bluuebunny/crossref_metadata_2025_split huggingface dataset:
Breast Animation Deformity
Authors: Casella Donato , Lo Torto Federico , Marcasciano Marco , Barellini Leonardo , Frattaroli Jacopo Maria , Turriziani Gianmarco , Ribuffo Diego 
Published: August 2020

Background
We evaluated the aesthetic outcomes and quality of life of patients who underwent neurotomy of the lateral and medial branch of the pectoralis nerve for animation deformity after breast reconstruction.

Material and Methods
Health-related quality of life questionnaire and cosmetic outcome evaluation were conducted using the preoperative and the postoperative BREAST-Q modules for reconstructive surgery. An external author also assessed the general aesthetic outcome before and after surgery.

Results
Sixty-two patients with animation deformity after breast reconstruction were enrolled: 43 in group 1 (second-stage breast reconstruction), 10 in group 2 (permanent breast prosthesis), and 9 in group 3 (Baker III-IV capsular contraction). Patients scored high level of satisfaction with outcome concerning all aspects of the survey. Overall satisfaction with breast was significantly increased after surgery in all the 3 groups, whereas physical well-being was improved in group 1 and group 3 and psychosocial well-being was improved in group 1. General outcome evaluation by an external author, compared with the preoperative condition, also showed significant improvement.

Conclusions
Section of the lateral and medial branches of the pectoralis nerve represents an easy and reproducible technique, associated with low morbidity and very good results in terms of patient satisfaction, comfort, and hospitalization.
Autotaxin Activity Predicts 30-Day Mortality in Sepsis Patients and Correlates With Platelet Count and Vascular Dysfunction
Authors: Sexton Travis , Chalhoub George , Ye Shaojing , Morris William , Annabathula Rahul , Dugan Adam , Smyth Susan 
Published: August 2020

ABSTRACT

Objectives:
We investigated whether platelet count associated with biomarkers of endothelial function, and additionally sought to identify novel predictors of outcomes in a cohort of patients with severe sepsis at a quaternary care academic medical center.

Design:
Prospective, observational cohort.

Patients:
Eighty-six sepsis patients admitted into intensive care units were prospectively enrolled into an on-site sepsis registry and biobank.

Interventions:
None.

Measurements and Main Results:
Platelet count, mean platelet volume, platelet mass, plasma angiopoietin-1 and angiopoietin-2, syndecan-1, platelet factor 4, sCD40L concentrations, and plasma autotaxin activity were determined for each patient at enrollment. Patient mortality was recorded up to 30 days following hospital discharge. Platelet count and plasma sCD40L was significantly lower in patients who did not survive up to 30 days following hospital discharge. Angiopoietin-2 and the angiopoietin-2/1 ratio were significantly higher in patients who did not survive up to 30 days following discharge. Furthermore, plasma autotaxin activity was significantly higher in patients who did not survive up to 30 days. Interestingly, autotaxin activity correlated with platelet count and the ratio of angiopoietin-2/1 across our population.

Conclusions:
Platelet count, the ratio of angiopoietin-2/1, and autotaxin activity all predicted 30-day mortality. Autotaxin activity within the plasma correlates with both platelet counts and vascular dysfunction biomarkers across both survivors and non-survivors indicating a possible involvement of autotaxin within sepsis.
Endothelial Dysfunction is Associated With Increased Incidence, Worsened Severity, and Prolonged Duration of Acute Kidney Injury After Severe Trauma
Authors: Hatton Gabrielle E. , Isbell Kayla D. , Henriksen Hanne H. , Stensballe Jakob , Brummerstedt Martin , Johansson Pär I. , Kao Lillian S. , Wade Charles E. 
Published: August 2020

ABSTRACT

Introduction:
Nearly half of severely injured patients suffer acute kidney injury (AKI), but little is known about its pathogenesis or optimal management. We hypothesized that endothelial dysfunction, evidenced by elevated systemic soluble thrombomodulin (sTM) and syndecan-1, would be associated with higher incidence, worsened severity, and prolonged duration of AKI after severe trauma.

Methods:
A single-center cohort study of severely injured patients surviving ≥24 h from 2012 to 2016 was performed. Arrival plasma sTM and syndecan-1 were measured by ELISA. Outcomes included 7-day AKI incidence, stage, and prolonged AKI ≥2 days. The Kidney Disease Improving Global Outcomes guidelines were used for AKI diagnosis and staging. Univariate and multivariable analyses were performed.

