bluuebunny/crossref_metadata_2025 huggingface dataset:
Executive Function-Related Improvements on a Commercial CBT-Based Weight Management Intervention: Pilot Randomized Controlled Trial
Authors: Michaelides Andreas , Mitchell Ellen Siobhan , Behr Heather , Ho Annabell Suh , Hanada Grant , Lee Jihye , McPartland Sue
Published: July 2022

Executive functioning is a key component involved in many of the processes necessary for effective weight management behavior change (e.g., setting goals). Cognitive behavioral therapy (CBT) and third-wave CBT (e.g., mindfulness) are considered first-line treatments for obesity, but it is unknown to what extent they can improve or sustain executive functioning in a generalized weight management intervention. This pilot randomized controlled trial examined if a CBT-based generalized weight management intervention would affect executive functioning and executive function-related brain activity in individuals with obesity or overweight. Participants were randomized to an intervention condition (N = 24) that received the Noom Weight program or to a control group (N = 26) receiving weekly educational newsletters. EEG measurements were taken during Flanker, Stroop, and N-back tasks at baseline and months 1 through 4. After 4 months, the intervention condition evidenced greater accuracy over time on the Flanker and Stroop tasks and, to a lesser extent, neural markers of executive function compared to the control group. The intervention condition also lost more weight than controls (−7.1 pounds vs. +1.0 pounds). Given mixed evidence on whether weight management interventions, particularly CBT-based weight management interventions, are associated with changes in markers of executive function, this pilot study contributes preliminary evidence that a multicomponent CBT-based weight management intervention (i.e., that which provides both support for weight management and is based on CBT) can help individuals sustain executive function over 4 months compared to controls.
Development and Validation of Recreational Sport Well-Being Scale
Authors: Pi Lu-Luan , Chang Chia-Ming , Lin Hsi-Han
Published: July 2022

The purpose of this study is to develop the “Recreational Sport Well-being Scale”, which will be used to investigate the subjective recreational sport well-being individuals’ experience after participating in recreational sports. The study participants were Taiwanese who were over 20 years old and participated in recreational sports. Four sets of samples and 4050 questionnaires in total were collected. Using exploratory factor analysis, four factors were extracted from the scale –life satisfaction, physical and mental health, family flourishing, and positive feelings. Confirmatory factor analysis indicated that the scale’s overall goodness of fit, convergent validity, and composite reliability all passed the thresholds. The results of cross-validation indicated that the model passed configural invariance, metric invariance, covariance invariance, and error variance invariance, which suggested that the scale has cross validity. Nomological validity analysis was conducted, showing that Recreational Sport Well-being Scale is nomologically valid since it is positively correlated to Subjective Health Scale. Test-retest reliability analysis suggested that the test results were stable when a retest was carried out two weeks later. The developed “Recreational Sport Well-being Scale” is highly reliable and valid and can be applied to measure future recreational sports participants’ well-being.
Multi-Agent Evolutionary Game in the Recycling Utilization of Sulfate-Rich Wastewater
Authors: Ding Meng , Zeng Hui
Published: July 2022

Current industrial development has led to an increase in sulfate-rich industrial sewage, threatening industrial ecology and the environment. Incorrectly treating high-concentration sulfate wastewater can cause serious environmental problems and even harm human health. Water with high sulfate levels can be treated as a resource and treated harmlessly to meet the needs of the circular economy. Today, governments worldwide are working hard to encourage the safe disposal and reuse of industrial salt-rich wastewater by recycling sulfate-rich wastewater (SRW) resources. However, the conflict of interests between the SRW production department, the SRW recycling department, and the governments often make it challenging to effectively manage sulfate-rich wastewater resources. This study aims to use the mechanism of evolutionary game theory (EGT) to conduct theoretical modelling and simulation analysis on the interaction of the behaviour of the above three participants. This paper focuses on the impact of government intervention and the ecological behaviour of wastewater producers on the behavioural decisions of recyclers. The results suggest that the government should play a leading role in developing the SRW resource recovery industry. SRW producers protect the environment in the mature stage, and recyclers actively collect and recover compliant sulfate wastewater resources. Governments should gradually deregulate and eventually withdraw from the market. Qualified recyclers and environmentally friendly wastewater producers can benefit from a mature SRW resources recovery industry.
Research on Expansion Characteristics of Aquaculture Ponds and Variations in Ecosystem Service Value from the Perspective of Protecting Cultivated Lands: A Case Study of Liyang City, China
Authors: Zhao Bochuan , Li Yongfu , Wang Yazhu , Zhi Guoqing
Published: July 2022

In the context of global food insecurity, a large amount of cultivated land in China has been occupied by aquaculture ponds, leading to a series of variations in the ecological environment. The Chinese government pays close attention to the problem. In order to achieve sustainable development and ensure the safety of China’s cultivated land, the paper uses Liyang City as an example to discuss the spatial characteristics of the expansion of aquaculture ponds through occupying cultivated lands and analyzes the variations in ecosystem service value and cultivated land function. The conclusions are as follows: (1) 2073.24 hectares of cultivated lands were occupied for expanding aquaculture ponds in Liyang from 2009 to 2019, and there was a small number of new aquaculture ponds in the ecological protection area, which shows that the aquaculture ponds in Liyang City are at the stage of disorderly expansion; (2) the total value of ecosystem services increased by 1.43%; supply and support services values decreased, but the increase in regulation and cultural services values was sufficient to more than compensate for the mentioned losses; and (3) the expansion of aquaculture ponds leads to a decrease in the carbon storage of cultivated land, which in turn has negative impacts such as an increase in atmospheric carbon concentration.
The Problem of Wound Healing in Diabetes—From Molecular Pathways to the Design of an Animal Model
Authors: Mieczkowski Mateusz , Mrozikiewicz-Rakowska Beata , Kowara Michał , Kleibert Marcin , Czupryniak Leszek
Published: July 2022

