bluuebunny/crossref_metadata_2025_split huggingface dataset:
Precise capture and dynamic relocation of nanoparticulate biomolecules through dielectrophoretic enhancement by vertical nanogap architectures
Authors: Yu Eui-Sang , Lee Hyojin , Lee Sun-Mi , Kim Jiwon , Kim Taehyun , Lee Jongsu , Kim Chulki , Seo Minah , Kim Jae Hun , Byun Young Tae , Park Seung-Chul , Lee Seung-Yeol , Lee Sin-Doo , Ryu Yong-Sang 
Published: June 2020

AbstractToward the development of surface-sensitive analytical techniques for biosensors and diagnostic biochip assays, a local integration of low-concentration target materials into the sensing region of interest is essential to improve the sensitivity and reliability of the devices. As a result, the dynamic process of sorting and accurate positioning the nanoparticulate biomolecules within pre-defined micro/nanostructures is critical, however, it remains a huge hurdle for the realization of practical surface-sensitive biosensors and biochips. A scalable, massive, and non-destructive trapping methodology based on dielectrophoretic forces is highly demanded for assembling nanoparticles and biosensing tools. Herein, we propose a vertical nanogap architecture with an electrode-insulator-electrode stack structure, facilitating the generation of strong dielectrophoretic forces at low voltages, to precisely capture and spatiotemporally manipulate nanoparticles and molecular assemblies, including lipid vesicles and amyloid-beta protofibrils/oligomers. Our vertical nanogap platform, allowing low-voltage nanoparticle captures on optical metasurface designs, provides new opportunities for constructing advanced surface-sensitive optoelectronic sensors.
Structural and functional evidence of bacterial antiphage protection by Thoeris defense system via NAD+ degradation
Authors: Ka Donghyun , Oh Hyejin , Park Eunyoung , Kim Jeong-Han , Bae Euiyoung 
Published: June 2020

AbstractThe intense arms race between bacteria and phages has led to the development of diverse antiphage defense systems in bacteria. Unlike well-known restriction-modification and CRISPR-Cas systems, recently discovered systems are poorly characterized. One such system is the Thoeris defense system, which consists of two genes, thsA and thsB. Here, we report structural and functional analyses of ThsA and ThsB. ThsA exhibits robust NAD+ cleavage activity and a two-domain architecture containing sirtuin-like and SLOG-like domains. Mutation analysis suggests that NAD+ cleavage is linked to the antiphage function of Thoeris. ThsB exhibits a structural resemblance to TIR domain proteins such as nucleotide hydrolases and Toll-like receptors, but no enzymatic activity is detected in our in vitro assays. These results further our understanding of the molecular mechanism underlying the Thoeris defense system, highlighting a unique strategy for bacterial antiphage resistance via NAD+ degradation.
Specific Electrogram Characteristics Identify the Extra-Pulmonary Vein Arrhythmogenic Sources of Persistent Atrial Fibrillation – Characterization of the Arrhythmogenic Electrogram Patterns During Atrial Fibrillation and Sinus Rhythm
Authors: Jadidi Amir , Nothstein Mark , Chen Juan , Lehrmann Heiko , Dössel Olaf , Allgeier Jürgen , Trenk Dietmar , Neumann Franz-Josef , Loewe Axel , Müller-Edenborn Björn , Arentz Thomas 
Published: June 2020

