bluuebunny/crossref_metadata_2025 huggingface dataset:
Selection and Evaluation of Reference Genes for ddPCR-Based Transcript Abundance Studies in Oidiodendron Maius Across Varying Carbon Sources
Authors: Feldman Erin , Martino Elena , Kohler Annegret , Durall Daniel , Jones Melanie
Published: January 2021

Background When identifying transcript abundance in response to treatment, accurate quantification is critical, especially when examining subtle differences in expression. In particular, data normalization is necessary to account for differences among samples including those associated with RNA quantity and quality. Due to the capacity of droplet digital PCR to absolutely quantify the copy number of the target gene in a given sample, normalization, such as the use of an internal control gene, has not customarily been considered obligatory. Decades of quantitative PCR research have shown, however, that the use of endogenous controls undoubtedly aid in correcting sample variability. With our limited knowledge of gene function in many fungi, typical ‘housekeeping genes’ commonly used as internal references may not be relevant in these organisms. This study aimed to identify and validate suitable reference genes for transcript abundance studies in Oidiodendron maius, a globally distributed, model ericoid mycorrhizal fungus. Results A shortlist of 251 non-differentially expressed genes was generated from RNA-Seq analyses of O. maius grown on three different carbon sources or in symbiosis with Vaccinium myrtillus. Subsequently, a set of criteria (stable expression, valid annotation and relatively high expression) was applied to select three candidate reference genes. These three genes were validated across a further eleven carbon sources using ddPCR and the application of geNorm and NormFinder stability analysis algorithms. Expression stability analysis of three genes - EfTu, vma, and sar - confirmed their reliability as internal references; the geometric mean of their expression values demonstrated the highest stability as a normalization factor.Conclusions We propose the use of the geometric mean of O. maius genes EfTu, vma and sar as a reference tool to normalize RNA expression in ddPCR assays. These newly selected and validated reference genes will increase reliability and reproducibility when studying transcriptional responses of O. maius at different developmental stages and/or under a range of physiological conditions. In addition, the list of 251 non-differentially expressed genes can serve as a valuable resource for selecting reference genes for related experiments and enhances the limited information available on O. maius.
Take-Home Naloxone Programs for Suspected Opioid Overdose in Community Settings: A Scoping Umbrella Review
Authors: Moustaqim-Barrette Amina , Dhillon Damon , Ng Justin , Sundvick Kristen , Ali Farihah , Elton-Marshall Tara , Leece Pamela , Rittenbach Katherine , Ferguson Max , Buxton Jane
Published: January 2021

Background: Opioid related overdoses and overdose deaths continue to constitute an urgent public health crisis. The implementation of naloxone programs, such as ‘take-home naloxone’ (THN), has emerged as a key intervention in reducing opioid overdose deaths. These programs aim to train individuals at risk of witnessing or experiencing an opioid overdose to recognize an opioid overdose and respond with naloxone. Naloxone effectively reverses opioid overdoses on a biological level; however, there are outstanding questions on community THN program effectiveness (adverse events, dosing requirements, dose-response between routes of administration) and implementation (accessibility, availability, and affordability). The objective of this scoping review is to identify existing systematic reviews and best practice guidelines relevant to clinical and operational guidance on the distribution of THN.Methods: Using the Arksey & O’Malley framework for scoping reviews, we searched both academic literature and grey literature databases using keywords (Naloxone) AND (Overdose) AND (Guideline OR Review OR Recommendation OR Toolkit). Only documents which had a structured review of evidence and/or provided summaries or recommendations based on evidence were included (systematic reviews, meta-analyses, scoping reviews, short-cut or rapid reviews, practice/clinical guidelines, and reports). Data were extracted from selected evidence in two key areas: (1) study identifiers; and (2) methodological characteristics. Results: A total of 47 articles met inclusion criteria: 20 systematic review; 10 grey literature articles; 8 short-cut or rapid reviews; 4 scoping reviews; and 5 other review types (e.g. mapping review and comprehensive reviews). The most common subject themes were: naloxone effectiveness, safety, provision feasibility/acceptability of naloxone distribution, dosing and routes of administration, overdose response after naloxone administration, cost-effectiveness, naloxone training and education, and recommendations for policy, practice and gaps in knowledge. Conclusions: Several recent systematic reviews address the effectiveness of take-home naloxone programs, naloxone dosing/route of administration, and naloxone provision models. Gaps remain in the evidence around evaluating cost-effectiveness, training parameters and strategies, and adverse events following naloxone administration. As THN programs continue to expand in response to opioid overdose deaths, this review will contribute to understanding the evidence 60 base for policy and THN program development and expansion.
Relationship Between Renal Function and Blood Pressure Dipping Status in Renal Transplant Recipients: A Longitudinal Study.
Authors: Jaques David , Saudan Patrick , Martinez Chantal , Andres Axel , Martin Pierre-Yves , Pechère-Bertschi Antoinette , Ponte Belen
Published: January 2021

