tbuckley/cabot-search huggingface dataset:
Abstract 15263: Co-existing Systemic Lupus Erythematosus Does Not Negatively Impact Outcomes of Patients Admitted for Acute Coronary Syndrome: Analysis of the National Inpatient Sample
Authors: Ehizogie Edigin, precious O Eseaton, Iriagbonse R Asemota, Emmanuel Akuna, Hafeez Shaka, Pius E Ojemolon, augustine manadan
Journal: Circulation (2020)

Introduction: Systemic Lupus Erythematosus (SLE) is a chronic inflammatory autoimmune disease with effects on multiple organ systems and a wide range of clinical manifestations. Cardiovascular diseases from accelerated atherosclerosis are one of the major causes of mortality in SLE patients. This study aims to compare the outcomes of patients primarily admitted for Acute Coronary Syndrome (ACS) with and without a secondary diagnosis of SLE. Methods: Data were abstracted from the National Inpatient Sample (NIS) 2016 and 2017 Database. This database is the largest collection of inpatient hospitalization data in the United States (U.S). The NIS was searched for hospitalizations for adult patients with ACS as principal diagnosis with and without SLE as secondary diagnosis using ICD 10 codes. The primary outcome was inpatient mortality. Secondary outcomes of interest are showed in Table 1. Multivariate logistic and linear regression analysis was used accordingly to adjust for confounders. STATA software was used to analyze the data. Results: There were over 71 million discharges included in the combined 2016 and 2017 NIS database. Out of 1.3 million patients with ACS, 5,485 (0.42%) had SLE. The adjusted odds ratio (AOR) for inpatient mortality for ACS with co-existing SLE compared to those without SLE was 1.16 (95% CI 0.86-1.56, P=0.333). Hospitalizations for ACS with co-existing SLE had a decrease in adjusted mean total hospital charge of $5,164 compared to those without SLE (95% CI - {10,202-126}, P=0.045). Conclusions: Patients admitted primarily for ACS with a secondary diagnosis of SLE had less total hospital charges, but similar inpatient mortality, LOS, revascularization strategies, rates of IABP and PEAD placement compared to those without SLE. Though SLE is known to increase the risk of cardiovascular diseases, SLE does not negatively impact outcomes in patients primarily admitted for ACS based on U.S. national hospital billing data.
Inositol Trisphosphate Receptors and Nuclear Calcium in Atrial Fibrillation
Authors: Xiao-Yan Qi, Faezeh Vahdati Hassani, Dennis Hoffmann, Jiening Xiao, Feng Xiong, Louis R. Villeneuve, Senka Ljubojevic-Holzer, Markus Kamler, Issam Abu-Taha, Jordi Heijman, Donald M. Bers, Dobromir Dobrev, Stanley Nattel
Journal: Circulation Research (2020)

