tbuckley/cabot-search huggingface dataset:
Hypoxic-Ischemic Encephalopathy Evaluated by Brain Autopsy and Neuroprognostication After Cardiac Arrest
Authors: Christian Endisch, Erik Westhall, Martin Kenda, Kaspar J. Streitberger, Hans Kirkegaard, Werner Stenzel, Christian Storm, Christoph J. Ploner, Tobias Cronberg, Hans Friberg, Elisabet Englund, Christoph Leithner
Journal: JAMA Neurology (2020)

<h3>Importance</h3> Neuroprognostication studies are potentially susceptible to a self-fulfilling prophecy as investigated prognostic parameters may affect withdrawal of life-sustaining therapy. <h3>Objective</h3> To compare the results of prognostic parameters after cardiac arrest (CA) with the histopathologically determined severity of hypoxic-ischemic encephalopathy (HIE) obtained from autopsy results. <h3>Design, Setting, and Participants</h3> In a retrospective, 3-center cohort study of all patients who died following cardiac arrest during their intensive care unit stay and underwent autopsy between 2003 and 2015, postmortem brain histopathologic findings were compared with post-CA brain computed tomographic imaging, electroencephalographic (EEG) findings, somatosensory-evoked potentials, and serum neuron-specific enolase levels obtained during the intensive care unit stay. Data analysis was conducted from 2015 to 2020. <h3>Main Outcomes and Measures</h3> The severity of HIE was evaluated according to the selective eosinophilic neuronal death (SEND) classification and patients were dichotomized into categories of histopathologically severe and no/mild HIE. <h3>Results</h3> Of 187 included patients, 117 were men (63%) and median age was 65 (interquartile range, 58-74) years. Severe HIE was found in 114 patients (61%) and no/mild HIE was identified in 73 patients (39%). Severe HIE was found in all 21 patients with bilaterally absent somatosensory-evoked potentials, all 15 patients with gray-white matter ratio less than 1.10 on brain computed tomographic imaging, all 9 patients with suppressed EEG, 15 of 16 patients with burst-suppression EEG, and all 29 patients with neuron-specific enolase levels greater than 67 μg/L more than 48 hours after CA without confounders. Three of 7 patients with generalized periodic discharges on suppressed background and 1 patient with burst-suppression EEG had a SEND 1 score (&lt;30% dead neurons) in the cerebral cortex, but higher SEND scores (&gt;30% dead neurons) in other oxygen-sensitive brain regions. <h3>Conclusions and Relevance</h3> In this study, histopathologic findings suggested severe HIE after cardiac arrest in patients with bilaterally absent cortical somatosensory-evoked potentials, gray-white matter ratio less than 1.10, highly malignant EEG, and serum neuron-specific enolase concentration greater than 67 μg/L.
OP0089 EFFICACY OF CLOMIPRAMINE FOR CHRONIC LUMBAR RADICULAR PAIN A RANDOMIZED CLINICAL TRIAL
Authors: S. Afilal, S. Fellous, A. Ilham, R. Abouqal, I. Hmamouchi, N. Alami, T. Latifa, H. Rkain, F. Allali
Journal: Annals of the Rheumatic Diseases (2020)

Background: Lumbar radicular pain is the most common chronic neuropathic pain syndrome. Antidepressants are highly recommended for neuropathic pain, but there is no evidence for their efficacy. Objectives: The aim of this double-blind, randomised, placebo-controlled trial is to determine whether Clomipramine (an antidepressant) is more effective than placebo in reducing pain in individuals with resistant chronic lumbar radicular pain. Methods: A double-blind, randomized, clinical trial. Sixty-two patients with resistant chronic lumbar radicular pain were included. (The sample size was calculated on the assumption that clomipramine would reduce the incidence of lumbar radicular pain of 35%, compared with placebo, with a two-sided test, an alpha level of 0.05, and a power of 85%). Patients were randomly allocated to receive either Clomipramine by slow intravenous infusion for 10 days in a hospital setting with progressively increasing doses, 25 mg on the first day, 50 mg