bluuebunny/crossref_metadata_2025 huggingface dataset:
Optimization of Receptor Occupancy Assays in Mass Cytometry: Standardization Across Channels with QSC Beads
Authors: Bringeland Gerd Haga , Bader Lucius , Blaser Nello , Budzinski Lisa , Schulz Axel R. , Mei Henrik E. , Myhr Kjell‐Morten , Vedeler Christian A. , Gavasso Sonia
Published: January 2019

Receptor occupancy, the ratio between amount of drug bound and amount of total receptor on single cells, is a biomarker for treatment response to therapeutic monoclonal antibodies. Receptor occupancy is traditionally measured by flow cytometry. However, spectral overlap in flow cytometry limits the number of markers that can be measured simultaneously. This restricts receptor occupancy assays to the analysis of major cell types, although rare cell populations are of potential therapeutic relevance. We therefore developed a receptor occupancy assay suitable for mass cytometry. Measuring more markers than currently available in flow cytometry allows simultaneous receptor occupancy assessment and high‐parameter immune phenotyping in whole blood, which should yield new insights into disease activity and therapeutic effects. However, varying sensitivity across the mass cytometer detection range may lead to misinterpretation of the receptor occupancy when drug and receptor are detected in different channels. In this report, we describe a method for optimization of mass cytometry receptor occupancy measurements by using antibody‐binding quantum simply cellular (QSC) beads for standardization across channels with different sensitivities. We evaluated the method in a mass cytometry‐based receptor occupancy assay for natalizumab, a therapeutic antibody used in multiple sclerosis treatment that binds to α4‐integrin, which is expressed on leukocyte cell surfaces. Peripheral blood leukocytes from a treated patient were stained with a panel containing metal‐conjugated antibodies for detection of natalizumab and α4‐integrin. QSC beads with known antibody binding capacity were stained with the same metal‐conjugated antibodies and were used to standardize the signal intensity in the leukocyte sample before calculating receptor occupancy. We found that QSC bead standardization across channels corrected for sensitivity differences for detection of drug and receptor and generated more accurate results than observed without standardization. © 2019 The Authors. Cytometry Part A published by Wiley Periodicals, Inc. on behalf of International Society for Advancement of Cytometry.
An efficient algorithm for dynamic task offloading using cloudlets in mobile cloud computing
Authors: D Shobha Rani , M Pounambal , V Saritha
Published: January 2019

It is a visible fact that the growth of mobile devices is enormous. More computations are required to be carried out for various applications in these mobile devices. But the drawback of the mobile devices is less computation power and low available energy. The mobile cloud computing helps in resolving these issues by integrating the mobile devices with cloud technology. Again, the issue is increased in the latency as the task and data to be offloaded to the cloud environment uses WAN. Hence, to decrease the latency, this paper proposes cloudlet‐based dynamic task offloading (CDTO) algorithm where the task can be executed in device environment, cloudlet environment, cloud server environment, and integrated environment. The proposed algorithm, CDTO, is tested in terms of energy consumption and completion time.
Potential limitations of behavioral plasticity and the role of egg relocation in climate change mitigation for a thermally sensitive endangered species
Authors: Liles Michael J. , Peterson Tarla Rai , Seminoff Jeffrey A. , Gaos Alexander R. , Altamirano Eduardo , Henríquez Ana V. , Gadea Velkiss , Chavarría Sofía , Urteaga José , Wallace Bryan P. , Peterson Markus J.
Published: January 2019

Anthropogenic climate change is widely considered a major threat to global biodiversity, such that the ability of a species to adapt will determine its likelihood of survival. Egg‐burying reptiles that exhibit temperature‐dependent sex determination, such as critically endangered hawksbill turtles (Eretmochelys imbricata), are particularly vulnerable to changes in thermal regimes because nest temperatures affect offspring sex, fitness, and survival. It is unclear whether hawksbills possess sufficient behavioral plasticity of nesting traits (i.e., redistribution of nesting range, shift in nesting phenology, changes in nest‐site selection, and adjustment of nest depth) to persist within their climatic niche or whether accelerated changes in thermal conditions of nesting beaches will outpace phenotypic adaption and require human intervention. For these reasons, we estimated sex ratios and physical condition of hatchling hawksbills under natural and manipulated conditions and generated and analyzed thermal profiles of hawksbill nest environments within highly threatened mangrove ecosystems at Bahía de Jiquilisco, El Salvador, and Estero Padre Ramos, Nicaragua. Hawksbill clutches protected in situ at both sites incubated at higher temperatures, yielded lower hatching success, produced a higher percentage of female hatchlings, and produced less fit offspring than clutches relocated to hatcheries. We detected cooler sand temperatures in woody vegetation (i.e., coastal forest and small‐scale plantations of fruit trees) and hatcheries than in other monitored nest environments, with higher temperatures at the deeper depth. Our findings indicate that mangrove ecosystems present a number of biophysical (e.g., insular nesting beaches and shallow water table) and human‐induced (e.g., physical barriers and deforestation) constraints that, when coupled with the unique life history of hawksbills in this region, may limit behavioral compensatory responses by the species to projected temperature increases at nesting beaches. We contend that egg relocation can contribute significantly to recovery efforts in a changing climate under appropriate circumstances.
The influence of warming on the biogeographic and phylogenetic dependence of herbivore–plant interactions
Authors: Mu Xidong , Xu Meng , Ricciardi Anthony , Dick Jaimie T. A. , Luo Du , Wei Hui , Hu Yinchang , Wei Qiwei
Published: January 2019

