bluuebunny/crossref_metadata_2025_split huggingface dataset:
Juvenile idiopathic inflammatory myopathies with anti‐3‐hydroxy‐3‐methylglutaryl‐coenzyme A reductase antibodies in a Chinese cohort
Authors: Hou Ying , Shao Kai , Zhao Bing , Dai Tingjun , Wang Qinzhou , Zhao Yuying , Yan Chuanzhu , Yan Yaping , Ma Xiaotian , Li Wei 
Published: May 2021

AbstractAimsTo characterize the clinical and histopathological characteristics and treatment outcomes of juvenile idiopathic inflammatory myopathies (JIIMs) with anti‐3‐hydroxy‐3‐methylglutaryl‐coenzyme A reductase (HMGCR) antibodies in a Chinese cohort.MethodsWe detected anti‐HMGCR antibodies in a series of Chinese JIIM by ELISA and indirect immunofluorescence assay on HEK293 cells, and summarized the clinical findings of these anti‐HMGCR antibody‐positive patients.ResultsOf 32 JIIM patients, 5 (15.63%) were found to be anti‐HMGCR antibody‐positive. The disease duration was 1.20 ± 0.45 months. Statin exposure was not found. Four patients had skin lesions, while typical pathological features of dermatomyositis such as perifascicular atrophy or myxovirus resistance protein A expression were not found. The mean creatine kinase level was 16771.60 U/L. Among the four patients who received long‐term (10.46 ± 1.42 years) follow‐up, three exhibited favorable outcomes with prednisone and additional immunosuppressants.ConclusionsOur study indicates that anti‐HMGCR antibodies may not be rare in Chinese JIIM. These anti‐HMGCR‐positive JIIMs were characterized by acute onset, substantially elevated creatine kinase level, and skin lesions without perifascicular changes in muscle pathology. The treatment outcome is generally favorable with the combination of steroid and immunosuppressant.
Patch testing of budesonide in Italy: The SIDAPA baseline series experience, 2018–2019
Authors: Stingeni Luca , Marietti Rossella , Bianchi Leonardo , Guarneri Fabrizio , Ferrucci Silvia Mariel , Faraci Andrea Giuseppe , Foti Caterina , Romita Paolo , Patruno Cataldo , Napolitano Maddalena , Gallo Rosella , Corazza Monica , Schena Donatella , Milanesi Nicola , Bruni Francesca , Pigatto Paolo , Musumeci Maria Letizia , Martina Emanuela , Piras Viviana , Tramontana Marta , Hansel Katharina 
Published: May 2021

AbstractBackgroundBudesonide was included in the European Baseline Series in 2000 as the most suitable marker forcorticosteroid hypersensitivity. In the last two decades, a decreasing trend of budesonide allergy has been observed.ObjectivesTo estimate the prevalence of positive patch test reactions to budesonide in a large, Italian patch test population, characterizing patients according to MOAHLFA index and evaluating the benefit with extended readings of budesonide patch test.MethodsRetrospective analysis of patient demographics and patch test results over a 2‐year period (2018–2019) was performed at 14 patch test clinics in Italy.ResultsNinety out of 14 544 (0.6%) patients reacted to budesonide 0.01% pet.. Positive reactions were mild in 54.4% and late readings at day 7 showed new positive reactions in 37.8% of patients. The MOAHLFA index showed a significant positive association with male gender, atopic dermatitis, and age >40 years and a significant negative association with hand and face dermatitis.ConclusionsWe documented a low prevalence of budesonide allergy in Italy, confirming its decreasing trend recently reported in the literature. Nevertheless, budesonide needs to be maintained in the baseline series for its good ability to detect corticosteroid sensitization.
Prevalence and trend of allergen sensitization in patients referred for patch testing with a final diagnosis of psoriasis: North American Contact Dermatitis Group data, 2001‐2016
Authors: Silverberg Jonathan I. , Hou Alexander , DeKoven Joel G. , Warshaw Erin M. , Maibach Howard I. , Atwater Amber R. , Belsito Donald V. , Zug Kathryn A. , Taylor James S. , Sasseville Denis , Fransway Anthony F. , DeLeo Vincent A. , Pratt Melanie D. , Reeder Margo J. , Fowler Joseph F. , Zirwas Matthew J. , Marks James G. , Dunnick Cory A. , Houle Marie‐Claude 
Published: May 2021

