bluuebunny/crossref_metadata_2025_split huggingface dataset:
When human guanylate-binding proteins meet viral infections
Authors: Zhang Rongzhao , Li Zhixin , Tang Yan-Dong , Su Chenhe , Zheng Chunfu 
Published: March 2021

AbstractInnate immunity is the first line of host defense against viral infection. After invading into the cells, pathogen-associated-molecular-patterns derived from viruses are recognized by pattern recognition receptors to activate the downstream signaling pathways to induce the production of type I interferons (IFN-I) and inflammatory cytokines, which play critical functions in the host antiviral innate immune responses. Guanylate-binding proteins (GBPs) are IFN-inducible antiviral effectors belonging to the guanosine triphosphatases family. In addition to exerting direct antiviral functions against certain viruses, a few GBPs also exhibit regulatory roles on the host antiviral innate immunity. However, our understanding of the underlying molecular mechanisms of GBPs' roles in viral infection and host antiviral innate immune signaling is still very limited. Therefore, here we present an updated overview of the functions of GBPs during viral infection and in antiviral innate immunity, and highlight discrepancies in reported findings and current challenges for future studies, which will advance our understanding of the functions of GBPs and provide a scientific and theoretical basis for the regulation of antiviral innate immunity.
Cell-based high-throughput screening of polysaccharide biosynthesis hosts
Authors: Liu Zi-Xu , Huang Si-Ling , Hou Jin , Guo Xue-Ping , Wang Feng-Shan , Sheng Ju-Zheng 
Published: March 2021

AbstractValuable polysaccharides are usually produced using wild-type or metabolically-engineered host microbial strains through fermentation. These hosts act as cell factories that convert carbohydrates, such as monosaccharides or starch, into bioactive polysaccharides. It is desirable to develop effective in vivo high-throughput approaches to screen cells that display high-level synthesis of the desired polysaccharides. Uses of single or dual fluorophore labeling, fluorescence quenching, or biosensors are effective strategies for cell sorting of a library that can be applied during the domestication of industrial engineered strains and metabolic pathway optimization of polysaccharide synthesis in engineered cells. Meanwhile, high-throughput screening strategies using each individual whole cell as a sorting section are playing growing roles in the discovery and directed evolution of enzymes involved in polysaccharide biosynthesis, such as glycosyltransferases. These enzymes and their mutants are in high demand as tool catalysts for synthesis of saccharides in vitro and in vivo. This review provides an introduction to the methodologies of using cell-based high-throughput screening for desired polysaccharide-biosynthesizing cells, followed by a brief discussion of potential applications of these approaches in glycoengineering.
Development of a chitosan‐modified PLGA nanoparticle vaccine for protection against Escherichia coli K1 caused meningitis in mice
Authors: Zhang Jin , Sun Hongwu , Gao Chen , Wang Ying , Cheng Xin , Yang Yun , Gou Qiang , Lei Langhuang , Chen Yanping , Wang Xingyong , Zou Quanming , Gu Jiang 
Published: March 2021

Abstract
Background
Escherichia coli K1 (E. coli K1) caused neonatal meningitis remains a problem, which rises the urgent need for an effective vaccine. Previously, we rationally designed and produced the recombinant protein OmpAVac (Vo), which elicited protective immunity against E. coli K1 infection. However, Vo has limited stability, which hinders its future industrial application.

Method
Chitosan-modified poly (lactic-co-glycolic acid) (PLGA) nanoparticles were prepared and used as carried for the recombinant Vo. And the safety, stability and immunogenicity of Vo delivered by chitosan-modified PLGA nanoparticles were tested in vitro and in a mouse model of bacteremia.

Results
We successfully generated chitosan-modified PLGA nanoparticles for the delivery of recombinant Vo (VoNP). In addition, we found that a freeze-drying procedure increases the stability of the VoNPs without changing the shape, size distribution and encapsulation of the Vo protein. Unlike aluminum adjuvant, the nanoparticles that delivered Vo were immunoprotective in mice even after storage for as long as 180 days.

