bluuebunny/crossref_metadata_2025 huggingface dataset:
StEER: A Community-Centered Approach to Assessing the Performance of the Built Environment after Natural Hazard Events
Authors: Kijewski-Correa Tracy , Roueche David B. , Mosalam Khalid M. , Prevatt David O. , Robertson Ian
Published: May 2021

Since its founding in 2018, the Structural Extreme Events Reconnaissance (StEER) Network has worked to deepen the capacity of the Natural Hazards Engineering (NHE) community for coordinated and standardized assessments of the performance of the built environment following natural hazard events. This paper positions StEER within the field of engineering reconnaissance and the Natural Hazards Engineering Research Infrastructure (NHERI), outlining its organizational model for coordinated community-led responses to wind, seismic, and coastal hazard events. The paper’s examination of StEER’s event response workflow, engaging a range of hardware and delivering a suite of products, demonstrates StEER’s contributions in the areas of: workflow and data standardization, data reliability to enable field-observation-driven research & development, efficiency in data collection and dissemination to speed knowledge sharing, near-real- time open data access for enhanced coordination and transparency, and flexibility in collaboration modes to reduce the “overhead” associated with reconnaissance and foster broad NHE community engagement in event responses as part of field and virtual assessment structural teams (FAST/VAST). StEER’s creation of efficient systems to deliver well-documented, reliable data suitable for diverse re-uses as well as rapidly disseminated synopses of the impact of natural hazard events on the built environment provide a distinctive complement to existing post-event reconnaissance initiatives. The implementation of these policies, protocols and workflows is then demonstrated with case studies from five events illustrating StEER’s different field response strategies: the Nashville, Tennessee Tornadoes (2020) – a Hazard Gradient Survey; the Palu Earthquake and Tsunami in Indonesia (2018) – a Representative Performance Study; the Puerto Rico Earthquakes (2019/2020) – using Targeted Case Studies; Hurricane Laura (2020) – leveraging Rapid Surveys to enable virtual assessments; and Hurricane Dorian (2019) in the Bahamas – a Phased Multi-Hazard Investigation. The use of these strategies has enabled StEER to respond to 36 natural hazard events, involving over 150 different individuals to produce 45 published reports/briefings, over 5000 publicly available app-based structural assessments, and over 1600 km (1000 mi) of street-level panoramic imagery in its first 2years of operation.
Amino Acid Trafficking and Skeletal Muscle Protein Synthesis: A Case of Supply and Demand
Authors: White James P.
Published: May 2021

Skeletal muscle protein synthesis is a highly complex process, influenced by nutritional status, mechanical stimuli, repair programs, hormones, and growth factors. The molecular aspects of protein synthesis are centered around the mTORC1 complex. However, the intricacies of mTORC1 regulation, both up and downstream, have expanded overtime. Moreover, the plastic nature of skeletal muscle makes it a unique tissue, having to coordinate between temporal changes in myofiber metabolism and hypertrophy/atrophy stimuli within a tissue with considerable protein content. Skeletal muscle manages the push and pull between anabolic and catabolic pathways through key regulatory proteins to promote energy production in times of nutrient deprivation or activate anabolic pathways in times of nutrient availability and anabolic stimuli. Branched-chain amino acids (BCAAs) can be used for both energy production and signaling to induce protein synthesis. The metabolism of BCAAs occur in tandem with energetic and anabolic processes, converging at several points along their respective pathways. The fate of intramuscular BCAAs adds another layer of regulation, which has consequences to promote or inhibit muscle fiber protein anabolism. This review will outline the general mechanisms of muscle protein synthesis and describe how metabolic pathways can regulate this process. Lastly, we will discuss how BCAA availability and demand coordinate with synthesis mechanisms and identify key factors involved in intramuscular BCAA trafficking.
Bursa-Derived Cells Show a Distinct Mechano-Response to Physiological and Pathological Loading in vitro
Authors: Klatte-Schulz Franka , Bormann Nicole , Voss Isabel , Melzer Josephine , Schmock Aysha , Bucher Christian H. , Thiele Kathi , Moroder Philipp , Haffner-Luntzer Melanie , Ignatius Anita , Duda Georg N. , Wildemann Britt
Published: May 2021

