bluuebunny/crossref_metadata_2025_split huggingface dataset:
Associations between Vascular Function and Tau PET Are Associated with Global Cognition and Amyloid
Authors: Albrecht Daniel , Isenberg A. Lisette , Stradford Joy , Monreal Teresa , Sagare Abhay , Pachicano Maricarmen , Sweeney Melanie , Toga Arthur , Zlokovic Berislav , Chui Helena , Joe Elizabeth , Schneider Lon , Conti Peter , Jann Kay , Pa Judy 
Published: October 2020

Tau pathology and vascular dysfunction are important contributors to Alzheimer's disease (AD), but vascular–tau associations and their effects on cognition are poorly understood. We investigated these associations in male and female humans by conducting voxelwise comparisons between cerebral blood flow (CBF) and tau positron emission tomography (PET) images in independent discovery [cognitively normal (CN), 19; mild cognitive impairment (MCI) risk, 43; MCI, 6] and replication (CN,73; MCI, 45; AD, 20) cohorts. In a subgroup, we assessed relationships between tau and soluble platelet-derived growth factor β (sPDGFRβ), a CSF marker of pericyte injury. We tested whether CBF/sPDGFRβ–tau relationships differed based on Montreal Cognitive Assessment (MoCA) global cognition performance, or based on amyloid burden. Mediation analyses assessed relationships among CBF/sPDGFRβ, tau, and cognition. Negative CBF–tau correlations were observed predominantly in temporal-parietal regions. In the replication cohort, early negative CBF–tau correlations increased in spatial extent and in strength of correlation with increased disease severity. Stronger CBF–tau and sPDGFRβ–tau correlations were observed in participants with greater amyloid burden and lower MoCA scores. Importantly, when stratifying by amyloid status, stronger CBF–tau relationships in individuals with lower MoCA scores were driven by amyloid+participants. Tau PET was a significant mediator CBF/sPDGFRβ–MoCA relationships in numerous regions. Our results demonstrate vascular–tau associations across the AD spectrum and suggest that early vascular–tau associations are exacerbated in the presence of amyloid, consistent with a two-hit model of AD on cognition. Combination treatments targeting vascular health, as well as amyloid-β and tau levels, may preserve cognitive function more effectively than single-target therapies.SIGNIFICANCE STATEMENTEmerging evidence demonstrates a role for vascular dysfunction as a significant contributor to Alzheimer's pathophysiology. However, associations between vascular dysfunction and tau pathology, and their effects on cognition remain poorly understood. Multimodal neuroimaging data from two independent cohorts were analyzed to provide novelin vivoevidence of associations between cerebral blood flow (CBF), an MRI measure of vascular health, and tau pathology using PET. CBF–tau associations were related to cognition and driven in part by amyloid burden. Soluble platelet-derived growth factor β, an independent CSF vascular biomarker, confirmed vascular–tau associations in a subgroup analysis. These results suggest that combination treatments targeting vascular health, amyloid-β, and tau levels may more effectively preserve cognitive function than single-target therapies.
Efficient Low-Pass Dendro-Somatic Coupling in the Apical Dendrite of Layer 5 Pyramidal Neurons in the Anterior Cingulate Cortex
Authors: Marti Mengual Ulisses , Wybo Willem A.M. , Spierenburg Lotte J.E. , Santello Mirko , Senn Walter , Nevian Thomas 
Published: October 2020

