tbuckley/cabot-search huggingface dataset:
Increased serum QUIN/KYNA is a reliable biomarker of post-stroke cognitive decline
Authors: Adrien Cogo, Gabrielle Mangin, Benjamin Maïer, Jacques Callebert, Mikael Mazighi, Hughes Chabriat, Jean-Marie Launay, Gilles Huberfeld, Nathalie Kubis
Journal: Molecular Neurodegeneration (2021)

Abstract Background Strokes are becoming less severe due to increased numbers of intensive care units and improved treatments. As patients survive longer, post-stroke cognitive impairment (PSCI) has become a major health public issue. Diabetes has been identified as an independent predictive factor for PSCI. Here, we characterized a clinically relevant mouse model of PSCI, induced by permanent cerebral artery occlusion in diabetic mice, and investigated whether a reliable biomarker of PSCI may emerge from the kynurenine pathway which has been linked to inflammatory processes. Methods Cortical infarct was induced by permanent middle cerebral artery occlusion in male diabetic mice (streptozotocin IP). Six weeks later, cognitive assessment was performed using the Barnes maze, hippocampi long-term potentiation using microelectrodes array recordings, and neuronal death, white matter rarefaction and microglia/macrophages density assessed in both hemispheres using imunohistochemistry. Brain and serum metabolites of the kynurenin pathway were measured using HPLC and mass fragmentography. At last, these same metabolites were measured in the patient’s serum, at the acute phase of stroke, to determine if they could predict PSCI 3 months later. Results We found long-term spatial memory was impaired in diabetic mice 6 weeks after stroke induction. Synaptic plasticity was completely suppressed in both hippocampi along with increased neuronal death, white matter rarefaction in both striatum, and increased microglial/macrophage density in the ipsilateral hemisphere. Brain and serum quinolinic acid concentrations and quinolinic acid over kynurenic acid ratios were significantly increased compared to control, diabetic and non-diabetic ischemic mice, where PSCI was absent. These putative serum biomarkers were strongly correlated with degradation of long-term memory, neuronal death, microglia/macrophage infiltration and white matter rarefaction. Moreover, we identified these same serum biomarkers as potential predictors of PSCI in a pilot study of stroke patients. Conclusions we have established and characterized a new model of PSCI, functionally and structurally, and we have shown that the QUIN/KYNA ratio could be used as a surrogate biomarker of PSCI, which may now be tested in large prospective studies of stroke patients.
Abstract 11260: Circulating Heat Shock Protein 70 as a Prognosis Marker of Stemi
Authors: Thomas Bochaton, Alexandre Paccalet, Pierre Jeantet, Claire Crola Ad Silva, Claire Jossan, Camille Amaz, Delphine Baetz, Cyril Prieur, Nathalie Genot, Danka Tomasevic, Nathalie Dufay, Régine Cartier, Gilles Rioufol, Eric Bonnefoy-Cudraz, Nathan Mewton, Michel Ovize
Journal: Circulation (2019)

Introduction: Increased intracellular expression of the stress-inducible protein heat Shock Protein 70 (HSP70) improves the tolerance of cardiomyocytes to ischemia/reperfusion (I/R). Alternatively,...
The cost of trauma operating theatre inefficiency
Authors: W. Wei Ang, S. Sabharwal, R. Bhattacharya, H. Johannsson, C. Gupte
Journal: International Journal of Surgery (2016)

