bluuebunny/crossref_metadata_2025_split huggingface dataset:
A multi-centre, randomized, double-blind, placebo-controlled clinical trial of the efficacy and safety of chloroquine phosphate, hydroxychloroquine sulphate and lopinavir/ritonavir for the treatment of COVID-19 in Lagos State: study protocol for a randomized controlled trial
Authors: Abayomi A. , Osibogun A. , Ezechi O. , Wright K. , Ola B. , Ojo O. , Kuyinu Y. , Zamba E. , Abdur-Razzaq H. , Erinoso O. A. , Anya S. E. 
Published: December 2021

Abstract
Background
The coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that was first identified in Wuhan, Hubei, China, in December 2019. It was recognized as a pandemic by the World Health Organization on 11 March 2020. Outbreak forecasting and mathematical modelling suggest that these numbers will continue to rise. Early identification of effective remedies that can shorten the duration and severity of illness is critical for Lagos State, which is the epi-centre of the disease in Nigeria.

Methods
This is a multi-centre, randomized, double-blind placebo-controlled superiority trial. The study investigates the efficacy of chloroquine phosphate, hydroxychloroquine sulphate and lopinavir/ritonavir added on to standard of care compared to standard of care only in patients with COVID-19 disease. The primary outcome is the clinical status of patients measured using a 7-point ordinal scale at day 15. Research participants and clinicians will be blinded to the allocated intervention. Outcome measures will be directly assessed by clinicians. Statistical analysis will be done by a team blinded to the identity and allocation of research participants. Data analysis will follow intention-to-treat methods, using R software.

Discussion
The current study is of strategic importance for Lagos State in potentially curbing the health, social and economic burden of COVID-19 disease. Should the current study demonstrate that either of the three intervention drugs is more efficacious than standard therapy alone, the State Ministry of Health will develop an evidence-based guideline for the management of COVID-19 in Lagos State. The findings will also be shared nationally and with other states which may lead to a standardized national guideline for the treatment of COVID-19 in Nigeria.

Trial registration
Pan African Clinical Trials Register PACTR202004801273802. Registered prospectively on April 2, 2020
SToRytelliing to Improve Disease outcomes in Gout (STRIDE-GO) in African American veterans with gout: a trial study protocol
Authors: Singh Jasvinder A. 
Published: December 2021

Abstract
Objective
Medication adherence in gout is suboptimal, and the lack of effective interventions to address it presents a huge challenge. Medication adherence and gout outcomes are worse in racial/ethnic minorities. The objective of this paper was to provide the details of the study protocol for randomized, controlled trial (RCT) in African Americans (AAs) with gout that will test the effectiveness of a culturally appropriate gout storytelling intervention.

Methods
The SToRytelliing to Improve Disease outcomes in Gout (STRIDE-GO) study will be a 12-month, multicenter, open-label RCT that will assess the effect of a culturally appropriate gout storytelling in at least 300 AA veterans with gout. Participants will be randomized to gout-storytelling intervention vs. a stress reduction video in a 1:1 ratio. The primary outcome is urate-lowering therapy (ULT) adherence measured with MEMSCap™, an electronic monitoring system (efficacy, 6 months; sustenance of efficacy, 12 months). Secondary outcomes include gout flares, serum urate (SU), gout-specific health-related quality of life [HRQOL], self-reported ULT adherence, patient satisfaction with treatment, and patient understanding of the intervention. AA veterans with gout who met the 1977 Preliminary American College of Rheumatology (ACR) classification criteria for gout, currently prescribed an oral ULT medication (allopurinol or febuxostat) for at least 6 months, and not using a pillbox to redistribute their medications, will be invited to an in-person study visit. After the study coordinators obtain informed consent, and ensure that participants meet the inclusion criteria, the eligible participants will be provided with their current ULT in a MEMSCap™ bottle for the 1-month run-in period and asked to return to the clinic in 1 month. ULT adherence with MEMSCap™ will be recorded at a 1-month return visit. Interested participants will complete the baseline assessments, randomized using the computerized system to either gout-storytelling intervention or a stress reduction intervention video arm and watch the respective video in-clinic. Patients will be interviewed on the phone at 2 and 4 months regarding the viewing of the videos at home at each time. Participants will be assessed in-clinic at 3, 6, 9, and 12 months; MEMSCap™ data and patient surveys will be captured at each visit. For any missed visit, assessments will be completed on the phone and MEMSCap™ data captured at the next in-clinic visit.

