bluuebunny/crossref_metadata_2025_split huggingface dataset:
Time of Onset to Changes in Skin Condition During Exposure to Synthetic Urine
Authors: Phipps LeeAnn , Gray Mikel , Call Evan 
Published: July 2019

PURPOSE:
The purpose of this study was to evaluate the impact of incontinence on epithelial-moisture barrier function and the subsequent risk for incontinence-associated dermatitis by exposing healthy volunteers to a premium incontinence pad wet with synthetic urine.

DESIGN:
Prospective, single-group study.

PARTICIPANTS AND SETTING:
Thirty women 65 years or older participated in the study. Participants had healthy skin of the buttocks, perineal, and perigenital areas and were not incontinent of urine or stool. The study was conducted at a contracted clinical research facility in Southeastern United States.

METHODS:
Four hundred milliliters of synthetic urine was distributed across the width of a premium incontinence pad with wicking technology containing a superabsorbent polymer core. Participants laid supine for a total of 4 hours, with the wet pad under the buttocks. Skin assessments were conducted at baseline prior to contact with the wet pad, at 15 minutes, 30 minutes, and 1, 2, and 4 hours after exposure to the synthetic urine. Outcome measures were skin moisture content, cutaneous pH, transepidermal water loss (TEWL), mean coefficient of friction values (static and dynamic), and tolerability evaluations (expert clinical grader–assessed erythema and participant-assessed discomfort).

RESULTS:
Mean moisture content of the skin increased from 46.19 ± 22.1 to 1845.28 ± 542.7 micro-Siemens (μS) after just 15 minutes of exposure and was significantly increased at all time points compared to baseline (P < .001). Cutaneous pH increased from 5.67 ± 0.5 to 6.25 ± 0.1 after 15 minutes; pH was higher at all time points compared to baseline (P < .001). Passive transfer of water through the stratum corneum (TEWL) showed an increase from 9.02 ± 2.2 g/m2/h at baseline to 16.83 ± 5.2 g/m2/h at 4 hours (P < .001). There was a significant increase from baseline to 4 hours in mean coefficient of static friction (0.32 ± 0.01 vs 0.47 ± 0.03; P < .00001) as well as mean coefficient of dynamic friction (0.29 ± 0.01 vs 0.42 ± 0.02; P < .00001). There was a significant increase in erythema and an increase in participant-assessed discomfort at all time points (P < .005).

CONCLUSIONS:
Our findings suggest that impairment of the skin's epithelial-moisture barrier function associated with inflammation and development of incontinence-associated dermatitis begins rapidly after an incontinence event, even with the use of a premium pad with wicking technology. Study findings also suggest that prompt attention to incontinence events is needed to prevent moisture-associated skin damage (incontinence-associated dermatitis) even when absorbent pads are used.
Phenome-wide association study of TTR and RBP4 genes in 361,194 individuals reveals novel insights in the genetics of hereditary and senile systemic amyloidoses
Authors: De Lillo Antonella , De Angelis Flavio , Di Girolamo Marco , Luigetti Marco , Frusconi Sabrina , Manfellotto Dario , Fuciarelli Maria , Polimanti Renato 
Published: July 2019

ABSTRACTTransthyretin (TTR) gene has a causal role in a hereditary form of amyloidosis (ATTRm) and is potentially involved in the risk of senile systemic amyloidosis (SSA). To understand the genetics of ATTRm and SSA, we conducted a phenome-wide association study of TTR gene in 361,194 participants of European descent testing coding and non-coding variants. Among the 382 clinically-relevant phenotypes tested, TTR non-coding variants were associated with 26 phenotypic traits after multiple testing correction. These included signs related to both ATTRm and SSA such as chronic ischaemic heart disease (rs140226130, p=2.00×10−6), heart failure (rs73956431, p=2.74×10−6), atrial fibrillation (rs10163755, p=4.63×10−6), dysphagia (rs2949506, p=3.95×10−6), intestine diseases (rs970866, p=7.14×10−6) and anxiety (rs554521234, p=8.85×10−6). Consistent results were observed for TTR disease-causing mutation Val122Ile (rs76992529) with respect to carpal tunnel syndrome (p=6.41×10−6) and mononeuropathies of upper limbs (p=1.22×10−5). Sex differences were also observed in line with ATTRm and SSA epidemiology. Additionally, we explored possible modifier genes related to TTR function, observing convergent associations of RBP4 variants with the clinical phenotypes associated with TTR locus. In conclusion, we provide novel insights regarding the molecular basis of ATTRm and SSA based on large-scale cohort, expanding our understanding of the phenotypic spectrum associated with TTR gene variation.
Localization of a feline autosomal dominant dwarfism locus: a novel model of chondrodysplasia
Authors: Lyons L.A. , Fox D.B. , Chesney K.L. , Britt L.G. , Buckley R.M. , Coates J.R. , Gandolfi B. , Grahn R.A. , Hamilton M.J. , Middleton J.R. , Sellers S.T. , Villani N.A. , Pfleuger S. ,   the 99 Lives Consortium
Published: July 2019