Chronic wounds are becoming an increasingly common clinical problem due to an aging population and an increased incidence of diabetes, atherosclerosis, and venous insufficiency, which are the conditions that impair and delay the healing process. Patients with diabetes constitute a group of subjects in whom the healing process is particularly prolonged regardless of its initial etiology. Circulatory dysfunction, both at the microvascular and macrovascular levels, is a leading factor in delaying or precluding wound healing in diabetes. The prolonged period of wound healing increases the risk of complications such as the development of infection, including sepsis and even amputation. Currently, many substances applied topically or systemically are supposed to accelerate the process of wound regeneration and finally wound closure. The role of clinical trials and preclinical studies, including research based on animal models, is to create safe medicinal products and ensure the fastest possible healing. To achieve this goal and minimize the wide-ranging burdens associated with conducting clinical trials, a correct animal model is needed to replicate the wound conditions in patients with diabetes as closely as possible. The aim of the paper is to summarize the most important molecular pathways which are impaired in the hyperglycemic state in the context of designing an animal model of diabetic chronic wounds. The authors focus on research optimization, including economic aspects and model reproducibility, as well as the ethical dimension of minimizing the suffering of research subjects according to the 3 Rs principle (Replacement, Reduction, Refinement).
A Systematic Review of Keratinocyte Secretions: A Regenerative Perspective
Authors: El-Serafi Ahmed T. , El-Serafi Ibrahim , Steinvall Ingrid , Sjöberg Folke , Elmasry Moustafa
Published: July 2022

Cell regenerative therapy is a modern solution for difficult-to-heal wounds. Keratinocytes, the most common cell type in the skin, are difficult to obtain without the creation of another wound. Stem cell differentiation towards keratinocytes is a challenging process, and it is difficult to reproduce in chemically defined media. Nevertheless, a co-culture of keratinocytes with stem cells usually achieves efficient differentiation. This systematic review aims to identify the secretions of normal human keratinocytes reported in the literature and correlate them with the differentiation process. An online search revealed 338 references, of which 100 met the selection criteria. A total of 80 different keratinocyte secretions were reported, which can be grouped mainly into cytokines, growth factors, and antimicrobial peptides. The growth-factor group mostly affects stem cell differentiation into keratinocytes, especially epidermal growth factor and members of the transforming growth factor family. Nevertheless, the reported secretions reflected the nature of the involved studies, as most of them focused on keratinocyte interaction with inflammation. This review highlights the secretory function of keratinocytes, as well as the need for intense investigation to characterize these secretions and evaluate their regenerative capacities.
Comprehensive Cytokine Profiling of Patients with COVID-19 Receiving Tocilizumab Therapy
Authors: Lebedeva Anna , Molodtsov Ivan , Anisimova Alexandra , Berestovskaya Anastasia , Dukhin Oleg , Elizarova Antonina , Fitzgerald Wendy , Fomina Darya , Glebova Kseniya , Ivanova Oxana , Kalinskaya Anna , Lebedeva Anastasia , Lysenko Maryana , Maryukhnich Elena , Misyurina Elena , Protsenko Denis , Rosin Alexander , Sapozhnikova Olga , Sokorev Denis , Shpektor Alexander , Vorobyeva Daria , Vasilieva Elena , Margolis Leonid
Published: July 2022

Coronavirus disease 2019 (COVID-19) is characterized by immune activation in response to viral spread, in severe cases leading to the development of cytokine storm syndrome (CSS) and increased mortality. Despite its importance in prognosis, the pathophysiological mechanisms of CSS in COVID-19 remain to be defined. Towards this goal, we analyzed cytokine profiles and their interrelation in regard to anti-cytokine treatment with tocilizumab in 98 hospitalized patients with COVID-19. We performed a multiplex measurement of 41 circulating cytokines in the plasma of patients on admission and 3–5 days after, during the follow-up. Then we analyzed the patient groups separated in two ways: according to the clusterization of their blood cytokines and based on the administration of tocilizumab therapy. Patients with and without CSS formed distinct clusters according to their cytokine concentration changes. However, the tocilizumab therapy, administered based on the standard clinical and laboratory criteria, did not fully correspond to those clusters of CSS. Furthermore, among all cytokines, IL-6, IL-1RA, IL-10, and G-CSF demonstrated the most prominent differences between patients with and without clinical endpoints, while only IL-1RA was prognostically significant in both groups of patients with and without tocilizumab therapy, decreasing in the former and increasing in the latter during the follow-up period. Thus, CSS in COVID-19, characterized by a correlated release of multiple cytokines, does not fully correspond to the standard parameters of disease severity. Analysis of the cytokine signature, including the IL-1RA level in addition to standard clinical and laboratory parameters may be useful to define the onset of a cytokine storm in COVID-19 as well as the indications for anti-cytokine therapy.
Identification and Characterization of Specific Nanobodies against Trop-2 for Tumor Targeting
Authors: Hu Yaozhong , Wang Yi , Lin Jing , Wu Sihao , Lv Huan , Ji Xuemeng , Wang Shuo
Published: July 2022