Rationale: The mechanisms underlying atrial fibrillation (AF), the most common clinical arrhythmia, are poorly understood. Nucleoplasmic Ca 2+ regulates gene expression, but the nature and significance of nuclear Ca 2+ -changes in AF are largely unknown. Objective: To elucidate mechanisms by which AF alters atrial-cardiomyocyte nuclear Ca 2+ ([Ca 2+ ] Nuc ) and CaMKII (Ca 2+ /calmodulin-dependent protein kinase-II)-related signaling. Methods and Results: Atrial cardiomyocytes were isolated from control and AF dogs (kept in AF by atrial tachypacing [600 bpm × 1 week]). [Ca 2+ ] Nuc and cytosolic [Ca 2+ ] ([Ca 2+ ] Cyto ) were recorded via confocal microscopy. Diastolic [Ca 2+ ] Nuc was greater than [Ca 2+ ] Cyto under control conditions, while resting [Ca 2+ ] Nuc was similar to [Ca 2+ ] Cyto ; both diastolic and resting [Ca 2+ ] Nuc increased with AF. IP 3 R (Inositol-trisphosphate receptor) stimulation produced larger [Ca 2+ ] Nuc increases in AF versus control cardiomyocytes, and IP 3 R-blockade suppressed the AF-related [Ca 2+ ] Nuc differences. AF upregulated nuclear protein expression of IP 3 R1 (IP 3 R-type 1) and of phosphorylated CaMKII (immunohistochemistry and immunoblot) while decreasing the nuclear/cytosolic expression ratio for HDAC4 (histone deacetylase type-4). Isolated atrial cardiomyocytes tachypaced at 3 Hz for 24 hours mimicked AF-type [Ca 2+ ] Nuc changes and L-type calcium current decreases versus 1-Hz-paced cardiomyocytes; these changes were prevented by IP 3 R knockdown with short-interfering RNA directed against IP 3 R1. Nuclear/cytosolic HDAC4 expression ratio was decreased by 3-Hz pacing, while nuclear CaMKII phosphorylation was increased. Either CaMKII-inhibition (by autocamtide-2-related peptide) or IP 3 R-knockdown prevented the CaMKII-hyperphosphorylation and nuclear-to-cytosolic HDAC4 shift caused by 3-Hz pacing. In human atrial cardiomyocytes from AF patients, nuclear IP 3 R1-expression was significantly increased, with decreased nuclear/nonnuclear HDAC4 ratio. MicroRNA-26a was predicted to target ITPR1 (confirmed by luciferase assay) and was downregulated in AF atrial cardiomyocytes; microRNA-26a silencing reproduced AF-induced IP 3 R1 upregulation and nuclear diastolic Ca 2+ -loading. Conclusions: AF increases atrial-cardiomyocyte nucleoplasmic [Ca 2+ ] by IP 3 R1-upregulation involving miR-26a, leading to enhanced IP 3 R1-CaMKII-HDAC4 signaling and L-type calcium current downregulation. Graphic Abstract: A graphic abstract is available for this article.
Racial Differences in AKI Incidence Following Percutaneous Coronary Intervention
Authors: Joseph Lunyera, Robert M. Clare, Karen Chiswell, Julia J. Scialla, Patrick H. Pun, Kevin L. Thomas, Monique A. Starks, Clarissa J. Diamantidis
Journal: Journal of the American Society of Nephrology (2020)

Significance Statement Percutaneous coronary intervention is linked with greater risk of AKI incidence; however, differences in this link by race remain less clear. This study quantified the association of race (White, Black, or other) with odds for AKI incidence within 7 days after percutaneous coronary intervention. After adjustment for demographics, comorbidities, medications, and procedural characteristics, the study found that, compared with Whites, odds for AKI incidence were substantially greater among Black but not other patients. Racial difference in odds for AKI incidence after percutaneous coronary intervention did not differ by baseline kidney function. These findings highlight the need to investigate factors that predispose Black individuals to greater risk for AKI after percutaneous coronary intervention. Background Undergoing percutaneous coronary intervention (PCI) is a risk factor for AKI development, but few studies have quantified racial differences in AKI incidence after this procedure. Methods We examined the association of self-reported race (Black, White, or other) and baseline eGFR with AKI incidence among patients who underwent PCI at Duke University Medical Center between January 1, 2003, and December 31, 2013. We defined AKI as a 0.3 mg/dl absolute increase in serum creatinine within 48 hours, or ≥1.5-fold relative elevation within 7 days post-PCI from the reference value ascertained within 30 days before PCI. Results Of 9422 patients in the analytic cohort (median age 63 years; 33% female; 75% White, 20% Black, 5% other race), 9% developed AKI overall (14% of Black, 8% of White, 10% of others). After adjustment for demographics, socioeconomic status, comorbidities, predisposing medications, PCI indication, periprocedural AKI prophylaxis, and PCI procedural characteristics, Black race was associated with increased odds for incident AKI compared with White race (odds ratio [OR], 1.79; 95% confidence interval [95% CI], 1.48 to 2.15). Compared with Whites, odds for incident AKI were not significantly higher in other patients (OR, 1.30; 95% CI, 0.93 to 1.83). Low baseline eGFR was associated with graded, higher odds of AKI incidence ( P value for trend &lt;0.001); however, there was no interaction between race and baseline eGFR on odds for incident AKI ( P value for interaction = 0.75). Conclusions Black patients had greater odds of developing AKI after PCI compared with White patients. Future investigations should identify factors, including multiple domains of social determinants, that predispose Black individuals to disparate AKI risk after PCI.
Functional Characterization Of The Semi-Synthetic Bile Acid Derivative Int-767, A Dual Fxr And Tgr5 Agonist
Authors: Giovanni Rizzo, Daniela Passeri, Francesca De Franco, Gianmario Ciaccioli, Loredana Donadio, Giorgia Rizzo, Stefano Orlandi, Bahman Sadeghpour, Xiaoxin X. Wang, Tao Jiang, Moshe Levi, Mark Pruzanski, Luciano Adorini
Journal: Journal of Hepatology (2010)
Molecular mechanisms and clinical implications of multiple forms of mitophagy in the heart
Authors: Toshiro Saito, Kimikazu Hamano, Junichi Sadoshima
Journal: Cardiovascular Research (2020)

