bluuebunny/crossref_metadata_2025_split huggingface dataset:
Growth Differentiation Factor 15 is a potential biomarker of therapeutic response for TK2 deficient myopathy
Authors: Dominguez-Gonzalez Cristina , Badosa Carmen , Madruga-Garrido Marcos , Martí Itxaso , Paradas Carmen , Ortez Carlos , Diaz-Manera Jordi , Berardo Andres , Alonso-Pérez Jorge , Trifunov Selena , Cuadras Daniel , Kalko Susana G. , Blázquez-Bermejo Cora , Cámara Yolanda , Martí Ramon , Mavillard Fabiola , Martin Miguel A. , Montoya Julio , Ruiz-Pesini Eduardo , Villarroya Joan , Montero Raquel , Villarroya Francesc , Artuch Rafael , Hirano Michio , Nascimento Andrés , Jimenez-Mallebrera Cecilia 
Published: June 2020

AbstractGDF-15 is a biomarker for mitochondrial diseases. We investigated the application of GDF-15 as biomarker of disease severity and response to deoxynucleoside treatment in patients with thymidine kinase 2 (TK2) deficiency and compared it to FGF-21. GDF-15 and FGF-21 were measured in serum from 24 patients with TK2 deficiency treated 1–49 months with oral deoxynucleosides. Patients were grouped according to age at treatment and biomarkers were analyzed at baseline and various time points after treatment initiation. GDF-15 was elevated on average 30-fold in children and 6-fold in adults before the start of treatment. There was a significant correlation between basal GDF-15 and severity based on pretreatment distance walked (6MWT) and weight (BMI). During treatment, GDF-15 significantly declined, and the decrease was accompanied by relevant clinical improvements. The decline was greater in the paediatric group, which included the most severe patients and showed the greatest clinical benefit, than in the adult patients. The decline of FGF-21 was less prominent and consistent. GDF-15 is a potential biomarker of severity and of therapeutic response for patients with TK2 deficiency. In addition, we show evidence of clinical benefit of deoxynucleoside treatment, especially when treatment is initiated at an early age.
Resilience of cactus pear genotypes in a tropical semi-arid region subject to climatic cultivation restriction
Authors: Edvan Ricardo Loiola , Mota Rute Ribeiro Marins , Dias-Silva Tairon Pannunzio , do Nascimento Romilda Rodrigues , de Sousa Sheila Vilarindo , da Silva Alex Lopes , Araújo Marcos Jácome de , Araújo Jucilene Silva 
Published: June 2020

AbstractThe cactus pear has demonstrated productive potential in arid and semi-arid regions due to its photosynthetic process of crassulacean acid metabolism. Thus, this study aimed to evaluate agronomic characteristics and chemical composition of three genotypes of cactus pear at different locations of a tropical semiarid region classified as non-suitable for cactus pear cultivation. A completely randomized design in a factorial arrangement (3 × 7) (three genotypes of cactus pear [Miúda, Baiana (Nopalea cochenillifera) and Orelha de Efefante Mexicana - OEM (Opuntia stricta)] and seven locations) was used. The climatic conditions characterized an environment that restricts the growth of cactus pear genotypes, mainly due to the air relative humidity values. All morphological characteristics of the cactus pear genotypes were influenced by the interaction genotype x location, with higher expression of the characteristics on the different genotypes under hot semi-arid climate and tropical wet and dry climate. An effect of the interaction genotype x location was observed (p < 0.05) on water use efficiency, water accumulation and carrying capacity, where the highest values were observed for genotype Baiana at location 1. Also, there was influence of the interaction genotype x location over the chemical composition of the cactus pear. The cultivation of cactus pear is recommended under restricted climatic conditions in semi-arid tropical regions, especially the genotype Baiana, based on growth factors, biomass production and chemical composition.
Albumin-neprilysin fusion protein: understanding stability using small angle X-ray scattering and molecular dynamic simulations
Authors: Kulakova Alina , Indrakumar Sowmya , Sønderby Tuelung Pernille , Mahapatra Sujata , Streicher Werner W. , Peters Günther H. J. , Harris Pernille 
Published: June 2020