Results:
Of 477 patients, 78% were male. Patients had a median age of 38 (interquartile ranges [IQR] 27–54) and injury severity score of 17 (IQR 10–26). AKI developed in 51% of patients. Those with AKI were older and displayed worse arrival physiology. Patients with AKI had higher plasma levels of syndecan-1 (median 34.9 ng/mL vs. 20.1 ng/mL) and sTM (6.5 ng/mL vs. 4.8 ng/mL). After adjustment, sTM and syndecan-1 were both associated with higher AKI incidence, worse AKI severity, and prolonged AKI duration. The strength and precision of the association of sTM and these outcomes were greater than those for syndecan-1. A sensitivity analysis excluding patients with AKI on arrival demonstrated the same relationship.

Conclusions:
Elevated sTM and syndecan-1, indicating endothelial dysfunction, were associated with higher incidence, worsened severity, and prolonged duration of AKI after severe trauma. Treatments that stabilize the endothelium hold promise for AKI treatment in severely injured patients.
ERK1/2 Has Divergent Roles in LPS-Induced Microvascular Endothelial Cell Cytokine Production and Permeability
Authors: Wong Erika , Xu Fengyun , Joffre Jérémie , Nguyen Nina , Wilhelmsen Kevin , Hellman Judith 
Published: August 2020

ABSTRACT
Endothelial cells play a major role in inflammatory responses to infection and sterile injury. Endothelial cells express Toll-like receptor 4 (TLR4) and are activated by LPS to express inflammatory cytokines/chemokines, and to undergo functional changes, including increased permeability. The extracellular signal-regulated kinase 1/2 (ERK1/2) mediates pro-inflammatory signaling in monocytes and macrophages, but the role of ERK1/2 in LPS-induced activation of microvascular endothelial cells has not been defined. We therefore studied the role of ERK1/2 in LPS-induced inflammatory activation and permeability of primary human lung microvascular endothelial cells (HMVEC). Inhibition of ERK1/2 augmented LPS-induced IL-6 and vascular cell adhesion protein (VCAM-1) production by HMVEC. ERK1/2 siRNA knockdown also augmented IL-6 production by LPS-treated HMVEC. Conversely, ERK1/2 inhibition abrogated permeability and restored cell–cell junctions of LPS-treated HMVEC. Consistent with the previously described pro-inflammatory role for ERK1/2 in leukocytes, inhibition of ERK1/2 reduced LPS-induced cytokine/chemokine production by primary human monocytes. Our study identifies a complex role for ERK1/2 in TLR4-activation of HMVEC, independent of myeloid differentiation primary response gene (MyD88) and TIR domain-containing adaptor inducing IFN-β (TRIF) signaling pathways. The activation of ERK1/2 limits LPS-induced IL-6 production by HMVEC, while at the same time promoting HMVEC permeability. Conversely, ERK1/2 activation promotes IL-6 production by human monocytes. Our results suggest that ERK1/2 may play an important role in the nuanced regulation of endothelial cell inflammation and vascular permeability in sepsis and injury.
Skeletal Muscle Interleukin-6 Contributes to the Innate Immune Response in Septic Mice
Authors: Laitano Orlando , Robinson Gerard P. , Garcia Christian K. , Mattingly Alex J. , Sheikh Laila H. , Murray Kevin O. , Iwaniec John D. , Alzahrani Jamal , Morse Deborah , Hidalgo Juan , Clanton Thomas L. 
Published: August 2020

