bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Ebola virus matrix protein clusters phosphatidylserine, a critical step in viral budding
Authors: Husby Monica L. , Amiar Souad , Prugar Laura I. , David Emily A. , Plescia Caroline B. , Huie Kathleen E. , Brannan Jennifer M. , Dye John M. , Pienaar Elsje , Stahelin Robert V. 
Published: June 2021

AbstractPhosphatidylserine (PS) has been shown to be a critical lipid factor in the assembly and spread of numerous lipid enveloped viruses. Here, we describe the ability of the Ebola virus (EBOV) matrix protein eVP40 to induce clustering of PS and promote viral budding in vitro, as well as the ability of an FDA approved drug, fendiline, to reduce PS clustering subsequently reducing virus budding and entry. To gain mechanistic insight into fendiline inhibition of EBOV replication, multiple in vitro assays were employed including imaging, viral budding and viral entry assays. Fendiline reduced the PS content in mammalian cells and PS in the plasma membrane, reducing the ability of VP40 to form new virus particles. Further, particles that do form from fendiline treated cells have altered particle morphology and decreased infectivity capacity. These complementary studies reveal the mechanism by which filovirus matrix proteins cluster PS to enhance viral assembly, budding, and spread from the host cell while also laying the groundwork for fundamental drug targeting strategies.
Potential therapy for progressive vision loss due to PCDH15-associated Usher Syndrome developed in an orthologous Usher mouse
Authors: Sethna Saumil , Zein Wadih M. , Riaz Sehar , Giese Arnaud P. J. , Schultz Julie M. , Duncan Todd , Hufnagel Robert B. , Brewer Carmen C. , Griffith Andrew J. , Redmond T. Michael , Riazuddin Saima , Friedman Thomas B. , Ahmed Zubair M. 
Published: June 2021

AbstractUsher syndrome type I (USH1) is characterized by congenital deafness, vestibular areflexia, and progressive retinal degeneration with age. The protein-truncating p.Arg245* founder variant of PCDH15 has an ~2% carrier frequency among Ashkenazi Jews, accounting for nearly 60% of their USH1 cases. Here, longitudinal ocular phenotyping in thirteen USH1F individuals harboring the p.Arg245* variant revealed progressive retinal degeneration, leading to severe loss of vision with macular atrophy by the sixth decade. Half of the affected individuals met either the visual acuity or visual field loss definition for legal blindness by the middle of their fifth decade of life. Mice homozygous for p.Arg250* (Pcdh15R250X; equivalent to human p.Arg245*) also have early visual deficits evaluated using electroretinography. Light-dependent translocation of phototransduction cascade proteins, arrestin and transducin, was found to be impaired in Pcdh15R250X mice. Retinal pigment epithelium-(RPE) specific visual retinoid cycle proteins, RPE65 which converts all-trans retinoids to 11-cis retinoids and CRALBP that transports retinoids, and key retinoid levels were also reduced in Pcdh15R250X mice, suggesting a dual role for protocadherin-15 in photoreceptors and RPE. Administration of exogenous 9-cis retinal, an analog of the naturally occurring 11-cis retinal, improved ERG amplitudes in these mutant mice, suggesting a basis for a clinical trial of exogenous FDA approved retinoids to preserve vision in USH1F patients.SummaryIn a preclinical setting studying exogenous retinoids using a novel Usher syndrome mouse model, we describe a potential therapy to treat PCDH15-mediated visual dysfunction.
HAUSP Stabilizes SOX2 through Deubiquitination to Maintain Self-renewal and Tumorigenic Potential of Glioma Stem Cells
Authors: Huang Zhi , Zhai Kui , Wu Qiulian , Fang Xiaoguang , Huang Qian , Tao Weiwei , Lathia Justin D. , Yu Jennifer S. , Rich Jeremy N. , Bao Shideng 
Published: June 2021

