tbuckley/cabot-search huggingface dataset:
Cow’s Milk and Vitamin D Supplementation in Infants—Timing Is Everything
Authors: George du Toit, Arnon Elizur, Kari C. Nadeau
Journal: JAMA Pediatrics (2019)

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Abstract 602: Mir-182-5p is a Conserved Downstream Effector of Tbx5 Involved in Heart Development and Arrhythmia in Zebrafish
Authors: Elena Guzzolino, Mario Pellegrino, Neha Ahuja, Deborah Garrity, Romina D'Aurizio, Marco Groth, Mario Baumgart, Cathy Hatcher, Alberto Mercatanti, Monica Evangelista, Chiara Ippolito, Elisabetta Tognoni, Ryuichi Fukuda, Vincenzo Lionetti, Letizia Pitto
Journal: Circulation Research (2019)

Background: TBX5 mutations cause Holt-Oram syndrome (HOS) characterized by upper limb and cardiac malformations, but can also contribute to early-onset of atrial fibrillation. Focusing on miRNAs involved in TBX5 regulatory circuits with a cardiac relevant role, we identified miR-182-5p, belonging to miR-183 cluster, found upregulated in Tbx5-depleted hearts of mouse and zebrafish embryos. Methods: To functionally analyse the miR-182-5p role in developing heart, miR-182-5p was dysregulated in zebrafish zygotes of Tg(Myl7:EGFP) and Tg(myl7:gCaMP) transgenic lines. To stably deregulate miR-182-5p in zebrafish heart we exploited the Gal4/UAS system to restrict the miR-182 expression into cardiac context. For physiological analyses we performed the mechanogram of cardiac contraction and electrocardiogram recording. To understand miR-182-5p downstream regulation, in silico analyses, followed by ddPCR/real-time quantifications on dissected zebrafish hearts and rescue experiments both in transient and stable miR-182-5p overexpressing zebrafish embryos were performed. Results: Depletion of Tbx5 from cardiomyocytes increased the expression of miR-182 cluster family that is controlled by Kruppel-like factor 4 (KLF4), a transcription factor repressed by Tbx5. Both transient and stable upregulation of miR-182 in zebrafish affect heart morphology, calcium handling and the onset of arrhythmia while its cardiac-specific downregulation decreases cardiac defects in zebrafish HOS hearts. Expression analyses on selected miR-182-5p putative targets revealed that several calcium channel proteins resulted downregulated in miR-182-5p overexpressing hearts. Transgenic zebrafish line stably overexpressing miR-182-5p in the heart manifested arrhythmia overtime with or without cardiac structural defects. Conclusion: We identified miR-182-5p as a potential suitable target to interfere in the circuit between upstream genetic abnormalities and downstream effectors leading to arrhythmia occurrence.
Abstract 146: Investigating and Inhibiting Neutrophil Extracellular Trap Formation in the Heart
Authors: Michael N Sayegh, Lanfang Wang, Eric Y Shin, Woojin M Han, Milton E Brown, Michael E Davis, Andres J Garcia, Rebecca D Levit
Journal: Circulation Research (2019)

