tbuckley/cabot-search huggingface dataset:
Repeated <i>Plasmodium falciparum</i> infection in humans drives the clonal expansion of an adaptive γδ T cell repertoire
Authors: Anouk von Borstel, Priyanka Chevour, Daniel Arsovski, Jelte M. M. Krol, Lauren J. Howson, Andrea A. Berry, Cheryl L. Day, Paul Ogongo, Joel D. Ernst, Effie Y. H. Nomicos, Justin A. Boddey, Edward M. Giles, Jamie Rossjohn, Boubacar Traore, Kirsten E. Lyke, Kim C. Williamson, Peter D. Crompton, Martin S. Davey
Journal: Science Translational Medicine (2021)

Malaria drives the adaptive differentiation of the human γδ T cell repertoire.
Safety and Early Efficacy of Obinutuzumab in Combination with Chemotherapy in Treatment Naive Patients with Follicular Lymphoma - Report of Polish Lymphoma Research Group (PLRG)
Authors: Ewa Paszkiewicz-Kozik, Iwona Hus, Monika Palka, Malgorzata Debowska, Agnieszka Konska, Martyna Kotarska, Agata Tyczynska, Monika Joks, Maja Twardosz, Agnieszka Giza, Ewa Wasik-Szczepanek, Elzbieta Kalicinska, Anna Wisniewska, Marta Morawska, Joanna Romejko-Jarosinska, Barbara Lewicka, Lukasz Targonski, Michal Osowiecki, Lidia Poplawska, Marcin Szymanski, Kamila Kruczkowska-Taranowicz, Joanna Drozd-Sokolowska, Ryszard Swoboda, Katarzyna Domanska-Czyz, Beata Ostrowska, Monika Swierkowska, Anna Paulina Dabrowska-Iwanicka, Agnieszka Druzd-Sitek, Robert Konecki, Anna Borawska, Monika Dlugosz-Danecka, Ewa Lech-Marańda, Jan Walewski
Journal: Blood (2021)
下肢静脈血栓症に血栓吸引カテーテル(OASIS)を用い,奏功した一例
Authors: 柳大三郎, 福島幹生, 児玉直, 太田岳暁, 森戸夏美, 八尋英二, 三好恵, 三原宏之, 山之内良雄
Journal: Circulation (2004)
The Impact of the Immunophenotyping Characteristics of Patients' Peripheral Blood on the Manufacturing and Clinical Outcome of CD7-Targeted Chimeric Antigen Receptor T Cells
Authors: Mingzhi Zhang, Xiaorui Fu, Huimin Meng, Min Wang, Yu Wang, Guifang Pan, Lei Zhang, Ling Li, Xin Li, Xinhua Wang, Zhenchang Sun, Hui Yu, Zhaoming Li, Feifei Nan, Yu Chang, Zhiyuan Zhou, Jiaqin Yan, Jiwei Li, Xiaolong Wu, Yanmei Zhao, Yu-Sheng Chen, Fengtao You, Dan Chen, Tingting Zhang, Bozhen Zhang, Lin Yang
Journal: Blood (2021)
EXTH-26. LAYER-BY-LAYER NANOPARTICLES DESIGNED FOR DUAL BLOOD-BRAIN BARRIER AND GLIOMA TARGETING
Authors: Joelle Straehla, Cynthia Hajal, Hannah Safford, Giovanni Offeddu, Jeffrey Wyckoff, Roger Kamm, Paula Hammond
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND While biologically diverse, high grade gliomas (HGGs) have a dismal prognosis in both adults and children. Promising therapeutics have been identified for HGGs based on common genomic alterations and aberrant signaling pathways, but achieving effective drug exposure at the tumor site remains a challenge largely due to the blood-brain barrier (BBB). HYPOTHESIS: A tunable nanocarrier platform can improve nanoparticle delivery across the (BBB) and into glioma cells. METHODS We synthesized layer-by-layer nanoparticles by coating anionic, fluorescent liposomes with nanometers-thick layers of oppositely charged polyelectrolytes, creating a library of organic, nontoxic drug carriers with varied surface chemistries. We characterized the library using dynamic light scattering and quantified interactions with a range of pediatric and adult glioma cell lines using flow cytometry. We used intravital two-photon microscopy to quantify nanoparticle trafficking across the intact BBB through a cranial window in anesthetized mice. RESULTS Nanoparticle surface chemistry strongly influences cellular trafficking in vitro, with two polymers identified as particularly high-performing across brain tumors lines: poly-L-aspartic acid (semi-synthetic) and hyaluronic acid (natural polysaccharide). The addition of the angiopep-2 targeting moiety