tbuckley/cabot-search huggingface dataset:
Luspatercept restores SDF-1-mediated hematopoietic support by MDS-derived mesenchymal stromal cells
Authors: Manja Wobus, Anna Mies, Nandini Asokan, Uta Oelschlägel, Kristin Möbus, Susann Winter, Michael Cross, Heike Weidner, Martina Rauner, Lorenz C. Hofbauer, Martin Bornhäuser, Uwe Platzbecker
Journal: Leukemia (2021)

Abstract The bone marrow microenvironment (BMME) plays a key role in the pathophysiology of myelodysplastic syndromes (MDS), clonal blood disorders affecting the differentiation, and maturation of hematopoietic stem and progenitor cells (HSPCs). In lower-risk MDS patients, ineffective late-stage erythropoiesis can be restored by luspatercept, an activin receptor type IIB ligand trap. Here, we investigated whether luspatercept can modulate the functional properties of mesenchymal stromal cells (MSCs) as key components of the BMME. Luspatercept treatment inhibited Smad2/3 phosphorylation in both healthy and MDS MSCs and reversed disease-associated alterations in SDF-1 secretion. Pre-treatment of MDS MSCs with luspatercept restored the subsequent clonogenic potential of co-cultured HSPCs and increased both their stromal-adherence and their expression of both CXCR4 and ß3 integrin. Luspatercept pre-treatment of MSCs also increased the subsequent homing of co-cultured HSPCs in zebrafish embryos. MSCs derived from patients who had received luspatercept treatment had an increased capacity to maintain the colony forming potential of normal but not MDS HSPCs. These data provide the first evidence that luspatercept impacts the BMME directly, leading to a selective restoration of the ineffective hematopoiesis that is a hallmark of MDS.
Abstract 13161: Acceptability and Feasibility of Novel Screening Models and Family Communication Methods for Familial Hypercholesterolemia
Authors: Laney K Jones, Nicole Walters, Andrew Brangan, Catherine D Ahmed, Gemme Campbell Salome, Amanda Sheldon, Mary McGowan, Alanna K Rahm, Amy C Sturm
Journal: Circulation (2020)

Introduction: Despite familial hypercholesterolemia (FH) being a common cardiovascular genetic disorder, it is vastly underdiagnosed and undertreated. This is partly due to the lack of systematic screening methods to identify possible FH and little to no implementation of cascade screening approaches in the US. Screening models, such as machine learning algorithms, and family communication methods for cascade screening, such as chatbot technology and direct contact of at-risk relatives by a clinician, may help close the gap in FH identification. Methods: Focus groups were conducted with individuals with FH and clinicians. Focus groups were audio-recorded, transcribed, and coded for acceptability and feasibility of implementing screening models and family communication methods. Results: Individuals with FH and clinicians felt that models analyzing different data sources, including electronic health records, to screen for FH have the potential to activate patients and stimulate patient-clinician conversations about FH. While some expressed privacy and confidentiality concerns, individuals with FH found screening models acceptable, stating that these could have led to an earlier diagnosis and treatment and expressing their frustration with the status quo. Most had a strong desire to be notified of screening models’ outcomes at the same time as their clinician. Clinicians felt strongly that automated models would be helpful in identifying FH. Many with FH felt responsible for notifying their family about FH first; however, some indicated comfort with their clinician, healthcare system, or other professionals helping to communicate FH risk to their relatives via direct contact methods. Further, they indicated a strong willingness to use chatbots to share FH risk information with their relatives. Clinicians felt the need to support their patients and offer their services when sharing FH risk information with relatives, while individuals with FH expressed doubt that their clinicians would have time and resources to provide active support. Conclusions: Individuals with FH and clinicians agreed that FH screening models and enhanced family communication methods would be beneficial, acceptable, and feasible to implement in US healthcare systems.
A Machine-Learning Framework to Identify Distinct Phenotypes of Aortic Stenosis Severity
Authors: Partho P. Sengupta, Sirish Shrestha, Nobuyuki Kagiyama, Yasmin Hamirani, Hemant Kulkarni, Naveena Yanamala, Rong Bing, Calvin W.L. Chin, Tania A. Pawade, David Messika-Zeitoun, Lionel Tastet, Mylène Shen, David E. Newby, Marie-Annick Clavel, Phillippe Pibarot, Marc R. Dweck, Éric Larose, Ezequiel Guzzetti, Mathieu Bernier, Jonathan Beaudoin, Marie Arsenault, Nancy Côté, Russell Everett, William S.A. Jenkins, Christophe Tribouilloy, Julien Dreyfus, Tiffany Mathieu, Cedric Renard, Mesut Gun, Laurent Macron, Jacob W. Sechrist, Joan M. Lacomis, Virginia Nguyen, Laura Galian Gay, Hug Cuéllar Calabria, Ioannis Ntalas, Bernard Prendergast, Ronak Rajani, Arturo Evangelista, João L. Cavalcante
Journal: JACC. Cardiovascular imaging (2021)
High-Risk Morphological and Physiological Coronary Disease Attributes as Outcome Markers After Medical Treatment and Revascularization
Authors: Seokhun Yang, Bon-Kwon Koo, Doyeon Hwang, Jinlong Zhang, Masahiro Hoshino, Joo Myung Lee, Tadashi Murai, Jiesuck Park, Eun-Seok Shin, Joon-Hyung Doh, Chang-Wook Nam, Jianan Wang, Shaoliang Chen, Nobuhiro Tanaka, Hitoshi Matsuo, Takashi Akasaka, Hyuk-Jae Chang, Tsunekazu Kakuta, Jagat Narula
Journal: JACC. Cardiovascular imaging (2021)
Abstract 14839: High-resolution Spatiotemporal Changes in Dominant Frequency and Structural Organization During Persistent Atrial Fibrillation
Authors: Terrence Pong, Joy Aparicio Valenzuela, Kevin J Cyr, Cody Carlton, Sasank Sakhamuri, Anson M LEE
Journal: Circulation (2020)

