bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hyperbaric oxygen therapy for spinal cord injury
Authors: Li Tong , Wang Yiran , Feng Chaoqun , Li Qianchun , Ran Qiang , Chen Botao , Yu Yang , Jiang Leiming , Fan Xiaohong 
Published: December 2020

Abstract

Background:
Hyperbaric oxygen (HBO) therapy can prevent further spinal cord injury (SCI) caused by spinal cord ischemia-reperfusion injury to the maximum extent, which has been reported increasingly in recent years. However its security and effectiveness still lack of high-quality medical evidence. In this study, we will perform a systematic review of previously published randomized controlled trials (RCTs) to evaluate the efficacy and safety of HBO therapy for SCI.

Methods:
All potential RCTs on HBO therapy for SCI will be searched from the following electronic databases: PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure, Chinese Science and Technology Periodical Database, Wanfang database and Chinese Biomedical Literature Database. We will search all electronic databases from their initiation to the September 30, 2020 in spite of language and publication date. Two contributors will independently select studies from all searched literatures, extract data from included trials, and evaluate study quality for all eligible RCTs using Cochrane risk of bias tool, respectively. Any confusion will be resolved by consulting contributor and a consensus will be reached. We will utilize RevMan 5.3 software to pool the data and to conduct the data analysis.

Results:
The quality of the assessments will be assessed through Grading of Recommendations Assessment, Development, and Evaluation. Data will be disseminated through publications in peer-reviewed journals.

Conclusion:
This study will provide evidence to evaluate the efficacy and safety of HBO therapy for SCI at evidence-based medicine level.

Trial registration number:
INPLASY 2020100084.
Association between functional polymorphisms in the flanking region of miR-143/145 and risk of papillary thyroid carcinoma
Authors: Wang Yichao , Zhou Shengliang , Zhao Wanjun , Li Zhihui , Zhu Jingqiang , Wei Tao , Song Haolan 
Published: December 2020

Abstract
MiR-143 and miR-145 were down-regulated in papillary thyroid carcinoma (PTC) involving in cell proliferation, apoptosis, migration, invasion, and epithelial to mesenchymal transition. In this study, we aimed to investigate the association between 2 functional polymorphisms (ie, rs4705342 and rs353292) in the flanking region of miR-143/145 and risk of PTC.
A case-control study including 316 PTC patients and 347 controls was performed. The rs4705342 and rs353292 were genotyped by using the TaqMan allelic discrimination. The results were confirmed by DNA sequencing.
For the rs4705342, a reduced risk of PTC was observed in heterozygous comparison, dominant genetic model and allele comparison (CC vs TT: adjusted OR = 0.37, 95% CI = 0.19–0.74, P = .003; CT/CC vs TT: adjusted OR = 0.64, 95% CI = 0.47–0.87, P = .005; C vs T: adjusted OR = 0.66, 95% CI = 0.52–0.85, P = .001, respectively). No significant difference was found in the genotypic distributions of the rs353292 between cases and controls.
These findings indicate that the rs4705342 in the flanking region of miR-143/145 may be a protective factor against the occurrence of PTC. Further study is therefore required to investigate the correlation between the genotype and V-raf murine sarcoma viral oncogene homolog B1 V600E, rat sarcoma viral oncogene homolog mutations, rearranged in transformation/PTC1 and rearranged in transformation/PTC3.
Evaluation of an Osteoporosis Outreach Program for Men With a Fragility Fracture and Their Physicians
Authors: Pasquale Margaret K. , Sheer Richard L. , Yehoshua Alon , McFadden Adrienne , Chines Arkadi , Caloyeras John 
Published: December 2020

Background:
Many health plans have outreach programs aimed at appropriately screening, evaluating, and treating women experiencing fragility fractures; however, few programs exist for men.

Objective:
The objective of this study was to develop, implement, and evaluate an osteoporosis outreach program for men with a recent fragility fracture and their physicians.

Research Design and Subjects:
A total of 10,934 male patients enrolled in a Medicare Advantage with Prescription Drug Plan with a recent fragility fracture were randomized to a program or control group. Patients and their physicians received letters followed by phone calls on osteoporosis and the importance of screening and treatment. The evaluation compared bone mineral density (BMD) test utilization and osteoporosis medication treatment (OPT) among patients who received the outreach versus no outreach at 12 months. The effect of the program was estimated through univariate and multivariable logistic regressions.