AbstractDespite the contribution of a few major genes for disproportionate dwarfism in humans, many dwarf patients are yet genetically undiagnosed. In domestic cats, disproportionate dwarfism has led to the development of a defined breed, the Munchkin or Minuet. This study examined the genetic aspects of feline dwarfism to consider cats as a new biomedical model. DNA from dwarf cats was genetically analyzed using parentage, linkage, and genome-wide association studies as well as whole genome sequencing. Each genetic approach localized the dwarfism phenotype to a region on cat chromosome B1. No coding variants suspected as causal for the feline dwarfism were identified but a critical region of ∼5.7 Mb from B1:170,278,183-175,975,857 was defined, which implicates a novel gene controlling disproportionate dwarfism. A yet unidentified but novel gene variant, likely structural or regulatory, produces disproportionate dwarfism in cats, which may define undiagnosed human patients.
Genetic analysis of the STIM1 gene in chronic pancreatitis
Authors: Masson Emmanuelle , Zou Wen-Bin , Ruffert Claudia , Holste Vanessa , Michl Patrick , Mössner Joachim , Ewers Maren , Laumen Helmut , Wu Hao , Zhou Dai-Zhan , Li Zhao-Shen , Yu Dong , Boulling Arnaud , Maréchal Cédric Le , Cooper David N. , Chen Jian-Min , Witt Heiko , Rosendahl Jonas , Liao Zhuan , Férec Claude 
Published: July 2019

ABSTRACTChronic pancreatitis is a complex disease that involves many factors, both genetic and environmental. Over the past two decades, molecular genetic analysis of five genes that are highly expressed in human pancreatic acinar cells, namely PRSS1, PRSS2, SPINK1, CTRC and CTRB1/CTRB2, has established that a trypsin-dependent pathway plays a key role in the etiology of chronic pancreatitis. Since Ca2+ deregulation can lead to intracellular trypsin activation in experimental acute pancreatitis, we analyzed STIM1 (encoding stromal interaction molecule-1, the main regulator of Ca2+ homeostasis in pancreatic acinar cells) as a candidate modifier gene in French, German and Chinese patients with chronic pancreatitis. The French and German subjects were analyzed by Sanger sequencing whereas the Chinese subjects were analyzed by targeted next-generation sequencing confirmed by Sanger sequencing. A total of 37 rare coding variants (35 missense and 2 nonsense) were identified, which were enriched in patients as compared with controls [2.28% (47/2,057) vs. 0.99% (33/3,322); odds ratio = 2.33, P = 0.0001]. This is the first large case-control study to demonstrate a putative association of rare STIM1 coding variants with chronic pancreatitis. Functional analysis will be required to clarify whether or not the rare STIM1 variants detected predispose to pancreatitis.
Population genetics of the highly polymorphicRPP8gene family
Authors: MacQueen Alice , Tian Dacheng , Chang Wenhan , Holub Eric , Kreitman Martin , Bergelson Joy 
Published: July 2019