Trophoblast cell-surface antigen 2 (Trop-2) is a tumor-associated antigen that is connected with the development of various tumors and has been identified as a promising target for tumor immunotherapy. To date, the immunotherapy against Trop-2 mainly relies on the specific targeting by monoclonal antibody in antibody-drug conjugate (ADC). Alternatively, the single domain antibodies of nanobodies (Nbs) possesses unique properties such as smaller size, better tissue penetration, etc., to make them good candidates for tumor targeting. Thus, it was proposed to develop anti-Trop-2 Nbs for tumor targeting in this study. Generally, three consecutive rounds of bio-panning were performed against immobilized recombinant Trop-2, and yielded three Nbs (Nb60, Nb65, and Nb108). The affinity of selected Nbs was determined in the nanomolar range, especially the good properties of Nb60 were verified as a promising candidate for tumor labeling. The binding to native Trop-2 was confirmed by flow cytometry against tumor cells. The inhibitory effects of the selected Nbs on tumor cell proliferation and migration were confirmed by wound healing and Transwell assay. The clear localization of the selected Nbs on the surface of tumor cells verified the potent labeling efficiency. In conclusion, this study provided several Nbs with the potential to be developed as targeting moiety of drug conjugates.
A Novel Cartesian Plot Analysis for Fixed Monolayers That Relates Cell Phenotype to Transfer of Contents between Fibroblasts and Cancer Cells by Cell-Projection Pumping
Authors: Mahadevan Swarna , Kwong Kenelm , Lu Mingjie , Kelly Elizabeth , Chami Belal , Romin Yevgeniy , Fujisawa Sho , Manova Katia , Moore Malcolm A. S. , Zoellner Hans
Published: July 2022

We recently described cell-projection pumping as a mechanism transferring cytoplasm between cells. The uptake of fibroblast cytoplasm by co-cultured SAOS-2 osteosarcoma cells changes SAOS-2 morphology and increases cell migration and proliferation, as seen by single-cell tracking and in FACS separated SAOS-2 from co-cultures. Morphological changes in SAOS-2 seen by single cell tracking are consistent with previous observations in fixed monolayers of SAOS-2 co-cultures. Notably, earlier studies with fixed co-cultures were limited by the absence of a quantitative method for identifying sub-populations of co-cultured cells, or for quantitating transfer relative to control populations of SAOS-2 or fibroblasts cultured alone. We now overcome that limitation by a novel Cartesian plot analysis that identifies individual co-cultured cells as belonging to one of five distinct cell populations, and also gives numerical measure of similarity to control cell populations. We verified the utility of the method by first confirming the previously established relationship between SAOS-2 morphology and uptake of fibroblast contents, and also demonstrated similar effects in other cancer cell lines including from melanomas, and cancers of the ovary and colon. The method was extended to examine global DNA methylation, and while there was no clear effect on SAOS-2 DNA methylation, co-cultured fibroblasts had greatly reduced DNA methylation, similar to cancer associated fibroblasts.
Novel Insights on Human Carbonic Anhydrase Inhibitors Based on Coumalic Acid: Design, Synthesis, Molecular Modeling Investigation, and Biological Studies
Authors: Pontecorvi Virginia , Mori Mattia , Picarazzi Francesca , Zara Susi , Carradori Simone , Cataldi Amelia , Angeli Andrea , Berrino Emanuela , Chimenti Paola , Ciogli Alessia , Secci Daniela , Guglielmi Paolo , Supuran Claudiu T.
Published: July 2022

Human carbonic anhydrase (hCA, EC 4.2.1.1) isoforms IX and XII are overexpressed in solid hypoxic tumors, and they are considered as prognostic tools and therapeutic targets for cancer. Based on a molecular simplification of the well-known coumarin scaffold, we developed a new series of derivatives of the pyran-2-one core. The new compounds are endowed with potent and selective inhibitory activity against the tumor-related hCA isoforms IX and XII, in the low nanomolar range, whereas they are inactive against the two cytosolic off-targets hCA I and II. The compounds exhibiting the best hCA inhibition were further investigated against the breast adenocarcinoma cell line (MCF7) in hypoxic conditions, evaluating their ability to eventually synergize with doxorubicin. The compounds’ biocompatibility on healthy cells was also tested and confirmed on Human Gingival Fibroblasts (HGFs). Furthermore, the possible binding mode of all compounds to the active site of the tumor-associated human CA IX was investigated by computational techniques which predicted the binding conformations and the persistency of binding poses within the active site of the enzyme, furnishing relevant data for the design of tight binding inhibitors.
Mechanical Stretch-Induced NLRP3 Inflammasome Expression on Human Annulus Fibrosus Cells Modulated by Endoplasmic Reticulum Stress
Authors: Chang Hsin-I , Chen Cheng-Nan , Huang Kuo-Yuan
Published: July 2022

