bluuebunny/crossref_metadata_2025 huggingface dataset:
Climate Change and Water Governance: Decision Making for Individual Vineyard Owners in Global Wine Regions
Authors: Upton Erin , Nielsen-Pincus Max
Published: June 2021

This study investigates the institutional, social, and ecological dynamics that influence regional water governance and individual vineyard owners' decision making in global wine regions. Global wine grape production has grown steadily over the past 20 years, and climate change has emerged as a driver of transformation in wine regions resulting in a range of impacts. Changes to the climate are anticipated to accelerate in the future and present a number of challenges for wine regions; including risks to human systems, e.g., agriculture, labor, and economics, as well as ecological systems, e.g., surface and groundwater. Water is a critical resource for environmental and economic sustainability in wine regions, and vulnerability to freshwater resources in wine producing regions is expected to increase as wine regions experience climate extremes like heat and drought. We use the Institutional-Social-Ecological Dynamics (ISED) framework to help understand individual vineyard owner decision making about water management within the context of institutional, social, and ecological systems. We ask how the relationships between these systems impact outcomes for individual grape farmers adapting to climate challenges. Our empirical research uses document review and interviews with vineyard owners, planners, and natural resource managers in wine regions in Oregon, USA and Tasmania, Australia as a means to explore climate vulnerabilities and adaptation approaches. Subsequently we focus on an example vignette in each region to better understand individual decision making at the farm scale within the unique institutional, social, and ecological contexts identified in each region. Our cases highlight the finding that entrenched institutional regimes, in the context of ecological variability contribute to a social unevenness in access to water. Landowner conflict over water resources is likely to increase in the context of a hotter, drier climate in regions with wine industry growth. Individual vineyard owners have a range of attitudes and approaches to climate change planning and management; and adaptation around water is dependent on both economic resources and social values. Lessons from the individual farm scale help to inform broader implications of how institutional, social, and ecological drivers influence opportunities or barriers to the implementation of climate change adaptation practices in wine regions.
Blood Flow Within Bioengineered 3D Printed Vascular Constructs Using the Porcine Model
Authors: Galván Nhu Thao N. , Paulsen Samantha J. , Kinstlinger Ian S. , Marini Juan C. , Didelija Inka C. , Yoeli Dor , Grigoryan Bagrat , Miller Jordan S.
Published: June 2021

Recently developed biofabrication technologies are enabling the production of three-dimensional engineered tissues containing vascular networks which can deliver oxygen and nutrients across large tissue volumes. Tissues at this scale show promise for eventual regenerative medicine applications; however, the implantation and integration of these constructs in vivo remains poorly studied. Here, we introduce a surgical model for implantation and direct in-line vascular connection of 3D printed hydrogels in a porcine arteriovenous shunt configuration. Utilizing perfusable poly(ethylene glycol) diacrylate (PEGDA) hydrogels fabricated through projection stereolithography, we first optimized the implantation procedure in deceased piglets. Subsequently, we utilized the arteriovenous shunt model to evaluate blood flow through implanted PEGDA hydrogels in non-survivable studies. Connections between the host femoral artery and vein were robust and the patterned vascular channels withstood arterial pressure, permitting blood flow for 6 h. Our study demonstrates rapid prototyping of a biocompatible and perfusable hydrogel that can be implanted in vivo as a porcine arteriovenous shunt, suggesting a viable surgical approach for in-line implantation of bioprinted tissues, along with design considerations for future in vivo studies. We further envision that this surgical model may be broadly applicable for assessing whether biomaterials optimized for 3D printing and cell function can also withstand vascular cannulation and arterial blood pressure. This provides a crucial step toward generated transplantable engineered organs, demonstrating successful implantation of engineered tissues within host vasculature.
Coronary Stent Healing in Cancer Patients—An Optical Coherence Tomography Perspective
Authors: Aziz Moez Karim , Herrmann Joerg , Marmagkiolis Konstantinos , Balanescu Dinu Valentin , Donisan Teodora , Pushparaji Bala , Lin Heather Y. , Tomakin Gerryross , Hoyt Taylor , Pham Martin , Dijkstra Jouke , Cilingiroglu Mehmet , Lopez-Mattei Juan , Zaha Vlad , Anderson H. Vernon , Feldman Marc D. , Molony Donald A. , Iliescu Cezar A.
Published: June 2021

Objective: This study assessed stent healing patterns and cardiovascular outcomes by optical coherence tomography (OCT) in cancer patients after drug-eluting stent (DES) placement.

Background: Cancer treatment, owing to its cytotoxic and antiproliferative effects, could delay stent healing and increase stent thrombosis risk, especially when dual antiplatelet therapy (DAPT) is discontinued early for oncological treatment. OCT can assess stent endothelialization and other healing parameters, which may provide clinical guidance in these challenging scenarios.

Methods: This single-center retrospective study enrolled all cancer patients who underwent OCT for assessment of vascular healing patterns after prior DES placement from November 2009 to November 2018. Primary study endpoints were stent healing parameters, including stent coverage, apposition, degree of expansion, neointimal hyperplasia heterogeneity, in-stent restenosis, stent thrombosis, and overall survival (OS).

