tbuckley/cabot-search huggingface dataset:
Municipality-Level Variation in Severe Maternal Morbidity and Association With Municipal Expenditures in New Jersey
Authors: Felix M. Muchomba, Julien Teitler, Lakota Kruse, Nancy E. Reichman
Journal: JAMA Network Open (2021)

<h3>Importance</h3> Severe maternal morbidity (SMM) is a major risk factor for maternal mortality, yet little is known about geographic variation in SMM or factors associated with geographical variation at the local level. Municipal governments incur substantial expenditures providing services that are an essential part of residents' lives, but associations between municipal expenditures and SMM have not been previously examined. <h3>Objective</h3> To investigate variation in rates of SMM across municipalities in New Jersey, the contributions of individual-level characteristics and municipal expenditures to that variation, and associations between municipal expenditures and SMM. <h3>Design, Setting, and Participants</h3> This cross-sectional study analyzed 2008 to 2018 New Jersey birth files linked to maternal hospital discharge records and US Census municipal expenditures data. The birth files contain all birth records for New Jersey, and hospital discharge records contain information from all in-patient hospitalizations in New Jersey over the study period. Birth records were matched to maternal discharge records and expenditures data. Data were analyzed from August 2020 to August 2021. <h3>Exposures</h3> Individual-level characteristics and per capita municipal expenditures on education; public health; fire and ambulance; parks, recreation, and natural resources; housing and community development; public welfare; police; transportation; and libraries. <h3>Main Outcomes and Measures</h3> SMM was identified using diagnosis and procedure codes developed by the Centers for Disease Control and Prevention to measure SMM. <h3>Results</h3> Of 1 001 410 individuals (mean [SD] age, 29.8 [5.9] years; 108 665 Asian individuals [10.9%]; 147 910 Black individuals [14.8%]; 280 697 Hispanic individuals [28.0%]; 447 442 White individuals [44.7%]) who gave birth in New Jersey hospitals from 2008 to 2018, 19 962 individuals (2.0%) had SMM. There was substantial municipality-level variation in SMM that was not fully explained by demographic characteristics. Municipal expenditures on fire and ambulance, transportation, health, housing, and libraries were negatively associated with SMM; $1000 higher annual expenditures per capita in these categories were associated with 35.4% to 67.3% lower odds of SMM (odds ratios, 0.33 [95% CI, 0.15-0.72] to 0.65 [95% CI, 0.46-0.91]). Expenditures on police were positively associated with SMM (odds ratio, 1.15 [95% CI, 1.04-1.28]). <h3>Conclusions and Relevance</h3> The findings in this study regarding associations between spending on various types of services at the municipal level and SMM, holding constant overall spending, population size, and socioeconomic status at the municipal level, indicate that municipal budget allocation decisions were associated with SMM rates and point to the importance of future research investigating potential causal connections.
Outcome with Intensive Chemotherapy Compared to Hypomethylating Agent- Based Induction in Patients Aged 70 Years or Older with Newly Diagnosed Favorable Risk Acute Myeloid Leukemia
Authors: Somedeb Ball, Akriti G Jain, Luis E. E. Aguirre, Najla Al Ali, Jan Philipp Bewersdorf, Alexander Hayden, Alexa J. Siddon, Jillian Lykon, Ellen Madarang, David A. Sallman, Eric Padron, Kendra Sweet, Jeffrey E. Lancet, Justin M Watts, David M Swoboda, Daniel A. Pollyea, Amer M. Zeidan, Rami S. Komrokji
Journal: Blood (2021)
Abstract 9297: Assessing Cardiovascular Health in Pediatric Hypertrophic Cardiomyopathy Using the CANHEART Index
Authors: Aamir Jeewa, Tara Pidborochynski, Alyssa Power, Alliya Remtulla Tharani, Diana Balmer-Minnes, Santokh S DHILLON, Laurence Vaujois, Frederic Dallaire, Virginie Carrier, Michael Khoury, Jennifer Conway
Journal: Circulation (2021)

