bluuebunny/crossref_metadata_2025 huggingface dataset:
Attenuation of Live-Attenuated Yellow Fever 17D Vaccine Virus Is Localized to a High-Fidelity Replication Complex
Authors: Davis Emily H. , Beck Andrew S. , Strother Ashley E. , Thompson Jill K. , Widen Steven G. , Higgs Stephen , Wood Thomas G. , Barrett Alan D. T.
Published: October 2019

Live-attenuated viral vaccines are highly safe and efficacious but represent complex and often multigenic attenuation mechanisms. Most of these vaccines have been generated empirically by serial passaging of a wild-type (WT) virus in cell culture. One of the safest and most effective live-attenuated vaccines is yellow fever (YF) virus strain 17D, which has been used for over 80 years to control YF disease. The availability of the WT parental strain of 17D, Asibi virus, and large quantities of clinical data showing the effectiveness of the 17D vaccine make this WT parent/vaccine pair an excellent model for investigating RNA virus attenuation. Here, we investigate a mechanism of 17D attenuation and show that the vaccine virus is resistant to the antiviral compound ribavirin. The findings suggest that attenuation is in part due to a low probability of reversion or mutation of the vaccine virus genome to WT, thus maintaining a stable genotype despite external pressures.
Neurotropism of Enterovirus D68 Isolates Is Independent of Sialic Acid and Is Not a Recently Acquired Phenotype
Authors: Rosenfeld Amy B. , Warren Audrey L. , Racaniello Vincent R.
Published: October 2019

Since 2014, numerous outbreaks of childhood infections with enterovirus D68 (EV-D68) have occurred worldwide. Most infections are associated with flu-like symptoms, but paralysis may develop in young children. It has been suggested that infection only with recent viral isolates can cause paralysis. To address the hypothesis that EV-D68 has recently acquired neurotropism, murine organotypic brain slice cultures, induced human motor neurons and astrocytes, and mice lacking the alpha/beta interferon receptor were infected with multiple virus isolates. All EV-D68 isolates, from 1962 to the present, can infect neural cells, astrocytes, and neurons. Furthermore, our results show that sialic acid binding does not play a role in EV-D68 neuropathogenesis. The study of EV-D68 infection in organotypic brain slice cultures, induced motor neurons, and astrocytes will allow for the elucidation of the mechanism by which the virus infection causes disease.
Wide Distribution of Phage That Infect Freshwater SAR11 Bacteria
Authors: Chen Lin-Xing , Zhao Yanlin , McMahon Katherine D. , Mori Jiro F. , Jessen Gerdhard L. , Nelson Tara Colenbrander , Warren Lesley A. , Banfield Jillian F.
Published: October 2019

Fonsibacter
represents a significant microbial group of freshwater ecosystems. Although the genomic and metabolic features of these bacteria have been well studied, no phage infecting them has been reported. In this study, we reconstructed complete genomes of
Fonsibacter
and infecting phage and revealed their close relatedness to the phage infecting marine SAR11 members. Also, we illustrated that phage that infect
Fonsibacter
are widely distributed in freshwater habitats. In summary, the results contribute new insights into the ecology and evolution of
Fonsibacter
and phage.
ANALYSIS OF A STOCHASTIC HBV INFECTION MODEL WITH NONLINEAR INCIDENCE RATE
Authors: HUI HONGWEN , NIE LIN-FEI
Published: October 2019

Considering that environmental factors, diet, subconscious mind and other uncertainties play an important role in the process of delaying and treating diseases, we propose, in this paper, an amended Hepatitis B virus (HBV) model with stochastic perturbation, and investigate the longtime dynamics of this stochastic model. First, if the basic reproductive number of the corresponding deterministic model is less than 1, some sufficient conditions for almost surely exponentially stable in the sense of the infected cells and free virus are established, and the stationary probability density function of the uninfected sell is also obtained. Further, some sufficient conditions for the existence of the stationary distribution are obtained for the basic reproductive number more than 1. In addition, oscillatory behaviors of this model about the equilibrium of the corresponding deterministic model are discussed. Finally, numerical simulations demonstrate the main theoretical results and show stochastic virus model has more dynamic behaviors relative to its corresponding deterministic model. Theoretical results and numerical simulations imply that the intensity and “type (divided into positive and negative)” of white noise play very important roles in the treatment of infectious disease, which can make the disease more and more repetitive and unpredictable. Of course, comfortable environment, reasonable diet, optimistic mood and other positive uncertainty factors have active effects on the treatment and delaying of diseases, but not the converse.
Synthesis of the Graphene Supported Pd Composites as Catalyst for the Heck Reaction of Iodobenzene, Acrylic Acid and Triethylamine
Authors: Yang Ping , Liu Songlan , Ni Huiqiong , Shi Jianjun
Published: October 2019

Graphene-supported Palladium composites were prepared through irradiation of the mixture of K2C2O4, Pd and graphene oxide (GO) with UV light in the presence of ethylene glycol (EG). Since the two-dimensional sheet of GO has a huge surface area, the as-synthesized graphene supported Pd composites kept excellent catalytic activity. There is no reduction agents that were used in the process of synthesis of graphene supported Pd composites. The good yield of cinnamic acid could be obtained when using the as-synthesized graphene-supported Pd composites as a catalyst in the reaction of iodobenzene, acrylic acid and triethylamine in the water system. Furthermore, no obvious mass loss of catalyst could be observed when being used to catalyze the heck reaction multiple times.
Distributional Semantics and Linguistic Theory
Authors: Boleda Gemma
Published: October 2019