Mitochondria, the primary ATP-producing organelles, are highly abundant in cardiomyocytes. Mitochondrial function readily deteriorates in the presence of stress and, thus, maintenance of mitochondrial quality is essential for sustaining pump function in the heart. Cardiomyocytes under stress attempt to maintain mitochondrial quality primarily through dynamic changes in their morphology, namely fission and fusion, degradation, and biogenesis. Mitophagy, a mitochondria-specific form of autophagy, is a major mechanism of degradation. The level of mitophagy is altered in stress conditions, which, in turn, significantly affects mitochondrial function, cardiomyocyte survival, and death and cardiac function. Thus, mitophagy has been emerging as a promising target for treatment of cardiac conditions. To develop specific interventions, modulating the activity of mitophagy in the heart, understanding how mitochondria are degraded in a given condition is important. Increasing lines of evidence suggest that there are multiple mechanisms by which mitochondria are degraded through mitophagy in the heart. For example, in addition to the well-established mechanism commonly utilized by general autophagy, involving Atg7 and LC3, recent evidence suggests that an alternative mechanism, independent of Atg7 and LC3, also mediates mitophagy in the heart. Here, we describe molecular mechanisms through which mitochondria are degraded in the heart and discuss their functional significance. We also discuss molecular interventions to modulate the activity of mitophagy and their potential applications for cardiac conditions.
Minimal clinically important differences for Dyspnea-12 and MDP scores are similar at 2 weeks and 6 months: follow-up of a longitudinal clinical study
Authors: Magnus Ekström, Hans Bornefalk, C. Magnus Sköld, Christer Janson, Anders Blomberg, Jacob Sandberg, Anna Bornefalk-Hermansson, David C. Currow, Miriam J. Johnson, Josefin Sundh
Journal: European Respiratory Journal (2020)

Chronic breathlessness is a dominating symptom that restricts daily life for many people with cardiorespiratory disease [1]. Different dimensions of the symptom, such as the intensity, sensory qualities (SQs) and emotional responses, can be assessed using the instruments Dyspnea-12 (D-12) [2] and the Multidimensional Dyspnea Profile (MDP) [3], which share similarities in the underlying constructs of what is measured [4] and have emerged as widely used instruments for multi-dimensional measurement of breathlessness. Footnotes This manuscript has recently been accepted for publication in the European Respiratory Journal . It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article. Conflict of interest: Dr. Ekström has nothing to disclose. Conflict of interest: Dr. Bornefalk has nothing to disclose. Conflict of interest: Dr. Sköld has nothing to disclose. Conflict of interest: Dr. Jansson has nothing to disclose. Conflict of interest: Dr. Blomberg has nothing to disclose. Conflict of interest: Dr. Sandberg has nothing to disclose. Conflict of interest: Dr. Bornefalk-Hermansson has nothing to disclose. Conflict of interest: Dr. Currow reports he is an unpaid advisory board member for Helsinn Pharmaceuticals. He is a paid consultant and receives payment for intellectual property with Mayne Pharma and is a consultant with Specialised Therapeutics Australia Pty. Ltd. Conflict of interest: Dr. Johnson has nothing to disclose. Conflict of interest: Dr. Sundh has nothing to disclose.
Advanced glycation end products and wheeze: a plausible association?
Authors: Jonathan Grigg
Journal: Thorax (2020)

