bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bioprosthetic Versus Synthetic Mesh: Analysis of Tissue Adherence and Revascularization in an Experimental Animal Model
Authors: Adelman David M. , Cornwell Kevin G. 
Published: May 2018

Background:
Both synthetic and bioprosthetic meshes play important roles in surgical procedures such as ventral hernia repair. Although sometimes used interchangeably, these devices have inherently different properties. We therefore sought to better understand how these materials interact with the host environment to optimize surgical techniques and to improve outcomes.

Methods:
Synthetic mesh (polypropylene, Prolene) or bioprosthetic mesh (acellular fetal/neonatal bovine dermis, SurgiMend) was implanted intraperitoneally into rats lateral to a ventral incision in a novel intra-abdominal implant model. Two variables were modified with each material: (1) tight or loose tissue apposition, altered by modifying suture placement; and (2) abdominal wall injury, altered by selective abrasion of the peritoneal lining. After 5 weeks, the meshes and abdominal wall were evaluated grossly and histologically. The analysis focused on the degree of inflammatory response, neovascularization, and mesh adherence to the surrounding tissues.

Results:
Synthetic mesh adhered to the abdominal wall and visceral organs, regardless of the degree of apposition or tissue injury, due to a foreign body–mediated inflammatory reaction. In areas of noninjured peritoneal lining, SurgiMend was adherent peri-suture. Neovascularization entered the mesh from these apposition points and spread outward. In areas of denuded peritoneal lining, the adherent and vascularized areas were significantly greater and not merely coincident with suture placement.

Conclusions:
The inflammatory and wound healing responses with bioprosthetic mesh seem fundamentally different from synthetic mesh. Understanding these differences may lead to varied outcomes in adherence and vascularization of the materials, and ultimately the efficacy of hernia repair. Additionally, these differences highlight the need for further basic research to optimize mesh selection for surgical technique.
Managing Complications of Submental Artery Involvement after Hyaluronic Acid Filler Injection in Chin Region
Authors: Fang Martha , Rahman Eqram , Kapoor Krishan Mohan 
Published: May 2018

Summary:
Hyaluronic acid dermal fillers are becoming popular all over the world, but due to the presence of many blood vessels in the face, there is always a small possibility of vascular complications. We present a case with the ischemic involvement of chin and neck skin after accidental submental artery involvement after hyaluronic acid filler injection for chin region. Impending skin necrosis on the chin and upper neck on the right side was diagnosed quickly by observing the skin changes in the immediate postfiller phase. Pain in the mandible and in the muscles during swallowing due to possible ischemia of muscles supplied by submental artery was another crucial diagnostic feature. All parts of the affected zone were treated with high-dose pulsed hyaluronidase protocol using 4 pulses of hyaluronidase injection in first 24 hours after filler injection. Complete resolution of cutaneous ischemic changes and painful swallowing was achieved within days after treatment. Knowledge of presenting features of postfiller vascular complications and the extent of vascular territory of the involved artery is quite helpful in quickly instituting treatment leading to the near-complete recovery with minimal sequelae.
Biliary tract external drainage improves inflammatory mediators and pathomorphology of the intestine, liver, and lung in septic rats
Authors: Liu Yong-Jun , Sun Qing , Chen Juan , Chen Min-Ying , Ouyang Bin , Sun Hua-Dong , Nie Yao , Wang Ping-Ping , Ma Jie , Guan Xiang-Dong 
Published: May 2018

BACKGROUNDTo investigate the effect of biliary tract external drainage (BTED) on inflammatory mediators and pathomorphism of intestine, liver, and lung in septic rats.METHOD48 SD rats (n = 8 per group) were randomized into six groups: control, sepsis, sepsis plus BTED, normal bile (obtained from eight healthy rats), and septic bile infusion for 6 hours respectively to test the effects of BTED bile infusion on cytokines’ expression and tissue injury in the intestine, liver, and lung of septic/normal rats. Co-cultivation of intestinal epithelial cells (IEC-6) with bile for 12 hours was performed to evaluate the potential cytotoxicity of septic bile. Survival rate for sepsis plus BTED rats was detected compared with sepsis without BTED group (n = 20 per group) at 24, 48, and 72 hours, respectively.RESULTSBTED for 6 hours significantly reduced the mRNA expression levels of tumor necrosis factor alpha (TNF-α) and IL-1β (allp< 0.05 vs. sepsis group), whereas mRNA expression of TNF-α and IL-1β in the intestine was increased after 6 hours’ septic bile infusion compared with normal bile infusion group (allp< 0.05). TNF-α concentration in septic bile was significantly higher than that in the control group (p< 0.001). Tissue injury was significantly attenuated after 6 hours’ BTED.CONCLUSIONSBTED can significantly restrain the mRNA expression of TNF-α and IL-1β in the intestine, liver, and lung and attenuate histological damage in septic rats.
Outcomes following trauma laparotomy for hypotensive trauma patients: A UK military and civilian perspective
Authors: Marsden Max , Carden Rich , Navaratne Lalin , Smith Iain M. , Penn-Barwell Jowan G. , Kraven Luke M. , Brohi Karim , Tai Nigel R.M. , Bowley Douglas M. 
Published: May 2018