AbstractFusion technology is widely used in protein-drug development to increase activity, stability, and bioavailability of protein therapeutics. Fusion proteins, like any other type of biopharmaceuticals, need to remain stable during production and storage. Due to the high complexity and additional intramolecular interactions, it is not possible to predict the behavior of fusion proteins based on the behavior the individual proteins. Therefore, understanding the stability of fusion proteins on the molecular level is crucial for the development of biopharmaceuticals. The current study on the albumin-neprilysin (HSA-NEP) fusion protein uses a combination of thermal and chemical unfolding with small angle X-ray scattering and molecular dynamics simulations to show a correlation between decreasing stability and increasing repulsive interactions, which is unusual for most biopharmaceuticals. It is also seen that HSA-NEP is not fully flexible: it is present in both compact and extended conformations. Additionally, the volume fraction of each conformation changes with pH. Finally, the presence of NaCl and arginine increases stability at pH 6.5, but decreases stability at pH 5.0.
Generation of intense and coherent sub-femtosecond X-ray pulses in electron storage rings
Authors: Hwang J.-G. , Schiwietz G. , Abo-Bakr M. , Atkinson T. , Ries M. , Goslawski P. , Klemz G. , Müller R. , Schälicke A. , Jankowiak A. 
Published: June 2020

AbstractTemporally short X-ray pulses are an indispensable tool for the study of electron transitions close to the Fermi energy and structural changes in molecules undergoing chemical reactions which take place on a time-scale of hundreds of femtoseconds. The time resolution of experiments at 3rdgeneration light sources which produce intense synchrotron radiation is limited fundamentally by the electron-bunch length in the range of tens of picoseconds. Here we propose a new scheme for the generation of intense and coherent sub-femtoseconds soft X-ray pulses in storage rings by applying the Echo-Enabled Harmonic Generation (EEHG) method. Many issues for obtaining the EEHG structure such as two modulators and a radiator are solved by a paradigm shift in an achromatic storage ring cell. Numerical demonstration of the feasibility of the scheme for the BESSY II beam parameters is presented.
Novel EGFP reporter cell and mouse models for sensitive imaging and quantification of exon skipping
Authors: Hara Yuko , Mizobe Yoshitaka , Inoue Yukiko U. , Hashimoto Yasumasa , Motohashi Norio , Masaki Yoshiaki , Seio Kohji , Takeda Shin’ichi , Nagata Tetsuya , Wood Matthew J. A. , Inoue Takayoshi , Aoki Yoshitsugu 
Published: June 2020

AbstractDuchenne muscular dystrophy (DMD) is a fatal X-linked disorder caused by nonsense or frameshift mutations in the DMD gene. Among various treatments available for DMD, antisense oligonucleotides (ASOs) mediated exon skipping is a promising therapeutic approach. For successful treatments, however, it is requisite to rigorously optimise oligonucleotide chemistries as well as chemical modifications of ASOs. To achieve this, here, we aim to develop a novel enhanced green fluorescence protein (EGFP)-based reporter assay system that allows us to perform efficient and high-throughput screenings for ASOs. We design a new expression vector with a CAG promoter to detect the EGFP fluorescence only when skipping of mdx-type exon 23 is induced by ASOs. Then, an accurate screening was successfully conducted in C57BL/6 primary myotubes using phosphorodiamidate morpholino oligomer or locked nucleic acids (LNA)/2′-OMe mixmers with different extent of LNA inclusion. We accordingly generated a novel transgenic mouse model with this EGFP expression vector (EGFP-mdx23 Tg). Finally, we confirmed that the EGFP-mdx23 Tg provided a highly sensitive platform to check the effectiveness as well as the biodistribution of ASOs for exon skipping therapy. Thus, the assay system provides a simple yet highly sensitive platform to optimise oligonucleotide chemistries as well as chemical modifications of ASOs.
Phosphorylation of the Anaphase Promoting Complex activator FZR1/CDH1 is required for Meiosis II entry in mouse male germ cell
Authors: Tanno Nobuhiro , Kuninaka Shinji , Fujimura Sayoko , Takemoto Kazumasa , Okamura Kaho , Takeda Naoki , Araki Kimi , Araki Masatake , Saya Hideyuki , Ishiguro Kei-ichiro 
Published: June 2020