AbstractBackgroundLittle is known about the relationship between psoriasis and allergic contact dermatitis (ACD).ObjectiveTo examine the associations with ACD, related clinical characteristics, and common positive and clinically relevant allergens of patients with a final diagnosis of psoriasis who were referred for patch testing.MethodsRetrospective analysis of 38 723 patients from the North American Contact Dermatitis Group.ResultsPatients with a final diagnosis of psoriasis had lower proportions of ACD than those without psoriasis (32.7% vs 57.8%). In multivariable logistic regression models, psoriasis was inversely associated with female sex, Black or Asian race, and history of atopic dermatitis and hay fever. Patients with a final diagnosis of psoriasis were less likely to have one or more positive allergic patch‐test reactions or to have a current clinically relevant patch‐test reaction to the majority of the most commonly positive and/or relevant allergens. The most clinically relevant allergens included nickel sulfate, methylisothiazolinone, and fragrance mix I.ConclusionApproximately one‐third of patients who were referred for patch testing with a final diagnosis of psoriasis were also diagnosed with ACD. In select patients with suspected psoriasis who also have a clinical presentation suggestive of ACD, patch testing may be helpful.
All that glitters is not gold! Independent directors' attributes and earnings quality: Beyond formal independence
Authors: Marra Antonio 
Published: May 2021

AbstractResearch Question/IssueThis paper examines the effect of additional independent directors' attributes, beyond formal independence, on earnings management practices.Research Findings/InsightsI find that being non‐busy, having accounting expertise, and being appointed by non‐controlling shareholders are relevant directors' attributes—beyond formal independence—in their earnings management monitoring task, among the directors' attributes I have tested. Additionally, the paper shows that independent directors who possess such features simultaneously outclass all other directors—included the touted effective formally independent directors—in mitigating earnings management activities.Theoretical/Academic ImplicationsI respond to calls for dismantling common wisdom on board independence, investigating factors leading to better monitoring, showing that independent directors are not all‐alike. With specific reference to directors' monitoring task, when controlling for additional directors' attributes, formal independence becomes uninfluential in constraining earnings management activities. I also show that the co‐existence of attributes makes independent directors more effective relative to board mates not sharing such attributes.Practitioner/Policy ImplicationsFindings of this work might be useful for practitioners in attempting to design corporate governance mechanisms better able to monitor earnings management practices through independent directors and may serve as a stimulus for regulators when re‐thinking regulations on board composition and structure.
The basic route of nuclear‐targeted transport of IGF‐1/IGF‐1R and potential biological functions in intestinal epithelial cells
Authors: Xiu Ming , Huan Xia , Ou Yang , Ying Sha , Wang Jianmeng 
Published: May 2021

AbstractObjectivesInsulin‐like growth factor (IGF‐1) plays an important role in many biological processes in the intestinal tract. However, the cellular behaviour and characteristics of IGF‐1/IGF‐1R in intestinal cells remain unclear.Materials and MethodsA series of techniques (such as indirect immunofluorescence, co‐localization and Western blot) have been used to systematically study the cellular behaviour of IGF‐1/IGF‐1R on intestinal cells.ResultsWe found that IGF‐1 can not only internalize into the cytoplasm, but also transport into the cell nuclei. We systematically studied the detailed molecular pathways of IGF‐1/IGF‐1R’s nuclear translocation. We found that IGF‐1R underwent clathrin‐mediated endocytosis into cells and then entered into Rab‐5‐positive endosomes. Dynein/dynactin were used as motors to drive Rab‐5‐positive endosomes carrying IGF‐1R (cargo molecule) to Golgi apparatus (transit station) along the surface of the microtubule. IGF‐1 and/or IGF‐1R entered the cell nuclei through NPC (nuclear pore complex), a process mediated by NUP358. Further study indicated that nuclear localization of IGF‐1 and/or IGF‐1R promoted cell proliferation and increased the nuclear residence time of signalling molecules activated by IGF‐1. Further experiments showed that IGF‐1R may regulate the transcription of genes in the cell nuclei, indicating that nuclear‐localized IGF‐1R plays an important in cell proliferation.ConclusionsIn short, we revealed the molecular mechanism by which IGF‐1/IGF‐1R transports into the cell nuclei of intestinal cells. More importantly, the current work showed that the nuclear‐localized IGF‐1R has important biological functions.
PINK1‐mediated mitophagy maintains pluripotency through optineurin
Authors: Wang Chaoqun , Liu Kun , Cao Jiani , Wang Liang , Zhao Qian , Li Zheng , Zhang Honghai , Chen Quan , Zhao Tongbiao 
Published: May 2021