Signal propagation in the dendrites of many neurons, including cortical pyramidal neurons in sensory cortex, is characterized by strong attenuation toward the soma. In contrast, using dual whole-cell recordings from the apical dendrite and soma of layer 5 (L5) pyramidal neurons in the anterior cingulate cortex (ACC) of adult male mice we found good coupling, particularly of slow subthreshold potentials like NMDA spikes or trains of EPSPs from dendrite to soma. Only the fastest EPSPs in the ACC were reduced to a similar degree as in primary somatosensory cortex, revealing differential low-pass filtering capabilities. Furthermore, L5 pyramidal neurons in the ACC did not exhibit dendritic Ca2+spikes as prominently found in the apical dendrite of S1 (somatosensory cortex) pyramidal neurons. Fitting the experimental data to a NEURON model revealed that the specific distribution ofIleak,Iir,Im, andIhwas sufficient to explain the electrotonic dendritic structure causing a leaky distal dendritic compartment with correspondingly low input resistance and a compact perisomatic region, resulting in a decoupling of distal tuft branches from each other while at the same time efficiently connecting them to the soma. Our results give a biophysically plausible explanation of how a class of prefrontal cortical pyramidal neurons achieve efficient integration of subthreshold distal synaptic inputs compared with the same cell type in sensory cortices.SIGNIFICANCE STATEMENTUnderstanding cortical computation requires the understanding of its fundamental computational subunits. Layer 5 pyramidal neurons are the main output neurons of the cortex, integrating synaptic inputs across different cortical layers. Their elaborate dendritic tree receives, propagates, and transforms synaptic inputs into action potential output. We found good coupling of slow subthreshold potentials like NMDA spikes or trains of EPSPs from the distal apical dendrite to the soma in pyramidal neurons in the ACC, which was significantly better compared with S1. This suggests that frontal pyramidal neurons use a different integration scheme compared with the same cell type in somatosensory cortex, which has important implications for our understanding of information processing across different parts of the neocortex.
Long non‐coding RNA ELDR enhances oral cancer growth by promoting ILF3‐cyclin E1 signaling
Authors: Sur Subhayan , Nakanishi Hiroshi , Steele Robert , Zhang Dapeng , Varvares Mark A , Ray Ratna B 
Published: October 2020

AbstractOral squamous cell carcinoma (OSCC) is the sixth most common cancer with a 5‐year overall survival rate of 50%. Thus, there is a critical need to understand the disease process, and to identify improved therapeutic strategies. Previously, we found the long non‐coding RNA (lncRNA) EGFR long non‐coding downstream RNA (ELDR) induced in a mouse tongue cancer model; however, its functional role in human oral cancer remained unknown. Here, we show that ELDR is highly expressed in OSCC patient samples and in cell lines. Overexpression of ELDR in normal non‐tumorigenic oral keratinocytes induces cell proliferation, colony formation, and PCNA expression. We also show that ELDR depletion reduces OSCC cell proliferation and PCNA expression. Proteomics data identifies the RNA binding protein ILF3 as an interacting partner of ELDR. We further show that the ELDR‐ILF3 axis regulates Cyclin E1 expression and phosphorylation of the retinoblastoma (RB) protein. Intratumoral injection of ELDR‐specific siRNA reduces OSCC and PDX tumor growth in mice. These findings provide molecular insight into the role of ELDR in oral cancer and demonstrate that targeting ELDR has promising therapeutic potential.
Transitional Care Interventions for Youth With Disabilities: A Systematic Review
Authors: Levy Ben B. , Song Jessica Z. , Luong Dorothy , Perrier Laure , Bayley Mark T. , Andrew Gail , Arbour-Nicitopoulos Kelly , Chan Brian , Curran Cynthia J. , Dimitropoulos Gina , Hartman Laura , Huang Lennox , Kastner Monika , Kingsnorth Shauna , McCormick Anna , Nelson Michelle , Nicholas David , Penner Melanie , Thompson Laura , Toulany Alene , Woo Amanda , Zee Joanne , Munce Sarah E.P. 
Published: October 2020

CONTEXT:
Transition from the pediatric to the adult health care system is a complex process that should include medical, psychosocial, educational, recreational, and vocational considerations.

OBJECTIVE:
In this systematic review, we aim to synthesize the evidence on transitional care interventions (TCIs) to improve the quality of life (QoL) for adolescents and young adults with childhood-onset disabilities, including neurodevelopmental disorders.

DATA SOURCES:
Four electronic databases (Medline, Embase, PsycINFO, and Cumulative Index to Nursing and Allied Health Literature) were searched.

STUDY SELECTION:
In the included studies, researchers examined TCIs for adolescents and young adults (12–24 years of age) with childhood-onset disabilities. Studies were experimental, quasi-experimental, and observational studies published in the last 26 years.

DATA EXTRACTION:
Two reviewers independently completed study screening, data extraction, and risk-of-bias assessment.

RESULTS:
Fifty-two studies were included. Five studies reported on QoL, but statistically significant improvements were noted in only 1 of these studies. Significant improvements were also found in secondary outcomes including disability-related knowledge and transitional readiness. TCIs targeted patients, families and/or caregivers, and health care providers and exhibited great heterogeneity in their characteristics and components.