Conclusions
We identified an effective strategy to improve the stability of Vo to maintain its immunogenicity, which will contribute to the future development of vaccines against E. coli K1.
Take home injectable opioids for opioid use disorder during and after the COVID-19 Pandemic is in urgent need: a case study
Authors: Oviedo-Joekes Eugenia , MacDonald Scott , Boissonneault Charles , Harper Kelli 
Published: March 2021

Abstract
Background
In North America the opioid poisoning crisis currently faces the unprecedented challenges brought by the COVID-19 pandemic, further straining people and communities already facing structural and individual vulnerabilities. People with opioid use disorder (OUD) are facing unique challenges in response to COVID-19, such as not being able to adopt best practices (e.g., physical distancing) if they’re financially insecure or living in shelters (or homeless). They also have other medical conditions that make them more likely to be immunocompromised and at risk of developing COVID-19. In response to the COVID-19 public health emergency, national and provincial regulatory bodies introduced guidance and exemptions to mitigate the spread of the virus. Among them, clinical guidance for prescribers were issued to allow take home opioid medications for opioid agonist treatment (OAT). Take Home for injectable opioid agonist treatment (iOAT) is only considered within a restrictive regulatory structure, specific to the pandemic. Nevertheless, this risk mitigation guidance allowed carries, mostly daily dispensed, to a population that would not have access to it prior to the pandemic. In this case it is presented and discussed that if a carry was possible during the pandemic, then the carry could continue post COVID-19 to address a gap in our approach to individualize care for people with OUD receiving iOAT.

Case presentation
Here we present the first case of a patient in Canada with long-term OUD that received take home injectable diacetylmorphine to self-isolate in an approved site after being diagnosed with COVID-19 during a visit to the emergency room where he was diagnosed with cellulitis and admitted to receive antibiotics.

Conclusion
In the present case we demonstrated that it is feasible to provide iOAT outside the community clinic with no apparent negative consequences. Improving upon and making permanent these recently introduced risk mitigating guidance during COVID-19, have the potential not just to protect during the pandemic, but also to address long-overdue barriers to access evidence-based care in addiction treatment.
A comprehensive comparison between cementless and cemented fixation in the total knee arthroplasty: an updated systematic review and meta-analysis
Authors: Liu Yuan , Zeng Yi , Wu Yuangang , Li Mingyang , Xie Huiqi , Shen Bin 
Published: March 2021

AbstractBackgroundWhether the cement should be used in the total knee arthroplasty (TKA) was still in controversy. This meta-analysis was performed to compare the efficacy of two kinds of fixation.MethodsRandomized controlled trials (RCTs), prospective/retrospective observational studies from PubMed (on 2019 September), EMBASE (on 2019 September), and the Cochrane Central Register of Controlled Trials (CENTRAL) and Web of Science (on 2019 September) were searched. Only studies followed more than 2 years was included for the review. The PRISMA guidelines and Cochrane Handbook were adopted to assess the quality of the results reported in included studies to ensure that the results of our meta-analysis were reliable and veritable. The continuous and dichotomous outcomes were collected in a standard form, and the data were analyzed by Review Manager 5.3 software. Finally, the results were presented in the Forest plots.ResultsTwenty-six studies involving 2369 patients in cementless TKA and 2654 patients in cemented TKA were included. The rate of revision was not significantly different in two groups (p= 0.55). More than eight reasons caused revision were found in our study, the aseptic loosing was the most common, followed by the periprosthetic joint infection (PJI), neither was significantly different (p= 0.88 and 0.45, respectively). While significantly better long-term functional recovery was found in cementless TKA in terms of Knee Society Function Score (p= 0.004) and manipulation under anesthesia (p= 0.007).ConclusionCementless fixation did not decrease the rate of revision after the total knee arthroplasty compared with the cemented fixation, while the long-term functional recovery was significantly better in the cementless group.
A thematic study: impact of COVID-19 pandemic on rare disease organisations and patients across ten jurisdictions in the Asia Pacific region
Authors: Chung Claudia Ching Yan , Ng Yvette Nga Chung , Jain Ritu , Chung Brian Hon Yin 
Published: March 2021

Abstract
Background
This study assesses the areas and extent of impact of the Coronavirus Disease of 2019 (COVID-19) pandemic on rare disease (RD) organisations in the Asia Pacific region. There is no existing literature that focuses on such impact on RD organisations in any jurisdictions, nor RD populations across multiple jurisdictions in the Asia Pacific region. A cross-sectional survey was distributed to RD organisations between April and May 2020. Quantitative and qualitative data on the impact of COVID-19 on RD organisations and patients were collected from the organisation representative’s perspective. Qualitative data was analysed using thematic analysis. A follow-up focus group meeting was conducted in August 2020 to validate the survey findings and to discuss specific needs, support and recommendations for sustainable healthcare systems during the pandemic.