Distributional semantics provides multidimensional, graded, empirically induced word representations that successfully capture many aspects of meaning in natural languages, as shown by a large body of research in computational linguistics; yet, its impact in theoretical linguistics has so far been limited. This review provides a critical discussion of the literature on distributional semantics, with an emphasis on methods and results that are relevant for theoretical linguistics, in three areas: semantic change, polysemy and composition, and the grammar–semantics interface (specifically, the interface of semantics with syntax and with derivational morphology). The goal of this review is to foster greater cross-fertilization of theoretical and computational approaches to language as a means to advance our collective knowledge of how it works.
Stem cell-derived extracellular vesicles for renal repair: do cardiovascular comorbidities matter?
Authors: Eirin Alfonso , Lerman Lilach O.
Published: October 2019

Extracellular vesicle (EV)-based regenerative therapy has shown promising results in preclinical models of renal disease and might be useful for patients with several forms of chronic kidney disease. However, individuals with chronic kidney disease often present with comorbidities, including obesity, hypertension, diabetes, or even metabolic syndrome, which may alter the endogenous characteristics and impair the reparative capacity of stem cells and their daughter EVs. This brief review summarizes evidence of alterations in the morphology, cargo, and function of mesenchymal stem cells and mesenchymal stem cell-derived EVs in the face of cardiovascular disease. We further discuss the important ramifications for their use in patients with kidney disease.
Aeroacoustic Investigation of Passive and Active Control on Cavity Flowfields Using Delayed Detached Eddy Simulation
Authors: Liu Yu , Shi Yong , Tong Mingbo , Zhao Fei , Chen Binqi
Published: October 2019

In the present study, CFD simulation with delayed detached eddy simulation (DDES) is performed to investigate an open cavity at Mach 0.85. A clean cavity and cavity with passive and active control methods, including sawtooth spoiler, flat-top spoiler, crossflow rod, and steady leading edge blowing, are analyzed. The results obtained from all the control methods are compared with clean cavity, and all the flow control methods show positive effect on the overall sound pressure level reduction with the decrement up to 8 dB. The effect of active control on sound pressure level in the cavity is much better than that of passive control, with the magnitude of tone noise decreasing by 20-30 dB. The main focus of this investigation is to test the noise suppression effect by passive and active control methods.
Neglected Pediatric Osteochondral Fracture Dislocation of the Patella
Authors: Hsu Ta-Li , Lin Shang-Ming , Chang Chih-Hung , Lan Tsung-Yu
Published: October 2019

Pediatric osteochondral fracture dislocation of the patella is sometimes difficult to diagnose on the basis of physical examination or plain film radiography. Magnetic resonance imaging plays an important role in its early diagnosis, and early treatment can prevent damage to the articular cartilage as well as decrease the dislocation rate. Currently, many treatment choices have been reported with good results, but there is no consensus on which treatment option may lead to the best outcome. Herein, we describe the case of a 14-year-old girl with neglected osteochondral fracture dislocation of the patella. The outcome was optimal on the basis of a 2-year postoperative follow-up; thus, we believe that fixation with headless screws is a simple and effective method if the fracture fragment is large enough.
Optimization of Protease and Amylase Production by Rhizopus oryzae Cultivated on Bread Waste Using Solid-State Fermentation
Authors: Benabda Olfa , M’hir Sana , Kasmi Mariam , Mnif Wissem , Hamdi Moktar
Published: October 2019

This research was carried for the coproduction of two industrial enzymes: α-amylase and protease via SSF by Rhizopus oryzae on humidified bread waste. Fermentation time, inoculum size, initial moisture content, salt solutions, and the thickness of the substrate were investigated one by one. Fungus culture was carried out in sterile aluminum trays, and pH was adjusted to 5.5. The main results showed that the highest levels of enzyme production were obtained at 120 h, 65% relative humidity, height media of 1 cm, 105 spore/g, and M-9 solution (g/L): NaH2PO4, 12.8; KH2PO4, 3; NaCl, 0.5; NH4Cl, 1; MgSO4 7H2O, 0.5; CaCl2 2H2O, 0.01. α-Amylase (100 U/g) and protease (2400 U/g) produced by SSF from Rhizopus oryzae (CH4) on BW as substrate are of great interest in industries and could be valorized as enhancers of the bread making process.
Differential Expression of Inflammation-Related Genes in Down Syndrome Patients with or without Periodontal Disease
Authors: Baus-Domínguez M. , Gómez-Díaz R. , Torres-Lagares D. , Corcuera-Flores J. R. , Ruiz-Villandiego J. C. , Machuca-Portillo G. , Gutiérrez-Pérez J. L. , Serrera-Figallo M. A.
Published: October 2019

Aim. Aware that Down Syndrome patients present among their clinical characteristics impaired immunity, the aim of this study is to identify the statistically significant differences in inflammation-related gene expression by comparing Down Syndrome patients with Periodontal Disease (DS+PD+) with Down Syndrome patients without Periodontal Disease (DS+PD-), and their relationship with periodontitis as a chronic oral inflammatory clinical feature. Materials and Methods. Case study and controls on eleven Down Syndrome patients (DS+PD+ vs. DS+PD-). RNA was extracted from peripheral blood using a Qiagen PAXgene Blood miRNA Kit when performing an oral examination. A search for candidate genes (92 selected) was undertaken on the total genes obtained using a Scientific GeneChip® Scanner 3000 (Thermo Fisher Scientific) and Clariom S solutions for human, mouse, and rat chips, with more than 20,000 genes annotated for measuring expression levels. Results. Of the 92 inflammation-related genes taken initially, four genes showed a differential expression across both groups with a p value of <0.05 from the data obtained using RNA processing of the patient sample. Said genes were TNFSF13B (p=0.0448), ITGB2 (p=0.0033), ANXA3 (p=0.0479), and ANXA5 (p=0.016). Conclusions. There are differences in inflammation-related gene expression in Down Syndrome patients when comparing patients who present a state of chronic oral inflammation with patients with negative rates of periodontal disease.
Rapid Formation of Kinetically Sprayed Cu-Sn Intermetallic Film
Authors: Choi Dahyun , Kang Suhee , Kim Hyungsub , Kim Hyojun , Lee Caroline Sunyong
Published: October 2019