Evolutionary experience and the phylogenetic relationships of plants have both been proposed to influence herbivore–plant interactions and plant invasion success. However, the direction and magnitude of these effects, and how such patterns are altered with increasing temperature, are rarely studied. Through laboratory functional response experiments, we tested whether the per capita feeding efficiency of an invasive generalist herbivore, the golden apple snail,Pomacea canaliculata, is dependent on the biogeographic origin and phylogenetic relatedness of host plants, and how increasing temperature alters these dependencies. The feeding efficiency of the herbivore was highest on plant species with which it had no shared evolutionary history, that is, novel plants. Further, among evolutionarily familiar plants, snail feeding efficiency was higher on those species more closely related to the novel plants. However, these biogeographic dependencies became less pronounced with increasing temperature, whereas the phylogenetic dependence was unaffected. Collectively, our findings indicate that the susceptibility of plants to this invasive herbivore is mediated by both biogeographic origin and phylogenetic relatedness. We hypothesize that warming erodes the influence of evolutionary exposure, thereby altering herbivore–plant interactions and perhaps the invasion success of plants.
Impact of cardiac myosin light chain kinase gene mutation on development of dilated cardiomyopathy
Authors: Hodatsu Akihiko , Fujino Noboru , Uyama Yuki , Tsukamoto Osamu , Imai‐Okazaki Atsuko , Yamazaki Satoru , Seguchi Osamu , Konno Tetsuo , Hayashi Kenshi , Kawashiri Masa‐aki , Asano Yoshihiro , Kitakaze Masafumi , Takashima Seiji , Yamagishi Masakazu
Published: January 2019

Aims

Cardiac myosin light chain kinase (cMLCK) phosphorylates ventricular myosin regulatory light chain 2 (MLC2v) and regulates sarcomere and cardiomyocyte organization. However, few data exist regarding the relationship between cMLCK mutations and MLC2v phosphorylation, particularly in terms of developing familial dilated cardiomyopathy (DCM) in whom cMLCK gene mutations were identified. The purpose of the present study was to investigate functional consequences of cMLCK mutations in DCM patients.

Methods and results

The diagnosis of DCM was based on the patients' history and on echocardiography. We screened cMLCK gene mutations in DCM probands with high resolution melting analysis. Known DCM‐causing genes mutations were excluded by exome sequencing of family members. MLC2v phosphorylation was analysed by Phos‐tag sodium dodecyl sulfate–polyacrylamide gel electrophoresis assays. We also performed ADP‐Glo assays for determining the total amount of adenosine triphosphate used in the kinase reaction. Unrelated DCM probands (109 males and 40 females) were enrolled in this study, of which 16 were familial and 133 sporadic. By mutation screening, a truncation variant of c1915‐1 g>t (p.Pro639Valfs*15) was identified, which was not detected in 400 chromosomes of 200 healthy volunteers; it is listed in the Human Genetic Variation Database with an allele frequency < 0.001. In the proband, the presence of mutations in known DCM‐causing genes was excluded with exome analysis. Familial analysis identified a 19‐year‐old male carrier who manifested slight left ventricular dilation with preserved systolic function. Phosphorylation assays analysed by Phos‐tag SDS‐PAGE revealed that the identified p.Pro639Valfs*15 mutation results in a complete lack of kinase activity, although it did not affect wild‐type cMLCK activity. ADP‐Glo assays confirmed that the mutant cMLCK had no kinase activity, whereas wild‐type cMLCK had a Km value of 5.93 ± 1.47 μM and a Vmax of 1.28 ± 0.03 mol/min/mol kinase.

Conclusions

These results demonstrate that a truncation mutation in the cMLCK gene p.Pro639Valfs*15 can be associated with significant impairment of MLC2v phosphorylation and possibly with development of DCM, although a larger study of DCM patients is required to determine the prevalence of this mutation and further strengthen its association with disease development.
Click regulation of cyclodextrin primary face for the preparation of novel chiral stationary phases
Authors: Jin Xuan , Li Xiaoxuan , Wang Yong
Published: January 2019

In this study, a series of novel CD chiral stationary phases were fabricated by immobilization of mono‐6A‐deoxy‐N3‐cyclodextrin onto silica surfaces followed by click regulation of CD primary face with 4‐pentynoic acid (acidic moiety), 2‐propynylamine (alkaline moiety) and L‐propargylglycine (chiral amino acid moiety), respectively. Enantioseparations of various kinds of racemates including dansyl‐amino acids, chiral lactides and diketones were conducted in reversed phase modes on these chiral stationary phases, where nearly forty diketones and chiral lactides were firstly separated on cyclodextrin stationary phases. 4‐Pentynoic acid moiety can make the retention ability decline while amine moiety significantly enhanced the retention ability of the stationary phases. For most of the studied analytes, the chiral amino acid moiety had the most positive effects on both the retention time and the resolution. The inclusion complexation between chiral analytes and cyclodextrins were also investigated by fluorescence method.
Methods for studying cultural attraction
Authors: Heintz Christophe , Blancke Stefaan , Scott‐Phillips Thom
Published: January 2019

