tbuckley/cabot-search huggingface dataset:
Abstract 12968: Impact of Loop Diuretics Use on Skeletal Muscle Depletion Among Patients Being Evaluated for Known or Suspected Coronary Artery Disease a Propensity Score Matching Analysis
Authors: Yuki Sahashi
Journal: Circulation (2020)

Background: It is well known that sarcopenia worsens the prognosis among patients with heart failure (HF). Causes and incidence of sarcopenia in patients with HF have become more important because of the increasing number of elderly HF patients worldwide. Although previous basic research suggested that loop diuretics can lead skeletal muscle depletion, the relationship has not been clarified in the clinical settings. The purpose of this study is to investigate the relationship between skeletal muscle loss and use of loop diuretics in patients with HF. Methods: We retrospectively evaluated 178 patients being evaluated for known or suspected coronary artery disease with cardiac catheterization from January 2010 to January 2019 and receiving abdominal computed tomography (CT) both baseline and at follow-up (mean 522 days).The skeletal muscle cross-sectional area was measured using CT scan at the level of third vertebra and total volume of the skeletal muscle cross-sectional area with five slices every 1mm apart was evaluated. Impact of loop-diuretics use on skeletal muscle depletion and overall survival was evaluated using 1:1 propensity score (PS) matching analysis. Results: A total of fifty-eight patients were evaluated (twenty-nine patients in both loop-diuretics use group and non-loop group) after 1:1 PS matching. The median absolute muscle-loss volume was significantly larger in loop diuretics use group (714 cm 2 ) compared to non-loop group (73.3cm 2 ). (p=0.026) Univariable analysis revealed that duration-adjusted skeletal muscle depletion volume was significantly associated with loop diuretic use (Δ=480cm 2 /year: 95% confidence interval, 64.1-897: p=0.024). Median overall survival was 796 days in the loop-diuretics use group and 865 days in the non-loop diuretics group (hazard ratio 0·99, 95% CI 0·35-2.75; p=0.979). Conclusion: Our study suggested that the use of loop diuretics can be related with skeletal muscle loss among patients being evaluated for known or suspected coronary artery disease.
Viral infection of the ovaries compromises pregnancy and reveals innate immune mechanisms protecting fertility
Authors: Jelena Tomac, Marija Mazor, Berislav Lisnić, Mijo Golemac, Daria Kveštak, Marina Bralić, Lidija Bilić Zulle, Melanie M. Brinkmann, Lars Dölken, Line S. Reinert, Soren R. Paludan, Astrid Krmpotić, Stipan Jonjić, Vanda Juranić Lisnić
Journal: Immunity (2021)
Nanoparticle encapsulation of non-genotoxic p53 activator Inauhzin-C for improved therapeutic efficacy
Authors: Nimisha Bhattarai, Jieqiong Wang, Daniel Nguyen, Xiaoxiao Yang, Linh Helmers, Jennifer Paruch, Li Li, Yiwei Zhang, Kun Meng, Alun Wang, Janarthanan Jayawickramarajah, Binghe Wang, Shelya Zeng, Hua Lu
Journal: Theranostics (2021)

The tumor suppressor protein p53 remains in a wild type but inactive form in ~50% of all human cancers. Thus, activating it becomes an attractive approach for targeted cancer therapies. In this regard, our lab has previously discovered a small molecule, Inauhzin (INZ), as a potent p53 activator with no genotoxicity.
Abstract 14871: APD588, a Novel, Selective S1P Receptor Modulator, Regulates Inflammatory Responses and Attenuates Cardiac Dysfunction Following Experimental Myocardial Infarction in Mice
Authors: Nathalie Nguyen, Martina Zarak Crnkovic, Liomar A Neves, Hongjian Wang, Teresa Martinez, Michael R Gralinski, John W Adams
Journal: Circulation (2020)