The National Health Service (NHS) is currently facing a financial crisis with a projected deficit of £2billion by the end of financial year 2015/16. As operating rooms (OR) are one of the costliest components in secondary care, improving theatre efficiency should be at the forefront of efforts to improve health service efficiency. The objectives of this study were to characterize the causes of trauma OR delays and to estimate the cost of this inefficiency. A 1-month prospective single-centre study in St. Mary's Hospital. Turnaround time (TT) was used as the surrogate parameter to measure theatre efficiency. Factors including patient age, ASA score and presence of surgical and anaesthetic consultant were evaluated to identify positive or negative associations with theatre delays. Inefficiency cost was calculated by multiplying the time wasted with staff capacity costs and opportunity costs, found to be £24.77/minute. The commonest causes for increased TT were delays in sending for patients (50%) and problems with patient transport to the OR (31%). 461 min of delay was observed in 12 days, equivalent to loss of £951.58/ theatre/day. Non-statistically significant trends were seen between length of delays and advancing patient age, ASA score and absence of either a senior clinician or an anaesthetic consultant. Interestingly, the trend was not as strong for absence of an anaesthetic consultant. This study found delays in operating TT to represent a sizable cost, with potential efficiency savings based on TT of £347,327/theatre/year. Further study of a larger sample is warranted to better evaluate the identified trends. © 2016 The Authors. Published by Elsevier Ltd on behalf of IJS Publishing Group Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
A Single Institution Comparison of Mitoxantrone, Etoposide and Cytarabine (MEC) Vs High-Dose Cytarabine and Mitoxantrone (Ara-C Couplets) for Treatment of Patients with Relapsed or Refractory Acute Myeloid Leukemia
Authors: Sonia Christian, Pritesh Patel, Aysenur Esen, Irum Khan, Karen Sweiss, Fares Ghanem, Christopher A. Sequeira, Ardaman Shergill, John G. Quigley
Journal: Blood (2017)
High‐Dose Steroid Dissolving Microneedle for Relieving Atopic Dermatitis
Authors: Mingyu Jang, Bo Mi Kang, Huisuk Yang, Jungyoon Ohn, Ohsang Kwon, Hyungil Jung
Journal: Advanced Healthcare Materials (2021)

Abstract Dissolving microneedles (DMN) supplemented with therapeutic molecules have been developed to enhance transdermal delivery efficiency of topically applied drugs in a minimally invasive manner. However, the dose of the drugs in DMN system is limited owing to the low solubility of drug. In fact, although triamcinolone acetonide (TA) is one of the most widely prescribed drugs for relieving atopic dermatitis (AD), its poor dissolving nature makes it difficult to design and fabricate DMN containing therapeutic dosage of TA. In this study, TA suspension is introduced to encapsulate therapeutic dosage of TA. Sonication and composition optimization of polymers is key to fabricate high dose TA–DMN to induce particle size reduction and dispersion stability of suspension, respectively. After confirming the physical performance of TA–DMN using the selected formulation in vitro, the anti‐inflammatory effects of TA–DMN are evaluated in vivo using a mouse model affected with skin inflammation to mimic AD in humans. Herein, high‐dose TA–DMN is presented as a candidate agent for relieving AD and, furthermore, for wide application in the treatment of skin inflammatory diseases in which high‐dose steroid drugs are required.
Abstract PS6-21: High expression of MicroRNA-223 indicates better prognosis in triple negative breast cancer
Authors: Li Chen, Xiuzhi Zhu, Ling Yao, Zonghua Wang
Journal: Cancer Research (2021)

