bluuebunny/crossref_metadata_2025 huggingface dataset:
Neutrophil activation and NETosis are the major drivers of thrombosis in heparin-induced thrombocytopenia
Authors: Perdomo José , Leung Halina H. L. , Ahmadi Zohra , Yan Feng , Chong James J. H. , Passam Freda H. , Chong Beng H.
Published: March 2019

Heparin-induced thrombocytopenia/thrombosis (HIT) is a serious immune reaction to heparins, characterized by thrombocytopenia and often severe thrombosis with high morbidity and mortality. HIT is mediated by IgG antibodies against heparin/platelet factor 4 antigenic complexes. These complexes are thought to activate platelets leading to thrombocytopenia and thrombosis. Here we show that HIT immune complexes induce NETosis via interaction with FcγRIIa on neutrophils and through neutrophil-platelet association. HIT immune complexes induce formation of thrombi containing neutrophils, extracellular DNA, citrullinated histone H3 and platelets in a microfluidics system and in vivo, while neutrophil depletion abolishes thrombus formation. Absence of PAD4 or PAD4 inhibition with GSK484 abrogates thrombus formation but not thrombocytopenia, suggesting they are induced by separate mechanisms. NETs markers and neutrophils undergoing NETosis are present in HIT patients. Our findings demonstrating the involvement of NETosis in thrombosis will modify the current concept of HIT pathogenesis and may lead to new therapeutic strategies.
Female genitalia can evolve more rapidly and divergently than male genitalia
Authors: Simmons Leigh W. , Fitzpatrick John L.
Published: March 2019

Male genitalia exhibit patterns of divergent evolution driven by sexual selection. In contrast, for many taxonomic groups, female genitalia are relatively uniform and their patterns of evolution remain largely unexplored. Here we quantify variation in the shape of female genitalia across onthophagine dung beetles, and use new comparative methods to contrast their rates of divergence with those of male genitalia. As expected, male genital shape has diverged more rapidly than a naturally selected trait, the foretibia. Remarkably, female genital shape has diverged nearly three times as fast as male genital shape. Our results dispel the notion that female genitalia do not show the same patterns of divergent evolution as male genitalia, and suggest that female genitalia are under sexual selection through their role in female choice.
AKT1low quiescent cancer cells in ductal carcinoma in situ of the breast
Authors: Kabraji Sheheryar , Sole Xaiver , Huang Ying , Bango Clyde , Sgroi Dennis , Loda Massimo , Ramaswamy Sridhar
Published: March 2019

Ductal carcinoma in situ (DCIS) of the breast precedes the development of invasive breast cancer and reflects the genomic changes and protein expression profile of invasive disease. AKT1low cancer cells (QCC) are a rare, drug-tolerant, epigenetically plastic, and quiescent cancer cell subset that we previously identified at a frequency of 0.5–1% in primary breast tumors using the marker profile: AKTlow/H3K9me2low/HES1high. Here we used quantitative immunofluorescence microscopy with computational image analysis to show that AKT1low QCCs are present in DCIS from patients with and without co-existing invasive breast cancer. These data suggest that a drug-resistant, quiescent cancer cell state is present in premalignant breast lesions prior to the development of invasive disease. These findings warrant further study of whether AKT1low QCCs contribute to invasive tumor development and recurrence, similar to their role in more advanced malignancy.
Transgenic substitution with Greater Amberjack Seriola dumerili fish insulin 2 in NOD mice reduces beta cell immunogenicity
Authors: Foo Kylie S. , Skowronski Alicja A. , Baum Danielle , Firdessa-Fite Rebuma , Thams Sebastian , Shang Linshan , Creusot Rémi J. , LeDuc Charles A. , Egli Dieter , Leibel Rudolph L.
Published: March 2019

Type I diabetes (T1D) is caused by immune-mediated destruction of pancreatic beta cells. This process is triggered, in part, by specific (aa 9–23) epitopes of the insulin Β chain. Previously, fish insulins were used clinically in patients allergic to bovine or porcine insulin. Fish and human insulin differ by two amino acids in the critical immunogenic region (aa 9–23) of the B chain. We hypothesized that β cells synthesizing fish insulin would be less immunogenic in a mouse model of T1D. Transgenic NOD mice in which Greater Amberjack fish (Seriola dumerili) insulin was substituted for the insulin 2 gene were generated (mouse Ins1−/− mouse Ins2−/− fish Ins2+/+). In these mice, pancreatic islets remained free of autoimmune attack. To determine whether such reduction in immunogenicity is sufficient to protect β cells from autoimmunity upon transplantation, we transplanted fish Ins2 transgenic (expressing solely Seriola dumerili Ins2), NOD, or B16:A-dKO islets under the kidney capsules of 5 weeks old female NOD wildtype mice. The B:Y16A Β chain substitution has been previously shown to be protective of T1D in NOD mice. NOD mice receiving Seriola dumerili transgenic islet transplants showed a significant (p = 0.004) prolongation of their euglycemic period (by 6 weeks; up to 18 weeks of age) compared to un-manipulated female NOD (diabetes onset at 12 weeks of age) and those receiving B16:A-dKO islet transplants (diabetes onset at 12 weeks of age). These data support the concept that specific amino acid sequence modifications can reduce insulin immunogenicity. Additionally, our study shows that alteration of a single epitope is not sufficient to halt an ongoing autoimmune response. Which, and how many, T cell epitopes are required and suffice to perpetuate autoimmunity is currently unknown. Such studies may be useful to achieve host tolerance to β cells by inactivating key immunogenic epitopes of stem cell-derived β cells intended for transplantation.
Gut microbiota profile in children affected by atopic dermatitis and evaluation of intestinal persistence of a probiotic mixture
Authors: Reddel Sofia , Del Chierico Federica , Quagliariello Andrea , Giancristoforo Simona , Vernocchi Pamela , Russo Alessandra , Fiocchi Alessandro , Rossi Paolo , Putignani Lorenza , El Hachem May
Published: March 2019