Results: A total of 67 patients were included in this study. Mean time between DES placement and OCT evaluation was 154 ± 82 days. Stent healing matched published values for DES in non-cancer patients (P ≥ 0.063). At 1 year, the OS was 86% (95% confidence interval [CI]: 78–96%) with 0% incidence of acute coronary syndrome. Advanced cancers and active chemotherapies were associated with inferior OS (P = 0.024, hazard ratio [HR]: 3.50, 95% CI: 1.18–10.42 and P = 0.026, HR: 2.65, 95% CI: 1.13–6.22, respectively), while stent healing parameters were unassociated with OS. Forty-one patients (61%) had DAPT duration ≤6 months.

Conclusions: Stent healing of contemporary DES appears similar in cancer and non-cancer patients. Cardiovascular risk of cancer patients after DES placement can be managed to facilitate timely cancer therapies, as the underlying malignancy and active chemotherapy ultimately determine survival.
What Is the Clinical Impact of Stress CMR After the ISCHEMIA Trial?
Authors: Pezel Théo , Silva Luis Miguel , Bau Adriana Aparecia , Teixiera Adherbal , Jerosch-Herold Michael , Coelho-Filho Otávio R.
Published: June 2021

After progressively receding for decades, cardiovascular mortality due to coronary artery disease has recently increased, and the associated healthcare costs are projected to double by 2030. While the 2019 European Society of Cardiology guidelines for chronic coronary syndromes recommend non-invasive cardiac imaging for patients with suspected coronary artery disease, the impact of non-invasive imaging strategies to guide initial coronary revascularization and improve long-term outcomes is still under debate. Recently, the ISCHEMIA trial has highlighted the fundamental role of optimized medical therapy and the lack of overall benefit of early invasive strategies at a median follow-up of 3.2 years. However, sub-group analyses excluding procedural infarctions with longer follow-ups of up to 5 years have suggested that patients undergoing revascularization had better outcomes than those receiving medical therapy alone. A recent sub-study of ISCHEMIA in patients with heart failure or reduced left ventricular ejection fraction (LVEF <45%) indicated that revascularization improved clinical outcomes compared to medical therapy alone. Furthermore, other large observational studies have suggested a favorable prognostic impact of coronary revascularization in patients with severe inducible ischemia assessed by stress cardiovascular magnetic resonance (CMR). Indeed, some data suggest that stress CMR-guided revascularization assessing the extent of the ischemia could be useful in identifying patients who would most benefit from invasive procedures such as myocardial revascularization. Interestingly, the MR-INFORM trial has recently shown that a first-line stress CMR-based non-invasive assessment was non-inferior in terms of outcomes, with a lower incidence of coronary revascularization compared to an initial invasive approach guided by fractional flow reserve in patients with stable angina. In the present review, we will discuss the current state-of-the-art data on the prognostic value of stress CMR assessment of myocardial ischemia in light of the ISCHEMIA trial results, highlighting meaningful sub-analyses, and still unanswered opportunities of this pivotal study. We will also review the available evidence for the potential clinical application of quantifying the extent of ischemia to stratify cardiovascular risk and to best guide invasive and non-invasive treatment strategies.
Archaeological Investigation and Hazard Assessment Using Magnetic, Ground-Penetrating Radar, and GPS Tools at Dahshour Area, Giza, Egypt
Authors: El Emam A. E. , Lethy A. , Radwan Ali M. , Awad A.
Published: June 2021

An archeological study using magnetic and ground-penetrating radar methods has been performed at the Dahshour region (Giza, Egypt), where various covered structures have not been found because of the long coercion of the zone under the military specialists. Dahshour is the southern extension of the Saqqara and Giza Pyramids plateau, around 25 km south of Cairo. The area is known for its colored pyramids—the white, red, and black pyramids, and the famous Bent Pyramid. Four investigation sites were chosen around the Bent Pyramid complex. The geophysical investigation has revealed the presence of some buried structures made up of mud bricks such as tombs, mud-brick walls, causeway, and remains of an ancient temple. Numerous limestone blocks were also detected. The study indicates the possible existence of an older valley temple made up of mud bricks and confirms the existence of another causeway that led to the Nile Valley. To protect the Egyptian heritage around this vital area, a detailed computation of the current crustal stress/strain state has been performed by taking into account all the available GPS observations. Achieved results indicated that the southern and the southeastern sectors of the investigated area are currently accumulating strain, and this means that there is a possibility for future earthquakes to occur around this vital archaeological area. Buried structures are preserved by confinement in the burial materials like a large mold. However, external load or stress can still cause damage. Therefore, during excavation, the stress should be reduced to avoid wall collapsing and structure damage. Therefore, it is recommended to start excavation from the stress direction from the southern side.
The Impact of COVID-19 on Interpersonal Aspects in Elementary School
Authors: Herrmann Lukas , Nielsen Birgitte Lund , Aguilar-Raab Corina
Published: June 2021

