bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessment of cardiac function in syncopal children without organic causes
Authors: Kim Heoungjin , Eun Lucy Youngmin
Published: March 2021

Background: Syncope is a common problem in children and adolescents. However, a large proportion of syncope cases have no underlying cause.Purpose: This study aimed to identify the factors affecting the severity of syncope using tissue Doppler imaging (TDI).Methods: This retrospective study included 61 children and adolescents with syncope who underwent echocardiography. The head-up-tilt test (HUT) was performed when there was a more severe syncopal event. We compared the echocardiographic findings between the execute HUT and nonexecute HUT, negative HUT result and positive HUT result, and normal electrocardiogram (ECG) and abnormal ECG groups. Data were analyzed using an unpaired t test post hoc analysis.Results: In the execute and nonexecute HUT groups, the odds ratios were 0.55 for medial E/E′ (P=0.040) and 0.64 for lateral E/E′ (P=0.049). Comparison of the results of the decreased, normal, and increased groups for lateral E/E′ revealed a significant difference in the execution HUT and nonexecute HUT groups (overall, P=0.004; decreased vs. increased, P= 0.003; normal vs. increased, P=0.050).Conclusion: Medial E/E′ and lateral E/E′ were decreased in patients with severe syncopal events. These findings suggest that the presence of left ventricular diastolic deterioration may cause hypoperfusion even in the absence of organic causes and, consequently, increase syncope severity and frequency. The TDI measured by echocardiography can be used as an index to predict syncope recurrence and/or severity.
INTRODUCTION OF A NEW VEGETABLE CULTURE SMALLANTHUS SONCHIFOLIUS IN DAGESTAN
Authors:   Mountain Botanical Garden of DFRC RAS, Asadulaev Z.M. , Abdurakhmanova Z.I. ,   Mountain Botanical Garden of DFRC RAS
Published: March 2021

The paper presents a primary results of introduction of unconventional food and medicinal plant Smallanthus sonchifolius in the soil and climatic conditions of Dagestan. For planting, we used rhizomes with sprouts obtained from Pyatigorsk in the second decade of May. As a result of the research, the success of the introduction of S. sonchifolius in Lowland Dagestan was noted. Plants developed normally, the most active period of their growth and development was noted in August–October, the productivity of the root mass was 900 grams. In the conditions of mountain Dagestan, richer soils and watering are needed to grow a new culture. As in other regions of Russia in Dagestan, S. sonchifolius do not go through a full development cycle, only vegetative growth phases are noted.
ALIEN PLANT SPECIES OF THE MASHUK MOUNTAIN
Authors:   Perkalski arboretum of Komarov Botanical Institute RAS, Shilnikov D.S. , Soltani G.А. ,   Sochi National Park
Published: March 2021

The preservation of biological diversity is impossible without the preservation of natural vegetation. Changes in physical and geographical conditions, succession of phytocenoses, lead to transformation of growing conditions and loss of ecological niches by species. Simultaneously with these processes, the number of alien species increases. Their expansion is facilitated by violations of habitats with natural vegetation cover. Surveys of the slopes of mount Mashuk revealed the distribution of 30 alien species of tree flora from 17 families. Half of them overcame the restrictions of reproduction, but could not pass the barrier associated with the spread of diasporas: Acer negundo, Aesculus hippocastanum, Catalpa speciosa, Celtis occidenatalis, Colutea orientalis, Gleditsia triacanthos, Hedera helix, Juglans regia, Lonicera tatarica, Mahonia repens, Malus domestica, Prunus armeniaca, Robinia viscosa, Spiraea vanhoutei, Vitis vinifera. Nine species — Acer pseudoplatanus, Amorpha fruticosa, Laburnum anagyroides, Morus alba, Morus nigra, Prunus mahaleb, Robinia pseudoacacia, Rubus ibericus and Vinca minor — settle and naturalize in disturbed, seminatural, and natural habitats. Fraxinus pennsylvanica, Platycladus orientalis, Syringa vulgaris are phytoceno-sotransformers, and Clematis vitalba is a biogeocenosotransformer.
PENERAPAN BACK MASSAGE TERHADAP FATIGUE (KELELAHAN) PASIEN KANKER PAYUDARA YANG MENJALANI KEMOTERAPI
Authors: P Dyah Restuning
Published: March 2021

Kanker payudara ialah penyakit yang tidak terkendali pembelahan selnya dan kemampuan untuk menyerang jaringan biologis baik langsung di jaringan yang bersebelahan (invasi) atau dengan migrasi sel yang jauh (metastasis). Salah satu penatalaksanaan kanker payudara adalah kemoterapi. Yaitu kemoterapi yang menyebabkan fatigue (kelelahan). Untuk mengurangi fatigue (kelelahan) saat kemoterapi dengan pemberian back massage karena memberikan efek relaksasi secara menyeluruh dan mengurangi kelelahan karena dapat memperbaiki sirkulasi darah dan mengurangi ketegangan tubuh serta pengeluaran ampas tubuh semakin sempurna dengan pengeluaran racun dalam tubuh. Tujuan studi kasus ini menyusun resume asuhan keperawatan dalam pemberian back massage untuk mengurangi kelelahan saat kemoterapi pada pasien kanker payudara. Jenis penelitian ini adalah deskriptif dengan metode studi kasus dalam bentuk rancangan one grup pretest posttest. Subyek dari penelitian ini adalah 2 pasien dengan kanker payudara yang menjalani kemoterapi, dengan skala kelelahan 4-7 (kelelahan sedang), pasien kanker payudara dengan stadium 1-3, pasien yang bersedia menjadi responden. Hasil studi menunjukkan bahwa ada perubahan tingkat kelelahan yang awalnya kelelahan sedang menjadi kelelahan ringan setelah pemberian back massage selama 3 hari sehingga diharapkan keluarga pasien dapat melakukan tindakan back massage untuk mengurangi kelelahan pada pasien kanker payudara yang menjalani kemoterapi.