Background Hypertension (HT) is associated with adverse outcomes in renal transplant (RTX) recipients. Blunting of physiological decrease in nighttime compared to daytime blood pressure (non-dipping status) is frequent in this setting. However, weather non-dipping is independently associated with renal function decline in RTX patients is unknown.Methods We retrospectively screened RTX outpatients attending for a routine ambulatory blood pressure monitoring (ABPM) (T1) at a single tertiary hospital. Patients had two successive follow-up visits, one (T2) and two (T3) years later respectively. Routine clinical and laboratory data were collected at each visit. Mixed linear regression models were used with estimated glomerular filtration rate (eGFR) as the dependent variable.Results A total of 123 patients were included with a mean follow-up of 2.12 +/- 0.45 years after ABPM. Mean age and eGFR at T1 were 56.0 +/- 15.1 and 54.9 +/- 20.0 mL/min/1.73m2 respectively. 61 patients (50.4%) had sustained HT and 81 (65.8%) were non-dippers. In multivariate analysis, systolic dipping status was positively associated with eGFR (p=0.009) and compared to non-dippers, dippers had a 10.4 mL/min/1.73m2 higher eGFR. HT was negatively associated with eGFR (p=0.003).Conclusions We confirm a high prevalence of non-dippers in RTX recipients. We show that preserved systolic dipping is associated with improved renal function in this setting independently of potential confounders, including HT and proteinuria. Whether modification of dipping status by chronotherapy would preserve renal function remains to be tested in clinical trials.
Vaccine monitoring shows that focused immunization with SARS-CoV-2 receptor-binding domain provides a better neutralizing antibody response than full-length spike protein
Authors: Bayarri-Olmos Rafael , Idorn Manja , Rosbjerg Anne , Pérez-Alós Laura , Hansen Cecilie , Johsen Laust , Helgstrand Charlotte , Öberg Fredrik Kryh , Søgaard Max , Paludan Søren , Bak-Thomsen Theresa , Jardine Joseph , Skjoedt Mikkel-Ole , Garred Peter
Published: January 2021

Effective tools to monitor SARS-CoV-2 transmission and humoral immune responses are highly needed. Protective humoral immunity involves neutralizing antibodies and will be a hallmark for the evaluation of a vaccine response efficacy. Here we present a sensitive, fast and simple neutralization ELISA method to determine the levels of antibody-mediated virus neutralization. We can show that it is strongly correlated with the more elaborate plaque reduction neutralization test (PRNT) (ρ = 0.9231, p < 0.0001). Furthermore, we present pre-clinical vaccine models using recombinant receptor binding domain (RBD) and full-length spike antigen as immunogens showing a profound antibody neutralization capacity that exceeds the highest neutralization titers from convalescent individuals. Using a panel of novel high-affinity murine monoclonal antibodies (mAbs) we also show that majority of the RBD-raised mAbs have inhibitory properties while only a few of the spike-raised mAbs do. In conclusion, the ELISA-based viral neutralization test offers a time- and cost-effective alternative to the PRNT. The immunization results indicate that vaccine strategies focused only on the RBD region may have major advantages over those based on the full spike sequence.
On the Impact of Vessel Wall Stiffness on Quantitative Flow Dynamics in a Synthetic Model of the Thoracic Aorta
Authors: Zimmermann Judith , Loecher Michael , Kolawole Fikunwa , Bäumler Kathrin , Gifford Kyle , Dual Seraina , Levenston Marc , Marsden Alison , Ennis Daniel
Published: January 2021

Aortic wall stiffening is a predictive marker for morbidity in hypertensive patients. Arterial pulse wave velocity (PWV) correlates with the level of stiffness and can be derived using non-invasive 4D-flow magnetic resonance imaging (MRI). The objectives of this study were twofold: to develop subject-specific thoracic aorta models embedded into an MRI-compatible flow circuit operating under controlled physiological conditions; and to evaluate how a range of aortic wall stiffness impacts 4D-flow-based quantification of hemodynamics, particularly PWV. Three aorta models were 3D-printed using a novel photopolymer material at two compliant and one nearly rigid stiffnesses and characterized via tensile testing. Luminal pressure and 4D-flow MRI data were acquired for each model and cross-sectional net flow, peak velocities, and PWV were measured. In addition, the confounding effect of temporal resolution on all metrics was evaluated. Stiffer models resulted in increased systolic pressures (112, 116, and 133 mmHg), variations in velocity patterns, and increased peak velocities, peak flow rate, and PWV (5.8 to 7.3 m/s). Lower temporal resolution (20 ms down to 62.5 ms per image frame) impacted estimates of peak velocity and PWV (7.31 down to 4.77 m/s). Using compliant aorta models is essential to produce realistic flow dynamics and conditions that recapitulated in vivo hemodynamics.
Clinical Characteristics of Severe Neonatal Enterovirus Infection: A Systematic Review
Authors: Zhang Meng , Wang Haoran , Tang Jun , He Yang , Xiong Tao , Li Wenxing , Qu Yi , Mu Dezhi
Published: January 2021

