tbuckley/cabot-search huggingface dataset:
Continuous vs Routine Electroencephalogram in Critically Ill Adults With Altered Consciousness and No Recent Seizure
Authors: Andrea O. Rossetti, Kaspar Schindler, Raoul Sutter, Stephan Rüegg, Frédéric Zubler, Jan Novy, Mauro Oddo, Loane Warpelin-Decrausaz, Vincent Alvarez
Journal: JAMA Neurology (2020)

In critically ill patients with altered consciousness, continuous electroencephalogram (cEEG) improves seizure detection, but is resource-consuming compared with routine EEG (rEEG). It is also uncertain whether cEEG has an effect on outcome.To assess whether cEEG is associated with reduced mortality compared with rEEG.The pragmatic multicenter Continuous EEG Randomized Trial in Adults (CERTA) was conducted between 2017 and 2018, with follow-up of 6 months. Outcomes were assessed by interviewers blinded to interventions.The study took place at 4 tertiary hospitals in Switzerland (intensive and intermediate care units). Depending on investigators' availability, we pragmatically recruited critically ill adults having Glasgow Coma Scale scores of 11 or less or Full Outline of Responsiveness score of 12 or less, without recent seizures or status epilepticus. They had cerebral (eg, brain trauma, cardiac arrest, hemorrhage, or stroke) or noncerebral conditions (eg, toxic-metabolic or unknown etiology), and EEG was requested as part of standard care. An independent physician provided emergency informed consent.Participants were randomized 1:1 to cEEG for 30 to 48 hours vs 2 rEEGs (20 minutes each), interpreted according to standardized American Clinical Neurophysiology Society guidelines.Mortality at 6 months represented the primary outcome. Secondary outcomes included interictal and ictal features detection and change in therapy.We analyzed 364 patients (33% women; mean [SD] age, 63 [15] years). At 6 months, mortality was 89 of 182 in those with cEEG and 88 of 182 in those with rEEG (adjusted relative risk [RR], 1.02; 95% CI, 0.83-1.26; P = .85). Exploratory comparisons within subgroups stratifying patients according to age, premorbid disability, comorbidities on admission, deeper consciousness reduction, and underlying diagnoses revealed no significant effect modification. Continuous EEG was associated with increased detection of interictal features and seizures (adjusted RR, 1.26; 95% CI, 1.08-1.15; P = .004 and 3.37; 95% CI, 1.63-7.00; P = .001, respectively) and more frequent adaptations in antiseizure therapy (RR, 1.84; 95% CI, 1.12-3.00; P = .01).This pragmatic trial shows that in critically ill adults with impaired consciousness and no recent seizure, cEEG leads to increased seizure detection and modification of antiseizure treatment but is not related to improved outcome compared with repeated rEEG. Pending larger studies, rEEG may represent a valid alternative to cEEG in centers with limited resources.ClinicalTrials.gov Identifier: NCT03129438.
High-flow nasal cannula oxygen therapy to treat patients with hypoxemic acute respiratory failure consequent to SARS-CoV-2 infection
Authors: Andrea Vianello, Giovanna Arcaro, Beatrice Molena, Cristian Turato, Andi Sukthi, Gabriella Guarnieri, Francesca Lugato, Gianenrico Senna, Paolo Navalesi
Journal: Thorax (2020)

This observational study aims to assess the outcome and safety of O 2 -therapy by high-flow nasal cannula (HFNC) in 28 consecutive patients with severe hypoxemic acute respiratory failure (hARF) consequent to SARS-CoV-2 infection, unresponsive to conventional O 2 -therapy. Nineteen patients had a positive response. Nine patients required escalation of treatment to non-invasive ventilation (five subsequently intubated). None of the staff had a positive swab testing during the study period and the following 14 days. Severity of hypoxemia and C reactive protein level were correlated with HFNC failure. These data suggest HFNC to be a safe treatment for less severe patients with SARS-CoV-2 hARF and efficacy will need to be assessed as part of a clinical trial.
Smart Scaffolds: z‐Wire: A Microscaffold That Supports Guided Tissue Assembly and Intramyocardium Delivery for Cardiac Repair (Adv. Healthcare Mater. 14/2020)
Authors: Luis Eduardo Portillo‐Esquivel, Vibudha Nanduri, Feng Zhang, Wenbin Liang, Boyang Zhang
Journal: Advanced Healthcare Materials (2020)

