tbuckley/cabot-search huggingface dataset:
Lentiviral Mediated Gene Therapy for Pyruvate Kinase Deficiency: Interim Results of a Global Phase 1 Study for Adult and Pediatric Patients
Authors: Ami J Shah, José Luis López Lorenzo, Susana Navarro, Julián Sevilla, Lucía Llanos, Begoña Pérez de Camino Gaisse, Sol Sanchez, Bert Glader, May Chien, Oscar Quintana Bustamante, Brian C Beard, Kenneth M Law, Miriam Zeini, Grace Choi, Eileen Nicoletti, Gayatri R Rao, Maria Grazia Roncarolo, Juan A Bueren, Jonathan D Schwartz, José C Segovia
Journal: Blood (2021)
PoreScript: Semi-automated pore size algorithm for scaffold characterization
Authors: Dana Jenkins, Karim Salhadar, Grant Ashby, Anita Mishra, Joy Cheshire, Felipe Beltran, Melissa Grunlan, Sébastien Andrieux, Cosima Stubenrauch, Elizabeth Cosgriff-Hernandez
Journal: Bioactive Materials (2021)

The scaffold pore size influences many critical physical aspects of tissue engineering, including tissue infiltration, biodegradation rate, and mechanical properties. Manual measurements of pore sizes from scanning electron micrographs using ImageJ/FIJI are commonly used to characterize scaffolds, but these methods are both time-consuming and subject to user bias. Current semi-automated analysis tools are limited by a lack of accessibility or limited sample size in their verification process. The work here describes the development of a new MATLAB algorithm, PoreScript, to address these limitations. The algorithm was verified using three common scaffold fabrication methods (e.g., salt leaching, gas foaming, emulsion templating) with varying pore sizes and shapes to demonstrate the versatility of this new tool. Our results demonstrate that the pore size characterization using PoreScript is comparable to manual pore size measurements. The PoreScript algorithm was further evaluated to determine the effect of user-input and image parameters (relative image magnification, pixel intensity threshold, and pore structure). Overall, this work validates the accuracy of the PoreScript algorithm across several fabrication methods and provides user-guidance for semi-automated image analysis and increased throughput of scaffold characterization.
Molecular Responses Are Observed across Mutational Spectrum in Treatment-Naïve Higher-Risk Myelodysplastic Syndrome Patients Treated with Venetoclax Plus Azacitidine
Authors: Jacqueline S. Garcia, Andrew H. Wei, Meagan A. Jacoby, Chun Yew Fong, Uma Borate, Maria R. Baer, Ilona Cunningham, Olatoyosi Odenike, Joseph G. Jurcic, Daniel Nowak, Pierre Peterlin, Uwe Platzbecker, Diana Dunshee, Ying Zhou, David Hoffman, Yan Sun, Relja Popovic, Barrett Ainsworth, Kiran Naqvi, Steve Kye, Leah Hogdal, Guillermo Garcia-Manero
Journal: Blood (2021)
Modulation of RNA Splicing Enhances Response to BCL2 Inhibition in Acute Myeloid Leukemia
Authors: Eric Wang, Jose Mario Bello Pineda, Jessie Bourcier, Maximilian Stahl, Alexander V Penson, Isaac Wakiro, Michael E Singer, Daniel Cui, Caroline Erickson, Katherine Knorr, Robert Stanley, Xufeng Chen, Elizabeth A. McMillan, Carine Bossard, Iannis Aifantis, Robert K. Bradley, Omar Abdel-Wahab
Journal: Blood (2021)
Primary Progression on Frontline Therapy for Diffuse Large B-Cell Lymphoma Is Associated with a Poor Outcome Despite Subsequent CD19 Targeted CAR T-Cell Therapy
Authors: Ariel Perez Perez, Grace Johnson, Kedar Patel, Brian Arciola, Anthony Wood, Christina A Bachmeier, Julio C. Chavez, Bijal D. Shah, Farhad Khimani, Taiga Nishihori, Aleksandr Lazaryan, Marco L. Davila, Rahul Mhaskar, Frederick L. Locke, Sameh Gaballa, Michael D. Jain
Journal: Blood (2021)
