bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nurr1 repression mediates cardinal features of Parkinson’s disease in α-synuclein transgenic mice
Authors: Argyrofthalmidou Maria , Spathis Athanasios D , Maniati Matina , Poula Amalia , Katsianou Maira A , Sotiriou Evangelos , Manousaki Maria , Perier Celine , Papapanagiotou Ioanna , Papadopoulou-Daifoti Zeta , Pitychoutis Pothitos M , Alexakos Pavlos , Vila Miquel , Stefanis Leonidas , Vassilatis Demetrios K 
Published: April 2021

AbstractDuplication/triplication mutations of the SNCA locus, encoding alpha-synuclein (ASYN), and loss of function mutations in Nurr1, a nuclear receptor guiding midbrain dopaminergic neuron development, are associated with familial Parkinson’s disease (PD). As we age, the expression levels of these two genes in midbrain dopaminergic neurons follow opposite directions and ASYN expression increases while the expression of Nurr1 decreases. We investigated the effect of ASYN and Nurr1 age-related expression alterations in the pathogenesis of PD by coupling Nurr1 hemizygous with ASYN(s) (heterozygote) or ASYN(d) (homozygote) transgenic mice. ASYN(d)/Nurr1+/− (2-hit) mice, contrary to the individual genetic traits, developed phenotypes consistent with dopaminergic dysfunction. Aging ‘2-hit’ mice manifested kyphosis, severe rigid paralysis, L-DOPA responsive movement impairment and cachexia and died prematurely. Pathological abnormalities of phenotypic mice included SN neuron degeneration, extensive neuroinflammation and enhanced ASYN aggregation. Mice with two wt Nurr1 alleles [ASYN(d)/Nurr1+/+] or with reduced ASYN load [ASYN(s)/Nurr1+/−] did not develop the phenotype or pathology. Critically, we found that aging ASYN(d), in contrast to ASYN(s), mice suppress Nurr1-protein levels in a brain region–specific manner, which in addition to Nurr1 hemizygosity is necessary to instigate PD pathogenesis. Our experiments demonstrate that ASYN-dependent PD-related pathophysiology is mediated at least in part by Nurr1 down-regulation.
How Internet Access Drives Global Vaccine Skepticism
Authors: Lunz Trujillo Kristin , Motta Matthew 
Published: April 2021

Abstract
Counterintuitively, wealthier countries tend to be more vaccine skeptical than poorer countries. One possible explanation—the Online Accessibility hypothesis—posits that internet access facilitates the spread of antivaccine misinformation, particularly for those lower in scientific and medical expert trust. Another explanation—the Out of Sight hypothesis—is that some citizens in richer countries fail to consider the risks of vaccine-preventable diseases because they are rarely experienced directly. Merging country-level data with nationally representative survey data (N = 149,014) from 144 countries, we find evidence for the Online Accessibility hypothesis. These findings are robust to alternate measures of wealth and modeling strategies.
Lipopolysaccharide endotoxin injections elevated salivary TNFα and corneal temperatures and induced dynamic changes in circulating leukocytes, inflammatory cytokines, and metabolic indicators in wether lambs
Authors: Cadaret Caitlin N , Abebe Marytza D , Barnes Taylor L , Posont Robert J , Yates Dustin T 
Published: April 2021