Introduction: Spatiotemporal differences in atrial activity are thought to contribute to the maintenance of atrial fibrillation (AF). While recent evidence has identified changes in dominant frequency (DF) during the transition from paroxysmal to persistent AF, little is known about the frequency characteristics of the epicardium during this transition. The purpose of this study was to perform high-resolution mapping of the atrial epicardium and to characterize changes in frequency activity and structural organization during the transition from paroxysmal to persistent AF. Hypothesis: In a porcine model of persistent AF, we tested the hypothesis that the epicardium undergoes spatiotemporal changes in atrial activity and structural organization during persistent AF. Methods: Paroxysmal and persistent AF was induced in adult Yorkshire swine by atrial tachypacing. Atrial morphology was segmented from magnetic resonance imaging and high-resolution patient-specific flexible mapping arrays were 3D printed to match the epicardial contours of the atria. Epicardial activation and DF mapping was performed in four paroxysmal and four persistent AF animals using personalized mapping arrays. Histological analysis was performed to determine structural differences between paroxysmal and persistent AF. Results: The left atrial epicardium was associated with a significant increase in DF between paroxysmal and persistent AF (6.5 ± 0.2 vs. 7.4 ± 0.5 Hz, P = 0.03). High-resolution spatiotemporal mapping identified organized clusters of DF during paroxysmal AF which were lost during persistent AF. The development of persistent AF led to structural remodeling with increased atrial epicardial fibrosis. The organization index (OI) significantly decreased during persistent AF in both the left atria (0.3 ± 0.03 vs. 0.2 ± 0.03, P = 0.01) and right atria (0.33 ± 0.04 vs. 0.23 ± 0.02, P = 0.02). Conclusions: In the porcine model of persistent AF, the epicardium undergoes structural remodeling with increased epicardial fibrosis, reflected by changes in atrial organization index and dominant frequency.
Differential effects of the blood pressure state on pulse rate variability and heart rate variability in critically ill patients
Authors: Elisa Mejía-Mejía, James M. May, Mohamed Elgendi, Panayiotis A. Kyriacou
Journal: npj Digital Medicine (2021)

Abstract Heart rate variability (HRV) utilizes the electrocardiogram (ECG) and has been widely studied as a non-invasive indicator of cardiac autonomic activity. Pulse rate variability (PRV) utilizes photoplethysmography (PPG) and recently has been used as a surrogate for HRV. Several studies have found that PRV is not entirely valid as an estimation of HRV and that several physiological factors, including the pulse transit time (PTT) and blood pressure (BP) changes, may affect PRV differently than HRV. This study aimed to assess the relationship between PRV and HRV under different BP states: hypotension, normotension, and hypertension. Using the MIMIC III database, 5 min segments of PPG and ECG signals were used to extract PRV and HRV, respectively. Several time-domain, frequency-domain, and nonlinear indices were obtained from these signals. Bland–Altman analysis, correlation analysis, and Friedman rank sum tests were used to compare HRV and PRV in each state, and PRV and HRV indices were compared among BP states using Kruskal–Wallis tests. The findings indicated that there were differences between PRV and HRV, especially in short-term and nonlinear indices, and although PRV and HRV were altered in a similar manner when there was a change in BP, PRV seemed to be more sensitive to these changes.
Abstract 17432: We Are Baffled: An Unusual Presentation of STEMI
Authors: Muhammad Soofi, Swapnil Garg, Srikanth Sadhu
Journal: Circulation (2020)