AbstractGlioblastoma (GBM) is the most lethal brain tumor containing glioma stem cells (GSCs) that promote malignant growth and therapeutic resistance. The self-renewal and tumorigenic potential of GSCs are maintained by core stem cell transcription factors including SOX2. Defining the posttranslational regulation of SOX2 may offer new insights into GSC biology and potential therapeutic opportunity. Here, we discover that HAUSP stabilizes SOX2 through deubiquitination to maintain GSC self-renewal and tumorigenic potential. HAUSP is preferentially expressed in GSCs in perivascular niches in GBMs. Disrupting HAUSP by shRNA or its inhibitor P22077 promoted SOX2 degradation, induced GSC differentiation, impaired GSC tumorigenic potential, and suppressed GBM tumor growth. Importantly, pharmacological inhibition of HAUSP synergized with radiation to inhibit GBM growth and extended animal survival, indicating that targeting HAUSP may overcome GSC-mediated radioresistance. Our findings reveal an unappreciated crucial role of HAUSP in the GSC maintenance and provide a promising target for developing effective anti-GSC therapeutics to improve GBM treatment.HighlightsHAUSP deubiquitinates and stabilizes SOX2 in glioma stem cells (GSCs).HAUSP is preferentially expressed by GSCs in perivascular niches in GBMs.HAUSP is required for maintaining GSC self-renewal and tumorigenic potential.Targeting HAUSP inhibited malignant growth in GSC-derived GBM xenografts.Inhibition of HAUSP synergized with radiation to suppress GBM tumor growth.
Craft beer vs industrial beer: chemical and sensory differences
Authors: Rosales Alicia , Talaverano M. Inmaculada , Lozano Jesús , Sánchez-Vicente Carlos , Santamaría Óscar , García-Latorre Carlos , Rodrigo Sara 
Published: June 2021

PurposeThe aim of this paper is to determine chemical and sensory differences of between craft and industrial/or commercial beers. Beer market is nowadays booming and consumers are in the search of new and healthier products.Design/smethodology/approachHere, commercial and craft beers were chemically analyzed and sensory evaluated. Chemical analysis included pH, bitterness, color, total polyphenol content and antioxidant activity. Likewise, 40 sensory descriptors were evaluated by trained panelists, including visual, olfactory and gustatory attributes. In addition, an electronic nose (e-nose) was tested to determine its suitability to discriminate beer type and/or style according to their volatiles profile.FindingsCraft beers presented higher values of color, bitterness and antioxidant activity when compared to commercial beers. Sensory descriptors showed craft beers to be associated with the highest scores in visual, olfactory and gustatory descriptors. Data from e-nose explained 97% of the total variability of the volatile compounds in the analyzed beers, indicating the suitability of this device to discriminate beer types.Originality/valueResults are of interest for design of marketing and selling techniques for craft brewery managers. In addition, cheap and easy-managing device as e-nose resulted in a valuable tool to monitoring beer quality.
What companies can learn from unicorn startups to overcome the COVID-19 crisis
Authors: Rodrigues Cristina Doritta , Noronha Matheus Eurico Soares de 
Published: June 2021

PurposeThis paper aims to search measures that unicorn startups have implemented during the pandemic and show what lessons can be learned to help entrepreneurs and small and medium businesses to overcome the crisis.Design/methodology/approachThe method is a multiple case study with five unicorn startups. This study collected data through interviews and analyzed them by the content analysis technique.FindingsThe findings show that the pandemic affects negatively unicorns’ businesses; that a digital business model innovation affects them positively; and that innovations moderate positively the negative impact of the crisis.Research limitations/implicationsMost interviewees hold operational positions.Practical implicationsThree actions stand out to overcome the crisis: adoption of new digital platforms; strategies to increase the network of partners; and adaptations in the provision of payment services.Originality/valueThe cases show that entrepreneurs and small and medium enterprises need to develop capabilities to innovate in their business models, and digitalization is a solution to face the crisis and overcome it in the future.
Effect of thickness and build orientation on the water vapor and oxygen permeation properties of laser-sintered polyamide 12 sheets
Authors: Liebrich Anna , Langowski Horst-Christian , Schreiber Regina , Pinzer Bernd R. 
Published: June 2021

Purpose
This study aims to investigate the effect of the material thickness and build orientation on the mass transfer of low molecular weight substances through polyamide 12 (PA12) structures produced by laser sintering (LS).

Design/methodology/approach
Disc-shaped PA12 sheets having a nominal thickness ranging from 700 to 2,000 µm were built in horizontal, vertical and diagonal orientations and their permeation properties to oxygen and water vapor were measured. The structural properties of the sheets were examined by X-ray micro-computed tomography, differential scanning calorimetry and polarized light microscopy.

Findings
All the LS sheets that were investigated had water vapor and oxygen permeation coefficients that are in the range of those of PA12 produced by traditional manufacturing technologies. Despite significant differences in the porosity characteristics, the permeation properties of sheets built in different orientations were similar. The pores seem to have no measurable effect on the mass transfer rates in the sheets, and the transport processes seem to predominantly follow the rules of a regular solution-diffusion mechanism. The results showed a non-significant trend toward thickness-dependent permeation coefficients, which agrees with the observed differences in the crystal structures of the sheets.