Abstract Background: MicroRNAs (miRNAs) can influence many biological processes and also show promise as biomarkers for cancer. Few researches have focused on the expression of microRNA-223 (miR-223) and its precise role in breast cancer (BC). We aimed to examine the expression level of miR-223 and further explored the prognostic value in BC.Methods: Tissue microarray-based miRNA detection in situ hybridization with LNA probe was used to detect miR-223 expression in 450 BC tissue. Overall survival (OS) and disease-free survival (DFS) were compared between two groups using the Kaplan-Meier method and Cox regression model.Results: Better OS and DFS were observed in the high-miR-223 expression patients compared to those of low expression patients (P &amp;lt; 0.0001 and P = 0.017, respectively), especially in the triple-negative breast cancer (TNBC) subtype (P = 0.046and P &amp;lt; 0.001, respectively). Combined with the univariate and multivariate Cox regression analysis, TNM stage (p = 0.008), molecular subtype (p =0.049) and miR-223 (p &amp;lt; 0.001) were independently linked to OS and DFS. External validation was performed in METABRIC and TCGA database via online webtool and consistent with the data above.Conclusions: This study provided evidence that high-miR-223 expression at diagnosis was associated with better DFS and OS for BC, especially for the TNBC subtype. miR-223 is a valid and independent prognostic biomarker in BC. Table Univariate and multivariate survival analysis for disease-free survivalUnivariate MultivariateVariableHR95% CIP valueHR95% CIP valueAge0.594≤40 vs &amp;gt;601.3510.626-2.9140.44440-60 vs &amp;gt;600.9940.548-1.8030.984Menopausal statuspre vs post0.7370.487-1.1130.147DifferentiationII vs III0.7300.457-1.1640.186TNM stage0.0080.008II vs I1.4210.860-2.3460.1701.4850.887-2.4850.132III vs I2.7581.446-5.2590.0022.8581.469-5.5630.002Molecular subtype0.1940.049Luminal B vs Luminal A1.1060.580-2.1070.7600.8130.415-1.5930.546HER2+ vs Luminal A0.9860.497-1.9560.9670.7010.337-1.4580.342Triple-negative vs Luminal A1.6260.930-2.8430.0881.4930.849-2.6260.164MicroRNA-223low vs high3.9602.201-7.126&amp;lt;0.0013.7892.098-6.843&amp;lt;0.001Abbreviations: CI, confidence interval; HR, hazard ratio.The covariates in the Cox model were all categorical variables, and the adjusted p value and HR were derived from the model. Citation Format: Li Chen, Xiuzhi Zhu, Ling Yao, Zonghua Wang. High expression of MicroRNA-223 indicates better prognosis in triple negative breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS6-21.
Abstract 11574: Ventricular Arrhythmia Ablation Lesions in Children and Adolescents: Acute Magnetic Resonance Imaging With Outcome Correlation
Authors: Elena K Grant, Charles I Berul, Russell R Cross, Jeffrey P Moak, Karin S Hamann, Kendall J O'Brien, Michael Hansen, Peter Kellman, Kanishka Ratnayaka, Laura J Olivieri
Journal: Circulation (2015)

