bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacokinetic Analysis of Rosmarinic Acid and its Analog in Rat Plasma Using Liquid Chromatography–Tandem Mass Spectrometry
Authors: Jiang Minjie , Fu Shujie , Chen Kebei , Li Qing , Jiang Weizhe 
Published: June 2021

Abstract
The anticancer effects of rosmarinic acid (RA) are a hotspot of current research. In order to enhance its pharmacological activity, N-substituted RA was prepared, and it has been shown to exhibit notable antitumor effects. In order to elucidate the underlying mechanisms of action, pharmacokinetic analysis is necessary. In the present study, liquid chromatography–tandem mass spectrometric method, was used to determine the concentrations of RA and its analog, (E)-3-(3,4-dihydroxyphenyl)-2-(3-(3,4-dihydroxyphenyl)acrylamido)propanoic acid (A2) in plasma from rats. The analyses were divided into a C18 column (1.9 μm, 2.1 mm × 100 mm) with a security guard C18 column (5 μm, 2.1 mm × 10 mm) and a triple-quadrupole mass spectrometry with an electrospray ionization ion-source generates ions. The sample pretreatment is relevant to the one-step protein precipitation with isopropanol:ethyl acetate (v/v, 1:1) This method presented a linear association within ranges at the concentration of 5–2000 ng/mL for A2 and RA. Relative standard deviations in daily courses were &lt;15% and the relative errors registered within 15%. The methods used in the present study make the unambiguous quantification and identification of RA and A2 possible in vivo. The present study is the first to focus on determining A2 and RA in rat plasma following oral administration. The results may provide a meaningful basis for the evaluation of the application of RA and its analog in clinical practice and also provide a reference method for the pharmacokinetic analysis of RA analogs.
Variants of Concern Are Overrepresented Among Postvaccination Breakthrough Infections of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in Washington State
Authors: McEwen Abbye E , Cohen Seth , Bryson-Cahn Chloe , Liu Catherine , Pergam Steven A , Lynch John , Schippers Adrienne , Strand Kathy , Whimbey Estella , Mani Nandita S , Zelikoff Allison J , Makarewicz Vanessa A , Brown Elizabeth R , Bakhash Shah A Mohamed , Baker Noah R , Castor Jared , Livingston Robert J , Huang Meei-Li , Jerome Keith R , Greninger Alexander L , Roychoudhury Pavitra 
Published: June 2021

Abstract
Across 20 vaccine breakthrough cases detected at our institution, all 20 (100%) infections were due to variants of concern (VOCs) and had a median Ct of 20.2 (IQR, 17.1–23.3). When compared with 5174 contemporaneous samples sequenced in our laboratory, VOCs were significantly enriched among breakthrough infections (P &lt; .05).
Time to press the reset button—can we use the COVID-19 pandemic to rethink the process of transplant assessment?
Authors: Kumar Mukesh , Dellen David van , Loughton Holly , Woywodt Alexander 
Published: June 2021

Abstract
Coronavirus disease 2019 has taken a severe toll on the transplant community, with significant morbidity and mortality not just among transplant patients and those on the waiting list, but also among colleagues. It is therefore not surprising that clinicians in this field have viewed the events of the last 18 months as predominantly negative. As the pandemic is gradually ebbing away, we argue that this is also a unique opportunity to rethink transplant assessment. First, we have witnessed a step-change in the use of technology and virtual assessments. Another effect of the pandemic is that we have had to make do with what was available—which has often worked surprisingly well. Finally, we have learned to think the unthinkable: maybe things do not have to continue the way they have always been. As we emerge on the other side of the pandemic, we should rethink which parts of the transplant assessment process are necessary and evidence-based. We emphasize the need to involve patients in the redesign of pathways and we argue that the assessment process could be made more transparent to patients. We describe a possible roadmap towards transplant assessment pathways that are truly fit for the 21st century.
Concomitant myocardial injury and valvular disease in Sneddon syndrome: a case report
Authors: Scadi Soukaina , Huttin Olivier , Selton Suty Christine , Wahl Denis 
Published: June 2021

Abstract

Background
Cardiac involvement in Sneddon syndrome (SS) is rare, the physiopathology is still unclear. We report a first case of SS without antiphospholipid antibodies who had coexisting ischaemia with no obstructive coronary arteries and aortic valve diseases.

