bluuebunny/crossref_metadata_2025 huggingface dataset:
Experimental Study and Numerical Simulation on Failure Process of Reinforced Concrete Box Culvert
Authors: Gong Yafeng , Ma Yulin , Tan Guojin , Bi Haipeng , Pang Yunze , Ma Chen
Published: August 2020

Culvert is an important part of roads whose healthy operation is related to the efficiency and safety of road transportation. Therefore, it is very important to evaluate the safety of culvert structure by load test. Four types of prefabricated reinforced concrete box culverts (integral BC, round hinged BC, flat seam BC, and mortise BC) were designed in this paper. By designing a scale model test, the sensor system was used to test the mechanical properties of BC, which included dial indicators, strain gauges, and a pressure sensor. The finite element analysis based on material nonlinearity and contact nonlinearity of round hinged BC and integral BC was carried out. After validating the finite element models, mechanical properties of reinforcement and concrete of BCs were analyzed. The experimental results show that the failure mode of BC was tensile failure of concrete at the bottom of top slab under bending action, and integral BC had the maximum carrying capacity. The contact behaviour of sliding and rotating at hinge joints caused the first principal tensile stress of concrete at the internal surface of the side wall below hinge joints.
The Association between Trimethylamine N-Oxide and Its Predecessors Choline, L-Carnitine, and Betaine with Coronary Artery Disease and Artery Stenosis
Authors: Guo Fei , Zhou Jun , Li Zhenyu , Yu Zaixin , Ouyang Dongsheng
Published: August 2020

Background. Trimethylamine N-oxide (TMAO) and its predecessor products, choline, L-carnitine, and betaine, were reported to be associated with cardiovascular events risk. However, the association of TMAO and its predecessors with extent of artery stenosis in coronary artery disease (CAD) and in different gender is still unknown. Our aim is to investigate the association of plasma TMAO and its predecessors in CAD and extent of artery lesion in different gender. Methods. 94 CAD patients and 75 healthy controls (CON) were enrolled. Fasting plasma TMAO, choline, L-carnitine, and betaine were detected using liquid chromatography-tandem mass spectrometry. Results. Elevated plasma TMAO but not choline, L-carnitine, or betaine was observed in CAD (1.46(0.8–2.32) μM) and severe artery stenosis patients (S) (1.62(0.91–2.81) μM) compared with controls and mild artery stenosis (M) (1.18(0.67–1.7) μM in CON; 1.27(0.77–1.82) μM in M, p<0.05). TMAO was an independent risk factor of CAD and severe artery stenosis (CAD : OR = 1.81, 95%CI: 1.07–3.09, p=0.03; S : OR = 1.36, 95%CI: 1.01–1.84, p=0.04). TMAO was more sensitive in diagnosing CAD and severe artery stenosis from controls in men rather than in women by ROC analysis (AUC for men and women in CAD: 0.64 versus 0.57; AUC for men and women in S: 0.64 versus 0.58), while the combined four metabolites greatly improved diagnostic accuracy in women with CAD and severe artery stenosis (AUC in CAD: 0.64, AUC in S: 0.68). Conclusion. The associations of TMAO with CAD and severe artery stenosis were sex-related. TMAO alone was more powerful in determining CAD and artery stenosis in men than women, while a combination of TMAO, choline, L-carnitine, and betaine could be potential biomarkers for diagnosing CAD and artery stenosis in both men and women.
Impaired Glomerular Filtration Rate in Type 2 Diabetes Mellitus Subjects: A Nationwide Cross-Sectional Study in Thailand
Authors: Nata Naowanit , Rangsin Ram , Supasyndh Ouppatham , Satirapoj Bancha
Published: August 2020

Background. Type 2 diabetic mellitus (T2DM) patients with impaired renal function have a higher risk of mortality, and often progress to end-stage renal disease. The study aims to determine the prevalence of kidney disease and investigate the relationship between various factors and impaired renal function in a large population of patients with T2DM. Methods. We conducted a cross-sectional study among 30,377 patients from a nationwide diabetes study involving 602 Thai hospitals. Impaired glomerular filtration rate (GFR) was defined as <60 mL/min per 1.73 m2. Multivariate logistic regression was used to determine the association between standard risk factors and impaired GFR. Results. The prevalence of impaired GFR in a T2DM population was 39.2%. After adjusting for multiple risk factors, advanced age (adjusted OR 11.69 (95%CI=3.13 to 43.61)), macroalbuminuria (adjusted OR 3.54 (95%CI=1.50 to 8.40)), high serum uric acid (adjusted OR 2.06 (95%CI=1.73 to 2.46)), systolic BP 130-139 mmHg (adjusted OR 3.21 (95%CI=1.30 to 7.96)), hemoglobinA1C (HA1C) <6% (adjusted OR 3.71 (95%CI=1.65 to 8.32)), and HA1C >7% (adjusted OR 2.53 (95%CI=1.38 to 4.63)) were found to be associated with a significantly increased risk of impaired GFR among T2DM patients. Conclusion. Almost 40% of patients with T2DM in a nationwide cross-sectional study in Thailand had impaired GFR. Advanced age, albuminuria, hyperuricemia, hypertension, HA1C <6%, and HA1C >7% were independently associated with increased prevalence of impaired GFR.
Mitochondrial and Peroxisomal Alterations Contribute to Energy Dysmetabolism in Riboflavin Transporter Deficiency
Authors: Colasuonno Fiorella , Niceforo Alessia , Marioli Chiara , Fracassi Anna , Stregapede Fabrizia , Massey Keith , Tartaglia Marco , Bertini Enrico , Compagnucci Claudia , Moreno Sandra
Published: August 2020

