bluuebunny/crossref_metadata_2025_split huggingface dataset:
Factors related to colorectal cancer in advanced adenomas and serrated polyps: a further step toward individualized surveillance
Authors: Adán Merino Luisa , Mercedes Aldeguer-Martínez , Jose Barrio-Antoranz , Ana Burdaspal-Moratilla , Sonia Martín Chávarri 
Published: August 2018

AimThe risk of presenting synchronous or metachronous neoplasm, either adenoma or carcinoma, increases after an initial colonic lesion develops. It is known as tumor multicentricity and constitutes the rationale for surveillance programs. This study was designed to identify the clinical, pathologic, and molecular features related to previous or synchronous colorectal cancer (CRC) in patients with advanced adenomas (AA) or serrated polyps (SP).Patients and methodsWe carried out a prospective analysis of 4143 colonoscopies performed at our medical department between 1 September 2014 and 30 September 2015. Patients with AA/SP associated with previous or synchronous CRC are compared with patients with solitary AA/SP. We also performed immunohistochemical for the mismatch repair proteins in 120 AA or SP, 60 of them related to CRC.ResultsThree-hundred and seventy-nine AA or SP were removed. Among these, 66 (17.3%) were associated with a previous (n=31) or synchronous CRC (n=35). Age older than or equal to 65 years (odds ratio: 1.15, 95% confidence interval: 1.05–1.26,P=0.002) and male sex (odds ratio: 2.13, 95% confidence interval: 1.3–3.49,P=0.003) were found to be independent predictive factors for CRC in patients with AA/SP by multivariate analysis. Only one of the 120 AA/SP available for immunohistochemical testing showed loss of staining and it was not related to CRC.ConclusionIn patients with AA or SP, it is possible to identify a subgroup that is more likely to be associated with CRC and then prone to tumor multicentricity. These results have potential implications for establishing criteria for a more targeted surveillance.
The Research of Acellular Pancreatic Bioscaffold as a Natural 3-Dimensional Platform In Vitro
Authors: Wang Xin , Li Yue-Guang , Du Yue , Zhu Ji-Ye , Li Zhao 
Published: August 2018

ObjectiveThe aim of the study was to investigate the biochemical and functional properties of a rat acellular pancreatic bioscaffolds (APBs).MethodsFresh pancreata from 10 rats were soaked and perfused through portal veins using Easy-Load Digital Drive peristaltic pumps. The histological structure, extracellular matrix composition, and the DNA content of the APBs were evaluated. Biocompatibility studies had also been performed. The proliferation and differentiation of AR42J pancreatic acinar cells were assessed.ResultsThe pancreatic tissue became translucent after decellularization. There were no visible vascular endothelial cells, cellular components, or cracked cellular debris. The extracellular matrix components were not decreased after decellularization (P> 0.05); however, the DNA content was decreased significantly (P< 0.05). The subcutaneous implantation sites showed low immunological response and low cytotoxicity around the APB. The proliferation rate was higher and the apoptosis rate was lower when AR42J cells were cultured on APB (P< 0.05). The gene expression and the protein expression were higher for the APB group (P< 0.001).ConclusionsOur findings support the biological utility of whole pancreas APBs as biomaterial scaffolds, which provides an improved approach for regenerative medicine.
Staff’s Experiences of Preparing and Caring for Children With Cancer and Their Families During the Child’s Radiotherapy
Authors: Ångström-Brännström Charlotte , Lindh Viveca , Nyholm Tufve , Lindh Jack , Engvall Gunn 
Published: August 2018

Background
Approximately one-third of children diagnosed with cancer are treated with radiotherapy (RT). Staff experiences of preparing and distracting the children and their families during a child’s RT are sparsely described.

Objective
The aim of this study was to describe staff experiences of preparing and caring for children with cancer and their families during the child’s RT.

Intervention/Methods
Semistructured interviews with staff were performed at 3 Swedish RT centers. The interviews were analyzed using inductive qualitative content analysis.

Results
The analysis revealed 5 categories summarizing the staff members’ experiences. These include the following: experiences of various emotions; care for the child and the child’s family; commitments before, during, and after RT; organizational issues; and experiences of the intervention and suggestions for improvement.

Conclusions
The preparatory intervention facilitated the ability of staff members to conduct their work, although the intervention should be specifically tailored to each child. Meeting children and their families and providing care to both during RT were challenging. The staff strived to provide optimal care for each child and family. Interdisciplinary teamwork and organizational acceptance for the importance of preparation and distraction were essential.