Results
A total of 80 RD organisations from Australia, Hong Kong Special Administrative Region of China, India, Japan, mainland China, Malaysia, New Zealand, the Philippines, Singapore and Taiwan participated in the study. Of all, 89% were concerned about the impact of pandemic on their organisations. Results indicate that 63% of the organisations functioned at a reduced capacity and 42% stated a decrease in funding as their biggest challenge. Overall, 95% believed their patients were impacted, particularly in healthcare access, social lives, physical health, psychological health and financial impact. Specifically, 43% identified the reduced healthcare access as their top impact, followed by 26% about the impact on daily living and social life. Focus group meeting discussed differential impact across jurisdictions and point towards telemedicine and digitalisation as potential solutions.

Conclusions
This serves as the first study to assess the impact of COVID-19 on RD patients and organisations across multiple jurisdictions in the Asia Pacific region, identifying major themes on the impact on both RD patients and organisations. By including 80 organisations from ten jurisdictions, our study presents the most comprehensive assessment of the pandemic’s impact to date. It highlights the need for mental health support and sheds light on moving towards telemedicine and digitalisation of organisation operation, which constitutes a sustainable model in times of pandemics and beyond.
TP53 drives abscopal effect by secretion of senescence-associated molecular signals in non-small cell lung cancer
Authors: Tesei Anna , Arienti Chiara , Bossi Gianluca , Santi Spartaco , De Santis Ilaria , Bevilacqua Alessandro , Zanoni Michele , Pignatta Sara , Cortesi Michela , Zamagni Alice , Storci Gianluca , Bonafè Massimiliano , Sarnelli Anna , Romeo Antonino , Cavallo Carola , Bartolazzi Armando , Rossi Stefania , Soriani Antonella , Strigari Lidia 
Published: March 2021

Abstract
Background
Recent developments in abscopal effect strongly support the use of radiotherapy for the treatment of metastatic disease. However, deeper understanding of the molecular mechanisms underlying the abscopal effect are required to best benefit a larger proportion of patients with metastasis. Several groups including ours, reported the involvement of wild-type (wt) p53 in radiation-induced abscopal effects, however very little is known on the role of wtp53 dependent molecular mechanisms.

Methods
We investigated through in vivo and in vitro approaches how wtp53 orchestrates radiation-induced abscopal effects. Wtp53 bearing (A549) and p53-null (H1299) NSCLC lines were xenotransplanted in nude mice, and cultured in 2D monolayers and 3D tumor spheroids. Extracellular vesicles (EVs) were isolated from medium cell culture by ultracentrifugation protocol followed by Nanoparticle Tracking Analysis. Gene expression was evaluated by RT-Real Time, digital qRT-PCR, and dot blot technique. Protein levels were determined by immunohistochemistry, confocal anlysis, western blot techniques, and immunoassay.

Results
We demonstrated that single high-dose irradiation (20 Gy) induces significant tumor growth inhibition in contralateral non-irradiated (NIR) A549 xenograft tumors but not in NIR p53-null H1299 or p53-silenced A549 (A549sh/p53) xenografts. We further demonstrates that irradiation of A549 cells in vitro induces a senescence-associated secretory phenotype (SASP) producing extracellular vesicles (EVs) expressing CD63 and carrying DNA:RNA hybrids and LINE-1 retrotransposon. IR-A549 EVs also hamper the colony-forming capability of recipient NIR A549 cells, induce senescent phenotype, nuclear expression of DNA:RNA hybrids, and M1 macrophage polarization.