The mechano-response of highly loaded tissues such as bones or tendons is well investigated, but knowledge regarding the mechano-responsiveness of adjacent tissues such as the subacromial bursa is missing. For a better understanding of the physiological role of the bursa as a friction-reducing structure in the joint, the study aimed to analyze whether and how bursa-derived cells respond to physiological and pathological mechanical loading. This might help to overcome some of the controversies in the field regarding the role of the bursa in the development and healing of shoulder pathologies. Cells of six donors seeded on collagen-coated silicon dishes were stimulated over 3 days for 1 or 4 h with 1, 5, or 10% strain. Orientation of the actin cytoskeleton, YAP nuclear translocation, and activation of non-muscle myosin II (NMM-II) were evaluated for 4 h stimulations to get a deeper insight into mechano-transduction processes. To investigate the potential of bursa-derived cells to adapt their matrix formation and remodeling according to mechanical loading, outcome measures included cell viability, gene expression of extracellular matrix and remodeling markers, and protein secretions. The orientation angle of the actin cytoskeleton increased toward a more perpendicular direction with increased loading and lowest variations for the 5% loading group. With 10% tension load, cells were visibly stressed, indicated by loss in actin density and slightly reduced cell viability. A significantly increased YAP nuclear translocation occurred for the 1% loading group with a similar trend for the 5% group. NMM-II activation was weak for all stimulation conditions. On the gene expression level, only the expression of TIMP2 was down-regulated in the 1 h group compared to control. On the protein level, collagen type I and MMP2 increased with higher/longer straining, respectively, whereas TIMP1 secretion was reduced, resulting in an MMP/TIMP imbalance. In conclusion, this study documents for the first time a clear mechano-responsiveness in bursa-derived cells with activation of mechano-transduction pathways and thus hint to a physiological function of mechanical loading in bursa-derived cells. This study represents the basis for further investigations, which might lead to improved treatment options of subacromial bursa-related pathologies in the future.
Mesenchymal Stromal Cells From Emphysematous Donors and Their Extracellular Vesicles Are Unable to Reverse Cardiorespiratory Dysfunction in Experimental Severe Emphysema
Authors: Antunes Mariana A. , Braga Cassia L. , Oliveira Tainá B. , Kitoko Jamil Z. , Castro Ligia L. , Xisto Debora G. , Coelho Mariana S. , Rocha Nazareth , Silva-Aguiar Rodrigo P. , Caruso-Neves Celso , Martins Eduarda G. , Carvalho Clara Fernandes , Galina Antônio , Weiss Daniel J. , Lapa e Silva José R. , Lopes-Pacheco Miquéias , Cruz Fernanda F. , Rocco Patricia R. M.
Published: May 2021

Although bone marrow-derived mesenchymal stromal cells (BM-MSCs) from patients with chronic obstructive pulmonary disease (COPD) appear to be phenotypically and functionally similar to BM-MSCs from healthy sources in vitro, the impact of COPD on MSC metabolism and mitochondrial function has not been evaluated. In this study, we aimed to comparatively characterize MSCs from healthy and emphysematous donors (H-MSCs and E-MSCs) in vitro and to assess the therapeutic potential of these MSCs and their extracellular vesicles (H-EVs and E-EVs) in an in vivo model of severe emphysema. For this purpose, C57BL/6 mice received intratracheal porcine pancreatic elastase once weekly for 4 weeks to induce emphysema; control animals received saline under the same protocol. Twenty-four hours after the last instillation, animals received saline, H-MSCs, E-MSCs, H-EVs, or E-EVs intravenously. In vitro characterization demonstrated that E-MSCs present downregulation of anti-inflammatory (TSG-6, VEGF, TGF-β, and HGF) and anti-oxidant (CAT, SOD, Nrf2, and GSH) genes, and their EVs had larger median diameter and lower average concentration. Compared with H-MSC, E-MSC mitochondria also exhibited a higher respiration rate, were morphologically elongated, expressed less dynamin-related protein-1, and produced more superoxide. When co-cultured with alveolar macrophages, both H-MSCs and E-MSCs induced an increase in iNOS and arginase-1 levels, but only H-MSCs and their EVs were able to enhance IL-10 levels. In vivo, emphysematous mice treated with E-MSCs or E-EVs demonstrated no amelioration in cardiorespiratory dysfunction. On the other hand, H-EVs, but not H-MSCs, were able to reduce the neutrophil count, the mean linear intercept, and IL-1β and TGF-β levels in lung tissue, as well as reduce pulmonary arterial hypertension and increase the right ventricular area in a murine model of elastase-induced severe emphysema. In conclusion, E-MSCs and E-EVs were unable to reverse cardiorespiratory dysfunction, whereas H-EVs administration was associated with a reduction in cardiovascular and respiratory damage in experimental severe emphysema.
Elevated Hydrostatic Pressure Causes Retinal Degeneration Through Upregulating Lipocalin-2
Authors: Yoneshige Azusa , Hagiyama Man , Takashima Yasutoshi , Ueno Satoru , Inoue Takao , Kimura Ryuichiro , Koriyama Yoshiki , Ito Akihiko
Published: May 2021

Elevation of intraocular pressure is a major risk factor for glaucoma development, which causes the loss of retinal ganglion cells (RGCs). Lipocalin 2 (Lcn2) is upregulated in glaucomatous retinae; however, whether Lcn2 is directly involved in glaucoma is debated. In this study, retinal explant cultures were subjected to increased water pressure using a two-chamber culture device, and Lcn2 protein levels were examined by immunoblotting. In situ TdT-mediated dUTP nick and labeling (TUNEL) and glial fibrillary acidic protein (GFAP) immunohistochemical assays were performed to assess apoptosis and gliosis, respectively. The neurotoxicity of Lcn2 in the retinal explant culture was determined with exogenous administration of recombinant Lcn2. The Lcn2 protein levels, percentage of TUNEL-positive cells, and GFAP-positive area were significantly higher in retinae cultured under 50 cm H2O pressure loads compared to those cultured under 20 cm H2O. We found that Lcn2 exhibited neurotoxicity in retinae at dose of 1 μg/ml. The negative effects of increased hydrostatic pressure were attenuated by the iron chelator deferoxamine. This is the first report demonstrating the direct upregulation of Lcn2 by elevating hydrostatic pressure. Modulating Lcn2 and iron levels may be a promising therapeutic approach for retinal degeneration.
SARS-CoV-2 Causes Acute Kidney Injury by Directly Infecting Renal Tubules
Authors: Chen Zhaohui , Hu Junyi , Liu Lilong , Chen Rong , Wang Miao , Xiong Ming , Li Zhen-Qiong , Zhao Yi , Li Hong , Guan Chuhuai , Zhang Jie , Liu Liang , Chen Ke , Wang Yu-Mei
Published: May 2021