Abstract
Pathogenic infections increase morbidity and reduce performance in livestock, and thus understanding the comprehensive physiological changes associated with infections can benefit production sustainability. In this study, we sought to investigate such physiological responses to an acute immune challenge in lambs. Polypay wethers received single IV injections of 1.5 µg/kg lipopolysaccharide endotoxin (LPS-injected; n = 6) or saline (controls; n = 6). Corneal temperatures (via infrared thermography), rectal temperatures, blood, plasma, and saliva were assessed every 2 hr for 10 hr after injections. Blood was also assessed at 24 hr. LPS-injected lambs exhibited elevated (P &lt; 0.05) corneal and rectal temperatures that peaked at 4 hr but were still slightly greater (P &lt; 0.05) than controls at 10 hr. Circulating total white blood cells, monocytes, and granulocytes were reduced (P &lt; 0.05) in LPS-injected lambs within the first 4 hr but were subsequently greater (P &lt; 0.05) than in controls. Lymphocytes were reduced (P &lt; 0.05) in LPS-injected lambs over the first 8 hr and did not differ from controls thereafter. Red blood cells, hematocrit, and hemoglobin were increased (P &lt; 0.05) in LPS-injected lambs over the first 6 hr, indicating mild dehydration. Blood glucose briefly increased (P &lt; 0.05) in LPS-injected lambs at 2 hr but was less (P &lt; 0.05) than in controls thereafter. Blood lactate was greater (P &lt; 0.05) in LPS-injected lambs between 6 and 10 hr after injections, which together with reduced (P &lt; 0.05) CO2 partial pressure indicated a metabolic shift toward glycolysis. LPS-injected lambs exhibited a transient increase (P &lt; 0.05) in plasma TNFα at 2 and 4 hr only and sustained increases (P &lt; 0.05) in CXCL9 and CXCL10 beginning at 6 and 4 hr, respectively. They also exhibited a mild, paradoxical increase (P &lt; 0.05) in the anti-inflammatory sFRP3. Salivary TNFα was increased (P &lt; 0.05) in LPS-injected lambs at 2 hr only. Regression analyses indicated that rectal temperatures were a generally poor predictor of the other inflammatory components in this study, with the exception of circulating leukocyte populations. Likewise, correlations among the 10 cytokines measured in this study were generally weak, with notable exceptions between CXCL9 and CXCL10 and between IL-21 and IFNγ. These findings demonstrate that physiological changes to even short-lived immune challenges are dynamic in nature and persist beyond the time frame of febrile responses and other common assessments.
Two New Species of Chiggers (Trombidiformes: Trombiculidae) From Brazil
Authors: Bassini-Silva Ricardo , Welbourn Cal , Ochoa Ron 
Published: April 2021

AbstractChigger mites are parasites of terrestrial vertebrates, including humans. Here, we describe two new species belonging to the American genera Colicus Brennan and Parasecia Loomis. Both species were described on the base of museum specimens originated from Minas Gerais State, Brazil, Colicus barrosbattestiae n. sp. parasitizing the rodent, Oligoryzomys fornesi and Parasecia jacinaviciusi n. sp. parasitizing the marsupial, Monodelphis domestica.
Atraumatic Vertebral Artery Dissection in a Patient With a Migraine Headache
Authors: Lloyd Michael L , Billingslea Samuel , Slama Richard 
Published: April 2021

ABSTRACT
This case discusses a 34-year-old active duty male who presented to the emergency department with a 2-week persistent headache. His initial review of symptoms was reassuring until a detailed neurologic examination on his second visit revealed a visual deficit in the left upper quadrant. Additionally, he complained of intermittent tension headaches for the last several years but had no history of diagnosed migraines until he was seen 4 days prior for empiric migraine therapy in the same emergency department and left without improvement in symptoms. On his return visit, computerized tomography scan with intravenous contrast revealed a left vertebral artery dissection and hematoma. The patient was admitted for medical management and subsequently found to have suffered a small infarction of right lingual gyrus cortex on magnetic resonance imaging. This case illustrates the importance of maintaining a broad differential diagnosis and high index of suspicion in the patient with new focal neurologic findings in order to diagnose a potentially fatal disease.
Slow chromatin dynamics enhances promoter accessibility to transcriptional condensates
Authors: Yamamoto Tetsuya , Sakaue Takahiro , Schiessel Helmut 
Published: April 2021

Abstract
Enhancers are DNA sequences at a long genomic distance from target genes. Recent experiments suggest that enhancers are anchored to the surfaces of condensates of transcription machinery and that the loop extrusion process enhances the transcription level of their target genes. Here, we theoretically study the polymer dynamics driven by the loop extrusion of the linker DNA between an enhancer and the promoter of its target gene to calculate the contact probability of the promoter to the transcription machinery in the condensate. Our theory predicts that when the loop extrusion process is active, the contact probability increases with increasing linker DNA length. This finding reflects the fact that the relaxation time, with which the promoter stays in proximity to the surface of the transcriptional condensate, increases as the length of the linker DNA increases. This contrasts the equilibrium case for which the contact probability between the promoter and the transcription machineries is smaller for longer linker DNA lengths.
Characteristics of diffuse hemispheric gliomas, H3 G34-mutant in adults
Authors: Picart Thiébaud , Barritault Marc , Poncet Delphine , Berner Lise-Prune , Izquierdo Cristina , Tabouret Emeline , Figarella-Branger Dominique , Idbaïh Ahmed , Bielle Franck , Bourg Véronique , Vandenbos Fanny Burel , Moyal Elizabeth Cohen-Jonathan , Uro-Coste Emmanelle , Guyotat Jacques , Honnorat Jérôme , Gabut Mathieu , Meyronet David , Ducray François 
Published: April 2021

Abstract

Background
Diffuse hemispheric gliomas, H3 G34-mutant (DHG H3G34-mutant) constitute a distinct type of aggressive brain tumors. Although initially described in children, they can also affect adults. The aims of this study were to describe the characteristics of DHG H3G34-mutant in adults and to compare them to those of established types of adult WHO grade IV gliomas.