Social-emotional education and the relational competence of school staff and leaders are emphasized in research since they strongly impact childrens’ social, emotional, and cognitive development. In a longitudinal project—Empathie macht Schule (EmS)—we aim at evaluating the outcome and process of an empathy training for the whole school staff, including leaders. We compare three treatments to three control elementary schoolsviaa mixed-methods approach employing qualitative and quantitative research methods targeting both, the school staff and the schoolchildren. Since the start of the project in 2019, the COVID-19 pandemic has disrupted the global education process, that is, the range of training activities for school staff in an unprecedented manner. First the lockdown and then the hygienic measures impact the habits and certainties in schools on multiple levels, including artifacts (e.g., physical distancing measures and virtual platforms), processes (e.g., virtual learning and home-schooling), social structures (e.g., separation of a high-risk group), and values (e.g., difficulties in building relations and showing empathy due to physical distance). Leaders and staff are facing an uncertain situation, while their actions and decisions may—also unintentionally—shape the social reality that will be inhabited to a significant extent. In this context, a number of questions become salient. How does the disruption of the pandemic affect interpersonal relationships, interactions, and the social field—the sum of relationships within the system of a school—as a whole? And specifically, how do the actors reflect on changes in the social field, their relationships, and the schools’ and classrooms’ overall relationship quality due to the crisis? The assessment combines qualitative interviews with leaders and teachers (N= 10) along with a self-report survey (N= 80) addressing the effects of the pandemic on interpersonal aspects in schools. Surprisingly, a number of positive effects were mentioned regarding the learning environment in the smaller-sized classes, which were caused by hygienic measures, as well as increased cohesion among faculty. The potential influence of these effects by consciously shaping relationships and cultivating empathy is discussed in the article.
Satisfying Students’ Psychological Needs During the COVID-19 Outbreak in German Higher Education Institutions
Authors: Teuber Ziwen , Jia Hao , Niewöhner Thomas
Published: June 2021

The COVID-19 outbreak has been a worldwide challenge for the higher education community. Under lockdown measures, meeting students’ needs and encouraging their engagement in academic work have never been more urgent and challenging. In this study, we investigated the relationship between students’ satisfaction with institutional strategies, students’ optimism and pessimism, satisfaction with basic psychological needs, engagement in academic work, intention to drop out from studies, depression, and well-being. We conducted an online self-report study on N = 477 German college and university students (77.25% females, mean age = 23.96 years, SD = 4.78). The results of structural equation models showed that students’ satisfaction with institutional strategies was positively related to their basic psychological need satisfaction and engagement. Students’ optimism was positively associated with need satisfaction and engagement, whereas pessimism was negatively associated with them. Furthermore, students’ academic engagement was negatively linked to dropout intentions, whereas psychological need satisfaction was linked to depression and well-being. The findings of this study suggest that acknowledging students timely about the institutional strategies of examinations and courses and supporting students to engage academic activities are important institutional tasks during crisis.
Modelling of Epithelial Growth, Fission and Lumen Formation During Embryonic Thyroid Development: A Combination of Computational and Experimental Approaches
Authors: Gonay Leolo , Spourquet Catherine , Baudoin Matthieu , Lepers Ludovic , Lemoine Pascale , Fletcher Alexander G. , Hanert Emmanuel , Pierreux Christophe E.
Published: June 2021

Organogenesis is the phase of embryonic development leading to the formation of fully functional organs. In the case of the thyroid, organogenesis starts from the endoderm and generates a multitude of closely packed independent spherical follicular units surrounded by a dense network of capillaries. Follicular organisation is unique and essential for thyroid function, i.e. thyroid hormone production. Previous in vivo studies showed that, besides their nutritive function, endothelial cells play a central role during thyroid gland morphogenesis. However, the precise mechanisms and biological parameters controlling the transformation of the multi-layered thyroid epithelial primordium into a multitude of single-layered follicles are mostly unknown. Animal studies used to improve understanding of organogenesis are costly and time-consuming, with recognised limitations. Here, we developed and used a 2-D vertex model of thyroid growth, angiogenesis and folliculogenesis, within the open-source Chaste framework. Our in silico model, based on in vivo images, correctly simulates the differential growth and proliferation of central and peripheral epithelial cells, as well as the morphogen-driven migration of endothelial cells, consistently with our experimental data. Our simulations further showed that reduced epithelial cell adhesion was critical to allow endothelial invasion and fission of the multi-layered epithelial mass. Finally, our model also allowed epithelial cell polarisation and follicular lumen formation by endothelial cell abundance and proximity. Our study illustrates how constant discussion between theoretical and experimental approaches can help us to better understand the roles of cellular movement, adhesion and polarisation during thyroid embryonic development. We anticipate that the use of in silico models like the one we describe can push forward the fields of developmental biology and regenerative medicine.
Living up to the Hype of Hyperspectral Aquatic Remote Sensing: Science, Resources and Outlook
Authors: Dierssen Heidi M. , Ackleson Steven G. , Joyce Karen E. , Hestir Erin L. , Castagna Alexandre , Lavender Samantha , McManus Margaret A.
Published: June 2021