Conclusions
In our models, we demonstrate that high radiation dose in wtp53 tumors induce the onset of SASP and secretion of CD63+ EVs loaded with DNA:RNA hybrids and LINE-1 retrotransposons that convey senescence messages out of the irradiation field triggering abscopal effect in NIR tumors.
Pre-implantation exogenous progesterone and pregnancy in sheep: I. polyamines, nutrient transport, and progestamedins
Authors: Hoskins Emily C. , Halloran Katherine M. , Stenhouse Claire , Moses Robyn M. , Dunlap Kathrin A. , Satterfield Michael C. , Seo Heewon , Johnson Gregory A. , Wu Guoyao , Bazer Fuller W. 
Published: March 2021

Abstract
Background
Administration of exogenous progesterone (P4) to ewes during the pre-implantation period advances conceptus development and implantation. This study determined effects of exogenous P4 on transport of select nutrients and pathways that enhance conceptus development. Pregnant ewes (n = 38) were treated with either 25 mg P4 in 1 mL corn oil (P4, n = 18) or 1 mL corn oil alone (CO, n = 20) from day 1.5 through day 8 of pregnancy and hysterectomized on either day 9 or day 12 of pregnancy. Endometrial expression of genes encoding enzymes for synthesis of polyamines, transporters of glucose, arginine, and glycine, as well as progestamedins was determined by RT-qPCR.

Results
On day 12 of pregnancy, conceptuses from P4-treated ewes had elongated while those from CO-treated ewes were spherical. The mRNA expression of AZIN2, an arginine decarboxylase, was lower in endometria of P4-treated than CO-treated ewes on day 9 of pregnancy. Expression of FGF10, a progestamedin, was greater in endometria of CO and P4-treated ewes on day 12 of gestation in addition to P4-treated ewes necropsied on day 9 of gestation. Treatment with P4 down-regulated endometrial expression of amino acid transporter SLC1A4 on day 12 of pregnancy.

Conclusions
Results indicated that administration of exogenous P4 during the pre-implantation period advanced the expression of FGF10, which may accelerate proliferation of trophectoderm cells, but also was correlated with decreased expression of glycine and serine transporters and polyamine synthesis enzyme AZIN2. Further research with increased sample sizes may determine how differential expression affects endometrial functions and potentially embryonic loss.
The abrupt transition from face-to-face to online treatment for eating disorders: a pilot examination of patients’ perspectives during the COVID-19 lockdown
Authors: Lewis Yael Doreen , Elran-Barak Roni , Grundman-Shem Tov Rinat , Zubery Eynat 
Published: March 2021

AbstractBackgroundStudies investigating patients’ perspectives towards an abrupt transition from face-to-face to online treatment in eating disorders (EDs) are scarce. The current study aimed to (1) conduct a preliminary assessment of patients’ perspectives regarding this transition, and (2) explore potential demographic, clinical, and treatment-related factors associated with these perspectives.MethodsSixty-three patients with EDs whose treatment was moved to an online format, were surveyed during the COVID-19 lockdown (April–May 2020). A 6-item measure was developed to examine their perspectives toward this transition. Exploratory factor analyses (EFAs) were conducted to confirm the rational-theoretical structure of the measure (Eigenvalue = 3.745, explaining 62.4% of variance). The Cronbach’s alpha value was excellent (α = 0.878). Validated questionnaires were used to measure ED symptoms, general psychopathology, therapeutic alliance, and pandemic anxiety, and their associations with our transition-focused scale and telemedicine satisfaction were examined.ResultsMixed views were found regarding the transition, with the majority (68%) stating that they would not choose to continue online therapy given the option. Longer duration of treatment (r = 0.291,p = 0.022), stronger therapeutic alliance (r = 0.293,p = 0.028), and higher COVID-19 anxiety (r = 0.276,p = 0.029) were linked with more positive views towards the transition.ConclusionsAnalyses suggest that patients’ perspectives towards the transition can be measured using a Likert-type 6-item scale. Findings highlight the various responses to online treatment and indicate a need to identify patients who may face difficulties in the transition to this newly ubiquitous treatment mode. Clinicians should be cognizant of these potential difficulties and consider appropriate modes of treatment in the ongoing pandemic situation.
Diogene-CT: tools and methodologies for teaching and learning coding
Authors: Mecca Giansalvatore , Santoro Donatello , Sileno Nazzareno , Veltri Enzo 
Published: March 2021