Practical implications
The results are an important basis for the qualification of LS technology for direct manufacturing in applications requiring special barrier performance.

Originality/value
This study provides new information on mechanisms of mass transport through LS PA12 and the effect of the material thickness and build orientation. Furthermore, the results enhance understanding of the structural properties of thin polymeric sheets produced by LS.
Microscopic and biomolecular complementary approaches to characterize bioweathering processes at petroglyph sites from the Negev Desert, Israel
Authors: Nir Irit , Barak Hana , Kramarsky‐Winter Esti , Kushmaro Ariel , de los Ríos Asunción 
Published: June 2021

SummaryThroughout the Negev Desert highlands, thousands of ancient petroglyphs sites are susceptible to deterioration processes that may result in the loss of this unique rock art. Therefore, the overarching goal of the current study was to characterize the composition, diversity and effects of microbial colonization of the rocks to find ways of protecting these unique treasures. The spatial organization of the microbial colonizers and their relationships with the lithic substrate were analysed using scanning electron microscopy. This approach revealed extensive epilithic and endolithic colonization and close microbial–mineral interactions. Shotgun sequencing analysis revealed various taxa from the archaea, bacteria and some eukaryotes. Metagenomic coding sequences (CDS) of these microbial lithobionts exhibited specific metabolic pathways involved in the rock elements' cycles and uptake processes. Thus, our results provide evidence for the potential participation of the microorganisms colonizing these rocks during different solubilization and mineralization processes. These damaging actions may contribute to the deterioration of this extraordinary rock art and thus threaten this valuable heritage. Shotgun metagenomic sequencing, in conjunction with the in situ scanning electron microscopy study, can thus be considered an effective strategy to understand the complexity of the weathering processes occurring at petroglyph sites and other cultural heritage assets.
Development of a nursing outcome for a percutaneous procedure
Authors: Reich Rejane , Rabelo‐Silva Eneida Rejane , Swanson Elizabeth , Moorhead Sue , Almeida Miriam de Abreu 
Published: June 2021

ABSTRACTObjectivesTo develop a nursing outcome, consistent with the standardized format of outcomes within the nursing Outcomes Classification (NOC). This outcome will include an outcome label, an outcome definition, and clinical indicators. The proposed use for this outcome is to evaluate the access site of a percutaneous procedure.MethodsConcept analysis with a scoping review. Initially, content experts were recruited to validate the indicators of the proposed outcome in order to complete a consensus validation. After consensus validation, a review of the proposed outcome and its indicators was completed by two of the editors of the NOC team to confirm that the outcome label, definition, and indicators were consistent with the NOC taxonomy. During this review, edits were made on the label name and definition.FindingsAfter a series of reviews, the initial outcome of Vascular Status: Percutaneous Procedure Access was changed to Tissue Injury Severity: Percutaneous Procedure. In addition, the original definition of the condition of an access site for percutaneous procedure by venous or arterial puncture and health of surrounding tissues was edited to: Severity of complications from a needle‐puncture access through the skin and into deeper tissues. The outcome has 11 indicators to be used to formulate a target rating for use in the clinical setting. The indicators were not edited over the course of the reviews.ConclusionThe proposed outcome will assist nurses in evaluating the access site of percutaneous procedures and in identifying possible complications.Implications for the Nursing PracticeThis research contributes to the refinement of the NOC taxonomy by having a new outcome that meets clinical practice needs.
Christmas, Crescents, and Crosses: When Is Symbolic Religious Establishment Permissible?
Authors: Bardon Aurélia 
Published: June 2021

AbstractSymbolic religious establishment (SRE), that is, the noncoercive recognition of religion by the state, has become the object of a growing debate in political philosophy. Although SRE is purely symbolic, some have argued that it can be wrong because of the message of political inequality that it sends. The indeterminacy of this expressive argument makes its application problematic, however. The objective of this article is to improve the applicability of the expressivist argument by providing clear guidelines of evaluation of SRE. I develop a three‐step test that helps distinguish permissible from impermissible cases of SRE: religious symbols that are divisive, political, and not appropriately justified are impermissible because of their exclusionary message. One important upshot of the argument is that the appeal to the value of heritage does not provide a plausible justification for the introduction of new religious symbols, and therefore that such neo‐establishment is always impermissible.
Type D personality is associated with depressive symptoms and clinical activity in inflammatory bowel disease
Authors: Jordi Sebastian Bruno Ulrich , Botte Federica , Lang Brian Matthew , Greuter Thomas , Krupka Niklas , Auschra Bianca , Schreiner Philipp , Sulz Michael Christian , Biedermann Luc , von Känel Roland , Rogler Gerhard , Begré Stefan , Misselwitz Benjamin ,   the Swiss IBD cohort study group
Published: June 2021

