bluuebunny/crossref_metadata_2025_split huggingface dataset:
Strategies to Overcome Vaccine Hesitancy: A Systematic Review
Authors: Singh Prem , Dhalaria Pritu , Ghosh Shreeparna , Mohapatra Mrinal Kar , Kashyap Satabdi , Soni Gopal Krishna , Nandi Partha 
Published: May 2020

Abstract
Background: Vaccination, albeit a necessity in the prevention of infectious diseases, requires appropriate strategies for addressing vaccine hesitancy at an individual and community level. However, there remains a glaring scarcity of available literature in that regard. Therefore, this review aims to scrutinize globally tested interventions to increase the vaccination uptake by addressing vaccine hesitancy at various stages of these interventions across the globe and help policy makers in implementing appropriate strategies to address the issue.Methods: A systematic review of descriptive and analytic studies was conducted using specific key word searches to identify literature containing information about interventions directed at vaccine hesitancy. The search was done using PubMed, Global Health, and Science Direct databases. Data extraction was based on study characteristics such as author details; study design; and type, duration, and outcome of an intervention.Results: A total of 105 studies were identified of which 33 studies were included in the final review. Community-based interventions, monetary incentives, and technology-based health literacy demonstrated significant improvement in the utilization of immunization services. On the other hand, media-based intervention studies did not bring about a desired change in overcoming vaccine hesitancy.Conclusion: This study indicates that the strategies should be based on the need and reasons for vaccine hesitancy for the targeted population. A multidimensional approach involving community members, families, and individuals is required to address this challenging issue.
Role of mitochondrial dynamics in microglial activation and metabolic switch
Authors: Montilla Alejandro , Ruiz Asier , Matute Carlos , Domercq Maria 
Published: May 2020

Abstract
Background
Microglia are the endogenous immune cells of the central nervous system (CNS) and act as sensors of injury in the brain, favouring its homeostasis. Their activation and polarization towards a pro-inflammatory phenotype are associated to injury and disease. These processes are linked to a metabolic reprogramming of the cells, characterized by high rates of glycolytic function and suppressed levels of oxidative phosphorylation. This metabolic switch can be reproduced in vitro by stimulation with lipopolysaccharide (LPS) plus Interferon-γ (IFNγ). In an attempt to understand the mechanisms regulating mitochondrial respiration abolishment, we examined potential alterations in mitochondrial features during the metabolic switch. In addition, we studied the possible implication of mitochondrial dynamics in the metabolic switch using the mitochondrial division inhibitor-1 (Mdivi-1), which blocks Drp1-dependent mitochondrial fission.
Methods
Cultured microglia was treated with LPS + IFNγ to reproduce the metabolic switch under pro-inflammatory stimuli in the absence or in the presence of Mdivi-1 to block mitochondrial fission. Mitochondrial membrane potential and mitochondrial calcium were measured with living cell imaging, and microglial polarization was assessed by immunofluorescence and qRT-PCR. The metabolic profile of the cells was measured using the Seahorse XFe96 Extracellular Flux Analyzer.
Results
Under conditions of mitochondrial respiration abolishment, microglia did not show any change in mitochondria morphology, nor in mitochondrial membrane potential, indicative of a limited impact in its viability. We provided evidence that reverse operation of F0F1-ATP synthase contributes to mitochondrial membrane potential. On the other hand. mitochondrial fission blockage significantly reduced the expression of pro-inflammatory markers in LPS + IFNγ-treated microglia, such as the inducible nitric oxide synthase (iNOS). However, this inhibition did not lead to a recovery of the oxidative phosphorylation ablation by LPS + IFNγ or to a microglia repolarization.
Conclusions
Altogether, these results suggest that Drp1-dependent mitochondrial fission, although potentially involved in microglial activation, does not play an essential role in metabolic reprogramming and repolarization of microglia.
Air Pollution as a Contributor to the Inflammatory Activity of Multiple Sclerosis
Authors: Cortese Andrea , Lova Luca , Comoli Patrizia , Volpe Elisabetta , Villa Silvia , Mallucci Giulia , Salvia Sabrina La , Romani Alfredo , Franciotta Diego , Bollati Valentina , Basso Sabrina , Guido Ilaria , Quartuccio Giuseppe , Battistini Luca , Cereda Cristina , Bergamaschi Roberto 
Published: May 2020