The kinetically spraying method was used to fabricate an in situ copper- (Cu-) tin (Sn) intermetallic compound (IMC) film with its thickness of approximately 1 μm using a Cu-Sn mixed powder. Microsized Cu (~5 μm) and Sn (~10 μm) powders were mixed at its ratio of 45 : 55 wt.%, respectively, and then deposited onto a silicon substrate, forming an IMC layer. The actual composition of the deposited film was measured to be at a Cu : Sn ratio of 36 : 64 wt.% (in situ kinetically sprayed at 200°C). This kinetically sprayed process uses the energy source of collision and heat energy simultaneously, leading to the formation of an IMC phase. The IMC phase of Cu6Sn5 was formed successfully within 3 minutes of in situ deposition. Moreover, we obtained a Cu6Sn5 phase when the thin film was annealed in a furnace for 1 hour immediately after kinetically spraying at room temperature. However, an IMC phase was not formed in the thin film when kinetically sprayed at room temperature followed by heating on a hot plate for 3 minutes. It seems that the simultaneous supply of collision and heat energy is crucial to result in phase formation. Therefore, we have proven that the kinetically spraying process is capable of fabricating a super-thin layer of IMC film within a short time.
Lats2-Underexpressing Bone Marrow-Derived Mesenchymal Stem Cells Ameliorate LPS-Induced Acute Lung Injury in Mice
Authors: Dong Liang , Li Lang
Published: October 2019

The pathophysiology of the acute lung injury (ALI) is characterized by the damage of alveolar epithelial cells, which can be repaired by exogenous bone marrow-derived mesenchymal stem cells (BMSCs). However, the migration and differentiation abilities of BMSCs are not sufficient for the purpose, and a new approach that could strengthen the repair effects of BMSCs in ALI still needs to be clarified. We have previously proved that in vitro large tumor suppressor kinase 2- (Lats2-) underexpressing BMSCs may enhance their tissue repair effects in ALI; thus, in the present study, we tried to explore whether Lats2-underexpressing BMSCs could rescue lipopolysaccharide- (LPS-) induced ALI in vivo. BMSCs from C57BL/6 mice transfected with Lats2-interfering lentivirus vector or lentivirus blank controls were transplanted intratracheally into LPS-induced ALI mice. The retention and differentiation of BMSCs in the lung were evaluated by in vivo imaging, immunofluorescence staining, and Western blotting. The lung edema and permeability were assessed by lung wet weight/body weight ratio (LWW/BW) and measurements of proteins in bronchoalveolar lavage fluid (BALF) using ELISA. Acute lung inflammation was measured by the cytokines in the lung homogenate and BALF using RT-qPCR and ELISA, respectively. Lung injury was evaluated by HE staining and lung injury scoring. Pulmonary fibrosis was evaluated by Picrosirius red staining, immunohistochemistry for α-SMA and TGF-β1, and hydroxyproline assay and RT-qPCR for Col1α1 and Col3α1. Lats2-mediated inhibition of the Hippo pathway increased the retention of BMSCs and their differentiation toward type II alveolar epithelial cells in the lung. Furthermore, Lats2-underexpressing BMSCs improved lung edema, permeability of the lung epithelium, and lung inflammation. Finally, Lats2-underexpressing BMSCs alleviated lung injury and early pulmonary fibrosis. Our studies suggest that underexpression of Lats2 could further enhance the repair effects of BMSCs against epithelial impair and the therapeutic potential of BMSCs in ALI mice.
Cancer Nanomedicine: A New Era of Successful Targeted Therapy
Authors: El-Readi Mahmoud Zaki , Althubiti Mohammad Ahmad
Published: October 2019

Cancer is considered as one of the most challenging health care problems. Though there are many approved drugs that can be used for cancer therapy, drug resistance and delivery are among of the barriers of the treatment. In addition, pathological characteristics of tumors and their abnormal blood vessel architecture and function also reduce the efficiency of the conventional cancer treatment. Therefore, looking for techniques that can increase the efficacy of the therapy such as nanoparticles (NPs) is vital. NPs have many properties such as their small size, ability to load various drugs and large surface area, and ability to increase the absorption of conjugated. Therefore, the NPs have been considered as excellent tumor-targeting vehicles. The recent nanoscale vehicles include liposomes, polymeric nanoparticles, magnetic nanoparticles, dendrimers, and nanoshells; lipid-based NPs have been used as conjugates. There are few examples of approved conjugated anticancer NPs including AmBisome® (amphotericin B liposomal) and Doxil® (liposomal doxorubicin). There are many other conjugated anticancer drugs at different stages of clinical trials for treatment of various cancers. This review will discuss the properties of different NPs in cancer treatment and their benefits of overcoming multidrug resistance. In addition, recent advances of using nanomedicine in different approaches of cancer treatment such as chemotherapy, radiotherapy, and immunotherapy will be highlighted in this review.
Information Characteristics, Processes, and Mechanisms of Self‐Organization Evolution
Authors: Wu Kun , Nan Qiong
Published: October 2019