ABSTRACT
Interleukin-6 (IL-6) is a major cytokine released by skeletal muscle. Although IL-6 plays complex but well-known roles in host defense, the specific contribution of skeletal muscle IL-6 to innate immunity remains unknown. We tested its functional relevance by exposing inducible skeletal muscle IL-6 knockdown (skmIL-6KD) mice to a cecal slurry model of polymicrobial peritonitis and compared responses to strain-matched controls and skeletal muscle Cre-matched controls at 3, 6, and 12 h postinfection. In both sexes, skmIL-6KD mice at 6 h of infection exhibited marked changes to leukocyte trafficking in the peritoneum, characterized by ∼1.75-fold elevation in %neutrophils, a ∼3-fold reduction in %lymphocytes and a ∼2 to 3-fold reduction in %basophils. A similar pattern was seen at 12 h. No changes were observed in plasma leukocyte counts. Circulating cytokines in female skmIL-6KD mice at 6 h consistently showed modest reductions in IL-6, but marked reductions in a broad range of both pro- and anti-inflammatory cytokines, e.g., TNFα and IL-10. In both sexes at 12 h, a generalized suppression of plasma cytokines was also seen after the effects of Cre-induction with raloxifene were addressed. There were no significant effects of skmIL-6KD on mortality in either sex. Collectively, our results are consistent with skmIL-6 playing an important and previously unrecognized role in immune cell trafficking and cytokine regulation during septic shock.
Effects of Acute Subdural Hematoma-Induced Brain Injury On Energy Metabolism in Peripheral Blood Mononuclear Cells
Authors: Zink Fabian , Vogt Josef , Wachter Ulrich , Hartert Jens , Horchler Mirco , Zhang Xiaomin , Hezel Felix , Kapapa Thomas , Datzmann Thomas , Hoffmann Andrea , Wepler Martin , Calzia Enrico , Radermacher Peter , Hartmann Clair 
Published: August 2020

ABSTRACT
In activated immune cells, differentiation and function are determined by cell type-specific modifications of metabolic patterns. After traumatic brain injury both immune cell activation and suppression were reported. Therefore, we sought to explore immune cell energy metabolism in a long-term, resuscitated porcine model of acute subdural hematoma (ASDH)-induced acute brain injury devoid of impaired systemic hemodynamics and oxygen transport.
Before and up to 50 h after induction of ASDH, peripheral blood mononuclear cells (PBMCs) were separated by density gradient centrifugation, and cell metabolism was analyzed using high-resolution respirometry for mitochondrial respiration and electron spin resonance for reactive oxygen species production. After incubation with stable isotope-labeled 1,2-13C2-glucose or 13C5-glutamine, distinct labeling patterns of intermediates of glycolysis or tricarboxylic acid (TCA) cycle and 13CO2 production were measured by gas chromatography-mass spectroscopy. Principal component analysis was followed by a varimax rotation on the covariance across all measured variables and all measured time points.
After ASDH induction, average PBMC metabolic activity remained unaffected, possibly because strict adherence to intensive care unit guidelines limited trauma to ASDH induction without any change in parameters of systemic hemodynamics, oxygen transport, and whole-body metabolism. Despite decreased glycolytic activity fueling the TCA cycle, the principal component analysis indicated a cell type-specific activation pattern with biosynthetic and proliferative characteristics.
Angiogenesis: A Cellular Response to Traumatic Injury
Authors: Pecoraro Anthony R. , Hosfield Brian D. , Li Hongge , Shelley William Christopher , Markel Troy A. 
Published: August 2020

ABSTRACT
The development of new vasculature plays a significant role in a number of chronic disease states, including neoplasm growth, peripheral arterial disease, and coronary artery disease, among many others. Traumatic injury and hemorrhage, however, is an immediate, often dramatic pathophysiologic insult that can also necessitate neovascularization to promote healing. Traditional understanding of angiogenesis involved resident endothelial cells branching outward from localized niches in the periphery. Additionally, there are a small number of circulating endothelial progenitor cells that participate directly in the process of neovessel formation. The bone marrow stores a relatively small number of so-called pro-angiogenic hematopoietic progenitor cells—that is, progenitor cells of a hematopoietic potential that differentiate into key structural cells and stimulate or otherwise support local cell growth/differentiation at the site of angiogenesis. Following injury, a number of cytokines and intercellular processes are activated or modulated to promote development of new vasculature. These processes initiate and maintain a robust response to vascular insult, allowing new vessels to canalize and anastomose and provide timely oxygen delivering to healing tissue. Ultimately as we better understand the key players in the process of angiogenesis we can look to develop novel techniques to promote healing following injury.
Expired But Not Yet Dead: Examining the Red Blood Cell Storage Lesion in Extended-Storage Whole Blood
Authors: Pulliam Kasiemobi E. , Joseph Bernadin , Veile Rosalie A. , Friend Lou Ann , Makley Amy T. , Caldwell Charles C. , Lentsch Alex B. , Goodman Michael D. , Pritts Timothy A. 
Published: August 2020