Introduction: Catheter ablation for arrhythmias is not always 100% effective when using current techniques. Failure of ablation may be secondary to inadequate lesion development. Peri-procedural visualization of ablation lesions may identify inadequate lesions or gaps to guide further ablation and reduce risk of arrhythmia recurrence. Methods: This pilot feasibility study assessed acute post-procedure ablation lesions by MRI, and correlated these findings with clinical outcomes. Six patients who underwent ventricular tachycardia ablation were transferred immediately post-ablation to a 1.5T MRI scanner for imaging. Late gadolinium enhancement (LGE) imaging was performed using a novel motion-corrected, phase sensitive inversion recovery sequence while free breathing. Immediate and short term arrhythmia recurrences were assessed. Results: Patient characteristics include median age 14.5 yrs (11 - 17 yrs), median weight 59 kg (43 - 81kg), normal cardiac anatomy (n = 4), anomalous coronary artery post repair (n = 1), and cardiac rhabdomyomas (n = 1). All patients underwent radiofrequency catheter ablation of ventricular arrhythmia with acute procedural success. LGE was identified at the reported ablation site in 5/6 patients, and not seen in 1 patient. The 5 patients with identifiable lesions were arrhythmia- and symptom-free at follow-up, ranging 1-6 months. The 1 patient in whom a lesion could not be identified had recurrence of frequent premature ventricular contractions within 2 hours post-procedure, confirmed on Holter monitoring 1 month later. Conclusions: Ventricular ablation lesion visibility by MRI in the acute post-procedure setting is feasible, and lesions identifiable with MRI may correlate with clinical outcomes. MRI identification of gaps or inadequate lesions may provide the unique temporal opportunity for additional ablation therapy to decrease arrhythmia recurrence.
Diet-dependent regulation of TGFβ impairs reparative innate immune responses after demyelination
Authors: Mar Bosch-Queralt, Ludovico Cantuti-Castelvetri, Alkmini Damkou, Martina Schifferer, Kai Schlepckow, Ioannis Alexopoulos, Dieter Lütjohann, Christian Klose, Lenka Vaculčiaková, Takahiro Masuda, Marco Prinz, Kathryn M. Monroe, Gilbert Di Paolo, Joseph W. Lewcock, Christian Haass, Mikael Simons
Journal: Nature Metabolism (2021)
Sudden Cardiac Arrest in Young Women
Authors: Orianne Weizman, Ardalan Sharifzadehgan, Wulfran Bougouin, Kumar Narayanan, Noémie Tence, Florence Dumas, Victor Waldmann, Lionel Lamhaut, Daniel Jost, Karim Wahbi, Olivier Varenne, Rodrigue Garcia, Nicole Karam, Alain Cariou, Xavier Jouven, Eloi Marijon, JM Agostinucci, V Algalarrondo, F Alla, C Alonso, W Amara, D Annane, C Antoine, P Aubry, E Azoulay, F Beganton, D Benhamou, C Billon, W Bougouin, J Boutet, C Bruel, P Bruneval, A Cariou, P Carli, E Casalino, C Cerf, A Chaib, B Cholley, Y Cohen, A Combes, JM Coulaud, M Crahes, D Da Silva, V Das, A Demoule, I Denjoy, N Deye, G Dhonneur, JL Diehl, S Dinanian, L Domanski, D Dreyfuss, D Duboc, JL Dubois-Rande, F Dumas, JP Empana, F Extramiana, M Fartoukh, F Fieux, M Gabbas, E Gandjbakhch, G Geri, B Guidet, F Halimi, P Henry, F Hidden Lucet, P Jabre, L Jacob, L Joseph, D Jost, X Jouven, N Karam, J Lacotte, F Lapostolle, K Lahlou-Laforet, L Lamhaut, A Lanceleur, O Langeron, T Lavergne, E Lecarpentier, A Leenhardt, N Lellouche, V Lemiale, F Lemoine, F Linval, T Loeb, B Ludes, A Maltret, N Mansencal, N Mansouri, E Marijon, J Marty, E Maury, V Maxime, B Megarbane, A Mekontso-Dessap, JP Mira, X Monnet, K Narayanan, N Ngoyi, MC Perier, O Piot, P Plaisance, I Plu, M Raux, F Revaux, JD Ricard, C Richard, B Riou, F Roussin, F Santoli, F Schortgen, A Sharifzadehgan, G Sideris, C Spaulding, JL Teboul, JF Timsit, P Tuppin, C Ursat, O Varenne, A Vieillard-Baron, S Voicu, K Wahbi, V Waldmann
Journal: Circulation (2021)
Granzyme A inhibition reduces inflammation and increases survival during abdominal sepsis
Authors: Marcela Garzón-Tituaña, José L Sierra-Monzón, Laura Comas, Llipsy Santiago, Tatiana Khaliulina-Ushakova, Iratxe Uranga-Murillo, Ariel Ramirez-Labrada, Elena Tapia, Elena Morte-Romea, Sonia Algarate, Ludovic Couty, Eric Camerer, Phillip I Bird, Cristina Seral, Pilar Luque, José R Paño-Pardo, Eva M Galvez, Julián Pardo, Maykel Arias
Journal: Theranostics (2021)