Riboflavin transporter deficiency (RTD) is a childhood-onset neurodegenerative disorder characterized by progressive pontobulbar palsy, sensory and motor neuron degeneration, sensorineural hearing loss, and optic atrophy. As riboflavin (RF) is the precursor of FAD and FMN, we hypothesize that both mitochondrial and peroxisomal energy metabolism pathways involving flavoproteins could be directly affected in RTD, thus impacting cellular redox status. In the present work, we used induced pluripotent stem cells (iPSCs) from RTD patients to investigate morphofunctional features, focusing on mitochondrial and peroxisomal compartments. Using this model, we document the following RTD-associated alterations: (i) abnormal colony-forming ability and loss of cell-cell contacts, revealed by light, electron, and confocal microscopy, using tight junction marker ZO-1; (ii) mitochondrial ultrastructural abnormalities, involving shape, number, and intracellular distribution of the organelles, as assessed by focused ion beam/scanning electron microscopy (FIB/SEM); (iii) redox imbalance, with high levels of superoxide anion, as assessed by MitoSOX assay accompanied by abnormal mitochondrial polarization state, evaluated by JC-1 staining; (iv) altered immunofluorescence expression of antioxidant systems, namely, glutathione, superoxide dismutase 1 and 2, and catalase, as assessed by quantitatively evaluated confocal microscopy; and (v) peroxisomal downregulation, as demonstrated by levels and distribution of fatty acylβ-oxidation enzymes. RF supplementation results in amelioration of cell phenotype and rescue of redox status, which was associated to improved ultrastructural features of mitochondria, thus strongly supporting patient treatment with RF, to restore mitochondrial- and peroxisomal-related aspects of energy dysmetabolism and oxidative stress in RTD syndrome.
Upper Bound Limit Stability Analysis for Soil Slope with Nonuniform Multiparameter Distribution Based on Discrete Algorithm
Authors: Wang Zhen , Yang Xumeng , Li Ang
Published: August 2020

Slope stability analysis is a core issue in geotechnical engineering. This paper proposes a method of upper bound limit stability analysis for a slope with multiparameter coordinated variation based on the comprehensive consideration of the nonuniform distribution of slope soil parameters. This method starts from the perspective of energy balance, establishes a slope failure mechanism which meets velocity separation requirements, deduces its calculation formula for external force power and internal energy dissipation power, develops a cycle program for the most dangerous slip surface searching and stability coefficient calculation through computer programming technology, and finally forms a calculation method of upper bound limit stability analysis for the soil slope with nonuniform multiparameter distribution. At the same time, this method takes a dump slope in an open‐pit mine as the engineering background, considers the nonuniformity of density, cohesion, and internal friction angle of the slope soil under subsidence, applies upper bound limit analysis to analyze the slope stability, and evaluates the accuracy of analysis results by using the residual thrust method. The results show that upper bound limit analysis has highly accuracy in stability coefficient calculation; compared with the residual thrust method, the stability coefficient calculation result by upper bound limit analysis is a strict upper bound solution, and the calculation error is easy to be estimated and eliminated. Simultaneously, the most dangerous slip surface obtained by upper bound limit analysis can fully satisfy the velocity separation requirement and has a greater engineering reference value.
Adsorption Behaviour and Kinetics of Zearalenone on Hydroxyl-Fe-Al-Intercalated Montmorillonite
Authors: Fang Shengqiong , Xiao Yueqi , Wang Huiqiang
Published: August 2020

Pristine montmorillonite (Mont) was used as raw materials to prepare hydroxyl-Fe-pillared Mont, hydroxyl-Al-pillared Mont, and hydroxyl-Fe-Al-pillared Mont composites. By varying the OH/Fe and Fe/Al molar ratios during the preparation of the pillared Mont, the adsorption capacity of zearalenone (ZEA) and the kinetics were elucidated. The characterization of X-ray diffraction (XRD) and Fourier transform infrared (FT-IR) spectroscopy reveals the adsorption mechanism of pristine and modified Mont. The results indicated that the ZEA adsorption capacity is Mont (0.05 mg/g) << 1.5OH/Fe-Mont (0.28 mg/g) << OH/Al-Mont (0.51 mg/g) < 0.5Fe/Al-Mont (0.56 mg/g) in the condition of pH = 8 and 37°C, in which both 0.5Fe/Al-Mont and OH/Al-Mont reached maximum adsorption capacity and 1.5OH/Fe-Mont attained 5 times the capacity of Mont. Adsorption isotherm studies revealed that Freundlich adsorption isotherms best represented the experimental data. The kinetic data for ZEA adsorption revealed that the Mont adsorption capacity for ZEA equilibrates in 1 hour and is best described using the pseudo-second-order rate equation. The XRD analysis indicated that the amplification of Fe-dominant pillared Mont interlayer spacing is the main reason for the observed increases in the adsorption capacity of ZEA, while Al-dominant pillared Mont has a relatively stable Keggin structure; therefore, interlayer spacing is not the primary mechanism for changes in the adsorption capacity of both OH/Al-Mont and Al-dominant pillared Mont. An FT-IR analysis demonstrated that cationic exchange was the dominant mechanism that allowed ZEA and hydroxyl-Al ions to enter the Mont interlayers, while this cationic exchange mechanism was not the dominant mechanism used by hydroxyl-Fe entering the Mont layers.
Identification and Characterization of MAPK Signaling Pathway Genes and Associated lncRNAs in the Ileum of Piglets Infected by Clostridium perfringens Type C
Authors: Luo Ruirui , Huang Xiaoyu , Yan Zunqiang , Gao Xiaoli , Wang Pengfei , Yang Qiaoli , Wang Wei , Xie Kaihui , Gun Shuangbao
Published: August 2020

