bluuebunny/crossref_metadata_2025 huggingface dataset:
Modeling of lamprey reticulospinal neurons: multiple distinct parameter sets yield realistic simulations
Authors: Ruffolo Jeffrey A. , McClellan Andrew D.
Published: July 2020

A computer model of lamprey reticulospinal neurons with a default parameter set produced simulations of action potentials and repetitive firing that scored favorably compared with the properties of these neurons. A dual-annealing search algorithm explored ~50 million parameter sets and identified 4,302 distinct viable parameter sets within parameter space that yielded higher/much higher scores than the default parameter set. In addition, 5- and 2-conductance grid searches identified significant correlations between maximum conductances for pairs of ion channels.
Cancer Incidence Characteristic Evolution Based on the National Cancer Registry in Taiwan
Authors: Huang Yu-Ching , Chen Yu-Hung
Published: July 2020

Introduction. Taiwan has committed itself to cancer prevention. This study investigates the impact of cancer prevention on cancer incidence in Taiwan. Objective. This study describes the secular trends and present status of cancer incidence in Taiwan during the years of 1988 to 2016. Methods. Age-standardized incidence rates (ASRs), age-specific incidence, and sex ratios for all cancers were calculated using data from the Taiwan Cancer Registry System for the years 1988 to 2016. Results and Conclusions. ASRs of cancer for males increased from 150.93 per 105 individuals in 1988 to 330.03 per 105 individuals in 2016, and, for females, they increased from 124.18 per 105 individuals in 1988 to 269.5 per 105 individuals in 2016. We found that cancer incidence has begun at younger ages and that the rates of cancer incidence are increasing faster. This study shows that the incidence of cancer in males has decreased slightly in recent years, while the incidence of cancer in females has continued to increase. The continuous promotion of health literacy, lifestyle modification, HBV and HPV vaccination, and cancer early screening can improve the effectiveness of cancer prevention.
Clinical Impact of Preexisting Right Bundle Branch Block after Transcatheter Aortic Valve Replacement: A Systematic Review and Meta-Analysis
Authors: Saint Croix Garly R. , Lacy Spencer C. , Hrachian Hakop , Beohar Nirat
Published: July 2020

Introduction. Transcatheter aortic valve replacement (TAVR) is now the treatment of choice for patients with severe aortic stenosis regardless of their surgical risk. Right bundle branch block (RBBB) can be a predictor for development of significant atrioventricular (AV) block after TAVR, requiring permanent pacemaker implantation (PPI). However, data related to the risk of PPI requirement with preexisting RBBB is scarce. Hence, this systematic review and meta-analysis aims to assess clinical outcomes of patients undergoing TAVR with RBBB on preexisting electrocardiogram. Methods. We performed a systematic literature review to identify randomized and nonrandomized clinical studies that reported any clinical impact of patients undergoing TAVR with preexisting RBBB. A total of eight databases including PubMed (Medline), Embase, Cochrane Library, ACP Journal Club, Scopus, DARE, and Ovid containing articles from January 2000 to May 2020 were analyzed. Results. We identified and screened 224 potential eligible publications through the databases and found 14 relevant clinical trials for a total of 15,319 participants. There was an increased 30-day pacemaker implantation rate of 38.1% in the RBBB group compared to 11.4% in the no RBBB group with a risk ratio of 3.56 (RR 3.56 (95% CI 3.21–3.93, p<0.01)). There was an increased 30-day all-cause mortality in the RBBB group of 9.5% compared with 6.3% in the no RBBB group with an odds ratio of 1.60 (OR 1.60 (95% CI 1.14–2.25, p<0.01)). Conclusion. This study indicates that patients with preexisting RBBB have higher incidence of PPI and all-cause mortality after TAVR compared with patients without RBBB. Further trials are needed to compare the clinical outcomes based on TAVR valve types and assess the benefit of PPI in patients with new-onset RBBB after TAVR.
Optimal Operational Decision Making of Manufacturers and Authorized Remanufacturers with Patent Licensing under Carbon Cap-and-Trade Regulations
Authors: Liu Biyu , Hua Zhongsheng , Zhang Qinhong , Yang Haidong , Migdalas Athanasios
Published: July 2020

Constrained by production capacity and the pressure to reduce emissions, many original equipment manufacturers (OEMs) authorize third-party remanufacturers (TPRs) to remanufacture patented products. We investigate the operational decisions of OEMs and authorized TPRs under carbon cap-and-trade regulations in a two-echelon supply chain. We first formulate an operational decision model for OEMs before a TPR enters. Then, for the cases of centralized and decentralized decision making, we formulate an operational decision-making model for the TPR and, subsequently, establish one for the OEM after the TPR enters. We further analyze the effects of carbon emissions cap, trading price of carbon permits, yield rate, and consumer willingness to pay (WTP) on optimal decisions. Our results indicate: whether TPRs accept authorization remanufacturing depending on the ratio of carbon emissions cap to carbon emissions for producing per remanufactured product; royalty rate is negatively affected by trading price of carbon permits and per remanufactured product’ carbon emissions other than that for per new product, and can offset the threat caused by TPRs; the implementation of carbon cap-and-trade regulations causes OEMs to charge TPRs lower royalty rate; centralized decision making increases the total profit of the supply chain and delivers superior environmental benefits. As yield rate and WTP increase, the total profit increases, increasingly sensitive to WTP.
Dexmedetomidine Attenuates LPS-Induced Monocyte-Endothelial Adherence via Inhibiting Cx43/PKC-α/NOX2/ROS Signaling Pathway in Monocytes
Authors: Chai Yunfei , Cao Zhongming , Yu Runying , Liu Yong , Yuan Dongdong , Lei Liming
Published: July 2020

