bluuebunny/crossref_metadata_2025_split huggingface dataset:
Carboxymethyl Cellulose‐Coated Tacrolimus Nonspherical Microcrystals for Improved Therapeutic Efficacy of Dry Eye
Authors: Zhang Caijie , Zheng Yingying , Li Min , Zhang Zhongfang , Chang Lianqing , Ai Mingyue , Wang Jingjie , Zhao Shaozhen , Li Chen , Zhou Zhimin 
Published: June 2020

AbstractDry eye (DE) is a highly prevalent ocular surface disease which affects the quality of life and results in low working efficiency. Frequent instillation is required due to low bioavailability of conventional eye drops. The aim of this study is to develop a novel formulation of tacrolimus (TAC), routinely prescribed for DE, by combination of the microcrystal technology and layer‐by‐layer assembly. First, nonspherical tacrolimus microcrystals (TAC MCs) are synthesized by antisolvent‐induced precipitation. These TAC MCs are modified by alternate deposition of poly(allylamine hydrochloride) (PAH) and carboxymethyl cellulose (CMC) subsequently to obtain CMC‐coated TAC MCs (TAC‐(PAH/CMC)3). The resultant formulations are evaluated in vivo in a mouse DE model induced by an intelligently controlled environmental system. Compared with commercially available TAC eye drops and the TAC MCs counterpart, TAC‐(PAH/CMC)3 exhibits superior therapeutic performance with reduced drug instillation frequency, which is attributed to the nonspherical geometry of MCs, the lubricant, mucoadhesive effect of CMC, and the anti‐inflammatory function of TAC. Therefore, TAC‐(PAH/CMC)3 represents a better option for the management of DE.
Genomic insights into a plant growth‐promoting Pseudomonas koreensis strain with cyclic lipopeptide‐mediated antifungal activity
Authors: Gu Yilin , Ma Yi‐Nan , Wang Jing , Xia Zhenyuan , Wei Hai‐Lei 
Published: June 2020

AbstractStrain S150 was isolated from the tobacco rhizosphere as a plant growth‐promoting rhizobacterium. It increased plant fresh weight significantly and lateral root development, and it antagonized plant pathogenic fungi but not phytobacteria. Further tests showed that strain S150 solubilized organic phosphate and produced ammonia, siderophore, protease, amylase, and cellulase, but it did not produce indole‐3‐acetic acid. Using morphology, physiological characteristics, and multi‐locus sequence analysis, strain S150 was identified as Pseudomonas koreensis. The complete genome of strain S150 was sequenced, and it showed a single circular chromosome of 6,304,843 bp with a 61.09% G + C content. The bacterial genome contained 5,454 predicted genes that occupied 87.7% of the genome. Venn diagrams of the identified orthologous clusters of P. koreensis S150 with the other three sequenced P. koreensis strains revealed up to 4,167 homologous gene clusters that were shared among them, and 21 orthologous clusters were only present in the genome of strain S150. Genome mining of the bacterium P. koreensis S150 showed that the strain possessed 10 biosynthetic gene clusters for secondary metabolites, which included four clusters of non‐ribosomal peptide synthetases (NRPSs) involved in the biosynthesis of cyclic lipopeptides (CLPs). One of the NRPSs possibly encoded lokisin, a cyclic lipopeptide produced by fluorescent Pseudomonas. Genomic mutation of the lokA gene, which is one of the three structural NRPS genes for lokisin in strain S150, led to a deficiency in fungal antagonism that could be restored fully by gene complementation. The results suggested that P. koreensis S150 is a novel plant growth‐promoting agent with specific cyclic lipopeptides and contains a lokisin‐encoding gene cluster that is dominant against plant fungal pathogens.
RETRACTED: Haplotypic diversity and population genetic study of a population in Kashi region by 27 Y‐chromosomal short tandem repeat loci
Authors: Liu Yaoshun , Jin Xiaoyue , Guo Yuxi , Zhang Xingrui , Zhu Wu , Zhang Wenli , Mei Ting 
Published: June 2020