Background: Enterovirus (EV) is a common cause of infection in neonates. Neonates are at high risk of enterovirus infection with serious clinical manifestations and high mortality. This review systematically summarized the clinical characteristics of neonates with severe enteroviral infection to provide evidence for the identification and treatment of severe neonatal EV infection. Methods: PubMed, Embase, and Web of Science were searched for original studies on neonates with severe EV infections from January 1, 2000, to November 27, 2020. Two reviewers independently screened the literature, extracted the data, and performed a descriptive analysis.Results: In total, 66 articles with 237 cases of severe neonatal enterovirus infection were included. All patients developed severe complications. Among them, 46.0% patients had hepatitis or coagulopathy, 37.1% had myocarditis, 11.0% had meningoencephalitis, and 5.9% had other complications such as hemophagocytic lymphohistiocytosis and pulmonary hemorrhage. The mortality rate of patients with severe infection was 30.4%. The highest mortality rate was 38.6%, which was observed in patients with myocarditis. In 70.5% patients, the age at the onset of symptoms was less than 7 days. Coxsackievirus B infection was seen in 52.3% patients. The most common symptoms included temperature abnormalities (127, 53.6%), rash (88, 37.1%), poor feeding (58, 24.5%), and respiratory symptoms (52, 21.9%). The main treatment included transfusion of blood components (42.2%), intravenous immunoglobulin (IVIG; 40.9%), mechanical ventilation (21.5%), and extracorporeal membrane oxygenation (ECMO; 18.1%). Additionally, antiviral medications pleconaril (14, 5.9%) and pocapavir (3, 1.3%) were administered. Conclusions: Mortality was high in patients with severe enterovirus infection, especially in those complicated with myocarditis. The most common symptoms included temperature abnormalities, rash, and poor feeding. The chief supportive treatment consisted of transfusion of blood components, mechanical ventilation, and ECMO. IVIG were widely used. Antiviral medications included pocapavir and pleconaril; however, more clinical evidence regarding their efficacy is needed.
Prediction of A Positive Surgical Margin and Biochemical Recurrence After Robot-Assisted Radical Prostatectomy 
Authors: Yang Ching-Wei , Wang Hsiao-Hsien , Hassouna Mohamed , Chand Manish , Chung Hsiao-Jen
Published: January 2021

A positive surgical margin (PSM) detected in a prostatectomy specimen is associated with poor oncotherapeutic outcomes. Certain aspects regarding the determination of surgical margins and their effects on biochemical recurrence (BCR) remain unclear. This study investigated the predictive factors for PSM and BCR. We prospectively included 419 robot-assisted radical prostatectomy cases. The number of PSM cases was 126 (30.1%), stratified as 22 (12.2%) in stage T2 and 103 (43.6%) in stage T3. Preoperative prostate-specific antigen (PSA) > 10 ng/mL (p = 0.047; odds ratio [OR] 1.712), intraoperative blood loss > 200 mL (p = 0.006; OR 4.01), and postoperative pT3 stage (p < .001; OR 6.901) were three independent predictors for PSM in multivariate analysis. PSA > 10 ng/mL (p < 0.015; hazard ratio [HR] 1.8), pT3 stage (p = 0.012; HR 2.264), ISUP grade > 3 (p = 0.02; HR 1.964), and PSM (p = 0.027; HR 1.725) were four significant predictors for BCR in multivariate analysis. Among PSM cases, ISUP grade > 3 (p = 0.002; HR 2.689) was a significant BCR predictor. These results indicate that PSA level and pathological stage markedly influence the PSM and BCR.
A roadmap to using randomization in clinical trials
Authors: Berger Vance , Bour Louis , Carter Kerstine , Chipman Jonathan , Everett Colin , Heussen Nicole , Hewitt Catherine , Hilgers Ralf-Dieter , Luo Y. Abigail , Renteria Jone , Ryeznik Yevgen , Sverdlov Oleksandr , Uschner Diane
Published: January 2021

Background: Randomization is the foundation of any clinical trial involving treatment comparison. It helps mitigate selection bias, promotes similarity of treatment groups with respect to important known and unknown confounders, and contributes to the validity of statistical tests. Various restricted randomization procedures with different probabilistic structures and different statistical properties are available.Methods: We survey available restricted randomization procedures for sequential allocation of subjects in a randomized, comparative, parallel group clinical trial with equal (1:1) allocation. We explore statistical properties of these procedures, including balance/randomness tradeoff, type I error rate and power. We perform head-to-head comparisons of different procedures through simulation under various experimental scenarios, including cases when common model assumptions are violated. We also provide some real-life clinical trial examples to illustrate the thinking process for selecting a randomization procedure for implementation in practice. Results: Restricted randomization procedures targeting 1:1 allocation vary in the degree of balance/randomness they induce, and more importantly, they vary in terms of validity and efficiency of statistical inference when common model assumptions are violated (e.g. when outcomes are affected by a linear time trend; measurement error distribution is misspecified; or selection bias is introduced in the experiment). Some procedures are more robust than others. Covariate-adjusted analysis may be essential to ensure validity of the results. Special considerations are required when selecting a randomization procedure for a clinical trial with very small sample size.Conclusions: The choice of randomization design, data analytic technique (parametric or nonparametric), and analysis strategy (randomization-based or population model-based) are all very important considerations. Randomization-based tests are robust and valid alternatives to likelihood-based tests and should be considered more frequently by clinical investigators.
The evolutionary fate of rpl32 and rps16 losses in the Euphorbia schimperi (Euphorbiaceae) plastome
Authors: Alqahtani Aldanah , Jansen Robert
Published: January 2021

