bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abnormal α‐synuclein deposits in skin nerves: intra‐ and inter‐laboratory reproducibility
Authors: Donadio V. , Doppler K. , Incensi A. , Kuzkina A. , Janzen A. , Mayer G. , Volkmann J. , Rizzo G. , Antelmi E. , Plazzi G. , Sommer C. , Liguori R. , Oertel W. H. 
Published: February 2019

Background and purposeVisualization of phosphorylated α‐synuclein at serine 129 (p‐syn) in skin nerves is a promising test for the in vivo diagnosis of synucleinopathies. Here the aim was to establish the intra‐ and inter‐laboratory reproducibility of measurement of intraneural p‐syn immunoreactivity in two laboratories with major expertise (Würzburg and Bologna).MethodsIn total, 43 patients affected by Parkinson's disease (PD 21 patients), dementia with Lewy bodies (DLB 1), rapid eye movement sleep behaviour disorder (RBD 11), multiple system atrophy (MSA‐P 4) and small fibre neuropathy (SFN 6) were enrolled. Skin biopsy was performed at the C7 paravertebral spine region and distal skin sites (thigh or leg). The analysis was standardized in both laboratories and carried out blinded on a single skin section double stained with antibodies to p‐syn and the pan‐axonal marker protein gene product 9.5. Fifty skin sections were randomly selected for the analysis: 25 from C7 and 25 from distal sites. Differently classified sections were re‐evaluated to understand the reasons for the discrepancy.ResultsThe intra‐laboratory analysis showed an excellent reproducibility both in Würzburg (concordance of classification 100% of sections; K = 1; P < 0.001) and Bologna (96% of sections; K = 0.92; P < 0.001). Inter‐laboratory analysis showed reproducibility in 45 sections (90%; K = 0.8; P < 0.001) and a different classification in five sections, which was mainly due to fragmented skin samples or weak fluorescent signals.ConclusionsAnalysis of p‐syn showed excellent inter‐ and intra‐laboratory reproducibility supporting the reliability of this technique. The few ascertained discordances were important to further improve the standardization of this technique.
Indoleamine 2,3‐dioxygenase 1 deletion promotes Theiler's virus–induced seizures in C57BL/6J mice
Authors: Juda Michal B. , Brooks Alexandra K. , Towers Albert E. , Freund Gregory G. , McCusker Robert H. , Steelman Andrew J. 
Published: February 2019

SummaryObjectiveViral encephalitis increases the risk for developing seizures and epilepsy. Indoleamine 2,3‐dioxygenase 1 (Ido1) is induced by inflammatory cytokines and functions to metabolize tryptophan to kynurenine. Kynurenine can be further metabolized to produce kynurenic acid and the N‐methyl‐d‐aspartate receptor agonist quinolinic acid (QuinA). In the present study, we sought to determine the role of Ido1 in promoting seizures in an animal model of viral encephalitis.MethodsC57BL/6J and Ido1 knockout mice (Ido1‐KO) were infected with Theiler's murine encephalomyelitis virus (TMEV). Quantitative real‐time polymerase chain reaction was used to evaluate hippocampal expression of proinflammatory cytokines, Ido1, and viral RNA. Body weights and seizure scores were recorded daily. Elevated zero maze was used to assess differences in behavior, and hippocampal pathology was determined by immunohistochemistry.ResultsInfected C57BL/6J mice up‐regulated proinflammatory cytokines, Ido1, and genes encoding the enzymatic cascade responsible for QuinA production in the kynurenine pathway prior to the onset of seizures. Seizure incidence was elevated in Ido1‐KO compared to C57BL/6J mice. Infection increased locomotor activity in Ido1‐KO compared to C57BL/6J mice. Furthermore, the occurrence of seizures was associated with hyperexcitability. Neither expression of proinflammatory cytokines nor viral RNA was altered as a result of genotype. Immunohistochemical analysis revealed increased hippocampal pathology in Ido1‐KO mice.SignificanceOur findings suggest that Ido1 deletion promotes seizures and neuropathogenesis during acute TMEV encephalitis.
The C‐terminal domain of HpDprA is a DNA‐binding winged helix domain that does not bind double‐stranded DNA
Authors: Lisboa Johnny , Celma Louisa , Sanchez Dyana , Marquis Mathilde , Andreani Jessica , Guérois Raphael , Ochsenbein Françoise , Durand Dominique , Marsin Stéphanie , Cuniasse Philippe , Radicella J. Pablo , Quevillon‐Cheruel Sophie 
Published: February 2019