Methods
The characteristics of 17 adult DHG H3G34-mutant, 32 H3.3 K27M-mutant diffuse midline gliomas (DMG), 100 IDH-wildtype, and 36 IDH-mutant glioblastomas were retrospectively analyzed.

Results
Median age at diagnosis in adult DHG H3G34-mutant was 25 years (range: 19–33). All tumors were hemispheric. For 9 patients (56%), absent or faint contrast enhancement initially suggested another diagnosis than a high-grade glioma, and diffusion-weighted imaging seemed retrospectively more helpful to suspect an aggressive tumor than MR-spectroscopy and perfusion MRI. All cases were IDH-wildtype. Most cases were immunonegative for ATRX (93%) and Olig2 (100%) and exhibited MGMT promoter methylation (82%). The clinical and radiological presentations of adult DHG H3G34-mutant were different from those of established types of adult grade IV gliomas. Median overall survival of adult DHG H3G34-mutant was 12.4 months compared to 19.6 months (P = .56), 11.7 months (P = .45), and 50.5 months (P = .006) in H3.3 K27M-mutant DMG, IDH-wildtype, and IDH-mutant glioblastomas, respectively.

Conclusions
Adult DHG H3G34-mutant are associated with distinct characteristics compared to those of established types of adult WHO grade IV gliomas. This study supports considering these tumors as a new type of WHO grade IV glioma in future classifications.
An overview of speciation and species limits in birds
Authors: Winker Kevin 
Published: April 2021

Abstract
Accurately determining avian species limits has been a challenge and a work in progress for most of a century. It is a fascinating but difficult problem. Under the biological species concept, only lineages that remain essentially independent when they are in sympatry are clearly species. Otherwise, there is no clear line yet found that marks when a pair of diverging lineages (e.g., in allopatry) become different enough to warrant full biological species status. Also, with more data, species limits often require reevaluation. The process of divergence and speciation is itself very complex and is the focus of intense research. Translating what we understand of that process into taxonomic names can be challenging. A series of issues are important. Single-locus criteria are unlikely to be convincing. Genetic independence is not a species limits requirement, but the degree of independence (gene flow) needs to be considered when there is opportunity for gene flow and independence is not complete. Time-based species (limits determined by time of separation) are unsatisfactory, though integrating time more effectively into our datasets is warranted. We need to disentangle data signal due to neutral processes vs. selection and prioritize the latter as the main driver of speciation. Assortative mating is also not likely to be an adequate criterion for determining species limits. Hybridization and gene flow are more important than ever, and there is a condition not being treated evenly in taxonomy: evolutionary trysts of 2 or more lineages stuck together through gene flow just short of speciation over long periods. Comparative methods that use what occurs between good species in contact to infer species limits among allopatric forms remain the gold standard, but they can be inaccurate and controversial. Species-level taxonomy in birds is likely to remain unsettled for some time. While the study of avian speciation has never been more exciting and dynamic, there is no silver bullet for species delimitation, nor is it likely that there will ever be one. Careful work using integrative taxonomy in a comparative framework is the most promising way forward.
“Reasonable” Force at the U.S.-Mexico Border
Authors: Vega Irene I 
Published: April 2021

Abstract
While social scientists have studied the relationship between police culture and use of force for decades, federal immigration agents have been left out of these analyses. Addressing this gap is urgent given patterns of excessive force at the militarized U.S.-Mexico border. Drawing on bureaucratic documents and interviews with active Border Patrol agents, this article examines the culture of force within this organization. I show that the Border Patrol produces a sense of exceptional threat and power among agents through 1) narratives that construct the border as a uniquely dangerous work environment, and 2) lessons that encourage an overly-individualistic view of reasonableness, the constitutional standard that governs police force in the United States. Together, these organizational messages foster in agents a disproportionate sense of threat coupled with an awareness of the low probability of legal sanction for force violations. This paradoxical combination of vulnerability and power undergirds agents’ conceptions of their force authority.
Gender Differences in a Sample of Egyptian University Students With Opioid Use Disorders Attributed to Tramadol
Authors: Bassiony Medhat M. , El-Deen Ghada Salah , Saad Abdallah , Abdelghani Mohamed 
Published: April 2021

Background and Objective:
Tramadol use is an overwhelming problem in Egypt. Males and females who use tramadol differ in their sociodemographic and clinical profiles. The aim of this study was to identify gender differences in tramadol use in students at Zagazig University, Egypt.

