bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cell‐synthesized extracellular matrix particles for tissue engineering and aesthetic applications (87.2)
Authors: L'Heureux Nicolas , Young D , Dusserre Nathalie , Sonnenberg Sonya , Johnson Todd , McAllister Todd , Rodriguez Ricardo , Christman Karen 
Published: June 2021

With age, or after injury, subcutaneous adipose and conjunctive tissue loss can cause poor aesthetic appearance. Current injectable tissue fillers trigger foreign body responses that eventually lead to their degradation or encapsulation. The ideal dermal filler would provide initial structural support but also trigger a regenerative process and lead to the creation of a new permanent tissue. The goal of this project is to develop a new class of fillers that provides long‐term results by triggering the regeneration of a stable, living and vascularized adipose tissue.Using the Tissue Engineering by Self‐Assembly (TESA) approach, sheets of ECM produced by normal human fibroblasts in vitro were dehydrated and reduced to a particulate form that could be injected subcutaneously in nude mice. The ECM particles caused minimal inflammation or encapsulations. Most notably, vascularization and adipogenesis were observed at the injection site, neither of which was noted when using two popular dermal fillers (Juvederm® or Radiesse®). Progression of adipogenesis around the ECM particles was noted throughout the duration of the study (3 months). In separate studies, particles were cast in vitro to produce finely channelized structures that could be seeded with endothelial cells. This approach offers a viable strategy for the production pre‐vascularized bulk tissue to address secretory organ tissue engineering.Conclusion: Fibroblast‐synthesized particles combine “off‐the‐shelf” availability and a persistent ECM that provides mechanical support while triggering the development of a vascularized adipose tissue. Clinical studies are underway to compare this new regenerative dermal filler with the standard of care.
Biocompatibility of halloysite clay nanotubes in a rat dermal model (87.4)
Authors: Mills David 
Published: June 2021

The cytocompatibility of halloysite nanotubes (HNTs) have been firmly established. The biocompatibility of HNTs has yet to be established. The host‐immune response to dermally implanted HNTs in a rat skin wound model was assessed over a one‐month experimental period. Adult Sprague Dawley rats (27, male, 300g) comprised the study population. A calibrated microinjector was used to inject a 25μl PBS solution, plus/minus HNTs. Control group I animals received implant site preparation and microneedle penetration only while Control group II animals received implant site preparation, microneedle penetration, and a PBS injection. Clear bandages were applied over each implant site permitting daily visual observations. Animals were monitored and photodocumented on a daily basis for changes in coloration, infection, and healing pattern. Animals (n=3, each group) were sacrificed at one, two and four week intervals. Tissue blocks, containing implant sites and representing full thickness skin tissue sections, were harvested, fixed in 4% buffered formalin, paraffin embedded and sectioned at six microns. Histochemical and Immunohistochemical analysis were used to assess the host immune response. All analyses showed that implanted HNTs did not provoke either a local or systemic immune response. As HNTs are proving to be a potent drug delivery vehicle, our data provides support for their future use in clinical medicine.Grant Funding Source: Governor's Biotechnology Initiative
An animated 3D model of the synchronous movements of the suprasyringeal structures and organs in the neck of a vocalizing songbird, the Northern Cardinal (Cardinalis cardinalis) (918.8)
Authors: Blevins Caroline , Ge Jinghua , Suthers Roderick , Homberger Dominique 
Published: June 2021

In birds, sound is generated in the syrinx and is filtered by suprasyringeal structures that move relative to one another. The larynx moves relative to the hyoid apparatus, which moves relative to the mandible, which in turn moves relative to the skull. The cervical vertebral column moves the head relative to the thorax. The esophagus and trachea move relative to the vertebral column. The interplay of these elements was analyzed in a songbird, the Northern Cardinal, through an animated 3D model that was created from a CT scan based on prior anatomical analyses. The movements of the vocalizing behavior were modeled by matching the configuration of the 3D model to individual images of a 2D x‐ray video of a singing bird in lateral view. To estimate the degree of yaw and roll of the head, the x‐ray video was synchronized with a video recorded from above. To compensate for side‐to‐side movements of the bird, the images of the 2D x‐ray video were enlarged or reduced. A separately recorded x‐ray video in frontal view was used to verify the proper spatial configuration of the skeletal elements in the individual images of the animated 3D video. The video of the 3D model was synchronized with the audio recording to analyze the movements required to produce specific sounds.Grant Funding Source: Supported by NIH grant NINDS R01 NS029467 to RAS; LSU Foundation to DGH
A new approach to study site‐specific protein sumoylation (925.3)
Authors: Albuquerque Claudio , Yeung Eyan , Ma Shawn , Fu Ting , Zhou Huilin 
Published: June 2021