AbstractIdentification of atrial sites that perpetuate atrial fibrillation (AF), and ablation thereof terminates AF, is challenging. We hypothesized that specific electrogram (EGM) characteristics identify AF-termination sites (AFTS). Twenty-one patients in whom low-voltage-guided ablation after pulmonary vein isolation terminated clinical persistent AF were included. Patients were included if short RF-delivery for <8sec at a given atrial site was associated with acute termination of clinical persistent AF. EGM-characteristics at 21 AFTS, 105 targeted sites without termination and 105 non-targeted control sites were analyzed. Alteration of EGM-characteristics by local fibrosis was evaluated in a three-dimensional high resolution (100 µm)-computational AF model. AFTS demonstrated lower EGM-voltage, higher EGM-cycle-length-coverage, shorter AF-cycle-length and higher pattern consistency than control sites (0.49 ± 0.39 mV vs. 0.83 ± 0.76 mV, p < 0.0001; 79 ± 16% vs. 59 ± 22%, p = 0.0022; 173 ± 49 ms vs. 198 ± 34 ms, p = 0.047; 80% vs. 30%, p < 0.01). Among targeted sites, AFTS had higher EGM-cycle-length coverage, shorter local AF-cycle-length and higher pattern consistency than targeted sites without AF-termination (79 ± 16% vs. 63 ± 23%, p = 0.02; 173 ± 49 ms vs. 210 ± 44 ms, p = 0.002; 80% vs. 40%, p = 0.01). Low voltage (0.52 ± 0.3 mV) fractionated EGMs (79 ± 24 ms) with delayed components in sinus rhythm (‘atrial late potentials’, respectively ‘ALP’) were observed at 71% of AFTS. EGMs recorded from fibrotic areas in computational models demonstrated comparable EGM-characteristics both in simulated AF and sinus rhythm. AFTS may therefore be identified by locally consistent, fractionated low-voltage EGMs with high cycle-length-coverage and rapid activity in AF, with low-voltage, fractionated EGMs with delayed components/ ‘atrial late potentials’ (ALP) persisting in sinus rhythm.
Statistical analysis of longitudinal data on tumour growth in mice experiments
Authors: Zavrakidis Ioannis , Jóźwiak Katarzyna , Hauptmann Michael 
Published: June 2020

AbstractWe consider mice experiments where tumour cells are injected so that a tumour starts to grow. When the tumour reaches a certain volume, mice are randomized into treatment groups. Tumour volume is measured repeatedly until the mouse dies or is sacrificed. Tumour growth rates are compared between groups. We propose and evaluate linear regression for analysis accounting for the correlation among repeated measurements per mouse. More specifically, we examined five models with three different variance-covariance structures in order to recommend the least complex method for small to moderate sample sizes encountered in animal experiments. We performed a simulation study based on data from three previous experiments to investigate the properties of estimates of the difference between treatment groups. Models were estimated via marginal modelling using generalized least squares and restricted maximum likelihood estimation. A model with an autoregressive (AR-1) covariance structure was efficient and unbiased retaining nominal coverage and type I error when the AR-1 variance-covariance matrix correctly specified the association between repeated measurements. When the variance-covariance was misspecified, that model was still unbiased but the type I error and the coverage rates were affected depending on the degree of misspecification. A linear regression model with an autoregressive (AR-1) covariance structure is an adequate model to analyse experiments that compare tumour growth rates between treatment groups.
Vasopressin receptor 2 mutations in the nephrogenic syndrome of inappropriate antidiuresis show different mechanisms of constitutive activation for G protein coupled receptors
Authors: Vezzi Vanessa , Ambrosio Caterina , Grò Maria Cristina , Molinari Paola , Süral Gökçe , Costa Tommaso , Onaran H. Ongun , Cotecchia Susanna 
Published: June 2020

