bluuebunny/crossref_metadata_2025_split huggingface dataset:
Histological Evidence of Intrinsic Muscle Degeneration in Compression Ulnar Neuropathy
Authors: Cha Soo Min , Shin Hyun Dae , Kim Kyeong Hee , Kim Jin Hyun 
Published: April 2019

Purpose
We investigated the histological characteristics of the tissues in the intrinsic hand muscles of patients with compressive ulnar neuropathy (CUN) to determine how the compromised nerve influences the target muscle.

Methods
In total, 83 patients underwent surgery for CUN in our institution between March 2015 and August 2017. Of these, 45 patients who met our inclusion/exclusion criteria were initially included in this study. Basic demographic data including age, sex, hand dominance, duration of symptoms, bone mineral density, and clinical stage were evaluated. During the ulnar nerve decompression surgery, a biopsy of the ipsilateral adductor pollicis was performed. Using the biopsy samples, we analyzed the tissue composition and degree of degeneration, and investigated the association with demographic factors and clinical status.

Results
The ratio of muscle/connective tissue/fat was 62.62 ± 8.27%/23.44 ± 4.10%/14.16 ± 6.68% in the affected muscle. The ratio was different than that of samples taken from control groups. In samples containing muscle fibers, although the total fat content remained low, fat was consistently concentrated at the fascicular borders, between fascicles (perifascicular fat, 62.3 ± 18.2% of fascicles), and within fascicles (intrafascicular fat, 35.6 ± 11.8% of fascicles). The proportion of centrally nucleated muscle fibers was also significantly elevated (5.58 ± 4.25%; P < 0.001) compared with that of both controls (1.09 ± 1.26%) and the clinical threshold for abnormal central nuclei (3%). Preoperative scores assessed using Gabel and Amadio criteria were positively correlated with the muscle composition (r = 0.89, P < 0.001). In addition, the clinical status was negatively correlated with the degree of fat accumulation and the proportion of centrally nucleated muscle fibers (r = −0.94, P < 0.001, r = −0.82, P < 0.001).

Conclusions
We demonstrated that target muscle in CUN underwent degeneration, which was potentially exacerbated by inflammation, and that the degree of degeneration was correlated with the patient's clinical status. Histologically, reversible recovery of the hand muscles may be possible if decompression of the ulnar nerve is performed at earlier stages.
Serum Lactate and A Relative Change in Lactate as Predictors of Mortality in Patients With Cardiogenic Shock – Results from the Cardshock Study
Authors: Lindholm Matias Greve , Hongisto Mari , Lassus Johan , Spinar Jindrich , Parissis John , Banaszewski Marek , Silva-Cardoso Jose , Carubelli Valentina , Salvatore diSomma , Sionis Alessandro , Mebazaa Alexandre , Veli-Pekka Harjola , Kober Lars 
Published: April 2019

ABSTRACT

Introduction:
Cardiogenic shock complicating acute myocardial infarction has a very high mortality. Our present study focuses on serial measurement of lactate during admission due to cardiogenic shock and the prognostic effect of lactate and a relative change in lactate in patients after admission and the institution of intensive care treatment.

Methods and Results:
This is a secondary analysis of the CardShock study. Data on lactate at baseline were available on 217 of 219 patients.
In the study population, the median baseline lactate was 2.8 mmol/L (min–max range, 0.5–23.1 mmol/L).
At admission, lactate was predictive of 30-day mortality with an adjusted Hazard ratio (HR) of 1.20 mmol/L (95% confidence interval, CI 1.14–1.27). Within the first 24 h of admission, baseline lactate remained predictive of 30-day mortality. Lactate at 6 h had a HR of 1.14 (95% CI 1.06–1.24) and corresponding values at 12 and 24 h had a HR of 1.10 (1.04–1.17), and of HR 1.19 (95% CI 1.07–1.32), respectively. A 50% reduction in lactate within 6 h resulted in a HR of 0.82 (95% CI 0.72–0.94). Corresponding hazard ratios at 12 and 24 h, were 0.87 (95% CI 0.76–0.98) and 0.74 (95% CI 0.60–0.91), respectively.

