bluuebunny/crossref_metadata_2025_split huggingface dataset:
Split dose versus full single-dose regimen of polyethylene glycol for bowel preparation in pediatric colonoscopy: a pilot study of randomized controlled trial
Authors: Sriphongphankul Hansa , Tanpowpong Pornthep , Lertudomphonwanit Chatmanee , Treepongkaruna Suporn 
Published: September 2019

Objectives
Previous meta-analyses in adults comparing a full single dose vs. split doses of polyethylene glycol with electrolyte solution demonstrated that the split-dose group had a higher rate of successful bowel preparation. To date, no similar study in children has been conducted. Therefore, we compared the efficacy of bowel preparation between the two regimens of polyethylene glycol with electrolyte solution in pediatric colonoscopy. The secondary outcomes were tolerability, acceptability, and compliance.

Methods
An investigator-blinded randomized controlled trial was conducted to enroll children aged 2–18 years who underwent an elective colonoscopy at a teaching hospital between March 2018 and February 2019. Patients were randomly assigned to receive polyethylene glycol with electrolyte solution as a full single dose or two split doses. The Boston Bowel Preparation Scale was used for the efficacy (i.e. successful bowel preparation if score ≥ 6). Secondary outcomes were evaluated by using a standardized questionnaire.

Results
A total of 45 colonoscopies (22 in the full single-dose and 23 in the split-dose group) were performed. Mean age was 9.2 years old (SD 4.4). We noted a higher rate of successful bowel preparation in the split-dose group (95% vs. 72%, P = 0.047). Significant higher rate of willingness to repeat the same protocol (83% vs. 36%, P = 0.002) and a trend of lower rate of nausea/vomiting (39% vs. 68%, P = 0.051) in the split-dose group were found.

Conclusion
The split-dose regimen of polyethylene glycol with electrolyte solution for bowel preparation suggests superior efficacy, potential tolerability, and acceptability as compared to the traditional full single-dose regimen.
The Role of the National Health Service Corps Clinicians in Enhancing Staffing and Patient Care Capacity in Community Health Centers
Authors: Han Xinxin , Pittman Patricia , Erikson Clese , Mullan Fitzhugh , Ku Leighton 
Published: September 2019

Objective:
The National Health Service Corps (NHSC) is a federal program to increase the supply of health professionals in underserved communities, but its role in enhancing the capacity of community health centers (CHCs) has not been investigated. This study examined the role of NHSC clinicians in improving staffing and patient care capacity in primary, dental, and mental health care in CHCs.

Methods:
Using 2013–2016 administrative data from CHCs and the NHSC, we used a generalized estimating equation approach to examine whether NHSC clinicians [staff full-time equivalents (FTEs)] complement non-NHSC clinicians in CHCs and whether their productivity (patient visits per staff FTE) was greater than that of non-NHSC clinicians in primary, dental, and mental health care.

Results:
Each additional NHSC clinician FTE was associated with a significant gain of 0.72 non-NHSC clinician FTEs in mental health care in CHCs and an increase of 0.04 non-NHSC FTEs in primary care in CHCs with more severe staffing shortages. On average, every additional NHSC clinician was associated with an increase of 2216 primary care visits, 2802 dental care visits, and 1296 mental health care visits per center-year. The adjusted visits per additional staff for NHSC clinicians were significantly greater in dental (difference=992) and mental health (difference=423) care, compared with non-NHSC clinicians.

Conclusions:
The NHSC clinicians complement non-NHSC clinicians in primary care and mental health care. They help enhance the provision of patient care in CHCs, particularly in dental and mental health services, the 2 major areas of service gaps.
Predictive Factors and Risk Model for Positive Circumferential Resection Margin Rate After Transanal Total Mesorectal Excision in 2653 Patients With Rectal Cancer
Authors: Roodbeen Sapho X. , de Lacy F. B. , van Dieren Susan , Penna Marta , Ris Frédéric , Moran Brendan , Tekkis Paris , Bemelman Willem A. , Hompes Roel 
Published: September 2019

Objective:
The aim of this study was to determine the incidence of, and preoperative risk factors for, positive circumferential resection margin (CRM) after transanal total mesorectal excision (TaTME).

Background:
TaTME has the potential to further reduce the rate of positive CRM for patients with low rectal cancer, thereby improving oncological outcome.

