bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tetrahydrobiopterin prevents chronic ischemia-related lower urinary tract dysfunction through the maintenance of nitric oxide bioavailability
Authors: Akaihata Hidenori , Hata Junya , Tanji Ryo , Honda-Takinami Ruriko , Matsuoka Kanako , Sato Yuichi , Kataoka Masao , Ogawa Soichiro , Kojima Yoshiyuki 
Published: November 2020

AbstractThis study aimed to investigate the influence of chronic ischemia on nitric oxide biosynthesis in the bladder and the effect of administering tetrahydrobiopterin (BH4), a cofactor for endothelial nitric oxide synthase (eNOS), on chronic ischemia-related lower urinary tract dysfunction (LUTD). This study divided male Sprague–Dawley rats into Control, chronic bladder ischemia (CBI) and CBI with oral BH4 supplementation (CBI/BH4) groups. In the CBI group, bladder capacity and bladder muscle strip contractility were significantly lower, and arterial wall was significantly thicker than in Controls. Significant improvements were seen in bladder capacity, muscle strip contractility and arterial wall thickening in the CBI/BH4 group as compared with the CBI group. Western blot analysis of bladder showed expressions of eNOS (p = 0.043), HIF-1α (p < 0.01) and dihydrofolate reductase (DHFR) (p < 0.01), which could regenerate BH4, were significantly higher in the CBI group than in Controls. In the CBI/BH4 group, HIF-1α (p = 0.012) and DHFR expressions (p = 0.018) were significantly decreased compared with the CBI group. Our results suggest that chronic ischemia increases eNOS and DHFR in the bladder to prevent atherosclerosis progression. However, DHFR could not synthesize sufficient BH4 relative to the increased eNOS, resulting in LUTD. BH4 supplementation protects lower urinary tract function by promoting eNOS activity.
Metabolic interaction between amino acid deprivation and cisplatin synergistically reduces phosphoribosyl-pyrophosphate and augments cisplatin cytotoxicity
Authors: Wahwah Nisreen , Dhar Debanjan , Chen Hui , Zhuang Shunhui , Chan Adriano , Casteel Darren E. , Kalyanaraman Hema , Pilz Renate B. , Boss Gerry R. 
Published: November 2020

AbstractCisplatin is a mainstay of cancer chemotherapy. It forms DNA adducts, thereby activating poly(ADP-ribose) polymerases (PARPs) to initiate DNA repair. The PARP substrate NAD+ is synthesized from 5-phosphoribose-1-pyrophosphate (PRPP), and we found that treating cells for 6 h with cisplatin reduced intracellular PRPP availability. The decrease in PRPP was likely from (1) increased PRPP consumption, because cisplatin increased protein PARylation and PARP1 shRNA knock-down returned PRPP towards normal, and (2) decreased intracellular phosphate, which down-regulated PRPP synthetase activity. Depriving cells of a single essential amino acid decreased PRPP synthetase activity with a half-life of ~ 8 h, and combining cisplatin and amino acid deprivation synergistically reduced intracellular PRPP. PRPP is a rate-limiting substrate for purine nucleotide synthesis, and cisplatin inhibited de novo purine synthesis and DNA synthesis, with amino acid deprivation augmenting cisplatin’s effects. Amino acid deprivation enhanced cisplatin’s cytotoxicity, increasing cellular apoptosis and DNA strand breaks in vitro, and intermittent deprivation of lysine combined with a sub-therapeutic dose of cisplatin inhibited growth of ectopic hepatomas in mice. Augmentation of cisplatin’s biochemical and cytotoxic effects by amino acid deprivation suggest that intermittent deprivation of an essential amino acid could allow dose reduction of cisplatin; this could reduce the drug’s side effects, and allow its use in cisplatin-resistant tumors.
The architecture of corneal stromal striae on optical coherence tomography and histology in an animal model and in humans
Authors: Napoli Pietro Emanuele , Nioi Matteo , d’Aloja Ernesto , Loy Francesco , Fossarello Maurizio 
Published: November 2020