Neutrophil extracellular traps (NETs) have been observed in multiple diseases of the cardiovascular system, such as myocardial infarction and atherosclerosis. We have recently shown that adenosine (ADO) inhibits NET formation and may be an important endogenous regulator. CD73 is expressed on many cell types and catalyzes the extracellular formation of ADO from AMP. Here, we first attempt to implicate NETs in cardiac injury, and we posit that human NETs negatively impact cardiac function by influencing native leukocyte recruitment and activation. Second, we prototype a CD73-functionalized hydrogel delivery vehicle for adenosine and test its function in vitro. We introduced NETs obtained from stimulated neutrophils into healthy hearts by intramyocardial injection in two-month-old rats. We used echo to assess cardiac function at days 0, 1 and 3 of injection. We measured the abundance of cardiac leukocyte subpopulations by flow cytometry at days 1 and 3 after injection, with immunostaining for CD45 (all leukocytes), myeloperoxidase (MPO, neutrophils), CD68 (macrophages), CD3 (T-cells), B220 (B-cells) and citrullinated histone 3 (citH3, NETs). To deliver adenosine as a NET antagonist, we designed a polyethylene (PEG) hydrogel composed of a 4-armed PEG incorporating a VPM protease-degradable crosslinker for cargo release, and an RGD peptide to enhance gel-tissue attachment. We tested gel polymerization by measuring storage and loss moduli at 4% and 6% PEG content (w/v) and 0, 1 uM and 1mM RGD concentrations. We functionalized the gel with CD73 to test its adenosine production capability. We found a significant decreased in cardiac function assessed by global longitudinal strain at day 1 in the NET group compared to saline. By flow cytometry, we found an increase in neutrophils, macrophages and NET formation at day 1, while B- and T-cells were increased at day 3. We found that increasing the PEG content of our hydrogel, but not RGD, increases gel stiffness. We also found that the CD73 functionalized hydrogel successfully catalyzes the formation of adenosine in vitro. In conclusion, we found that NETs negatively impact cardiac function, and successfully tested an adenosine hydrogel source in vitro. Next, we will study the effect of our gel on NETs in vivo.
Real Life Use of Bendamustine Plus Rituximab Versus Chlorambucil Plus Rituximab As Front-Line Therapy for Elderly CLL Patients. Retrospective Multicenter Study in the Lazio Region
Authors: Francesco Autore, Idanna Innocenti, Francesco Corrente, Maria Ilaria Del Principe, Serena Rosati, Paolo Falcucci, Esmeralda Conte, Maria Assunta Limongiello, Daniela Renzi, Laura De Padua, Alessandro Andriani, Francesco Pisani, Giuseppe Cimino, Agostino Tafuri, Marco Montanaro, Francesca Romana Mauro, Giovanni Del Poeta, Luca Laurenti
Journal: Blood (2018)
Response by du Fay de Lavallaz et al to Letter Regarding Article, “B-Type Natriuretic Peptides and Cardiac Troponins for Diagnosis and Risk-Stratification of Syncope”
Authors: Jeanne du Fay de Lavallaz, Patrick Badertscher, Christian Müller
Journal: Circulation (2019)

We thank Dr Nguyen et al for their critical review of our manuscript "B-Type Natriuretic Peptides and Cardiac Troponins for Diagnosis and Risk-Stratification of Syncope." 1 As correctly highlighted by Nguyen et al, further biomarkers or prohormones such as copeptin, pro-endothelin-1, and proadrenomedullin were collected as originally planned during study design and have already been evaluated in a previous publication. 2s noted by Nguyen et al, the etiologies underlying cardiac syncope are heterogenous, ranging from arrhythmias to structural and valvular heart disease.Structural heart diseases, such as myocardial infarction or valvular diseases, as well as tachyarrhythmias or pulmonary embolism, all lead to changes in intracardiac volumes and filling pressures.Numerous studies have shown that natriuretic peptides are reliable surrogates for these changes in hemodynamic stress, mediated by volume or pressure overload. 3As highlighted in our analysis, bradyarrhythmias seem to be less correlated to natriuretic peptide concentrations than tachyarrhythmias, but previous research suggested that loss of atrioventricular synchrony during the bradycardic event could lead to an increased wall tension, therefore increasing these biomarkers' circulating concentrations. 4he establishment of an exact diagnosis in syncope patients is challenging and other studies tended to focus on prognostic endpoints.To the best of our knowledge, a single other study 5 also focused on the diagnostic endpoint of cardiac syncope, which were defined by using the work-up available during the index event only.BASEL IX (Basel Syncope Evaluation Study) goes beyond the initial patient evaluation by incorporating all relevant cardiovascular findings and events detected during the first year of follow-up.Our stringent methodology moreover requires 2 fully trained physicians to agree on the exact syncope etiology, which further bolster the validity of our diagnostic evaluation.A systematic diagnostic work-up encompassing, for instance, an electrophysiologic study or a loop recorder implantation in all participants goes beyond the observational design of our study.We do, however, agree that further well-structured, possibly controlled, and randomized studies are required to definitively highlight the importance of biomarkers in the diagnostic evaluation of patients presenting with syncope.
Ranitidine: doctors should switch patients to alternative, says health department
Authors: Elisabeth Mahase
Journal: BMJ (2019)

Doctors must identify and review patients with prescriptions for ranitidine tablets for gastrointestinal conditions and switch them to an alternative drug if ongoing treatment is still needed, the Department of Health and Social Care for England has said.1

In an alert sent on 15 October the department warned that all oral formulations of ranitidine were “anticipated to be out of stock, with no date for resupply until further notice.”

