bluuebunny/crossref_metadata_2025 huggingface dataset:
Application of Experimental Design Approaches and in Silico Molecular Docking on the Host-Guest Complexes with Cyclodextrin for the Analysis of Benazepril Hydrochloride in Pharmaceutical Formulation
Authors: Elsonbaty Ahmed , Attala Khaled
Published: May 2021

The presented work was explicitly concentrated on creating a correlated connection between theoretical and experimental applications via designing and developing three membrane electrodes, including three different cyclodextrins as modifier ionophores. They were decorated with sodium tetraphenylborate as an anionic exchanger and dioctyl phthalate as a plasticizer to analyze benazepril hydrochloride in the pure and pharmaceutical dosage form. Molecular modeling applications were applied to expect the structure of the inclusion complexes of benazepril hydrochloride and cyclodextrins. Experimental design approaches were used for the optimization of the composition of the most promising candidate sensor. Three independent parameters, including the amount of plasticizer (DOP), ion-pair, and ionophore (β-CD), were utilized to build up the mathematical design. Here the Response Surface Methodology (RSM) relied on central composite design (CCD) to estimate and optimize these independent factors. Derringer’s desirability function was proceeded to optimize the slope of benazepril using the most promising candidate sensor. The suggested optimum conditions were 0.29 mg of DOP, 9.54 mg of β-CD, and 9.03 mg of the ion-pair. The optimized sensor had a linear range of (1 × 10−5–1 × 10−2 mol.l−1) and a limit of detection of 5.01 × 10−6 mol.l−1. The developed methods were validated according to IUPAC recommendations.
Maternal high-fructose diet induced early-onset retinopathy via the suppression of synaptic plasticity mediated by mitochondrial dysfunction
Authors: Huang Hsiu-Mei , Wu Chih-Wei , Chen I-Chun , Lee Yu-Chi , Huang Yao-Sheng , Hung Chun-Ying , Wu Kay L. H.
Published: May 2021

In this study, we provide novel evidence that maternal high-fructose diet during gestation and lactation could induce early-onset retinopathy in adult female offspring. Of note, the insufficient energy content, downregulated mitochondrial respiratory complex 4-2, and impaired mitochondrial biogenesis might contribute to the decrease of synaptic plasticity resulting in retinal function suppression. Oral application with coenzyme Q10 for 4 wk could at least partially reverse the aforementioned molecular events and retinal function.
Cost-Effectiveness of Contraceptive Use in Indonesia after the Implementation of the National Health Insurance System
Authors: Suwantika Auliya A. , Zakiyah Neily , Puspitasari Irma M. , Abdulah Rizky
Published: May 2021

Since 2014, Indonesia has initiated to implement a national health insurance system, which included both of short- (SARC) and long-acting reversible contraceptive (LARC) into the benefit package. The aim of this study was to analyze the cost-effectiveness of contraceptive use in Indonesia after the implementation of the national health insurance in 2014-2017. A decision tree model was developed to analyze the cost-effectiveness of contraceptive use in Indonesia in 2014-2017 by comparing two strategies of pregnancy prevention: contraceptive and non-contraceptive. For contraceptive strategy, we took into account SARC and LARC. In a comparison with non-contraceptive, we calculated that the incremental cost-effectiveness ratio (ICER) of SARC would be $5.18, $4.80 and $3.76 per pregnancy averted for injection, condom, and pill, respectively. For LARC, we calculated that the ICER would be $1.67 and $0.84 for implant and intrauterine device (IUD), respectively, compared with non-contraceptive. In general, the cost-effectiveness value of LARC ($1.25) was much better than SARC ($4.58). The cost of contraceptive was considered to be the most influential parameter affecting both the ICER of SARC and LARC. In conclusion, the use of LARC in Indonesia was considered to be more cost-effective than SARC since the implementation of national health insurance system. In particular, IUD yielded the greatest cost-effectiveness value, compared with other methods.
Anticancer and Antimicrobial Activity Evaluation of Cowpea-Porous-Starch-Formulated Silver Nanoparticles
Authors: Ramdath Shiara , Mellem John , Mbatha Londiwe Simphiwe
Published: May 2021

Health issues involving inadequate treatment of diseases such as cancer and microbial infections continue to be the subject of much ongoing recent research. Biosynthesized silver nanoparticles (AgNPs) were characterized using Transmission Electron Microscopy (TEM), Zeta Sizer, Ultraviolet (UV), and Fourier Transform Infrared (FTIR) spectroscopy. Their antimicrobial activity was evaluated on selected Gram-positive and Gram-negative bacterial strains, using the disc diffusion and broth dilution assays. Cell viability profiles were evaluated using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and apoptosis studies on selected human noncancer and cancer cells. The biosynthesized AgNPs were evaluated to be spherical clusters, with sizes between 40 and 70 nm. The absorption peak at 423 nm and the presence of polyphenols confirmed the synthesis and stabilization of these tested AgNPs. The AgNPs showed a good stability of −23.9 ± 1.02 mV. Good antimicrobial activity (6.0–18.0 mm) was seen on all tested bacteria at a minimum inhibitory concentration (MIC) ranging from 5 to 16 μg/ml, with the highest activity seen against Gram-negative Escherichia coli (18 ± 0.5 mm), and the lowest activity was seen against Gram-positive Listeria monocytogenes (6.0 ± 0.4 mm) after treatment with the AgNPs. These NPs showed a concentration-dependent and cell-specific cytotoxicity with low IC50 values (41.7, 56.3, and 63.8 μg/ml). The NPs were well tolerated by tested cells as indicated by a more than 50% cell viability at the high dose tested and low apoptotic indices (<0.2). These findings indicated that these biosynthesized AgNPs showed great potential as effective antibacterial agents and anticancer drug delivery modalities.
Complete Convergence for END Random Variables under Sublinear Expectations
Authors: Wu Qunying
Published: May 2021