AbstractThe purpose of this study was to use a portable optical coherence tomography (OCT) for characterization of corneal stromal striae (CSS) in an ovine animal model and human corneas with histological correlation, in order to evaluate their architectural pattern by image analysis. Forty-six eyes from female adult sheep (older than 2 years), and 12 human corneas, were included in our study. The eyes were examined in situ by a portable OCT, without enucleation. All OCT scans were performed immediately after death, and then the eyes were delivered to a qualified histology laboratory. In the ovine animal model, CSS were detected with OCT in 89.1% (41/46) of individual scans and in 93.4% (43/46) of histological slices. In human corneas, CSS were found in 58.3% (7/12) of cases. In both corneal types, CSS appeared as “V”- or “X”-shaped structures, with very similar angle values of 70.8° ± 4° on OCT images and 71° ± 4° on histological slices (p ≤ 0.01). Data analysis demonstrated an excellent degree of reproducibility and inter-rater reliability of measurements (p < 0.001). The present study demonstrated that by using a portable OCT device, CSS can be visualized in ovine and human corneas. This finding suggests their generalized presence in various mammals. The frequent observation, close to 60%, of such collagen texture in the corneal stroma, similar to a ‘truss bridge’ design, permits to presume that it plays an important structural role, aimed to distribute tensile and compressive forces in various directions, conferring resilience properties to the cornea.
The power struggle: assessing interacting global change stressors via experimental studies on sharks
Authors: Bouyoucos Ian A. , Watson Sue-Ann , Planes Serge , Simpfendorfer Colin A. , Schwieterman Gail D. , Whitney Nicholas M. , Rummer Jodie L. 
Published: November 2020

AbstractOcean warming and acidification act concurrently on marine ectotherms with the potential for detrimental, synergistic effects; yet, effects of these stressors remain understudied in large predatory fishes, including sharks. We tested for behavioural and physiological responses of blacktip reef shark (Carcharhinus melanopterus) neonates to climate change relevant changes in temperature (28 and 31 °C) and carbon dioxide partial pressures (pCO2; 650 and 1050 µatm) using a fully factorial design. Behavioural assays (lateralisation, activity level) were conducted upon 7–13 days of acclimation, and physiological assays (hypoxia tolerance, oxygen uptake rates, acid–base and haematological status) were conducted upon 14–17 days of acclimation. Haematocrit was higher in sharks acclimated to 31 °C than to 28 °C. Significant treatment effects were also detected for blood lactate and minimum oxygen uptake rate; although, these observations were not supported by adequate statistical power. Inter-individual variability was considerable for all measured traits, except for haematocrit. Moving forward, studies on similarly ‘hard-to-study’ species may account for large inter-individual variability by increasing replication, testing larger, yet ecologically relevant, differences in temperature and pCO2, and reducing measurement error. Robust experimental studies on elasmobranchs are critical to meaningfully assess the threat of global change stressors in these data-deficient species.
Investigation of COSMO-SAC model for solubility and cocrystal formation of pharmaceutical compounds
Authors: Mahmoudabadi Samane Zarei , Pazuki Gholamreza 
Published: November 2020

AbstractIn this study, a predictive model named COSMO-SAC was investigated in solid/liquid equilibria for pharmaceutical compounds. The examined properties were the solubility of drug in the pure and mixed solvents, octanol/water partition coefficient, and cocrystal formation. The results of the original COSMO-SAC model (COSMO-SAC (2002)) was compared with a semi-predictive model named Flory–Huggins model and a revised version of the COSMO-SAC (COSMO-SAC (2010)). The results indicated the acceptable accuracy of the COSMO-SAC (2002) in the considered scope. The results emphasized on the suitability of the COSMO-SAC model for simple molecules containing C, H, and O by covalent and hydrogen bonding interactions. Applicability of the COSMO-SAC for more complicated molecules made of various functional groups such as COO and COOH doubly requires more modification in the COSMO-SAC.
Synthesis and initial screening of lactate dehydrogenase inhibitor activity of 1,3-benzodioxole derivatives
Authors: Annas Dicky , Cheon Se-Yun , Yusuf Mohammad , Bae Sung-Jin , Ha Ki-Tae , Park Kang Hyun 
Published: November 2020