Clostridium perfringens type C (C. perfringens type C) is one of the main microbial pathogens responsible for piglet diarrhea worldwide, causing substantial economic losses for pig‐rearing industries. The mitogen‐activated protein kinase (MAPK) signaling pathway is a key regulator of inflammatory bowel disease, especially necrotic enteritis. However, whether and how the MAPK signaling pathway is involved in regulating the process of piglet diarrhea when challenged by C. perfringens type C are still unknown. Here, we screened 38 differentially expressed genes (DEGs) in piglets’ ileum tissues experimentally infected with C. perfringens type C that were enriched in the Sus scrofa MAPK signaling pathway, based on our previous transcriptome data. Of these DEGs, 12 genes (TRAF2, MAPK8, and GADD45G, among others) were upregulated whereas 26 genes (MAPK1, TP53, and CHUK, among others) were downregulated in the infected group. Our results showed that MAPK1, TP53, MAPK8, MYC, and CHUK were in the core nodes of the PPI network. Additionally, we obtained 35 lncRNAs from the sequencing data, which could be trans‐targeted to MAPK signaling pathway genes and were differentially expressed in the ileum tissues infected with C. perfringens. We used qRT‐PCR to verify the expression levels of genes and lncRNAs related to the MAPK signaling pathway; their expression patterns were consistent with RNA sequencing data. Our results provide strong support for deeply exploring the role of the MAPK signaling pathway in diarrhea caused by C. perfringens type C.
A Case of Kratom Overdose in a Pediatric Patient
Authors: Wong Andrew , Mun Monique
Published: August 2020

Kratom is a synthetic opioid that is federally unregulated and thus available for purchase through online retail and smoke shops in most states. Due to its availability, there is concern for misuse in the pediatric population. There is existing literature describing toxicity of kratom in adults; yet, to the best of our knowledge, there are no cases describing kratom toxicity in the pediatric population. Thus, we present the case of kratom overdose in a pediatric patient.
Performance of Super‐Large‐Span Tunnel Portal Excavated by Upper Bench CD Method Based on Field Monitoring and Numerical Modeling
Authors: Luo Yanbin , Chen Jianxun , Shi Zhou , Zhang Shaoqiang , Liu Weiwei , Li Yao , Chen Lijun
Published: August 2020

The number of super‐large‐span tunnels is increasing in both new construction and reconstruction projects in China recently. In super‐large‐span tunneling engineering, the deformation properties and mechanical behaviors of tunnel portal structure are more complex than those of common tunnel due to the flatter shape and larger construction span. The mechanical behaviors of rock mass change in response to different sequential excavation methods and supporting parameters. The upper bench CD method has been gradually applied in the construction of super‐large‐span tunnels in China. In this paper, the design parameters for the supporting structure of super‐large‐span tunnel were studied by the field monitoring and numerical modeling in a case study of Laohushan tunnel. It was found that the crown settlement was larger than the clearance convergence, and the stress of arch was greater than that of the side wall in tunnel portal section. The invert structure was flat with small curvature. Therefore, the shotcrete was mainly subjected to tensile stress. The use of H200 × 200 steel rib with spacing of 60 cm and C25 shotcrete with thickness of 30 cm is recommended. The results of this paper provide basis for the development of design specifications and construction standards for super‐large‐span tunnels and provide reference for similar projects in the future.
Field Static Load Tests of Post‐Grouted Piles under Various Failure Conditions
Authors: Zhou Jialin , Zhang Jianwei , Wang Yuzhuo , Oh Erwin
Published: August 2020

In practice, inappropriate test set‐up and design will result in pile eccentricity, reducing pile bearing capacity. Also, inappropriate piling will reduce the strength of the upper part of concrete. These pile elements under inappropriate design and construction are easy to be overlooked since they are invisible. Because the research focuses on the pile failure behaviour under different conditions, this paper aims to determine the outcomes of pile foundation under eccentric loading, pile with inadequate concrete strength, and pile with punching failure. Four concrete piles were cast, and compressive static load tests (SLTs) were performed. The top part of the first pile was cast with inadequate concrete strength. The other two piles were cast with achieved concrete strength; however, one of these applied with eccentric loading. The third pile was the standard pile, and the fourth pile was tested until punching failure occurred. For the fourth pile, the T‐Z method was used for determining the failure characteristics. It is discovered that, for the pile with inadequate concrete strength, the cracks occurred at the pile head, and the concrete crushed at 0.9–1.2 m below the ground; for the pile suffering eccentricity, the partial concrete crushed, and the concrete from the opposite side suffered tension fracture; for the pile suffering punching failure, the crack on the soil extends up to 50 mm. Traditional result presentations and interpretations were also provided. Furthermore, it was found that, for the pile suffering punching failure, the shaft resistance increased as the loads increased, and after the loading achieved the maximum resistance, the loading transferred to the pile tip and finally led to the destruction of the pile‐soil system.
Abstract IA25: Molecular biomarkers of chemoradiation response in bladder preservation therapy
Authors: Miyamoto David T.
Published: August 2020