AbstractFZR1/CDH1 is an activator of Anaphase promoting complex/Cyclosome (APC/C), best known for its role as E3 ubiquitin ligase that drives the cell cycle. APC/C activity is regulated by CDK-mediated phosphorylation of FZR1 during mitotic cell cycle. Although the critical role of FZR1 phosphorylation has been shown mainly in yeast and in vitro cell culture studies, its biological significance in mammalian tissues in vivo remained elusive. Here, we examined the in vivo role of FZR1 phosphorylation using a mouse model, in which non-phosphorylatable substitutions were introduced in the putative CDK-phosphorylation sites of FZR1. Although ablation of FZR1 phosphorylation did not show substantial consequences in mouse somatic tissues, it led to severe testicular defects resulting in male infertility. In the absence of FZR1 phosphorylation, male juvenile germ cells entered meiosis normally but failed to enter meiosis II or form differentiated spermatids. In aged testis, male mutant germ cells were overall abolished, showing Sertoli cell-only phenotype. In contrast, female mutants showed apparently normal progression of meiosis. The present study demonstrated that phosphorylation of FZR1 is required for temporal regulation of APC/C activity at meiosis II entry, and for maintenance of spermatogonia, which raised an insight into the sexual dimorphism of FZR1-regulation in germ cells.
Difference in Presence and Number of CD83+ Dendritic Cells in Patients with Ulcerative Colitis and Crohn’s Disease
Authors: Despalatović Bruna Rošić , Babić Marija , Bratanić Andre , Tonkić Ante , Vilović Katarina 
Published: June 2020

AbstractDifferent pathophysiological models provide insight into the important role of CD83+ dendritic cells (DCs) in the pathogenesis of Crohn’s disease (CD) and ulcerative colitis (UC). There were 154 subjects included in this study: 60 with UC, 19 with CD and 75 in the control group. Colonic biopsy was performed in all subjects. Specimens were incubated with a primary anti-CD83 antibody. Intraepithelial DCs per 100 enterocytes were counted. The results were analysed according to demographic data, type of IBD and histological inflammation pattern. The odds ratio for CD83+ DCs=0 in the UC group was 3.4 times higher than that in the control group (OR = 3.4; 95% CI: 1.63–7.14; p = 0.001), and the odds ratio for CD83+ DCs ≥1 in the CD group was 5.3 times higher than that in the UC group (OR = 5.3; 95% CI: 1.4–20.2; p = 0.014). The odds ratio for CD83+ DCs=0 in the acute inflammation group was 2.7 times higher than that in the group without inflammation (OR = 2.7; 95% CI: 1.2–5.9; p = 0.011). In the group of patients with CD and acute inflammation (n = 11), there was only one subject without CD83+ DCs (p = 0,024). These results suggest an association of CD83+ DCs with the type of IBD and the histological inflammation pattern.
The presence of dominant follicles and corpora lutea does not perturb response to controlled ovarian stimulation in random start protocols
Authors: Filippi Francesca , Somigliana Edgardo , Busnelli Andrea , Guarneri Cristina , Noli Stefania , Restelli Liliana , Vercellini Paolo 
Published: June 2020

AbstractThe advent of random start protocols to shorten the time needed to store oocytes in women with malignancies has represented an important improvement in the field of fertility preservation. However, Randomized Controlled Trials are difficult to implement in this area and available evidence that supports this approach remains modest. To shed more light on this issue, we compared the follicular development between the ovary carrying the dominant follicle or the corpus luteum and the contralateral resting ovary in 90 women who underwent random start controlled ovarian stimulation (COS). In fact, ovarian response did not differ between the two ovaries. Subgroup analyses according to the phase of the cycle at the initiation of COS, the type of malignancy, the use of letrozole and the magnitude of the ovarian response did not allow to identify any condition showing a difference in the follicular response between the active and the resting ovaries. In conclusion, follicular growth does not seem to be perturbed by the presence of a dominant follicle or a corpus luteum.
Traditional versus blended CPR training program: A randomized controlled non-inferiority study
Authors: Chien Cheng-Yu , Fang Shao-Yu , Tsai Li-Heng , Tsai Shang-Li , Chen Chen-Bin , Seak Chen-June , Weng Yi-Ming , Lin Chi-Chun , Chien Wei-Che , Huang Chien-Hsiung , Lin Cheng-Yu , Chaou Chung-Hsien , Liu Peng-Huei , Tseng Hsiao-Jung , Chen Jih-Chang , Peng Shu-Yuan , Cheng Tsung-Hsuan , Hsu Kuang-Hung , Ng Chip-Jin 
Published: June 2020

