bluuebunny/crossref_metadata_2025_split huggingface dataset:
Spinal anesthesia in a designated block bay for total joint arthroplasty: improving operating room efficiency
Authors: Kagan Ryland , Zhao Stephanie , Stone Andrew , Johnson Alicia J , Huff Thomas , Schabel Kathryn , Woodworth Glenn E , Ivie Ryan MJ 
Published: October 2020

Background
Creating highly efficient operating room (OR) protocols for total joint arthroplasty (TJA) is a challenging and multifactorial process. We evaluated whether spinal anesthesia in a designated block bay (BBSA) would reduce time to incision, improve first case start time and decrease conversion to general anesthesia (GA).

Methods
Retrospective cohort study on the first 86 TJA cases with BBSA from April to December 2018, compared with 344 TJA cases with spinal anesthesia performed in the OR (ORSA) during the same period. All TJA cases were included if the anesthetic plan was for spinal anesthesia. Patients were excluded if circumstances delayed start time or time to incision (advanced vascular access, pacemaker interrogation, surgeon availability). Data were extracted and analyzed via a linear mixed effects model to compare time to incision, via a Wilcoxon rank-sum test to compare first case start time, and via a Fisher’s exact test to compare conversion to GA between the groups.

Results
In the mixed effect model, the BBSA group time to incision was 5.37 min less than the ORSA group (p=0.018). The BBSA group had improved median first case start time (30.0 min) versus the ORSA group (40.5 min, p<0.0001). There was lower conversion to GA 2/86 (2.33%) in the BBSA group versus 36/344 (10.47%) in the ORSA group (p=0.018). No serious adverse events were noted in either group.

Conclusions
BBSA had limited impact on time to incision for TJA, with a small decrease for single OR days and no improvement on OR days with two rooms. BBSA was associated with improved first case start time and decreased rate of conversion to GA. Further research is needed to identify how BBSA affects the efficiency of TJA.
Interhemispheric inhibition to the biceps brachii during arm cycling
Authors: Benson Ryan J. , Lockyer Evan J. , Compton Chris T. , Power Kevin E. 
Published: October 2020

This is the first demonstration of interhemispheric inhibition (IHI) during a locomotor output, arm cycling. IHI was quantified by assessing the depth of the ipsilateral silent period (iSP) evoked via transcranial magnetic stimulation of the motor cortex. There was a significant reduction in electromyography (EMG) amplitude of the iSP during cycling compared with the control EMG (16.8% ± 17.1%; p < 0.001). Depth and area for measuring the iSP during arm cycling are discussed. Novelty: This is the first study to demonstrate activation of the cortical circuit, interhemispheric inhibition, during a locomotor output.
Two-current correlations in the pion in the Nambu and Jona-Lasinio model
Authors: Courtoy Aurore , Noguera Santiago , Scopetta Sergio 
Published: October 2020

AbstractWe present an analysis of two-current correlations for the pion in the Nambu–Jona-Lasinio model, with Pauli–Villars regularization. We provide explicit expressions in momentum space for two-current correlations corresponding to the zeroth component of the vector Dirac bilinear in the quark vertices, which has been evaluated on the lattice, thinking to applications in a high energy framework, as a step towards the calculation of pion double parton distributions. The numerical results show a remarkable qualitative agreement with recent lattice data. The factorization approximation into one-body currents is discussed based on previous evaluation of the relevant low energy matrix elements in the Nambu–Jona-Lasinio model, confirming the lattice result.
Epigenetic Control of Cdkn2a.Arf Protects Tumor-Infiltrating Lymphocytes from Metabolic Exhaustion
Authors: Koss Brian , Shields Bradley D. , Taylor Erin M. , Storey Aaron J. , Byrum Stephanie D. , Gies Allen J. , Washam Charity L. , Choudhury Samrat Roy , Hyun Ahn Jeong , Uryu Hidetaka , Williams Jason B. , Krager Kimberly J. , Chiang Tung-Chin , Mackintosh Samuel G. , Edmondson Rick D. , Aykin-Burns Nukhet , Gajewski Thomas F. , Wang Gang Greg , Tackett Alan J. 
Published: October 2020

