tbuckley/cabot-search huggingface dataset:
Azacarbazole n-3 and n-6 polyunsaturated fatty acids ethyl esters nanoemulsion with enhanced efficacy against Plasmodium falciparum
Authors: Anna Jaromin, Silvia Parapini, Nicoletta Basilico, Magdalena Zaremba-Czogalla, Agnieszka Lewińska, Agnieszka Zagórska, Maria Walczak, Bożena Tyliszczak, Aleksandra Grzeszczak, Marcin Łukaszewicz, Łukasz Kaczmarek, Jerzy Gubernator
Journal: Bioactive Materials (2020)

Alternative therapies are necessary for the treatment of malaria due to emerging drug resistance. However, many promising antimalarial compounds have poor water solubility and suffer from the lack of suitable delivery systems, which seriously limits their activity. To address this problem, we synthesized a series of azacarbazoles that were evaluated for antimalarial activity against D10 (chloroquine-sensitive) and W2 (chloroquine-resistant) strains of P. falciparum. The most active compound, 9H-3-azacarbazole (3), was encapsulated in a novel o/w nanoemulsion consisting of ethyl esters of polyunsaturated fatty acids n-3 and n-6 obtained from flax oil as the oil phase, Smix (Tween 80 and Transcutol HP) and water. This formulation was further analyzed using transmission electron microscopy, dynamic light scattering and in vitro and in vivo studies. It was shown that droplets of the 3-loaded nanosystem were spherical, with satisfactory stability, without cytotoxicity towards fibroblasts and intestinal cell lines at concentrations corresponding to twice the IC50 for P. falciparum. Moreover, the nanoemulsion with this type of oil phase was internalized by Caco-2 cells. Additionally, pharmacokinetics demonstrated rapid absorption of compound 3 (tmax = 5.0 min) after intragastric administration of 3-encapsulated nanoemulsion at a dose of 0.02 mg/kg in mice, with penetration of compound 3 to deep compartments. The 3-encapsulated nanoemulsion was found to be 2.8 and 4.2 times more effective in inhibiting the D10 and W2 strains of the parasite, respectively, compared to non-encapsulated 3. Our findings support a role for novel o/w nanoemulsions as delivery vehicles for antimalarial drugs.
TCT CONNECT-153 Double-Kissing Culotte Technique for Coronary Bifurcation Stenting: Technical Evaluation and Comparison With Conventional Double-Stenting Techniques
Authors: Gabor Toth, Viktor Sasi, Danilo Franco, Luigi Di Serafino, Anton Prassl, Jaryl Ng, Gyula Szanto, Gernot Plank, Hui Ying Ang, William Wijns, Emanuele Barbato
Journal: Journal of the American College of Cardiology (2020)
Abstract 2223: Carotid Intima Media Thickness Progression is Modest in Statin-Treated Familial Hypercholesterolemia Patients - Results from a Patient Level Meta-Analysis of 1257 Patients
Authors: Menno Vergeer, Rong Zhou, Raphael Duivenvoorden, Joerg Koglin, Yale B Mitchel, Roeland Huijgen, Aditi Sapre, Michiel L Bots, Richard C Pasternak, Claude Gagné, A D Marais, Christie M Ballantyne, Jonathan L Isaacsohn, Anton F Stalenhoef, John J Kastelein
Journal: Circulation (2008)

In the past, patients with heterozygous familial hypercholesterolemia (HeFH) were believed to be an ideal population to study changes in carotid intima media thickness (cIMT) based on their aggressive lipid disorder and high incidence of atherosclerotic events. However, following publication of recent cIMT trials in this population, the feasibility of demonstrating a reduction of cIMT progression in statin-treated HeFH patients has come under scrutiny. To inform future study designs, we evaluated cIMT progression and baseline predictors of cIMT progression (change in mean cIMT for all segments and common carotid artery (CCA) cIMT over 1 and 2 years), in merged data of 1257 patients from the statin arms of the ASAP, RADIANCE 1, CAPTIVATE and ENHANCE studies and performed backward regression analyses with prespecified co-variates. Based on this analysis, bootstrap analyses were performed to estimate cIMT progression for various hypothetical in- and exclusion criteria. For all studies combined, 2-year mean cIMT progression was 0.0102 ± 0.1348 mm. Positive predictors of this progression were prior use of high dose statins and use of other lipid-modifying therapy. Positive predictors of 1-year mean cIMT progression and 1 &amp; 2 year CCA cIMT progression were age, history