This came after the US …
BMP4 Gene Therapy Inhibits Myeloma Tumor Growth, but Has a Negative Impact on Bone
Authors: Toril Holien, Marita Westhrin, Siv Helen Moen, Muhammad Zahoor, Glenn Buene, Berit Størdal, Hanne Hella, Huipin Yuan, Joost D de Bruijn, Anton Martens, Richard WJ Groen, Fatima Bosch, Ulf Smith, Anders Sundan, Therese Standal
Journal: Blood (2018)
Incidence of Direct Thrombin Inhibitor Therapy for Presumed Heparin Induced Thrombocytopenia Before and After Implementation of Heparin Induced Thrombocytopenia IgG Subtype Antibody Test
Authors: Randall R Ingham, John L. Reagan, Samir Dalia, Joseph D. Sweeney, James N. Butera
Journal: Blood (2012)
Statins Potentiate Aminopeptidase Inhibitor (pro)Drug Activity in Acute Myeloid Leukemia Cells
Authors: Jacqueline Cloos, Godefridus J Peters, Marjon Al, Yehuda G Assaraf, Lixia Wang, Jack W. Singer, Jorge E. Cortes, Gert J. Ossenkoppele, Gerrit Jansen
Journal: Blood (2018)
Real world implementation of patient report outcomes: Sustainability constraints and impact on patients health outcomes.
Authors: Rosana Faria, Adrian Langleben, Ashley Kushneryk, Jennifer Wilson
Journal: Journal of Clinical Oncology (2019)

291 Background: St Mary’s Hospital, an affiliated McGill Teaching University Hospital, receives ~700 new cancer patients yearly. In 2014-17, electronic PROs were implemented through the Improving Patient Experience and Health in Outcomes Collaborative in partnership with Cancer Care Ontario, granted by Canadian Partnership against Cancer and Rossy Cancer Network, as part of a PRO Canadian Initiative to improve the Patient Experience across Canada through standardized measurement of health-related outcomes for patients. Methods: The PROs measures included the Edmonton Symptom Assessment Scale (ESAS), additional measures for Fatigue, Anxiety, Depression, and Pain, the Social Difficulties Inventory-21 and Quality of Life. PRO-data was scored in real-time; nurses and patients received a printed summary report. Nurses were provided with an algorithm and instructions. Monthly Distress Screening Dashboard were generated with key indicators. In 2016, all patients receiving chemotherapy were assessed at each cycle of treatment. After project completion, due to nursing staff shortage, the frequency of screenings was reduced. Yearly Dashboard results were used to promote discussion with clinicians and address sustainability constraints of PROs in real-word oncology practice. Results: In 2016 1366 total screens completed ( 376 patients) and in 2018, 753 total screens (325 patients). This comparison indicates that a decrease in frequency of screenings resulted in an increase in symptom severity in all health-related outcomes. Physicians’ participation was proposed as mitigation plan to increase screening frequency. We propose to present a three year retrospectively cross analyzed patient data to examine symptom change over time, frequencies of screening, impact on patients’ health outcomes, overlapping sustainability constraints encountered and mitigation plans. Conclusions: Embedding the use of PRO into existing hospital structures requires constant review involving administrative, clinician and patient engagement.
The Cardinal Manifestations of Paroxysmal Tachycardia
Authors: I. Anginal Pain, Louis Wolff
Journal: New England Journal of Medicine (1945)