Methods:
A cross-sectional study included a total of 1135 undergraduate students, aged 17 to 34 years, from both sexes; males (n=674, 59.4%) and females (n=461, 40.6%), from 10 colleges in Zagazig University. Respondents were randomly selected to assess their tramadol use utilizing the drug use disorders identification test (DUDIT) and the drug use disorders identification test-extended (DUDIT-E).

Results:
Tramadol use was more prevalent in male than female students (19.7% vs. 2.4%). Both smoking and alcohol use were shared predictive factors for tramadol use in both sexes. The mean years of education and cannabis use predicted tramadol use in males, while only mean age predicted tramadol use in females. Among tramadol users, males were more likely than females to be smokers, polysubstance, and cannabis users, and to have a positive attitude toward tramadol use.

Conclusions:
Tramadol use was common among university students, with higher prevalence among males. Sex-related similarities and differences were present. Results can guide health policymakers to develop appropriate prevention and management strategies. Population-based longitudinal studies are warranted to explore the causal relationship between tramadol use and progression to other substances in both sexes.
The Impact of Earplugs and Eye Masks on Sleep Quality in Surgical ICU Patients at Risk for Frequent Awakenings
Authors: Obanor Osamudiamen O. , McBroom Mandy M. , Elia Jennifer M. , Ahmed Farzin , Sasaki Jun D. , Murphy Kelly M. , Chalk Shannon , Menard Gloria A. , Pratt Nadia V. , Venkatachalam Aardhra M. , Romito Bryan T. 
Published: April 2021

OBJECTIVES:
Sleep disturbances may contribute to the development of delirium, prolonged ICU stay, and increased mortality. There is conflicting data on the effectiveness of earplugs and eye masks for sleep promotion in the ICU. This study evaluates the impact of earplugs and eye masks on sleep quality in postoperative surgical ICU patients at risk for frequent awakenings.

DESIGN:
Prospective randomized controlled trial.

SETTING:
Surgical ICU within the University of Texas Southwestern Medical Center.

PATIENTS:
Adult, female patients admitted to the surgical ICU requiring hourly postoperative assessments following breast free flap surgery between February 2018 and October 2019.

INTERVENTIONS:
Patients were randomized into an intervention group or a control group. The intervention group received earplugs and eye masks in addition to standard postoperative care, whereas the control group received standard postoperative care.

MEASUREMENTS AND MAIN RESULTS:
The primary outcome was overall sleep quality assessed via the Richards-Campbell Sleep Questionnaire. Secondary outcomes of patient satisfaction and rates of ICU delirium were assessed with a modified version of the Family Satisfaction in the ICU survey and the Confusion Assessment Method for the ICU. After a planned interim analysis, the study was stopped early because prespecified criteria for significance were attained. Compared with the control group’s average Richards-Campbell Sleep Questionnaire total score of 47.3 (95% CI, 40.8–53.8), the intervention group’s average Richards-Campbell Sleep Questionnaire total score was significantly higher at 64.5 (95% CI, 58.3–70.7; p = 0.0007). There were no significant between-group differences for Confusion Assessment Method for the ICU scores or modified Family Satisfaction in the ICU survey scores.

CONCLUSIONS:
These results suggest that earplugs and eye masks are effective in improving sleep quality in ICU patients undergoing frequent assessments. The results strengthen the evidence for nonpharmacologic sleep-promoting adjuncts in the ICU.
Mitochondria-Rich Fraction Isolated From Mesenchymal Stromal Cells Reduces Lung and Distal Organ Injury in Experimental Sepsis*
Authors: de Carvalho Luiza Rachel Pinheiro , Abreu Soraia Carvalho , de Castro Ligia Lins , Andrade da Silva Luísa Helena , Silva Paula Matos , Vieira Juliana Borges , Santos Renata Trabach , Cabral Marianna Ribeiro , Khoury Maroun , Weiss Daniel J. , Lopes-Pacheco Miquéias , Silva Pedro Leme , Cruz Fernanda Ferreira , Rocco Patricia Rieken Macedo 
Published: April 2021

OBJECTIVES:
To ascertain whether systemic administration of mitochondria-rich fraction isolated from mesenchymal stromal cells would reduce lung, kidney, and liver injury in experimental sepsis.