Gene transfers from mitochondria and plastids to the nucleus are an important process in the evolution of the eukaryotic cell. Plastid (pt) gene losses have been documented in multiple angiosperm lineages and are often associated with functional transfers to the nucleus or substitutions by duplicated nuclear genes targeted to both the plastid and mitochondrion. The plastid genome sequence of Euphorbia schimperi was completed and losses of rpl32, rps16 and infA genes were detected. The nuclear transcriptome of E. schimperi was sequenced to investigate the transfer/substitution of the rpl32 and rps16 genes to the nucleus. Transfer of plastid-encoded rpl32 to the nucleus was identified previously in three families of Malpighiales, Rhizophoraceae, Salicaceae and Passifloraceae. An E. schimperi transcript of pt SOD-1-RPL32 confirmed that the transfer in Euphorbiaceae is similar to other Malpighiales indicating that it occurred early in the divergence of the order. Ribosomal protein S16 (rps16) is encoded in the plastome in most angiosperms but not in Salicaceae and Passifloraceae. Substitution of the E. schimperi pt rps16 was likely due to a duplication of nuclear-encoded mitochondrial-targeted rps16 resulting in copies dually targeted to the mitochondrion and plastid. Sequences of RPS16-1 and RPS16-2 in the three families of Malpighiales (Salicaceae, Passifloraceae and Euphorbiaceae) have high sequence identity suggesting that the substitution event dates to the early divergence of Malpighiales.
On the shape and structure of the murine pulmonary heart valve
Authors: Liu Yifei , Feng Xinzeng , Liu Hao , McComb David , Breuer Christopher , Sacks Michael
Published: January 2021

Murine animal models are an established standard in translational research and provides a potential platform for studying heart valve disease. To date, studies on heart valve disease using murine models have been hindered by a lack of appropriate methodologies due to their small scale. In the present study, we developed a multi-scale, imaging-based approach to extract the functional structure and geometry for the murine heart valve. We chose the pulmonary valve (PV) to study, due to its importance in congenital heart valve disease. Excised pulmonary outflow tracts from eleven 1-year old C57BL/6J mice were fixed at 10, 20, and 30 mmHg to simulate physiological loading. Micro-computed tomography was used to reconstruct the 3D organ-level PV geometry, which was then spatially correlated with serial en-face scanning electron microscopy imaging to quantify local collagen fiber distributions. From the acquired volume renderings, we obtained the geometric descriptors of the murine PV under increasing transvalvular pressures, which demonstrated remarkable consistency. We also observed that the preferred collagen orientation was predominantly in the circumferential direction, as in larger mammalian valves. The present study represents a first step in establishing organ-level murine models for the study of heart valve disease.
Morphological and Molecular Characterization of Iranian Wild Blackberry Species Using Multivariate Statistical Analysis and Inter-Simple Sequence Repeats (ISSR) Markers
Authors: Gharaghani Ali , Garazhian Mehdi , Eshghi Saeid , Tahmasebi Ahmad
Published: January 2021

This study was carried out to estimate the genetic diversity and relationships of 74 Iranian blackberry genotypes assigned to 5 different species using inter-simple sequence repeats (ISSR) marker analysis and morphological trait characterization. Sixteen traits including phenological, vegetative and reproductive attributes were recorded, and 10 ISSR primers were screened. Results showed that yield and leaf width have the highest and lowest genetic diversity, (diversity index = 62.57 and 13.74), respectively. Flowering and ripening date recorded as traits having the strongest correlations (r = 0.98). The selected 10 ISSR primers produced a total of 161 amplified fragments (200 to 3500 bp) of which 113 were polymorphic. The highest, lowest and average PIC values were 0.53, 0.38 and 0.44, respectively. Principle component analysis (PCA) based on morphological traits showed that the first six components explained 84.9% of the variations of traits studied, whilst the principal coordinate analysis (PCoA) based on ISSR data implied the first eight principal coordinates explained 67.06% of the total variation. Cluster analysis based on morphological traits and ISSR data classified all genotypes into two and three major groups, respectively, and the distribution pattern of genotypes was mainly based on species and the geographic origins.
Three-Dimensional Quantitative Measurement of Buccal Augmented Tissue After MCAT Technique With SCTG: Preliminary Results of a Prospective Case Series
Authors: Xue Fei , Zhang Rui , Cai Yu , Zhang Yong , Kang Ni , Luan Qingxian
Published: January 2021

Background: The aim of this study to investigate three-dimensional quantitative analysis buccal augmented tissue alterations after modified coronally advanced tunnel (MCAT) technique combined with subepithelial connective tissue graft (SCTG) within 1-year based on intraoral scanning.Methods: 25 Cairo class I gingival recession defects were treated by MCAT technique with SCTG. Two examiners performed digital three-dimensional measurements, including the preoperative gingival recession height (GH), width (GW) and root exposed area (REA), postoperative gingival height gain (HG), area gain (AG), volume gain (VG) and mean thickness gain (MTG) of region of interest (ROI). Then, dynamic alterations of ROI and buccal tissue at 2 weeks, 6 weeks, 3 months and 1-year post-op were analysis. Results: Intra-class correlation coefficients (ICC) showed almost perfect inter-examiner reliability for digital measurement (ICC > 0.89). Postoperative HG, AG, VG and MTG were encountered distinct at 2 weeks post-op, then gradually decreased. At 1-year, AG, VG and MTG were 7.614 ± 2.511mm2, 7.690 ± 4.335mm3 and 0.965±0.372mm, respectively. Significant decreases were recorded between 6 weeks and 1-year in terms of HG, AG and VG. The MTG was sustained after 6 weeks with an increase of nearly 1mm at 1-year.Conclusions: Digital measurement by intraoral scanning offered an advantage of clinically feasible, non-invasive and reliable evaluation method for achieving volumetric outcomes after periodontal plastic surgery. Augmented tissue acquired by MCAT with SCTG tends to be stable after 3 months post-op.Trial registration：This study was retrospectively registered in Chinese Clinical Trial Registry: ChiCTR1900026768. Date of registration: 21/10/2019.
METTL3-mediated M6a Modification Regulates Cell Cycle Progression of Dental Pulp Stem Cells
Authors: Luo Haiyun , Liu Wenjing , Zhang Yanli , Jiang Xiao , Wu Shiqing , Shao Longquan
Published: January 2021