Methods:
A prospective registry-based study including all cases recorded on the international TaTME registry between July 2014 and January 2018 was performed. Endpoints were the incidence of, and predictive factors for, positive CRM. Univariate and multivariate logistic regressions were performed, and factors for positive CRM were then assessed by formulating a predictive model.

Results:
In total, 2653 patients undergoing TaTME for rectal cancer were included. The incidence of positive CRM was 107 (4.0%). In multivariate logistic regression analysis, a positive CRM after TaTME was significantly associated with tumors located up to 1 cm from the anorectal junction, anterior tumors, cT4 tumors, extra-mural venous invasion (EMVI), and threatened or involved CRM on baseline MRI (odds ratios 2.09, 1.66, 1.93, 1.94, and 1.72, respectively). The predictive model showed adequate discrimination (area under the receiver-operating characteristic curve >0.70), and predicted a 28% risk of positive CRM if all risk factors were present.

Conclusion:
Five preoperative tumor-related characteristics had an adverse effect on CRM involvement after TaTME. The predicted risk of positive CRM after TaTME for a specific patient can be calculated preoperatively with the proposed model and may help guide patient selection for optimal treatment and enhance a tailored treatment approach to further optimize oncological outcomes.
Nucleus accumbens volume is related to obesity measures in an age-dependent fashion
Authors: García-García Isabel , Morys Filip , Dagher Alain 
Published: September 2019

AbstractMotivation theories of obesity suggest that one of the brain mechanisms underlying pathological eating and weight gain is the dysregulation of dopaminergic circuits. While these dysregulations occur likely at the microscopic level, studies on gray matter volume reported macroscopic differences associated with obesity. One region suggested to play a key role in the pathophysiology of obesity is the nucleus accumbens (NAcc). We performed a meta-analysis of findings regarding NAcc volume and overweight/obesity. We additionally examined whether gray matter volume in the NAcc and other mesolimbic areas depends on the longitudinal trajectory of obesity, using the UK Biobank dataset. To this end, we analysed the data using a latent growth model, which identifies whether certain variables of interest (e.g. NAcc volume) is related to another variable’s (BMI) initial values or longitudinal trajectories. Our meta-analysis showed that, overall, NAcc volume is positively related to BMI. However, further analyses revealed that the relationship between NAcc volume and BMI is dependent on age. For younger individuals such relationship is positive, while for older adults it is negative. This was corroborated by our analysis in the UK Biobank dataset, which includes older adults, where we found that higher BMI was associated with lower NAcc and thalamus volume. Overall, our study suggests that increased NAcc volume in young age might be a vulnerability factor for obesity, while in the older age decreased NAcc volume with increased BMI might be an effect of prolonged influences of neuroinflammation on the brain.
Computational Justice: Simulating Structural Bias and Interventions
Authors: Momennejad Ida , Sinclair Stacey , Cikara Mina 
Published: September 2019

AbstractGender inequality has been documented across a variety of high-prestige professions. Both structural bias (e.g., lack of proportionate representation) and interpersonal bias (e.g., sexism, discrimination) generate costs to underrepresented minorities. How can we estimate these costs and what interventions are most effective for reducing them? We used agent-based simulations, removing gender differences in interpersonal bias to isolate and quantify the impact and costs of structural bias (unequal gender ratios) on individuals and institutions. We compared the long-term impact of bias-confrontation strategies. Unequal gender ratios led to higher costs for female agents and institutions and increased sexism among male agents. Confronting interpersonal bias by targets and allies attenuated the impact of structural bias. However, bias persisted even after a structural intervention to suddenly make previously unequal institutions equal (50% women) unless the probability of interpersonal bias-confrontation was further increased among targets and allies. This computational approach allows for comparison of various policies to attenuate structural equality, and informs the design of new experiments to estimate parameters for more accurate predictions.
More affordable and effective noninvasive SNP genotyping using high-throughput amplicon sequencing
Authors: Eriksson Charlotte E. , Ruprecht Joel , Levi Taal 
Published: September 2019