BACKGROUND
The management of trauma patients has changed radically in the last decade, and studies have shown overall improvements in survival. However, reduction in mortality for the many may obscure a lack of progress in some high-risk patients. We sought to examine the outcomes for hypotensive patients requiring laparotomy in UK military and civilian cohorts.

METHODS
We undertook a review of two prospectively maintained trauma databases: the UK Joint Theatre Trauma Registry for the military cohort (February 4, 2003, to September 21, 2014) and the trauma registry of the Royal London Hospital major trauma center (January 1, 2012, to January 1, 2017) for civilian patients. Adults undergoing trauma laparotomy within 90 minutes of arrival at the emergency department (ED) were included.

RESULTS
Hypotension was present on arrival at the ED in 155 (20.4%) of 761 military patients. Mortality was higher in hypotensive casualties (25.8% vs. 9.7% in normotensive casualties; p < 0.001). Hypotension was present on arrival at the ED in 63 (35.7%) of 176 civilian patients. Mortality was higher in hypotensive patients (47.6% vs. 12.4% in normotensive patients; p < 0.001). In both cohorts of hypotensive patients, neither the average injury severity, the prehospital time, the ED arrival systolic blood pressure, nor mortality rate changed significantly during the study period.

CONCLUSIONS
Despite improvements in survival after trauma for patients overall, the mortality for patients undergoing laparotomy who arrive at the ED with hypotension has not changed and appears stubbornly resistant to all efforts. Specific enquiry and research should continue to be directed at this high-risk group of patients.

LEVEL OF EVIDENCE
Prognostic/Epidemiologic, level IV.
Time to stroke: A Western Trauma Association multicenter study of blunt cerebrovascular injuries
Authors: Burlew Clay Cothren , Sumislawski Joshua J. , Behnfield Charles D. , McNutt Michelle K. , McCarthy James , Sharpe John P. , Croce Martin A. , Bala Miklosh , Kashuk Jeffry , Spalding M. Chance , Beery Paul R. , John Scott , Hunt Darren J. , Harmon Laura , Stein Deborah M. , Callcut Rachael , Wybourn Chris , Sperry Jason , Anto Vincent , Dunn Julie , Veith Jacob P. , Brown Carlos V. R. , Celii Amanda , Zander Tyler L. , Coimbra Raul , Berndtson Allison E. , Moss Tovah Z. , Malhotra Ajai K. , Hazelton Joshua P. , Linden Kimberly , West Michaela , Alam Hasan B. , Williams Aaron M. , Kim Jennie , Inaba Kenji , Moulton Steve , Choi Young Mee , Warren Harry L. , Collier Bryan , Ball Chad G. , Savage Stephanie , Hartwell Jennifer L. , Cullinane Daniel C. , Zielinski Martin D. , Ray-Zack Mohamed D. , Morse Bryan C. , Rhee Peter , Rutherford Edmund J. , Udekwu Pascal , Reynolds Cassandra , Toschlog Eric , Gondek Steve , Ju Tammy , Haan James M. , Lightwine Kelly L. , Kulvatunyou Narong , Coates Brian , Khouqeer Ahmed F. , Todd S. Rob , Zarzaur Ben , Waller Christine J. , Kallies Kara J. , Neideen Todd , Eddine Savo Bou Zein , Peck Kimberly A. , Dunne Casey E. , Kramer Kristina , Bokhari Faran , Dhillon Tejveer S. , Galante Joseph M. , Cohen Mitchell J. 
Published: May 2018

BACKGROUND
Screening for blunt cerebrovascular injuries (BCVIs) in asymptomatic high-risk patients has become routine. To date, the length of this asymptomatic period has not been defined. Determining the time to stroke could impact therapy including earlier initiation of antithrombotics in multiply injured patients. The purpose of this study was to determine the time to stroke in patients with a BCVI-related stroke. We hypothesized that the majority of patients suffer stroke between 24 hours and 72 hours after injury.