AbstractPlant NLR resistance genes provide some of the most extreme examples of polymorphism in eukaryotic genomes, rivalling even the vertebrate major histocompatibility complex. Surprisingly, this is also true inArabidopsis thaliana, a predominantly selfing species with low heterozygosity. Here, we investigate how gene duplication and intergenic exchange contribute to this extraordinary variation.RPP8is a three-locus system that is configured chromosomally as either a direct-repeat tandem duplication or as a single copy locus, plus a locus 2 Mb distant. We sequenced 48RPP8alleles from 37 accessions ofA. thalianaand 12RPP8alleles fromA. lyratato investigate the patterns of interlocus shared variation. The tandem duplicates display fixed differences and share less variation with each other than either shares with the distant paralog. A high level of shared polymorphism among alleles at one of the tandem duplicates, the single-copy locus and the distal locus, must involve both classical crossing over and intergenic gene conversion. Despite these polymorphism-enhancing mechanisms, the observed nucleotide diversity could not be replicated under neutral forward-in-time simulations. Only by adding balancing selection to the simulations do they approach level of polymorphism observed atRPP8. In this NLR gene triad, genetic architecture, gene function and selection all combine to generate diversity.
Individual Variation in Control Network Topography Supports Executive Function in Youth
Authors: Cui Zaixu , Li Hongming , Xia Cedric H. , Larsen Bart , Adebimpe Azeez , Baum Graham L. , Cieslak Matt , Gur Raquel E. , Gur Ruben C. , Moore Tyler M. , Oathes Desmond J. , Alexander-Bloch Aaron , Raznahan Armin , Roalf David R. , Shinohara Russell T. , Wolf Daniel H. , Davatzikos Christos , Bassett Danielle S. , Fair Damien A. , Fan Yong , Satterthwaite Theodore D. 
Published: July 2019

ABSTRACTThe spatial distribution of large-scale functional networks on the anatomic cortex differs between individuals, and is particularly variable in networks responsible for executive function. However, it remains unknown how this functional topography evolves in development and supports cognition. Capitalizing upon advances in machine learning and a large sample of youth (n=693, ages 8-23y) imaged with 27 minutes of high-quality fMRI data, we delineate how functional topography evolves during youth. We found that the functional topography of association networks is refined with age, allowing accurate prediction of an unseen individual’s brain maturity. Furthermore, the cortical representation of executive networks predicts individual differences in executive function. Finally, variability of functional topography is associated with fundamental properties of brain organization including evolutionary expansion, cortical myelination, and cerebral blood flow. Our results emphasize the importance of considering both the plasticity and diversity of functional neuroanatomy during development, and suggest advances in personalized therapeutics.
Transcriptome assembly from long-read RNA-seq alignments with StringTie2
Authors: Kovaka Sam , Zimin Aleksey V. , Pertea Geo M. , Razaghi Roham , Salzberg Steven L. , Pertea Mihaela 
Published: July 2019

AbstractRNA sequencing using the latest single-molecule sequencing instruments produces reads that are thousands of nucleotides long. The ability to assemble these long reads can greatly improve the sensitivity of long-read analyses. Here we present StringTie2, a reference-guided transcriptome assembler that works with both short and long reads. StringTie2 includes new computational methods to handle the high error rate of long-read sequencing technology, which previous assemblers could not tolerate. It also offers the ability to work with full-length super-reads assembled from short reads, which further improves the quality of assemblies. On 33 short-read datasets from humans and two plant species, StringTie2 is 47.3% more precise and 3.9% more sensitive than Scallop. On multiple long read datasets, StringTie2 on average correctly assembles 8.3 and 2.6 times as many transcripts as FLAIR and Traphlor, respectively, with substantially higher precision. StringTie2 is also faster and has a smaller memory footprint than all comparable tools.
Monosynaptic projections to excitatory and inhibitory preBötzinger Complex neurons
Authors: Yang Cindy F. , Kim Euiseok J. , Callaway Edward M. , Feldman Jack L. 
Published: July 2019

AbstractThe key driver of breathing rhythm is the preBötzinger Complex (preBötC) whose activity is modulated by various categorical inputs, e.g., volitional, physiological, emotional. While the preBötC is highly interconnected with other regions of the breathing central pattern generator (bCPG) in the brainstem, there is no data about the direct projections to either excitatory and inhibitory preBötC subpopulations from other elements of the bCPG or from suprapontine regions. Using modified rabies tracing, we identified neurons throughout the brain that send monosynaptic projections to identified excitatory and inhibitory preBötC neurons. Within the brainstem, neurons from sites in the bCPG, including the contralateral preBötC, Bötzinger Complex (BötC), the nucleus of the solitary tract (NTS), parafacial region (pFL/pFVor RTN/pFRG), and parabrachial nuclei, send direct projections to both excitatory and inhibitory preBötC neurons. Suprapontine inputs to the excitatory and inhibitory preBötC neurons include the superior colliculus, red nucleus, amygdala, hypothalamus, and cortex; these projections represent potential direct pathways for volitional, emotional, and physiological control of breathing.
Dynamic brain network changes in resting-state reflect neuroplasticity: molecular and cognitive evidence
Authors: Liu Zhaowen , Xiao Xiao , Zhang Kai , Zhao Qi , Cao Xinyi , Li Chunbo , Wang Min , Lin Wei , Qiu Jiang , Sahakian Barbara J. , Feng Jianfeng , Robbins Trevor W. , Zhang Jie 
Published: July 2019

