bluuebunny/crossref_metadata_2025_split huggingface dataset:
Splice variant in ARX leading to loss of C‐terminal region in a boy with intellectual disability and infantile onset developmental and epileptic encephalopathy
Authors: Shoubridge Cheryl , Jackson Matilda , Grinton Bronwyn , Berkovic Samuel F. , Scheffer Ingrid E. , Huskins Shannon , Thomas Alison , Ware Tyson 
Published: May 2019

AbstractPathogenic variants in the X‐chromosome Aristaless‐related homeobox (ARX) gene contribute to intellectual disability, epilepsy, and associated comorbidities in affected males. Here, we report a novel splice variant in ARX in a family with three affected individuals. The proband had early onset developmental and epileptic encephalopathy, his brother and mother had severe and mild intellectual disability, respectively. Massively parallel sequencing identified a novel c.1449‐1G>C in intron 4 of the ARX gene, predicted to abolish the splice acceptor site, retaining intron 4 and leading to a premature termination codon immediately after exon 4. As exon 5 is the last exon of the ARX gene, the premature termination codon at position p.L484* would be predicted to escape nonsense‐mediated mRNA decay, potentially producing at least some C‐terminally truncated protein. Analysis of cDNA from patient lymphoblastoid cells confirmed retention of intron 4 and loss of detectable expression of ARX mRNA across exon 4 to exon 5. We review published cases of variants that lead to altered or early termination of the ARX protein, but not complete loss of function, and are associated with phenotypes of intellectual disability and infantile onset developmental and epileptic encephalopathies, including Ohtahara and West syndromes. Taken together, this novel splice variant retaining intron 4 is likely to be the cause of the early onset developmental and epileptic encephalopathy in the proband.
Kovalente organische Gerüstverbindungen: chemische Ansätze für Designerstrukturen und integrierte Funktionen
Authors: Chen Xinyi , Geng Keyu , Liu Ruoyang , Tan Ke Tian , Gong Yifan , Li Zhongping , Tao Shanshan , Jiang Qiuhong , Jiang Donglin 
Published: May 2019

AbstractDie Fortschritte der Chemie im letzten Jahrzehnt ebnen neue Wege zur Gestaltung organischer Polymere über Topologiediagramme. Dieser Ansatz ermöglicht das kovalente Zusammenfügen organischer Einheiten zu geordneten Topologien einer neuen Polymerform, den kovalenten organischen Gerüstverbindungen. Dies bedeutet einen Durchbruch in der Chemie, da nunmehr eine molekulare Plattform für die Synthese von Polymeren mit vorbestimmbaren Primärstrukturen und Strukturen höherer Ordnung zur Verfügung steht, ein zentrales Ziel, das über ein Jahrhundert lang angestrebt wurde, mit herkömmlichen Gestaltungsprinzipien aber nicht erreichbar war. Das neue Gebiet entwickelt seine eigenen Eigenschaften, die sich von jenen herkömmlicher Polymere unterscheiden. Unser Aufsatz fasst die Grundlagen und wichtigsten Fortschritte zusammen, wobei der Schwerpunkt auf der Chemie des Strukturdesigns liegt, einschließlich der Grundgedanken, Synthesestrategien und Kontrollverfahren. Wir prüfen integrierte, für die Strukturen spezifische Funktionen, indem wir verschiedene Wechselspiele und Mechanismen aufzeigen, die an der Expression der Funktion beteiligt sind. Wir benennen grundlegende Probleme, die in der Chemie und in zukünftigen Forschungsrichtungen der Physik und Materialwissenschaft zu adressieren sind, und beschreiben Anwendungsmöglichkeiten.
Covalency‐Driven Preservation of Local Charge Densities in a Metal‐to‐Ligand Charge‐Transfer Excited Iron Photosensitizer
Authors: Jay Raphael M. , Eckert Sebastian , Vaz da Cruz Vinícius , Fondell Mattis , Mitzner Rolf , Föhlisch Alexander 
Published: May 2019

AbstractCovalency is found to even out charge separation after photo‐oxidation of the metal center in the metal‐to‐ligand charge‐transfer state of an iron photosensitizer. The σ‐donation ability of the ligands compensates for the loss of iron 3d electronic charge, thereby upholding the initial metal charge density and preserving the local noble‐gas configuration. These findings are enabled through element‐specific and orbital‐selective time‐resolved X‐ray absorption spectroscopy at the iron L‐edge. Thus, valence orbital populations around the central metal are directly accessible. In conjunction with density functional theory we conclude that the picture of a localized charge‐separation is inadequate. However, the unpaired spin density provides a suitable representation of the electron–hole pair associated with the electron‐transfer process.
Synthesis, characterization and cytotoxicity of new 2‐isonicotinoyl‐N‐phenylhydrazine‐1‐carbothioamide and its metal complexes
Authors: Hosny Nasser M. , Hassan Nader Y. , Mahmoud Heba M. , Abdel‐Rhman Mohamed H. 
Published: May 2019

