bluuebunny/crossref_metadata_2025_split huggingface dataset:
Methotrexate inhibits SARS‐CoV‐2 virus replication “in vitro”
Authors: Caruso Arnaldo , Caccuri Francesca , Bugatti Antonella , Zani Alberto , Vanoni Marco , Bonfanti Paolo , Cazzaniga Marina E. , Perno Carlo F. , Messa Cristina , Alberghina Lilia 
Published: September 2020

AbstractIn early 2020 the new respiratory syndrome COVID‐19 (caused by the zoonotic SARS‐CoV‐2 virus) spread like a pandemic, starting from Wuhan, China, causing severe economic depression. Despite some advances in drug treatments of medical complications in the later stages of the disease, the pandemic's death toll is tragic, as no vaccine or specific antiviral treatment is currently available. By using a systems approach, we identify the host‐encoded pathway, which provides ribonucleotides to viral RNA synthesis, as a possible target. We show that methotrexate, an FDA‐approved inhibitor of purine biosynthesis, potently inhibits viral RNA replication, viral protein synthesis, and virus release. The effective antiviral methotrexate concentrations are similar to those used for established human therapies using the same drug. Methotrexate should be most effective in patients at the earliest appearance of symptoms to effectively prevent viral replication, diffusion of the infection, and possibly fatal complications.
Research progress and challenges to coronavirus vaccine development
Authors: Zhou Peiwen , Li Zonghui , Xie Linqing , An Dong , Fan Yaohua , Wang Xiao , Li Yiwei , Liu Xiaohong , Wu Jianguo , Li Geng , Li Qin 
Published: September 2020

AbstractCoronaviruses (CoVs) are nonsegmented, single‐stranded, positive‐sense RNA viruses highly pathogenic to humans. Some CoVs are known to cause respiratory and intestinal diseases, posing a threat to the global public health. Against this backdrop, it is of critical importance to develop safe and effective vaccines against these CoVs. This review discusses human vaccine candidates in any stage of development and explores the viral characteristics, molecular epidemiology, and immunology associated with CoV vaccine development. At present, there are many obstacles and challenges to vaccine research and development, including the lack of knowledge about virus transmission, pathogenesis, and immune response, absence of the most appropriate animal models.
Racial disparities in local therapy for early stage non‐small‐cell lung cancer
Authors: Lutfi Waseem , Martinez‐Meehan Deirdre , Sultan Ibrahim , Evans Nathaniel , Dhupar Rajeev , Luketich James D. , Christie Neil A. , Okusanya Olugbenga T. 
Published: September 2020

AbstractObjectivesThis study investigated disparities in the delivery of definitive therapy for early stage non‐small‐cell lung cancer (ESNSCLC) between Caucasian (CS) and African American (AA) populations.MethodsThe National Cancer Data Base was queried for AA and CS patients, diagnosed with c stage I Non small cell lung cancer between 2004 and 2015. Trends in surgery, stereotactic ablative radiotherapy (SABR), or external beam radiation therapy (EBRT) were compared. Kaplan–Meier and Cox hazards models were used to compare 5‐year overall survival (5YOS).ResultsA total of 174,338 (90.6%) patients were CS and 18,077 (9.4%) patients were AA. AA patients were less likely to receive surgery (60.3% vs. 66.9%; p < .001) and more likely to receive EBRT (12.4% vs. 10.6%; p < .001); however, there was no significant difference in rates of SABR (8.8% vs. 9.2%; p = .066). From 2004 to 2015, the surgery rates increased for AA patients from 44.4% to 61.8% and for CS patients from 57.6% to 65.6%. AA patients had worse 5YOS on an unadjusted analysis (46.7% vs. 47.9%; p = .009). When adjusted for definitive treatment, AA patients had improved survival (hazard ratio = 0.97, 95% confidence interval = 0.94–0.99).ConclusionImprovements in the delivery of surgery and equal utilization of definitive radiation therapy are at least partially responsible for closing the survival gap between AA and CS patients with ESNSCLC.
Unraveling chemical structure of laminar premixed tetralin flames at low pressure with photoionization mass spectrometry and kinetic modeling
Authors: Li Yuyang , Zou Jiabiao , Yuan Wenhao , Cao Chuangchuang , Zhang Yan , Qi Fei , Yang Jiuzhong 
Published: September 2020