Dexmedetomidine is widely used for sedating patients in operation rooms or intensive care units. Its protective functions against oxidative stress, inflammation reaction, and apoptosis have been widely reported. In present study, we explored the effects of dexmedetomidine on monocyte-endothelial adherence. We built lipopolysaccharide- (LPS-) induced monocyte-endothelial adherence models with U937 monocytes and human umbilical vein endothelial cells (HUVECs) and observed the effects of dexmedetomidine on U937-HUVEC adhesion. Specific siRNA was designed to knock-down Connexin43 (Cx43) expression in U937 monocytes. Gö6976, GSK2795039, and NAC were used to inhibit PKC-α, NOX2, and ROS, respectively. Then, we detected whether dexmedetomidine could downregulate Cx43 expression and its downstream PKC-α/NOX2/ROS signaling pathway activation and ultimately result in the decrease of U937-HUVEC adhesion. The results showed that dexmedetomidine, at its clinically relevant concentrations (0.1 nM and 1 nM), could inhibit adhesion of molecule expression (VLA-4 and LFA-1) and U937-HUVEC adhesion. Simultaneously, it also attenuated Cx43 expression in U937 monocytes. With the downregulation of Cx43 expression, the activity of PKC-α and its related NOX2/ROS signaling pathway were reduced. Inhibiting PKC-α/NOX2/ROS signaling pathway with Gö6976, GSK2795039, and NAC, respectively, VLA-4, LFA-1 expression, and U937-HUVEC adhesion were all decreased. In summary, we concluded that dexmedetomidine, at its clinically relevant concentrations (0.1 nM and 1 nM), decreased Cx43 expression in U937 monocytes and PKC-α associated with carboxyl-terminal domain of Cx43 protein. With the downregulation of PKC-α, the NOX2/ROS signaling pathway was inhibited, resulting in the decrease of VLA-4 and LFA-1 expression. Ultimately, U937-HUVEC adhesion was reduced.
Balanced Suspension versus Pillow on Preoperative Pain for Proximal Femur Fractures: A Randomized Controlled Trial
Authors: Yuenyongviwat Varah , Jiarasrisatien Chonthawat , Iamthanaporn Khanin , Hongnaparak Theerawit , Tangtrakulwanich Boonsin
Published: July 2020

Introduction. To evaluate the efficacy of a balanced suspension system, using the Thomas splint, with Pearson attachment, compared with a pillow for preoperative pain in patients with proximal femoral fractures. Materials and Methods. Sixty patients with proximal femur fractures were randomized into two groups: a balanced suspension group and a pillow group. In the first group, a balanced suspension was applied after length adjustment, to match the patient’s leg and thigh. In the pillow group, a pillow was placed below the patient’s leg, to position the patient’s hip in a semiflexion and external rotation position. Preoperative pain severity, by using a verbal numerical rating scale (VNRS), the amount of morphine consumed, and complication were recorded. Results. There were no differences in patient characteristics between the groups. The mean VNRS for pain was not statistically different between the groups, from the start of the study up to 48 hours. The mean of morphine consumption was not different between the groups at the start of the study, on day 1, and on day 2 (p=0.25, 0.89, and 0.053, respectively). Conclusions. A balanced suspension did not improve patient outcome to the same level as other tractions in previous studies. Hence, other methods for reducing pain, while waiting for definite operations, should be focused on. The clinical trial is registered with TCTR20150514002.
Research of Epidemic Big Data Based on Improved Deep Convolutional Neural Network
Authors: Wang Wendong
Published: July 2020

In recent years, with the acceleration of the aging process and the aggravation of life pressure, the proportion of chronic epidemics has gradually increased. A large amount of medical data will be generated during the hospitalization of diabetics. It will have important practical significance and social value to discover potential medical laws and valuable information among medical data. In view of this, an improved deep convolutional neural network (“CNN+” for short) algorithm was proposed to predict the changes of diabetes. Firstly, the bagging integrated classification algorithm was used instead of the output layer function of the deep CNN, which can help the improved deep CNN algorithm constructed for the data set of diabetic patients and improve the accuracy of classification. In this way, the “CNN+” algorithm can take the advantages of both the deep CNN and the bagging algorithm. On the one hand, it can extract the potential features of the data set by using the powerful feature extraction ability of deep CNN. On the other hand, the bagging integrated classification algorithm can be used for feature classification, so as to improve the classification accuracy and obtain better disease prediction effect to assist doctors in diagnosis and treatment. Experimental results show that compared with the traditional convolutional neural network and other classification algorithm, the “CNN+” model can get more reliable prediction results.
Crystal Structure, Lattice Strain, Morphology, and Electrical Properties of SnO2 Nanoparticles Induced by Low Calcination Temperature
Authors: Khaenamkaew Panya , Manop Dhonluck , Tanghengjaroen Chaileok , Palakawong Na Ayuthaya Worasit
Published: July 2020