of hypertension, Framingham risk score, female gender, high dose statin use and history of CAD; negative predictors were screening LDL-C and ApoA-I. In simulations, HeFH patients previously taking statin and over 50 years of age had an estimated 2-year mean cIMT progression of 0.0216 ± 0.155 mm (based on n = 380). Two year progression for patients with a history of CAD or a Framingham risk score ≥ 10 would be estimated at 0.0197 ± 0.158 mm (based on n = 334). This study shows that cIMT progression in a contemporary HeFH patient population is substantially lower than anticipated, limiting the usefulness of cIMT studies to test new therapies in this population. While focus on individual subgroups characterized by population-specific predictors of cIMT progression results in slightly higher cIMT progression, the current analysis suggests that other patient populations should be considered for future cIMT studies.
Sex-disaggregated data confirm serum ferritin as an independent predictor of disease severity both in male and female COVID-19 patients
Authors: O. Gandini, A. Criniti, M.C. Gagliardi, L. Ballesio, S. Giglio, A. Balena, A. Caputi, A. Angeloni, C. Lubrano
Journal: Journal of Infection (2020)
TCT CONNECT-382 Feasibility and Safety of High-Risk Percutaneous Coronary Intervention Without Mechanical Circulatory Support
Authors: Nauman Khalid, Nausharwan Butt, Toby Rogers, Cheng Zhang, Corey Shea, Evan Shlofmitz Dupe, Anees Musallam, Brian Case, Charan Yerasi, Chava Chezar-Azerrad, Brian Forrestal, Hayder Hashim, Itsik Ben-Dor, Lowell Satler, Ron Waksman
Journal: Journal of the American College of Cardiology (2020)
Part 6: Resuscitation Education Science: 2020 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care
Authors: Adam Cheng, David J. Magid, Marc Auerbach, Farhan Bhanji, Blair L. Bigham, Audrey L. Blewer, Katie N. Dainty, Emily Diederich, Yiqun Lin, Marion Leary, Melissa Mahgoub, Mary E. Mancini, Kenneth Navarro, Aaron Donoghue
Journal: Circulation (2020)
TCT CONNECT-172 Clinical Features and Outcomes of Acute Myocardial Infarction and Cardiogenic Shock Patients Treated With Impella: Early Compared With Recent Experience
Authors: Hemindermeet Singh, Rajendra Mehta, William O'Neill, Thomas Lalonde, Ioana Ghiu, Yen Chen-Hsing, Karey Dutcheshen, Theodore Schreiber, Howard Rosman
Journal: Journal of the American College of Cardiology (2020)
TCT CONNECT-403 Serial Measurements of Absolute Coronary Blood Flow Post-CTO PCI and Predictors of Its Recovery
Authors: Osama Alsanjari, Grigoris Karamasis, Danielle Keulards, Paul Kelly, Kare Tang, Klio Konstantinou, James Cockburn, David Hildick-Smith, Koen Teeuwen, Thomas Keeble, John Davies
Journal: Journal of the American College of Cardiology (2020)
Biobased polyurethanes for biomedical applications
Authors: Sophie Wendels, Luc Avérous
Journal: Bioactive Materials (2020)

Polyurethanes (PUs) are a major family of polymers displaying a wide spectrum of physico-chemical, mechanical and structural properties for a large range of fields. They have shown suitable for biomedical applications and are used in this domain since decades. The current variety of biomass available has extended the diversity of starting materials for the elaboration of new biobased macromolecular architectures, allowing the development of biobased PUs with advanced properties such as controlled biotic and abiotic degradation. In this frame, new tunable biomedical devices have been successfully designed. PU structures with precise tissue biomimicking can be obtained and are adequate for adhesion, proliferation and differentiation of many cell's types. Moreover, new smart shape-memory PUs with adjustable shape-recovery properties have demonstrated promising results for biomedical applications such as wound healing. The fossil-based starting materials substitution for biomedical implants is slowly improving, nonetheless better renewable contents need to be achieved for most PUs to obtain biobased certifications. After a presentation of some PU generalities and an understanding of a biomaterial structure-biocompatibility relationship, recent developments of biobased PUs for non-implantable devices as well as short- and long-term implants are described in detail in this review and compared to more conventional PU structures.