Self‐organization is a general mechanism for the creation of new structural pattern of systems. A pattern, in essence, is a relationship, an architecture, a way of organizing, and a structure of order, which can only be explained by information activities. The characteristics of self‐organization behavior, such as openness, nonlinearity, inner randomness, inner feedback, information network, and holographic construction, provide corresponding conditions and basis for the self‐organizing evolution of the system from the aspects of environmental information function, maintenance and construction of the overall information framework of the system, and exploration of new information mode of the system. Based on the general process and mechanism of self‐organization system evolution, its corresponding basic stages have the significance and value of information activities. Generally speaking, the process of system elements differentiating from the original system is the decoupling of information association between relevant elements and original systems. The convergence process of forming system elements is the initial exploration of forming a new information model; the nucleation process of some initial stabilization modes is the creation of information codons; the development of the system according to a particular pattern is ergodic construction of information feedback chain indicated by information codon; the diffusion of system self‐replication is the expansion of the quantity of the information model; the variation in system self‐replication is the innovation process of introducing new information pattern; environment‐based selection and evolution correspond to the complex development of information pattern; and the alternation of old and new structures in system evolution corresponds to the formation process of the whole information network framework of the new system. In order to explain the self‐organization’s characteristics, processes, and mechanisms of system evolution at a more comprehensive level, the complexity research program must pay enough attention to and give due status to the information factors and information science creed. Moreover, the information science research creed may also provide some basic theoretical paradigms with core theoretical significance for complex system research.
Effects of Anesthetics on Barrier Tissue Function
Authors: Wang Fujing , Li Yanhui , Cui Changlei , Xue Zhaoping , Ma Haichun
Published: October 2019

Anesthetics have long been proven to have additional effects other than anesthesia on different organs and tissues of the human body. Barrier tissues play critical roles in human health and diseases, yet the impacts of anesthetics on barrier tissues are still not clear. This review article is aimed at summarizing different effects of anesthetics on the skin, the respiratory, and intestinal membranes from two aspects: inflammation/immunity and ischemia-reperfusion. Among volatile, intravenous, and local anesthetics, volatile anesthetics are less influential on barrier ischemia-perfusion function. Although direct comparisons between volatile and the other two types of anesthetics are still lacking, volatile anesthetics appear to have stronger anti-inflammatory effects on different barrier tissues through various mechanisms. These results suggested that when treating patients with barrier tissue complications, volatile anesthetics can provide better therapeutic outcomes.
Analysis of the Profits of Banks and Supply Chain Enterprises under Noncollaborative and Collaborative Financing
Authors: Dong Xinglin , Pan Jian
Published: October 2019

In order to solve the problem of how to choose a financing strategy for supply chain enterprises with financial constraints, including the manufacturer and the retailer, this paper puts forward two financing strategies in the bilateral supply chain with uncertain output and certain demand. The two financing strategies are the noncollaborative financing (finance from a bank separately (FBS)) and the collaborative financing (finance from a bank uniformly (FBU)). It derives the production order formula of the supply chain enterprises under financial constraints. Under the complete information, according to this formula, it analyzes how the bank prices the loan interest rates and finds the optimal decisions under the two financing strategies. The following results are found: (1) The manufacturer’s planned output is negatively correlated with the bank’s loan interest rate. The increased interest rates do not necessarily lead to the increased bank’s loan profits. (2) The bank’s loan profit is higher, when the supply chain enterprises choose the FBS strategy. (3) The FBU strategy does not necessarily make the profits of the manufacturer and the retailer better. It is affirmative only if some parameters in the supply chain meet certain conditions. The above‐mentioned conclusions supply a policy guiding the supply chain enterprises with financial constraints to make a choice of the financing strategy.
Bloodstream Infection and Its Clinical Characteristics and Relevant Factors Associated with Interventional Therapy in a Large Tertiary Hospital: A Six Years Surveillance Study
Authors: Bai Yanling , Zheng Zhigang , Du Mingmei , Yao Hongwu , Liu Yunxi , Suo Jijiang
Published: October 2019

Background. Interventional therapy has been widely used in the medical field as its advantages of minimally invasive, safe and quick recovery. Bloodstream infection (BSI) is the most common healthcare-associated infections (HAIs) after interventional therapy, but there are few reports about it. This study intends to analyze the clinical characteristics and relevant factors of BSI after six years of interventional therapy in a large tertiary teaching hospital, in order to provide guidances for the prevention and control of BSI after interventional operations. Methods. The case information of patients with BSI after interventional therapy from 2013 to 2018 were collected through the "real-time monitoring system of healthcare-associated infections". All BSI was determined by the infection control full-time staff and clinicians. Questionnaires were designed to review case by case and register the relevant patient information into a database. A total of 18 relevant factors were counted. Statistical software was used for analysis. Results. 174 cases of BSI occurred in 25401 patients, the incidence was 0.69%, and BSI accounted for 50% of all infected sites. Gram-positive bacteria accounted for 56.05%, coagulase-negative Staphylococcus was the main infectious bacteria. Relevant risk factor analysis showed that hepatocellular carcinoma, had undergone surgery, biliary complications, prophylactic antibiotic, replacement of antibiotics, number of interventional operations, days of prophylactic antibiotic use were the related risk factors associated with BSI (P<0.05). Multivariate analysis showed that days of prophylactic antibiotic use (OR = 1.586, P<0.05) and replacement of antibiotics (OR = 13.349, P<0.05) were the main risk factors associated with the development of BSI. Conclusions. BSI is the main infection site after interventional surgery. For patients with the risk factors as hepatocellular carcinoma/biliary complications/had undergone surgery etc., the time of prophylactic antibiotic use can be prolonged properly before interventional surgery, and selection of single antibiotic appropriate for use could significantly aid preventive measures to avoid occurrence of BSI.
Oxidative Stress Mediates Anxiety-Like Behavior Induced by High Caffeine Intake in Zebrafish: Protective Effect of Alpha-Tocopherol
Authors: de Carvalho Tayana Silva , Cardoso Patrick Bruno , Santos-Silva Mateus , Lima-Bastos Sávio , Luz Waldo Lucas , Assad Nadyme , Kauffmann Nayara , Passos Adelaide , Brasil Alódia , Bahia Carlomagno Pacheco , Moraes Suellen , Gouveia Amauri , de Jesus Oliveira Batista Evander , Oliveira Karen Renata Matos Herculano , Herculano Anderson Manoel
Published: October 2019