on the second day and 75 mg on the third day until the tenth day, or placebo (500 ml of physiological serum a day). For both groups, paracetamol is added intravenously at a dose of 3g per day for ten days, Parecoxib for 3 days and ten sessions of lumbar spine rehabilitation including analgesic massage, muscle strengthening and joint maintenance. At the exit, clomipramine was relayed with 25 mg per day orally until the 90th day for clomipramine group, and paracetamol was authorized in both groups, in case of severe pain. The primary outcome was pain intensity, measured at baseline, 5th day, 10th day and 90th day using VAS pain (10 mm). Secondary outcome included DN4-questionnaire, lumbar radicular discomfort (VAS 10 mm), pain-free perimeter of walking (min), disability assessed using the Roland Morris Disability questionnaire and severity of mood symptoms assessed using the Hospital Anxiety and Depression scale (HAD), measured on days 0, 5, 10 and 90. Results: 31 patients were assigned to the clomipramine group and 31 to the placebo group. There were no differences between the groups in demographic characteristics. Treatment by Clomipramine had a significantly greater reduction in pain, discomfort and DN4 from the 5 th day (p = 0.000, p = 0.001 and p = 0.004 respectively) than the placebo, with an improvement maintained until 90th day. There was a statistically significant improvement in pain-free walking distance and disability for the clomipramine group from the 10 th day (p = 0.02 and 0.001 respectively) and that maintained until 90 th day. However, there was no significant improvement in HAD between the 2 groups. (p ≥ 0.1). Conclusion: This double-blind, randomized, clinical trial shows that clomipramine is quickly effective and maintained over time in the management of resistant chronic lumbar radicular pain. It can therefore be part of the therapeutic arsenal in this sense. Disclosure of Interests: None declared
The Theory and Applications of Measuring Broad-Range and Chromosome-Wide Recombination Rate from Allele Frequency Decay around a Selected Locus
Authors: Kevin H -C Wei, Aditya Mantha, Doris Bachtrog
Journal: Molecular Biology and Evolution (2020)

Recombination is the exchange of genetic material between homologous chromosomes via physical crossovers. High-throughput sequencing approaches detect crossovers genome wide to produce recombination rate maps but are difficult to scale as they require large numbers of recombinants individually sequenced. We present a simple and scalable pooled-sequencing approach to experimentally infer near chromosome-wide recombination rates by taking advantage of non-Mendelian allele frequency generated from a fitness differential at a locus under selection. As more crossovers decouple the selected locus from distal loci, the distorted allele frequency attenuates distally toward Mendelian and can be used to estimate the genetic distance. Here, we use marker selection to generate distorted allele frequency and theoretically derive the mathematical relationships between allele frequency attenuation, genetic distance, and recombination rate in marker-selected pools. We implemented nonlinear curve-fitting methods that robustly estimate the allele frequency decay from batch sequencing of pooled individuals and derive chromosome-wide genetic distance and recombination rates. Empirically, we show that marker-selected pools closely recapitulate genetic distances inferred from scoring recombinants. Using this method, we generated novel recombination rate maps of three wild-derived strains of Drosophila melanogaster, which strongly correlate with previous measurements. Moreover, we show that this approach can be extended to estimate chromosome-wide crossover interference with reciprocal marker selection and discuss how it can be applied in the absence of visible markers. Altogether, we find that our method is a simple and cost-effective approach to generate chromosome-wide recombination rate maps requiring only one or two libraries.