Acute kidney injury (AKI) is one of the most prevalent complications among hospitalized coronavirus disease 2019 (COVID-19) patients. Here, we aim to investigate the causes, risk factors, and outcomes of AKI in COVID-19 patients. We found that angiotensin-converting enzyme II (ACE2) and transmembrane protease serine 2 (TMPRSS2) were mainly expressed by different cell types in the human kidney. However, in autopsy kidney samples, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleoprotein was detected in ACE2+ or TMPRSS2+ renal tubular cells, whereas the RNAscope® Assay targeting the SARS-CoV-2 Spike gene was positive mainly in the distal tubular cells and seldom in the proximal tubular cells. In addition, the TMPRSS2 and kidney injury marker protein levels were significantly higher in the SARS-CoV-2-infected renal distal tubular cells, indicating that SARS-CoV-2-mediated AKI mainly occurred in the renal distal tubular cells. Subsequently, a cohort analysis of 722 patients with COVID-19 demonstrated that AKI was significantly related to more serious disease stages and poor prognosis of COVID-19 patients. The progressive increase of blood urea nitrogen (BUN) level during the course of COVID-19 suggests that the patient’s condition is aggravated. These results will greatly increase the current understanding of SARS-CoV-2 infection.
Diabetic Endothelial Cells Differentiated From Patient iPSCs Show Dysregulated Glycine Homeostasis and Senescence Associated Phenotypes
Authors: Su Liping , Kong Xiaocen , Loo Sze Jie , Gao Yu , Kovalik Jean-Paul , Su Xiaofei , Ma Jianhua , Ye Lei
Published: May 2021

Induced pluripotent stem cells derived cells (iPSCs) not only can be used for personalized cell transfer therapy, but also can be used for modeling diseases for drug screening and discovery in vitro. Although prior studies have characterized the function of rodent iPSCs derived endothelial cells (ECs) in diabetes or metabolic syndrome, feature phenotypes are largely unknown in hiPSC-ECs from patients with diabetes. Here, we used hiPSC lines from patients with type 2 diabetes mellitus (T2DM) and differentiated them into ECs (dia-hiPSC-ECs). We found that dia-hiPSC-ECs had disrupted glycine homeostasis, increased senescence, and impaired mitochondrial function and angiogenic potential as compared with healthy hiPSC-ECs. These signature phenotypes will be helpful to establish dia-hiPSC-ECs as models of endothelial dysfunction for understanding molecular mechanisms of disease and for identifying and testing new targets for the treatment of endothelial dysfunction in diabetes.
Regulation of Rho GTPases in the Vasculature by Cullin3-Based E3 Ligase Complexes
Authors: Podieh Fabienne , Hordijk Peter L.
Published: May 2021

Cullin3-based ubiquitin E3 ligases induce ubiquitination of substrates leading to their proteasomal or lysosomal degradation. BTB proteins serve as adaptors by binding to Cullin3 and recruiting substrate proteins, which enables specific recognition of a broad spectrum of targets. Hence, Cullin3 and its adaptors are involved in myriad cellular processes and organ functions. Cullin3-based ubiquitin E3 ligase complexes target small GTPases of the Rho subfamily, which are key regulators of cytoskeletal dynamics and cell adhesion. In this mini review, we discuss recent insights in Cullin3-mediated regulation of Rho GTPases and their impact on cellular function and disease. Intriguingly, upstream regulators of Rho GTPases are targeted by Cullin3 complexes as well. Thus, Rho GTPase signaling is regulated by Cullin3 on multiple levels. In addition, we address current knowledge of Cullin3 in regulating vascular function, focusing on its prominent role in endothelial barrier function, angiogenesis and the regulation of blood pressure.
Endoplasmic Reticulum Stress and Tumor Microenvironment in Bladder Cancer: The Missing Link
Authors: Nie Zhenyu , Chen Mei , Wen Xiaohong , Gao Yuanhui , Huang Denggao , Cao Hui , Peng Yanling , Guo Na , Ni Jie , Zhang Shufang
Published: May 2021

Bladder cancer is a common malignant tumor of the urinary system. Despite recent advances in treatments such as local or systemic immunotherapy, chemotherapy, and radiotherapy, the high metastasis and recurrence rates, especially in muscle-invasive bladder cancer (MIBC), have led to the evaluation of more targeted and personalized approaches. A fundamental understanding of the tumorigenesis of bladder cancer along with the development of therapeutics to target processes and pathways implicated in bladder cancer has provided new avenues for the management of this disease. Accumulating evidence supports that the tumor microenvironment (TME) can be shaped by and reciprocally act on tumor cells, which reprograms and regulates tumor development, metastasis, and therapeutic responses. A hostile TME, caused by intrinsic tumor attributes (e.g., hypoxia, oxidative stress, and nutrient deprivation) or external stressors (e.g., chemotherapy and radiation), disrupts the normal synthesis and folding process of proteins in the endoplasmic reticulum (ER), culminating in a harmful situation called ER stress (ERS). ERS is a series of adaptive changes mediated by unfolded protein response (UPR), which is interwoven into a network that can ultimately mediate cell proliferation, apoptosis, and autophagy, thereby endowing tumor cells with more aggressive behaviors. Moreover, recent studies revealed that ERS could also impede the efficacy of anti-cancer treatment including immunotherapy by manipulating the TME. In this review, we discuss the relationship among bladder cancer, ERS, and TME; summarize the current research progress and challenges in overcoming therapeutic resistance; and explore the concept of targeting ERS to improve bladder cancer treatment outcomes.
Oxymatrine Attenuates Osteoclastogenesis via Modulation of ROS-Mediated SREBP2 Signaling and Counteracts Ovariectomy-Induced Osteoporosis
Authors: Jiang Chao , Ma Qingliang , Wang Shiyu , Shen Yang , Qin An , Fan Shunwu , Jie Zhiwei
Published: May 2021

