tbuckley/cabot-search huggingface dataset:
Pandemic treatments on trial: the bigger picture. <i>N of many thinking in an N of one scenario</i>
Authors: Tom Kotsimbos, Marc Humbert
Journal: European Respiratory Journal (2020)

<b>The tension between immediately using any potentially useful novel therapy in COVID-19 and trialling all novel therapies as rigorously as possible is addressed from a bigger picture perspective.</b>https://bit.ly/3fZVuxg
Abstract B36: A novel model of osteosarcomagenesis reveals dysregulation of oxidative phosphorylation
Authors: Brittany E. Jewell, An Xu, Ruoji Zhou, Dandan Zhu, Linchao Lu, Ruying Zhao, Lisa L. Wang, Dung-Fang Lee
Journal: Cancer Research (2020)

Abstract The purpose of this study is to develop a new model to study osteosarcoma in order to elucidate cellular pathways important in osteosarcomagenesis that are potential therapeutic targets. Osteosarcoma is the most common bone malignancy in childhood and early adolescence. Thirty percent of patients with the rare genetic disorder Type II Rothmund-Thomson syndrome (RTS) develop osteosarcoma. Patients with RTS have biallelic mutations in the RECQL4 gene, which encodes an ATP-dependent DNA helicase. Unfortunately, many attempts to model RTS-associated osteosarcoma have not been successful. Here, we describe a patient-derived induced pluripotent stem cell (iPSC) model capable of recapitulating the process of osteosarcomagenesis. Briefly, RTS patient fibroblasts are reprogrammed to iPSCs, then subsequently differentiated to mesenchymal stem cells. These cells are validated and further differentiated to early and late osteoblasts, the potential precursors of osteosarcoma. Because the iPSC-derived osteoblasts retain the genetic fidelity of the patient from which they were derived, we believe these cells are the ideal model to study the molecular mechanism associated with RTS-associated osteosarcoma. Utilizing the patient-derived osteoblasts, we have performed RNAseq and subsequent GSEA analyses to explore the transcriptome of RTS osteoblasts and found the dysregulation of oxidative phosphorylation in RTS osteoblasts. Interestingly, it has been reported that specific vacuolar ATPases are upregulated in patient cells. It has been reported that vacuolar ATPases function to increase proton concentration within the mitochondria and also within the extracellular environment. Understanding key mechanisms of osteosarcomagenesis is critical to making steps toward novel therapeutics. Citation Format: Brittany E. Jewell, An Xu, Ruoji Zhou, Dandan Zhu, Linchao Lu, Ruying Zhao, Lisa L. Wang, Dung-Fang Lee. A novel model of osteosarcomagenesis reveals dysregulation of oxidative phosphorylation [abstract]. In: Proceedings of the AACR Special Conference on the Advances in Pediatric Cancer Research; 2019 Sep 17-20; Montreal, QC, Canada. Philadelphia (PA): AACR; Cancer Res 2020;80(14 Suppl):Abstract nr B36.
Repeated leftover serosurvey of SARS-CoV-2 IgG antibodies, Greece, March and April 2020
Authors: Zacharoula Bogogiannidou, Alexandros Vontas, Katerina Dadouli, Maria A Kyritsi, Soteris Soteriades, Dimitrios J Nikoulis, Varvara Α Mouchtouri, Michalis Koureas, Evangelos I Kazakos, Emmanouil G Spanos, Georgia Gioula, Evangelia E Ntzani, Alexandros A Eleftheriou, Alkiviadis Vatopoulos, Efthimia Petinaki, Vassiliki Papaevangelou, Matthaios Speletas, Sotirios Tsiodras, Christos Hadjichristodoulou
Journal: Eurosurveillance (2020)

A serosurvey of IgG antibodies against severe acute respiratory coronavirus 2 (SARS-CoV-2) was performed during March and April 2020. Among 6,586 leftover sera, 24 (0.36%) were positive, with higher prevalence in females, older individuals and residents of large urban areas. Seroprevalence was estimated at 0.02% and 0.25%, respectively, in March and April, infection fatality rate at 2.66% and 0.54%. Our findings confirm low COVID-19 incidence in Greece and possibly the effectiveness of early measures.
When Standard Markers Are Not Sufficient for Monitoring Minimal Residual Disease or Targeted Treatment: New Transcriptome Derived Flow Cytometry Markers for Switching B Cell Precursor Leukemias
Authors: Michaela Novakova, Alena Musilova, Lucie Slamova, Barbora Vakrmanova, Monika Brüggemann, Matthias Ritgen, Eva Fronkova, Tomas Kalina, Ondrej Hrusak, Jan Trka, Jan Stary, Martina Vaskova, Lucie Winkowska, Marketa Zaliova, Karel Fiser, Ester Mejstrikova
Journal: Blood (2017)
Acute onset rash in a limited distribution
Authors: Remus T Winn, Suzy Leech
Journal: BMJ (2020)