Implications for Practice
A future challenge will be to provide opportunities for all staff involved in the treatment of children with cancer to develop their skills continuously in order to provide high-quality preparation and distraction to all children undergoing RT, regardless of the geographical location of the RT center.
Extracellular Matrix and Adhesion Molecule Gene Expression in the Normal and Injured Murine Intervertebral Disc
Authors: Zhang Yejia , Tian Zuozhen , Ashley Jason W. , Wang Luqiang , Tower Robert J. , Wei Yulong , Qin Ling , Yang Shuying , Enomoto-Iwamoto Motomi 
Published: August 2018

AbstractObjectiveThe aim of the study was to determine the transcription profile of the mouse nucleus pulposus and annulus fibrosus with an unbiased method. Furthermore, pathophysiological relevance of selected genes was demonstrated in the mouse tail intervertebral disc injury model.DesignPaired normal mouse nucleus pulposus and annulus fibrosus tissue from C57BL/6j mice was examined by a polymerase chain reaction array. Key gene expression in the normal and injured intervertebral discs was confirmed by real-time polymerase chain reaction.ResultsAmong the 84 genes studied, 63 were expressed higher in annulus fibrosus than in nucleus pulposus; only four genes were expressed higher in nucleus pulposus than in annulus fibrosus (n= 4,P≤ 0.05). Real-time polymerase chain reaction confirmed that cadherin (cdh) 2 gene expression was higher in nucleus pulposus than in annulus fibrosus, and type I collagen (col1) gene expression was higher in the annulus fibrosus than in nucleus pulposus (n= 8,P< 0.01). One week after tail intervertebral disc injury, cdh2 gene expression decreased, while col1 expression increased (n= 8,P< 0.01).ConclusionsThis is the first study to examine the relative expression of 84 genes in normal mouse nucleus pulposus and annulus fibrosus. Key genes in the normal and injured mouse intervertebral discs were confirmed with real-time polymerase chain reaction. This information should be useful for studying the mouse model of intervertebral disc degeneration and guide future cell therapy approaches.
Heme oxygenase-1 inducer and carbon monoxide–releasing molecule enhance the effects of gabapentinoids by modulating glial activation during neuropathic pain in mice
Authors: Godai Kohei , Kanmura Yuichi 
Published: August 2018

Abstract

Introduction:
Neuropathic pain is one of the most difficult-to-treat symptoms. Although gabapentinoids are classified as first-line drugs, they have only modest efficacy.

Objectives:
The aim of this study was to investigate whether treatment with the heme oxygenase-1 (HO-1) inducer cobalt protoporphyrin IX (CoPP) or the carbon monoxide–releasing molecule tricarbonyldichlororuthenium (II) dimer (CORM-2) can enhance the antinociceptive effects produced by gabapentinoids in mice with neuropathic pain.

Methods:
Neuropathic pain was induced by spared nerve injury (SNI) of the sciatic nerve. The mechanical threshold was tested using von Frey filaments. The expression of spinal HO-1, HO-2, the Ca2+ channel α2δ1 subunit, microglial markers, and M1 or M2 microglial markers was examined using reverse transcription polymerase chain reaction.

Results:
Treatment with CoPP or CORM-2 alleviated mechanical allodynia induced by SNI. CoPP or CORM-2 enhanced the antiallodynic effects of gabapentinoids (pregabalin or gabapentin) during SNI-induced mechanical allodynia. HO-1 inhibitor tin protoporphyrin IX (SnPP) prevented the antiallodynic effects of gabapentinoids (pregabalin or gabapentin) during SNI-induced mechanical allodynia. CoPP or CORM-2 increased HO-1 and Ca2+ channel α2δ1 subunit gene expression and the decreased gene expression of microglial markers, M1 microglial marker, or tumor necrosis factor in the ipsilateral spinal dorsal horn of mice with SNI. SnPP prevented HO-1 induction and glial inhibition, which were produced by gabapentinoids during SNI-induced mechanical allodynia.

Conclusions:
This study suggests that HO-1 plays crucial roles in the antiallodynic effects of gabapentinoids. Gabapentinoids attenuate the glial activation induced by SNI and some of these effects are mediated by HO-1.
Sacral Soft Tissue Deformations When Using a Prophylactic Multilayer Dressing and Positioning System
Authors: Peko Cohen Lea , Levy Ayelet , Shabshin Nogah , Neeman Ziv , Gefen Amit 
Published: August 2018

PURPOSE:
The sacrum is the most common location of pressure injuries (PIs) in bedridden patients. The purpose of this study was to measure the effect of specific pressure preventive devices on sacral skeletal muscle, subcutaneous fat, and skin tissue deformations.