The electrical properties of tin dioxide (SnO2) nanoparticles induced by low calcination temperature were systematically investigated for gas sensing applications. The precipitation method was used to prepare SnO2 powders, while the sol‐gel method was adopted to prepare SnO2 thin films at different calcination temperatures. The characterization was done by X‐ray diffraction, scanning electron microscopy (SEM), and atomic force microscopy (AFM). The samples were perfectly matched with the rutile tetragonal structure. The average crystallite sizes of SnO2 powders were 45 ± 2, 50 ± 2, 62 ± 2, and 65 ± 2 nm at calcination temperatures of 300, 350, 400, and 450°C, respectively. SEM images and AFM topographies showed an increase in particle size and roughness with the rise in calcination temperature. The dielectric constant decreased with the increase in the frequency of the applied signals but increased on increasing calcination temperature. By using the UV‐Vis spectrum, the direct energy bandgaps of SnO2 thin films were found as 4.85, 4.80, 4.75, and 4.10 eV for 300, 350, 400, and 450°C, respectively. Low calcination temperature as 300°C allows smaller crystallite sizes and lower dielectric constants but increases the surface roughness of SnO2, while lattice strain remains independent. Thus, low calcination temperatures of SnO2 are promising for electronic devices like gas sensors.
Ameloblastic Carcinoma in a 2-Year-Old Child: A Case Report and Review of the Literature
Authors: Vu Ngoc Bao , Le Ngoc Tuyen , Chaisuparat Risa , Thunyakitpisal Pasutha , Tran Ngoc Minh
Published: July 2020

Ameloblastic carcinoma (AC) is a rare malignant odontogenic tumor in pediatric patients, only 22 cases have been reported in literature since 1932. We present an extremely rare case in which AC occurred in a 2-year-old girl, who had a tumor in the right mandible. Radiographic findings showed a multilocular, poorly defined, and mixed radiolucent-radiopaque lesion in the region of teeth #84 to #85, with bone and tooth root resorption. Computed tomography revealed buccal cortex destruction, tumor infiltration of soft tissue, and enlarged nodes. Incisional biopsy showed histomorphological features of AC. Immunohistochemical analysis exhibited a positive result for Cytokeratin (CK) 19 and overexpression of p53 and Ki67. The patient underwent right hemimandibulectomy and neck dissection. The final pathology was consistent with the initial diagnosis of AC. The patient did not exhibit signs of recurrence or metastasis within 2 years postoperatively. Given the rarity of this disease and the age of the patient, this report constitutes a valuable contribution to the current literature.
Strategies for Datacenters Participating in Demand Response by Two-Stage Decisions
Authors: Li Yuling , Wang Xiaoying , Luo Peicong
Published: July 2020

Modern smart grids have proposed a series of demand response (DR) programs and encourage users to participate in them with the purpose of maintaining reliability and efficiency so as to respond to the sustainable development of demand-side management. As a large load of the smart grid, a datacenter could be regarded as a potential demand response participant. Encouraging datacenters to participate in demand response programs can help the grid to achieve better load balancing effect, while the datacenter can also reduce its own power consumption so as to save electricity costs. In this paper, we designed a demand response participation strategy based on two-stage decisions to reduce the total cost of the datacenter while considering the DR requirements of the grid. The first stage determines whether to participate in demand response by predicting real-time electricity prices of the power grid and incentive information will be sent to encourage users to participate in the program to help shave the peak load. In the second stage, the datacenter interacts with its users by allowing users to submit bid information by reverse auction. Then, the datacenter selects the tasks of the winning users to postpone processing them with awards. Experimental results show that the proposed strategy could help the datacenter to reduce its cost and effectively meet the demand response requirements of the smart grid at the same time.
Cyphellophora sp. Isolated from a Corneal Ulcer in the Human Eye
Authors: Rajandran Satheitra , Razali Kursiah Mohd , Mustapha Mushawiahti , Palaniappan Prem Ananth , Amran Fairuz
Published: July 2020

Cyphellophora is a black yeast-like fungus with most of the strains being isolated from soil and plants. It tends to cause sooty blotch and flyspeck disease in plants. In humans, it is known to cause superficial skin and nail infections. This report highlights the case of a patient who initially presented with a small corneal abrasion which rapidly progressed into a corneal ulcer after the patient did not respond to the initial conventional treatment. The laboratory results from the corneal scraping found it to be Cyphellophora sp.
Crystal Growth and Kinetic Behaviour of Pseudoalteromonas espejiana Assisted Biosynthesized Gold Nanoparticles
Authors: Gupta Rashmi , Kumar Gourav , Das Sabya Sachi , Alkahtani Saad , Alkahtane Abdullah , Aldahmash Badr , Alarifi Saud , Almutairi Bader , Albasher Gadah , Nayak Amit Kumar , Hasnain Md Saquib
Published: July 2020

Pseudoalteromonas espejiana (P. espejiana) is a marine bacterium known for its high resistance to alkalinity. The ability of P. espejiana to reduce Au (III) and biosynthesize gold nanoparticles (AuNPs) is found positive and was confirmed using UV-VIS, EDS, SEM, and TEM studies. Previously, many studies have been reported regarding the crystalline nature of AuNPs; therefore, this research aims at studying the crystal growth behaviour of AuNPs through DLS and TEM studies. Spherically shaped and monodispersed, AuNPs ranging between 5 to 160 nm were obtained with an average particle size of 62 nm. Also, to achieve maximum production of AuNPs, the reaction kinetic study was performed using an ICP-OES method and the effect of various parameters including pH, temperature, rpm, and concentration of substrate was analyzed. During the biosynthesis process, an appropriate phase of nucleation, crystal growth, and saturation was observed and this helped to determine the rate constants and order of reaction. The parameters such as pH profile (pH 9), temperature (30°C), agitation speed (150 rpm), and enzyme substrate ratio (2 : 3) were found to be the best fits for maximum production of low size AuNPs. This demonstrates that in initial few hours, a quick conversion of the ionic gold precursor takes place into metallic gold nuclei, trailed by crystal growth via coalescence of small nuclei. Subsequently, it can be concluded that coalescence processes drive the crystal growth process of AuNPs over a time interval and finally leads to saturation and no newer particle formation in the solution.
Cosine Similarity Measure of Complex Fuzzy Sets and Robustness of Complex Fuzzy Connectives
Authors: Guo Wenping , Bi Lvqing , Hu Bo , Dai Songsong
Published: July 2020

