bluuebunny/crossref_metadata_2025_split huggingface dataset:
Global Fund Financing and Human Resources for Health Investments in the Eastern Mediterranean Region
Authors: Okunogbe Adeyemi , Bowser Diana , Gedik Gulin , Naseri Saha , Abu-Agla Ayat , Safi Najibullah 
Published: February 2020

Abstract
Background: Despite the large investments in donor-related health activities in areas of the globe prone to tension and conflict, few studies have examined in detail the impact of these donor investments on human resources for health (HRH). Methods: We used a mixed-methods research methodology comprising both quantitative and qualitative analysis to analyze the Enhanced Financial Reporting System of the Global Fund to Fight AIDS, Tuberculosis and Malaria budget and expenditure data from 2003-2017 for 13 countries in the Eastern Mediterranean Region (EMR). We analysed additional detailed budgetary data over the period 2013-2017 for a sub-set of these countries. Two country-case studies were conducted in Afghanistan and Sudan for a more in-depth understanding of the HRH-related activities that occurred as a result of Global Fund grants. Results: The results show that US$2.2 billion Global Fund dollars had been budgeted and US$1.6 billion were expended over the period 2003-2017 in the 13 Eastern Mediterranean countries. The average expenditures for human resources for health (training and human resources) as a percentage of total expenditure is 28%. Additional detailed budgetary data analysis shows a more conservative investment in HRH with 13% of total budgets allocated to “direct” HRH activities such as salaries, training costs, and technical assistance. HRH-related activities supported by the Global Fund in Afghanistan and Sudan are similar, including pre-service and in-services training, hiring of program coordinators and staff, and top-ups for clinical staff. Conclusions: HRH remains a key issue in strengthening the health systems of low- and middle-income countries. While this study suggests that Global Fund’s HRH investments in the EMR are not lagging behind the global average, there appears to be a need to further scale up these investments considering this region’s unique HRH challenges.
Cloacal swabs are unreliable sources for estimating lower gastro-intestinal tract microbiota in chicken.
Authors: Williams Travis John , Athrey Giridhar N 
Published: February 2020

Abstract
Background The gastrointestinal microbiota in chicken ( Gallus gallus domesticus ) has a central role in health and performance. The ceca are a vital site of functional activity, but assessing cecal microbiota in longitudinal studies remains a challenge. The cecal communities are broadly similar to large intestine samples. Cloacal sampling, due to their proximity to the large intestine, is an alternative, non-invasive method used for assaying and monitoring disease-causing agents, and maybe a viable option for longitudinal studies. Results We collected paired cecal content, and cloacal swab samples from twenty randomly selected commercial broilers raised on two dietary treatments. The microbiota of each sample was assessed using 16S rRNA V4 hypervariable region sequencing on an Illumina MiSeq platform and analyzed using the MOTHUR pipeline. Analysis of fourteen paired samples resulted in 1603 OTU’s assigned to 82 Families. Eleven families were shared between the cecal and cloacal samples, with seven and eleven families unique to cecal content and cloacal swabs, respectively. Paired t-test and Wilcoxon Signed-Rank test showed significant differences in the Chao1 index between the cecal content and cloacal swabs (p-value = 0.000845 and p-value = 0.001397, respectively). However, the Inverse Simpson species diversity estimator was not different using the Wilcoxon Signed-Rank test (p-value = 0.3258) and a paired t-test (p-value = 0.3864). β-diversity between the cloacal swabs and cecal microbiota also showed significant differences based on PERMANOVA (p-value = <0.001), HOMOVA (p-value <0.001), and Weighted Unifrac (WSig = <0.001) testing. Conclusions Cloacal swabs do not approximate either the α or β diversity of cecal samples, based on a paired sample analysis. The high variability of cloacal microbiota has been reported previously, and this study provides additional evidence of the randomness of cloacal microbiota in contrast to cecal microbiota. Our findings indicate that cloacal samples are not suitable for longitudinal studies of gut microbiota patterns. High inter-individual variation of cloacal swab data warrants further assessment of their reliability as a targeted diagnostic method.
Microglial-associated responses to comorbid amyloid pathology and hyperhomocysteinemia in an aged knock-in mouse model of Alzheimer’s disease
Authors: Braun David James , Dimayuga Edgardo , Morganti Josh M. , Eldik Linda J Van 
Published: February 2020