AbstractCardiopulmonary resuscitation (CPR) training and its quality are critical in improving the survival rate of cardiac arrest. This randomized controlled study investigated the efficacy of a newly developed CPR training program for the public in a Taiwanese setting. A total of 832 adults were randomized to either a traditional or blended (18-minute e-learning plus 30-minute hands-on) compression-only CPR training program. The primary outcome was compression depth. Secondary outcomes included CPR knowledge test, practical test, quality of CPR performance, and skill retention. The mean compression depth was 5.21 cm and 5.24 cm in the blended and traditional groups, respectively. The mean difference in compression depth between groups was −0.04 (95% confidence interval −0.13 to infinity), demonstrating that the blended CPR training program was non-inferior to the traditional CPR training program in compression depth after initial training. Secondary outcome results were comparable between groups. Although the mean compression depth and rate were guideline-compliant, only half of the compressions were delivered with adequate depth and rate in both groups. CPR knowledge and skill retained similarly in both groups at 6 and 12 months after training. The blended CPR training program was non-inferior to the traditional CPR training program. However, there is still room for improvement in optimizing initial skill performance as well as skill retention. Clinical Trial Registration: NCT03586752; www.clinicaltrial.gov
Clinicopathological analysis of T2-FLAIR mismatch sign in lower-grade gliomas
Authors: Deguchi Shoichi , Oishi Takuma , Mitsuya Koichi , Kakuda Yuko , Endo Masahiro , Sugino Takashi , Hayashi Nakamasa 
Published: June 2020

AbstractT2-FLAIR mismatch sign is known as a highly specific imaging marker of IDH-mutant astrocytomas. This study was intended to clarify what the T2-FLAIR mismatch sign represents by pathological analysis of lower-grade gliomas rediagnosed in accordance with the WHO 2016 classification. We retrospectively analyzed the records of 64 patients diagnosed with WHO grade II and III diffuse gliomas between June 2009 and November 2018. T2-FLAIR mismatch sign was found in 10 (45%) out of 22 patients with IDH-mutant astrocytoma, 1 (5%) out of 20 with oligodendroglioma, and 1 (5%) out of 22 with IDH-wild-type astrocytoma. T2-FLAIR mismatch sign as a marker of IDH-mutant astrocytomas showed positive predictive value of 83%. Among 22 patients with IDH-mutant astrocytomas, microcystic change was found in eight, of which seven showed T2-FLAIR mismatch sign. Microcystic change was significantly associated with T2-FLAIR mismatch sign (P < 0.01). From multi-sampling in a patient, abundant microcysts were observed upon HE staining of specimens from the T2-FLAIR mismatched region, while microcysts were hardly observed from the T2-FLAIR matched one. All three protoplasmic astrocytomas among our IDH-mutant astrocytomas presented T2-FLAIR mismatch sign. In conclusion, T2-FLAIR mismatch sign may reflect microcyst formation in IDH-mutant astrocytomas and be common in IDH-mutant protoplasmic astrocytoma.
Perceived Professional and Institutional Factors Influencing Clinical Adoption of Pharyngeal High-Resolution Manometry
Authors: Rogus-Pulia Nicole M. , Jones Corinne A. , Forgues Angela L. , Orne Jason , Macdonald Cameron L. , Connor Nadine P. , McCulloch Timothy M. 
Published: June 2020

Purpose
We assessed experienced clinicians' perceptions of benefits and drawbacks to the clinical adoption of pharyngeal high-resolution manometry (HRM). This article focuses on the professional and institutional factors that influence the clinical adoption of pharyngeal HRM by speech-language pathologists (SLPs).

Method
Two surveys (closed- and open-ended questions) and a series of focus groups were completed with SLP members of both the American Speech-Language-Hearing Association and the Dysphagia Research Society (DRS). Transcripts were inductively coded for emergent themes.

Results
Thirteen SLPs were recruited to attend focus group sessions at the American Speech-Language-Hearing Association. Eighty-seven SLPs responded to the DRS open-set response survey. Two additional focus groups of 11 SLPs were convened at the DRS meeting. Conventional content analysis revealed overall SLP enthusiasm for the clinical use of HRM, with some concerns about the technology adoption process. The following themes related to the professional and institutional factors influencing clinical adoption were identified: (a) scope of practice, (b) access, (c) clinical workflow, and (d) reimbursement.