 

Kata kunci: kanker payudara, kelelahan, back massage
‘Aren't you Maria?’: The Uncanny and the Gothic in Silent Hill 2
Authors: Green James Aaron
Published: March 2021

The attractiveness of the ‘moving image’ to the gothic imagination has begun to receive scholarly attention from the perspective of videogames, and it has been argued that the digital medium renovates gothic ‘milieus’ (transmedial genre labels) by its combination of ludic and narrative properties. This article focuses in particular on the gothic milieu of the uncanny as it appears in Team Silent's 2001 videogame Silent Hill 2. Examining its depictions of the double, animism, and involuntary repetition, this article claims that Silent Hill 2 is sui generis in its depiction of the uncanny, and in this regard must be considered distinctly from the rest of the series. Following Isabella van Elferen's contention that ‘the participatory uncanny of certain games can be identified as the main ingredient of video game Gothic’, this study argues for Silent Hill 2 as a superlative case of the gothic potential of videogames, and of the uncanniness of contemporary, digital media.
Designing Quantum Bodies: A New Calculus of Responsibility
Authors: Moran Stacey
Published: March 2021

Critical Design has embraced Karen Barad's theory of agential realism for rethinking design as a discipline, an artifact, and a profession. This article meditates on an exploratory question: what if we consider Barad to be in some way ‘doing design’? The article draws attention to the fact that Barad's 2007 book, Meeting the Universe Halfway, does not begin with physics or feminism, but rather, with a close reading of a play. I suggest that Barad situates literature and fiction as central features in her analysis of historical experiments in physics, that she doesn't treat these experiments as historical events or even conceptual questions, but entangles them with a type of ‘experimental’ physics. Barad confronts the unsatisfactory ethical conclusions in the play, and thereby isolates a pressing design problem: how to loosen the hold of individualism on feminist ethics? This article proposes a provocation: that Barad engages in a project to ‘design away’ the classical body that stands in the way of more ethical quantum futures. The article highlights the need for speculative design methods because they transcend disciplinary divisions and help to overcome design problems as enduring as individualism. Engaging with fictional worlds that touch upon our contemporary technoscientific present, Barad's science fictional story, I argue, asks us to ponder our relations, imagine new ones, and open pathways to more ethical and equitable futures.
(Re)Thinking Design with New Materialism: Towards a Critical Anthropology of Design
Authors: Büsse Michaela
Published: March 2021

The article proposes an empirical and discursive understanding of design as engaging and intensifying uneven power relations. By affiliating with the ontological turn in anthropology, such re-defined reading of design acknowledges design's complicity with extractive capitalism while aiming to open up possibilities to think design otherwise. In recent years, inspired by the resurgence of materialism, abstract notions of design as mediating practice between human and environment have gained popularity. Yet, these more-than-human-centred design theories tend to obscure the material and immaterial infrastructures that still shape human and nonhuman realities. By utilising the example of sand's transformation into land and tracing its journey across sites, actors and continents, the infrastructures of planetary transformation – as well as what eludes them – are investigated. Turning matter into medium emphasises thresholds and ruptures in the human-material relationship and thus transcends both a socially constructed and material reading of reality. Through a historical and empirical relocation of the current more-than-human-centred design discourse, the research presented in this article aims to support the establishment of a critical anthropology of design.
KOMUNIKASI PASANGAN MENIKAH ANTAR BUDAYA SIPIL DENGAN MILITER MELALUI PENDEKATAN TEORI MANAJEMEN IDENTITAS
Authors: Christanti Maria Febiana
Published: March 2021

Penelitian ini mendeskripsikan manajemen identitas pasangan menikah berbeda budaya sipil dengan militeryang berdampak pada komunikasi mereka saat beradaptasi. Identitas selalu mengalami perubahan dan identitas setiap pasangan tidak akan sama satu dengan yang lain, seperti: identitas suku, agama, usia, keluarga, lingkungan sosial, organisasi, dll. Proses manajemen identitas yang terjadi diantara kedua pasangan berbeda budaya sipil dengan militer akan diuraikan melalui tiga fase manajemen identitas dari Cupach & Imahori yaitu: trial and error, enmeshment, and renegotiation. Penelitian ini menggunakan pendekatan konstruktivis dengan menggunakan teori manajemen identitas Sifat penelitian adalah deskriptif dan memakai metode fenomenologi. Teknik pengumpulan data menggunakan wawancara mendalam. Hasil dari penelitian ini terungkap bahwa pasangan yang memiliki banyak perbedaan lebih sulit melakukan proses renegotiation yakni mengelola face diri sendiri atau face pasangan dengan mencari persamaan perspektif apakah mengutamakan nilai atau norma budaya sendiri sebagai warga sipil atau mengutamakan nilai atu norma sebagai militer.
Fragile, Yet Resilient: Adaptive Decline in a Collaboration Network of Firms
Authors: Schweitzer Frank , Casiraghi Giona , Tomasello Mario V. , Garcia David
Published: March 2021