Cultural attraction theory (CAT) describes a general evolutionary process, cultural attraction, by which the spread and stability of cultural items (beliefs, practices, artifacts, etc.) result not just from differential reproduction, but also from transformations that systematically favor the reconstruction of cultural items of specific types. In this way, CAT aims to provide a general framework for the study of cultural evolution. In a thoughtful critical analysis, Buskell questions the ability of CAT to provide methodological guidance for research in cultural evolution. Can CAT be used to develop the sort of mid‐range theories and models that often drive empirical work? Here we argue that CAT can indeed be used in this way, and we outline the methodological practices that students of cultural attraction have used and are currently developing.
Effects of crab shell extract as a coagulant on the textural and sensorial properties of tofu (soybean curd)
Authors: Jun Joon‐Young , Jung Min‐Jeong , Jeong In‐Hak , Kim Gwang‐Woo , Sim Jae‐Man , Nam Si‐Youl , Kim Byoung‐Mok
Published: January 2019

To find an economic use of red snow crab (Chionoecetes japonicus) shell waste, we focused on its high mineral content. To evaluate its usability as a coagulant for tofu making, the effects of the crab shell extracts on the textural and sensorial properties of the tofu samples were investigated. The crab shell powder (CSP) and ash (CSA) were used for their extract preparation, and 1%–5% acetic acid treatment led to an abundance of calcium in the resulting extracts. The tofu yields of all the acetic acid extracts were comparable with those of the commercial coagulants MgCl2 and glucono‐δ‐lactone (GDL). Furthermore, the results for the textural attributes and sensorial acceptability demonstrated that either the extract from CSP prepared with 3% acetic acid or the extracts from CSA prepared with 1% or 3% acetic acid could be used as coagulants, because all the values of the extracts were statistically equivalent to those of the MgCl2 and GDL (p < 0.05).
Depth of invasion in patients with early stage oral cancer staged by sentinel node biopsy
Authors: den Toom Inne J. , Janssen Luuk M. , van Es Robert J.J. , Karagozoglu K. Hakki , de Keizer Bart , van Weert Stijn , Willems Stefan M. , Bloemena Elisabeth , Leemans C. René , de Bree Remco
Published: January 2019

Background

To investigate if depth of invasion (DOI) can predict occult nodal disease in patients with cT1‐2N0 (7th TNM) oral squamous cell carcinoma (OSCC) staged by sentinel lymph node biopsy (SLNB).

Methods

In 199 OSCC patients, DOI measurements and SLNB were performed.

Results

Metastases were found in 64 of 199 patients (32%). Of these 64 patients, the mean DOI was 6.6 mm compared to 4.7 mm in patients without metastases (P = .003). The ROC‐curve showed an area under the curve of 0.65 with a most optimal cutoff point of 3.4 mm DOI (sensitivity 83% and specificity 47%). Regional metastases were found in 15% of patients with DOI ≤ 3.4 mm.

Conclusion

DOI seems to be a poor predictor for regional metastasis in patients with cT1‐2N0 OSCC. Therefore, staging of the neck using SLNB in patients with early stage oral cancer should also be performed in tumors with limited DOI and probably in T3 (8th TNM) OSCC ≤4 cm diameter.
Burden of Primary Biliary Cholangitis Among Inpatient Population in the United States
Authors: Shahab Omer , Sayiner Mehmet , Paik James , Felix Sean , Golabi Pegah , Younossi Zobair M.
Published: January 2019

Primary biliary cholangitis (PBC) is an autoimmune liver disease that can lead to cirrhosis and liver failure. Our aim was to assess the recent trends in the mortality rates and health care utilization of patients with PBC seen in the inpatient setting in the United States. We used the National (Nationwide) Inpatient Sample data (2005‐2014). The study population included adults with PBC, using International Classification of Diseases, Ninth Revision codes. Trends in PBC‐related discharges, total charges, length of stay (LoS), and in‐hospital mortality were evaluated. Hierarchical generalized linear models were performed for determining predictors of mortality and total hospital charges. Between the study years of 2005 and 2014, a total of 22,665 hospitalized cases with PBC were identified (mean age 63 years; 84% female, 76% white). The number of PBC‐related discharges increased from 3.24 per 100,000 in 2005 to 3.68 per 100,000 in 2014, with an average annual increase of 1.4% (95% confidence interval [CI]: 0.4%‐2.4%). Fifty‐seven percent had Medicare as their primary payer, 37% had cirrhosis, and 1.3% had hepatocellular carcinoma. Between 2005 and 2014, the average total charges for PBC increased from $53,901 to $57,613 (annual percent change [APC], 1.7%; 95% CI: −0.2%‐3.5%), LoS decreased from 6.9 days to 5.4 days (APC, −2.2%; 95% CI: −3.2% to −1.1%), and mortality rate decreased from 3.8% to 2.8% (APC, −5.4%; 95% CI: −8.4% to −2.4%). Multivariable analysis revealed that ascites were independently associated with increased risk of in‐hospital mortality (odds ratio: 1.77; 95% CI: 1.50‐2.08), increased charge (percent change: 22.5%; 95% CI: 18.6%‐26.7%), and increased LoS (percent change: 29.7%; 95% CI: 25.7%‐33.9%). Conclusion: The number of PBC cases has increased in recent years. Mortality and LoS have decreased, and the total charges have remained the same.
Anticancer effect of novel platinum nanocomposite beads on oral squamous cell carcinoma cells
Authors: Tanaka Mai , Okinaga Toshinori , Iwanaga Kenjiro , Matsuo Kou , Toyono Takashi , Sasaguri Masaaki , Ariyoshi Wataru , Tominaga Kazuhiro , Enomoto Yasushi , Matsumura Yasufumi , Nishihara Tatsuji
Published: January 2019