SummaryBackgroundInflammatory bowel disease (IBD) can be exacerbated by stress and depression. Type D personality, characterised by high negative affectivity and social inhibition, represents a vulnerability towards stressors and is associated with adverse outcomes in coronary heart disease.AimsTo assess the prevalence of Type D personality in IBD patients and investigate potential associations with disease course.MethodsWe tested for associations between Type D (Type D Scale‐14), depressive symptoms (Hospital Anxiety and Depression Scale's depression subscore ≥11) and recurrent IBD amongst Swiss IBD cohort patients. We built regression models for cross‐sectional and Cox proportional hazards models for time‐to‐event analyses. IBD disease course was assessed by the future occurrence of active disease (Crohn's Disease Activity Index ≥150/Modified Truelove & Witts activity index ≥10) and several IBD‐relevant endpoints.ResultsAmongst 2275 patients (1005 ulcerative colitis, 1270 Crohn's disease), 672 (29.5%) had Type D. Type D was a significant risk factor for future active disease (adjusted hazard ratio, aHR: 1.60, corrected P value, q = 0.007) and predicted the future presence of depressive symptoms (aHR: 3.30, P < 0.001). The combination of Type D and depressive symptoms further increased the risk for active disease (aHR: 3.98, q < 0.001). However, Type D associated depressive symptoms seemed to be the main contributor to this effect as Type D's predictive power decreased considerably in models corrected for depressive symptoms (aHR: 1.32, CI: 0.97‐1.79, q = 0.292).ConclusionsType D personality's prevalence amongst IBD patients was comparable with its prevalence in the general population. Type D was strongly associated with depressive symptoms and showed modest independent associations with IBD prognosis.
Fusion of engineered albumin with factor IX Padua extends half‐life and improves coagulant activity
Authors: Lombardi Silvia , Aaen Kristin H. , Nilsen Jeannette , Ferrarese Mattia , Gjølberg Torleif T. , Bernardi Francesco , Pinotti Mirko , Andersen Jan T. , Branchini Alessio 
Published: June 2021

SummaryThe short half‐life of coagulation factor IX (FIX) for haemophilia B (HB) therapy has been prolonged through fusion with human serum albumin (HSA), which drives the neonatal Fc receptor (FcRn)‐mediated recycling of the chimera. However, patients would greatly benefit from further FIX‐HSA half‐life extension. In the present study, we designed a FIX‐HSA variant through the engineering of both fusion partners. First, we developed a novel cleavable linker combining the two FIX activation sites, which resulted in improved HSA release. Second, insertion of the FIX R338L (Padua) substitution conferred hyperactive features (sevenfold higher specific activity) as for FIX Padua alone. Furthermore, we exploited an engineered HSA (QMP), which conferred enhanced human (h)FcRn binding [dissociation constant (KD) 0·5 nM] over wild‐type FIX‐HSA (KD 164·4 nM). In hFcRn transgenic mice, Padua‐QMP displayed a significantly prolonged half‐life (2·7 days, P < 0·0001) versus FIX‐HSA (1 day). Overall, we developed a novel FIX‐HSA protein with improved activity and extended half‐life. These combined properties may result in a prolonged functional profile above the therapeutic threshold, and thus in a potentially widened therapeutic window able to improve HB therapy. This rational engineering of both partners may pave the way for new fusion strategies for the design of engineered biotherapeutics.
Impact of histological variants on outcomes in patients with urothelial carcinoma treated with pembrolizumab: a propensity score matching analysis
Authors: Kobayashi Mizuki , Narita Shintaro , Matsui Yoshiyuki , Kanda Souhei , Hidaka Yu , Abe Hiroyasu , Tsuzuki Toyonori , Ito Katsuhiro , Kojima Takahiro , Kato Minoru , Hatakeyama Shingo , Matsushita Yuto , Naito Sei , Shiga Masanobu , Miyake Makito , Muro Yusuke , Nakanishi Shotaro , Kato Yoichiro , Shibuya Tadamasa , Hayashi Tetsutaro , Yasumoto Hiroaki , Yoshida Takashi , Uemura Motohide , Taoka Rikiya , Kamiyama Manabu , Morita Satoshi , Habuchi Tomonori , Ogawa Osamu , Nishiyama Hiroyuki , Kitamura Hiroshi , Kobayashi Takashi ,   the Japan Urological Oncology Group
Published: June 2021

