bluuebunny/crossref_metadata_2025 huggingface dataset:
Indices of Defective Autophagy in Whole Muscle and Lysosome Enriched Fractions From Aged D2-mdx Mice
Authors: Krishna Swathy , Spaulding Hannah R. , Quindry Tiffany S. , Hudson Matthew B. , Quindry John C. , Selsby Joshua T.
Published: July 2021

Duchenne muscular dystrophy (DMD) is a fatal, progressive muscle disease caused by the absence of functional dystrophin protein. Previous studies in mdx mice, a common DMD model, identified impaired autophagy with lysosomal insufficiency and impaired autophagosomal degradation as consequences of dystrophin deficiency. Thus, we hypothesized that lysosomal abundance would be decreased and degradation of autophagosomes would be impaired in muscles of D2-mdx mice. To test this hypothesis, diaphragm and gastrocnemius muscles from 11 month-old D2-mdx and DBA/2J (healthy) mice were collected. Whole muscle protein from diaphragm and gastrocnemius muscles, and protein from a cytosolic fraction (CF) and a lysosome-enriched fraction (LEF) from gastrocnemius muscles, were isolated and used for western blotting. Initiation of autophagy was not robustly activated in whole muscle protein from diaphragm and gastrocnemius, however, autophagosome formation markers were elevated in dystrophic muscles. Autophagosome degradation was impaired in D2-mdx diaphragms but appeared to be maintained in gastrocnemius muscles. To better understand this muscle-specific distinction, we investigated autophagic signaling in CFs and LEFs from gastrocnemius muscles. Within the LEF we discovered that the degradation of autophagosomes was similar between groups. Further, our data suggest an expanded, though impaired, lysosomal pool in dystrophic muscle. Notably, these data indicate a degree of muscle specificity as well as model specificity with regard to autophagic dysfunction in dystrophic muscles. Stimulation of autophagy in dystrophic muscles may hold promise for DMD patients as a potential therapeutic, however, it will be critical to choose the appropriate model and muscles that most closely recapitulate findings from human patients to further develop these therapeutics.
Going to Extremes of Lung Physiology–Deep Breath-Hold Diving
Authors: Tetzlaff Kay , Lemaitre Frederic , Burgstahler Christof , Luetkens Julian A. , Eichhorn Lars
Published: July 2021

Breath-hold diving involves environmental challenges, such as water immersion, hydrostatic pressure, and asphyxia, that put the respiratory system under stress. While training and inherent individual factors may increase tolerance to these challenges, the limits of human respiratory physiology will be reached quickly during deep breath-hold dives. Nonetheless, world records in deep breath-hold diving of more than 214 m of seawater have considerably exceeded predictions from human physiology. Investigations of elite breath-hold divers and their achievements revised our understanding of possible physiological adaptations in humans and revealed techniques such as glossopharyngeal breathing as being essential to achieve extremes in breath-hold diving performance. These techniques allow elite athletes to increase total lung capacity and minimize residual volume, thereby reducing thoracic squeeze. However, the inability of human lungs to collapse early during descent enables respiratory gas exchange to continue at greater depths, forcing nitrogen (N2) out of the alveolar space to dissolve in body tissues. This will increase risk of N2 narcosis and decompression stress. Clinical cases of stroke-like syndromes after single deep breath-hold dives point to possible mechanisms of decompression stress, caused by N2 entering the vasculature upon ascent from these deep dives. Mechanisms of neurological injury and inert gas narcosis during deep breath-hold dives are still incompletely understood. This review addresses possible hypotheses and elucidates factors that may contribute to pathophysiology of deep freediving accidents. Awareness of the unique challenges to pulmonary physiology at depth is paramount to assess medical risks of deep breath-hold diving.
Using Positive Empathy Interventions to Reduce Stigma Toward People Who Inject Drugs
Authors: Clinton Alex J. , Pollini Robin A.
Published: July 2021

People who inject drugs are often the target of stigma that puts this already at-risk group at greater risk of harm. Past research has shown that holding stigmatizing views of people who inject drugs increases risky behaviors and is a barrier to their engagement in important medical and public health interventions. One explanation is that the negativity surrounding the group causes increased levels of anticipated emotional exhaustion, discouraging positive engagement. However, there has been minimal research focused on addressing this negativity to reduce levels of held stigma against people who inject drugs. We hypothesized that giving people an imagined positive contact exercise about people who inject would lead to a reduction in stigma, since exposure to positive empathy may create new mental associations between stigmatized groups and more positive emotions and experiences. Secondarily, we hypothesized that positive empathy strategies would be more effective than traditional informational or learning based techniques, and that the latter would be more effective than a control condition. Our sample consisted of 375 participants recruited online. Participants were assigned to one of three study conditions: a positive empathy condition, an informational learning condition, or a control condition, and completed a posttest social distance measure. Results demonstrated that subjects exposed to the positive empathy stigma reduction condition experienced a significant reduction in held stigma while participants exposed to traditional informational learning techniques showed no significant reduction in held stigma. Positive empathy-based stigma interventions should be further researched as a promising avenue to reduce the effects of drug-related stigma.
The Perils of Misspecified Priors and Optional Stopping in Multi-Armed Bandits
Authors: Loecher Markus
Published: July 2021