Nanoparticles are used in industry and medicine, because of their physiochemical properties, such as size, charge, large surface area and surface reactivity. Recently, metal nanoparticles were reported to show cell toxicity on cancer cells. In this study, we focused novel platinum nanoparticles‐conjugated latex beads (P2VPs), platinum nanocomposite (PtNCP) beads, and investigated the possibility to incorporate novel anti‐cancer effect of these combined nanoparticles. Oral squamous cell carcinoma cell lines, HSC‐3‐M3 cells were injected subcutaneously into the back of nude mice to produce a xenograft model. PtNCP beads were injected locally and examined by measuring tumor volume and comparing pathological histology. PtNCP beads treatment suppressed tumor growth and identified increasing pathological necrotic areas, in vivo. PtNCP beads inhibited the cell viability of HSC‐3‐M3 cells in dose‐dependent manner and induced the cytotoxicity with extracellular LDH value, in vitro. Furthermore, SEM images were morphologically observed in PtNCP beads‐treated HSC‐3‐M3 cells. The aggregation of the PtNCP beads on the cell membrane, the destructions of the cell membrane and globular structures were observed in the SEM image. Our results indicated that a potential anti‐cancer effect of the PtNCP beads, suggesting the possibility as a therapeutic tool for cancer cell‐targeted therapy. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 2281–2287, 2019.
Rapid optical tissue clearing using poly(acrylamide‐co‐styrenesulfonate) hydrogels for three‐dimensional imaging
Authors: Ono Yuta , Nakase Ikuhiko , Matsumoto Akikazu , Kojima Chie
Published: January 2019

Optical tissue clearing methods are attractive for three‐dimensional imaging of intact tissues and organs. A CLARITY (clear lipid‐exchanged acrylamide‐hybridized rigid imaging/immunostaining/in situ‐hybridization‐compatible tissue‐hydrogel) method using polyacrylamide gels was recently developed. In the current study, we used poly(acrylamide‐co‐styrenesulfonate) gels as a polyelectrolyte gel for a passive CLARITY method. First, radical copolymerization of acrylamide (AAm) and sodium p‐styrenesulfonate (SS) at different ratios was performed. The composition of the copolymer could be controlled by changing the monomer ratio. With increased SS content, the molecular weight decreased and the refractive index slightly increased. The poly(AAm‐co‐SS) hydrogels with a higher SS content were more swollen and looser. The clearing time could be reduced using the poly(AAm‐co‐SS) hydrogel with a higher SS content. Three‐dimensional fluorescence imaging of the poly(AAm‐co‐SS) hydrogel‐cleared tissues was successfully performed after treatment using a blue fluorescent DNA stain. Therefore, the use of the poly(AAm‐co‐SS) hydrogel improved the clearing process in the passive CLARITY method, and the technique is useful for fluorescence imaging of DNA. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 2297–2304, 2019.
Design of novel organic–inorganic composite bone cements with high compressive strength, in vitro bioactivity and cytocompatibility
Authors: Ji Mizhi , Ding Zhengwen , Chen Hong , Peng Haitao , Yan Yonggang
Published: January 2019

In this work, novel bioactive organic–inorganic composite bone cements consisting of tricalcium silicate (C3S), sodium alginate (SA), and calcium sulfate hemihydrate (CS) were successfully fabricated for the first time via a special method designing material composition and internal structure simultaneously, which was intended to enhance mechanical performance by combining progressive hydration process of C3S with distinctive gelation capacity of SA and further improve degradability and self‐setting properties with the addition of CS. Depending on the synergistic combination of hydration and gelation, the C3S/SA/CS composite cements (45/45/10 wt %) obtained extremely higher compressive strength up to 92.41 MPa as compared with each single component. The reinforcing mechanisms involving interfacial interaction and interior microstructure were proposed to explain this enhancement phenomenon. Additionally, the final setting time could be reduced from 68 min to 21 min with the increasing CS content. The composite cements possessed good apatite mineralization ability in simulated body fluid solution and moderate degradation rate in phosphate buffer solution. What's more, the composite cements exhibited excellent cytocompatibility and increased proliferation of rat bone‐marrow stem cells. This study could provide guidelines for the preparation of bioactive composite cements with enhanced mechanical performance, which may be suitable for load‐bearing bone repair. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 2365–2377, 2019.
The investigation of proton transfer and fluorescence‐sensing mechanisms of [2‐(2‐hydroxy‐phenyl)‐1H‐benzoimidazol‐5‐yl]‐phenyl‐methanone
Authors: Yang Dapeng , Zhao Zhongjian , Jia Min , Song Xiaoyan , Zhang Qiaoli , Zhang Tianjie
Published: January 2019

Given the tremendous potential of fluorescence sensors in recent years, in this present work, we theoretically explore a novel fluorescence chemosensor [2‐(2‐Hydroxy‐phenyl)‐1H‐benzoimidazol‐5‐yl]‐phenyl‐methanone (HBPM) about its excited state behaviors and probe‐response mechanism. Using density functional theory (DFT) and time‐dependent density functional theory (TDDFT) methods, we explore the S0‐state and S1‐state hydrogen bond dynamical behaviors and confirm that the strengthening intramolecular hydrogen bond in the S1 state may promote the excited state intramolecular proton transfer (ESIPT) reaction. In view of the photoexcitation process, we find that the charge redistribution around the hydroxyl moiety plays important roles in providing driving force for ESIPT. And the constructed potential energy curves further verify that the ESIPT process of HBPM should be ultrafast. That is the reason why the normal HBPM fluorescence cannot be detected in previous experiment. Furthermore, with the addition of fluoride anions, the exothermal deprotonation process occurs spontaneously along with the intermolecular hydrogen bond O–H⋯F. It reveals the uniqueness of detecting fluoride anions using HBPM molecules. As a whole, the fluoride anions inhibit the initial ESIPT process of HBPM, which results in different fluorescence behaviors. This work presents the clear ESIPT process and fluoride anion‐sensing mechanism of a novel HBPM chemosensor.
Adsorptive filtration of As(III) from drinking water by CuFe2O4 particles embedded in carbon nanotube membranes
Authors: Luan Hongyan , Xu Jingwen , Tan Zhiqiang , Zheng Aihua , Huang Haiou
Published: January 2019

BACKGROUND

For effective removal of arsenite [As(III)] from drinking water, copper ferrite (CuFe2O4) particles were prepared by using a hydrothermal method and incorporated into layered carbon nanotube (CNT) membranes. The prepared composite membranes were used in the filtration of As(III) under conditions representative of drinking water treatment.