The dynamics of collaboration networks of firms follow a life cycle of growth and decline. That does not imply they also become less resilient. Instead, declining collaboration networks may still have the ability to mitigate shocks from firms leaving and to recover from these losses by adapting to new partners. To demonstrate this, we analyze 21.500 R&D collaborations of 14.500 firms in six different industrial sectors over 25 years. We calculate time-dependent probabilities of firms leaving the network and simulate drop-out cascades to determine the expected dynamics of decline. We then show that deviations from these expectations result from the adaptivity of the network, which mitigates the decline. These deviations can be used as a measure of network resilience.
Volumetric Brain Changes in Older Fallers: A Voxel-Based Morphometric Study
Authors: Le Floch Maxime , Ali Pauline , Asfar Marine , Sánchez-Rodríguez Dolores , Dinomais Mickaël , Annweiler Cédric
Published: March 2021

Background

Falls are frequent and severe in older adults, especially among those with cognitive impairments due to altered motor control. Which brain areas are affected among fallers remains yet not elucidated. The objective of this cross-sectional analysis was to determine whether the history of falls correlated with focal brain volume reductions in older adults.

Methods

Participants from the MERE study (n = 208; mean, 71.9 ± 5.9 years; 43% female; 38% cognitively healthy, 41% with mild cognitive impairment and 21% with dementia) were asked about their history of falls over the preceding year and received a 1.5-Tesla MRI scan of the brain. Cortical gray and white matter subvolumes were automatically segmented using Statistical Parametric Mapping. Age, gender, use of psychoactive drugs, cognitive status, and total intracranial volume were used as covariates.

Results

Fifty-eight participants (28%) reported history of falls. Fallers were older (P = 0.001), used more often psychoactive drugs (P = 0.008) and had more often dementia (P = 0.004) compared to non-fallers. After adjustment, we found correlations between the history of falls and brain subvolumes; fallers exhibiting larger gray matter subvolumes in striatum, principally in bilateral caudate nucleus, than non-fallers. By stratifying on cognitive status, these neuroanatomical correlates were retrieved only in participants with MCI or dementia. There were no correlations with the subvolumes of white matter.

Conclusion

Older fallers had larger subvolumes in bilateral striatum than non-fallers, principally within the caudate nucleus. This suggests a possible brain adaptative mechanism of falls in people with neurocognitive decline.
Rational Design of Hyaluronic Acid-Based Copolymer-Mixed Micelle in Combination PD-L1 Immune Checkpoint Blockade for Enhanced Chemo-Immunotherapy of Melanoma
Authors: Zhou Chaopei , Dong Xiuxiu , Song Chunxiang , Cui Shuang , Chen Tiantian , Zhang Daji , Zhao Xiuli , Yang Chunrong
Published: March 2021

The application of combinational therapy breaks the limitation of monotherapy and achieves better clinical benefit for tumor therapy. Herein, a hyaluronic acid/Pluronic F68-based copolymer-mixed micelle was constructed for targeted delivery of chemotherapeutical agent docetaxel (PHDM) in combination with programmed cell death ligand-1(PD-L1) antibody. When PHDM+anti-PDL1 was injected into the blood system, PHDM could accumulate into tumor sites and target tumor cells via CD44-mediated endocytosis and possess tumor chemotherapy. While anti-PDL1 could target PD-L1 protein expressed on surface of tumor cells to the immune checkpoint blockade characteristic for tumor immunotherapy. This strategy could not only directly kill tumor cells but also improve CD8+ T cell level and facilitate effector cytokines release. In conclusion, the rational-designed PHDM+anti-PDL1 therapy strategy creates a new way for tumor immune-chemotherapy.
Rapid Degradation of Nitrochlorobenzene by Activated Persulfate Oxidation With Biochar Supported Nanoscaled Zero Valent Iron
Authors: Wang Xiang , Deng Rufeng , Shen Wenbo , Huang Jianbo , Li Qun , Zhao Yuanchao , Wan Jinzhong , Zhou Yan , Long Tao , Zhang Shengtian
Published: March 2021

Although pesticide intermediates are a kind of typical toxic pollutant in contaminated sites, the remediation of these contaminants in groundwater and soils is of limited concern. In the present study we investigated the performance of a novel heterogeneous oxidation system, biochar supported nanoscaled-zero valent iron (nZVI/BC) activated persulfate (PS), in the oxidative degradation of nitrochlorobenzene (NCB), a typical pesticide intermediate. Peanut shell based nZVI/BC was prepared and used as the PS activator. The degradation kinetics of m-, p-, and o-NCB isomers in the aqueous phase were investigated. The effects of BC/nZVI composition (Fe/BC mass ratio), the amount of BC/nZVI and PS, and initial contaminant concentration on NCB removal were also examined. Results suggest that over 90% removals of three NCB isomers could be obtained by the nZVI/BC activated PS system at initial NCB concentration of 10 mg L−1. The combination of nZVI/BC composite and PS showed superior performance to PS alone. The optimal treatment condition was supposed as the Fe: BC ratio of 1:1, Fe amount of 6 mmol L−1, and the mole ratio of Fe to perfulfate of 1:1.
Probiotic Gastrointestinal Transit and Colonization After Oral Administration: A Long Journey
Authors: Han Shengyi , Lu Yanmeng , Xie Jiaojiao , Fei Yiqiu , Zheng Guiwen , Wang Ziyuan , Liu Jie , Lv Longxian , Ling Zongxin , Berglund Björn , Yao Mingfei , Li Lanjuan
Published: March 2021

