bluuebunny/crossref_metadata_2025_split huggingface dataset:
Human immune cell mobilization during exercise: effect of IL‐6 receptor blockade
Authors: Bay Marie Lund , Heywood Sarah , Wedell‐Neergaard Anne‐Sophie , Schauer Tim , Lehrskov Louise Lang , Christensen Regitse Højgaard , Legård Grit Elster , Jensen Peter Østrup , Krogh‐Madsen Rikke , Ellingsgaard Helga 
Published: October 2020

New Findings
What is the central question of this study?Does blockade of the IL‐6 receptor by tocilizumab inhibit immune cell mobilization to the blood stream in humans during an acute bout of exercise?
What is the main finding and its importance?Blockade of IL‐6 receptor signalling by tocilizumab attenuates mobilization of NK cells and dendritic cells to the blood stream during exercise. This implies an inhibitory effect of tocilizumab on the innate immune response to physical stress, which could be considered in clinical settings.
AbstractImmune cells are recruited from their storage organs and the endothelial walls to the blood stream in response to physiological stress. This is essential for the recognition and clearing of infected, transformed or damaged cells. One of the most potent stimuli to recruit immune cells to the circulation is exercise. Accordingly, exercise has proven beneficial in disease settings, such as cancer and diabetes. Interleukin‐6 (IL‐6) is released from contracting skeletal muscle in response to exercise, and rodent studies have established a link between exercise‐induced IL‐6 and recruitment of natural killer (NK) cells. Whether exercise‐induced IL‐6 is involved in regulating NK cell mobilization in humans is unclear. This study explored the effect of IL‐6 receptor blockade on immune cell mobilization during an acute bout of exercise in humans. In a randomized, placebo‐controlled clinical study, abdominally obese humans receiving placebo infusions or tocilizumab infusions performed an acute bout of exercise before and after the intervention. Immune cell recruitment was measured by flow cytometry. IL‐6 receptor blockade attenuated the increase of NK cells by 53% (mean difference −0.49 (95% CI: −0.89 to −0.08) × 109 cells L−1, P < 0.001) and dendritic cells by 66% (mean difference −0.14 (95% CI: −0.28 to 0.010) × 109 cells L−1, P < 0.001) induced by an acute bout of exercises. No changes were observed for T cells, monocytes and neutrophils. Treatments which interact with the exercise‐mediated immune surveillance provide relevant clinical information in pursuing the ‘exercise as medicine’ concept.
Kinesthetic Metaphors for Precise Spatial Manipulation: A Study of Object Rotation
Authors: Mohanty Ronak R. , Krishnamurthy Vinayak R. 
Published: October 2020

AbstractIn this article, we report on our investigation of kinesthetic feedback as a means to provide precision, accuracy, and mitigation of arm fatigue in spatial manipulation tasks. Most works on spatial manipulation discuss the use of haptics (kinesthetic/force and tactile) primarily as a means to offer physical realism in spatial user interfaces (SUIs). Our work offers a new perspective in terms of how force-feedback can promote precise manipulations in spatial interactions to aid manual labor, controllability, and precision. To demonstrate this, we develop, implement, and evaluate three new haptics-enabled interaction techniques (kinesthetic metaphors) for precise rotation of 3D objects. The quantitative and qualitative analyses of experiments reveal that the addition of force-feedback improves precision for each of the rotation techniques. Self-reported user feedback further exposes a novel aspect of kinesthetic manipulation in its ability to mitigate arm fatigue for close-range spatial manipulation tasks.
A clinician's guide to managing atopic dermatitis in dogs
Authors: Barnard Natalie 
Published: October 2020

BackgroundAtopic dermatitis is a complex condition in dogs that requires lifelong management. As such, veterinarians and owners must work together to manage these difficult cases to get the best clinical outcome for the animal.Aim of the articleThis article provides a guide to the different management options available for dealing with cases of atopic dermatitis in dogs, and things to consider when deciding on the best course of action.
Lithostratigraphic and structural data from Hardangervidda, southern Norway supporting extended interaction between Avalonia and Baltica
Authors: Andresen Arild 
Published: October 2020

Abstract
Lithostratigraphic and structural data from the Early Paleozoic Hardangervidda Group in southern Norway indicate that SW Baltica was affected several hundred kilometres NE of the inferred collision zone with Avalonia (Thor Suture). The first sign of plate interaction was the deposition of a 50–60 m-thick quartz arenite (Holberg Formation) of Floian/Dapingian age in an otherwise mud- and carbonate-dominated shelf. An overlying 5–6 m-thick marble unit of Dapingian–Darriwilian age (‘Orthoceratite Limestone’) marks a change into greenish-grey, calcareous phyllite, locally with beds of impure marble and poorly sorted metasandstone (Solnut Formation).

