bluuebunny/crossref_metadata_2025_split huggingface dataset:
Autonomic Dysregulation in Adolescent Concussion Is Sex- and Posture-Dependent
Authors: Balestrini Christopher S. , Moir Marcy Erin , Abbott Kolten C. , Klassen Stephen A. , Fischer Lisa K. , Fraser Douglas D. , Shoemaker Joel Kevin 
Published: April 2019

Objective:
To study autonomic responses to postural changes in concussed adolescents. The influence of sex was also studied.

Design:
Longitudinal cohort observational study.

Participants:
Concussed adolescents (CONC; n = 65; 26 male adolescents; age 15 ± 1 years, range = 12-18 years) and a control (CTRL) group of nonconcussed adolescents of similar age and sport (CTRL; n = 54; 29 male adolescents; age 14 ± 1 years, range = 12-18 years).

Interventions:
Concussed participants were monitored through 6 weekly visits throughout usual physician care. Control participants underwent 2 visits separated by at least 1 week to account for intrapersonal variation in testing measures.

Main Outcome Measures:
Heart rate variability as the root mean square of successive differences in R–R intervals (RMSSD), heart rate (HR), and blood pressure [mean arterial pressure (MAP) and diastolic blood pressure (DBP)] were measured in supine, sitting, and standing postures.

Results:
A mixed analysis of variance revealed a group × sex × posture interaction (P = 0.04) where seated values of RMSSD were less in concussed female participants versus control female participants (42 ± 4 vs 61 ± 7 ms; P = 0.01; Mann–Whitney rank test). Compared with CTRL, CONC exhibited increased pretesting seated DBP (69 ± 1 vs 74 ± 1 mm Hg; P < 0.01), MAP (83 ± 1 vs 86 ± 1 mm Hg; P = 0.02), and baseline seated HR (72 ± 1 vs 77 ± 2 bpm; P = 0.03). Values of DBP (P = 0.03) and MAP (P < 0.01) improved at clinical discharge, whereas the RMSSD in female participants did not (P > 0.5). Data are mean ± SEM.

Conclusions:
A modest reduction in female cardiac autonomic regulation was observed during seated postures. Alterations in seated concussed DBP and MAP, but not RMSSD, resolved at clinical discharge (median = 37 days). The results indicate that, in adolescents, concussion may impair cardiovagal function in a sex- and posture-dependent manner. The findings also suggest that BP metrics, but not RMSSD, are associated with clinical concussion recovery.
Pediatric Patients With SHH Medulloblastoma Fail Differently as Compared With Adults: Possible Implications for Treatment Modifications
Authors: Dasgupta Archya , Gupta Tejpal , Sridhar Epari , Shirsat Neelam , Krishnatry Rahul , Goda Jayant Sastri , Chinnaswamy Girish , Jalali Rakesh 
Published: April 2019

Purpose:
The purpose of this work was to study the diversity of sonic hedgehog (SHH) medulloblastoma across different age groups with an emphasis on patterns of relapse.

Methods:
All data for the study were obtained through review of medical records, imaging, radiation charts, treatment planning, and chemotherapy details.

Results:
Sixty-three patients with SHH medulloblastoma were identified from a prospectively maintained database and classified into 3 groups—infantile: ≤3 years (i-SHH, n=11); pediatric: >3 to <18 years (p-SHH, n=21); and adult: ≥18 years (a-SHH; n=31). Lateralized tumors were common with increasing age (81% a-SHH, 67% p-SHH, 27% i-SHH; P=0.01). Large cell anaplastic histology was relatively common for p-SHH (33%), while the nodular/desmoplastic variant was more frequent in i-SHH (64%) and adults (51%). Median follow-up was 38 months (range, 5 to 91 mo). Five-year event-free survival was 80%, 31%, and 52% for i-SHH, p-SHH, and a-SHH, respectively (P=0.001). Median time to failure for p-SHH and a-SHH were 12 and 36 months, respectively. For p-SHH, 83% were metastatic relapses compared with localized failure in 75% for a-SHH. Five-year overall survival for i-SHH, p-SHH, and a-SHH were 91%, 31%, and 70%, respectively (P=0.001). On univariate analysis, event-free survival was significantly worse for superiorly located tumors (P=0.01), nondesmoplastic histology (P=0.02), and histology alone for overall survival (P=0.04) (none on multivariate analysis).