AbstractCancer is one of the main causes of mortality in the world. Many cancer cells produce ATP through high-level lactic acid fermentation catalyzed by lactate dehydrogenase (LDH), which converts pyruvic acid to lactic acid. LDH plays a dominant role in the Warburg effect, wherein aerobic glycolysis is favored over oxidative phosphorylation. Due to the high lactic acid production level in cancer cells, LDH-targeting could be a potential cancer treatment strategy. A few approaches, such as drug treatment, reportedly inhibited LDH activity. In this study, we describe new 1,3-benzodioxole derivatives that might be potential small molecule candidates for LDHA inhibition. The synthesis was carried out by trans-esterification between aryl ester and alcohol groups from piperonyl alcohol. Compounds 2 and 10 exhibited a selective LDHA IC50 value of 13.63 µM and 47.2 µM, respectively. Whereas only compound 10 showed significant cytotoxicity in several lines of cancer cells, especially in human pancreatic cancer PANC-1 cells. These synthesized compounds possess 2 aromatic rings and –CF3 moiety, which expectedly contributes to LDHA inhibition. The presented products have the potential to become a promising LDHA inhibitor drug candidate.
Foveal crack sign as a predictive biomarker for development of macular hole in fellow eyes of patients with full-thickness macular holes
Authors: Furashova Olga , Matthé Egbert 
Published: November 2020

AbstractTo investigate the prevalence and predictive value of the foveal crack sign (FCS) in fellow eyes of patients with full-thickness macular holes (FTMH) regarding future macular hole (MH) formation. In a retrospective observational case series, 113 fellow eyes of 113 patients with FTMH have been observed during a mean follow-up time of 21 months. According to baseline SD-OCT images, patients were divided into 4 separate groups: patients with FCS and vitreous adhesion, patients with FCS and vitreous detachment, patients without FCS with vitreous adhesion, patients without FCS with vitreous detachment. Progression rate to MH formation, predictive value of FCS and of vitreous interface status were calculated and compared across the four groups. FCS was observed in 19 of 113 fellow eyes (17%) of patients with FTMH, 10 of them with progression to MH during the mean follow up time of 21 months. 2 other eyes with progression to MH showed no FCS at baseline. Progression rate was shown to be 77% (10 of 13 eyes) in patients with FCS and vitreous adhesion, 0% (none of 6 eyes) in patients with FCS and vitreous detachment, 4% (2 of 48 eyes) in patients without FCS with vitreous adhesion, 0% (none of 46 eyes) in patients without FCS with vitreous detachment. FCS had sensitivity of 83.3% (95% CI 50.9–97.1%) and specificity of 91.1% (95% CI 83.3–95.6%) in predicting MH formation, positive predictive value of FCS was 52.6% (95% CI 29.5–74.8%) and negative predictive value 97.9% (95% CI 91.8–99.6%). Having simultaneously FCS and vitreous adhesion showed 83.3% (95% CI 50.9–97.1%) sensitivity and 97.1% (95% CI 91.1–99.2%) specificity in predicting macular hole formation; positive predictive value was 76.9% (95% CI 46.0–93.8%) and negative predictive value was 98.0% (95% CI 92.4–99.7%). Fellow eyes of patients with FTMH with foveal crack sign are at a very high risk (77%) of FTMH development, as long as posterior vitreous adhesion is present.
New insights into quetiapine metabolism using molecular networking
Authors: Le Daré Brendan , Ferron Pierre-Jean , Allard Pierre-Marie , Clément Bruno , Morel Isabelle , Gicquel Thomas 
Published: November 2020