LIMITATIONS:
Inconsistent reporting on interventions between studies hindered synthesis of the relationships between specific intervention characteristics and outcomes.

CONCLUSIONS:
Although there is limited evidence on the impact of TCIs on the QoL for youth with childhood-onset disabilities, there is indication that they can be effective in improving patient and provider outcomes. The initiation of transition-focused care at an early age may contribute to improved long-term health outcomes in this population.
Web-Based Tailored Messaging to Increase Vaccination: A Randomized Clinical Trial
Authors: Glanz Jason M. , Wagner Nicole M. , Narwaney Komal J. , Pyrzanowski Jennifer , Kwan Bethany M. , Sevick Carter , Resnicow Kenneth , Dempsey Amanda F. 
Published: October 2020

BACKGROUND:
To increase vaccine acceptance, we created a Web-based the “Vaccines and Your Baby” intervention (VAYB) that provided new parents with vaccine information messages tailored to vaccine beliefs and values. We evaluated the effectiveness of the VAYB by comparing timely uptake of infant vaccines to an untailored version of the intervention (UT) or usual care intervention (UC) only.

METHODS:
Between April 2016 and June 2019, we conducted a randomized clinical trial. Pregnant women and new parents were randomly assigned to the VAYB, UT, or UC arms. In the VAYB and UT arms, participants were exposed to interventions at 4 time points from pregnancy until their child was 15 months of age. The primary outcome was up-to-date status for recommended vaccines from birth to 200 days of age. A modified intent-to-treat analysis was conducted. Data were analyzed with logistic regression to generate odds ratios (ORs) and 95% confidence intervals (CIs).

RESULTS:
We enrolled 824 participants (276 VAYB, 274 UT, 274 UC), 143 (17.4%) of whom were lost to follow-up. The up-to-date rates in the VAYB, UT, and UC arms were 91.44%, 92.86%, and 92.31%, respectively. Infants in the VAYB arm were not more likely to be up to date than infants in the UC arm (OR = 0.89; 95% CI, 0.45–1.76) or in the UT arm (OR = 0.82; 95% CI, 0.42–1.63). The odds of being up to date did not differ between UT and UC arms (OR = 1.08; 95% CI, 0.54–2.18).

CONCLUSIONS:
Delivering Web-based vaccine messages tailored to parents’ vaccine attitudes and values did not positively impact the timely uptake of infant vaccines.
Direct Injection of Biomineralizing Agents to Restore Injectivity and Wellbore Integrity
Authors: Kirkland Catherine M. , Hiebert Randy , Hyatt Robert , McCloskey Jay , Kirksey Jim , Thane Abby , Cunningham Alfred B. , Gerlach Robin , Spangler Lee , Phillips Adrienne J. 
Published: October 2020

SummaryIn this manuscript, we describe the second of two field demonstrations of microbially induced calcium carbonate precipitation (MICP) performed in a failed waterflood injection well in Indiana. In 2012, fracture-related flow pathways developed in the wellbore cement, causing injection water to bypass the oil-bearing formation and enter a high-permeability sandstone thief zone, thereby substantially decreasing injection pressure. In the first field demonstration, our study team characterized the well's mode of failure and successfully applied MICP to decrease flow through the defective cement. However, because the MICP treatment was conducted using a bailer delivery system, the degree of permeability reduction achievable was not adequate to fully restore the historic injection pressure of 1,400 psi at 1 gal/min. For the second field demonstration (reported herein), a direct injection system was developed that substantially increased the injection volume of MICP-promoting fluids. Two strategies were implemented to produce more ureolytic microbes: resuspending concentrated frozen cells immediately before injection and scaling up the bioreactor growth capacity. Multiple pulses of microbes and urea-calcium media were pumped into a string of 1-in.-diameter tubing separated by brine spacers and injected continuously at a flow rate of 3.4 to 1.4 gal/min. During the third day of injection, an injection pressure of 1,384 psi at a flow rate of 1.4 gal/min was achieved, and the experiment was terminated. This study demonstrates that MICP can be successfully used in large-volume applications where the time frame for the delivery of reactants is limited. This finding has significant relevance for commercialization of the MICP biotechnology in the oil and gas industry.
enChIP systems with MSCV-based retroviral plasmids expressing 3xFLAG-Sp-dCas9
Authors: Yuno Miyuki , Fujita Toshitsugu , Fujii Hodaka 
Published: October 2020