Excessive mechanical loading is a major cause of spinal degeneration, typically originating from a tear in the annulus fibrosus (AF). Endoplasmic reticulum (ER) stress and NLRP3 (NOD-, LRR- and pyrin domain-containing protein 3) inflammasome have been implicated in the pathogenesis of intervertebral disc (IVD) degeneration. However, the causal relationship between the mechanical stretching of AF cells and the NLRP3 inflammasome response associated with ER stress remains scarce. To elucidate the pathogenesis and regulatory mechanisms of mechanical stretch-induced IVD degeneration, human AF cell lines were subjected to different degrees of cyclic stretching to simulate daily spinal movements. Our results indicated that 15% high cyclic stretch (HCS) induced the expression of NLRP3 and interleukin-1 beta (IL-1β) and was also responsible for the increased expression of NADPH (nicotinamide adenine dinucleotide phosphate) oxidase 2 (NOX2) and reactive oxygen species (ROS) in human AF cells. In addition, HCS increased the expression of glucose-regulated protein 78 (GRP78), an ER stress chaperone, which was neutralized with tauroursodeoxycholic acid (TUDCA), an ER stress inhibitor. In addition, HCS was found to induce thioredoxin-interacting protein (TXNIP) expression and NLRP3 inflammasome activation, which can be suppressed by si-NOX2 or the NOX2 inhibitor GSK2795039. Consequently, HCS upregulated ER stress and ROS production, leading to increased NLRP3 and IL-1β expression in human AF cells, and may further accelerate IVD degeneration.
Bridging between Mouse and Human Enhancer-Promoter Long-Range Interactions in Neural Stem Cells, to Understand Enhancer Function in Neurodevelopmental Disease
Authors: D’Aurizio Romina , Catona Orazio , Pitasi Mattia , Li Yang Eric , Ren Bing , Nicolis Silvia Kirsten
Published: July 2022

Non-coding variation in complex human disease has been well established by genome-wide association studies, and is thought to involve regulatory elements, such as enhancers, whose variation affects the expression of the gene responsible for the disease. The regulatory elements often lie far from the gene they regulate, or within introns of genes differing from the regulated gene, making it difficult to identify the gene whose function is affected by a given enhancer variation. Enhancers are connected to their target gene promoters via long-range physical interactions (loops). In our study, we re-mapped, onto the human genome, more than 10,000 enhancers connected to promoters via long-range interactions, that we had previously identified in mouse brain-derived neural stem cells by RNApolII-ChIA-PET analysis, coupled to ChIP-seq mapping of DNA/chromatin regions carrying epigenetic enhancer marks. These interactions are thought to be functionally relevant. We discovered, in the human genome, thousands of DNA regions syntenic with the interacting mouse DNA regions (enhancers and connected promoters). We further annotated these human regions regarding their overlap with sequence variants (single nucleotide polymorphisms, SNPs; copy number variants, CNVs), that were previously associated with neurodevelopmental disease in humans. We document various cases in which the genetic variant, associated in humans to neurodevelopmental disease, affects an enhancer involved in long-range interactions: SNPs, previously identified by genome-wide association studies to be associated with schizophrenia, bipolar disorder, and intelligence, are located within our human syntenic enhancers, and alter transcription factor recognition sites. Similarly, CNVs associated to autism spectrum disease and other neurodevelopmental disorders overlap with our human syntenic enhancers. Some of these enhancers are connected (in mice) to homologs of genes already associated to the human disease, strengthening the hypothesis that the gene is indeed involved in the disease. Other enhancers are connected to genes not previously associated with the disease, pointing to their possible pathogenetic involvement. Our observations provide a resource for further exploration of neural disease, in parallel with the now widespread genome-wide identification of DNA variants in patients with neural disease.
Differential In Vitro Effects of SGLT2 Inhibitors on Mitochondrial Oxidative Phosphorylation, Glucose Uptake and Cell Metabolism
Authors: Zügner Elmar , Yang Hsiu-Chiung , Kotzbeck Petra , Boulgaropoulos Beate , Sourij Harald , Hagvall Sepideh , Elmore Charles S. , Esterline Russell , Moosmang Sven , Oscarsson Jan , Pieber Thomas R. , Peng Xiao-Rong , Magnes Christoph
Published: July 2022

(1) The cardio-reno-metabolic benefits of the SGLT2 inhibitors canagliflozin (cana), dapagliflozin (dapa), ertugliflozin (ertu), and empagliflozin (empa) have been demonstrated, but it remains unclear whether they exert different off-target effects influencing clinical profiles. (2) We aimed to investigate the effects of SGLT2 inhibitors on mitochondrial function, cellular glucose-uptake (GU), and metabolic pathways in human-umbilical-vein endothelial cells (HUVECs). (3) At 100 µM (supra-pharmacological concentration), cana decreased ECAR by 45% and inhibited GU (IC5o: 14 µM). At 100 µM and 10 µM (pharmacological concentration), cana increased the ADP/ATP ratio, whereas dapa and ertu (3, 10 µM, about 10× the pharmacological concentration) showed no effect. Cana (100 µM) decreased the oxygen consumption rate (OCR) by 60%, while dapa decreased it by 7%, and ertu and empa (all 100 µM) had no significant effect. Cana (100 µM) inhibited GLUT1, but did not significantly affect GLUTs’ expression levels. Cana (100 µM) treatment reduced glycolysis, elevated the amino acids supplying the tricarboxylic-acid cycle, and significantly increased purine/pyrimidine-pathway metabolites, in contrast to dapa (3 µM) and ertu (10 µM). (4) The results confirmed cana´s inhibition of mitochondrial activity and GU at supra-pharmacological and pharmacological concentrations, whereas the dapa, ertu, and empa did not show effects even at supra-pharmacological concentrations. At supra-pharmacological concentrations, cana (but not dapa or ertu) affected multiple cellular pathways and inhibited GLUT1.
A Qualitative Study: Mothers’ Experiences of Their Child’s Late-Onset Pompe Disease Diagnosis Following Newborn Screening
Authors: Crossen Kaylee , Berry Lisa , Myers Melanie F. , Leslie Nancy , Goueli Cecilia
Published: July 2022