Orally administered probiotics encounter various challenges on their journey through the mouth, stomach, intestine and colon. The health benefits of probiotics are diminished mainly due to the substantial reduction of viable probiotic bacteria under the harsh conditions in the gastrointestinal tract and the colonization resistance caused by commensal bacteria. In this review, we illustrate the factors affecting probiotic viability and their mucoadhesive properties through their journey in the gastrointestinal tract, including a discussion on various mucosadhesion-related proteins on the probiotic cell surface which facilitate colonization.
Salivary Microbiota for Gastric Cancer Prediction: An Exploratory Study
Authors: Huang Kun , Gao Xuefeng , Wu Lili , Yan Bin , Wang Zikai , Zhang Xiaomei , Peng Lihua , Yu Jiufei , Sun Gang , Yang Yunsheng
Published: March 2021

To characterize the salivary microbiota in patients at different progressive histological stages of gastric carcinogenesis and identify microbial markers for detecting gastric cancer, two hundred and ninety-three patients were grouped into superficial gastritis (SG; n = 101), atrophic gastritis (AG; n = 93), and gastric cancer (GC; n = 99) according to their histology. 16S rRNA gene sequencing was used to access the salivary microbiota profile. A random forest model was constructed to classify gastric histological types based on the salivary microbiota compositions. A distinct salivary microbiota was observed in patients with GC when comparing with SG and AG, which was featured by an enrichment of putative proinflammatory taxa including Corynebacterium and Streptococcus. Among the significantly decreased oral bacteria in GC patients including Haemophilus, Neisseria, Parvimonas, Peptostreptococcus, Porphyromonas, and Prevotella, Haemophilus, and Neisseria are known to reduce nitrite, which may consequently result in an accumulation of carcinogenic N-nitroso compounds. We found that GC can be distinguished accurately from patients with AG and SG (AUC = 0.91) by the random forest model based on the salivary microbiota profiles, and taxa belonging to unclassified Streptophyta and Streptococcus have potential as diagnostic biomarkers for GC. Remarkable changes in the salivary microbiota functions were also detected across three histological types, and the upregulation in the isoleucine and valine is in line with a higher level of these amino acids in the gastric tumor tissues that reported by other independent studies. Conclusively, bacteria in the oral cavity may contribute gastric cancer and become new diagnostic biomarkers for GC, but further evaluation against independent clinical cohorts is required. The potential mechanisms of salivary microbiota in participating the pathogenesis of GC may include an accumulation of proinflammatory bacteria and a decline in those reducing carcinogenic N-nitroso compounds.
Chronic Stress-Related Neural Activity Associates With Subclinical Cardiovascular Disease in a Community-Based Cohort: Data From the Washington, D.C. Cardiovascular Health and Needs Assessment
Authors: Powell-Wiley Tiffany M. , Dey Amit K. , Rivers Joshua P. , Chaturvedi Abhishek , Andrews Marcus R. , Ceasar Joniqua N. , Claudel Sophie E. , Mitchell Valerie M. , Ayers Colby , Tamura Kosuke , Gutierrez-Huerta Cristhian A. , Teague Heather L. , Oeser Steffen G. , Goyal Aditya , Joshi Aditya A. , Collins Billy S. , Baumer Yvonne , Chung Stephanie T. , Sumner Anne E. , Playford Martin P. , Tawakol Ahmed , Mehta Nehal N.
Published: March 2021

Background: Psychosocial stress correlates with cardiovascular (CV) events; however, associations between physiologic measures of stressors and CVD remain incompletely understood, especially in racial/ethnic minority populations in resource-limited neighborhoods. We examined associations between chronic stress-related neural activity, measured by amygdalar 18Fluorodeoxyglucose (18FDG) uptake, and aortic vascular FDG uptake (arterial inflammation measure) in a community-based cohort.

Methods: Forty participants from the Washington, DC CV Health and Needs Assessment (DC-CHNA), a study of a predominantly African-American population in resource-limited urban areas and 25 healthy volunteers underwent detailed phenotyping, including 18FDG PET/CT for assessing amygdalar activity (AmygA), vascular FDG uptake, and hematopoietic (leukopoietic) tissue activity. Mediation analysis was used to test whether the link between AmygA and vascular FDG uptake was mediated by hematopoietic activity.

Results: AmygA (1.11 ± 0.09 vs. 1.05 ± 0.09, p = 0.004) and vascular FDG uptake (1.63 ± 0.22 vs. 1.55 ± 0.17, p = 0.05) were greater in the DC-CHNA cohort compared to volunteers. Within the DC-CHNA cohort, AmygA associated with vascular FDG uptake after adjustment for Framingham score and body mass index (β = 0.41, p = 0.015). The AmygA and aortic vascular FDG uptake relationship was in part mediated by splenic (20.2%) and bone marrow (11.8%) activity.