Abstract

T-cell exhaustion in cancer is linked to poor clinical outcomes, where evidence suggests T-cell metabolic changes precede functional exhaustion. Direct competition between tumor-infiltrating lymphocytes (TIL) and cancer cells for metabolic resources often renders T cells dysfunctional. Environmental stress produces epigenome remodeling events within TIL resulting from loss of the histone methyltransferase EZH2. Here, we report an epigenetic mechanism contributing to the development of metabolic exhaustion in TIL. A multiomics approach revealed a Cdkn2a.Arf-mediated, p53-independent mechanism by which EZH2 inhibition leads to mitochondrial dysfunction and the resultant exhaustion. Reprogramming T cells to express a gain-of-function EZH2 mutant resulted in an enhanced ability of T cells to inhibit tumor growth in vitro and in vivo. Our data suggest that manipulation of T-cell EZH2 within the context of cellular therapies may yield lymphocytes that are able to withstand harsh tumor metabolic environments and collateral pharmacologic insults.

Significance:
These findings demonstrate that manipulation of T-cell EZH2 in cellular therapies may yield cellular products able to withstand solid tumor metabolic–deficient environments.
Rethinking Environmental Carcinogenesis
Authors: Kripke Margaret , Brody Julia Green , Hawk Ernest , Hernandez Amanda B. , Hoppin Polly J. , Jacobs Molly M. , Rudel Ruthann A. , Rebbeck Timothy R. 
Published: October 2020

Abstract
The 2010 report of the President's Cancer Panel concluded that the burden of cancer from chemical exposures is substantial, while the programs for testing and regulation of carcinogens remain inadequate. New research on the role of early life exposures and the ability of chemicals to act via multiple biological pathways, including immunosuppression, inflammation, and endocrine disruption as well as mutagenesis, further supports the potential for chemicals and chemical mixtures to influence disease. Epidemiologic observations, such as higher leukemia incidence in children living near roadways and industrial sources of air pollution, and new in vitro technologies that decode carcinogenesis at the molecular level, illustrate the diverse evidence that primary prevention of some cancers may be achieved by reducing harmful chemical exposures. The path forward requires cross-disciplinary approaches, increased environmental research investment, system-wide collaboration to develop safer economic alternatives, and community engagement to support evidence-informed action. Engagement by cancer researchers to integrate environmental risk factors into prevention initiatives holds tremendous promise for reducing the rates of disease.
See all articles in this CEBP Focus section, “Environmental Carcinogenesis: Pathways to Prevention.”
Helicobacter pylori Induces a Novel NF-kB/LIN28A/let-7a/hTERT Axis to Promote Gastric Carcinogenesis
Authors: Shen Li , Zeng Jiping , Ma Lin , Li Shuyan , Chen Chunyan , Jia Jihui , Liang Xiuming 
Published: October 2020

Abstract

Reactivated telomerase is a crucial event in the development and progression of a variety of tumors. However, how telomerase is activated in gastric carcinogenesis has not been fully uncovered yet. Here, we identified a key role of the NF-κB/LIN28A/let-7a axis to promote human telomerase reverse transcriptase (hTERT) expression for gastric cancer initiation. Mechanistically, LIN28A expression was upregulated by H. pylori–induced NF-κB activation. And LIN28A, in turn, suppressed let-7a expression, forming the NF-κB/LIN28A/let-7a axis to regulate gene expression upon H. pylori infection. Of note, we first discovered hTERT as a direct target of let-7a, which inhibited hTERT expression by binding to its 3′UTR of mRNA. Therefore, H. pylori–triggered let-7a downregulation enhanced hTERT protein translation, resulting in telomerase reactivation. Furthermore, hTERT enhanced LIN28A expression, forming the positive feedback regulation between hTERT and NF-κB/LIN28A/let-7a axis to maintain the sustained overexpression of hTERT in gastric cancer.

Implications:
The NF-κB/LIN28A/Let-7a axis was crucial for the overexpression of hTERT upon H. pylori infection during gastric cancer development and may serve as a potential target to suppress hTERT expression for gastric cancer prevention and treatment.
Cell Adhesion Molecules in Plasticity and Metastasis
Authors: Smart Jessica A. , Oleksak Julia E. , Hartsough Edward J. 
Published: October 2020

AbstractPrior to metastasis, modern therapeutics and surgical intervention can provide a favorable long-term survival for patients diagnosed with many types of cancers. However, prognosis is poor for patients with metastasized disease. Melanoma is the deadliest form of skin cancer, yet in situ and localized, thin melanomas can be biopsied with little to no postsurgical follow-up. However, patients with metastatic melanoma require significant clinical involvement and have a 5-year survival of only 34% to 52%, largely dependent on the site of colonization. Melanoma metastasis is a multi-step process requiring dynamic changes in cell surface proteins regulating adhesiveness to the extracellular matrix (ECM), stroma, and other cancer cells in varied tumor microenvironments. Here we will highlight recent literature to underscore how cell adhesion molecules (CAM) contribute to melanoma disease progression and metastasis.
Environment Influences Tumor Progression and Transcriptional Subtype in a New Model of Pancreatic Cancer
Authors: Pickering Karen A. , Morton Jennifer P. 
Published: October 2020