Abstract
Background: Elevated blood homocysteine levels, termed hyperhomocysteinemia (HHcy), is a prevalent risk factor for Alzheimer’s disease (AD) in elderly populations. While dietary supplementation of B-vitamins is a generally effective method to lower homocysteine levels, there is little if any benefit to cognition. In the context of amyloid pathology, dietary-induced HHcy is known to enhance amyloid deposition and certain inflammatory responses. Little is known, however, about the specific effects on microglia resulting from combined amyloid and HHcy pathologies. Methods: The present study used a knock-in mouse model of amyloidosis, aged to 12 months, given 8 weeks of dietary deficiency-induced HHcy to better understand how microglia are affected in this comorbidity context. Results: We found that HHcy-inducing diet increased amyloid plaque burden, altered the neuroinflammatory milieu, and upregulated the expression of multiple damage-associated and “homeostatic” microglial genes. Conclusions: Taken together, these data indicate complex effects of comorbid pathologies on microglial function that are not driven solely by increased amyloid burden. Given the highly dynamic nature of microglia, their central role in AD pathology, and the frequent occurrence of various comorbidities in AD patients, it is increasingly important to understand how microglia respond to mixed pathological processes.
The local transcriptional regulators SacR1 and SacR2 act as repressors of fructooligosaccharides metabolism in Lactobacillus plantarum
Authors: Chen Chen , Wang Linlin , Yu Haiyan , tian huaixiang 
Published: February 2020

Abstract
Background In Lactobacillus plantarum, fructooligosaccharides (FOS) metabolism is controlled by both global and local regulatory mechanisms. Although catabolite control protein A has been identified as a global regulator of FOS metabolism, the functions of local regulators remain unclear. This study aimed to elucidate the roles of two local regulators, SacR1 and SacR2, in the regulation of FOS metabolism in L. plantarum both in vitro and in vivo. Results A reverse transcription-quantitative PCR analysis of one wild-type and two mutant strains ( ΔsacR1 and ΔsacR2 ) of L. plantarum grown on FOS and ribose identified SacR1 and SacR2 as repressors of FOS metabolism in the absence of FOS. Moreover, genes relevant to FOS metabolism could be induced or derepressed by the addition of FOS. The analysis predicted four potential SacR1 and SacR2 transcription factor binding sites (TFBS) in the putative promoter regions of two FOS-related clusters. The binding of SacR1 and SacR2 to these TFBSs both in vitro and in vivo was verified using electrophoretic mobility shift assays and chromatin immunoprecipitation, respectively. A consensus sequence of WNNNNNAACGNNTTNNNNNW was deduced for the TFBS of SacR1 and SacR2. Conclusion Our results identified SacR1 and SacR2 as local regulators that repress FOS utilization by L. plantarum by binding to TFBSs in the promoter regions of FOS-related clusters. The results provide new insights into the complex network regulating oligosaccharide metabolism by lactic acid bacteria.
Effects of contact stress on patellarfemoral joint and quadriceps force in fixed and mobile-bearing medial unicompartmental knee arthroplasty
Authors: Kwon Hyuck Min , Lee Jin-Ah , Koh Yong-Gon , Park Kwan Kyu , Kang Kyoung-Tak 
Published: February 2020