Atopic dermatitis (AD) has been hypothesised to be associated with gut microbiota (GM) composition. We performed a comparative study of the GM profile of 19 AD children and 18 healthy individuals aimed at identifying bacterial biomarkers associated with the disease. The effect of probiotic intake (Bifidobacterium breve plus Lactobacillus salivarius) on the modulation of GM and the probiotic persistence in the GM were also evaluated. Faecal samples were analysed by real-time PCR and 16S rRNA targeted metagenomics. Although the probiotics, chosen for this study, did not shape the entire GM profile, we observed the ability of these species to pass through the gastrointestinal tract and to persist (only B. breve) in the GM. Moreover, the GM of patients compared to CTRLs showed a dysbiotic status characterised by an increase of Faecalibacterium, Oscillospira, Bacteroides, Parabacteroides and Sutterella and a reduction of short-chain fatty acid (SCFA)-producing bacteria (i.e., Bifidobacterium, Blautia, Coprococcus, Eubacterium and Propionibacterium). Taken togheter these results show an alteration in AD microbiota composition with the depletion or absence of some species, opening the way to future probiotic intervention studies.
Biological Cardiac Tissue Effects of High-Energy Heavy Ions – Investigation for Myocardial Ablation
Authors: Rapp Felicitas , Simoniello Palma , Wiedemann Julia , Bahrami Karola , Grünebaum Valeria , Ktitareva Svetlana , Durante Marco , Lugenbiel P. , Thomas D. , Lehmann H. Immo , Packer Douglas L. , Graeff Christian , Fournier Claudia
Published: March 2019

Noninvasive X-ray stereotactic treatment is considered a promising alternative to catheter ablation in patients affected by severe heart arrhythmia. High-energy heavy ions can deliver high radiation doses in small targets with reduced damage to the normal tissue compared to conventional X-rays. For this reason, charged particle therapy, widely used in oncology, can be a powerful tool for radiosurgery in cardiac diseases. We have recently performed a feasibility study in a swine model using high doses of high-energy C-ions to target specific cardiac structures. Interruption of cardiac conduction was observed in some animals. Here we report the biological effects measured in the pig heart tissue of the same animals six months after the treatment. Immunohistological analysis of the target tissue showed (1.) long-lasting vascular damage, i.e. persistent hemorrhage, loss of microvessels, and occurrence of siderophages, (2.) fibrosis and (3.) loss of polarity of targeted cardiomyocytes and wavy fibers with vacuolization. We conclude that the observed physiological changes in heart function are produced by radiation-induced fibrosis and cardiomyocyte functional inactivation. No effects were observed in the normal tissue traversed by the particle beam, suggesting that charged particles have the potential to produce ablation of specific heart targets with minimal side effects.
Changes in the Urinary Proteome in a Patient-Derived Xenograft (PDX) Nude Mouse Model of Colorectal Tumor
Authors: Liu Yongtao , Wang Youzhu , Cao Zhixiang , Gao Youhe
Published: March 2019

In this report, the urinary proteome from a patient-derived xenograft (PDX) model was examined at the peptide level to study the origins of urinary proteins in tumor-bearing nude mice. Urine was collected from PDX mice before and after colorectal tumor implantation. A total of 4,318 unique peptides were identified, and 78 unambiguous human-origin peptides were discerned in the PDX model urine. Unlike the differential urinary protein composition of tumor-bearing immunocompetent rat models, the differential urinary proteins in the PDX model did not include host immune-response proteins. This study demonstrates that tumor-secreted proteins can be observed in the urine proteome of the PDX model. However, immune-response proteins, which are very early candidate tumor biomarkers, are not present in the urine of PDX model mice; this absence is due to immune deficiency. Therefore, immunodeficient animals may not be suitable models for searching for early immunity-associated tumor biomarkers in the urine.
A complex of novel protease inhibitor, ovostatin homolog, with its cognate proteases in immature mice uterine luminal fluid
Authors: Huang Hsien-Lu , Li Szu-Chin , Wu Jin-Fong
Published: March 2019

A predominant gelatinolytic enzyme with approximately 26 kDa was observed in gelatin zymogram of immature mice uterine luminal fluid (ULF). Size exclusion analysis revealed that the native size of this enzyme was close to that of human α2-macroglobulin (α2-MG), a 725 kDa protein. This large protease was isolated by a series of chromatographic steps on the Sephacryl S-400 and DEAE-Sepharose columns. The results from gelatin zymography and SDS-PAGE analysis supported that this large protease consists of gelatinolytic enzyme and a 360 kDa protein. Through tandem mass spectrometry analysis followed by MASCOT database search, the 360 kDa protein was identified as ovostatin homolog (accession: NP_001001179.2) assigned as a homolog of chicken ovostatin, a protease inhibitor. The co-fractionation analysis by gel filtration and mouse ovostatin homolog (mOH) co-immunoprecipitation experiments demonstrated that the mOH formed a complex with three gelatinolytic enzymes in immature mice ULF. Substrate zymography analysis revealed that the mOH-associated gelatinolytic enzymes were suitable to digest type I collagen rather than type IV collagen. In addition, the refolded mOH-associated 26 kDa gelatinolytic enzyme displayed the type I collagen-digesting activity in the assay, but the other two enzymes did not have this function. RT-PCR analysis showed that mOH gene was abundantly expressed in brain, spinal cord, lung, uterus, and in 17-day embryo. Taken together, our data suggest that mOH/cognate protease system may play a potential role in regulation of tissue remodeling and fetal development.
Genome-wide analysis of long non-coding RNAs unveils the regulatory roles in the heat tolerance of Chinese cabbage (Brassica rapa ssp.chinensis)
Authors: Wang Aihua , Hu Jihong , Gao Changbin , Chen Guanglong , Wang Bingcai , Lin Chufa , Song Liping , Ding Yi , Zhou Guolin
Published: March 2019