In this paper, the complete convergence theorems of partial sums and weighted sums for extended negatively dependent random variables in sublinear expectation spaces have been studied and established. Our results extend the corresponding results of classical probability spaces to the case of sublinear expectation spaces.
Dietary Bioactive Peptide Alanyl‐Glutamine Attenuates Dextran Sodium Sulfate‐Induced Colitis by Modulating Gut Microbiota
Authors: Xu Qingbiao , Hu Mingyang , Li Min , Hou Jinxiu , Zhang Xianghua , Gao Ya , Chachar Bahram , Li Xiang
Published: May 2021

Inflammatory bowel disease (IBD) is a chronic intestinal disorder threatening human health. Di‐peptide alanyl‐glutamine (Ala‐Gln) has various beneficial effects on gut health. However, its role and functional mechanism in treating IBD are still not clear. Therefore, the protective effects of Ala‐Gln and glutamine (Gln) on dextran sulfate sodium‐ (DSS‐) induced colitic mice were investigated in this study. The results showed that oral supplementation of Ala‐Gln or Gln significantly attenuated the colitis symptoms in mice, including body weight loss, colon length, disease activity index, histological scores, and tissue apoptosis. The concentrations of interleukin‐ (IL‐) 1β, IL‐6, tumor necrosis factor‐α, and myeloperoxidase were significantly decreased, while the concentrations of immunoglobulins (IgA, IgG, and IgM) and superoxide dismutase were significantly increased by Ala‐Gln or Gln supplementation. The expression of occludin and peptide transporter 1 (PepT1) was significantly increased by Ala‐Gln or Gln. Interestingly, Ala‐Gln had better beneficial effects than Gln in alleviating colitis. In addition, 16S rDNA sequencing showed that the DSS‐induced shifts of the microbiome (community diversity, evenness, richness, and composition) in the mouse colon were restored by Gln and Ala‐Gln, including Lactobacillus, Bacteroides_acidifaciens, Bacteroidales, Firmicutes, Clostridia, Helicobacter, and Bacteroides. Correspondingly, the functions of the microflora metabolism pathways were also rescued by Ala‐Gln, including fatty acid metabolism, membrane transporters, infectious diseases, and immune system. In conclusion, the results revealed that Ala‐Gln can prevent colitis through PepT1, enhancing the intestinal barrier and modulating gut microbiota and microflora metabolites.
Evolutionary Prediction of Nonstationary Event Popularity Dynamics of Weibo Social Network Using Time-Series Characteristics
Authors: Chen Xiaoliang , Lan Xiang , Wan Jihong , Lu Peng , Yang Ming
Published: May 2021

A growing number of web users around the world have started to post their opinions on social media platforms and offer them for share. Building a highly scalable evolution prediction model by means of evolution trend volatility plays a significant role in the operations of enterprise marketing, public opinion supervision, personalized recommendation, and so forth. However, the historical patterns cannot cover the systematical time-series dynamic and volatility features in the prediction problems of a social network. This paper aims to investigate the popularity prediction problem from a time-series perspective utilizing dynamic linear models. First, the stationary and nonstationary time series of Weibo hot events are detected and transformed into time-dependent variables. Second, a systematic general popularity prediction model N-

SEP

2

M is proposed to recognize and predict the nonstationary event propagation of a hot event on the Weibo social network. Third, the explanatory compensation variable social intensity (SI) is introduced to optimize the model N-

SEP

2

M. Experiments on three Weibo hot events with different subject classifications show that our prediction approach is effective for the propagation of hot events with burst traffic.
The Effects of Various Restorative Techniques on the Fracture Resistance of Pulpotomized Permanent Premolars
Authors: Ghahramani Yasamin , Shafiei Fereshteh , Jowkar Zahra , Kazemian Sepideh
Published: May 2021

Aim. This study aimed to evaluate the effects of various restorative techniques on the fracture resistance of pulpotomized premolars with mesioocclusodistal (MOD) cavities treated with mineral trioxide aggregate (MTA) or calcium enriched mixture (CEM) cement. Materials and Methods. One hundred and eight sound extracted maxillary premolars were randomly assigned to nine experimental groups (n = 12). The teeth in group 1 did not receive any preparation. Class II MOD cavities were prepared in the other experimental groups. In groups 2, 4, 6, and 8, tooth-colored MTA was used for pulpotomy. In groups 3, 5, 7, and 9, CEM cement was used for pulpotomy. Groups 2 and 3 were left unrestored. Groups 4 and 5 were restored with amalgam. Groups 6 and 7 were restored with a conventional composite resin, and groups 8 and 9 were restored with bulk-fill giomers. Fracture resistance was measured, the fracture pattern of each specimen was assessed, and the results were statistically analyzed. Results. The fracture resistance of group 1 was significantly higher than those of the other groups (

p
<
0.05

). The fracture resistance of group 2 (MTA + amalgam) was statistically lower than those of all experimental groups (

p

values < 0.05) except groups 3, 4, and 5 (

p

values > 0.05). No statistically significant differences were found between the groups restored with amalgam, conventional composite resin, and bulk-fill giomer (groups 4, 5, 6, 7, 8, and 9) (

p

values < 0.05). The highest rate of mode 1 fracture (restorable fracture) was observed in group 1 followed by groups 8 and 9. Conclusion. No significant differences were found among the fracture resistances of the restored teeth using various restorative techniques. Bulk-fill giomers followed by conventional composite resin were better able to prevent unfavorable fractures compared to amalgam. Therefore, they seem to be more reliable for the restoration of pulpotomized teeth with MOD cavities.
The Effectiveness of Conbercept Combined with Panretinal Photocoagulation vs. Panretinal Photocoagulation in the Treatment of Diabetic Retinopathy: A Meta-Analysis
Authors: Huang Chao , Ji Haiqing , Han Xuguang
Published: May 2021