Long-Term Outcome of Treatment-Naïve and Relapsed/Refractory Patients with CLL and <i>TP53</i> Aberrations Treated with Ibrutinib, with or without Rituximab
Authors: Mariela Sivina, Ekaterina Kim, William G. Wierda, Alessandra Ferrajoli, Nitin Jain, Philip A. Thompson, Zeev E. Estrov, Hagop Kantarjian, Michael J. Keating, Jan A. Burger
Journal: Blood (2021)
Fear learning induces α7-nicotinic acetylcholine receptor-mediated astrocytic responsiveness that is required for memory persistence
Authors: Kuan Zhang, Rita Förster, Wenjing He, Xiang Liao, Jin Li, Chuanyan Yang, Han Qin, Meng Wang, Ran Ding, Ruijie Li, Tingliang Jian, Yanhong Wang, Jianxiong Zhang, Zhiqi Yang, Wenjun Jin, Yonghai Zhang, Song Qin, Yacheng Lu, Tao Chen, Jillian Stobart, Bruno Weber, Helmuth Adelsberger, Arthur Konnerth, Xiaowei Chen
Journal: Nature Neuroscience (2021)
Hyperpolarized 1-[13C]-Pyruvate Magnetic Resonance Imaging Detects an Early Metabolic Response to Immune Checkpoint Inhibitor Therapy in Prostate Cancer
Authors: Ivan de Kouchkovsky, Hsin-Yu Chen, Michael A. Ohliger, Zhen J. Wang, Robert A. Bok, Jeremy W. Gordon, Peder E.Z. Larson, Mary Frost, Kimberly Okamoto, Matthew R. Cooperberg, John Kurhanewicz, Daniel B. Vigneron, Rahul Aggarwal
Journal: European Urology (2021)
Abstract 9957: Totum-070 Prevents Diet-Induced Hypercholesterolemia in Western Diet Fed Mice
Authors: Cedric Langhi, Yolanda F Otero, Florian Le Joubioux, Bruno Guigas, Sébastien PELTIER, Pascal Sirvent
Journal: Circulation (2021)

It is well known that hypercholesterolemia is an important modifiable risk factor in the development of cardiovascular disease. Lowering blood cholesterol level reduces the incidence of atherosclerotic disease. TOTUM-070 (T070) is a clinical stage polyphenol-rich active substance composed by the association of 5 plant extracts. We assessed the hypothesis that administration of T070 prevents hypercholesterolemia in western diet fed mice and explored the potential mechanisms involved. C57BL/6 mice were fed either a normal diet (ND) or western diet (WD) for 6 weeks and received either vehicle or T070 (1mg/kg or 3mg/kg) daily by gavage (n=14 mice per group). Supplementation with T070 had no effect on food intake along the study duration. At the end of the study, body weight in WD-fed mice was increased to 28.3 ± 0.8 g compared to the ND group (24.5 ± 0.4 g, p&lt;0.001). Interestingly, a significant (p&lt;0.01) 29% reduction in body weight gain was observed in the T070 3mg/kg group compared to the WD group at the end of the study. Compared to WD group (298 ± 8 mg/dl), total-cholesterol in mice supplemented by T070 was reduced in a dose dependent manner (276 ± 9 mg/dl T070 1mg/kg, (p=0.19) and 265 ± 8 mg/dl T070 3mg/kg, p&lt;0.05). There was no change in triglyceridemia among the groups compared to the ND mice. However, hepatic steatosis induced by the WD was reduced by 73% (p&lt;0.001) in the T070 3mg/kg group. Hepatic and intestinal gene expression were drastically altered by WD feeding compared to ND, while supplementation with T070 tended to restore normal level of expression of many genes implicated in lipid and lipoprotein metabolism. A significant increase in feces production was observed in mice supplemented with T070 3 mg/g compared to the mice fed with WD alone (234 ± 7 mg/day WD+T070 3mg/g vs 207 ± 6 mg/day WD, p&lt;0.01), probably contributing to the beneficial phenotype induced by T070 administration. In conclusion, our results demonstrate the beneficial effect of supplementation with TOTUM-070 to prevent induction of hypercholesterolemia in a nutritional mouse model. This study highlights the interest of using TOTUM-070 for management of mild hypercholesterolemia.