Long non-coding RNAs (lncRNAs) mediate important epigenetic regulation in various biological processes related to the stress response in plants. However, the systematic analysis of the lncRNAs expressed in Brassica rapa under heat stress has been elusive. In this study, we performed a genome-wide analysis of the lncRNA expression profiles in non-heading Chinese cabbage leaves using strand-specific RNA-sequencing. A total of 4594 putative lncRNAs were identified with a comprehensive landscape of dynamic lncRNA expression networks under heat stress. Co-expression networks of the interactions among the differentially expressed lncRNAs, mRNAs and microRNAs revealed that several phytohormones were associated with heat tolerance, including salicylic acid (SA) and brassinosteroid (BR) pathways. Of particular importance is the discovery of 25 lncRNAs that were highly co-expressed with 10 heat responsive genes. Thirty-nine lncRNAs were predicted as endogenous target mimics (eTMs) for 35 miRNAs, and five of them were validated to be involved in the heat tolerance of Chinese cabbage. Heat responsive lncRNA (TCONS_00048391) is an eTM for bra-miR164a, that could be a sponge for miRNA binding and may be a competing endogenous RNA (ceRNA) for the target gene NAC1 (Bra030820), affecting the expression of bra-miR164a in Chinese cabbage. Thus, these findings provide new insights into the functions of lncRNAs in heat tolerance and highlight a set of candidate lncRNAs for further studies in non-heading Chinese cabbage.
Single step synthesis of highly conductive room-temperature stable cation-substituted mayenite electride target and thin film
Authors: Khan Karim , Tareen Ayesha khan , Khan Usman , Nairan Adeela , Elshahat Sayed , Muhammad Naseer , Saeed Muhammad , Yadav Ashish , Bibbò Luigi , Ouyang Zhengbiao
Published: March 2019

Novel approaches to synthesize efficient inorganic electride [Ca24Al28O64]4+(e−)4 (thereafter, C12A7:e−) at ambient pressure under nitrogen atmosphere, are actively sought out to reduce the cost of massive formation of nanosized powder as well as compact large size target production. It led to a new era in low cost industrial applications of this abundant material as Transparent Conducting Oxides (TCOs) and as a catalyst. Therefore, the present study about C12A7:e− electride is directed towards challenges of cation doping in C12A7:e− to enhance the conductivity and form target to deposit thin film. Our investigation for cation doping on structural and electrical properties of Sn- and Si-doped C12A7:e− (Si-C12A7:e, and Sn-C12A7:e−) reduced graphene oxide (rGO) composite shows the maximum achieved conductivities of 5.79 S·cm−1 and 1.75 S·cm−1 respectively. On the other hand when both samples melted, then rGO free Sn-C12A7:e− and Si-C12A7:e− were obtained, with conductivities ~280 S.cm−1 and 300 S·cm−1, respectively. Iodometry based measured electron concentration of rGO free Sn-C12A7:e− and Si-C12A7:e−, 3 inch electride targets were ~2.22 × 1021 cm−3, with relative 97 ± 0.5% density, and ~2.23 × 1021 cm−3 with relative 99 ± 0.5% density, respectively. Theoretical conductivity was already reported excluding any associated experimental support. Hence the above results manifested feasibility of this sol-gel method for different elements doping to further boost up the electrical properties.
Convergence of TGFβ and BMP signaling in regulating human bone marrow stromal cell differentiation
Authors: Elsafadi Mona , Shinwari Tasneem , Al-Malki Sami , Manikandan Muthurangan , Mahmood Amer , Aldahmash Abdullah , Alfayez Musaad , Kassem Moustapha , Alajez Nehad M.
Published: March 2019

Targeting regulatory signaling pathways that control human bone marrow stromal (skeletal or mesenchymal) stem cell (hBMSC) differentiation and lineage fate determination is gaining momentum in the regenerative medicine field. Therefore, to identify the central regulatory mechanism of osteoblast differentiation of hBMSCs, the molecular phenotypes of two clonal hBMSC lines exhibiting oppositein vivophenotypes, namely, bone forming (hBMSC+bone) and non-bone forming (hBMSC−Bone) cells, were studied. Global transcriptome analysis revealed significant downregulation of several TGFβ responsive genes, namely, TAGLN, TMP1, ACTA2, TGFβ2, SMAD6, SMAD9, BMP2, and BMP4 in hBMSC−Bonecells and upregulation on SERPINB2 and NOG. Transcriptomic data was associated with marked reduction in SMAD2 protein phosphorylation, which thereby implies the inactivation of TGFβ and BMP signaling in those cells. Concordantly, activation of TGFβ signaling in hBMSC−Bonecells using either recombinant TGFβ1 protein or knockdown ofSERPINB2 TGFβ-responsive gene partially restored their osteoblastic differentiation potential. Similarly, the activation of BMP signaling using exogenous BMP4 orviasiRNA-mediated knockdown of NOG partially restored the differentiation phenotype of hBMSC−Bonecells. Concordantly, recombinant NOG impairedex vivoosteoblastic differentiation of hBMSC+Bonecells, which was associated with SERBINB2 upregulation. Our data suggests the existence of reciprocal relationship between TGFB and BMP signaling that regulates hBMSC lineage commitment and differentiation, whilst provide a plausible strategy for generating osteoblastic committed cells from hBMSCs for clinical applications.
A genome-wide association study on photic sneeze reflex in the Chinese population
Authors: Wang Mengqiao , Sun Xinghan , Shi Yang , Song Xiaojun , Mi Hao
Published: March 2019