Results:
The program had a significant impact on BMD evaluation and OPT initiation. At 12 months, 10.7% of participants and 4.9% of nonparticipants received a BMD evaluation. The odds ratio (OR) (95% confidence interval) was 2.31 (1.94, 2.76), and the number needed to outreach to receive a BMD test was 18. OPT was initiated in 4.0% of participants and 2.5% of nonparticipants. The OR (95% confidence interval) of receiving OPT was 1.60 (1.24, 2.07), and the number needed to outreach was 69. Adjusted ORs were similar in magnitude and significance.

Conclusion:
The program was highly effective by more than doubling the rate of BMD evaluation; however, more intensive interventions may yield an even higher screening rate.
Drivers of Cost Differences Between Nurse Practitioner and Physician Attributed Medicare Beneficiaries
Authors: Razavi Moaven , O’Reilly-Jacob Monica , Perloff Jennifer , Buerhaus Peter 
Published: December 2020

Background:
Although recent research suggests that primary care provided by nurse practitioners costs less than primary care provided by physicians, little is known about underlying drivers of these cost differences.

Research Objective:
Identify the drivers of cost differences between Medicare beneficiaries attributed to primary care nurse practitioners (PCNPs) and primary care physicians (PCMDs).

Study Design:
Cross-sectional cost decomposition analysis using 2009–2010 Medicare administrative claims for beneficiaries attributed to PCNPs and PCMDs with risk stratification to control for beneficiary severity. Cost differences between PCNPs and PCMDs were decomposed into payment, service volume, and service mix within low-risk, moderate-risk and high-risk strata.

Results:
Overall, the average PCMD cost of care is 34% higher than PCNP care in the low-risk stratum, and 28% and 21% higher in the medium-risk and high-risk stratum. In the low-risk stratum, the difference is comprised of 24% service volume, 6% payment, and 4% service mix. In the high-risk stratum, the difference is composed of 7% service volume, 9% payment, and 4% service mix. The cost difference between PCNP and PCMD attributed beneficiaries is persistent and significant, but narrows as risk increases. Across the strata, PCNPs use fewer and less expensive services than PCMDs. In the low-risk stratum, PCNPs use markedly fewer services than PCMDs.

Conclusions:
There are differences in the costs of primary care of Medicare beneficiaries provided by nurse practitioners and MDs. Especially in low-risk populations, the lower cost of PCNP provided care is primarily driven by lower service volume.
Fecal Microbiota Transplantation for Treatment of Severe Clostridioides difficile Colitis in a Pediatric Patient With Non-Hodgkin Lymphoma
Authors: Sabus Ashley , Merrow Mya , Heiden Alyssa , Boster Julia , Koo Jane , Franklin Anna R.K. 
Published: December 2020

Background:
Patients with malignant diseases are at high risk for refractory Clostridioides difficile infections (CDI). Fecal microbiota transplantation (FMT) restores the gastrointestinal microbiome and may be an effective treatment for patients who fail pharmacotherapy. However, FMT is not commonly used in the oncology population because of risk for donor-derived infection.

Observations:
The authors report successful use of FMT in a pediatric patient with refractory CDI actively receiving chemotherapy. The patient’s symptoms improved 1 day following FMT. He did not experience infectious complications or other adverse effects.

Conclusions:
FMT may be a feasible option for treatment of refractory CDI in pediatric oncology patients.
Fas-threshold signalling in MSCs causes tumour progression and metastasis
Authors: Mohr Andrea , Tianyuan Chu , Clarkson Christopher T. , Brooke Greg N. , Teif Vladimir B. , Zwacka Ralf M. 
Published: December 2020

AbstractMesenchymal stem cells (MSCs) are part of the tumour microenvironment and have been implicated in tumour progression. We found the number of MSCs significantly increased in tumour-burdened mice driven by Fas-threshold signalling. Consequently, MSCs lacking Fas lost their ability to induce metastasis development in a pancreatic cancer model. Mixing of MSCs with pancreatic cancer cells led to sustained production of the pro-metastatic cytokines CCL2 and IL6 by the stem cells. The levels of these cytokines depended on the number of MSCs, linking Fas-mediated MSC-proliferation to their capacity to promote tumour progression. Furthermore, we discovered that CCL2 and IL6 were induced by pancreatic cancer cell-derived IL1. Analysis of patient transcriptomic data revealed that high FasL expression correlates with high levels of MSC markers as well as increased IL6 and CCL2 in pancreatic tumours. Moreover, both FasL and CCL2 are linked to elevated levels of markers specific for monocytes known to possess further pro-metastatic activities. These results confirm our experimental findings of a FasL-MSC-IL1-CCL2/IL6 axis in pancreatic cancer and highlight the role MSCs play in tumour progression.
In VitroAnalysis of the Anti-viral Potential of nasal spray constituents against SARS-CoV-2
Authors: Cannon Mark L , Westover Jonna B. , Bleher Reiner , Sanchez-Gonzalez Marcos A. , Ferrer Gustavo 
Published: December 2020