Abstract
OBJECTIVE
Air pollution has been recently identified as a risk factor for multiple sclerosis. Aim of this study was to investigate the immunological mechanism underlying the clinical association between air pollution, namely exposure to particulate matter 10 (PM10), and inflammatory activity of multiple sclerosis (MS)
METHODS
Daily recording of PM10 was obtained by monitors depending on the residence of subjects. Expression of molecules involved in activation, adhesion and migration of T lymphocytes were tested by flow-cytometry in 57 MS patients. We next assessed in vitro the effect of PM10 on expression of C-C chemokine receptors 6 (CCR6) by peripheral blood mononuclear cells (PBMCs), on cytokine production by monocyte-derived dendritic cells (mdDC) and on T cell polarization in PBMC/mdDC mixed cultures.
RESULTS
We identified a significant correlation between mean PM10 levels and expression of CCR6 CD4 + T circulating cells in MS patients. This was paralleled by the observation in vitro of a higher level of CCR6 expression on PBMC following treatment with increased doses of particulate matter. Moreover, in mdDC cultures particulate matter induced the secretion by mdDC of Th17 polarizing IL1 beta, IL6 and IL23 and, in mdDC/PBMC mixed cultures, enhanced generation of IL17-producing T cells.
CONCLUSIONS
Ex vivo and in vitro studies support the pro-inflammatory role of PM in MS, by upregulating expression of CCR6 on circulating CD4 + T cells and inducing in innate immune cells the production of Th17 polarizing cytokines. Therefore, we speculate that in MS respiratory exposure to PM10 may induce the production in the lung of autoreactive Th17 lymphocytes and boost their migratory properties through the blood-brain barrier.
Antimicrobial Resistance and Extended Spectrum Beta-Lactamase Profile of Uropathogens Among Pregnant Women Attending Antenatal Care at Edna Adan Hospital, Hargeisa, Somaliland
Authors: Mohamoud Hussien , Tadesse Senait , Derbie Awoke 
Published: May 2020

Abstract
Background The emergence and spread of antimicrobial resistance (AMR) among uropathogens is increasing, especially in resource limited settings due to a number of reasons. The emergence of drug resistance and particularly the production of Extended Spectrum β-Lactamase (ESBL) by some strains of E. coli and methicillin resistance of Staphylococcus species, limits the choice of antimicrobials in the treatment of urinary tract infection (UTI). However, little is known about the bacteriology of UTI among pregnant women in Hargeisa, SomalilandMethods A cross-sectional study was conducted in the period of 1 Feb to 30 May 2019 among pregnant women at Edna Adan Hospital (EAH), Hargeisa. Following the standard procedure, clean-catch mid-stream urine samples were collected and processed for bacteriological culture. A urine sample was considered positive for significant bacteriuria (SBU) when a single organism was cultured at a concentration of ≥ 105 Colony Forming Units/ml. Antimicrobial sensitivity testing (AST) was done using Kirby-Bauer disc diffusion technique. Ceftazidime (30 µg) and Cefotaxime (30 µg) disks were used for ESBL screening as per CLSI guideline and each ESBL screening positive isolate were phenotypically confirmed by a combination disk test.Results Among 376 study participants, 79 (21.0%) had SBU. Majority at 58(73.4%) of the isolates were Gram-negative. The most predominant isolate was E.coli at 36(45.6%) followed by K. pneumonea 16(20.3%) and S. aureus at 9(11.4%). The proportion of ESBL producing isolates was at 25(32.9%). Gram-negative bacteria showed high level resistance to ampicillin, amoxicillin, cefotaxime, and cephalexin at 87%, 85%, 57%, and 52%, respectively. Previous history of UTI, monthly income, educational status and having dysuria were significantly associated with SBU (p < 0.05).Conclusions Most of the isolates were found resistant to the commonly prescribed antimicrobial drugs. Therefore, actions to minimize AMR should be in place to reduce the impact of urinary tract infections among pregnant women. Future large scale study is warranted to find out bacteriological and other factors associated with ESBL producing uropathogenes.
Multiple circulating alkaloids and saponins from intravenous Kang-Ai injection inhibit human cytochromes P450 and UDP-glucuronosyltransferase isozymes: potential drug-drug interactions
Authors: Qin Zifei , Jia Mengmeng , Yang Jing , Xing Hang , Yin Zhao , Yao Zhihong , Zhang Xiaojian , Yao Xinsheng 
Published: May 2020