onto these polymers improved nanoparticle uptake into brain microvascular endothelial cells in vitro without abrogating tumor affinity. We developed a new algorithm to quantify permeability of fluorescent compounds across the BBB in vivo and validated our method by measuring dextran permeability at varied molecular weights. In our initial study in non-tumor-bearing mice (n=12), we successfully quantified nanoparticle permeability across the BBB. In this study, surface functionalization did not increase BBB permeability above the control nanoparticle, though it did improve nanoparticle half-life in circulation and may still impart a therapeutic benefit when loaded with drug. Additional investigations in orthotopic tumor-bearing mice are ongoing. In summary, we report the development of layer-by-layer nanocarriers as a modular drug delivery platform with therapeutic potential for gliomas.
Evaluation of Stillbirth Among Pregnant People With Sickle Cell Trait
Authors: Silvia P. Canelón, Samantha Butts, Mary Regina Boland
Journal: JAMA Network Open (2021)

<h3>Importance</h3> Relative to what is known about pregnancy complications and sickle cell disease (SCD), little is known about the risk of pregnancy complications among those with sickle cell trait (SCT). There is a lack of clinical research among sickle cell carriers largely due to low sample sizes and disparities in research funding. <h3>Objective</h3> To evaluate whether there is an association between SCT and a stillbirth outcome. <h3>Design, Setting, and Participants</h3> This retrospective cohort study included data on deliveries occurring between January 1, 2010, and August 15, 2017, at 4 quaternary academic medical centers within the Penn Medicine health system in Pennsylvania. The population included a total of 2482 deliveries from 1904 patients with SCT but not SCD, and 215 deliveries from 164 patients with SCD. Data were analyzed from May 3, 2019, to September 16, 2021. <h3>Exposures</h3> The primary exposure of interest was SCT, identified using clinical diagnosis codes recorded in the electronic health record. <h3>Main Outcomes and Measures</h3> A multivariate logistic regression model was constructed to assess the risk of stillbirth using the following risk factors: SCD, numbers of pain crises and blood transfusions before delivery, delivery episode (as a proxy for parity), prior cesarean delivery, multiple gestation, patient age, marital status, race and ethnicity, ABO blood type, Rhesus (Rh) factor, and year of delivery. <h3>Results</h3> This cohort study included 50 560 patients (63 334 deliveries), most of whom were aged 25 to 34 years (29 387 of 50 560 [58.1%]; mean [SD] age, 29.5 [6.1] years), were single at the time of delivery (28 186 [55.8%]), were Black or African American (23 777 [47.0%]), had ABO blood type O (22 879 [45.2%]), and were Rhesus factor positive (44 000 [87.0%]). From this general population, 2068 patients (4.1%) with a sickle cell gene variation were identified: 1904 patients (92.1%) with SCT (2482 deliveries) and 164 patients (7.9%) with SCD (215 deliveries). In the fully adjusted model, SCT was associated with an increased risk of stillbirth (adjusted odds ratio [aOR], 8.94; 95% CI, 1.05-75.79;<i>P</i> = .045) while adjusting for the risk factors of SCD (aOR, 26.40; 95% CI, 2.48-280.90;<i>P</i> = .007) and multiple gestation (aOR, 4.68; 95% CI, 3.48-6.29;<i>P</i> &lt; .001). <h3>Conclusions and Relevance</h3> The results of this large, retrospective cohort study indicate an increased risk of stillbirth among pregnant people with SCT. These findings underscore the need for additional risk assessment during pregnancy for sickle cell carriers.