Osteoporosis, mainly caused by osteoclast-induced bone resorption, has become a major health problem in post-menopausal women and the elderly. Growing evidence indicates that inhibiting osteoclastogenesis is an efficient approach to develop alternative therapeutic agents for treating osteoporosis. In this study, we identified the potential regulating role of Oxymatrine (OMT), a quinazine alkaloid extracted from Sophora flavescens with various therapeutic effects in many diseases, on osteoclastogenesis for the first time. We found that OMT attenuated RANKL-induced osteoclast formation in both time- and dose-dependent manners. Further, OMT significantly suppressed RANKL-induced sterol regulatory element-binding protein 2 (SREBP2) activation and the expression of the nuclear factor of activated T cells 1 (NFATc1). Moreover, OMT inhibited the generation of RANKL-induced reactive oxygen species (ROS), and the upregulation of ROS could rescue the inhibition of SREBP2 by OMT. More importantly, ovariectomy (OVX) mouse model showed that OMT could effectively improve ovariectomy (OVX)-induced osteopenia by inhibiting osteoclastogenesis in vivo. In conclusion, our data demonstrated that OMT impaired ROS mediated SREBP2 activity and downstream NFATc1 expression during osteoclastogenesis, suppressed OVX-induced osteopenia in vivo, which suggested that OMT could be a promising compound for medical treatment against osteoporosis.
Proton-Binding Motifs of Membrane-Bound Proteins: From Bacteriorhodopsin to Spike Protein S
Authors: Bondar Ana-Nicoleta
Published: May 2021

Membrane-bound proteins that change protonation during function use specific protein groups to bind and transfer protons. Knowledge of the identity of the proton-binding groups is of paramount importance to decipher the reaction mechanism of the protein, and protonation states of prominent are studied extensively using experimental and computational approaches. Analyses of model transporters and receptors from different organisms, and with widely different biological functions, indicate common structure-sequence motifs at internal proton-binding sites. Proton-binding dynamic hydrogen-bond networks that are exposed to the bulk might provide alternative proton-binding sites and proton-binding pathways. In this perspective article I discuss protonation coupling and proton binding at internal and external carboxylate sites of proteins that use proton transfer for function. An inter-helical carboxylate-hydroxyl hydrogen-bond motif is present at functionally important sites of membrane proteins from archaea to the brain. External carboxylate-containing H-bond clusters are observed at putative proton-binding sites of protonation-coupled model proteins, raising the question of similar functionality in spike protein S.
NIR-II Upconversion Photoluminescence of Er3+ Doped LiYF4 and NaY(Gd)F4 Core-Shell Nanoparticles
Authors: Feng Qilong , Zheng Wenjing , Pu Jie , Chen Qiaoli , Shao Wei
Published: May 2021

The availability of colloidal nano-materials with high efficiency, stability, and non-toxicity in the near infrared-II range is beneficial for biological diagnosis and therapy. Rare earth doped nanoparticles are ideal luminescent agents for bio-applications in the near infrared-II range due to the abundant energy level distribution. Among them, both excitation and emission range of Er3+ ions can be tuned into second biological window range. Herein, we report the synthesis of ∼15 nm LiYF4, NaYF4, and NaGdF4 nanoparticles doped with Er3+ ions and their core-shell structures. The luminescent properties are compared, showing that Er3+ ions with single-doped LiYF4 and NaYF4 nanoparticles generate stronger luminescence than Er3+ ions with doped NaGdF4, despite the difference in relative intensity at different regions. By epitaxial growth an inert homogeneous protective layer, the surface luminescence of the core-shell structure is further enhanced by about 5.1 times, 6.5 times, and 167.7 times for LiYF4, NaYF4, and NaGdF4, respectively. The excellent luminescence in both visible and NIR range of these core-shell nanoparticles makes them potential candidate for bio-applications.
Graphene-Assisted Sensor for Rapid Detection of Antibiotic Resistance in Escherichia coli
Authors: Li Chunlei , Sun Feng
Published: May 2021

In recent years, antibiotic-resistant bacteria caused by antibiotic abuse in the medical industry have become a new environmental pollutant that endangers public health. Therefore, it is necessary to establish a detection method for evaluating drug-resistant bacteria. In this work, we used Escherichia coli as a target model and proposed a method to evaluate its drug resistance for three antibiotics. Graphene dispersion was used to co-mix with E. coli cells for the purpose of increasing the current signal. This electrochemical-based sensor allows the evaluation of the activity of E. coli on the electrode surface. When antibiotics were present, the electrocatalytic reduction signal was diminished because of the reduced activity of E. coli. Based on the difference in the electrochemical reduction signal, we can evaluate the antibiotic resistance of different E. coli strains.
Three Multimodal Action Packages in Responses to Proposals During Joint Decision-Making: The Embodied Delivery of Positive Assessments Including the Finnish Particle Ihan “Quite”
Authors: Stevanovic Melisa
Published: May 2021