Intensifying pressure on global aquatic resources and services due to population growth and climate change is inspiring new surveying technologies to provide science-based information in support of management and policy strategies. One area of rapid development is hyperspectral remote sensing: imaging across the full spectrum of visible and infrared light. Hyperspectral imagery contains more environmentally meaningful information than panchromatic or multispectral imagery and is poised to provide new applications relevant to society, including assessments of aquatic biodiversity, habitats, water quality, and natural and anthropogenic hazards. To aid in these advances, we provide resources relevant to hyperspectral remote sensing in terms of providing the latest reviews, databases, and software available for practitioners in the field. We highlight recent advances in sensor design, modes of deployment, and image analysis techniques that are becoming more widely available to environmental researchers and resource managers alike. Systems recently deployed on space- and airborne platforms are presented, as well as future missions and advances in unoccupied aerial systems (UAS) and autonomous in-water survey methods. These systems will greatly enhance the ability to collect interdisciplinary observations on-demand and in previously inaccessible environments. Looking forward, advances in sensor miniaturization are discussed alongside the incorporation of citizen science, moving toward open and FAIR (findable, accessible, interoperable, and reusable) data. Advances in machine learning and cloud computing allow for exploitation of the full electromagnetic spectrum, and better bridging across the larger scientific community that also includes biogeochemical modelers and climate scientists. These advances will place sophisticated remote sensing capabilities into the hands of individual users and provide on-demand imagery tailored to research and management requirements, as well as provide critical input to marine and climate forecasting systems. The next decade of hyperspectral aquatic remote sensing is on the cusp of revolutionizing the way we assess and monitor aquatic environments and detect changes relevant to global communities.
Microplastic Fiber Emissions From Wastewater Effluents: Abundance, Transport Behavior and Exposure Risk for Biota in an Arctic Fjord
Authors: Herzke Dorte , Ghaffari Peygham , Sundet Jan Henry , Tranang Caroline Aas , Halsband Claudia
Published: June 2021

Microfibers (MF) are one of the major classes of microplastic found in the marine environment on a global scale. Very little is known about how they move and distribute from point sources such as wastewater effluents into the ocean. We chose Adventfjorden near the settlement of Longyearbyen on the Arctic Svalbard archipelago as a case study to investigate how microfibers emitted with untreated wastewater will distribute in the fjord, both on a spatial and temporal scale. Fiber abundance in the effluent was estimated from wastewater samples taken during two one-week periods in June and September 2017. Large emissions of MFs were detected, similar in scale to a modern WWTP serving 1.3 million people and providing evidence of the importance of untreated wastewater from small settlements as major local sources for MF emissions in the Arctic. Fiber movement and distribution in the fjord mapped using an online-coupled hydrodynamic-drift model (FVCOM-FABM). For parameterizing a wider spectrum of fibers from synthetic to wool, four different density classes of MFs, i.e., buoyant, neutral, sinking, and fast sinking fibers are introduced to the modeling framework. The results clearly show that fiber class has a large impact on the fiber distributions. Light fibers remained in the surface layers and left the fjord quickly with outgoing currents, while heavy fibers mostly sank to the bottom and deposited in the inner parts of the fjord and along the northern shore. A number of accumulation sites were identified within the fjord. The southern shore, in contrast, was much less affected, with low fiber concentrations throughout the modeling period. Fiber distributions were then compared with published pelagic and benthic fauna distributions in different seasons at selected stations around the fjord. The ratios of fibers to organisms showed a very wide range, indicating hot spots of encounter risk for pelagic and benthic biota. This approach, in combination with in-situ ground-truthing, can be instrumental in understanding microplastic pathways and fate in fjord systems and coastal areas and help authorities develop monitoring and mitigation strategies for microfiber and microplastic pollution in their local waters.
Imprints of Past Habitat Area Reduction on Extant Taxonomic, Functional, and Phylogenetic Composition
Authors: Barthelemy Elizabeth , Fortunel Claire , Jaunatre Maxime , Munoz François
Published: June 2021

Past environmental changes have shaped the evolutionary and ecological diversity of extant organisms. Specifically, climatic fluctuations have made environmental conditions alternatively common or rare over time. Accordingly, most taxa have undergone restriction of their distribution to local refugia during habitat contraction, from which they could expand when suitable habitat became more common. Assessing how past restrictions in refugia have shaped species distributions and genetic diversity has motivated much research in evolutionary biology and biogeography. But there is still lack of clear synthesis on whether and how the taxonomic, functional and phylogenetic composition of extant multispecies assemblages retains the imprint of past restriction in refugia. We devised an original eco-evolutionary model to investigate the temporal dynamics of a regional species pool inhabiting a given habitat today, and which have experienced habitat reduction in the past. The model includes three components: (i) a demographic component driving stochastic changes in population sizes and extinctions due to habitat availability, (ii) a mutation and speciation component representing how divergent genotypes emerge and define new species over time, and (iii) a trait evolution component representing how trait values have changed across descendants over time. We used this model to simulate dynamics of multispecies assemblages that occupied a restricted refugia in the past and could expand their distribution subsequently. We characterized the past restriction in refugia in terms of two parameters representing the ending time of past refugia, and the extent of habitat restriction in the refugia. We characterized extant patterns of taxonomic, functional and phylogenetic diversity depending on these parameters. We found that extant relative abundances reflect the lasting influence of more recent refugia on demographic dynamics, while phylogenetic composition reflects the influence of more ancient habitat change. Extant functional diversity depends on the interplay between diversification dynamics and trait evolution, offering new options to jointly infer current trait adaptation and past trait evolution dynamics.
Animal Models of Multiple Myeloma Bone Disease
Authors: Mehdi Syed Hassan , Nafees Sana , Mehdi Syed Jafar , Morris Carol A. , Mashouri Ladan , Yoon Donghoon
Published: June 2021