The standard definitive treatment options for muscle-invasive bladder cancer are radical cystectomy or bladder-sparing trimodality therapy (TMT), consisting of maximal transurethral resection of bladder tumor followed by chemoradiation therapy. Although multiple series show these two treatment approaches have similar overall long-term outcomes, recent studies suggest that molecular biomarkers may identify subgroups of patients who may preferentially benefit from one type of therapy over the other. Such biomarkers include tumor-intrinsic genes involved in DNA repair and signal transduction, which confer sensitivity or resistance to radiation therapy based on the intrinsic biology of the tumor. Emerging biomarkers also include molecular signatures of the tumor microenvironment, suggesting an important role for tumor-extrinsic factors in governing therapeutic sensitivity or resistance. This presentation will review the evidence and rationale underlying potential prognostic and predictive molecular biomarkers in bladder preservation therapy. A specific focus will be on our recent gene expression profiling of 136 muscle-invasive bladder cancer patients treated with bladder-sparing TMT. Our analysis showed that higher immune infiltration was associated with improved disease-specific survival after TMT, whereas higher stromal infiltration was associated with shorter disease-specific survival in a comparison cohort treated with radical cystectomy after neoadjuvant chemotherapy. These findings require validation studies in additional cohorts, which are currently ongoing. An additional focus of the presentation will be on emerging liquid biopsy biomarkers of minimal residual disease after bladder cancer therapy. The standard follow-up for patients after bladder-sparing TMT includes cystoscopies with biopsies and imaging studies at regular intervals. Liquid biopsy approaches such as circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) may enable noninvasive monitoring of response and detection of minimal residual disease after therapy, with a substantial lead time over conventional follow-up approaches including imaging. If validated in prospective clinical trials, molecular biomarkers may guide the tailored selection of appropriate treatments for individual patients with muscle-invasive bladder cancer, as well as enable noninvasive monitoring of patients after therapy. Such biomarkers also have potential to guide the use of synergistic combinations of immunotherapy with chemoradiation therapy for bladder cancer.

Citation Format: David T. Miyamoto. Molecular biomarkers of chemoradiation response in bladder preservation therapy [abstract]. In: Proceedings of the AACR Special Conference on Bladder Cancer: Transforming the Field; 2019 May 18-21; Denver, CO. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(15_Suppl):Abstract nr IA25.
A Comparison of the Postoperative Analgesic Effectiveness of Ultrasound-Guided Dorsal Penile Nerve Block and Ultrasound-Guided Pudendal Nerve Block in Circumcision
Authors: Ozen Volkan , Yigit Dogakan
Published: August 2020

Aim: The aim of this study was to compare the postoperative analgesic effectiveness of the 2 block types. We also aimed to evaluate the effect of these block types on the postoperative complications and parental satisfaction. Materials and Methods: This prospective observational study was conducted between April and July 2019 at a training and research hospital. Patients aged between 5 and 12 years in the ASA I-II group, who were scheduled for circumcision, were included in the study. The primary outcome was the pain measured using the Children’s Hospital Eastern Ontario Pain Scale and the Faces Pain Scale-Revised. The secondary outcomes were the postoperative complications and parenteral satisfactions. Results: The number of patients receiving a pudendal block (n = 40) and dorsal penile nerve block (DPNB) block (n = 40) was equal. No statistically significant difference was found between the groups that were administered a DPNB and pudendal block in terms of pain scores (p > 0.05). We did not observe any postoperative block-related complications or side effects. Parents reported excellent satisfaction in both groups. Discussion: Ultrasound (US)-guided pudendal nerve block and US-guided DPNB provided effective and long-lasting postoperative analgesia for circumcision surgery. Conclusions: This study has shown that both blocks provide postoperative analgesia with similar effectiveness and ensured a very comfortable period at the circumcision surgery. Clinicians can use either of these techniques depending on their clinical circumstances and experience.
Prediction of Radioresistant Prostate Cancer Based on Differentially Expressed Proteins
Authors: Nestler Tim , Wittersheim Maike , Schaefer Stephan , Hellmich Martin , Pfister David , Odenthal Margarete , von Brandenstein Melanie , Buettner Reinhard , Heidenreich Axel
Published: August 2020

Introduction: Although relapses after radiotherapy are common in prostate cancer (PCA) patients, those with a high risk for radioresistance cannot be identified prior to treatment yet. Therefore, this proof-of-concept study was performed to compare protein expression profiles of patients with radio-recurrent PCA to patients treated with primary radical prostatectomy separated by Gleason risk groups. We hypothesized that radio-recurrent PCA have a similar protein expression as high-risk Gleason PCA. Methods: Patient cohorts consisted of (i) 31 patients treated with salvage prostatectomy for locally recurrent PCA after primary radiotherapy and (ii) 94 patients treated with primary prostatectomy split into a Gleason high-risk (≥4 + 3; n = 42 [44.7%]) versus a low-risk group (≤3 + 4; n = 52 [55.3%]). Immunohistochemistry was performed using 15 antibodies with known association to radioresistance in PCA in vitro. ELISA was used for validation of selected markers in serum. Results: Androgen receptor (AR) was overexpressed in most radio-recurrent PCA (89.7%) and in most primary high-risk Gleason PCA (87.8%; p = 0.851), while only 67.3% of the low-risk group showed an expression (p = 0.017). Considering the highest Gleason pattern in primary PCA, aldo-keto reductase family 1 member C3 (AKR1C3) was most similarly expressed by patients with radio-recurrent PCA and patients with Gleason patterns 4 and 5 (p = 0.827 and p = 0.893) compared to Gleason pattern 3 (p = 0.20). These findings were supported by ELISA. Conclusion: This is the first study to evaluate protein markers in order to predict radioresistance in PCA. Our results point to AR and AKR1C3 as the most promising markers that might help stratify patients for radiotherapy.
Clinical Characteristics of Intramucosal Gastric Cancers with Lymphovascular Invasion Resected by Endoscopic Submucosal Dissection
Authors: Hashimoto Minami , Hikichi Takuto , Nakamura Jun , Watanabe Ko , Takasumi Mika , Kato Tsunetaka , Suzuki Rei , Sugimoto Mitsuru , Irie Hiroki , Takagi Tadayuki , Ohira Hiromasa
Published: August 2020