In 1912 the French scientist Louis Camille Maillard, while attempting to synthesise proteins in his laboratory, ended up creating a byproduct that had a meaty aroma and flavour. The eponymous Maillard reaction produces many chemical compounds depending on the type of food, cooking time, temperature and presence of air. One class of Maillard-generated compounds receiving recent research attention is advanced glycation end products (AGEs), which are generated during high-temperature cooking. Animal-derived foods high in fat and protein are generally AGE-rich and prone to new formation of AGE s during cooking. Once ingested, AGEs act via engaging with the type I receptor for advanced glycation end-products (RAGE), and increasing evidence shows a role …
A distinct innate immune signature marks progression from mild to severe COVID-19
Authors: Stéphane Chevrier, Yves Zurbuchen, Carlo Cervia, Sarah Adamo, Miro E. Raeber, Natalie de Souza, Sujana Sivapatham, Andrea Jacobs, Esther Bachli, Alain Rudiger, Melina Stüssi-Helbling, Lars C. Huber, Dominik J. Schaer, Jakob Nilsson, Onur Boyman, Bernd Bodenmiller
Journal: Cell Reports Medicine (2020)

Coronavirus disease 2019 (COVID-19) manifests with a range of severities, but immune signatures of mild and severe disease are still not fully understood. Here, we use mass cytometry and targeted proteomics to profile the innate immune response of patients with mild or severe COVID-19 and of healthy individuals. Sampling at different stages allows us to reconstruct a pseudo-temporal trajectory of the innate response. A surge of CD169+ monocytes associated with an IFN-γ+MCP-2+ signature rapidly follows symptom onset. At later stages, we observe a persistent inflammatory phenotype in patients with severe disease, dominated by high CCL3 and CCL4 abundance correlating with the re-appearance of CD16+ monocytes, whereas the response of mild COVID-19 patients normalizes. Our data provide insights into the dynamic nature of inflammatory responses in COVID-19 patients and identify sustained innate immune responses as a likely mechanism in severe patients, thus supporting the investigation of targeted interventions in severe COVID-19.
Rescue of male fertility following faecal microbiota transplantation from alginate oligosaccharide-dosed mice
Authors: Cong Zhang, Bohui Xiong, Liang Chen, Wei Ge, Shen Yin, Yanni Feng, Zhongyi Sun, Qingyuan Sun, Yong Zhao, Wei Shen, Hongfu Zhang
Journal: Gut (2020)