Background: Adult congenital heart disease is most commonly complicated by arrhythmias and very rarely by acute coronary syndromes. We present a rare case of ST elevation myocardial infarction (STEMI) in a young 35-year-old patient with congenital transposition of great vessels. Case Presentation: A 35-year-old female with a past medical history of transposition of the great vessels (d-TGA) status post arterial baffle operation in infancy, with prior atrial arrhythmias and severe RV failure, presented to our facility with crushing substernal chest pain radiating down her left arm. ECG was significant for ST elevation in the inferior leads and high sensitivity troponin was elevated. She was taking Rivaroxaban. She was taken emergently to the catheterization lab where she was found to have 100% occlusion of the apical left anterior descending artery secondary to an embolus with no angiographic disease in any other epicardial vessel. Transthoracic echocardiography showed severe dilation of the right ventricle with severe tricuspid regurgitation. The embolic lesion was deemed not amenable to percutaneous intervention and the patient was treated conservatively with a heparin drip. The embolus was presumed to originate from the hyper-trabeculated and distended right ventricle in spite of chronic rivaroxaban therapy and she was started on warfarin. Presently she is stable, awaiting a heart transplant. Discussion: Extensive literature review revealed four reported cases of acute coronary syndrome secondary to emboli in patients with surgically corrected TGA. Patients with d-TGA are most often surgically corrected with an arterial switch procedure. But in Baffle procedures (Mustard or Senning) such as the one in this patient, the right ventricle becomes the systemic ventricle. The most common complications as an adult are right ventricular dilation, severe tricuspid regurgitation and atrial arrhythmias, all three of which were noted in our patient. Conclusion: Our patient developed all three of the most common adult complications of surgically corrected d-TGA, ultimately resulting in the rare and extreme manifestation of an embolic STEMI.
Progressive Ataxia and Downbeat Nystagmus in an Adult
Authors: Alejandra Collía Fernández, Begoña Huete Antón, Juan Carlos García-Moncó
Journal: JAMA Neurology (2021)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Neurology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Neurology journal
Abstract P189: Greater Purpose In Life Is Associated With Lower Allostatic Load Among Hispanics/ Latinos: The Hispanic Community Health Study/study Of Latinos (hchs/sol) Sociocultural Ancillary Study (scas)
Authors: Mayra L Estrella, Melissa Lamar, Ramon A Durazo-Arvizu, Josiemer Mattei, Lisa A Sanchez-Johnsen, Sara Gonzalez, Jianwen Cai, Krista M Perreira, Carmen R Isasi, Linda C Gallo, Martha L Daviglus
Journal: Circulation (2021)