Recent studies have determined that chronic inflammation contributes to left ventricular (LV) remodeling following myocardial infarction (MI) leading to heart failure (HF). Evidence points to a critical role of T lymphocytes in driving the maladaptive inflammatory process associated with adverse tissue remodeling and cardiac dysfunction. FTY720, a non-selective sphingosine 1-phosphate (S1P) receptor modulator, elicits anti-inflammatory effects via inhibition of lymphocyte egress from secondary lymphoid organs and has been reported to improve cardiac remodeling and function post-MI. We hypothesized that APD588, a next-generation S1P receptor modulator with optimized S1P 1,5 receptor selectivity, would prevent cardiac remodeling and dysfunction following MI through modulation of T lymphocyte-mediated inflammatory responses. Efficacy of APD588 on cardiac function was assessed using C57BL/6N mice (n=7-10 mice/group) with experimental MI induced by coronary artery occlusion. Vehicle (VEH) or APD588 (0.3 mg/kg) was administered orally once daily starting at Day 3 post-MI and continued until Day 28. Blood samples were collected at Days 7 and 28 for lymphocyte count. Echocardiographic measurements, including LV ejection fraction (LVEF), were performed on Days 7, 14, and 28 post-MI. Administration of APD588 following MI resulted in a reduction of lymphocyte count at Days 7 and 28 post-MI, but only reached significance in the latter (VEH: 3.3 ± 0.5 x10 3 /μL; APD588: 1.3 ± 0.2 x10 3 /μL). Decreased cardiac function was observed at Day 7 post-MI (LVEF: 27.7 ± 3.6%, MI vs 45.7 ± 0.6%, Sham). No difference in LVEF was observed 7 days post-MI, however APD588 significantly improved LVEF at Day 28 post-MI, compared to vehicle (APD588: 35.7 ± 3.9%; VEH: 25.3 ± 3.9%). Therapies targeting inflammation in the pathophysiology of HF have shown limited success in the clinic. Novel strategies based on advancements in understanding the underlying immunobiology are warranted. Our results demonstrate that APD588 was effective at regulating lymphocyte activity and improved cardiac functional recovery following MI in mice. This supports the potential of S1P receptor modulation and other T lymphocyte-directed strategies as a targeted anti-inflammatory approach in HF.
Histiocytosis and the nervous system: from diagnosis to targeted therapies
Authors: Fleur Cohen Aubart, Ahmed Idbaih, Jean-François Emile, Zahir Amoura, Omar Abdel-Wahab, Benjamin H Durham, Julien Haroche, Eli L Diamond
Journal: Neuro-Oncology (2021)

Abstract Histiocytoses are heterogeneous hematopoietic diseases characterized by the accumulation of CD68(+) cells with various admixed inflammatory infiltrates. The identification of the pivotal role of the mitogen-activated protein kinase (MAPK) pathway has opened new avenues of research and therapeutic approaches. We review the neurologic manifestations of 3 histiocytic disorders with frequent involvement of the brain and spine: Langerhans cell histiocytosis (LCH), Erdheim-Chester disease (ECD), and Rosai-Dorfman-Destombes disease (RDD). Central nervous system (CNS) manifestations occur in 10%-25% of LCH cases, with both tumorous or neurodegenerative forms. These subtypes differ by clinical and radiological presentation, pathogenesis, and prognosis. Tumorous or degenerative neurologic involvement occurs in 30%-40% of ECD patients and affects the hypothalamic-pituitary axis, meninges, and brain parenchyma. RDD lesions are typically tumorous with meningeal or parenchymal masses with strong contrast enhancement. Unlike LCH and ECD, neurodegenerative lesions or syndromes have not been described with RDD. Familiarity with principles of evaluation and treatment both shared among and distinct to each of these 3 diseases is critical for effective management. Refractory or disabling neurohistiocytic involvement should prompt the consideration for use of targeted kinase inhibitor therapies.
Abstract 13546: Chromogranin-A Levels Differentiate Takotsubo From Acute Coronary Syndrome and Congestive Heart Failure in Women: A Single-center Case-control Study
Authors: Nicola Tarantino, Francesco Santoro, Luigi Di Biase, Vito Di Terlizzi, Domenico G Della Rocca, Eric D Manheimer, CHINTAN TRIVEDI, Enrica Vitale, Michela Faggioni, Nicole S De Leon De La Cruz, Matteo Di Biase, Natale D Brunetti
Journal: Circulation (2020)