ABSTRACT
Whole blood is a powerful resuscitation strategy for trauma patients but has a shorter shelf life than other blood products. The red blood cell storage lesion in whole blood has not previously been investigated beyond the standard storage period. In the present study, we hypothesized that erythrocytes in stored whole blood exhibit similar aspects of the red blood cell storage lesion and that transfusion of extended storage whole blood would not result in a more severe inflammatory response after hemorrhage in a murine model. To test this hypothesis, we stored low-titer, O-positive, whole blood units, and packed red blood cells (pRBCs) for up to 42 days, then determined aspects of the red blood cell storage lesion. Compared with standard storage pRBCs, whole blood demonstrated decreased microvesicle and free hemoglobin at 21 days of storage and no differences in osmotic fragility. At 42 days of storage, rotational thromboelastometry demonstrated that clotting time was decreased, alpha angle was increased, and clot formation time and maximum clot firmness similar in whole blood as compared with pRBCs with the addition of fresh frozen plasma. In a murine model, extended storage whole blood demonstrated decreased microvesicle formation, phosphatidylserine, and cell-free hemoglobin. After hemorrhage and resuscitation, TNF-a, IL-6, and IL-10 were decreased in mice resuscitated with whole blood. Red blood cell survival was similar at 24 h after transfusion. Taken together, these data suggest that red blood cells within whole blood stored for an extended period of time demonstrate similar or reduced accumulation of the red blood cell storage lesion as compared with pRBCs. Further examination of extended-storage whole blood is warranted.
Sepsis Induces Deregulation of IL-13 Production and PD-1 Expression in Lung Group 2 Innate Lymphoid Cells
Authors: Akama Yuichi , Park Eun Jeong , Satoh-Takayama Naoko , Gaowa Arong , Ito Atsushi , Kawamoto Eiji , Darkwah Samuel , Appiah Michael G. , Myint Phyoe Kyawe , Ohno Hiroshi , Imai Hiroshi , Shimaoka Motomu 
Published: August 2020

ABSTRACT
Deregulation of the immune system in sepsis plays the central role in the pathogenesis of multiple organ failure including septic lung injury. Group 2 innate lymphoid cells (ILC2s) have emerged as a new player in regulating immune homeostasis in the lung; however, the role of ILC2s in lung injury in sepsis remains poorly understood. Here, we investigated temporal changes in stimulatory and inhibitory receptor expression and intracellular type 2 cytokine expression of ILC2s in the lung using a cecal ligation and puncture mouse sepsis model. We found that IL-13 production by ILC2s, which were predominately composed of the resident natural ILC2 subset rather than the migratory inflammatory ILC2 subset, was reduced in the lungs of sepsis mice on day 1 and gradually restored through day 7. Although the expression levels of ST2 and inducible T-cell costimulator (stimulatory receptors) were high, IL-13 production by ILC2s was reduced while showing high programmed cell death 1 (PD-1) (inhibitory receptor) expression. Furthermore, using IL-33 knockout mice, we have shown that IL-33 regulates the capacity of ILC2s to produce IL-13, possibly through the modulation of ST2 and PD-1 expression and signaling in the septic lung. To the best of our knowledge, this is the first report showing differential costimulatory/inhibitory receptor expression on ILC2s in a septic lung in the context of an IL-33/IL-13 pathway-mediated type 2 immune response in the progression and resolution of inflammation. Our present findings contribute to a better understanding of the underlying immunological mechanism of ILC2s and may fill the critical knowledge gap regarding immune homeostasis in the lung that hampers the development of new therapeutic strategies for sepsis-induced acute lung injury.
Septic Stability? Gut Microbiota in Young Adult Mice Maintains Overall Stability After Sepsis Compared to Old Adult Mice
Authors: Mankowski Robert T. , Thomas Ryan M. , Darden Dijoia B. , Gharaibeh Raad Z. , Hawkins Russell B. , Cox Michael C. , Apple Camille , Nacionales Dina C. , Ungaro Ricardo F. , Dirain Marvin L. , Moore Fredrick A. , Leeuwenburgh Christiaan , Brakenridge Scott C. , Clanton Thomas L. , Laitano Orlando , Moldawer Lyle L. , Mohr Alicia M. , Efron Philip A. 
Published: August 2020

ABSTRACT

Background:
Older adults have worse outcomes after sepsis than young adults. Additionally, alterations of the gut microbiota have been demonstrated to contribute to sepsis-related mortality. We sought to determine if there were alterations in the gut microbiota with a novel sepsis model in old adult mice, which enter a state of persistent inflammation, immunosuppression, and catabolism (PICS), as compared with young adult mice, which recover with the sepsis model.