Pompe disease was added to the United States recommended uniform screening panel in 2015 to avoid diagnostic delay and implement prompt treatment, specifically for those with infantile-onset Pompe disease (IOPD). However, most newborns with abnormal newborn screening (NBS) for Pompe disease have late-onset Pompe disease (LOPD). An early diagnosis of LOPD raises the question of when symptoms will arise which is challenging for parents, patients, and providers managing an LOPD diagnosis. This study aimed to characterize mothers’ experiences of their child’s LOPD diagnosis and medical monitoring. A qualitative descriptive approach was chosen to gain an in-depth understanding of parental experiences. Eight mothers were interviewed about their experiences with positive NBS and diagnosis, experiences with living with the diagnosis, and experiences with medical monitoring. Interview transcripts were analyzed through conventional content analysis. Negative emotions like fear were more frequent with communication of NBS results. Participants expressed uncertainty surrounding age of symptom onset and the future. The medical monitoring experience increased worry but participants expressed that being vigilant with management reassured them. Parental emotions shifted to thankfulness and reassurance with time and education. These findings can provide guidance to providers about the psychosocial implications of receiving positive NBS results and an LOPD diagnosis.
Computational Offloading of Service Workflow in Mobile Edge Computing
Authors: Fu Shuang , Ding Chenyang , Jiang Peng
Published: July 2022

Mobile edge computing (MEC) sinks the functions and services of cloud computing to the edge of the network to provide users with storage and computing resources. For workflow tasks, the interdependency and the sequence constraint being among the tasks make the offloading strategy more complicated. To obtain the optimal offloading and scheduling scheme for workflow tasks to minimize the total energy consumption of the system, a workflow task offloading and scheduling scheme based on an improved genetic algorithm is proposed in an MEC network with multiple users and multiple virtual machines (VMs). Firstly, the system model of the offloading and scheduling of workflow tasks in a multi-user and multi-VMs MEC network is built. Then, the problem of how to determine the optimal offloading and scheduling scheme of workflow to minimize the total energy consumption of the system while meeting the deadline constraint is formulated. To solve this problem, the improved genetic algorithm is adopted to obtain the optimal offloading strategy and scheduling. Finally, the simulation results show that the proposed scheme can achieve a lower energy consumption than other benchmark schemes.
Pulsar Wind Nebulae and Unidentified Galactic Very High Energy Sources
Authors: Tibolla Omar , Kaufmann Sarah , Chadwick Paula
Published: July 2022

The riddle of the origin of Cosmic Rays (CR) has been an open question for over a century. Gamma ray observations above 100 MeV reveal the sites of cosmic ray acceleration to energies where they are unaffected by solar modulation; recent evidence supports the existence of hadronic acceleration in Supernova Remnants (SNR), as expected in the standard model of cosmic ray acceleration. Nevertheless, the results raise new questions, and no final answer has been provided thus far. Among the suggested possible alternative accelerators in the Very High Energy (VHE) gamma ray sky, pulsar wind nebulae (PWNe, which together with dark matter are the main candidates to explain the local positron excess as well) are the dominant population among known Galactic sources. However, the most numerous population in absolute terms is represented by unidentified sources (~50% of VHE gamma ray sources). The relationship between PWNe and unidentified sources seems very close; in fact, in a PWN, the lifetime of inverse Compton (IC) emitting electrons not only exceeds the lifetime of its progenitor pulsar, but also exceeds the age of the electrons that emit via synchrotron radiation. Therefore, during its evolution, a PWN can remain bright in IC such that its GeV-TeV gamma ray flux remains high for timescales much larger than the lifetimes of the pulsar and the X-ray PWN. In addition, the shell-type remnant of the supernova explosion in which the pulsar was formed has a much shorter lifetime than the electrons responsible for IC emission. Hence, understanding PWNe and VHE unidentified sources is a crucial piece of the solution to the riddle of the origin of cosmic rays. Both theoretical aspects (with particular emphasis on the ancient pulsar wind nebulae scenario) and their observational proofs are discussed in this paper. Specifically, the scientific cases of HESS J1616-508 and HESS J1813-126 are examined in detail.
Mycetoma: Development of Diagnosis and Treatment
Authors: Hao Xingpei , Cognetti Marcus , Burch-Smith Rhonda , Mejia Emerald O’Sullivan , Mirkin Gene
Published: July 2022