METHODS
Patients with a BCVI-related stroke from January 2007 to January 2017 from 37 trauma centers were reviewed.

RESULTS
During the 10-year study, 492 patients had a BCVI-related stroke; the majority were men (61%), with a median age of 39 years and ISS of 29. Stroke was present at admission in 182 patients (37%) and occurred during an Interventional Radiology procedure in six patients. In the remaining 304 patients, stroke was identified a median of 48 hours after admission: 53 hours in the 144 patients identified by neurologic symptoms and 42 hours in the 160 patients without a neurologic examination and an incidental stroke identified on imaging. Of those patients with neurologic symptoms, 88 (61%) had a stroke within 72 hours, whereas 56 had a stroke after 72 hours; there was a sequential decline in stroke occurrence over the first week. Of the 304 patients who had a stroke after admission, 64 patients (22%) were being treated with antithrombotics when the stroke occurred.

CONCLUSIONS
The majority of patients suffer BCVI-related stroke in the first 72 hours after injury. Time to stroke can help inform clinicians about initiation of treatment in the multiply injured patient.

LEVEL OF EVIDENCE
Prognostic/Epidemiologic, level III.
Tandem duplications lead to loss of fitness effects in CRISPR-Cas9 data
Authors: Gonçalves Emanuel , Behan Fiona M , Louzada Sandra , Arnol Damien , Stronach Euan , Yang Fengtang , Yusa Kosuke , Stegle Oliver , Iorio Francesco , Garnett Mathew J 
Published: May 2018

AbstractCRISPR-Cas9 gene-editing is widely used to study gene function and is being advanced for therapeutic applications. Structural rearrangements are a ubiquitous feature of cancers and their impact on CRISPR-Cas9 gene-editing has not yet been systematically assessed. Utilising CRISPR-Cas9 knockout screens for 163 cancer cell lines, we demonstrate that targeting tandem amplified regions is highly detrimental to cellular fitness, in contrast to amplifications caused by chromosomal duplications which have little to no effect. Genomically clustered Cas9 double-strand DNA breaks are associated with a strong gene-independent decrease in cell fitness. We systematically identified collateral vulnerabilities in 25% of cancer cells, introduced by tandem amplifications of tissue non-expressed genes. Our analysis demonstrates the importance of structural rearrangements in mediating the effect of CRISPR-Cas9-induced DNA damage, with implications for the use of CRISPR-Cas9 gene-editing technology, and how resulting collateral vulnerabilities are a generalisable strategy to target cancer cells.
Nucleus- and plastid-targeted annexin 5 promotes reproductive development in Arabidopsis and is essential for pollen and embryo formation
Authors: Lichocka Malgorzata , Rymaszewski Wojciech , Morgiewicz Karolina , Barymow-Filoniuk Izabela , Chlebowski Aleksander , Sobczak Miroslaw , Samuel Marcus A. , Schmelzer Elmon , Krzymowska Magdalena , Hennig Jacek 
Published: May 2018

AbstractBackgroundPollen development is a strictly controlled post-meiotic process during which microspores differentiate into microgametophytes and profound structural and functional changes occur in organelles. Annexin 5 is a calcium- and lipid-binding protein that is highly expressed in pollen grains and regulates pollen development and physiology. To gain further insights into the role of ANN5 in Arabidopsis development, we performed detailed phenotypic characterization of Arabidopsis plants with modified ANN5 levels. In addition, interaction partners and subcellular localization of ANN5 were analyzed to investigate potential functions of ANN5 at cellular level.ResultsHere, we report that RNAi-mediated suppression of ANN5 results in formation of smaller pollen grains, enhanced pollen lethality, and delayed pollen tube growth. ANN5 RNAi knockdown plants also displayed aberrant development during the transition from the vegetative to generative phase and during embryogenesis, reflected by delayed bolting time and reduced embryo size, respectively. At the subcellular level, ANN5 was delivered to the nucleus, nucleolus, and cytoplasm, and was frequently localized in plastid nucleoids, suggesting a likely role in interorganellar communication. Furthermore, ANN5-YFP co-immunoprecipitated with RABE1b, a putative GTPase, and interaction in planta was confirmed in plastidial nucleoids using FLIM-FRET analysis.ConclusionsOur findings let us to propose that ANN5 influences basal cell homeostasis via modulation of plastid activity during pollen maturation. We hypothesize that the role of ANN5 is to orchestrate the plastidial and nuclear genome activities via protein-protein interactions however not only in maturing pollen but also during the transition from the vegetative to the generative growth and embryo development.
Eradication ofENO1-deleted Glioblastoma through Collateral Lethality
Authors: Lin Yu-Hsi , Satani Nikunj , Hammoudi Naima , Ackroyd Jeffrey J. , Khadka Sunada , Yan Victoria C. , Georgiou Dimitra K. , Sun Yuting , Zielinski Rafal , Tran Theresa , Pando Susana Castro , Wang Xiaobo , Maxwell David , Peng Zhenghong , Pisaneschi Federica , Mandal Pijus , Leonard Paul G. , Xu Quanyu , Wu Qi , Jiang Yongying , Czako Barbara , Kang Zhijun , Asara John M. , Priebe Waldemar , Bornmann William , Marszalek Joseph R. , DePinho Ronald A. , Muller Florian L. 
Published: May 2018