Abstract
Background
Kang-Ai injection is widely used as an adjuvant therapy drug for many cancers, leukopenia and chronic hepatitis B. Circulating alkaloids and saponins are believed to be responsible for therapeutic effects. However, their pharmacokinetics and excretion in vivo and the risk of drug-drug interactions (DDI) through inhibiting human cytochrome P450 (CYP) and UDP-glucuronosyltransferase (UGT) enzymes remain unclear.
Methods
Pharmacokinetics and excretion of circulating compounds were investigated in rats using a validated ultra high-performance liquid chromatography tandem mass spectrometry (UHPLC-MS) method. Further, the inhibitory effects of nine major compounds against eleven CYP and UGT isozymes were assayed using well-accepted specific substrate for each enzyme.
Results
After dosing, 9 alkaloids were found with Cmax and t1/2 values of 0.17–422.70 µmol/L and 1.78–4.33 h, respectively. Additionally, 28 saponins exhibited considerable systemic exposure with t1/2 values of 0.63–7.22 h, whereas other trace saponins could be negligible or undetected. Besides, over 90% of alkaloids were excreted through hepatobiliary and renal excretion. Likewise, astragalosides and PPT-type ginsenosides also involved in hepatobiliary and/or renal excretion. PPD-type ginsenosides were mainly excreted to urine. Furthermore, PPD-type ginsenosides were extensively bound (fu−plasma approximately 1%), whereas astragalosides and PPT-type ginsenosides displayed fu−plasma values of 12.35% and 60.23–87.36%, respectively. Moreover, matrine and oxymatrine both exhibited weak inhibition against CYP3A4 with IC50 values of 387.40 and 604.60 µM. Similar results were observed for astragaloside IV towards CYP2C9, ginsenoside Rg1 against UGT1A1, ginsenoside Re against CYP2C8, ginsenoside Rd against CYP2B6and CYP3A4, and ginsenoside Rc against UGT1A9 with IC50 values between 20.19 and 92.21 µM. Ginsenoside Rb1 showed moderate inhibitory effect against CYP2C9 (IC50 = 8.81 µM). Through kinetic modeling, their inhibition mechanisms towards those CYP and UGT isozymes were explored with obtained Ki values. In vitro-in vivo extrapolation ([I]/Ki = 1.15 for oxymatrine) showed the inhibition of systemic clearance for CYP3A4 substrates seemed more possible, while other major circulating compounds displayed negligible DDI risk due to [I]/Ki no more than 0.1.
Conclusions
These facts lead to better understanding of chemical basis responsible for therapeutic action of Kang-Ai injection, and facilitate to pay more attention on the DDI for informing its rational clinical use.
Research methodology and characteristics of journal articles with original data, preprint articles and registered clinical trial protocols about COVID-19
Authors: Fidahic Mahir , Nujic Danijela , Runjic Renata , Civljak Marta , Markotic Filipa , Makaric Zvjezdana Lovric , Puljak Livia 
Published: May 2020

Abstract
Background The research community reacted rapidly to the emergence of COVID-19. We aimed to assess characteristics of journal articles, preprint articles, and registered trial protocols about COVID-19 and its causal agent SARS-CoV-2.Methods We analyzed characteristics of journal articles with original data indexed by March 19, 2020, in World Health Organization (WHO) COVID-19 collection, articles published on preprint servers medRxiv and bioRxiv by April 3, 2010. Additionally, we assessed characteristics of clinical trials indexed in the WHO International Clinical Trials Registry Platform (WHO ICTRP) by April 7, 2020.Results Among the first 2118 articles on COVID-19 published in scholarly journals, 533 (25%) contained original data. The majority was published by authors from China (75%) and funded by Chinese sponsors (75%); a quarter was published in the Chinese language. Among 312 articles that self-reported study design, the most frequent were retrospective studies (N = 88; 28%) and case reports (N = 86; 28%), analyzing patients’ characteristics (38%). Median Journal Impact Factor of journals where articles were published was 5.099.
A comparison of HER2 tumor accumulations of Ga-67 labeled anti-HER2 antibody with chemically and site-specifically conjugated bifunctional chelators
Authors: Kono Yumiko , Utsunomiya Keita , Ohira Yuta , Satoh Hirokazu , Kan Naoki , Matsumoto Yohei , Tanigawa Noboru 
Published: May 2020