Conclusions:
SHH medulloblastoma demonstrates varied outcomes depending on age, with p-SHH associated with early and metastatic relapses, while for a-SHH it tends to be delayed and localized.
Short-term and Long-term Outcomes Following Laparoscopic Gastrectomy for Advanced Gastric Cancer Compared With Open Gastrectomy
Authors: Shibuya Kazuaki , Kawamura Hideki , Takahashi Shusaku , Ohno Yosuke , Ichikawa Nobuki , Yoshida Tadashi , Homma Shigenori , Ishizu Hiroyuki , Takahashi Masahiro , Taketomi Akinobu 
Published: April 2019

Introduction:
To investigate the oncological feasibility and technical safety of laparoscopic gastrectomy with D2 lymphadenectomy for advanced gastric cancer.

Methods:
A total of 186 advanced gastric cancer patients treated by gastrectomy with D2 lymphadenectomy were eligible for inclusion including those with invasion into the muscularis propria, subserosa, and serosa without involvement of other organs, and stages N0-2 and M0. We retrospectively compared the short-term and long-term outcomes between laparoscopic gastrectomy and open gastrectomy.

Results:
We analyzed short-term outcomes by comparing distal with total gastrectomy results. We found no significant difference for distal gastrectomy for postoperative morbidity [laparoscopic vs. open: n=4 (4.6%) vs. n=1 (3.6%); P=1.00]. We also found no significant difference in postoperative morbidity for total gastrectomy [laparoscopic vs. open: n=2 (4.0%) vs. n=1 (4.0%); P=1.00]. No deaths occurred in any group.
The entire cohort analysis revealed no statistically significant differences in overall-free or recurrence-free survival between the laparoscopic and open groups. For overall survival, there were no significant differences between open and laparoscopic groups for clinical stage II or III (P=0.29 and 0.27, respectively), and for pathologic stage II or III (P=0.88 and 0.86, respectively). For recurrence-free survival, there were no significant differences between open and laparoscopic groups for clinical stage II or III (P=0.63 and 0.60, respectively), and for pathologic stage II or III (P=0.98 and 0.72, respectively).

Conclusion:
Laparscopic gastrectomy for advanced gastric cancer compared favorably with open gastrectomy regarding short-term and long-term outcomes.
Active head motion reduction in Magnetic Resonance Imaging using tactile feedback
Authors: Krause Florian , Benjamins Caroline , Eck Judith , Luehrs Michael , van Hoof Rick , Goebel Rainer 
Published: April 2019

AbstractHead motion is a common problem in clinical as well as empirical (functional) Magnetic Resonance Imaging applications, as it can lead to severe artefacts that reduce image quality. The scanned individuals themselves, however, are often not aware of their head motion. The current study explored whether providing subjects with this information using tactile feedback would reduce their head motion and consequently improve image quality. In a single session that included six runs, 24 participants performed three different cognitive tasks: (1) passive viewing, (2) mental imagery, and (3) speeded responses. These tasks occurred in two different conditions: (a) with a strip of medical tape applied from one side of the MR head-coil, via the participant’s forehead, to the other side, and (b) without the medical tape being applied. Results revealed that application of medical tape to the forehead of subjects to provide tactile feedback significantly reduced both translational as well as rotational head motion. While this effect did not differ between the three cognitive tasks, there was a negative quadratic relationship between head motion with and without feedback. That is, the more head motion a subject produced without feedback, the stronger the motion reduction given the feedback. In conclusion, the here tested method provides a simple and cost-efficient way to reduce subjects’ head motion, and might be especially beneficial when extensive head motion is expected a priori.
Gene modules associated with human diseases revealed by network analysis
Authors: Ma Shisong , Gong Jiazhen , Zuo Wanzhu , Geng Haiying , Zhang Yu , Wang Meng , Han Ershang , Peng Jing , Wang Yuzhou , Wang Yifan , Chen Yanyan 
Published: April 2019

