tbuckley/cabot-search huggingface dataset:
Single-cell RNA-seq with spike-in cells enables accurate quantification of cell-specific drug effects in pancreatic islets
Authors: Brenda Marquina-Sanchez, Nikolaus Fortelny, Matthias Farlik, Andhira Vieira, Patrick Collombat, Christoph Bock, Stefan Kubicek
Journal: Genome biology (2020)

Abstract Background Single-cell RNA-seq (scRNA-seq) is emerging as a powerful tool to dissect cell-specific effects of drug treatment in complex tissues. This application requires high levels of precision, robustness, and quantitative accuracy—beyond those achievable with existing methods for mainly qualitative single-cell analysis. Here, we establish the use of standardized reference cells as spike-in controls for accurate and robust dissection of single-cell drug responses. Results We find that contamination by cell-free RNA can constitute up to 20% of reads in human primary tissue samples, and we show that the ensuing biases can be removed effectively using a novel bioinformatics algorithm. Applying our method to both human and mouse pancreatic islets treated ex vivo, we obtain an accurate and quantitative assessment of cell-specific drug effects on the transcriptome. We observe that FOXO inhibition induces dedifferentiation of both alpha and beta cells, while artemether treatment upregulates insulin and other beta cell marker genes in a subset of alpha cells. In beta cells, dedifferentiation and insulin repression upon artemether treatment occurs predominantly in mouse but not in human samples. Conclusions This new method for quantitative, error-correcting, scRNA-seq data normalization using spike-in reference cells helps clarify complex cell-specific effects of pharmacological perturbations with single-cell resolution and high quantitative accuracy.
Periodontitis and rheumatoid arthritis: An update 2012‐2017
Authors: Peter Mark Bartold, Isabel Lopez‐Oliva
Journal: Periodontology 2000 (2020)

Abstract Rheumatoid arthritis and chronic periodontitis are both chronic inflammatory diseases characterized by an exacerbated inflammatory reaction that leads to destruction of bone and other connective tissue. Owing to these similarities, the relationship between these two diseases has been investigated for over two decades. In the 2013 proceedings from a workshop jointly held by the European Federation of Periodontology and American Academy of Periodontology in 2012 it was concluded that there was at least minimal evidence of an association between periodontitis and rheumatoid arthritis. In this review, we consider publications in the field over the past 5 years and determine whether the evidence for this relationship has increased.
The impact of extended half‐life factor concentrates on prophylaxis for severe hemophilia in the United States
Authors: Lynn M. Malec, Dunlei Cheng, Char M. Witmer, Julie Jaffray, Peter A. Kouides, Kristina M. Haley, Robert F. Sidonio, Kelsey Johnson, Michael Recht, Gilbert White, Stacy E. Croteau, Margaret V. Ragni
Journal: American Journal of Hematology (2020)

Abstract With licensure of extended half‐life (EHL) factor products and the changing landscape of available hemophilia products, patients and providers have options for less treatment‐intense prophylaxis. The impact of these products in clinical practice to date remains understudied. We aimed to quantify the use of EHL products in prophylaxis in the US using the ATHN‐dataset, a database of 145 ATHN‐affiliated hemophilia treatment centers (HTCs). Further, we aimed to quantify the impact of EHL on key hemophilia indicators including annualized bleed rates (ABRs), hemophilia joint health scores (HJHS) and quality of life (QOL) metrics. The use of EHL vs standard half‐life (SHL) products in severe hemophilia was compared between June 2018 and March 2019 using the ATHN‐dataset. A cohort of patients was also recruited from seven participating HTCs in order to compare ABR, HJHS and QOL between product classes. By March 2019 the number of individuals with severe Hemophilia A (SHA) receiving EHLs remained relatively stable (28.4%), whereas the number of prescribed non‐factor products increased to 7.1%, with a diminishing majority of patients (64.0%) continuing to receive SHLs. The majority of patients with severe hemophilia B (SHB) received treatment with EHLs including 57.5% by March 2019. There was a trend toward lower ABR with use of EHLs in SHA and SHB, although this did not result in improved HJHS nor QOL. EHL use in the United States in severe hemophilia continues to increase, although at a slower rate in SHA with the availability of non‐factor therapy. The impact of the EHL therapies in clinical practice should continue to be examined prospectively.
ICU outcomes can be predicted by noninvasive muscle evaluation: a meta-analysis
Authors: Clément Medrinal, Yann Combret, Roger Hilfiker, Guillaume Prieur, Nadine Aroichane, Francis-Edouard Gravier, Tristan Bonnevie, Olivier Contal, Bouchra Lamia
Journal: European Respiratory Journal (2020)