A series of décollement folds (D
2
structures) with axes orientated NW–SE (cross-folds) which superimposed a thin-skinned fold thrust with a NE–SW trend (D
1
structures) are interpreted as having developed during the progressive underthrusting of Baltica underneath Avalonia. Support for this model is seen in detrital zircon populations: with the Holberg and underlying formations having a Baltican signature, in contrast to the overlying Solnut Formation with a peri-Gondwana signature, including a distinct Late Neoproterozoic zircon population. It is further speculated that the
c.
471–458 Ma Garborg eclogite and surrounding paragneisses in the Stavanger area are related to the suture zone between Baltica and Avalonia rather than being related to the Iapetus Ocean and Laurentia, as generally thought.
Area-Level Variation and Human Papillomavirus Vaccination among Adolescents and Young Adults in the United States: A Systematic Review
Authors: Do Elizabeth K. , Rossi Brianna , Miller Carrie A. , Ksinan Albert J. , Wheeler David C. , Chukmaitov Askar , Cyrus John W. , Fuemmeler Bernard F. 
Published: October 2020

Abstract
Understanding how human papillomavirus (HPV) vaccination coverage varies by geography can help to identify areas of need for prevention and control efforts. A systematic review of the literature was conducted using a combination of keywords (HPV vaccination, geography, neighborhoods, and sociodemographic factors) on Medline and Embase databases. Studies had to provide information on HPV vaccination by area-level variables, be conducted in the United States, and be published in English (analyzing data from January 2006 to February 2020). Conference abstracts and opinion pieces were excluded. Of 733 records identified, 25 were included for systematic review. Across studies, the average initiation rate was 40.5% (range, 6.3%–78.0%). The average rate of completion was 23.4% (range, 1.7%–55.2%). Geographic regions and area-level factors were associated with HPV vaccination, including zip code tabulation area-level poverty, urbanicity/rurality, racial/ethnic composition, and health service region characteristics. Only three studies utilized geospatial approaches. None accounted for geospatial–temporal associations. Individual-level and area-level factors and their interactions are important for characterizing HPV vaccination. Results demonstrate the need to move beyond existing multilevel methods and toward the adoption of geospatial approaches that allow for the mapping and detection of geographic areas with low HPV vaccination coverage.
Genetic Variants in the Regulatory T cell–Related Pathway and Colorectal Cancer Prognosis
Authors: Neumeyer Sonja , Hua Xinwei , Seibold Petra , Jansen Lina , Benner Axel , Burwinkel Barbara , Halama Niels , Berndt Sonja I. , Phipps Amanda I. , Sakoda Lori C. , Schoen Robert E. , Slattery Martha L. , Chan Andrew T. , Gala Manish , Joshi Amit D. , Ogino Shuji , Song Mingyang , Herpel Esther , Bläker Hendrik , Kloor Matthias , Scherer Dominique , Ulrich Alexis , Ulrich Cornelia M. , Win Aung K. , Figueiredo Jane C. , Hopper John L. , Macrae Finlay , Milne Roger L. , Giles Graham G. , Buchanan Daniel D. , Peters Ulrike , Hoffmeister Michael , Brenner Hermann , Newcomb Polly A. , Chang-Claude Jenny 
Published: October 2020

AbstractBackground:High numbers of lymphocytes in tumor tissue, including T regulatory cells (Treg), have been associated with better colorectal cancer survival. Tregs, a subset of CD4+ T lymphocytes, are mediators of immunosuppression in cancer, and therefore variants in genes related to Treg differentiation and function could be associated with colorectal cancer prognosis.Methods:In a prospective German cohort of 3,593 colorectal cancer patients, we assessed the association of 771 single-nucleotide polymorphisms (SNP) in 58 Treg-related genes with overall and colorectal cancer–specific survival using Cox regression models. Effect modification by microsatellite instability (MSI) status was also investigated because tumors with MSI show greater lymphocytic infiltration and have been associated with better prognosis. Replication of significant results was attempted in 2,047 colorectal cancer patients of the International Survival Analysis in Colorectal Cancer Consortium (ISACC).Results:A significant association of the TGFBR3 SNP rs7524066 with more favorable colorectal cancer–specific survival [hazard ratio (HR) per minor allele: 0.83; 95% confidence interval (CI), 0.74–0.94; P value: 0.0033] was replicated in ISACC (HR: 0.82; 95% CI, 0.68–0.98; P value: 0.03). Suggestive evidence for association was found with two IL7 SNPs, rs16906568 and rs7845577. Thirteen SNPs with differential associations with overall survival according to MSI in the discovery analysis were not confirmed.Conclusions:Common genetic variation in the Treg pathway implicating genes such as TGFBR3 and IL7 was shown to be associated with prognosis of colorectal cancer patients.Impact:The implicated genes warrant further investigation.
Low Subcutaneous Adiposity and Mortality in Esophageal Cancer
Authors: Zhou Margaret J. , Tseng Luke , Guo Xiaotao , Jin Zhezhen , Bentley-Hibbert Stuart , Shen Sherry , Araujo James L. , Spinelli Cathy F. , Altorki Nasser K. , Sonett Joshua R. , Neugut Alfred I. , Abrams Julian A. 
Published: October 2020