Cerebral microdialysis in patients with fulminant hepatic failure
Authors: Flemming Tofteng, Linda Jorgensen, Bent Adel Hansen, Peter Ott, Jens Kondrup, Fin Stolze Larsen
Journal: Hepatology (2002)

Fulminant hepatic failure (FHF) is often complicated by high intracranial pressure (ICP) and fatal brain damage. In this study, we determined if a rise in [glutamate] ec and [lactate] ec preceded surges of high ICP in patients with FHF (median age, 42; range, 20-55 years; 7 women; 3 men) by inserting a microdialysis catheter into the brain-cortex together with an ICP catheter. The microdialysis catheter was perfused with artificial cerebrospinal-fluid at a rate of 0.3 μL/min. Dialysate was collected approximately every 30 minutes or when ICP increased. A total of 352 microdialysis samples were collected during a median of 3 days and allowed for ˜ 1,760 bedside analyses of the collected dialysate. In 5 patients that later developed surges of high ICP, the initial values of [glutamate]ec and [lactate]ec were 2 to 5 times higher compared with patients with normal ICP. [Glutamate] ec then tended to vanish with time in both groups of patients. An increase in [glutamate] ec did not precede high ICP in any of the cases. In contrast, [lactate] ec was high throughout the study in the high ICP group and increased further before surges of high ICP. We conclude that in patients with FHF, cerebral [glutamate] ec and [lactate] ec are elevated. However, the elevated [glutamate] ec is not correlated to high ICP. In contrast, elevations in [lactate] ec preceded surges of high ICP. In conclusion, accelerated glycolysis with lactate accumulation is implicated in vasodilatation and high ICP in patients with FHF. The data suggest that bedside cerebral microdialysis is a valuable tool in monitoring patients with FHF and severe hyperammonemia. (Hepatology2002;36:1333-1340).
Association of Uncommon, Noncoding Variants in the <i>APOE</i> Region With Risk of Alzheimer Disease in Adults of European Ancestry
Authors: Elizabeth E. Blue, Anqi Cheng, Sunny Chen, Chang-En Yu
Journal: JAMA Network Open (2020)

<h3>Importance</h3> The ε2 and ε4 alleles of the apolipoprotein E (<i>APOE</i>) gene are associated with Alzheimer disease (AD) risk. Although nearby genetic variants have also been shown to be associated with AD, including rs2075650 in the<i>TOMM40</i>gene and rs4420638 near the<i>APOC1</i>gene, it is unknown whether these associations are independent of the ε2 and ε4 alleles. <h3>Objective</h3> To assess whether variants near<i>APOE</i>are associated with AD independently of the ε2/ε3/ε4 genotype. <h3>Design, Setting, and Participants</h3> In this genetic association study of the Alzheimer's Disease Genetics Consortium imputed genotype at data, 14 415 variants near<i>APOE</i>(±500 kilobase) for 18 795 individuals with European ancestry were tested for association with AD using 4 logistic mixed models adjusting for sex, cohort, population structure, and relatedness. Model 1 had no<i>APOE</i>adjustment, and model 2 adjusted for the count of ε2 and ε4 alleles. Model 3 was restricted to ε3 homozygotes, and model 4 was restricted to ε4 homozygotes. Data were downloaded from May 31, 2018, to June 3, 2018, and analyzed from November 1, 2018, to June 24, 2020. <h3>Main Outcomes and Measures</h3> Alzheimer disease affectation status was defined by clinicians using standard National Institute of Neurological and Communicative Disorders and Stroke and Alzheimer Disease and Related Disorders Association criteria. Association was evaluated using Score tests; results with<i>P</i> &lt; .05 divided by the number of independent