Abstract 13275: Eastern-European and African Immigrants Have Higher Risk of Out-of-Hospital Cardiac Arrest Compared to Other Danish Immigrants
Authors: Rodrigue Garcia, Deepthi Rajan, Carlo Barcella, Jesper Svane, Peder Warming, Reza Jabbari, Gunnar Gislason, Christian Torp-Pedersen, Fredrik Folke, Jacob Tfelt-hansen
Journal: Circulation (2021)

Introduction: American studies have pointed out racial disparities regarding Out-of-Hospital Cardiac Arrest (OHCA) occurrence, but to date, no data exists among immigrants in Europe. Hypothesis: The risk of OHCA may vary according to region of origin among immigrants. Methods: This nationwide study included all immigrants identified from the Danish Cardiac Arrest Register with OHCA with presumed cardiac cause between 18 and 80 years from 2001 to 2014. Regions of origin were defined as Asia, Western countries, Eastern Europe, Africa, South America, and Arabic countries. Results: Overall, among 940,207 immigrants present in Denmark, a total of 1,724 (0.2%) OHCA (median 62 (IQR 50,71) years 70% males) were recorded. History of myocardial infarction, heart failure, and diabetes were present in 23%, 18%, and 16% respectively. 217 OHCA occurred in Asians, 673 in Westerners, 347 in Eastern Europeans, 107 in Africans, 19 in South Americans, and 361 in Arabic immigrants.Crude incidence rate (/ 100 000 person-years) was 15.2 (95%CI 9.14-23.7) in South American, 19.4 (95%CI 16.9-22.2) in Asian, 22.8 (95%CI 18.7-27.5) in African, 24.7 (95%CI 22.2-27.3) in Arabic, 26.2 (95%CI 23.5-29.1) in Eastern European and 32.4 (95%CI 30.0-34.9) in Western immigrants.After Cox regression, factors associated with OHCA were Eastern European origin (HR 1.28, 95%CI 1.13-1.47; P&lt;0.001), African origin (HR 1.31, 95%CI 1.07-1.61; P=0.01), male sex (HR 1.89, 95%CI 1.70-2.10; P&lt;0.001), age (HR 1.05, 95%CI 1.04-1.06; P&lt;0.001), ischemic heart disease (HR 52.02; 95%CI 39.41-68.67; P&lt;0.001), diabetes (HR 7.04; 95%CI 5.42-9.16; P&lt;0.001), and heart failure (HR 1.33, 95%CI 1.06-1.64; P=0.01). Conclusions: This is the first European study assessing the incidence of OHCA among immigrants according to their region of origin. Eastern European and African immigrants had a higher risk of OHCA compared to South American, Asian, Arabic and Western immigrants.
Abstract 10298: Improving the Ability to Assess and Detect Delirium in Postoperative Cardiac Surgery Patients
Authors: Myra F Ellis, Rachel Civale, Debra Farrell, Jordan Simon, Linnea Mangodt, Mavis Awuku, Sophia Corbitt, Tonda Thomas, Bradi B Granger
Journal: Circulation (2021)

Introduction: Delirium is common in cardiac intensive care units due to illness related stress, polypharmacy, interventions, excessive light and noise, disorientation and sleep disruption. Delirium assessment is poor due to limited nursing knowledge and the lack of integrated features in electronic health platforms (EHR) to support accurate assessment and documentation. Hypothesis: We hypothesized that education on use of the Confusion Assessment Method for the ICU (CAM-ICU) and enhanced features in the EHR would improve the ability to detect delirium in our CTICU. Methods: We conducted a QI intervention using a PDSA approach and pre-post evaluation design. In the Planning phase audited 100 randomly selected charts to determine baseline documentation of delirium. We conducted a survey of nurses’ knowledge of delirium and documentation criteria and identified a knowledge deficit. In the Do phase, a multi-stage educational initiative was used to address delirium awareness, knowledge, and CAM-ICU documentation competency. Enhancements in the EHR were made to enable accurate assessment, documentation and scoring using embedded logic. Post-intervention audits (n=100) were performed. Results: Survey respondents (n=64) averaged 31 years old (SD 1.4) and had 6 years nursing experience on average (median=3, range &lt;1-40). Nurses believed patients with delirium had longer ICU LOS and worse outcomes and patients would benefit from screening. Most lacked training in delirium screening (88.1%, n=58). Baseline documentation of at least one assessment of delirium was 44% (n=44) and post-intervention was 100% (p&lt;0.001). Accuracy of CAM-ICU assessments at baseline was challenging to determine due to a single field (YES/NO/UTA) in the EHR, however, positivity of pre-intervention assessments was 1% (n=1) and post- intervention at least 1 positive CAM score was recorded in 33% (n=33) of patients (p&lt;0.001). Conclusions: Findings suggest that a multi-stage educational intervention paired with EHR integrated scoring logic improves awareness, knowledge and documentation accuracy for delirium in the ICU, which may improve patient safety and ICU outcomes. Better assessment and documentation may improve patient safety and ICU outcomes.