Discussion
The study will assess the efficacy of a behavioral intervention to improve ULT adherence in minority populations with gout.

Trial registration
ClinicalTrials.gov NCT 02741700. Registered on 14 September 2018
Wood-feeding termite gut symbionts as an obscure yet promising source of novel manganese peroxidase-producing oleaginous yeasts intended for azo dye decolorization and biodiesel production
Authors: Al-Tohamy Rania , Sun Jianzhong , Khalil Maha A. , Kornaros Michael , Ali Sameh Samir 
Published: December 2021

Abstract
Background
The ability of oxidative enzyme-producing micro-organisms to efficiently valorize organic pollutants is critical in this context. Yeasts are promising enzyme producers with potential applications in waste management, while lipid accumulation offers significant bioenergy production opportunities. The aim of this study was to explore manganese peroxidase-producing oleaginous yeasts inhabiting the guts of wood-feeding termites for azo dye decolorization, tolerating lignocellulose degradation inhibitors, and biodiesel production.

Results
Out of 38 yeast isolates screened from wood-feeding termite gut symbionts, nine isolates exhibited high levels of extracellular manganese peroxidase (MnP) activity ranged between 23 and 27 U/mL after 5 days of incubation in an optimal substrate. Of these MnP-producing yeasts, four strains had lipid accumulation greater than 20% (oleaginous nature), with Meyerozyma caribbica SSA1654 having the highest lipid content (47.25%, w/w). In terms of tolerance to lignocellulose degradation inhibitors, the four MnP-producing oleaginous yeast strains could grow in the presence of furfural, 5-hydroxymethyl furfural, acetic acid, vanillin, and formic acid in the tested range. M. caribbica SSA1654 showed the highest tolerance to furfural (1.0 g/L), 5-hydroxymethyl furfural (2.5 g/L) and vanillin (2.0 g/L). Furthermore, M. caribbica SSA1654 could grow in the presence of 2.5 g/L acetic acid but grew moderately. Furfural and formic acid had a significant inhibitory effect on lipid accumulation by M. caribbica SSA1654, compared to the other lignocellulose degradation inhibitors tested. On the other hand, a new MnP-producing oleaginous yeast consortium designated as NYC-1 was constructed. This consortium demonstrated effective decolorization of all individual azo dyes tested within 24 h, up to a dye concentration of 250 mg/L. The NYC-1 consortium's decolorization performance against Acid Orange 7 (AO7) was investigated under the influence of several parameters, such as temperature, pH, salt concentration, and co-substrates (e.g., carbon, nitrogen, or agricultural wastes). The main physicochemical properties of biodiesel produced by AO7-degraded NYC-1 consortium were estimated and the results were compared to those obtained from international standards.

Conclusion
The findings of this study open up a new avenue for using peroxidase-producing oleaginous yeasts inhabiting wood-feeding termite gut symbionts, which hold great promise for the remediation of recalcitrant azo dye wastewater and lignocellulosic biomass for biofuel production.
Transcriptome analysis of Rhizopus oryzae seed pellet formation using triethanolamine
Authors: Wu Na , Zhang Jiahui , Ou Wen , Chen Yaru , Wang Ru , Li Ke , Sun Xiao-man , Li Yingfeng , Xu Qing , Huang He 
Published: December 2021

AbstractRhizopus oryzae (R. oryzae) can effectively produce organic acids, and its pellet formation in seed cultures has been shown to significantly enhance subsequent fermentation processes. Despite advances in strain development, simple and effective methods for inducing pellet morphology and a basic understanding of the mechanisms controlling this process could facilitate substantial increases in efficiency and product output. Here, we report that 1.5% triethanolamine (TEOA) in seed culture medium can activate the growth of R. oryzae spores in compact and uniform pellets which is optimal for fermentation conditions. Analysis of fermentation kinetics showed that the production of fumaric and L-malic acid increases 293% and 177%, respectively. Transcriptomic analysis revealed that exposure of R. oryzae to 1.5% TEOA during the seed culture activated the phosphatidylinositol and mitogen-activated protein kinase signaling pathways. Theses pathways subsequently stimulated the downstream carbohydrate-active synthases and hydrolases that required for cell wall component synthesis and reconstruction. Our results thus provide insight into the regulatory pathways controlling pellet morphology germane to the viability of seed cultures, and provide valuable reference data for subsequent optimization of organic acid fermentation by R. oryzae.
Introduction of ultrasound-based living anatomy into the medical curriculum: a survey on medical students’ perceptions
Authors: Kefala-Karli Pelagia , Sassis Leandros , Sassi Marina , Zervides Constantinos 
Published: December 2021