Anxiety is a common symptom associated with high caffeine intake. Although the neurochemical mechanisms of caffeine-induced anxiety remain unclear, there are some evidences suggesting participation of oxidative stress. Based on these evidences, the current study is aimed at evaluating the possible protective effect of alpha-tocopherol (TPH) against anxiety-like behavior induced by caffeine (CAF) in zebrafish. Adult animals were treated with CAF (100 mg/kg) or TPH (1 mg/kg)+CAF before behavioral and biochemical evaluations. Oxidative stress in the zebrafish brain was evaluated by a lipid peroxidation assay, and anxiety-like behavior was monitored using light/dark preference and novel tank diving test. Caffeine treatment evoked significant elevation of brain MDA levels in the zebrafish brain, and TPH treatment prevented this increase. Caffeine treatment also induced anxiety-like behavior, while this effect was not observed in the TPH+CAF group. Taken together, the current study suggests that TPH treatment is able to inhibit oxidative stress and anxiety-like behavior evoked by caffeine.
Intraligamentous Hematoma of the Anterior Cruciate Ligament
Authors: Tamaki Yasuaki , Hamada Daisuke , Mitsuhashi Tadashi , Kasai Tokio , Mishiro Takuya , Tsutsui Takahiko , Kita Kenichiro , Sairyo Koichi
Published: October 2019

Lesions of the anterior cruciate ligament (ACL) are rare entities in clinical practice. Here, we present the case of an intraligamentous hematoma of the ACL. A 20-year-old man (height 173 cm, weight 62.9 kg, body mass index 21) with no significant past medical history developed progressively worsening pain and limitation of range of motion in the left knee due to minor trauma. No abnormality was found on plain radiography; however, magnetic resonance imaging revealed a cystic lesion in the intercondylar fossa that was hypointense on T1-weighted imaging and hyperintense on T2-weighted imaging. We performed knee arthroscopy, made a longitudinal incision in the anterior aspect of the ACL, and identified a hematoma. The patient’s postoperative course was uneventful. There is no evidence of recurrence at one year after surgery. Although the ACL is a relatively hypovascular structure, it does contain microscopic blood vessels. In this case, we speculate that the intraligamentous hematoma was the result of rupture of these very small blood vessels in response to a minor injury.
Investigation of the Mechanism Underlying Calcium Dobesilate-Mediated Improvement of Endothelial Dysfunction and Inflammation Caused by High Glucose
Authors: Zhou Yijun , Qi Chaojun , Li Shu , Shao Xinghua , Ni Zhaohui
Published: October 2019

Background/Aims. Diabetic kidney disease (DKD) is a leading cause of end-stage renal disease. Calcium dobesilate (CaD) is widely used to treat diabetic retinopathy. Recent studies have demonstrated that CaD exerts protective effects against diabetic nephropathy. The aim of this study was to elucidate the molecular and cellular mechanisms underlying the protective effects of CaD. Methods. Human umbilical vein endothelial cells (HUVECs) were cultured with different D-glucose concentrations to determine the effects of high glucose on HUVEC gene expression. HUVECs were also incubated with CaD (25 μM, 50 μM, and 100 μM) for 3 days to determine the effects of CaD on HUVEC viability. db/db mice were treated with CaD. 2-[(Aminocarbonyl)amino]-5-(4-fluorophenyl)-3-thiophenecarboxamide (TPCA-1) blocked the nuclear factor-κB (NF-κB) pathway in HUVECs. A pentraxin 3 (PTX3) small interfering RNA (siRNA) intervention experiment was performed in the cells. An adenovirus-encapsulated PTX3 siRNA intervention experiment was performed in db/db mice. Western blot and real-time PCR analyses were used to detect PTX3, p-IKBa/IKBa (I-kappa-B-alpha), and p-eNOS/eNOS (endothelial nitric oxide synthase) expression in mice and HUVECs. Hematoxylin-eosin (HE) staining and periodic acid-Schiff (PAS) staining were used to observe renal tissue damage in mice. PTX3 expression was observed by immunohistochemical staining. Results. CaD downregulated the expression of PTX3 and p-IKBa/IKBa and upregulated the expression of p-eNOS/eNOS in vitro. When TPCA-1 was used, high glucose induced high PTX3 expression, and the expression of p-eNOS/eNOS increased. After PTX3 gene silencing, the expression of p-eNOS/eNOS also increased. In vivo, CaD reduced the expression of PTX3 and p-IKBa/IKBa in the kidneys of db/db mice and increased the expression of p-eNOS/eNOS. After PTX3 gene silencing, the urine protein and renal function of db/db mice were ameliorated, the glomerular extracellular matrix was decreased, and the expression of p-eNOS/eNOS was increased. Conclusions. Our results suggested that CaD may inhibit the expression of PTX3 by altering the IKK/IKB/NF-κB pathway, thereby improving endothelial dysfunction in HUVECs. PTX3 may be a potential therapeutic target for DKD.
Fumarate Metabolic Signature for the Detection of Reed Syndrome in Humans
Authors: Casey Ruth T. , McLean Mary A. , Challis Benjamin G. , McVeigh Terri P. , Warren Anne Y. , Mendil Lee , Houghton Richard , De Sanctis Stefano , Kosmoliaptsis Vasilis , Sandford Richard N. , Gallagher Ferdia A. , Maher Eamonn R.
Published: October 2019