Protein sumoylation is a reversible post‐translational modification that regulates nuclear processes including gene transcription, nuclear transport and DNA repair. Like ubiquitin, SUMO is attached to the lysine side chains of target proteins via a cascade of E1‐activating, E2‐conjugating, and E3‐ligating enzymes, and it is removed by SUMO‐specific isopeptidases. Hundreds of proteins are known to be sumoylated in the yeast saccharomyces cerevisiae, however, relatively little is known about the precise sumoylation site(s) of most proteins. This is due to a lack of suitable method to map sumoylation sites in vivo. As a result, the function of sumoylation has remained mysterious in most cases. We have recently identified a novel role of protein sumoylation in preventing genome rearrangements and developed proteome‐wide approach to identify and quantify sumoylated proteins. Here we will report a new proteome‐wide method for the identification of site‐specific sumoylation in yeast, which greatly expanded the current knowledge of protein sumoylation. In addition, we will describe new approaches for the analysis of protein sumoylation in vitro. Results will be presented on the functional analysis of sumyolation of the sumoylation enzymes in yeast.Grant Funding Source: LICR
Unnatural covalent bond formation inside and between proteins through proximity‐enhanced reaction (972.6)
Authors: Xiang Zheng , Ren Haiyan , Hu Ying , Coin Irene , Wei Jing , Cang Hu , Wang Lei 
Published: June 2021

The cysteine disulfide bond plays a crucial role as intramolecular linkage in protein folding, stability and function. However, its inherent redox sensitivity and reversibility limit its applications in biotechnology and therapeutics. We envisioned that a new irreversible and stable covalent bond formed between a genetically incorporated unnatural amino acid (Uaa) and the residue of a natural amino acid would complement our ability of protein engineering and provide new tools for biological studies. We genetically incorporated a new electrophilic Uaa, p‐2’‐fluoroacetylphenylalanine (Ffact), into different proteins in E. coli and mammalian cells using the orthogonal tRNA‐synthetase pair, and demonstrated its applications in three ways. First, the incorporation of Ffact into the Z protein affibody at a specific position enabled it to form a covalent bond with Z protein mutant with Cys mutation. The reaction was enhanced by the proximity of the Uaa and the Cys residue and did not happen between distal Uaa and Cys residue. Second, we incorporated Ffact into the corticotropin release factor receptor type 1 (CRF‐R1), a class B G protein‐coupled receptor (GPCR), at the ligand‐receptor binding region. Different urocortin‐1 (Ucn‐1) ligand analogs of CRF‐R1 with cysteine mutation were incubated individually with HEK293T cells expressing the Ffact‐CRF‐R1 mutant. The Ffact‐cysteine reaction happened site‐specifically. The data enabled us to further explore the mechanism of the class B GPCR activation. Third, we incorporated Ffact into fluorescent proteins (FP) to form intramolecular linkage between the fluorophore and the β‐barrel. The linked FP mutants showed a higher quantum yield and greater photon output compared to the unlinked FP mutants. These results indicated that it is possible to add a new covalent bond to proteins by incorporating Uaas with proximity‐enhanced reactivity, which will provide new tools for biological studies and protein engineering.Grant Funding Source: Supported by CIRM (RN1‐00577‐1) and US NIH (1DP2OD004744‐01, P30CA014195)
Link between antioxidant effect and antiinflammatory response in butyrate arrested vascular smooth muscle cells (VSMC) proliferation (LB250)
Authors: Ranganna Kasturi , Mathew Omana , Milton Shirlette 
Published: June 2021