DESIGN:
Animal study.

SETTING:
Laboratory investigation.

SUBJECTS:
Sixty C57BL/6 male mice.

INTERVENTIONS:
Sepsis was induced by cecal ligation and puncture; sham-operated animals were used as control. At 24 hours after surgery, cecal ligation and puncture and Sham animals were further randomized to receive saline or mitochondria-rich fraction isolated from mesenchymal stromal cells (3 × 106) IV. At 48 hours, survival, peritoneal bacterial load, lung, kidney, and liver injury were analyzed. Furthermore, the effects of mitochondria on oxygen consumption rate and reactive oxygen species production of lung epithelial and endothelial cells were evaluated in vitro.

MEASUREMENTS AND MAIN RESULTS:
In vitro exposure of lung epithelial and endothelial cells from cecal ligation and puncture animals to mitochondria-rich fraction isolated from mesenchymal stromal cells restored oxygen consumption rate and reduced total reactive oxygen species production. Infusion of exogenous mitochondria-rich fraction from mesenchymal stromal cells (mitotherapy) reduced peritoneal bacterial load, improved lung mechanics and histology, and decreased the expression of interleukin-1β, keratinocyte chemoattractant, indoleamine 2,3-dioxygenase-2, and programmed cell death protein 1 in lung tissue, while increasing keratinocyte growth factor expression and survival rate in cecal ligation and puncture-induced sepsis. Mitotherapy also reduced kidney and liver injury, plasma creatinine levels, and messenger RNA expressions of interleukin-18 in kidney, interleukin-6, indoleamine 2,3-dioxygenase-2, and programmed cell death protein 1 in liver, while increasing nuclear factor erythroid 2-related factor-2 and superoxide dismutase-2 in kidney and interleukin-10 in liver.

CONCLUSIONS:
Mitotherapy decreased lung, liver, and kidney injury and increased survival rate in cecal ligation and puncture-induced sepsis.
In-hospital Bleeding Outcomes of Oral Anticoagulant and Dual Antiplatelet Therapy During Percutaneous Coronary Intervention: An Analysis From the Japanese Nationwide Registry
Authors: Yashima Fumiaki , Inohara Taku , Nishida Hiroaki , Shimoji Kenichiro , Ueno Koji , Noma Shigetaka , Yamaji Kyohei , Ishii Hideki , Tanaka Nobuhiro , Kohsaka Shun , Amano Tetsuya , Ikari Yuji 
Published: April 2021

Abstract:
The type of periprocedural antithrombotic regimen that is the safest and most effective in percutaneous coronary intervention (PCI) patients on oral anticoagulant (OAC) therapy has not been fully investigated. We aimed to retrospectively investigate the in-hospital bleeding outcomes of patients receiving OAC and antiplatelet therapies during PCI using Japanese nationwide multicenter registry data. A total of 26,938 patients who underwent PCI with OAC and antiplatelet therapies between 2016 and 2017 were included. We investigated in-hospital bleeding requiring blood transfusion, mortality, and stent thrombosis according to the antithrombotic regimens used at the time of PCI: OAC + single antiplatelet therapy (double therapy) and OAC + dual antiplatelet therapy (triple therapy). The antiplatelet agents included aspirin, clopidogrel, and prasugrel. The OAC agents included warfarin and direct OACs. Adjusting the dose of OAC or intermitting OAC before PCI was at each operator's discretion. In the study population [mean age (SD), 73.5 (9.5) years; women, 21.5%], the double therapy and triple therapy groups comprised 5546 (20.6%) and 21,392 (79.4%) patients, respectively. Bleeding requiring transfusion was not significantly different between the groups [adjusted odds ratio (aOR), 0.700; 95% confidence interval (CI), 0.420–1.160; P = 0.165] (triple therapy as a reference). Mortality was not significantly different (aOR, 1.370; 95% CI, 0.790–2.360; P = 0.258). Stent thrombosis was significantly different between the groups (aOR, 3.310; 95% CI, 1.040–10.500; P = 0.042) (triple therapy as a reference). In conclusion, for patients on OAC therapy who underwent PCI, periprocedural triple therapy may be safe with respect to in-hospital bleeding risks. However, further investigations are warranted to establish the safety and efficacy of periprocedural triple therapy.