Conclusion:
The main findings of the present study are that baseline lactate is a powerful predictor of 30-day mortality, lactate at 6, 12, and 24 h after admission are predictors of 30-day mortality, and a relative change in lactate is a significant predictor of survival within the first 24 h after instituting intensive care treatment adding information beyond the information from baseline values.
Changing the Paradigm of Craniofacial Reconstruction
Authors: Bourne Debra A. , Bliley Jacqueline , James Isaac , Donnenberg Albert D. , Donnenberg Vera S. , Branstetter Barton F. , Haas Gretchen L. , Radomsky Elizabeth , Meyer Ernest Michael , Pfeifer Melanie E. , Brown Spencer A. , Marra Kacey G. , Coleman Sydney , Rubin J. Peter 
Published: April 2019

Objective:This study aimed to prospectively assess outcomes for surgical autologous fat transfer (AFT) applied for traumatic and postsurgical craniofacial deformities. The minimally invasive nature of AFT has potential for reduced risk and superior outcomes compared with current reconstructive options.Background:Craniofacial deformities have functional and psychosocial sequelae and can profoundly affect quality of life. Traditional reconstructive options are invasive, invasive, complex, and often lack precision in outcomes. Although AFT is safe, effective, and minimally invasive, only anecdotal evidence exists for reconstruction of craniofacial deformities.Methods:In this Institutional Review Board-approved prospective cohort study, 20 subjects underwent AFT (average volume: 23.9 ± 13.2 mL). Volume retention over time was determined using high-resolution computed tomography. Flow cytometry was used to assess cellular subpopulations and viability in the stromal vascular fraction. Quality of life assessments were performed. After the completion of 9-month follow-up, 5 subjects were enrolled for a second treatment.Results:No serious adverse events occurred. Volume retention averaged 63 ± 17% at 9 months. Three-month retention strongly predicted 9-month retention (r=0.996,P< 0.0001). There was no correlation between the total volume injected and retention. Patients undergoing a second procedure had similar volume retention as the first (P= 0.05). Age, sex, body mass index, and stromal vascular fraction cellular composition did not impact retention. Surprisingly, former smokers had greater volume retention at 9 months compared with nonsmokers (74.4% vs 56.2%,P= 0.009). Satisfaction with physical appearance (P= 0.002), social relationships (P= 0.02), and social functioning quality of life (P= 0.05) improved from baseline to 9 months.Conclusions:For craniofacial defects, AFT is less invasive and safer than traditional reconstructive options. It is effective, predictable, and reaches volume stability at 3 months. Patient-reported outcomes demonstrate a positive life-changing impact.
Mindfulness-based interventions for cancer-related pain and depression: a narrative review of current evidence and future potential
Authors: Baxter Jennie , Welsh Holly , Grayer Justin 
Published: April 2019

Purpose of review
People with cancer commonly experience persistent pain and psychological distress. Interventions are needed which address the multifactorial nature of pain and depression, yet few studies have examined the impact of mindfulness-based interventions (MBIs) for cancer-related pain and depression.

Recent findings
MBIs for cancer-related pain and depression can be effectively delivered across a range of modalities and show promise for alleviating mood and some physical health symptoms, although not always pain. There is some evidence for the cost-effectiveness of MBIs.

Summary
The field of MBIs would benefit from greater methodological rigour and investigation into a broader range of cancer populations to increase the knowledge base and in turn the evidence base on which interventions can be developed to the benefit to patients with cancer-related pain and depression.
Controlling Cell-Free Gene Expression Behavior by Tuning Membrane Transport Properties
Authors: Caveney Patrick M. , Dabbs Rosemary M. , McClintic William T. , Elizabeth Norred S. , Patrick Collier C. , Simpson Michael L. 
Published: April 2019