AbstractThis work reports an investigation on laminar premixed flames of tetralin at 30 Torr and equivalence ratios of 0.7 and 1.7. Measurements of the chemical structure including identification and mole fraction measurements of free radicals, isomers, and polycyclic aromatic hydrocarbons (PAHs) were performed using synchrotron vacuum ultraviolet photoionization mass spectrometry (SVUV‐PIMS). A kinetic model with 296 species and 1 577 reactions was developed and validated against the flame chemical structure data measured in this work. Modeling analysis reveals the key reaction pathways in tetralin decomposition and PAHs formation. The H‐atom abstraction reactions by H, O, and OH are found to control the consumption of tetralin in the lean flame, while those by H play the dominant role in the rich flame. Indene and naphthalene have very high concentration levels in the rich tetralin flame due to the existence of direct formation pathways from the decomposition of tetralin. The two bicyclic PAHs and their radicals play significant roles in the PAHs growth process of tetralin combustion, which results in the high sooting tendency of tetralin compared to those of alkylbenzenes with smaller or same carbon atom numbers.
The FACT Network: Philosophy, Evolution, and Management of a Collaborative Coastal Tracking Network
Authors: Young Joy M. , Bowers Mary E. , Reyier Eric A. , Morley Danielle , Ault Erick R. , Pye Jonathan D. , Gallagher Riley M. , Ellis Robert D. 
Published: September 2020

Abstract
The FACT Network (originally the Florida Atlantic Coast Telemetry working group), established in 2007, is a grassroots collaboration that is dedicated to improving the conservation and management of aquatic animals by facilitating data sharing amongst researchers using acoustic telemetry technology, providing a community for scientists, and building stakeholder partnerships. Founded along the eastern Florida coastline, FACT quickly grew in both membership and geographical range to include 93 partner groups along a large portion of the southern U.S. Atlantic seaboard and western Caribbean. This rapid expansion was facilitated by adapting FACT's policies and procedures to meet the growing needs of its members, including implementing an online data sharing system capable of exchanging information with other compatible systems designed by the Ocean Tracking Network (OTN). Less than 13 months from its inception, the FACT database housed 129.5 million detections and metadata for 5,979 tags from 101 projects (85 FACT projects and 16 OTN-based projects). Twice-yearly meetings allow FACT members to interact, building relationships between individuals, which in turn promotes collaboration and data sharing. The success of FACT is attributable to a combination of biogeographical factors; partnerships with the Animal Tracking Network, OTN, and Southeast Coastal Ocean Observing Regional Association; and active membership. In a survey of FACT members, data management services and belonging to a community ranked highest as reasons for joining the network. Future success of the FACT Network will depend on how effectively it can adapt to changing needs and conditions in the scientific landscape. In this paper, we describe the origins, philosophy, and management approach of the FACT Network, with the hope that this information can provide insights into the benefits (and limitations) of future acoustic tracking networks in other regions.
Grouper Tales: Use of Acoustic Telemetry to Evaluate Grouper Movements at Western Dry Rocks in the Florida Keys
Authors: Keller Jessica A , Herbig Jennifer L. , Morley Danielle , Wile Ariel , Barbera Paul , Acosta Alejandro 
Published: September 2020

Abstract
The Western Dry Rocks (WDR) area off Key West, Florida, is an open fishing area that contains a multispecies fish spawning aggregation site, but grouper spawning there has yet to be confirmed. The movements of 18 adult and subadult grouper at WDR were tracked using acoustic telemetry to determine how this area is used by grouper species and whether it contains a grouper spawning aggregation site. Tagged fish consisted of 10 Black Grouper Mycteroperca bonaci, 5 Nassau Grouper Epinephelus striatus, 2 Gag M. microlepis, and 1 Yellowfin Grouper M. venenosa. Overall, tagged grouper were more likely to be present in the WDR array during winter spawning months, with species-specific seasonal differences. Our results indicated that grouper presence increased during spawning months, although some adults and subadults were present year-round. Grouper made more movements per day during non-spawning months compared to spawning months, although the north side of WDR was the most heavily used area, regardless of the time of year. Additionally, spatial graphs of grouper movement suggested that different grouper species utilized different areas of WDR. Increased presence of grouper during spawning months suggests that the WDR area may contain a grouper spawning aggregation site, which would mean that fish species aggregate to spawn at this location year-round. The success of the Florida Keys fisheries critically depends on the protection of multispecies spawning aggregations like that potentially contained at WDR.
Automated Analysis of Diffusion‐Weighted Magnetic Resonance Imaging for the Differential Diagnosis of Multiple System Atrophy from Parkinson's Disease
Authors: Krismer Florian , Beliveau Vincent , Seppi Klaus , Mueller Christoph , Goebel Georg , Gizewski Elke R. , Wenning Gregor K. , Poewe Werner , Scherfler Christoph 
Published: September 2020

