) were calculated at standard recombination fractions. The summarised LS for informative families are presented below: D14S261 – LS = +1.50 (RF = 0), TVRD – LS = +1.65 (RF = 0.05), TCRDpv – LS = +0.65 (RF = 0), TCRA – LS = +0.94 (RF = 0), D14S283 – LS = +0.1 (RF = 0.1). <h3>Conclusion</h3> These findings show evidence that 14 q11.1–11.2 are bands which may contain one of the RA susceptibility genes. This is study was supported by Russian Foundation basic Research grant N 99–04–48643.
Identification of clonal skin myeloid cells by next‐generation sequencing in myelodysplasia cutis
Authors: J. Delaleu, M. Battistella, K. Rathana, M.‐D. Vignon‐Pennamen, C. Laurent, C. Ram‐Wolff, P. Fenaux, M. Jachiet, E. Zuelgaray, M. Bagot, J.‐D. Bouaziz, A. Masson
Journal: British Journal of Dermatology (2020)
ROR2 blockade as a therapy for osteoarthritis
Authors: Anne-Sophie Thorup, Danielle Strachan, Sara Caxaria, Blandine Poulet, Bethan L. Thomas, Suzanne E. Eldridge, Giovanna Nalesso, James R. Whiteford, Costantino Pitzalis, Thomas Aigner, Roger Corder, Jessica Bertrand, Francesco Dell’Accio
Journal: Science Translational Medicine (2020)

Osteoarthritis is characterized by the loss of the articular cartilage, bone remodeling, pain, and disability. No pharmacological intervention can currently halt progression of osteoarthritis. Here, we show that blocking receptor tyrosine kinase-like orphan receptor 2 (ROR2) improves cartilage integrity and pain in osteoarthritis models by inhibiting yes-associated protein (YAP) signaling. ROR2 was up-regulated in the cartilage in response to inflammatory cytokines and mechanical stress. The main ligand for ROR2, WNT5A, and the targets YAP and connective tissue growth factor were up-regulated in osteoarthritis in humans. In vitro, ROR2 overexpression inhibited chondrocytic differentiation. Conversely, ROR2 blockade triggered chondrogenic differentiation of C3H10T1/2 cells and suppressed the expression of the cartilage-degrading enzymes a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)-4 and ADAMTS-5. The chondrogenic effect of ROR2 blockade in the cartilage was independent of WNT signaling and was mediated by down-regulation of YAP signaling. ROR2 signaling induced G protein and Rho-dependent nuclear accumulation of YAP, and YAP inhibition was required but not sufficient for ROR2 blockade-induced chondrogenesis. ROR2 silencing protected mice from instability-induced osteoarthritis with improved structural outcomes, sustained pain relief, and without apparent side effects or organ toxicity. Last, ROR2 silencing in human articular chondrocytes transplanted in nude mice led to the formation of cartilage organoids with more and better differentiated extracellular matrix, suggesting that the anabolic effect of ROR2 blockade is conserved in humans. Thus, ROR2 blockade is efficacious and well tolerated in preclinical animal models of osteoarthritis.
Theoretical model of pediatric orbital trapdoor fractures and provisional personalized 3D printing-assisted surgical solution
Authors: Guangrui Chai, Deming Zhang, Weijian Hua, Jun Yin, Yifei Jin, Ming Chen
Journal: Bioactive Materials (2020)

Pediatric orbital trapdoor fractures are common in children and adolescents and usually require emergency surgical intervention. Herein, a personalized 3D printing-assisted approach to surgical treatment is proposed, serving to accurately and effectively repair pediatric orbital trapdoor fractures. We first investigated stress distribution in external force-induced orbital blowout fractures via numerical simulation, determining that maximum stresses on inferior and medial walls exceed those on superior and lateral walls and thus confer higher probability of fracture. We also examined 36 pediatric patients treated for orbital trapdoor fractures between 2014 and 2019 to verify our theoretical construct. Using 3D printing technique, we then created orbital models based on computed tomography (CT) studies of these patients. Absorbable implants were tailor-made, replicating those of 3D-printed models during surgical repairs of fractured orbital bones. As follow-up, we compared CT images and clinical parameters (extraocular movements, diplopia, enophthalmos) before and 12 months after operative procedures. There were only two patients with diplopia and six with enophthalmos >2 mm at 12 months, attesting to the efficacy of our novel 3D printing-assisted strategy.
Resurgence of an international hepatitis A outbreak linked to imported frozen strawberries, Germany, 2018 to 2020
Authors: Claudia Ruscher, Mirko Faber, Dirk Werber, Klaus Stark, Julia Bitzegeio, Kai Michaelis, Daniel Sagebiel, Jürgen J Wenzel, Julia Enkelmann
Journal: Eurosurveillance (2020)

Following outbreaks linked to frozen strawberries in Sweden and Austria in 2018, 65 cases linked to the same hepatitis A virus strain were detected in Germany between October 2018 and January 2020, presenting in two waves. Two case–control studies and a comparison of cases’ consumption frequencies with purchase data from a large consumer panel provided strong evidence for frozen strawberry cake as the main vehicle of transmission. Of 46 cases interviewed, 27 reported consuming frozen strawberry cake and 25 of these identified cake(s) from brand A spontaneously or in product picture-assisted recall. Trace back investigations revealed that the Polish producer involved in the previous outbreaks in Sweden and Austria had received frozen strawberries from Egypt via a wholesaler that also delivered frozen strawberries to manufacturer of brand A. Phylogenetic analyses linked the outbreak strain to similar strains formerly isolated from sewage, stool and strawberries in Egypt. Complete trace back and timely recall of products with strong evidence of contamination is important to control an outbreak and prevent later resurgence, particularly for food items with a long shelf life. Continued molecular surveillance of hepatitis A is needed to identify outbreaks and monitor the success of food safety interventions.
How can we better predict pulmonary blood clots in patients hospitalised for COVID-19?
Authors: Laurent Bertoletti, Menno V. Huisman
Journal: European Respiratory Journal (2020)