Abstract
Engineered DNA-binding molecule–mediated chromatin immunoprecipitation (enChIP) is a technology for purifying specific genomic regions to facilitate identification of their associated molecules, including proteins, RNAs, and other genomic regions. In enChIP, the target genomic region is tagged with engineered DNA-binding molecules, e.g., a variant of the clustered regularly interspaced short palindromic repeats (CRISPR) system consisting of a guide RNA (gRNA) and a catalytically inactive form of Cas9 (dCas9). In this study, to increase the flexibility of enChIP and expand the range of target cells, we generated murine stem cell virus (MSCV)-based retroviral plasmids for expressing dCas9. We constructed MSCV-based retroviral plasmids expressing Streptococcus pyogenes dCas9 fused to a 3xFLAG-tag (3xFLAG-Sp-dCas9) and various drug resistance genes. We showed that it is feasible to purify target genomic regions with high yields using these plasmids. These systems might give enChIP users greater flexibility in choosing optimal systems for drug selection of transduced cells. In addition, they could be used to analyze different types of target cells.
Overexpression of chalcone synthase gene improves flavonoid accumulation and drought tolerance in tobacco
Authors: Hu Ben , Yao Heng , Gao Yulong , Wang Ran , Li Feng , Guo Jinggong , Li Kun , Zhao Mingyue , jin lifeng 
Published: October 2020

Abstract
Flavonoids are important secondary metabolites in plants that play important roles in maintaining the cellular redox balance of cells. Chalcone synthase (CHS) is the key enzyme in the flavonoid biosynthesis pathway and has been found to monitor changes due to drought stress tolerance. In this study, a CHS gene in tobacco ( Nicotiana tabacum ) was overexpressed. Results revealed that transgenic tobacco plants were more tolerant than control plants to drought stress. Transcription levels of the key genes involved in the flavonoid pathway and the contents of seven flavonoids significantly increased in transgenic tobacco plants ( p < 0.01). Overexpression of the CHS gene led to lower concentrations of the oxidative stress product, malondialdehyde (MDA). Additionally, 11 CHS family genes were mined from the tobacco genome. Based on the phylogenetic tree, these genes split into two groups with eight genes clustered together with the bona fide Arabidopsis CHS gene, suggesting that those tobacco genes are CHS genes. Further phylogenetic analyses indicated that the tobacco CHS genes grouped further into three independent clades with the cloned tobacco CHS gene located within Clade iii. The tobacco CHS family genes exhibited a highly conserved CDS length, pI, and molecular weight of the encoded peptides. All CHS peptides contained two conserved domains, and the genes harbored two or three exons. Based on the results of this study, the NtCHS gene is considered a possible candidate gene for genetically engineering enhanced drought tolerance and improved responses to oxidative stress in plants.
Pulmonary cavitation in patients with thyroid cancer receiving antiangiogenic agents
Authors: Datar Saumil , Cabanillas Maria , Dadu Ramona , Ost David , Grosu Horiana 
Published: October 2020

Abstract
Background:Thyroid malignancies are among the most common endocrine cancers worldwide. Owing to the angiogenic nature of these malignancies, tyrosine kinase inhibitors (TKIs) are an attractive potential treatment. However, TKIs have been associated with an increased risk of tumor cavitation, in turn linked to poor outcomes, in patients with malignancies in the lungs, where thyroid cancer commonly metastasizes. Method:We performed a retrospective cohort study of patients with thyroid cancer and evidence of metastatic disease to the lung that were treated with multi-targeted antiangiogenic TKIs. The primary objective of this study was to determine the incidence of pulmonary cavitation. The secondary objective was to evaluate the effect of pulmonary cavitation on survival. Results: Of the 83 patients with pulmonary nodules,10 developed cavitation during treatment. Of these 83 patients, two patients had to stop the treatment due to pneumothorax. Additionally, cavitation did not demonstrate any significant effect on survival. Conclusion:In patients with thyroid cancer and evidence of metastatic disease to the chest, the use of multi-targeted TKIs led to cavitations that were not uncommon but clinical consequences were marginal. Treatment was stopped only in two patients that developed pneumothorax, however the small sample is a strong limitation of our study.
A systematic evaluation of the design, orientation, and sequence context dependencies of massively parallel reporter assays
Authors: Klein Jason , Agarwal Vikram , Inoue Fumitaka , Keith Aidan , Martin Beth , Kircher Martin , Ahituv Nadav , Shendure Jay 
Published: October 2020