Photic sneeze reflex (PSR) is an interesting but yet mysterious phenotype featured by individuals’ response of sneezing in exposure to bright light. To uncover the underlying genetic markers (single nucleotide polymorphisms, SNPs), a genome-wide association study (GWAS) was conducted exclusively in a Chinese population of 3417 individuals (PSR prevalence at 25.6%), and reproducibly identified both a replicative rs10427255 on 2q22.3 and a novel locus of rs1032507 on 3p12.1 in various effect models (additive, as well as dominant and recessive). Minor alleles respectively contributed to increased or reduced risk for PSR with odds ratio (95% confidence interval) at 1.68 ([1.50, 1.88]) for rs10427255 and 0.65 ([0.58, 0.72]) for rs1032507. The two independent SNPs were intergenic, and collectively enhanced PSR classification by lifting the area-under-curve value in ROC curve to 0.657. Together with previous GWAS in other populations, the result substantiated the polygenic and non-ethnicity-specific nature behind the PSR phenotype.
A chimeric, multivalent assembly of galectin-1 and galectin-3 with enhanced extracellular activity
Authors: Fettis Margaret M. , Farhadi Shaheen A. , Hudalla Gregory A.
Published: March 2019

Assembly of a fusion of galectin-1 and galectin-3 with higher carbohydrate binding affinity and a significantly lower effective dose than galectin-1.
Enzymatic synthesis and polymerisation of β-mannosyl acrylates produced from renewable hemicellulosic glycans
Authors: Rosengren Anna , Butler Samuel J. , Arcos-Hernandez Monica , Bergquist Karl-Erik , Jannasch Patric , Stålbrand Henrik
Published: March 2019

A biocatalytic route for the synthesis of novel glycosyl acrylate monomers produced from hemicellulosic glycans.
Synthesis of new mixed-bistriarylmethanes and novel 3,4-dihydropyrimidin-2(1H)one derivatives
Authors: Mohammadiannejad Kazem , Ranjbar-Karimi Reza , Haghighat Farzaneh
Published: March 2019

Formylated-triarylmethanes were realized as ideal precursors for the design and synthesis of mixed-bistriarylmethanes and 3,4-dihydropyrimidin-2(1H)one-triarylmethane hybrid derivatives.
Linear control of the oxidation level on graphene oxide sheets using the cyclic atomic layer reduction technique
Authors: Mallick Bikash Chandra , Hsieh Chien-Te , Yin Ken-Ming , Li Jianlin , Ashraf Gandomi Yasser
Published: March 2019

Precise control of the oxidation level on graphene oxide (GO) sheets is still a big challenge.
Automated identification and quantification of microfibres and microplastics
Authors: Primpke S. , A. Dias P. , Gerdts G.
Published: March 2019

Microplastics (MP) and microfibers (MF), were simultaneously identified and quantified by data analysis of FTIR imaging measurements.
Chiral separation of d/l-arginine with whole cells through an engineered FhuA nanochannel
Authors: Anand Deepak , Dhoke Gaurao V. , Gehrmann Julia , Garakani Tayebeh M. , Davari Mehdi D. , Bocola Marco , Zhu Leilei , Schwaneberg Ulrich
Published: March 2019

Development of a novel whole cell system for chiral separation of arginine enantiomers through an engineered outer membrane channel protein ferric hydroxamate uptake protein A (FhuA).
Dehydrocurvularin is a potent antineoplastic agent irreversibly blocking ATP-citrate lyase: evidence from chemoproteomics
Authors: Deng Zhangshuang , Wong Nai-Kei , Guo Zhiyong , Zou Kun , Xiao Youli , Zhou Yiqing
Published: March 2019

Dehydrocurvularin irreversibly inhibits human ATP-citrate lyase.
Effect of proton uptake on the structure of energy levels in the band-gap of Sr-doped LaScO3: diffuse reflectance spectroscopy and coherent potential approximation calculations
Authors: Vlasov Maxim I. , Zainullina Veronika M. , Korotin Michael A. , Farlenkov Andrei S. , Ananyev Maxim V.
Published: March 2019

The obtained results explain features of LaScO3 optical properties and the effect of acceptor doping and H2 and H2O uptake on them.
An efficient, bifunctional catalyst for lithium–oxygen batteries obtained through tuning the exterior Co2+/Co3+ ratio of CoOx on N-doped carbon nanofibers
Authors: Zhang Xiuling , Fan Wei , Zhao Shuyu , Cao Ran , Li Congju
Published: March 2019

CoOx NPs@N-doped carbon nanofibers were obtained by an electrospinning technique and served as an excellent catalyst for Li–O2 cells. The enhanced electrochemical performance can be ascribed to the rich Co2+ toward the ORR and OER on the surface of CoOx.
Correction: Lipid composition modulates the intestine digestion rate and serum lipid status of different edible oils: a combination of in vitro and in vivo studies
Authors: Ye Zhan , Cao Chen , Li Ruizhi , Cao Peirang , Li Qiu , Liu Yuanfa
Published: March 2019

Correction for ‘Lipid composition modulates the intestine digestion rate and serum lipid status of different edible oils: a combination of in vitro and in vivo studies’ by Zhan Ye et al., Food Funct., 2019, DOI: 10.1039/c8fo01290c.
A facile phase transformation strategy for fabrication of novel Z-scheme ternary heterojunctions with efficient photocatalytic properties
Authors: Yu Changlin , Chen Fanyun , Zeng Debin , Xie Yu , Zhou Wanqin , Liu Zhen , Wei Longfu , Yang Kai , Li Dehao
Published: March 2019

With increasing pollution of water resources and demand for hydrogen energy, photocatalysis, as a “green chemistry” technology, has attracted great attention.
A modular and concise approach to MIDA acylboronates via chemoselective oxidation of unsymmetrical geminal diborylalkanes: unlocking access to a novel class of acylborons
Authors: Lin Shengjia , Wang Lucia , Aminoleslami Negin , Lao Yanting , Yagel Chelsea , Sharma Abhishek
Published: March 2019