Purpose:

Inherited pathogenic variants in genes encoding the metabolic enzymes succinate dehydrogenase (SDH) and fumarate hydratase predispose to tumor development through accumulation of oncometabolites (succinate and fumarate, respectively; ref. 1). Noninvasive in vivo detection of tumor succinate by proton magnetic resonance spectroscopy (1H-MRS) has been reported in SDH-deficient tumors, but the potential utility of this approach in the management of patients with hereditary leiomyomatosis and renal cell cancer syndrome or Reed syndrome is unknown.

Experimental Design:

Magnetic resonance spectroscopy (1H-MRS) was performed on three cases and correlated with germline genetic results and tumor IHC when available.

Results:

Here, we have demonstrated a proof of principle that 1H-MRS can provide a noninvasive diagnosis of hereditary leiomyomatosis and renal cell cancer syndrome or Reed syndrome through detection of fumarate accumulation in vivo.

Conclusions:

This study demonstrates that in vivo detection of fumarate could be employed as a functional biomarker.
Symptoms and Needs of Patients with Advanced Lung Cancer: Early Prevalence Assessment
Authors: Kuon Jonas , Vogt Jeannette , Mehnert Anja , Alt-Epping Bernd , van Oorschot Birgitt , Sistermanns Jochen , Ahlborn Miriam , Ritterbusch Ulrike , Stevens Susanne  , Kahl Christoph , Ruellan Anne , Matthias Kathrin , Kubin Thomas , Stahlhut Kerstin , Heider Andrea , Lordick Florian , Thomas Michael ,   on behalf of the Arbeitsgemeinschaft Palliativmedizin (APM) of the German Cancer Society (DKG)
Published: October 2019

Background: Little is known on symptom burden, psychosocial needs, and perception of prognosis in advanced lung cancer patients at the time of diagnosis, although early assessment is strongly recommended within the setting of daily routine care. Methods: Twelve study sites cross-sectionally assessed symptoms and psychosocial needs of patients suffering from newly diagnosed incurable lung cancer. Assessment comprised NCCN distress thermometer, FACT-L, SEIQoL-Q, PHQ-4, and shortened and modified SCNS-SF-34 questionnaires. Additional prognostic information from both patients and physicians were collected. Results: A total of 208 patients were evaluated. Mean age was 63.6 years, 58% were male, 84% suffered from stage IV lung cancer, and 71% had an ECOG performance status of 0–1. Mean distress level was 5.4 (SD 2.5), FACT-L total score was 86 (21.5), and TOI 50.5 (14.9). PHQ-4 was 4.6 (3.3), and shortened and modified SCNS-SF-34 showed 9 (8.7) unmet needs per patient. According to their physicians’ perspective, 98.1% of patients were reflecting on and 85.2% were accepting incurability, while 26.5% of patients considered the treatment to be of curative intent. Conclusion: Our findings emphasize substantial domains of symptom burden seen in newly diagnosed, incurable lung cancer patients. Oncologists should be aware of these features and address prognostic issues early in the disease trajectory to facilitate opportunities to improve coping, advance care planning, and appropriate integration of palliative care, thus improving quality of life.
Hypertrophic Cardiomyopathy–Related Sudden Cardiac Death in Young People in Ontario
Authors: Weissler-Snir Adaya , Allan Katherine , Cunningham Kristopher , Connelly Kim A. , Lee Douglas S. , Spears Danna A. , Rakowski Harry , Dorian Paul
Published: October 2019

Background:

Hypertrophic cardiomyopathy (HCM) is considered a leading cause of sudden cardiac death (SCD) in younger people. The incidence of HCM-related SCD and its relationship to exercise have not been well studied in large comprehensive studies outside of tertiary care settings. This study sought to estimate the incidence of HCM-related SCD and its association with exercise in a large unselected population.

Methods:

Using the Office of the Chief Coroner of Ontario database encompassing all deaths attended by the coroner, we identified all HCM-related SCDs in individuals 10 to 45 years of age between 2005 and 2016 (70 million person-years). Confirmation of HCM was based on typical macroscopic and microscopic features (definite HCM-related SCD). Sudden deaths with a prior clinical diagnosis of HCM but no autopsy were considered probable HCM-related SCDs. Cases with typical features but no myofiber disarray were considered possible HCM. The completeness of data was verified in a subset of patients in the Toronto area with the use of a registry of all emergency medical services–attended cardiac arrests, with an autopsy rate of 94%. To estimate the number of HCM-related aborted cardiac arrests and lives potentially saved by implantable cardioverter-defibrillators, all de novo implantations for secondary prevention and all implantations and appropriate shocks for primary prevention in patients with HCM 10 to 45 years of age, respectively, were identified with the use of a registry containing data on implantable cardioverter-defibrillator implantations from all implanting sites throughout Ontario.