Background The relationship between muscle function in critically ill patients assessed using bedside techniques and clinical outcomes has not been systematically described. We aimed to evaluate the association between muscle weakness assessed by bedside evaluation and mortality or weaning from mechanical ventilation, and the capacity of each evaluation tool to predict outcomes. Methods Five databases (PubMed, Embase, CINAHL, Cochrane Library, Science Direct) were searched from January 2000 to December 2018. Data were extracted and random effects meta-analyses were performed. Results 60 studies were analysed, including 4382 patients. Intensive care unit (ICU)-related muscle weakness was associated with an increase in overall mortality with odds ratios ranging from 1.2 (95% CI 0.60–2.40) to 4.48 (95% CI 1.49–13.42). Transdiaphragmatic twitch pressure had the highest predictive capacity for overall mortality, with a sensitivity of 0.87 (95% CI 0.76–0.93) and a specificity of 0.36 (95% CI 0.27–0.43). The area under the curve (AUC) was 0.74 (95% CI 0.70–0.78). Muscle weakness was associated with an increase in mechanical ventilation weaning failure rate with an odds ratio ranging from 2.64 (95% CI 0.72–9.64) to 19.07 (95% CI 9.35–38.9). Diaphragm thickening fraction had the highest predictive capacity for weaning failure with a sensitivity of 0.76 (95% CI 0.67–0.83) and a specificity of 0.86 (95% CI 0.78–0.92). The AUC was 0.86 (95% CI 0.83–0.89). Conclusion ICU-related muscle weakness detected by bedside techniques is a serious issue associated with a high risk of death or prolonged mechanical ventilation. Evaluating diaphragm function should be a clinical priority in the ICU.
Guidelines for the Diagnosis and Management of Food Allergy in the United States: Summary of the NIAID-Sponsored Expert Panel Report
Authors: Joshua A. Boyce, Amal Assa'ad, A. Wesley Burks, Stacie M. Jones, Hugh A. Sampson, Robert A. Wood, Marshall Plaut, Susan F. Cooper, Matthew J. Fenton, S. Hasan Arshad, Sami L. Bahna, Lisa A. Beck, Carol Byrd-Bredbenner, Carlos A. Camargo, Lawrence Eichenfield, Glenn T. Furuta, Jon M. Hanifin, Carol Jones, Monica Kraft, Bruce D. Levy, Phil Lieberman, Stefano Luccioli, Kathleen M. McCall, Lynda C. Schneider, Ronald A. Simon, F. Estelle R. Simons, Stephen J. Teach, Barbara P. Yawn, Julie M. Schwaninger
Journal: Journal of the American Academy of Dermatology (2010)
Ventilation/Perfusion SPECT Imaging Diagnosing PE and Other Cardiopulmonary Diseases
Authors: Marika Bajc, Ari Lindqvist
Journal: Clinical Nuclear Medicine (2020)

Ventilation/perfusion single photon emission computed tomography (V/P SPECT) is the recommended method for the diagnosis of pulmonary embolism (PE). Apart from PE, other changes can be identified and reported, such as the sign of chronic obstructive pulmonary disease (COPD), pneumonia, left heart failure (LHF), chronic PE, pulmonary hypertension and suspicion of other parenchymal processes like tumours. Recent studies have shown that for the ventilation study, Technegas® particles have an advantage over radiolabelled liquid aerosols due to the better penetration to the periphery. Therefore, Technegas® enables studies in patients with obstructive lung disease. Radiolabelled macroaggregated human albumin (MAA) is the imaging agent of choice for perfusion scintigraphy. An adequate V/P SPECT acquisition starting with ventilation and continuing with perfusion can be done in 20 min by using an optimal combination of nuclide activities, collimators and imaging matrix. It is recommended that the 1-day protocol starts with a ventilation examination, immediately followed by perfusion. This allows for presentation of matching ventilation and perfusion slices in all projections. It also allows for rotating volume images based upon maximum intensity projections (MIPs) and quantification of V/P quotient. V/P SPECT is interpreted according to the European Association of Nuclear Medicine (EANM) guideline.
Tumor-Stroma Ratio within the Primary Tumor Is a Prognostic Factor in Early Breast Cancer Patients, Especially in Triple-Negative-Carcinoma Patients.
Authors: E. de Kruijf, J. van Nes, C. van de Velde, H. Putter, V. Smit, G. Liefers, P. Kuppen, R. Tollenaar, W. Mesker
Journal: Cancer Research (2009)