AbstractNon-invasive genotyping methods have become key elements of wildlife research over the last two decades, but their widespread adoption is limited by high costs, low success rates, and high error rates. The information lost when genotyping success is low may lead to decreased precision in animal population densities which could misguide conservation and management actions. Single nucleotide polymorphisms (SNPs) provide a promising alternative to traditionally used microsatellites as SNPs allow amplification of shorter DNA fragments, are less prone to genotyping errors, and produce results that are easily shared among laboratories. Here, we outline a detailed protocol for cost-effective and accurate noninvasive SNP genotyping using highly multiplexed amplicon sequencing optimized for degraded DNA. We validated this method for individual identification by genotyping 216 scats, 18 hairs and 15 tissues from coyotes (Canis latrans). Our genotyping success rate for scat samples was 93%, and 100% for hair and tissue, representing a substantial increase compared to previous microsatellite-based studies at a cost of under $5 per PCR replicate (excluding labor). The accuracy of the genotypes was further corroborated in that genotypes from scats matching known, GPS-collared coyotes were always located within the territory of the known individual. We also show that different levels of multiplexing produced similar results, but that PCR product cleanup strategies can have substantial effects on genotyping success. By making noninvasive genotyping more affordable, accurate, and efficient, this research may allow for a substantial increase in the use of noninvasive methods to monitor and conserve free-ranging wildlife populations.
Gaussian embedding-based functional brain connectomic analysis for amnestic mild cognitive impairment patients with cognitive training
Authors: Xu Mengjia , Wang Zhijiang , Zhang Haifeng , Pantazis Dimitrios , Wang Huali , Li Quanzheng 
Published: September 2019

AbstractIdentifying heterogeneous cognitive impairment markers at an early stage is vital for Alzheimer’s disease diagnosis. However, due to complex and uncertain brain connectivity features in the cognitive domains, it remains challenging to quantify functional brain connectomic changes during non-pharmacological interventions for amnestic mild cognitive impairment (aMCI) patients. We present a new quantitative functional brain network analysis of fMRI data based on the multi-graph unsupervised Gaussian embedding method (MG2G). This neural network-based model can effectively learn low-dimensional Gaussian distributions from the original high-dimensional sparse functional brain networks, quantify uncertainties in link prediction, and discover the intrinsic dimensionality of brain networks. Using the Wasserstein distance to measure probabilistic changes, we discovered that brain regions in the default mode network and somatosensory/somatomotor hand, fronto-parietal task control, memory retrieval, and visual and dorsal attention systems had relatively large variations during non-pharmacological training, which might provide distinct biomarkers for fine-grained monitoring of aMCI cognitive alteration.
CRISPR-Cas9 generated Pompe knock-in murine model exhibits early-onset hypertrophic cardiomyopathy and skeletal muscle weakness
Authors: Huang Jeffrey Y. , Kan Shih-Hsin , Sandfeld Emilie K. , Dalton Nancy D. , Rangel Anthony D. , Chan Yunghang , Davis-Turak Jeremy , Neumann Jon , Wang Raymond Y. 
Published: September 2019

AbstractInfantile-onset Pompe Disease (IOPD), caused by mutations in lysosomal acid alpha-glucosidase (Gaa), manifests rapidly progressive fatal cardiac and skeletal myopathy incompletely attenuated by synthetic GAA intravenous infusions. The currently available murine model does not fully simulate human IOPD, displaying skeletal myopathy with late-onset hypertrophic cardiomyopathy. Bearing a Cre-LoxP induced exonic disruption of the murine Gaa gene, this model is also not amenable to genome-editing based therapeutic approaches. We report the early onset of severe hypertrophic cardiomyopathy in a novel murine IOPD model generated utilizing CRISPR-Cas9 homology-directed recombination to harbor the orthologous Gaa mutation c.1826dupA (p.Y609*), which causes human IOPD. We demonstrate the dual sgRNA approach with a single-stranded oligonucleotide donor is highly specific for the Gaac.1826 locus without genomic off-target effects or rearrangements. Cardiac and skeletal muscle were deficient in Gaa mRNA and enzymatic activity and accumulated high levels of glycogen. The mice demonstrated skeletal muscle weakness but did not experience early mortality. Altogether, these results demonstrate that the CRISPR-Cas9 generated Gaac.1826dupA murine model recapitulates hypertrophic cardiomyopathy and skeletal muscle weakness of human IOPD, indicating its utility for evaluation of novel therapeutics.
Early developmental exposure to Fluoxetine and Citalopram results in different neurodevelopmental outcomes
Authors: Liu Karine , Garcia Alfonso , Park Jenn J. , Toliver Alexis A. , Ramos Lizmaylin , Aizenman Carlos D. 
Published: September 2019