AbstractObjectivesDysfunction of autophagy results in accumulation of depolarized mitochondria and breakdown of self‐renewal and pluripotency in ESCs. However, the regulators that control how mitochondria are degraded by autophagy for pluripotency regulation remains largely unknown. This study aims to dissect the molecular mechanisms that regulate mitochondrial homeostasis for pluripotency regulation in mouse ESCs.Materials and methodsParkin+/+ and parkin−/− ESCs were established from E3.5 blastocysts of parkin+/− x parkin+/− mating mice. The pink1−/−, optn−/− and ndp52−/− ESCs were generated by CRISPR‐Cas9. shRNAs were used for function loss assay of target genes. Mito‐Keima, ROS and ATP detection were used to investigate the mitophagy and mitochondrial function. Western blot, Q‐PCR, AP staining and teratoma formation assay were performed to evaluate the PSC stemness.ResultsPINK1 or OPTN depletion impairs the degradation of dysfunctional mitochondria during reprogramming, and reduces the reprogramming efficiency and quality. In ESCs, PINK1 or OPTN deficiency leads to accumulation of dysfunctional mitochondria and compromised pluripotency. The defective mitochondrial homeostasis and pluripotency in pink1−/− ESCs can be compensated by gain expression of phosphomimetic Ubiquitin (Ub‐S65D) together with WT or a constitutively active phosphomimetic OPTN mutant (S187D, S476D, S517D), rather than constitutively inactive OPTN (S187A, S476A, S517A) or a Ub‐binding dead OPTN mutant (D477N).ConclusionsThe mitophagy receptor OPTN guards ESC mitochondrial homeostasis and pluripotency by scavenging damaged mitochondria through TBK1‐activated OPTN binding of PINK1‐phosphorylated Ubiquitin.
The case for reintroduction: The jaguar (Panthera onca) in the United States as a model
Authors: Sanderson Eric W. , Beckmann Jon P. , Beier Paul , Bird Bryan , Bravo Juan Carlos , Fisher Kim , Grigione Melissa M. , López González Carlos A. , Miller Jennifer R. B. , Mormorunni Cristina , Paulson Laura , Peters Rob , Polisar John , Povilitis Tony , Robinson Michael J. , Wilcox Sharon 
Published: May 2021

AbstractReintroduction—defined here as the return of a species to a part of its range where it has been extirpated—is a critical pathway to conservation in the 21st century. As late as the 1960s, jaguars (Panthera onca) inhabited an expansive region in the central mountain ranges of Arizona and New Mexico in the United States, a habitat unique in all of jaguar range. Here, we make the case for reintroduction, building a rhetorical bridge between conservation science and practice. First, we present a rationale rooted in the philosophy of wildlife conservation. Second, we show that the species once occupied this territory and was extirpated by human actions that should no longer pose a threat. Third, we demonstrate that the proposed recovery area provides suitable ecological conditions. Fourth, we discuss how return of the species could be a net benefit to people, explicitly recognizing a diversity of values and concerns. Fifth, we show that reintroduction is practical and feasible over a realistic time horizon. Returning the jaguar to this area will enhance the recovery of an endangered species in the United States, further its range‐wide conservation, and restore an essential part of North America's cultural and natural heritage.
Oxypurinol pharmacokinetics and pharmacodynamics in healthy volunteers: Influence of BCRP Q141K polymorphism and patient characteristics
Authors: Vora Bianca , Brackman Deanna J. , Zou Ling , Garcia‐Cremades Maria , Sirota Marina , Savic Radojka M. , Giacomini Kathleen M. 
Published: May 2021