AbstractVasopressin receptor 2 (V2R) mutations causing the nephrogenic syndrome of inappropriate antidiuresis (NSIAD) can generate two constitutively active receptor phenotypes. One type results from residue substitutions in several V2R domains and is sensitive to vaptan inverse agonists. The other is only caused by Arg 137 replacements and is vaptan resistant. We compared constitutive and agonist-driven interactions of the vaptan-sensitive F229V and vaptan-resistant R137C/L V2R mutations with β-arrestin 1, β-arrestin 2, and Gαs, using null fibroblasts reconstituted with individual versions of the ablated transduction protein genes. F229V displayed very high level of constitutive activation for Gs but not for β-arrestins, and enhanced or normal responsiveness to agonists and inverse agonists. In contrast, R137C/L mutants exhibited maximal levels of constitutive activation for βarrestin 2 and Gs, minimal levels for β-arrestin 1, but a sharp decline of ligands sensitivity at all transducer interactions. The enhanced constitutive activity and reduced ligand sensitivity of R137 mutants on cAMP signaling persisted in cells lacking β-arrestins, indicating that these are intrinsic molecular properties of the mutations, not the consequence of altered receptor trafficking. The results suggest that the two groups of NSIAD mutations represent two distinct molecular mechanisms of constitutive activation in GPCRs.
Amyloid Aggregation of Insulin: An Interaction Study of Green Tea Constituents
Authors: Gancar Miroslav , Kurin Elena , Bednarikova Zuzana , Marek Jozef , Mucaji Pavel , Nagy Milan , Gazova Zuzana 
Published: June 2020

AbstractExogenous insulin, used as a therapeutic agent for diabetes, forms insoluble deposits containing amyloid fibrillar structures near the administration site. We have analyzed the in vitro anti-amyloid activity of four green tea constituents: (-)-epigallocatechin gallate (EGCG), (-)-epicatechin (EC), gallic acid (GA), caffeine (CF), and their equimolar mixtures. Regarding individually tested compounds, only EGCG inhibited the fibrillization process. The individual EC, GA, and CF molecules were ineffective. The presence of EGCG in equimolar combinations with GA, EC, or CF was required for the inhibitory activity of most mixtures. Molecular docking revealed that EGCG interacts with an essential amyloidogenic region of insulin chain B. Individually inactive GA had a potentiating effect on the activity of EGCG. In contrast, EC and CF had a negative impact on the activity of the mixtures. We have observed diverse morphology and the amount of insulin amyloid aggregates formed in the presence of studied compounds. The distinct types of amyloid aggregates created in vitro in the presence of EGCG and other green tea constituents were characterized. Results indicate that the biological activity of individual molecules is not directly applicable to the pooled samples effects prediction.
Discriminatory ability and prognostic evaluation of presepsin for sepsis-related acute respiratory distress syndrome
Authors: Zhao Jiangnan , Tan Yan , Wang Li , Shi Yi 
Published: June 2020

AbstractSepsis-related acute respiratory distress syndrome (ARDS) has worse clinical outcomes than non-sepsis-related ARDS. Presepsin is known to be elevated in sepsis, but little is known about its discriminatory ability and prognostic evaluation in patients with sepsis-related ARDS. This study was a multicenter prospective cohort study of 225 consecutive ARDS patients. Patients with sepsis-related ARDS had higher presepsin levels than patients with non-sepsis-related ARDS (P < 0.001). The area under the receiver operating characteristic (ROC) curve of presepsin (0.81) was significantly greater than that of PCT (0.62) in diagnosing sepsis-related ARDS (P = 0.001). Among patients with sepsis-related ARDS, presepsin levels were significantly higher in non-survivors than in survivors (P < 0.001). Presepsin was found to be an independent predictor of in-hospital mortality in sepsis-related ARDS. Based on ROC analysis, the addition of presepsin improved discrimination based on SOFA or APACHE II scores from 0.77 to 0.87 or 0.73 to 0.85 (all P < 0.05), respectively. The levels of plasma presepsin were positively correlated with disease severity, as determined by the SOFA score in the sepsis-related ARDS group (P < 0.001). Presepsin is a valuable biomarker for early stratification of sepsis-related ARDS. Higher plasma presepsin levels are associated with increased mortality in sepsis-related ARDS.
Expression profiling of small intestinal neuroendocrine tumors identified pathways and gene networks linked to tumorigenesis and metastasis
Authors: Wang Qiang , Yu Chaoran 
Published: June 2020