Case summary
A 34-year-old woman with SS without antiphospholipid antibodies, was admitted for aphasia, and paresthaesia with confirmed right opercular ischaemic lesions at brain magnetic resonance imaging. Transthoracic echocardiographic examination showed akinesis of apical segments, moderate aortic valve stenosis, and moderate aortic insufficiency. Coronary angiogram was normal. Cardiac magnetic resonance showed transmural necrosis in the territory of the left anterior descending artery. Seven years later, our patient had no change or progression of myocardial ischaemic lesions or valvular disease.

Conclusion
We will discuss different hypothesis, diagnosis, treatment, and evolution of cardiac involvement in SS. Close follow-up should be regularly performed for early diagnosis, hence the importance of multimodality imaging, to guide treatment and prevent further complications.
Remnant cholesterol predicts cardiovascular disease beyond LDL and ApoB: a primary prevention study
Authors: Quispe Renato , Martin Seth Shay , Michos Erin Donelly , Lamba Isha , Blumenthal Roger Scott , Saeed Anum , Lima Joao , Puri Rishi , Nomura Sarah , Tsai Michael , Wilkins John , Ballantyne Christie Mitchell , Nicholls Stephen , Jones Steven Richard , Elshazly Mohamed Badreldin 
Published: June 2021

Abstract

Aims
Emerging evidence suggests that remnant cholesterol (RC) promotes atherosclerotic cardiovascular disease (ASCVD). We aimed to estimate RC-related risk beyond low-density lipoprotein cholesterol (LDL-C) and apolipoprotein B (apoB) in patients without known ASCVD.

Methods and results
We pooled data from 17 532 ASCVD-free individuals from the Atherosclerosis Risk in Communities study (n = 9748), the Multi-Ethnic Study of Atherosclerosis (n = 3049), and the Coronary Artery Risk Development in Young Adults (n = 4735). RC was calculated as non-high-density lipoprotein cholesterol (non-HDL-C) minus calculated LDL-C. Adjusted Cox models were used to estimate the risk for incident ASCVD associated with log RC levels. We also performed discordance analyses examining relative ASCVD risk in RC vs. LDL-C discordant/concordant groups using difference in percentile units (&gt;10 units) and clinically relevant LDL-C targets. The mean age of participants was 52.3 ± 17.9 years, 56.7% were women and 34% black. There were 2143 ASCVD events over the median follow-up of 18.7 years. After multivariable adjustment including LDL-C and apoB, log RC was associated with higher ASCVD risk [hazard ratio (HR) 1.65, 95% confidence interval (CI) 1.45–1.89]. Moreover, the discordant high RC/low LDL-C group, but not the low RC/high LDL-C group, was associated with increased ASCVD risk compared to the concordant group (HR 1.21, 95% CI 1.08–1.34). Similar results were shown when examining discordance across clinical cutpoints.

Conclusions
In ASCVD-free individuals, elevated RC levels were associated with ASCVD independent of traditional risk factors, LDL-C, and apoB levels. The mechanisms of RC association with ASCVD, surprisingly beyond apoB, and the potential value of targeted RC-lowering in primary prevention need to be further investigated.
The iron transporter Transferrin 1 mediates homeostasis of the endosymbiotic relationship betweenDrosophila melanogasterandSpiroplasma poulsonii
Authors: Marra Alice , Masson Florent , Lemaitre Bruno 
Published: June 2021

ABSTRACTIron is involved in numerous biological processes in both prokaryotes and eukaryotes and is therefore subject to a tug-of-war between host and microbes upon pathogenic infections. In the fruit fly Drosophila melanogaster, the iron transporter Transferrin 1 (Tsf1) mediates iron relocation from the hemolymph to the fat body upon infection as part of the nutritional immune response. The sequestration of iron in the fat body renders it less available for pathogens, hence limiting their proliferation and enhancing the host ability to fight the infection. Here we investigate the interaction between host iron homeostasis and Spiroplasma poulsonii, a facultative, vertically transmitted, endosymbiont of Drosophila. This low-pathogenicity bacterium is devoid of cell wall and is able to thrive in the host hemolymph without triggering pathogen-responsive canonical immune pathways. However, hemolymph proteomics revealed an enrichment of Tsf1 in infected flies. We find that S. poulsonii induces tsf1 expression and triggers an iron sequestration response similarly to pathogenic bacteria. We next demonstrate that free iron cannot be used by Spiroplasma while Tsf1-bound iron promotes bacterial growth, underlining the adaptation of Spiroplasma to the intra-host lifestyle where iron is mostly protein-bound. Our results show that Tsf1 is used both by the fly to sequester iron and by Spiroplasma to forage host iron, making it a central protein in endosymbiotic homeostasis.
Adaptation and Validation of the Preparation for Future Care Needs Scale for Chinese Older Adults in Hong Kong
Authors: Bai Xue , Liu Chang , Song Yajun , Sörensen Silvia 
Published: June 2021