ABSTRACTBackgroundManual region‐of‐interest analysis of putaminal and middle cerebellar peduncle diffusivity distinguishes patients with multiple system atrophy (MSA) and Parkinson's disease (PD) with high diagnostic accuracy. However, a recent meta‐analysis found substantial between‐study heterogeneity of diagnostic accuracy due to the lack of harmonized imaging protocols and standardized analyses pipelines.ObjectiveEvaluation of diagnostic accuracy of observer‐independent analysis of microstructural integrity as measured by diffusion‐tensor imaging in patients with MSA and PD.MethodsA total of 29 patients with MSA and 19 patients with PD (matched for age, gender, and disease duration) with 3 years of follow‐up were investigated with diffusion‐tensor imaging and T1‐weighted magnetic resonance imaging. Automated localization of relevant brain regions was obtained, and mean diffusivity and fractional anisotropy values were averaged within the regions of interest. The classification was performed using a C5.0 hierachical decision tree algorithm.ResultsMean diffusivity of the middle cerebellar peduncle and cerebellar gray and white matter compartment as well as the putamen were significantly increased in patients with MSA and showed superior effect sizes compared to the volumetric analysis of these regions. A classifier model identified mean diffusivity of the middle cerebellar peduncle and putamen as the most predictive parameters. Cross‐validation of the classification model yields a Cohen's κ and overall diagnostic accuracy of 0.823 and 0.914, respectively.ConclusionAnalysis of microstructural integrity within the middle cerebellar peduncle and putamen yielded a superior effect size compared to the volumetric measures, resulting in excellent diagnostic accuracy to discriminate patients with MSA from PD in the early to moderate disease stages. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society
Novel mutation identification and copy number variant detection via exome sequencing in congenital muscular dystrophy
Authors: Cauley Edmund S. , Pittman Alan , Mummidivarpu Swati , Karimiani Ehsan G. , Martinez Samantha , Moroni Isabella , Boostani Reza , Podini Daniele , Mora Marina , Jamshidi Yalda , Hoffman Eric P. , Manzini M. Chiara 
Published: September 2020

AbstractBackgroundCongenital muscular dystrophy type 1A (MDC1A), also termed merosin‐deficient congenital muscular dystrophy (CMD), is a severe form of CMD caused by mutations in the laminin α2 gene (LAMA2). Of the more than 300 likely pathogenic variants found in the Leiden Open Variant Database, the majority are truncating mutations leading to complete LAMA2 loss of function, but multiple copy number variants (CNVs) have also been reported with variable frequency.MethodsWe collected a cohort of individuals diagnosed with likely MDC1A and sought to identify both single nucleotide variants and small and larger CNVs via exome sequencing by extending the analysis of sequencing data to detect splicing changes and CNVs.ResultsStandard exome analysis identified multiple novel LAMA2 variants in our cohort, but only four cases carried biallelic variants. Since likely truncating LAMA2 variants are often found in heterozygosity without a second allele, we performed additional splicing and CNV analysis on exome data and identified one splice change outside of the canonical sequences and three CNVs, in the remaining four cases.ConclusionsOur findings support the expectation that a portion of MDC1A cases may be caused by at least one CNV allele and show how these changes can be effectively identified by additional analysis of existing exome data.
Expression of sirtuins in ovarian follicles of postnatal mice
Authors: Kong Deqi , Yao Guidong , Bai Yucheng , Yang Guang , Xu Ziwen , Kong Yue , Fan Huiying , He Qina , Sun Yingpu 
Published: September 2020