tests per model were considered statistically significant. <h3>Results</h3> Among the 18 795 individuals in the study, 9704 were affected by AD and 9066 were control individuals; the median age at onset/evaluation was 76 (interquartile range, 70-82) years; and 11 167 were female (59.4%). Associations with AD were found for rs2075650 (odds ratio [OR], 2.59; 95% CI, 2.45-2.75;<i>P</i> = 3.19 × 10<sup>−228</sup>) and rs4420638 (OR, 2.77; 95% CI, 2.62-2.94;<i>P</i> = 2.99 × 10<sup>−254</sup>) without<i>APOE</i>adjustment. Although rs2075650 was nominally associated with AD among the ε4 homozygotes (OR, 1.33; 95% CI, 1.00-1.77;<i>P</i> = .047), the association between rs4420638 and AD was eliminated by<i>APOE</i>adjustment (model 2 OR, 1.06 [95% CI, 0.96-1.18;<i>P</i> = .24]; model 3 OR, 1.13 [95% CI, 0.95-1.34;<i>P</i> = .18]; model 4 OR, 0.90 [95% CI, 0.56-1.45;<i>P</i> = .66]). There was a significant association between rs192879175 and AD among ε3 homozygotes (OR, 0.50; 95% CI, 0.37-0.68;<i>P</i> = 8.30 × 10<sup>−6</sup>). <h3>Conclusions and Relevance</h3> The results of this genetic association study suggest that ε2/ε3/ε4 alleles are not the only variants in the<i>APOE</i>region that are associated with AD risk. Additional work with independent data is needed to replicate these results.
Trends in mortality and cause-specific mortality among patients with psoriasis and psoriatic arthritis in Ontario, Canada
Authors: Keith Colaco, Jessica Widdifield, Jin Luo, Cheryl F. Rosen, Raed Alhusayen, J. Michael Paterson, Willemina Campbell, Karen Tu, Sasha Bernatsky, Dafna D. Gladman, Lihi Eder
Journal: Journal of the American Academy of Dermatology (2020)
TCT CONNECT-335 Association of MitraClip Availability and Hospital Surgical Mitral Valve Repair Outcomes: An Evaluation of the STS Adult Cardiac Surgical Database
Authors: Angela Lowenstern, Maria Grau-Sepulveda, Andrew Wang, Vinay Badhwar, Vinod Thourani, David Cohen, Sreekanth Vemulapalli
Journal: Journal of the American College of Cardiology (2020)
TCT CONNECT-482 Association of Annual Hospital Transcatheter Aortic Valve Replacement Volume With Incidence and Outcomes of Periprocedural Ischemic Stroke
Authors: Toshiaki Isogai, Anas Saad, Nobuaki Michihata, Shashank Shekhar, Omar Abdelfattah, Mohamed Gad, Keerat Rai Ahuja, Grant Reed, Amar Krishnaswamy, Rishi Puri, Samir Kapadia
Journal: Journal of the American College of Cardiology (2020)
TCT CONNECT-146 Concomitant Invasive Versus Echocardiographic Mean Gradients in Degenerated Surgical Aortic Valve Prostheses: A Multicenter Study
Authors: Amer N. Kadri, George Hanzel, Francis Shannon, Sammy Elmariah, Karim Al-Azizi, Sara Khodor, Ahmed Ali, Alexander Camacho, Alexandra Selberg, Katherine Harrington, Alessandro Vivacqua, Molly Szerlip, Michael Mack, Amr Abbas
Journal: Journal of the American College of Cardiology (2020)
Timed Ang2-Targeted Therapy Identifies the Angiopoietin–Tie Pathway as Key Regulator of Fatal Lymphogenous Metastasis
Authors: Nicolas Gengenbacher, Mahak Singhal, Carolin Mogler, Ling Hai, Laura Milde, Ashik Ahmed Abdul Pari, Eva Besemfelder, Claudine Fricke, Daniel Baumann, Stephanie Gehrs, Jochen Utikal, Moritz Felcht, Junhao Hu, Matthias Schlesner, Rienk Offringa, Sudhakar R. Chintharlapalli, Hellmut G. Augustin
Journal: Cancer Discovery (2020)