The reaction of the newly synthesized ligand, 2‐isonicotinoyl‐N‐phenylhydrazine‐1‐carbothioamide (H3L), with acetate salt of Co (II), Cu (II),Ni (II) and Zn (II) led to isolation of four solid complexes. The ligand and complexes structure elucidation were based on elemental analyses, spectral analyses (IR, UV–Visible, 1H and13C‐NMR, MS and ESR), TGA, molar conductivity and magnetic moments measurements. The results indicated that the ligand exists in the thioketo form, while on coordination to the metal ions; it behaves as mono‐negative bidentate chelate and exists in enol form. The optical band gap measurements of the ligand and its metal complexes are in the range 3.83–4.48 eV indicating their semi‐conducting character. The cytotoxicity examination of H3L and its Zn (II) complex showed that the ligand have very strong cytotoxicity against both HCT‐116 and HEPG‐2 cell lines while, Zn (II) complex has moderate activity.
Study on physisorption between phycocyanin and gold nanoparticles
Authors: Zhao Xiujuan , Zhao Xinyu , Yuan Ming , Han Rong , Lian Jiaqi , Zhao Xinmin , Ji Xiang , Zhang Feng 
Published: May 2019

AbstractInteractions between nanoparticles (NPs) and biomolecules, especially proteins, have attracted increasing attention. Photoresponsive proteins have shown high potential for optogenetic research. The combination between optogenetics and nanotechnology will bring a new biological era in which photoresponsive proteins will inevitably encounter NPs, therefore their interactions will be a key point to investigate. Here, we have systematically studied the interactions between a photoresponsive protein (called phycocyanin, PC) and a typical kind of amphiphilic polymer‐coated gold NPs (AP–AuNPs) using fluorescence quenching methods. The results showed that the binding constant between PCs and AP–AuNPs is 4.427 × 106 M–1 with a positive cooperativity, and the robust affinity was hydrophobic interaction driven mortise–tenon conjugation, which could even resist gel electrophoresis. These results could also shed light on potential designs for building up artificial protein–NP light‐harvesting systems.
Impact of automated response systems on in‐class cell phone use
Authors: Moorleghen Dylan M. , Oli Naresh , Crowe Alison J. , Liepkalns Justine S. , Self Casey J. , Doherty Jennifer H. 
Published: May 2019

AbstractCell phones have long been known as a potential distraction from attention intensive activities such as studying and driving. Many, however, are developing the cell phone as a powerful tool to augment some of these same activities. Audience response systems (ARSs) are a type of teaching tool that allows educators to poll audience members in real time. Increasingly, cell phones are being integrated into ARSs to make them more versatile and affordable. As cell phones and other personal electronic devices (tablets, laptops) are becoming more common classroom learning tools, we sought to explore how student cell phone use is impacted by this change. Additionally, we studied how a student's seat location and how the time during a term impacts students' cell phone use. To measure student cell phone use in lecture, we observed introductory biology classes at the University of Washington and recorded when students' cell phones were visible. We found that students sitting in the back of the room showed an increased likelihood of having a cell phone out. However contrary to our expectations, students using personal device (cell phone) based polling technology were no more likely to be using cell phones during lecture than their peers using traditional ARSs. Our results suggest that the downsides to using cell phones as teaching tools may be limited. © 2019 The International Union of Biochemistry and Molecular Biology, 47(5):538–546, 2019.
Cordycepin‐induced unfolded protein response‐dependent cell death, and AKT/MAPK‐mediated drug resistance in mouse testicular tumor cells
Authors: Chang Ming‐Min , Pan Bo‐Syong , Wang Chia‐Yih , Huang Bu‐Miin 
Published: May 2019