Methods:
Mixed sex old (∼20 mo) and young (∼4 mo) C57Bl/6J mice underwent cecal ligation and puncture with daily chronic stress (CLP+DCS) and were compared with naive age-matched controls. Mice were sacrificed at CLP+DCS day 7 and feces collected for bacterial DNA isolation. The V3–V4 hypervariable region was amplified, 16S rRNA gene sequencing performed, and cohorts compared. α-Diversity was assessed using Chao1 and Shannon indices using rarefied counts, and β-diversity was assessed using Bray-Curtis dissimilarity.

Results:
Naive old adult mice had significantly different α and β-diversity compared with naive adult young adult mice. After CLP+DCS, there was a significant shift in the α and β-diversity (FDR = 0.03 for both) of old adult mice (naive vs. CLP+DCS). However, no significant shift was displayed in the microbiota of young mice that underwent CLP+DCS in regards to α-diversity (FDR = 0.052) and β-diversity (FDR = 0.12), demonstrating a greater overall stability of their microbiota at 7 days despite the septic insult. The taxonomic changes in old mice undergoing CLP+DCS were dominated by decreased abundance of the order Clostridiales and genera Oscillospira.

Conclusion:
Young adult mice maintain an overall microbiome stability 7 days after CLP+DCS after compared with old adult mice. The lack of microbiome stability could contribute to PICS and worse long-term outcomes in older adult sepsis survivors. Further studies are warranted to elucidate mechanistic pathways and potential therapeutics.
Dependence Clusters in Alzheimer Disease and Medicare Expenditures
Authors: Zhu Carolyn W. , Lee Seonjoo , Ornstein Katherine A. , Cosentino Stephanie , Gu Yian , Andrews Howard , Stern Yaakov 
Published: August 2020

Introduction:
Dependence in Alzheimer disease has been proposed as a holistic, transparent, and meaningful representation of disease severity. Modeling clusters in dependence trajectories can help understand changes in disease course and care cost over time.

Methods:
Sample consisted of 199 initially community-living patients with probable Alzheimer disease recruited from 3 academic medical centers in the United States followed for up to 10 years and had ≥2 Dependence Scale recorded. Nonparametric K-means cluster analysis for longitudinal data (KmL) was used to identify dependence clusters. Medicare expenditures data (1999-2010) were compared between clusters.

Results:
KmL identified 2 distinct Dependence Scale clusters: (A) high initial dependence, faster decline, and (B) low initial dependence, slower decline. Adjusting for patient characteristics, 6-month Medicare expenditures increased over time with widening between-cluster differences.

Discussion:
Dependence captures dementia care costs over time. Better characterization of dependence clusters has significant implications for understanding disease progression, trial design and care planning.
Aquitalea aquatilis sp. nov., isolated from Jungwon waterfall
Authors: Ngo Hien T.T. , Kim HongYong , Trinh Huan , Yi Tae-Hoo 
Published: August 2020

A Gram-stain-negative, facultative anaerobic, motile, short rods and yellow-pigmented bacterium, designated strain THG-DN7.12T, was isolated from water collected at Jungwon waterfall on Yongmun mountain, Republic of Korea. According to 16S rRNA gene sequence comparisons, strain THG-DN7.12T was found to be most closely related to

Aquitalea denitrificans

5YN1-3T (98.9 % sequence similarity),

Aquitalea magnusonii

TRO-001DR8T (98.7 %) and

Aquitalea pelogenes

P1297T (98.0 %). The DNA–DNA relatedness between strain THG-DN7.12T and its phylogenetically closest neighbours was below 70.0 %. The strain's DNA G+C content was 59.7 mol%. The major polar lipid was found to be phosphatidylethanolamine. Summed feature 3 (C16 : 1
ω7c and/or C16 : 1
ω6c) and C16 : 0 were identified as the major fatty acids. Ubiquinone Q-8 was detected as the only respiratory quinone. These data supported the affiliation of strain THG-DN7.12T to the genus

Aquitalea

. Strain THG-DN7.12T was distinguished from related

Aquitalea

species by physiological and biochemical tests. Therefore, the novel isolate represents a novel species, for which the name Aquitalea aquatilis sp. nov. is proposed, with THG-DN7.12T as the type strain (=KACC 18847T=CCTCC AB 2016185T).