Aims: Peritonitis is one of the most common causes of sepsis, a serious syndrome characterized by a dysregulated systemic inflammatory response. Recent evidence suggests that Granzyme A (GzmA), a serine protease mainly expressed by NK and T cells, could act as a proinflammatory mediator and could play an important role in the pathogenesis of sepsis. This work aims to analyze the role and the therapeutic potential of GzmA in the pathogenesis of peritoneal sepsis. Methods: The level of extracellular GzmA as well as GzmA activity were analyzed in serum from healthy volunteers and patients with confirmed peritonitis and were correlated with the Sequential Organ Failure Assessment (SOFA) score. Peritonitis was induced in C57Bl/6 (WT) and GzmA-/- mice by cecal ligation and puncture (CLP). Mice were treated intraperitoneally with antibiotics alone or in combination serpinb6b, a specific GzmA inhibitor, for 5 days. Mouse survival was monitored during 14 days, levels of some proinflammatory cytokines were measured in serum and bacterial load and diversity was analyzed in blood and spleen at different times. Results: Clinically, elevated GzmA was observed in serum from patients with abdominal sepsis suggesting that GzmA plays an important role in this pathology. In the CLP model GzmA deficient mice, or WT mice treated with an extracellular GzmA inhibitor, showed increased survival, which correlated with a reduction in proinflammatory markers in both serum and peritoneal lavage fluid. GzmA deficiency did not influence bacterial load in blood and spleen and GzmA did not affect bacterial replication in macrophages in vitro, indicating that GzmA has no role in bacterial control. Analysis of GzmA in lymphoid cells following CLP showed that it was mainly expressed by NK cells. Mechanistically, we found that extracellular active GzmA acts as a proinflammatory mediator in macrophages by inducing the TLR4-dependent expression of IL-6 and TNFα. Conclusions: Our findings implicate GzmA as a key regulator of the inflammatory response during abdominal sepsis and provide solid evidences about its therapeutic potential for the treatment of this severe pathology.
First Month of COVID-19 Vaccine Safety Monitoring — United States, December 14, 2020–January 13, 2021
Authors: Julianne Gee, Paige Marquez, John Su, Geoffrey M. Calvert, Ruiling Liu, Tanya Myers, Narayan Nair, Stacey Martin, Thomas Clark, Lauri Markowitz, Nicole Lindsey, Bicheng Zhang, Charles Licata, Amelia Jazwa, Mark Sotir, Tom Shimabukuro
Journal: MMWR Morbidity and Mortality Weekly Report (2021)

death, life-threatening illness, hospitalization or prolongation of hospitalization, permanent disability, congenital anomaly, or birth defect.https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/cfrsearch.cfm?fr
Silencing of SARS‐CoV‐2 with modified siRNA‐peptide dendrimer formulation
Authors: Musa Khaitov, Alexandra Nikonova, Igor Shilovskiy, Ksenia Kozhikhova, Ilya Kofiadi, Lyudmila Vishnyakova, Alexander Nikolskii, Pia Gattinger, Valeria Kovchina, Ekaterina Barvinskaia, Kirill Yumashev, Valeriy Smirnov, Artem Maerle, Ivan Kozlov, Artem Shatilov, Anastasiia Timofeeva, Sergey Andreev, Olesya Koloskova, Nadezhda Kuznetsova, Daria Vasina, Maria Nikiforova, Sergei Rybalkin, Ilya Sergeev, Dmitriy Trofimov, Alexander Martynov, Igor Berzin, Vladimir Gushchin, Aleksey Kovalchuk, Sergei Borisevich, Rudolf Valenta, Rakhim Khaitov, Veronica Skvortsova
Journal: Allergy (2021)