Abstract

Summary:
In this issue, Miyabayashi and colleagues describe a novel intraductal model of pancreatic cancer that allows modeling of the transcriptional subtypes of pancreatic cancer. Using this model, they are able to observe subtype switching driven by the microenvironment, a process at least partially mediated by RAS signaling.
See related article by Miyabayashi et al., p. 1566.
Understanding and Overcoming the Inflammatory Toxicities of Immunotherapy
Authors: Dougan Michael 
Published: October 2020

Abstract
Checkpoint blockade immunotherapy has led to impressive therapeutic responses in a wide variety of tumors, but also leads to a spectrum of inflammatory toxicities that can involve any organ system in the body. Although most inflammatory toxicities resolve with systemic immune suppression, fatal toxicities can occur, and interruption and discontinuation of immunotherapy because of toxicity are common. In addition to their clinical impact, these inflammatory toxicities also provide a window into immune regulation in humans. By studying the cellular and molecular mechanisms that drive this inflammation, we have an opportunity to learn how the immune checkpoints, cytotoxic T lymphocyte antigen-4 and programmed death-1 and its ligand, maintain immune homeostasis throughout the body. Although we have an increasingly detailed understanding of the mechanisms that drive effective antitumor immunity, we have a rudimentary picture of the mechanisms of toxicity. Most toxicities involve barrier organs, suggesting an important role for interactions with the environment, including the microbiome. Early analyses have implicated cytotoxic T cells, although the antigens recognized by these cells, and the pathways activated by and around them are still unknown. By gaining a detailed understanding of the immune mechanisms of toxicity, we have the potential to develop novel interventions for them. These treatments should take advantage of differences between effective antitumor immunity and the principal drivers of organ inflammation. By targeting these mechanistic differences, we can develop therapies that can be used alongside immunotherapy, blocking inflammatory toxicity while preserving or even enhancing the response to cancer.
Internalization of HMGB1 (High Mobility Group Box 1) Promotes Angiogenesis in Endothelial Cells
Authors: Lan Jiaoli , Luo Haihua , Wu Rong , Wang Juan , Zhou Biying , Zhang Yun , Jiang Yong , Xu Jia 
Published: October 2020

Objective:
In patients with peripheral artery disease, blockages in arterioles <1 mm cannot be treated surgically, and there are currently few effective medicines. Studies have shown that inflammation in ischemic tissue is related to injury recovery and angiogenesis, but insufficient attention has been paid to this area. Studies have suggested that HMGB1 (high mobility group protein 1), which is released by ischemic tissue, promotes angiogenesis, but the mechanism is not entirely clear. In this study, we tested the internalization of HMGB1 in endothelial cells and investigated a novel proangiogenic pathway.

Approach and Results:
Using green fluorescent protein–tagged HMGB1 to stimulate endothelial cells, we demonstrated HMGB1 internalization via dynamin and RAGE (receptor for advanced glycation end products)-dependent signaling. Using a fluorescence assay, we detected internalized protein fusion to lysosomes, followed by activation of CatB (cathepsin B) and CatL (cathepsin L). The latter promoted the release of VEGF (vascular endothelial growth factor)-A and endoglin and upregulated the capacities of cell migration, proliferation, and tube formation in endothelial cells. We identified that the cytokine-induced fragment—a key functional domain in HMGB1—mediates the internalization and angiogenic function of HMGB1. We further confirmed that HMGB1 internalization also occurs in vivo in endothelial cells and promotes angiogenesis in mouse femoral artery ligation.

Conclusions:
In this study, we identified a novel pathway of HMGB1 internalization–induced angiogenesis in endothelial cells. This finding sheds light on the regulatory role of inflammatory factors in angiogenesis through cell internalization and opens a new door to understand the relationship between inflammation and angiogenesis in ischemic diseases.
Comparison of the Postprandial Metabolic Fate of U-
13
C Stearic Acid and U-
13
C Oleic Acid in Postmenopausal Women
Authors: Rodríguez-Morató Jose , Galluccio Jean , Dolnikowski Gregory G. , Lichtenstein Alice H. , Matthan Nirupa R. 
Published: October 2020

Objective:

Compare the postprandial fatty acid metabolism of isotopically labeled stearate (U-
13
C18:0) and oleate (U-
13
C18:1).