SummaryControlled transport of molecules across boundaries for energy exchange, sensing, and communication is an essential step toward cell-like synthetic systems. This communication between the gene expression compartment and the external environment requires reaction chambers that are permeable to molecular species that influence expression. In lipid vesicle reaction chambers, species that support expression – from small ions to amino acids – may diffuse across membranes and amplify protein production. However, vesicle-to-vesicle variation in membrane permeability may lead to low total expression and high variability in this expression. We demonstrate a simple optical treatment method that greatly reduces the variability in membrane permeability. When transport across the membrane was essential for expression, this optical treatment increased mean expression level by ~6-fold and reduced expression variability by nearly two orders of magnitude. These results demonstrate membrane engineering may enable essential steps toward cell-like synthetic systems. The experimental platform described here provides a means of understanding controlled transport motifs in individual cells and groups of cells working cooperatively through cell-to-cell molecular signaling.
Urine proteome changes in rats with approximately ten tumor cells subcutaneous inoculation
Authors: Wei Jing , Meng Wenshu , Gao Youhe 
Published: April 2019

AbstractBiomarkers are changes associated with the disease. Without homeostatic control, urine accumulates very early changes and is an ideal biomarker source. Usually, we performed urinary biomarker studies involving at least thousands of tumor cells. But no tumor starts from a thousand tumor cells. Can we observe any urine proteome changes in rats with approximately ten tumor cells subcutaneous inoculation? Here, we serially diluted Walker-256 carcinosarcoma cells to a concentration of 102/mL and subcutaneously inoculated 0.1 mL of these cells into nine rats. Urine proteomes on days 0, 13 and 21 were profiled by LC-MS/MS analysis and studied with unsupervised clustering analysis. Samples at three time points were almost clustered together, indicating a good consistency in these nine rats. Differential proteins on days 13 and 21 were mainly associated with cell adhesion, autophagic cell death, changes in extracellular matrix organization, angiogenesis, and the pentose phosphate pathway. All of these enriched functional processes were reported to contribute to tumor progression and could not be enriched through random allocation analysis. Our results indicated that 1) the urine proteome reflects changes associated with cancer even with approximately ten tumor cells in the body and that 2) the urine proteome reflects pathophysiological changes in the body with extremely high sensitivity and provides potential for a very early screening process of clinical patients.
Small Glycols Discover Cryptic Pockets on Proteins for Fragment-based Approaches
Authors: Bansia Harsh , Mahanta Pranjal , Yennawar Neela H , Ramakumar Suryanarayanarao 
Published: April 2019

AbstractCryptic pockets are visible in ligand-bound protein structures but are occluded in unbound structures. Utilizing these pockets in fragment-based drug-design provides an attractive option for proteins not tractable by classical binding sites. However, owing to their hidden nature, they are difficult to identify. Here, we show that small glycols find cryptic pockets on diverse set of proteins. Initial crystallography experiments serendipitously revealed the ability of ethylene glycol, a small glycol, to identify a cryptic pocket on W6A mutant of RBSX protein (RBSX-W6A). Explicit-solvent molecular dynamics (MD) simulations of RBSX-W6A with exposed-state of the cryptic pocket (ethylene glycol removed) revealed closure of the pocket reiterating that cryptic pockets in general prefer to stay in closed-state in absence of the ligands. Also, no change in the pocket was observed for simulations of RBSX-W6A with occluded-state of the cryptic pocket, suggesting that water molecules are not able to open the cryptic pocket. “Cryptic-pocket finding” potential of small glycols was then supported and generalized through additional crystallography experiments, explicit-cosolvent MD simulations, protein dataset construction and analysis. The cryptic pocket on RBSX-W6A was found again upon repeating the crystallography experiments with another small glycol, propylene glycol. Use of ethylene glycol as probe molecule in cosolvent MD simulations led to the enhanced sampling of the exposed-state of experimentally observed cryptic sites on test set of two proteins (Niemann-Pick C2, Interleukin-2). Further, analyses of protein structures with validated cryptic sites showed that ethylene glycol molecules binds to sites on proteins (G-actin, Myosin II, Bcl-xL, Glutamate receptor 2) which become apparent upon binding of biologically relevant ligands. Our study thus suggests potential application of the small glycols in experimental and computational fragment-based approaches to identify cryptic pockets in apparently undruggable and/or difficult targets, making these proteins amenable to drug-design strategies.
Human Aging DNA Methylation Signatures are Conserved but Accelerated in Cultured Fibroblasts
Authors: Sturm Gabriel , Cardenas Andres , Bind Marie-Abèle , Horvath Steve , Wang Shuang , Wang Yunzhang , Hägg Sara , Hirano Michio , Picard Martin 
Published: April 2019