Complex fuzzy set (CFS), as a generalization of fuzzy set (FS), is characterized by complex-valued membership degrees. By considering the complex-valued membership degree as a vector in the complex unit disk, we introduce the cosine similarity measures between CFSs. Then, we investigate some invariance properties of the cosine similarity measure. Finally, the cosine similarity measure is applied to measure the robustness of complex fuzzy connectives and complex fuzzy inference.
Eliminating Boundary Layer Separation on a Cylinder with Nonuniform Suction
Authors: Ramsay James , Sellier Mathieu , Ho Wei Hua
Published: July 2020

Boundary layer separation negatively influences the performance of aerospace vehicles, for example, by triggering static stall or reducing combustion engine efficiency. Developing effective flow control to delay or eliminate separation is therefore of real use to the field. In this paper, numerical studies were carried out to optimise distributed suction profiles for preventing boundary layer separation on a circular cylinder in the fully laminar regime (Re<188), with the least control effort. Relationships were found between the Reynolds number, the separation angle of the uncontrolled case, and the uniform suction needed to eliminate separation. It was found that for Re>20, the uniform suction required to eliminate separation followed a quadratic profile, as a function of Re. Maximum uniform suction effort was needed at Re=20, requiring a suction coefficient of CQ=49.14 (as a percentage of the free-stream velocity) to eliminate separation. To resolve the best nonuniform suction profile at Re=180, a variety of optimisation studies were performed using the coordinate search method. It was determined that the use of six control segments on each half of the cylinder provided the best control and efficient convergence to the optimal solution. 6-segment nonuniform suction eliminated separation at Re=180 with net suction effort of CQ=13.26 compared to CQ=31.25 for the uniform case. These optimal suction profiles were compared using time-dependent simulations to confirm that both methods eliminate separation when introduced to an already unsteady case. Nonuniform suction eliminated separation faster, though uniform suction was more stable.
Methylation of HSP70 Orchestrates Its Binding to and Stabilization of BCL2 mRNA and Renders Pancreatic Cancer Cells Resistant to Therapeutics
Authors: Wang Liang , Jia Zhiliang , Xie Dacheng , Zhao Tiansuo , Tan Zhi , Zhang Shuxing , Kong Fanyang , Wei Daoyan , Xie Keping
Published: July 2020

Pancreatic cancer is a lethal disease owing to its intrinsic and acquired resistance to therapeutic modalities. The altered balance between pro- and antiapoptosis signals within cancer cells is critical to therapeutic resistance. However, the molecular mechanisms underlying increased antiapoptosis signals remain poorly understood. In this study, we report that PRMT1 expression is increased in pancreatic cancer tissues and is associated with higher tumor grade, increased aggressiveness, and worse prognosis. PRMT1 overexpression increased arginine methylation of HSPs of 70 kDa (HSP70); this methylation enhanced HSP70 binding and stabilization of BCL2 mRNA through AU-rich elements in 3′-untranslated region and consequentially increased BCL2 protein expression and protected cancer cells from apoptosis induced by cellular stresses and therapeutics. RNA binding and regulation function of HSP70 was involved in pancreatic cancer drug resistance and was dependent on protein arginine methylation. These findings not only reveal a novel PRMT1–HSP70–BCL2 signaling axis that is crucial to pancreatic cancer cell survival and therapeutic resistance, but they also provide a proof of concept that targeted inhibition of this axis may represent a new therapeutic strategy.

Significance:

This study demonstrates that a PRMT1-mediated stabilization of BCL2 mRNA contributes to therapeutic resistance in pancreatic cancer and that targeting this pathway could overcome said resistance.
Spatial Density and Distribution of Tumor-Associated Macrophages Predict Survival in Non–Small Cell Lung Carcinoma
Authors: Zheng Xiang , Weigert Andreas , Reu Simone , Guenther Stefan , Mansouri Siavash , Bassaly Birgit , Gattenlöhner Stefan , Grimminger Friedrich , Savai Pullamsetti Soni , Seeger Werner , Winter Hauke , Savai Rajkumar
Published: July 2020

The respective antitumoral and protumoral roles of M1 and M2 tumor-associated macrophages (TAM) typify the complexity of macrophage function in cancer. In lung cancer, density and topology of distinct TAM phenotypes at the tumor center (TC) versus the invasive margin (IM) are largely unknown. Here, we investigated TAM subtype density and distribution between TC and IM in human lung cancer and TAM associations with overall survival. Macrophages isolated from adjacent nontumor tissue (NM), the TC (TC-TAM), and the IM (IM-TAM) were analyzed with RNA-sequencing (RNA-seq). Lung tumor tissue microarrays from 104 patient samples were constructed. M1 and M2 TAMs were identified using multiplex immunofluorescence staining and a tumor cell-TAM proximity analysis was performed. RNA-seq identified marked differences among NM, TC-TAM, and IM-TAM. On the basis of a panel of five selected markers (CD68, IL12, CCR7, CD163, and ALOX15), M2 predominance over M1 and M2 proximity to tumor cells was observed, especially at IM. Tumor cell proximity to TAM was linked with tumor cell survival and hypoxia was associated with accumulation of M2 TAM. Notably, lower density of M1 TC-TAM and higher proximity of tumor cells to M2 IM-TAM or lower proximity to M1 IM-TAM were linked with poor survival. In addition, three novel molecules (UBXN4, MFSD12, and ACTR6) from RNA-seq served as potential prognostic markers for lung cancer, and M2 predominance and juxtaposition of M2 TAM near tumor cells were associated with poor survival. Together, our results reveal the marked heterogeneity of TAM populations in different tumor regions, with M2 TAM predominance, particularly at IM.