Objective. This meta-analysis aimed to compare the effect and safety of conbercept with panretinal photocoagulation (PRP) vs. PRP in the treatment of diabetic retinopathy (DR). Methods. Relevant studies were identified through systemic searches of PubMed, EMBASE, China National Knowledge Infrastructure, and Wanfang database up to December 2020. The results of conbercept and PRP in patients with DR were analyzed, including overall effectiveness, best corrected visual acuity, central macular thickness, and complications. Results. 12 articles involving 1244 patients with DR were identified for this meta-analysis. The results of the meta-analysis showed that conbercept combined with PRP significantly increased the level of overall effectiveness and significantly reduced the central thickness of macula and the incidence of complications compared with the control group. Conclusions. Conbercept with PRP tended to be more effective than PRP alone in terms of functional outcomes for treating DR.
Perilla Leaf Extract Attenuates Asthma Airway Inflammation by Blocking the Syk Pathway
Authors: Yang Hui , Sun Wei , Fan Yan-nan , Li Shu-yi , Yuan Ji-qiao , Zhang Zi-qian , Li Xu-yu , Lin Ming-bao , Hou Qi
Published: May 2021

Perilla frutescens (L.) Britton is a classic herbal plant used widely against asthma in China. But its mechanism of beneficial effect remains undermined. In the study, the antiallergic asthma effects of Perilla leaf extract (PLE) were investigated, and the underlying mechanism was also explored. Results showed that PLE treatment significantly attenuated airway inflammation in OVA-induced asthma mice, by ameliorating lung pathological changes, inhibiting recruitment of inflammatory cells in lung tissues and bronchoalveolar lavage fluid (BALF), decreasing the production of inflammatory cytokines in the BALF, and reducing the level of immunoglobulin in serum. PLE treatment suppressed inflammatory response in antigen-induced rat basophilic leukemia 2H3 (RBL-2H3) cells as well as in OVA-induced human peripheral blood mononuclear cells (PBMCs). Furthermore, PLE markedly inhibited the expression and phosphorylation of Syk, NF-κB, PKC, and cPLA2 both in vivo and in vitro. By cotreating with inhibitors (BAY61-3606, Rottlerin, BAY11-7082, and arachidonyl trifluoromethyl ketone) in vitro, results revealed that PLE’s antiallergic inflammatory effects were associated with the inhibition of Syk and its downstream signals NF-κB, PKC, and cPLA2. Collectively, the present results suggested that PLE could attenuate allergic inflammation, and its mechanism might be partly mediated through inhibiting the Syk pathway.
A Method of Surface Defect Detection of Irregular Industrial Products Based on Machine Vision
Authors: Li Mengkun , Jia Junying , Lu Xin , Zhang Yue
Published: May 2021

In recent years, the surface defect detection technology of irregular industrial products based on machine vision has been widely used in various industrial scenarios. This paper takes Bluetooth headsets as an example, proposes a Bluetooth headset surface defect detection algorithm based on machine vision to quickly and accurately detect defects on the headset surface. After analyzing the surface characteristics and defect types of Bluetooth headsets, we proposed a surface scratch detection algorithm and a surface glue‐overflowed detection algorithm. The result of the experiment shows that the detection algorithm can detect the surface defect of Bluetooth headsets fast as well as effectively, and the accuracy of defect recognition reaches 98%. The experiment verifies the correctness of the theory analysis and detection algorithm; therefore, the detection algorithm can be used in the recognition and detection of surface defect of Bluetooth headsets.
Noyes‐Whitney Dissolution Model‐Based pH‐Sensitive Slow Release of Paclitaxel (Taxol) from Human Hair‐Derived Keratin Microparticle Carriers
Authors: Wimalasiri V. W. , Dunuweera S. P. , Dunuweera A. N. , Rajapakse R. M. G.
Published: May 2021

This paper describes a convenient and straightforward method developed to extract keratin particles (KPs) from human hair. It also involves their characterization by several methods and encapsulation of the anticancer drug Paclitaxel (Taxol) within them, aiming for targeted delivery to cancerous sites and slow release at their vicinity. The KPs obtained were in micrometer in size. They are capable of encapsulating Taxol within them with a high encapsulation efficiency of 56% and a drug loading capacity of 2.360 g of Taxol per g keratin. As revealed by the SEM elemental analysis, KPs do not contain any toxic metal ion, and hence, they pose no toxicity to human cells. The pH‐dependent release kinetics of the drug from KPs indicates that the drug is released faster when the pH of the solution is increased in the 5.0 to 7.0 pH range. The release kinetics obtained is impressive, and once targeted to the cancerous sites, using cancer directing agents, such as folic acid; a glutamate urea ligand known as DUPA; aminopeptidase N, also known as CD13; and FAP‐α‐targeting agents, the slow release of the drug is expected to destroy only the cancerous cells. The Noyes‐Whitney dissolution model was used to analyze the release behavior of Taxol from KPs, which shows excellent fitting with experimental data. The pH dependence of drug release from keratin is also explained using the 3‐D structures and keratin stability at different pH values.
Quantitative Phosphoproteomic Comparison of Lens Proteins in Highly Myopic Cataract and Age‐Related Cataract
Authors: Zhang Shaohua , Zhang Keke , He Wenwen , Lu Yi , Zhu Xiangjia
Published: May 2021