SUBJECTS AND SETTING:
The sample comprised 3 healthy adults residing in a community setting in Tel Aviv, Israel.

DESIGN:
Descriptive, comparative design.

METHODS:
Tissue thickness changes of 3 healthy adults were measured using magnetic resonance imaging (MRI) in weight-bearing sacral skin, subcutaneous fat, and muscle. Changes in tissue thickness were compared under the following conditions: (1) lying supine on a rigid surface (unpadded MRI table), (2) lying on a standard foam mattress, (3) lying on a mattress after application of a prophylactic multilayer dressing, and (4) lying on a standard foam mattress with a prophylactic multilayer dressing and a positioning system. One-way analysis of variance and post hoc Tukey-Kramer multiple pairwise comparisons were used to compare outcomes.

RESULTS:
The mattress, the prophylactic multilayer dressing, and the turning and positioning device when applied together resulted in significantly lower deformation levels of each of the soft tissue layers (ie, skin, subcutaneous fat, and muscle separately) as well as of the total soft tissue bulk, with respect to the rigid MRI table (P < .05).

CONCLUSION:
Study findings suggest that a combination of preventive interventions may reduce the risk of developing a sacral PI.
An assay for de novo kinetochore assembly reveals a key role for the CENP-T pathway in budding yeast
Authors: Lang Jackie , Barber Adrienne , Biggins Sue 
Published: August 2018

ABSTRACTChromosome segregation depends on the kinetochore, the machine that establishes force-bearing attachments between DNA and spindle microtubules. Kinetochores are formed every cell cycle via a highly regulated process that requires coordinated assembly of multiple subcomplexes on specialized chromatin. To elucidate the underlying mechanisms, we developed an assay to assemble kinetochores de novo using centromeric DNA and budding yeast extracts. Assembly is enhanced by mitotic phosphorylation of the Dsn1 kinetochore protein and generates kinetochores capable of binding microtubules. We used this assay to investigate why kinetochores recruit the microtubule-binding Ndc80 complex via two receptors: the Mis12 complex and CENP-T. Although the CENP-T pathway is non-essential in yeast, we demonstrate that it becomes essential for viability and Ndc80c recruitment when the Mis12 pathway is crippled by defects in Dsn1 phosphorylation. Assembling kinetochores de novo in yeast extracts provides a powerful and genetically tractable method to elucidate critical regulatory events in the future.
Decision-making through integration of sensory evidence at prolonged timescales
Authors: Waskom Michael L. , Kiani Roozbeh 
Published: August 2018

SummaryWhen multiple pieces of information bear on a decision, the best approach is to combine the evidence provided by each one. Evidence integration models formalize the computations underlying this process [1–3], explain human perceptual discrimination behavior [4–11], and correspond to neuronal responses elicited by discrimination tasks [12–17]. These findings indicate that evidence integration is key to understanding the neural basis of decision-making [18–21]. Evidence integration has most often been studied with simple tasks that limit the timescale of deliberation to hundreds of milliseconds, but many natural decisions unfold over much longer durations. Because neural network models imply acute limitations on the timescale of evidence integration [22–26], it is unknown whether current computational insights can generalize beyond rapid judgments. Here, we introduce a new psychophysical task and report model-based analyses of human behavior that demonstrate evidence integration at long timescales. Our task requires probabilistic inference using brief samples of visual evidence that are separated in time by long and unpredictable gaps. We show through several quantitative assays how decision-making can approximate a normative integration process that extends over tens of seconds without accruing significant memory leak or noise. These results support the generalization of evidence integration models to a broader class of behaviors while posing new challenges for models of how these computations are implemented in biological networks.
Parallelized analysis of spatial gene expression patterns by database integration
Authors: Miyamoto Daisuke , Ikeno Hidetoshi , Okamura-Oho Yuko , Sato Akira , Furuichi Teiichi , Okumura Yoshihiro , Yamaguchi Yoko , Kanzaki Ryohei 
Published: August 2018

