bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mendelian Randomization Analyses Suggest Childhood Body Size Indirectly Influences End Points From Across the Cardiovascular Disease Spectrum Through Adult Body Size
Authors: Power Grace M. , Tyrrell Jessica , Frayling Timothy M. , Davey Smith George , Richardson Tom G. 
Published: September 2021

Background
Obesity is associated with long‐term health consequences including cardiovascular disease. Separating the independent effects of childhood and adulthood obesity on cardiovascular disease risk is challenging as children with obesity typically remain overweight throughout the lifecourse.

Methods and Results
This study used 2‐sample univariable and multivariable Mendelian randomization to estimate the effect of childhood body size both independently and after accounting for adult body size on 12 endpoints across the cardiovascular disease disease spectrum. Univariable analyses identified strong evidence of a total effect between genetically predicted childhood body size and increased risk of atherosclerosis, atrial fibrillation, coronary artery disease, heart failure, hypertension, myocardial infarction, peripheral artery disease, and varicose veins. However, evidence of a direct effect was weak after accounting for adult body size using multivariable Mendelian randomization, suggesting that childhood body size indirectly increases risk of these 8 disease outcomes via the pathway involving adult body size.

Conclusions
These findings suggest that the effect of genetically predicted childhood body size on the cardiovascular disease outcomes analyzed in this study are a result of larger body size persisting into adulthood. Further research is necessary to ascertain the critical timepoints where, if ever, the detrimental impact of obesity initiated in early life begins to become immutable.
Anxiety Disorders Are Associated With Coronary Endothelial Dysfunction in Women With Chest Pain and Nonobstructive Coronary Artery Disease
Authors: Sara Jaskanwal D. S. , Ahmad Ali , Toya Takumi , Suarez Pardo Laura , Lerman Lilach O. , Lerman Amir 
Published: August 2021

Background
Anxiety disorders are the most prevalent mental disorders and are an emerging risk factor for coronary artery disease and its complications. We determine the relationship between having a clinical diagnosis of an anxiety disorder and coronary endothelial dysfunction (CED) using invasive coronary reactivity testing across both sexes.

Methods and Results

Patients presenting with chest pain and nonobstructive coronary artery disease (stenosis <40%) at coronary angiography underwent an invasive assessment of CED. Patients were categorized as having a clinical diagnosis of an anxiety disorder at the time of coronary angiography by chart review. The frequency of CED was compared between patients with versus without an anxiety disorder and after stratifying patients by sex. Between 1992 and 2020, 1974 patients (mean age, 51.3 years; 66.2% women) underwent invasive coronary reactivity testing, of which 550 (27.9%) had a documented anxiety disorder at the time of angiography. There was a significantly higher proportion of patients with any type of CED in those with an anxiety disorder in all patients (343 [62.7%] versus 790 [56.4%];
P
=0.011) that persisted in women but not in men. After adjusting for covariables, anxiety was significantly associated with any CED among all patients (odds ratio [95% CI], 1.36 [1.10–1.68];
P
=0.004), and after stratifying by sex in women but not in men.

Conclusions
Anxiety disorders are significantly associated with CED in women presenting with chest pain and nonobstructive coronary artery disease. Thus, CED may represent a mechanism underpinning the association between anxiety disorders and coronary artery disease and its complications, highlighting the role of anxiety as a potential therapeutic target to prevent cardiovascular events.
Recombinant Interleukin‐19 Suppresses the Formation and Progression of Experimental Abdominal Aortic Aneurysms
Authors: Tanaka Hiroki , Xu Baohui , Xuan Haojun , Ge Yingbin , Wang Yan , Li Yankui , Wang Wei , Guo Jia , Zhao Sihai , Glover Keith J. , Zheng Xiaoya , Liu Shuai , Inuzuka Kazunori , Fujimura Naoki , Furusho Yuko , Ikezoe Toru , Shoji Takahiro , Wang Lixin , Fu Weiguo , Huang Jianhua , Unno Naoki , Dalman Ronald L. 
Published: August 2021

Background
Interleukin‐19 is an immunosuppressive cytokine produced by immune and nonimmune cells, but its role in abdominal aortic aneurysm (AAA) pathogenesis is not known. This study aimed to investigate interleukin‐19 expression in, and influences on, the formation and progression of experimental AAAs.