Introduction: Pediatric hypertrophic cardiomyopathy (HCM) is associated with sudden death often resulting in restriction from strenuous physical activity and competitive sports. Restrictions may increase the risk of poor cardiovascular (CV) health. Hypothesis: CV health, as measured by the Cardiovascular Health in Ambulatory Care Research Team (CANHEART) health index (https://www.cmaj.ca/content/cmaj/186/3/180.full.pdf) are lower in pediatric HCM compared to other Canadian children. Methods: Pediatric HCM patients between age 10 and 18 years were prospectively recruited at 5 Canadian sites and assessed using the CANHEART health index. The index uses four factors for the definition of ideal CV health: never smoked, body mass index (BMI), fruit and vegetable (veg) consumption &gt; 5 times/day and walking &gt;60 minutes walking or 20 mins of running/jogging per day. Ideal health is defined by the presence of all four factors and poor health 0-2 factors. Results: There were 36 subjects enrolled in the study [27 males; median age 14.8 years (10-18); median BMI 24 (17-37)]. With regards to CANHEART health index results, 50% (n=18) were overweight/obese, 56% (n= 20) walked &lt;60 minutes or ran/jogged &lt;20 min per day, 70% consumed fruits/veg &lt; 5 times/day and 94.4% had never smoked. The mean CANHEART index score was 2.19 (95 th CI 1.87-2.52) compared to the previously reported for Canadian youths without HCM (2.49 95% CI 2.47-2.52). Ideal CV health was seen in 11.1% (n=5) of HCM patients with poor health in 66.7% (n=24) [See Table 1]. Conclusions: A small percentage of pediatric HCM patients had ideal CV health as defined by the CANHEART index and the mean score was lower than previous reported in the CANHEART population study. These finding are predominantly driven by a lack of fruit/veg consumption, poor physical activity and BMI. CV profiling for pediatric HCM patients should be considered as part of the longitudinal care to help decrease the risk of premature CV disease in adulthood.
Functional Roles of <i>DDX41</i> Mutations in the Development of Myeloid Malignancies
Authors: Ayana Kon, Masahiro Marshall Nakagawa, Keisuke Kataoka, Hideki Makishima, Manabu Nakayama, Haruhiko Koseki, Yasuhito Nannya, Seishi Ogawa
Journal: Blood (2021)
Venetoclax, Obinutuzumab and Atezolizumab (PD-L1 Checkpoint Inhibitor) for Treatment for Patients with Richter Transformation
Authors: Nitin Jain, Alessandra Ferrajoli, Philip A. Thompson, Marina Konopleva, Michael R Green, Deepa Sampath, Sattva S. Neelapu, Koichi Takahashi, Paolo Strati, Jan A. Burger, Rashmi Kanagal-Shamanna, Joseph D. Khoury, Naveen Garg, Xiaoping Su, Xuemei Wang, Hinalben Patel, Ana Ayala, Hagop Kantarjian, Michael J. Keating, William G. Wierda
Journal: Blood (2021)
Impact of Timing and Precision of Histopathological Diagnosis on Outcomes of Patients with Burkitt and High-Grade B-Cell Lymphoma
Authors: Jan-Michel Heger, Claus Moritz Graef, Philipp Falderbaum, Philipp Gödel, Hyatt Balke-Want, Florian Simon, Noëlle Sieg, Jan-Hendrik Naendrup, Marie Anne-Catherine Neumann, Sarah Gillessen, Paul J Bröckelmann, Dennis A. Eichenauer, Peter Borchmann, Bastian Von Tresckow
Journal: Blood (2021)
TRAF6 prevents fatal inflammation by homeostatic suppression of MALT1 protease
Authors: Thomas J. O’Neill, Thomas Seeholzer, Andreas Gewies, Torben Gehring, Florian Giesert, Isabel Hamp, Carina Graß, Henrik Schmidt, Katharina Kriegsmann, Marie J. Tofaute, Katrin Demski, Tanja Poth, Marc Rosenbaum, Theresa Schnalzger, Jürgen Ruland, Martin Göttlicher, Mark Kriegsmann, Ronald Naumann, Vigo Heissmeyer, Oliver Plettenburg, Wolfgang Wurst, Daniel Krappmann
Journal: Science Immunology (2021)