Abstract
Small intestinal neuroendocrine tumors (SI-NETs) remain the most common subset in gastrointestinal neuroendocrine tumors and featured by aggressiveness. However, the molecular feature of SI-NETs remains largely unclear with key genes and pathways yet to be identified. The gene expression profile GSE65286 was retrieved for analysis. Artificial neural networks (ANNs) were constructed for the hub genes network models. A total of 613 differentially expressed genes (DEGs) were identified between normal (N) and primary tumor (T) groups, whereas 61 DEGs were identified between T and liver metastases (LM) groups. The top Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways for the DEGs of N versus T were fat digestion and absorption pathway. For T versus LM the top KEGG pathways were complement and coagulation. In gene set enrichment analysis (GSEA), five gene sets, including Notch signaling, inflammatory response, coagulation, KRAS signaling, and allograft rejection were significantly enriched in the T group. The hub genes in the DEGs of T versus LM included albumin, fibrinogen gamma chain, alpha 2-HS glycoprotein, transferrin and GC, vitamin D binding protein. A distinct correlational alteration of hub genes was observed between T and LM groups. In ANN analysis, ALB and TF were the top predictors of metastasis. Moreover, the expression of ALB≤ showed the highest support to T whereas ALB&gt;15.97 supports LM. TF≤7.54 showed the highest negative correlation to the T. This bioinformatics analysis provided insights on potential key pathways and genes networks involved in SI-NETs and established an ANN-based hub gene model for metastatic prediction.
Screening for the Identification of Oral Language Difficulties in Brazilian Preschoolers: A Validation Study
Authors: Puglisi Marina L. , Blasi Helena F. , Snowling Margaret J. 
Published: June 2020

Purpose
This study aimed to develop and validate a screening questionnaire for the early identification of language difficulties in Brazilian Portuguese–speaking preschool children.

Method
The article is divided into two studies. In the first study, we reported the theoretical principles that guided the development of the Screening for Identification of Oral Language Difficulties by Preschool Teachers (SIOLD) and tested the validity of its structure. The psychometric properties of the SIOLD were tested using a sample of 754 children attending Year 1 of preschool. Thirty-two teachers coming from eight different schools completed individual questionnaires for all their students. Confirmatory factor analysis was used to assess the validity of the SIOLD. In the second study, we investigated the accuracy of the questionnaire for identifying children with oral language difficulties using a different sample of 100 preschool children. Using receiver operating characteristic and precision recall curves, we assessed the sensitivity and specificity of the SIOLD to identify children who showed impaired language performance in a short battery of tests.

Results
The SIOLD has been shown to be a valid and accurate questionnaire for assessing the form and content of oral language in preschool children. It showed good accuracy, with sensitivity ranging between .750 and .857 and specificity of .946 for the identification of language difficulties. Among the cases positively identified by the SIOLD as having language difficulties, 54.5% were true cases of language disorders, while 45.5% were false alarms. The combination of these findings shows that the SIOLD overpredicts positive cases but identifies most children with true language disorders and passes most children without language disorders, as required of a good screening test.

Conclusions
The questionnaire provides a useful tool for enabling Brazilian teachers to refer children with language difficulties to the speech-language services. The theoretical and clinical implications are discussed.
Die Replikationskrise in der Psychologie
Authors: Spitzer Markus W. H. , Spitzer Manfred 
Published: June 2020