Approach and Results:

In conjunction with a randomized-controlled crossover trial, 6 hypercholesterolemic postmenopausal women (≥50 years; body mass index: 25.6±3.0 kg/m
2
; LDL [low-density lipoprotein]-cholesterol ≥110 mg/dL) consumed isocaloric diets enriched in 18:0 or 18:1 (10%–15% E) for 5 weeks each. On day 1 of week 5, following a 12-hour fast, participants receive their experimental diet divided into 13 hourly meals beginning at 8
am
. U-
13
C18:0 or U-
13
C18:1 was incorporated into the 1:00
pm
meal (1.0 mg/kg body weight). Serial blood and breath samples were collected over 12 hours and fasting samples at 24 and 48 hours. Plasma and lipid subfraction fatty acid profiles were assessed by gas chromatography-flame ionization detector, isotope-enrichment by liquid chromatography time-of-flight mass spectrometry, and fatty acid oxidation rate (expired
13
CO
2
) by isotope ratio mass spectrometry. Both diets resulted in similar plasma LDL-cholesterol concentrations. Kinetic curves showed that U-
13
C18:0 had a higher plasma area under the curve (66%), lower plasma clearance rate (−46%), and a lower cumulative oxidation rate (−34%) than U-
13
C18:1. Three labeled plasma metabolites of U-
13
C18:0 were detected:
13
C16:0,
13
C16:1, and
13
C18:1. No plasma metabolites of U-
13
C18:1 were detected within the study time-frame. Higher incorporation of 18:0 in cholesteryl ester and triglyceride fractions was observed on the 18:0 compared with the 18:1 diet.

Conclusions:
The neutrality of 18:0 on plasma LDL-cholesterol concentrations is not attributable to a single factor. Compared with 18:1, 18:0 had higher plasma area under the curve because of lower clearance and oxidation rates, underwent both a direct and a multistage conversion to 18:1, and was preferentially incorporated into cholesteryl esters and triglycerides.
Optimal Continuous Positive Airway Pressure Treatment of Obstructive Sleep Apnea Reduces Daytime Resting Heart Rate in Prediabetes: A Randomized Controlled Study
Authors: Pamidi Sushmita , Chapotot Florian , Wroblewski Kristen , Whitmore Harry , Polonsky Tamar , Tasali Esra 
Published: October 2020

Background
It has been widely recognized that obstructive sleep apnea (OSA) is linked to cardiovascular disease. Yet, randomized controlled studies failed to demonstrate a clear cardiovascular benefit from OSA treatment, mainly because of poor adherence to continuous positive airway pressure (CPAP). To date, no prior study has assessed the effect of CPAP treatment on daytime resting heart rate, a strong predictor of adverse cardiovascular outcomes and mortality.

Methods and Results

We conducted a randomized controlled study in 39 participants with OSA and prediabetes, who received either in‐laboratory all‐night (ie, optimal) CPAP or an oral placebo for 2 weeks. During daytime, participants continued daily activities outside the laboratory. Resting heart rate was continuously assessed over 19 consecutive days and nights using an ambulatory device consisting of a single‐lead ECG and triaxis accelerometer. Compared with placebo, CPAP reduced daytime resting heart rate (treatment difference, −4.1 beats/min; 95% CI, −6.5 to −1.7 beats/min;
P
=0.002). The magnitude of reduction in daytime resting heart rate after treatment significantly correlated with the magnitude of decrease in plasma norepinephrine, a marker of sympathetic activity (
r
=0.44;
P
=0.02), and the magnitude of decrease in OSA severity (ie, apnea‐hypopnea index [
r
=0.48;
P
=0.005], oxygen desaturation index [
r
=0.50;
P
=0.003], and microarousal index [
r
=0.57;
P
<0.001]).

Conclusions
This proof‐of‐concept randomized controlled study demonstrates, for the first time, that CPAP treatment, when optimally used at night, reduces resting heart rate during the day, and therefore has positive cardiovascular carry over effects. These findings suggest that better identification and treatment of OSA may have important clinical implications for cardiovascular disease prevention.