Abstract

Background:
Recent data suggest that subcutaneous adiposity represents an independent prognostic marker in cancer. We aimed to determine whether subcutaneous adiposity estimated by the subcutaneous adiposity tissue index (SATI) was associated with mortality in esophageal cancer.

Methods:
We conducted a retrospective analysis of a prospectively enrolled cohort from 2009 to 2015 with esophageal cancer at two major cancer centers. CT scans for initial staging were used to quantify adiposity and skeletal muscle areas. Subjects were categorized as above or below median SATI using sex-specific values. Sarcopenia was defined using previously established skeletal muscle area cutoffs. Cox proportional hazards modeling was performed to determine associations between SATI and all-cause mortality.

Results:
Of the original 167 patients, 78 met inclusion criteria and had CT images available. Mean age was 67 years, 81.8% had adenocarcinoma, and 58.9% had stage 3 or 4 disease. Median follow-up time was 29.5 months. Overall 5-year survival was 38.9% [95% confidence interval (CI), 26.8–50.7]. Lower body mass index, higher Charlson comorbidity score, and more advanced stage were independently associated with low SATI. Patients with low SATI had increased mortality (unadjusted HR 2.23; 95% CI, 1.20–4.12), even when adjusted for sarcopenia or for percent weight loss. In a multivariable model including age, histology, stage, and receipt of curative surgery, the association between low SATI and mortality was attenuated (adjusted HR 1.64; 95% CI, 0.81–3.34).

Conclusions:
Low subcutaneous adiposity as estimated by SATI may be associated with increased mortality in esophageal cancer.

Impact:
Interventions to reduce loss of subcutaneous fat may improve survival in esophageal cancer.
Adiposity and Endometrial Cancer Risk in Postmenopausal Women: A Sequential Causal Mediation Analysis
Authors: Dashti S. Ghazaleh , English Dallas R. , Simpson Julie A. , Karahalios Amalia , Moreno-Betancur Margarita , Biessy Carine , Rinaldi Sabina , Ferrari Pietro , Tjønneland Anne , Halkjær Jytte , Dahm Christina C. , Vistisen Helene Tilma , Menegaux Florence , Perduca Vittorio , Severi Gianluca , Aleksandrova Krasimira , Schulze Matthias B. , Masala Giovanna , Sieri Sabina , Tumino Rosario , Macciotta Alessandra , Panico Salvatore , Hiensch Anouk E. , May Anne M. , Quirós J. Ramón , Agudo Antonio , Sánchez Maria-Jose , Amiano Pilar , Colorado-Yohar Sandra , Ardanaz Eva , Allen Naomi E. , Weiderpass Elisabete , Fortner Renée Turzanski , Christakoudi Sofia , Tsilidis Konstantinos K. , Riboli Elio , Kaaks Rudolf , Gunter Marc J. , Viallon Vivian , Dossus Laure 
Published: October 2020