RESULTS

The results demonstrated that the CNT membrane successfully immobilized CuFe2O4 particles and prevented their release into the filtered water. Moreover, the composite membrane consistently removed >90% of As(III) under various solution chemical conditions. Besides, the CuFe2O4/CNT membrane was readily regenerated with 0.001 mol L–1 NaOH solution, allowing repeated and sustained use of the membrane for As(III) removal. However, the presence of phosphate or high concentration of natural organic matter (NOM) suppressed arsenic (As) removal, which necessitates consideration of feedwater properties in the application of the composite membrane.

CONCLUSIONS

This study developed a facile method for the integration of CuFe2O4 particles with a membrane filtration technique for efficient As decontamination. The novel composite membranes have a promising potential for As(III) removal from drinking water. © 2019 Society of Chemical Industry
Environmental sustainability assessment of renewables‐based propylene glycol at full industrial scale production
Authors: Nachtergaele Pieter , De Meester Steven , Dewulf Jo
Published: January 2019

BACKGROUND

Glycerol, a by‐product from oleochemical or biodiesel production, can be used to produce renewables‐based propylene glycol (PG). The environmental sustainability of PG was evaluated using life‐cycle assessment. The effect of shifting from petrochemical to renewables‐based PG was assessed by using data from an industrial scale renewables‐based PG production plant. A contribution analysis was performed to identify the hotspots in the production process. The effects of implementing a sustainable sourcing strategy and producing steam/electricity by combined heat and power (CHP) were assessed.

RESULTS

A switch from petrochemical to renewables‐based PG results in a reduction of the climate change impact between 40% and 60% kg CO2 eq. A shift of burden is found to agriculture‐related indicators. For the biodiesel and oleochemical production route, respectively, 73% and 59% of the impact on climate change is related to feedstock production. By implementing two improvements, the emitted CO2 eq. for biodiesel PG could be reduced by 38%.

CONCLUSIONS

Switching from petrochemical to renewables‐based PG has a clear environmental benefit for slowing climate change. However, the shift of burden towards agriculture‐related indicators shows the need to ensure sustainable agricultural practices. Combining both on‐site improvements and a more sustainable supply chain effectively decreases the environmental impact. © 2019 Society of Chemical Industry
Three‐dimensional echocardiography of mitral Barlow's disease with infective endocarditis: Perforations or cleft‐like indentations?
Authors: Pang Bo , Wang Yonghuai , Liu Shuang , Yang Jun , Gu Tianxiang , Ma Chunyan
Published: January 2019

Barlow's disease is a complicated form of degenerative mitral valve (MV) disease. Infective endocarditis (IE) often occurs on the basis of primary heart diseases and may be combined with valve perforations. Cleft‐like indentations (CLIs) were suggested by Ring et al. in 2013. They are located at the inter‐scallop position and involve at least one‐half of the valve. Herein, we report a case of Barlow's disease combined with IE and CLIs, which was confirmed intra‐operatively and by histopathological examination. The CLIs were misdiagnosed by two‐dimensional transthoracic echocardiography as perforations, but rightly interpreted by preoperative three‐dimensional echocardiography. The possibility of CLIs should be considered in the evaluation of mitral regurgitation caused by myxomatous MV diseases.
Clinical, radiological, and genetic characteristics of 16 patients with ACO2 gene defects: Delineation of an emerging neurometabolic syndrome
Authors: Sharkia Rajech , Wierenga Klaas J. , Kessel Amit , Azem Abdussalam , Bertini Enrico , Carrozzo Rosalba , Torraco Alessandra , Goffrini Paola , Ceccatelli Berti Camilla , McCormick M. Eileen , Plecko Barbara , Klein Andrea , Abela Lucia , Hengel Holger , Schöls Ludger , Shalev Stavit , Khayat Morad , Mahajnah Muhammad , Spiegel Ronen
Published: January 2019

Mitochondrial aconitase is the second enzyme in the tricarboxylic acid (TCA) cycle catalyzing the interconversion of citrate into isocitrate and encoded by the nuclear gene ACO2. A homozygous pathogenic variant in the ACO2 gene was initially described in 2012 resulting in a novel disorder termed “infantile cerebellar retinal degeneration” (ICRD, OMIM#614559). Subsequently, additional studies reported patients with pathogenic ACO2 variants, further expanding the genetic and clinical spectrum of this disorder to include milder and later onset manifestations. Here, we report an international multicenter cohort of 16 patients (of whom 7 are newly diagnosed) with biallelic pathogenic variants in ACO2 gene. Most patients present in early infancy with severe truncal hypotonia, truncal ataxia, variable seizures, evolving microcephaly, and ophthalmological abnormalities of which the most dominant are esotropia and optic atrophy with later development of retinal dystrophy. Most patients remain nonambulatory and do no acquire any language, but a subgroup of patients share a more favorable course. Brain magnetic resonance imaging (MRI) is typically normal within the first months but global atrophy gradually develops affecting predominantly the cerebellum. Ten of our patients were homozygous to the previously reported c.336C>G founder mutation while the other six patients were all compound heterozygotes displaying 10 novel mutations of whom 2 were nonsense predicting a deleterious effect on enzyme function. Structural protein modeling predicted significant impairment in aconitase substrate binding in the additional missense mutations. This study provides the most extensive cohort of patients and further delineates the clinical, radiological, biochemical, and molecular features of ACO2 deficiency.
Tissue-type plasminogen activator neutralizes LPS but not protease-activated receptor-mediated inflammatory responses to plasmin
Authors: Zalfa Cristina , Azmoon Pardis , Mantuano Elisabetta , Gonias Steven L
Published: January 2019