The connection between optimal stopping times of American Options and multi-armed bandits is the subject of active research. This article investigates the effects of optional stopping in a particular class of multi-armed bandit experiments, which randomly allocates observations to arms proportional to the Bayesian posterior probability that each arm is optimal (Thompson sampling). The interplay between optional stopping and prior mismatch is examined. We propose a novel partitioning of regret into peri/post testing. We further show a strong dependence of the parameters of interest on the assumed prior probability density.
Understanding Determinants of Hunting Trip Productivity in an Arctic Community
Authors: Naylor Angus W. , Pearce Tristan , Ford James D. , Fawcett David , Collings Peter , Harper Sherilee L.
Published: July 2021

We examine factors underlying hunting productivity among Inuit in Ulukhaktok, Northwest Territories, Canada. Specifically, we focus on the role of gasoline use as the main variable of interest—commonly cited as a crucial determinant of hunting participation. Over the course of 12 months, 10 hunters recorded their on-the-land activities using a GPS tracking system, participatory mapping sessions, and bi-weekly interviews. A multivariable linear regression model (MvLRM) was applied to assess whether factors such as consumables used (i.e. heating fuel, gasoline, oil, food), distances traveled, or the number of companions on a trip were associated with the mass of edible foods returned to the community. Results indicate that, despite being positively associated with hunting trip productivity when assessed through a univariable linear regression model, gasoline is not a statistically significant determinant of standalone trip yield when adjusting for other variables in a multivariable linear regression. Instead, factors relating to seasonality, number of companions, and days on the land emerged as more significant and substantive drivers of productivity while out on the land. The findings do not suggest that access to, or the availability of, gasoline does not affect whether a hunting trip commences or is planned, nor that an increase in the amount of gasoline available to a hunter might increase the frequency of trips (and therefore annual productivity). Rather, this work demonstrates that the volume of gasoline used by harvesters on standalone hunting trips represent a poor a priori predictor of the edible weight that harvesters are likely to return to the community.
AppliedChem: Modern Challenges in the Chemical Sciences
Authors: Love Jason B.
Published: July 2021

While pure chemistry aims to enhance knowledge within the chemical sciences, applied chemistry exploits the principles and theories of chemistry to answer specific questions or solve real-world challenges [...]
Utility of Transcranial Magnetic Simulation in Studying Upper Motor Neuron Dysfunction in Amyotrophic Lateral Sclerosis
Authors: Geevasinga Nimeshan , Van den Bos Mehdi , Menon Parvathi , Vucic Steve
Published: July 2021

Amyotrophic lateral sclerosis (ALS) is characterised by progressive dysfunction of the upper and lower motor neurons. The disease can evolve over time from focal limb or bulbar onset to involvement of other regions. There is some clinical heterogeneity in ALS with various phenotypes of the disease described, from primary lateral sclerosis, progressive muscular atrophy and flail arm/leg phenotypes. Whilst the majority of ALS patients are sporadic in nature, recent advances have highlighted genetic forms of the disease. Given the close relationship between ALS and frontotemporal dementia, the importance of cortical dysfunction has gained prominence. Transcranial magnetic stimulation (TMS) is a noninvasive neurophysiological tool to explore the function of the motor cortex and thereby cortical excitability. In this review, we highlight the utility of TMS and explore cortical excitability in ALS diagnosis, pathogenesis and insights gained from genetic and variant forms of the disease.
Metformin and Niclosamide Synergistically Suppress Wnt and YAP in APC-Mutated Colorectal Cancer
Authors: Kang Hee Eun , Seo Yoojeong , Yun Jun Seop , Song Sang Hyun , Han Dawool , Cho Eunae Sandra , Cho Sue Bean , Jeon Yoon , Lee Ho , Kim Hyun Sil , Kang Joyeon , Yook Jong In , Kim Nam Hee , Kim Tae Il
Published: July 2021

The Wnt and Hippo pathways are tightly coordinated and understanding their reciprocal regulation may provide a novel therapeutic strategy for cancer. Anti-helminthic niclosamide is an effective inhibitor of Wnt and is now in a phase II trial for advanced colorectal cancer (CRC) patients. We found that Axin2, an authentic target gene of canonical Wnt, acts as aYAP phosphorylation activator in APC-mutated CRC. While niclosamide effectively suppresses Wnt, it also inhibits Hippo, limiting its therapeutic potential for CRC. To overcome this limitation, we utilized metformin, a clinically available AMPK activator. This combinatory approach not only suppresses canonical Wnt activity, but also inhibits YAP activity in CRC cancer cells and in patient-derived cancer organoid through the suppression of cancer stemness. Further, combinatory oral administration suppressed in vivo tumorigenesis and the cancer progression of APC-MIN mice models. Our observations provide not only a reciprocal link between Wnt and Hippo, but also clinically available novel therapeutics that are able to target Wnt and YAP in APC-mutated CRC.
Correction: Liquori et al. Acute Promyelocytic Leukemia: A Constellation of Molecular Events around a Single PML-RARA Fusion Gene. Cancers 2020, 12, 624
Authors: Liquori Alessandro , Ibañez Mariam , Sargas Claudia , Sanz Miguel Ángel , Barragán Eva , Cervera José
Published: July 2021