Epigenetic mechanisms by altering the expression and in turn, functions of target genes, without changing their primary structure have potential to modify cellular processes that are characteristics of atherosclerosis such as inflammation, proliferation, migration and apoptosis/cell death. Butyrate, a natural epigenetic modifier and a histone deacetylase inhibitor (HDACi), is an inhibitor of VSMC proliferation, a critical event in the pathogenesis of atherosclerosis, and alters cellular ROS and glutathione levels suggesting involvement of redox‐component in antiproliferation effect of butyrate. Here the goal is to explore whether the antioxidant effect of butyrate contributes to antiproliferation action on VSMC via modulation of inflammatory response by using western blotting and immunostaining methods. The results show treatment of VSMC with butyrate not only upregulates glutathione peroxidase (GPx)‐3 and GPx‐4, but also increases overall catalytic activity of GPx further supporting antioxidant effect of butyrate in proliferation arrested VSMC. Moreover, analysis of NF‐kB transcription factor system, the target of GPx, reveals butyrate treatment of VSMC causes downregulation of p65NF‐kB, IkBα, IKKα and IKKβ expression and inhibits phosphorylation of p65NF‐kB resulting in downregulation of NF‐kB target inflammatory genes such as inducible nitric oxide synthase, vascular cell adhesion molecule and cyclooxygenase‐2. Overall these observations suggest a link between antioxidant effect and antiinflammatory response in butyrate arrested VSMC proliferation and emphasize the atheroprotective and therapeutic potential of natural products such as butyrate in vascular proliferative diseases.Grant Funding Source: G12RR03045‐21 and C06RR012537 from NIH/NCRR
Consumption of frozen meals as compared to quick service restaurant meals is associated with better diet quality in adult participants of the National Health and Nutrition Examination Survey (2003‐2010) (LB383)
Authors: Papanikolaou Yanni , Comerford Kevin , Krumhar Kim , Fulgoni Victor 
Published: June 2021

What We Eat In America (WWEIA)/NHANES (2003‐2010) data were used to determine associations between diet quality in adult (19+yrs) frozen meal (FM) consumers as compared to consumers of meals from quick service restaurants (QSR). Intake was determined using a 24 hour recall; FM consumers were defined as those who reported consumption of any of the 91 specific frozen meal codes while QSR meal consumers were those who reported obtaining meals from “restaurant fast food/pizza.” ANOVA and covariate adjusted means were determined using appropriate sample weights; significance was set at p<0.01. Diet quality was calculated using the Healthy Eating Index‐2010 (HEI), which is designed to measure conformance to the 2010 Dietary Guidelines for Americans. Compared to QSR consumers (n=6,238), FM consumers (n=287) had lower intakes of energy (2326±20 v 2073±51 kcal/d) and higher total HEI scores (53.0±1.5 v 44.4±0.4). FM consumers had higher HEI sub‐component scores for higher intakes of total vegetables (3.4±0.1 v 2.9±0.03), greens and beans (1.7±0.2 v 0.9±0.04), whole grains (2.9±0.3 v 1.8±0.1), total protein foods (4.4±0.1 v 4.1±0.03), and lower intakes of refined grains (6.6±0.4 v 5.4±0.1), and empty calories (13.1±0.5 v 9.9±0.2). Other HEI sub‐components (sodium, total fruit, whole fruit, dairy, seafood and plant protein, and fatty acid ratio) were not different among FM or QSR consumers. Frozen meal consumption was associated with lower energy intake and a better diet quality as compared to those consuming QSR meals.Grant Funding Source: Supported by Nestlé
The Impact of Acute Exercise on Brain‐Derived Neurotropic Factor (BDNF) and Cognitive Performance (LB694)
Authors: Calvert Hannah , Hwang Jungyun , Kim Kiyoung , Harrison Michelle , Brothers R. , Glowacki Elizabeth , Van Dongen Daniel , Castelli Darla 
Published: June 2021

PURPOSE: To investigate the effects of an acute bout of vigorous exercise on BDNF and cognitive performance in emerging adults aged 18‐25 years.METHODS: Twenty‐nine emerging adults were recruited to assess aerobic exercise‐induced changes in BDNF and cognitive performance. At baseline (T_0), blood samples were taken to measure BDNF, and cardiorespiratory fitness (VO_2 max) was assessed on a cycle ergometer. At rest, cognitive performance was assessed via the Kaufman Brief Intelligence Test, Stroop Test and Trail Making Test (TMT) A and B , followed by 10 minutes of acute treadmill running at 85‐90% maximum heart rate . A second blood draw (T_1) immediately followed the exercise bout. Stroop and TMT were administered again once heart rate returned to 10% of baseline. BDNF was measured 30 minutes post exercise (T_2).RESULTS: There was a significant increase in BDNF from T_0 to T_1 (p < 0.05) and a significant decrease from T_1 to T_2 ( p < 0.05). Post exercise cognitive performance improved for Stroop word (t = ‐10.36, p <0.05), color (t = ‐6.69, p <0.05), and color word (t = ‐6.16, p <0.05), and TMT A (t=4.32 p<0.001) and B (t=4.46 p<0.001). There were trending relationships between BDNF and both cognitive tests.CONCLUSIONS: Acute exercise had a significantly positive effect on BDNF and cognition immediately after exercise. Further research is needed to determine whether cognitive performance after exercise is mediated by BDNF.
Positive regulation of STIM1/Orai1‐mediated store operated calcium entry by reactive oxygen species in human mesangial cells (LB731)
Authors: Chaudhari Sarika , Wang Yanxia , Wu Peiwen , Yuan Joseph , Ma Rong 
Published: June 2021