AbstractBackground and ObjectivesCare planning can protect against or offset potential stressors in the caregiving stage and mitigate their detrimental effects. This study aimed to translate, adapt, and validate 2 short forms of the multidimensional, theory-guided scale measuring preparation for future care needs (PFCN) among Chinese older adults in Hong Kong.Research Design and MethodsData were derived from a cross-sectional survey of 862 community-dwelling individuals aged 60 years and older. Exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) were conducted to assess the structural validity of the scales. Criterion-related validity, known-groups validity, and internal consistency were also examined.ResultsEFA yielded a 14-item 4-factor (awareness, avoidance, decision making, and concrete planning) model, which was supported by CFA and explained 68.9% of the total variance. CFA also supported the structural validity of the 5-item scale. Criterion-related validity of the 2 scales was supported by their significant and positive correlations with domain-specific planning behaviors for retirement. Known-groups validity of the 2 scales was demonstrated by significant differences in scores between male and female older adults and scores between different educational levels and socioeconomic status. Cronbach’s alphas for the internal consistency of the 14-item and 5-item scales were 0.889 and 0.774, respectively.Discussion and ImplicationsPFCN scales enable researchers and service practitioners to accurately understand and assess older adults’ processes and efforts in care planning, facilitate the identification of individuals at risk from inadequate planning, and inform the development of interventions to enhance care preparation in target domains.
Pervasiveness of Biological Impacts of Artificial Light at Night
Authors: Gaston Kevin J , Ackermann Simone , Bennie Jonathan , Cox Daniel T C , Phillips Benjamin B , Sánchez de Miguel Alejandro , Sanders Dirk 
Published: June 2021

AbstractArtificial light at night (ALAN) and its associated biological impacts have regularly been characterized as predominantly urban issues. Although far from trivial, this would imply that these impacts only affect ecosystems that are already heavily modified by humans and are relatively limited in their spatial extent, at least as compared with some key anthropogenic pressures on the environment that attract much more scientific and public attention, such as climate change or plastic pollution. However, there are a number of reasons to believe that ALAN and its impacts are more pervasive, and therefore need to be viewed from a broader geographic perspective rather than an essentially urban one. Here we address, in turn, 11 key issues when considering the degree of spatial pervasiveness of the biological impacts of ALAN. First, the global extent of ALAN is likely itself commonly underestimated, as a consequence of limitations of available remote sensing data sources and how these are processed. Second and third, more isolated (rural) and mobile (e.g., vehicle headlight) sources of ALAN may have both very widespread and important biological influences. Fourth and fifth, the occurrence and impacts of ALAN in marine systems and other remote settings, need much greater consideration. Sixth, seventh, and eighth, there is growing evidence for important biological impacts of ALAN at low light levels, from skyglow, and over long distances (because of the altitudes from which it may be viewed by some organisms), all of which would increase the areas over which impacts are occurring. Ninth and tenth, ALAN may exert indirect biological effects that may further expand these areas, because it has a landscape ecology (modifying movement and dispersal and so hence with effects beyond the direct extent of ALAN), and because ALAN interacts with other anthropogenic pressures on the environment. Finally, ALAN is not stable, but increasing rapidly in global extent, and shifting toward wavelengths of light that often have greater biological impacts.
Connected While Distant: Networking CUREs Across Classrooms to Create Community and Empower Students
Authors: Connors Patrice K , Lanier Hayley C , Erb Liesl P , Varner Johanna , Dizney Laurie , Flaherty Elizabeth A , Duggan Jennifer M , Yahnke Christopher J , Hanson John D 
Published: June 2021