Introduction: In patients with intramucosal gastric cancer (MGC) who have undergone endoscopic submucosal dissection (ESD), lymphovascular invasions (LVIs) such as lymphatic invasion or venous invasion are considered risk factors of lymph node metastasis (LNM). However, the rate of LNM in MGCs with LVI and their clinicopathological features are unclear. Objective: This study aimed to examine the rate of LNM and clinical characteristics of MGCs with LVI as compared to MGCs without LVI and minimally invasive submucosal gastric cancers (mSMGCs) with LVI. Methods: Among the early gastric cancers excluding the remnant stomach who underwent ESD at our hospital from July 2003 to September 2018, the MGCs with LVI were included as the target in this study. MGCs without LVI and mSMGCs with LVI were also included as control. Results: Seventeen lesions in 17 patients with MGCs with LVI, 1,149 lesions in 865 patients with MGCs without LVI, and 29 lesions in 29 patients with mSMGCs with LVI were analyzed. LVI was noted in 1.5% (17/1,166) of MGC cases. During follow-up of the MGC cases with LVI, there were no LNM or recurrences reported, and 14 patients survived and 3 died of other diseases. However, LNM occurred in 2 cases of mSMGC. Among the MGC cases, univariate analysis showed that the pap component, elevated type, and tumor diameters of 20 mm or more were statistically significant factors with respect to LVI, while multivariate analysis showed that the pap component was the only significant factor. Conclusion: Careful follow-up may be appropriate for MGCs with LVI due to the low risk of LNM. Additionally, the pap component is a significant factor in MGCs with LVI.
The Effect of Bronchoconstriction by Methacholine Inhalation in a Murine Model of Asthma
Authors: Miyata Yoshito , Ohta Shin , Tanaka Akihiko , Kashima Ayaka , Suganuma Hiromitsu , Uno Tomoki , Sato Haruna , Ida Hitomi , Kimura Tomoyuki , Jinno Megumi , Hirai Kuniaki , Homma Tetsuya , Yamamoto Mayumi , Watanabe Yoshio , Suzuki Shintaro , Sagara Hironori
Published: August 2020

Introduction: Bronchoconstriction was recently shown to cause airway remodeling and induce allergic airway inflammation in asthma. However, the mechanisms how mechanical stress via bronchoconstriction could induce airway inflammation and remodeling remain unclear. Objective: We investigated the effect of bronchoconstriction induced by methacholine inhalation in a murine model of asthma. Methods: BALB/c female mice were sensitized and challenged with ovalbumin (OVA), followed by treatment with methacholine by a nebulizer twice a day for 7 days. Twenty-four hours after the last methacholine treatment, the bronchoalveolar lavage fluid (BALF) and lung tissues were collected. The BALF was analyzed for total and differential cell counts and cytokine levels. The lung tissues were analyzed for goblet cell metaplasia, thickness of the smooth muscle, and lung fibrosis. The expression of cytokines in the lung was also examined. Results: OVA sensitization and challenge induced infiltration of total cells, macrophages, and eosinophils in the BALF along with goblet cell metaplasia and increased airway smooth muscle hypertrophy. Seven days after the last OVA challenge, untreated mice achieved reduction in airway inflammation, while methacholine maintained the number of BALF total cells, macrophages, and eosinophils. The percentage of goblet cells and the thickness of airway smooth muscle were also maintained by methacholine. Moreover, the treatment of methacholine induced the expression of transforming growth factor (TGF)-β in the lung. This result indicates that the production of TGF-β is involved in induction of airway remodeling caused by bronchoconstriction with methacholine. Conclusions: Repeated bronchoconstriction caused by methacholine inhalation elicited allergic airway inflammation and airway remodeling.
Investigation of the Causal Association between Long-Chain n-6 Polyunsaturated Fatty Acid Synthesis and the Risk of Type 2 Diabetes: A Mendelian Randomization Analysis
Authors: Zulyniak Michael A. , Fuller Harriett , Iles Mark M.
Published: August 2020

Background: Globally, 1 in 11 adults has diabetes mellitus, and most of these cases are type 2 diabetes (T2D). The risk of T2D is influenced by many factors, including diet. The synthesis of long-chain n-6 polyunsaturated fatty acids (LC n-6 PUFA) has been posited as a risk factor for T2D; however, its causal role is uncertain. Aim: To test the causal effect of LC n-6 PUFA synthesis on insulin resistance and transgenerational T2D risk in a large cohort of men and women. Methods: Two-sample mendelian randomization (MR) was conducted to evaluate the effect of low or high levels of LC n-6 PUFA synthesis on glycemia and development of T2D in the UK Biobank (n = 463,010) and Meta-Analysis of Glucose- and Insulin-Related Traits Consortium (MAGIC; n = 5,130) cohorts. The increased likelihood of a predisposition to low or high LC n-6 PUFA synthesis and the risk of T2D was also investigated using the participants’ siblings and parents. In MR-Base, 4 genetic variants associated with LC n-6 PUFA synthesis were found (p < 10–8). After pruning, 1 variant (rs174547) on the FADS1 gene was retained. Results: Lower LC n-6 PUFA synthesis and abundance (per % unit decrease) are associated with small reductions in the insulin disposition index (–0.038 ± 0.012 mM–1; p = 0.002) within MAGIC. In the UK Biobank, we report negligible effects of low n-6 PUFA synthesis on the odds of T2D (OR <1%; p < 0.05). Additionally, reduced LC n-6 PUFA synthesis does not appear to be a contributor to familial T2D risk. No significant association was observed between LC n-6 PUFA synthesis and BMI. Conclusion: In a primarily white European population, LC n-6 PUFA synthesis is not a major contributor to T2D risk.
Use of a Supportive Kidney Care Video Decision Aid in Older Patients: A Randomized Controlled Trial
Authors: Eneanya Nwamaka D. , Percy Shananssa G. , Stallings Taylor L. , Wang Wei , Steele David J.R. , Germain Michael J. , Schell Jane O. , Paasche-Orlow Michael K. , Volandes Angelo E.
Published: August 2020