Background: Dental pulp stem cells (DPSCs) exhibited self-renewal, pluripotency capacity and served as promising cells source in endodontic regeneration and tissue engineering. Meanwhile, the regenerative capacity of DPSCs is limited and reduced in long lifespan. N6-methyladenosine (m6A) is the most prevalent, reversible internal modification in RNAs. The methyltransferases complex and demethylases mediated m6A methylation and cooperated to impact various biological processes associated with stem cell fate determination. However, the biological effect of m6A methylation in DPSCs remained unclear. Methods: Cell surface markers and differentiation potential of primary DPSCs were identified and m6A immunoprecipitation with deep sequencing (m6A RIP-seq) was used to uncover characteristics of m6A modifications in DPSCs transcriptome. Expression level of m6A-related genes were evaluated in immature/mature pulp tissues and cells. Lentiviral vectors were constructed to knockdown or overexpress methyltransferase like 3 (METTL3). Cell morphology, viability, senescence and apoptosis were further analyzed by β-galactosidase, TUNEL staining and flow cytometry. Bioinformatic analysis combing m6A RIP and shMETTL3 RNA-seq was used to functionally enrich overlapped genes and screen target of METTL3. Cell cycle distributions were assayed by flow cytometry and m6A RIP-qPCR was used to confirm METTL3 mediated m6A methylation in DPSCs. Results: Here, m6A peaks distribution, binding area and motif in DPSCs were first revealed by m6A RIP-seq. We also found a relative high expression level of METTL3 in immature DPSCs with superior regenerative potential and METTL3 knockdown induced cell apoptosis and senescence. Furthermore, Conjoint analysis of m6A RIP and RNA-sequencing showed differentially expressed genes affected by METTL3 depletion was mainly enriched in cell cycle, mitosis and alteration of METTL3 expression resulted in cell cycle arrest which indicated METTL3 make essential effect in cell cycle control. To further investigate underlying mechanisms, we explored proteins interaction network of differentially expressed genes and Polo-like Kinase 1 (PLK1), a critical cycle modulator was identified as target of METTL3-mediated m6A methylation in DPSCs. Conclusions: These results revealed m6A methylated hallmarks in DPSCs and a regulatory role of METTL3 in cell cycle control. Our study shed light on therapeutic approaches in vital pulp therapy and serve new insight in stem cells based tissue engineering.
Robust Expansion and Functional Maturation of Human Hepatoblasts by Chemical Strategy
Authors: Pan Tingcai , Tao Jiawang , Chen Yan , Zhang Jiaye , Getachew Anteneh , Zhuang Yuanqi , Wang Ning , Xu Yingying , Tan Shenglin , Fang Ji , Yang Fan , Lin Xianhua , You Kai , Gao Yi , Li Yin-xiong
Published: January 2021

Background: Chemically strategies to generate hepatic cells from human pluripotent stem cells (hPSCs) for the potential clinical application have been improved. However, producing high quality and large quantities of hepatic cells remain challenging, especially in terms of step-wise efficacy and cost-effective production requires more improvements. Methods: Here, we systematically evaluated chemical compounds for hepatoblasts (HBs) expansion and maturation to establish a robust, cost-effective and reproducible methodology for self-renewal HBs and functional hepatocyte-like cells (HLCs) production. Results: The established chemical cocktail could enable HBs to proliferate nearly 3000 folds within 3 weeks with preserved bipotency. Moreover, those expanded HBs could be further efficiently differentiated into homogenous HLCs displayed typical morphologic and functionality as mature hepatocytes, including hepatocyte identity markers expression and key functional activities such as cytochrome P450 metabolism activities and urea secretion. Importantly, the transplanted HBs in injured liver of immune-defect mice differentiated as hepatocytes, engraft and repopulate in the injured loci of the recipient liver. Conclusion: Together, this chemical compound based HLCs generation method presents an efficient and cost-effective platform for the large-scale production of functional human hepatic cells for cell-based therapy and drug discovery application.
Networks to strengthen community social capital for suicide prevention in regional Australia: The LifeSpan Suicide Prevention Initiative
Authors: Long Janet C. , Ruane Colum , Ellis Louise A. , Lake Rebecca , Roux Anneke Le , Testa Luke , Shand Fiona , Torok Michelle , Zurynski Yvonne
Published: January 2021