Store operated calcium entry (SOCE) plays a pivotal role in physiological responses of glomerular mesangial cells (MCs). STIM1 and Orai1 proteins are the essential components of SOCE pathway. We have previously demonstrated that STIM1and Orai1 were required for SOCE in cultured human MCs. Reactive oxygen species (ROS) can function as intracellular second messengers and as pathogenic factors in a variety of cell types. Whether and how ROS regulate the STIM1/Orai1‐dependent SOCE in MCs is unknown. The aim of the present study was to explore the effect of ROS on SOCE and the mechanism involved in cultured human MCs. Using fura‐2 fluorescence ratiometry approach, we found that the cyclopiazonic acid (CPA, 25 μM)‐stimulated SOCE was significantly enhanced in MCs with H2O2 treatment (100 μM for 5 days). Consistent with the functional data, western blot analysis of whole cell lysates showed significant increases in expressions of STIM1 and Orai1 proteins by H2O2 treatment in the range of 10‐100 μM for the same time period. However, H2O2 treatment did not affect mRNA expression levels of both STIM1 and Orai1. Furthermore, NAC (4 mM), an antioxidant, had tendency to attenuation of high glucose‐stimulated STIM1 protein expression. Taken together, our results indicate that ROS promote SOCE by increasing STIM1/Orai1 protein expression via a post‐transcriptional mechanism.Grant Funding Source: NIH
Transcriptional profiling reveals an aberrant hepatic regenerative response underlying acetaminophen (APAP)‐induced acute liver failure (ALF) (LB84)
Authors: Rogler Leslie , Pattamanuch Nicole , Bandi Sriram , Viswanathan Preeti , Gupta Sanjeev 
Published: June 2021

Acetaminophen (APAP) toxicity is the leading cause of ALF in United States. To understand mechanisms in APAP‐induced ALF, we performed transcriptional profiling of healthy livers and severely damaged explanted livers from people receiving liver transplants with Affymetrix Human Genome U133 Plus 2.0 arrays. In parallel, microRNA (miRNA) expression profiles were obtained with µParaflo® technology platform (LC Sciences.com). The most significantly down regulated gene categories were: acute phase response and LXR/RXR signaling, mitochondrial dysfunction, coagulation and complement systems, and xenobiotic metabolism. Genes involved in cholesterol and lipid metabolism or cholesterol, lipid and bile acid transport were globally down regulated. Also, hsa‐mir‐193, ‐26a, ‐23a, ‐122, ‐let7c, ‐92a were significantly down regulated. The gene expression pattern suggested activation of hepatic stellate cells. The biliary marker, KR19, was up regulated, as was the NOTCH ligand, JAG1. The proliferation markers, PCNA and Ki67, were up regulated, although growth inhibitory genes, e.g., PTCH2, TGFB1, PTTG1 and WNT signaling inhibitors, e.g., BICC1, were simultaneously up regulated. Several of these up regulated genes are targeted by miRNAs that we found were down regulated in liver with APAP toxicity. These data indicated that liver regeneration was aberrant and that miRNAs could represent suitable targets for therapeutic intervention in APAP‐induced ALF.Grant Funding Source: NIH and NYSTEM
Prediction of Impending Septic Shock in Children With Sepsis
Authors: Liu Ran , Greenstein Joseph L. , Fackler James C. , Bergmann Jules , Bembea Melania M. , Winslow Raimond L. 
Published: June 2021

Objectives:
Sepsis and septic shock are leading causes of in-hospital mortality. Timely treatment is crucial in improving patient outcome, yet treatment delays remain common. Early prediction of those patients with sepsis who will progress to its most severe form, septic shock, can increase the actionable window for interventions. We aim to extend a time-evolving risk score, previously developed in adult patients, to predict pediatric sepsis patients who are likely to develop septic shock before its onset, and to determine whether or not these risk scores stratify into groups with distinct temporal evolution once this prediction is made.