Results:

Forty-four, 3, and 6 cases of definite, probable, and possible HCM-related SCDs, respectively, were identified, corresponding to estimated annual incidence rates of 0.31 per 1000 HCM person-years (95% CI, 0.24–0.44) for definite HCM-related SCD, 0.33 per 1000 HCM person-years (95% CI, 0.34–0.62) for definite or probable HCM-related SCD, and 0.39 per 1000 HCM person-years (95% CI, 0.28–0.49) for definite, probable, or possible HCM-related SCD (estimated 140 740 HCM person-years of observation). The estimated annual incidence rate for HCM-related SCD plus aborted cardiac arrest and HCM-related life-threatening arrhythmia (SCD, aborted cardiac arrest, and appropriate implantable cardioverter-defibrillator shocks) was 0.84 per 1000 HCM person-years (95% CI, 0.70–1.0). The majority (70%) of SCDs occurred in previously undiagnosed individuals. Most SCDs occurred during rest (64.8%) or light activity (18.5%).

Conclusions:

The incidence of HCM-related SCD in the general population 10 to 45 years of age is substantially lower than previously reported, with most cases occurring in previously undiagnosed individuals. SCDs are infrequently related to exercise.
Copeptin Kinetics in Acute Ischemic Stroke May Differ According to Revascularization Strategies
Authors: Spagnolello Ornella , De Michele Manuela , Lorenzano Svetlana , Cerulli Irelli Emanuele , Naitana Federico , Falcou Anne , Letteri Federica , Bachetoni Alessandra , Collepardo Daniela , Bertazzoni Giuliano , Toni Danilo
Published: October 2019

Background and Purpose—

Prognostic value of copeptin in acute ischemic stroke has been widely reported. This study aimed to evaluate copeptin temporal profile according to revascularization strategies and the development of brain edema and hemorrhagic transformation.

Methods—

Plasma copeptin and brain edema and hemorrhagic transformation assessed by computed tomography/magnetic resonance imaging were evaluated upon admission (
T0
), at 24 hours (
T1
), and between the third and fifth day of hospitalization (
T2
) in 34 acute ischemic stroke patients.

Results—

Median copeptin concentration was 50.71 pmol/L at
T0
, 18.31 pmol/L at
T1
, and 10.92 pmol/L at
T2
. Copeptin at
T1
was higher in patients with medium/severe brain edema at
T2
(32.25 versus 13.67 pmol/L;
P
=0.038) and hemorrhagic transformation at
T1
(93.10 versus 13.67 pmol/L;
P
<0.003) and
T2
(85.70 versus 14.45 pmol/L;
P
=0.024). Copeptin level drop (CopΔ

T1−T0

) was significantly steeper in patients receiving revascularization, particularly in those undergoing combined therapy (−129.34 versus −5.43 pmol/L;
P
=0.038). Δ

T1−T0

also correlated with Thrombolysis in Cerebral Infarction score (
P
<0.001).

Conclusions—

Copeptin resulted associated with brain edema and hemorrhagic transformation in acute ischemic stroke, and its drop at 24 hours may mirror effective brain vessel recanalization.
When Temporal Certainty Doesn't Help
Authors: Kusnir Flor , Pesin Slav , Moscona Gal , Landau Ayelet N.
Published: October 2019

In a dynamically changing environment, the ability to capture regularities in our sensory input helps us generate predictions about future events. In most sensory systems, the basic finding is clear: Knowing when something will happen improves performance on it [Nobre, A. C., & van Ede, F. (2017). Anticipated moments: Temporal structure in attention. Nature Reviews Neuroscience, 19, 34–48, 2017]. We here examined the impact of temporal predictions on a less-explored modality: touch. Participants were instructed to detect a brief target embedded in an ongoing vibrotactile stimulus. Unbeknownst to them, the experiment had two timing conditions: In one part, the time of target onset was fixed and thus temporally predictable, whereas in the other, it could appear at a random time within the ongoing stimulation. We found a clear modulation of detection thresholds due to temporal predictability: Contrary to other sensory systems, detecting a predictable tactile target was worse relative to unpredictable targets. We discuss our findings within the framework of tactile suppression.
Human Depth Sensitivity Is Affected by Object Plausibility
Authors: Wong Nicole H. L. , Ban Hiroshi , Chang Dorita H. F.
Published: October 2019

Using behavioral and fMRI paradigms, we asked how the physical plausibility of complex 3-D objects, as defined by the object's congruence with 3-D Euclidean geometry, affects behavioral thresholds and neural responses to depth information. Stimuli were disparity-defined geometric objects rendered as random dot stereograms, presented in plausible and implausible variations. In the behavior experiment, observers were asked to complete (1) a noise-based depth task that involved judging the depth position of a target embedded in noise and (2) a fine depth judgment task that involved discriminating the nearer of two consecutively presented targets. Interestingly, results indicated greater behavioral sensitivities of depth judgments for implausible versus plausible objects across both tasks. In the fMRI experiment, we measured fMRI responses concurrently with behavioral depth responses. Although univariate responses for depth judgments were largely similar across cortex regardless of object plausibility, multivariate representations for plausible and implausible objects were notably distinguishable along depth-relevant intermediate regions V3 and V3A, in addition to object-relevant LOC. Our data indicate significant modulations of both behavioral judgments of and neural responses to depth by object context. We conjecture that disparity mechanisms interact dynamically with the object recognition problem in the visual system such that disparity computations are adjusted based on object familiarity.
Notes on Afrotropical Enicocephalidae and Reduviidae (Hemiptera: Heteroptera) with emphasis on vehicle-mounted net samples from Liberia, West Africa
Authors: KRÜGER ANDREAS
Published: October 2019