BackgroundLifeSpan is a recently implemented suicide prevention initiative developed by the Black Dog Institute that draws upon nine evidence-based community-wide prevention strategies. We examined how the implementation of LifeSpan used the strategy of forming a suicide prevention Collaborative group (The Collaborative) at each site. We evaluated how this had affected the social capital of the community and the effectiveness of the group through the growth of the key stakeholders’ socio-professional network. MethodsThis was a mixed methods study. Participants were The Collaborative and working group members at four sites implementing the LifeSpan initiative in New South Wales. Quantitative social network data was collected through an online survey and qualitative data through focus groups with The Collaborative members and interviews with LifeSpan Coordinators.ResultsThere was clear quantitative evidence of increased engagement across key stakeholders in the region, who were not previously working together. This extended beyond the formal structure of The Collaborative. LifeSpan Coordinators were empirically identified as key players in the networks. Benefits of this collaborative approach included greater capacity to run activities, better communication between groups, identification of “who’s who” locally, improvement in the integration of priorities, services and activities, and personal support for previously isolated members. It was noted that the LifeSpan Coordinators were key to the smooth running of The Collaborative and its resulting combined effort, but this may represent a risk to its sustainability if they left. The model of collaboration that suited metropolitan sites was seen as difficult to sustain in one rural site but gains at this site were seen in better coordinated postvention efforts. Engagement was difficult with some clinically based services at some sites.ConclusionLifeSpan Coordinators were noted to be exceptional people that magnified the benefits of collaboration. Geographic proximity was also seen as a potent driver of social capital. Initial engagement with local stakeholders was seen as essential but time consuming (and “invisible”) work in the implementation phase.
A Global Measure of Patient-reported Outcomes After Injury – Life Back on Track
Authors: Chen Gang , Woode Maame Esi , Sia Kah Ling , Ellis Nina , Citroen Cassie , Harris Anthony
Published: January 2021

Background The study assessed the psychometric properties of the Life Back on Track (LBoT) measure, a new self-reported single-item global measure of the trajectory of wellbeing after a transport accident. Methods The data come from four waves of the Transport Accident Commission Longitudinal Study (n=1,556 in wave 1), and two repeated cross-sectional surveys– a Client Outcome Survey (n=5,238) and a Client Experience Survey (n=1,964) of individuals injured in a transport accident in Victoria. The conceptual basis of the measure was confirmed in a qualitative analysis of open-ended survey responses. The psychometric performance of the measure, including known-groups validity, test-retest reliability, sensitivity, and responsiveness was investigated. Results The LBoT measure was found to have a conceptual basis of recovery towards a normal life with domains of independence, control, happiness, work, social life, pain, physical function, cognitive function, work and leisure activities, income, anxiety, and depression. There were significant differences in the distribution of the LBoT scores based on the respondent’s depression, pain, return to work status, financial ability to get by, ability to cope, and ability to bounce back. The LBoT measure was a reasonable predictor of future work status and was moderately responsive to change. Conclusions LBoT is a valid measure to track the individual’s trajectory of subjective wellbeing in the context of recovery after a trauma, and it covers wider concepts than health-related quality of life. For use as a performance or tracking measure, however, further evidence is needed on its responsiveness.
Enzalutamide, a prostate cancer therapeutic, downregulates TMPRSS2 in lung and reduces cellular entry of SARS-CoV-2
Authors: Leach D. A. , Mohr A. , Giotis E. S. , Isac A. M. , Yates L. L. , Barclay W. S. , Zwacka R. M. , Bevan C. L. , Brooke G. N.
Published: January 2021

The COVID-19 pandemic, caused by the novel human coronavirus SARS-CoV-2 coronavirus, attacks various organs but most destructively the lung. It has been shown that SARS-CoV-2 entry into lung cells requires two host cell surface proteins: ACE2 and TMPRSS2. Downregulation of one or both of these is thus a potential therapeutic approach for COVID-19. TMPRSS2 is a known target of the androgen receptor, a ligand-activated transcription factor; activation of the androgen receptor increases TMPRSS2 levels in various tissues, most notably the prostate. We show here that treatment with the antiandrogen enzalutamide – a well-tolerated drug widely used in advanced prostate cancer – reduces TMPRSS2 levels in human lung cells. Further, enzalutamide treatment of mice dramatically decreased Tmprss2 levels in the lung. To determine therapeutic potential, we assessed uptake of SARS-CoV-2 Spike protein pseudotyped lentivirus and live SARS-CoV-2 into human lung cells and saw a significant reduction in viral entry and infection upon treatment with the antiandrogens enzalutamide and bicalutamide. In support of this new experimental data, analysis of existing datasets shows striking co-expression of AR and TMPRSS2, including in specific lung cell types that are targeted by SARS-CoV-2. Together, the data presented provides strong evidence to support clinical trials to assess the efficacy of antiandrogens as a treatment option for COVID-19.
Determinants of uptake of malaria preventive interventions among pregnant women in eastern Uganda
Authors: Wafula Solomon Tsebeni , Mendoza Hilbert , Nalugya Aisha , Musoke David , Waiswa Peter
Published: January 2021

