bluuebunny/crossref_metadata_2025_split huggingface dataset:
Regeneration of injured skin and peripheral nerves requires control of wound contraction, not scar formation
Authors: Yannas Ioannis V. , Tzeranis Dimitrios S. , So Peter T. C. 
Published: April 2017

AbstractWe review the mounting evidence that regeneration is induced in wounds in skin and peripheral nerves by a simple modification of the wound healing process. Here, the process of induced regeneration is compared to the other two well‐known processes by which wounds close, i.e., contraction and scar formation. Direct evidence supports the hypothesis that the mechanical force of contraction (planar in skin wounds, circumferential in nerve wounds) is the driver guiding the orientation of assemblies of myofibroblasts (MFB) and collagen fibers during scar formation in untreated wounds. We conclude that scar formation depends critically on wound contraction and is, therefore, a healing process secondary to contraction. Wound contraction and regeneration did not coincide during healing in a number of experimental models of spontaneous (untreated) regeneration described in the literature. Furthermore, in other studies in which an efficient contraction‐blocker, a collagen scaffold named dermis regeneration template (DRT), and variants of it, were grafted on skin wounds or peripheral nerve wounds, regeneration was systematically observed in the absence of contraction. We conclude that contraction and regeneration are mutually antagonistic processes. A dramatic change in the phenotype of MFB was observed when the contraction‐blocking scaffold DRT was used to treat wounds in skin and peripheral nerves. The phenotype change was directly observed as drastic reduction in MFB density, dispersion of MFB assemblies and loss of alignment of the long MFB axes. These observations were explained by the evidence of a surface‐biological interaction of MFB with the scaffold, specifically involving binding of MFB integrins α1β1 and α2β1 to ligands GFOGER and GLOGER naturally present on the surface of the collagen scaffold. In summary, we show that regeneration of wounded skin and peripheral nerves in the adult mammal can be induced simply by appropriate control of wound contraction, rather than of scar formation.
Thermal injury model in the rabbit ear with quantifiable burn progression and hypertrophic scar
Authors: Friedrich Emily E. , Niknam‐Bienia Solmaz , Xie Ping , Jia Sheng‐Xian , Hong Seok J. , Mustoe Thomas A. , Galiano Robert D. 
Published: April 2017

AbstractHypertrophic scar is a major clinical outcome of deep‐partial thickness to full thickness thermal burn injury. Appropriate animal models are a limitation to burn research due to the lack of, or access to, animal models which address the endpoint of hypertrophic scar. Lower species, such as rodents, heal mainly by contracture, which limits the duration of study. Higher species, such as pigs, heal more similarly to humans, but are associated with high cost, long duration for scar development, challenges in quantifying scar hypertrophy, and poor manageability. Here, we present a quantifiable deep‐partial thickness burn model in the rabbit ear. Burns were created using a dry‐heated brass rod for 10 and 20 seconds at 90 °C. At the time of eschar excision on day 3, excisional wounds were made on the contralateral ear for comparison. Burn wound progression, in which the wound size expands over time is a major distinction between excisional and thermal injuries, was quantified at 1 hour and 3 days after the injuries using calibrated photographs and histology and the size of the wounds was found to be unchanged from the initial wound size at 1 hour, but 10% in the 20 seconds burn wounds at 3 days. A quantifiable hypertrophic scar, measured by histology as the scar elevation index, was present in both 20 seconds burn wounds and excisional wounds at day 35. ImageJ measurements revealed that the 20 seconds burn wound scars were 22% larger than the excisional wound scars and the 20 seconds burn scar area measurements from histology were 26% greater than in the excisional wound scar. The ability to measure both burn progression and scar hypertrophy over a 35‐day time frame suits this model to screening early intervention burn wound therapeutics or scar treatments in a burn‐specific scar model.
Harnessing electronic healthcare data for wound care research: Standards for reporting observational registry data obtained directly from electronic health records
Authors: Fife Caroline E. , Eckert Kristen A. 
Published: April 2017