Tissue-type plasminogen activator (tPA) activates fibrinolysis and also suppresses innate immune system responses to LPS in bone marrow-derived macrophages (BMDMs) and in vivo in mice. The objective of this study was to assess the activity of tPA as a regulator of macrophage physiology in the presence of plasmin. Enzymatically active and enzymatically inactive (EI) tPA appeared to comprehensively block the response to LPS in BMDMs, including expression of proinflammatory cytokines such as TNF-α and IL-1β and anti-inflammatory cytokines such as IL-10 and IL-1 receptor antagonist. The activity of EI-tPA as an LPS response modifier was conserved in the presence of plasminogen. By contrast, in BMDMs treated with tPA and plasminogen or preactivated plasmin, in the presence or absence of LPS, increased proinflammatory cytokine expression was observed and tPA failed to reverse the response. Plasmin independently activated NF-κB, ERK1/2, c-Jun N-terminal kinase, and p38 mitogen-activated protein kinase in BMDMs, which is characteristic of proinflammatory stimuli. Plasmin-induced cytokine expression was blocked by ε-aminocaproic acid, aprotinin, and inhibitors of the known plasmin substrate, Protease-activated receptor-1 (PAR-1), but not by N-methyl-d-aspartate receptor inhibitor, which blocks the effects of tPA on macrophages. Cytokine expression by BMDMs treated with the PAR-1 agonist, TFLLR, was not inhibited by EI-tPA, possibly explaining why EI-tPA does not inhibit macrophage responses to plasmin and providing evidence for specificity in the ability of tPA to oppose proinflammatory stimuli. Regulation of innate immunity by the fibrinolysis system may reflect the nature of the stimulus and a balance between the potentially opposing activities of tPA and plasmin.
Persistent systemic rotavirus vaccine infection in a child with X‐linked severe combined immunodeficiency
Authors: Yoshikawa Tetsushi , Ihira Masaru , Higashimoto Yuki , Hattori Fumihiko , Miura Hiroki , Sugata Ken , Komoto Satoshi , Taniguchi Koki , Iguchi Akihiro , Yamada Masafumi , Ariga Tadashi
Published: January 2019

Objective

The main aims of the present study were to elucidate the systemic group A rotavirus (RVA) infection and to clarify the genetic changes of persistent virus in the X‐linked severe combined immunodeficiency (SCID) patient.

Methods

RotaTeq vaccine (RV5) genotype‐specific real‐time reverse transcription polymerase chain reaction was used to monitor viral RNA load in serially collected serum and stool samples. Next‐generation sequence analysis was used to determine the genotype of the virus by sequencing 11 gene segments. Polyacrylamide gel electrophoresis (PAGE) analysis was used to identify rearrangement of viral genes. The gene rearrangement was examined in NSP5 gene by using Sanger sequence.

Results

A 7‐month‐old boy demonstrated chronic diarrhea following the third administration of RV5 and failure to thrive. He was diagnosed with X‐linked SCID and successfully underwent cord blood transplantation. High copy numbers of RV5 genotype G1 RNA were detected in serially collected stool and serum samples and the kinetics of viral RNA loads were correlated with the degree of clinical disease. Next‐generation sequence analysis revealed genetic reassortment at least between the strains WI79‐9/G1P7[5] and WI79‐4/G6P1A[8] in the VP7 gene and the VP4 gene among the vaccine‐derived rotavirus strains. In addition, PAGE analysis suggested genetic rearrangements in several genes, and it was confirmed in the NSP5 gene by sequence analysis.

Conclusions

The kinetics of RVA RNA load in serum and stool samples was consistent with the clinical course of the patient. Among five genotypes of RV5 vaccine, G1 genotype replicated well in this patient. Reassortment and rearrangements were demonstrated in persistently infected G1 genotype of RV5.
Periodontal disease may induce liver fibrosis in an experimental study on Wistar rats
Authors: Mester Alexandru , Ciobanu Lidia , Taulescu Marian , Apostu Dragos , Lucaciu Ondine , Filip Gabriela Adriana , Feldrihan Vasile , Licarete Emilia , Ilea Aranka , Piciu Andra , Oltean‐Dan Daniel , Scurtu Iuliu , Berce Cristian , Campian Radu Septimiu
Published: January 2019

Background

The aim was to assess the effects of periodontal disease in promoting liver fibrosis in a rat model of ligature‐induced periodontitis.