Purpose. To investigate and compare the lens phosphoproteomes in patients with highly myopic cataract (HMC) or age‐related cataract (ARC). Methods. In this study, we undertook a comparative phosphoproteome analysis of the lenses from patients with HMC or ARC. Intact lenses from ARC and HMC patients were separated into the cortex and nucleus. After protein digestion, the phosphopeptides were quantitatively analyzed with TiO2 enrichment and liquid chromatography‐mass spectrometry. The potential functions of different phosphopeptides were assessed by Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Results. In total, 522 phosphorylation sites in 164 phosphoproteins were identified. The number of phosphorylation sites was significantly higher in the cortex than in the nucleus, in both ARC and HMC lenses. The differentially phosphorylated peptides in the lens cortex and nucleus in HMC eyes were significantly involved in the glutathione metabolism pathway. The KEGG pathway enrichment analysis indicated that the differences in phosphosignaling mediators between the ARC and HMC lenses were associated with glycolysis and the level of phosphorylated phosphoglycerate kinase 1 was lower in HMC lenses than in ARC lenses. Conclusions. We provide an overview of the differential phosphoproteomes of HMC and ARC lenses that can be used to clarify the molecular mechanisms underlying their different phenotypes.
A Rare Case of Endometriosis of the Small Bowel
Authors: Zepeda Moisés R. , Win Su K.
Published: May 2021

Endometriosis of the small bowel is a rare clinical event. The clinical condition presents with vague abdominal symptoms and is usually not diagnosed acutely, unless clinicians have a high index of suspicion. Most patients are diagnosed after multiple clinical encounters. We present a case of endometriosis causing small bowel obstruction diagnosed postsurgically.
The Effectiveness of Advanced Platelet-Rich Fibrin in comparison with Leukocyte-Platelet-Rich Fibrin on Outcome after Dentoalveolar Surgery
Authors: Makki Alaa Z. , Alsulami Anoud M. , Almatrafi Arwa S. , Sindi Moroj Z. , Sembawa Shahinaz N.
Published: May 2021

Background and Purpose. Some physiological changes may occur following tooth extraction, and symptoms during the postextraction period may affect the patient’s quality of life. Many techniques have been developed to improve postextraction pain and soft tissue healing. Accordingly, this study will compare the postextraction pain and early soft tissue healing characteristics of extraction sites treated with leukocyte-platelet-rich fibrin (L-PRF) and advanced platelet-rich fibrin (A-PRF). The aim is to evaluate the effect of advanced PRF in comparison with L-PRF on soft tissue healing and pain after teeth extraction and to advice dental practitioner to use the advanced PRF in clinic to enhance soft tissue healing and decrease pain. Methods. The study included 60 patients according to sample size calculation, recruited from patients seeking tooth extraction at oral and maxillofacial surgery clinic at Umm Al-Qura University, Faculty of Dentistry. Patients were divided into three groups. Group Ӏ included 20 patients managed by advanced platelet-rich fibrin after extraction. Group ӀӀ included 20 patients managed by leukocyte-platelet-rich fibrin after tooth extraction. Group ӀII included 20 patients left without any addition. Each group was further subdivided into surgical and nonsurgical extraction. Afterwards, patients in each group were assessed for postextraction pain by VAS, number of analgesics, and early soft tissue healing by LWHI. Results. The study outcomes demonstrate that the use of A-PRF significantly reduces postoperative pain in the 1st and 2nd day. VAS pain scores on the first day were significantly higher in the control surgical extraction group and L-PRF nonsurgical extraction group. In early soft tissue healing. The Landry Wound Healing Index (LWHI) was used after 1 and 2 weeks of extraction to evaluate the extraction site. In first week, the A-PRF group and L-PRF group (nonsurgical extraction) had a better healing index when compared to control group, and A-PRF group (surgical extraction) had a best healing index when compared to L-PRF and control groups. In the second week, individuals in the A-PRF group (surgical and nonsurgical extraction) had a better healing index when compared to L-PRF and control groups.
Neuroprotective Effects of Asparagus officinalis Stem Extract in Transgenic Mice Overexpressing Amyloid Precursor Protein
Authors: Peng Zhanglong , Bedi Supinder , Mann Vivek , Sundaresan Alamelu , Homma Kohei , Gaskey Gregory , Kowada Minoru , Umar Shahid , Kulkarni Anil D. , Eltzschig Holger K. , Doursout Marie-Francoise
Published: May 2021

To mimic Alzheimer’s disease, transgenic mice overexpressing the amyloid precursor protein (APP) were used in this study. We hypothesize that the neuroprotective effects of ETAS®50, a standardized extract of Asparagus officinalis stem produced by Amino Up Co., Ltd. (Sapporo, Japan), are linked to the inhibition of the apoptosis cascade through an enhancement of the stress-response proteins: heat shock proteins (HSPs). APP-overexpressing mice (double-transgenic APP and PS1 mouse strains with a 129s6 background), ages 6-8 weeks old, and weighing 20-24 grams were successfully bred in our laboratory. The animals were divided into 5 groups. APP-overexpressing mice and wild-type (WT) mice were pretreated with ETAS®50 powder (50% elemental ETAS and 50% destrin) at 200 mg/kg and 1000 mg/kg body weight. Saline, the vehicle for ETAS®50, was administered in APP-overexpressing mice and WT mice. ETAS®50 and saline were administered by gavage daily for 1 month. Cognitive assessments, using the Morris Water Maze, demonstrated that memory was recovered following ETAS®50 treatment as compared to nontreated APP mice. At euthanization, the brain was removed and HSPs, amyloid β, tau proteins, and caspase-3 were evaluated through immunofluorescence staining with the appropriate antibodies. Our data indicate that APP mice have cognitive impairment along with elevated amyloid β, tau proteins, and caspase-3. ETAS®50 restored cognitive function in these transgenic mice, increased both HSP70 and HSP27, and attenuated pathogenic level of amyloid β, tau proteins, and caspsase-3 leading to neuroprotection. Our results were confirmed with a significant increase in HSP70 gene expression in the hippocampus.
An Effective and Efficient Sample Preparation Method for 2-Methyl-Isoborneol and Geosmin in Fish and Their Analysis by Gas Chromatography-Mass Spectrometry
Authors: Tian Liang-liang , Han Feng , Fodjo Essy Kouadio , Zhai Wenlei , Huang Xuan-Yun , Kong Cong , Shi Yong-Fu , Cai You-Qiong
Published: May 2021