Joint decision-making is a thoroughly collaborative interactional endeavor. To construct the outcome of the decision-making sequence as a “joint” one necessitates that the participants constantly negotiate their shared activity, not only with reference to the content of the decisions to be made, but also with reference to whether, when, and upon what exactly decisions are to be made in the first place. In this paper, I draw on a dataset of video-recorded dyadic planning meetings between two church officials as data, investigating a collection of 35 positive assessments with the Finnish particle ihan “quite” occurring in response to a proposal (e.g.,tää on ihan kiva“this is quite nice”). The analysis focuses on the embodied delivery of these assessments in combination with their other features: their sequential location and immediate interactional consequences (i.e., accounts, decisions, abandoning of the proposal), their auxiliary verbal turn-design features (i.e., particles), and the “agent” of the proposals that they are responsive to (i.e., who has made the proposal and whether it is based on some written authoritative material). Three multimodal action packages are described, in which the assessment serves 1) to accept an idea in principle, which is combined with no speaker movement, 2) to concede to a plan, which is associated with notable expressive speaker movement (e.g., head gestures, facial expressions) and 3) to establish a joint decision, which is accompanied by the participants’ synchronous body movements. The paper argues that the relative decision-implicativeness of these three multimodal action packages is largely based on the management and distribution of participation and agency between the two participants, which involves the participants using their bodies to position themselves toward their co-participants and toward the proposals “in the air” in distinct ways.
A Comparison of Connected Speech Tasks for Detecting Early Alzheimer’s Disease and Mild Cognitive Impairment Using Natural Language Processing and Machine Learning
Authors: Clarke Natasha , Barrick Thomas R. , Garrard Peter
Published: May 2021

Alzheimer’s disease (AD) has a long pre-clinical period, and so there is a crucial need for early detection, including of Mild Cognitive Impairment (MCI). Computational analysis of connected speech using Natural Language Processing and machine learning has been found to indicate disease and could be utilized as a rapid, scalable test for early diagnosis. However, there has been a focus on the Cookie Theft picture description task, which has been criticized. Fifty participants were recruited – 25 healthy controls (HC), 25 mild AD or MCI (AD+MCI) – and these completed five connected speech tasks: picture description, a conversational map reading task, recall of an overlearned narrative, procedural recall and narration of a wordless picture book. A high-dimensional set of linguistic features were automatically extracted from each transcript and used to train Support Vector Machines to classify groups. Performance varied, with accuracy for HC vs. AD+MCI classification ranging from 62% using picture book narration to 78% using overlearned narrative features. This study shows that, importantly, the conditions of the speech task have an impact on the discourse produced, which influences accuracy in detection of AD beyond the length of the sample. Further, we report the features important for classification using different tasks, showing that a focus on the Cookie Theft picture description task may narrow the understanding of how early AD pathology impacts speech.
Plasma Amino Acids and Residual Hypertriglyceridemia in Diabetic Patients Under Statins: Two Independent Cross-Sectional Hospital-Based Cohorts
Authors: Wang Shuang , Cao Yun-Feng , Sun Xiao-Yu , Hong Mo , Fang Zhong-Ze , Luo Hui-Huan , Sun Huan , Yang Ping
Published: May 2021

Objective: The objective of the study was to investigate the relationship of amino acid metabolism with hypertriglyceridemia in diabetic patients under statins free of prior cardiovascular diseases.

Methods: Two independent cross-sectional hospital based cohorts, i.e., Liaoning Medical University First Affiliated Hospital (LMUFAH, n = 146) and the Second Affiliated Hospital of Dalian Medical University (SAHDMU, n = 294) were included in the current analysis. Hypertriglyceridemia was defined as triglyceride ≥1.7 mmol/L, and well-controlled LDL-C was defined as <2.6 mmol/L. The adjusted ORs (95% CI) of circulating metabolic measures for hypertriglyceridemia were assessed using logistic regression. Pooled results of metabolites with the same direction of association in both cohorts were combined using inverse variance-weighted fixed-effect meta-analysis. Difference of identified metabolites in patients with and without hypertriglyceridemia were also obtained in the context of LDL-C.

Results: Patients, 86 and 106, were with hypertriglyceridemia in LMUFAH and SAHDMU, respectively. We observed that elevated alanine, asparagine, leucine, and valine were consistently associated with increased hypertriglyceridemia in both cohorts. In fixed-effect pooled analysis, the OR (95% CI) per SD increase was 1.71 (1.32–2.20) for alanine, 1.62 (1.20–2.19) for asparagine, 1.64 (1.22–2.20) for leucine, and 1.62 (1.22–2.13) for valine (all P values ranged from 0.0018 to <0.0001); adjusting for C-peptide attenuated effect sizes of Ala, Leu, and Val for hypertriglyceridemia. The difference were robust in groups with well- or bad-controlled LDL-C.