Abstract P417: Cardiomyopathy-associated Variant In Troponin T Tail Domain Promotes Disruption Of Both Frank-starling Mechanism And Cardiac Myofilament Performance
Authors: Maicon Landim-Vieira, Weikang Ma, Taejeong Song, Coen Ottenheijm, Hyun Hwang, Bjorn C Knollmann, Sakthivel Sadayappan, Thomas Irving, P. Bryant Chase, Jose Pinto
Journal: Circulation Research (2021)

Missense variant Ile79Asn in human cardiac troponin T (HcTnT-I79N) tail region has been linked to familial hypertrophic cardiomyopathy (HCM), arrhythmia, and sudden cardiac death. It has been reported that inotropic stimulation with high extracellular Ca 2+ or isoproterenol led to diastolic dysfunction in both isolated and in vivo HcTnT-I79N mice hearts. Although HcTnT-I79N effects are acknowledged to be dependent on the inotropic state of the cardiac muscle, little is known about how this pathogenic variant affects the Frank-Starling law of the heart. To further investigate the functional and structural consequences of this deadly variant in a stretch-dependent manner, cardiac tissues were harvested from non-transgenic (NTg) control mice and transgenic mice bearing HcTnT-I79N. Left ventricular papillary muscle bundles were permeabilized and mounted for mechanical measurements. Sarcomere length (SL 1.9, 2.1 or 2.3 μm) was set at pCa 8 using HeNe laser diffraction and then Ca 2+ -dependence of isometric force, sinusoidal stiffness (SS, 0.2% PTP length oscillation) and rate of tension redevelopment ( k TR ) were measured. We observed that HcTnT-I79N tissue exhibited increased myofilament Ca 2+ -sensitivity of force, increased SS, slower k TR at all levels of Ca 2+ -activation, and diminished length-dependent activation (LDA). Small-angle X-ray diffraction revealed that HcTnT-I79N permeabilized cardiac muscles exhibit smaller myofilament lattice spacing at longer SLs (2.1 μm and 2.3 μm) compared to NTg. Using 3% Dextran T500 to osmotically compress the myofilament lattice (SL 2.1 μm), HcTnT-I79N showed no change in myofilament lattice spacing and little change in contractile indices associated with LDA. Interestingly, upon osmotic compression, HcTnT-I79N displayed a decrease in disordered relaxed state (DRX, ON state) of myosin and an increase in super-relaxed state (SRX, OFF state) of myosin. We conclude that altered cardiac myofilament performance, lack of responsiveness to osmotic compression, and reduced LDA observed with HcTnT-I79N are partially due to a combination of smaller myofilament lattice and disturbed ON and OFF states of myosin.
Abstract 13170: Mechanical Thrombectomy or Bridging Therapy for Anterior Circulation Large Vessel Occlusion Strokes?