AbstractThe missense variant, breast cancer resistance protein (BCRP) p.Q141K, which encodes a reduced function BCRP, has been linked to poor response to allopurinol. Using a multifaceted approach, we aimed to characterize the relationship(s) between BCRP p.Q141K, the pharmacokinetics (PK) and pharmacodynamics (PD) of oxypurinol (the active metabolite of allopurinol), and serum uric acid (SUA) levels. A prospective clinical study (NCT02956278) was conducted in which healthy volunteers were given a single oral dose of 300 mg allopurinol followed by intensive blood sampling. Data were analyzed using noncompartmental analysis and population PK/PD modeling. Additionally, electronic health records were analyzed to investigate whether clinical inhibitors of BCRP phenocopied the effects of the p.Q141K variant with respect to SUA. Subjects homozygous for p.Q141K had a longer half‐life (34.2 ± 12.2 h vs. 19.1 ± 1.42 h) of oxypurinol. The PK/PD model showed that women had a 24.8% lower volume of distribution. Baseline SUA was affected by p.Q141K genotype and renal function; that is, it changed by 48.8% for every 1 mg/dl difference in serum creatinine. Real‐world data analyses showed that patients prescribed clinical inhibitors of BCRP have higher SUA levels than those that have not been prescribed inhibitors of BCRP, consistent with the idea that BCRP inhibitors phenocopy the effects of p.Q141K on uric acid levels. This study identified important covariates of oxypurinol PK/PD that could affect its efficacy for the treatment of gout as well as a potential side effect of BCRP inhibitors on increasing uric acid levels, which has not been described previously.
Immune response profiling in patients with traumatic injuries associated with alcohol ingestion
Authors: Breslin Adam W. , Limkakeng Alexander T. , Silvius Elizabeth , Staton Catherine A. , Almond Chandra , Joshi Mary‐Beth , Adams Bartley , Johnston Bria , McGowan Lauren , Kirk Allan D. , Elster Eric 
Published: May 2021

AbstractTraumatic injuries afflict more than 5 million people globally every year. Current and past animal research has demonstrated association among alcohol, trauma, and impaired immune function, whereas human registries have shown association between alcohol and morbidity as well as mortality. The purpose of this study is to elucidate the immune interactions with alcohol in traumatically injured patients. We prospectively enrolled 379 patients after trauma at three medical centers in the Surgical Critical Care Initiative. Plasma was analyzed using Luminex for up to 35 different cytokines. Collected samples were grouped by patients with detectable plasma alcohol levels versus those without. Univariate testing determined differences in analytes between groups. We built Bayesian belief networks with multiple minimum descriptive lengths to compare the two groups. All 379 patient samples were analyzed. Two hundred eighty‐two (74.4%) patients were men, and 143 (37.7%) were White. Patients had a median intensive care unit length of stay (LOS) of 5.8 days and hospital LOS of 12 days. Using single variate analyses, eight different cytokines were differentially associated with alcohol. Cytokines IL‐12 and IL‐6 were important nodes in both models and IL‐10 was a prominent node in the nonalcohol model. This study found select immune function differed between traumatically injured patients with measurable serum alcohol levels as compared with those without. Traumatically injured patients with positive blood alcohol content appear less able to inhibit inflammatory stress. Alcohol appears to suppress pro‐inflammatory IL‐12 and IL‐6, whereas patients without alcohol have greater levels of anti‐inflammatory IL‐10 expressed at injury and may better regulate anti‐inflammatory pathways. Future studies should determine the relationship with these markers with clinically oriented outcomes.
Development of sacral/buttock retiform purpura as an ominous presenting sign of COVID‐19 and clinical and histopathologic evolution during severe disease course
Authors: McBride Jeffrey D. , Narang Jatin , Simonds Robert , Agrawal Shruti , Rodriguez E. Rene , Tan Carmela D. , Baldwin William M. , Dvorina Nina , Krywanczyk Alison R. , Fernandez Anthony P. 
Published: May 2021