Mycetoma describes a heterogeneous group of cutaneous and subcutaneous infections caused by either fungi (eumycetomas) or bacteria (actinomycetomas). It is characterized by a triad of clinical symptoms: painless subcutaneous tumor-like swelling, multiple sinuses and fistulas, and discharged grains in pus. This predominantly affects the feet in more than 70% of patients. It is endemic in the “mycetoma belt” regions, including Africa, South America, and South Asia. Autochthonous mycetoma is rare in the United States of America (USA). We recently reported a Latin American immigrant with eumycetoma in the State of Maryland, USA. With millions of immigrants from endemic regions, the true number of mycetomas in the USA is most likely higher than currently recognized. With the aim to raise the awareness of clinicians about mycetoma, especially dermatologists and podiatrists, we update the development of the epidemiology, etiology, clinical presentations, pathogenesis, diagnosis, differential diagnosis, and treatment of mycetoma.
Spatiotemporal Patterns in and Key Influences on Cultivated-Land Multi-Functionality in Northeast China’s Black-Soil Region
Authors: Gong Heyang , Zhao Zhibo , Chang Lei , Li Guanghui , Li Ying , Li Yuefen
Published: July 2022

Cultivated-land multi-functionality has become an important way to achieve sustainable cultivated-land protection, and it has become a hot spot in the field of land-management policy. Taking the cultivated black soils in the grain-producing area of Jilin Province, Northeast China, as a case study, this paper assessed the multi-functions of cultivated land over the past 30 years by applying the improved TOPSIS model. Furthermore, the key limiting factors and influencing factors of the multi-functions of cultivated land were identified through the obstacle-degree model and the Geo-detector. The results show that the level of multi-functionality rose from 1990 to 2020, but an increase in both economic and social functions hindered improvements in the ecological function of cultivated land. There were obvious spatial differences in the functions of cultivated land in different counties, with ecological functions showing the highest degree of differentiation, followed by social and economic functions. The per capita agricultural output, the degree of agricultural mechanization, the average output from cultivated land, and the agricultural-labor productivity had the most restrictive effects on the functions of cultivated land, with barrier-degree values of 15.90, 13.90, 11.76, and 10.30, respectively. Coupling–coordination in the multi-functions and sub-functions of cultivated land showed an upward trend, from “low coupling coordination–antagonistic coupling coordination” to “high coupling coordination-optimal coupling coordination”. The government should include the level of multi-functional utilization in future policies for the management and utilization of cultivated land and take measures to reduce the differences in the functions of cultivated land among regions. Quantifying the multi-functional value of cultivated land and subsidizing land cultivation should encourage farmers to protect the land and help to strengthen multi-functional planning and functional design, improve ecological utilization, and promote the sustainable use of cultivated land.
Functional Tradeoffs and Feature Recognition of Rural Production–Living–Ecological Spaces
Authors: Zhao Tianyi , Cheng Yuning , Fan Yiyang , Fan Xiangnan
Published: July 2022

Recently, the spatial contradiction in rural construction has intensified. Production–living–ecological (PLE) spaces, as important load-bearing spatial patterns of rural revitalization, have become a research focus of territorial space planning. Because of the lack of studies on the scale and accuracy at the township level in rural PLE spaces, the objective of this study is to quantify the subfunctional and functional areas of PLE spaces, weigh the relationship between PLE functions, and conduct feature identification and strategy formulation of the PLE synergistic functional areas. Combined with multitype measurement methods, the study constructed a township-level PLE space evaluation system composed of 12 subfunctional indicators. Taking Guli Street in Nanjing city as an example, Spearman correlation analysis, spatial local autocorrelation analysis, and cold/hot spot identification were used to analyze the synergies and tradeoffs between PLE functions. On this basis, the evaluation model of the PLE synergies area was constructed. The results showed that the production function showed a fragmented distribution pattern. The proportion of high-intensity living function areas was very small. The ecological function area had good patch integrity. In the PLE functions, obvious synergies exist between any two functions, and the tradeoff between the third one and any of the two functions. The seven types of PLE synergistic potential areas were dominated by the dual-function high synergistic zone (DF-H-Z). The zoning scheme and governance strategy proposed in this paper have important practical value for solving the contradiction of sustainable and coordinated development of township-scale spatial resources.
Green Synthesis of Silver Nanoparticles Using Populi gemmae Extract: Preparation, Physicochemical Characterization, Antimicrobial Potential and In Vitro Antiproliferative Assessment
Authors: Kis Brigitta , Moacă Elena-Alina , Tudoran Lucian Barbu , Muntean Delia , Magyari-Pavel Ioana Zinuca , Minda Daliana Ionela , Lombrea Adelina , Diaconeasa Zorita , Dehelean Cristina Adriana , Dinu Ștefania , Danciu Corina
Published: July 2022