ZUSAMMENFASSUNGWährend des letzten Jahrzehnts war die Replikationskrise eines der am meisten diskutierten Themen in der Psychologie. Doch wie konnte es überhaupt zu dieser Krise kommen, welche Studien sind von der Replikationskrise betroffen und welche Maßnahmen wurden bisher ergriffen, um dieser Krise zu begegnen? In dieser Übersicht werden eine Reihe von Problemen der bislang üblichen Methodik wissenschaftlichen Arbeitens beschrieben, klassische Beispiele von bekannten Studien, die nicht repliziert werden konnten, aufgelistet die Verwurzelung der Probleme in der gängigen Wissenschaftspraxis, wie sie sich in unserer Gesellschaft darstellt aufgezeigt und Änderungen im Wissenschaftsbetrieb der letzten Jahre beschrieben, die Abhilfe schaffen sollen. Die Weiterentwicklung der Wissenschaftskultur ist Teil des reflektierten wissenschaftlichen Arbeitens, wird sie doch von niemand anderem getragen als von angehenden und bereits praktizierenden Wissenschaftlern selbst.
Leberchirurgie – Setup, Port Placement, strukturierte OP-Schritte
Authors: Schmelzle Moritz , Schöning Wenzel , Pratschke Johann 
Published: June 2020

ZusammenfassungErfahrungen in der robotergestützten Leberchirurgie sind bisher auf wenige internationale Zentren begrenzt. Unter Chirurgen mit Erfahrung in der laparoskopischen und robotergestützten Leberchirurgie besteht Einigkeit, dass die Bedeutung robotergestützter Techniken in den kommenden Jahren deutlich zunehmen wird. Anhand eigener Zentrumserfahrungen im Rahmen der Etablierung unseres leberchirurgischen Roboterprogramms und durch den regen Austausch mit international führenden Kollegen haben wir an unserem Zentrum „Standard Operating Procedures“ etabliert, die wir in der vorliegenden Arbeit zusammengefasst haben.
Endoscopic ultrasound-guided tissue acquisition with or without macroscopic on-site evaluation: randomized controlled trial
Authors: Chong Charing C. N. , Lakhtakia Sundeep , Nguyen Nam , Hara Kazuo , Chan Wah Kheong , Puri Rajesh , Almadi Majid A. , Ang Tiing Leong , Kwek Andrew , Yasuda Ichiro , Doi Shinpei , Kida Mitsuhiro , Wang Hsiu-Po , Cheng Tsu-Yao , Jiang Qingwei , Yang Aiming , Chan Anthony W. H. , Chan Shannon , Tang Raymond , Iwashita Takuji , Teoh Anthony Y. B. 
Published: June 2020

AbstractBackground The use of macroscopic on-site evaluation (MOSE) to estimate the adequacy of a specimen for histological diagnosis during endoscopic ultrasound (EUS)-guided fine-needle tissue acquisition (FNTA) has recently been advocated. This study aimed to evaluate the diagnostic yield of MOSE compared with conventional EUS-FNTA without rapid on-site evaluation (ROSE).Methods This was an international, multicenter, prospective, randomized controlled study. After providing informed consent, consecutive adult patients referred for EUS-FNTA for solid lesions larger than 2 cm were randomized to a MOSE arm or to a conventional arm without ROSE. A designated cytopathologist from each center performed all cytopathological examinations for that center and was blinded to the randomization results. The primary outcome measure was the diagnostic yield, and the secondary outcomes included sensitivity, specificity, positive predictive value, negative predictive value, diagnostic accuracy, and the rate of procedure-related complications.Results 244 patients (122 conventional, 122 MOSE) were enrolled during the study period. No significant differences between the two arms were found in procedure time or rate of procedure-related adverse events. The diagnostic yield for the MOSE technique (92.6 %) was similar to that for the conventional technique (89.3 %; P  = 0.37), with significantly fewer passes made (median: conventional 3, MOSE 2; P  < 0.001).Conclusions EUS-FNTA with the MOSE technique provided a similar diagnostic yield to conventional EUS-FNTA technique in the absence of ROSE but with fewer passes. This technique can be used when ROSE is not available.
Endoscopic ultrasound-guided fine-needle aspiration for the diagnosis and grading of pancreatic neuroendocrine tumors: a retrospective analysis of 110 cases
Authors: Paiella Salvatore , Landoni Luca , Rota Roberta , Valenti Matteo , Elio Giovanni , Crinò Stefano Francesco , Manfrin Erminia , Parisi Alice , Cingarlini Sara , D’Onofrio Mirko , Scarpa Aldo , Lawlor Rita Teresa , Bernardoni Laura , Capelli Paola , Nessi Chiara , Miotto Marco , Gabbrielli Armando , Bassi Claudio , Salvia Roberto 
Published: June 2020