Registration

URL:
https:///
www.clini​caltr​ials.gov
; Unique identifier: NCT01156116.
Association Between Thrombus Perviousness Assessed on Computed Tomography and Stroke Cause
Authors: Kufner Anna , Erdur Hebun , Endres Matthias , Nolte Christian H. , Scheel Michael , Schlemm Ludwig 
Published: October 2020

Background and Purpose:
A recent study proposed that thrombus perviousness (TP)—the degree to which contrast agents penetrate the thrombus in an occluded vessel measured on noncontrast computed tomography (NCCT) and CT angiography—may be associated with cardioembolic stroke cause with high specificity. Our aim was to investigate which clinical and laboratory parameters affect measures of TP and to validate its diagnostic accuracy in an independent cohort of patients with acute ischemic stroke.

Methods:
Seventy-five patients from a prospectively maintained database with proximal occlusions of the middle cerebral artery (M1) were retrospectively analyzed. Thrombi were segmented on coregistered noncontrast computed tomography and CT angiography to determine the thrombus attenuation increase and void fraction (attenuation increase relative to contralateral side).

Results:

TP measures were significantly higher in patients with cardioembolic stroke compared to patients with stroke attributed to large artery atherosclerosis (median thrombus attenuation increase [interquartile range], 2.79 [–3.54 to 8.85] versus –5.11 [–11.23 to –1.47];
P
=0.001). In linear regression analysis for TP including age, time to scan, prior medication with antiplatelets or anticoagulants, and selected laboratory parameters, only stroke cause was significantly associated with TP. In multivariable binary logistic regression analysis for dichotomized stroke cause (ie, cardioembolic versus noncardioembolic stroke), only thrombus attenuation increase was independently associated with cardioembolic stroke (odds ratio of 1.12 [95% CI, 1.04–1.22];
P
=0.004). Receiver operating characteristic analysis indicated that TP can identify cardioembolic stroke with an area under the curve of 0.75 (95% CI, 0.63–0.87) for thrombus attenuation increase. With a cutoff value of 6.23 Hounsfield units, cardioembolic strokes were identified with 100% specificity. Results for void fraction were similar.

Conclusions:
The assessment of TP on baseline noncontrast computed tomography/CT angiography in patients with M1 occlusion may aid in determining cardioembolic stroke cause and guide secondary prevention. Selected clinical and laboratory parameters other than stroke cause did not affect TP measures.
Behavioural repeatability in the Big Brown Bat, Eptesicus fuscus
Authors: Boyer Amanda , Karevold Hanna , Kreuger Derek T. , Dochtermann Ned A. , Gillam Erin H. 
Published: October 2020

Abstract
Work on animal personality, characterized by high behavioural repeatability, shows that animals exhibit limits to plasticity, with an individual’s range of variation only covering a portion of the range observed across the entire population. This work is particularly important for understanding the underlying genetic basis of behaviours. While research on behavioural repeatability has spanned many taxa, little work has focused on bats. Our objective was to determine if big brown bats (Eptesicus fuscus) exhibit moderate to high repeatability of different behavioural traits and if behavioural syndromes (among-individual correlations between behaviours) are present. Using a captive population, repeatability was assessed for aggression, exploration, and activity. Moderate repeatabilities were observed for all behaviours, indicating that individuals exhibit consistent behaviour over time. There were no significant correlations among behaviours. Future research aimed at assessing how changes in social structure impact behavioural repeatability will be valuable for understanding behavioural plasticity in social bat species.
Locomotion and habituation to novel experimental environments in a social fish species
Authors: Diaz Pazmino Santiago , Kent Maud I.A. , Ward Ashley J.W. 
Published: October 2020

Abstract
The response of animals to novel environments forms the basis of open field tests, an assay extensively used in the study of animal behaviour. However, to assess an animal’s routine behaviour or measure their response to novel environments, researchers must provide enough time for proper exploration and habituation. Unfortunately, no study has ever explicitly characterized the habituation process, except on isolated individuals, which represents an unusual situation for many social species. We analysed the movement characteristics and group-level dynamics of a shoaling fish species (Gambusia holbrooki) in an open-field arena for 1.5 h. We tested groups of 4 fish with varying sex ratios and found that behaviour changed over time with exploratory behaviour followed by a decreasing then plateauing trend, which only stabilised after 29 min. This movement pattern was consistent across all different sex ratios, however, female-skewed groups showed higher levels of activity during the first few minutes. Finally, median nearest neighbour distance was initially low before increasing and finally stabilising at around 9 min (with some exceptions) following the introduction of fish to the arena.