Abstract
Massively parallel reporter assays (MPRAs) functionally screen thousands of sequences for regulatory activity in parallel. Here, we further develop and apply a novel method to assemble and functionally test libraries of greater than 2000 of the same putative enhancers as 192-mers, 354-mers, and 678-mers. We achieved a yield of 95% for 354-mers and 84% for 678-mers. Importantly, we observe surprisingly large differences in functional activity. This work provides a framework for the experimental design of high-throughput reporter assays, suggesting that the extended sequence context of tested elements, and to a lesser degree the precise assay, influence MPRA results.
Echocardiography-Guided Hemodynamic Management of Severe Sepsis and Septic Shock in Adults: A Randomized Controlled Trial
Authors: Alhabashy Walid S. , Shalaby Osama M. , Elgebaly Ahmed S. , Ghafar Mohammed S. Abd El 
Published: October 2020

Abstract
Background: Echocardiography (ECHO) is used to guide septic shock resuscitation, but without evidence for efficacy. Therefore, we compared the outcome of early goal-directed therapy (EGDT) and ECHO-guided management of hemodynamics in severe sepsis and septic shock. Materials and Methods: This is a single center, randomized controlled trial conducted on 100 adult patients with severe sepsis or septic shock. Patients were assessed and treated with either EGDT protocol (EGDT group) or ECHO-guided resuscitation protocol (ECHO group). Results: Only 87 patients (45 in group I and 42 in group II) were analyzed. There was a significant increase of mean norepinephrine and dobutamine doses and a significant decrease in total fluids in the first 24 hours, time to normalization, time to weaning of vasopressors, total MV days, MV free days and ICU and hospital stays in ECHO group. At 30 days, the mortality rate in EGDT group was 35.6% which was significantly higher compared to 14.3% in ECHO group. At 90 days, the overall mortality was significantly higher in EGDT group compared to Echo group (40.0% vs 16.7% respectively). Hazardous ratio of mortality was 1.630 (95% confidence interval (CI): 1.123 - 2.366) and 1.653 (95% CI: 1.137 - 2.404) at 30 and 90 days respectively in EGDT group compared to ECHO group. Conclusions: In severe sepsis and septic shock, ECHO-guided management of hemodynamics resulted in a decrease in mortality, lower total fluid intake, higher vasopressor and inotrope support, earlier weaning of vasopressors and less MV days, ICU and hospital stay.
Sex differences in the association between self-rated health and high-sensitivity C-reactive protein levels in Koreans: A cross-sectional study using data from the Korea National Health and Nutrition Examination Survey
Authors: Park Se-Won , Park Seong-Sik , Kim Eun-Jung , Sung Won-Suk , Ha In-Hyuk , Jung boyoung 
Published: October 2020

Abstract
Background: No studies have investigated the association between self-rated health (SRH) and high-sensitivity C-reactive protein (hs-CRP) levels in South Koreans. We explored this association and analyzed differences between sexes. Methods: Using cross-sectional data from the 2015–2017 Korea National Health and Nutrition Examination Survey, we analyzed the association between SRH and high hs-CRP levels (>1.0 mg/L) in 14,544 Koreans aged ≥19 years who responded to the SRH survey and had available hs-CRP test results. Differences in sociodemographic factors were analyzed using the Pearson’s chi-square test for categorical variables or the Mann-Whitney U test for continuous variables. Multiple logistic regression analysis was used to measure the association between hs-CRP levels and SRH according to sex while adjusting for other possible confounders.Results: The percentage of very poor to poor SRH was higher in the high hs-CRP group (22.4%) than in the low hs-CRP group (17.66%). Among men, the risk of a high hs-CRP level increased with worse SRH (adjusted for confounders; P for trend <0.001). After adjusting for all confounders, including chronic diseases, men with very poor SRH showed a higher odds ratio (OR) for high hs-CRP levels than those with very good SRH (fully adjusted OR, 1.74; 95% confidence interval, 1.04–2.90). Significant correlations were absent among women. Conclusions: Poor SRH was correlated with low-grade inflammation (high hs-CRP levels) among Korean male adults. These findings could be useful for developing health improvement programs and in goal setting at a national scale.