ObjectivesTo assess the impact of histological variants on survival and response to treatment with pembrolizumab in patients with chemo‐resistant urothelial carcinoma (UC).Patients and MethodsThe medical records of 755 patients with advanced UC who received pembrolizumab were reviewed retrospectively. Patients were classified into pure UC (PUC) and each variant. Best overall response (BOR) and overall survival (OS) were compared between the groups using a propensity score matching (PSM).ResultsOverall, 147 (19.5%) patients harboured any histological variant UC (VUC). After PSM, there were no significant differences in the objective response rate (ORR, 24.5% vs 17.3%, P = 0.098) or disease control rate (DCR, 36.7% vs 30.2%, P = 0.195) when comparing patients with any VUC and PUC. Furthermore, any VUC, as compared with PUC, was associated with a similar risk of death (hazard ratio [HR] 0.90, 95% confidence interval [CI] 0.68–1.20; P = 0.482). Squamous VUC, which was the most frequent variant in the cohort, had a comparable ORR, DCR and OS as compared with PUC or non‐squamous VUC. The patients with sarcomatoid VUC (n = 19) had significantly better ORR (36.8%, P = 0.031), DCR (52.6%, P = 0.032), and OS (HR 0.37, 95% CI 0.15–0.90; P = 0.023) compared to patients with PUC.ConclusionsThe presence of variant histology did not seem to affect BOR or OS after pembrolizumab administration in patients with chemo‐resistant UC. The patients with sarcomatoid VUC achieved favourable responses and survival rates compared to PUC.
Chromosome alignment‐maintaining phosphoprotein CHAMP1 plays a role in cell survival through regulating Mcl‐1 expression
Authors: Hino Maho , Iemura Kenji , Ikeda Masanori , Itoh Go , Tanaka Kozo 
Published: June 2021

AbstractAntimitotic drugs such as vinca alkaloids and taxanes cause mitotic cell death after prolonged mitotic arrest. However, a fraction of cells escape from mitotic arrest by undergoing mitotic slippage, which is related to resistance to antimitotic drugs. Tipping the balance to mitotic cell death thus can be a way to overcome the drug resistance. Here we found that depletion of a mitotic regulator, CHAMP1 (chromosome alignment‐maintaining phosphoprotein, CAMP), accelerates the timing of mitotic cell death after mitotic arrest. Live cell imaging revealed that CHAMP1‐depleted cells died earlier than mock‐treated cells in the presence of antimitotic drugs that resulted in the reduction of cells undergoing mitotic slippage. Depletion CHAMP1 reduces the expression of antiapoptotic Bcl‐2 family proteins, especially Mcl‐1. We found that CHAMP1 maintains Mcl‐1 expression both at protein and mRNA levels independently of the cell cycle. At the protein level, CHAMP1 maintains Mcl‐1 stability by suppressing proteasome‐dependent degradation. Depletion of CHAMP1 reduces cell viability, and exhibits synergistic effects with antimitotic drugs. Our data suggest that CHAMP1 plays a role in the maintenance of Mcl‐1 expression, implying that CHAMP1 can be a target to overcome the resistance to antimitotic drugs.
A myriad of roles of dendritic cells in atherosclerosis
Authors: Zhao Yanfang , Zhang Jing , Zhang Wenjie , Xu Yuekang 
Published: June 2021

Abstract
Atherosclerosis is an inflammatory disease with break-down of homeostatic immune regulation of vascular tissues. As a critical initiator of host immunity, dendritic cells (DCs) have also been identified in the aorta of healthy individuals and atherosclerotic patients, whose roles in regulating arterial inflammation aroused great interest. Accumulating evidence has now pointed to the fundamental roles for DCs in every developmental stage of atherosclerosis due to their myriad of functions in immunity and tolerance induction, ranging from lipid uptake, efferocytosis and antigen presentation to pro- and anti-inflammatory cytokine or chemokine secretion. In this study we provide a timely summary of the published works in this field, and comprehensively discuss both the direct and indirect roles of DCs in atherogenesis. Understanding the pathogenic roles of DCs during the development of atherosclerosis in vascular tissues would certainly help to open therapeutic avenue to the treatment of cardiovascular diseases.