The authors wish to make the following corrections to this paper [...]
Generation and Characterization of a New Preclinical Mouse Model of EGFR-Driven Lung Cancer with MET-Induced Osimertinib Resistance
Authors: Mancini Maicol , Thomas Quentin-Dominique , Bourdel Sylvia , Papon Laura , Bousquet Emilie , Jalta Prisca , La Monica Silvia , Travert Camille , Alfieri Roberta , Quantin Xavier , Cañamero Marta , Maraver Antonio
Published: July 2021

Despite the introduction of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) to treat advanced lung cancer harboring EGFR-activating mutations, the prognosis remains unfavorable because of intrinsic and/or acquired resistance. We generated a new state-of-the-art mouse strain harboring the human EGFRT790M/L858R oncogene and MET overexpression (EGFR/MET strain) that mimics the MET amplification occurring in one out of five patients with EGFR-mutated lung cancer that relapsed after treatment with osimertinib, a third-generation anti-EGFR TKI. We found that survival was reduced in EGFR/MET mice compared with mice harboring only EGFRT790M/L858R (EGFR strain). Moreover, EGFR/MET-driven lung tumors were resistant to osimertinib, recapitulating the phenotype observed in patients. Conversely, as also observed in patients, the crizotinib (anti-MET TKI) and osimertinib combination improved survival and reduced tumor burden in EGFR/MET mice, further validating the model’s value for preclinical studies. We also found that in EGFR/MET mice, MET overexpression negatively regulated EGFR activity through MIG6 induction, a compensatory mechanism that allows the coexistence of the two onco-genic events. Our data suggest that single EGFR or MET inhibition might not be a good therapeutic option for EGFR-mutated lung cancer with MET amplification, and that inhibition of both pathways should be the best clinical choice in these patients.
Interleukin-33-Enhanced CXCR4 Signaling Circuit Mediated by Carcinoma-Associated Fibroblasts Promotes Invasiveness of Head and Neck Cancer
Authors: Lin Yu-Chun , Huang Wen-Yen , Lee Tsai-Yu , Chang Yi-Ming , Chen Su-Feng , Lin Yaoh-Shiang , Nieh Shin
Published: July 2021

Despite recent advances, treatment for head and neck squamous cell carcinoma (HNSCC) has limited efficacy in preventing tumor progression. We confirmed previously that carcinoma-associated fibroblasts (CAF)-induced interleukin-33 (IL-33) contributed to cancer progression. However, the molecular mechanisms underlying the complex communication network of the tumor microenvironment merited further evaluation. To simulate the IL-33-induced autocrine signaling, stable clones of IL-33-overexpressing HNSCC cells were established. Besides well-established IL-33/ST2 and SDF1/CXCR4 (stromal-derived factor 1/C-X-C motif chemokine receptor 4) signaling, the CAF-induced IL-33 upregulated CXCR4 via cancer cell induction of IL-33 self-production. The IL-33-enhanced-CXCR4 regulatory circuit involves SDF1/CXCR4 signaling activation and modulates tumor behavior. An in vivo study confirmed the functional role of IL-33/CXCR4 in tumor initiation and metastasis. The CXCR4 and/or IL-33 blockade reduced HNSCC cell aggressiveness, with attenuated invasions and metastases. Immunohistochemistry confirmed that IL-33 and CXCR4 expression correlated significantly with disease-free survival and IL-33-CXCR4 co-expression predicted a poor outcome. Besides paracrine signaling, the CAF-induced IL-33 reciprocally enhanced the autocrine cancer-cell self-production of IL-33 and the corresponding CXCR4 upregulation, leading to the activation of SDF1/CXCR4 signaling subsequent to cancer progression. Thus, targeting the IL-33-enhanced-CXCR4 regulatory circuit attenuates tumor aggressiveness and provides a potential therapeutic option for improving the prognosis in HNSCC patients.
Translational Utility of Liquid Biopsies in Thyroid Cancer Management
Authors: Wijewardene Ayanthi A. , Chehade Marthe , Gild Matti L. , Clifton-Bligh Roderick J. , Bullock Martyn
Published: July 2021

Liquid biopsies are a novel technique to assess for either circulating tumor cells (CTC) or circulating tumor DNA (ctDNA and microRNA (miRNA)) in peripheral blood samples of cancer patients. The diagnostic role of liquid biopsy in oncology has expanded in recent years, particularly in lung, colorectal and breast cancer. In thyroid cancer, the role of liquid biopsy in either diagnosis or prognosis is beginning to translate from the lab to the clinic. In this review, we describe the evolution of liquid biopsies in detecting CTC, ctDNA and miRNA in thyroid cancer patients, together with its limitations and future directions in clinical practice.
KYP-2047, an Inhibitor of Prolyl-Oligopeptidase, Reduces GlioBlastoma Proliferation through Angiogenesis and Apoptosis Modulation
Authors: Scuderi Sarah Adriana , Casili Giovanna , Ardizzone Alessio , Forte Stefano , Colarossi Lorenzo , Sava Serena , Paterniti Irene , Esposito Emanuela , Cuzzocrea Salvatore , Campolo Michela
Published: July 2021