SummaryAging is associated with progressive and site-specific changes in DNA methylation (DNAm). These global changes are captured by DNAm clocks that accurately predict chronological age in humans but relatively little is known about how clocks perform in vitro. Here we culture primary human fibroblasts across the cellular lifespan (∼6 months) and use four different DNAm clocks to show that age-related DNAm signatures are conserved and accelerated in vitro. The Skin & Blood clock shows the best linear correlation with chronological time (r=0.90), including during replicative senescence. Although similar in nature, the rate of epigenetic aging is approximately 62x times faster in cultured cells than in the human body. Consistent with in vivo data, cells aged under hyperglycemic conditions exhibit an approximately three years elevation in baseline DNAm age. Moreover, candidate gene-based analyses further corroborate the conserved but accelerated biological aging process in cultured fibroblasts. Fibroblasts mirror the established DNAm topology of the age-related ELOVL2 gene in human blood and the rapid hypermethylation of its promoter cg16867657, which correlates with a linear decrease in ELOVL2 mRNA levels across the lifespan. Using generalized additive modeling on twelve timepoints across the lifespan, we also show how single CpGs exhibit loci-specific, linear and nonlinear trajectories that reach rates up to −47% (hypomethylation) to +23% (hypermethylation) per month. Together, these high temporal resolution global, gene-specific, and single CpG data highlight the conserved and accelerated nature of epigenetic aging in cultured fibroblasts, which may constitute a system to evaluate age-modifying interventions across the lifespan.Graphical Abstract
TRIM5α restricts flavivirus replication by targeting the viral protease for proteasomal degradation
Authors: Chiramel Abhilash I. , Meyerson Nicholas R. , McNally Kristin L. , Broeckel Rebecca M. , Montoya Vanessa R. , Méndez-Solís Omayra , Robertson Shelly J. , Sturdevant Gail L. , Lubick Kirk J. , Nair Vinod , Youseff Brian H. , Ireland Robin M. , Bosio Catharine M. , Kim Kyusik , Luban Jeremy , Hirsch Vanessa M. , Taylor R. Travis , Bouamr Fadila , Sawyer Sara L. , Best Sonja M. 
Published: April 2019

AbstractTripartite motif-containing protein 5α (TRIM5α) functions as a cellular antiviral restriction factor with exquisite specificity towards the capsid lattices of retroviruses. The relative avidity of TRIM5α binding to retrovirus capsids directly impacts primate species susceptibility to infection, but the antiviral role of TRIM5α is thought limited to retroviruses. In contrast to this current understanding, here we show that both human and rhesus TRIM5α possess potent antiviral function against specific flaviviruses through interaction with the viral protease (NS2B/3) to inhibit virus replication. Importantly, TRIM5α was essential for the antiviral function of IFN-I against sensitive flaviviruses in human cells. However, TRIM5α was ineffective against mosquito-borne flaviviruses (yellow fever, dengue, and Zika viruses) that establish transmission cycles in humans following emergence from non-human primates. Thus, TRIM5α is revealed to possess remarkable plasticity in recognition of diverse virus families, with potential to influence human susceptibility to emerging flaviviruses of global concern.
An Integrative Approach for Fine-Mapping Chromatin Interactions
Authors: Jaroszewicz Artur , Ernst Jason 
Published: April 2019

AbstractChromatin interactions play an important role in genome architecture and regulation. The Hi-C assay generates such interactions maps genome-wide, but at relatively low resolutions (e.g., 5-25kb), which is substantially larger than the resolution of transcription factor binding sites or open chromatin sites that are potential sources of such interactions. To predict the sources of Hi-C identified interactions at a high resolution (e.g., 100bp), we developed a computational method that integrates ChIP-seq data of transcription factors and histone marks and DNase-seq data. Our method,χ-SCNN, uses this data to first train a Siamese Convolutional Neural Network (SCNN) to discriminate between called Hi-C interactions and non-interactions.χ-SCNN then predicts the high-resolution source of each Hi-C interaction using a feature attribution method. We show these predictions recover original Hi-C peaks after extending them to be coarser. We also showχ-SCNN predictions enrich for evolutionarily conserved bases, eQTLs, and CTCF motifs, supporting their biological significance.χ-SCNN provides an approach for analyzing important aspects of genome architecture and regulation at a higher resolution than previously possible.χ-SCNN software is available on GitHub (https://github.com/ernstlab/X-SCNN).
chromoMap: An R package for Interactive Visualization and Annotation of Chromosomes
Authors: Anand Lakshay , Rodriguez Lopez Carlos M. 
Published: April 2019