DNA‐processing protein A, a ubiquitous multidomain DNA‐binding protein, plays a crucial role during natural transformation in bacteria. Here, we carried out the structural analysis of DprA from the human pathogen Helicobacter pylori by combining data issued from the 1.8‐Å resolution X‐ray structure of the Pfam02481 domain dimer (RF), the NMR structure of the carboxy terminal domain (CTD), and the low‐resolution structure of the full‐length DprA dimer obtained in solution by SAXS. In particular, we sought a molecular function for the CTD, a domain that we show here is essential for transformation in H. pylori. Albeit its structural homology to winged helix DNA‐binding motifs, we confirmed that the isolated CTD does not interact with ssDNA nor with dsDNA. The key R52 and K137 residues of RF are crucial for these two interactions. Search for sequences harboring homology to either HpDprA or Rhodopseudomonas palustris DprA CTDs led to the identification of conserved patches in the two CTD. Our structural study revealed the similarity of the structures adopted by these residues in RpDprA CTD and HpDprA CTD. This argues for a conserved, but yet to be defined, CTD function, distinct from DNA binding.
Tyrosine metabolism: identification of a key residue in the acquisition of prephenate aminotransferase activity by 1β aspartate aminotransferase
Authors: Giustini Cecile , Graindorge Matthieu , Cobessi David , Crouzy Serge , Robin Adeline , Curien Gilles , Matringe Michel 
Published: February 2019

Alternative routes for the post‐chorismate branch of the biosynthetic pathway leading to tyrosine exist, the 4‐hydroxyphenylpyruvate or the arogenate route. The arogenate route involves the transamination of prephenate into arogenate. In a previous study, we found that, depending on the microorganisms possessing the arogenate route, three different aminotransferases evolved to perform prephenate transamination, that is, 1β aspartate aminotransferase (1β AAT), N‐succinyl‐l,l‐diaminopimelate aminotransferase, and branched‐chain aminotransferase. The present work aimed at identifying molecular determinant(s) of 1β AAT prephenate aminotransferase (PAT) activity. To that purpose, we conducted X‐ray crystal structure analysis of two PAT competent 1β AAT from Arabidopsis thaliana and Rhizobium meliloti and one PAT incompetent 1β AAT from R. meliloti. This structural analysis supported by site‐directed mutagenesis, modeling, and molecular dynamics simulations allowed us to identify a molecular determinant of PAT activity in the flexible N‐terminal loop of 1β AAT. Our data reveal that a Lys/Arg/Gln residue in position 12 in the sequence (numbering according to Thermus thermophilus 1β AAT), present only in PAT competent enzymes, could interact with the 4‐hydroxyl group of the prephenate substrate, and thus may have a central role in the acquisition of PAT activity by 1β AAT.
The burden of proof: The process of involving young people in research
Authors: Dovey‐Pearce Gail , Walker Sophie , Fairgrieve Sophie , Parker Monica , Rapley Tim 
Published: February 2019

AbstractPatient and public involvement in research includes non‐academics working with researchers, on activities from consultative tasks, to joint working, and on user‐led initiatives. Health and social care funding bodies require involvement in research projects. A current debate focuses on a perceived lack of empirical “proof” to demonstrate the impact of involvement upon the quality of research. It is also argued that the working relationships between researchers and those becoming involved need to be understood more fully. These areas are beginning to be reported upon but there are few studies of young people involved in health research. This study describes the experiences of adult academics and young people, working together on a large‐scale, UK health research programme. Using qualitative interview and focus group methods, the aim was to explore participants’ perceptions about the process and outcomes of their work together. The importance of cyclical, dynamic and flexible approaches is suggested. Enablers include having clear mechanisms for negotiation and facilitation, stakeholders having a vision of “the art of the possible,” and centrally, opportunities for face‐to‐face working. What is needed is a continuing discourse about the challenges and benefits of working with young people, as distinct from younger children and adults, understanding the value of this work, without young people having to somehow “prove” themselves. Involvement relies on complex social processes. This work supports the view that an improved understanding of how key processes are enabled, as well as what involvement achieves, is now needed.
Factors associated with readmission and mortality in adult patients with skin and soft tissue infections
Authors: Raya‐Cruz Manuel , Payeras‐Cifre Antonio , Ventayol‐Aguiló Lola , Díaz‐Antolín Paz 
Published: February 2019