Methods and Results
Human specimens were obtained at aneurysm repair surgery or from transplant donors. Experimental AAAs were created in 10‐ to 12‐week‐old male mice via intra‐aortic elastase infusion. Influence and potential mechanisms of interleukin‐19 treatment on AAAs were assessed via ultrasonography, histopathology, flow cytometry, and gene expression profiling. Immunohistochemistry revealed augmented interleukin‐19 expression in both human and experimental AAAs. In mice, interleukin‐19 treatment before AAA initiation via elastase infusion suppressed aneurysm formation and progression, with attenuation of medial elastin degradation, smooth‐muscle depletion, leukocyte infiltration, neoangiogenesis, and matrix metalloproteinase 2 and 9 expression. Initiation of interleukin‐19 treatment after AAA creation limited further aneurysmal degeneration. In additional experiments, interleukin‐19 treatment inhibited murine macrophage recruitment following intraperitoneal thioglycolate injection. In classically or alternatively activated macrophages in vitro, interleukin‐19 downregulated mRNA expression of inducible nitric oxide synthase, chemokine C‐C motif ligand 2, and metalloproteinases 2 and 9 without apparent effect on cytokine‐expressing helper or cytotoxic T‐cell differentiation, nor regulatory T cellularity, in the aneurysmal aorta or spleen of interleukin‐19–treated mice. Interleukin‐19 also suppressed AAAs created via angiotensin II infusion in hyperlipidemic mice.

Conclusions
Based on human evidence and experimental modeling observations, interleukin‐19 may influence the development and progression of AAAs.
Laryngotracheobronchial Amyloidosis: Patterns of Presentation and Management
Authors: Dermody Sarah M. , Campagnaro Erica L. , Kupfer Robbi A. , Hogikyan Norman D. , Morrison Robert J. 
Published: August 2021

Objective: To evaluate the pattern of presentation and management of laryngotracheobronchial amyloidosis at a tertiary care academic center over a 27 year period. Methods: In a retrospective review, the electronic medical record at a tertiary care academic center was queried for encounters with 3 laryngologists between 1996 and 2019 which included the ICD-9 or ICD-10 diagnosis of amyloidosis. Demographics, clinical presentation, referral diagnoses, medical history, family history, laboratory values, radiology studies, and treatment modalities of subjects were collated. Results were analyzed using standard univariate descriptive statistics. Results: Seventeen subjects were identified with an average age at diagnosis of 58 years (range 26-76 years). The most common amyloid type on biopsy was immunoglobulin light chain (AL) subtype. The most common location of laryngeal amyloid at diagnosis was the glottis and disease was more likely to be bilateral at the time of diagnosis in this location. Supraglottic disease more often had a unilateral presentation and had a tendency to spread to additional laryngeal subsites. Nearly 25% of subjects had associated systemic disease, including multiple myeloma, auto-immune disease, and familial ATTR mutation. Conclusions: The overall rate of associated systemic disease was low in our study cohort; however, it is higher than typically referenced in extant literature. Our cohort demonstrates that while laryngeal amyloidosis is a chronic condition, the behavior is generally indolent with a low treatment burden.
Efficiency of castor oil–based polyurethane foams for oil sorption S10 and S500: Influence of porous size and statistical analysis
Authors: Alves Fillip C , dos Santos Vanessa F , Monticeli Francisco M , Ornaghi Heitor , Barud Hernane da Silva , Mulinari Daniella R 
Published: August 2021

This study evaluates the efficiency of castor oil–based polyurethane foams for oil sorption S10 and S500, focusing on the influence of the pores’ size. Different foams were produced by varying the polyol: isocyanate ratio (1:0.3; 1:0.5; 1:1.0; 1:1.5; and 1:2.0). The physicochemical properties, morphology, density, and Hg porosity were determined. The sorption capacity was influenced by exposure time, oil viscosity, and concentration of the reagents, considering variations in the hydrophobicity, void content, and morphology. The results showed that the foam produced at an in the same mass proportion (PUC) has a higher sorption capacity in exposure time from 25 to 40 h due to higher void content and larger pore diameter size. It was observed that the lower viscosity of S10 diesel contributes to the higher sorption efficiency compared to S500 one. The Taguchi method corroborated the mentioned results, indicating a higher sorption trend by varying the reagent concentration and exposure times.
Outcome Benefits Seen With 1 Year of Optimized Sacubitril/Valsartan for the Treatment of Systolic Heart Failure Managed by Pharmacists in a Cardiology Practice
Authors: Davis Lindsay E. , Pogge Elizabeth K. 
Published: August 2021