AbstractTesticular cancer is the most commonly diagnosed cancer in men at 15‐44 years of age, and radical orchidectomy combined with chemotherapy is currently considered as the standard treatment. However, drugs resistance and side effects that impact the quality of life for patients with testicular cancer have not been markedly improved in recent decades. In this study, we characterized the pharmacological exacerbation of the unfolded protein response (UPR), which is an effective approach to kill testicular cancer cells, by carrying out a clustering analysis of mRNA expression profiles and the immunobloting examination of cordycepin‐treated MA‐10 cells. The UPR is executed in response to endoplasmic reticulum stress to complement by an apoptotic response if the defect cannot be resolved. Results showed that cordycepin significantly modulated FoxO/P15/P27, PERK‐eIF2α (apoptotic), and the IRE1‐XBP1 (adaptive) UPR pathways. Interestingly, a fraction of MA‐10 cells survived after cordycepin treatment, the AKT, LC3 I/II, and MAPK signaling pathways were highly induced in attached cells as compared to the suspended cells, illustrating the drug resistance to cordycepin via activating AKT and MAPK pathways in MA‐10 cells. In summary, PERK‐eIF2α signaling pathway is required for pro‐apoptotic UPR in MA‐10 cell death following cordycepin treatment, suggesting a potential therapeutic application in treating testicular cancer. However, activation of AKT and MAPK pathways could possibly result in drug resistance to cordycepin in MA‐10 cells.
Conjugated‐Polymer‐Based Nanoparticles with Efficient NIR‐II Fluorescent, Photoacoustic and Photothermal Performance
Authors: Miao Yawei , Gu Chuantao , Yu Bing , Zhu Yaowei , Zou Wentao , Shen Youqing , Cong Hailin 
Published: May 2019

AbstractFluorescence imaging (FI) and photoacoustic imaging (PA) play important roles in the real‐time assessment of cell‐based therapies. However, the limitations of conventional organic fluorescence contrast agents and the narrow range of the emission wavelength in the first near‐infrared (NIR‐I) window (750–900 nm) hamper applications of fluorescence imaging in living subjects. Herein, we report the design and synthesis of a short‐wave infrared FI contrast agent and PA contrast agent based on a conjugated polymer—poly{2,5‐bis[(5‐thiophen‐2‐yl)methylene]‐3,6‐bis(2‐octyldodecyl)‐2,5‐dihydropyrazine}—and its use to construct multifunctional nanoparticles to simplify photothermal therapy.
Reirradiation of pulmonary artery intimal sarcoma: A case report
Authors: Chiola Ilaria , Belgioia Liliana , Vaccara Elena M. L. , Gusinu Marco , Corvò Renzo 
Published: May 2019

AbstractWe report here the case of a patient with 4 years long‐term survival after treatment with surgery, chemotherapy, and radiotherapy with good local control. This case highlights the possible role of radiation therapy in this tumor.
Triggering Tautomerization of Curcumin by Confinement into Liposomes
Authors: Girardon Maxime , Parant Stéphane , Monari Antonio , Dehez François , Chipot Christophe , Rogalska Ewa , Canilho Nadia , Pasc Andreea 
Published: May 2019

AbstractAlthough solvent polarity, pH and temperature have been reported to affect the keto‐enol equilibrium of curcumin, the synergistic effect of concentration and confinement is demonstrated for the first time herein. To this end, curcumin was encapsulated into vesicles of soy lecithin of about 100 nm in diameter. The keto form is favoured in the dilute regime (up to 2 μM). Above this concentration, tautomerization is shifted towards the enol form, as shown by fluorescence and compression isotherm studies. Moreover, molecular modeling and free‐energy profiles, together with simulation of the optical properties of the curcumin isomers, allowed us to dissect the interaction of the keto and enol forms with a model membrane and confirm the concentration‐triggered tautomerization of curcumin under confinement.
Plasma levels of von Willebrand factor in type 2 diabetes patients with and without cardiovascular diseases: A meta‐analysis
Authors: Peng Xun , Wang Xia , Fan Mengge , Zhao Junyu , Lin Liao , Liu Ju 
Published: May 2019

SummaryChronic vascular complications are the major causes of death and disability of type 2 diabetes mellitus (T2DM) patients. von Willebrand factor (vWF) is involved in pathogenesis of cardiovascular diseases (CVD). Previous studies showed elevated plasma levels of vWF in T2DM patients with CVD, but the association has not been validated. The aim of this meta‐analysis was to compare plasma levels of vWF in T2DM patients with and without CVD. We performed a meta‐analysis based on published case‐control studies of vWF in T2DM patients with and without CVD indexed in PubMed and other databases updated to April 2018. After independently assessing methodological quality and extracting data, 9 eligible studies were obtained including 576 cases and 632 controls. The standard mean difference (SMD) and 95% confidence intervals (95% CI) were calculated using random‐effects model. Meta‐analysis showed that plasma level of vWF was significantly higher in T2DM patients with CVD than T2DM patients without CVD (SMD = 0.61; 95% CI, 0.32‐0.90; P < .00001). Subgroup and sensitivity analyses confirmed the robustness of the results. Plasma levels of vWF are significantly elevated in patients with T2DM complicated by CVD. This study helps further characterize the prognostic value of vWF for cardiovascular complications in T2DM patients.
Ecosystem services provided by bromeliad plants: A systematic review
Authors: Ladino Geraldine , Ospina‐Bautista Fabiola , Estévez Varón Jaime , Jerabkova Lucie , Kratina Pavel 
Published: May 2019