ABSTRACTDespite many genes associated with human diseases have been identified, disease mechanisms often remain elusive due to the lack of understanding how disease genes are connected functionally at pathways level. Within biological networks, disease genes likely map to modules whose identification facilitates etiology studies but remains challenging. We describe a systematic approach to identify disease-associated gene modules. A gene co-expression network based on the graphical Gaussian model (GGM) was constructed using the GTEx dataset and assembled into 652 gene modules. Screening these modules identified those with disease genes enrichment for obesity, cardiomyopathy, hypertension, and autism, which illuminated the molecular pathways underlying their pathogenesis. Using mammalian phenotypes derived from mouse models, potential disease candidate genes were identified from these modules. Also analyzed were epilepsy, schizophrenia, bipolar disorder, and depressive disorder, revealing shared and distinct disease modules among brain disorders. Thus, disease genes converge on modules within our GGM gene co-expression network, which provides a general framework to dissect genetic architecture of human diseases.
DNA Methylation Associated with Postpartum Depressive Symptoms Overlaps Findings from a Genome-wide Association Meta-Analysis of Depression
Authors: Lapato Dana M. , Roberson-Nay Roxann , Kirkpatrick Robert M. , Webb Bradley T. , York Timothy P. , Kinser Patricia 
Published: April 2019

AbstractBackgroundPerinatal depressive symptoms have been linked to adverse maternal and infant health outcomes. The etiology associated with perinatal depressive psychopathology is poorly understood, but accumulating evidence suggests that understanding inter-individual differences in DNA methylation (DNAm) patterning may provide insight regarding the genomic regions salient to the risk liability of perinatal depressive psychopathology.ResultsGenome-wide DNAm was measured in maternal peripheral blood using the Infinium MethylationEPIC microarray. Ninety-two participants (46% African-American) had DNAm samples that passed all quality control metrics, and all participants were within seven months of delivery. Linear models were constructed to identify differentially methylated sites and regions, and permutation testing was utilized to assess significance. Differentially methylated regions (DMRs) were defined as genomic regions of consistent DNAm change with at least two probes within 1kb of each other. Maternal age, current smoking status, estimated cell-type proportions, ancestry-relevant principal components, days since delivery, and chip position served as covariates to adjust for technical and biological factors. Current postpartum depressive symptoms were measured using the Edinburgh Postnatal Depression Scale. Ninety-eight DMRs were significant (False Discovery Rate < 5%) and overlapped 92 genes. Synaptic signaling, neural development, and platelet formation were the most represented biological processes in gene set analysis, and comparison to the 44 loci discovered in the latest Psychiatric Genomics Consortium meta-analysis of depression revealed 3 overlapping regions and significant enrichment (p<0.03).ConclusionsMany of the genes identified in this analysis corroborate previous allelic, transcriptomic, and DNAm association results related to depressive phenotypes. Future work should integrate data from multi-omic platforms to understand the functional relevance of these DMRs and refine DNAm association results by limiting phenotypic heterogeneity and clarifying if DNAm differences relate to the timing of onset, severity, duration of perinatal mental health outcomes of the current pregnancy or to previous history of depressive psychopathology.
ecTMB: a robust method to estimate and classify tumor mutational burden
Authors: Yao Lijing , Fu Yao , Mohiyuddin Marghoob , Lam Hugo YK 
Published: April 2019

AbstractTumor Mutational Burden (TMB) is a measure of the abundance of somatic mutations in a tumor, which has been shown to be an emerging biomarker for both anti-PD-(L)1 treatment and prognosis. Nevertheless, multiple challenges still hinder the adoption of TMB for clinical decision-making. The key challenges are the inconsistency of TMB measurement among assays and a lack of meaningful threshold for TMB classification. We describe a powerful and flexible statistical framework for estimation and classification of TMB (ecTMB). ecTMB uses an explicit background mutation model to predict TMB robustly and consistently. In addition to the two known TMB subtypes, TMB-high and TMB-low, we discovered a novel TMB subtype, named TMB-extreme, which was significantly associated with patient survival outcome. This discovery enabled ecTMB to classify samples to biologically and clinically relevant subtypes defined by TMB.
Prospects for transcranial temporal interference stimulation in humans: a computational study
Authors: Rampersad Sumientra , Roig-Solvas Biel , Yarossi Mathew , Kulkarni Praveen P. , Santarnecchi Emiliano , Dorval Alan D. , Brooks Dana H. 
Published: April 2019