Multiple myeloma (MM) is a clonal B-cell disorder characterized by the proliferation of malignant plasma cells (PCs) in the bone marrow, the presence of monoclonal serum immunoglobulin, and osteolytic lesions. It is the second most common hematological malignancy and considered an incurable disease despite significant treatment improvements. MM bone disease (MMBD) is defined as the presence of one or more osteolytic bone lesions or diffused osteoporosis with compression fracture attributable to the underlying clonal PC disorder. MMBD causes severe morbidity and increases mortality. Cumulative evidence shows that the interaction of MM cells and bone microenvironment plays a significant role in MM progression, suggesting that these interactions may be good targets for therapy. MM animal models have been developed and studied in various aspects of MM tumorigenesis. In particular, MMBD has been studied in various models, and each model has unique features. As the general features of MM animal models have been reviewed elsewhere, the current review will focus on the features of MMBD animal models.
Absence of Non-Canonical, Inhibitory MYD88 Splice Variants in B Cell Lymphomas Correlates With Sustained NF-κB Signaling
Authors: Cardona Gloria Yamel , Bernhart Stephan H. , Fillinger Sven , Wolz Olaf-Oliver , Dickhöfer Sabine , Admard Jakob , Ossowski Stephan , Nahnsen Sven , Siebert Reiner , Weber Alexander N. R.
Published: June 2021

Gain-of-function mutations of the TLR adaptor and oncoprotein MyD88 drive B cell lymphomagenesis via sustained NF-κB activation. In myeloid cells, both short and sustained TLR activation and NF-κB activation lead to the induction of inhibitory MYD88 splice variants that restrain prolonged NF-κB activation. We therefore sought to investigate whether such a negative feedback loop exists in B cells. Analyzing MYD88 splice variants in normal B cells and different primary B cell malignancies, we observed that MYD88 splice variants in transformed B cells are dominated by the canonical, strongly NF-κB-activating isoform of MYD88 and contain at least three novel, so far uncharacterized signaling-competent splice isoforms. Sustained TLR stimulation in B cells unexpectedly reinforces splicing of NF-κB-promoting, canonical isoforms rather than the ‘MyD88s’, a negative regulatory isoform reported to be typically induced by TLRs in myeloid cells. This suggests that an essential negative feedback loop restricting TLR signaling in myeloid cells at the level of alternative splicing, is missing in B cells when they undergo proliferation, rendering B cells vulnerable to sustained NF-κB activation and eventual lymphomagenesis. Our results uncover MYD88 alternative splicing as an unappreciated promoter of B cell lymphomagenesis and provide a rationale why oncogenic MYD88 mutations are exclusively found in B cells.
Overexpression of lncRNA TUG1 Alleviates NLRP3 Inflammasome-Mediated Cardiomyocyte Pyroptosis Through Targeting the miR-186-5p/XIAP Axis in Coronary Microembolization-Induced Myocardial Damage
Authors: Zhou You , Li Tao , Chen Zhiqing , Huang Junwen , Qin Zhenbai , Li Lang
Published: June 2021

Coronary microembolization (CME) is a complicated problem that commonly arises in the context of coronary angioplasty. The lncRNA taurine-up regulated gene 1 (TUG1), significantly contributes to cardiovascular diseases; however, its contribution to CME-induced myocardial damage remains elusive. Herein, we establish the rat CME model and investigate the role of TUG1 in CME. The cell viability was evaluated via CCK-8 assay. Serum and cell culture supernatant samples were evaluated via ELISA. The dual luciferase reporter (DLR) assay, RIP, and RNA-pull down were conducted to validate the associations between TUG1 and miR-186-5p as well as miR-186-5p and XIAP. The expression of TUG1, miR-186-5p, and XIAP mRNA were determined by RT-qPCR, and proteins were evaluated via immuneblotting. As a result, TUG1 and XIAP were significantly down-regulated, and the miR-186-5p level was found to be remarkably up-regulated in CME myocardial tissues. Overexpression of TUG1 alleviated CME-induced myocardial injury and pyroptosis, whereas TUG1 knockdown showed the opposite effects. The DLR assay, RIP, and RNA-pull down results reveal that TUG1 directly targets miR-186-5p and miR-186-5p directly targets XIAP. In vitro rescue experiments show that TUG1 overexpression alleviates LPS-caused cardiomyocyte injury and pyroptosis via sponging miR-186-5p and regulating XIAP, and depression of miR-186-5p reduces LPS-induced cardiomyocyte injury and pyroptosis by targeting XIAP. Concludingly, the overexpression of TUG1 alleviates NLRP3 inflammasome-mediated cardiomyocyte pyroptosis through targeting the miR-186-5p/XIAP axis in CME-induced myocardial injury.
Glycolysis Inhibition Induces Functional and Metabolic Exhaustion of CD4+ T Cells in Type 1 Diabetes
Authors: Martins Christina P. , New Lee A. , O’Connor Erin C. , Previte Dana M. , Cargill Kasey R. , Tse Isabelle L. , Sims- Lucas Sunder , Piganelli Jon D.
Published: June 2021