Abstract Background: Breast cancer patients comprise a prognostic heterogeneous group. Stroma-tissue surrounding cancer cells plays an important role in tumor behavior. The prognostic value of the tumor-stroma ratio was evaluated.Material and Methods: A cohort of 574 patients with early breast cancer, primarily treated by surgery between 1985 and 1994 was analyzed. The percentage of intra-tumoral stroma was visually estimated on haematoxylin-eosin-stained histological sections from primary tumor tissue by two observers. Patients with more than 50% intra-tumor stroma were quantified as stroma-rich and patients with less than 50% intra-tumor stroma as stroma-poor.Results: Of all tumors, 68% were classified as stroma-rich and 32% as stroma-poor. Cohen's kappa coefficient revealed an almost perfect agreement in classification (kappa=0.85; 94% concordance in classification) between the two observers. For the total group of patients, stroma-rich tumors had a shorter relapse free period (RFP) (Hazard ratio (HR) 1.62; 95%CI 1.23-2.13; p=0.001) and overall survival (OS) (HR1.29; 95%CI 1.03-1.60; p=0.025) compared to stroma-poor tumors. Tumor-stroma ratio was an independent prognostic parameter for all patients (p&amp;lt;0.001) and in stratified analysis for patients that received systemic treatment. Importantly, within the triple-negative-cancer (TNC) subpopulation, patients with stroma-rich tumors had a 3.19 times higher risk of relapse (p=0.003) compared to patients with stroma-poor tumors, independently of grade and lymph node status. Five year RFP-rates for patients with stroma-rich compared to stroma-poor tumors were 56% and 81% respectively.Discussion: Tumor-stroma ratio was an independent prognostic factor for RFP in breast cancer patients, especially in TNC. The tumor-stroma ratio is easy to apply, of low cost and reproducible. It is a candidate parameter that can easily be implemented in routine daily diagnostics to optimize risk-stratification for breast cancer patients and should therefore be considered to be implemented in standard pathology reports. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 3049.
Assessment of Health Status and Barriers to Employment Among Medicaid Beneficiaries Not Meeting Work Requirements After Accounting for State Medical Frailty Exemptions
Authors: David M. Silvestri, Abbe R. Gluck, Joseph S. Ross
Journal: JAMA Internal Medicine (2020)

This cross-sectional study quantifies the proportion of nonexempt Medicaid beneficiaries not meeting work requirements, compares their health with nonexempt beneficiaries fulfilling requirements, and assesses their inability to work for health-related reasons.
Endothelial Progenitor Cell‐Derived Extracellular Vesicles: A Novel Candidate for Regenerative Medicine and Disease Treatment
Authors: Zheng Xing, Chen Zhao, Haifeng Liu, Yubo Fan
Journal: Advanced Healthcare Materials (2020)

Abstract Extracellular vesicles (EVs) are a heterogeneous group of membranous structures, which can be secreted by most cell types. As a product of paracrine secretion, EVs are considered to be a regulatory mediator for intercellular communication. There are many bioactive cargos in EVs, such as proteins, lipids, and nucleic acids. As the precursor cell of vascular endothelial cells (ECs), endothelial progenitor cells (EPCs) are first discovered in peripheral blood. With the development of studies about the functions of EPCs, an increasing number of researchers focus on EPC‐derived EVs (EPC‐EVs). EPC‐EVs exert key functions for promoting angiogenesis in regenerative medicine and show significant therapeutic effects on a variety of diseases such as circulatory diseases, kidney diseases, diabetes, bone diseases, and tissue/organ damages. This article reviews the current knowledge on the role of EPC‐EVs in regenerative medicine and disease treatment, discussing the main challenges and future directions in this field.
Lack of Flvcr2 impairs brain angiogenesis without affecting the blood-brain barrier
Authors: Nicolas Santander, Carlos O. Lizama, Eman Meky, Gabriel L. McKinsey, Bongnam Jung, Dean Sheppard, Christer Betsholtz, Thomas D. Arnold
Journal: Journal of Clinical Investigation (2020)