AbstractBackgroundY‐chromosomal short tandem repeats (Y‐STRs) have been certified to be the serviceable markers for some paternity cases in the last few years.MethodsWe presented the gene diversity, haplotypic diversity, and forensic statistical parameters of 340 unrelated Uighur males from Kashi region based on the 27 Y‐STRs. Genomic DNA was extracted from bloodstain samples using the Chelex‐100 method and amplified by Yfiler® Plus PCR Amplification kit.ResultsGene diversity values on the 27 Y‐STRs ranged from 0.4749 (at DYS437 locus) to 0.9416 (at DYS385a,b loci). According to forensic parameters of the 27 Y‐STR loci, 295 disparate haplotypes were acquired, 258 of which were unique. The haplotypic diversities and discrimination capacities at Yfiler plus 27 loci, Yfiler 17 loci, extended 11 loci, and minimal 9 loci were 0.9990 and 0.8676; 0.9961 and 0.6912; 0.9952 and 0.5941; and 0.9919 and 0.5676, respectively. Multidimensional scaling plot and neighbor‐joining tree between the studied Uighur group and 17 reference populations were conducted, and the obtained results indicated the Kashi Uighur group had the closer genetic relationships with Uighur groups living in different regions.ConclusionTo sum up, the present study may provide valuable population data and background information of Kashi Uighur group.
Retracted: LncRNA SNHG4 promotes osteosarcoma proliferation and migration by sponging miR‐377‐3p
Authors: Huang Yi‐Feng , Lu Lei , Shen Hai‐Liang , Lu Xin‐Xiang 
Published: June 2020

AbstractBackgroundLong non‐coding RNAs (lncRNAs) have been identified as crucial regulatory factors in the occurrence and progression of osteosarcoma.MethodsQuantitative real‐time polymerase chain reaction was used for detecting small nucleolar RNA host gene 4 (SNHG4) and miR‐377‐3p in osteosarcoma cells and tissues. Kaplan–Meier method was applied for evaluating the association between SNHG4 expression and the overall survival of osteosarcoma patients. CCK8, EdU, flow cytometry, and transwell assay were performed to examine the cell proliferation, apoptosis, cycle, and migration of osteosarcoma cells.ResultsIn our study, we found that lncRNA SNHG4 was highly expressed in osteosarcoma tissues and cell lines. Additionally, the SNHG4 expression was related to distant metastasis, TNM stage, and survival of osteosarcoma patients. Through SNHG4 knockdown, the proliferation of osteosarcoma cells was considerably restrained and the cell apoptosis was induced in vivo and in vitro. Moreover, downregulated SNHG4 inhibited the cell migration and epithelial‐mesenchymal transition in HOS and MG63 cells. In mechanism, we found that SNHG4 acts as a competing endogenous RNA to sponge miR‐377‐3p, which is downregulated in osteosarcoma. Our results showed that there is a negative correlation between SNHG4 and miR‐377‐3p expression in osteosarcoma patients.ConclusionTaken together, SNHG4 promotes cell proliferation and migration by sponging miR‐377‐3p in osteosarcoma.
Serotonin transporter gene (SLC6A4) variation and sensory processing sensitivity—Comparison with other anxiety‐related temperamental dimensions
Authors: Licht Cecilie L. , Mortensen Erik L. , Hjordt Liv V. , Stenbæk Dea S. , Arentzen Tine E. , Nørremølle Anne , Knudsen Gitte M. 
Published: June 2020

AbstractBackgroundThe short (s) allele of the 5‐HTTLPR polymorphism in the promoter region of the human serotonin transporter (5‐HTT) gene SLC6A4 has previously been associated with anxiety‐related personality dimensions. However, this relationship has not been confirmed in all studies and may be modified by environmental circumstances and/or psychiatric illness. This study examined whether the temperamental trait sensory processing sensitivity (SPS), characterized by increased responsivity to environmental stimuli, is related to 5‐HTTLPR/rs25531 genotype.Methods5‐HTTLPR and rs25531 genotypes, level of SPS, self‐reported Revised NEO Personality Inventory (NEO‐PI‐R) and Temperament and Character Inventory (TCI) personality profiles, and symptoms of psychological distress (SCL‐90R Global Severity Index) were determined for 405 healthy volunteers.ResultsSensory processing sensitivity was highly correlated with the anxiety‐related dimensions of the NEO‐PI‐R and the TCI models of personality, Neuroticism, and Harm Avoidance, respectively. However, the level of SPS was not associated with the combined 5‐HTTLPR and rs25531 s′/s′ genotype. Neuroticism and Harm Avoidance were also not associated with 5‐HTTLPR/rs25531 s′/s′ genotype. Correcting for symptoms of psychological distress had no effect on the relationships between personality and genotype.ConclusionThe level of SPS was not associated with serotonin transporter gene variation. Further, combined 5‐HTTLPR and rs25531 genotype was not associated with other anxiety‐related dimensions.
Rivaroxaban was found to be noninferior to warfarin in routine clinical care: A retrospective noninferiority cohort replication study
Authors: Althunian Turki A. , de Boer Anthonius , Groenwold Rolf H. H. , Rengerink Katrien O. , Souverein Patrick C. , Klungel Olaf H. 
Published: June 2020