AbstractAlthough selective serotonin reuptake inhibitors (SSRIs) are commonly prescribed for prenatal depression, there exists controversy over the adverse effects of SSRI use on fetal development. Few studies have adequately isolated outcomes due to SSRI exposure and those due to maternal psychiatric conditions. Here, we directly investigated the outcomes of exposure to widely-used SSRIs fluoxetine and citalopram on the developing nervous system of Xenopus laevis tadpoles, using an integrative experimental approach. We exposed tadpoles to low doses of citalopram and fluoxetine during a critical developmental period and found that the different groups of tadpoles displayed opposing behavioral effects. While both groups showed reduced schooling behavior, the fluoxetine group showed increased seizure susceptibility and reduced startle habituation. In contrast, the citalopram treated tadpoles had decreased seizure susceptibility and increased habituation. Both groups had abnormal dendritic morphology in the optic tectum, a brain area important for all three behaviors tested. Whole-cell electrophysiological recordings of tectal neurons showed no differences in synaptic function across groups; however, tectal cells from fluoxetine-treated tadpoles had decreased voltage gated K+ currents while cells in the citalopram group had increased K+ currents. Both the behavior and electrophysiological findings indicate that cells and circuits in the fluoxetine treated optic tecta are hyperexcitable, while the citalopram group exhibits decreased excitability. Taken all together, these results show that early developmental exposure to SSRIs is sufficient to induce neurodevelopmental effects, however these effects can be complex and vary depending on the SSRI used. This may explain some of the discrepancies across human studies, and further underscores the importance of serotonergic signaling for the developing nervous system.
Dendritic calcium signals in rhesus macaque motor cortex drive an optical brain-computer interface
Authors: Trautmann Eric M. , O’Shea Daniel J. , Sun Xulu , Marshel James H. , Crow Ailey , Hsueh Brian , Vesuna Sam , Cofer Lucas , Bohner Gergő , Allen Will , Kauvar Isaac , Quirin Sean , MacDougall Matthew , Chen Yuzhi , Whitmire Matthew P. , Ramakrishnan Charu , Sahani Maneesh , Seidemann Eyal , Ryu Stephen I. , Deisseroth Karl , Shenoy Krishna V. 
Published: September 2019

AbstractCalcium imaging has rapidly developed into a powerful tool for recording from large populations of neuronsin vivo. Imaging in rhesus macaque motor cortex can enable the discovery of new principles of motor cortical function and can inform the design of next generation brain-computer interfaces (BCIs). Surface two-photon (2P) imaging, however, cannot presently access somatic calcium signals of neurons from all layers of macaque motor cortex due to photon scattering. Here, we demonstrate an implant and imaging system capable of chronic, motion-stabilized two-photon (2P) imaging of calcium signals from in macaques engaged in a motor task. By imaging apical dendrites, some of which originated from deep layer 5 neurons, as as well as superficial cell bodies, we achieved optical access to large populations of deep and superficial cortical neurons across dorsal premotor (PMd) and gyral primary motor (M1) cortices. Dendritic signals from individual neurons displayed tuning for different directions of arm movement, which was stable across many weeks. Combining several technical advances, we developed an optical BCI (oBCI) driven by these dendritic signals and successfully decoded movement direction online. By fusing 2P functional imaging with CLARITY volumetric imaging, we verify that an imaged dendrite, which contributed to oBCI decoding, originated from a putative Betz cell in motor cortical layer 5. This approach establishes new opportunities for studying motor control and designing BCIs.
A processive rotary mechanism couples substrate unfolding and proteolysis in the ClpXP degradation machinery
Authors: Ripstein Zev A. , Vahidi Siavash , Houry Walid A. , Rubinstein John L. , Kay Lewis E. 
Published: September 2019