Conclusion
These data serve to elucidate the most salient factors relating to the clinical adoption of pharyngeal HRM into routine speech-language pathology clinical practice. While enthusiasm exists, a variety of systems-level issues must be addressed to support this process.
Non‐isolated bidirectional DC–DC converters with multi‐converter functionality employing novel start‐up and mode transition techniques
Authors: Sharma Ambuj , Nag Soumya Shubhra , Bhuvaneswari Gurumoorthy , Veerachary Mummadi 
Published: June 2020

This work targets reducing the mode transition time drastically, for two of the bidirectional DC–DC converters (BDCs) employed in energy storage systems, simultaneously proposing a smooth start‐up process. Two different mode transition techniques are introduced for topology A (proposed) and topology B, respectively, whose transition times are much smaller than the existing transition techniques. Topologies A and B are capable of performing all basic converter operations, i.e. buck, boost, inverting buck–boost and non‐inverting buck–boost in bidirectional mode, which allows the operating voltage ranges of both V 1 and V 2 to be increased perceivably. Both topologies are compared based on mode transition methodology, stress on the converter switches, inductor size and rating. A start‐up technique is also advocated for both topologies so that the start‐up response could be smooth. Two 400 W BDCs are designed with voltage levels of 60 and 120 V and experimentally verified for efficient start‐up, mode transition and steady‐state operations. Both mode‐transition techniques proposed here, take 2 μs for the current reversal on the battery side from +5 to −5 A.
High step‐up dc–dc converter based on modified active switched‐inductor and switched‐capacitor cells
Authors: Melo de Andrade Jessika , Coelho Roberto Francisco , Lazzarin Telles Brunelli 
Published: June 2020

A new high gain step‐up dc–dc converter based on modified active switched‐inductor (MASL) and switched‐capacitor (SC) is proposed in this study. The proposed converter is based on the classical boost topology, in which the inductor is changed by the proposed MASL cell. This new cell allows the addition of more than two switched‐inductors (SLs) to the classical boost topology, which is the most significant limitation of conventional active SL. Additionally, in the proposed converter, the output capacitor is replaced by an SC cell, increasing still more the voltage gain of it, which can be higher than 20 without using transformers or coupled inductors, and with lower voltage stress on the semiconductors and high efficiency. The principle of operation, theoretical static and dynamic analysis, design methodology and comparison with other non‐isolated topologies present in the literature are approached in this study. The performance of the proposed converter is validated by interesting experimental results obtained from a 200 W prototype with an input voltage of 20 V, an output voltage of 400–600 V, switched frequency at 50 kHz and peak efficiency of 95%.
The soft excess of the NLS1 galaxy Mrk 359 studied with an XMM-Newton-NuSTAR monitoring campaign
Authors: Middei R. , Petrucci P.-O. , Bianchi S. , Ursini F. , Cappi M. , Clavel M. , De Rosa A. , Marinucci A. , Matt G. , Tortosa A. 
Published: June 2020

Context. Joint XMM-Newton and NuSTAR multiple exposures allow us to disentangle the different emission components of active galactic nuclei (AGNs) and to study the evolution of their different spectral features. In this work, we present the timing and spectral properties of five simultaneous XMM-NewtonandNuSTAR observations of the Narrow Line Seyfert 1 galaxy Mrk 359.
Aims. We aim to provide the first broadband spectral modeling of Mrk 359 describing its emission spectrum from the UV up to the hard X-rays.
Methods. We performed temporal and spectral data analysis, characterising the amplitude and spectral changes of the Mrk 359 time series and computing the 2–10 keV normalised excess variance. The spectral broadband modelling assumes the standard hot Comptonising corona and reflection component, while for the soft excess we tested two different models: a warm, optically thick Comptonising corona (the two-corona model) and a reflection model in which the soft-excess is the result of a blurred reflected continuum and line emission (the reflection model).
Results. High and low flux states were observed during the campaign. The former state has a softer spectral shape, while the latter shows a harder one. The photon index is in the 1.75–1.89 range, and only a lower limit to the hot-corona electron temperature can be found. A constant reflection component, likely associated with distant matter, is observed. Regarding the soft excess, we found that among the reflection models we tested, the one providing the better fit (reduced χ2 = 1.14) is the high-density one. However, a significantly better fit (reduced χ2 = 1.08) is found by modelling the soft excess with a warm Comptonisation model.
Conclusions. The present analysis suggests the two-corona model as the best scenario for the optical-UV to X-ray emission spectrum of Mrk 359.