Background: Takotsubo syndrome (TTS) has been reported in up to 10% of women with a clinical presentation suggestive of acute coronary syndrome (ACS), making the differential diagnosis challenging. Chromogranin-A (CgA) is a pro-hormone co-released with catecholamines. Elevated levels of CgA are found in ACS and in exacerbations of congestive heart failure (CHF), indicating an imbalance of the neuroendocrine system. Hypothesis: CgA levels in women with TTS might differ from levels in other conditions featuring acute heart failure. Methods: We systematically screened CgA levels in 54 consecutive women admitted with TTS (n=29) or either CHF exacerbation or ACS (n=25) between November 2016 and September 2019. Clinical parameters including left ventricle ejection fraction, in-hospital events, troponin I (TnI), creatinine, and natriuretic peptide type B (NT-pro-BNP) values were recorded. Only samples obtained within 24 hours from symptom onset were analyzed. We excluded 18 subjects with TTS and 6 with ACS/CHF because of a history of cancer, chronic kidney disease &gt;III stage, liver cirrhosis, or autoimmune disease. Results: Patients with TTS (Group 1, n=11) were compared with patients with ACS/CHF (Group 2, n=19). Subjects in Group 1 were significantly younger (mean age 67 vs 80, p&lt;0.01) and presented with remarkably lower levels of CgA compared to Group 2 (1.57 nMol/l, IQR 0.56-4.6 vs 7.46, IQR 1.1-17.15, normal value &lt;3 nMol/l, p&lt;0.002), even adjusting for confounders such as the use of proton pump inhibitors, hypertension, and renal function. When controlling for age, there was a significant association between being in Group 2 and higher mean levels of CgA (p&lt;0.03). At ROC curve analysis, CgA was the best predictor of TTS vs ACS/CHF when compared with TnI and NT-pro-BNP levels (AUC 0.85, 95% C.I. 0.72-0.98; 0.59, 95% C.I. 0.31-0.86; 0.5, 95% C.I. 0.28-0.72, respectively). CgA levels &lt;5.32 could discriminate TTS from ACS/CHF with positive and negative predictive values of 22 and 100% respectively (accuracy 68%). Conclusion: In our population, systemic CgA levels collected within 24 hours from symptom onset were significantly lower in women with TTS compared to ACS/CHF, possibly indicating a different acute neuroendocrine pattern.
Distinct immune signatures in chronic lymphocytic leukemia and Richter syndrome
Authors: Yucai Wang, Sutapa Sinha, Linda E. Wellik, Charla R. Secreto, Karen L. Rech, Timothy G. Call, Sameer A. Parikh, Saad S. Kenderian, Eli Muchtar, Suzanne R. Hayman, Amber B. Koehler, Daniel L. Van Dyke, Jose F. Leis, Susan L. Slager, Haidong Dong, Neil E. Kay, Rong He, Wei Ding
Journal: Blood Cancer Journal (2021)