AbstractThe unprecedented loss of biological diversity has negative impacts on ecosystems and the associated benefits which they provide to humans. Bromeliads have high diversity throughout the Neotropics, but they have been negatively affected by habitat loss and fragmentation, climate change, invasive species, and commercialization for ornamental purpose. These plants provide direct benefits to the human society, and they also form microecosystems in which accumulated water and nutrients support the communities of aquatic and terrestrial species, thus maintaining local diversity. We performed a systematic review of the contribution of bromeliads to ecosystem services across their native geographical distribution. We showed that bromeliads provide a range of ecosystem services such as maintenance of biodiversity, community structure, nutrient cycling, and the provisioning of food and water. Moreover, bromeliads can regulate the spread of diseases, and water and carbon cycling, and they have the potential to become important sources of chemical and pharmaceutical products. The majority of this research was performed in Brazil, but future research from other Neotropical countries with a high diversity of bromeliads would fill the current knowledge gaps and increase the generality of these findings. This systematic review identified that future research should focus on provisioning, regulating, and cultural services that have been currently overlooked. This would enhance our understanding of how bromeliad diversity contributes to human welfare, and the negative consequences that loss of bromeliad plants can have on communities of other species and the healthy functioning of the entire ecosystems.
Biomarker guidance allows a more personalized allocation of patients for remote patient management in heart failure: results from the TIM‐HF2 trial
Authors: Möckel Martin , Koehler Kerstin , Anker Stefan D. , Vollert Jörn , Moeller Volker , Koehler Magdalena , Gehrig Stefan , Wiemer Jan C. , von Haehling Stephan , Koehler Friedrich 
Published: May 2019

AimsThe TIM‐HF2 study showed less days lost due to unplanned cardiovascular hospitalization or all‐cause death and improved survival in patients randomly assigned to remote patient management (RPM) instead of standard of care.Methods and resultsThis substudy explored whether the biomarkers mid‐regional pro‐adrenomedullin (MR‐proADM) and N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP) could be used to identify low‐risk patients unlikely to benefit from RPM, thereby allowing more efficient allocation of the intervention. For 1538 patients of the trial (median age 73 years, interquartile range 64–78 years, 30% female), baseline biomarkers were used to select subpopulations recommended for RPM with various safety endpoints (100%, 98%, 95% sensitivity), and efficacy of RPM was assessed. Both biomarkers were strongly associated with events. The primary endpoint of lost days increased from 1.0% (1.4%) in the lowest to 17.3% (17.6%) in the highest quintile of NT‐proBNP (MR‐proADM). After combining biomarkers to identify patients recommended for RPM with 95% sensitivity, in the most efficient scenario (excluding 27% of patients; NT‐proBNP < 413.7 pg/mL and MR‐proADM < 0.75 nmol/L), the effect of RPM on patients was highly similar to the original trial (ratio of lost days: 0.78, hazard ratio for all‐cause death: 0.68). Number needed to treat for all‐cause death was lowered from 28 to 21. Rates of emergencies and telemedical efforts were significantly lower among patients not recommended for RPM. Biomarker guidance would have saved about 150 h effort/year per 100 patients of the eligible population.ConclusionsThe combined use of MR‐proADM and NT‐proBNP may allow safe, more precise, effective and cost‐saving allocation of patients with heart failure to RPM and warrants further prospective studies.
A new approach to forecasting intermittent demand based on the mixed zero‐truncated Poisson model
Authors: Jiang Aiping , Tam Kwok Leung , Guo Xiaoyun , Zhang Yufeng 
Published: May 2019