Abstract
Background
Traditional anatomy teaching methods are based on the models and cadaveric dissections, providing fixed views of the anatomical structures. However, in the last few years, the emerging concept of ultrasound-based teaching in anatomy has started to gain ground among medical curricula. This study aims to evaluate the integration of ultrasound as an adjunct tool to traditional anatomy teaching methods and explore students’ perceptions of whether ultrasound-based teaching enhances their interest and knowledge of anatomy. A cross-sectional study was carried out among the students of the 6-year undergraduate entry (MD) and 4-year graduate entry (MBBS) program of the University of Nicosia. A questionnaire was distributed to them after the delivery of several twenty minutes ultrasound sessions by an expert in the field during anatomy practicals. The data were analyzed utilizing SPSS software, and the statistical significance was determined as p value < 0.05.

Results
107 MD and 42 MBBS students completed the questionnaire. Both groups agreed that their ultrasound-based learning experience was good or excellent (79.4% MD students; 92.9% MBBS students), that it enhanced their knowledge of anatomy (68.2% MD students; 90.5% MBBS students) and boosted their confidence regarding their examination skills practice (69.2% MD students; 85.7% MBBS students). Although most students desired more time allocated to the ultrasound station (72% MD students; 85.7% MBBS students), they believed that ultrasound-based teaching is a necessary adjunct to the traditional teaching methods of anatomy (89.7% MD students; 92.9% MBBS students).

Conclusions
Overall, MBBS students were more confident about the benefits of ultrasound-based teaching. Most of the students agreed that cross-sectional sessions of traditional teaching and ultrasound-based teaching strengthened their knowledge of anatomy and enhanced their confidence concerning their clinical examination skills. Medical schools should embrace the advantages that ultrasound-based teaching offers in order future doctors to be qualified to utilize ultrasound for procedural and diagnostical purposes.
Convalescence plasma treatment of COVID-19: results from a prematurely terminated randomized controlled open-label study in Southern Sweden
Authors: Holm Karin , Lundgren Maria N. , Kjeldsen-Kragh Jens , Ljungquist Oskar , Böttiger Blenda , Wikén Christian , Öberg Jonas , Fernström Nils , Rosendal Ebba , Överby Anna K. , Wigren Byström Julia , Forsell Mattias , Landin-Olsson Mona , Rasmussen Magnus 
Published: December 2021

Abstract
Objective
Convalescent plasma has been tried as therapy for various viral infections. Early observational studies of convalescent plasma treatment for hospitalized COVID-19 patients were promising, but randomized controlled studies were lacking at the time. The objective of this study was to investigate if convalescent plasma is beneficial to hospitalized patients with COVID-19.

Results
Hospitalized patients with confirmed COVID-19 and an oxygen saturation below 94% were randomized 1:1 to receive convalescent plasma in addition to standard of care or standard of care only. The primary outcome was number of days of oxygen treatment to keep saturation above 93% within 28 days from inclusion. The study was prematurely terminated when thirty-one of 100 intended patients had been included. The median time of oxygen treatment among survivors was 11 days (IQR 6–15) for the convalescent plasma group and 7 days (IQR 5–9) for the standard of care group (p = 0.4, median difference -4). Two patients in the convalescent plasma group and three patients in the standard of care group died (p = 0.64, OR 0.49, 95% CI 0.08–2.79). Thus no significant differences were observed between the groups.
Trial registration ClinicalTrials NCT04600440, retrospectively registered Oct 23, 2020.
Clinical and analytical comparison of six Simoa assays for plasma P-tau isoforms P-tau181, P-tau217, and P-tau231
Authors: Bayoumy Sherif , Verberk Inge M. W. , den Dulk Ben , Hussainali Zulaiga , Zwan Marissa , van der Flier Wiesje M. , Ashton Nicholas J. , Zetterberg Henrik , Blennow Kaj , Vanbrabant Jeroen , Stoops Erik , Vanmechelen Eugeen , Dage Jeffrey L. , Teunissen Charlotte E. 
Published: December 2021