Abstract
Background

Monoclonal antibodies (mAb) developed to target specific cancers have achieved considerable success to-date. To further enhance therapeutic efficacy monoclonal antibodies may be conjugated with a cytotoxic drug or radioisotope. We present the development of new method based on site-specific conjugation (SSC) for targeting HER2. The study design involves a comparison of the accumulation of Ga-67 labeled anti-HER2 antibodies with SSC versus conventional chemical conjugation in HER2-positive tumors. Anti-HER2 antibodies were chemically conjugated (Chem) with the bifunctional chelator deferoxamine (Chem-mAb). The resulting chemical conjugate was radiolabeled with Ga-67 yielding Ga-67-Chem -mAb. The SSC anti-HER2 antibodies enzymatically conjugated with deferoxamine using transglutaminase (SSC-mAb) and radiolabeled with Ga-67 yielding Ga-67-SSC-mAb. In vitro, the binding activity of HER2 to both conjugated antibodies was measured using surface Plasmon resonance. In vivo, a xenograft mouse model consisting of transplanted CHO/HER2 were divided into two groups, the Chem and the SSC group. Planar images were acquired over three days after each mAb injection, respectively. Pharmacokinetic analysis was used to compare the Chem group to the SSC group, for Ga-67 accumulation.
Result

The SSC and Chem groups were found to have similar HER2 binding capacity, however the tumor accumulation ratio gradually increased in the SSC group. The pharmacokinetic studies also found that radiolabeled mAb accumulation was significantly higher in the SSC group than the Chem group in not only the tumors, but also in blood and in other organs.
Conclusion

The new site-specific conjugation may improve targeted antigen-specific cancer radioimmunotherapy and may, due to higher retention, require a lower dose.
Fluid Overload is Associated with Underestimation of Serum Creatinine in Cardiac Surgery Patients: A Retrospective Analysis
Authors: Jin Jifu , Xu Jiarui , Xu Sujuan , Hu Jiachang , Jiang Wuhua , Shen Bo , Wang Chunsheng , Teng Jie , Ding Xiaoqiang 
Published: May 2020

Abstract
Background: Fluid overload is related to the development and prognosis of cardiac surgery-associated acute kidney injury (CSA-AKI). The study is to investigate the influence of serum creatinine (SCr) corrected by fluid balance on the prognosis of patients with cardiac surgery. Methods: A retrospective study was conducted in 1334 patients who underwent elective cardiac surgery from January 1 to December 31, 2015. Kidney Disease: Improving Global Outcomes (KDIGO) criteria for AKI were applied to identify CSA-AKI. SCr was measured every 24 hours during ICU period and was accordingly adjusted for cumulative fluid balance. Change in SCr, defined as ∆Crea, was determined by difference between before and after adjustment for cumulative fluid balance. All patients were divided as three groups: underestimation group (∆Crea ≥ P 75 ), normal group (P 25 < ∆Crea < P 75 ) and overestimation group (∆Crea ≤ P 25 ). Results: The incidence of AKI increased from 29.5% to 31.8% after adjustment for fluid balance. Patients in underestimation group showed prolonged length of ICU stay compared with normal group and overestimation group (3.2[1.0-3.0] vs 2.1[1.0-3.0] d, P < 0.001; 3.2[1.0-3.0] vs 2.3[1.0-3.0] d, P < 0.001). Length of hospital stay and mechanical ventilation dependent days in underestimation group were significantly longer than normal group ( P < 0.001). Multivariate analysis showed age, baseline SCr and left ventricular ejection fraction were independently associated with underestimation of creatinine. Conclusions: Cumulative fluid balance after cardiac surgery disturbs accurate measurement of serum creatinine. Patients with underestimation of SCr were associated with poor prognosis.
MicroRNA expression analysis for identification of biomarkers in inflammatory bowel disease subtypes
Authors: Mandal Manisha , Mandal Shyamapada 
Published: May 2020