<h3>Abstract</h3> Synchronous release at neuronal synapses is accomplished by a machinery that senses calcium influx and fuses the synaptic vesicle and plasma membranes to release neurotransmitters. Previous studies suggested the calcium sensor Synaptotagmin (Syt) is a facilitator of vesicle docking and both a facilitator and inhibitor of fusion. On phospholipid monolayers, the Syt C2AB domain spontaneously oligomerized into rings that are disassembled by Ca<sup>2+</sup>, suggesting Syt rings may clamp fusion as membrane-separating "washers" until Ca<sup>2+</sup>-mediated disassembly triggers fusion and release (Wang <i>et al.</i>, 2014). Here we combined mathematical modeling with experiment to measure mechanical properties of Syt rings and to test this mechanism. Consistent with experiment, the model quantitatively recapitulates observed Syt ring-induced dome and volcano shapes on phospholipid monolayers, and predicts rings are stabilized by anionic phospholipid bilayers or bulk solution with ATP. The selected ring conformation is highly sensitive to membrane composition and bulk ATP levels, a property that may regulate vesicle docking and fusion in ATP-rich synaptic terminals. We find the Syt molecules hosted by a synaptic vesicle oligomerize into a halo, unbound from the vesicle, but in proximity to sufficiently PIP2-rich plasma membrane (PM) domains the PM-bound trans Syt ring conformation is preferred. Thus, the Syt halo serves as landing gear for spatially directed docking at PIP2-rich sites that define the active zones of exocytotic release, positioning the Syt ring to clamp fusion and await calcium. Our results suggest the Syt ring is both a Ca<sup>2+</sup>-sensitive fusion clamp and a high-fidelity sensor for directed docking. <h3>Significance</h3> Synchronous neurotransmitter release relies on directed docking of synaptic vesicles at active zones in axon terminals, where calcium influx activates membrane fusion and release. In vitro, the calcium sensor Synaptotagmin oligomerizes into rings disassembled by calcium. Here, experiment and modeling suggest the Synaptotagmin molecules hosted by an undocked vesicle oligomerize into a tethered, unbound halo in ATP-rich synaptic terminals. The halo directs vesicle docking to PIP2-rich plasma membrane domains in active zones, where the <i>trans</i>-bound ring conformation is favored, interposed between the membranes to clamp fusion until calcium triggers ring disassembly and neurotransmitter release. The mechanism exploits the extreme sensitivity of Synaptotagmin ring binding preferences to solution and membrane composition, with ~15 -fold-enhanced sensitivity for rings of ~15 molecules.
A Genetics-First Approach to Dissecting the Heterogeneity of Autism: Phenotypic Comparison of Autism Risk Copy Number Variants
Authors: Samuel J.R.A. Chawner, Joanne L. Doherty, Richard J. L. Anney, Kevin M. Antshel, Carrie E. Bearden, Raphael Bernier, Wendy K. Chung, Caitlin C. Clements, Sarah R. Curran, Goran Cuturilo, Ania M. Fiksinski, Louise Gallagher, Robin P. Goin-Kochel, Raquel E. Gur, Ellen Hanson, Sebastien Jacquemont, Wendy R. Kates, Leila Kushan, Anne M. Maillard, Donna M. McDonald-McGinn, Marina Mihaljevic, Judith S. Miller, Hayley Moss, Milica Pejovic-Milovancevic, Robert T. Schultz, LeeAnne Green-Snyder, Jacob A. Vorstman, Tara L. Wenger, Jeremy Hall, Michael J. Owen, Marianne B.M. van den Bree
Journal: American Journal of Psychiatry (2021)

Certain copy number variants (CNVs) greatly increase the risk of autism. The authors conducted a genetics-first study to investigate whether heterogeneity in the clinical presentation of autism is underpinned by specific genotype-phenotype relationships.
College Campuses and COVID-19 Mitigation: Clinical and Economic Value
Authors: Elena Losina, Valia Leifer, Lucia Millham, Christopher Panella, Emily P. Hyle, Amir M. Mohareb, Anne M. Neilan, Andrea L. Ciaranello, Pooyan Kazemian, Kenneth A. Freedberg
Journal: Annals of Internal Medicine (2020)

Colleges in the United States are determining how to operate safely amid the coronavirus disease 2019 (COVID-19) pandemic.
Calcium Carbonate-Pre-Added Cheese to Improve Compliance, Nutrition, and Metabolic Balance of Patients on Renal Replacement Treatment
Authors: Gianluigi Ardissino, Valentina Capone, Elisabetta Margiotta, Isabella Cropanese, Francesca Raffiotta, Giovanni Montini, Piergiorgio Messa
Journal: Journal of the American Society of Nephrology (2020)