Significance:

This study underlines the significance of the density, spatial distribution, and gene expression of TAM phenotypes as prognostic factors for overall survival in lung cancer.
Risk of Breast Cancer Associated with Estrogen DNA Adduct Biomarker
Authors: Reding Kerryn W. , Han Claire J. , Whittington Dale , Zahid Muhammad , Rogan Eleanor G. , Langford Dale , Rohan Thomas E. , Chlebowski Rowan T. , Cheng Ting-Yuan David , Barrington Wendy E. , Tinker Lesley F.
Published: July 2020

Background:

It is biologically plausible that genotoxic estrogens, namely estrogen DNA adducts (EDA), have a role in breast cancer development. Support comes from three prior studies that reported elevated concentrations of EDA relative to estrogen metabolites and conjugates (EDA:EMC) in women with breast cancer relative to control women.

Methods:

In postmenopausal women in the Women's Health Initiative (WHI), EDA:EMC in 191 controls was compared with findings in 194 prediagnosis urine samples from breast cancer cases. EDA:EMC determinations were by mass spectrometry as previously described, and logistic regression was employed to estimate ORs.

Results:

EDA:EMC did not differ in breast cancer cases compared with controls overall [0.93 (95% confidence interval, 0.71–1.23)], with a mean (SD) of 2.3 (0.8) and 2.4 (1.1) in cases and controls, respectively. Similarly, the ratio did not differ when examined by estrogen receptor or recency of biospecimen collection prior to breast cancer.

Conclusions:

Despite the demonstrated genotoxic properties of certain catechol estrogens resulting in EDAs, this analysis did not provide evidence for an increased breast cancer risk in relation to an elevated EDA:EMC.

Impact:

This analysis, conducted prospectively within postmenopausal women in the WHI study, suggests that a strong association between EDA:EMC and breast cancer could be ruled out, as this study was powered to detect an OR of 2.2 or greater.
Genetic Determinants of Lung Cancer Prognosis in Never Smokers: A Pooled Analysis in the International Lung Cancer Consortium
Authors: Brhane Yonathan , Yang Ping , Christiani David C. , Liu Geoffrey , McLaughlin John R. , Brennan Paul , Shete Sanjay , Field John K. , Tardón Adonina , Kohno Takashi , Shiraishi Kouya , Matsuo Keitaro , Bossé Yohan , Amos Christopher I. , Hung Rayjean J.
Published: July 2020

Background:

Lung cancer remains the leading cause of cancer death worldwide, with 15% to 20% occurring in never smokers. To assess genetic determinants for prognosis among never smokers, we conducted a genome-wide investigation in the International Lung Cancer Consortium (ILCCO).

Methods:

Genomic and clinical data from 1,569 never-smoking patients with lung cancer of European ancestry from 10 ILCCO studies were included. HRs and 95% confidence intervals of overall survival were estimated. We assessed whether the associations were mediated through mRNA expression–based 1,553 normal lung tissues from the lung expression quantitative trait loci (eQTL) dataset and Genotype-Tissue Expression (GTEx). For cross-ethnicity generalization, we assessed the associations in a Japanese study (N = 887).

Results:

One locus at 13q22.2 was associated with lung adenocarcinoma survival at genome-wide level, with carriers of rs12875562-T allele exhibiting poor prognosis [HR = 1.71 (1.41–2.07), P = 3.60 × 10−8], and altered mRNA expression of LMO7DN in lung tissue (GTEx, P = 9.40 × 10−7; Lung eQTL dataset, P = 0.003). Furthermore, 2 of 11 independent loci that reached the suggestive significance level (P < 10−6) were significant eQTL affecting mRNA expression of nearby genes in lung tissues, including CAPZB at 1p36.13 and UBAC1 at 9q34.3. One locus encoding NWD2/KIAA1239 at 4p14 showed associations in both European [HR = 0.50 (0.38–0.66), P = 6.92 × 10−7] and Japanese populations [HR = 0.79 (0.67–0.94), P = 0.007].

Conclusions:

Based on the largest genomic investigation on the lung cancer prognosis of never smokers to date, we observed that lung cancer prognosis is affected by inherited genetic variants.

Impact:

We identified one locus near LMO7DN at genome-wide level and several potential prognostic genes with cis-effect on mRNA expression. Further functional genomics work is required to understand their role in tumor progression.
Perforated Goblet Cell Carcinoid of the Appendix
Authors: Kubo Kimitoshi , Kimura Noriko , Suzuoki Masato , Matsuda Soichiro , Tsuda Momoko , Ohara Masanori , Kato Mototsugu
Published: July 2020

Goblet cell carcinoid (GCC) of the perforated appendix is rare, and its pathological features and prognosis remain poorly described. A 71-year-old woman was admitted to our hospital for right lower abdominal pain, vomiting, and high-grade fever. She was diagnosed with acute appendicitis and underwent emergency laparoscopic appendectomy. Intraoperative examination revealed an enlarged and perforated appendix. Histopathological examination revealed GCC of the appendix with subserosal invasion. She underwent laparoscopic ileocecal resection with lymph node dissection (D3) following appendectomy. Histopathological findings showed no residual tumor or lymph node metastases. To the best of our knowledge, this report is a valuable addition to the GCC literature, describing a case of GCC of the appendix presenting as perforated appendix.
An Eltrombopag Red (Plasma) Alert
Authors: Al-Samkari Hanny , Goodarzi Katayoon
Published: July 2020