Synopsis
Connections, collaborations, and community are key to the success of individual scientists as well as transformative scientific advances. Intentionally building these components into science, technology, engineering and mathematics (STEM) education can better prepare future generations of researchers. Course-based undergraduate research experiences (CUREs) are a new, fast-growing teaching practice in STEM that expand opportunities for undergraduate students to gain research skills. Because they engage all students in a course in an authentic research experience focused on a relevant scientific problem, CUREs provide an opportunity to foster community among students while promoting critical thinking skills and positively influencing their identities as scientists. Here, we review CUREs in the biological sciences that were developed as multi-institutional networks, and highlight the benefits gained by students and instructors through participation in a CURE network. Throughout, we introduce Squirrel-Net, a network of ecology-focused and field-based CUREs that intentionally create connections among students and instructors. Squirrel-Net CUREs can also be scaffolded into the curriculum to form connections between courses, and are easily transitioned to distance-based delivery. Future assessments of networked CUREs like Squirrel-Net will help elucidate how CURE networks create community and how a cultivated research community impacts students’ performance, perceptions of science, and sense of belonging. We hypothesize networked CUREs have the potential to create a broader sense of belonging among students and instructors alike, which could result in better science and more confident scientists.
Introduction to Material Displacements
Authors: Lichtman Sarah A , Traganou Jilly 
Published: June 2021

Abstract
This special issue on Material Displacements explores the intersection of materiality, design, and displacement, conceived of as rupture, transition, and traversal of borders, boundaries, and forms. This introduction outlines the role of displacement in various disciplines and theoretical approaches, highlighting those of new materialism, critical urbanism, deterritorialization, and border thinking. It then presents work published in the Journal of Design History by design historians and theorists who have envisioned design’s relation with displacement through diverse perspectives. Each author contributing to this issue reveals the power and role of materiality in inducing movement in/out of the borders broadly conceived, as well as materials’ susceptibility to external forces of displacement.
Wild Bee Response to Application of the Douglas-fir Beetle Anti-Aggregation Pheromone, 3-Methylcyclohex-2-En-1-One
Authors: Foote Gabriel G , Runyon Justin B , Fettig Christopher J , Foote Nathaniel E , Ross Darrell W 
Published: June 2021

Abstract
Douglas-fir beetle, Dendroctonus pseudotsugae Hopkins (DFB), is the most damaging insect pest of Douglas-fir, Pseudotsuga menziesii (Mirb.) Franco, in western North America. Individual high-value trees and stands can be protected during DFB outbreaks using the beetle's anti-aggregation pheromone, 3-methylcyclohex-2-en-1-one (MCH), which is available in several commercial formulations. However, other methylcyclohexanones similar in molecular structure to MCH have been shown to repel bees from agricultural areas. In forest systems, wild bees (Hymenoptera: Apiformes) provide essential pollination services to many forb and shrub species. Therefore, it is important to determine whether resident wild bee communities are affected in forests treated with MCH. To address this, the bee community was sampled within experimental sites located in Idaho and Montana, USA in 2016. At both sites, there was no significant difference in overall bee abundance, species richness, or diversity between MCH-treated plots and untreated control plots. Overall, these results indicate that treatment of Douglas-fir with MCH does not negatively impact the resident wild bee community.
Simultaneous Morscher’s osteotomy and arthroscopic debridement in the management of Legg–Calvé–Perthes disease: a case report and literature review
Authors: Bosakhar Batool , Baldawi Hassan , Liu Kathy , Ayeni Olufemi R , Kishta Waleed 
Published: June 2021

Abstract
There is a lack of consensus around optimal surgical management for Legg–Calvé–Perthes Disease (LCPD). This case report discusses the benefits of combining arthroscopic femoral neck osteochondroplasty and labral repair with Morscher’s Osteotomy (MO) for LCPD. S.A. is a 17-year-old female diagnosed with LCPD at the age of 6 years and has long-standing right hip symptoms. An arthroscopic femoral neck osteochondroplasty and labral repair followed by MO was performed. The pre-operative and 8 months post-operative International Hip Outcome Tool (iHOT-12) scores were 16.3 and 79.8 out of 100, respectively, indicating better quality-of-life. Also, the femoral neck-shaft-angle (NSA) changed from 120 pre-operative to 138.7 post-operative to represent the correction of coxa vara. The literature review revealed no published reports describing combined MO with hip arthroscopic interventions in managing LCPD. Combined arthroscopic femoral neck osteochondroplasty (with labral repair) and MO provides high patient satisfaction and improves radiographic parameters in patients with LCPD.
Bilateral femoral head reshaping and mosaicplasty in Legg–Calvé–Perthes disease residual deformity
Authors: Palazón-Quevedo Ángel , Galán-Olleros María , Egea-Gámez Rosa M 
Published: June 2021