Abstract Richter syndrome (RS) refers to transformation of chronic lymphocytic leukemia (CLL) to an aggressive lymphoma, most commonly diffuse large B-cell lymphoma. RS is known to be associated with a number of genetic alterations such as TP53 and NOTCH1 mutations. However, it is unclear what immune microenvironment changes are associated with RS. In this study, we analyzed expression of immune checkpoint molecules and infiltration of immune cells in nodal samples, and peripheral blood T-cell diversity in 33 CLL and 37 RS patients. Compared to CLL, RS nodal tissue had higher PD-L1 expression in histiocytes and dendritic cells (median 16.6% vs. 2.8%, P &lt; 0.01) and PD1 expression in neoplastic B cells (median 26.0% vs. 6.2%, P &lt; 0.01), and higher infiltration of FOXP3-positive T cells (median 1.7% vs. 0.4%, P &lt; 0.01) and CD163-positive macrophages (median 23.4% vs. 9.1%, P &lt; 0.01). In addition, peripheral blood T-cell receptor clonality was significantly lower in RS vs. CLL patients (median [25th–75th], 0.107 [0.070–0.209] vs. 0.233 [0.111–0.406], P = 0.046), suggesting that T cells in RS patients were significantly more diverse than in CLL patients. Collectively these data suggest that CLL and RS have distinct immune signatures. Better understanding of the immune microenvironment is essential to improve immunotherapy efficacy in CLL and RS.
Effects of speech therapy for transgender women: A systematic review
Authors: Clara Leyns, Tine Papeleu, Peter Tomassen, Guy T’Sjoen, Evelien D’haeseleer
Journal: International Journal of Transgender Health (2021)

Background: For transgender women, communication and speech characteristics might not be congruent with their gender expressions. This can have a major influence on their psychosocial functioning. Higher quality of life scores were observed the more their voice was perceived as feminine. Speech language pathologists may play an important role in this, as the gender affirming hormone treatment for transgender women does not affect the voice.Aim: This systematic review aimed to provide speech and language pathologists with the current literature concerning the effects of speech therapy in transgender women in terms of acoustic and perceptual outcomes.Methods: Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) was used for reporting this systematic review. The Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (using the PubMed interface) and Embase (using the embase.com interface) were used as electronic databases. All individual studies which measured the effects of speech therapy in transgender women were evaluated with a risk of bias assessment tool and levels of evidence. Relevant data were extracted from these studies and a narrative synthesis was performed.Results: 14 studies were identified through the databases and other sources. These studies show positive outcome results concerning pitch elevation, oral resonance, self-perception and listener perception. However, methodological issues contribute to problems with generalization and reproducibility of the studies.Conclusion: There is an urgent need for effectiveness studies using RCT designs, larger sample sizes, multidimensional voice assessments, well-described therapy programs, investigators blinded to study process, and longer-term follow-up data. Speech and language pathologists who work with transgender women may find these results essential for defining therapy goals.
Abstract 16195: Socioeconomic Disadvantage is Associated With Higher Long-Term Cardiovascular Mortality Following Myocardial Infarction: The YOUNG-MI Registry
Authors: Adam N Berman, David W Biery, Avinainder Singh, Jonggyu Baek, Wanda Y Wu, Rishi K Wadhera, Sanjay Divakaran, Ersilia M DeFilippis, Jon Hainer, Christopher P Cannon, Jorge Plutzky, Donna M Polk, Khurram Nasir, MARCELO F DI CARLI, Arlene Ash, Deepak L Bhatt, Ron Blankstein
Journal: Circulation (2020)