Conclusion: Among 23 amino acids, alanine, asparagine, leucine, and valine were positively associated with increased residual risk of hypertriglyceridemia in diabetic patients with statin treatment.
A Functional Indel Polymorphism Within MIR155HG Is Associated With Sudden Cardiac Death Risk in a Chinese Population
Authors: Zhang Qing , Yu Huan , Yang Zhenzhen , Li Lijuan , He Yan , Zhu Shaohua , Li Chengtao , Zhang Suhua , Luo Bin , Gao Yuzhen
Published: May 2021

Sudden cardiac death (SCD) is a devastating complication of multiple disease processes and has gradually became a major public health issue. miR-155 is one of the best characterized miRNAs and plays a critical role in several physiological and pathological process, including cardiovascular diseases. In this study, we systematically screened the whole region of miR-155 host gene (MIR155HG) and identified a 4-bp insertion/deletion variant (rs72014506) residing in the intron region of MIR155HG as the candidate polymorphism. The association of rs72014506 with SCD susceptibility was evaluated using 166 SCD cases and 830 healthy controls in a Chinese population. Logistic regression analysis suggested that the homozygote del/del genotype significantly decreased the risk of SCD [odds ratio (OR) = 0.29; 95% confidence interval (CI) = 0.12–0.74; Ptrend = 0.0004]. Further genotype–expression association study using human myocardium tissue samples suggested that the deletion allele was intimately linked to lower the expression of both MIR155HG and mature miR155. Luciferase activity assay also revealed that the deletion allele of rs72014506 inhibited gene transcriptional activity. Finally, we performed electrophoretic mobility shift assay and verified the preferential binding affinity of the deletion allele with POU2F1 (POU domain class 2 transcription factor 1). Collectively, we have successfully identified a SCD risk conferring polymorphism in the MIR155HG gene and a likely biological mechanism for the decreased risk of SCD associated with the deletion allele. This novel variant may thus serve as a potential genetic marker for SCD diagnosis and prevention in natural populations, if validated by further studies with a larger sample size.
Cardiac Rehabilitation: A Bibliometric Review From 2001 to 2020
Authors: Yuan Guozhen , Shi Jingjing , Jia Qiulei , Shi Shuqing , Zhu Xueping , Zhou Yan , Shi Shuai , Hu Yuanhui
Published: May 2021

Cardiovascular disease (CVD) is a serious threat to global public health due to its high prevalence and disability rate. Meanwhile, cardiac rehabilitation (CR) has attracted increasing attention for its positive effects on the cardiovascular system. There is overwhelming evidence that CR for patients with CVD is effective in reducing cardiovascular morbidity and mortality. To learn more about the development of CR, 5,567 papers about CR and related research were retrieved in the Web of Science Core Collection from 2001 to 2020. Then, these publications were scientometrically analyzed based on CiteSpace in terms of spatiotemporal distribution, author distribution, subject categories, topic distribution, and references. The results can be elaborated from three aspects. Firstly, the number of annual publications related to CR has increased year by year in general over the past two decades. Secondly, a co-occurrence analysis of the output countries and authors shows that a few developed countries such as the United States, Canada, and the UK are the most active in carrying out CR and where regional academic communities represented by Sherry Grace and Ross Arena were formed. Thirdly, an analysis of the subject categories and topic distribution of the papers reveals that CR is a typical interdiscipline with a wide range of disciplines involved, including clinical medicine, basic medicine, public health management, and sports science. The research topics cover the participants and implementers, components, and the objectives and requirements of CR. The current research hotspots are the three core modalities of CR, namely patient education, exercise training and mental support, as well as mobile health (mHealth) dependent on computer science. In conclusion, this work has provided some useful information for acquiring knowledge about CR, including identifying potential collaborators for researchers interested in CR, and discovering research trends and hot topics in CR, which can offer some guidance for more extensive and in-depth CR-related studies in the future.
Hydroclimatic Controls on the Isotopic (δ18 O, δ2 H, d-excess) Traits of Pan-Arctic Summer Rainfall Events
Authors: Mellat Moein , Bailey Hannah , Mustonen Kaisa-Riikka , Marttila Hannu , Klein Eric S. , Gribanov Konstantin , Bret-Harte M. Syndonia , Chupakov Artem V. , Divine Dmitry V. , Else Brent , Filippov Ilya , Hyöky Valtteri , Jones Samantha , Kirpotin Sergey N. , Kroon Aart , Markussen Helge Tore , Nielsen Martin , Olsen Maia , Paavola Riku , Pokrovsky Oleg S. , Prokushkin Anatoly , Rasch Morten , Raundrup Katrine , Suominen Otso , Syvänperä Ilkka , Vignisson Sölvi Rúnar , Zarov Evgeny , Welker Jeffrey M.
Published: May 2021

Arctic sea-ice loss is emblematic of an amplified Arctic water cycle and has critical feedback implications for global climate. Stable isotopes (δ18O, δ2H, d-excess) are valuable tracers for constraining water cycle and climate processes through space and time. Yet, the paucity of well-resolved Arctic isotope data preclude an empirically derived understanding of the hydrologic changes occurring today, in the deep (geologic) past, and in the future. To address this knowledge gap, the Pan-Arctic Precipitation Isotope Network (PAPIN) was established in 2018 to coordinate precipitation sampling at 19 stations across key tundra, subarctic, maritime, and continental climate zones. Here, we present a first assessment of rainfall samples collected in summer 2018 (n = 281) and combine new isotope and meteorological data with sea ice observations, reanalysis data, and model simulations. Data collectively establish a summer Arctic Meteoric Water Line where δ2H = 7.6⋅δ18O–1.8 (r2 = 0.96, p < 0.01). Mean amount-weighted δ18O, δ2H, and d-excess values were −12.3, −93.5, and 4.9‰, respectively, with the lowest summer mean δ18O value observed in northwest Greenland (−19.9‰) and the highest in Iceland (−7.3‰). Southern Alaska recorded the lowest mean d-excess (−8.2%) and northern Russia the highest (9.9‰). We identify a range of δ18O-temperature coefficients from 0.31‰/°C (Alaska) to 0.93‰/°C (Russia). The steepest regression slopes (>0.75‰/°C) were observed at continental sites, while statistically significant temperature relations were generally absent at coastal stations. Model outputs indicate that 68% of the summer precipitating air masses were transported into the Arctic from mid-latitudes and were characterized by relatively high δ18O values. Yet 32% of precipitation events, characterized by lower δ18O and high d-excess values, derived from northerly air masses transported from the Arctic Ocean and/or its marginal seas, highlighting key emergent oceanic moisture sources as sea ice cover declines. Resolving these processes across broader spatial-temporal scales is an ongoing research priority, and will be key to quantifying the past, present, and future feedbacks of an amplified Arctic water cycle on the global climate system.
Probabilistic Assessment of Slip Rates and Their Variability Over Time of Offshore Buried Thrusts: A Case Study in the Northern Adriatic Sea
Authors: Panara Yuri , Maesano Francesco Emanuele , Amadori Chiara , Fedorik Jakub , Toscani Giovanni , Basili Roberto
Published: May 2021