Conclusions: AmygA, or chronic stress-related neural activity, associates with subclinical CVD risk in a community-based cohort. This may in part be mediated by the hematopoietic system. Our findings of this hypothesis-generating study are suggestive of a potential relationship between chronic stress-related neural activity and subclinical CVD in an African American community-based population. Taken together, these findings suggest a potential mechanism by which chronic psychosocial stress, such as stressors that can be experienced in adverse social conditions, promotes greater cardiovascular risk amongst resource-limited, community-based populations most impacted by cardiovascular health disparities. However, larger prospective studies examining these findings in other racially and ethnically diverse populations are necessary to confirm and extend these findings.
Development of a Health Information Technology Tool for Behavior Change to Address Obesity and Prevent Chronic Disease Among Adolescents: Designing for Dissemination and Sustainment Using the ORBIT Model
Authors: Kepper Maura M. , Walsh-Bailey Callie , Brownson Ross C. , Kwan Bethany M. , Morrato Elaine H. , Garbutt Jane , de las Fuentes Lisa , Glasgow Russell E. , Lopetegui Marcelo A. , Foraker Randi
Published: March 2021

Health information technology (HIT) has not been broadly adopted for use in outpatient healthcare settings to effectively address obesity in youth, especially among disadvantaged populations that face greater barriers to good health. A well-designed HIT tool can deliver behavior change recommendations and provide community resources to address this gap, and the Obesity-Related Behavioral Intervention Trials (ORBIT) model can guide its development and refinement. This article reports the application of the ORBIT model to (1) describe the characteristics and design of a novel HIT tool (the PREVENT tool) using behavioral theory, (2) illustrate the use of stakeholder-centered “designing for dissemination and sustainability” principles, and (3) discuss the practical implications and directions for future research. Two types of stakeholder engagement (customer discovery and user testing) were conducted with end users (outpatient healthcare teams). Customer discovery interviews (n = 20) informed PREVENT tool components and intervention targets by identifying (1) what healthcare teams (e.g., physicians, dietitians) identified as their most important “jobs to be done” in helping adolescents who are overweight/obese adopt healthy behaviors, (2) their most critical “pains” and “gains” related to overweight/obesity treatment, and (3) how they define success compared to competing alternatives. Interviews revealed the need for a tool to help healthcare teams efficiently deliver tailored, evidence-based behavior change recommendations, motivate patients, and follow-up with patients within the constraints of clinic schedules and workflows. The PREVENT tool was developed to meet these needs. It facilitates prevention discussions, delivers tailored, evidence-based recommendations for physical activity and food intake, includes an interactive map of community resources to support behavior change, and automates patient follow-up. Based on Self-Determination Theory, the PREVENT tool engages the patient to encourage competence and autonomy to motivate behavior change. The use of this intentional, user-centered design process should increase the likelihood of the intended outcomes (e.g., behavior change, weight stabilization/loss) and ultimately increase uptake, implementation success, and long-term results. After initial tool development, user-testing interviews (n = 13) were conducted using a think-aloud protocol that provided insight into users' (i.e., healthcare teams) cognitive processes, attitudes, and challenges when using the tool. Overall, the PREVENT tool was perceived to be useful, well-organized, and visually appealing.
Disentangle Kinetic From Equilibrium Fractionation Using Primary (δ17O, δ18O, δD) and Secondary (Δ17O, dex) Stable Isotope Parameters on Samples From the Swiss Precipitation Network
Authors: Leuenberger Markus C. , Ranjan Shyam
Published: March 2021

Since 1971 water isotope measurements are being conducted by the Climate and Environmental Physics Division at the University of Bern on precipitation, river- and groundwater collected at several places within Switzerland. The water samples were stored in glass flasks for later analyses with improved instrumentation. Conventional isotope ratio measurements on precipitated water from all stations of the network are well correlated as expected. However, Δ17O as well as dex is anticorrelated to these isotope ratio. The combination of these parameters allow to investigate dependencies on temperature, turbulence factor, and humidity of these values as well as to look into the importance and relative contributions of kinetic to equilibrium fractionations. We used published temperature dependent fractionation factors in combination with a simple Rayleigh model approach to investigate the importance of the meteorological parameters on the isotope ratios. A direct comparison of measured and modeled isotope ratios for primary (δ17O, δ18O and (δD) as well as secondary isotope parameters (Δ17O and dex) is shown.
Sclerostin and Osteocalcin: Candidate Bone-Produced Hormones
Authors: Wang Jialiang S. , Mazur Courtney M. , Wein Marc N.
Published: March 2021

In addition to its structural role, the skeleton serves as an endocrine organ that controls mineral metabolism and energy homeostasis. Three major cell types in bone - osteoblasts, osteoclasts, and osteocytes – dynamically form and maintain bone and secrete factors with systemic activity. Osteocalcin, an osteoblast-derived factor initially described as a matrix protein that regulates bone mineralization, has been suggested to be an osteoblast-derived endocrine hormone that regulates multiple target organs including pancreas, liver, muscle, adipose, testes, and the central and peripheral nervous system. Sclerostin is predominantly produced by osteocytes, and is best known as a paracrine-acting regulator of WNT signaling and activity of osteoblasts and osteoclasts on bone surfaces. In addition to this important paracrine role for sclerostin within bone, sclerostin protein has been noted to act at a distance to regulate adipocytes, energy homeostasis, and mineral metabolism in the kidney. In this article, we aim to bring together evidence supporting an endocrine function for sclerostin and osteocalcin, and discuss recent controversies regarding the proposed role of osteocalcin outside of bone. We summarize the current state of knowledge on animal models and human physiology related to the multiple functions of these bone-derived factors. Finally, we highlight areas in which future research is expected to yield additional insights into the biology of osteocalcin and sclerostin.
Structure of Urban Landscape and Surface Temperature: A Case Study in Philadelphia, PA
Authors: Mitz Erik , Kremer Peleg , Larondelle Neele , Stewart Justin D.
Published: March 2021