In article number 2000358 by Boyang Zhang and co-workers, a biodegradable z-wire scaffold supports gel-free production of functional cardiac tissues in a 384-well plate format. Individual z-wire tissues can be aligned and assembled under magnetic guidance. The z-wire tissues can be delivered via intramyocardium injection while preserving anisotropic muscle alignment. This modular, smart-scaffold tissue engineering approach can expand opportunity in functional tissue delivery and assembly.
COVID‐19 in severe asthmatic patients during ongoing treatment with biologicals targeting type 2 inflammation: Results from a multicenter Italian survey
Authors: Andrea Matucci, Marco Caminati, Emanuele Vivarelli, Andrea Vianello, Claudio Micheletto, Francesco Menzella, Ernesto Crisafulli, Giovanni Passalacqua, Diego Bagnasco, Carlo Lombardi, Paola Parronchi, Mariaangiola A. Crivellaro, Fulvia Chieco‐Bianchi, Maria Rita Marchi, Gabriella Guarnieri, Lorenzo Cosmi, Oliviero Rossi, Fabio Almerigogna, Gianenrico Senna, Alessandra Vultaggio
Journal: Allergy (2020)

Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Flubendazole elicits anti-cancer effects via targeting EVA1A-modulated autophagy and apoptosis in Triple-negative Breast Cancer
Authors: Yongqi Zhen, Rongyan Zhao, Minjuan Wang, Xing Jiang, Feng Gao, Leilei Fu, Lan Zhang, Xian-Li Zhou
Journal: Theranostics (2020)

Background: Triple-negative breast cancer (TNBC) is one of the most prevalent neoplastic diseases worldwide, but efficacious treatments for this pathological condition are still challenging. The lack of an effective targeted therapy also leads to a poor prognosis for patients affected by TNBC. In the present study, we repurposed the distinctive inhibitory effects of flubendazole, a traditional anthelmintic drug, towards the putative modulation of proliferation and migration of TNBC in vitro and in vivo. Methods: According to a series of experimental approaches, including immunofluorescence (IF), immunoblotting (IB), siRNA and GFP-mRFP-LC3 plasmid transfection, respectively, we have found that flubendazole is capable of inducing autophagic cell death and apoptosis, thus exerting some anti-proliferative and anti-migration activity in TNBC cells. The therapeutic effects of flubendazole were evaluated by xenograft mouse models, followed by immunohistochemistry (IHC), IF and IB. Changes in the gene expression profiles of flubendazole-treated TNBC cells were analyzed by RNA sequencing (RNA-seq) and validated by IB. The potential binding mode of flubendazole and EVA1A was predicted by molecular docking and demonstrated by site-directed mutagenesis. Results: We have presently found that flubendazole exhibits a considerable anti-proliferative activity in vitro and in vivo. Mechanistically, the induction of autophagic cell death appears to be pivotal for flubendazole-mediated growth inhibition of TNBC cells, whereas blocking autophagy was able to improve the survival rate and migration ability of flubendazole-treated TNBC cells. Specifically, RNA-seq analysis showed that flubendazole treatment could promote the up-regulation of EVA1A. Flubendazole may regulate autophagy and apoptosis by targeting EVA1A, thus affecting the mechanisms of TNBC proliferation and migration. Furthermore, Thr113 may be the key amino acid residues for the binding of flubendazole to EVA1A. Conclusion: Our results provide novel insights towards the putative anti-cancer efficacy of flubendazole. Furthermore, here we show that flubendazole could serve as a potential therapeutic drug in TNBC. Altogether, this study highlights the possibility of this repurposed autophagic inducer for future cancer treatments.
Missing in Action: African Ancestry Brain Research
Authors: Daniel R. Weinberger, Kafui Dzirasa, Lesia L. Crumpton-Young
Journal: Neuron (2020)