When sedimentation rates overtake tectonic rates, the detection of ongoing tectonic deformation signatures becomes particularly challenging. The Northern Apennines orogen is one such case where a thick Plio-Pleistocene foredeep sedimentary cover blankets the fold-and-thrust belt, straddling from onshore (Po Plain) to offshore (Adriatic Sea), leading to subtle or null topo-bathymetric expression of the buried structures. The seismic activity historically recorded in the region is moderate; nonetheless, seismic sequences nearing magnitude 6 punctuated the last century, and even some small tsunamis were reported in the coastal locations following the occurrence of offshore earthquakes. In this work, we tackled the problem of assessing the potential activity of buried thrusts by analyzing a rich dataset of 2D seismic reflection profiles and wells in a sector of the Northern Apennines chain located in the near-offshore of the Adriatic Sea. This analysis enabled us to reconstruct the 3D geometry of eleven buried thrusts. We then documented the last 4 Myr slip history of four of such thrusts intersected by two high-quality regional cross-sections that were depth converted and restored. Based on eight stratigraphic horizons with well-constrained age determinations (Zanclean to Middle Pleistocene), we determined the slip and slip rates necessary to recover the observed horizon deformation. The slip rates are presented through probability density functions that consider the uncertainties derived from the horizon ages and the restoration process. Our results show that the thrust activation proceeds from the inner to the outer position in the chain. The slip history reveals an exponential reduction over time, implying decelerating slip-rates spanning three orders of magnitudes (from a few millimeters to a few hundredths of millimeters per year) with a major slip-rate change around 1.5 Ma. In agreement with previous works, these findings confirm the slip rate deceleration as a widespread behavior of the Northern Apennines thrust faults.
Provenance and Climatic Implications of the Middle-Pleistocene Loess Deposit, Southern China
Authors: Fan Qingbin , Liao Jie , Li Yan , Ye Wei , Wang Tao , Feng Xiao
Published: May 2021

The middle-Pleistocene Xiashu loess deposit in the lower reaches of the Yangtze River (LRYR), southern China, may yield evidence with significant climatic and environmental significance. However, its provenance remains controversial. In this study, grain size analysis, and quartz grain surface microtextural and morphological observations, enabled comparison of the provenance of loess in the LRYR with those on the Loess Plateau in northern China. The results show that the grain size characteristics of the Xiashu loess do not follow the coarse-fine NW-SE trend in northern China, and the surface microtextures of the quartz grains in the Xiashu loess are distinctly different from those on the Loess Plateau in northern China, indicating that the loess deposits in the two regions have different provenances. The Gobi Desert in inland northwestern China are not considered as the primary provenance of the Xiashu loess. Instead, the adjacent floodplains in the LRYR, the alluvial plains of the Huai River and the Yellow River to the north during glacial periods are suggested as the dominant source materials for the Xiashu loess. Under the background of middle-Pleistocene climate transition (MPT), regional aridity and a strengthened east Asian winter monsoon (driven by global cooling and the rapid uplift of the Tibetan Plateau) were considered as the primary drivers for the development of the Xiashu loess. The sustained eolian loess accumulation represent a regional response of the northern subtropical area of southern China to the MPT global cooling event at around 0.9 Ma.
Are We Missing the Target? A Bias-Variance Perspective on Multi-Hazard Risk Assessment
Authors: Dunant Alexandre
Published: May 2021

This paper presents a generalization of the bias-variance tradeoff applied to the recent trend toward natural multi-hazard risk assessment. The bias-variance dilemma, a well-known machine learning theory, is presented in the context of natural hazard modeling. It is then argued that the bias-variance statistical concept can provide an analytical framework for the necessity to direct efforts toward systemic risk assessment using multi-hazard catastrophe modeling and inform future mitigation practices.
Developing Pre-service Teachers Conceptualization of STEM and STEM Pedagogical Practices
Authors: Berisha Fatlume , Vula Eda
Published: May 2021

Science, Technology, Engineering, and Mathematics (STEM) integrated curricular approach has become the leading type of education reform worldwide. This paper presents a STEM integrated collaborative activity to enhance STEM knowledge among pre-service mathematics and chemistry teachers. Well-structured and planned on-site workshops on STEM activities were delivered to pre-service teachers while growing mathematics and science content knowledge and pedagogical practices. The qualitative content analysis research methodology was used to identify relevant topics related to post reflective questions regarding pre-service teacher perspectives on the experience gained through the collaborative practices at the STEM workshop. The results show that the workshop had a positive effect on pre-service teachers’ conceptualization of STEM—through collaborative, participatory practices, an effective learning environment while bringing attention to teacher professional development and education policymakers. Key elements of this study approach included: (1) collaboration between university professors to teach and incorporate STEM in higher education; (2) unique partnership among mathematical and chemistry pre-service teachers; and (3) professional development, which is devoted and adopted into a study course.
Familial Acromegaly and Bilateral Asynchronous Pheochromocytomas in a Female Patient With a MAX Mutation: A Case Report
Authors: Mamedova Elizaveta , Vasilyev Evgeny , Petrov Vasily , Buryakina Svetlana , Tiulpakov Anatoly , Belaya Zhanna
Published: May 2021