Fowler syndrome is a rare autosomal recessive brain vascular disorder caused by mutation in FLVCR2 in humans. The disease occurs during a critical period of brain vascular development, is characterized by glomeruloid vasculopathy and hydrocephalus, and is almost invariably prenatally fatal. Here, we sought to gain insights into the process of brain vascularization and the pathogenesis of Fowler syndrome by inactivating Flvcr2 in mice. We showed that Flvcr2 was necessary for angiogenic sprouting in the brain, but surprisingly dispensable for maintaining the blood-brain barrier. Endothelial cells lacking Flvcr2 had altered expression of angiogenic factors, failed to adopt tip cell properties, and displayed reduced sprouting, leading to vascular malformations similar to those seen in humans with Fowler syndrome. Brain hypovascularization was associated with hypoxia and tissue infarction, ultimately causing hydrocephalus and death of mutant animals. Strikingly, despite severe vascular anomalies and brain tissue infarction, the blood-brain barrier was maintained in Flvcr2 mutant mice. Our Fowler syndrome model therefore defined the pathobiology of this disease and provided new insights into brain angiogenesis by showing uncoupling of vessel morphogenesis and blood-brain barrier formation.
Palliation of Metastatic Bone Pain with Radiolabeled Phosphonates
Authors: Jiaqiong Wang, Aldo N. Serafini
Journal: Clinical Nuclear Medicine (2020)

This chapter reviews the role of various radiolabeled phosphonates in the palliation of bone pain from osteoblastic metastatic and primary bone disease. Various radiophosphonates are available for this purpose. These include Samarium-153 ethylenediaminetetramethylenephosphonate (Samarium-153 EDTMP), Rhenium-188 hydroxyethylidenediphosphonate (Rhenium-188 HEDP), and Lutetium-177 ethylenediaminetetramethylene phosphonic acid (Lutetium-177 EDTMP). They generally have comparatively short physical half-lives and high dose rates and can be administered as either monotherapy or fractionated therapy with low toxicity. They also can be imaged to both assess efficacy and conduct dosimetry studies. One agent that has been studied extensively and approved for bone palliation in a variety of cancers, including prostrate, breast, lung, and other primary cancers, is Samarium-153 EDTMP. It has been shown to be effective with single-dose treatment in 65–85% of patients, with pain relief seen within 4–6 weeks of treatment. Initial positive responses have been sustainable over longer periods, with significant reduction in opioid and other analgesic needs, overall improvement in quality of life, and survival benefits with minimal short- and long-term adverse events. Additionally, more recent studies have demonstrated that it can be safe to combine Samarium-153 EDTMP with chemotherapy, external beam radiation therapy, and nonradioactive bisphosphonates, to palliate metastatic bone pain and provide an antitumor strategy especially for metastatic castration-resistant prostate cancer. More recently, studies have shown that Rhenium-188 HEDP holds promise because it appears to be effective in rapidly relieving pain and improving overall survival in patients with prostate cancer when given as repeated therapy, it is readily available from a generator, and it is cost-effective.
The association of periodontal diseases with metabolic syndrome and obesity
Authors: Søren Jepsen, Jean Suvan, James Deschner
Journal: Periodontology 2000 (2020)