Introduction: Living in a disadvantaged neighborhood is associated with developing cardiovascular disease and poor health outcomes. We hypothesized that socioeconomic disadvantage - as measured by neighborhood level factors - is associated with cardiovascular (CV) mortality for patients who experienced a myocardial infarction (MI) at a young age. Methods: Retrospective cohort study of patients with a first MI at age &lt;50 years treated at two medical centers from 2000 - 2016. Each patient’s home address was mapped to their census block group (CBG), a geographically compact region containing ~ 600 to 3000 people. For each CBG, we obtained the Neighborhood Stress Score (NSS) - a standardized score based on 7 census variables that Massachusetts Medicaid uses to measure socioeconomic stress. Patients were assigned an NSS score based on their CBG and stratified into tertiles of risk. Higher scores indicate greater socioeconomic disadvantage. We used Cox proportional hazards modeling to evaluate the association of NSS with CV mortality. Results: Of 2097 patients (median age 44; 19% female), addresses were available for 96%. The median NSS score was -0.31, with scores ranging from -1.11 to 5.33. Higher NSS scores were associated with public insurance, hypertension, diabetes, smoking cigarettes, and illicit drug use. Over a median follow-up of 11 years, 12.7% of individuals in the top tertile died versus 7.5% in the bottom tertile, p=0.002. After adjusting for age, sex, race, diabetes, hypertension, dyslipidemia, creatinine, tobacco smoking, use of alcohol or illicit drugs, cardiac catheterization, and statin or aspirin at discharge, each 1-point increase in NSS was associated with a 25% increase in CV mortality (adjusted HR = 1.25, [95% CI 1.01 - 1.55], p=0.045). Conclusion: Among patients experiencing an MI at a young age, socioeconomic disadvantage was associated with higher CV mortality. Our data suggest that neighborhood factors have an important effect on post-MI survival.
<i>SGK1</i> mutations in DLBCL generate hyperstable protein neoisoforms that promote AKT independence
Authors: Jie Gao, Eirini Sidiropoulou, Ieuan Walker, Joanna A. Krupka, Karol Mizielinski, Zelvera Usheva, Shamith A. Samarajiwa, Daniel J. Hodson
Journal: Blood (2021)
Bacterial Evolutionary Precursors of Eukaryotic Copper–Zinc Superoxide Dismutases
Authors: Gareth S A Wright
Journal: Molecular Biology and Evolution (2021)

Abstract Internalization of a bacteria by an archaeal cell expedited eukaryotic evolution. An important feature of the species that diversified into the great variety of eukaryotic life visible today was the ability to combat oxidative stress with a copper–zinc superoxide dismutase (CuZnSOD) enzyme activated by a specific, high-affinity copper chaperone. Adoption of a single protein interface that facilitates homodimerization and heterodimerization was essential; however, its evolution has been difficult to rationalize given the structural differences between bacterial and eukaryotic enzymes. In contrast, no consistent strategy for the maturation of periplasmic bacterial CuZnSODs has emerged. Here, 34 CuZnSODs are described that closely resemble the eukaryotic form but originate predominantly from aquatic bacteria. Crystal structures of a Bacteroidetes bacterium CuZnSOD portray both prokaryotic and eukaryotic characteristics and propose a mechanism for self-catalyzed disulfide maturation. Unification of a bacterial but eukaryotic-like CuZnSOD along with a ferredoxin-fold MXCXXC copper-binding domain within a single polypeptide created the advanced copper delivery system for CuZnSODs exemplified by the human copper chaperone for superoxide dismutase-1. The development of this system facilitated evolution of large and compartmentalized cells following endosymbiotic eukaryogenesis.
Abstract P098: Effects Of Occupational Radiation Exposure On The Prevalence Of Hypertension And Its Complications
Authors: Rithika Thirumal, Catherine Vanchiere, Ruchi Bhandari, Sania Jiwani, Ronald Horswell, San Chu, Surbhi Chamaria, Pavan Katikaneni, Marjan Boerma, Steven R Bailey, Paari Dominic
Journal: Circulation (2021)