Methods

Twenty‐four Wistar rats were divided into four groups: control (CTRL), experimental periodontitis group at day 7 (PER7), at day 14 (PER14), at day 21 (PER21). Experimental periodontitis was induced by the placement of a silk ligature around mandibular incisors. The following parameters were assessed: gingival index, tooth mobility; liver status, and portal vein caliber by ultrasound examination; bone retraction, bone mineral density (BMD), bone volume/tissue volume (BV/TV) by micro‐CT analysis; aspartate aminotransferase (ASAT) and alanine aminotransferase (ALAT); oxidative stress (malondialdehyde [MDA], reduced glutathione/oxidative glutathione ratio [GSH/GSSG]), and matrix metalloproteinase‐8 (MMP‐8) levels; and histopathological evaluation of periodontal and liver tissues.

Results

Periodontal parameters showed the development of periodontitis in experimental groups. Micro‐CT results indicates an increase of bone retraction and BMD values and a decrease of BV/TV value in PER groups. Liver fibrosis could not be diagnosed with ultrasound examination in any of the groups. Elevated levels of ASAT and ALAT in PER groups compared with CTRL group were found. MDA have indicated elevated levels and a decrease of GSH/GSSG ratio in PER group compared with the CTRL group. Levels of MMP‐8 have indicated high values in PER21 compared with the other groups. Histological analysis of the periodontal and liver tissues sustains the link between periodontal and hepatic injury.

Conclusion

This study demonstrates a positive correlation between periodontal lesions and liver disease. Periodontitis may be an independent risk factor for liver fibrosis.
Posttraumatic Stress Symptoms and Disorders in Parents of Children and Adolescents With Chronic Physical Illnesses: A Meta‐Analysis
Authors: Pinquart Martin
Published: January 2019

The present meta‐analysis analyzed whether parents of young people with pediatric chronic physical illnesses experience higher levels of posttraumatic stress symptoms (PTSS) and higher rates of posttraumatic stress disorder (PTSD) than other adults and searched for correlates of PTSS in these parents. Based on a systematic search in electronic databases, 184 studies were included in the meta‐analysis. On average, 18.9% of the parents fulfilled the criteria for PTSD, and PTSS were more common among parents of young people with pediatric chronic physical illnesses than in other adults, with Hedges' g showing a 0.85 increase in standard deviation units. Parental PTSS were most prevalent among parents of children with epilepsy, g = 1.25, and diabetes, g = 1.16, and were positively associated with being the mother, r = .19; illness severity, r = .18; treatment duration/intensity, r = .21; and PTSS of the child, r = .34. In contrast, longer illness duration, r = −.19; longer time since active treatment, r = −.10; and better social resources, rs = −.17 to −.07, were associated with lower parental PTSS. The findings indicate that parents who have faced traumatic events in the context of their child's chronic illnesses should be screened for PTSS and PTSD and receive psychological interventions when needed.
A Cross‐Cultural Comparison of ICD‐11 Complex Posttraumatic Stress Disorder Symptom Networks in Austria, the United Kingdom, and Lithuania
Authors: Knefel Matthias , Lueger‐Schuster Brigitte , Bisson Jonathan , Karatzias Thanos , Kazlauskas Evaldas , Roberts Neil P.
Published: January 2019

The 11th revision of the World Health Organization's International Classification of Diseases (ICD‐11) includes a new disorder, complex posttraumatic stress disorder (CPTSD). The network approach to psychopathology enables investigation of the structure of disorders at the symptom level, which allows for analysis of direct symptom interactions. The network structure of ICD‐11 CPTSD has not yet been studied, and it remains unclear whether similar networks replicate across different samples. We investigated the network models of four different trauma samples that included a total of 879 participants (M age = 47.17 years, SD = 11.92; 59.04% women) drawn from Austria, Lithuania, and Scotland and Wales in the United Kingdom. The International Trauma Questionnaire was used to assess symptoms of ICD‐11 CPTSD in all samples. The prevalence of PTSD and CPTSD ranged from 23.7% to 37.3% and from 9.3% to 53.1%, respectively. Regularized partial correlation networks were estimated and the resulting networks compared. Despite several differences in the symptom presentation and cultural background, the networks across the four samples were considerably similar, with high correlations between symptom profiles (ρs = .48–.87), network structures (ρs = .69–.75), and centrality estimates (ρs = .59–.82). These results support the replicability of CPTSD network models across different samples and provide further evidence about the robust structure of CPTSD. The most central symptom in all four sample‐specific networks and the overall network was “feelings of worthlessness.” Implications of the network approach in research and practice are discussed.
Effect of partial immunity on transmission dynamics of dengue disease with optimal control
Authors: Jan Rashid , Xiao Yanni
Published: January 2019

Dengue fever is one of the most dangerous vector‐borne diseases in the world in terms of death and economic cost. Hence, the modeling of dengue fever is of great significance to understand the dynamics of dengue. In this paper, we extend dengue disease transmission models by including transmit vaccinated class, in which a portion of recovered individual loses immunity and moves to the susceptibles with limited immunity and hence a less transmission probability. We obtain the threshold dynamics governed by the basic reproduction number R0; it is shown that the disease‐free equilibrium is locally asymptotically stable if R0 ≤ 1, and the system is uniformly persistence if R0 > 1. We do sensitivity analysis in order to identify the key factors that greatly affect the dengue infection, and the partial rank correlation coefficient (PRCC) values for R0 shows that the bitting rate is the most effective in lowering dengue new infections, and moreover, control of mosquito size plays an essential role in reducing equilibrium level of dengue infection. Hence, the public are highly suggested to control population size of mosquitoes and to use mosquito nets. By formulating the control objective, associated with the low infection and costs, we propose an optimal control question. By the application of optimal control theory, we analyze the existence of optimal control and obtain necessary conditions for optimal controls. Numerical simulations are carried out to show the effectiveness of control strategies; these simulations recommended that control measures such as protection from mosquito bites and mosquito eradication strategies effectively control and eradicate the dengue infections during the whole epidemic.
Asymptotic profile of solutions for strongly damped Klein‐Gordon equations
Authors: D'Abbicco Marcello , Ikehata Ryo
Published: January 2019