AbstractSummarychromoMap is an R package for constructing interactive visualizations of chromosomes/chromosomal regions, and mapping of chromosomal elements (like genes) onto them, of any living organism. The package takes separate tab-delimited files (BED like) to specify the genomic co-ordinates of the chromosomes and the elements to annotate. Each rendered chromosome is composed of continuous loci of specific ranges where each locus, on hover, displays detailed information about the elements annotated within that locus range. By just tweaking parameters of a single function, users can generate a variety of plots that can either be saved as static image or shared as HTML documents. Users can utilize the various prominent features of chromoMap including, but not limited to, visualizing polyploidy, creating chromosome heatmaps, mapping groups of elements, adding hyperlinks to elements, multi-species chromosome visualization.Availability and implementationThe R package chromoMap is available under the GPL-3 Open Source license. It is included with a vignette for comprehensive understanding of its various features, and is freely available from: https://CRAN.R-project.org/package=chromoMap.Contactlakshayanand15@gmail.comSupplementary informationSupplementary data are available online.
Chemogenomic profiling of anti-leishmanial efficacy and resistance in the related kinetoplastid parasite Trypanosoma brucei
Authors: Collett Clare F , Kitson Carl , Baker Nicola , Steele-Stallard Heather B. , Santrot Marie-Victoire , Hutchinson Sebastian , Horn David , Alsford Sam 
Published: April 2019

AbstractThe arsenal of drugs used to treat leishmaniasis, caused by Leishmania spp., is limited and beset by toxicity and emergent resistance. Furthermore, our understanding of drug mode-of-action and potential routes to resistance is limited. Forward genetic approaches have revolutionised our understanding of drug mode-of-action in the related kinetoplastid parasite, Trypanosoma brucei. Therefore, we screened our genome-scale T. brucei RNAi library in the current anti-leishmanial drugs, sodium stibogluconate (antimonial), paromomycin, miltefosine and amphotericin-B. Identification of T. brucei orthologues of the known Leishmania antimonial and miltefosine plasma membrane transporters effectively validated our approach, while a cohort of 42 novel drug efficacy determinants provides new insights and serves as a resource. Follow-up analyses revealed the antimonial selectivity of the aquaglyceroporin, TbAQP3. A lysosomal major facilitator superfamily transporter contributes to paromomycin/aminoglycoside efficacy. The vesicle-associated membrane protein, TbVAMP7B, and a flippase contribute to amphotericin-B and miltefosine action, and are potential cross-resistance determinants. Finally, multiple phospholipid-transporting flippases, including the T. brucei orthologue of the Leishmania miltefosine transporter, a putative β-subunit/CDC50 co-factor, and additional membrane-associated hits, affect amphotericin-B efficacy, providing new insights into mechanisms of drug uptake and action. The findings from this orthology-based chemogenomic profiling approach substantially advance our understanding of anti-leishmanial drug action and potential resistance mechanisms, and should facilitate the development of improved therapies, as well as surveillance for drug-resistant parasites.ImportanceLeishmaniasis is a devastating disease caused by the Leishmania parasites and is endemic to a wide swathe of the tropics and sub-tropics. While there are drugs available for the treatment of leishmaniasis, these suffer from various challenges, including the spread of drug resistance. Our understanding of anti-leishmanial drug action and the modes of drug resistance in Leishmania is limited. The development of genetic screening tools in the related parasite, Trypanosoma brucei, has revolutionised our understanding of these processes in this parasite. Therefore, we applied these tools to the anti-leishmanial drugs, identifying T. brucei orthologues of known Leishmania proteins that drive drug uptake, as well as a panel of novel proteins not previously associated with anti-leishmanial drug action. Our findings substantially advance our understanding of anti-leishmanial mode-of-action and provide a valuable starting point for further research.