Novel and mild synthesis of MIDA acylboronates including a novel class of acylborons and first chemoselective oxidation of geminal diborylalkanes.
Carbonyl-based polyimide and polyquinoneimide for potassium-ion batteries
Authors: Tian Bingbing , Zheng Ji , Zhao Chenxi , Liu Cuibo , Su Chenliang , Tang Wei , Li Xing , Ning Guo-Hong
Published: March 2019

A 2D conjugated polymer (PI-CMP) can be used as an organic cathode for KIBs and exhibits excellent cycling stability and rate performance.
Promoting electrocatalytic activity of cobalt cyclotetraphosphate in full water splitting by titanium-oxide-accelerated surface reconstruction
Authors: Lv Cuncai , Xu Shichen , Yang Qianpeng , Huang Zhipeng , Zhang Chi
Published: March 2019

An inactive material (TiO2) promotes remarkably another inactive material (Co2P4O12) to be a highly efficient electrocatalyst in hydrogen evolution reaction in alkaline solution.
Development of an injectable thiolated icariin functionalized collagen/hyaluronic hydrogel to promote cartilage formation in vitro and in vivo
Authors: Liu Yanbo , Yang Jirong , Luo Zhaocong , Li Dongxiao , Lu Jian , Wang Qiguang , Xiao Yumei , Zhang Xingdong
Published: March 2019

We have developed an injectable thiolated icariin functionalized hyaluronic acid/collagen hydrogel under physiological conditions to facilitate cell proliferation, maintain chondrocyte phenotype and promote the secretion of the cartilage extracellular matrix.
Viologen-based electrochromic materials and devices
Authors: Madasamy Kanagaraj , Velayutham David , Suryanarayanan Vembu , Kathiresan Murugavel , Ho Kuo-Chuan
Published: March 2019

This review describes recent developments relating to the synthesis of viologen-based electrochromes with co-redox species and their ECD performance.
Homoleptic platinum(ii) complexes with pyridyltriazole ligands: excimer-forming phosphorescent emitters for solution-processed OLEDs
Authors: Walden Melissa T. , Pander Piotr , Yufit Dmitry S. , Dias Fernando B. , Williams J. A. Gareth
Published: March 2019

Two new homoleptic platinum(ii) complexes are reported that feature aryl-appended 5-(2-pyridyl)-1,2,4-triazole chelates acting as N^N− ligating ions, PtL12 and PtL22. They have been used to prepare high-efficiency OLEDs, in which unimolecular and bimolecular excited states contribute green and red emission respectively.
Baicalin suppresses lung cancer growth by targeting PDZ-binding kinase/T-LAK cell-originated protein kinase
Authors: Diao Xin , Yang Danfen , Chen Yu , Liu Wentian
Published: March 2019

Baicalin is the main bioactive component extracted from the traditional Chinese medicine Baical Skullcap Root, and its anti-tumor activity has been studied in previous studies. PDZ-binding kinase/T-LAK cell-originated protein kinase (PBK/TOPK), a serine/threonine protein kinase, is highly expressed in many cancer cells and stimulates the tumorigenic properties, and so, it is a pivotal target for agent to cure cancers. We reported for the first time that baicalin suppressed PBK/TOPK activities by directly binding with PBK/TOPK in vitro and in vivo. Ex vivo studies showed that baicalin suppressed PBK/TOPK activity in JB6 Cl41 cells and H441 lung cancer cells. Moreover, knockdown of PBK/TOPK in H441 cells decreased their sensitivity to baicalin. In vivo study indicated that injection of baicalin in H441 tumor-bearing mice effectively suppressed cancer growth. The PBK/TOPK downstream signaling molecules Histone H3 and ERK2 in tumor tissues were also decreased after baicalin treatment. Taken together, baicalin can inhibit proliferation of lung cancer cells as a PBK/TOPK inhibitor both in vitro and in vivo.
Interleukin-1 in cerebrospinal fluid for evaluating the neurological outcome in traumatic brain injury
Authors: Yue Yingming , Shang Chongzhi , Dong Huajiang , Meng Kun
Published: March 2019

Objective Severe traumatic brain injury (TBI) is associated with unfavorable outcomes secondary to injury from activation of the inflammatory cascade, the release of excitotoxic neurotransmitters, and changes in the reactivity of cerebral vessels, causing ischemia. Inflammation induced by TBI is complex, individual-specific, and associated with morbidity and mortality. The aim of the present study was to discover the differentially expressed cerebrospinal fluid (CSF) proteins and identify which can improve the clinical outcomes in TBI patients.

Methods In the present study, we reported 145 patients with TBI and found the change in patients’ leukocytes in serum and interleukin-1 (IL-1) in CSF, which strongly correlated with the neurological outcome. In terms of results of leukocytes in blood and IL-1 in CSF, we retained the patient’s CSF specimens and conducted a proteomic analysis.

Results A total of 119 differentially expressed proteins were detected between samples of TBI and the normal, which were commonly expressed in all samples, indicating the differentially expressed proteins. When the patients’ Glasgow outcome score (GOS) improved, IL-1 was down-regulated, and when the patients’ GCS score deteriorated, IL-1 was up-regulated accompanied with the progression in TBI.