In Type 1 Diabetes (T1D), CD4+ T cells initiate autoimmune attack of pancreatic islet β cells. Importantly, bioenergetic programs dictate T cell function, with specific pathways required for progression through the T cell lifecycle. During activation, CD4+ T cells undergo metabolic reprogramming to the less efficient aerobic glycolysis, similarly to highly proliferative cancer cells. In an effort to limit tumor growth in cancer, use of glycolytic inhibitors have been successfully employed in preclinical and clinical studies. This strategy has also been utilized to suppress T cell responses in autoimmune diseases like Systemic Lupus Erythematosus (SLE), Multiple Sclerosis (MS), and Rheumatoid Arthritis (RA). However, modulating T cell metabolism in the context of T1D has remained an understudied therapeutic opportunity. In this study, we utilized the small molecule PFK15, a competitive inhibitor of the rate limiting glycolysis enzyme 6-phosphofructo-2-kinase/fructose-2,6- biphosphatase 3 (PFKFB3). Our results confirmed PFK15 inhibited glycolysis utilization by diabetogenic CD4+ T cells and reduced T cell responses to β cell antigen in vitro. In an adoptive transfer model of T1D, PFK15 treatment delayed diabetes onset, with 57% of animals remaining euglycemic at the end of the study period. Protection was due to induction of a hyporesponsive T cell phenotype, characterized by increased and sustained expression of the checkpoint molecules PD-1 and LAG-3 and downstream functional and metabolic exhaustion. Glycolysis inhibition terminally exhausted diabetogenic CD4+ T cells, which was irreversible through restimulation or checkpoint blockade in vitro and in vivo. In sum, our results demonstrate a novel therapeutic strategy to control aberrant T cell responses by exploiting the metabolic reprogramming of these cells during T1D. Moreover, the data presented here highlight a key role for nutrient availability in fueling T cell function and has implications in our understanding of T cell biology in chronic infection, cancer, and autoimmunity.
Interstitial Lung Disease in Connective Tissue Disease: A Common Lesion With Heterogeneous Mechanisms and Treatment Considerations
Authors: Shao Tihong , Shi Xiaodong , Yang Shanpeng , Zhang Wei , Li Xiaohu , Shu Jingwei , Alqalyoobi Shehabaldin , Zeki Amir A. , Leung Patrick S. , Shuai Zongwen
Published: June 2021

Connective tissue disease (CTD) related interstitial lung disease (CTD-ILD) is one of the leading causes of morbidity and mortality of CTD. Clinically, CTD-ILD is highly heterogenous and involves rheumatic immunity and multiple manifestations of respiratory complications affecting the airways, vessels, lung parenchyma, pleura, and respiratory muscles. The major pathological features of CTD are chronic inflammation of blood vessels and connective tissues, which can affect any organ leading to multi-system damage. The human lung is particularly vulnerable to such damage because anatomically it is abundant with collagen and blood vessels. The complex etiology of CTD-ILD includes genetic risks, epigenetic changes, and dysregulated immunity, which interact leading to disease under various ill-defined environmental triggers. CTD-ILD exhibits a broad spectra of clinical manifestations: from asymptomatic to severe dyspnea; from single-organ respiratory system involvement to multi-organ involvement. The disease course is also featured by remissions and relapses. It can range from stability or slow progression over several years to rapid deterioration. It can also present clinically as highly progressive from the initial onset of disease. Currently, the diagnosis of CTD-ILD is primarily based on distinct pathology subtype(s), imaging, as well as related CTD and autoantibodies profiles. Meticulous comprehensive clinical and laboratory assessment to improve the diagnostic process and management strategies are much needed. In this review, we focus on examining the pathogenesis of CTD-ILD with respect to genetics, environmental factors, and immunological factors. We also discuss the current state of knowledge and elaborate on the clinical characteristics of CTD-ILD, distinct pathohistological subtypes, imaging features, and related autoantibodies. Furthermore, we comment on the identification of high-risk patients and address how to stratify patients for precision medicine management approaches.
Reconstructing Bioinvasion Dynamics Through Micropaleontologic Analysis Highlights the Role of Temperature Change as a Driver of Alien Foraminifera Invasion
Authors: Guastella Roberta , Marchini Agnese , Caruso Antonio , Evans Julian , Cobianchi Miriam , Cosentino Claudia , Langone Leonardo , Lecci Rita , Mancin Nicoletta
Published: June 2021

Invasive alien species threaten biodiversity and ecosystem structure and functioning, but incomplete assessments of their origins and temporal trends impair our ability to understand the relative importance of different factors driving invasion success. Continuous time-series are needed to assess invasion dynamics, but such data are usually difficult to obtain, especially in the case of small-sized taxa that may remain undetected for several decades. In this study, we show how micropaleontologic analysis of sedimentary cores coupled with radiometric dating can be used to date the first arrival and to reconstruct temporal trends of foraminiferal species, focusing on the alien Amphistegina lobifera and its cryptogenic congener A. lessonii in the Maltese Islands. Our results show that the two species had reached the Central Mediterranean Sea several decades earlier than reported in the literature, with considerable implications for all previous hypotheses of their spreading patterns and rates. By relating the population dynamics of the two foraminifera with trends in sea surface temperature, we document a strong relationship between sea warming and population outbreaks of both species. We conclude that the micropaleontologic approach is a reliable procedure for reconstructing the bioinvasion dynamics of taxa having mineralized remains, and can be added to the toolkit for studying invasions.
Sole Excited-State InAs Quantum Dot Laser on Silicon With Strong Feedback Resistance
Authors: Chen Jia-Jian , Wang Zi-Hao , Wei Wen-Qi , Wang Ting , Zhang Jian-Jun
Published: June 2021