THE symptoms accompanying paroxysmal tachycardia are numerous and varied. Most of them are not caused directly by the tachycardia, nor are they directly or specifically related to the underlying heart condition. Inquiry into the circumstances under which they arise throws no light on their meaning or on the underlying cardiovascular status. A few of the symptoms, however, arise under such constant conditions that they create a uniform clinical pattern. Because these symptoms —palpitation, pulmonary congestion, anginal pain, congestive failure, vascular collapse, Central-nervous-system manifestations and embolism — may be correlated with significant variables, such as the type of patient, the heart . . .
Changes in employment and insurance for patients with cancer receiving safety net services.
Authors: Nicole Caston, Courtney Williams, Alan James Balch, Kathleen D. Gallagher, Gabrielle Betty Rocque
Journal: Journal of Clinical Oncology (2019)

104 Background: Under-resourced patients with cancer often face financial burdens due, not only to costs of treatment, but also from side effects that prevent individuals’ ability to work, which impact employment status and may cause insurance coverage loss. Financial assistance may be sought from safety net programs, which provide both material support and financial counseling. However, knowledge of the impact of cancer on employment and insurance in a population seeking safety net services is limited. Methods: This observational, cross-sectional study uses data on safety net services from a nationwide survey conducted in July 2017 and distributed by the Patient Advocate Foundation (PAF). The survey respondents included patients with cancer who received services from PAF from July 2016 to June 2017. Descriptive statistics were calculated using frequencies for categorical variables. Results: A total of 508 patients with cancer completed the survey. Most patients had a diagnosis of breast cancer (47%), followed by myeloma (13%), and prostate cancer (8%). The majority of patients reported that their illness affected their employment (67%); by either job loss (13%), income loss (24%), or inability to work as usual (27%). Of these patients, 27% lost their insurance coverage. Those able to enroll in a new insurance plan reported having more expensive rates (40%) and fewer covered services (36%) compared to their previous coverage. The most commonly utilized governmental safety net services were Social Security Disability Insurance (19%) and Medicaid (12%). Non-governmental safety net services such as financial assistance from non-profits (27%) and free medication from drug companies (13%) were also frequently used. Beyond their insurance coverage, cancer patients still needed assistance paying for diagnostic tests (18%), clinic visit fees (23%), and prescription drugs (15%) from the safety net program. Conclusions: Cancer patients commonly experience financial burden due to losses in employment and insurance, resulting in need for safety net programs. Further work is needed to identify approaches to reducing the adverse financial impact of cancer care.
Abstract 14736: Long-term Change in Cardiorespiratory Fitness in Relation to Risk of Incident Heart Failure and Atrial Fibrillation
Authors: Hassan Khan, Danesh Kella, Setor K Kunutsor, Abhishek J Deshmukh, Rainer Rauraama, Faisal Merchant, Jari A Laukkanen
Journal: Circulation (2017)

Introduction: Benefit of aerobic fitness in relation to all cause and cardiovascular mortality is well established, however the association of long-term change in cardiorespiratory fitness on incid...
Infections in Patients with Lymphoproliferative Diseases Treated with Target Therapy. Italian Multicentric Retrospective Study Seifem 2017
Authors: Gianpaolo Nadali, Gessica Marchesini, Davide Facchinelli, Francesca Farina, Maria Chiara Tisi, Federica Lessi, Francesco Marchesi, Chiara Cattaneo, Anna Candoni, Rosa Fanci, Lucia Prezioso, Luisa Verga, Luca Laurenti, Fabio Trastulli, Marco Picardi, Maria Ilaria Del Principe, Ronaldo Silva, Alessandro Busca
Journal: Blood (2018)
Shaping the heart: Structural and functional maturation of iPSC-cardiomyocytes in 3D-micro-scaffolds
Authors: Nicole Silbernagel, Arlene Körner, Jakob Balitzki, Mona Jaggy, Sarah Bertels, Benjamin Richter, Marc Hippler, Andrea Hellwig, Markus Hecker, Martin Bastmeyer, Nina D. Ullrich
Journal: Biomaterials (2019)
Abstract 883: Nadph Oxidase Nox1-dependent Endocytosis and Activation is Regulated by a Conserved Trafficking Motif in Vascular Smooth Muscle Cells
Authors: Brandon M Schickling, Jennifer Streeter, Francis J Miller
Journal: Circulation Research (2019)