AbstractViral pandemics have taken a significant toll on humanity and the world now is contending with the SARS-CoV-2 epidemic. Readily available economical preventive measures should be immediately explored. Xylitol has been reported to reduce the severity of viral infections as well as the severity of pneumonia, and increase the survivability of animal subjects. Since pneumonia and acute respiratory distress syndrome are potentially fatal complications of COVID-19, the present study tested thein vitroeffectiveness of xylitol against SARS-CoV-2. Virus titers and LRV of SARS-CoV-2, were incubated with a single concentration of nasal spray. Toxicity was observed in the top dilution (1/10). Virus was seen below that dilution so it did not affect calculations of virus titer or LRV. After a 25-minute contact time, the nasal spray (11% Pure Xylitol, 0.85%NaCL (Saline), and 0.20% grapefruit seed extract) reduced virus from 4.2 to 1.7 log10 CCID50 per 0.1 mL, a statistically significant reduction (P<0.001) of 2.5 log10 CCID50. STEM Images obtained at the BIoCryo Laboratory revealed virus contained on the cell wall but none intra-cellular, possibly due to D-xylose (xylitol) production of glycoaminoglycans decoy targets. Xylitol and grapefruit seed extract are not exotic nor expensive rare high technology answers to viral epidemics. The potential in saving lives and the economies of the world by using X-GSE combination therapy should inspire large clinical trials, especially in those nations whereas the healthcare system would be dangerously compromised by the adoption of less effective and significantly more financially demanding therapies. Because there are no risk factors in using the X/GSE combination therapy, and the nasal spray is over the counter available without a prescription, and the spray allows for comfortable long term mask-wearing, adoption of this preventive anti-viral therapy should be encouraged.
A single intranasal or intramuscular immunization with chimpanzee adenovirus vectored SARS-CoV-2 vaccine protects against pneumonia in hamsters
Authors: Bricker Traci L. , Darling Tamarand L. , Hassan Ahmed O. , Harastani Houda H. , Soung Allison , Jiang Xiaoping , Dai Ya-Nan , Zhao Haiyan , Adams Lucas J. , Holtzman Michael J. , Bailey Adam L. , Case James Brett , Fremont Daved H. , Klein Robyn , Diamond Michael S. , Boon Adrianus C. M. 
Published: December 2020

ABSTRACTThe development of an effective vaccine against SARS-CoV-2, the etiologic agent of COVID-19, is a global priority. Here, we compared the protective capacity of intranasal and intramuscular delivery of a chimpanzee adenovirus-vectored vaccine encoding a pre-fusion stabilized spike protein (ChAd-SARS-CoV-2-S) in Golden Syrian hamsters. While immunization with ChAd-SARS-CoV-2-S induced robust spike protein specific antibodies capable or neutralizing the virus, antibody levels in serum were higher in hamsters immunized by an intranasal compared to intramuscular route. Accordingly, ChAd-SARS-CoV-2-S immunized hamsters were protected against a challenge with a high dose of SARS-CoV-2. After challenge, ChAd-SARS-CoV-2-S-immunized hamsters had less weight loss and showed reductions in viral RNA and infectious virus titer in both nasal swabs and lungs, and reduced pathology and inflammatory gene expression in the lungs, compared to ChAd-Control immunized hamsters. Intranasal immunization with ChAd-SARS-CoV-2-S provided superior protection against SARS-CoV-2 infection and inflammation in the upper respiratory tract. These findings support intranasal administration of the ChAd-SARS-CoV-2-S candidate vaccine to prevent SARS-CoV-2 infection, disease, and possibly transmission.
Microarthropod contributions to fitness variation in the common mossCeratodon purpureus
Authors: Shortlidge Erin E. , Payton Adam C. , Carey Sarah B. , McDaniel Stuart F. , Rosenstiel Todd N. , Eppley Sarah M. 
Published: December 2020