Authors: Gabriela Trifan, Jose Biller, Fernando Testai
Journal: Circulation (2021)

Introduction: The superiority of intravenous thrombolysis plus mechanical thrombectomy in combination, also known as bridging therapy (BT), relative to mechanical thrombectomy (MT) alone in large vessel occlusion (LVO) stroke has not been established. Hypothesis: BT may have similar efficacy an safety profiles as MT for anterior circulation LVO. Methods: A systematic search of biomedical literature databases was performed up to March 2021, to identify prospective and retrospective studies that reported the rates for functional independence (defined as modified Rankin Scale 0-2) and mortality at 90 days, in-hospital symptomatic hemorrhage (sICH), and successful recanalization rates for MT and BT. Effect size was represented by odds ratio (OR) and analysis was done using random effects meta-analyses. Heterogeneity was assessed by I 2 and Cochrane’s Q statistics. Results: Overall, 35 studies with 11,332 patients were included in the analysis. Mean age ± standard deviation for BT and MT was 69±12 and 70±12 years, respectively. BT group had 28% higher odds for functional independence (OR=1.28, 95% CI 1.13-1.46, I 2 =53%), 33% higher odds of successful reperfusion (OR=1.33, 95% CI=1.13-1.56, I 2 =43%) and a 31% decrease in odds for mortality (OR=0.69, 95% CI 0.59-0.81, I 2 =49%) compared with MT. The sICH prevalence was similar between groups (OR=1.03, 95% CI=0.87-1.22, I 2 =0%). When only RCTs with intention-to-treat analysis comparing BT to MT were included in the analysis (n=1,633), there were no differences in functional independence (OR=0.99, 95% CI=0.81-1.20, I 2 =0%), successful reperfusion (OR=1.33, 95% CI=0.95-1.87, I 2 =0%), sICH (OR=1.23, 95% CI=0.82-1.83, I 2 =0%) or mortality (OR=0.94, 95% CI=0.72-1.21, I 2 =0%) between the groups. Conclusions: The odds for functional independence, successful reperfusion and mortality favored the use of BT over MT. The study had medium heterogeneity and low quality of the evidence. However, when the analysis was restricted to RCTs intention to treat analyses, BT and MT had similar efficacy and safety outcomes, with no heterogeneity.
Immune Senescence-Related Gene Expression Profile in CD4+ T-Lymphocytes of HTLV-1 Asymptomatic Carriers and Patients with Adult T-Cell Leukemia/Lymphoma (ATLL): A Brazilian Preliminary Study
Authors: José Roberto Assis Filho, Hebert Fabricio Culler, Debora Levy, Karolliny Silva de Oliveira, Daniel Silva Nogueira, Lis Vilela de Almeida, Vanderson Rocha, Youko Nukui, Luis Alberto de Padua Covas Lage, Juliana Pereira
Journal: Blood (2021)
Abstract 10791: Regeneration-Associated Cells Derived Exosomes Beneficial Than Mesenchymal Stromal Cells Derived Exosome in the Context of Myocardial Ischemia-Injury
Authors: Amankeldi A Salybekov, Ainur Salybekova, Yin Sheng, Shuzo Kobayashi, Takayuki Asahara
Journal: Circulation (2021)

Introduction: Vasculogenic conditioning of pro-inflammatory cells such as macrophages type 1, T cells, and primitive EPCs shifted their phenotype to pro-regenerative cells such as vasculogenic EPCs, M2 macrophages, and reg T cells, also known as regeneration-associated cells (RACs). Here, we investigated therapeutic efficacy of RAC-derived extracellular vesicles (RACev) in comparison with MSC-derived EVs (MSCev) in the context of myocardial ischemia-reperfusion injury (IRI). Methods: RACev and MSCev were isolated via ultracentrifugation. EVs quantity and quality were characterized by nanotracking analysis and CD9, CD63, Alix expression. EVs miR was sequenced and regenerative responsible miRs were validated using TargetScan and miRBase. Allogeneic immune response to the RACev and MSCev were evaluated. The function of RACev and MSCev were evaluated using HUVECs proliferation/cell-cycle assays in vitro, and repetitive (30min, d1, and d3 after IRI) systemic infusion with either RACev or MSCev in a myocardial IRI model. Results: Nanotracking analysis showed significant differences in quantity RACev vs. MSC (P= 0.03). In vitro , RACev markedly enhanced cell viability, proliferation, and migration of HUVECs in a dose-dependent manner compared to MSCev. Systemic injection of RACs (5x10 5 ) derived EVs improved cardiac functions such as ejection fraction (P= 0.005) than MSCev treated group. In histology, RACev transplanted group showed less interstitial fibrosis and enhanced capillary densities (P =0.05) compared to MSCev. These beneficial effects are coupled with significant expression of angiogenesis, anti-inflammation, cardiomyogenesis, and anti-fibrosis-related miRs in RACev but not in MSCev. In vivo bioluminescence and labeled EVs histology tracking analyses depicted preferential accumulation of RACev into the IRI myocardium (P=0.01) than MSCev. Immune phenotyping analysis confirmed similar immunomodulatory effects of MSCev and RACev. Conclusion: Repetitive systemic transplantation of RACev is superior to MSCev in terms of cardiac function enhancements via crucial angiogenesis, anti-fibrosis, anti-inflammation, cardiomyogenesis, and anti-apoptosis-related miRs delivery to the ischemic tissue.