Background: Pharmacists’ care in heart failure (HF) management has been shown to better clinical outcomes, including use of guideline-directed medical therapy and hospital readmission, although the impact observed has varied among studies. Objective: To investigate the rates of all-cause hospitalization and hospitalization from HF (hHF) and changes in surrogate markers (left-ventricular ejection fraction, New York Heart Association Functional Classification [NYHA FC], diuretic requirements) for patients with HF with reduced ejection fraction (HFrEF) on angiotensin receptor-neprilysin inhibitor (ARNi) therapy optimized within a pharmacist clinic. Methods: Retrospective chart review of patients with HFrEF on sacubitril/valsartan from July 7, 2015, through January 1, 2018. Results: For the primary outcome analysis, 70 patients with pre/post hospitalization data had a reduction in the rate of all-cause hospitalization from 45.7% in the 12 months prior to ARNi therapy initiation to 24.3% during the first year on optimized ARNi therapy ( P = 0.004). The rate of hHF reduced from 24.3% to 8.6% ( P = 0.003). For the secondary outcome analyses at the 6-month assessment point, which included 104 patients, ejection fraction improved from 26% to 34% ( P < 0.001), NYHA FC improved or remained unchanged in 86.6% of patients, and weekly loop diuretic dosing requirements were significantly reduced. Conclusion and Relevance: Real-world use of sacubitril/valsartan optimized within a pharmacist clinic was associated with reduced prevalence of all-cause and hHF during the first year of ARNi therapy. This study corroborates pharmacist involvement in HF management, which could be used to support further research and expanded pharmacist services.
Parent-Mediated Home Intervention for Delayed Sleep-Onset and Night Waking in a Child With Autism Spectrum Disorder
Authors: Linnehan Anna , Cannon Barbara , Luiselli James K. 
Published: August 2021

We report the case of a 10-year-old boy with autism spectrum disorder who had difficulty initiating and maintaining sleep. Through home consultation, his parents were trained to implement a multicomponent sleep intervention that included (a) faded bedtime, (b) regimented pre-bedtime routines, and (c) elimination of positive social consequences contingent on sleep problems including unwanted co-sleeping. A critical element in the case was functional assessment of the conditions associated with poor sleeping and matching intervention to parent preferences. Compared to a baseline phase, intervention reduced night waking frequency and duration as well as the time required for the boy to fall asleep. Follow-up results one and 2 months post-intervention documented sustained improvement.
Determination of the Median Effective Dose of Dexmedetomidine for the Prevention of Emergence Agitation in Geriatric Patients Undergoing Major Open Surgery With General Anesthesia: A Prospective, Double-Blinded, Dose-Response Trial
Authors: Wang WeiBing , Zhou Hui , Sun AiJiao , Xiao JinBo , Dong JingChong , Xu Huang 
Published: August 2021

Dexmedetomidine can effectively decrease the incidences of emergence agitation (EA) in adult patients, but there are major side effects related to increased dose of dexmedetomidine. The purpose of this study was to determine the median effective dose of dexmedetomidine in the prevention of EA among geriatric patients undergoing major open surgery with general anesthesia. A total of 50 geriatric patients were enrolled in this study. Dexmedetomidine 0.5 μg·kg−1·h−1 continuous intravenous infusion was administered to the first patient. The next dose was increased or decreased by .05 depending on the response of the previous patient, according to the Dixon up-and-down method. An “effective” or “ineffective” response was determined based on the Riker sedation-agitation score (RSAS), we defined “effective” as RSAS<5, and “ineffective” as RSAS≥5. The ED50 of dexmedetomidine in prevention of EA was .30 μg·kg−1·h−1 (95% CI, .27–.33) and the predicted ED95 was .42 μg·kg−1·h−1 (95% CI, .38–.51). The incidence of bradycardia was significantly increased in the group without EA compared to the group with EA (57.1% vs 13.6%, P = .002). The ED50 of dexmedetomidine in prevention of EA was .30 μg·kg−1·h−1 (95% CI, .27–.33) and the predicted ED95 was .42 μg·kg−1·h−1 (95% CI, .38–.51). Bradycardia was the main complication.
Preoperative high lymphocyte-to-monocyte ratio is associated with intraoperative type I endoleak in patients with TAA with TEVAR
Authors: Xie Xin-sheng , Zhao Yu-fei , Xu Dan-dan , Wang En-ci , Shu Xiao-long , Guo Da-qiao , Fu Wei-guo , Wang Li-xin 
Published: August 2021