Background: There are few studies of patient-facing decision aids that include supportive kidney care as an option. We tested the efficacy of a video decision aid on knowledge of supportive kidney care among older patients with advanced CKD. Methods: Participants (age ≥ 65 years with advanced CKD) were randomized to receive verbal or video education. Primary outcome was knowledge of supportive kidney care (score range 0–3). Secondary outcomes included preference for supportive kidney care, and satisfaction and acceptability of the video. Results: Among all participants (n = 100), knowledge of supportive kidney care increased significantly after receiving education (p < 0.01); however, there was no difference between study arms (p = 0.68). There was no difference in preference for supportive kidney care between study arms (p = 0.49). In adjusted analyses, total health literacy score (aOR 1.08 [95% CI: 1.003–1.165]) and nephrologists’ answer of “No” to the Surprise Question (aOR 4.87 [95% CI: 1.22–19.43]) were associated with preference for supportive kidney care. Most felt comfortable watching the video (96%), felt the content was helpful (96%), and would recommend the video to others (96%). Conclusions: Among older patients with advanced CKD, we did not detect a significant difference between an educational verbal script and a video decision aid in improving knowledge of supportive kidney care or preferences. However, patients who received video education reported high satisfaction and acceptability ratings. Future research will determine the effectiveness of a supportive kidney care video decision aid on real-world patient outcomes. Trial Registration: NCT02698722 (ClinicalTrials.gov).
Why Cannot BCLC 0- or A-Stage Patients Receive Curative Treatment?
Authors: Kuo Tse-Ming , Chang Kai-Ming , Kao Kuo-Jang
Published: August 2020

Introduction: Barcelona Clinic Liver Cancer (BCLC) staging has been an important clinical guideline for the management of hepatocellular carcinoma (HCC). BCLC 0 and A stages (BCLC 0/A) have been designated as the early-stage HCC, and the curative treatment is recommended as the primary therapeutic modality. However, a recent study indicated that a significant number of BCLC 0/A patients were not initially managed with the curative treatment without knowing why. Methods: We, therefore, conducted a study on BCLC 0/A patients who had and had not received initial curative treatment cared at our cancer center from January 2011 to December 2015 and analyzed causes contributing to not having the initial curative treatment. Results: One hundred and sixty-nine BCLC 0/A patients were identified and included in the study. Seventy two patients (43%) received the initial curative treatment and 97 patients (57%) did not. After careful review of medical records, all 97 patients without the initial curative treatment had identifiable reasons for not having the initial curative treatment. Two main reasons for not having the initial curative treatment were “probable presence of additional HCC and requiring diagnostic angiography” (28%) and “difficult or complicating anatomical location of tumors” (17%). When the relevant clinical parameters were compared between the 2 groups of patients, it was found that patients without the initial curative treatment had more serious clinical conditions and worse overall and recurrence-free survival outcomes compared with those who had the initial curative treatment. Discussion/Conclusion: Our finding indicates that a significant fraction of the BCLC 0/A HCC patients is unable to have initial curative treatment as recommended by BCLC guidelines. These early stages of HCC patients represent a distinctive subpopulation and are in need of further investigation to improve their survival outcomes.
Antiplatelet Effect of Carbon Monoxide Is Mediated by NAD
+
and ATP Depletion
Authors: Kaczara Patrycja , Sitek Barbara , Przyborowski Kamil , Kurpinska Anna , Kus Kamil , Stojak Marta , Chlopicki Stefan
Published: August 2020

Objectives:

Carbon monoxide (CO) produced by haem oxygenases or released by CO-releasing molecules (CORM) affords antiplatelet effects, but the mechanism involved has not been defined. Here, we tested the hypothesis that CO–induced inhibition of human platelet aggregation is mediated by modulation of platelet bioenergetics.

Approach and Results:

To analyze the effects of CORM-A1 on human platelet aggregation and bioenergetics, a light transmission aggregometry, Seahorse XFe technique and liquid chromatography tandem-mass spectrometry–based metabolomics were used. CORM-A1–induced inhibition of platelet aggregation was accompanied by the inhibition of mitochondrial respiration and glycolysis. Interestingly, specific inhibitors of these processes applied individually, in contrast to combined treatment, did not inhibit platelet aggregation considerably. A CORM-A1–induced delay of tricarboxylic acid cycle was associated with oxidized nicotinamide adenine dinucleotide (NAD
+
) depletion, compatible with the inhibition of oxidative phosphorylation. CORM-A1 provoked an increase in concentrations of proximal (before GAPDH [glyceraldehyde 3-phosphate dehydrogenase]), but not distal glycolysis metabolites, suggesting that CO delayed glycolysis at the level of NAD
+
–dependent GAPDH; however, GAPDH activity was directly not inhibited. In the presence of exogenous pyruvate, CORM-A1–induced inhibition of platelet aggregation and glycolysis were lost, but were restored by the inhibition of lactate dehydrogenase, involved in cytosolic NAD
+
regeneration, pointing out to the key role of NAD
+
depletion in the inhibition of platelet bioenergetics by CORM-A1.