Eltrombopag is a thrombopoietin receptor agonist frequently used to manage immune thrombocytopenia and aplastic anemia. At the high doses used for aplastic anemia, but not the doses used for immune thrombocytopenia, eltrombopag can cause reddish-brown discoloration of plasma, which can interfere with bilirubin measurement and cause false clinical alarm. This case report and clinical image describes a patient with aplastic anemia managed with eltrombopag who developed reddish-brown plasma initially concerning for possible hemolysis or rhabdomyolysis.
Prophylaxis Using a Mixture of Plasma-Derived Activated Factor VII and Factor X (pdFVIIa/FX) in a Patient with Hemophilia B Complicated by Inhibitors and Allergy to Factor IX Concentrates: A Case Report
Authors: Uchida Eriko , Komori Kazutoshi , Kurata Takashi , Taki Masashi , Sakashita Kazuo
Published: July 2020

Treating patients with hemophilia and inhibitors is often problematic. The presence of inhibitors negatively impacts the effectiveness of treatment to achieve hemostasis especially in patients with hemophilia B, owing mainly to allergic reactions to factor IX (FIX) concentrates and the low success rate of immune tolerance therapy. A 9-month-old boy had intracranial hemorrhage and was diagnosed with hemophilia B. After replacement therapy, he developed inhibitors and an allergic reaction to FIX. Prophylactic therapy was initiated with recombinant activated factor VII (rFVIIa) and later switched to pdFVIIa/factor X (FX; 120 μg/kg as the FVII dose, every other day) because of a recurrence of intracranial hemorrhage. Since then, he remained well without life-threatening bleeding for more than 2 years. Our case suggests that pdFVIIa/FX may be useful for prophylactic therapy in hemophilia B complicated by inhibitors and allergic reaction to FIX concentrates.
Covering Post-Endoscopic Submucosal Dissection Ulcers in Miniature Swine with Hexanoyl (Hx:C6) Group-Modified Alkaline-Treated Gelatin Porous Film (HAG) Induces Proper Healing by Decreasing Inflammation and Fibrosis
Authors: Maeda Hidehito , Sasaki Fumisato , Morinaga Yuko , Kabayama Masayuki , Iwaya Hiromichi , Komaki Yuga , Arima Shiho , Nasu Yuichiro , Tanoue Shiroh , Hashimoto Shinichi , Kanmura Shuji , Nishiguchi Akihiro , Taguchi Tetsushi , Ido Akio
Published: July 2020

Background and Aims: Hexanoyl (Hx:C6) group-modified alkaline-treated gelatin porous film (HAG) is a newly developed degradable hydrogel characterized by strong adhesiveness and high affinity for vascular endothelial growth factor (VEGF). The aim of this study was to clarify the effect of HAG sheets on the healing process of post-endoscopic submucosal dissection (ESD) porcine gastric artificial ulcers. Methods: (1) To evaluate the adhesiveness of HAG sheets over time, we performed ESD to create 1 artificial ulcer and covered the lesion with 1 HAG sheet using 1 miniature swine. We observed 2 ulcers by endoscopic and microscopic examinations. (2) To examine the effect of HAG sheets on post-ESD ulcer healing, we performed ESD using 5 miniature swine. The artificial ulcers were covered with HAG sheets, or left uncovered after ESD (day 0), followed by macroscopic and microscopic examinations. On days 7 and 14, we observed 2 ulcers by endoscopic examinations. On day 14, the animals were sacrificed, and histological examination was performed on the 3 stomachs that could be extirpated. Results: (1) On day 7, adhesion of HAG sheets was observed. (2) Gastric ulcer area on day 7 was significantly larger in the covered ulcers than in the non-covered ulcers (p = 0.046). On day 14, although there was no significant difference in ulcer area irrespective of covering (p = 0.357), the covered ulcers tended to repair less fold convergence than non-covered ulcers. The covered ulcer sheets significantly decreased inflammatory cell infiltration (p = 0.011), but significantly increased the abundance of macrophages (p = 0.033), in submucosal layers. Also, the abundance of alpha-smooth muscle actin-positive cells in submucosal layers of the covered ulcers was significantly reduced (p = 0.044), leading to a decrease in collagen accumulation. In addition, fibrosis and atrophy of the muscularis propria were significantly lower for covered ulcers than for non-covered ulcers. Furthermore, microvessels and VEGF-positive cells were significantly more abundant in the submucosal layers of the covered ulcers (p < 0.001 and p = 0.024, respectively). Conclusions: HAG sheets induced post-ESD ulcer healing with less submucosal inflammation and muscularis propria injury and have the potential to decrease excess scarring.
Factors Influencing Participation in Biospecimen Research among Parents of Youth with Mental Health Conditions
Authors: Owen-Smith Ashli A. , Sesay Musu M. , Lynch Frances L. , Massolo Maria , Cerros Hilda , Croen Lisa A.
Published: July 2020