The emergence of coronavirus disease 2019 (COVID-19) has put pressure on health systems around the world [1, 2]. This coronavirus has also questioned much of our medical knowledge, with each day seeing the appearance of a new possible clinical expression of the virus [3]. Although its physiopathology is still poorly understood, the vascular tropism of the disease now seems to be a major pathway [4]. Recent studies highlight the development of a specific pulmonary vascular endothelialitis associated with thrombosis and angiogenesis [5]. D-dimer threshold at 2590 ng·mL−1 is able to predict pulmonary embolism in COVID-19 patients with clinical deterioration <https://bit.ly/3kYObc3>
The future of digital health with federated learning
Authors: Nicola Rieke, Jonny Hancox, Wenqi Li, Fausto Milletarì, Holger R. Roth, Shadi Albarqouni, Spyridon Bakas, Mathieu N. Galtier, Bennett A. Landman, Klaus Maier-Hein, Sébastien Ourselin, Micah Sheller, Ronald M. Summers, Andrew Trask, Daguang Xu, Maximilian Baust, M. Jorge Cardoso
Journal: npj Digital Medicine (2020)

Abstract Data-driven machine learning (ML) has emerged as a promising approach for building accurate and robust statistical models from medical data, which is collected in huge volumes by modern healthcare systems. Existing medical data is not fully exploited by ML primarily because it sits in data silos and privacy concerns restrict access to this data. However, without access to sufficient data, ML will be prevented from reaching its full potential and, ultimately, from making the transition from research to clinical practice. This paper considers key factors contributing to this issue, explores how federated learning (FL) may provide a solution for the future of digital health and highlights the challenges and considerations that need to be addressed.
Risk of physical activity and hepatobiliary diseases: east meets west
Authors: Howard Chi Ho Yim, Emad M El-Omar
Journal: British Journal of Sports Medicine (2020)

Total and leisure-time physical activity are inversely associated with risk of liver cancer, non-alcoholic liver disease and gallbladder disease. This has been shown in Western populations but until now not in the Chinese and other Asian populations. In BJSM, Pang et al 1 address this gap by reporting a large prospective study that involved 461K participants in the China Kadoorie Biobank (CKB). These participants, aged from 30 to 79 years from 10 regions of China, were recruited before they had cancer and hepatobillary diseases. They were then prospectively followed up for 10 years.

We consider Pang et al have made at least four valuable contributions . First, they found that the total and occupational physical activity was inversely associated with hospitalised non-alcoholic fatty liver disease, cirrhosis and liver cancer.1 These results are consistent with those reports done in Western countries.2 Second, they found that viral hepatitis was inversely associated with total and occupational physical activity in the CKB cohort.1 Third, they revealed that the total and occupational physical activity was inversely associated with gallstone disease and gallbladder cancer.1 This is consistent with the previous studies performed in Western populations.2 However, excessive volumes of physical activity …
Covid-19: RECOVERY trial will evaluate “antiviral antibody cocktail”
Authors: Elisabeth Mahase
Journal: BMJ (2020)

Covid-19: RECOVERY trial will evaluate "antiviral antibody cocktail" Elisabeth MahaseThe RECOVERY trial, which discovered that dexamethasone shows benefit in patients seriously ill with covid-19, will investigate the impact of an "antiviral antibody cocktail" specifically designed for covid-19, known as REGN-COV2.
Seven-Year Outcomes of Uveitic Macular Edema: The Multicenter Uveitis Steroid Treatment Trial and Follow-up Study Results
Authors: Oren Tomkins-Netzer, Susan L. Lightman, Alyce E. Burke, Elizabeth A. Sugar, Lyndell L. Lim, Glenn J. Jaffe, Michael M. Altaweel, John H. Kempen, Janet T. Holbrook, Douglas A. Jabs
Journal: Ophthalmology (2020)
Gene Networks Constructed Through Simulated Treatment Learning can Predict Proteasome Inhibitor Benefit in Multiple Myeloma
Authors: Joske Ubels, Pieter Sonneveld, Martin H. van Vliet, Jeroen de Ridder
Journal: Clinical Cancer Research (2020)

Proteasome inhibitors are widely used in treating multiple myeloma, but can cause serious side effects and response varies among patients. It is, therefore, important to gain more insight into which patients will benefit from proteasome inhibitors.We introduce simulated treatment learned signatures (STLsig), a machine learning method to identify predictive gene expression signatures. STLsig uses genetically similar patients who have received an alternative treatment to model which patients will benefit more from proteasome inhibitors than from an alternative treatment. STLsig constructs gene networks by linking genes that are synergistic in their ability to predict benefit.In a dataset of 910 patients with multiple myeloma, STLsig identified two gene networks that together can predict benefit to the proteasome inhibitor, bortezomib. In class "benefit," we found an HR of 0.47 (P = 0.04) in favor of bortezomib, while in class "no benefit," the HR was 0.91 (P = 0.68). Importantly, we observed a similar performance (HR class benefit, 0.46; P = 0.04) in an independent patient cohort. Moreover, this signature also predicts benefit for the proteasome inhibitor, carfilzomib, indicating it is not specific to bortezomib. No equivalent signature can be found when the genes in the signature are excluded from the analysis, indicating that they are essential. Multiple genes in the signature are linked to working mechanisms of proteasome inhibitors or multiple myeloma disease progression.STLsig can identify gene signatures that could aid in treatment decisions for patients with multiple myeloma and provide insight into the biological mechanism behind treatment benefit.