A fit and well man in his 60s presented to the dermatology urgent assessment clinic with a 4 week history of a worsening pruritic eruption, limited to his elbows and posterior legs. In view of the limited distribution, further questioning was directed towards identifying potential contact factors. In the 1-2 weeks before the rash onset, the patient identified having acquired a new reclining chair made of tanned leather. He reported daily morning episodes of running in his garden to the point of perspiration before lying in T-shirt and shorts upon his new leather recliner for 8 hours a day. Examination revealed a substantial follicular eruption comprising papules and pustules in a strikingly restricted distribution on both legs (fig 1). The distribution and the follicular …
Response to: ‘Hydroxychloroquine ineffective for COVID-19 prophylaxis in lupus and rheumatoid arthritis’ by Singer et al
Authors: Manuel Francisco Ugarte-Gil, Maximilian F Konig, Peter Korsten, Francis Berenbaum, Alfred Hyoungju Kim, Jeffrey A Sparks
Journal: Annals of the Rheumatic Diseases (2020)

We thank Singer et al for their correspondence1 about our article related to hydroxychloroquine (HCQ) use, COVID-19 and rheumatology.2 The authors present an interesting analysis using electronic health records from 36 US healthcare organisations, including patients with systemic lupus erythematosus (SLE) or rheumatoid arthritis (RA). They found no association of HCQ use versus non-use with COVID-19, influenza/pneumonia/other lower respiratory infections and any outpatient visit, suggesting that baseline use of antimalarials such as HCQ does not prevent COVID-19.

These results suggesting no prophylactic benefit for antimalarials complement findings from the physician-based registry of the COVID-19 Global Rheumatology Alliance (GRA). Among 80 patients with SLE and COVID-19 in the GRA registry, the rates of hospitalisation and requirement of supplemental oxygen were similar in those who were using antimalarials prior to the onset of COVID-19 and those who were not.3 In the entire registry, which included 600 patients with systemic rheumatic disease (RMD) at that time, antimalarials were not associated with lower odds of hospitalisation after adjustment for …
Evidence-Based Orthopedic Surgery—From Synthesis to Practice
Authors: Ahmed K. Emara, Alison K. Klika, Nicolas S. Piuzzi
Journal: JAMA Surgery (2020)

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ESMO consensus conference recommendations on the management of metastatic melanoma: under the auspices of the ESMO Guidelines Committee
Authors: U. Keilholz, P.A. Ascierto, R. Dummer, C. Robert, P. Lorigan, A. van Akkooi, A. Arance, C.U. Blank, V. Chiarion Sileni, M. Donia, M.B. Faries, C. Gaudy-Marqueste, H. Gogas, J.J. Grob, M. Guckenberger, J. Haanen, A.J. Hayes, C. Hoeller, C. Lebbé, I. Lugowska, M. Mandalà, I. Márquez-Rodas, P. Nathan, B. Neyns, R. Olofsson Bagge, S. Puig, P. Rutkowski, B. Schilling, V.K. Sondak, H. Tawbi, A. Testori, O. Michielin
Journal: Annals of Oncology (2020)
Serum HBsAg clearance has minimal impact on CD8+ T cell responses in mouse models of HBV infection
Authors: Valeria Fumagalli, Pietro Di Lucia, Valentina Venzin, Elisa B. Bono, Robert Jordan, Christian R. Frey, William Delaney, Francis V. Chisari, Luca G. Guidotti, Matteo Iannacone
Journal: The Journal of Experimental Medicine (2020)