AbstractBackground:Adiposity increases endometrial cancer risk, possibly through inflammation, hyperinsulinemia, and increasing estrogens. We aimed to quantify the mediating effects of adiponectin (anti-inflammatory adipocytokine); IL6, IL1-receptor antagonist, TNF receptor 1 and 2, and C-reactive protein (inflammatory status biomarkers); C-peptide (hyperinsulinemia biomarker); and free estradiol and estrone (estrogen biomarkers) in the adiposity–endometrial cancer link in postmenopausal women.Methods:We used data from a case–control study within the European Prospective Investigation into Cancer and Nutrition (EPIC). Eligible women did not have cancer, hysterectomy, and diabetes; did not use oral contraceptives or hormone therapy; and were postmenopausal at recruitment. Mediating pathways from adiposity to endometrial cancer were investigated by estimating natural indirect (NIE) and direct (NDE) effects using sequential mediation analysis.Results:The study included 163 cases and 306 controls. The adjusted OR for endometrial cancer for body mass index (BMI) ≥30 versus ≥18.5−&lt;25 kg/m2 was 2.51 (95% confidence interval, 1.26–5.02). The ORsNIE were 1.95 (1.01–3.74) through all biomarkers [72% proportion mediated (PM)] decomposed as: 1.35 (1.06–1.73) through pathways originating with adiponectin (33% PM); 1.13 (0.71–1.80) through inflammation beyond (the potential influence of) adiponectin (13% PM); 1.05 (0.88–1.24) through C-peptide beyond adiponectin and inflammation (5% PM); and 1.22 (0.89–1.67) through estrogens beyond preceding biomarkers (21% PM). The ORNDE not through biomarkers was 1.29 (0.54–3.09). Waist circumference gave similar results.Conclusions:Reduced adiponectin and increased inflammatory biomarkers, C-peptide, and estrogens mediated approximately 70% of increased odds of endometrial cancer in women with obesity versus normal weight.Impact:If replicated, these results could have implications for identifying targets for intervention to reduce endometrial cancer risk in women with obesity.
Implications of MYC Rearrangements in Newly Diagnosed Multiple Myeloma
Authors: Abdallah Nadine , Baughn Linda B. , Rajkumar S. Vincent , Kapoor Prashant , Gertz Morie A. , Dispenzieri Angela , Lacy Martha Q. , Hayman Suzanne R. , Buadi Francis K. , Dingli David , Go Ronald S. , Hwa Yi L. , Fonder Amie , Hobbs Miriam , Lin Yi , Leung Nelson , Kourelis Taxiarchis , Warsame Rahma , Siddiqui Mustaqeem , Lust John , Kyle Robert A. , Ketterling Rhett , Bergsagel Leif , Greipp Patricia , Kumar Shaji K. 
Published: October 2020

Abstract

Purpose:
Rearrangements involving the MYC protooncogene are common in newly diagnosed multiple myeloma, but their prognostic significance is still unclear. The purpose of this study was to assess the impact of MYC rearrangement on clinical characteristics, treatment response, and survival in patients with newly diagnosed multiple myeloma.

Experimental Design:
This is a retrospective study including 1,342 patients seen in Mayo Clinic in Rochester, MN, from January 2006 to January 2018, who had cytogenetic testing by FISH at diagnosis, including MYC testing using the break apart FISH probe (8q24.1).

Results:
A rearrangement involving MYC was found in 8% of patients and was associated with elevated β2-microglobulin, ≥50% bone marrow plasma cells, IgA multiple myeloma, and the cooccurrence of trisomies. There were no differences in overall response rates between patients with and without MYC rearrangement when induction chemotherapy was proteasome inhibitor (PI)-based, immunomodulatory drug (IMiD)-based or PI + IMiD-based. Overall survival was shorter in patients with MYC rearrangement compared with patients without MYC rearrangement (5.3 vs. 8.0 years, P &lt; 0.001). MYC rearrangement was associated with increased risk of death on multivariate analysis when high-risk cytogenetic abnormalities, ISS stage III, and ≥70 years of age were included (risk ratio: 1.5; P = 0.007).

Conclusions:
MYC rearrangement is associated with high disease burden and is an independent adverse prognostic factor in patients with newly diagnosed multiple myeloma.
Antegrade Blood Flow on 4‐Dimensional Computed Tomography Angiography Predict Stroke Subtype in Patients With Acute Large Artery Occlusion
Authors: Zhang Meixia , Chen Zhicai , Xu Jinjin , Gong Xiaoxian , Shi Feina , Lou Min 
Published: October 2020

Background
The purpose of this study was to determine whether the presence of antegrade blood flow was related to stroke subtype in patients with acute intracranial large artery occlusion.

Methods and Results

The prospectively collected data for consecutive patients who had occlusion of the unilateral M1 segment of the middle cerebral artery with or without internal carotid artery and received reperfusion therapy were retrospectively reviewed. Stroke causes were determined according to the Trial of
ORG
10172 in Acute Stroke Treatment standard. We defined antegrade flow as early opacification at the distal interface of the clot with subsequent distal extension on 4‐dimensional computed tomography angiography. A total of 387
large artery occlusion
patients were analyzed (229 men and 158 women; mean age, 71±14 years), including 77 (19.9%) with large artery atherosclerosis (
LAA
), 206 (53.2%) with cardioembolism, and 104 (26.9%) with undetermined causes. Antegrade flow was found in 206 (53.2%) patients, and 181 (46.8%) presented with retrograde flow. The rate of antegrade flow was much higher in patients with
LAA
than in those with cardioembolism (85.7% versus 42.2%,
P
<0.001). Multivariable logistic regression revealed that presence of antegrade flow was significantly associated with cuse of
LAA
after adjusting for confounding factors, when setting cardioembolism as reference (odds ratio, 5.650; 95% confidence interval, 2.451–13.158;
P
<0.001). The sensitivity, specificity, and positive and negative predictive values of the antegrade flow for predicting
LAA
were 43.1%, 91.5%, 85.7%, and 57.8%, respectively.