The intensive aquaculture strategy and recirculating aquaculture system often lead to the production of off-flavor compounds such as 2-methyl-isoborneol (2-MIB) and Geosmin (GSM). The regular purge and trap extraction followed by analysis with gas chromatography-mass spectrometry (GC-MS) usually involve a complicated assembly of facilities, more working space, long sample preparation time, and headspace solid-phase microextraction (SPME). In this work, a method with easier sample preparation, fewer and simplified facilities, and without SPME on GC-MS analysis is developed for the determination of 2-MIB and GSM in fish samples. Unlike previous methods, solvent extract from samples, QuEChERS-based cleanup, and solid-phase extraction for concentration are applied. The LOD (S/N > 3) and LOQ (S/N > 10) of this method were validated at 0.6 μg/kg and 1.0 μg/kg for both 2-MIB and GSM, which are under the sensory limit (1 μg/kg). Application of this method for incurred fish samples demonstrated acceptable analytical performance. This method is suitable for large-scale determination of 2-MIB and GSM in fish samples, owing to the use of simple facility and easy-to-operate procedure, rapid sample preparation, and shorter time for GC-MS analysis without SPME.
Fracture Characteristics and Fatigue Damage of Noncoplanar Fractured Rocklike Specimens under Uniaxial Graded Cyclic Loading and Unloading
Authors: He Gui-cheng , Wu Wen-yuan , Wang Yun , Xue Yong-ming , Dai Bing , Zhang Zhi-jun
Published: May 2021

To study the fracture characteristics and fatigue damage of fractured rock masses, noncoplanar fractured rocklike specimens prepared using cement mortar were used for a graded cyclic loading–unloading test. The results showed that the two ends of the horizontal crack were the main stress concentration areas, and they inhibited crack initiation of the inclined fracture. With increasing crack inclination, the inhibitory effect became more obvious. Under the condition that the lower limit stress is constant, as the upper limit stress increases, energy dissipation of the specimen increases, becoming relatively stable in each stage of the cycle. With increasing crack inclination, the increase in the energy dissipation value decreases. Specimens with large changes in the shape of their hysteresis loop tend to exhibit large fluctuations in the elastic modulus. As the loading progressed, the elastic modulus exhibited a downward trend, and the damping ratio tended to be stable. The change in the damping ratio is affected by the dynamic elastic modulus and area of the hysteresis loop. Based on the Weibull probability distribution function, the evolution curve of the damage variable of the specimen can be obtained. This curve reflects the trend of the damage change of the rocklike specimens under various levels of cyclic loading and unloading.
Comparison of Cytokines in Skin Biopsies and Tape Strips from Adults with Atopic Dermatitis
Authors: Simonsen Stine , Brøgger Peter , Kezic Sanja , Thyssen Jacob P. , Skov Lone
Published: May 2021

Skin biomarkers for disease severity and treatment response in atopic dermatitis (AD) are needed. Biopsies cause scarring and tape stripping represents an alternative minimally invasive method for stratum corneum sampling. In this study, we examined the gene expression of cytokines in skin biopsies and cytokines in stratum corneum tape strips collected from adults with AD. We collected punch biopsies and tape strips from healthy controls (n = 6) and subjects with AD (n = 12) at baseline and after 2 weeks of topical treatment with mometasone furoate 0.1% cream. We found that IFN-γ, IL-13, and IL-10 mRNA (biopsies) and IL-1β protein expression levels (tape strips) were significantly increased in lesional AD skin compared to healthy control skin. Treatment with topical corticosteroid led to a significant decrease in mRNA levels for IL-13 and IL-4R but no significant differences in cytokine protein levels measured in tape strips. Finally, we found no significant correlations between cytokine levels in tape strips and mRNA levels in skin biopsies.
Early Experience with Comaneci, a Newly FDA-Approved Controllable Assist Device for Wide-Necked Intracranial Aneurysm Coiling
Authors: Taqi M. Asif , Raz Eytan , Vechera Anastasia , Shapiro Maksim , Gupta Rishi , Haynes Joseph , Taussky Philipp , Grandhi Ramesh , Riina Howard A. , Nelson Peter Kim , Nossek Erez
Published: May 2021

Background: Comaneci (Rapid Medical) is a compliant, adjustable mesh that provides temporary scaffolding during coiling of wide-necked intracranial aneurysms (WNAs) that preserves antegrade flow. We report our early multi-institutional experience with the Comaneci device in the USA. Method: We reviewed all patients with WNAs that were treated using the Comaneci device for coil remodeling of ruptured and unruptured aneurysms at 4 institutions between July 2019 and May 2020. Clinical characteristics, angiographic variables, and endovascular results were assessed. Results: A total of 26 patients were included (18 women). The mean age was 62.7 years (range 44–81). Fifteen patients presented with ruptured aneurysms and 11 with unruptured aneurysms. The mean aneurysm neck width was 3.91 mm (range 1.9–6.5) with a mean dome-to-neck ratio of 1.57 (range 0.59–3.39). The mean maximum width was 5.80 mm (range 3.0–9.9) and the mean maximum height was 5.61 mm (range 2.0–11.8). Successful aneurysm occlusion was achieved in 25 of 26 patients. Complete occlusion was achieved in 16 patients, near-complete occlusion was observed in 9 patients, and 1 patient demonstrated residual filling. The mean time of device exposure was 24 min (range 8–76). No vasospasm was observed at the device location. Clot formation on the device was noted in 2 separate cases, but there were no clinical sequelae. There was 1 intraprocedural complication in a case that involved the simultaneous use of 2 Comaneci devices. Conclusions: Our initial experience shows that the Comaneci device is a promising and reliable tool that can safely support coil remodeling of WNAs.
Comparisons of Efficacy and Safety between Triple (Inhaled Corticosteroid/Long-Acting Muscarinic Antagonist/Long-Acting Beta-Agonist) Therapies in Chronic Obstructive Pulmonary Disease: Systematic Review and Bayesian Network Meta-Analysis
Authors: Lee Hyun Woo , Kim Hyung Jun , Jang Eun Jin , Lee Chang-Hoon
Published: May 2021