Extreme Acetylation of the Cardiac Mitochondrial Proteome Does Not Promote Heart Failure
Authors: Michael T. Davidson, Paul A. Grimsrud, Ling Lai, James A. Draper, Kelsey H. Fisher-Wellman, Tara M. Narowski, Dennis M. Abraham, Timothy R. Koves, Daniel P. Kelly, Deborah M. Muoio
Journal: Circulation Research (2020)

Circumstantial evidence links the development of heart failure to posttranslational modifications of mitochondrial proteins, including lysine acetylation (Kac). Nonetheless, direct evidence that Kac compromises mitochondrial performance remains sparse.This study sought to explore the premise that mitochondrial Kac contributes to heart failure by disrupting oxidative metabolism.A DKO (dual knockout) mouse line with deficiencies in CrAT (carnitine acetyltransferase) and Sirt3 (sirtuin 3)-enzymes that oppose Kac by buffering the acetyl group pool and catalyzing lysine deacetylation, respectively-was developed to model extreme mitochondrial Kac in cardiac muscle, as confirmed by quantitative acetyl-proteomics. The resulting impact on mitochondrial bioenergetics was evaluated using a respiratory diagnostics platform that permits comprehensive assessment of mitochondrial function and energy transduction. Susceptibility of DKO mice to heart failure was investigated using transaortic constriction as a model of cardiac pressure overload. The mitochondrial acetyl-lysine landscape of DKO hearts was elevated well beyond that observed in response to pressure overload or Sirt3 deficiency alone. Relative changes in the abundance of specific acetylated lysine peptides measured in DKO versus Sirt3 KO hearts were strongly correlated. A proteomics comparison across multiple settings of hyperacetylation revealed ≈86% overlap between the populations of Kac peptides affected by the DKO manipulation as compared with experimental heart failure. Despite the severity of cardiac Kac in DKO mice relative to other conditions, deep phenotyping of mitochondrial function revealed a surprisingly normal bioenergetics profile. Thus, of the >120 mitochondrial energy fluxes evaluated, including substrate-specific dehydrogenase activities, respiratory responses, redox charge, mitochondrial membrane potential, and electron leak, we found minimal evidence of oxidative insufficiencies. Similarly, DKO hearts were not more vulnerable to dysfunction caused by transaortic constriction-induced pressure overload.The findings challenge the premise that hyperacetylation per se threatens metabolic resilience in the myocardium by causing broad-ranging disruption to mitochondrial oxidative machinery.
Correction: Dependency on the TYK2/STAT1/MCL1 axis in anaplastic large cell lymphoma
Authors: Nicole Prutsch, Elisabeth Gurnhofer, Tobias Suske, Huan Chang Liang, Michaela Schlederer, Simone Roos, Lawren C. Wu, Ingrid Simonitsch-Klupp, Andrea Alvarez-Hernandez, Christoph Kornauth, Dario A. Leone, Jasmin Svinka, Robert Eferl, Tanja Limberger, Astrid Aufinger, Nitesh Shirsath, Peter Wolf, Thomas Hielscher, Christina Sternberg, Fritz Aberger, Johannes Schmoellerl, Dagmar Stoiber, Birgit Strobl, Ulrich Jäger, Philipp B. Staber, Florian Grebien, Richard Moriggl, Mathias Müller, Giorgio G. Inghirami, Takaomi Sanda, A. Thomas Look, Suzanne D. Turner, Lukas Kenner, Olaf Merkel
Journal: Leukemia (2020)

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Immunotherapy and Thyroid Dysfunction
Authors: Maria Laura Gregorio, Juan Sebastian Gomez, Surender Arora, Anil Ramachandran, Amol Takalkar
Journal: Clinical Nuclear Medicine (2020)

Abstract We report a case of a 66-year-old woman with small cell lung cancer (stage IIB, T2N1M0), who received immunotherapy with nivolumab monthly for 2 months and then presented with thyrotoxic symptoms associated with suppressed thyroid-stimulating hormone levels and elevated free thyroid hormone levels, although previous thyrotropin performed 1 month ago was normal. Thyroid uptake and scan demonstrated diffusely decreased uptake in both thyroid lobes. The 4-hour percentage uptake was 0.7%, and the 24-hour percentage uptake was 0.3%. This was followed by development of hypothyroidism within few weeks. Findings suggested drug-induced thyroiditis secondary to nivolumab therapy.