AbstractComputational thinking is the capacity of undertaking a problem-solving process in various disciplines (including STEM, i.e. science, technology, engineering and mathematics) using distinctive techniques that are typical of computer science. It is nowadays considered a fundamental skill for students and citizens, that has the potential to affect future generations. At the roots of computational-thinking abilities stands the knowledge of computer programming, i.e. coding. With the goal of fostering computational thinking in young students, we address the challenging and open problem of using methods, tools and techniques to support teaching and learning of computer-programming skills in school curricula of the secondary grade and university courses. This problem is made complex by several factors. In fact, coding requires abstraction capabilities and complex cognitive skills such as procedural and conditional reasoning, planning, and analogical reasoning. In this paper, we introduce a new paradigm called ACME (“Code Animation by Evolved Metaphors”) that stands at the foundation of the Diogene-CT code visualization environment and methodology. We develop consistent visual metaphors for both procedural and object-oriented programming. Based on the metaphors, we introduce a playground architecture to support teaching and learning of the principles of coding. To the best of our knowledge, this is the first scalable code visualization tool using consistent metaphors in the field of the Computing Education Research (CER). It might be considered as a new kind of tools named as code visualization environments.
Thymol ameliorates ammonium toxicity via repressing polyamine oxidase-derived hydrogen peroxide and modulating ammonium transporters in rice root
Authors: Guo Kai , An Guangchi , Wang Ning , Pang Bingdong , Shi Zhiqi , Bai Hongwu , Zhang Li , Chen Jian , Xu Weimin 
Published: March 2021

Abstract
Background
Ammonium is an indispensable nutrient for crop growth, but anoxic conditions or inappropriate fertilizer usage result in the increase in ammonium content in soil. Excessive ammonium causes phytotoxicity. Thymol is a kind of natural phenolic compound with anti-microbial properties. However, little is known about the role of thymol in modulating plant physiology. Here we find the novel role of thymol in protecting rice from ammonium toxicity.

Results
Thymol remarkably rescued rice seedlings growth from ammonium stress, which may resulted from the attenuation of reactive oxygen species (ROS) accumulation, oxidative injury, and cell death in both shoots and roots. Polyamine oxidase (PAO) metabolizes polyamines to produce ROS in plants in response to stress conditions. Thymol blocked ammonium-induced upregulation of a set of rice PAOs, which contributed to the decrease in ROS content. In rice seedlings upon ammonium stress, thymol downregulate the expression of ammonium transporters (AMT1;1 and AMT1;2); thymol upregulated the expression of calcineurin B-like interacting protein kinase 23 (CIPK23) and calcineurin B-like binding protein 1 (CBL1), two negative regulators of AMTs. This may help rice avoid ammonium overload in excessive ammonium environment. Correlation analysis indicated that PAOs, AMTs, and CBL1 were the targets of thymol in the detoxification of excessive ammonium.

Conclusion
Thymol facilitates rice tolerance against ammonium toxicity by decreasing PAO-derived ROS and modulating ammonium transporters. Such findings may be applicable in the modulation of nutrient acquisition during crop production.

Graphical abstract
Designing reversible multi-level resistance states in a half-doped manganite
Authors: Banik Sanjib , Das Kalipada , Pradhan Kalpataru , Das Indranil 
Published: March 2021

Abstract
We design reversible multi-level resistance states in a half-doped charge-ordered manganite,

(SCSMO). By exploiting the electronic phase separation in SCSMO at 10 K, we show that the system can be stabilized into several metastable states, against thermal cycling, up to 62 K. The magnetization and the resistivity remain unaltered in each metastable states during the thermal cycling. Monte Carlo calculations using a two-band double-exchange model, including super-exchange, electron-phonon coupling, and quenched disorder, show that the system freezes into a phase-separated metastable state due to the disorder during the thermal cycling. We outline pathway to control the multi-level switching between four reversible metastable states. Our results may open the door for future investigations to engineer memory devices based on multi-level resistance switching using phase-separated transition metal oxides.