BackgroundConsistent use of insecticide-treated nets (ITNs) and intermittent preventive treatment in pregnancy (IPTp) have been recommended as cost-effective interventions for malaria prevention during pregnancy in endemic areas. However, the coverage of these interventions during pregnancy in sub-Saharan Africa is still suboptimal. This study aimed to determine the uptake of IPTp and ITNs and associated factors among women during their recent pregnancy in Eastern Uganda. MethodsThis was a cross-sectional study conducted among 2,062 women who had delivered within the last 12 months prior to the start of the study in three districts of Eastern Uganda. The primary outcomes were consistent ITN use and optimal uptake (at least 3 doses) of IPTp. A modified Poisson regression was used to examine the association between consistent ITN use and the uptake of optimal doses of IPTp with independent variables. Data were analysed using Stata 14 software.Results The level of uptake of IPTp3 (at least three doses) was 14.7 %, while IPTp2 (at least two doses) was 60.0%. The majority (86.4%) of mothers reported regularly sleeping under mosquito nets for the full duration of pregnancy. Uptake of IPTp3 was associated with engaging in farming (adjusted PR = 1.71, 95% CI [1.28 – 2.28]) or business (adjusted PR = 1.60, 95% CI [1.05 – 2.44]), and attending at least 4 antenatal care (ANC) visits (adjusted PR = 1.72, 95%CI [1.34 – 2.22]). On the other hand, consistent ITN use was associated with belonging to the fourth wealth quintile (adjusted PR = 1.08, 95% CI [1.02 – 1.14]) or fifth wealth quintile (adjusted PR = 1.08, 95% CI [1.02- 1.15]), and attending at least 4 ANC visits (adjusted PR = 1.07, 95% CI [1.03- 1.11]). Conclusion Uptake of IPTp3 and consistent ITN use during pregnancy were lower and higher than the current Ugandan national targets, respectively. Study findings highlight the need for more efforts to enhance utilization of ANC services, which is likely to increase the uptake of these two key malaria preventive measures during pregnancy.
Citizens’ Expectations from Government in Response to COVID-19 Pandemic: A Qualitative Study in Iran
Authors: Zarei Leila , Shahabi Saeed , Sadati Ahmad Kalateh , Tabrizi Reza , Heydari Seyed Taghi , Lankarani Kamran Bagheri
Published: January 2021

Background: The government is the main body in charge of controlling epidemics; hence, expectations from government’s intention and capacity would affect citizens’ behavior and flexibility. Given the severity of COVID-19 pandemic and an urgent need for people's cooperation in the prevention and combat processes, understanding the public perspectives would be crucial and instructive. This study aimed to explore such perspectives towards the current pandemic among the Iranian. Indeed, we sought to provide a favorable platform for effective policies in the face of the COVID-19 pandemic by recognizing public expectations.Methods: This cross sectional study used an open-ended online questionnaire to investigate the common perspectives of the Iranian towards government’s response to COVID-19 pandemic. The participants were selected using snowball and convenient sampling techniques across the country. The collected data were analyzed and described using thematic content analysis. Results: In general, 2547 participants agreed to participate in this study and completed the online questionnaire. According to the findings, the Iranian exhibited several expectations regarding the government's response to COVID-19 pandemic, based on which three main themes were extracted: (1) health-related expectations, (2) policy-related expectations, and (3) mass media-related expectations. In this study, a majority of the participants highlighted the need to consider and follow-up the patients and their families, provide financial and hygiene support during the pandemic, apply strict restrictions, and have close monitoring and controlling procedures. Furthermore, they mentioned that authorities and news agencies should observe honesty and transparency principals. Conclusions: Our findings revealed that people expect the government and other responsible institutions to minimize the burden of this pandemic on them through adopting effective policies. The study findings could help policy-makers become aware of people's expectations and develop better strategies.
Evaluation of Right Myocardial Performance Index of In Vitro Fertilization Fetuses and Spontaneous Pregnancy Fetuses:A Cross-Sectional Study
Authors: Chen Shaoqi , Zhuang Zemin , Chen Qingzi , Du Xiya , Tan Xuerui
Published: January 2021

Background Whether the in vitro fertilization (IVF) has an effect on the cardiac function of the fetus is very important to evaluate the safety of the technique. The aim of this paper is to establish normal reference range for the fetal right myocardial performance index (RMPI), and compare the reference range between IVF fetuses and spontaneous pregnancy (SP) fetuses by automatic measurement of the RMPI.Methods 371 spontaneous singleton pregnancies (the control group) and 39 singleton pregnancies conceived by IVF (the experimental group) were enrolled into the current study. An automatic measurement system was used to acquire the RMPI. The cardiac function of the two groups was compared by t-test. Results There was no significant difference in normal reference range of RMPI between IVF fetuses and SP fetuses (RMPI 0.42 ±0.05 vs 0.43±0.05). No strong correlation was also noted between RMPI with gestational age and heart rate.Conclusions Normal reference ranges of RMPI of IVF fetuses and SP fetuses were established, and no significant difference between IVF fetuses and SP fetuses in RMPI was found.
Craniofacial morphology/phenotypes influence on mandibular range of movement in the design of a mandibular advancement device
Authors: Sanz Pedro Mayoral , Reyes Mariano Garcia , Torras Alex Bataller , Castillo JA Cabrera , Lagravere Manuel
Published: January 2021

Background. The mandibular opening path movements have different directions according to the craniofacial morphology of the patient but always downward and backward, therefore increasing the collapse of the upper airway. The aim of this work is to determine if there is a relationship between the craniofacial morphology and the mandibular movement to help understand the impact on the mandibular position. Methods. 52 students with full permanent dentition aged 19 to 23 years (mean 21.3 SD 1.7; 29 females and 23 males), participated in the study. Each subject had a lateral cephalometric radiograph taken. The opening angle was determined for two levels of vertical openings at 5 and 10 mm. Results. The opening angle showed a greater variability between subjects ranging from 63.15 to 77.08 for 5 mm angle and from for 61.65 to 75.72 for the 10 mm angle. Differences of facial phenotypes was evident when comparing the individual dissoccluding angle of the low angle horizontal pattern and high angle vertical pattern. Conclusions. The opening angle is related to craniofacial morphology with higher vertical anterior and shorter anteroposterior faces having a more horizontal path of mandibular movement than shorter vertical anterior and longer anteroposterior subjects who have a more vertical path.
Clinical Characteristics and Predictors of Mortality in Young Adults with Severe COVID-19. A Retrospective Observational Study
Authors: Lu Yanjiao , Huang Zhenli , Wang Meijia , Tang Kun , Wang Shanshan , Gao Pengfei , Xie Jungang , Wang Tao , Zhao Jinping
Published: January 2021