Abstract 9216: Fontaine Leads and Their Further Modifications in Arrhythmogenic Cardiomyopathy
Authors: Muzaffar Ali, Deepak Padmanabhan, Bharatraj Banavalikar, Khalil Kanjwal, Ajaz A Lone, Imran Hafeez, Aamir Rashid, Hilal A Rather, Jayaprakash Shenthar
Journal: Circulation (2021)

Introduction: Epsilon wave, one of the major criteria for the diagnosis of arrhythmogenic cardiomyopathy (ACM), is present in only 30% of ACM patients. Fontaine Leads have been shown to facilitate the visualization of Epsilon waves. Hypothesis: Modified Fontaine leads may help in better visualization of Epsilon waves in ACM patients than standard Fontaine leads. Methods: We prospectively enrolled ACM patients under our follow-up. Fontaine and the modified Fontaine EKGs were recorded ( Figure 1A ). The duration and amplitude of Epsilon waves, when present, were measured. Duration-amplitude product (DAP) was computed and compared. Results: EKGs of seventeen patients were available for analysis. Four patients (24%) had an Epsilon wave on a 12 lead EKG. Thirteen patients (76%) had Epsilon waves either on 12 lead EKG or Fontaine modification leads. These 13 patients (10 males and 3 females; mean age: 40.5 ±13 years) were included in the analysis. ( Table 1 ) Epsilon waves were seen in 10 (77%) patients in Standard Fontaine Leads. In the rest of the modifications, Epsilon waves were seen in 85% (11), 77% (10), 80% (8), and 80% (8) in Right, Left, Right-Left, and Left-Right Fontaine leads, respectively. ( Table 1 ) In only one patient (8%), the Standard Fontaine Epsilon wave had maximum DAP. Right, Left, Right-Left, and Left-Right Fontaine leads had maximum DAP in 5 (39%), 3 (23%), 2 (20%), and 3 (30%) patients, respectively. Conclusions: A modified Fontaine lead position may facilitate the Epsilon wave visualization in patients suffering from ACM when standard EKG and Fontaine lead EKGs fail to do so. A well-designed randomized study may be needed to evaluate the utility of modified Fontaine Leads in ACM.
Glycomic Characterization of Platelets from Patients with Immune Thrombocytopenia
Authors: Nora V. Butta, Stuart M Haslam, Anne Dell, Leow Ke Xuan, Sophie Ball, Elena G Arias-Salgado, Elena Monzón Manzano, Paula Acuña, Miguel Canales, Víctor Jiménez-Yuste, María Teresa Alvarez Román
Journal: Blood (2021)
Changes in COVID-19 outbreak severity and duration in long-term care facilities following vaccine introduction, England, November 2020 to June 2021
Authors: Rebecca Giddings, Maria Krutikov, Tom Palmer, Christopher Fuller, Borscha Azmi, Madhumita Shrotri, Aidan Irwin-Singer, Gokhan Tut, Paul Moss, Andrew Copas, Laura Shallcross
Journal: Eurosurveillance (2021)

We describe the impact of changing epidemiology and vaccine introduction on characteristics of COVID-19 outbreaks in 330 long-term care facilities (LTCF) in England between November 2020 and June 2021. As vaccine coverage in LTCF increased and national incidence declined, the total number of outbreaks and outbreak severity decreased across the LTCF. The number of infected cases per outbreak decreased by 80.6%, while the proportion of outbreaks affecting staff only increased. Our study supports findings of vaccine effectiveness in LTCF.