Antibody-mediated clearance of hepatitis B surface antigen (HBsAg) from the circulation of chronically infected patients (i.e., seroconversion) is usually associated with increased HBV-specific T cell responsiveness. However, a causative link between serum HBsAg levels and impairment of intrahepatic CD8+ T cells has not been established. Here we addressed this issue by using HBV replication-competent transgenic mice that are depleted of circulating HBsAg, via either spontaneous seroconversion or therapeutic monoclonal antibodies, as recipients of HBV-specific CD8+ T cells. Surprisingly, we found that serum HBsAg clearance has only a minimal effect on the expansion of HBV-specific naive CD8+ T cells undergoing intrahepatic priming. It does not alter their propensity to become dysfunctional, nor does it enhance the capacity of IL-2–based immunotherapeutic strategies to increase their antiviral function. In summary, our results reveal that circulating HBsAg clearance does not improve HBV-specific CD8+ T cell responses in vivo and may have important implications for the treatment of chronic HBV infection.
Recent Developments of Biomaterials for Additive Manufacturing of Bone Scaffolds
Authors: You Chen, Weilin Li, Chao Zhang, Zhaoying Wu, Jie Liu
Journal: Advanced Healthcare Materials (2020)

Recent years have witnessed surging demand for bone repair/regeneration implants due to the increasing number of bone defects caused by trauma, cancer, infection, and arthritis worldwide. In addition to bone autografts and allografts, biomaterial substitutes have been widely used in clinical practice. Personalized implants with precise and personalized control of shape, porosity, composition, surface chemistry, and mechanical properties will greatly facilitate the regeneration of bone tissue and satiate the clinical needs. Additive manufacturing (AM) techniques, also known as 3D printing, are drawing fast growing attention in the fabrication of implants or scaffolding materials due to their capability of manufacturing complex and irregularly shaped scaffolds in repairing bone defects in clinical practice. This review aims to provide a comprehensive overview of recent progress in the development of materials and techniques used in the additive manufacturing of bone scaffolds. In addition, clinical application, pre-clinical trials and future prospects of AM based bone implants are also summarized and discussed.
Selective Routing of Spatial Information Flow from Input to Output in Hippocampal Granule Cells
Authors: Xiaomin Zhang, Alois Schlögl, Peter Jonas
Journal: Neuron (2020)

Dentate gyrus granule cells (GCs) connect the entorhinal cortex to the hippocampal CA3 region, but how they process spatial information remains enigmatic. To examine the role of GCs in spatial coding, we measured excitatory postsynaptic potentials (EPSPs) and action potentials (APs) in head-fixed mice running on a linear belt. Intracellular recording from morphologically identified GCs revealed that most cells were active, but activity level varied over a wide range. Whereas only ∼5% of GCs showed spatially tuned spiking, ∼50% received spatially tuned input. Thus, the GC population broadly encodes spatial information, but only a subset relays this information to the CA3 network. Fourier analysis indicated that GCs received conjunctive place-grid-like synaptic input, suggesting code conversion in single neurons. GC firing was correlated with dendritic complexity and intrinsic excitability, but not extrinsic excitatory input or dendritic cable properties. Thus, functional maturation may control input-output transformation and spatial code conversion.
Abstract B59: Cardiometabolic complications after pediatric cancer: Associations with chemotherapeutic agents and body-mass-index fluctuations
Authors: Veronique Belanger, Alexandre Warin, Elitsa Tonova, Isabelle Bouchard, Caroline Meloche, Daniel Curnier, Serge Sultan, Caroline Laverdiere, Daniel Sinnett, Valerie Marcil
Journal: Cancer Research (2020)