Introduction: Biospecimens are tools that have the potential to improve early identification and treatment for autism spectrum disorders (ASD) and bipolar disorders (BPD). Unfortunately, most biobanks lack racial/ethnic diversity. One challenge to including a diverse sample of youth is recruiting and engaging families. Objective: We sought to better understand facilitators and barriers to participation in biospecimen research among a diverse group of parents of youth with ASD and BPD. Methods: The current study involved 3 Mental Health Research Network sites. At each site, parents participated in an interview that explored attitudes and beliefs about genetic research. Interviews were audio-recorded, and audio files were transcribed and coded using content analysis. Results: A total of 58 interviews were conducted. Four challenges emerged: (1) contacting and engaging potential research participants, (2) motivating potential participants to read recruitment and consent materials, (3) motivating participation in research, in general, and (4) motivating participation in research involving biospecimen donation, specifically. Conclusions: Participants were eager to participate as long as the research process involved trust, clarity, and flexibility. Future research involving youth with mental health conditions would benefit from implementing multimodal strategies for recruitment and data collection and sharing knowledge gained by the research with study participants.
Is the Voided Volume at Office Uroflowmetry Physiological and Reliable? A Comparison between Voiding Diary and Uroflowmetry
Authors: Rubilotta Emanuele , Righetti Rita , Trabacchin Nicolò , Curti Pier Paolo , Costantini Elisabetta , Antonelli Alessandro , Balzarro Matteo
Published: July 2020

Introduction: We compared voided volumes (VV) at voiding diaries (VD) and at uroflowmetry (UF) in men with lower urinary tract symptoms (LUTS). Methods: This was a prospective, multicenter study. In a cohort of males with LUTS, VV reported in 3-day VD was compared to VV recorded at UF. Demographic data were analyzed. The patients were stratified according to VV. A sub-analysis dividing males by age strata was also performed. Results: We enrolled 169 patients. Mean VV were higher at UF than at VD in the entire population and in each group, stratified by age. VV significantly decreased with aging. Males with the lowest threshold difference (50 mL) were 29%, with a moderate threshold difference (<100 mL) 55.6%, with an intermediate threshold difference 49.1% (51–150 mL), whereas 21.9% of men had a large threshold difference (>150 mL). Discussion/Conclusion: VV correlation between VD and UF was poor. A large part of men performed UF with VV which were poorly comparable to the habitual VV assessed by 3-day VD. Therefore, our results indicate the relevance to obtain more than 1 UF in these patients.
Categorias pluricêntricas no ensino de Alemão como Língua Estrangeira: uma proposta de análise
Authors: Savedra Mônica Maria Guimarães , Meirelles Camila
Published: July 2020

Neste artigo abordamos o pluricentrismo da língua alemã através de uma revisão da literatura sobre o tema que privilegia os estudos sobre variantes e variedades do alemão. Após uma retrospectiva histórica, a partir de uma noção pluricêntrica para o ensino de Alemão como Língua Estrangeira, apresentamos uma proposta para análise de material didático a partir de seis categorias. Três categorias são baseadas no Quadro Europeu Comum de Referência para as Línguas: competência, tema e tipo de fonte textual, e três se referem às questões de base do DACH-Prinzip: tópicos discursivos de pluricentricidade, abordagem e variedade pluricêntrica. Os resultados da implementação da análise com as categorias propostas apontam para uma relativa incipiência da conscientização da língua alemã como língua pluricêntrica em uso em diferentes centros.
Fritz Kalmar: a memória de uma Europa artificial nos Andes bolivianos
Authors: Krausz Luis
Published: July 2020

Este artigo propõe-se a analisar a trajetória do escritor austríaco Fritz Kalmar e seu conto “Der Austrospinner” (“O austro-louco”), incluído na antologia Das Herz europaschwer, de 1997, à luz das identidades surgidas no contexto da emancipação e da assimilação judaicas na Áustria. Georg von Winternitz, protagonista desta narrativa, encarna, em seu exílio boliviano, os fundamentos de uma identidade austríaca cultivada na velha Monarquia Habsburga, legatária do Sacro Império Romano Germânico, e organiza sua existência no novo país de acordo com valores éticos e com princípios católicos, humanistas e universalistas, cultivados, sobretudo, por literatos austríacos do fim do século XIX e do início do século XX, que se dedicaram à construção da identidade imperial austríaca. Esse sistema de valores, particularmente caro aos judeus austríacos da época do Kaiser Franz Josef, revela uma surpreendente sobrevida nos Andes bolivianos depois de 1938. Ao adotar um menino indígena que está em vias de tornar-se um ladrão, esse personagem não só pretende educá-lo como, sobretudo, pretende fazer dele “um austríaco”, o que significa, para o personagem, nele instilar um sistema de valores vinculado à extinta Áustria imperial. A discussão sobre esse conceito, “o austríaco”, presente na literatura austríaca do século XIX e do início do século XX, é trazida à tona para tentar compreender o que se encontra por trás deste projeto. Para além dessa questão surge, ao longo da narrativa, uma alusão ao fato de que tanto o narrador quanto o protagonista da narrativa são descendentes de judeus que também “se tornaram” austríacos. “Tornar-se austríaco”, assim, e com isto o conceito de gelernter Österreicher, temas inextricavelmente ligados ao processo de emancipação e assimilação judaica na Áustria do século XIX, são questões que ressurgem, de forma distópica e anacrônica, na Bolívia dos anos 1950, na trajetória de Kalmar tanto quanto na de seu personagem.
Impact of Self‐Monitoring of Blood Pressure on Processes of Hypertension Care and Long‐Term Blood Pressure Control
Authors: Bryant Kelsey B. , Sheppard James P. , Ruiz‐Negrón Natalia , Kronish Ian M. , Fontil Valy , King Jordan B. , Pletcher Mark J. , Bibbins‐Domingo Kirsten , Moran Andrew E. , McManus Richard J. , Bellows Brandon K.
Published: July 2020

Background

Self‐monitoring of blood pressure (SMBP) improves blood pressure (BP) outcomes at 12‐months, but information is lacking on how SMBP affects hypertension care processes and longer‐term BP outcomes.