AbstractThe evolution of mutualism depends critically upon genetic variation in the fitness benefit to both partners. Estimates of these quantities are rare, however, because genetic variation for the interaction may be absent, aspects of the interaction may not be amenable to experimental manipulation, or the benefits to one partner may be unknown. In vitro experiments show that female mosses produce odors which attract sperm-dispersing microarthropods, but the fitness consequences of this interaction for either partner are unknown. Here we established experimental mesocosms to test for a commensal effect of sperm-dispersing microarthropods on moss reproduction. We found that of moss grown with microarthropods showed increased moss reproductive rates by five times, relative to control mesocosms, but remarkably also increased the number of reproducing genotypes, and changed the rank-order of fitness for both male and female genotypes. These results provide an estimate of the fitness benefit for mosses in the presence of microarthropods, and highlight the potential for biotic dispersal agents to alter fitness among moss genotypes in this relationship.
Differences in evolutionary accessibility determine which equally effective regulatory motif evolves to generate pulses
Authors: Xiong Kun , Gerstein Mark , Masel Joanna 
Published: December 2020

ABSTRACTTranscriptional regulatory networks (TRNs) are enriched for certain “motifs”. Motif usage is commonly interpreted in adaptationist terms, i.e. that the optimal motif evolves. But certain motifs can also evolve more easily than others. Here, we computationally evolved TRNs to produce a pulse of an effector protein. Two well-known motifs, type 1 incoherent feed-forward loops (I1FFLs) and negative feedback loops (NFBLs), evolved as the primary solutions. Which motif evolves more often depends on selection conditions, but under all conditions, either motif achieves similar performance. I1FFLs generally evolve more often than NFBLs, unless we select for a tall pulse. I1FFLs are more evolutionarily accessible early on, before the effector protein evolves high expression; when NFBLs subsequently evolve, they tend to do so from a conjugated I1FFL-NFBL genotype. In the empiricalS. cerevisiaeTRN, output genes of NFBLs had higher expression levels than those of I1FFLs. These results suggest that evolutionary accessibility, and not relative functionality, shapes which motifs evolve in TRNs, and does so as a function of the expression levels of particular genes.
Functional and genomic adaptations of blood monocytes to pregravid obesity during pregnancy
Authors: Sureshchandra Suhas , Marshall Nicole E. , Mendoza Norma , Jankeel Allen , Zulu Michael Z. , Messaoudi Ilhem 
Published: December 2020

ABSTRACTPre-pregnancy obesity is associated with several adverse maternal health outcomes, notably increased risk of infection as well as the incidence of gestational diabetes, preeclampsia, and preterm birth. However, the mechanisms by which pregravid obesity disrupts the pregnancy associated “immune clock” are still unknown. To address this question, we collected blood samples from women during the first and third trimesters and determined the impact of both pregnancy and pregravid obesity on circulating immune mediators, immune cell subset frequencies, and peripheral immune responses. While regardless of BMI, pregnancy was associated with an elevation in both Th1 and Th2 cytokines, pregravid obesity was associated with a dysregulation in circulating myeloid factors at term. Moreover, pregnancy in lean subjects was associated with enhanced monocyte activation, augmented chromatin accessibility at inflammatory loci, and heightened responses to LPS. Pregravid obesity disrupted this trajectory and was accompanied by a lack of transcriptional and epigenetic changes and alterations in metabolic status strongly suggesting a skewing towards immunotolerance. These findings provide novel insight into the increased susceptibility to infections observed with obesity during pregnancy.SUMMARYA healthy pregnancy is associated with progressive innate immune activation. Maternal factors such as obesity compromise this myeloid cell activation trajectory at genomic, epigenomic, functional, and metabolic levels, resulting in stagnant immune responses, suggestive of a state of tolerance.
Genome-wide association of PCSK9 (Proprotein Convertase Subtilisin/Kexin Type 9) plasma levels in the ELSA-Brasil study
Authors: Bensenor Isabela , Padilha Kallyandra , Lima Isabella Ramos , Santos Raul Dias , Lambert Gilles , Ramin-Mangata Stéphane , Bittencourt Marcio S , Goulart Alessandra C , Santos Itamar S. , Mill Jose G , Krieger Jose E , Lotufo Paulo A. , Pereira Alexandre C. 
Published: December 2020