AbstractIntroductionStudies using different assays and technologies showed highly promising diagnostic value of plasma phosphorylated (P-)tau levels for Alzheimer’s disease (AD). We aimed to compare six P-tau Simoa assays, including three P-tau181 (Eli Lilly, ADx, Quanterix), one P-tau217 (Eli Lilly), and two P-tau231 (ADx, Gothenburg).MethodsWe studied the analytical (sensitivity, precision, parallelism, dilution linearity, and recovery) and clinical (40 AD dementia patients, age 66±8years, 50%F; 40 age- and sex-matched controls) performance of the assays.ResultsAll assays showed robust analytical performance, and particularly P-tau217 Eli Lilly; P-tau231 Gothenburg and all P-tau181 assays showed robust clinical performance to differentiate AD from controls, with AUCs 0.936–0.995 (P-tau231 ADx: AUC = 0.719). Results obtained with all P-tau181 assays, P-tau217 Eli Lilly assay, and P-tau231 Gothenburg assay strongly correlated (Spearman’s rho > 0.86), while correlations with P-tau231 ADx results were moderate (rho < 0.65).DiscussionP-tau isoforms can be measured robustly by several novel high-sensitive Simoa assays.
MiRNA-221-5p suppressed the Th17/Treg ratio in asthma via RORγt/Foxp3 by targeting SOCS1
Authors: Guan Yuanyuan , Ma Yuemei , Tang Yao , Liu Xiaolei , Zhao Yan , An Lixin 
Published: December 2021

Abstract
Background
This study was designed to investigate the mechanism and effects of miRNA-221-5p on the T-helper 17 (Th17)/T-regulatory (Treg) ratio in asthma.

Methods
BALB/c mice were intranasally challenged with 100 µg OVA on 14 and 21 day. Mice were rechallenged with 2.5% OVA-PBS on 22 and 28 day. Mice were sacrificed using on day 30 under 35 mg/kg pentobarbital sodium. PBMCs were induced vitro model of asthma using 500 ng of lipopolysaccharides (LPS) for 4 h.

Results
The expression of miRNA-221-5p was reduced in in vivo model, compared sham group. The vitro model of asthma treated with miRNA-221-5p mimic resulted in the reduction of IL-6, IL-17, IL-21 and IL-22 levels, and induction of IL-10, IL-35 and TGF-β levels. In addition, down-regulation of miRNA-221-5p induced the protein expression of suppressor of cytokine signaling 1 (SOCS1) and receptor-related orphan receptor-gamma-t (RORγt) and suppressed that of FOXP3 in in vitro model of asthma. Over-expression of miRNA-221-5p induced the protein expression of FOXP3, and suppressed that of SOCS1 and RORγt in in vitro model of asthma. The inhibition of SOCS1 or RORγt attenuated the effects of anti-miRNA-221-5p on Th17/Treg ratio in asthma.

Conclusion
miRNA-221-5p may play critical roles in driving the differentiation of Th17/Treg ratio via RORγt/Foxp3 by Targeting SOCS1, reduced the function of Th17 cells by directly inhibiting RORγt/SOCS1 and promoted the function of Treg cells via Foxp3/ SOCS1 in asthma.
The European Society of Head and Neck Radiology Mentoring Programme: development and feedback during the first phase of the initiative
Authors: Connor Steve , Robinson Soraya 
Published: December 2021

AbstractThere is increasing awareness of the benefits of formal mentorship programmes in radiology. In the context of the COVID 19 pandemic which impacted on education, professional engagement and networking within the wider radiological community, the European Society of Head and Neck Radiology (ESHNR) decided to develop a formal mentoring programme. The ESHNR mentoring initiative is novel in its scope, whereby European and international members of a subspecialty radiology society are matched into mentor–mentee pairings to disseminate good practice, knowledge and ideas. The purpose of this report is to describe the motivations, planning, challenges and early experience of the ESHNR mentoring programme together with initial feedback from the scheme.The development of the programme and iterative modifications during the first phase of the scheme are described. The programme has enrolled 33 mentors and 27 mentees with international representation and 24 mentor–mentee pairs have participated in 2.6 (mean) meetings. The experience and benefits reported by the participating ESHNR members (mentees and mentors) were evaluated by a questionnaire at six months following the start of the programme. There were 80% of mentors and 88% of mentees who strongly agreed that the mentoring programme was rewarding rather than an obligation, and all participants reported that they would recommend the scheme to colleagues.A formal mentoring programme has been established for an international subspecialty radiology society. The early experience is encouraging and suggests that it is both useful and sustainable. Our experiences may be of benefit to other subspecialty societies considering a mentoring programme.
Graphene oxide-modified silk fibroin/nanohydroxyapatite scaffold loaded with urine-derived stem cells for immunomodulation and bone regeneration
Authors: Sun Jiachen , Li Lang , Xing Fei , Yang Yun , Gong Min , Liu Guoming , Wu Shuang , Luo Rong , Duan Xin , Liu Ming , Zou Min , Xiang Zhou 
Published: December 2021