Introduction: Allostatic load (AL), a multi-system measure of physiological dysregulation that represents cumulative wear-and-tear due to chronic stressors, is related to higher risk of cardiovascular disease (CVD). Evidence on the association of psychosocial factors with AL is mixed despite accruing research that suggests that psychosocial factors are related to CVD, in part, through AL. We examined the associations of psychosocial factors with AL among Hispanics/Latinos. Hypothesis: Psychosocial intrapersonal ( ethnic identity , optimism, and purpose in life) and interpersonal ( family cohesion , social network embeddedness , and social support ) resources will each be inversely associated with AL while stressors ( perceived ethnic discrimination , familism, and loneliness ) will each be positively associated. Methods: Data from the HCHS/SOL SCAS were used (n=4,914; ages 18-74). AL was assessed using 16 biomarkers representing cardiometabolic, glucose, cardiopulmonary, parasympathetic, and inflammatory systems. The AL score (0-16) was computed as the number of biomarkers for which a participant had a high-risk quartile; higher scores represent greater physiological dysregulation. Psychosocial factors were self-reported. Survey-weighted linear regression models adjusted for sociodemographic factors examined associations of each psychosocial factor with AL. We also examined whether sex modified these associations. Results: Mean AL score was 4.0 (SD=3.2). In fully-adjusted models (Table), the purpose in life score was inversely associated with AL. No other significant associations were observed, although regression estimates were generally in the hypothesized direction. Sex did not modify the association of psychosocial factors with AL. Conclusions: Greater sense of purpose in life, an intrapersonal psychosocial resource, is associated with lower physiological dysregulation in Hispanics/Latinos. Findings highlight the need to examine prospective associations of purpose in life with AL.
The New Immunoreceptor SLAMF3 Promotes Aggressive Biological and Clinical Characteristics in Multiple Myeloma
Authors: Mariko Ishibashi, Hideto Tamura, Toshio Asayama, Yasuko Kuribayashi-hamada, Asaka Onodera, Keiichi Moriya, Makoto Sasaki, Hiroshi Handa, Yoichi Imai, Norina Tanaka, Junji Tanaka, Sakae Tanosaki, Shigeki Ito, Norio Komatsu, Koiti Inokuchi
Journal: Blood (2017)
Abstract 061: Comparison Of Diagnostic Methods For Diabetes Diagnosis In Patients With Heart Failure: A National Health And Nutrition Examination Survey Analysis
Authors: Yuta Ishikawa, Emma M Laing, Alex K Anderson, Donglan Zhang, Rupal Trivedi-Kapoor, Elisabeth L Sattler
Journal: Circulation (2021)

Introduction: The use of hemoglobin A1c (HbA1c) to screen for diabetes in patients with cardiovascular disease has shown low sensitivity, and the currently recommended cutoff point may leave many patients undiagnosed. The objective of the study was to examine the degree of agreement among current diagnostic methods for diabetes, including HbA1c, fasting plasma glucose (FPG), and two-hour plasma glucose (2hPG) after oral glucose tolerance test (OGTT) among community-dwelling heart failure (HF) patients. Methods: We included 237 HF participants (20+ years) without history of diabetes or diabetes medication use, using data from the 2005-2016 National Health and Nutrition Examination Survey cycles. Diagnostic criteria for diabetes were based on the American Diabetes Association (ADA) guidelines: (1) HbA1c ≥ 6.5%, (2) FPG ≥ 126 mg/dL, and (3) 2hPG after OGTT ≥ 200 mg/dL. The sensitivity, specificity, and Receiver Operating Characteristic (ROC) curve for HbA1c and FPG were examined against the OGTT (FPG ≥ 126 mg/dL and/or 2hPG ≥ 200 mg/dL) as the reference method. Results: Included participants had a mean age of 65±1 (SE) years, 45.5% were female, and 12.5% were non-Hispanic black. Among included participants, 50 patients were newly diagnosed with diabetes based on ADA guidelines. Hemoglobin A1c alone identified only 27.0% of patients, whereas the OGTT identified 90.1% of patients. The area under the ROC curve, assessing HbA1c performance for the diagnosis of diabetes defined by OGTT, was 0.76 (95% CI, 0.67-0.84). Sensitivity and specificity using the HbA1c cutoff at ≥ 6.5% were 19.1% and 97.5%, respectively. The Youden’s J statistic for HbA1c was maximized at 5.8-5.9% (69.9-64.3% sensitivity and 63.9-70.1% specificity). Conclusion: Our data show that identification of diabetes among HF patients was inadequate on the basis of HbA1c screening alone. Our findings suggest diabetes screening on the basis of the OGTT or an HbA1c cutoff point of 5.8-5.9%.
Abstract 16997: Reaffirmation of GPD1L-A280V as a Brugada Syndrome Disease-Causing Variant
Authors: Alexander Greiner, Haider Mehdi, Chloe Cevan, Rebecca A Gutmann, Barry London
Journal: Circulation (2020)