Background: Various combinations of inhaled corticosteroid (ICS), long-acting muscarinic antagonist (LAMA), and long-acting beta-agonist (LABA) have been used as triple therapy for stable chronic obstructive pulmonary disease (COPD). Objective: Our study was conducted to answer whether there were significant differences among various combinations in efficacy, for reducing exacerbation or mortality, and in safety, for increasing cardiovascular events or pneumonia. Method: We searched parallel-group randomized controlled trials (RCTs) comparing ICS/LAMA/LABA with other inhaled drugs in patients with stable COPD for at least 12 weeks in PubMed, EMBASE, the Cochrane Library, and clinical trial registries from inception to December 31, 2019. We conducted a network meta-analysis with Bayesian statistics using a random-effects model with heterogeneous variance structure (PROSPERO, CRD42019126757). Results: Nine different combinations of ICS/LAMA/LABA were identified in 21 RCTs containing 29,892 patients with moderate to very severe COPD. We could not find any significant evidence suggesting a better treatment for reducing total exacerbations or all-cause mortality among ICS/LAMA/LABA combinations. There were also no significant differences in moderate to severe exacerbation, COPD-related mortality, or cardiovascular disease-related mortality among ICS/LAMA/LABA combinations, and the risk of major adverse cardiovascular events was not different. A significantly lower risk of pneumonia was found in fluticasone propionate (FP)/glycopyrrolate/salmeterol (SAL) than FP/tiotropium/SAL {median odds ratio [OR] (95% credible interval [CrI]) = 0 [0–0.72]} and FP/umeclidinium/SAL {median OR (95% Crl) = 0 [0–0.97]}. Conclusion: There were no significant differences in clinical outcomes, including acute exacerbation and all-cause mortality among various ICS/LAMA/LABA combinations in patients with moderate to very severe COPD.
Neonatal Withdrawal Syndrome following Late in utero Exposure to Selective Serotonin Reuptake Inhibitors: A Systematic Review and Meta-Analysis of Observational Studies
Authors: Wang Jianjun , Cosci Fiammetta
Published: May 2021

Introduction: A clear picture of neonatal withdrawal signs due to in utero selective serotonin reuptake inhibitor (SSRI) exposure and its consequences is still missing. Objective: A systematic review and a meta-analysis were performed to provide an overview of neonatal withdrawal signs following late in utero exposure to SSRIs and to quantify the corresponding risks. Methods: MEDLINE, Web of Science, and Embase were searched from inception to January 2021. The Meta-Analysis of Observational Studies in Epidemiology (MOOSE) guidelines were followed. English-language observational studies reporting on acute postpartum outcomes following late in utero exposure to SSRIs or SSRIs/venlafaxine were evaluated. Results: Of 2,269 citations reviewed, 79 studies were assessed for eligibility; 13 were included in the qualitative analysis of the literature, which allowed us to identify 26 signs. A meta-analysis was run separately for studies on SSRI exposure (n = 3) and those on SSRI/venlafaxine exposure (n = 6). Hypoglycemia was identified as a withdrawal sign based on the SSRI studies. Tremors, hypotonia, tachycardia, rapid breathing, respiratory distress, and hypertonia were identified as withdrawal signs based on the SSRI/venlafaxine studies. Conclusions: The present work provides a framework for the identification of neonatal SSRI withdrawal syndrome. Tapering and discontinuation of antidepressant drugs before and during the early phase of pregnancy are worth attempting to prevent the occurrence of this syndrome.
The Miracles of Surfactant: Less Invasive Surfactant Administration, Nebulization, and Carrier of Topical Drugs
Authors: Härtel Christoph , Glaser Kirsten , Speer Christian P.
Published: May 2021

Surfactant replacement therapy (SRT) has long become the standard of care in the treatment of neonatal respiratory distress syndrome (RDS), significantly decreasing acute pulmonary morbidity and mortality in preterm infants. For decades, this beneficial replacement therapy has been administered via endotracheal tube. Despite significantly improving the outcome of RDS, however, the burden of bronchopulmonary dysplasia remains, in particular, in very immature preterm infants. Acknowledging the direct relationship between exposure to and duration of invasive mechanical ventilation and chronic lung disease, the latter has been gradually replaced by noninvasive ventilation strategies in neonatal RDS. This replacement is strongly related to the demand for similarly noninvasive modes of surfactant administration. Alternative techniques in spontaneously breathing infants have evolved, including less invasive techniques using thin catheters (less invasive surfactant administration and minimally invasive surfactant treatment) as well as nebulization of surfactant, although the latter is not ready for clinical application yet. In addition, given their therapeutic delivery to the lungs and subsequent alveolar distribution, surfactant preparations represent an attractive vehicle for pulmonary deposition of drugs in preterm infants. Further improvement of SRT and expansion of the field of application of lung surfactant may hold additional benefits, especially in the treatment of the most immature preterm infants.
Dyspepsia in Primary Care Medicine: A European Prospective
Authors: Fracasso Pierluigi
Published: May 2021