Abstract
Residual hip deformity secondary to Perthes disease may lead to early symptomatic joint degeneration. The altered anatomy results in biomechanical and biological problems that can be surgically addressed in adolescents or young adults with hip preservation procedures. This case report aims to demonstrate a customized surgical treatment performed on a 15-year-old male who developed painful hips with significant intra- and extra-articular impingement, secondary to bilateral Leg–Calvé–Perthes disease residual deformity. Intra-articular procedures were executed through a safe surgical dislocation of the hip, with a mosaicplasty using osteochondral autografts from the exceeding peripheral ipsilateral femoral head, a femoral head–neck osteochondroplasty and a labrum repair. A relative lengthening of the femoral neck was also carried out with a trochanteric advancement to solve the extra-articular issues. On follow-up, he referred to a substantial improvement in pain and function, being his radiographic studies satisfactory. At 4 and 5 years from surgery, the patient was able to exercise regularly with minimal complaints, with a Harris Hip Score of 85.85% and a Hip Outcome Score of 94.1% for activities of daily life and 86.1% for sports. In patients with hip deformity after healed Perthes disease, treatment strategies that address both the morphological disturbance of coxa magna, plana and breva, as well as the biological concerns arising from osteochondral injuries or labral tears, and mechanical dysfunctions lead to improvements in symptomatology, function and medium-term prognosis. Further procedures to address residual adaptative acetabular dysplasia would favor outcomes of conservative hip surgery in the sequelae of LCPD.
Identification of the JNK-Active Triple-Negative Breast Cancer Cluster Associated With an Immunosuppressive Tumor Microenvironment
Authors: Semba Takashi , Wang Xiaoping , Xie Xuemei , Cohen Evan N , Reuben James M , Dalby Kevin N , Long James P , Phi Lan Thi Hanh , Tripathy Debu , Ueno Naoto T 
Published: June 2021

Abstract

Background
Although an immunosuppressive tumor microenvironment (TME) is key for tumor progression, the molecular characteristics associated with the immunosuppressive TME remain unknown in triple-negative breast cancer (TNBC). Our previous functional proteomic study of TNBC tumors identified that C-JUN N-terminal kinase (JNK) pathway–related molecules were enriched in a cluster associated with the inflammatory pathway. However, the role of the JNK pathway in the TNBC TME is still unclear.

Methods
Transcriptomic analysis was conducted using The Cancer Genome Atlas datasets. The effect of JNK-IN-8, a covalent pan-JNK inhibitor, on TNBC tumor growth, lung metastasis, and the TME was measured in TNBC syngeneic mouse models (n = 13 per group). Tumor (n = 43) or serum (n = 46) samples from TNBC patients were analyzed using multiplex immunohistochemistry or Luminex assay. All statistical tests were 2-sided.

Results
CIBERSORT analysis revealed that TNBC patients with high phosphorylated JNK level (n = 47) had more regulatory T cell (Treg) infiltration than those with a low phosphorylated JNK level (n = 47) (P = .02). Inhibition of JNK signaling statistically significantly reduced tumor growth (P &lt; .001) and tumor-infiltrating Tregs (P = .02) while increasing the infiltration of CD8+ T cells in TNBC mouse models through the reduction of C-C motif ligand 2 (CCL2). Tumor-associated macrophages were the predominant cells secreting CCL2, and inhibition of JNK signaling reduced CCL2 secretion of human primary macrophages. Moreover, in patients with TNBC (n = 43), those with high levels of CCL2+ tumor-associated macrophages had more Treg and less CD8+ T cell infiltration (P = .04), and the serum CCL2 level was associated with poor overall survival (hazard ratio = 2.65, 95% confidence interval = 1.29 to 5.44, P = .008) in TNBC patients (n = 46).

Conclusions
The JNK/C-JUN/CCL2 axis contributes to TNBC aggressiveness via forming an immunosuppressive TME and can offer novel therapeutic strategies for TNBC.