AbstractBackgroundSkin and soft tissue infections (SSTIs) are a common cause of consultation, and complicated cases require hospitalization. We describe factors that are related to readmission and/or mortality of hospitalized patients diagnosed with SSTIs.MethodsRetrospective review of hospital‐admitted patients with a diagnosis of cellulitis, abscess, hidradenitis, fasciitis, and Fournier's gangrene. Cases from January 2002 to October 2015 were extracted from the diagnostic codification database of the Archives and Clinical Documentation Department.FindingsWe studied 1,482 episodes of hospitalized patients diagnosed with SSTIs. There were 187 (12.3%) readmissions, the most frequent diagnosis was cellulitis (72.7%), and the most commonly isolated microorganism was Staphylococcus aureus (25; 30.1%). Factors associated with readmissions were healthcare‐related infections (P = 0.002), prior antibiotic therapy (P < 0.001), ischemic heart disease (P = 0.01), chronic liver disease (P = 0.001), and diabetes mellitus (DM) (P = 0.006). The number of patients who died as a result of an infection was 34 (2.2%) and, in these patients, the most common diagnosis was also cellulitis (79.4%), which in 52.9% (P = 0.001) was community acquired. DM (P = 0.01), heart failure (P = 0.001), and chronic liver disease (P = 0.003) were the most frequent comorbidities. This group presented more complications (P < 0.005) such as endocarditis (P < 0.005), amputation (P = 0.018), severe sepsis (P < 0.005), and septic shock (P < 0.001).ConclusionsReadmitted patients had healthcare‐related S. aureus infection, had received prior antibiotic therapy, and presented comorbid conditions such as ischemic heart disease, peripheral vascular disease, chronic liver disease, or DM. Comorbidities such as advanced age, DM, heart failure, and chronic liver disease were associated with complications and higher infection‐related mortality.
Longitudinal active sampling for respiratory viral infections across age groups
Authors: Galanti Marta , Birger Ruthie , Ud‐Dean Minhaz , Filip Ioan , Morita Haruka , Comito Devon , Anthony Simon , Freyer Greg A. , Ibrahim Sadiat , Lane Benjamin , Ligon Chanel , Rabadan Raul , Shittu Atinuke , Tagne Eudosie , Shaman Jeffrey 
Published: February 2019

BackgroundRespiratory viral infections are a major cause of morbidity and mortality worldwide. However, their characterization is incomplete because prevalence estimates are based on syndromic surveillance data. Here, we address this shortcoming through the analysis of infection rates among individuals tested regularly for respiratory viral infections, irrespective of their symptoms.MethodsWe carried out longitudinal sampling and analysis among 214 individuals enrolled at multiple New York City locations from fall 2016 to spring 2018. We combined personal information with weekly nasal swab collection to investigate the prevalence of 18 respiratory viruses among different age groups and to assess risk factors associated with infection susceptibility.Results17.5% of samples were positive for respiratory viruses. Some viruses circulated predominantly during winter, whereas others were found year round. Rhinovirus and coronavirus were most frequently detected. Children registered the highest positivity rates, and adults with daily contacts with children experienced significantly more infections than their counterparts without children.ConclusionRespiratory viral infections are widespread among the general population with the majority of individuals presenting multiple infections per year. The observations identify children as the principal source of respiratory infections. These findings motivate further active surveillance and analysis of differences in pathogenicity among respiratory viruses.
Intrinsic dielectric properties of columbite ZnNb2O6 ceramics studied by P–V–L bond theory and Infrared spectroscopy
Authors: Yang Hongyu , Zhang Shuren , Yang Hongcheng , Yuan Ying , Li Enzhu 
Published: February 2019

AbstractIn this study, intrinsic dielectric properties of ZnNb2O6 ceramics were investigated using P–V–L chemical bond theory and far‐infrared reflectivity spectra. The largest bond ionicity and bond susceptibility of Nb–O bonds suggest that the dielectric polarizability is mainly determined by Nb–O bonds. Relative permittivity, calculated via P–V–L bond theory, is close to experimental value determined using TE011 mode. The Nb–O bonds are also crucial for the structural stability. According to far‐infrared reflectivity spectra and complex dielectric function analysis, a relatively consistent result between calculated and measured dielectric properties, fit using classical damped oscillator mode, indicate that the B1u mode at 168.87 cm−1 provides majority contribution to the dielectric properties.
Nanostructure‐enhanced magnetoelectric/magnetostrictive properties and reduced losses in self‐assembled epitaxial CuFe2O4–BiFeO3 layers on Pb(Mg1/3Nb2/3)O3–33at%PbTiO3 crystals
Authors: Tang Xiao , Leung Chung Ming , Gao Min , Winkler Christopher , Luo Haosu , Li Jiefang , Viehland Dwight 
Published: February 2019