AbstractRetiform purpura has been described as a relatively frequent cutaneous finding in patients with coronavirus disease 2019 (COVID‐19). The etiology is hypothesized to be related to thrombotic vasculopathy based on lesional biopsy specimen findings, but the pathogenesis of the vasculopathy is not completely understood. Here, we present a case of a retiform purpuric patch on the sacrum/buttocks in a hospitalized patient prior to subsequent diagnosis of COVID‐19 and an eventual fatal disease course. Two lesional biopsy specimens at different time points in the disease course revealed thrombotic vasculopathy, despite therapeutic anticoagulation. Detailed histopathologic evaluation using immunohistochemical markers suggest the etiology of the vasculopathy involves both persistent complement activation and platelet aggregation, which possibly promote ongoing thrombus formation. This case highlights that sacral/buttock retiform purpuric patches may be a presenting sign of infection with SARS‐CoV‐2 virus and may represent an ominous sign supporting a future severe disease course. In addition, biopsy specimen findings at separate time points demonstrate that cutaneous vasculopathy may persist despite adequate systemic anticoagulation, possibly due to the combination of persistent complement and platelet activation. Finally, occlusive thrombi in sacral/buttock retiform purpuric patches may contribute to future ulceration and significant cutaneous morbidity in patients who survive COVID‐19.
Becoming a Learning Organization
Authors: Korn Randi , Chandler Katie , Marzec Colleen 
Published: May 2021

AbstractWhen staff at the National Museum of Natural History (NMNH) opened their newest visitor‐experience space, Q?rius (pronounced curious), in 2013, they intended to create an innovative science‐learning space that would provide visitors with hands‐on access to the museum’s world‐renowned natural history collections, skill‐building experiences, and personal encounters with science experts. Over the years since Q?rius opened, education staff noticed changes in how their colleagues from different departments were working together and suspected that in some contexts the organization was operating differently. In 2018, RK&A studied institutional‐level changes at NMNH as a result of Q?rius, and, more broadly, helped staff and leadership understand the ways in which NMNH is a “learning organization” and where there is room for development. In this article we explore the concept of a learning organization, present key takeaways of the NMNH study and how they have been applied in practice, and for those who wish for their organization to grow into a learning organization, provide essential concepts to help them think through how they might pursue such work in their museum.
Redefining Curatorial Leadership and Activating Community Expertise to Build Equitable and Inclusive Art Museums
Authors: Pegno Marianna , Brindza Christine 
Published: May 2021

AbstractLeadership in art museums is a changing construct: historically, these institutions were established as hierarchical, top‐down structures that prioritized sole expertise to dictate success. Today, museums are searching for ways to become more responsive, collaborative, and multivocal institutions that value community voices and expertise. A growing variety of museum professionals ask how to better reflect and integrate local communities within their museums. We share reflections, insights, and lessons learned from a multi‐year case study at the Tucson Museum of Art and Historic Block (TMA), which focuses on redefining curatorial leadership as community‐based and collaborative to expand approaches to exhibition development and interpretation. The authors of this article highlight how network governance/collaborative leadership can be applied to curatorial practice to develop exhibitions rooted in collaborative stewardship, multivocality, and community‐based approaches. Here, leadership is defined as a way in which a museum influences its communities and vice versa. In addition, we discuss strategies for building multi‐directional and collaborative initiatives to shape a more equitable and inclusive museum.
Museum Leadership for Engaging, Equitable Education: The Transformative Potential of Digitized Collections for Authentic Learning Experiences
Authors: Butcher Kirsten R. , Power Mitchell J. , Larson Madlyn , Orr Matthew P. , Velásquez‐Franco Susana , Hudson Michelle A. , Bailey Vanessa J. 
Published: May 2021

AbstractMuseums are local‐to‐global organizations operating in a digitized, distributed, and diverse 21st century world. Museums leaders face significant challenges in achieving broader relevance, meaningful engagement, and equitable outreach. This article examines the transformative potential of digitized collections to increase public engagement and enhance authentic educational efforts of museums, with specific emphasis on visual media as a key resource to achieve these outcomes. Using digitized collections to broaden learning opportunities and support a wide range of users will require museum leaders to engage in strategic digitization efforts—supplementing research images, making conscious decisions about meeting educational needs when setting digitization policies, and investing in meaningful outreach with digitized collections. Educational opportunities are contextualized with brief case studies of authentic investigations for middle school learners using digitized objects from a natural history museum. Three lessons learned during development and evaluation are described and implications for museum leaders are discussed.