Abstract
Background Unicompartmental knee arthroplasty (UKA) is an effective treatment for end-stage, symptomatic unicompartmental osteoarthritis (OA) of the knee joint. However, patellofemoral (PF) joint degeneration is a contraindication to medial UKA. Therefore, the objective of this study is to evaluate the biomechanical effect on the PF joint in medial UKA using fixed-bearing (FB) and mobile-bearing (MB) design prostheses. Methods A three-dimensional finite-element model of a normal knee joint was developed using medical image data. We performed statistical analysis for each model. The differences in the contact stress on the PF joint and the quadriceps force between the FB and MB designs were evaluated under a deep-knee-bend condition. Results At an early flexion angle, the results of the contact stress were showed that there was no significant difference between the FB and MB medial UKA models compared with the intact model. However, at a large flexion angle, we observed a significant increase in the contact stress of FB models. On the contrary, in the case of the MB models, there was no statistically significant increment compared to the intact model. Our results indicate that with medial UKA, the contact stress increased, and a greater quadriceps force was applied to the PF joint. However, there should be no difficulty in performing UKA on a PF joint with OA, unless there is anterior knee pain. This is because the increase in the contact stress is negligible. Conclusions Our results showed that there was no significant difference in contact stress on the PF joint between medial UKA and intact knee joints. In particular, such a mechanism was easily found in mobile-bearing medial UKA. Therefore, this study biomechanically showed that degenerative changes in the PF joint should not be considered an absolute contraindication for treatment with medial UKA.
Dynamic spinal posture and pelvic position analysis using a rasterstereographic device
Authors: Michalik Roman , Hamm Juliane , Quack Valentin , Eschweiler Jörg , Gatz Matthias , Betsch Marcel 
Published: February 2020

Abstract
Background: Until recently, rasterstereographic analysis of the spine was limited to static measurements. However, understanding and evaluating the motion of the spine under dynamic conditions is an important factor in the diagnosis and treatment of spinal pathologies. Aim of this study was to study the spinal posture and pelvic position under dynamic conditions and compare it to static measurements using a dynamic rasterstereographic system. Methods: A total of 121 healthy volunteers (56 females; 65 males) were included in this observational study. The parameters trunk inclination, trunk imbalance, pelvic obliquity, kyphotic angle, lordotic angle, surface rotation and lateral deviation were studied and compared under static and dynamic (1,2,4,5 km/h) conditions using the system “Formetric 4D Motion ® “ (DIERS International GmbH, Germany). Results: Female volunteers had a higher lordotic angle than males under static conditions (p<0.001). Trunk inclination (5.31° vs. 6.74°), vertebral kyphotic angle (42.53° vs. 39,59°) and surface rotation (3.35° vs. 3.81°) increase under dynamic conditions (p<0.001). Trunk inclination and lordotic angle both show significant changes during walking compared to static conditions (p<0.001). Conclusion: The spinal posture differs between females and males during standing and during walking. Rasterstereography is a valuable tool for the dynamic evaluation of spinal posture and pelvic position, which can also be used to quantify motion in the spine and therefore it has the potential to improve the understanding and treatment of spinal pathologies. Trial registration: retrospectively registered
Custom-made talar component of total ankle replacement implant, with or without lateral articular facet: A finite element analysis
Authors: Zhu Min , Tang Kang-lai , Jin Zhong-min , Xu Zhi , Feng Guo-cheng , Xu Yong-qing 
Published: February 2020

Abstract
Background: The present patient dissatisfaction with and high failure rates of total ankle replacement (TAR) are likely due to current prosthesis designs, which are not patient-specific and anatomy-based, leading to unphysiological motion at the replaced joint. The design of customized prostheses is already possible by means of medical imaging and additive manufacturing technology.Methods: In this study, dome and geometric fixtures of custom-made talar components for TAR were designed, and we investigated two kinds of talar components: 2-surface contact type (Type-1, without lateral articular facet) and 3-surface contact type (Type-2, with lateral articular facet). The effects of the above two prostheses on the loading stress of the prosthesis contact surface were comparatively analysed with three-dimensional finite element models.Results: The maximum and average von Mises stress values of the 3-surface prosthesis were smaller than those of the 2-surface prosthesis. In terms of contact surface pressure, the maximum and average values of the 3-surface prosthesis are almost equal to those of the 2- surface type. In terms of the tangential slip distribution of the contact surface, the maximum and average values of the 3-surface prosthesis were smaller than those of the 2-surface prosthesis.Conclusions: The custom-made talar component of the total ankle replacement implant reproduced the anatomical morphology of the natural articular surfaces well. The 3-surface contact type prosthesis with lateral articular facet, compared to the 2-surface contact type without lateral articular facet, offers better static stability by affecting the internal and external forces.
Topography of the respiratory tract bacterial microbiota in cattle
Authors: McMullen Christopher , Alexander Trevor W. , Léguillette Renaud , Workentine Matthew , Timsit Edouard 
Published: February 2020