Recent clinical and preclinical advances have highlighted the existence of a previously hypothesized lymphogenous route of metastasis. However, due to a lack of suitable preclinical modeling tools, its contribution to long-term disease outcome and relevance for therapy remain controversial. Here, we established a genetically engineered mouse model (GEMM) fragment-based tumor model uniquely sustaining a functional network of intratumoral lymphatics that facilitates seeding of fatal peripheral metastases. Multiregimen survival studies and correlative patient data identified primary tumor-derived Angiopoietin-2 (Ang2) as a potent therapeutic target to restrict lymphogenous tumor cell dissemination. Mechanistically, tumor-associated lymphatic endothelial cells (EC), in contrast to blood vascular EC, were found to be critically addicted to the Angiopoietin-Tie pathway. Genetic manipulation experiments in combination with single-cell mapping revealed agonistically acting Ang2-Tie2 signaling as key regulator of lymphatic maintenance. Correspondingly, acute presurgical Ang2 neutralization was sufficient to prolong survival by regressing established intratumoral lymphatics, hence identifying a therapeutic regimen that warrants further clinical evaluation. SIGNIFICANCE: Exploiting multiple mouse tumor models including a unique GEMM-derived allograft system in combination with preclinical therapy designs closely matching the human situation, this study provides fundamental insight into the biology of tumor-associated lymphatic EC and defines an innovative presurgical therapeutic window of migrastatic Ang2 neutralization to restrict lymphogenous metastasis.This article is highlighted in the In This Issue feature, p. 211.
Familial risk and incidence of alopecia areata among first degree relatives—A nationwide population-based study in Korea
Authors: Hyun Jung Kim, Sayada Zartasha Kazmi, Taeuk Kang, Jung Won Shin, Hei Sung Kim, Dong-Sook Kim, Hoo Jae Hann, Hyeong Sik Ahn
Journal: Journal of the American Academy of Dermatology (2020)
Double trouble: combined cardiovascular effects of particulate matter exposure and coronavirus disease 2019
Authors: Vineeta Tanwar, Jeremy M Adelstein, Loren E Wold
Journal: Cardiovascular Research (2020)

Abstract The coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly grown into a pandemic. According to initial reports, the lungs were thought to be the primary target, but recent case studies have shown its reach can extend to other organs including the heart and blood vessels. The severity of cardiac complications of COVID-19 depends on multiple underlying factors, with air pollutant exposure being one of them, as reported by several recent studies. Airborne particulate matter (PM) attracts heightened attention due to its implication in various diseases, especially respiratory and cardiovascular diseases. Inhaled PM not only carries microorganisms inside the body but also elicits local and systemic inflammatory responses resulting in altering the host’s immunity and increasing susceptibility to infection. Previous and recent studies have documented that PM acts as a ‘carrier’ for the virus and aids in spreading viral infections. This review presents the mechanisms and effects of viral entry and how pollution can potentially modulate pathophysiological processes in the heart. We aimed to concisely summarize studies examining cardiovascular outcomes in COVID-19 patients and postulate on how PM can influence these outcomes. We have also reviewed evidence on the use of renin–angiotensin system inhibitors, namely angiotensin-converting enzyme inhibitors and angiotensin receptor blockers, in patients with COVID-19. The interplay of pollution and SARS-CoV-2 is essential to understanding the effects of accentuated cardiovascular effects of COVID-19 and deserves in-depth experimental investigations.
Identification of putative colon cancer protein biomarker by mass spectrometry.