We previously reported that TNF-α-mediated Nox1-dependent redox signaling of vascular smooth muscle cells (SMC) requires endocytosis. However, the molecular mechanisms regulating Nox1 endocytosis are not known. The goal of this study was to identify motifs in the Nox1 protein sequence necessary for Nox1 endocytosis and reactive oxygen species (ROS) generation. Immunoprecipitation of Nox1, after treatment of SMC with TNF-α, showed it to be associated with Early Endosome Antigen 1 (EEA1) and Ras-related protein Rab-5A (Rab5), markers of early endosomes. Analysis of the Nox1 protein sequence identified two conserved putative trafficking motifs, Leucine-Leucine (LL), and Valine-Leucine-Valine (VLV). Biotinylation of SMC plasma membrane proteins under non-stimulated conditions suggested increased levels of Nox1 VLV mutant in the plasma membrane, whereas levels of Nox1 LL mutant where comparable to wildtype (WT) Nox1. Furthermore, cells expressing the VLV mutant showed impaired endocytosis of Nox1 following TNF-α as compared to cells expressing WT Nox1 or the LL mutant. SMC were treated with TNF-α in the presence of Oxyburst, a non-cell permeable redox-sensitive fluorophore whose internalization requires endocytosis. Cells expressing WT or Nox1 LL, but not Nox1 VLV, exhibited punctate intracellular fluorescence, indicating endosomal ROS production. Next, we examined whether the VLV motif is required for Nox1-dependent SMC migration. Transwell migration of SMC was similar in cells expressing WT or the LL Nox1 mutant; however, migration was decreased in cells expressing the Nox1 VLV mutant. Finally, we identified proteins whose association with Nox1 during endocytosis were dependent on the VLV motif. Nox1 WT and VLV mutant were cloned in frame with the biotin ligase BioID2. Following stimulation with TNF-α, Western blotting for anti-biotin, and subsequent mass spectrometry, identified several proteins directly associated with WT Nox1 but not Nox1 VLV. These findings suggest that endosomal compartmentalization of Nox1 and its redox signaling is regulated by a specific motif on Nox1 that is necessary for protein interactions. Targeted inhibition of Nox1 activation is a novel therapeutic strategy in the prevention of vascular disease.
A Novel Algorithm to Differentiate Between Multiple Primary Lung Cancers and Intrapulmonary Metastasis in Multiple Lung Cancers With Multiple Pulmonary Sites of Involvement
Authors: Young Joo Suh, Hyun-Ju Lee, Pamela Sung, Heera Yoen, Sewoo Kim, Seungchul Han, Sungeun Park, Jung Hee Hong, Heekyung Kim, Jiyeon Lim, Hyungjin Kim, Soon Ho Yoon, Yoon Kyung Jeon, Young Tae Kim
Journal: Journal of Thoracic Oncology (2019)

Differentiating between multiple primary lung cancer (MPLC) and intrapulmonary metastasis (IPM) is critical for developing a therapeutic strategy to treat multiple lung cancers with multiple pulmonary sites of involvement.We retrospectively included 252 lesions (126 pairs) from 126 patients with surgically resected multiple lung adenocarcinomas. Each pair was classified as MPLC or IPM based on histopathologic findings as the reference standard. A novel algorithm was established with four sequential decision steps based on the combination of computed tomography (CT) lesion types (step 1), CT lesion morphology (step 2), difference of maximal standardized uptake values on positron-emission tomography/CT (step 3), and presence of N2/3 lymph node metastasis or distant metastasis (step 4). The diagnostic accuracy of the algorithm was analyzed. Performances of 11 observers were assessed without and with knowledge of algorithm.Among 126 pairs, 90 (71.4%) were classified as MPLCs and 36 (28.6%) as IPMs. On applying the diagnostic algorithm, the overall accuracy for diagnosis of IPM among conclusive cases up to step 4 was 88.9%, and 65 and 44 pairs were correctly diagnosed based on step 1 and step 2, respectively. Specificity and positive predictive value for diagnosis of IPM increased significantly in all observers compared with reading rounds without the algorithm.Application of the algorithm based on comprehensive information on clinical and imaging variables can allow differentiation between MPLCs and IPMs. When both of two suspected malignant lesions appear as solid predominant lesions without spiculation or air-bronchogram on CT, IPM should be considered.