IgE‐mediated chlorhexidine allergy—Cross‐reactivity with other biguanide disinfectants
Authors: Nicole Mueller‐Wirth, Antonia Buenter, Lukas Jörg, Didier G. Ebo, Martin Glatz, Suran L. Fernando, David Spoerl, Arthur Helbling, Oliver Hausmann, Nisha Gupta, Werner J. Pichler
Journal: Allergy (2020)

Abstract Background Chlorhexidine (CHX) is a widely utilized disinfectant that can cause IgE‐mediated urticaria/anaphylaxis. The cross‐reactivity of patients with IgE‐mediated CHX allergy with other disinfectants, which share structural similarities with CHX like polyhexanide (polyhexamethylene biguanide; PHMB), alexidine (ALX), or octenidine (OCT), is unknown. Methods Forty‐four patients with anaphylaxis or urticaria upon CHX exposure and positive skin prick test (SPT) and/or positive CHX ImmunoCAP test (Phadia TFS, Uppsala, Sweden) were recruited. IgE to the biguanide and/or hexamethylene structure was investigated with PHMB ImmunoCAP (n = 32) and by basophil activation tests (BAT) with CHX and ALX (n = 37). Inhibition tests of CHX and PHMB ImmunoCAPs by CHX, ALX, PHMB, and OCT were performed. Results IgE reactivity to PHMB as surrogate marker for biguanide/hexamethylene reactivity was detected in 5/32 sera. Seven of 37 patients showed a positive BAT with ALX, but only under optimized conditions. Binding to CHX ImmunoCAP was inhibited by ALX in 1/32 sera, and binding to PHMB was blocked by ALX (1/5) and by OCT in another (1/5). In SPT, 9/10 patients were positive for CHX and 3 of them with ALX (only at highest concentration at 5 mg/mL). A further patient reacted primarily with OCT and showed IgE cross‐reactivity with CHX, ALX, and PHMB. Conclusion The IgE response to CHX seems polyclonal. The chloroguanide ending of CHX is the main epitope for the IgE and is suitable as screening assay to detect CHX reactivity. IgE‐reactivities with the biguanide or hexamethylene components of other disinfectants (ALX, PHMB) can be detected by SPT, PHMB ImmunoCAP, and ALX‐BAT in 15%‐33% of CHX‐allergic patients.
Safety and immunogenicity of the live attenuated intranasal pertussis vaccine BPZE1: a phase 1b, double-blind, randomised, placebo-controlled dose-escalation study
Authors: Maja Jahnmatz, Laura Richert, Nabil al-Tawil, Jann Storsaeter, Céline Colin, Claire Bauduin, Marcel Thalen, Ken Solovay, Keith Rubin, Nathalie Mielcarek, Rigmor Thorstensson, Camille Locht, Lena Dager, Nina Ekholm, Margareta Gustafsson, Åsa Linde, Cecilia Lång, Maria Nastase, Inga-Lill Reinholdsson, Erla Sigurdardottir, Anneli Wahlberg, Izabella Zarea, Teodora Aktas, Ingrid Andersson, Eva Hanson Pihlainen, Margaretha Ljungman, Maj Ringman, Teghesti Tecleab, Lena Wehlin, Florence Allais, Alex Assuied, Geneviève Chêne, Camille Gilbert, Delphine Jean, Fabien Le Marec, Laetitia Moinot, Philippe Reboud, Emilie Rousseau, Céline Roy, Christine Schwimmer, Ludivine Taïeb, Cédrick Wallet, Gabrielle Derocle, Sonia Gueguen, Claire Lévy-Marchal, Hélène Esperou, Anne-Sophie Debrie, Dominique Raze, Loïc Coutte, Alpha Diallo, Noémie Mercier
Journal: The Lancet Infectious Diseases (2020)
THU0225 Complementary medicine in rheumatic diseases
Authors: SK Chow, SS Yeap, E Goh, K Veerapen, K Lim
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Traditional medicine is widely practised in our country due to the ethnic diversity of this country. It is estimated to account for more than 50% of our local practice. This study is to assess the usage of traditional medicine among patients who have rheumatological problems. <h3>Objectives</h3> To determine the incidence of traditional medicine usage as a form of complementary therapy in a cohort of Malaysian rheumatology patients. <h3>Methods</h3> A prospective survey by using a standard questionnaire; the questionnaire was translated into 3 languages and was validated. The survey was conducted in December 2000 in the rheumatology clinic of the University of Malaya and Sunway Medical Centre. Patients who have rheumatological problem were interviewed after obtained verbal consent. Patients' demographic data, monthly income, educational status, diagnosis, duration of disease and the usage of food supplements and traditional medicine were surveyed. <h3>Results</h3> A total of 141 patients were interviewed. The mean age of the patients was 48.9 and the female: male ratio was 3:1. Racial breakdown was as follows: Malay = 23%, Chinese = 43%, Indian = 31% and others = 3%. 