Balanced control of T cell signaling is critical for adaptive immunity and protection from autoimmunity. By combining genetically engineered mouse models, biochemical analyses and pharmacological interventions, we describe an unexpected dual role of the tumor necrosis factor receptor–associated factor 6 (TRAF6) E3 ligase as both a positive and negative regulator of mucosa-associated lymphoid tissue 1 (MALT1) paracaspase. Although MALT1-TRAF6 recruitment is indispensable for nuclear factor κB signaling in activated T cells, TRAF6 counteracts basal MALT1 protease activity in resting T cells. In mice, loss of TRAF6-mediated homeostatic suppression of MALT1 protease leads to severe autoimmune inflammation, which is completely reverted by genetic or therapeutic inactivation of MALT1 protease function. Thus, TRAF6 functions as a molecular brake for MALT1 protease in resting T cells and a signaling accelerator for MALT1 scaffolding in activated T cells, revealing that TRAF6 controls T cell activation in a switch-like manner. Our findings have important implications for development and treatment of autoimmune diseases.
Abstract 9156: P-Wave Axis is an Independent Predictor of Mortality in Type II Diabetes Mellitus: The Diabetes Heart Study
Authors: Pooja D Patil, Matthew J Singleton, Georgia Saylor, Donald Bowden, Joseph Yeboah
Journal: Circulation (2021)

Introduction: Abnormal P-wave axis (PWA) has been associated with an increased risk of all-cause and cardiovascular mortality in various populations. However, the correlation of this prognostic indicator with mortality has not been systematically studied in patients with type II diabetes mellitus (T2DM) over a long-term period. The aim of this study was to investigate the association between abnormal PWA and all-cause mortality in participants from the Diabetes Heart Study (DHS). Methods: Out of the 1,443 participants in the DHS, 1,101 participants with T2DM and PWA data from electrocardiogram were included in the analysis. Kaplan-Meier (KM) and Cox proportional hazards models were used to analyze the association between PWA and mortality, adjusting for demographics and other potential confounding variables. Results: 85 of the 1,101 participants (7.7%) had abnormal PWA. The mean age of all participants was 61.8 ± 8.9 years, with 45.7% of participants being male. Over a mean follow-up of 12.1 ± 4.4 years, a total of 504 deaths (45.8%) occurred. KM analysis showed that participants with abnormal PWA had a significantly higher rate of death than those with normal PWA (Log-Rank p&lt;0.0001). Abnormal PWA was associated with increased risk of mortality (HR: 1.75, 95% CI: 1.31-2.29). After multivariable adjustment, the association remained significant (HR: 1.55, 95% CI: 1.14-2.06). Interaction analysis demonstrated a significant interaction between race and PWA group (p=0.03). Subgroup analysis showed increased risk of mortality with abnormal PWA in white participants, but no significant association between mortality and abnormal PWA in black participants (p=0.81). Conclusions: Abnormal PWA is independently associated with increased risk of mortality in a cohort of participants with T2DM. Further research on the association between race, PWA, and mortality risk is warranted. PWA may serve as an independent prognostic indicator of mortality risk in patients with T2DM.
Safety and Tolerability of Cael-101 in Combination with Anti-Plasma Cell Dyscrasia Therapy in Patients with AL Amyloidosis: 1-Year Results from an Open-Label Phase 2 Trial
Authors: Jason Valent, Jeffrey A. Zonder, Michaela Liedtke, John Silowsky, Michael R. Kurman, Eileen Daniel, Janet Jobes, Mark Harnett, Jessica Raviwong, Michael Spector, Susan B. Sobolov
Journal: Blood (2021)
Cell transplantation and secretome based approaches in spinal cord injury regenerative medicine
Authors: Rita C. Assunção Silva, Luísa Pinto, António J. Salgado
Journal: Medicinal Research Reviews (2021)

Abstract The axonal growth‐restrictive character of traumatic spinal cord injury (SCI) makes finding a therapeutic strategy a very demanding task, due to the postinjury events impeditive to spontaneous axonal outgrowth and regeneration. Considering SCI pathophysiology complexity, it has been suggested that an effective therapy should tackle all the SCI‐related aspects and provide sensory and motor improvement to SCI patients. Thus, the current aim of any therapeutic approach for SCI relies in providing neuroprotection and support neuroregeneration. Acknowledging the current SCI treatment paradigm, cell transplantation is one of the most explored approaches for SCI with mesenchymal stem cells (MSCs) being in the forefront of many of these. Studies showing the beneficial effects of MSC transplantation after SCI have been proposing a paracrine action of these cells on the injured tissues, through the secretion of protective and trophic factors, rather than attributing it to the action of cells itself. This manuscript provides detailed information on the most recent data regarding the neuroregenerative effect of the secretome of MSCs as a cell‐free based therapy for SCI. The main challenge of any strategy proposed for SCI treatment relies in obtaining robust preclinical evidence from in vitro and in vivo models, before moving to the clinics, so we have specifically focused on the available vertebrate and mammal models of SCI currently used in research and how can SCI field benefit from them.
Abstract 9154: Sex Differences in Mortality from Covid-19 Pandemic: Are Men Vulnerable and Women Protected. Why?
Authors: Khalida Soomro, Muhammad Ali Soomro
Journal: Circulation (2021)