Individuals of African ancestry have been starkly underrepresented in the pursuit of personalized medicine for brain illnesses. The African Ancestry Neuroscience Research Initiative will seek to generate much-needed brain gene and protein expression profiles for people of African ancestry.
COVID-19 Response in Lebanon
Authors: Petra Khoury, Eid Azar, Eveline Hitti
Journal: JAMA (2020)

OnFebruary21,2020,thefirstcaseofcoronavirusdisease 2019 (COVID-19) was identified in Lebanon.This occurred amid a backdrop of political and economic turmoil that began in October 2019, when a banking crisis and a civil uprising led to a change in political leadership and pushed the country into an economic crisis.On January 31, approximately 2 weeks after cases started to emerge outside of China,thenewlyappointedgovernmentinLebanonestablished a National Committee for COVID-19 (NCC) to oversee the COVID-19 national preparedness and response.Lebanon had specific challenges preparing for the emerging pandemic: in addition to economic and political unrest, the country is densely populated, with 6.9 million residents-87.2% of whom live in urban areasincluding 2 million displaced persons and 500 000 migrant workers, all within 10 452 km 2 (approximately the size of the state of Connecticut or Kosovo).Households are largely multigenerational, averaging 5 persons per household.The health care sector is fragmented with hospitals of varying capabilities, 84% of which are private and mainly concentrated in large cities.Furthermore, 80% of the health care budget is spent on acute care in private hospitals, leaving the public health systems underresourced.In addition, Lebanon relies heavily on foreign supply chains and has no local manufacturing capability to produce essential COVID-19 supplies, including N95 masks and ventilators.On February 21, with the confirmation of the first case of COVID-19, the government initiated a "whole government response" through a public-private partnership, with the NCC directing the strategy and the Ministry of Health (MoH)-alongside other ministriesoverseeing the implementation.Given the significant resource challenges in the country, the approach was centered around early aggressive containment to allow for building capacity to respond to COVID-19 cases.On February 22, Lebanon shut down public transport and banned flights to countries that had experienced exponential growth patterns of COVID-19, including Iran, Italy, China, and South Korea.Six days after the first case (at 3 cases), day care centers, schools, and universities were closed.A week later (March 6; 22 cases), nightclubs, pubs, gyms, and theaters were closed.Soon after (March 11; 64 cases), all malls, restaurants, tourist sites, and public gardens also were closed.By mid-March, when the infection count reached 99 cases, the government declared "public mobilization," issued stay-at-home orders, and closed the borders, with full lockdown of nonessential services.After these measures, the average growth factor per week (defined as the number of cases on a given day compared with the prior day, averaged over 1 week) declined from a peak of 4.6 (week 2, February 28-March 5) to less than 1 (week 6, March 27-April 2).During this time, hos-
Inhibition of Oxphos with Iacs-010759 Depletes AML Leukemia Initiating Cells (LIC) in Vitro and Improves Survival in Pre-Clinical AML Models
Authors: Natalia Baran, Lina Han, Shannon Renee Sweeney, Alessia Lodi, Shelley Herbrich, Antonio Cavazos, Helen Ma, Ningping Feng, Hsiang-Chun Chen, Marcin Kaminski, Kenneth Dunner, Guilin Tang, Gheath Alatrash, Jennifer Molina, Monica L. Guzman, Jing Ning, Stefano Tiziani, Joseph R Marszalek, Marina Konopleva
Journal: Blood (2017)
Cardiovascular changes during peanut-induced allergic reactions in human subjects
Authors: Monica Ruiz-Garcia, Joan Bartra, Olaya Alvarez, Ashna Lakhani, Shalinee Patel, Alistair Tang, Marcus Sim, Mohamed H Shamji, Isabel Skypala, E N Clare Mills, Alexander R Lyon, Carl Hayward, Stephen R Durham, Paul J Turner, Robert J Boyle
Journal: Journal of Allergy and Clinical Immunology (2020)