A feedback insensitive laser is a prerequisite for a desirable laser source for silicon photonic integration, as it is not possible to include an on-chip optical isolator. This work investigates the feedback insensitivity of an InAs/GaAs quantum dot laser epitaxially grown on an Si (001) substrate by operating in a sole excited state. The experimental results show that the sole excited-state lasing InAs quantum dot lasers on Si are less sensitive to external optical feedback than both Fabry-Perot and distributed-feedback quantum-well lasers. By comparing the laser behavior under different feedback levels, sole excited-state InAs quantum dot lasers on Si exhibit at least a 28 dB stronger feedback tolerance than quantum-well lasers. This result proposes a possible route for a high feedback insensitive laser as an on-chip light source towards Si waveguide integration with the absence of an optical isolator.
Report of the Pathogenesis and Pathophysiology of Lyme Disease Subcommittee of the HHS Tick Borne Disease Working Group
Authors: Donta Sam T. , States Leith J. , Adams Wendy A. , Bankhead Troy , Baumgarth Nicole , Embers Monica E. , Lochhead Robert B. , Stevenson Brian
Published: June 2021

An understanding of the pathogenesis and pathophysiology of Lyme disease is key to the ultimate care of patients with Lyme disease. To better understand the various mechanisms underlying the infection caused by Borrelia burgdorferi, the Pathogenesis and Pathophysiology of Lyme Disease Subcommittee was formed to review what is currently known about the pathogenesis and pathophysiology of Lyme disease, from its inception, but also especially about its ability to persist in the host. To that end, the authors of this report were assembled to update our knowledge about the infectious process, identify the gaps that exist in our understanding of the process, and provide recommendations as to how to best approach solutions that could lead to a better means to manage patients with persistent Lyme disease.
Successful Treatment of a Critically Ill COVID-19 Patient Using Continuous Renal Replacement Therapy With Enhanced Cytokine Removal and Tocilizumab: A Case Report
Authors: Huang Thomas Tao-Min , Chien Ying-Chun , Wang Chih-Hsien , Chang Sui-Yuan , Wang Jann-Tay , Hsieh Song-Chou , Yeh Yu-Chang , Ku Shih-Chi , Yu Chong-Jen , Chiang Bor-Luen , Chang Shan-Chwen , Tolwani Ashita
Published: June 2021

The COVID-19 pandemic has caused multiple deaths worldwide. Since no specific therapies are currently available, treatment for critically ill patients with COVID-19 is supportive. The most severe patients need sustained life support for recovery. We herein describe the course of a critically ill COVID-19 patient with multi-organ failure, including acute respiratory failure, acute kidney injury, and fulminant cytokine release syndrome (CRS), who required mechanical ventilation and extracorporeal membrane oxygenation support. This patient with a predicted high mortality risk was successfully managed with a careful strategy of oxygenation, uremic toxin removal, hemodynamic support, and most importantly, cytokine-targeted intervention for CRS, including cytokine/endotoxin removal, anti-cytokine therapy, and immune modulation. Comprehensive cytokine data, CRS parameters, and biochemical data of extracorporeal removal were provided to strengthen the rationale of this strategy. In this report, we demonstrate that timely combined hemoperfusion with cytokine adsorptive capacity and anti-cytokine therapy can successfully treat COVID-19 patients with fulminant CRS. It also highlights the importance of implementing cytokine-targeted therapy for severe COVID-19 guided by the precise measurement of disease activity.
Gastric Mucosa-Associated Lymphoid Tissue Lymphomas Diagnosed by Jumbo Biopsy Using Endoscopic Submucosal Dissection: A Case Report
Authors: Han Jian , Wang Jun , Xie Hua-ping
Published: June 2021

The stomach is the most common primary site of mucosa-associated lymphoid tissue (MALT) lymphoma, and sometimes the histopathological diagnosis is particularly difficult. An endoscopic forceps biopsy is the primary diagnostic test, but false negative results are very common. Therefore, a jumbo biopsy is essential for accurate diagnosis of clinically suspected cases. Here we diagnosed two cases of gastric MALT lymphomas using endoscopic submucosal dissection (ESD). The first patient was suspected of gastric lymphoma at the first endoscopic forceps biopsy, but the second endoscopic forceps biopsy showed chronic inflammation. The second patient was also firstly diagnosed with chronic inflammation by endoscopic forceps biopsy. Both cases were finally confirmed with the diagnosis of gastric MALT lymphoma by jumbo biopsy using ESD. The application of ESD can provide a new diagnostic strategy for clinically suspicious cases of gastric MALT lymphoma with negative endoscopic forceps biopsy.
Covariance of Phytoplankton, Bacteria, and Zooplankton Communities Within Microcystis Blooms in San Francisco Estuary
Authors: Lehman Peggy W. , Kurobe Tomofumi , Huynh Khiet , Lesmeister Sarah , Teh Swee J.
Published: June 2021