Conclusions:

The antiplatelet effect of CO is mediated by inhibition of mitochondrial respiration—attributed to the inhibition of cytochrome c oxidase, and inhibition of glycolysis—ascribed to cytosolic NAD
+
depletion.
Aberrant Exon 8/8a Splicing by Downregulated PTBP (Polypyrimidine Tract-Binding Protein) 1 Increases Ca
V
1.2 Dihydropyridine Resistance to Attenuate Vasodilation
Authors: Lei Jianzhen , Liu Xiaoxin , Song Miaomiao , Zhou Yingying , Fan Jia , Shen Xiaowei , Xu Xiaohan , Kapoor Isha , Zhu Guoqing , Wang Juejin
Published: August 2020

Objective:

Calcium channel blockers, such as dihydropyridines, are commonly used to inhibit enhanced activity of vascular Ca
V
1.2 channels in hypertension. However, patients who are insensitive to such treatments develop calcium channel blocker-resistant hypertension. The function of Ca
V
1.2 channel is diversified by alternative splicing, and the splicing factor PTBP (polypyrimidine tract-binding protein) 1 influences the utilization of mutually exclusive exon 8/8a of the Ca
V
1.2 channel during neuronal development. Nevertheless, whether and how PTBP1 makes a role in the calcium channel blocker sensitivity of vascular Ca
V
1.2 channels, and calcium channel blocker-induced vasodilation remains unknown.

Approach and Results:

We detected high expression of PTBP1 and, inversely, low expression of exon 8a in Ca
V
1.2 channels (Ca
V
1.2
E8a
) in rat arteries. In contrast, the opposite expression patterns were observed in brain and heart tissues. In comparison to normotensive rats, the expressions of PTBP1 and Ca
V
1.2
E8a
channels were dysregulated in mesenteric arteries of hypertensive rats. Notably, PTBP1 expression was significantly downregulated, and Ca
V
1.2
E8a
channels were aberrantly increased in dihydropyridine-resistant arteries compared with dihydropyridine-sensitive arteries of rats and human. In rat vascular smooth muscle cells, PTBP1 knockdown resulted in shifting of Ca
V
1.2 exon 8 to 8a. Using patch-clamp recordings, we demonstrated a concomitant reduction of sensitivity of Ca
V
1.2 channels to nifedipine, due to the higher expression of Ca
V
1.2
E8a
isoform. In vascular myography experiments, small interfering RNA-mediated knockdown of PTBP1 attenuated nifedipine-induced vasodilation of rat mesenteric arteries.

Conclusions:

PTBP1 finely modulates the sensitivities of Ca
V
1.2 channels to dihydropyridine by shifting the utilization of exon 8/8a and resulting in changes of responses in dihydropyridine-induced vasodilation.
Cholesterol Efflux-Independent Modification of Lipid Rafts by AIBP (Apolipoprotein A-I Binding Protein)
Authors: Low Hann , Mukhamedova Nigora , Capettini Luciano dos Santos Aggum , Xia Yining , Carmichael Irena , Cody Stephen H. , Huynh Kevin , Ditiatkovski Michael , Ohkawa Ryunosuke , Bukrinsky Michael , Meikle Peter J. , Choi Soo-Ho , Field Seth , Miller Yury I. , Sviridov Dmitri
Published: August 2020

Objective:

AIBP (apolipoprotein A-I binding protein) is an effective and selective regulator of lipid rafts modulating many metabolic pathways originating from the rafts, including inflammation. The mechanism of action was suggested to involve stimulation by AIBP of cholesterol efflux, depleting rafts of cholesterol, which is essential for lipid raft integrity. Here we describe a different mechanism contributing to the regulation of lipid rafts by AIBP.

Approach and Results:

We demonstrate that modulation of rafts by AIBP may not exclusively depend on the rate of cholesterol efflux or presence of the key regulator of the efflux, ABCA1 (ATP-binding cassette transporter A-I). AIBP interacted with phosphatidylinositol 3-phosphate, which was associated with increased abundance and activation of Cdc42 and rearrangement of the actin cytoskeleton. Cytoskeleton rearrangement was accompanied with reduction of the abundance of lipid rafts, without significant changes in the lipid composition of the rafts. The interaction of AIBP with phosphatidylinositol 3-phosphate was blocked by AIBP substrate, NADPH (nicotinamide adenine dinucleotide phosphate), and both NADPH and silencing of Cdc42 interfered with the ability of AIBP to regulate lipid rafts and cholesterol efflux.

Conclusions:

Our findings indicate that an underlying mechanism of regulation of lipid rafts by AIBP involves PIP-dependent rearrangement of the cytoskeleton.
Predictors of Mortality in Patients With Biopsy‐Proven Viral Myocarditis: 10‐Year Outcome Data
Authors: Greulich Simon , Seitz Andreas , Müller Karin A. L. , Grün Stefan , Ong Peter , Ebadi Nawid , Kreisselmeier Klaus Peter , Seizer Peter , Bekeredjian Raffi , Zwadlo Carolin , Gräni Christoph , Klingel Karin , Gawaz Meinrad , Sechtem Udo , Mahrholdt Heiko
Published: August 2020

Background

There is scarce data about the long‐term mortality as well as the prognostic value of cardiovascular magnetic resonance and late gadolinium enhancement (LGE) in patients with biopsy‐proven viral myocarditis. We sought to investigate: (1) mortality and (2) prognostic value of LGEcardiovascular magnetic resonance (location, pattern, extent, and distribution) in a >10‐year follow‐up in patients with biopsy‐proven myocarditis.