AbstractThis paper proposes a new approach to forecasting intermittent demand by considering the effects of external factors. We classify intermittent demand data into two parts—zero value and nonzero value—and fit nonzero values into a mixed zero‐truncated Poisson model. All the parameters in this model are obtained by an EM algorithm, which regards external factors as independent variables of a logistic regression model and log‐linear regression model. We then calculate the probability of occurrence of zero value at each period and predict demand occurrence by comparing it with critical value. When demand occurs, we use the weighted average of the mixed zero‐truncated Poisson model as predicted nonzero demands, which are combined with predicted demand occurrences to form the final forecasting demand series. Two performance measures are developed to assess the forecasting methods. By presenting a case study of electric power material from the State Grid Shanghai Electric Power Company in China, we show that our approach provides greater accuracy in forecasting than the Poisson model, the hurdle shifted Poisson model, the hurdle Poisson model, and Croston's method.
Freezing point temperature is in favor of not‐from‐concentrate apple juice storage
Authors: Gou Xiaoju , Tian You , Yang Xi , Sun Lijun , Guo Yurong 
Published: May 2019

AbstractThe short storage period is still a problem hindering the promotion of not‐from‐concentrate (NFC) apple juice, despite the fact it possesses higher nutritional value and more attractive taste compared with its concentrated counterparts. In this study, we compared the effects of temperature range including room temperature (25°C), refrigerator temperature (4°C), freezing point temperature (−1.5°C), and frozen temperature (−18°C), respectively, on the quality of NFC apple juices during a long storage period (150 days). The results suggested that all the juices exhibited good safety during the storage, and the juice stored at −1.5°C possessed higher polyphenol contents, physicochemical properties, less color alteration, and less loss of aroma and taste than 25 and 4°C. Besides, although an exceedingly low temperature (−18°C) could greatly retard the juice deterioration, the loss of aroma and taste was significant. Overall, our results indicated that the NFC juice was most favored by storage at freezing point temperature (−1.5°C), with the highest similarity to the freshly squeezed apple juice.
A comparison of two workflows for regulome and transcriptome‐based prioritization of genetic variants associated with myocardial mass
Authors: Manduchi Elisabetta , Hemerich Daiane , van Setten Jessica , Tragante Vinicius , Harakalova Magdalena , Pei Jiayi , Williams Scott M. , van der Harst Pim , Asselbergs Folkert W. , Moore Jason H. 
Published: May 2019

AbstractA typical task arising from main effect analyses in a Genome Wide Association Study (GWAS) is to identify single nucleotide polymorphisms (SNPs), in linkage disequilibrium with the observed signals, that are likely causal variants and the affected genes. The affected genes may not be those closest to associating SNPs. Functional genomics data from relevant tissues are believed to be helpful in selecting likely causal SNPs and interpreting implicated biological mechanisms, ultimately facilitating prevention and treatment in the case of a disease trait. These data are typically used post GWAS analyses to fine‐map the statistically significant signals identified agnostically by testing all SNPs and applying a multiple testing correction. The number of tested SNPs is typically in the millions, so the multiple testing burden is high. Motivated by this, in this study we investigated an alternative workflow, which consists in utilizing the available functional genomics data as a first step to reduce the number of SNPs tested for association. We analyzed GWAS on electrocardiographic QRS duration using these two workflows. The alternative workflow identified more SNPs, including some residing in loci not discovered with the typical workflow. Moreover, the latter are corroborated by other reports on QRS duration. This indicates the potential value of incorporating functional genomics information at the onset in GWAS analyses.
An 11‐lncRNA expression could be potential prognostic biomarkers in head and neck squamous cell carcinoma
Authors: Xu Qingyong , Yin Hang , Ao Haijiao , Leng Xue , Liu Mingdong , Liu Yang , Ma Jianqun , Wang Xiaoyuan 
Published: May 2019

AbstractThe aim of our study is to construct the competing endogenous RNA (ceRNA) network of head and neck squamous cell carcinoma (HNSCC) and identify key long noncoding RNAs (lncRNAs) to predict prognosis. The genes whose expression were differentially in HNSCC and normal tissues were explored by the Cancer Genome Atlas database. The ceRNA network was constructed by the Cytoscape software. The lncRNAs which could estimate the overall survival were explored from Cox proportional hazards regression. There are 1997, 589, and 82 mRNAs, lncRNAs, and miRNAs whose expression were statistically significant different, respectively. Then, the network between miRNA and mRNA or miRNA and lncRNA was constructed by miRcode, miRDB, TargetScan, and miRanda. Five mRNAs, 10 lncRNAs, and 3 miRNAs were associated with overall survival. Then, 11‐lncRNAs were found to be prognostic factors. Therefore, our research analyzed the potential signature of novel 11‐lncRNA as candidate prognostic biomarker from the ceRNA network for patients with HNSCC.