Abstract Introduction: Survivors of childhood cancer are at risk of cardiometabolic complications including dyslipidemia, obesity, insulin resistance, and hypertension. In addition, children undergoing chemotherapy often suffer from substantial side effects including rapid weight gain, transient hypertension, and elevated blood glucose and lipids. However, little is known about the cardiometabolic health of children shortly after cancer treatment. This study aims to describe the cardiometabolic profile of children after treatment and to study the factors associated with these complications. Methods: Participants were recruited at Sainte-Justine UHC in Montreal as part of the VIE Program (Valorization, Implication, Education). Cardiometabolic health was assessed with biochemical, clinical, and anthropometric measures. Data on treatment (diagnosis, chemotherapeutic agents, and doses) were obtained from medical files. Results: Evaluations were performed on 71 participants (45% boys; median age: 9.8 years; 42% with acute lymphoblastic leukemia; median time since last treatment: 1.4 years, range: 0.2-3.5 years). Our assessment showed that 28% had hypertension, 27% were obese, 19% had altered glucose metabolism, and 33% had dyslipidemia. The risk of having dyslipidemia was associated with higher age [relative risk (RR): 1.28, 95%CI: 1.14-1.44, P&amp;lt;0.01] and body mass index (BMI) (RR: 1.76, 95%CI: 1.11-2.78, P=0.02). Participants who increased their BMI during treatment were at higher risk of obesity (RR: 3.01, 95%CI: 1.44-6.29, P&amp;lt;0.01). The increase of BMI during treatment was associated with exposure to glucocorticoids (coefficient β: 0.56, 95%CI: 0.13-0.98, P=0.01) and to methotrexate (coefficient β: 0.73, 95%CI: 0.34-1.11, P&amp;lt;0.01). Conclusion: We found important alterations of children’s cardiometabolic profile shortly after the end of cancer treatment. Increased BMI during and after treatment and exposure to corticosteroids and methotrexate were factors associated with cardiometabolic health. This stresses the importance of maintaining a favorable nutritional status during cancer therapy. Early nutritional interventions promoting sustainable healthy eating habits may contribute to limit cardiometabolic complications in the short and long term. Citation Format: Veronique Belanger, Alexandre Warin, Elitsa Tonova, Isabelle Bouchard, Caroline Meloche, Daniel Curnier, Serge Sultan, Caroline Laverdiere, Daniel Sinnett, Valerie Marcil. Cardiometabolic complications after pediatric cancer: Associations with chemotherapeutic agents and body-mass-index fluctuations [abstract]. In: Proceedings of the AACR Special Conference on the Advances in Pediatric Cancer Research; 2019 Sep 17-20; Montreal, QC, Canada. Philadelphia (PA): AACR; Cancer Res 2020;80(14 Suppl):Abstract nr B59.
Novel Human Anti-HLA-Bw4 and B61 Monoclonal Antibodies Kill Malignant B Cells Via CDC/ADCC While Sparing Normal Peripheral Blood Cells
Authors: Hiroyuki Takamatsu, Tatsuhiko Ozawa, Yoshitaka Zaimoku, Akinori Tsuji, Ichiro Hanamura, Junya Kuroda, Hidenori Tanaka, Shintaro Kawai, Hiroyuki Kishi, Shinji Nakao
Journal: Blood (2017)
Modifications to the Classical Autologous Hematopoietic Stem Cell Transplantation in Multiple Sclerosis: Efficacy and Safety Study of a Less Toxic Approach Which Improves the Neurological Condition. a Mexican Perspective
Authors: Guillermo Jose Ruiz-Argüelles, Juan Carlos Olivares Gazca, Ivan Murrieta-Alvarez, David Blumenkron-Marroquin, Elias Eugenio Gonzalez-Lopez, Alejandro Ruiz-Argüelles, Guillermo Jose Ruiz-Delgado, Andres Gomez De Leon, David Gomez-Almaguer
Journal: Blood (2017)
Coca-Cola’s work with academics was a “low point in history of public health”
Authors: Shaun Griffin
Journal: BMJ (2020)

An analysis of thousands of emails has shown the extent to which Coca-Cola sought to obscure its relationship with scientists, minimise perception of its role, and use researchers to promote industry friendly messaging. The findings represented a “low point in the history of public health,” said one of the authors.

Academics the UK and Italy worked with US Right to Know, an investigative public health and consumer group, to obtain and analyse more than 18 000 pages of email correspondence between the Coca-Cola Company, West Virginia University, and the University of Colorado.1

Both universities were part of a “front group” funded by Coca-Cola called the Global Energy Balance Network (GEBN), a global network of scientists1 said to have been created by Coke to downplay links between obesity and sugary drinks.2

Thematic and narrative …
Preclinical Pulmonary Fibrosis Circulating Protein Biomarkers
Authors: Susan K. Mathai, Jonathan Cardwell, Fabian Metzger, Julia Powers, Avram D. Walts, Jonathan A. Kropski, Oliver Eickelberg, Stefanie M. Hauck, Ivana V. Yang, David A. Schwartz
Journal: American Journal of Respiratory and Critical Care Medicine (2020)
Impaired retinal microvascular function predicts long-term adverse events in patients with cardiovascular disease
Authors: James D Theuerle, Ali H Al-Fiadh, Fakir M Amirul Islam, Sheila K Patel, Louise M Burrell, Tien Yin Wong, Omar Farouque
Journal: Cardiovascular Research (2020)