AbstractWe developed a computational framework for automated integration of a large number of two-dimensional (2D) images with three-dimensional (3D) image datasets located in the standard 3D coordinate. We applied the framework to 2,810 para-sagittal sectioned mouse brain 2D images of in situ hybridization (ISH), archived in the BrainTx database (http://www.cdtdb.neuroinf.jp). We registered the ISH images into the mouse standard coordinate space for MR images, Waxholm space (WHS, https://www.nitrc.org/projects/incfwhsmouse) by linearly transforming them into each of a series of para-sagittal MR image slices, and identifying the best-fit slice by calculating the similarity metric value (δ). Transformed 2D images were compared with 3D gene expression image datasets, which were made using a microtomy-based microarray assay system, Transcriptome Tomography, and archived in the ViBrism DB (http://vibrism.neuroinf.jp): the 3D images are located in the WHS.We first transformed ISH images of 10 regionally expressed genes and compared them to signals of corresponding 3D expression images in ViBrism DB for evaluating the integration schema: two types of data, produced with different modalities and originally located in different dimensions, were successfully compared after enhancing ISH signals against background noise. Then, for the massive transformation of BrainTx database images, we parallelized our framework, using the IPython cluster package, and implemented it on the PC cluster provided for the Brain Atlasing Hackathon activity hosted by Neuroinformatics Japan Center in Japan. We could identify the best-fit positions for all of the ISH images. All programs were made available through the GitHub repository, at the web site of neuroinformatics/bah2016_registration (https://github.com/neuroinformatics/bah2016_registration).
Neuropsychiatric Phenotypes and a Distinct Constellation of ASD Features in 3q29 Deletion Syndrome: Results from the 3q29 Registry
Authors: Pollak Rebecca M , Murphy Melissa M , Epstein Michael P , Zwick Michael E , Klaiman Cheryl , Saulnier Celine A ,   the Emory 3q29 Project, Mulle Jennifer G 
Published: August 2018

ABSTRACTBackgroundThe 1.6 Mb 3q29 deletion is associated with neurodevelopmental and psychiatric phenotypes, including increased risk for autism spectrum disorder (ASD) and a 20-40-fold increased risk for schizophrenia. However, the phenotypic spectrum of the deletion, particularly with respect to ASD, remains poorly described.MethodsWe ascertained individuals with 3q29 deletion syndrome (3q29Del, “cases”, n=93, 58.1% male) and typically developing controls (n=64, 51.6% male) through the 3q29 registry (https://3q29deletion.patientcrossroads.org). Self-report of neuropsychiatric illness was evaluated for 93 cases. Subsets of participants were evaluated with the Social Responsiveness Scale (SRS, n=48 cases, 56 controls), Social Communication Questionnaire (SCQ, n=33 cases, 46 controls), Autism Spectrum Screening Questionnaire (ASSQ, n=24 cases, 35 controls), and Achenbach Behavior Checklists (n=48 cases, 57 controls).Results3q29Del cases report a higher prevalence of autism diagnoses versus the general population (29.0% vs. 1.47%, p<2.2E-16). Notably, 3q29 deletion confers a greater influence on risk for ASD in females (OR=41.8, p=4.78E-05) than in males (OR=24.6, p=6.06E-09); this is aligned with the reduced male:female bias from 4:1 in the general population to 2:1 in our study sample. Although 71% of cases do not report a diagnosis of ASD, there is evidence of significant social disability (3q29Del SRST-score=71.8, control SRST-score=45.9, p=2.16E-13). Cases also report increased frequency of generalized anxiety disorder compared to controls (28.0% vs. 6.2%, p=0.001), which is mirrored by elevated mean scores on the Achenbach DSM-oriented sub-scales (p<0.001). Finally, cases show a distinct constellation of ASD features on the SRS as compared to idiopathic ASD, with substantially elevated Restricted Interests and Repetitive Behaviors, but only mild impairment in Social Motivation.ConclusionsOur sample of 3q29Del is significantly enriched for ASD diagnosis, especially among females, and features of autism may be present even when an ASD diagnosis is not reported. Further, the constellation of ASD features in this population is distinct from idiopathic ASD, with substantially less impaired social motivation. Our study implies that ASD evaluation should be the standard of care for individuals with 3q29Del. From a research perspective, the distinct ASD subtype present in 3q29Del is an ideal entry point for expanding understanding of ASD.
Multi-modal regulation ofC. eleganshermaphrodite spermatogenesis by the GLD-1-FOG-2 complex
Authors: Hu Shuang , Ryan Lauren E. , Kaymak Ebru , Freeberg Lindsay , Lo Te-Wen , Kuersten Scott , Ryder Sean P. , Haag Eric S. 
Published: August 2018