Discerning the relationship between urban structure and function is crucial for sustainable city planning and requires examination of how components in urban systems are organized in three-dimensional space. The Structure of Urban Landscape (STURLA) classification accounts for the compositional complexity of urban landcover structures including the built and natural environment. Building on previous research, we develop a STURLA classification for Philadelphia, PA and study the relationship between urban structure and land surface temperature. We evaluate the results in Philadelphia as compared to previous case studies in Berlin, Germany and New York City, United States. In Philadelphia, STURLA classes hosted ST that were unique and significantly different as compared to all other classes. We find a similar distribution of STURLA class composition across the three cities, though NYC and Berlin showed strong correlation with each other but not with Philadelphia. Our research highlights the use of STURLA classification to capture a physical property of the urban landscape
An Indirect Impact of Sika Deer Overpopulation on Eutrophication of an Aquatic Ecosystem via Understory Vegetation: An Individual-Based Approach Using Nitrate Reductase Activity
Authors: Tsuboike Yasuo , Fujii Masanori , Yoshida Yumiko , Kamata Naoto
Published: March 2021

Eutrophication of aquatic ecosystems is a serious global issue. Stream nitrate concentrations at the University of Tokyo Chichibu Forest have increased since 2000 after the opening of the new highway in 1998. Nitrogen oxide emissions from automobile exhausts were the most likely source of increased nitrate input in the forest ecosystem. Around the area, the sika deer Cervus nippon Temminck population has greatly increased since around 2000 and intensively browsed the understory vegetation. We hypothesized that the degradation of the understory vegetation caused by the deer overpopulation was one of the causes of increased nitrate output. Monthly observations were carried out from April to October 2013 to investigate the understory vegetation at the heights of 0–30 and 100–150 cm above the ground inside (without deer) and outside (with deer) of a deer exclusion fence. Plant taxa and % coverage of each taxon at each layer were recorded. The in vivo nitrate reductase activity (NRA) (≈ nitrate assimilation rate) was determined for each plant taxa each month. Compared to inside the fence, the understory vegetation outside was poor with smaller % coverage and less diverse community structure, and was occupied by unpalatable plant taxa that were uncommon or absent inside the fence. Contrary to our expectation, the phylogenetic diversity of the community assemblage outside the fence showed greater evenness (less clustering) than inside. The NRA peaked in early in the season or late in the season. In contrast to a previous report, no significant difference in the NRA was found between woody and herbaceous plants. Although the difference was no more than that of vegetation coverage, the estimated community-level NRA inside the fence was 5.6 times higher than that of the outside. The difference was greatest early in the season. These results support our hypothesis.
Whole Exome Sequencing Aids the Diagnosis of Fetal Skeletal Dysplasia
Authors: Tang Hui , Zhang Qin , Xiang Jingjing , Yin Linliang , Wang Jing , Wang Ting
Published: March 2021

Skeletal dysplasia is a complex group of bone and cartilage disorders with strong clinical and genetic heterogeneity. Several types have prenatal phenotypes, and it is difficult to make a molecular diagnosis rapidly. In this study, the genetic cause of 16 Chinese fetuses with skeletal dysplasia were analyzed, and 12 cases yielded positive results including one deletion in DMD gene detected by SNP-array and 14 variants in other 6 genes detected by whole exome sequencing (WES). In addition, somatic mosaicism was observed. Our study expanded the pathogenic variant spectrum and elucidated the utilization of WES in improving the diagnosis yield of skeletal dysplasia.
Reduction of Allergic Lung Disease by Mucosal Application of Toxoplasma gondii-Derived Molecules: Possible Role of Carbohydrates
Authors: Korb Elke , Drinić Mirjana , Wagner Angelika , Geissler Nora , Inic-Kanada Aleksandra , Peschke Roman , Joachim Anja , Wiedermann Ursula , Schabussova Irma
Published: March 2021

Background

The hygiene hypothesis suggests a link between parasitic infections and immune disorders, such as allergic diseases. We previously showed that infection withToxoplasma gondiior systemic application ofT. gondiitachyzoites lysate antigen (TLA) in a prophylactic, but not therapeutic protocol, prevented allergic airway inflammation in mice. Here we tested the effect of prophylactic and therapeutic application of TLAviathe mucosal route.

Methods

Mice were intranasally treated with TLA either i) prior to sensitization, ii) during sensitization and challenge, or iii) after sensitization with ovalbumin (OVA). Recruitment of inflammatory cells to the lung, cytokine levels in restimulated lung and spleen cell cultures as well as levels of OVA-specific antibodies in serum were measured. In parallel, the effect of native TLA, heat-inactivated (hiTLA) or deglycosylated TLA (dgTLA) on sensitized splenocytes was evaluatedex vivo.

Results

When applied together with OVA i) during systemic sensitization and local challenge or ii) exclusively during local challenge, TLA reduced infiltration of eosinophils into the lung, OVA-specific type 2 cytokines in restimulated lung cell cultures, and partially, type 2 cytokines in restimulated spleen cell cultures in comparison to allergic controls. No beneficial effect was observed when TLA was applied prior to the start of sensitization. Analysis of epitope sugars on TLA indicated a high abundance of mannose, fucose, N-acetylglucosamine, and N-acetylgalactosamine. Deglycosylation of TLA, but not heat-inactivation, abolished the potential of TLA to reduce type 2 responsesex vivo, suggesting a significant role of carbohydrates in immunomodulation.