AbstractPurposeTo compare the effectiveness and safety of a drug in daily practice with the outcomes of a target non‐inferiority trial by rigorously mimickingin an observational study the trial's design features.MethodsThis cohort study was conducted using the British Clinical Practice Research Datalink (CPRD) to emulate the ROCKET AF (Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation) trial. Patients with atrial fibrillation who were newly prescribed (>=12 months of no use) either rivaroxaban or warfarinfrom October 2008 to December 2017 were included. Non‐inferiority of rivaroxaban to warfarin in the prevention of stroke or systemic embolism was assessed in different analysis populations (intention‐to‐treat [ITT], per‐protocol [PP], and as‐treated populations) using a hazardratio (HR) of 1.46 as the non‐inferiority margin. Major bleeding (safety outcome) was also assessed and compared to that of the target trial. All outcomes were analyzed using Cox‐proportional hazard analyses.ResultsWe included 25,473 incident users of rivaroxaban (n=4,008) or warfarin(n=21,465). Similar to the trial, non‐inferiority in the primary out come was demonstrated in all three analysis populations: HR=1.04 (95%CI 0.84 to 1.30) (ITT), HR=0.98 (95%CI 0.70 to 1.38) (PP), and HR=1.11 (95%CI 0.86 to 1.42) (as‐treated). Risk of major bleeding was also similar to the target trial.ConclusionThe results of this study provide supportive evidence to the effectiveness of rivaroxaban and adds knowledge on the usefulness of emulating a non‐inferiority trial to assess drug effectiveness.
Bearing‐only control of directed cycle formations: Almost global convergence and hardware implementation
Authors: Ko Gwihan , Hoang Trinh Minh , Ahn Hyo‐Sung 
Published: June 2020

SummaryIn this article, we study bearing‐only control of directed cyclic formations. First, we provide a necessary and sufficient condition on the bearing constraints so that the directed cycle formation of n‐agents in (n−1)‐dimensional space is infinitesimally bearing rigid. Second, a bearing‐only control law which only allows motions perpendicular to the desired bearing vector is proposed. Under this control law, the agents globally asymptotically converge to a desired formation which is fully determined from their initial positions and desired bearing vectors. Finally, the proposed formation control law is implemented on mobile robots to support the analysis.
A Glucose/Oxygen‐Exhausting Nanoreactor for Starvation‐ and Hypoxia‐Activated Sustainable and Cascade Chemo‐Chemodynamic Therapy
Authors: Guo Yuxin , Jia Hao‐Ran , Zhang Xiaodong , Zhang Xinping , Sun Qing , Wang Shao‐Zhe , Zhao Jing , Wu Fu‐Gen 
Published: June 2020

AbstractFenton reaction‐mediated chemodynamic therapy (CDT) can kill cancer cells via the conversion of H2O2 to highly toxic HO•. However, problems such as insufficient H2O2 levels in the tumor tissue and low Fenton reaction efficiency severely limit the performance of CDT. Here, the prodrug tirapazamine (TPZ)‐loaded human serum albumin (HSA)–glucose oxidase (GOx) mixture is prepared and modified with a metal–polyphenol network composed of ferric ions (Fe3+) and tannic acid (TA), to obtain a self‐amplified nanoreactor termed HSA–GOx–TPZ–Fe3+–TA (HGTFT) for sustainable and cascade cancer therapy with exogenous H2O2 production and TA‐accelerated Fe3+/Fe2+ conversion. The HGTFT nanoreactor can efficiently convert oxygen into HO• for CDT, consume glucose for starvation therapy, and provide a hypoxic environment for TPZ radical‐mediated chemotherapy. Besides, it is revealed that the nanoreactor can significantly elevate the intracellular reactive oxygen species content and hypoxia level, decrease the intracellular glutathione content, and release metal ions in the tumors for metal ion interference therapy (also termed “ion‐interference therapy” or “metal ion therapy”). Further, the nanoreactor can also increase the tumor’s hypoxia level and efficiently inhibit tumor growth. It is believed that this tumor microenvironment‐regulable nanoreactor with sustainable and cascade anticancer performance and excellent biosafety represents an advance in nanomedicine.
Intelligent supply chain performance measurement in Industry 4.0
Authors: Xie Yongping , Yin Yixuan , Xue Wei , Shi Hui , Chong Dazhi 
Published: June 2020