AbstractMetabolism is involved in both pharmacology and toxicology of most xenobiotics including drugs. Yet, visualization tools facilitating metabolism exploration are still underused, despite the availibility of pertinent bioinformatics solutions. Since molecular networking appears as a suitable tool to explore structurally related molecules, we aimed to investigate its interest in in vitro metabolism exploration. Quetiapine, a widely prescribed antipsychotic drug, undergoes well-described extensive metabolism, and is therefore an ideal candidate for such a proof of concept. Quetiapine was incubated in metabolically competent human liver cell models (HepaRG) for different times (0 h, 3 h, 8 h, 24 h) with or without cytochrom P450 (CYP) inhibitor (ketoconazole as CYP3A4/5 inhibitor and quinidine as CYP2D6 inhibitor), in order to study its metabolism kinetic and pathways. HepaRG culture supernatants were analyzed on an ultra-high performance liquid chromatography coupled with tandem mass spectrometry (LC-HRMS/MS). Molecular networking approach on LC-HRMS/MS data allowed to quickly visualize the quetiapine metabolism kinetics and determine the major metabolic pathways (CYP3A4/5 and/or CYP2D6) involved in metabolite formation. In addition, two unknown putative metabolites have been detected. In vitro metabolite findings were confirmed in blood sample from a patient treated with quetiapine. This is the first report using LC-HRMS/MS untargeted screening and molecular networking to explore in vitro drug metabolism. Our data provide new evidences of the interest of molecular networking in drug metabolism exploration and allow our in vitro model consistency assessment.
Polymerization inspired synthesis of MnO@carbon nanowires with long cycling stability for lithium ion battery anodes: growth mechanism and electrochemical performance
Authors: Zhou Fang , Li Shuangfu , Han Kai , Li Yajuan , Liu You-Nian 
Published: November 2020

MnO@carbon (MnO@C) nanowires are synthesized via the polymerization inspired in situ growth of [Mn–NTA] (NTA = nitrilotriacetic acid) precursor nanowires with a subsequent heat treatment process.
Successful Implicit Vocabulary Intervention for Three Cantonese-Speaking Toddlers: A Replicated Single-Case Design
Authors: S.-Y. Ng Christine , Stokes Stephanie F. , Alt Mary 
Published: November 2020

Purpose
We report on a replicated single-case design study that measured the feasibility of an expressive vocabulary intervention for three Cantonese-speaking toddlers with small expressive lexicons relative to their age. The aim was to assess the cross-cultural and cross-linguistic feasibility of an intervention method developed for English-speaking children.

Method
A nonconcurrent multiple-baseline design was used with four baseline data points and 16 intervention sessions per participant. The intervention design incorporated implicit learning principles, high treatment dosage, and control of the phonological neighborhood density of the stimuli. The children (24–39 months) attended 7–9 weeks of twice weekly input-based treatment in which no explicit verbal production was required from the child. Each target word was provided as input a minimum of 64 times in at least two intervention sessions. Treatment feasibility was measured by comparison of how many of the target and control words the child produced across the intervention period, and parent-reported expressive vocabulary checklists were completed for comparison of pre- and postintervention child spoken vocabulary size. An omnibus effect size for the treatment effect of the number of target and control words produced across time was calculated using Kendall's Tau.

Results
There was a significant treatment effect for target words learned in intervention relative to baselines, and all children produced significantly more target than control words across the intervention period. The effect of phonological neighborhood density on expressive word production could not be evaluated because two of the three children learned all target words.

Conclusion
The results provide cross-cultural evidence of the feasibility of a model of intervention that incorporated a high-dosage, cross-situational statistical learning paradigm to teach spoken word production to children with small expressive lexicons.
Analysis of Language Errors in Speakers Who Are Bilingual Under Quiet and Background Noise Conditions
Authors: Barbosa Bruna A. , Coles-White D'Jaris , Regal Darah , Kijai Jimmy 
Published: November 2020

Purpose
This study discusses the ways in which the presence of background noise may adversely affect bilingual students' ability to repeat speech, specifically, whether the presence of background noise increases lexical, grammatical, omission, and other errors on the AzBio Sentence Test.

Method
Participants consisted of 15 monolingual English (first language) speakers and 41 bilingual (second language [L2]) speakers from Spanish, Portuguese, and Korean language groups, ranging from students who learned English after the age of 4 years to adulthood. Participants completed the AzBio Sentence Test in both quiet and background noise environments. A language analysis was conducted, and errors were classified under categories of lexical, grammatical, omissions, and other.

Results
The results of this study show that L2 speakers made more lexical, grammatical, omissions, and other errors than first language speakers on the AzBio Sentence Test. In background noise, all bilingual language groups made more errors than monolinguals. Portuguese speakers notably made more omissions than other language groups. This study also shows that participants who were introduced to English at a younger age made fewer errors.