Background: Dyspepsia is a very frequent condition, affecting up to 50% of general population. Primary care is the logical setting for starting a management. In treating dyspeptic patients, it is a crucial point to distinguish between functional problems, common diseases such as reflux esophagitis or peptic ulcer, and life-threatening diseases such as upper gastrointestinal (GI) cancer. In Europe, there are different approaches to this problem. We describe the management of dyspepsia, with a particular focus on relationship between dyspepsia and gastric cancer. Summary: Initial treatment of dyspepsia includes empirical treatment, noninvasive testing for Helicobacter pylori, and upper GI tract endoscopy. Treatment choice is based on different variables, including alarm signs, patient preference, and possibility to perform a gastroscopy. General practitioners are not allowed in all European nations to order a gastroscopy. This may have some reflection on quality of cure. Key Message: In European countries, there are heterogeneities in terms of gastric cancer incidence, mortality, and quality of cure. Awareness of them is a first step in identifying possible solutions.
Abstract 12546: Major Adverse Cardiovascular Events and Hospital Readmissions in the 90 Days Following Acute Myocardial Infarction: Redefining the Risk Period
Authors: Allen Keith , Young Christopher , Alexander James , Gabriel Susan
Published: May 2021

Introduction:
Centers for Medicare & Medicaid Services (CMS) has implemented a voluntary bundled payment program centered on a 90-day period for acute myocardial infarction (AMI) to increase the quality of care and reduce costs. Tying payments and penalties to a 90-day period, versus the current 30-day period for quality metrics, redefines the risk period for recurrent events following AMI.

Objective:
To quantify the clinical burden of recurrent events in the 30- and 90-day period post AMI.

Methods:
A retrospective cohort analysis was conducted of 30- and 90-day major adverse cardiovascular events (MACE: mortality, AMI readmission and stroke), all-cause and cardiac rehospitalization among patients with a primary diagnosis of AMI within a Medicare population.

Results:
This analysis included 125,772 Medicare patients. At 90 days, the overall rate of all-cause and cardiac rehospitalization was 23.7% and 13.2%, respectively. The rate of MACE at 90 days was 10.2%. Rates of all outcomes increased significantly between day 30 and day 90 (p<0.0001, Figure 1). Relative increases were observed in all-cause rehospitalization (82.1%), cardiac rehospitalization (77.8%), MACE (99.8%), AMI readmission (374.3%), mortality (82.2%), and stroke (77.8%).

Conclusions:
The 90-day period post AMI is associated with significant healthcare burden, with approximately one quarter of AMI episodes associated with hospital readmissions. Rates of outcomes increase substantially between 30 and 90 days post AMI, in particular AMI readmission increases disproportionately relative to the increase in timeframe. These findings represent a significant impact when moving from a 30- to a 90-day payment bundling model.
Abstract 12563: Retrospective Analysis of Cardiovascular Events With the Use of Immune Checkpoint Inhibitors
Authors: Tarun Tushar , Bostick Brian P , Baswaraj Deepa , Basra Nishchayjit , Khan Meeshal , Bickel Trent
Published: May 2021

Introduction:
Immune checkpoint inhibitors have emerged as a promising, novel therapy for multiple malignancies. Immune-related adverse reactions pose a serious concern with use of these agents and reportedly involve multiple organ systems, notably cardiotoxicity. Early identification and management of these adverse events is essential in the prevention of morbidity and mortality.

Hypothesis:
Immune checkpoint inhibitors cause multiple cardiotoxic effects, and patients with prior cardiac history have a higher likelihood of cardiotoxicity.

Methods:
1. A retrospective analysis of 150 patients was performed who had received immunotherapy with either the cytotoxic T lymphocyte associated antigen 4 inhibitors (CTLA4) or with the programmed cell death inhibitors (PD1) or programmed death-ligand 1 (PD-L1) inhibitors for a period of two years at a Tertiary health Care from 7/1/2016-6/30/2018. 2. Patients' cardiac diagnoses prior to the initiation of therapy were noted and included, including history of heart failure, coronary artery disease, atrial fibrillation, and sudden cardiac arrest. 3. Patients’ clinic visits and hospitalizations with admitting and discharge diagnosis, electrocardiogram, echocardiogram, troponin T, and NT-proBNP were reviewed.

Results:
6% of patients had new onset heart failure (both preserved and reduced), 1.3% had evidence of myocardial infarction, 2% had new atrial fibrillation with rapid ventricular rate, and 0.6% had fulminant myocarditis. Of patients with new cardiac events, 60% had a history of cardiac disease, which was significantly higher than in patients without (p< 0.05). There were no age or sex differences between the groups with and without cardiotoxicity.

Conclusion:
Immunotherapy with immune checkpoint inhibitors have broadened the horizon for treatment of multiple solid and hematological malignancies. Nonetheless, new adverse effects on multiple organ systems, specifically cardiac involvement, occur with these therapies, which are important and potentially detrimental toxicities. Patients with a history of prior cardiovascular disease have higher likelihood to develop cardiotoxicity.
Abstract 12588: Characteristics and Survival After Transcatheter Aortic Valve Replacement in Immunocompromised Patients: A Cohort Study
Authors: Ghannam Alexander , Ball Colleen , Gharacholou Shahyar , Pollak Peter , Parikh Pragnesh , Landolfo Carolyn , Ali Mays , Landolfo Kevin
Published: May 2021

Background:
Immunocompromised (IC) patients are at greater risk from cardiac surgery. Transcatheter aortic valve replacement (TAVR) may be more preferable for treating severe aortic stenosis (AS), though data regarding outcomes of IC patients are limited.