Background and objective: Little is yet known whether pathogenesis of COVID-19 is different between young and elder patients. Our study aimed to investigate the clinical characteristics and provide predictors of mortality for young adults with severe COVID-19.Methods: A total of 77 young adults with confirmed severe COVID-19 were recruited retrospectively at Tongji Hospital. Clinical characteristics, laboratory findings, treatment and outcomes were obtained from electronic medical records. The prognostic effects of variables were analyzed using logistic regression model.Results: In this retrospective cohort, non-survivors showed higher incidence of dyspnea and co-existing laboratory abnormalities, compared with young survivals in severe COVID-19. Multivariate logistic regression analysis showed that lymphopenia, elevated level of d-dimer, hypersensitive cardiac troponin I (hs-CTnI) and high sensitivity C-reactive protein (hs-CRP) were independent predictors of mortality in young adults with severe COVID-19. Further analysis showed that severely young adults with two or more factors abnormalities above would be more prone to death. The similar predictive effect of above four factors had been observed in all-age patients with severe COVID-19.Conclusion: Lymphopenia, elevated level of d-dimer, hs-CTnI and hs-CRP predicted clinical outcomes of young adults with severe COVID-19.
Gastrointestinal Failure Score in Children with Traumatic Brain Injury
Authors: Zhou Ying , Lu Weifeng , Tang Weibing
Published: January 2021

Purposes: To review the value of the gastrointestinal failure (GIF) score in children with different degrees of traumatic brain injury (TBI) by analyzing the correlation between outcome and gastrointestinal function. Methods: A total of 165 children with TBI who were diagnosed and treated in the surgical intensive care unit (SICU) for longer than 72 h between August 2017 and September 2019 were retrospectively analyzed. Admission parameters included sex, age, Glasgow Coma Scale (GCS) score, body mass index (BMI), leukocyte count, C-reactive protein (CRP), hemoglobin (Hb) and hematocrit (Hct), blood glucose, lactic acid, procalcitonin (PCT), albumin, plasma osmotic pressure, prothrombin time (PT) and activated partial thromboplastin time (APTT). To predict outcomes, the Sequential Organ Failure Assessment (SOFA) score, Pediatric Clinical Illness Score (PCIS), and mean GIF score for the first three days were combined. Results: The percent of patients with gastrointestinal dysfunction on the first day was 78.8%. Food intolerance (FI) and intra-abdominal hypertension (IAH) developed in 36.4% and 21.8% of the patients, respectively. The GIF score and mean GIF score for the first three days in children with different degrees of TBI were significantly different (P<0.05); these scores were also significantly different between patients who died and those who survived (P<0.05). The mean GIF score for the first three days was identified as an independent risk factor for mortality (odds ratio>1, 95% confidence interval=1.457 to 16.016, P<0.01), as was the PCIS. Receiver operating characteristic (ROC) curve analysis suggested that the mean GIF score for the first three days had the same calibrating power as the PCIS in discriminating the risk of death of children. Conclusion: The incidence of gastrointestinal dysfunction in children with TBI is high. The GIF score has the ability to reflect the status of the gastrointestinal system. The mean GIF score for the first three days has high prognostic value for ICU mortality in the SICU.
Bacteroides, Butyric Acid and t10,c12-CLA Changes in Colorectal Adenomatous Polyp Patients
Authors: Chen Ciyan , Niu Min , Pan Junxi , Du Na , Liu Shumin , Li Huanqin , He Qiuyue , Mao Jian , Duan Yong , Du Yan
Published: January 2021

Background: Colorectal adenomatous polyps (CAPs) are considered precancerous lesions of colorectal cancer (CRC). The gut microbiota participates in the process of digestion and, in the process, produces metabolites, mainly short-chain fatty acids (SCFAs), secondary bile acids and conjugated linoleic acid (CLA). This study aimed to investigate the gut microbiota constituents and metabolites in the faeces of CAP patients to identify microbiota or metabolites that can be used as sensitive biological predictors and to provide a theoretical basis for the clinical treatment of CAPs.Methods: 16S rRNA sequence analysis was used to detect microbial changes in the faeces of CAP patients. qPCR analysis was used to evaluate the ability of the microbiota to produce metabolites, and the contents of metabolites in faeces were detected by ion chromatography and ultra-performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS).Results: Based on the detection of the gut microbiota, patients with CAPs had increased abundances of Bacteroides and Citrobacter, and the abundances of Weissella and Lactobacillus were decreased. We also explored gene expression, and the abundance of butyrate-producing bacterial genes was significantly increased in the faeces of CAP patients, but those of secondary bile acid-producing and CLA-producing bacterial genes showed no differences in faecal samples. The acetic acid and butyric acid contents were increased in the faeces of the CAP group, and the healthy control group had higher t10,c12-CLA contents. Conclusion: The gut microbiota analysis results, assessed in faeces, showed that Bacteroides and Citrobacter were positively correlated with CAPs, which indicated that changes in specific genera might be detrimental to intestinal health. In addition, t10,c12-CLA played an important role in protecting the intestine.