Conclusion

We showed that mucosal application of TLA reduced the development of experimental allergy in mice. The beneficial effects depended on the timing of the application in relation to the time point of sensitization. Not only co-application, but also therapy in sensitized/allergic animals with native TLA reduced local allergic responses. Furthermore, we show that TLA is highly glycosylated and glycoconjugates seem to play a role in anti-allergic effects. In summary, given the powerful modulatory effect that TLA exhibits, understanding its exact mechanisms of action may lead to the development of novel immunomodulators in clinical application.
In Vitro Culture Expansion Shifts the Immune Phenotype of Human Adipose-Derived Mesenchymal Stem Cells
Authors: Jeske Richard , Yuan Xuegang , Fu Qin , Bunnell Bruce A. , Logan Timothy M. , Li Yan
Published: March 2021

Human mesenchymal stem or stromal cells (hMSCs) are known for their potential in regenerative medicine due to their differentiation abilities, secretion of trophic factors, and regulation of immune responses in damaged tissues. Due to the limited quantity of hMSCs typically isolated from bone marrow, other tissue sources, such as adipose tissue-derived mesenchymal stem cells (hASCs), are considered a promising alternative. However, differences have been observed for hASCs in the context of metabolic characteristics and response to in vitro culture stress compared to bone marrow derived hMSCs (BM-hMSCs). In particular, the relationship between metabolic homeostasis and stem cell functions, especially the immune phenotype and immunomodulation of hASCs, remains unknown. This study thoroughly assessed the changes in metabolism, redox cycles, and immune phenotype of hASCs during in vitro expansion. In contrast to BM-hMSCs, hASCs did not respond to culture stress significantly during expansion as limited cellular senescence was observed. Notably, hASCs exhibited the increased secretion of pro-inflammatory cytokines and the decreased secretion of anti-inflammatory cytokines after extended culture expansion. The NAD+/NADH redox cycle and other metabolic characteristics associated with aging were relatively stable, indicating that hASC functional decline may be regulated through an alternative mechanism rather than NAD+/Sirtuin aging pathways as observed in BM-hMSCs. Furthermore, transcriptome analysis by mRNA-sequencing revealed the upregulation of genes for pro-inflammatory cytokines/chemokines and the downregulation of genes for anti-inflammatory cytokines for hASCs at high passage. Proteomics analysis indicated key pathways (e.g., tRNA charging, EIF2 signaling, protein ubiquitination pathway) that may be associated with the immune phenotype shift of hASCs. Together, this study advances our understanding of the metabolism and senescence of hASCs and may offer vital insights for the biomanufacturing of hASCs for clinical use.
IBT-V02: A Multicomponent Toxoid Vaccine Protects Against Primary and Secondary Skin Infections Caused by Staphylococcus aureus
Authors: Karauzum Hatice , Venkatasubramaniam Arundhathi , Adhikari Rajan P. , Kort Tom , Holtsberg Frederick W. , Mukherjee Ipsita , Mednikov Mark , Ortines Roger , Nguyen Nhu T. Q. , Doan Thien M. N. , Diep Binh An , Lee Jean C. , Aman M. Javad
Published: March 2021

Staphylococcus aureus causes a wide range of diseases from skin infections to life threatening invasive diseases such as bacteremia, endocarditis, pneumonia, surgical site infections, and osteomyelitis. Skin infections such as furuncles, carbuncles, folliculitis, erysipelas, and cellulitis constitute a large majority of infections caused by S. aureus (SA). These infections cause significant morbidity, healthcare costs, and represent a breeding ground for antimicrobial resistance. Furthermore, skin infection with SA is a major risk factor for invasive disease. Here we describe the pre-clinical efficacy of a multicomponent toxoid vaccine (IBT-V02) for prevention of S. aureus acute skin infections and recurrence. IBT-V02 targets six SA toxins including the pore-forming toxins alpha hemolysin (Hla), Panton-Valentine leukocidin (PVL), leukocidin AB (LukAB), and the superantigens toxic shock syndrome toxin-1 and staphylococcal enterotoxins A and B. Immunization of mice and rabbits with IBT-V02 generated antibodies with strong neutralizing activity against toxins included in the vaccine, as well as cross-neutralizing activity against multiple related toxins, and protected against skin infections by several clinically relevant SA strains of USA100, USA300, and USA1000 clones. Efficacy of the vaccine was also shown in non-naïve mice pre-exposed to S. aureus. Furthermore, vaccination with IBT-V02 not only protected mice from a primary infection but also demonstrated lasting efficacy against a secondary infection, while prior challenge with the bacteria alone was unable to protect against recurrence. Serum transfer studies in a primary infection model showed that antibodies are primarily responsible for the protective response.
Regulatory Dendritic Cells, T Cell Tolerance, and Dendritic Cell Therapy for Immunologic Disease
Authors: Ness Sara , Lin Shiming , Gordon John R.
Published: March 2021