AbstractMammalian ovarian follicular development is an intricate, elaborate, and well‐organized phenomenon regulated by various signaling pathways; however, the underlying mechanism remains unclear. Mammalian sirtuins (sirtuin 1 to sirtuin 7) are a group of NAD+‐dependent deacetylases implicated in various physiological processes including cell proliferation, apoptosis, cell cycle progression, and insulin signaling. Mammalian ovarian sirtuins have been studied using adult and aged bovine, porcine, and murine models. However, limited information is available regarding their precise expression patterns and the localization of follicle development in mice. This study aimed to assess the dynamic expression and localization of all seven sirtuins in early postnatal mouse ovaries through real‐time polymerase chain reaction analysis and immunohistochemistry, respectively. During postnatal ovarian follicle development, sirtuin 1, sirtuin 4, and sirtuin 6 were downregulated compared with those in 1‐day postnatal mouse ovaries (p < .05), indicating that these three sirtuin genes may be markers of follicular development. Combining their localization in granulosa cells through immunohistochemical studies, sirtuin 1, sirtuin 4, and sirtuin 6 are suggested to play negative regulatory roles in mammal ovarian follicular granulosa cell development. Furthermore, we found that sirtuin 2 (p < .05) and sirtuin 7 (p < .05) mRNA were constantly upregulated relative to sirtuin 1, although limited information is available regarding sirtuin 7. Among all sirtuins in mouse ovaries, sirtuin 1 was relatively and steadily downregulated. Upon sirtuin 1 overexpression in 1‐day postnatal mouse ovaries via sirtuin 1‐harboring adenoviruses in vitro, the emergence of primary follicles was delayed, as was the emergence of secondary follicles in 4‐day postnatal ovaries. Further studies on KGN cell lines reported that interfering with sirtuin 1 expression in granulosa cell significantly affected granulosa cell proliferation and the expression of mitochondrial genes. This study presents the first systemic analysis of dynamic patterns of sirtuin family expression in early postnatal mice ovaries, laying the foundation for further studies on less discussed sirtuin subtypes, such as sirtuin 5 and sirtuin 7.
MRI‐cytometry: Mapping nonparametric cell size distributions using diffusion MRI
Authors: Xu Junzhong , Jiang Xiaoyu , Devan Sean P. , Arlinghaus Lori R. , McKinley Eliot T. , Xie Jingping , Zu Zhongliang , Wang Qing , Chakravarthy A. Bapsi , Wang Yong , Gore John C. 
Published: September 2020

PurposeThis report introduces and validates a new diffusion MRI‐based method, termed MRI‐cytometry, which can noninvasively map intravoxel, nonparametric cell size distributions in tissues.MethodsMRI was used to acquire diffusion MRI signals with a range of diffusion times and gradient factors, and a model was fit to these data to derive estimates of cell size distributions. We implemented a 2‐step fitting method to avoid noise‐induced artificial peaks and provide reliable estimates of tumor cell size distributions. Computer simulations in silico, experimental measurements on cultured cells in vitro, and animal xenografts in vivo were used to validate the accuracy and precision of the method. Tumors in 7 patients with breast cancer were also imaged and analyzed using this MRI‐cytometry approach on a clinical 3 Tesla MRI scanner.ResultsSimulations and experimental results confirm that MRI‐cytometry can reliably map intravoxel, nonparametric cell size distributions and has the potential to discriminate smaller and larger cells. The application in breast cancer patients demonstrates the feasibility of direct translation of MRI‐cytometry to clinical applications.ConclusionThe proposed MRI‐cytometry method can characterize nonparametric cell size distributions in human tumors, which potentially provides a practical imaging approach to derive specific histopathological information on biological tissues.
Model‐based reconstruction for simultaneous multi‐slice mapping using single‐shot inversion‐recovery radial FLASH
Authors: Wang Xiaoqing , Rosenzweig Sebastian , Scholand Nick , Holme H. Christian M. , Uecker Martin 
Published: September 2020

PurposeTo develop a single‐shot multi‐slice
mapping method by combing simultaneous multi‐slice (SMS) excitations, single‐shot inversion‐recovery (IR) radial fast low‐angle shot (FLASH), and a nonlinear model–based reconstruction method.MethodsSMS excitations are combined with a single‐shot IR radial FLASH sequence for data acquisition. A previously developed single‐slice calibrationless model–based reconstruction is extended to SMS, formulating the estimation of parameter maps and coil sensitivities from all slices as a single nonlinear inverse problem. Joint‐sparsity constraints are further applied to the parameter maps to improve
precision. Validations of the proposed method are performed for a phantom and for the human brain and liver in 6 healthy adult subjects.ResultsPhantom results confirm good
accuracy and precision of the simultaneously acquired multi‐slice
maps in comparison to single‐slice references. In vivo human brain studies demonstrate the better performance of SMS acquisitions compared to the conventional spoke‐interleaved multi‐slice acquisition using model‐based reconstruction. Aside from good accuracy and precision, the results of 6 healthy subjects in both brain and abdominal studies confirm good repeatability between scan and re‐scans. The proposed method can simultaneously acquire
maps for 5 slices of a human brain (
) or 3 slices of the abdomen (
) within 4 seconds.ConclusionsThe IR SMS radial FLASH acquisition together with a nonlinear model–based reconstruction enable rapid high‐resolution multi‐slice
mapping with good accuracy, precision, and repeatability.
Nanomaterials in wound healing: From material sciences to wound healing applications
Authors: Barroso Andreia , Mestre Henrique , Ascenso Andreia , Simões Sandra , Reis Catarina 
Published: September 2020