AbstractSelf‐assembled two‐phase heterostructures of BiFeO3 and CuFe2O4 (BFO–CuFO) were deposited on (100)‐oriented SrRuO3‐buffered Pb(Mg1/3Nb2/3) O3–33at%PbTiO3 (PMN–PT) by using switching pulsed laser deposition (SPLD), and compared to single layers of CuFO on the same single crystal substrate. The CuFO phase of the self‐assembled layers had notably slimmer M‐H loops than for previously reported vertically integrated CoFe2O4 nanopillar ones, but wider ones than for CuFO/PMN–PT heterostructures. Notable changes in the magnetization of the CuFO nanopillars were found with applied DC electric field (EDC), where Mr/Ms exhibited typical butterfly‐shaped hysteresis with EDC. This was in distinct difference to CuFO/PMN–PT heterostructures which did not exhibit magnetoelectric coupling. The findings demonstrate a trade‐off between magnetoelectric/magnetostrictive properties and loss that can be controlled by nanostructure features.
Sr‐induced color‐tunable and thermal stability enhancing in the phosphor (Ba1‐xSrx)9Lu2Si6O24:Eu2+ for solid‐state lighting
Authors: Dong Rujia , Zou Haifeng , Zhang Xiangting , An Zhengce , Zhou Xiuqing , Zheng Keyan , Sheng Ye , Shi Zhan , Song Yanhua 
Published: February 2019

AbstractRare earth ions’ site occupation is significant for studying luminescence properties by changing the host composition. The (Ba1‐xSrx)9Lu2Si6O24:Eu2+ (x = 0‐0.4) tunable‐color phosphors were synthesized via a high temperature solid‐state reaction. With the Sr2+ ions concentration increase, the luminescent color could be tuned from blue to green. This phenomenon is discussed in detail through the ions occupation in the host lattice. More importantly, the temperature‐dependent luminescence of (Ba1‐xSrx)9Lu2Si6O24:Eu2+ phosphors was investigated and exhibited excellent thermal stability. Furthermore, white LED device has been fabricated using (Ba1‐xSrx)9Lu2Si6O24:Eu2+ phosphor mixed with commercial red phosphor Sr2Si5N8:Eu3+ combined with a 370 nm UV‐chip. This device showed correlated color temperature (CCT) of 5125 K and high color render index (CRI) of 91. This phosphor will be a promising candidate as a tunable‐color phosphor for UV‐based white LEDs.
Matrine attenuates high‐fat diet‐induced in vivo and ox‐LDL‐induced in vitro vascular injury by regulating the PKCα/eNOS and PI3K/Akt/eNOS pathways
Authors: Zhang Song , Guo Shun , Gao Xiao‐bo , Liu An , Jiang Wei , Chen Xi , Yang Peng , Liu Lin‐na , Shi Lei , Zhang Yan 
Published: February 2019

AbstractLipid metabolism disorders lead to vascular endothelial injury. Matrine is an alkaloid that has been used to improve obesity and diabetes and for the treatment of hepatitis B. However, its effect on lipid metabolism disorders and vascular injury is unclear. Here, we investigated the effect of matrine on high‐fat diet fed mice and oxidized low‐density lipoprotein (ox‐LDL)‐induced human umbilical vein endothelial cells (HUVECs). Computational virtual docking analyses, phosphoinositide 3‐kinase (PI3K) and protein kinase C‐α (PKCα) inhibitors were used to localize matrine in vascular injuries. The results showed that matrine‐treated mice were more resistant to abnormal lipid metabolism and inflammation than vehicle‐treated mice and exhibited significantly alleviated ox‐LDL‐stimulated dysfunction of HUVECs, restored diminished nitric oxide release, decreased reactive oxygen species generation and increased expression phosphorylation of AKT‐Ser473 and endothelial nitric oxide synthase (eNOS)‐Ser1177. Matrine not only up‐regulates eNOS‐Ser1177 but also down‐regulates eNOS‐Thr495, a PKCα‐controlled negative regulator of eNOS. Using computational virtual docking analyses and biochemical assays, matrine was also shown to influence eNOS/NO via PKCα inhibition. Moreover, the protective effects of matrine were significantly abolished by the simultaneous application of PKCα and the PI3K inhibitor. Matrine may thus be potentially employed as a novel therapeutic strategy against high‐fat diet‐induced vascular injury.
Ligustilide attenuates nitric oxide‐induced apoptosis in rat chondrocytes and cartilage degradation via inhibiting JNK and p38 MAPK pathways
Authors: Zhou Yan , Ming Jianghua , Li Yaming , Deng Ming , Chen Qing , Ma Yonggang , Chen Zhonghui , Zhang Yubiao , Liu Shiqing 
Published: February 2019