First vaccines for prevention of Coronavirus disease 2019 (COVID-19) are becoming available but there is a huge and unmet need for specific forms of treatment. In this study we aimed to evaluate the anti-SARS-CoV-2 effect of siRNA both in vitro and in vivo.To identify the most effective molecule out of a panel of 15 in silico designed siRNAs, an in vitro screening system based on vectors expressing SARS-CoV-2 genes fused with the firefly luciferase reporter gene and SARS-CoV-2-infected cells was used. The most potent siRNA, siR-7, was modified by Locked nucleic acids (LNAs) to obtain siR-7-EM with increased stability and was formulated with the peptide dendrimer KK-46 for enhancing cellular uptake to allow topical application by inhalation of the final formulation - siR-7-EM/KK-46. Using the Syrian Hamster model for SARS-CoV-2 infection the antiviral capacity of siR-7-EM/KK-46 complex was evaluated.We identified the siRNA, siR-7, targeting SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) as the most efficient siRNA inhibiting viral replication in vitro. Moreover, we showed that LNA-modification and complexation with the designed peptide dendrimer enhanced the antiviral capacity of siR-7 in vitro. We demonstrated significant reduction of virus titer and lung inflammation in animals exposed to inhalation of siR-7-EM/KK-46 in vivo.Thus, we developed a therapeutic strategy for COVID-19 based on inhalation of a modified siRNA-peptide dendrimer formulation. The developed medication is intended for inhalation treatment of COVID-19 patients.
Krishna Korlipara: founder of the National Association of GP Cooperatives and longest serving elected member of the GMC
Authors: Rebecca Wallersteiner
Journal: BMJ (2021)

Krishna Korlipara was born in Denduluru, a rural agricultural village in Andhra Pradesh state, south India. Korlipara grew up in a large family. His father was Laxminarayana Korlipara, his mother was Krishnaveni, nee Kodali, and he had three sisters and one brother. He studied medicine at Kasturba Medical College, Karnatak University of Mangalore.

In 1964, Korlipara travelled to London from India for the first time and boldly walked into the office of the medical director at Guy’s Hospital and asked him for a job. It worked, and he was offered a job at the Royal Free Hospital under Sheila Sherlock. After feeling homesick for his wife and family, however, he sailed back to India after a month and stayed for six months before moving back to England and securing a job as a senior house officer in Bristol. He later worked in Huddersfield, Sheffield, and Nottinghamshire, before being appointed registrar in general medicine at Bolton General Hospital in 1969. He had accepted a job at the Mount Sinai Hospital, New York, but was persuaded at the last minute to stay in the UK by his mentor, consultant physician Guy Coleson. In 1973 he decided to switch to general practice and became a partner in a practice in Horwich, Lancashire, where he remained serving his community for 40 years. The practice moved into Pike View Medical Centre, the first purpose built medical centre built in …
Base-resolution models of transcription-factor binding reveal soft motif syntax
Authors: Žiga Avsec, Melanie Weilert, Avanti Shrikumar, Sabrina Krueger, Amr Alexandari, Khyati Dalal, Robin Fropf, Charles McAnany, Julien Gagneur, Anshul Kundaje, Julia Zeitlinger
Journal: Nature Genetics (2021)
Removing One Barrier to Opioid Use Disorder Treatment
Authors: Melissa B. Weimer, Sarah E. Wakeman, Richard Saitz
Journal: JAMA (2021)

This Viewpoint discusses policy reforms necessary to advance medical management of opioid use disorder in the wake of retraction by the Biden adminstration of proposed federal Practice Guidelines for the Administration of Buprenorphine for Treating Opioid Use Disorder.
Doctors reject claim that US “no longer has a prescription opioid driven epidemic”
Authors: Elisabeth Mahase
Journal: BMJ (2021)

A group of US doctors that advocates for more cautious opioid prescribing has rebutted the claim from the American Medical Association (AMA) that the country “no longer has a prescription opioid driven epidemic” and condemned its call to remove “restrictions on controlled substances.”

Physicians for Responsible Opioid Prescribing (PROP), a group of 17 doctors, researchers, and patient advocates, wrote to Susan Bailey, president of the AMA, on 16 February expressing disappointment that the association seemed to “fight key elements of the US Centers for Disease Control and Prevention’s [CDC’s] effort to address the scourge of overprescribing of opioids.”1

The group referred to comments made by the AMA in …