Design:
Retrospective cohort study.

Setting:
Academic medical center from July 1, 2016, to December 11, 2020.

Patients:
Six-thousand one-hundred sixty-one patients under 18 admitted to the Johns Hopkins Hospital PICU.

Interventions:
None.

Measurements and Main Results:
We trained risk models to predict impending transition into septic shock and compute time-evolving risk scores representative of a patient’s probability of developing septic shock. We obtain early prediction performance of 0.90 area under the receiver operating curve, 43% overall positive predictive value, patient-specific positive predictive value as high as 62%, and an 8.9-hour median early warning time using Sepsis-3 labels based on age-adjusted Sequential Organ Failure Assessment score. Using spectral clustering, we stratified pediatric sepsis patients into two clusters differing in septic shock prevalence, mortality, and proportion of patients adequately fluid resuscitated.

CONCLUSIONS:
We demonstrate the applicability of our methodology for early prediction and stratification for risk of septic shock in pediatric sepsis patients. Through analyses of risk score evolution over time, we corroborate our past finding of an abrupt transition preceding onset of septic shock in children and are able to stratify pediatric sepsis patients using their risk score trajectories into low and high-risk categories.
The Implementation and Outcomes of a Nurse-Run Extracorporeal Membrane Oxygenation Program, a Retrospective Single-Center Study
Authors: Odish Mazen , Yi Cassia , Tainter Christopher , Najmaii Samira , Ovando Julio , Chechel Laura , Lipinski Jerry , Ignatyev Alex , Pile Alexander , Yeong Jang Yun , Lin Tuo , Tu Xin M. , Madani Michael , Patel Mitul , Meier Angela , Pollema Travis , Owens Robert L. 
Published: June 2021

Objectives:
Due to a shortage of perfusionists and increasing utilization of extracorporeal membrane oxygenation in the United States, many programs are training nurses as bedside extracorporeal membrane oxygenation specialists (i.e., nurse-run extracorporeal membrane oxygenation). Our objective was to evaluate if a nurse-run extracorporeal membrane oxygenation program has noninferior survival to discharge and complication rates compared with a perfusionist-run extracorporeal membrane oxygenation program. Additionally, to sought to describe increases in extracorporeal membrane oxygenation capacity and the potential for cost savings by implementing a nurse-run extracorporeal membrane oxygenation program.
Early Intubation and Increased Coronavirus Disease 2019 Mortality: A Propensity Score–Matched Retrospective Cohort Study
Authors: Parish Austin J. , West Jason R. , Caputo Nicholas D. , Janus Trevor M. , Yuan Denley , Zhang John , Singer Daniel J. 
Published: June 2021

Objectives:
There has been controversy about the timing and indications for intubation and mechanical ventilation in novel coronavirus disease 2019. This study assessed the effect of early intubation and mechanical ventilation on all-cause, inhospital mortality for coronavirus disease 2019 patients.

Design:
Multicenter retrospective cohort study.

Setting:
Eleven municipal hospitals in New York City from March 1, 2020, to December 1, 2020.

Patients:
Adult patients who tested positive for coronavirus disease 2019 in the emergency department were subsequently admitted. Patients with do-not-intubate orders at admission were excluded.

Interventions:
Intubation within 48 hours of triage and intubation at any point during hospital stay.

Measurements and Main Results:
Data from 7,597 coronavirus disease 2019 patients were included; of these, 1,628 (21%) were intubated overall and 807 (11%) were intubated within 48 hours of triage. After controlling for available confounders, intubation rates for coronavirus disease 2019 patients varied significantly across hospitals and decreased steadily as the pandemic progressed. After nearest neighbor propensity score matching, intubation within 48 hours of triage was associated with higher all-cause mortality (hazard ratio, 1.30 [1.15–1.48]; p < 0.0001), as was intubation at any time point (hazard ratio, 1.62 [1.45–1.80]; p < 0.0001). Among intubated patients, intubation within 48 hours of triage was not significantly associated with differences in mortality (hazard ratio, 1.09 [0.94–1.26]; p = 0.26). These results remained robust to multiple sensitivity analyses.

CONCLUSIONS:
Intubation within 48 hours of triage, as well as at any time point in the hospital course, was associated with increased mortality in coronavirus disease 2019 patients in this observational study.