Objectives Various inflammatory factors are closely associated with the incidence of thoracic aortic aneurysms (TAAs). Furthermore, the severity of inflammation is closely related to the absolute value and proportion of each leukocyte subgroup. Only few reports have analyzed the importance of lymphocyte–monocyte ratio (LMR) as a potential inflammatory marker in vascular diseases. Therefore, we aimed to investigate the effect of peripheral blood LMR on thoracic endovascular aortic repair (TEVAR) in patients with TAA. Methods A retrospective study of the clinical data collected in our hospital between January 2016 and January 2021 was performed on 162 patients with TAA treated with TEVAR, based on the inclusion and exclusion criteria for patient selection. Based on whether the patient had the clinical symptoms at admission and the occurrence of type I endoleaks during operation, patients were divided into two groups, respectively: an intraoperative type I endoleak group ( n = 34) and a group without intraoperative type I endoleak ( n = 128), and a group with clinical symptoms ( n = 31) and a group without clinical symptoms ( n = 131). The clinical data of these two groups were compared, the free from second intervention rates related to endoleak and the preoperatively LMR of the two groups was calculated. LMR was calculated preoperatively. Receiver-operating characteristic curve analysis was used to determine the cut-off for preoperative LMR values. Based on the cut-off point, patients were divided into a high LMR group ( n = 34) and a low LMR group ( n = 128). The clinical data of the two groups were compared, and further stratified analysis was performed. Results A total of 162 patients were included in the analysis. All patients were successfully implanted with a thoracic aorta stent graft. The preoperative LMR level and postoperative endoleak-related secondary intervention rate were higher in the type I endoleak group than those in the group without intraoperative type I endoleaks. The preoperative C-reactive protein (CRP) level of patients with TAA with clinical symptoms was higher than that of asymptomatic patients. There was a negative correlation between preoperative CRP and LMR levels. In addition, in symptomatic or asymptomatic patients, the LMR level was associated with the occurrence of intraoperative type I endoleaks. After excluding the influence of type of endografts, our results showed that the clinical symptoms did not affect the occurrence of the intraoperative type I endoleak, and patients with intraoperative type I endoleak had a higher rate of postoperative secondary intervention. Conclusion Patients with TAA with type I endoleaks during TEVAR had an increased rate of secondary intervention related to endoleaks. Patients with TAA with high LMR levels before TEVAR were more likely to have endoleaks during operation.
Mechanistic ion channel interactions in red cells of patients with Gárdos channelopathy
Authors: Jansen Julia , Qiao Min , Hertz Laura , Wang Xijia , Fermo Elisa , Zaninoni Anna , Colombatti Raffaella , Bernhardt Ingolf , Bianchi Paola , Kaestner Lars 
Published: September 2021

Abstract
In patients with Gárdos channelopathy (p.R352H), an increased concentration of intracellular Ca2+ was previously reported. This is a surprising finding because the Gárdos channel (KCa3.1) is a K+ channel. Here, we confirm the increased intracellular Ca2+ for patients with the KCa3.1 mutation p.S314P. Furthermore, we provide the concept of KCa3.1 activity resulting in a flickering of red blood cell (RBC) membranepotential, which activates the CaV2.1 channel allowing Ca2+ to enter the RBC. Activity of the nonselective cation channel Piezo1 modulates the aforementioned interplay in away that a closed Piezo1 is in favor of the KCa3.1-CaV2.1 interaction. In contrast, Piezo1 openings compromise the membrane potential flickering, thus limiting the activity of CaV2.1. With the compound NS309, we mimic a gain-of-function mutation of KCa3.1. Assessing the RBC Ca2+ response by Fluo-4–based flow cytometry and by measuring the membrane potential using the Macey-Bennekou-Egée method, we provide data that support the concept of the KCa3.1/CaV2.1/Piezo1 interplay as a partial explanation for an increased number of high Ca2+ RBCs. With the pharmacological inhibition of KCa3.1 (TRAM34 and Senicapoc), CaV2.1 (ω-agatoxin TK), and Piezo1 (GsMTx-4), we could project the NS309 behavior of healthy RBCs to the RBCs of Gárdos channelopathy patients.
Engraftment characterization of risk-stratified AML in NSGS mice
Authors: Díaz de la Guardia Rafael , Velasco-Hernandez Talía , Gutiérrez-Agüera Francisco , Roca-Ho Heleia , Molina Oscar , Nombela-Arrieta Cesar , Bataller Alex , Fuster Jose Luis , Anguita Eduardo , Vives Susana , Zamora Lurdes , Nomdedeu Josep , Gómez-Casares María Teresa , Ramírez-Orellana Manuel , Lapillonne Helene , Ramos-Mejia Verónica , Rodríguez-Manzaneque Juan Carlos , Bueno Clara , Lopez-Millan Belen , Menéndez Pablo 
Published: September 2021