Introduction: Brugada Syndrome (BrS) is an inherited arrhythmia syndrome characterized by ST-segment elevation in the right precordial leads (V1-V3) and sudden cardiac death; ~20% of cases are caused by mutations in SCN5A . Over the past two decades, over 20 genes that may cause BrS have been identified. We reported that a Glycerol-3-Phosphate Dehydrogenase 1-Like mutation (GPD1L;p.A280V, chromosome 3p22.3) was linked to BrS in a large, multigenerational family with a LOD score ~4. Recent efforts in the field have called into question the pathogenicity of non- SCN5A genetic variants in BrS. Hypothesis: We sought to confirm the role of GPD1L in this family using a high density SNP array to narrow the linkage region and whole exome sequencing (WES) of the proband to rule out other possible mutations. We also sought to test whether BrS susceptibility SNPs in SCN5A and SCN10A linked to GPD1L may play a role in this family. Methods: SNPs were identified on an Illumina Global Screening Array and used for fine mapping. The exome of the proband was captured with the Agilent V6+UTR kit. SNPs were called using GATK3. BrS susceptibility SNPs were confirmed by PCR amplification and Sanger Sequencing. Results: The linkage region in this family resolved to ~3.07 MB (hg19; 3:29,899,567-32,970,637; Figure). This region contained 14 genes including GPD1L , and lacking SCN5A , SCN10A , or any other BrS-associated gene. WES identified GPD1L;p.A280V as the only coding variant in the linkage region with an allele frequency ≤ 1%. Previously identified BrS risk alleles in SCN5A and SCN10A were linked to the GPD1L;p.A280V allele in most family members (Figure). Conclusions: Our data suggests that GPD1L;p.A280V causes BrS in this family. The pathogenicity of GPD1L;p.A280V may be increased by linkage with SCN5A and SCN10A risk SNPs. The role of GPD1L mutations in the pathogenesis of BrS should be reaffirmed.
Abstract P083: Sodium Content Of Menu And Commissary Provisions In Rural Jail Exceed Heart-healthy Dietary Recommendations
Authors: Bonnie Kuss, Nanette Lopez, Shakia T Hardy, Ricky L Camplain
Journal: Circulation (2021)

Introduction: Incarcerated populations experience nearly two times the risk of Hypertension (HT) and Cardiovascular Disease (CVD) relative to the general population. Incarcerated individuals lack the autonomy to make dietary changes to attenuate these risks. Dietary intake of sodium is considered the most critical and modifiable nutritional determinant to developing HT and CVD. The American Heart Association recommends the cardioprotective Dietary Approaches to Stop Hypertension (DASH) diet which restricts sodium intake to 1500 mg per day, 800 mg less than the recommended Dietary Reference Intake (DRI). Nutrition in jail is obtained through menu provisions and purchasable packaged food and beverage items from the commissary, yet previous research indicating the high sodium content in jail meals has failed to include commissary items in total sodium intake. Hypothesis: We hypothesized that estimated daily sodium in a 7 day cycle menu and commissary items at a county jail exceed DRI and DASH diet recommendations. Methods: A 7 day cycle menu and commissary food list were obtained from a southwest rural county jail, which included 3 daily meals. Commissary items included 4 purchasable, pre-bundled food snack packs. NutriCalc Dietary Analysis software was used to determine sodium content for each meal, and commissary snack pack. Total sodium from the 7 day menu was divided by the number of days (7) to determine a daily average. For snack pack analyses, sodium of each of the 4 snack packs was added to the 7 day menu provisions and divided by 7, individually. All estimates were compared to DRI and DASH recommendations. Results: The sodium content from the menu and commissary significantly exceeded both DRI and DASH recommendations. The daily average sodium from menu provisions was 167% (3847/2300) of the DRI and 256% (3847/1500) of the DASH diet recommendations. Lunch provisions contributed the largest proportion (45%, 12051/26931) of total weekly sodium. When sodium from commissary snack packs was included with the 7 day cycle menu, daily average sodium content ranged from 173 to 292% [(3971/2300) to ( 6712/2300)] of DRI and 265 to 447% [(3970/1500) to (6712/1500)] of DASH diet recommendations. Conclusions: Small changes to one meal within the cycle menu and the inclusion of fresh or frozen produce could reduce sodium content to align with DRI and DASH recommendations. Commissary items make up a substantial portion of dietary sodium intake within jails. The addition of reduced sodium options to commissary snack packs may help limit sodium intake without restricting what little autonomy incarcerated individuals have over their diet. These alterations may help alleviate HT and CVD burden for incarcerated populations.
Management of Recurrent Acute Otitis Media
Authors: Ellen R. Wald
Journal: New England Journal of Medicine (2021)

Acute otitis media is one of the most common indications for both seeking medical care and prescribing antibiotics for children.1 The disorder is attributable to eustachian-tube dysfunction, which is most often caused by viral upper respiratory infections, and its prevalence is highest in children between 6 and 12 months of age.2 Young children who have a first episode of acute otitis media early in life (<12 months) are susceptible to the development of recurrent acute otitis media — defined as the occurrence of at least three episodes of acute otitis media within 6 months or four episodes within 12 months, . . .