Food allergy is the most common cause of anaphylaxis. Changes in posture during acute reactions can trigger fatal outcomes, but the impact of allergic reactions on the cardiovascular system in nonfatal reactions remains poorly understood.
Screening for <i>in-vivo</i> regional contractile defaults to predict the delayed Doxorubicin Cardiotoxicity in Juvenile Rat
Authors: Nourdine Chakouri, Charlotte Farah, Stefan Matecki, Pascal Amedro, Marie Vincenti, Laure Saumet, Laurence Vergely, Nicolas Sirvent, Alain Lacampagne, Olivier Cazorla
Journal: Theranostics (2020)

Anthracyclines are key chemotherapeutic agents used in various adult and pediatric cancers, however, their clinical use is limited due to possible congestive heart failure (HF) caused by acute and irreversible cardiotoxicity. Currently, there is no method to predict the future development of the HF in these patients. In order to identify early biomarkers to predict anthracycline cardiotoxicity in long-term survivors of childhood cancer, this longitudinal study aimed to analyze early and late in-vivo regional myocardial anthracycline-induced cardiotoxicity, related to in-vitro cardiac myocytes dysfunction, in a juvenile rat model. Methods: Young male Wistar rats (4 weeks-old) were treated with different cumulative doses of doxorubicin (7.5, 10 or 12.5 mg/kg) or NaCl (0.9%) once a week for 6 weeks by intravenous injection. Cardiac function was evaluated in-vivo by conventional (left ventricular ejection fraction, LVEF) and regional two-dimensional (2D) speckle tracking echocardiography over the 4 months after the last injection. The animals were assigned to preserved (pEF) or reduced EF (rEF) groups at the end of the protocol and were compared to controls. Results: We observed a preferential contractile dysfunction of the base of the heart, further altered in the posterior segment, even in pEF group. The first regional alterations appeared 1 month after chemotherapy. Functional investigation of cardiomyocytes isolated from the LV base 1 month after doxorubicin treatment showed that early in-vivo contractile alterations were associated with both decreased myofilament Ca2+ sensitivity and length-dependent activation. Changes in post-translational modifications (phosphorylation; S-glutathionylation) and protein degradation of the cardiac myosin binding protein-C may contribute to these alterations. Conclusion: Our data suggest that screening of the contractile defaults of the base of the heart by regional 2D strain echocardiography is useful to detect subclinical myocardial dysfunction prior to the development of delayed anthracycline-induced cardiomyopathy in pediatric onco-cardiology.
Abstract 12640: Predictors of Delirium After Cardiac Surgery
Authors: Maria C Escarain, Alejandro Cicolini, Maria A Barbieri, Maria F Renedo, Luis H Varela Falcon, Federico I Zeppa, Juan P Ochoa, Roberto R Favaloro
Journal: Circulation (2013)

Objective: To identify predictors of delirium after cardiac surgery and its associated postoperative complications. Methods: Retrospective study including 542 consecutive patients (p) undergoing ca...
N1-Methylnicotinamide: An Anti-Ovarian Aging Hormetin?
Authors: Hamid Reza Nejabati, Kathrin Schmeisser, Vahideh Shahnazi, Deniz Samimifar, Yousef Faridvand, Zahra Bahrami-Asl, Nazila Fathi-Maroufi, Saba Nikanfar, Mohammad Nouri
Journal: Ageing Research Reviews (2020)
Association Between Switching to a High-Deductible Health Plan and Major Cardiovascular Outcomes
Authors: J. Frank Wharam, Jamie Wallace, Fang Zhang, Xin Xu, Christine Y. Lu, Adrian Hernandez, Dennis Ross-Degnan, Joseph P. Newhouse
Journal: JAMA Network Open (2020)