Glioblastoma (GB) is the most aggressive tumor of the central nervous system (CNS), characterized by excessive proliferation, necrosis and invasiveness. The survival rate for patients with GB still remains low. Angiogenesis and apoptosis play a key role in the development of GB. Thus, the modulation of angiogenesis and apoptosis processes represent a possible strategy to counteract GB progression. This study aimed to investigate the potential effect of KYP-2047, an inhibitor of the prolyl-oligopeptidase (POP), known to modulate angiogenesis, in an in vivo U87-xenograft model and in an in vitro study on human GB cells. Our results showed that KYP-2047 at doses of 2.5 mg/kg and 5 mg/kg was able to reduce tumor burden in the xenograft-model. Moreover, KYP-2047 significantly reduced vascular endothelial-growth-factor (VEGF), angiopoietins (Ang) and endothelial-nitric-oxide synthase (eNOS) expression. In vitro study revealed that KYP-2047 at different concentrations reduced GB cells’ viability. Additionally, KYP-2047 at the concentrations of 50 µM and 100 µM was able to increase the pro-apoptotic protein Bax, p53 and caspase-3 expression whereas Bcl-2 expression was reduced. Thus, KYP-2047 could represent a potential therapeutic treatment to counteract or reduce GB progression, thanks its abilities to modulate angiogenesis and apoptosis pathways.
Akt Isoforms: A Family Affair in Breast Cancer
Authors: Basu Alakananda , Lambring Christoffer Briggs
Published: July 2021

Akt, also known as protein kinase B (PKB), belongs to the AGC family of protein kinases. It acts downstream of the phosphatidylinositol 3-kinase (PI3K) and regulates diverse cellular processes, including cell proliferation, cell survival, metabolism, tumor growth and metastasis. The PI3K/Akt signaling pathway is frequently deregulated in breast cancer and plays an important role in the development and progression of breast cancer. There are three closely related members in the Akt family, namely Akt1(PKBα), Akt2(PKBβ) and Akt3(PKBγ). Although Akt isoforms share similar structures, they exhibit redundant, distinct as well as opposite functions. While the Akt signaling pathway is an important target for cancer therapy, an understanding of the isoform-specific function of Akt is critical to effectively target this pathway. However, our perception regarding how Akt isoforms contribute to the genesis and progression of breast cancer changes as we gain new knowledge. The purpose of this review article is to analyze current literatures on distinct functions of Akt isoforms in breast cancer.
Development of Randomized Trials in Adults with Medulloblastoma—The Example of EORTC 1634-BTG/NOA-23
Authors: Hau Peter , Frappaz Didier , Hovey Elizabeth , McCabe Martin G. , Pajtler Kristian W. , Wiestler Benedikt , Seidel Clemens , Combs Stephanie E. , Dirven Linda , Klein Martin , Anazodo Antoinette , Hattingen Elke , Hofer Silvia , Pfister Stefan M. , Zimmer Claus , Kortmann Rolf-Dieter , Sunyach Marie-Pierre , Tanguy Ronan , Effeney Rachel , von Deimling Andreas , Sahm Felix , Rutkowski Stefan , Berghoff Anna S. , Franceschi Enrico , Pineda Estela , Beier Dagmar , Peeters Ellen , Gorlia Thierry , Vanlancker Maureen , Bromberg Jacoline E. C. , Gautier Julien , Ziegler David S. , Preusser Matthias , Wick Wolfgang , Weller Michael
Published: July 2021

Medulloblastoma is a rare brain malignancy. Patients after puberty are rare and bear an intermediate prognosis. Standard treatment consists of maximal resection plus radio-chemotherapy. Treatment toxicity is high and produces disabling long-term side effects. The sonic hedgehog (SHH) subgroup is highly overrepresented in the post-pubertal and adult population and can be targeted by smoothened (SMO) inhibitors. No practice-changing prospective randomized data have been generated in adults. The EORTC 1634-BTG/NOA-23 trial will randomize patients between standard-dose vs. reduced-dosed craniospinal radiotherapy and SHH-subgroup patients between the SMO inhibitor sonidegib (OdomzoTM, Sun Pharmaceuticals Industries, Inc., New York, USA) in addition to standard radio-chemotherapy vs. standard radio-chemotherapy alone to improve outcomes in view of decreased radiotherapy-related toxicity and increased efficacy. We will further investigate tumor tissue, blood, and cerebrospinal fluid as well as magnetic resonance imaging and radiotherapy plans to generate information that helps to further improve treatment outcomes. Given that treatment side effects typically occur late, long-term follow-up will monitor classic side effects of therapy, but also health-related quality of life, cognition, social and professional outcome, and reproduction and fertility. In summary, we will generate unprecedented data that will be translated into treatment changes in post-pubertal patients with medulloblastoma and will help to design future clinical trials.
Some Information Geometric Aspects of Cyber Security by Face Recognition
Authors: Dodson C. , Soldera John , Scharcanski Jacob
Published: July 2021

Secure user access to devices and datasets is widely enabled by fingerprint or face recognition. Organization of the necessarily large secure digital object datasets, with objects having content that may consist of images, text, video or audio, involves efficient classification and feature retrieval processing. This usually will require multidimensional methods applicable to data that is represented through a family of probability distributions. Then information geometry is an appropriate context in which to provide for such analytic work, whether with maximum likelihood fitted distributions or empirical frequency distributions. The important provision is of a natural geometric measure structure on families of probability distributions by representing them as Riemannian manifolds. Then the distributions are points lying in this geometrical manifold, different features can be identified and dissimilarities computed, so that neighbourhoods of objects nearby a given example object can be constructed. This can reveal clustering and projections onto smaller eigen-subspaces which can make comparisons easier to interpret. Geodesic distances can be used as a natural dissimilarity metric applied over data described by probability distributions. Exploring this property, we propose a new face recognition method which scores dissimilarities between face images by multiplying geodesic distance approximations between 3-variate RGB Gaussians representative of colour face images, and also obtaining joint probabilities. The experimental results show that this new method is more successful in recognition rates than published comparative state-of-the-art methods.
Arc Fault Detection Algorithm Based on Variational Mode Decomposition and Improved Multi-Scale Fuzzy Entropy
Authors: Wang Lina , Qiu Hongcheng , Yang Pu , Mu Longhua
Published: July 2021