AbstractPharmacological inhibition of PCSK9 (proprotein convertase subtilisin/kexin type 9) is an established therapeutic option to treat hypercholesterolemia and plasma PCSK9 levels have been implicated in cardiovascular disease incidence. A number of genetic variants within the PCSK9 gene locus have been shown to modulate PCSK9 levels, but these only explain a very small percentage of the overall PCSK9 interindividual variation. Here we present data on the genetic association structure between PCSK9 levels and genome-wide genetic variation in a healthy sample from the general population.We performed a genome-wide association study of plasma PCSK9 levels in a sample of Brazilian individuals enrolled in the ELSA-Brasil cohort (n=810). Enrolled individuals were free from cardiovascular disease, diabetes and were not under lipid-lowering medication. Genome-wide genotyping was conducted using the Axiom_PMRA.r3 array and imputation used the TOPMED multi-ancestry sample panel. Total PCSK9 plasma concentrations were determined using the Quantikine SPC900 ELISA kit.We observed two genome-wide significant loci and seven loci that reached the pre-definedpvalue threshold of 1 × 10−6. Significant variants were nearKCNA5andKCNA1, andLINC00353. Genetic variation at thePCSK9locus was able to explain approximately 4% of the overall interindividual variation in PCSK9 levels. Colocalization analysis using eQTL data suggestedRWDD3,ATXN7L1,KCNA1, andFAM177A1to be potential mediators of some of the observed associations.Our results suggest that PCSK9 levels may be modulated bytransgenetic variation outside of thePCSK9gene and this may have clinical implications. Understanding both environmental and genetic predictors of PCSK9 levels may help identifying new targets for cardiovascular disease treatment and contribute to a better assessment of the benefits of long-term PCSK9 inhibition.
Accuracy and precision of citizen scientist animal counts from drone imagery
Authors: Wood Sarah A. , Robinson Patrick W. , Costa Daniel P. , Beltran Roxanne S. 
Published: December 2020

AbstractRepeated counts of animal abundance can reveal changes in local ecosystem health and inform conservation strategies. Unmanned aircraft systems (UAS) such as drones are commonly used to photograph animals in remote locations; however, counting animals in images is a laborious task. Crowd-sourcing can reduce the time required to conduct these censuses considerably, but must first be validated against expert counts to measure sources of error. Our objectives were to assess the accuracy and precision of citizen science counts and make recommendations for future citizen science projects. We uploaded drone imagery from Año Nuevo Island (California, USA) to a curated Zooniverse website that instructed citizen scientists to count seals and sea lions. Across 212 days, over 1,500 volunteers counted animals in 90,000 photographs. We quantified the error associated with several descriptive statistics to extract a single citizen science count per photograph from the 15 repeat counts and then compared the resulting citizen science counts to expert counts. Although proportional error was relatively low (9% for sea lions and 5% for seals during the breeding seasons) and improved with repeat sampling, the 12+ volunteers required to reduce error was prohibitively slow, taking on average 6 weeks to estimate animals from a single drone flight covering 25 acres, despite strong public outreach efforts. The single best algorithm was ‘Median without the lowest two values’, demonstrating that citizen scientists tended to under-estimate the number of animals present. Citizen scientists accurately counted adult seals, but accuracy was lower when sea lions were present during the summer and could be confused for seals. We underscore the importance of validation efforts and careful project design for researchers hoping to combine citizen science with drone imagery.
SARS-CoV-2 D614 and G614 spike variants impair neuronal synapses and exhibit differential fusion ability
Authors: Chen Chiung-Ya , Chou Yu-Chi , Hsueh Yi-Ping 
Published: December 2020

AbstractSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes Coronavirus disease 2019 (COVID-19) exhibits two major variants based on mutations of its spike protein, i.e., the D614 prototype and G614 variant. Although neurological symptoms have been frequently reported in patients, it is still unclear whether SARS-CoV-2 impairs neuronal activity or function. Here, we show that expression of both D614 and G614 spike proteins is sufficient to induce phenotypes of impaired neuronal morphology, including defective dendritic spines and shortened dendritic length. Using spike protein-specific monoclonal antibodies, we found that D614 and G614 spike proteins show differential S1/S2 cleavage and cell fusion efficiency. Our findings provide an explanation for higher transmission of the G614 variant and the neurological manifestations observed in COVID-19 patients.