AbstractProper germ cell sex determination inCaenorhabditisnematodes requires a network of RNA-binding proteins (RBPs) and their target mRNAs. In some species, changes in this network enabled limited XX spermatogenesis, and thus self-fertility. InC. elegans, one of these selfing species, the global sex-determining genetra-2is regulated in germ cells by a conserved RBP, GLD-1, via the 3’ untranslated region (3’UTR) of its transcript. AC. elegans-specific GLD-1 cofactor, FOG-2, is also required for hermaphrodite sperm fate, but how it modifies GLD-1 function is unknown. Germline feminization ingld-1andfog-2null mutants has been interpreted as due to cell-autonomous elevation of TRA-2 translation. Consistent with the proposed role of FOG-2 in translational control, the abundance of nearly all GLD-1 target mRNAs (includingtra-2)is unchanged infog-2mutants. Epitope tagging reveals abundant TRA-2 expression in somatic tissues, but an undetectably low level in wild-type germ cells. Loss ofgld-1function elevates germline TRA-2 expression to detectable levels, but loss offog-2function does not. A simple quantitative model oftra-2activity constrained by these results can successfully sort genotypes into normal or feminized groups. Surprisingly,fog-2andgld-1activity enable the sperm fate even when GLD-1 cannot bind to thetra-23’ UTR. This suggests the GLD-1-FOG-2 complex regulates uncharacterized sites withintra-2, or other mRNA targets. Finally, we quantify the RNA-binding capacities of dominant missense alleles of GLD-1 that act genetically as “hyperrepressors” oftra-2activity. These variants bind RNA more weaklyin vitrothan does wild-type GLD-1. These results indicate thatgld-1andfog-2regulate germline sex via multiple interactions, and that our understanding of the control and evolution of germ cell sex determination in theC. eleganshermaphrodite is far from complete.
Foxp1 controls neural stem cell competence and bias towards deep layer cortical fates
Authors: Pearson Caroline Alayne , Moore Destaye M. , Tucker Haley O. , Dekker Joseph D. , Hu Hui , Miquelajáuregui Amaya , Novitch Bennett G. 
Published: August 2018

SUMMARYThe laminar architecture of the mammalian neocortex depends on the orderly generation of distinct neuronal subtypes by apical radial glia (aRG) during embryogenesis. We identify critical roles for Foxp1 in maintaining RG identity and gating the temporal competency for early neurogenesis. High levels of Foxp1 are associated with early aRG and are required to promote proliferation and influence cell division symmetry, favoring aRG expansion and production of early born neurons. The potent pro-progenitor functions of Foxp1 are revealed through its ability to preserve a population of cells with aRG identity throughout development and extend the early neurogenic period into postnatal life. Foxp1 further promotes the formation of cells resembling basal RG (bRG), a progenitor group implicated in the increased size and complexity of the human cortex. Consistent with this role, we show that FOXP1 is associated with the initial formation and expansion of bRG during human corticogenesis.HIGHLIGHTSFoxp1 is transiently expressed by aRG during the early phase of corticogenesisFoxp1 promotes self-renewing vertical cell divisions and aRG maintenanceFoxp1 gates the time window of deep layer neurogenesisEctopic Foxp1 expression can elicit bRG formation
Allele-specific RNA imaging shows that allelic imbalances can arise in tissues through transcriptional bursting
Authors: Symmons Orsolya , Chang Marcello , Mellis Ian A. , Kalish Jennifer M. , Bartolomei Marisa S. , Raj Arjun 
Published: August 2018

AbstractExtensive cell-to-cell variation exists even among putatively identical cells, and there is great interest in understanding how the properties of transcription relate to this heterogeneity. Differential expression from the two gene copies in diploid cells could potentially contribute, yet our ability to measure from which gene copy individual RNAs originated remains limited, particularly in the context of tissues. Here, we demonstrate quantitative, single molecule allele-specific RNA FISH adapted for use on tissue sections, allowing us to determine the chromosome of origin of individual RNA molecules in formaldehyde-fixed tissues. We used this method to visualize the allele-specific expression ofXistand multiple autosomal genes in mouse kidney. By combining these data with mathematical modeling, we evaluated models for allele-specific heterogeneity, in particular demonstrating that apparent expression from only one of the alleles in single cells can arise as a consequence of low-level mRNA abundance and transcriptional bursting.