Background: Patients with chronic kidney disease have several dietary limitations that make their diet unappealing with detrimental consequences as adherence to prescriptions, malnutrition and overall poor quality of life  Cheese, an important component of the Western diet, has high phosphorus (P) content thus its consumption is generally restricted in patients on renal replacement therapy (RRT)  Methods: A special cheese was prepared by adding a fixed concentration of CaCO3 (5 gr/L) to cow milk prior to production procedures  The cheese was then provided to a cohort of patients on chronic RTT with the working hypothesis that while eating the modified cheese patients would have benefited from the phosphorus-binding effect of CaCO3  After a run-in period of 1 month, all patients were randomly assigned to receive standard cheese (SC) followed by modified cheese (FriP) or the opposite sequence in a double blind and cross-over fashion for 1 month for each product  The increase in interdialysis (48 hrs) P (DP) was regularly and repeatedly (n: 5) measured during each of the 2 periods  A washout period of 1 week was introduced between treatment periods  Results: Twenty-one patients were enrolled and 16 successfully completed the 2 treatment periods  Drop outs were due to transplantation, COVID-19 infection or to documented non-adherence to the protocol  Observed mean (sd) DP were as follows: Run-in: 2 8 (0 7) mg/dL, SC: 2 8 (0 85) mg/dL, FriP 2 4 (0 61) mg/dL with the latter being significantly lower compared with both other periods  Pre-dialysis P was also lower with FriP compared with SC: 5 00 (1 00) vs 4 66 (0 91) while Pre-dialysis Ca was not diffent: 9 24 (0 73) vs 9 24 (0 63) with SC and FriP, respectively  All patients appreciated both products equally and the mean amount consumed per week was not different: SC: 307 gr vs FriP: 283 gr (p: 0 56)  All patients reported a significant gratification by reintroducing cheese consumption in their diet  Conclusions: In conclusion, FriP cheese may reduce dietary limitations of patients on RRT mith significant benefits on: malnutrition, adherence to P binders prescription and ultimately to quality of life
Clinical impact of endoscopic ultrasound-guided through-the-needle microbiopsy in patients with pancreatic cysts
Authors: Stephen A. Firkins, Somashekar G. Krishna
Journal: Endoscopy (2020)

See also:Reply to Firkins and KrishnaEndoscopy 2021; 53(01): 104-104DOI: 10.1055/a-1288-0868See also:Clinical impact of endoscopic ultrasound-guided through-the-needle microbiopsy in patients with pancreatic cystsEndoscopy 2021; 53(01): 44-52DOI: 10.1055/a-1214-6043
Impact of Renal Replacement Therapy Modality on Prognosis of SARS-CoV2 Infection
Authors: Yannis Lombardi, Hafedh Fessi, Hélène François, Pierre A. Michel, Camille Petit-Hoang, Eric Rondeau
Journal: Journal of the American Society of Nephrology (2020)

Background: Prognosis of SARS-CoV2 infection among patients with Chronic Kidney Disease (CKD) is poorly known  In particular, the impact of renal replacement therapy (RRT) modality on prognosis is undetermined  Patients with kidney transplant exhibit treatment-induced immunodepression, while patients on dialysis are usually older and exhibit higher frailty  We aim to determine the impact of RRT modality on the prognosis of SARS-CoV2 infection among patient with advanced CKD  Methods: We conducted a retrospective cohort study using our institution's Clinical Data Warehouse  Health records of all patients with at least one hozpitalization or consultation in our nephrology department were screened based on ICD-10 codes  Inclusion criteria were: hospitalization in any of our institution's hospitals for SARSCoV2 infection (national Public Health agency criteria)  Patients were divided into two groups: active kidney transplant and dialysis  A Cox model stratifying on age and medical history of coronary artery disease was used to determine adjusted Hazard Ratio (HR) for death or intensive care unit (ICU) admission  Results: We included 72 patients: 47 in the transplant group and 25 in the dialysis group  First hospitalization was on 20/02/28 and last hospitalization on 20/05/19  Median follow-up was 21 5 days  Death or ICU admission occurred in 21 (29%) patients (transplant group: 15 (32%), dialysis group: 6 (24%), p=0 45)  In multivariate analysis, adjusted HR for death or ICU admission was 1 70 [95%CI:0 59- 4 86] for transplant vs  dialysis (p=0 32)  Conclusions: In our study, among patients hospitalized for SARS-CoV2 infection, no significant difference in risk for ICU hospitalization or death was found between CKD patients on dialysis or with active kidney transplant  A trend for higher risk was noted among patients with active kidney transplant  Further studies are required to confirm those findings