Gene Therapy for Fanconi Anemia [Group A]: Interim Results of RP-L102 Clinical Trials
Authors: Agnieszka Czechowicz, Julián Sevilla, Rajni Agarwal, Claire Booth, Josune Zubicaray, Paula Río, Susana Navarro, Philip Ancliff, Elena Sebastian, Brian C Beard, Kenneth M Law, Grace Choi, Miriam Zeini, Camilla Duran-Persson, Eileen Nicoletti, John E Wagner, Gayatri R Rao, Adrian J. Thrasher, Jonathan D Schwartz, Juan A Bueren, Maria Grazia Roncarolo
Journal: Blood (2021)
The metabolic growth limitations of petite cells lacking the mitochondrial genome
Authors: Jakob Vowinckel, Johannes Hartl, Hans Marx, Martin Kerick, Kathrin Runggatscher, Markus A. Keller, Michael Mülleder, Jason Day, Manuela Weber, Mark Rinnerthaler, Jason S. L. Yu, Simran Kaur Aulakh, Andrea Lehmann, Diethard Mattanovich, Bernd Timmermann, Nianshu Zhang, Cory D. Dunn, James I. MacRae, Michael Breitenbach, Markus Ralser
Journal: Nature Metabolism (2021)
Rescue of α-synuclein aggregation in Parkinson’s patient neurons by synergistic enhancement of ER proteostasis and protein trafficking
Authors: Iva Stojkovska, Willayat Y. Wani, Friederike Zunke, Nandkishore R. Belur, Egor A. Pavlenko, Nkatha Mwenda, Karan Sharma, Laetitia Francelle, Joseph R. Mazzulli
Journal: Neuron (2021)
A Phase II Study of Prophylactic Anakinra to Prevent CRS and Neurotoxicity in Patients Receiving CD19 CAR T Cell Therapy for Relapsed or Refractory Lymphoma
Authors: Jae H Park, Craig S. Sauter, M. Lia Palomba, Gunjan L Shah, Parastoo B Dahi, Richard J Lin, Michael Scordo, Connie Lee Batlevi, Miguel-Angel Perales, Peter Kane, Aishat Olaide Afuye, Elena Mead, Bianca Santomasso, Elizabeth Halton, Michel Sadelain, Renier J Brentjens
Journal: Blood (2021)
Differential Prognostic Relevance of Measurable Residual Disease in Acute Myeloid Leukemia Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplantation in First <i>Versus</i> Second Morphologic Remission
Authors: Madlen Jentzsch, Johannes Küpper, Dominic Brauer, Donata Backhaus, Julia Schulz, Georg-Nikolaus Franke, Vladan Vucinic, Dietger Niederwieser, Uwe Platzbecker, Sebastian Schwind
Journal: Blood (2021)
Fibrin(ogen) Mechanistically Contributes to Atopic Dermatitis Pathogenesis and Allergic Sensitization
Authors: Alyssa Filuta, Peter K Amezcua, Brandy Ruff, Hua He, Lisa J Martin, Joseph S. Palumbo, Gurjit K Khurana Hershey, Michael G Sherenian
Journal: Blood (2021)
Duration and Dose of Adjuvant Zoledronic Acid for Treatment of Early Breast Cancer
Authors: Steven Sorscher
Journal: JAMA Oncology (2021)

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A Phase 1/2 Study of Lentiviral-Mediated Ex-Vivo Gene Therapy for Pediatric Patients with Severe Leukocyte Adhesion Deficiency-I (LAD-I): Interim Results
Authors: Donald B. Kohn, Claire Booth, Julián Sevilla, Gayatri R Rao, Elena Almarza, Dayna Terrazas, Eileen Nicoletti, Augustine Fernandes, Caroline Kuo, Satiro de Oliveira, Theodore B. Moore, Kenneth M Law, Brian C Beard, Grace Choi, Miriam Zeini, Cristina Mesa-Núñez, Adrian J. Thrasher, Juan A Bueren, Jonathan D Schwartz
Journal: Blood (2021)
A Randomized, Phase 3 Trial of Fedratinib Versus Best Available Therapy in Patients with Intermediate-2 or High-Risk Myelofibrosis Previously Treated with Ruxolitinib (FREEDOM2)
Authors: Nicola Vianelli, Giulia Benevolo, Alessandro Vannucchi, Claire N. Harrison, Michael Loschi, Haifa Kathrin Al-Ali, Massimiliano Bonifacio, Francisco Cervantes, Tomasz Wrobel, Giovanni Barosi, Jean-Jaques Kiladjian, Srdan Verstovsek, Ruben A. Mesa, Shelonitda Rose, Vishwanath Gharpure, Christopher Hernandez, Jun Zhang, Francesco Passamonti
Journal: Blood (2021)
Completed Induction Phase Analysis of Magnify: Phase 3b Study of Lenalidomide + Rituximab (R 2) Followed By Maintenance in Relapsed/Refractory Indolent Non-Hodgkin Lymphoma
Authors: Frederick Lansigan, David Jacob Andorsky, Morton Coleman, Abdulraheem Yacoub, Jason Melear, Suzanne Fanning, Kathryn S. Kolibaba, Christopher M. Reynolds, Grzegorz S. Nowakowski, Mecide Gharibo, Jung Ryun Ahn, Ju Li, Mathias J. Rummel, Jeff P. Sharman
Journal: Blood (2021)
Abstract 9407: Health Related Quality of Life in the Spironolactone to Reduce Icd Therapy (SPIRIT) Trial
Authors: Ana Carolina Sauer Liberato, Merritt Raitt, Ignatius G Zarraga, Karen MacMurdy, Cynthia M Dougherty
Journal: Circulation (2021)