Conclusions
In conclusion, our results corroborate previous research, indicating that bilingual speakers have more difficulty accurately interpreting speech in the presence of background noise. These findings have implications for classroom instruction considering the statistically higher percentage of omissions made by L2 speakers.
Fast and Efficient Entropy Compression of ALICE Data using ANS Coding
Authors: Lettrich Michael 
Published: November 2020

In LHC Run 3, the upgraded ALICE detector will record 50 kHz Pb-Pb collisions using continuous readout. The resulting stream of raw data to be inspected increases to ~ 1 TB/s a hundredfold increase over Run 2 must be processed with a set of lossy and lossless compression and data reduction techniques to decrease the data rate to storage to 90 GB/s without affecting the physics.
This contribution focuses on lossless entropy coding for ALICE Run 3 data which is the final component in the compression stage. We analyze data from the ALICE TPC and point out the challenges imposed by the non-standard data with a patchy distribution and symbol sizes of up to 25 Bit. We then explain why rANS, a variant of Asymmetric Numeral System coders is suitable for compressing this data effectively. Finally we present first compression performance numbers and bandwidth measurements obtained from a prototype implementation and give an outlook for future developments.
The Heavy Photon Search (HPS) Software Environment
Authors: Graf Norman 
Published: November 2020

The Heavy Photon Search (HPS) is an experiment at the Thomas Jefferson National Accelerator Facility (JLab) designed to search for a hidden sector photon (A’) in fixed-target electro-production. It uses a silicon microstrip tracking and vertexing detector placed inside a dipole magnet to measure charged particle trajectories and a fast lead-tungstate crystal calorimeter located just downstream of the magnet to provide a trigger and to identify electromagnetic showers. The HPS experiment uses both invariant mass and secondary vertex signatures to search for the A’. The experimental collaboration is small and quite heterogeneous: it is composed of members of the nuclear physics as well as particle physics communities, from universities and national labs from around the US and Europe. Enabling such a disparate group to concentrate on the physics aspects of the experiment required that the software be easy to install and use, and having such limited manpower meant that existing solutions had to be exploited.HPS has successfully completed two engineering runs and completed its first physics run in the summer of 2019. We begin with an overview of the physics goals of the experiment followed by a short description of the detector design. We then describe the software tools used to design the detector layout and simulate the expected detector performance. Event reconstruction involving track, cluster and vertex finding and fitting for both simulated and real data was, to first order, adopted from existing software originally developed for Linear Collider studies. Bringing it all together into a cohesive whole involved the use of multiple software solutions with common interfaces.
Using Graph Databases
Authors: Hřivnáč Julius 
Published: November 2020

Data in High Energy Physics (HEP) usually consist of complext complex data structures stored in relational databases and files with internal schema. Such architecture exhibits many shortcomings, which could be fixed by migrating into Graph Database storage.
The paper describes basic principles of the Graph Database together with an overview of existing standards and implementations. The usefulness and usability are demonstrated using the concrete example of the Event Index of the ATLAS experiment at LHC in two approaches as the full storage (all data are in the Graph Database) and meta-storage (a layer of schema-less graph-like data implemented on top of more traditional storage). The usability, the interfaces with the surrounding framework and the performance of those solutions are discussed. The possible more general usefulness for generic experiments’ storage is also discussed.
Chopin Management System: improving Windows infrastructure monitoring and management
Authors: Pacuszka Marta , Bukowiec Sebastian , Puentes Esteban , Metral Guillaume 
Published: November 2020

CERN Windows server infrastructure consists of about 650 servers. The management and maintenance is often a challenging task as the data to be monitored is disparate and has to be collected from various sources. Currently, alarms are collected from the Microsoft System Center Operation Manager (SCOM) and many administrative actions are triggered through e-mails sent by various systems or scripts.
The objective of the Chopin Management System project is to maximize automation and facilitate the management of the infrastructure. The current status of the infrastructure, including essential health checks, is centralized and presented through a dashboard. The system collects information necessary for managing the infrastructure in the real-time, such as hardware configuration or Windows updates, and reacts to any change or failure instantly. As part of the system design, big data streaming technologies are employed in order to assure the scalability and fault-tolerance of the service, should the number of servers drastically grow. Server events are aggregated and processed in real-time through the use of these technologies, ensuring quick response to possible failures. This paper presents details of the architecture and design decisions taken in order to achieve a modern, maintainable and extensible system for Windows Server Infrastructure management at CERN.