AbstractBackground Data on the reliability of the Ki-67 index and grading calculations from endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) of pancreatic neuroendocrine tumors (PanNETs) are controversial. We aimed to assess the accuracy of these data compared with histology.Methods Cytological analysis from EUS-FNA in patients with suspected PanNETs (n = 110) were compared with resection samples at a single institution. A minimum of 2000 cells were considered to be adequate for grading. Correlation and agreement between cytology and histology in grading and Ki-67 values, respectively, were investigated. Secondary outcomes included the diagnostic performance of EUS-FNA.Results EUS-FNA samples were adequate for PanNET diagnosis and PanNET grading in 98/110 (89.1 %) and 77/110 (70.0 %) patients, respectively; thus, 77 samples were adequate for comparing cytology vs. histology. There were 67 (62.0 %), 40 (36.4 %), and 1 (0.9 %) patients with a final diagnosis of G1, G2, and G3 tumors, respectively. EUS-FNA grading was concordant with surgical pathology in 81.8 % of patients; under- and overgrading occurred in 15.6 % and 2.6 %, respectively. The overall level of agreement for grading was moderate (Cohen’s κ = 0.59, 95 % confidence interval [CI] 0.34 – 0.78). Spearman’s rho for Ki-67 in tumors ≤ 20 mm and > 20 mm was strong and moderate, respectively (rho = 0.68, 95 %CI 0.47 – 0.83; rho = 0.59, 95 %CI 0.35 – 0.75). The Bland – Altman plot showed that the Ki-67 values were comparable and reproducible between the two measurements.Conclusions Although they were not available for a significant number of patients, grading and Ki-67 values from cytology correlated with histology moderately to strongly.
Evolution of a Cycloaddition–Rearrangement Approach to the Squalestatins: A Quarter-Century Odyssey
Authors: Hodgson David M. , Almohseni Hasanain A. A. 
Published: June 2020

The highs, lows, and diversions of a journey leading to two syntheses of 6,7-dideoxysqualestatin H5 is described. Both syntheses relied on highly diastereoselective n-alkylations of a tartrate acetonide enolate and subsequent oxidation–hydrolysis to provide an asymmetric entry to β-hydroxy-α-ketoester motifs. The latter were differentially elaborated to diazoketones which underwent stereo- and regioselective Rh(II)-catalysed cyclic carbonyl ylide formation–cycloaddition and then acid-catalysed transketalisation to generate the 2,8-dioxabicyclo[3.2.1]octane core of the squalestatins/zaragozic acids at the correct tricarboxylate oxidation level. The unsaturated side chain was either protected with a bromide substituent during the transketalisation or introduced afterwards by a stereoretentive Ni-catalyzed Csp3–Csp2 cross-electrophile coupling.1	Introduction 2	Racemic Model Studies to the Squalestatin/Zaragozic Acid Core3	Asymmetric Model Studies to a Keto α-Diazoester3.1	Dialkyl Squarate Desymmetrisation3.2	Tartrate Alkylation3.2.1	Further Studies on Seebach’s Alkylation Chemistry 4	Failure at the Penultimate Step to DDSQ 5	Second-Generation Approach to DDSQ: A Bromide Substituent Strategy 5.1	Stereoselective Routes to E-Alkenyl Halides via β-Oxido Phosphonium Ylides 5.2	Back to DDSQ Synthesis6	An Alternative Strategy to DDSQ: By Cross-Electrophile Coupling7	Alkene Ozonolysis in the Presence of Diazo Functionality: Accessing α-Ketoester Intermediates8	Summary