Introduction: The Spi ronolactone to R educe I CD T herapy (SPIRIT) trial was designed to determine if once daily spironolactone would: 1) reduce the incidence of ventricular tachycardia (VT) and ventricular fibrillation (VF), and 2) improve health related quality of life (HRQOL) and symptoms over 24 months. The purpose of this study is to describe the long term HRQOL outcomes in the SPIRIT trial and compare QOL and symptoms in those who did or did not receive implantable cardioverter defibrillator (ICD) shocks. Hypothesis: Patients taking spironolactone would have higher HRQOL and fewer symptoms than those taking placebo. Methods: The SPIRIT trial was a RCT comparing spironolactone at 25 mg qd to placebo in determining impact on incidence of VT and VF and HRQOL in patients at high risk for ICD shocks. Patients were randomized to spironolactone (N=44) or placebo (N=46) and followed for 24-months. HRQOL was measured every 6 months for 24 months using 3 instruments: Patient Concerns Assessment (PCA), Short Form Health Survey-Veterans Version (SF-36V), and the Kansas City Cardiomyopathy Questionnaire (KCCQ). Linear mixed modeling was used to compare changes in HRQOL across 24-months. ANCOVA was used to compare HRQOL and symptoms between those getting an ICD shock or not. The study was conducted in the Veterans Administration (VA) health system. Results: Over 24-months, 90 patients age 66 + 10 years, 96% men, 75% with NYHA class II, with an ICD at moderately high risk for recurrent VT/VF participated. The spironolactone group received an average of 7.9 + 12.1 ICD shocks, while the placebo group received 6.8 + 14.9 ICD shocks, p=NS. There were no differences in HRQOL or symptoms between the spironolactone vs. placebo groups. The placebo group reported a lower number of symptoms over time (F=3.99, p=0.05). Those who experienced at least 1 ICD shock vs. those with no ICD shocks, reported significantly lower HRQOL (SF36V MCS, F=8.66, p=0.004) and more symptoms (PCA, F=14.5, p&lt;0.001) at 6-months and 24 months (PCA, F=9.61, p=0.003; KCCQ overall summary, F=8.68, p=0.005). Conclusions: Spironolactone had no significant impact on HRQOL or symptoms over time. Patients receiving one or more ICD shocks reported significant reductions in HRQOL and higher symptoms over 24 months.
Tiotropium treatment for bronchiectasis: a randomised, placebo-controlled, crossover trial
Authors: Lata Jayaram, Alain C. Vandal, Catherina L. Chang, Chris Lewis, Cecilia Tong, Christine Tuffery, Jill Bell, Wendy Fergusson, Gene Jeon, David Milne, Stuart Jones, Noel Karalus, Sandra Hotu, Conroy Wong
Journal: European Respiratory Journal (2021)

Background Tiotropium via the HandiHaler device is an established long-acting, anticholinergic bronchodilator that prevents exacerbations and improves lung function in patients with chronic obstructive pulmonary disease. We hypothesised that tiotropium would reduce pulmonary exacerbations and improve lung function in patients with stable bronchiectasis and airflow limitation, and assessed the effect of tiotropium on these outcomes. Methods In a randomised, double-blind, two-period crossover trial, we recruited adult patients from three hospitals in New Zealand. Patients were excluded if they had a smoking history of &gt;20 pack-years. Patients were assigned to either the tiotropium–placebo or placebo–tiotropium sequence in a 1:1 ratio, using randomly permuted blocks stratified by centre. Participants and investigators were masked to treatment allocation. Eligible patients received tiotropium 18 μg via HandiHaler daily for 6 months followed by 6 months of placebo, or vice versa , with a washout period of 4 weeks. The primary end-point was rate of event-based exacerbations during the 6-month period. Primary analyses were carried out in an intention-to-treat set. Results 90 patients were randomly assigned and 85 completed both treatment cycles. The rate of exacerbations was 2.17 per year under the tiotropium treatment and 2.27 per year under placebo (rate ratio 0.96, 95% CI 0.72–1.27; p=0.77). Tiotropium, compared with placebo, improved forced expiratory volume in 1 s by 58 mL (95% CI 23–92 mL; p=0.002). Adverse events were similar under both treatments. Conclusions Tiotropium via HandiHaler over 6 months significantly improved lung function but not frequency of exacerbations. Further research is required to understand the clinical context and significance of these findings.