AbstractResting-state functional brain networks demonstrate dynamic changes on the scale of seconds. However, their genetic mechanisms and profound cognitive relevance remain less explored. We identified 459 Bonferroni-corrected genes, by associating temporal variability of regional functional connectivity patterns with Allen Brain gene expression profiles across the whole brain. These genes are partially verified in developing human brain gene expression in the BrainSpan Atlas, and are found to be involved in the enrichment of short- and long-term plasticity processes. The former process depends on synaptic plasticity, involving ion transmembrane transport, action potential propagation, and modulation. The latter process depends on structural plasticity, including axonal genesis, development, and guidance. Results from a longitudinal cognitive training study further revealed that baseline variability of the hippocampal network predicted cognitive ability changes after three months of training. Our genetic association results suggest that the short-term plasticity processes may account for the rapid changes of regional functional connectivity, while the underlying long-term plasticity processes explain why temporal variability can predict long-term learning outcomes. To our knowledge, this is the first demonstration that measuring the dynamic brain network can lead to a non-invasive quantification of neuroplasticity in humans.
Alterations of the pro-survival Bcl-2 protein interactome in breast cancer at the transcriptional, mutational and structural level
Authors: Kønig Simon Mathis , Rissler Vendela , Terkelsen Thilde , Lambrughi Matteo , Papaleo Elena 
Published: July 2019

AbstractApoptosis is an essential defensive mechanism against tumorigenesis. Proteins of the B-cell lymphoma-2 (Bcl-2) family regulates programmed cell death by the mitochondrial apoptosis pathway. In response to intracellular stresses, the apoptotic balance is governed by interactions of three distinct subgroups of proteins; the activator/sensitizer BH3 (Bcl-2 homology 3)-only proteins, the pro-survival, and the pro-apoptotic executioner proteins. Changes in expression levels, stability, and functional impairment of pro-survival proteins can lead to an imbalance in tissue homeostasis. Their overexpression or hyperactivation can result in oncogenic effects. Pro-survival Bcl-2 family members carry out their function by binding the BH3 short linear motif of pro-apoptotic proteins in a modular way, creating a complex network of protein-protein interactions. Their dysfunction enables cancer cells to evade cell death. The critical role in homeostasis and tumorigenesis coupled with progress in their structural elucidation, has led to consider pro-survival Bcl-2 proteins as therapeutic targets.A better understanding of the transcriptomic level, mutational status and molecular mechanism underlying pro-survival Bcl-2 proteins in different cancer types, could help to clarify their role in cancer development and may guide advancement in drug discovery, targeting these proteins. Here, we shed light on pro-survival Bcl-2 proteins in breast cancer by proposing a ‘multiscale’ bioinformatic approach. We analyzed the changes in expression of the Bcl-2 proteins and their BH3-containing interactors, in breast cancer samples. We then studied, at the structural level, a selection of interactions, also accounting for effects induced by mutations found in the breast cancer samples. We identified the complexes between the up-regulated BCL2A1 and two down-regulated BH3-only candidates (HRK and NR4A1) as targets associated with reduced apoptosis in breast cancer samples, which could deserve future experimental validation. We predicted as damaging mutations altering protein stability L99R, M75R, along with Y120C as a possible allosteric mutation from an exposed surface to the BH3-binding site.
CarboLogR: a Shiny/R application for statistical analysis of bacterial utilisation of carbon sources
Authors: Vervier Kevin , Browne Hilary P. , Lawley Trevor D. 
Published: July 2019