Background: Advancement of fluoroscopy-assisted procedures in the field of medicine has led to an increase in the frequency of their use among cardiologists, radiologists and surgeons. The personal health risk involved with radiation exposure is of concern and has come under the limelight in recent times. In addition to other consequences, radiation has been linked to cardiovascular disease, but its significance is not well established. Methods: Self-reported demographic, social, occupational, and medical data was collected from board-certified cardiologists via an electronic survey. Bivariate and multivariable logistic regression analyses were performed. Results: 1478 responses were collected from board-certified cardiologists; 85.4% were males, 79% were Caucasian and 66.1% were ≤65 yrs of age. 35.6% of respondents were interventional cardiologists and 16.4% were electrophysiologists. Of those who performed procedures, 92.2% wore lead apparel during all times of radiation exposure. Exposure hours, stratified by less or more than 20,000, correlated positively with the presence of hypertension, and remained significant when adjusted for common risk factors such as age, sex, race, DM, OSA, and alcohol/tobacco use (OR 1.63 CI 1.16 to 2.29, p = 0.005). Conclusion: This study captures self-reported data of just over 4% of cardiologists in the US, and demonstrates a positive correlation between hypertension and procedural radiation exposure hours even post-adjustment for traditional risk factors. As the use of fluoroscopy-assisted procedures continues to grow, further research is necessary to inform operators of the personal health risks of radiation exposure and drive progress in protective attire and risk mitigation strategies.
CALR mutant protein rescues the response of MPL p.R464G variant associated with CAMT to eltrombopag
Authors: Francesca Basso-Valentina, Gabriel Levy, Leila N. Varghese, Myriam Oufadem, Benedicte Neven, Charlotte Boussard, Nathalie Balayn, Caroline Marty, William Vainchenker, Isabelle Plo, Paola Ballerini, Stefan N. Constantinescu, Remi Favier, Hana Raslova
Journal: Blood (2021)
Heterogeneous subpopulations of adventitial progenitor cells regulate vascular homeostasis and pathological vascular remodelling
Authors: Austin J Jolly, Sizhao Lu, Keith A Strand, Allison M Dubner, Marie F Mutryn, Raphael A Nemenoff, Mark W Majesky, Karen S Moulton, Mary C M Weiser-Evans
Journal: Cardiovascular Research (2021)

Cardiovascular diseases are characterized by chronic vascular dysfunction and provoke pathological remodelling events, such as neointima formation, atherosclerotic lesion development, and adventitial fibrosis. While lineage-tracing studies have shown that phenotypically modulated smooth muscle cells (SMCs) are the major cellular component of neointimal lesions, the cellular origins and microenvironmental signalling mechanisms that underlie remodelling along the adventitial vascular layer are not fully understood. However, a growing body of evidence supports a unique population of adventitial lineage-restricted progenitor cells expressing the stem cell marker, stem cell antigen-1 (Sca1; AdvSca1 cells) as important effectors of adventitial remodelling and suggests that they are at least partially responsible for subsequent pathological changes that occur in the media and intima. AdvSca1 cells are being studied in murine models of atherosclerosis, perivascular fibrosis, and neointima formation in response to acute vascular injury. Depending on the experimental conditions, AdvSca1 cells exhibit the capacity to differentiate into SMCs, endothelial cells, chondrocytes, adipocytes, and pro-remodelling cells, such as myofibroblasts and macrophages. These data indicate that AdvSca1 cells may be a targetable cell population to influence the outcomes of pathologic vascular remodelling. Important questions remain regarding the origins of AdvSca1 cells and the essential signalling mechanisms and microenvironmental factors that regulate both maintenance of their stem-like, progenitor phenotype and their differentiation into lineage-specified cell types. Adding complexity to the story, recent data indicate that the collective population of adventitial progenitor cells is likely composed of several smaller, lineage-restricted subpopulations, which are not fully defined by their transcriptomic profile and differentiation capabilities. The aim of this review is to outline the heterogeneity of Sca1+ adventitial progenitor cells, summarize their role in vascular homeostasis and remodelling, and comment on their translational relevance in humans.
Post-Thrombotic Syndrome and Recurrent Thromboembolism in Patients with Upper Extremity Deep Vein Thrombosis: A Systematic Review and Meta-Analysis of Proportions
Authors: Kartiga Thiyagarajah, Leah Ellingwood, Kaitlin Endres, Aaron Hegazi, James Radford, Alla Lansavitchene, Alejandro Lazo-Langner
Journal: Blood (2017)