Arc fault diagnosis is necessary for the safety and efficiency of PV stations. This study proposed an arc fault diagnosis algorithm formed by combining variational mode decomposition (VMD), improved multi-scale fuzzy entropy (IMFE), and support vector machine (SVM). This method first uses VMD to decompose the current into intrinsic mode functions (IMFs) in the time-frequency domain, then calculates the IMFE according to the IMFs associated with the arc fault. Finally, it uses SVM to detect arc faults according to IMFEs. Arc fault data gathered from a PV arc generation experiment platform are used to validate the proposed method. The results indicated the proposed method can classify arc fault data and normal data effectively.
Power Converters, Electric Drives and Energy Storage Systems for Electrified Transportation and Smart Grid Applications
Authors: Mihet-Popa Lucian , Saponara Sergio
Published: July 2021

The proposed special issue (SI) has invited submissions related to renewable energy, energy storage, power converters and electric drive systems for electrified transportation and smart grid applications [...]
State-Space Model of Quasi-Z-Source Inverter-PV Systems for Transient Dynamics Studies and Network Stability Assessment
Authors: Monjo Lluís , Sainz Luis , Mesas Juan José , Pedra Joaquín
Published: July 2021

Photovoltaic (PV) power systems are increasingly being used as renewable power generation sources. Quasi-Z-source inverters (qZSI) are a recent, high-potential technology that can be used to integrate PV power systems into AC networks. Simultaneously, concerns regarding the stability of PV power systems are increasing. Converters reduce the damping of grid-connected converter systems, leading to instability. Several studies have analyzed the stability and dynamics of qZSI, although the characterization of qZSI-PV system dynamics in order to study transient interactions and stability has not yet been properly completed. This paper contributes a small-signal, state-space-averaged model of qZSI-PV systems in order to study these issues. The model is also applied to investigate the stability of PV power systems by analyzing the influence of system parameters. Moreover, solutions to mitigate the instabilities are proposed and the stability is verified using PSCAD time domain simulations.
Driving Factors for the Spatiotemporal Heterogeneity in Technical Efficiency of China’s New Energy Industry
Authors: Liu Hongli , Yan Xiaoyu , Cheng Jinhua , Zhang Jun , Bu Yan
Published: July 2021

The new energy industry (NEI) is key to achieving a clean and low-carbon economy. Improving its technical efficiency, a factor reflecting the ability of an enterprise or industry to produce maximum economic outputs from a given set of inputs and production technologies, is vital for the healthy development of the NEI. Nevertheless, due to the fragmentation of industry data, it is still difficult to accurately measure the technical efficiency of China’s NEI and understand the driving factors behind it. Based on the panel data derived from 17,457 observations on new energy enterprises in 29 Chinese provinces during 1998 and 2013 (latest data available), this paper uses data envelopment analysis (DEA) and geographically and temporally weighted regression (GTWR) for the first time to investigate the spatiotemporal characteristics and driving factors of the technical efficiency of China’s NEI. The results show that the technical efficiency of China’s NEI was relatively low and increased modestly from 0.44 in 1998 to 0.52 in 2013. Exploring the reasons from the perspective of spatiotemporal heterogeneity, we find that enterprise scale and technological progress are the major driving factors for increasing NEI’s technical efficiency. However, the role of economic development in improving efficiency has gradually disappeared. Moreover, the negative effect of state-owned enterprises on efficiency becomes increasingly obvious. The effect of new energy resources is negligible. Our main contribution is the technical efficiency of China’s NEI which is measured at the provincial level and its main driving factors are explored by considering spatiotemporal heterogeneity. Accordingly, we put forward some specific recommendations to improve the technical efficiency of China’s NEI.
Determinants of COVID-19 Impact on the Private Sector: A Multi-Country Analysis Based on Survey Data
Authors: Olczyk Magdalena , Kuc-Czarnecka Marta Ewa
Published: July 2021

Our paper aims to investigate the impact of COVID-19 on private sector companies in terms of sales, production, finance and employment. We check whether the country and industry in which companies operate, government financial support and loan access matter to the behaviour and performances of companies during the pandemic. We use a microdata set from a worldwide survey of more than 15,729 companies conducted between April and September 2020 by the World Bank. Logistic regression is used to assess which factors increase the likelihood of businesses suffering due to the COVID-19 pandemic. Our results show that COVID-19 negatively impacts the performance of companies in almost all countries analysed, but a stronger effect is observed among firms from developing countries. The pandemic is more harmful to firms providing services than those representing the manufacturing sector. Due to the pandemic, firms suffer mainly in sales and liquidity decrease rather than employment reduction. The increase in the number of temporary workers is an important factor that significantly reduces the probability of sales, exports or supply decline. The analysis results indicate policy tools supporting enterprises during the pandemic, such as increasing the flexibility of the labour market or directing aid to developing countries.
The Equivalent Thermal Conductivity of the Micro/Nano Scaled Periodic Cubic Frame Silver and Its Thermal Radiation Mechanism Analysis
Authors: Yu Haiyan , Zhang Haochun , Wang Heming , Zhang Dong
Published: July 2021