Conclusions

Using 4‐dimensional computed tomography angiography, antegrade flow can be identified in more than half of acute anterior
large artery occlusion
patients and occurs more frequently in those with
LAA
as the cause of stroke.
HIV Protease Inhibitor Ritonavir Impairs Endothelial Function Via Reduction in Adipose Mass and Endothelial Leptin Receptor‐Dependent Increases in NADPH Oxidase 1 (Nox1), C‐C Chemokine Receptor Type 5 (CCR5), and Inflammation
Authors: Bruder‐Nascimento Thiago , Kress Taylor C. , Kennard Simone , Belin de Chantemèle Eric J. 
Published: October 2020

Background
Cardiovascular disease is currently the leading cause of death in patients with human immunodeficiency virus on combination antiretroviral therapy. Although the use of the protease inhibitor ritonavir has been associated with increased prevalence of cardiovascular disease, the underlying mechanisms remain ill‐defined. Herein, we tested the hypothesis that ritonavir‐mediated lipoatrophy causes endothelial dysfunction via reducing endothelial leptin signaling.

Methods and Results

Long‐term (4 weeks) but not short‐term (3 days) treatment with ritonavir reduced body weight, fat mass, and leptin levels and induced endothelial dysfunction in mice. Moreover, ritonavir increased vascular NADPH oxidase 1, aortic H
2
O
2
levels as well as interleukin‐1β, GATA3 (GATA binding protein 3), the macrophage marker (F4/80), and C‐C chemokine receptor type 5 (CCR5) expression. Reactive oxygen species scavenging with tempol restored endothelial function, and both NADPH oxidase 1 and CCR5 deletion in mice protected from ritonavir‐mediated endothelial dysfunction and vascular inflammation. Remarkably, leptin infusion markedly improved endothelial function and significantly reduced vascular NADPH oxidase 1, interleukin‐1β, GATA3, F4/80, and CCR5 levels in ritonavir‐treated animals. Selective deficiency in endothelial leptin receptor abolished the protective effects of leptin infusion on endothelial function. Conversely, selective increases in endothelial leptin signaling with protein tyrosine phosphatase deletion blunted ritonavir‐induced endothelial dysfunction.

Conclusions
All together, these data indicate that ritonavir‐associated endothelial dysfunction is a direct consequence of a reduction in adiposity and leptin secretion, which decreases endothelial leptin signaling and leads to a NADPH oxidase 1–induced, CCR5‐mediated reduction in NO bioavailability. These latter data also introduce leptin deficiency as an additional contributor to cardiovascular disease and leptin as a negative regulator of CCR5 expression, which may provide beneficial avenues for limiting human immunodeficiency virus infection.
Mating behavior and spermatophore morphology of the whip scorpion Typopeltis dalyi Pocock, 1900 (Uropygi, Thelyphonida)
Authors: Seiter Michael , Moser Marie Christine , Schwaha Thomas 
Published: October 2020

Abstract
Whip scorpions are an enigmatic group of terrestrial raptorial arachnids that show remarkable mating and courtship behavior in which the male forms a complex spermatophore. While whip spiders (Amblypygi) are relatively well-studied, whip scorpions (Uropygi) are poorly known. The two orders form the Pedipalpi, whip scorpions (Uropygi include Thelyphonida and Schizomida) and whip spiders (Amblypygi). Two major groups have been described based on the mode of sperm transfer that differ in the duration and mode of the typical female–male tandem mating dance. Because comprehensive studies are lacking, in this study we add to our knowledge of the reproductive biology of whip scorpions by analyzing the mating behavior and spermatophore morphology of the previously unstudied species Typopeltis dalyi Pocock, 1900. Our observations show that this species belongs to the second group and supports the hypothesis of P. Weygoldt that their mode of sperm transfer appears more effective than that of the first group and that sufficient sperm can be supplied with one mating. The mating behavior and spermatophore morphology in T. dalyi are similar to those of closely related species and add additional characters applicable for species classification and phylogenetic inferences.