Authors: John Roboz, Rong Wang, Georgia Dolios, Shouxun Zhao, Max Sung, James F. Holland
Journal: Cancer Research (2004)

3551  Using SELDI-TOF mass spectrometric technique (SELDI=surface-enhanced laser desorption ionization; TOF=time of flight) with H4-type chips, we have obtained protein profiles in plasma samples from patients with confirmed colon cancer (n=34) and control subjects (n=14). Peak mapping as well as gel viewing of the spectra revealed different expression levels at several masses. The most pronounced differences were observed for a peak at 8.9 kDa (8942.9±5.3), where the average differential expression of the intensities of the putative marker was approx. 3-fold higher in cancer patients (38.5±10.5) than in the controls (12.5±5.9). Molecular masses were determined to an accuracy of approx. 0.1%. In a second study (18 patients, 8 controls), the average differential expression of the intensities of the 8.9 kDa marker was approx. 2-fold higher in the cancer patients than in the controls. To identify this protein, plasma proteins were isolated with reversed-phase POROS R2 beads and further separated by SDS-PAGE. The protein bands of interest were excised from the gel and in-gel digested with trypsin. The resulting tryptic peptides were analyzed by μLC-electrospray-tandem (MS/MS), using an ion trap mass spectrometer. The MS/MS data were used to search a sequence and protein identification database (Knexus Sonar). Several candidates were found within the determined mass range, including complement component 3 precursor (C3). An analysis of the ion-chromatographic peak intensity of peptides corresponding to these candidates revealed that the highest peak intensities were associated with tryptic peptides of C3. The C3 is known to undergo multiple proteolytic hydrolysis and one of the hydrolysis products is the C3 peptide 672–748, known as anaphylatoxin C3a. The calculated molecular mass of C3a is 9094.6 Da. The average molecular mass of the 8.9 kDa peak is 8942.9 Da. Further examination of the tryptic peptides of C3 showed that all of the peptides identified were between the 713–736 of C3 sequence. All observed data suggested the 8.9 kDa protein to be a C3a-related protein. (Supported by T.J. Martell Foundation for Leukemia, Cancer and AIDS Research and NIH/NCI to R.W).
TCT CONNECT-434 Success, Safety, and Patency of the V-Wave Ventura Interatrial Shunt in Chronic Heart Failure
Authors: Gregg Stone, JoAnn Lindenfeld, Saibal Kar, John Gorcsan, Josep Rodes-Cabau, Stefan Anker, Richard Holcomb
Journal: Journal of the American College of Cardiology (2020)
HCQ use not protective against SARS-CoV-2
Authors: Sarah Onuora
Journal: Nature Reviews Rheumatology (2020)

HCQ use not protective against SARS-CoV-2Patients receiving treatment with hydroxychloroquine (HCQ) for rheumatological conditions are not protected from SARS-CoV-2 infection, according to the results of a retrospective study of data from a US Veterans Health Administration database.During the study period (March-June 2020), the incidence of active infections did not differ between patients who received HCQ (31 of 10,703 (0.3%)) and those who did not (78 of 21,406 (0.4%)).The two groups also did not differ in rate of hospital admission, requirement of intensive care and mortality associated with SARS-CoV-2 infection.
Informed consent procedures for emergency interventional research in patients with traumatic brain injury and ischaemic stroke
Authors: Erwin J O Kompanje, Jeroen T J M van Dijck, Vicky Chalos, Sophie A van den Berg, Paula M Janssen, Paul J Nederkoorn, Mathieu van der Jagt, Giuseppe Citerio, Nino Stocchetti, Diederik W J Dippel, Wilco C Peul
Journal: The Lancet Neurology (2020)
TCT CONNECT-222 Superimposing Stroke on Existent AMI Telemedicine Pathways
Authors: Sameer Mehta, Francisco Fernandez, Carlos Villagran, Daniel Vieira, Gladys Pinto, Lorena Pisana, Yogaraja Vijayan, Carmen Sanchez, Daniel Pinos, Saleha Ozair
Journal: Journal of the American College of Cardiology (2020)