Methods:
We reviewed TAVR procedures performed at our institution from 1/2015-12/2019.We defined IC as either active malignancy receiving oncologic treatment or post organ transplant on immunosuppression, HIV, chronic steroid use (>5mg/day), or autoimmune disorder. Survival probability was estimated using the Kaplan-Meier (KM) method. Cox regression was used to evaluate the association of IC with survival.

Results:
Of 173 patients who underwent TAVR, 56 (32%) were IC: 30 (54%) had active malignancy undergoing active treatment, 19 (34%) were IC without malignancy, and 7 (13%) had both. Among the 19 IC patients without malignancy, 4 were post organ transplant, 3 were taking chronic steroids, 2 had autoimmune disorder, 1 had HIV, and 10 had ≥2 combination of the above. IC patients, as compared to non-IC patients, had similar baseline demographics and STS risk score (median 4.3 vs. 4.4), respectively. There were 37 deaths (16 IC and 21 non-IC) over a median follow up of 1.4 years (IQR 1.0-2.0 years). 1-year survival after TAVR was 84.5% for IC patients and 89.0% for non-IC patients (log rank p = 0.51). After adjusting for age and sex, an association between IC and survival was observed but not found to be statistically significant (adjusted HR, 1.55; 95% CI, 0.80-3.00).

Conclusions:
IC patients undergoing TAVR have similar baseline characteristics as non-IC patients with a trend towards worse survival. Longer term follow-up may help clarify the impact of IC status on survival after TAVR.
Abstract 12602: Poor Quality of Life in Patients With and Without Frailty: Co-prevalence and Prognostic Implications in Patients Undergoing Percutaneous Coronary Interventions and Cardiac Catheterization
Authors: Kanwar Amrit , Roger Veronique L , Lennon Ryan J , Gharacholou Shahyar , Singh Mandeep
Published: May 2021

Introduction:
Relationship of QOL and frailty are poorly defined.

Hypothesis:
To study the prevalence and prognosis of poor QOL in frail patients.

Methods:
Predismissal standardized tests for frailty and QOL in 2 cohorts were administered. In cohort 1, 629 patients ≥ 65 years underwent percutaneous coronary intervention (PCI) from 2005-2008, frailty (Fried) and QOL [SF-36 and SAQ] were ascertained. Cohort 2 [921 patients, 535 PCI, ≥55 years] underwent cardiac catheterization from 2014-18, frailty (Rockwood) and QOL (Likert) were determined.

Results:
In cohort 1, 19%; and 20% in cohort 2 were frail. Lower median SAQ (58.9 vs. 82.2); physical (29.5 vs. 43.9) and mental (49.2 vs. 57.4) scores of SF-36 in cohort 1 higher rates of fair/poor health (56% vs 18%) in cohort 2 (all comparisons, p<0.001) was seen in frail patients. As compared to without, frail patients were 5 times more likely (59% vs. 11%, p<0.001) in cohort 1 and 7 times more likely (56% vs. 8%) in cohort 2 to have poor QOL. Adjusted three year all-cause death and death/myocardial infarction (MI) was significantly higher for patients undergoing PCI with frailty; [HR (95% CI) death, 4.20 (2.63, 6.68) and death or MI HR 2.72 (1.91, 3.87), p<0.001) and with poor QOL [HR death 2.47 (1.59, 3.84) and death or MI 1.61 (1.16, 2.24) p<0.001). There was no significant interaction between frailty and QOL (p=0.64) indicating their independent prognostic influence.

Conclusions:
Poor QOL is commonly seen with frailty. Both frailty and poor QOL had significant and independent association with long-term survival.
Abstract 12614: Total Thrombus Formation Analysis System Can Predict High Bleeding Risk in Coronary Artery Disease Patients Undergoing Percutaneous Coronary Intervention
Authors: Nakanishi Nobuhiro , Kaikita Koichi , Tsujita Kenichi
Published: May 2021

Introduction:
Antithrombotic therapy is established for the treatment in various cardiovascular events, however, it has shown to increase the bleeding risk. Total Thrombus-formation Analysis System (T-TAS) is reported to be useful for evaluating thrombogenicity.

Hypothesis:
We examined whether T-TAS might predict 1-year bleeding risk in patients undergoing percutaneous coronary intervention (PCI).

Methods:
This was a retrospective, observational study at Kumamoto University Hospital between April 2017 and March 2019. Blood samples obtained on the day of PCI were used in T-TAS to compute the thrombus formation area under the curve (AUC) (AR10-AUC30, AUC for AR chip). We divided the study population into 2 groups according to the Academic Research Consortium for High Bleeding Risk (ARC-HBR) (182 patients in ARC-HBR positive, 118 in ARC-HBR negative). The primary endpoint was 1-year bleeding events that were defined by Bleeding Academic Research Consortium type2, 3, or 5.

Results:
The AR10-AUC30 levels were significantly lower in the ARC-HBR positive group than in the ARC-HBR negative group (median [interquartile range] 1568.1 [1258.5-1744.1] vs. 1723.1 [1567.0-1799.5], p<0.001). The combination of ARC-HBR and AR10-AUC30 could discriminate the bleeding risk, and improved predictive capacity compared with ARC-HBR by c-statistics and integrated discrimination improvement. In multivariate Cox hazards analyses, combining ARC-HBR and lower AR10-AUC30 levels were significantly associated with 1-year bleeding events. Decision curve analysis revealed that combining AR10-AUC30 with ARC-HBR ameliorated risk-prediction of bleeding events.

Conclusions:
The results highlighted that AR10-AUC30 could be a potentially useful marker for predicting high bleeding risk in patients undergoing PCI.