Notes on the Enicocephalidae and Reduviidae (Hemiptera: Heteroptera) fauna in Liberia, sampled with various methods including a vehicle-mounted net, the species taxonomy and general distribution are presented, including 19 new country records. In addition, new country records are provided for Uganda, Togo, and Burkina Faso. Previously published Liberian records for 42 reduviids supplement the checklist.
Redescription of Polichnodes americana Giglio-Tos, 1898 (Orthoptera: Tettigoniidae) with a new record and habitat notes from Brazilian Amazon Rainforest
Authors: DE MELLO MENDES DIEGO MATHEUS , SOBRAL RAFAEL , DA SILVA NETO ALBERTO MOREIRA
Published: October 2019

In this work it was made the redescription of male of Polichnodes americana including new traits as internal genitalia and morphology of stridulatory files. Also it was recorded for the first time the distribution of this species to Brazil, in Amazonas, and notes on habitat.
Ensemble Postprocessing Using Quantile Function Regression Based on Neural Networks and Bernstein Polynomials
Authors: Bremnes John Bjørnar
Published: October 2019

The value of ensemble forecasts is well documented. However, postprocessing by statistical methods is usually required to make forecasts reliable in a probabilistic sense. In this work a flexible statistical method for making probabilistic forecasts in terms of quantile functions is proposed. The quantile functions are specified by linear combinations of Bernstein basis polynomials, and their coefficients are assumed to be related to ensemble forecasts by means of a highly adaptable neural network. This leads to many parameters to estimate, but a recent learning algorithm often applied to deep-learning problems makes this feasible and provides robust estimates. The method is applied to ~2 yr of ensemble wind speed forecasting data at 125 Norwegian stations for lead time +60 h. An intercomparison with two quantile regression methods shows improvements in quantile skill score of nearly 1%. The most appealing feature of the method is arguably its versatility.
Examining Anger’s Immobilizing Effect on Institutional Insiders’ Action Intentions in Social Movements
Authors: DeCelles Katherine A. , Sonenshein Scott , King Brayden G.
Published: October 2019

We theorize that anger incited by a social movement, which has a mobilizing effect among outsider activists, might immobilize collective action intentions for institutional insiders—those sympathetic to the movement and employed by its target. We conducted initial field surveys across a spectrum of social movements, including Occupy Wall Street and #metoo, as well as those related to business sustainability and gun control, which showed that institutional insiders are often just as angry as outsider activists. But the evidence from those surveys did not show that social movement anger translated into collective action intentions among institutional insiders. We tested our theory deductively with an experiment conducted with participants who were supportive of social movement issues in their organizations. Overall, our results show that anger about a social movement issue relates to greater collective action intentions among outsider activists but not among institutional insiders. Instead of anger emboldening institutional insiders to act despite the potential costs, anger triggers fear about the potential negative consequences of collective action in the workplace, which in turn results in withdrawal. While social movements often rely on anger frames to mobilize sympathizers, our work suggests that this practice may paradoxically cause fear that immobilizes those uniquely positioned to be able to influence organizations to change.
Validity, functional impairment and complications related to Internet gaming disorder in the DSM-5 and gaming disorder in the ICD-11
Authors: Ko Chih-Hung , Lin Huang-Chi , Lin Pai-Cheng , Yen Ju-Yu
Published: October 2019

Background:

Many concerns have been raised regarding the Diagnostic and Statistical Manual of Mental Disorders (5th ed.; DSM-5) criteria for Internet gaming disorder and International Classification of Diseases, 11th Revision (ICD-11) criteria for gaming disorder.

Aims:

In this study, we demonstrated the diagnostic validity of each criterion for Internet gaming disorder in the DSM-5 in terms of their intensity and frequency thresholds and evaluated functional impairments, unhealthy behaviors and complications among adults with Internet gaming disorder and gaming disorder.

Methods:

We recruited 69 subjects with Internet gaming disorder, 69 regular gamers and 69 controls without regular gaming based on diagnostic interviewing conducted by a psychiatrist according to the DSM-5 Internet gaming disorder criteria.

Results:

Except for the ‘deceiving’ and ‘escapism’ criteria, all criteria for Internet gaming disorder had a diagnostic accuracy ranging from 84.7% to 93.5% in differentiating between adults with Internet gaming disorder and regular gamers. A total of 44 participants with Internet gaming disorder (63.8%) fulfilled the gaming disorder criteria. In addition, 89% and 100% of the Internet gaming disorder and gaming disorder groups, respectively, had academic, occupational or social functional impairment. Both the Internet gaming disorder and gaming disorder groups had higher rates of delayed sleep phase syndrome and insomnia. The gaming disorder group also had a higher obesity proportion.

Conclusion:

The ‘deceiving’ and ‘escapism’ criteria had relatively lower diagnostic accuracy. Both the Internet gaming disorder and gaming disorder groups demonstrated functional impairments and unhealthy behaviors. They also exhibited complications, such as obesity and sleep disorders. These results support the utility of the DSM-5 Internet gaming disorder and ICD-11 gaming disorder criteria in identifying individuals who need treatment for both gaming addiction symptoms and complications resulting from the addiction.