Abstract
Background
The invasive and complicated procedures involving the use of traditional stem cells limit their application in bone tissue engineering. Cell-free, tissue-engineered bones often have complex scaffold structures and are usually engineered using several growth factors (GFs), thus leading to costly and difficult preparations. Urine-derived stem cells (USCs), a type of autologous stem cell isolated noninvasively and with minimum cost, are expected to solve the typical problems of using traditional stem cells to engineer bones. In this study, a graphene oxide (GO)-modified silk fibroin (SF)/nanohydroxyapatite (nHA) scaffold loaded with USCs was developed for immunomodulation and bone regeneration.

Methods
The SF/nHA scaffolds were prepared via lyophilization and cross-linked with GO using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC) and N-hydroxy succinimide (NHS). Scaffolds containing various concentrations of GO were characterized using scanning electron microscopy (SEM), the elastic modulus test, Fourier transform infrared spectroscopy (FTIR), and X-ray photoelectron spectrometer (XPS). Examinations of cell adhesion, proliferation, viability, morphology, alkaline phosphatase activity, and osteogenesis-related gene expression were performed to compare the osteogenesis-related biological behaviors of USCs cultured on the scaffolds. The effect of USC-laden scaffolds on the differentiation of macrophages was tested using ELISA, qRT-PCR, and immunofluorescence staining. Subcutaneous implantations in rats were performed to evaluate the inflammatory response of the USC-laden scaffolds after implantation. The scaffolds loaded with USCs were implanted into a cranial defect model in rats to repair bone defects. Micro-computed tomography (μCT) analyses and histological evaluation were performed to evaluate the bone repair effects.

Results
GO modification enhanced the mechanical properties of the scaffolds. Scaffolds containing less than 0.5% GO had good biocompatibility and promoted USC proliferation and osteogenesis. The scaffolds loaded with USCs induced the M2-type differentiation and inhibited the M1-type differentiation of macrophages. The USC-laden scaffolds containing 0.1% GO exhibited the best capacity for promoting the M2-type differentiation of macrophages and accelerating bone regeneration and almost bridged the site of the rat cranial defects at 12 weeks after surgery.

Conclusions
This composite system has the capacity for immunomodulation and the promotion of bone regeneration and shows promising potential for clinical applications of USC-based, tissue-engineered bones.
Emerging concepts in the treatment of optic neuritis: mesenchymal stem cell-derived extracellular vesicles
Authors: Aneesh Anagha , Liu Alice , Moss Heather E. , Feinstein Douglas , Ravindran Sriram , Mathew Biji , Roth Steven 
Published: December 2021

AbstractBackgroundOptic neuritis (ON) is frequently encountered in multiple sclerosis, neuromyelitis optica spectrum disorder, anti-myelin oligodendrocyte glycoprotein associated disease, and other systemic autoimmune disorders. The hallmarks are an abnormal optic nerve and inflammatory demyelination; episodes of optic neuritis tend to be recurrent, and particularly for neuromyelitis optica spectrum disorder, may result in permanent vision loss.Main BodyMesenchymal stem cell (MSC) therapy is a promising approach that results in remyelination, neuroprotection of axons, and has demonstrated success in clinical studies in other neuro-degenerative diseases and in animal models of ON. However, cell transplantation has significant disadvantages and complications. Cell-free approaches utilizing extracellular vesicles (EVs) produced by MSCs exhibit anti-inflammatory and neuroprotective effects in multiple animal models of neuro-degenerative diseases and in rodent models of multiple sclerosis (MS). EVs have potential to be an effective cell-free therapy in optic neuritis because of their anti-inflammatory and remyelination stimulating properties, ability to cross the blood brain barrier, and ability to be safely administered without immunosuppression.ConclusionWe review the potential application of MSC EVs as an emerging treatment strategy for optic neuritis by reviewing studies in multiple sclerosis and related disorders, and in neurodegeneration, and discuss the challenges and potential rewards of clinical translation of EVs including cell targeting, carrying of therapeutic microRNAs, and prolonging delivery for treatment of optic neuritis.Graphical Abstract