AbstractTranscranial alternating current stimulation (tACS) is a noninvasive method used to modulate activity of superficial brain regions. Deeper and more steerable stimulation could potentially be achieved using transcranial temporal interference stimulation (tTIS): two high-frequency alternating fields interact to produce a wave with an envelope frequency in the range thought to modulate neural activity. Promising initial results have been reported for experiments with mice. In this study we aim to better understand the electric fields produced with tTIS and examine its prospects in humans through simulations with murine and human head models. A murine head finite element model was used to simulate previously published experiments of tTIS in mice. With a total current of 0.776 mA, tTIS electric field strengths up to 383 V/m were reached in the modeled mouse brain, affirming experimental results indicating that suprathreshold stimulation is possible in mice. Using a detailed anisotropic human head model, tTIS was simulated with systematically varied electrode configurations and input currents to investigate how these parameters influence the electric fields. An exhaustive search with 88 electrode locations covering the entire head (146M current patterns) was employed to optimize tTIS for target field strength and focality. In all analyses, we investigated maximal effects and effects along the predominant orientation of local neurons. Our results showed that it was possible to steer the peak tTIS field by manipulating the relative strength of the two input fields. Deep brain areas received field strengths similar to conventional tACS, but with less stimulation in superficial areas. Maximum field strengths in the human model were much lower than in the murine model, too low to expect direct stimulation effects. While field strengths from tACS were slightly higher, our results suggest that tTIS is capable of producing more focal fields and allows for better steerability. Finally, we present optimal four-electrode current patterns to maximize tTIS in regions of the pallidum (0.37 V/m), hippocampus (0.24 V/m) and motor cortex (0.57 V/m).
Basal Contamination of Sequencing: Lessons from the GTEx dataset
Authors: Nieuwenhuis Tim O. , Yang Stephanie , Verma Rohan X. , Pillalamarri Vamsee , Arking Dan E. , Rosenberg Avi Z. , McCall Matthew N. , Halushka Marc K. 
Published: April 2019

AbstractOne of the challenges of next generation sequencing (NGS) is read contamination. We used the Genotype-Tissue Expression (GTEx) project, a large, diverse, and robustly generated dataset, to understand the factors that contribute to contamination. We obtained GTEx datasets and technical metadata and validating RNA-Seq from other studies. Of 48 analyzed tissues in GTEx, 26 had variant co-expression clusters of four known highly expressed and pancreas-enriched genes (PRSS1, PNLIP, CLPS, and/or CELA3A). Fourteen additional highly expressed genes from other tissues also indicated contamination. Sample contamination by non-native genes was associated with a sample being sequenced on the same day as a tissue that natively expressed those genes. This was highly significant for pancreas and esophagus genes (linear model, p=9.5e-237 and p=5e-260 respectively). Nine SNPs in four genes shown to contaminate non-native tissues demonstrated allelic differences between DNA-based genotypes and contaminated sample RNA-based genotypes, validating the contamination. Low-level contamination affected 4,497 (39.6%) samples (defined as 10 PRSS1 TPM). It also led ≥ to eQTL assignments in inappropriate tissues among these 18 genes. We note this type of contamination occurs widely, impacting bulk and single cell data set analysis. In conclusion, highly expressed, tissue-enriched genes basally contaminate GTEx and other datasets impacting analyses. Awareness of this process is necessary to avoid assigning inaccurate importance to low-level gene expression in inappropriate tissues and cells.
ViraMiner: Deep Learning on Raw DNA Sequences for Identifying Viral Genomes in Human Samples
Authors: Tampuu Ardi , Bzhalava Zurab , Dillner Joakim , Vicente Raul 
Published: April 2019