20% of the patients received primary education, 50% and 23% had education up to secondary and tertiary level respectively; however 7% had no formal education. 55% of the patients had monthly income of &lt; RM1000 (US$250). 12% had duration of disease of less than 1 year and 30% had more than 10 years' disease. 54% of the patients had Rheumatoid arthritis, 7% had osteoarthritis. 69% admitted consuming food supplements; vitamin C and B were the most common food supplement. 35% used traditional medicine and 69% used 2 or more type of traditional medicine at any one time for more than 2 months. 25% spent more than RM 100(US$25) for their traditional treatment. The most common reason for consuming traditional medicine as complementary medicine was the combination of both western and traditional treatment was thought to be more effective. There was no statistical significance between monthly income (P = 0.32) and duration of disease (p = 0.48) as to the usage of complementary therapy. <h3>Conclusion</h3> 35% of the 141 patients used traditional medicine as a form of complementary medicine; 69% used two or more types of traditional medicine for more than 2 months. 69% of them consumed food supplements and vitamin C and B was the most common food supplements.
Erratum to: “Macrophage p38 alpha promotes nutritional steatohepatitis through M1 polarization (J Hepatol 2019; 71(1):163-174)”
Authors: Xiang Zhang, Lina Fan, Jianfeng Wu, Hongzhi Xu, Wing Yan Leung, Kaili Fu, Jingtong Wu, Ken Liu, Kwan Man, Xiaoyong Yang, Jiahuai Han, Jianlin Ren, Jun Yu
Journal: Journal of Hepatology (2020)
Clinical application of an intelligent oropharyngeal swab robot: implication for the COVID-19 pandemic
Authors: Shao-Qiang Li, Wen-Liang Guo, Hao Liu, Tao Wang, Yuan-Yuan Zhou, Tao Yu, Chong-Yang Wang, Yong-Ming Yang, Nan-Shan Zhong, Nuo-Fu Zhang, Shi-Yue Li
Journal: European Respiratory Journal (2020)

Coronavirus disease 2019 (COVID-19), caused by infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is transmitted through respiratory droplets and close contact [1–4]. To diagnose COVID-19, oropharyngeal swab (OP swab) sampling is widely used for viral nucleic acid detection [3]. However, healthcare workers who perform OP swab are at high risk of infection due to aerosol from patients during the process of sampling. And the quality of manual OP swabs is inconsistent among different collectors, which may lead to misdiagnosis [5]. Use of a remote-controlled OP swab robot has the potential to avoid close contact between healthcare workers with patients, and thus reduce the risk of SARS-CoV-2 infection during sampling. Here, we invented a robotic sampling (RS) system and evaluated the safety and efficacy of this system on OP swab sampling during the period of pandemic. Clinical application of the safety and effectiveness of an intelligent oropharyngeal-swab robot, and its implication for the COVID-19 pandemic <https://bit.ly/2BUsV55>
Abstract 132: Endothelial Progenitor Cells Prevent Endothelial Barrier Injury by Cdc42-dependent Assembly of VE-cadherin
Authors: Hiroshi Ohkawra, Yidan D. Zhao, Asrar B. Malik
Journal: Circulation (2007)