Abstract
Background

Bacterial bronchopneumonia (BP) is the leading cause of morbidity and mortality in cattle. While the bacterial composition of the bovine upper respiratory tract (URT) has not been studied in detail, the nasopharynx is generally accepted as the primary source of pathogenic bacteria that cause BP. However, it has recently been shown in humans that the oropharynx may act as the primary reservoir for pathogens that reach the lung. The objective was therefore to describe the bacterial microbiota present along the entire cattle respiratory tract to determine which URT niches may contribute the most to the composition of the lung microbiota.

Methods

Seventeen upper and lower respiratory tract locations were sampled from 15 healthy feedlot steer calves. Samples were collected using a combination of swabs, protected specimen brushes, and saline washes. DNA was extracted from each sample and the 16S rRNA gene (V3-V4) was sequenced. Community composition, alpha-diversity, and beta-diversity were compared among sampling locations.

Results

Microbiota composition differed across sampling locations, with physiologically and anatomically distinct locations showing different relative abundances of 1,137 observed sequence variants (SVs). An analysis of similarities showed that the lung was more similar to the nasopharynx (R-statistic = 0.091) than it was to the oropharynx (R-statistic = 0.709) or any other URT sampling location. Five distinct metacommunities were identified across all samples after clustering at the genus level using Dirichlet multinomial mixtures. This included a metacommunity found primarily in the lung and nasopharynx that was dominated by Mycoplasma . Further clustering at the SV level showed a shared metacommunity between the lung and nasopharynx that was dominated by Mycoplasma dispar . Other metacommunities found in the nostrils, tonsils, and oral microbiotas were dominated by Moraxella , Fusobacterium , and Streptococcus , respectively.

Conclusions

The nasopharyngeal bacterial microbiota is most similar to the lung bacterial microbiota and therefore may serve as the primary source of bacteria to the lung. This finding confirms that the nasopharyngeal microbiota should be the focus of research as it relates to the role of the URT microbiota in BP. As well, this microbiota should be the main target for future interventions and pharmaceuticals aimed at controlling and preventing BP.
Hexanol biosynthesis from syngas by Clostridium carboxidivorans P7 is enhanced by in‑line extraction with a biocompatible solvent to avoid product toxicity
Authors: Kottenhahn Patrick , Philipps Gabriele , Jennewein Stefan 
Published: February 2020

Abstract
Background Clostridium carboxidivorans P7 has the rare ability to metabolize syngas – a mixture of H2, CO and CO2 – by converting it directly into industrially relevant alcohols (hexanol, butanol and ethanol) and the corresponding acids (caproate, butyrate and acetate). The product titers and ratios are highly dependent on the fermentation parameters and the composition of the syngas and growth medium. The hexanol titers produced by C. carboxidivorans P7 have recently been improved by optimizing these conditions, but little is known about the toxicity of hexanol towards Clostridium species. We hypothesized that the hexanol titers currently produced by C. carboxidivorans P7 are limited by product toxicity. Results We tested our hypothesis by exposing C. carboxidivorans P7 to different concentrations of hexanol and found that growth inhibition started at 10–12 mM, with an IC50 of 17.5 ± 1.6 mM. The presence of 20 mM hexanol was acutely toxic to C. carboxidivorans P7 as well as the model acetogen C. ljungdahlii, which does not produce hexanol. To avoid product toxicity, we added a biocompatible solvent (oleyl alcohol) to fed-batch bottle fermentations of C. carboxidivorans. This increased the total hexanol titers by 2.5-fold from 9.4 to 24.4 mM. Cell growth and product profiles in the aqueous phase after fermentation were similar in cultures with and without oleyl alcohol. The extraction phase contained high levels of hexanol (436 ± 101 mM) and butanol (100.3 ± 17.8 mM) as well as low levels of ethanol and traces of caproate. Conclusions Product toxicity was confirmed as a limiting factor during the conversion of syngas to hexanol by C. carboxidivorans P7. The addition of oleyl alcohol as a biocompatible solvent led to a significant increase in hexanol titers by facilitating the efficient and selective extraction of this product. We have therefore identified an in-line extraction strategy that increases the yield of hexanol and should allow for further improvements by genetic adaptation and/or process optimization.
PowerTools: A web based user-friendly tool for future translational study design
Authors: Acharjee Animesh , Larkman Joseph , Cardoso Victor Roth , Gkoutos Georgios V. 
Published: February 2020