ABSTRACTInhibiting glycolysis remains an aspirational approach for the treatment of cancer. We recently demonstrated that SF2312, a natural product phosphonate antibiotic, is a potent inhibitor of the glycolytic enzyme Enolase with potential utility for the collateral lethality-based treatment of Enolase-deficient glioblastoma (GBM). However, phosphonates are anionic at physiological pH, limiting cell and tissue permeability. Here, we show that addition of pivaloyloxymethyl (POM) groups to SF2312 (POMSF) dramatically increases potency, leading to inhibition of glycolysis and killing ofENO1-deleted glioma cells in the low nM range. But the utility of POMSFin vivois dose-limited by severe hemolytic anemia. A derivative, POMHEX, shows equipotency to POMSF without inducing hemolytic anemia. POMHEX can eradicate intracranial orthotopicENO1-deleted tumors, despite sub-optimal pharmacokinetic properties. Taken together, our data providein vivoproof-of-principal for collateral lethality in precision oncology and showcase POMHEX as a useful molecule for the study of glycolysis in cancer metabolism.
Establishing a cell-freeVibrio natriegensexpression system
Authors: Wiegand Daniel J. , Lee Henry H. , Ostrov Nili , Church George M. 
Published: May 2018

AbstractThe fast growing bacteriumVibrio natriegensis an emerging microbial host for biotechnology. Harnessing its productive cellular components may offer a compelling platform for rapid protein production and prototyping of metabolic pathways or genetic circuits. Here, we report the development of aV. natriegenscell-free expression system. We devised a simplified crude extract preparation protocol and achieved >260 μg/mL of super-folder GFP in a small-scale batch reaction after three hours. Culturing conditions, including growth media and cell density, significantly affect translation kinetics and protein yield of extracts. We observed maximal protein yield at incubation temperatures of 26°C or 30°C, and show improved yield by tuning ions crucial for ribosomal stability. This work establishes an initialV. natriegenscell-free expression system, enables probing ofV. natriegensbiology, and will serve as a platform to accelerate metabolic engineering and synthetic biology applications.
Linking single-cell measurements of mass, growth rate, and gene expression
Authors: Kimmerling Robert J. , Prakadan Sanjay M. , Gupta Alejandro J. , Calistri Nicholas L. , Stevens Mark M. , Olcum Selim , Cermak Nathan , Drake Riley S. , Shalek Alex K. , Manalis Scott R. 
Published: May 2018

AbstractWe introduce a microfluidic platform that enables single-cell mass and growth rate measurements upstream of single-cell RNA-sequencing (scRNA-seq) to generate paired single-cell biophysical and transcriptional data sets. Biophysical measurements are collected with a serial suspended microchannel resonator platform (sSMR) that utilizes automated fluidic state switching to load individual cells at fixed intervals, achieving a throughput of 120 cells per hour. Each single-cell is subsequently captured downstream for linked molecular analysis using an automated collection system. From linked measurements of a murine leukemia (L1210) and pro-B cell line (FL5.12), we identify gene expression signatures that correlate significantly with cell mass and growth rate. In particular, we find that both cell lines display a cell-cycle signature that correlates with cell mass, with early and late cell-cycle signatures significantly enriched amongst genes with negative and positive correlations with mass, respectively. FL5.12 cells also show a significant correlation between single-cell growth efficiency and a G1-S transition signature, providing additional transcriptional evidence for a phenomenon previously observed through biophysical measurements alone. Importantly, the throughput and speed of our platform allows for the characterization of phenotypes in dynamic cellular systems. As a proof-of-principle, we apply our system to characterize activated murine CD8+ T cells and uncover two unique features of CD8+ T cells as they become proliferative in response to activation: i) the level of coordination between cell cycle gene expression and cell mass increases, and ii) translation-related gene expression increases and shows a correlation with single-cell growth efficiency. Overall, our approach provides a new means of characterizing the transcriptional mechanisms of normal and dysfunctional cellular mass and growth rate regulation across a range of biological contexts.
Pioneering, chromatin remodeling, and epigenetic constraint in early T-cell gene regulation by PU.1
Authors: Ungerbäck Jonas , Hosokawa Hiroyuki , Wang Xun , Strid Tobias , Williams Brian A. , Sigvardsson Mikael , Rothenberg Ellen V. 
Published: May 2018