AbstractThe United States Food and Drug Administration will consider the expansion of coverage indications for some drugs and devices based on real‐world data. Real‐world data accrual in patient registries has historically been via manual data entry from the medical chart at a time distant from patient care, which is fraught with systematic error. The efficient automated transmission of data directly from electronic health records is replacing this labor‐intensive paradigm. However, real‐world data collection is unfamiliar. The potential sources of bias arising from the source of data and data accrual, documentation, and aggregation have not been well defined. Furthermore, the technological aspects of data acquisition and transmission are less transparent. We explore opportunities for harnessing direct‐from‐electronic health record registry reporting and propose the ABCs of Registries (Analysis of Bias Criteria of Registries), which are an evaluation framework for publications to minimize potential bias of real‐world data obtained directly from an electronic health record method. These standards are based on a point‐of‐care data documentation process using a common definitional framework and data dictionaries. By way of example, we describe a wound registry obtained directly from electronic health records. This qualified clinical data registry minimizes bias by ensuring complete and accurate point‐of‐care data capture, standardizes usual care linked to quality reporting, and prevents post‐hoc vetting of outcomes. The resulting data are of high quality and integrity and can be used for comparative effectiveness research in wound care. In this way, the effort needed to succeed with the Quality Payment Program is leveraged to obtain the real‐world data needed for comparative effectiveness research.
Foxn1 and Mmp‐9 expression in intact skin and during excisional wound repair in young, adult, and old C57Bl/6 mice
Authors: Kopcewicz Marta M. , Kur‐Piotrowska Anna , Bukowska Joanna , Gimble Jeffrey M. , Gawronska‐Kozak Barbara 
Published: April 2017

AbstractThe transcription factor Foxn1 is essential for skin development. Our previous studies performed on young C57BL/6J mice model showed that Foxn1 acts as regulator of the skin wound healing process. The present study extended our initial research regarding the expression and potential role of Foxn1 in the intact and wounded skin as a function of animal age and stage of the wound healing process. We analyzed Foxn1 and Mmp‐9 expression in the intact and postinjured skin of young, adult, and old C57BL/6J and transgenic Foxn1::Egfp mice. The similar levels of epidermal Foxn1 mRNA expression were detected in young and adult C57BL/6J mice and higher levels in old animals. Postinjured skin tissues displayed a gradual decrease of Foxn1 mRNA expression at Days 1, 5, and 7 after injury. Foxn1‐eGFP positive cells were abundant at wound margin and in re‐epithelialized epidermis at postwounded Days 1, 5, and 7 and colocalized with E‐cadherin and Mmp‐9. Postwounded skin at Days 14–36 displayed Foxn1‐eGFP cells in the epidermis and in the dermal part of the skin (papillary dermis). A subset of Foxn1‐eGFP positive cells in the papillary dermis expressed the myofibroblast marker αSMA. Flow cytometric analysis of cells isolated from postwounded (Day 7) skin tissues showed a significant increase in the percentage of Foxn1‐eGFP positive cells with phenotype of double positivity for E‐cadherin/N‐cadherin (epithelial/mesenchymal markers). Collectively, these data identify the transcription factor Foxn1 as a potential key epidermal regulator modifying both epidermal and dermal healing processes after cutaneous wounding.
On higher regulators of Siegel threefolds II: the connection to the special value
Authors: Lemma Francesco 
Published: April 2017

We establish a connection between motivic cohomology classes over the Siegel threefold and non-critical special values of the degree-four$L$-function of some cuspidal automorphic representations of$\text{GSp}(4)$. Our computation relies on our previous work [On higher regulators of Siegel threefolds I: the vanishing on the boundary, Asian J. Math.19(2015), 83–120] and on an integral representation of the$L$-function due to Piatetski-Shapiro.
Twists and Turns of a Senior Design Project
Authors: Azzouz M. Salim , Brink Jan 
Published: April 2017