Effects of Alvelestat, an Oral Neutrophil Elastase Inhibitor, on Elevated Elastase and Collagen Turnover Biomarkers in Patients with Bronchiolitis Obliterans Syndrome after Hematopoietic Cell Transplantation
Authors: Annie Im, Jacqueline Parkin, Noa G. Holtzman, William Moore, Lauren M. Curtis, Cody Peer, William D. Figg, Jeremy J. Rose, Laura Parsons-Wandell, Frances T. Hakim, Steven Z. Pavletic
Journal: Blood (2021)
Abstract 10193: Association of Inflammation with Decreased Myocardial Function in Covid Patients with Shock
Authors: Steven M Hollenberg, Matthew Fata, Brent Klinkhammer, Noha Gayed, Taya Glotzer, Ronaldo Go, Elli Gourna-Paleoudis, David Landers, Sameer Jamal, Lucy Safi, Neel Shah, Roshan Shah, Jana Tancredi, Zoltan Turi, Joseph E Parrillo
Journal: Circulation (2021)

Introduction: The response to COVID infection has been associated with intense inflammation, and some patients have cardiac involvement. In a group of patients with COVID infection and shock whose ventricular function was characterized by echocardiography, we examined the relationship between levels of ferritin, an inflammatory marker that is elevated in COVID, and LV ejection fraction (EF). Methods: Of 1275 patients hospitalized with COVID pneumonia, 215 had shock requiring vasopressors. 162 had echocardiography to assess ventricular function and stroke volume. EF was measured using Simpson’s rule and stroke volume (SV) by Doppler. Patients were divided into groups with low or preserved EF ( EF L or EF P , cutoff &amp;lte45%), and low or normal cardiac index, (CI, CI L or CI N , cutoff ≤&amp;lte2.2 L/min/m 2 ). Ferritin within 7 days of the echo was available in 147/162 patients. We examined the association between ferritin levels and ejection fraction. Results: Mean age was 66.7, EF 58.7±13.9; CI 2.41±0.89 L/min/m 2 , ferritin 3036±2318 ng/mL (normal &lt;336). Five patients had obstructive shock from pulmonary embolism (normal LVEF, low SV, RV dysfunction) and were excluded. The other 157 patients were divided into groups based on EF and CI ( Figure ). High ferritin levels correlated with low EF (r=-0.18, p=0.02), and ferritin levels were greatly increased in patients with a hemodynamic profile of cardiogenic shock. ( EF L CI L , Figure, p=0.017 by ANOVA) Conclusion: COVID-induced shock had a cardiogenic profile (EF L CI L ) in 10% of patients, and another 5% had low EF but normal CI. Ferritin correlated with low EF and was increased in patients with a profile of cardiogenic shock. This suggests that marked inflammation may depress myocardial function in COVID patients with shock - analogous to a similar myocardial depression seen with bacterial-associated septic shock.