Abstract Periodontitis is a multifactorial chronic inflammatory disease associated with dysbiotic plaque biofilms and characterized by progressive destruction of the tooth‐supporting apparatus. Globally, it is estimated that 740 million people are affected by its severe form. Periodontitis has been suggested to be linked to obesity and metabolic syndrome. Obesity, defined as excessive fat accumulation, is a complex multifactorial chronic inflammatory disease, with a high and increasing prevalence. Metabolic syndrome is defined as a cluster of obesity, dyslipidemia, hypertension, and dysglycemia. Obesity, metabolic syndrome and periodontitis are among the most common non‐communicable diseases and a large body of evidence from epidemiologic studies supports the association between these conditions. Extensive research has established plausible mechanisms to explain how these conditions can negatively impact each other, pointing to a bidirectional adverse relationship. At present there is only limited evidence available from a few intervention studies. Nevertheless, the global burden of periodontitis combined with the obesity epidemic has important clinical and public health implications for the dental team. In accordance with the common risk factor approach for tackling non‐communicable diseases, it has been proposed that oral healthcare professionals have an important role in the promotion of periodontal health and general well‐being through facilitation of healthy lifestyle behaviours.
Acute interstitial pneumonia: comparison of high-resolution computed tomography findings between survivors and nonsurvivors.
Authors: Kazuya Ichikado, Moritaka Suga, Nestor L Müller, Hiroyuki Taniguchi, Yasuhiro Kondoh, Masanori Akira, Takeshi Johkoh, Naoki Mihara, Hironobu Nakamura, Mutsumasa Takahashi, Masayuki Ando
Journal: American Journal of Respiratory and Critical Care Medicine (2002)

This study compared high-resolution computed tomography (CT) findings between 10 survivors and 21 nonsurvivors of acute interstitial pneumonia and evaluated whether the CT findings were predictive of patients' response to treatment. The survivor and nonsurvivor groups with pathologically or clinically diagnosed acute interstitial pneumonia were similar in age, sex, disease duration, and lung injury score. Retrospective, subjective evaluations of the CT scans were conducted by two independent observers without knowledge of patient outcomes. CT findings were graded on a one to six scale corresponding to consecutive pathologic phases as follows: areas of (1) normal attenuation, (2) ground-glass attenuation, (3) consolidation, (4) ground-glass attenuation associated with traction bronchiolectasis or bronchiectasis, (5) consolidation associated with traction bronchiolectasis or bronchiectasis, and (6) honeycombing. An overall score was obtained by quantifying the extent of each abnormality in three lung zones in each lung. The extent of ground-glass attenuation or consolidation associated with traction bronchiolectasis or bronchiectasis was less in survivors than nonsurvivors (p = 0.004 and p = 0.009, respectively). Architectural distortion was less frequent, and ground-glass attenuation or consolidation without traction bronchiolectasis or bronchiectasis was more extensive in survivors than in nonsurvivors (p = 0.007, p = 0.002, and p = 0.029, respectively). Overall CT scores of survivors were significantly lower than those of nonsurvivors (p = 0.0003). A CT score of less than 245 had an 80% positive and a 90% negative predictive value for survival. There was good interobserver agreement in the assessment of the CT findings (Kappa 0.75). The results indicate that CT assessment is potentially helpful in predicting patient prognosis in acute interstitial pneumonia regardless of the degree of physiologic abnormality.
CONSORT 2010 statement: extension checklist for reporting within person randomised trials
Authors: N. Pandis, B. Chung, R. W. Scherer, D. Elbourne, D. G Altman
Journal: British Journal of Dermatology (2019)

Evidence shows that the quality of reporting of randomised controlled trials (RCTs) is not optimal. The lack of transparent reporting impedes readers from judging the reliability and validity of trial findings and researchers from extracting information for systematic reviews and results in research waste. The Consolidated Standards of Reporting Trials (CONSORT) statement was developed to improve the reporting of RCTs. Within person trials are used for conditions that can affect two or more body sites, and are a useful and efficient tool because the comparisons between interventions are within people. Such trials are most commonly conducted in ophthalmology, dentistry, and dermatology. The reporting of within person trials has, however, been variable and incomplete, hindering their use in clinical decision making and by future researchers. This document presents the CONSORT extension to within person trials. It aims to facilitate the reporting of these trials. It extends 16 items of the CONSORT 2010 checklist and introduces a modified flowchart and baseline table to enhance transparency. Examples of good reporting and evidence based rationale for CONSORT within person checklist items are provided.
Optical Coherence Tomography Intensity Correlates with Extracellular Matrix Components in the Airway Wall
Authors: Orestes A. Carpaij, Annika W. M. Goorsenberg, Julia N. S. d’Hooghe, Daniel M. de Bruin, Richard M. van den Elzen, Martijn C. Nawijn, Jouke T. Annema, Maarten van den Berge, Peter I. Bonta, Janette K. Burgess
Journal: American Journal of Respiratory and Critical Care Medicine (2020)