Teaching senior design courses and labs has not been an easy task for the two authors. It has been rather a daunting working task associated with great learning experiences. It was decided early on from the initiation of the mechanical engineering program at the McCoy School of Engineering at Midwestern State University that the senior design project within the senior design class is a testing and enriching experience for senior mechanical engineering students as well as the teaching faculty. The senior design course and labs are conducted as a research experience for undergraduate students and their assigned faculty. The proposed senior project spans over two semesters, fall and spring, where the students experience a full mechanical engineering related project from the inception phase, through the design and construction phases, and finishing with the testing and analysis phases. The inception phase stands essentially for the brainstorming phase where the students are required to come-up with a set of diverse solutions to their assigned project problem. The design and construction phases stand for choosing an optimal particular solution for their problem according to a set of defined criteria. Then, the students start the preliminary design phase with related cost estimation, and then finalize the design with a set of final drawings.
After the design phase, the students start building a machine, an apparatus, a prototype or putting together the elements of a process. In this period they work intensely, with their faculty, the purchasing department, and mostly the department machinist, or the surrounding town machine shops. The testing and analysis phase stands for designing an experimental set-up, writing a testing procedure, and obtaining real time recorded data and proceeding with its analysis. In this technical paper, the authors talk about the requirements for a senior project known as the deliverables, the teaching tools used throughout the class work and labs, the students’ partial and final PowerPoints presentations and weekly and final reports. The authors describe the students overall achievements, and the archiving of the projects. Additionally, the authors talk about the twists and turns encountered during a senior project, with students, other faculty, the machinist, the lab technician, the secretary, and suppliers, and other difficulties experienced in running a full project with real final products. Finally, the authors talk about the aftermath of a senior project, eventual publications related to the project, and what is the view point of the American Board of Engineering and Technology (ABET) on these senior projects.
PCR-Dipstick Chromatography for Differential Detection of Carbapenemase Genes Directly in Stool Specimens
Authors: Shanmugakani Rathina Kumar , Akeda Yukihiro , Yamamoto Norihisa , Sakamoto Noriko , Hagiya Hideharu , Yoshida Hisao , Takeuchi Dan , Sugawara Yo , Kodera Takuya , Kawase Mitsuo , Laolerd Warawut , Chaihongsa Narong , Santanirand Pitak , Ishii Yoshikazu , Hamada Shigeyuki , Tomono Kazunori 
Published: April 2017

ABSTRACT

A PCR-dipstick chromatography technique was designed and evaluated for differential identification of
bla
NDM
,
bla
KPC
,
bla
IMP
, and
bla
OXA-48
carbapenemase genes directly in stool specimens within 2 h. It is a DNA-DNA hybridization-based detection system where PCR products can be easily interpreted by visual observation without electrophoresis. The PCR-dipstick showed high sensitivity (93.3%) and specificity (99.1%) in directly detecting carbapenemase genes in stool specimens compared with multiplex PCR for genomic DNA of the isolates from those stool specimens.
Structural Modification of Lipopolysaccharide Conferred by
mcr-1
in Gram-Negative ESKAPE Pathogens
Authors: Liu Yi-Yun , Chandler Courtney E. , Leung Lisa M. , McElheny Christi L. , Mettus Roberta T. , Shanks Robert M. Q. , Liu Jian-Hua , Goodlett David R. , Ernst Robert K. , Doi Yohei 
Published: April 2017

ABSTRACT

mcr-1
was initially reported as the first plasmid-mediated colistin resistance gene in clinical isolates of
Escherichia coli
and
Klebsiella pneumoniae
in China and has subsequently been identified worldwide in various species of the family
Enterobacteriaceae
.
mcr-1
encodes a phosphoethanolamine transferase, and its expression has been shown to generate phosphoethanolamine-modified bis-phosphorylated hexa-acylated lipid A in
E. coli
. Here, we investigated the effects of
mcr-1
on colistin susceptibility and on lipopolysaccharide structures in laboratory and clinical strains of the Gram-negative ESKAPE (
Enterococcus faecium
,
Staphylococcus aureus
,
K. pneumoniae
,
Acinetobacter baumannii
,
Pseudomonas aeruginosa
, and
Enterobacter
species) pathogens, which are often treated clinically by colistin. The effects of
mcr-1
on colistin resistance were determined using MIC assays of laboratory and clinical strains of
E. coli
,
K. pneumoniae
,
A. baumannii
, and
P. aeruginosa
. Lipid A structural changes resulting from MCR-1 were analyzed by mass spectrometry. The introduction of
mcr-1
led to colistin resistance in
E. coli
,
K. pneumoniae
, and
A. baumannii
but only moderately reduced susceptibility in
P. aeruginosa
. Phosphoethanolamine modification of lipid A was observed consistently for all four species. These findings highlight the risk of colistin resistance as a consequence of
mcr-1
expression among ESKAPE pathogens, especially in
K. pneumoniae
and
A. baumannii
. Furthermore, the observation that lipid A structures were modified despite only modest increases in colistin MICs in some instances suggests more sophisticated surveillance methods may need to be developed to track the dissemination of
mcr-1
or plasmid-mediated phosphoethanolamine transferases in general.
Efficacy, Safety, and Tolerability of Gepotidacin (GSK2140944) in the Treatment of Patients with Suspected or Confirmed Gram-Positive Acute Bacterial Skin and Skin Structure Infections
Authors: O'Riordan William , Tiffany Courtney , Scangarella-Oman Nicole , Perry Caroline , Hossain Mohammad , Ashton Teri , Dumont Etienne 
Published: April 2017