The epidemiological studies shows that compared to women, men infected with the novel COVID-19 have more severe and threatening disease and have a higher mortality globally. The population which is under real panic comprises older men. The reason could be linked to sex chromosome genes and sex hormones with differential regulation of immune responses between the sexes. Objectives of Study: We need to recognize the phenotypical differences in severe case manifestations of COVID-19 in men and women as a fundamental step to understand the effects of this health emergency. Study Design/Methodological/Approach: The study was designed upon factors that are the major cause of gender inequality of infection. The statistical data was collected from the official record of COVID-19 Emergency Centre established in OJHA Centre Dow University Karachi. Results: It was found that, the mortality rate is very high in men. Less deaths of patients younger than 40 years even in past coronavirus leading to severe acute respiratory SARS-CoV, were found to infect more men than women. This may be due to not required enhanced response to infections on reproductive function in young men population, enhanced immune reactivity along with changes in immune cells during aging and pleiotropic nature of many genes. Conclusion: Evidence from this study tells us that sex is an important driver of risk of mortality and response to the COVID-19 pandemic. Age distribution is related with increased mortality rate among men, especially the older age men. Further research is warranted to investigate hormonal, inflammatory, immunologic, and phenotypical differences in severe COVID-19 disease presentations.
Erythropoietic properties of human induced pluripotent stem cells‐derived red blood cells in immunodeficient mice
Authors: Jiusheng Deng, Moira Lancelot, Ryan Jajosky, Qiaomei Deng, Kristin Deeb, Natia Saakadze, Yongxing Gao, David Jaye, Senquan Liu, Sean R. Stowell, Linzhao Cheng, John D. Roback
Journal: American Journal of Hematology (2021)

Transfusion of red blood cells (RBCs) is a life-saving intervention for anemic patients. Human induced pluripotent stem cells (iPSC) have the capability to expand and differentiate into RBCs (iPSC-RBCs). Here we developed a murine model to investigate the in vivo properties of human iPSC-RBCs. iPSC lines were produced from human peripheral blood mononuclear cells by transient expression of plasmids containing OCT4, SOX2, MYC, KLF4, and BCL-XL genes. Human iPSC-RBCs were generated in culture supplemented with human platelet lysate, and were CD34- CD235a+ CD233+ CD49dlow CD71low ; about 13% of iPSC-RBCs were enucleated before transfusion. Systemic administration of clodronate liposomes (CL) and cobra venom factor (CVF) to NOD scid gamma (NSG) mice markedly promoted the circulatory survival of human iPSC-RBCs following transfusion. While iPSC-RBCs progressively decreased with time, 90% of circulating iPSC-RBCs were enucleated 1 day after transfusion (CD235a+ CD233+ CD49d- CD71- ). Surprisingly, human iPSC-RBCs reappeared in the peripheral circulation at 3 weeks after transfusion at levels more than 8-fold higher than at 1 h after transfusion. Moreover, a substantial portion of the transfused nucleated iPSC-RBCs preferentially homed to the bone marrow, and were detectable at 24 days after transfusion. These results suggest that nucleated human iPSC-derived cells that homed to the bone marrow of NSG mice retained the capability to complete differentiation into enucleated erythrocytes and egress the bone marrow into peripheral blood. The results offer a new model using human peripheral blood-derived iPSC and CL/CVF-treated NSG mice to investigate the development and circulation of human erythroid cells in vivo.
Platelet-Rich Plasma Injection vs Sham Injection and Tendon Dysfunction in Patients With Chronic Midportion Achilles Tendinopathy
Authors: Gerard A. Malanga, Ken Mautner, Don Buford
Journal: JAMA (2021)

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Development of allogeneic HSC-engineered iNKT cells for off-the-shelf cancer immunotherapy
Authors: Yan-Ruide Li, Yang Zhou, Yu Jeong Kim, Yanni Zhu, Feiyang Ma, Jiaji Yu, Yu-Chen Wang, Xianhui Chen, Zhe Li, Samuel Zeng, Xi Wang, Derek Lee, Josh Ku, Tasha Tsao, Christian Hardoy, Jie Huang, Donghui Cheng, Amélie Montel-Hagen, Christopher S. Seet, Gay M. Crooks, Sarah M. Larson, Joshua P. Sasine, Xiaoyan Wang, Matteo Pellegrini, Antoni Ribas, Donald B. Kohn, Owen Witte, Pin Wang, Lili Yang
Journal: Cell Reports Medicine (2021)