Methods and Results

Two‐hundred three consecutive patients with biopsy‐proven viral myocarditis and cardiovascular magnetic resonance were enrolled; 183 patients were eligible for standardized follow‐up. The median follow‐up was 10.1 years. End points were all‐cause death, cardiac death, and sudden cardiac death (SCD). We found substantial long‐term mortality in patients with biopsy‐proven myocarditis (39.3% all cause, 27.3% cardiac, and 10.9% SCD); 101 patients (55.2%) demonstrated LGE. The presence of LGE was associated with a more than a doubled risk of death (hazard ratio [HR], 2.40; 95% CI], 1.30–4.43), escalating to a HR of 3.00 (95% CI, 1.41–6.42) for cardiac death, and a HR of 14.79 (95% CI, 1.95–112.00) for SCD; all
P
≤0.009. Specifically, midwall, (antero‐) septal LGE, and extent of LGE were highly associated with death, all
P
<0.001. Septal LGE was the best independent predictor for SCD (HR, 4.59; 95% CI, 1.38–15.24;
P
=0.01).

Conclusions

In patients with biopsy‐proven viral myocarditis, the presence of midwall LGE in the (antero‐) septal segments is associated with a higher rate of mortality (including SCD) compared with absent LGE or other LGE patterns, underlining the prognostic benefit of a distinct LGE analysis in these patients.
Studies in Colombian Ensifera and adjacent countries: Gigagryllus, a new genus of giant field crickets (Orthoptera: Gryllidae) with comments on current Neotropical Gryllinae classification
Authors: CADENA-CASTAÑEDA OSCAR J. , GARCÍA ALEXANDER GARCÍA
Published: August 2020

Gigagryllus omayrae n. gen et n. sp., a new genus of giant field cricket, from the middle Magdalena of Colombia, more precisely from the department of Tolima, in the region of the Armero tragedy, for which this species is dedicated to the memory of Omayra Sanchez, a symbol of the most terrible natural tragedy that has occurred in the recent history of Colombia. Gigagryllus n. gen. is one of the largest genera in America, with a size similar to Titanogryllus, Megalogryllus and some species of Gryllita. The classification of the American Gryllinae is discussed, and a key to the American genera is provided. Besides, genera groups are proposed for the subtribe Brachytrupine (Gryllini) taxa, which differs from Old World genera. Geogryllus n. syn. and Rubrogryllus n. syn. are synonymized under Gryllita and Cophogryllus americanus is considered as nomen dubium, ruling out the presence of subtribe Cophogryllina in America.
Impacts of Low Self-control and Opportunity Structure on Cyberbullying Developmental Trajectories: Using a Latent Class Growth Analysis
Authors: Cho Sujung , Glassner Steven
Published: August 2020

This study tested self-control and opportunities theories to examine cyberbullying developmental trajectories through the estimation of a latent class growth analysis. Data from a 6-year longitudinal study of middle- and high-school students from South Korea were analyzed to examine if there are unique growth trajectories for cyberbullying perpetration when accounting for low self-control and opportunity factors. Results suggest that there are three distinct subgroups: (1) a normative trajectory group, (2) an increasing and late-peak group, and (3) an early onset and decreasing group. Low self-control was found to be significantly associated with early onset/decreasing cyberbullying. Opportunity to utilize cyberspace was significantly related with increasing/ late peak cyberbullying but did not significantly mediate the effect of low self-control on class membership.
Fabrication and mechanical characterization of glass fibre reinforced triaxially braided composites
Authors: Marrivada Gayatri Vineela , Chaganti Phaneendra Kiran , Sujith Ravindran
Published: August 2020

The aim of this research work is to study the mechanical behaviour of dry triaxially braided glass fibre sleeves and its composites experimentally and analytically. The braided glass fibre sleeves for three angles 30°, 45° and 60° were fabricated on a modified maypole vertical braider following a regular braid architecture. Tensile, flexural, short beam shear and impact tests were performed to evaluate the mechanical properties of the composites. A numerical model was developed, which can be used to find the elastic properties and mechanical strength values of the dry braided fabric and its composites. It was observed that the tensile, flexural and interlaminar properties of 30° specimens were more compared to 45° and 60°. The difference between the estimated and experimental values were found to be an average of 8% for tensile moduli and 24% for the tensile strength.
An artificial neural network (ANN) solution to the prediction of age-hardening and corrosion behavior of an Al/TiC functional gradient material (FGM)
Authors: Dikici Burak , Tuntas Remzi
Published: August 2020

In this theoretical study, the prediction of the corrosion resistance and age-hardening behavior of an Al/TiC functional gradient material (FGM) has been investigated by using the artificial neural network (ANN). The input parameters have been selected as TiC volume fraction of the composite layers, aging periods of the composite, environmental conditions, and applied potential during the corrosion tests. Current and microhardness were used as the one output in the proposed network. Also, a new three-layered composite has been imaginarily designed to demonstrate the predictive capability and flexibilities of the ANN model as a case study. Artificially aging (T6) process and potentiodynamic scanning (PDS) tests were used for heat-treating and corrosion response of the FGS, respectively. The results showed that the generated PDS curves of the FGM and calculated corrosion parameters of the case study are quite near and in acceptable limits for similar composites obtained values in experimental studies. Besides, this study has been a great success in predicting peak-aging times and its corresponding hardness values more precisely.
The Intermediary is the Message: US Public Diplomacy and the Marshall Plan Productivity Drive in the Netherlands, 1948–52
Authors: van den Berk Jorrit
Published: August 2020

This article analyzes the public diplomacy of the Economic Cooperation Administration (ECA) in the Netherlands during the Marshall Plan era. It shows that the impact of the ECA’s public diplomacy was shaped by its negotiations with local partners. The argument focuses on the operational level of US information campaigns, which sought to mobilize specific Dutch social groups behind a model of increased productivity and economic growth. By examining the interaction between the US country mission of the ECA and Dutch bureaucrats, managers, and labor leaders, the article demonstrates how the impact of public diplomacy was determined by a complex and at times contentious process of cooperation. While the Dutch readily accepted the US as a model of technological progress, local elites also managed to contain the threat that American propaganda posed to national recovery policies.