AbstractThe ClpXP degradation machine consists of a hexameric AAA+ unfoldase (ClpX) and a pair of heptameric serine protease rings (ClpP) that unfold, translocate, and subsequently degrade client proteins. ClpXP is an important target for drug development against infectious diseases. Although structures are available for isolated ClpX and ClpP rings, it remains unknown how symmetry mismatched ClpX and ClpP work in tandem for processive substrate translocation into the ClpP proteolytic chamber. Here we present cryo-EM structures of the substrate-bound ClpXP complex from Neisseria meningitidis at 2.3 to 3.3 Å resolution. The structures allow development of a model in which the cyclical hydrolysis of ATP is coupled to concerted motions of ClpX loops that lead to directional substrate translocation and ClpX rotation relative to ClpP. Our data add to the growing body of evidence that AAA+ molecular machines generate translocating forces by a common mechanism.
De novoidentification of satellite DNAs in the sequenced genomes ofDrosophila virilisandD. americanausing the RepeatExplorer and TAREAN pipelines
Authors: Silva Bráulio S.M.L. , Heringer Pedro , Dias Guilherme B. , Svartman Marta , Kuhn Gustavo C.S. 
Published: September 2019

AbstractSatellite DNAs are among the most abundant repetitive DNAs found in eukaryote genomes, where they participate in a variety of biological roles, from being components of important chromosome structures to gene regulation. Experimental methodologies used before the genomic era were not sufficient despite being too laborious and time-consuming to recover the collection of all satDNAs from a genome. Today, the availability of whole sequenced genomes combined with the development of specific bioinformatic tools are expected to foster the identification of virtually all of the “satellitome” from a particular species. While whole genome assemblies are important to obtain a global view of genome organization, most assemblies are incomplete and lack repetitive regions. Here, we applied short-read sequencing and similarity clustering in order to perform ade novoidentification of the most abundant satellite families in twoDrosophilaspecies from thevirilisgroup:Drosophila virilisandD. americana. These species were chosen because they have been used as a model to understand satDNA biology since early 70’s. We combined computational tandem repeat detection via similarity-based read clustering (implemented in Tandem Repeat Analyzer pipeline – “TAREAN”) with data from the literature and chromosome mapping to obtain an overview of satDNAs inD. virilisandD. americana. The fact that all of the abundant tandem repeats we detected were previously identified in the literature allowed us to evaluate the efficiency of TAREAN in correctly identifying true satDNAs. Our results indicate that raw sequencing reads can be efficiently used to detect satDNAs, but that abundant tandem repeats present in dispersed arrays or associated with transposable elements are frequent false positives. We demonstrate that TAREAN with its parent method RepeatExplorer, may be used as resources to detect tandem repeats associated with transposable elements and also to reveal families of dispersed tandem repeats.
CK2-dependent phosphorylation of the Brg1 chromatin remodeling enzyme occurs during mitosis
Authors: Padilla-Benavides Teresita , Haokip Dominic T. , Yoon Yeonsoo , Reyes-Gutierrez Pablo , Rivera-Pérez Jaime A. , Imbalzano Anthony N. 
Published: September 2019

ABSTRACTBrg1 (Brahma related gene 1) is one of two mutually exclusive ATPases that can act as the catalytic subunit of mammalian SWI/SNF chromatin remodeling enzymes that facilitate utilization of the DNA in eukaryotic cells. Brg1 is a phospho-protein and its activity is regulated by specific kinases and phosphatases. Previously, we showed that Brg1 interacts with and is phosphorylated by casein kinase 2 (CK2) in a manner that regulates myoblast proliferation. Here we demonstrate that the Brg1-CK2 interaction occurred during mitosis in embryonic somites and in primary myoblasts derived from satellite cells isolated from muscle tissue. The interaction of CK2 activity with Brg1 and the incorporation of a number of other subunits into the mSWI/SNF enzyme complex were independent of CK2 enzymatic activity. CK2-mediated hyperphosphorylation of Brg1 was observed in mitotic cells derived from multiple cell types and organisms, suggesting functional conservation across tissues and species. The mitotically hyperphosphorylated form of Brg1 was localized with soluble chromatin, demonstrating that CK2-mediated phosphorylation of Brg1 is associated with specific partitioning of Brg1 within sub-cellular compartments. Thus CK2 acts a mitotic kinase that regulates Brg1 phosphorylation and sub-cellular localization.HIGHLIGHTSInteractions between CK2 and the Brg1 chromatin remodeling enzyme occur during mitosisCK2-Brg1 interactions are independent of CK2 catalytic activityCK2-mediated phosphorylation of Brg1 is a mitotic eventCK2-mediated phosphorylation of Brg1 is conserved across mammalian cell typesThe mitotically hyperphosphorylated form of Brg1 is localized with soluble chromatin