ABSTRACTDespite its clinical importance, detection of highly divergent or yet unknown viruses is a major challenge. When human samples are sequenced, conventional alignments classify many assembled contigs as “unknown” since many of the sequences are not similar to known genomes. In this work, we developed ViraMiner, a deep learning-based method to identify viruses in various human biospecimens. ViraMiner contains two branches of Convolutional Neural Networks designed to detect both patterns and pattern-frequencies on raw metagenomics contigs. The training dataset included sequences obtained from 19 metagenomic experiments which were analyzed and labeled by BLAST. The model achieves significantly improved accuracy compared to other machine learning methods for viral genome classification. Using 300 bp contigs ViraMiner achieves 0.923 area under the ROC curve. To our knowledge, this is the first machine learning methodology that can detect the presence of viral sequences among raw metagenomic contigs from diverse human samples. We suggest that the proposed model captures different types of information of genome composition, and can be used as a recommendation system to further investigate sequences labeled as “unknown” by conventional alignment methods. Exploring these highly-divergent viruses, in turn, can enhance our knowledge of infectious causes of diseases.
FIN-Seq: Transcriptional profiling of specific cell types in frozen archived tissue from the human central nervous system
Authors: Amamoto Ryoji , Zuccaro Emanuela , Curry Nathan C. , Khurana Sonia , Chen Hsu-Hsin , Cepko Constance L. , Arlotta Paola 
Published: April 2019

ABSTRACTThousands of frozen, archived tissues from postmortem human central nervous system (CNS) are currently available in brain banks. As single cell and single nucleus technologies are beginning to elucidate the cellular diversity present within the human CNS, it is becoming clear that transcriptional analysis of the human CNS requires cell type specificity. Single cell and single nucleus RNA profiling provide one avenue to decipher this heterogeneity. An alternative, complementary approach is to profile isolated, pre-defined cell types and use methods that can be applied to many archived human tissue samples. Here, we developed FIN-Seq (FrozenImmunolabeledNucleiSequencing), a method that accomplishes these goals. FIN-Seq uses immunohisto-chemical isolation of nuclei of specific cell types from frozen human tissue, followed by RNA-Sequencing. We applied this method to frozen postmortem samples of human cerebral cortex and retina and were able to identify transcripts, including low abundance transcripts, in specific cell types.
Automated design of highly diverse riboswitches
Authors: Wu Michelle J , Andreasson Johan O L , Kladwang Wipapat , Greenleaf William , Das Rhiju 
Published: April 2019

AbstractRiboswitches that couple binding of ligands to recruitment of molecular machines offer sensors and control elements for RNA synthetic biology and medical biotechnology. Current approaches to riboswitch design enable significant changes in output activity in the presence vs. absence of input ligands. However, design of these riboswitches has so far required expert intuition and explicit specification of complete target secondary structures, both of which limit the structure-toggling mechanisms that have been explored. We present a fully automated method called RiboLogic for these design tasks and high-throughput experimental tests of 2,875 molecules using RNA-MaP (RNA on a massively parallel array) technology. RiboLogic designs explore an unprecedented diversity of structure-toggling mechanisms validated through experimental tests. These synthetic molecules consistently modulate their affinity to the MS2 bacteriophage coat protein upon binding of flavin mononucleotide, tryptophan, theophylline, and microRNA miR-208a, achieving activation ratios of up to 20 and significantly better performance than control designs. The data enable dissection of features of structure-toggling mechanisms that correlate with higher performance. The diversity of RiboLogic designs and their quantitative experimental characterization provides a rich resource for further improvement of riboswitch models and design methods.
Immunomodulatory effects of extract ofGanoderma lucidumbasidiocarps cultivated on alternative substrate
Authors: Nedeljković Biljana Božić , Ćilerdžić Jasmina , Zmijanjac Dragana , Marković Milan , Džopalić Tanja , Vasilijić Saša , Stajić Mirjana , Vučević Dragana 
Published: April 2019

AbstractThe aim of the study was to investigate if there are any differences in effects of extracts of commercially (GC) and alternatively (wheat straw) (GA) cultivatedGanoderma lucidumbasidiocarps on properties of peritoneal macrophages (PM) and monocyte-derived dendritic cells (MoDCs). GA extract stronger stimulated the metabolic and phagocytic activity of PMs, their adhesion capability and ability to produce ROS and NO compared to GC. Both tested extracts significantly increased allostimulatory and Th1 polarization capacity of simultaneous TLR3 and TLR7-activated MoDCs, but GA extract was more effective. The GA extract increased the production of ROS and NO by TLR4 stimulated PMs and up-regulated the production of certain cytokines as well as allostimulatory and Th1 polarization capacity of MoDCs. The GA extract could be a potent immunostimulatory agent for activation of MoDCs with the simultaneous engagement of TLRs that seems to be a promising strategy for preparation of DC-based anti-tumor vaccines.