We investigated the use of bone-marrow derived endothelial progenitor cells (EPCs) for the treatment of microvascular endothelial injury caused by inflammatory diseases. As activation of the monomeric RhoGTPase Cdc42 signals annealing of adherens junctions (AJs) in the endothelial barrier, we examined the possibility that EPCs could restore endothelial barrier dysfunction by promoting Cdc42 activation in endothelial cells (ECs). We observed that co-culture of EPCs with ECs prevented the decrease in transendothelial electrical resistance (TER), a measure of AJ assembly, and the decrease in VE-cadherin expression induced by thrombin (4 U/mL). EPCs also significantly reduced the formation of inter-endothelial gaps mediated by RhoA activation as well as myosin light chain phosphorylation in response to thrombin. We showed that EPCs induced activation of Cdc42 in ECs and increased TER within 15 min after the addition EPCs to ECs, indicating the enhancement of endothelial barrier function. Addition of EPCs after thrombin-induced disruption of AJs also promoted rapid recovery of TER compared to controls. Based on siRNA knockdown data, the endothelial barrier protective effect of EPCs was mediated by Cdc42 activation in ECs. Thus, EPC-mediated activation of Cdc42 in ECs decreases basal endothelial permeability and prevents endothelial hyper-permeability induced by the mediator thrombin. EPC/EC cross-talk is a critical mechanism regulating endothelial barrier function suggesting the value of EPCs in the treatment of microvascular injury associated with vascular inflammation.
Correlation of ThyroSeq Results with Surgical Histopathology in Cytologically Indeterminate Thyroid Nodules
Authors: Patrick D. Chin, Catherine Y. Zhu, Dipti P. Sajed, Gregory A. Fishbein, Michael W. Yeh, Angela M. Leung, Masha J. Livhits
Journal: Endocrine Pathology (2020)
The purinergic P2X7 receptor as a potential drug target to combat neuroinflammation in neurodegenerative diseases
Authors: Francesco Calzaferri, Cristina Ruiz‐Ruiz, Antonio M. G. de Diego, Ricardo de Pascual, Iago Méndez‐López, María F. Cano‐Abad, Victoria Maneu, Cristóbal de los Ríos, Luis Gandía, Antonio G. García
Journal: Medicinal Research Reviews (2020)

Abstract Neurodegenerative diseases (NDDs) represent a huge social burden, particularly in Alzheimer's disease (AD) in which all proposed treatments investigated in murine models have failed during clinical trials (CTs). Thus, novel therapeutic strategies remain crucial. Neuroinflammation is a common pathogenic feature of NDDs. As purinergic P2X7 receptors (P2X7Rs) are gatekeepers of inflammation, they could be developed as drug targets for NDDs. Herein, we review this challenging hypothesis and comment on the numerous studies that have investigated P2X7Rs, emphasizing their molecular structure and functions, as well as their role in inflammation. Then, we elaborate on research undertaken in the field of medicinal chemistry to determine potential P2X7R antagonists. Subsequently, we review the state of neuroinflammation and P2X7R expression in the brain, in animal models and patients suffering from AD, Parkinson's disease, amyotrophic lateral sclerosis, Huntington's disease, multiple sclerosis, and retinal degeneration. Next, we summarize the in vivo studies testing the hypothesis that by mitigating neuroinflammation, P2X7R blockers afford neuroprotection, increasing neuroplasticity and neuronal repair in animal models of NDDs. Finally, we reviewed previous and ongoing CTs investigating compounds directed toward targets associated with NDDs; we propose that CTs with P2X7R antagonists should be initiated. Despite the high expectations for putative P2X7Rs antagonists in various central nervous system diseases, the field is moving forward at a relatively slow pace, presumably due to the complexity of P2X7Rs. A better pharmacological approach to combat NDDs would be a dual strategy, combining P2X7R antagonism with drugs targeting a selective pathway in a given NDD.
Biocompatible Fe-Hematoporphyrin coordination nanoplatforms with efficient sonodynamic-chemo effects on deep-seated tumors
Authors: Hao Xu, Nuo Yu, Jiulong Zhang, Zhaojie Wang, Peng Geng, Mei Wen, Maoquan Li, Haijun Zhang, Zhigang Chen
Journal: Biomaterials (2020)