AbstractSummaryThe Biolog Phenotype Microarray (PM) and Anaerobic MicroPlates (AN) 96-well plates utilise colorimetric redox reactions to rapidly screen bacteria for the ability to utilise different carbon sources and other metabolites. Measurement of substrate utilisation as bacterial growth curves typically involves extended data normalization, outlier detection, and statistical analysis. The CarboLogR package streamlines this process with a Shiny application, guiding users from raw data generated from Biolog assays to growth profile comparison. We applied chemoinformatics approaches to define clusters of carbon sources, based on molecular similarities, increasing statistical power. Altogether, CarboLogR is a novel integrated tool providing automatic and high-level resolution for bacterial growth patterns and carbon source usage.Availability and ImplementationCarboLogR application can be downloaded and installed from Github repository https://github.com/kevinVervier/CarboLogR. Tutorial, data, and examples can be downloaded at https://github.com/kevinVervier/CarboLogR/vignettes.Contactkv4@sanger.ac.ukSupplementary InformationSupplementary data are available at Bioinformatics online.
Modulation of tactile detection threshold with rhythmic somatosensory entrainment
Authors: Wälti Michel J. , Bächinger Marc , Wenderoth Nicole 
Published: July 2019

AbstractOngoing neural activity in human somatosensory cortex has a strong impact on the detectability of weak tactile stimuli. Recent studies suggest that brain oscillations, which determine the state of excitability of a cortical area, play a crucial role in this process. Mainly two frequency bands have been reported to be involved in conscious sensory perception: alpha (8 – 12 Hz) and beta (15 – 30 Hz). In addition to correlative findings, more recent studies investigated causality by measuring the extent to which directly modulating brain oscillations affects sensory perception. While most of these studies use transcranial alternating current stimulation (tACS), rhythmic sensory stimulation has been suggested as a simple and safe alternative to entrain ongoing neural activity. However, convincing findings demonstrating the modulation of neural signals and related behavioral function are scarce.Here, we investigated whether rhythmically induced brain oscillations by means of vibrotactile stimulation (i.e. sensory entrainment) modulate tactile detection. In line with previous findings, we show in trials without sensory entrainment that preceding alpha power and phase-angles in beta oscillations predict the detection rate of a weak tactile stimulus. Further, we reveal a masking effect induced by sensory entrainment stimulation resulting in higher perception thresholds. Intriguingly, we find that the masking effect is modulated by the strength of neural entrainment resulting from 20 Hz stimulation. Our data provide evidence for the possibility to modulate sensory processing with rhythmic sensory stimulation. However, in light of the induced masking effects, the feasibility of this entrainment method to modulate human behavior remains questionable.
Isolation of antibiotic Producing Microorganisms from some water bodies within Eastern and Greater Accra Regions of Ghana
Authors: Amiteye Daniel , Dayie Nicholas Tete Kwaku Dzifa , Gbedema Stephen Yao , Boamah Vivian Etsiapa , Adu Francis , Bayor Marcel Tunkumgnen 
Published: July 2019

ABSTRACTBackgroundMost antimicrobial agents used today are isolated and extracted from microbial source. The emergence of antimicrobial resistance and need for better, broad spectrum antimicrobial agent is always in high demand. In this study, a total of 112 aquatic microbial isolates from 14 sample sites of water bodies in Ghana were screened by agar-well diffusion method for the ability of antimicrobial metabolites.ResultsOut of these antibacterial activities, 10 inhibited the growth of at least one test microorganism with zones of growth inhibitions ranged between 2.5±0.5 - 35.5±0.5 mm againstStaphylococcus aureus(ATCC25923),Streptococcus pyogenes(clinical isolates), Escherichia coli(NCTC9002),Pseudomonas aeruginosa(ATCC27853),Neisseria gonorrhoeae(clinical isolate),Klebsiella pneumoniae (Clinical isolate),Bacillus subtilis(NCTC10073) andSalmonella typhi(NCTC 6017). The extracts of the isolates showed minimum inhibitory concentrations of which extract NKSEW3againstEscherichia coli, Klebsiella pneumoniaeandPseudomonas aeruginosawere 25.00, 12.50 and 25.00 mg/mL respectively while that of NKLS6were 12.50, 6.25 and 25.00 mg/mL. The isolates NKSEW3and NKLS6were identified to bePseudomonas speciesusing chromagar and biochemical tests. The GC-MS result for NKLS62 (a fraction obtained from NKLS6) revealed five compounds including; Tridecanal, 17-octadecanal, ethanol, 2-(9-octadecenyloxy)-, (Z), 2-pentadecanone, 6, 10, 14-trimethyl diisooctyl phthalate and 17-octadecanal (C18H34O) as good pharmacological agents.ConclusionMicroorganisms isolated from water bodies in Ghana have the potential of producing antimicrobial agents.Author SummaryIn this study we use the agar well-diffusion to screen the isolates of water and soil samples collected within Greater Accra and Eastern Regions in Ghana against the test organisms.