ABSTRACT

Gepotidacin is a novel, first-in-class, triazaacenaphthylene antibacterial agent which has
in vitro
activity against causative pathogens of acute bacterial skin and skin structure infections (ABSSSIs). This phase 2, randomized, 2-part, multicenter, dose-ranging, response-adaptive study with optional intravenous-oral switch evaluated the efficacy and safety of gepotidacin for the treatment of Gram-positive ABSSSIs in 122 adult patients in the United States. The study had a double-blind phase (part 1; intravenous [750 mg or 1,000 mg every 12 h {q12h}]) and an open-label phase (part 2; intravenous [750 mg q12h, 1,000 mg q12h, or 1,000 q8h]). The primary endpoint was a composite of efficacy and safety which consisted of the early cure rate and the withdrawal rate due to drug-related adverse events and utilized a clinical utility index for dose selection. At the early efficacy visit (48 to 72 h after the first dose), the 750-mg q12h and 1,000-mg q8h groups met prespecified success criteria for clinical utility in terms of efficacy and safety; however, the 1,000-mg q12h group did not meet these criteria due to observed lower efficacy rates. The most frequently reported adverse events were nausea (20%) and diarrhea (13%). These encouraging phase 2 results demonstrate the potential for gepotidacin to meet the medical need for novel antibacterial agents to treat ABSSSIs due to drug-resistant pathogens through a unique mechanism of action. (This study has been registered at ClinicalTrials.gov under registration no. NCT02045797.)
A New Natural Product Analog of Blasticidin S Reveals Cellular Uptake Facilitated by the NorA Multidrug Transporter
Authors: Davison Jack R. , Lohith Katheryn M. , Wang Xiaoning , Bobyk Kostyantyn , Mandadapu Sivakoteswara R. , Lee Su-Lin , Cencic Regina , Nelson Justin , Simpkins Scott , Frank Karen M. , Pelletier Jerry , Myers Chad L. , Piotrowski Jeff , Smith Harold E. , Bewley Carole A. 
Published: April 2017

ABSTRACT

The permeation of antibiotics through bacterial membranes to their target site is a crucial determinant of drug activity but in many cases remains poorly understood. During screening efforts to discover new broad-spectrum antibiotic compounds from marine sponge samples, we identified a new analog of the peptidyl nucleoside antibiotic blasticidin S that exhibited up to 16-fold-improved potency against a range of laboratory and clinical bacterial strains which we named P10. Whole-genome sequencing of laboratory-evolved strains of
Staphylococcus aureus
resistant to blasticidin S and P10, combined with genome-wide assessment of the fitness of barcoded
Escherichia coli
knockout strains in the presence of the antibiotics, revealed that restriction of cellular access was a key feature in the development of resistance to this class of drug. In particular, the gene encoding the well-characterized multidrug efflux pump NorA was found to be mutated in 69% of all
S. aureus
isolates resistant to blasticidin S or P10. Unexpectedly, resistance was associated with inactivation of
norA
, suggesting that the NorA transporter facilitates cellular entry of peptidyl nucleosides in addition to its known role in the efflux of diverse compounds, including fluoroquinolone antibiotics.
Key Role of Capsular Polysaccharide in the Induction of Systemic Infection and Abortion by Hypervirulent Campylobacter jejuni
Authors: Sahin Orhan , Terhorst Samantha A. , Burrough Eric R. , Shen Zhangqi , Wu Zuowei , Dai Lei , Tang Yizhi , Plummer Paul J. , Ji Ju , Yaeger Michael J. , Zhang Qijing 
Published: April 2017