AbstractThe concept of Industry 4.0 has been widely recognized by the world since its introduction in 2011 Hannover Industrial Expo. Industry 4.0 strategy does not only revolutionize the manufacturing system and processes but also lead to the formation of the intelligent supply chain. Currently, Industry 4.0‐based intelligent supply chain has attracted a lot of attention from academia; however, studies on performance measurement indicator of intelligent supply chain are still lacking. To fill this gap, this paper first introduces the impact of Industry 4.0 on supply chain management. After analysing key characteristics of intelligent supply chain, the paper proposes a performance measurement indicator framework consisting of seven indicators. This indicator framework enriches the theoretical knowledge of supply chain performance evaluation and provides an efficient way to improve the operational performance of intelligent supply chain management.
Improving preclinical to clinical translation in Alzheimer's disease research
Authors: Sukoff Rizzo Stacey J. , Masters Andi , Onos Kristen D. , Quinney Sara , Sasner Michael , Oblak Adrian , Lamb Bruce T. , Territo Paul R ,   for the MODEL‐AD consortium
Published: June 2020

AbstractIntroductionPreclinical testing in animal models is a critical component of the drug discovery and development process. While hundreds of interventions have demonstrated preclinical efficacy for ameliorating cognitive impairments in animal models, none have confirmed efficacy in Alzheimer's disease (AD) clinical trials. Critically this lack of translation to the clinic points in part to issues with the animal models, the preclinical assays used, and lack of scientific rigor and reproducibility during execution. In an effort to improve this translation, the Preclinical Testing Core (PTC) of the Model Organism Development and Evaluation for Late‐onset AD (MODEL‐AD) consortium has established a rigorous screening strategy with go/no‐go decision points that permits unbiased assessments of therapeutic agents.MethodsAn initial screen evaluates drug stability, formulation, and pharmacokinetics (PK) to confirm appreciable brain exposure in the disease model at the pathologically relevant ages, followed by pharmacodynamics (PD) and predictive PK/PD modeling to inform the dose regimen for long‐term studies. The secondary screen evaluates target engagement and disease modifying activity using non‐invasive positron emission tomography/magnetic resonance imaging (PET/MRI). Provided the compound meets its “go” criteria for these endpoints, evaluation for efficacy on behavioral endpoints are conducted.ResultsValidation of this pipeline using tool compounds revealed the importance of critical quality control (QC) steps that researchers need to be aware of when executing preclinical studies. These include confirmation of the active pharmaceutical ingredient and at the precise concentration expected; and an experimental design that is well powered and in line with the Animal Research Reporting of In vivo Experiments (ARRIVE) guidelines.DiscussionTaken together our experience executing a rigorous screening strategy with QC checkpoints provides insight to the challenges of conducting translational studies in animal models. The PTC pipeline is a National Institute on Aging (NIA)‐supported resource accessible to the research community for investigators to nominate compounds for testing (https://stopadportal.synapse.org/), and these resources will ultimately enable better translational studies to be conducted.
Comparison of Cox proportional hazards regression and generalized Cox regression models applied in dementia risk prediction
Authors: Goerdten Jantje , Carrière Isabelle , Muniz‐Terrera Graciela 
Published: June 2020

AbstractIntroductionThe frequently used Cox regression applies two critical assumptions, which might not hold for all predictors. In this study, the results from a Cox regression model (CM) and a generalized Cox regression model (GCM) are compared.MethodsData are from the Survey of Health, Ageing and Retirement in Europe (SHARE), which includes approximately 140,000 individuals aged 50 or older followed over seven waves. CMs and GCMs are used to estimate dementia risk. The results are internally and externally validated.ResultsNone of the predictors included in the analyses fulfilled the assumptions of Cox regression. Both models predict dementia moderately well (10‐year risk: 0.737; 95% confidence interval [CI]: 0.699, 0.773; CM and 0.746; 95% CI: 0.710, 0.785; GCM).DiscussionThe GCM performs significantly better than the CM when comparing pseudo‐R2 and the log‐likelihood. GCMs enable researcher to test the assumptions used by Cox regression independently and relax these assumptions if necessary.
Understanding HPC Benchmark Performance on Intel Broadwell and Cascade Lake Processors
Authors: Alappat Christie L. , Hofmann Johannes , Hager Georg , Fehske Holger , Bishop Alan R. , Wellein Gerhard 
Published: June 2020