<h3>Importance</h3> Most people with commercial health insurance in the US have high-deductible plans, but the association of such plans with major health outcomes is unknown. <h3>Objective</h3> To describe the association between enrollment in high-deductible health plans and the risk of major adverse cardiovascular outcomes. <h3>Design, Setting, and Participants</h3> This cohort study examined matched groups before and after an insurance design change. Data were from a large national commercial (and Medicare Advantage) health insurance claims data set that included members enrolled between January 1, 2003, and December 31, 2014. The study group included 156 962 individuals with risk factors for cardiovascular disease who were continuously enrolled in low-deductible (≤$500) health plans during a baseline year followed by up to 4 years in high-deductible (≥$1000) plans with typical value-based features after an employer-mandated switch. The matched control group included 1 467 758 individuals with the same risk factors who were contemporaneously enrolled in low-deductible plans. Data were analyzed from December 2017 to March 2020. <h3>Exposures</h3> Employer-mandated transition to a high-deductible health plan. <h3>Main Outcomes and Measures</h3> Time to first major adverse cardiovascular event defined as myocardial infarction or stroke. <h3>Results</h3> The study group included 156 962 individuals and the control group included 1 467 758 individuals; the mean age of members was 53 years (SD: high-deductible group, 6.7 years; control group, 6.9 years), 47% were female, and approximately 48% lived in low-income neighborhoods. First major adverse cardiovascular events among high-deductible health plan members did not differ relative to controls at follow-up vs baseline (adjusted hazard ratio, 1.00; 95% CI, 0.89-1.13). Findings were similar among subgroups with diabetes (adjusted hazard ratio, 0.93; 95% CI, 0.75-1.16) and with other cardiovascular risk factors (adjusted hazard ratio, 0.93; 95% CI, 0.81-1.07). <h3>Conclusions and Relevance</h3> Mandated enrollment in high-deductible health plans with typical value-based features was not associated with increased risk of major adverse cardiovascular events.
The Urinary Tract Microbiome in Older Women Exhibits Host Genetic and Environmental Influences
Authors: A.S. Adebayo, G. Ackermann, R.C.E. Bowyer, P.M. Wells, G. Humphreys, R. Knight, T.D. Spector, C.J. Steves
Journal: Cell Host & Microbe (2020)