Abstract Aims Endothelial dysfunction is a precursor to the development of symptomatic atherosclerosis. Retinal microvascular reactivity to flicker light stimulation is a marker of endothelial function and can be quantified in vivo. We sought to determine whether retinal microvascular endothelial dysfunction predicts long-term major adverse cardiovascular events (MACE). Methods and results In a single-centre prospective observational study, patients with coronary artery disease (CAD) or cardiovascular risk factors underwent dynamic retinal vessel assessment in response to flicker light stimulation and were followed up for MACE. Retinal microvascular endothelial dysfunction was quantified by measuring maximum flicker light-induced retinal arteriolar dilatation (FI-RAD) and flicker light-induced retinal venular dilatation (FI-RVD). In total, 252 patients underwent dynamic retinal vessel assessment and 242 (96%) had long-term follow-up. Of the 242 patients, 88 (36%) developed MACE over a median period of 8.6 years (interquartile range 6.0–9.1). After adjustment for traditional risk factors, patients within the lowest quintile of FI-RAD had the highest risk of MACE [odds ratio (OR) 5.21; 95% confidence interval (CI) 1.78–15.28]. Patients with lower FI-RAD were also more likely to die (OR 2.09; 95% CI 1.00–4.40, per standard deviation decrease in FI-RAD). In Kaplan–Meier analysis, patients with FI-RAD responses below the cohort median of 1.4% exhibited reduced MACE-free survival (55.5 vs. 71.5%; log-rank P = 0.004). FI-RVD was not predictive of MACE. Conclusion Retinal arteriolar endothelial dysfunction is an independent predictor of MACE in patients with CAD or cardiovascular risk factors. Dynamic retinal vessel analysis may provide added benefit to traditional risk factors in stratifying patients at risk for cardiovascular events.
Transoral endoscopic ultrasound-guided fine-needle biopsy of a tumor of the parapharyngeal space
Authors: Marcin Polkowski, Jacek Lenartowicz, Jakub Zwoliński, Jakub Pałucki, Andrzej Mróz, Kamil Sokół, Jarosław Reguła
Journal: Endoscopy (2020)

The parapharyngeal space is a pyramid-shaped space located between the base of the skull and the hyoid bone, lateral to the naso-oropharynx and medial to the jaw [1] [2]. It contains the deep lobe of the parotid gland, cranial nerves IX – XII, the internal jugular vein, and the carotid artery [1]. A variety of benign and malignant tumors arise in the parapharyngeal space, the most common being of salivary gland and neurogenic origin [1]. Because of its deep location and concerns about damaging adjacent structures, the parapharyngeal space is difficult to access for biopsy [1] [2] [3]. Percutaneous, transoral, or transnasal approaches have been used; however, sampling may be challenging even under imaging guidance [2] [3] [4] [5]. Here we report for the first time a technique of transoral biopsy using a flexible gastrointestinal echoendoscope.
Demystifying “drop-outs” in single-cell UMI data
Authors: Tae Hyun Kim, Xiang Zhou, Mengjie Chen
Journal: Genome biology (2020)

Abstract Many existing pipelines for scRNA-seq data apply pre-processing steps such as normalization or imputation to account for excessive zeros or “drop-outs." Here, we extensively analyze diverse UMI data sets to show that clustering should be the foremost step of the workflow. We observe that most drop-outs disappear once cell-type heterogeneity is resolved, while imputing or normalizing heterogeneous data can introduce unwanted noise. We propose a novel framework HIPPO (Heterogeneity-Inspired Pre-Processing tOol) that leverages zero proportions to explain cellular heterogeneity and integrates feature selection with iterative clustering. HIPPO leads to downstream analysis with greater flexibility and interpretability compared to alternatives.
Hepatocyte pyroptosis and release of inflammasome particles induce stellate cell activation and liver fibrosis
Authors: Susanne Gaul, Aleksandra Leszczynska, Fernando Alegre, Benedikt Kaufmann, Casey D. Johnson, Leon A. Adams, Alexander Wree, Georg Damm, Daniel Seehofer, Carolina J. Calvente, Davide Povero, Tatiana Kisseleva, Akiko Eguchi, Matthew D. McGeough, Hal M. Hoffman, Pablo Pelegrin, Ulrich Laufs, Ariel E. Feldstein
Journal: Journal of Hepatology (2020)