Green route is an economic, facile and eco-friendly method, employed for the synthesis of various types of nanoparticles, having it as a starting point biological entity, especially as a plant extract. The present study aims to obtain silver nanoparticles (AgNPs) starting from an ethanolic extract of Populi gemmae (Pg), by adjusting the reaction parameters. The morphological and structural characterization exhibited that both the reaction temperature and the concentration of metal salt, contributes to the obtaining of Pg-AgNPs with adjustable size and shape. The newly synthesized nanoparticles exhibited a good antibacterial activity on Gram-positive bacteria as well as antifungal activity. The in vitro antiproliferative activity of Pg-AgNPs was assessed on two different cancer cell lines (breast cancer cells—MCF7 and lung carcinoma epithelial cells—A549). Results have shown that the green-synthetized Pg-AgNPs_S2 (obtained at 60 °C, using AgNO3 of 5 M) induced a substantial decrease in tumor cell viability in a dose-dependent manner with an IC50 ranging from 5.03 to 5.07 µg/mL on A549 cell line and 3.24 to 4.93 µg/mL on MCF7 cell line.
Research on the True Triaxial Mechanical Properties of Concrete under the Coupling Action of High Temperature and Biaxial Unequal Lateral Pressure
Authors: Ren Biao , Wang Tengjiao , Xu Jinyu , Wang Zhihang , Lv Yan , Ning Yipeng
Published: July 2022

Based on engineering practice and practical needs, this paper takes ordinary concrete specimens as the research object, and adopts a high-temperature true triaxial loading test system to carry out high-temperature uniaxial and true triaxial static compression tests of concrete under high-temperature conditions. By comparing with normal temperature conditions, this paper analyzes the influence of the coupling effect of high-temperature and biaxial unequal lateral pressure on the static mechanical properties of concrete. By analyzing the experimental data, we reached a series of conclusions and carried out theoretical research on this basis. High temperatures can significantly affect the uniaxial static pressure strength characteristics, deformation characteristics, and failure mode of concrete. When the temperature exceeds 400 °C, the compressive strength decreases significantly, the peak strain increases sharply, and the plasticity of concrete is further enhanced. The coupling effect of high-temperature deterioration and lateral pressure strengthening makes the true triaxial mechanical properties of concrete change significantly; 0.6:0.2 and 400 °C are the turning points of side pressure ratio and temperature that affect the change law of the true triaxial mechanical properties of concrete, respectively. Based on the study of the high-temperature deterioration factor and lateral pressure strengthening factor, this paper further puts forward a concrete strength formula under the coupling action of high temperature and biaxial unequal lateral pressure. It was verified that the formula has a high accuracy.
Influence Analysis of Geometric Error and Compensation Method for Four-Axis Machining Tools with Two Rotary Axes
Authors: Zhao Guojuan , Jiang Shengcheng , Dong Kai , Xu Quanwang , Zhang Ziling , Lu Lei
Published: July 2022

Four-axis machine tools with two rotary axes are widely used in the machining of complex parts. However, due to an irregular kinematic relationship and non-linear kinematic function with geometric error, it is difficult to analyze the influence the geometry error of each axis has and to compensate for such a geometry error. In this study, an influence analysis method of geometric error based on the homogeneous coordinate transformation matrix and a compensation method was developed, using the Newton iterative method. Geometric errors are characterized by a homogeneous coordinate transformation matrix in the proposed method, and an error matrix is integrated into the kinematic model of the four-axis machine tool as a means of studying the influence the geometric error of each axis has on the tool path. Based on the kinematic model of the four-axis machine tool considering the geometric error, a comprehensive geometric error compensation calculation model based on the Newton iteration was then constructed for calculating the tool path as a means of compensating for the geometric error. Ultimately, the four-axis machine tool with a curve tool path for an off-axis optical lens was chosen for verification of the proposed method. The results showed that the proposed method can significantly improve the machining accuracy.
Drape of Composite Structures Made of Textile and 3D Printed Geometries
Authors: Spahiu Tatjana , Zlatev Zlatin , Ibrahimaj Elita , Ilieva Julieta , Shehi Ermira
Published: July 2022

Applications of 3D printing in the fashion industry have continued to attract interest from academia and industry in order to improve and add functionalities to products. Among these applications, an interesting one is 3D printing on textile fabric. Composite structures created by 3D printing and textile fabric change a drape by improving or worsening its appearance. The scope of this work is to evaluate the effect of various 3D printed geometries on textile fabric regarding fabric drapes. The drape coefficient of the created composite structure is evaluated using a drape tester built according to EN ISO 9073-9. The results taken are compared with an algorithm developed for determining drape parameters and 3D form representation using color digital images and their image histograms. The measured values of the drape coefficient are close, with a minimal difference, up to 4%. The 3D printed patterns show a significant effect on the drape coefficient of textile fabrics by depicting another way to modify fabric drapes and create complex shapes by using less material. This can be seen as an advantage in the fashion industry where complex geometries can be added to textile fabrics, while changing fabric drape and product personalization and adding functionalities for garments and technical textiles.
Representation Theorem and Functional CLT for RKHS-Based Function-on-Function Regressions
Authors: Huang Hengzhen , Mo Guangni , Li Haiou , Fang Hong-Bin
Published: July 2022

We investigate a nonparametric, varying coefficient regression approach for modeling and estimating the regression effects caused by two functionally correlated datasets. Due to modern biomedical technology to measure multiple patient features during a time interval or intermittently at several discrete time points to review underlying biological mechanisms, statistical models that do not properly incorporate interventions and their dynamic responses may lead to biased estimates of the intervention effects. We propose a shared parameter change point function-on-function regression model to evaluate the pre- and post-intervention time trends and develop a likelihood-based method for estimating the intervention effects and other parameters. We also propose new methods for estimating and hypothesis testing regression parameters for functional data via reproducing kernel Hilbert space. The estimators of regression parameters are closed-form without computation of the inverse of a large matrix, and hence are less computationally demanding and more applicable. By establishing a representation theorem and a functional central limit theorem, the asymptotic properties of the proposed estimators are obtained, and the corresponding hypothesis tests are proposed. Application and the statistical properties of our method are demonstrated through an immunotherapy clinical trial of advanced myeloma and simulation studies.
Biomarkers for Alzheimer’s Disease: Context of Use, Qualification, and Roadmap for Clinical Implementation
Authors: Cummings Jeffrey , Kinney Jefferson
Published: July 2022