Conclusion The differentially expressed proteins in CSF may be the novel therapeutic targets for TBI treatment. The leukocytes in blood samples and the IL-1 in CSF may be two important indicators for predicting the prognosis of TBI patients.
Bioinformatics analysis revealing prognostic significance of RRM2 gene in breast cancer
Authors: Chen Wei-xian , Yang Liang-gen , Xu Ling-yun , Cheng Lin , Qian Qi , Sun Li , Zhu Yu-lan
Published: March 2019

Background: Ribonucleotide reductase M2 subunit (RRM2) plays vital roles in many cellular processes such as cell proliferation, invasiveness, migration, angiogenesis, senescence, and tumorigenesis. However, the prognostic significance of RRM2 gene in breast cancer remains to be investigated. Methods:RRM2 expression was initially evaluated using the Oncomine database. The relevance between RRM2 level and clinical parameters as well as survival data in breast cancer was analyzed using the Kaplan–Meier Plotter, PrognoScan, and Breast Cancer Gene-Expression Miner (bc-GenExMiner) databases. Results:RRM2 was overexpressed in different subtypes of breast cancer patients. Estrogen receptor (ER) and progesterone receptor (PR) were negatively correlated with RRM2 expression. Conversely, the Scarff–Bloom–Richardson (SBR) grade, Nottingham prognostic index (NPI), human epidermal growth factor receptor-2 (HER-2) status, nodal status, basal-like status, and triple-negative status were positively related to RRM2 level in breast cancer samples with respect to normal tissues. Patients with increased RRM2 showed worse overall survival, relapse-free survival, distant metastasis-free survival, disease-specific survival, and disease-free survival. RRM2 also exerted positive effect on metastatic relapse event. Besides, a positive correlation between RRM2 and KIF11 genes was confirmed. Conclusion: Bioinformatics analysis revealed that RRM2 might be used as a predictive biomarker for prognosis of breast cancer. Further studies are needed to more precisely elucidate the value of RRM2 in evaluating breast cancer prognosis.
Verbal Learning and Memory in Early-Implanted, Prelingually Deaf Adolescent and Adult Cochlear Implant Users
Authors: Chandramouli Suyog H. , Kronenberger William G. , Pisoni David B.
Published: March 2019

Purpose

The purpose of this study was to investigate the information-processing strategies of early-implanted, prelingually deaf cochlear implant (CI) users with the California Verbal Learning Test–Second Edition (CVLT-II;
Delis, Kramer, Kaplan, & Ober, 2000
), a well-established normed measure of verbal learning and memory used in neuropsychological assessments of memory loss.

Method

Verbal learning and memory skills were compared in 20 older adolescent and young adult prelingually deaf long-term early-implanted CI users and their 24 normal hearing (NH) peers using the CVLT-II, a widely used multitrial free recall test of verbal learning and memory.

Results

On average, CI users recalled fewer words than their NH peers across the immediate, delayed, and cued recall trials of the CVLT-II but were comparable to their NH peers on yes/no recognition memory. CI users showed little evidence of semantic clustering of words during free recall but greater serial clustering compared to their NH peers, suggesting fundamental disturbances in automatic semantic activation of words from long-term memory. No differences were found in verbal memory between CI users and their NH peers on measures of retroactive interference and encoding/retrieval interactions. Performance on the 2nd word list of the CVLT-II (List B) and amount of semantic clustering of words during recall were correlated with sentence recognition in the CI group.

Conclusion

Study findings demonstrate significant differences in free recall performance and information-processing strategies that early-implanted, prelingually deaf CI users use to encode, organize, store, and retrieve spoken words in conventional verbal list learning paradigms, compared to their NH peers. Because verbal learning and memory are core foundational processes routinely used in daily functioning for a wide range of neurocognitive and language processing operations, these findings suggest potential domains for assessment and novel interventions to promote the development of optimal outcomes in prelingually deaf early-implanted long-term CI users.
Line distance protection in the presence of SCFCL
Authors: Thute Rohit S. , Bahirat Himanshu J. , Khaparde Shrikrishna A. , Lubicki Piotr , Kodle Shankar , Dabeer Vikas
Published: March 2019

There is an increase in fault current levels seen by utilities due to grid expansion and the addition of new resources. Installation of superconducting fault current limiter (SCFCL) at transmission voltage levels is being explored to reduce the fault levels. The SCFCL limits the fault current by inserting an additional impedance in the network, which may impact the protection system. This paper discusses the impacts of SCFCL on the operation of line distance protection. It is observed that operation of SCFCL may not impact all the distance relays in the substation and near‐by substation in the same way, thus a boundary definition method is proposed in this study to identify the affected relays. The definitions of boundary condition based on steady‐state fault current values and critical current of the SCFCL are proposed in this study. The impact of SCFCL on the line distance relays which manifest as underreaching of the relays and may also lead to coordination issues and erroneous operation. An implementation method for mitigation which is compatible with existing substation relays is proposed and demonstrated to ensure proper operation of the relays. The proposed mitigation ensures that the system integrity is maintained during faults.
Development of multi-value circulation based on remanufacturing
Authors: Nakajima Kenichi , Matsumoto Mitsutaka , Murakami Hideyuki , Hayakawa Masao , Matsuno Yasunari , Takayanagi Wataru
Published: March 2019

Remanufacturing is an industrial process that turns used products into new ones with the same quality, functionality, and warranty as new products; it is a critical element for realizing a resource-efficient manufacturing industry and a circular economy. Remanufacturing may involve adding new and better functionality to used products, such as adding more wear-resistant materials to the surface or new sensor systems. Remanufacturing has been undertaken for products such as: automobile parts, machinery, photocopiers, single-use cameras, furniture, and turbine components, etc. It is generally superior to material recycling in terms of energy and material savings. Our project aims to develop technologies necessary for the promotion of remanufacturing and to establish a cooperative network related to remanufacturing. As technical development items, our aim is to develop methods to assess the reliability of parts/components, develop technologies to restore deteriorated metal surfaces of used products, introduce production management methods for remanufacturing, and design a circulation system to retain the added values of products. In this paper, we introduce an outline of the project and present some preliminary results. This paper shows the possibility to quantitatively evaluate the carbide distribution (size and density) of the carburized surface of a gear, and also shows the potential to repair materials exposed to a high-temperature oxidative atmosphere by Pr-Ir coating technology.
Investigation and optimization of influencing parameters on the copper extraction from a low-grade oxide deposit by acid leaching
Authors: Hosseinzadeh Mostafa , Hosseini Mohammad Raouf
Published: March 2019