The urinary microbiome is a relatively unexplored niche that varies with gender. Urinary microbes, especially in aging populations, are associated with morbidity. We present a large-scale study exploring factors defining urinary microbiome composition in community-dwelling older adult women without clinically active infection. Using 1,600 twins, we estimate the contribution of genetic and environmental factors to microbiome variation. The urinary microbiome is distinct from nearby sites and unrelated to stool microbiome with more Actinobacteria, Fusobacteria and Proteobacteria, but fewer Bacteroidetes, Firmicutes and Verrumicrobia. A quarter of variants had heritability estimates greater than 10% with most heritable microbes having potential clinical relevance, including Escherichia-Shigella linked to urinary tract infections. Age, menopausal status, prior UTI, and host genetics were top factors defining the urobiome with increased microbial diversity tending to associate with older age. These findings highlight the distinct composition of the urinary microbiome and significant contributions of host genetics.
FRI0169 Cyclosporin a versus Ýnterferon alfa in treatment of severe ocular involvement of behÇet’s disease
Authors: A Dýnc, S Pay, Z Bayraktar, H Erdem, M Turan
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Sight-threatening uveitis is a well-known complication of Behçet's Disease in which recurrent oral and genital aphthous ulcerations, arthritis, neurologic, and vascular involvement also frequently accompanied. <h3>Objectives</h3> In this study we compared the clinical efficacy of cyclosporin A (Cyc-A) and interferon-alfa (INF-alfa) in our patients with severe posterior uveitis. <h3>Methods</h3> All patients were classified and followed by means of fundus fluoressein angiography. At baseline, Cyc-A and INF-alfa were given in a dose of 5 mg/kg/day and 4,5 million U three times a week, respectively. In case of an attack, a prednison treatment course was added those monotherapy regimen. Twenty-one patients were included in the study. Eight and eleven patients were started on Cyc-A and INF-alfa regimens, respectively. Here, the results at the 3- and 6-month duration were presented. <h3>Results</h3> Two of 8 patients treated with Cyc-A were stopped to continue due to inefficacy and switched on INF-alpha therapy. In the same group one patient had gingival hyperplasia, which partially responded to dose tapering, however another patient with azotemia and hypertension had to be changed to other treatment group. Except one, all patients on INF-alpha regimen completed the study with adequate regression of inflammatory activity. In that patient depression unresponsive to drugs leaded to stop INF-alpha at the end of 6 months. <h3>Conclusion</h3> Although it is difficult to make a clear conclusion about the comperative efficacy of INF-alpha and Cyc-A due to small population and short follow-up. But it seems that INF-alfa more tolerable than Cyc-A in the treatment of Behçet' Disease with severe ocular involvement.
Dietary cholesterol drives fatty liver-associated liver cancer by modulating gut microbiota and metabolites
Authors: Xiang Zhang, Olabisi Oluwabukola Coker, Eagle SH Chu, Kaili Fu, Harry C H Lau, Yi-Xiang Wang, Anthony W H Chan, Hong Wei, Xiaoyong Yang, Joseph J Y Sung, Jun Yu
Journal: Gut (2020)

Objective Non-alcoholic fatty liver disease (NAFLD)-associated hepatocellular carcinoma (HCC) is an increasing healthcare burden worldwide. We examined the role of dietary cholesterol in driving NAFLD–HCC through modulating gut microbiota and its metabolites. Design High-fat/high-cholesterol (HFHC), high-fat/low-cholesterol or normal chow diet was fed to C57BL/6 male littermates for 14 months. Cholesterol-lowering drug atorvastatin was administered to HFHC-fed mice. Germ-free mice were transplanted with stools from mice fed different diets to determine the direct role of cholesterol modulated-microbiota in NAFLD–HCC. Gut microbiota was analysed by 16S rRNA sequencing and serum metabolites by liquid chromatography–mass spectrometry (LC–MS) metabolomic analysis. Faecal microbial compositions were examined in 59 hypercholesterolemia patients and 39 healthy controls. Results High dietary cholesterol led to the sequential progression of steatosis, steatohepatitis, fibrosis and eventually HCC in mice, concomitant with insulin resistance. Cholesterol-induced NAFLD–HCC formation was associated with gut microbiota dysbiosis. The microbiota composition clustered distinctly along stages of steatosis, steatohepatitis and HCC. Mucispirillum, Desulfovibrio, Anaerotruncus and Desulfovibrionaceae increased sequentially; while Bifidobacterium and Bacteroides were depleted in HFHC-fed mice, which was corroborated in human hypercholesteremia patients. Dietary cholesterol induced gut bacterial metabolites alteration including increased taurocholic acid and decreased 3-indolepropionic acid. Germ-free mice gavaged with stools from mice fed HFHC manifested hepatic lipid accumulation, inflammation and cell proliferation. Moreover, atorvastatin restored cholesterol-induced gut microbiota dysbiosis and completely prevented NAFLD–HCC development. Conclusions Dietary cholesterol drives NAFLD–HCC formation by inducing alteration of gut microbiota and metabolites in mice. Cholesterol inhibitory therapy and gut microbiota manipulation may be effective strategies for NAFLD–HCC prevention.