Yersinia pseudotuberculosis YopE prevents uptake by M cells and instigates M cell extrusion in human ileal enteroid-derived monolayers
Authors: Alyssa C. Fasciano, Gaya S. Dasanayake, Mary K. Estes, Nicholas C. Zachos, David T. Breault, Ralph R. Isberg, Shumin Tan, Joan Mecsas
Journal: Gut Microbes (2021)

Many pathogens use M cells to access the underlying Peyer's patches and spread to systemic sites via the lymph as demonstrated by ligated loop murine intestinal models. However, the study of interactions between M cells and microbial pathogens has stalled due to the lack of cell culture systems. To overcome this obstacle, we use human ileal enteroid-derived monolayers containing five intestinal cell types including M cells to study the interactions between the enteric pathogen, Yersinia pseudotuberculosis (Yptb), and M cells. The Yptb type three secretion system (T3SS) effector Yops inhibit host defenses including phagocytosis and are critical for colonization of the intestine and Peyer's patches. Therefore, it is not understood how Yptb traverses through M cells to breach the epithelium. By growing Yptb under two physiological conditions that mimic the early infectious stage (low T3SS-expression) or host-adapted stage (high T3SS-expression), we found that large numbers of Yptb specifically associated with M cells, recapitulating murine studies. Transcytosis through M cells was significantly higher by Yptb expressing low levels of T3SS, because YopE and YopH prevented Yptb uptake. YopE also caused M cells to extrude from the epithelium without inducing cell-death or disrupting monolayer integrity. Sequential infection with early infectious stage Yptb reduced host-adapted Yptb association with M cells. These data underscore the strength of enteroids as a model by discovering that Yops impede M cell function, indicating that early infectious stage Yptb more effectively penetrates M cells while the host may defend against M cell penetration of host-adapted Yptb.
Extended Characterization of Newly Diagnosed Multiple Myeloma (NDMM) Patients with <i>In</i>-Class Transition (<i>i</i>CT) from Parenteral Bortezomib to Oral Ixazomib Proteasome Inhibitor (PI) Therapy in the Community-Based United States (US) MM-6 Study: Updated Efficacy and Safety, and Reasons for Premature Discontinuation
Authors: Robert M. Rifkin, Stephen J. Noga, Saulius K. Girnius, Kimberly Bogard, Sudhir Manda, Habte Yimer, Presley Whidden, Ruemu E. Birhiray, Philip Twumasi-Ankrah, Yikun Guo, Rami Owera, Leon Bernal-Mizrachi, Roger Lyons
Journal: Blood (2021)
HLA-Haploidentical Hematopoietic Cell Transplantation of Ex Vivo Tcrαβ-Depleted Grafts with CD45RA-Depleted Memory T Cell Add-Back in Adults and Children with Hematological Malignancies: 4-Year Follow-up of Multicenter Study in Singapore
Authors: Ian Q Wu, Yeh Ching Linn, Yang Liang Boo, Rajat Bhattacharyya, Zi Yi Lim, Michelle Poon, Michaela Su-Fern Seng, Poh Lin Tan, Colin Phipps, Balamurugan Vellayappan, Ah Moy Tan, Lip Kun Tan, Yvonne Su Ming Loh, Teck Guan Soh, Gina Gan, Yin Jie Koh, Wing H. Leung, Liang Piu Koh
Journal: Blood (2021)