Recovery of copper (II) from a low-grade deposit obtained from the rejects of a crushing circuit was investigated by means of leaching using H2SO4solution. Sulfuric acid concentration was between 30–180 g/L, solid content was set at 10–60%, particles were in the size range of −1 + 2 mm, and the leaching time was 5–60 min. Initially, a screening step was utilized involving a full factorial design (FFD) with four factors at two levels and two replications. Normal probability plot of residuals, analysis of variance (ANOVA), surface plots, and contour plots were used to study the effects of the main operational parameters and their interactions. The results of ANOVA,F-test andt-student test showed that at 95% confidence level, the sulfuric acid, solid content, leaching time, and the 2-way interaction of them considerably affected Cu(II) extraction, and increasing their value positively influenced the Cu(II) extraction. A factorial regression model was developed to relate Cu(II) extraction and the operational variables. The fitted model presented a good agreement between the experimental data and the predicted values with a correlation coefficient (R2) of 0.9989. Optimization of Cu(II) extraction suggested that the optimum conditions for Cu(II) extraction (Re = 72%) were sulfuric acid: 90 g/L, solid content: 50%, particle size: under 2 mm, and leaching time: 30 min.
Endoscopic characterization of small colonic polyps: baseline performance of experienced endoscopists is no different to that of medical students
Authors: Basford Peter , Brown James , Cooper Sarah , Bhandari Pradeep
Published: March 2019

Background Studies examining the impact of training modules on characterization of diminutive colonic polyps (DCP) show varying results.

Aim We aimed to assess the impact of a novel web-based training module on the accuracy of in vivo characterization of DCPs using different imaging modalities. Differences between groups with varying degrees of endoscopic experience were also assessed.

Methods In total, 90 images of 30 DCPs viewed with high definition white light (HDWL), i-Scan, and indigo carmine chromoendoscopy were included in an online test module. Testing was undertaken before and after completing a novel web-based in vivo characterization training module. In total, 21 subjects (medical students (MS), gastroenterology trainees (GT), and gastroenterology consultants (GC)) undertook the tests and training module.

Results No statistically significant difference in overall accuracy was found between the three groups either pre- (MS 59.1 %, GR 65.7 %, GC 62.4 %, P = ns for all three comparisons) or post-training (MS 69.2 %, GR 71.1 %, GC 71.3 %, P = ns for all three comparisons). Accuracy improved significantly for all three groups post-training (P < 0.001) as did interobserver agreement. No significant differences in accuracy between modalities were found pre-training (HDWL 64.8 %, i-Scan 60.0 %, chromoendoscopy 62.2 %, P = ns). Post-training accuracy with HDWL and chromoendoscopy was better than with i-Scan (HDWL 72.9 % vs i-Scan 65.1 %, P = 0.002; i-Scan 65.1 % vs chromoendoscopy 73.7 %, P < 0.001). The proportion of high confidence predictions increased from 25.7 % to 41.5 %, with a high confidence prediction accuracy of 81.7 %.

Conclusions Skills for in vivo characterization of DCPs are not acquired through endoscopic experience alone. A novel web-based training intervention results in modest improvements in accuracy with further improvements likely to require more prolonged training.
Visuelle Lebensqualität bei starker Sehbehinderung – Messung und Messinstrumente
Authors: Terheyden Jan , Finger Robert
Published: March 2019

Patientenberichtete Endpunkte wie die Lebensqualität werden zunehmend häufiger in klinischen Studien eingesetzt, um patientenrelevante Aspekte einer Intervention oder eine Funktionsbeeinträchtigung zu messen. Bei Sehverlust erfasst z. B. die visuelle Lebensqualität die individuelle Beeinträchtigung im Alltag. Wichtig bei der Verwendung von Messinstrumenten zu patientenberichteten Endpunkten wie der Lebensqualität sind psychometrische Parameter wie die Reliabilität, Validität und Änderungssensitivität, um sicher sein zu können, dass die mit den jeweiligen Instrumenten erhobenen Daten robust sind. Zur visuellen Lebensqualität existieren zahlreiche allgemeine wie auch erkrankungsspezifische bzw. funktionsspezifische Fragebögen; nicht alle sind jedoch für Patienten mit schwerer Sehbeeinträchtigung geeignet. Zu empfehlen ist derzeit etwa der IVI- oder der NEI-VFQ-Fragebogen, die in einer validierten deutschen Übersetzung vorliegen. Zur breiteren Evaluation dieser Messinstrumente und ggf. der Neuentwicklung von besseren Instrumenten sind jedoch weitere Studien nötig, damit z. B. auch das wachsende Interesse am Einsatz von Patientenfragebögen als Endpunkte in der klinischen Forschung gedeckt werden kann.
Das phänotypische Spektrum der Augenveränderungen bei CEP290-Sequenzvariationen
Authors: Preising Markus , Schneider Ute , Friedburg Christoph , Gruber Hildegard , Lindner Susanne , Lorenz Birgit
Published: March 2019

Einleitung Eine häufige Ursache erblicher Netzhautdegenerationen sind Mutationen in Genen, die für den Aufbau des verbindenden Ziliums der Photorezeptoren und den interflagellaren Transport codieren. Diese Erkrankungen werden als Ziliopathien zusammengefasst. Eines der häufigsten Ziliopathiegene ist das CEP290, in dem die tief-intronische Splice-Mutation c.2991+1655A>G dominiert. Eine Übersicht über das ophthalmologische Spektrum verschiedener Mutationen des CEP290-Gens wird in dieser Studie dargestellt.