ABSTRACTCampylobacter jejuniis a zoonotic pathogen, and a hypervirulent clone, named clone SA, has recently emerged as the predominant cause of ovine abortion in the United States. To induce abortion, orally ingestedCampylobactermust translocate across the intestinal epithelium, spread systemically in the circulation, and reach the fetoplacental tissue. Bacterial factors involved in these steps are not well understood.C. jejuniis known to produce capsular polysaccharide (CPS), but the specific role that CPS plays in systemic infection and particularly abortion in animals remains to be determined. In this study, we evaluated the role of CPS in bacteremia using a mouse model and in abortion using a pregnant guinea pig model following oral challenge. Compared withC. jejuniNCTC 11168 and 81-176, a clone SA isolate (IA3902) resulted in significantly higher bacterial counts and a significantly longer duration of bacteremia in mice. The loss of capsule production via gene-specific mutagenesis in IA3902 led to the complete abolishment of bacteremia in mice and abortion in pregnant guinea pigs, while complementation of capsule expression almost fully restored these phenotypes. The capsule mutant strain was also impaired for survival in guinea pig sera and sheep blood. Sequence-based analyses revealed that clone SA possesses a unique CPS locus with a mosaic structure, which has been stably maintained in all clone SA isolates derived from various hosts and times. These findings establish CPS as a key virulence factor for the induction of systemic infection and abortion in pregnant animals and provide a viable candidate for the development of vaccines against hypervirulentC. jejuni.
Appropriate Regulation of the σ
E
-Dependent Envelope Stress Response Is Necessary To Maintain Cell Envelope Integrity and Stationary-Phase Survival in Escherichia coli
Authors: Nicoloff Hervé , Gopalkrishnan Saumya , Ades Sarah E. 
Published: April 2017

ABSTRACT

The alternative sigma factor σ
E
is a key component of the
Escherichia coli
response to cell envelope stress and is required for viability even in the absence of stress. The activity of σ
E
increases during entry into stationary phase, suggesting an important role for σ
E
when nutrients are limiting. Elevated σ
E
activity has been proposed to activate a pathway leading to the lysis of nonculturable cells that accumulate during early stationary phase. To better understand σ
E
-directed cell lysis and the role of σ
E
in stationary phase, we investigated the effects of elevated σ
E
activity in cultures grown for 10 days. We demonstrate that high σ
E
activity is lethal for all cells in stationary phase, not only those that are nonculturable. Spontaneous mutants with reduced σ
E
activity, due primarily to point mutations in the region of σ
E
that binds the −35 promoter motif, arise and take over cultures within 5 to 6 days after entry into stationary phase. High σ
E
activity leads to large reductions in the levels of outer membrane porins and increased membrane permeability, indicating membrane defects. These defects can be counteracted and stationary-phase lethality delayed significantly by stabilizing membranes with Mg
2+
and buffering the growth medium or by deleting the σ
E
-dependent small RNAs (sRNAs) MicA, RybB, and MicL, which inhibit the expression of porins and Lpp. Expression of these sRNAs also reverses the loss of viability following depletion of σ
E
activity. Our results demonstrate that appropriate regulation of σ
E
activity, ensuring that it is neither too high nor too low, is critical for envelope integrity and cell viability.

IMPORTANCE
The Gram-negative cell envelope and cytoplasm differ significantly, and separate responses have evolved to combat stress in each compartment. An array of cell envelope stress responses exist, each of which is focused on different parts of the envelope. The σ
E
response is conserved in many enterobacteria and is tuned to monitor pathways for the maturation and delivery of outer membrane porins, lipoproteins, and lipopolysaccharide to the outer membrane. The activity of σ
E
is tightly regulated to match the production of σ
E
regulon members to the needs of the cell. In
E. coli
, loss of σ
E
results in lethality. Here we demonstrate that excessive σ
E
activity is also lethal and results in decreased membrane integrity, the very phenotype the system is designed to prevent.