AbstractPU.1 is a dominant but transient regulator in early T-cell precursors and a potent transcriptional controller of developmentally important pro-T cell genes. Before T-lineage commitment, open chromatin is frequently occupied by PU.1, and many PU.1 sites lose accessibility when PU.1 is later downregulated. Pioneering activity of PU.1 was tested in in this developmentally dynamic context, by quantitating the relationships between PU.1 occupancy and site quality and accessibility as PU.1 levels naturally declined in pro-T cell development, and by using stage-specific gain and loss of function perturbations to relate binding to effects on target genes. PU.1 could bind closed genomic sites, but rapidly opened many of them, despite the absence of its frequent collaborators, C/EBP factors. The dynamic properties of PU.1 engagements implied that PU.1 binding affinity and concentration determine its occupancy choices, but with quantitative tradeoffs for occupancy between site sequence quality and stage-dependent site accessibility in chromatin. At non-promoter sites PU.1 binding criteria were more stringent than at promoters, and PU.1 was also much more effective as a transcriptional regulator at non-promoter sites where local chromatin accessibility depended on the presence of PU.1. Runx motifs and Runx1 binding were often linked to PU.1 at open sites, but highly expressed PU.1 could bind its sites without Runx1. Notably, closed chromatin presented a qualitative barrier to occupancy by the PU.1 DNA binding domain alone. Thus, effective pioneering at closed chromatin sites also depends on requirements beyond site recognition served by non-DNA binding domains of PU.1.
Protein design under competition for amino acids availability
Authors: Nerattini F. , Tubiana L. , Cardelli C. , Bianco V. , Dellago C. , Coluzza I. 
Published: May 2018

ABSTRACTUnderstanding the origin of the 20 letter alphabet of proteins is a long-lasting biophysical problem. In particular, studies focused extensively on the effect of a reduced alphabet size on the folding properties. However, the natural alphabet is a compromise between versatility and optimisation of the available resources.Here, for the first time, we include the additional impact of the relative availability of the amino acids. We present a protein design scheme that involves the competition for resources between a protein and a potential interaction partner that, additionally, gives us the chance to investigate the effect of the reduced alphabet on protein-protein interactions. We identify the optimal reduced set of letters for the design of the protein, and we observe that even alphabets reduced down to 4 letters allow for single protein folding. However, it is only with 6 letters that we achieve optimal folding, thus recovering experimental observations.Additionally, we notice that the binding between the protein and a potential interaction partner could not be avoided with the investigated reduced alphabets. Therefore, we suggest that aggregation could have been a driving force for the evolution of the large protein alphabet.
Estrogen Regulates the Satellite Cell Compartment in Females
Authors: Collins Brittany C. , Arpke Robert W. , Larson Alexie A. , Baumann Cory W. , Cabelka Christine A , Nash Nardina L. , Juppi Hanna-Kaarina , Laakkonen Eija K. , Sipilä Sarianna , Kovanen Vuokko , Spangenburg Espen E. , Kyba Michael , Lowe Dawn A. 
Published: May 2018

SUMMARYSkeletal muscle mass, strength, and regenerative capacity decline with age, with many measures showing greater deterioration in females about the time estrogen levels decrease at menopause. Here we show that maintenance of muscle stem cells, satellite cells, as well as self-renewal and differentiation into muscle fibers, are severely compromised by estrogen deficiency. Mechanistically, by hormone replacement, use of a selective estrogen-receptor modulator (bazedoxifene), and conditional estrogen receptor knockout, we implicate 17β-estradiol and satellite cell expression of estrogen receptorα(ERα) and show that estrogen signaling through this receptor is necessary to prevent apoptosis of satellite cells. Early data from a biopsy study of women who transitioned from peri-to post-menopause are consistent with the loss of satellite cells coincident with the decline in estradiol in humans. Together, these results demonstrate an important role for estrogen in satellite cell maintenance and muscle regeneration in females.