We consider the Cauchy problem in Rn for strongly damped Klein‐Gordon equations. We derive asymptotic profiles of solutions with weighted L1,1(Rn) initial data by a simple method introduced by the second author. Furthermore, from the obtained asymptotic profile, we get the optimal decay order of the L2‐norm of solutions. The obtained results show that the wave effect will be relatively weak because of the mass term, especially in the low‐dimensional case (n = 1,2) as compared with the strongly damped wave equations without mass term (m = 0), so the most interesting topic in this paper is the n = 1,2 cases to compare the difference.
Weakly coupled directional coupler with simultaneous wide bandwidth and high directivity
Authors: Hammad Akhtar M. , Ayaz Zakir M. , Cheema Hammad M.
Published: January 2019

Weakly coupled directional couplers are known to have poor directivities and narrow bandwidths. In order to improve both parameters simultaneously, this article demonstrates for the first time, that combination of shunt reactive loading and external impedance matching, results in high directivity, and wideband performance. The proposed directional coupler, fabricated on a Rogers 6035HTC substrate, demonstrates directivity greater than 20 dB over a fractional bandwidth of 35%, which is the highest reported for microstrip based design having weak coupling factor of 30 dB.
Experimental study of a printed ultra‐wideband modified circular monopole antenna
Authors: Kundu Surajit
Published: January 2019

A compact (35 × 30 × 0.8 mm3) co‐planar waveguide (CPW)‐fed circular monopole ultra‐wideband (UWB) antenna with improved impedance band is proposed in this article. A frequency band from 3.1 to more than 20 GHz is achieved by bending the upper edges of co‐planar ground plane. Antenna parameters are studied by simulation and then validated by experimental measurement. The proposed antenna provides monopole‐like radiation pattern with high radiation efficiency of more than 80% and flat gain variation between 2 and 5 dBi. The antenna also exhibits consistency in group delay variation and linearity in the transfer function response. A good agreement is found in between simulated and measured results of the proposed design. The proposed antenna performance is compared with previously reported similar antennas.
Dual‐band branch‐line coupler with shorted stepped‐impedance stubs arranged in a Π‐shaped topology
Authors: Seko Murilo Hiroaki , Correra Fatima Salete
Published: January 2019

This article presents a transmission‐line‐based 3‐dB dual‐band branch‐line coupler. The coupler is easily realizable for ratios between the upper and lower operating frequencies ranging from 1.270 to 2.628. This means that it can be designed for two operation frequencies that are closer to each other in comparison with existing simple circuit topologies based on transmission lines, when considering a compact design. The complete set of equations for all possible responses of this dual‐band 90° hybrid coupler is derived. To evaluate its practical feasibility, the proposed circuit is analyzed with respect to the characteristic impedances of its transmission lines. A step‐by‐step procedure is presented to help the circuit designer deal with the use of the equations and all their degrees of freedom. For experimental validation, a microstrip dual‐band branch‐line coupler has been designed for operation at 3.835 and 5.285 GHz. A good agreement is observed between simulated and measured results.
Loss of whole chromosome X predicts prognosis of neuroblastoma patients with numerical genomic profile
Authors: Parodi Stefano , Pistorio Angela , Erminio Giovanni , Ognibene Marzia , Morini Martina , Garaventa Alberto , Gigliotti Anna Rita , Haupt Riccardo , Frassoni Francesco , Pezzolo Annalisa
Published: January 2019

Background

Neuroblastoma (NB), a pediatric tumor of the sympathetic nervous system, is characterized by very frequent chromosomal aberrations at the onset of the disease. Identification of further risk factors for relapse, which could lead to increased survival and potentially reduced late effects among survivors, is still urgently needed. Segmental chromosome aberrations (SCA) are associated with poor prognosis, whereas numerical whole‐chromosome aberrations (NCA) are found in patients with a good prognosis; however, a small percentage of the latter patients (10%–15%) subsequently relapse and/or die of disease.

Procedure

DNA copy‐number data from 174 NB patients with an NCA genomic profile were analyzed. Association between NCA and event‐free survival (EFS) was investigated by the Kaplan–Meier estimator and prognostic decision tree (DT).

Results

DT identified 65 patients with normal chromosome X and an excellent five‐year EFS (100%) independently from the stage at diagnosis. The association between poor EFS and whole chromosome X alterations was confirmed after stratification into two groups of different expected prognosis and by internal validation via bootstrap analysis. Furthermore, the association was also observed in an independent cohort of NB patients extracted from the data set of the National Cancer Institute TARGET Project for Neuroblastoma, but sample size was small (n = 75) and statistical significance was not achieved.

Conclusions

Loss of whole chromosome X may represent a new prognostic marker for NB patients with an NCA genomic profile. If confirmed by further studies, this finding could indicate that such patients should be reclassified as intermediate risk and treated accordingly.
How Far Can You Measure?
Authors: Zinssmeister Andreas
Published: January 2019

If you recently bought a thermal camera, you might be wondering how far you can measure with it. Or maybe you're interested in purchasing one, but you aren't sure which one will both accurately measure your target and fit within your budget. The answer to “how far can you measure?” depends on factors such as resolution, instantaneous field of view (IFOV), lenses, the size of the object, and more.