Cell-based immunotherapy has become the new-generation cancer medicine, and "off-the-shelf" cell products that can be manufactured at large scale and distributed readily to treat patients are necessary. Invariant natural killer T (iNKT) cells are ideal cell carriers for developing allogeneic cell therapy because they are powerful immune cells targeting cancers without graft-versus-host disease (GvHD) risk. However, healthy donor blood contains extremely low numbers of endogenous iNKT cells. Here, by combining hematopoietic stem cell (HSC) gene engineering and in vitro differentiation, we generate human allogeneic HSC-engineered iNKT (AlloHSC-iNKT) cells at high yield and purity; these cells closely resemble endogenous iNKT cells, effectively target tumor cells using multiple mechanisms, and exhibit high safety and low immunogenicity. These cells can be further engineered with chimeric antigen receptor (CAR) to enhance tumor targeting or/and gene edited to ablate surface human leukocyte antigen (HLA) molecules and further reduce immunogenicity. Collectively, these preclinical studies demonstrate the feasibility and cancer therapy potential of AlloHSC-iNKT cell products and lay a foundation for their translational and clinical development.
ALK Inhibitor Plus Vinblasitine for Refractory/Relapsed Pediatric ALK+ Anaplastic Large Cell Lymphoma: A Prospective, One-Arm, Open-Label Real-World Study
Authors: Wenqun Zhang, Shan Wang, Jing Yang, Bo Hu, Ying Liu, Ling Jing, Qing Zhu, Yang Liu, Qinlong Zheng, Chunju Zhou, Zifen Gao, Yonghong Zhang
Journal: Blood (2021)
T-MDS Is a Distinct Clinical and Pathological Entity Characterized By Better Survival Compared to t-AML
Authors: Mithun V. Shah, Rakchha Chhetri, Urshila Durani, Monika Kutyna, Hassan B. Alkhateeb, Mark R. Litzow, William J Hogan, Deepak Singhal, Siddarth Nayar, Ayalew Tefferi, Kebede H. Begna, Devendra Hiwase
Journal: Blood (2021)
Correction: CXCL12γ Promotes Metastatic Castration-Resistant Prostate Cancer by Inducing Cancer Stem Cell and Neuroendocrine Phenotypes
Authors: Younghun Jung, Frank C. Cackowski, Kenji Yumoto, Ann M. Decker, Jingcheng Wang, Jin Koo Kim, Eunsohl Lee, Yugang Wang, Jae-Seung Chung, Amy M. Gursky, Paul H. Krebsbach, Kenneth J. Pienta, Todd M. Morgan, Russell S. Taichman
Journal: Cancer Research (2021)

In the original version of this article (1), there was an error in Fig. 3C.Specifically,
Azacitidine, Venetoclax and Pevonedistat As Frontline Therapy for Patients with Secondary Acute Myeloid Leukemia Who Are Unfit for Intensive Chemotherapy: Results from a Phase I/II Study
Authors: Nicholas J. Short, Guillermo Montalban-Bravo, Yesid Alvarado, Marina Konopleva, Elias J. Jabbour, Guillermo Garcia-Manero, Musa Yilmaz, Nitin Jain, Gautam Borthakur, Courtney D. DiNardo, Naval Daver, Ghayas C. Issa, Maro Ohanian, Naveen Pemmaraju, Koji Sasaki, Abhishek Maiti, Kelly S. Chien, Farhad Ravandi, Tapan M. Kadia, Michael Andreeff, Muharrem Muftuoglu, Ricardo Delumpa, Prithviraj Bose, Sherry A. Pierce, Lourdes Waller, Glenda Banks, Hagop Kantarjian, Jorge E. Cortes
Journal: Blood (2021)
Synergistic Combination Activity of the Novel GSPT1 Degrader CC-90009 in Acute Myeloid Leukemia Models
Authors: Daniel W. Pierce, Tsun-Wen Sheena Yao, Emily Pace, Hongbin Wang, Pierre Flandin-Blety, Alicia Benitez, Carla Guarinos, Matthew Hoffmann, Soraya Carrancio, Jinhong Fan, Michael Pourdehnad
Journal: Blood (2021)