Methoden Patienten mit ursächlichen Mutationen im CEP290-Gen wurden in einer umfassenden ophthalmologischen Diagnostik dokumentiert. Zusätzlich zur Sehschärfe und Refraktion wurde die Sehfunktion elektrophysiologisch erfasst. Bei ausreichender Kooperation erfolgte eine Dokumentation mit psychophysischen Methoden, des Augenhintergrundes und der Netzhautschichtung.

Ergebnisse 30 Patienten im Alter zwischen 1 Monat und 84 Jahren (Median der ersten Vorstellung 0,6 Jahre) wurden in einem Zeitraum zwischen 5 Monaten und 25,7 Jahren (Median 4,8 Jahre) erfasst. Bei 23 Patienten lag c.2991+1655A>G vor (30/60 Allele, 7 homozygot). Die zweithäufigste Mutation war p.K1575* (9/60 Allele). Im Ganzfeld-Elektroretinogramm fanden sich bei wenigen Patienten initial noch Restpotenziale. Im weiteren Verlauf waren bei allen Patienten keine Potenziale mehr nachweisbar. Die Sehschärfe war seit Geburt stark reduziert. Bei 8 Patienten lag ein quantifizierbarer Visus (logMAR 2 – 0,3) vor. Eine fehlende Fixation wurde bei 15 Patienten während der ersten Lebensmonate berichtet. Für 10 dieser Patienten fand keine Verbesserung statt. Die übrigen Patienten entwickelten Lichtscheinwahrnehmung (LSP) oder Erkennen von Handbewegungen. Eine bessere Sehschärfe war nicht auf Patienten mit c.2991+1655A>G-Mutation beschränkt. Der Augenhintergrund zeigte degenerative Veränderungen in der gesamten Fläche mit paramakulär ringförmig erhöhter Fundusautofluoreszenz (FAF) und punktförmig erhöhter FAF in der Peripherie (9/30 Patienten). Die Netzhautschichtung (6/30 Patienten) war im Bereich der Photorezeptoren (OPL bis OS) stark verdünnt bei erhaltener Dicke der inneren retinalen Schichten (RNFL bis INL). Die Schichtung der zentralen Netzhaut oder der Genotyp ließen keine Rückschlüsse auf die Sehschärfe zu.

Schlussfolgerungen
CEP290-Mutationen gehören zu den häufigsten Ursachen erblicher Netzhautdegenerationen. Von den 30 Patienten in dieser Studie hatten nur 33% keine Lichtwahrnehmung. Von den übrigen 67%, die zumindest LSP entwickelten, erreichten 26% einen quantifizierbaren Visus zwischen logMAR 2 und 0,3. Zusammen mit einem guten Erhalt der Ganglienzellschicht und der Nervenfaserschicht erscheint eine erfolgreiche Anwendung therapeutischer Verfahren möglich.
Entwicklung von cGMP-Analoga zur pharmakologischen Behandlung von neurodegenerativen Netzhauterkrankungen
Authors: Fischer Dominik , Paquet-Durand François
Published: March 2019

Erbliche Netzhautdegenerationen sind Erkrankungen der Photorezeptoren und/oder des Pigmentepithels, die zu einem weitgehenden Sehverlust bis hin zur vollständigen Erblindung führen. Bis heute sind diese seltenen Erkrankungen der Netzhaut zumeist nicht behandelbar und stellen eine erhebliche Belastung für die Betroffenen und ihre Angehörigen dar. Dieser Übersichtsartikel zeigt einige der Herausforderungen auf, die bei der Entwicklung von neuen Therapien für erbliche Netzhautdegenerationen auftreten, insbesondere wird auf das Problem der enormen genetischen Heterogenität dieser Erkrankungen eingegangen und die Frage, wie neue Behandlungsformen über die Blut-Netzhaut-Schranke zu den Nervenzellen der Netzhaut gebracht werden können. In diesem Rahmen wird die zentrale Rolle des Botenstoffs zyklisches Guanosinmonophosphat (cGMP) im Photorezeptor erklärt und wie dessen Funktion genutzt werden kann, um mutationsunabhängige Therapien zu entwickeln. Dies wird am Beispiel des DRUGSFORD-Projektes weiter ausgeführt, wobei auch darauf eingegangen wird, wie neue Medikamente formuliert werden können, um die Blut-Netzhaut-Schranke zu überwinden. Darüber hinaus werden weitere Schwierigkeiten diskutiert, die entstehen, wenn positive Ergebnisse aus der anwendungsbezogenen Forschung in die klinische Entwicklung überführt werden sollen. Hier wird zum einen auf Lücken und mangelnde Interdisziplinarität in der Ausbildung von Naturwissenschaftlern und Medizinern hingewiesen, zum anderen behindert aber auch das Fehlen von Verlaufsdaten und geeigneten Biomarkern die klinische Entwicklung.
Vom Röntgen zum PET/MRT, und dann? – Zukunftsweisende Bildgebung in der Kinderradiologie
Authors: Staatz Gundula , Daldrup-Link Heike , Herrmann Jochen , Hirsch Franz , Schäfer Jürgen , Seehofnerova Anna , Sorantin Erich , Theruvath Ashok , Lollert André
Published: March 2019

Die Kinderradiologie steht heute vor weitreichenden Veränderungen. Basismodalitäten wie Röntgen und Ultraschall werden zunehmend durch neuere, moderne Techniken ergänzt. Dieser Übersichtsartikel stellt Fortschritte in der Kinderradiologie sowie technische Innovationen vor, welche in Zukunft noch größere Bedeutung erlangen könnten. Hierzu werden CT-Dosisreduktionstechniken inklusive der Anwendung künstlicher Intelligenz sowie Fortschritte in den Gebieten der Magnetresonanztomografie und molekularen Bildgebung dargestellt.

Kernaussagen