Microcystis blooms have occurred in upper San Francisco Estuary (USFE) since 1999, but their potential impacts on plankton communities have not been fully quantified. Five years of field data collected from stations across the freshwater reaches of the estuary were used to identify the plankton communities that covaried with Microcystis blooms, including non-photosynthetic bacteria, cyanobacteria, phytoplankton, zooplankton, and benthic genera using a suite of analyses, including microscopy, quantitative PCR (qPCR), and shotgun metagenomic analysis. Coherence between the abundance of Microcystis and members of the plankton community was determined by hierarchal cluster analysis (CLUSTER) and type 3 similarity profile analysis (SIMPROF), as well as correlation analysis. Microcystis abundance varied with many cyanobacteria and phytoplankton genera and was most closely correlated with the non-toxic cyanobacterium Merismopoedia, the green algae Monoraphidium and Chlamydomonas, and the potentially toxic cyanobacteria Pseudoanabaena, Dolichospermum, Planktothrix, Sphaerospermopsis, and Aphanizomenon. Among non-photosynthetic bacteria, the xenobiotic bacterium Phenylobacterium was the most closely correlated with Microcystis abundance. The coherence of DNA sequences for phyla across trophic levels in the plankton community also demonstrated the decrease in large zooplankton and increase in small zooplankton during blooms. The breadth of correlations between Microcystis and plankton across trophic levels suggests Microcystis influences ecosystem production through bottom-up control during blooms. Importantly, the abundance of Microcystis and other members of the plankton community varied with wet and dry conditions, indicating climate was a significant driver of trophic structure during blooms.
Comparison of Gut Microbiota of Yaks From Different Geographical Regions
Authors: Liu Wenwen , Wang Qiang , Song Jiajia , Xin Jinwei , Zhang Songshan , Lei Yuanhua , Yang Yuanli , Xie Peng , Suo Huayi
Published: June 2021

Gut microbiota are closely linked to host health and adaptability to different geographical environments. However, information on the influence of different geographical conditions on the intestinal microbiota of yaks is limited. In this study, 18 yak fecal samples were collected from three regions of China, namely Shangri-la, Lhasa, and Yushu, and were analyzed via high-throughput sequencing. The alpha diversity, as measured by the Shannon, ACE, and Chao indices, was the highest in the Shangri-la samples. Principal coordinate analysis detected significant differences in the composition of the intestinal microbiota of yaks from different regions. A total of six phyla, 21 families, and 29 genera were identified in the fecal samples. The dominant phyla in the samples were Firmicutes and Bacteroidetes, and the most abundant family was Ruminococcaceae. In addition, Ruminococcaceae_UCG-005 was the predominant genus and was more abundant in Yushu samples than in other samples. However, the predicted functional gene composition of the gut microbiota of yaks from different regions was similar. Our results revealed that geographical conditions influence the diversity and composition of the intestinal microbiota of yaks.
Association and Occurrence of Bifidobacterial Phylotypes Between Breast Milk and Fecal Microbiomes in Mother–Infant Dyads During the First 2 Years of Life
Authors: Yan Wenli , Luo Baolong , Zhang Xuyao , Ni Yongqing , Tian Fengwei
Published: June 2021

Breast milk acts as an intermediary for the transfer of functionally important commensal bacteria from mother to infant, especially for Bifidobacterium that can colonize the infant gut. However, the vast majority of rRNA amplicon-based studies reported the conspicuous intercohort and interindividual variation for the prevalence of Bifidobacterium in breast milk. In order to elucidate whether Bifidobacterium phylotypes persistently co-occured at the species or strain level in mother–breast milk–infant triads, we analyzed collectively the next-generation sequencing (NGS) datasets of bacterial 16S rRNA gene and the Bifidobacterium-specific groEL gene from maternal feces, breast milk, and infant feces in a small yet very homogeneous cohort of 25 healthy Uyghur mother–infant pairs (lactation for 7–720 days) in Kashgar, Xinjiang, China. Overall, 16S rRNA gene analysis showed that microbiome in the newborn gut was closer to that of breast milk in the first 4 months of lactation, and subsequently showed an obvious trend of adulthood at 6–12 months. Based on the BLAST accurate taxonomic result of the representative sequences of all ASVs (amplicon sequencing variants), only three sets of ASVs could be clearly assigned into Bifidobacterium species, whereas the remaining eight sets of ASVs corresponded to four indefinite Bifidobacterium species group. By contrast, the groEL gene dataset was partitioned into 376 ASVs, at least belonging to 13 well-known Bifidobacterium species or subspecies, of which 15 ASVs, annotated to seven well-known Bifidobacterium species or subspecies, showed triadic synchronism in most 23 mother–infant pairs tested. However, several other rare bifidobacterial phylotypes, which were frequently encountered in animals, were found to display no correspondence of the presence between the three ecosystems of mother–infant pairs. Our test results were obviously to support the hypothesis that breast milk acts as an intermediary for the transfer of probiotic commensal bacteria from mother to infant, especially for endosymbiotic Bifidobacterium that can colonize the infant gut. Some oxygen-insensitive exogenous Bifidobacterium phylotypes with a cosmopolitan lifestyle may be indirectly transferred to breast milk and the infant’s intestinal tract through environmental contamination. Thus, the groEL gene proved to be a very effective target for the depth resolution of Bifidobacterium community by high-throughput sequencing technologies.