AbstractHardware platforms in high performance computing are constantly getting more complex to handle even when considering multicore CPUs alone. Numerous features and configuration options in the hardware and the software environment that are relevant for performance are not even known to most application users or developers. Microbenchmarks, i.e., simple codes that fathom a particular aspect of the hardware, can help to shed light on such issues, but only if they are well understood and if the results can be reconciled with known facts or performance models. The insight gained from microbenchmarks may then be applied to real applications for performance analysis or optimization. In this paper we investigate two modern Intel x86 server CPU architectures in depth: Broadwell EP and Cascade Lake SP. We highlight relevant hardware configuration settings that can have a decisive impact on code performance and show how to properly measure on-chip and off-chip data transfer bandwidths. The new victim L3 cache of Cascade Lake and its advanced replacement policy receive due attention. Finally we use DGEMM, sparse matrix-vector multiplication, and the HPCG benchmark to make a connection to relevant application scenarios.
Scalable Hierarchical Aggregation and Reduction Protocol (SHARP)TM Streaming-Aggregation Hardware Design and Evaluation
Authors: Graham Richard L. , Levi Lion , Burredy Devendar , Bloch Gil , Shainer Gilad , Cho David , Elias George , Klein Daniel , Ladd Joshua , Maor Ophir , Marelli Ami , Petrov Valentin , Romlet Evyatar , Qin Yong , Zemah Ido 
Published: June 2020

Abstract

This paper describes the new hardware-based streaming-aggregation capability added to Mellanox’s Scalable Hierarchical Aggregation and Reduction Protocol in its HDR InfiniBand switches. For large messages, this capability is designed to achieve reduction bandwidths similar to those of point-to-point messages of the same size, and complements the latency-optimized low-latency aggregation reduction capabilities, aimed at small data reductions. MPI_Allreduce() bandwidth measured on an HDR InfiniBand based system achieves about 95% of network bandwidth. For medium and large data reduction this also improves the reduction bandwidth by a factor of 2–5 relative to host-based (e.g., software-based) reduction algorithms. Using this capability also increased DL-Poly and PyTorch application performance by as much as 4% and 18%, respectively. This paper describes SHARP Streaming-Aggregation hardware architecture and a set of synthetic and application benchmarks used to study this new reduction capability, and the range of data sizes for which Streaming-Aggregation performs better than the low-latency aggregation algorithm.
Die Einführung der Antipsychotika an der Neurologisch-Psychiatrischen Klinik der Universität Leipzig und ihre Auswirkungen auf andere Therapieformen sowie auf die Verweildauern und Verlegungen
Authors: Oeser Christian , Steinberg Holger 
Published: June 2020

ZusammenfassungZielDie Auswirkungen der Einführung der Antipsychotika auf die psychiatrische Versorgung in einer Klinik sollen erstmals überhaupt untersucht werden – konkret in der Neurologisch-Psychiatrischen Klinik der Universität Leipzig von 1946 bis 1965.ForschungsfragenZu welchem Zeitpunkt wurden welche Antipsychotika erstmals eingesetzt, in welchem Umfang und wie wirkte sich dies auf den Einsatz der traditionellen Therapieformen aus.Material und MethodeNach psychopathologischen Kriterien wurden 306 Fälle aus dem Bestand an Patientenakten aus dem Archiv der Klinik ausgewählt und anhand der Fragestellungen systematisch erfasst.ErgebnisseDer Einsatz der Antipsychotika begann ab 1953 mit zunehmender Häufigkeit und Dauer. Traditionelle Therapien und Antipsychotika wurden häufig in Kombination eingesetzt. Insbesondere der Einsatz von Antipsychotika und Elektrokrampftherapie stellte die neue Basistherapie dar. Eine Herabsenkung der Verweildauer konnte nicht nachgewiesen werden. Ab 1955 erfolgten jedoch weniger Verlegungen in die Landesheilanstalten und mehr Patienten konnten als „gebessert“ in die Häuslichkeit entlassen werden. Ab 1961 konnten erste Vermerke zu Entlassungsmedikationen gefunden werden und es fanden sich Hinweise auf ambulant durchgeführte Behandlungen wie z. B. auch Krampftherapien.DiskussionDie Erleichterung der psychischen Rehabilitation durch die Antipsychotika kann nicht direkt belegt werden, jedoch liegt es nahe, dass die Gabe über eine zeitlich begrenzte „Kur“ hinaus zu dieser Entwicklung und auch zur Etablierung ambulanter Strukturen beigetragen haben. Somit konnte sowohl ein Einschnitt in der psychiatrischen Behandlung als auch ein Wandel für die Patienten selbst ausgemacht werden.