Currently, there are few studies on the influence of microscale thermal radiation on the equivalent thermal conductivity of microscale porous metal. Therefore, this paper calculated the equivalent thermal conductivity of high-porosity periodic cubic silver frame structures with cell size from 100 nm to 100 µm by using the microscale radiation method. Then, the media radiation characteristics, absorptivity, reflectivity and transmissivity were discussed to explain the phenomenon of the radiative thermal conductivity changes. Furthermore, combined with spectral radiation properties at the different cross-sections and wavelength, the radiative transmission mechanism inside high-porosity periodic cubic frame silver structures was obtained. The results showed that the smaller the cell size, the greater radiative contribution in total equivalent thermal conductivity. Periodic cubic silver frames fluctuate more in the visible band and have better thermal radiation modulation properties in the near infrared band, which is formed by the Surface Plasmon Polariton and Magnetic Polaritons resonance jointly. This work provides design guidance for the application of this kind of periodic microporous metal in the field of thermal utilization and management.
Urinary Extracellular Vesicles and Their miRNA Cargo in Patients with Fabry Nephropathy
Authors: Levstek Tina , Mlinšek Teo , Holcar Marija , Goričar Katja , Lenassi Metka , Dolžan Vita , Vujkovac Bojan , Trebušak Podkrajšek Katarina
Published: July 2021

Current biomarkers of Fabry nephropathy lack sensitivity in detecting early kidney damage and do not predict progression of nephropathy. Urinary extracellular vesicles (uEVs) and their molecular cargo could reflect early changes in renal impairment as they are secreted by the cells lining the urinary tract. We aimed to conduct a proof-of-concept study to investigate whether analysis of uEV characteristics and expression of uEV-derived microRNAs (miRNAs) could be applicable in studies to predict the development and progression of nephropathy in Fabry disease. A total of 20 Fabry patients were divided into two groups, depending on the presence of nephropathy. Chronological urine samples collected during 10-year follow-up were used for uEVs isolation with size exclusion chromatography. Nanoparticle tracking analysis was used to determine concentration and size of uEVs. We evaluated the expression of five uEV-derived miRNAs by qPCR (miR-23a-3p, miR-29a-3p, miR-30b-5p, miR-34a-5p, miR-200a-3p). There was no difference in the concentration and size of uEVs between patients with and without nephropathy at last follow-up or longitudinally. However, we found increased expression of miR-29a-3p and miR-200a-3p in uEVs isolated from chronological samples of patients with Fabry nephropathy. This may indicate an attempt by the organism to prevent the progression of renal damage leading to end-stage renal disease as previously reported in type 1 diabetes. In addition, we found an increased expression of miR-30b-5p in the 10-year period in uEVs of patients without renal dysfunction. miR-30b-5 was reported to have a protective role in podocyte injury and may possibly be important in Fabry nephropathy. These findings indicate that uEVs and their molecular cargo could be a promising target of studies focusing on elucidation of Fabry nephropathy. Nevertheless, total concentration and size of uEVs were neither indicative of the presence nor progression of Fabry nephropathy, while the role of the analyzed miRNAs in Fabry nephropathy progression was merely indicated and needs further in-depth studies.
The Impact of Pharmaceutical Home Care on Medical Utilization for Frequent Users of Outpatient Services in Taiwan
Authors: Lee Chien-Ying , Su Heng-Hsuan , Chang Yu-Chia , Tsai Tung-Han , Lai Yung-Rung , Huang Kuang-Hua
Published: July 2021

Due to the high-accessibility and low-copayment of healthcare system in Taiwan, the clinical visit frequency of people is relatively high, which often leads to an excessively high healthcare expenditure. The aim of this research was to explore the effectiveness of pharmaceutical home care for frequent users of outpatient service and to analyze the impact of pharmaceutical home care on medical utilization. The study was based on the Taiwan National Health Insurance Research Database. Patients with over 100 clinical visits during 2010 to 2012 were selected as subjects. Whether these patients participate the experimental plan of pharmaceutical home care in the following year and the medical utilization of the research subjects were analyzed to compare the difference between participating group and non-participating group in this plan. The generalized estimating equation was employed to examine the difference of medical utilization. A total of 3943 subjects were included in this study, including 591 patients (14.99%) participating in the experimental plan. The average number of physician visits during the following year of the participating group was higher than that of the non-participating group by 0.12 visits, and the outpatient medical expense was lower than the non-participating group by 18,302 points (1 point = 0.03 US dollars). After participating in the plan, the average number of clinical visits of frequent users of outpatient services was significantly reduced by 6.63 visits, and the outpatient expense was significantly decreased by 9871 points. After joining the experimental plan of pharmaceutical home care, the average number of outpatient visits decreased significantly and the medical expense was lower when compared with those who did not participate in the plan.
A Cumulative Muscle Index and Its Parameters for Predicting Future Cognitive Decline: Longitudinal Outcomes of the ASPRA Cohort
Authors: Baek Ji-Yeon , Lee Eunju , Kim Woo Jung , Jang Il-Young , Jung Hee-Won
Published: July 2021