Abstract
The potential biomarkers in inflammatory bowel diseases (IBDs) were analyzed from GSE53867 dataset. Differentially expressed microRNAs (DEMs)-genes and protein-protein interaction networks were constructed, and hub genes selected using Cytoscape. Differentially expressed genes were analyzed for GO and Reactome-pathway. Seven DEMs were upregulated in Crohn's disease (CD), 4 downregulated in ulcerative colitis (UC), 8 upregulated and 2 downregulated in IBD. A 620, 2377, and 1821 target-genes were in CD, UC, and IBD, respectively. SOCS3, upregulated by miR-650, was hub gene in CD, induced by cytokines, through NFKB-signalling pathway to mediate ubiquitin-proteasomal degradation. CIRH1A, downregulated by miR-16, was hub gene of UC, acted by impairing ribosome-biogenesis. SKP2 and ASB1, up- and downregulated, by miR-142 and miR-665, respectively, were hub genes of IBD, induced cytokines through activation of TLR- and TNF-signalling pathways to mediate ubiquitin-proteasomal degradation. SOCS3, CIRH1A, SKP2 and ASB1 genes might serve as valuable biomarkers to differentiate CD, UC and IBD.
Effect of inspiratory flow waveforms on the mechanical work of ventilation; a fluid dynamic analysis
Authors: Monjezi Mojdeh , Jamaati Hamidreza 
Published: May 2020

Abstract
In most intensive care patients, the mechanical work (MW) is increased due to airway obstruction and/or tracheal intubation. Increasing MW is known as a risk factor for ventilator induced lung injury (VILI). Moeover, minimizing of MW is crucial to facilitate weaning process. In this paper MW is compared between three different inspiratory flow waveforms. The fluid dynamic analysis is used to compute the resistive pressure drop and the resistive work. We have compared square, sinusoidal and decelerating flow waveforms under the same tidal volume. The results show that under the constant tidal volume and I:E ratio, for tidal volumes below 1 lit, an square flow profile is beneficial for minimizing MW while a sinusoidal flow profile is prefered for tidal volumes of 1 lit or higher. It is shown that for make a decision about most beneficial flow profile in terms of less MW, both tidal volume and I:E ratio is important. By the way the results suggest to use decelerating flow waveforms with higher 1:E ratio. The qualitative conclusion is that in order to lower the MW especially in patients with obstructive lung diseases, sinusoidal, square and decelerating flow became preferable respectively with increasing I:E ratio. Our study suggest the square and sinusoidal profile for tidal volumes below and equal or over 1 lit, respectively in pointwiew of less MW. This paper also encouraged the engineers to add an option to select sinusoidal flow waveform in VCV mode to lower MW when tidal volume is l lit or higher.
The Horse Gut Microbiome Responds in a Highly Individualized Manner to Forage Lignification
Authors: Gomez Andres , Sharma Ashok Kumar , Grev Amanda , Sheaffer Craig , Martinson Krishona 
Published: May 2020

Abstract
Background: Although contributions of the equine gut microbiome to forage utilization are well recognized, the impact of alfalfa lignification on the equine gut microbiome remains unknown. Here, we characterized microbial community dynamics in the equine distal gut when feeding reduced lignin (RL) and reference alfalfa hays (CON-control) ( Medicago sativa L.) to adult stock-type horses. Hay from RL and CON cultivars were similar in crude protein, neutral detergent fiber, and equine digestible energy, but differed in acid detergent lignin content (RL:74 g kg -1 vs. CON: 81 g kg -1 ). Dietary treatments were fed to six horses in a crossover study. Experimental periods consisted of a 9-d dietary adaptation phase followed by a 5-d total fecal collection phase, during which horses were housed in individual box stalls and manure was removed on a continuous 24-h basis. At 12-h intervals, feces were thoroughly mixed, frozen, and used for bacterial community composition analyses via V4, 16S rRNA amplicon MiSeq sequencing.Results: RL alfalfa did not result in specific fecal microbiome composition across all horses. However, upon incorporating individual horse in the model, it was shown that the microbiome of each subject did respond to hay lignin content in an individualized manner over time, in terms of alpha and beta diversity. Closer inspection of specific taxonomic changes upon feeding the two diets also revealed horse-specific trends, with unique amplicon sequence variants classified as Akkermansia , Fibrobacter succinogenes , Treponema, and Paludibacter fluctuating significantly in abundance when RL alfalfa was fed, depending on horse. Along these lines, horse-specific associations between individual gut microbiome traits and characteristics of the digested CON or RL alfalfa were observed, mainly in regards to dry matter digestibility and mean feed particle size.Conclusions: These results indicate that the horse gut microbiome responds in an individualized manner to small changes in the amount of acid detergent lignin in alfalfa hay, potentially impacting several feed digestibility characteristics. The implications of horse-specific responses to forage quality in regards to metabolic health and performance remain to be elucidated.