Background

There are very few cases of co-occurring pituitary adenoma (PA) and pheochromocytomas (PCC)/paragangliomas caused by MAX mutations. No cases of familial PA in patients with MAX mutations have been described to date.

Case Presentation

We describe a 38-year-old female patient, presenting with clinical and biochemical features of acromegaly and PCC of the left adrenal gland. Whole-exome sequencing was performed [NextSeq550 (Illumina, San Diego, CA, USA)] identifying a nonsense mutation in the MAX gene (NM_002382) [c.223C>T (p.R75X)]. The patient had a medical history of PCC of the right adrenal gland diagnosed aged 21 years and prolactinoma diagnosed aged 25 years. Cabergoline treatment was effective in achieving remission of prolactinoma at age 33 years. The patient’s father who died at age 56 years of a heart attack had a medical history of PA and prominent acromegalic features, which supports the familial presentation of the disease.

Conclusion

This clinical case gives an insight into the clinical presentation of familial PA and PCC probably associated with a MAX mutation.
Diffusion Mechanism of Leading Technology in the New Energy Industry Based on the Bass Model
Authors: Wang Hongying , Sun Bing
Published: May 2021

With the increasing difficulties associated with heating, the new energy industry has become the mainstay for property development. The effective diffusion of leading technologies supplies a social edge for enterprise core technologies, and this is also a necessary topic for industrial transformation and optimization. Within the international context of energy conservation and emission reduction, the scientific and in-depth study of the diffusion mechanisms underlying leading technologies in the new energy industry have vital theoretical significance for the promotion of the diffusion of leading technologies. Based on the introduction of the Bass model and one extension model, this paper constructs the diffusion model of the new energy industry’s leading technology and analyzes its diffusion mechanism. The identified mechanism indicates that in the case of imperfect market and policy environments, the diffusion of the leading technology of the new energy industry is mainly influenced by the “expected utility” of innovators and the “actual utility” of imitators. The diffusion of the leading technology in innovator enterprises of the new energy industry is mainly affected by the “expected utility,” while the diffusion in imitator enterprises is affected by the “actual utility.” These influences are verified by simulation analysis. Based on the diffusion mechanism, several suggestions are presented for the promotion of the diffusion mechanism of leading technology, with the aim to provide references for the government, industry associations, and enterprises for relevant decision-making.
Are the Responses of Sectoral Energy Imports Asymmetric to Exchange Rate Volatilities in Pakistan? Evidence From Recent Foreign Exchange Regime
Authors: Saqib Abdul , Chan Tze-Haw , Mikhaylov Alexey , Lean Hooi Hooi
Published: May 2021

Growing energy demand but stagnant production followed by volatile exchange rate leads Pakistan to energy imbalances and potential economic contraction. Yet, studies on sectoral energy imports are limited and inconclusive without accessing the asymmetric effect of currency fluctuations. We examine the impacts of Pakistani rupee volatility on monthly energy imports based on the nonlinear autoregressive distributed lag (NARDL) estimations. Augmented Dickey–Fuller and Phillips–Perron tests were used to conduct unit root testing, and the bound testing approach was used to examine the long-term cointegration. The long-run asymmetry was tested with the Wald test, and using the NARDL model, we examined both short-run and long-run asymmetric effects of exchange rate volatility on energy imports. The bound test was established and supported through ECMt−1 (t-test), cointegrating the relationship between exchange rate volatility and energy imports in a long term. Among others, both short-run and long-run asymmetric effects were found for crude oil, coal, electricity, and petroleum products. Rupee depreciation increased crude oil and electricity imports, while the appreciation effects were insignificant. Overall, the empirical assessment reveals that the foreign exchange volatility effect is sectoral specific and asymmetric in Pakistan. It offers new insights into re-strategizing the energy policy and refining the import substitution plan.
Acceleration of Load Changes by Controlling the Operating Parameters in CFB Co-Combustion
Authors: Peters Jens , Langner Eric , Ströhle Jochen , Epple Bernd
Published: May 2021

The integration of intermittent renewable energy sources into the electricity market requires flexible and efficient technologies that compensate for the fluctuating electricity demand. A circulating fluidized bed (CFB) boiler is a suitable solution due to its fuel flexibility, but the thermal inertia of the fluidized bed can have negative effects on the load following capabilities. This study investigates the influence of the operating parameters of the fire side on the speed of load changes on the waterside. Co-combustion of lignite, straw, and refuse derived fuel (RDF) was carried out. In a 1 MWth pilot CFB combustor fifteen load changes were performed with a varying step input of the primary air, the secondary air, and the fuel mass flow. The step input of the primary air had a large influence on the load ramps, as it strongly affects the solids concentration in the upper furnace. The step size of the fuel mass flow had a positive effect on the load change rate. Based on the results, concepts were developed to accelerate load ramping by controlling the hydrodynamic conditions and the temperature on the fireside.