AbstractAn increasing number of innovative therapies have emerged in the field of wound healing. Nanostructured systems have been used to improve wound healing at different stages. The drug itself may be formulated at a nanoscale such that it can function as its own “carrier” or nanomaterials may be used as drug delivery vehicles. The present work covers the latest advancements on innovative nano‐based organic and inorganic materials. These novel drug delivery systems possess high stability, large surface area and tunable compositions and have demonstrated their wound‐healing properties using in vitro and in vivo models. Key areas in the development of new systems for wound care are the assessment of biological compatibility, the evaluation of anti‐microbial activity and the in vivo efficacy assessment using full‐thickness skin models. Due to the multifactorial nature of chronic wound occurrence robust models should support the investigation of new materials in order to elucidate mechanisms involved in the sequence of physiologic processes that take place at wound healing. Although several nanoparticles have been successfully tested both in vitro and in vivo, researchers are still investigating the approaches to implementing large scale production of nanotechnological platforms to wound healing treatments.
Factors associated with pessary fitting in women with symptomatic pelvic organ prolapse: A large prospective cohort study
Authors: Ma Congcong , Xu Tao , Kang Jia , Zhang Ye , Ma Yidi , Liang Shuo , Zhu Lan 
Published: September 2020

AbstractAimTo identify factors associated with unsuccessful pessary fitting in a large cohort of patients with symptomatic pelvic organ prolapse (POP).MethodsThis prospective observational study included 611 consecutive women with symptomatic POP in a tertiary‐care hospital. Patients were initially fitted with a ring pessary with support. Those who failed were fitted with a Gellhorn pessary. A successful pessary fitting was defined as a patient who was fitted or refitted with a pessary and continued to use it 2 weeks later. Parametric and nonparametric tests were used for the data analysis.ResultsA total of 524 patients had successful pessary fittings (85.8% success rate). The success rate of the ring pessary with support was 57.9%, of the Gellhorn pessary was 69.1%. Stage IV prolapse (odds ratio [OR], 2.12), posterior compartment prolapse (OR, 1.92), genital hiatus (OR, 1.41), and vaginal introitus (OR, 1.40) were independent predictors of unsuccessful ring with support pessary fitting. Vaginal length (OR, 0.74/0.60 for ring with support/Gellhorn) and history of POP reconstructive surgery (OR, 2.50/2.58 for ring with support/Gellhorn) were independent predictors of both ring with support and Gellhorn pessary fitting.ConclusionsStage IV prolapse, posterior compartment prolapse, large genital hiatus, and wide vaginal introitus were risk factors for unsuccessful fitting of ring pessary with support. Short vaginal length and a history of POP reconstructive surgery were risk factors for unsuccessful fitting of both pessaries.
A Timely Oral Option: Single-Agent Vinorelbine in Desmoid Tumors
Authors: Gennatas Spyridon , Chamberlain Florence , Smrke Alannah , Stewart James , Hayes Andrew , Roden Lorna , Messiou Christina , Kowa Jie-Ying , Estival Anna , Chauhan Dharmisha , Thway Khin , Fisher Cyril , van der Graaf Winette T. A. , Jones Robin L. , Benson Charlotte 
Published: September 2020

Abstract

Introduction
Desmoid tumors (DT) are rare collagen-forming tumors that can exhibit locally aggressive patterns of behavior. The aim of this study was to evaluate the efficacy and safety of treatment of DT with single-agent oral vinorelbine.

Materials and Methods
A retrospective review of patients treated with vinorelbine 90 mg orally on days 1, 8, and 15 of a 28-day cycle from January 2004 to July 2019 was performed. Response was assessed using RECIST version 1.1. Descriptive statistics were employed.

Results
A total of 29 patients were included. Response rate was 20.7% (6/29), and clinical benefit rate (response by RECIST 1.1 and/or clinical symptom improvement) was 65.5% (19/29). No patient experienced grade 3 or above toxicity. Common toxicities were grade 1–2 nausea (14/26, 48.3%), fatigue (9/26, 31.0%), and diarrhea (4/26, 13.8%).

Conclusion
Single-agent oral vinorelbine is an effective, safe, and well-tolerated treatment for DT. It represents a new oral alternative for management of DT.