AbstractLigustilide (LIG) is the main lipophilic component of the Umbelliferae family of pharmaceutical plants, including Radix angelicae sinensis and Ligusticum chuanxiong. LIG shows various pharmacological properties associated with anti‐inflammation and anti‐apoptosis in several kinds of cell lines. However, the therapeutic effects of LIG on chondrocyte apoptosis remain unknown. In this study, we investigated whether LIG had an anti‐apoptotic activity in sodium nitroprusside (SNP)‐stimulated chondrocyte apoptosis and could delay cartilage degeneration in a surgically induced rat OA model, and elucidated the potential mechanisms. In vitro studies revealed that LIG significantly suppressed chondrocyte apoptosis and cytoskeletal remodelling, which maintained the nuclear morphology and increased the mitochondrial membrane potential. In terms of SNP, LIG treatment considerably reduced the expression levels of cleaved caspase‐3, Bax and inducible nitric oxide synthase and increased the expression level of Bcl‐2 in a dose‐dependent manner. The LIG‐treated groups presented a significantly suppressed expression of activating transcription factor 2 and phosphorylation of Jun N‐terminal kinase (JNK) and p38 mitogen‐activated protein kinase (MAPK). The inhibitory effect of LIG was enhanced by the p38 MAPK inhibitor SB203580 or the JNK inhibitor SP600125 and offset by the agonist anisomycin. In vivo studies demonstrated that LIG attenuated osteoarthritic cartilage destruction by inhibiting the cartilage chondrocyte apoptosis and suppressing the phosphorylation levels of activating transcription factor 2, JNK and p38 MAPK. This result was confirmed by histological analyses, micro‐CT, TUNEL assay and immunohistochemical analyses. Collectively, our studies indicated that LIG protected chondrocytes against SNP‐induced apoptosis and delayed articular cartilage degeneration by suppressing JNK and p38 MAPK pathways.
N‐myc and STAT interactor correlates with severity and prognosis in acute‐on‐chronic liver failure of hepatitis B virus
Authors: Xiong Lifu , Du Yanan , Zhou Tianhui , Du Bingying , Visalath Phimphone , Lin Lanyi , Bao Shisan , Cai Wei 
Published: February 2019

AbstractBackground and AimHepatitis B virus‐related acute‐on‐chronic liver failure (HBV‐ACLF) is characterized by acute deterioration of chronic liver disease with excessive inflammation. N‐myc and STAT interactor (NMI), an inflammation‐mediated protein, involves in various inflammatory‐related diseases, but the role of NMI in development and prognosis in HBV‐ACLF remains to be elucidated.MethodsSerum NMI from healthy controls (HCs, n = 20), chronic hepatitis B (CHB, n = 50) patients, and HBV‐ACLF patients (n = 50) was determined using ELISA. NMI from peripheral blood mononuclear cells and liver was confirmed using quantitative real‐time polymerase chain reaction, Western blot, and immunofluorescence.ResultsSerum NMI was increased 1.9‐fold or 2.2‐fold from HBV‐ACLF patients compared with that from HCs (P < 0.01) or CHB patients (P < 0.01). Consistently, NMI from peripheral blood mononuclear cells was upregulated significantly from HBV‐ACLF patients compared with that from HCs and CHB patients at mRNA and protein levels. Hepatic NMI from HBV‐ACLF patients was 2.8‐fold higher than that from HCs. Serum NMI was correlated with Model for End‐stage Liver Disease, Chronic Liver Failure Consortium ACLF score, and ACLF grades. In contrast, serum NMI was significantly decreased in HBV‐ACLF ameliorated patients during follow‐up, whereas serum NMI was sustained at high levels in non‐ameliorated patients. Elevated serum NMI (≥ 198.5 pg/mL) was correlated with poor survival rate of HBV‐ACLF patients. Using receiver operating characteristics curves, it was suggested that serum NMI was a potential biomarker in predicting 3‐month mortality of HBV‐ACLF patients.ConclusionsOur study highlights the potential role of NMI in assessing the development and prognosis of HBV‐ACLF.
Parry‐Romberg syndrome treatment with fat transfer and a new bleaching formula
Authors: Liapakis Ioannis E. , Tzouganakis Angelos C. , Paschalis Eleftherios I. , Englander Miriam , Christopoulos Athanasios , Gloustianou Georgia , Kontoes Paraskevas 
Published: February 2019

SummaryParry‐Romberg syndrome is a hemifacial atrophy which can be complicated by melasma. We present two cases of Parry‐Romberg syndrome, treated by fat transfer and bleaching of the skin using a modified “Kligman's formula.” The atrophy, as well as the skin dyschromia, improved, and the results were stable.