Sarcopenia and cognitive decline share the major risk factors of physical inactivity; previous studies have shown inconsistent associations. We aimed to identify the association of sarcopenia and its parameters with cognitive decline. The 3-year longitudinal outcomes of 1327 participants from the Aging Study of the Pyeongchang Rural Area (ASPRA) cohort were analyzed. Cognitive performance was evaluated using the Mini-Mental State Examination (MMSE), and sarcopenia was defined by the following: the original and revised Asian Working Group for Sarcopenia (AWGS), the original and revised European Working Group on Sarcopenia in Older People (EWGSOP), and the Cumulative Muscle Index (CMI), a novel index based on the number of impaired domains of sarcopenia. Approximately half of the participants showed meaningful cognitive decline. Sarcopenia by the original EWGSOP and the CMI were associated with cognitive decline. Only the CMI showed consistent predictability for cognitive impairment even with different criteria of the MMSE score (OR 1.23 [1.04–1.46]; OR 1.34 [1.12–1.59]; OR 1.22 [1.01–1.49], using the 1, 2, and 3 cut-off value, respectively). Of the CMI parameters, gait speed was satisfactorily predictive of 3-year cognitive impairment (OR 0.54 [0.30–0.97]). In conclusion, sarcopenia based on the CMI may be predictive of future cognitive impairment. Gait speed was the single most important indicator of cognitive decline.
Preferences for Indoor Environmental and Social Comfort of Outpatient Staff during the COVID-19 Pandemic, an Explanatory Study
Authors: Eijkelenboom AnneMarie , Ortiz Marco A. , Bluyssen Philomena M.
Published: July 2021

While the pressure on hospital workers keeps growing, they are generally more dissatisfied with their comfort than other occupants in hospitals or offices. To better understand the comfort of outpatient workers in hospitals, clusters for preferences and perceptions of the indoor environmental quality (IEQ) and social comfort were identified in a previous study before the outbreak of the coronavirus disease 2019 (COVID-19) pandemic. This qualitative study explains the outpatient workers’ main preferences for comfort during the COVID-19 pandemic. Semi-structured interviews and photo-elicitation were used. Contextual changes due to the COVID-19 pandemic were included. The questions in the interviews were based on the characteristics of the profiles, corresponding with the clusters. The data were analyzed with content analysis according to the steps defined by Gioia. Seventeen outpatient workers who had been part of the previous study participated. For some outpatient workers differentiation of preferences was illogical due to interrelations and equal importance of the comfort aspects. The main changes in perceptions of comfort due to the pandemic were worries about the indoor air quality and impoverished interaction. Because the occupants’ preferences for comfort can change over time, it was suggested that further development of occupant profiles needs to accommodate changes.
Mandibular Brown Tumor as a Result of Secondary Hyperparathyroidism: A Case Report with 5 Years Follow-Up and Review of the Literature
Authors: Shavlokhova Veronika , Goeppert Benjamin , Gaida Matthias M. , Saravi Babak , Weichel Frederic , Vollmer Andreas , Vollmer Michael , Freudlsperger Christian , Mertens Christian , Hoffmann Jürgen
Published: July 2021

Background: Brown tumor is a rare skeletal manifestation of secondary hyperparathyroidism. Although diagnosis of the disease is increasingly seen in early stages due to improved screening techniques, some patients still present in a progressed disease stage. The treatment depends on tumor mass and varies from a conservative approach with supportive parathyroidectomy to extensive surgical resection with subsequent reconstruction. Case presentation: We report a case of extensive mandibular brown tumor in a patient with a history of systemic lupus erythematosus, chronic kidney disease, and secondary hyperparathyroidism. Following radical resection of the affected bone, reconstruction could be successfully performed using a free flap. Conclusions: There were no signs of recurrence during five years of close follow-up. Increased awareness and multidisciplinary follow-ups could allow early diagnosis and prevent the need for radical therapeutical approaches.
Mitochondrial Heteroplasmy Shifting as a Potential Biomarker of Cancer Progression
Authors: Pérez-Amado Carlos Jhovani , Bazan-Cordoba Amellalli , Hidalgo-Miranda Alfredo , Jiménez-Morales Silvia
Published: July 2021

Cancer is a serious health problem with a high mortality rate worldwide. Given the relevance of mitochondria in numerous physiological and pathological mechanisms, such as adenosine triphosphate (ATP) synthesis, apoptosis, metabolism, cancer progression and drug resistance, mitochondrial genome (mtDNA) analysis has become of great interest in the study of human diseases, including cancer. To date, a high number of variants and mutations have been identified in different types of tumors, which coexist with normal alleles, a phenomenon named heteroplasmy. This mechanism is considered an intermediate state between the fixation or elimination of the acquired mutations. It is suggested that mutations, which confer adaptive advantages to tumor growth and invasion, are enriched in malignant cells. Notably, many recent studies have reported a heteroplasmy-shifting phenomenon as a potential shaper in tumor progression and treatment response, and we suggest that each cancer type also has a unique mitochondrial heteroplasmy-shifting profile. So far, a plethora of data evidencing correlations among heteroplasmy and cancer-related phenotypes are available, but still, not authentic demonstrations, and whether the heteroplasmy or the variation in mtDNA copy number (mtCNV) in cancer are cause or consequence remained unknown. Further studies are needed to support these findings and decipher their clinical implications and impact in the field of drug discovery aimed at treating human cancer.
Features of Retinal Neurogenesis as a Key Factor of Age-Related Neurodegeneration: Myth or Reality?
Authors: Telegina Darya V. , Kozhevnikova Oyuna S. , Antonenko Anna K. , Kolosova Nataliya G.
Published: July 2021