Methods and Results

We pooled individual participant data from 4 randomized clinical trials of SMBP in the United Kingdom (combined n=2590) with varying intensities of support. Multivariable random effects regression was used to estimate the probability of antihypertensive intensification at 12 months for usual care versus SMBP. Using these data, we simulated 5‐year BP control rates using a validated mathematical model. Trial participants were mostly older adults (mean age 66.6 years, SD 9.5), male (53.9%), and predominantly white (95.6%); mean baseline BP was 151.8/85.0 mm Hg. Compared with usual care, the likelihood of antihypertensive intensification increased with both SMBP with feedback to patient or provider alone (odds ratio 1.8, 95% CI 1.2–2.6) and with telemonitoring or self‐management (3.3, 2.5–4.2). Over 5 years, we estimated 33.4% BP control (<140/90 mm Hg) with usual care (95% uncertainty interval 27.7%–39.4%). One year of SMBP with feedback to patient or provider alone achieved 33.9% (28.3%–40.3%) BP control and SMBP with telemonitoring or self‐management 39.0% (33.1%–45.2%) over 5 years. If SMBP interventions and associated BP control processes were extended to 5 years, BP control increased to 52.4% (45.4%–59.8 %) and 72.1% (66.5%–77.6%), respectively.

Conclusions

One year of SMBP plus telemonitoring or self‐management increases the likelihood of antihypertensive intensification and could improve BP control rates at 5 years; continuing SMBP for 5 years could further improve BP control.
Impact of Kidney Function on the Blood Proteome and on Protein Cardiovascular Risk Biomarkers in Patients With Stable Coronary Heart Disease
Authors: Yang Joseph , Brody Edward N. , Murthy Ashwin C. , Mehler Robert E. , Weiss Sophie J. , DeLisle Robert K. , Ostroff Rachel , Williams Stephen A. , Ganz Peter
Published: July 2020

Background

Chronic kidney disease (
CKD
) confers increased cardiovascular risk, not fully explained by traditional factors. Proteins regulate biological processes and inform the risk of diseases. Thus, in 938 patients with stable coronary heart disease from the Heart and Soul cohort, we quantified 1054 plasma proteins using modified aptamers (
SOMA
scan) to: (1) discern how reduced glomerular filtration influences the circulating proteome, (2) learn of the importance of kidney function to the prognostic information contained in recently identified protein cardiovascular risk biomarkers, and (3) identify novel and even unique cardiovascular risk biomarkers among individuals with
CKD
.

Methods and Results

Plasma protein levels were correlated to estimated glomerular filtration rate (eGFR) using Spearman‐rank correlation coefficients. Cox proportional hazard models were used to estimate the association between individual protein levels and the risk of the cardiovascular outcome (first among myocardial infarction, stroke, heart failure hospitalization, or mortality). Seven hundred and nine (67.3%) plasma proteins correlated with
eGFR
at
P
<0.05 (ρ 0.06–0.74); 218 (20.7%) proteins correlated with
eGFR
moderately or strongly (ρ 0.2–0.74). Among the previously identified 196 protein cardiovascular biomarkers, just 87 remained prognostic after correction for
eGFR
. Among patients with
CKD
(
eGFR
<60 mL/min per 1.73 m
2
), we identified 21 protein cardiovascular risk biomarkers of which 8 are unique to CKD.

Conclusions

CKD
broadly alters the composition of the circulating proteome. We describe protein biomarkers capable of predicting cardiovascular risk independently of glomerular filtration, and those that are prognostic of cardiovascular risk specifically in patients with
CKD
and even unique to patients with
CKD
.
Self-Organization and Artificial Life
Authors: Gershenson Carlos , Trianni Vito , Werfel Justin , Sayama Hiroki
Published: July 2020

Self-organization can be broadly defined as the ability of a system to display ordered spatiotemporal patterns solely as the result of the interactions among the system components. Processes of this kind characterize both living and artificial systems, making self-organization a concept that is at the basis of several disciplines, from physics to biology and engineering. Placed at the frontiers between disciplines, artificial life (ALife) has heavily borrowed concepts and tools from the study of self-organization, providing mechanistic interpretations of lifelike phenomena as well as useful constructivist approaches to artificial system design. Despite its broad usage within ALife, the concept of self-organization has been often excessively stretched or misinterpreted, calling for a clarification that could help with tracing the borders between what can and cannot be considered self-organization. In this review, we discuss the fundamental aspects of self-organization and list the main usages within three primary ALife domains, namely “soft” (mathematical/computational modeling), “hard” (physical robots), and “wet” (chemical/biological systems) ALife. We also provide a classification to locate this research. Finally, we discuss the usefulness of self-organization and related concepts within ALife studies, point to perspectives and challenges for future research, and list open questions. We hope that this work will motivate discussions related to self-organization in ALife and related fields.
The UAE and Responsible Finance—Can Responsible Finance Ṣukūk Help the UAE in Fulfilling Its Sustainability Ambitions?
Authors: Richardson Edana
Published: July 2020

Responsible finance ṣukūk provide market participants with a capital markets instrument through which they can fulfil the dictates of Islamic law while also participating in green, social or sustainable economic activity. However, as centres for Islamic finance (such as Malaysia and Indonesia) become prominent markets for responsible finance ṣukūk, issuances of these instruments have been noticeably slower to develop in the United Arab Emirates (UAE). This has not been due to a lack of public enthusiasm for a sustainable economy from UAE authorities. However, the plethora of government sustainability initiatives, statements and targets has resulted in somewhat of a patchwork of policies, not all of which are publicly available or centrally curated. This article will aim to map the UAE’s sustainability agenda and consider where responsible finance ṣukūk fit within this agenda. Against this backdrop, it will analyse the contractual structure of the UAE’s first issuance of responsible finance ṣukūk.