Abstract
BackgroundBiomarker identification is one of the major goals of functional genomics and translational medicine research. The advent of NGS lead to a constant and exponential increase of large datasets that have the potential of providing the means for novel biomarker identification for the early diagnosis of complex diseases and/or for patient/disease stratification. Once a biomarker has been identified, a validation study is necessary to assess its value. A study design that considers its appropriateness and cost-effectiveness is paramount. The calculation of a sample size is a challenge that needs to be addressed.MethodsThe workflow of our tool, termed PowerTools, is based on based on the method described by Blaise et al., (2016) [1]. For a given number of input data sets, a simulation step with the random multivariate normal distribution including correlation is considered. As a next step, datasets of variable sizes are generated by random selection of samples. Based on the outcome variable, either classification or regression modes are available. For binary classification ANOVA and linear regression test can be performed and then performance matrices can be evaluated.ResultsWe developed an online framework to streamline power calculations to aid future omics study designs within a translational medicine research context. We make our code freely available on GitHub [2] and we have provided a web interface that can be accessed at online [3].ConclusionsPowerTools offers the potential for designing appropriate and cost-effective subsequent omics study designs.
Prevalence of central nervous system adverse effect and associated factors among HIV patients on efavirenz based ART regimen
Authors: Muche Esileman Abdela , Kiflu Mekdes 
Published: February 2020

Abstract
Background: Efavirenz based antiretroviral regimens served as a first line treatment in our country, however commonly lead to central nervous system toxicity, which is the main reason for non-adherence, switch and discontinuation to antiretroviral therapy. We aimed to assess prevalence of central nervous system adverse effect and associated factors among HIV patients taking efavirenz based regimens. Methods: Hospital based cross-sectional study was conducted on 345 patients who were taking efavirenz based ART medications on follow up at UoGCSH from March 15 to may15, 2018. Information on socio-demographic characteristics and detailed history regarding central nervous system adverse effect were taken from both the patient and medical record.. Both bivariate and multivariate analyses were done using binary logistic regression to find out the associated factors. Level of statistical significance was declared at P value of ≤ 0.05 levels. Result: The central nervous system adverse effects of EFV based ART regimen were observed in 52.8% of participants and vivid dream was the most commonly reported adverse effect. Upon computation of bivariate binary logistic regression economic status, EFV based regimen type, Stage of RVI, alcohol use and concomitant medical condition had shown association on the occurrence of central nervous system adverse effect of EFV based ART regimen. But in multivariate analysis alcohol use (p = 0.004; AOR = 4.450), stage I RVI (p = 0.001; AOR= 0.006) stage II RVI (p = 0.001; AOR=0.017) stage III RVI (P=0.01; AOR=4.13) became significantly associated with the occurrence of CNS adverse effect. Conclusion: More than half of HIV patients taking efavirenz based regimens at UOGCSH experience the central nervous system adverse effect. The most commonly reported central nervous system adverse effects were vivid dream, confusion, and insomnia. Stage III and IV HIV patient need special attention to prevent and decrease central nervous system adverse effect of EFV based regimen. Health workers need to tell the patients to avoid alcohol, especially in the initiation of the treatment.