Age-related macular degeneration (AMD) is a complex multifactorial neurodegenerative disease that constitutes the most common cause of irreversible blindness in the elderly in the developed countries. Incomplete knowledge about its pathogenesis prevents the search for effective methods of prevention and treatment of AMD, primarily of its “dry” type which is by far the most common (90% of all AMD cases). In the recent years, AMD has become “younger”: late stages of the disease are now detected in relatively young people. It is known that AMD pathogenesis—according to the age-related structural and functional changes in the retina—is linked with inflammation, hypoxia, oxidative stress, mitochondrial dysfunction, and an impairment of neurotrophic support, but the mechanisms that trigger the conversion of normal age-related changes to the pathological process as well as the reason for early AMD development remain unclear. In the adult mammalian retina, de novo neurogenesis is very limited. Therefore, the structural and functional features that arise during its maturation and formation can exert long-term effects on further ontogenesis of this tissue. The aim of this review was to discuss possible contributions of the changes/disturbances in retinal neurogenesis to the early development of AMD.
Folding and Intrinsic Disorder of the Receptor Tyrosine Kinase KIT Insert Domain Seen by Conventional Molecular Dynamics Simulations
Authors: Ledoux Julie , Trouvé Alain , Tchertanov Luba
Published: July 2021

The kinase insert domain (KID) of RTK KIT is the key recruitment region for downstream signalling proteins. KID, studied by molecular dynamics simulations as a cleaved polypeptide and as a native domain fused to KIT, showed intrinsic disorder represented by a set of heterogeneous conformations. The accurate atomistic models showed that the helical fold of KID is mainly sequence dependent. However, the reduced fold of the native KID suggests that its folding is allosterically controlled by the kinase domain. The tertiary structure of KID represents a compact array of highly variable α- and 310-helices linked by flexible loops playing a principal role in the conformational diversity. The helically folded KID retains a collapsed globule-like shape due to non-covalent interactions associated in a ternary hydrophobic core. The free energy landscapes constructed from first principles—the size, the measure of the average distance between the conformations, the amount of helices and the solvent-accessible surface area—describe the KID disorder through a collection of minima (wells), providing a direct evaluation of conformational ensembles. We found that the cleaved KID simulated with restricted N- and C-ends better reproduces the native KID than the isolated polypeptide. We suggest that a cyclic, generic KID would be best suited for future studies of KID f post-transduction effects.
Disease Differentiation and Monitoring of Anti-TNF Treatment in Rheumatoid Arthritis and Spondyloarthropathies
Authors: Bogunia-Kubik Katarzyna , Wojtowicz Wojciech , Swierkot Jerzy , Mielko Karolina Anna , Qasem Badr , Wielińska Joanna , Sokolik Renata , Pruss Łukasz , Młynarz Piotr
Published: July 2021

Rheumatoid arthritis (RA), ankylosing spondylitis (AS), and psoriatic arthritis (PsA) are comprehensive immunological disorders. The treatment of these disorders is limited to ameliorating the symptoms and improving the quality of life of patients. In this study, serum samples from RA, AS, and PsA patients were analyzed with metabolomic tools employing the 1H NMR method in combination with univariate and multivariate analyses. The results obtained in this study showed that the changes in metabolites were the highest for AS > RA > PsA. The study demonstrated that the time until remission or until low disease activity is achieved is shortest (approximately three months) for AS, longer for RA and longest for PsA. The statistically common metabolite that was found to be negatively correlated with the healing processes of these disorders is ethanol, which may indicate the involvement of the gut microflora and/or the breakdown of malondialdehyde as a cell membrane lipid peroxide product.
Single Exposure to the Cathinones MDPV and α-PVP Alters Molecular Markers of Neuroplasticity in the Adult Mouse Brain
Authors: Caffino Lucia , Mottarlini Francesca , Bilel Sabrine , Targa Giorgia , Tirri Micaela , Maggi Coralie , Marti Matteo , Fumagalli Fabio
Published: July 2021

Synthetic cathinones have gained popularity among young drug users and are widely used in the clandestine market. While the cathinone-induced behavioral profile has been extensively investigated, information on their neuroplastic effects is still rather fragmentary. Accordingly, we have exposed male mice to a single injection of MDPV and α-PVP and sacrificed the animals at different time points (i.e., 30 min, 2 h, and 24 h) to have a rapid readout of the effect of these psychostimulants on neuroplasticity in the frontal lobe and hippocampus, two reward-related brain regions. We found that a single, low dose of MDPV or α-PVP is sufficient to alter the expression of neuroplastic markers in the adult mouse brain. In particular, we found increased expression of the transcription factor Npas4, increased ratio between the vesicular GABA transporter and the vesicular glutamate transporter together with changes in the expression of the neurotrophin Bdnf, confirming the widespread impact of these cathinones on brain plasticity. To sum up, exposure to low dose of cathinones can impair cortical and hippocampal homeostasis, suggesting that abuse of these cathinones at much higher doses, as it occurs in humans, could have an even more profound impact on neuroplasticity.