Abstract
Acute myeloid leukemia (AML) is the most common acute leukemia in adults. Disease heterogeneity is well documented, and patient stratification determines treatment decisions. Patient-derived xenografts (PDXs) from risk-stratified AML are crucial for studying AML biology and testing novel therapeutics. Despite recent advances in PDX modeling of AML, reproducible engraftment of human AML is primarily limited to high-risk (HR) cases, with inconsistent or very protracted engraftment observed for favorable-risk (FR) and intermediate-risk (IR) patients. We used NSGS mice to characterize the engraftment robustness/kinetics of 28 AML patient samples grouped according to molecular/cytogenetic classification and assessed whether the orthotopic coadministration of patient-matched bone marrow mesenchymal stromal cells (BM MSCs) improves AML engraftment. PDX event-free survival correlated well with the predictable prognosis of risk-stratified AML patients. The majority (85-94%) of the mice were engrafted in bone marrow (BM) independently of the risk group, although HR AML patients showed engraftment levels that were significantly superior to those of FR or IR AML patients. Importantly, the engraftment levels observed in NSGS mice by week 6 remained stable over time. Serial transplantation and long-term culture-initiating cell (LTC-IC) assays revealed long-term engraftment limited to HR AML patients, fitter leukemia-initiating cells (LICs) in HR AML samples, and the presence of AML LICs in the CD34− leukemic fraction, regardless of the risk group. Finally, orthotopic coadministration of patient-matched BM MSCs and AML cells was dispensable for BM engraftment levels but favored peripheralization of engrafted AML cells. This comprehensive characterization of human AML engraftment in NSGS mice offers a valuable platform for in vivo testing of targeted therapies in risk-stratified AML patient samples.
Phase 2 study of venetoclax plus carfilzomib and dexamethasone in patients with relapsed/refractory multiple myeloma
Authors: Costa Luciano J. , Davies Faith E. , Monohan Gregory P. , Kovacsovics Tibor , Burwick Nicholas , Jakubowiak Andrzej , Kaufman Jonathan L. , Hong Wan-Jen , Dail Monique , Salem Ahmed Hamed , Yang Xiaoqing , Masud Abdullah A. , Munasinghe Wijith , Ross Jeremy A. , Bueno Orlando F. , Kumar Shaji K. , Stadtmauer Edward A. 
Published: September 2021

Abstract
Proteins in the antiapoptotic B-cell lymphoma 2 (BCL-2) family play a role in the pathophysiology of multiple myeloma (MM). Venetoclax is a highly selective, potent, oral BCL-2 inhibitor that induces apoptosis of MM cells, and its efficacy may be potentiated through combination with agents that increase BCL-2 dependency or have complementary mechanisms of action. The safety, tolerability, pharmacokinetics, and antitumor activity of venetoclax in combination with carfilzomib and dexamethasone (VenKd) in adults with relapsed/refractory MM (RRMM) were investigated in this phase 2 dose-escalation study. Oral venetoclax (400 or 800 mg) was administered daily in combination with intravenous carfilzomib (27, 56, or 70 mg/m2) and oral dexamethasone (20 or 40 mg) in 4 dose-finding cohorts. The expansion cohort received venetoclax 800 mg, carfilzomib 70 mg/m2, and dexamethasone 40 mg. Forty-nine patients received treatment. Median prior lines of therapy was 1 (range, 1-3), and median time in the study was 27 months. The most common treatment-emergent adverse events were diarrhea (65%), fatigue (47%), nausea (47%), and lymphopenia (35%). Serious adverse events occurred in 26 (53%) patients. Of 3 treatment-emergent deaths, 1 was considered treatment related. The overall response rate was 80% in all patients, 92% in patients with t(11;14) (n = 13), and 75% in patients without (n = 36). The rate of complete response or better was 41%. Median progression-free survival was 22.8 months. Treatment with VenKd was well tolerated and showed promising response rates in this RRMM patient population, with greater responses observed in patients with t(11;14). This trial is registered at www.clinicaltrials.gov as #NCT02899052.