Background and Objectives: The US Food and Drug Administration (FDA) defines a biomarker as a characteristic that is measured as an indicator of normal biological processes, pathogenic processes, or responses to an exposure or intervention. Biomarkers may be used in clinical care or as drug development tools (DDTs) in clinical trials. The goal of this review and perspective is to provide insight into the regulatory guidance for the use of biomarkers in clinical trials and clinical care. Materials and Methods: We reviewed FDA guidances relevant to biomarker use in clinical trials and their transition to use in clinical care. We identified instructive examples of these biomarkers in Alzheimer’s disease (AD) drug development and their application in clinical practice. Results: For use in clinical trials, biomarkers must have a defined context of use (COU) as a risk/susceptibility, diagnostic, monitoring, predictive, prognostic, pharmacodynamic, or safety biomarker. A four-stage process defines the pathway to establish the regulatory acceptance of the COU for a biomarker including submission of a letter of intent, description of the qualification plan, submission of a full qualification package, and acceptance through a qualification recommendation. Biomarkers used in clinical care may be companion biomarkers, in vitro diagnostic devices (IVDs), or laboratory developed tests (LDTs). A five-phase biomarker development process has been proposed to structure the biomarker development process. Conclusions: Biomarkers are increasingly important in drug development and clinical care. Adherence to regulatory guidance for biomarkers used in clinical trials and patient care is required to advance these important drug development and clinical tools.
Surgical Treatment and Rehabilitation Strategies for Upper and Lower Extremity Lymphedema: A Comprehensive Review
Authors: de Sire Alessandro , Losco Luigi , Lippi Lorenzo , Spadoni Davide , Kaciulyte Juste , Sert Gokhan , Ciamarra Paola , Marcasciano Marco , Cuomo Roberto , Bolletta Alberto , Invernizzi Marco , Cigna Emanuele
Published: July 2022

Lymphedema is a chronic disabling condition affecting a growing number of patients worldwide. Although lymphedema is not life-threatening, several reports underlined detrimental consequences in terms of distress, pain, functional impairment, and infections with a relevant decrease in quality of life. Currently, there is no cure, and the therapeutic management of this condition aims at slowing down the disease progression and preventing secondary complications. Early diagnosis is paramount to enhance the effects of rehabilitation or surgical treatments. On the other hand, a multidisciplinary treatment should be truly integrated, the combination of microsurgical and reductive procedures should be considered a valid strategy to manage extremity lymphedema, and rehabilitation should be considered the cornerstone of the multidisciplinary treatment not only for patients not suitable for surgical interventions but also before and after surgical procedures. Therefore, a specialized management of Plastic Reconstructive Surgeons and Physical and Rehabilitative Medicine physicians should be mandatory to address patients’ needs and optimize the treatment of this disabling and detrimental condition. Therefore, the aim of this review was to characterize the comprehensive management of lymphedema, providing a broad overview of the potential therapy available in the current literature to optimize the comprehensive management of lymphedema and minimize complications.
Timing, Provenance, and Tectonic Implications of Ore-Hosting Metasedimentary Rocks in the Giant Liba Gold Deposit, West Qinling Belt, China
Authors: Zhang Peng-Cong , Li Shan-Shan , Liu Bo , He Deng-Yang , Cai Quan-Sheng , Kaningu Germain Bishikwabo , Sun Xin-Chun
Published: July 2022

The closure time of the Shangdan Ocean is critical for understanding the tectonic evolution of the Proto-Tethys Ocean. However, the proposed closure time was prolonged from Ordovician to Devonian. In the present study, detrital zircon from the metasedimentary rocks of the Liba Group in the West Qinling Belt was analyzed to constrain the closure time of the Shangdan Ocean. The three youngest grains from the Liba Group yield a maximum deposition age of 418 ± 13 Ma, indicating the Middle Devonian deposition. Detrital zircon grains show two main U–Pb age peaks of 810 Ma and 440 Ma with εHf(t) values spanning from −24.3 to +8.8 and −6.3 to +4.1, respectively, suggesting that the sediments of the Liba Group were derived from both the North and South Qinling Belts. The Lower Devonian in the South Qinling Belt shows similar provenance to the Liba Group, whereas sediments from the North Qinling Belt are absent in the Silurian strata of the South Qinling Belt. From Late Silurian to Early Devonian, the tectonic setting changed from subduction to collision. This evidence consistently suggests the disappearance of the Shangdan Ocean. The noticeable decrease in magmatism from 510–420 Ma to 420–390 Ma and the shrinking of εHf(t) values from −15.5–+12.8 to −8.4–+4.2 reveal that the Shangdan Ocean, as the eastmost embranchment of the Proto-Tethys Ocean, was closed at ca. 420 Ma.