Dendritic cells (DC) are antigen-presenting cells that can communicate with T cells both directly and indirectly, regulating our adaptive immune responses against environmental and self-antigens. Under some microenvironmental conditions DC develop into anti-inflammatory cells which can induce immunologic tolerance. A substantial body of literature has confirmed that in such settings regulatory DC (DCreg) induce T cell tolerance by suppression of effector T cells as well as by induction of regulatory T cells (Treg). Many in vitro studies have been undertaken with human DCreg which, as a surrogate marker of antigen-specific tolerogenic potential, only poorly activate allogeneic T cell responses. Fewer studies have addressed the abilities of, or mechanisms by which these human DCreg suppress autologous effector T cell responses and induce infectious tolerance-promoting Treg responses. Moreover, the agents and properties that render DC as tolerogenic are many and varied, as are the cells’ relative regulatory activities and mechanisms of action. Herein we review the most current human and, where gaps exist, murine DCreg literature that addresses the cellular and molecular biology of these cells. We also address the clinical relevance of human DCreg, highlighting the outcomes of pre-clinical mouse and non-human primate studies and early phase clinical trials that have been undertaken, as well as the impact of innate immune receptors and symbiotic microbial signaling on the immunobiology of DCreg.
Roles of RNA Methylation on Tumor Immunity and Clinical Implications
Authors: Zhang Maorun , Song Junmin , Yuan Weitang , Zhang Wei , Sun Zhenqiang
Published: March 2021

RNA methylation is a kind of RNA modification that exists widely in eukaryotes and prokaryotes. RNA methylation occurs not only in mRNA but also in ncRNA. According to the different sites of methylation, RNA methylation includes m6A, m5C, m7G, and 2-O-methylation modifications. Modifications affect the splicing, nucleation, stability and immunogenicity of RNA. RNA methylation is involved in many physiological and pathological processes. In the immune system, especially for tumor immunity, RNA methylation affects the maturation and response function of immune cells. Through the influence of RNA immunogenicity and innate immune components, modifications regulate the innate immunity of the body. Some recent studies verified that RNA methylation can regulate tumor immunity, which also provides a new idea for the future of treating immunological diseases and tumor immunotherapy.
Extracellular HMGB1 Contributes to the Chronic Cardiac Allograft Vasculopathy/Fibrosis by Modulating TGF-β1 Signaling
Authors: Zou Huijuan , Ming Bingxia , Li Jun , Xiao Yifan , Lai Lin , Gao Ming , Xu Yong , Tan Zheng , Gong Feili , Zheng Fang
Published: March 2021

Cardiac allograft vasculopathy (CAV) charactered with aberrant remodeling and fibrosis usually leads to the loss of graft after heart transplantation. Our previous work has reported that extracellular high-mobility group box 1 (HMGB1) participated in the CAV progression via promoting inflammatory cells infiltration and immune damage. The aim of this study was to investigate the involvement of HMGB1 in the pathogenesis of CAV/fibrosis and potential mechanisms using a chronic cardiac rejection model in mice. We found high levels of transforming growth factor (TGF)-β1 in cardiac allografts after transplantation. Treatment with HMGB1 neutralizing antibody markedly prolonged the allograft survival accompanied by attenuated fibrosis of cardiac allograft, decreased fibroblasts-to-myofibroblasts conversion, and reduced synthesis and release of TGF-β1. In addition, recombinant HMGB1 stimulation promoted release of active TGF-β1 from cardiac fibroblasts and macrophagesin vitro, and subsequent phosphorylation of Smad2 and Smad3 which were downstream of TGF-β1 signaling. These data indicate that HMGB1 contributes to the CAV/fibrosis via promoting the activation of TGF-β1/Smad signaling. Targeting HMGB1 might become a new therapeutic strategy for inhibiting cardiac allograft fibrosis and dysfunction.
Development of the CSOMIO Coupled Ocean-Oil-Sediment- Biology Model
Authors: Dukhovskoy Dmitry S. , Morey Steven L. , Chassignet Eric P. , Chen Xu , Coles Victoria J. , Cui Linlin , Harris Courtney K. , Hetland Robert , Hsu Tian-Jian , Manning Andrew J. , Stukel Michael , Thyng Kristen , Wang Jiaze
Published: March 2021

The fate and dispersal of oil in the ocean is dependent upon ocean dynamics, as well as transformations resulting from the interaction with the microbial community and suspended particles. These interaction processes are parameterized in many models limiting their ability to accurately simulate the fate and dispersal of oil for subsurface oil spill events. This paper presents a coupled ocean-oil-biology-sediment modeling system developed by the Consortium for Simulation of Oil-Microbial Interactions in the Ocean (CSOMIO) project. A key objective of the CSOMIO project was to develop and evaluate a modeling framework for simulating oil in the marine environment, including its interaction with microbial food webs and sediments. The modeling system developed is based on the Coupled Ocean-Atmosphere-Wave-Sediment Transport model (COAWST). Central to CSOMIO’s coupled modeling system is an oil plume model coupled to the hydrodynamic model (Regional Ocean Modeling System, ROMS). The oil plume model is based on a Lagrangian approach that describes the oil plume dynamics including advection and diffusion of individual Lagrangian elements, each representing a cluster of oil droplets. The chemical composition of oil is described in terms of three classes of compounds: saturates, aromatics, and heavy oil (resins and asphaltenes). The oil plume model simulates the rise of oil droplets based on ambient ocean flow and density fields, as well as the density and size of the oil droplets. The oil model also includes surface evaporation and surface wind drift. A novel component of the CSOMIO model is two-way Lagrangian-Eulerian mapping of the oil characteristics. This mapping is necessary for implementing interactions between the ocean-oil module and the Eulerian sediment and biogeochemical modules. The sediment module is a modification of the Community Sediment Transport Modeling System. The module simulates formation of oil-particle aggregates in the water column. The biogeochemical module simulates microbial communities adapted to the local environment and to elevated concentrations of oil components in the water column. The sediment and biogeochemical modules both reduce water column oil components. This paper provides an overview of the CSOMIO coupled modeling system components and demonstrates the capabilities of the modeling system in the test experiments.