bluuebunny/crossref_metadata_2025 huggingface dataset:
Emerging Oncogenic Viruses in Head and Neck Cancers from Romanian Patients
Authors: Ursu Ramona Gabriela , Luchian Ionut , Ghetu Nicolae , Costan Victor Vlad , Stamatin Ovidiu , Palade Octavian Dragos , Damian Costin , Iancu Luminita Smaranda , Porumb-Andrese Elena
Published: October 2021

(1) Background: Head and neck squamous cell carcinomas (HNSCCs) are some of the most frequent malignancies globally. Oncogenic viruses MCPyV, EBV and HPVs are recognized to be related to HNSCCs and skin cancers. There are no data from Romania regarding the involvement of herpes viruses and polyomaviruses in these types of cancer. We aim to evaluate the association of oncogenic viruses from Papillomaviridae, Herpesviridae, and Polyomaviridae families in HNSCCs and skin cancers. (2) Methods: A total of 26 fresh tumors (6/26 women) were tested for 67 viral agents using a multiplex PCR genotyping assay. (3) Results: A total of 23/26 (88.5%) samples were positive for one or more viruses. All the tested tumors were negative for any HPV (alpha or beta types). In total, we detected as positive samples: 16 (61.63%) EBV1, 12 (46.15%) HHV7, 8 (30.76%) MCV, 6 (23.07%) CMV and HHV6, 2 (7.69%) HHV8, 1 (3.8%) HPyV6 and EBV2. (4) Conclusions: We detected HPV-negative cases that are HPyV and HHV positive. In these fractions of HPV-negative HNSCCs cases, other oncogenic viruses may be involved, such as EBV1, MCV or CMV. Additional research is required for clarifying the natural history of these viruses in HNSCCs, as virus detection would have a decisive impact on diagnostic and decisional algorithms.
Multivariate Time Series Data Prediction Based on ATT-LSTM Network
Authors: Ju Jie , Liu Fang-Ai
Published: October 2021

Deep learning models have been widely used in prediction problems in various scenarios and have shown excellent prediction effects. As a deep learning model, the long short-term memory neural network (LSTM) is potent in predicting time series data. However, with the advancement of technology, data collection has become more accessible, and multivariate time series data have emerged. Multivariate time series data are often characterized by a large amount of data, tight timeline, and many related sequences. Especially in real data sets, the change rules of many sequences will be affected by the changes of other sequences. The interacting factors data, mutation information, and other issues seriously impact the prediction accuracy of deep learning models when predicting this type of data. On the other hand, we can also extract the mutual influence information between different sequences and simultaneously use the extracted information as part of the model input to make the prediction results more accurate. Therefore, we propose an ATT-LSTM model. The network applies the attention mechanism (attention) to the LSTM to filter the mutual influence information in the data when predicting the multivariate time series data, which makes up for the poor ability of the network to process data. Weaknesses have greatly improved the accuracy of the network in predicting multivariate time series data. To evaluate the model’s accuracy, we compare the ATT-LSTM model with the other six models on two real multivariate time series data sets based on two evaluation indicators: Mean Absolute Error (MAE) and Root Mean Square Error (RMSE). The experimental results show that the model has an excellent performance improvement compared with the other six models, proving the model’s effectiveness in predicting multivariate time series data.
The Correlation between the Number of Asphalt Mixing Plants and the Production of Asphalt Mixtures in European Countries and the Baltic States
Authors: Sivilevičius Henrikas , Skrickij Viktor , Skačkauskas Paulius
Published: October 2021

The transport infrastructure’s pavement is made of asphalt layers, placed and compacted. The asphalt mixture is produced in an asphalt mixing plant (AMP) using expensive technological equipment which, when it becomes obsolete and worn out, is replaced with new equipment. One of the main problems related to the replacement process is that when it comes to purchasing new AMPs, the decision making involved is, in most cases, highly intuitive due to a lack of clearly defined criteria. In order to remedy this situation, this work presents an analysis of the correlation between the number of AMPs and the production of asphalt mixtures. Firstly, a correlation analysis was performed based on the European Asphalt Pavement Association (EAPA) data. Secondly, the current situation with the AMPs in European countries was analysed. Furthermore, a case study was performed and a system of nine criteria was created to identify why/when road construction companies operating in the Baltic States buy new AMPs. The weights of the criteria have been established by applying the Analytic Hierarchy Process (AHP) method. It was found that the most important criterion during the decision-making process for road construction companies is increased requirements for improving the quality of the asphalt mixture produced (criteria weight 25.0%). With a weight of 20.6%, the second vital criterion is the possibility of receiving support from European funds. The third criterion is the expectation of having a sizeable asphalt-paving site (weight 20.4%). The other six criteria are also significant, their weights varying between 1.6% and 13.5%. The industrial companies can use the obtained results for designing, producing and selling AMPs and adjusting strategic business plans.
Evolution of the Micropore Structure of Ammonium Perchlorate during Low-Temperature Decomposition and Its Combustion Characteristics
Authors: Zhang Haijun , Nie Jianxin , Jiao Gangling , Xu Xing , Yan Shi , Guo Xueyong , Zhang Tao
Published: October 2021

Ammonium perchlorate (AP) is a common oxidant in solid propellants, and its thermal decomposition characteristics at low temperatures (less than 240 °C) are key to the study of the thermal safety of propellants. Here, the low-temperature thermal decomposition characteristics of AP were investigated at 230 °C. The micromorphology of the low-temperature decomposition residues was characterized by scanning electron microscopy and 3D nano-computed tomography in order to analyse the evolution of microscopic pore structures, and the effect of the AP pore structure on combustion performance was then tested and analysed with a homemade closed bomb. The results demonstrate that the low-temperature decomposition of AP first occurs near the surface of the particles, simultaneously starting at multiple points and forming pores, and then gradually expands towards the interior until almost all of the pores connect with one other. Compared with ordinary AP, porous AP has a significantly improved combustion rate. When the ratio of porous AP to Al was 80:20, the peak pressure in the closed bomb was increased by 2.7 times; the rate of change in peak pressure increased 34 times, leading to a higher reaction speed and higher reaction intensity, and a typical explosion reaction occurred.
Analysis of Security Issues and Countermeasures for the Industrial Internet of Things
Authors: Pal Shantanu , Jadidi Zahra
Published: October 2021

Industrial Internet of Things (IIoT) can be seen as an extension of the Internet of Things (IoT) services and applications to industry with the inclusion of Industry 4.0 that provides automation, reliability, and control in production and manufacturing. IIoT has tremendous potential to accelerate industry automation in many areas, including transportation, manufacturing, automobile, marketing, to name a few places. When the benefits of IIoT are visible, the development of large-scale IIoT systems faces various security challenges resulting in many large-scale cyber-attacks, including fraudulent transactions or damage to critical infrastructure. Moreover, a large number of connected devices over the Internet and resource limitations of the devices (e.g., battery, memory, and processing capability) further pose challenges to the system. The IIoT inherits the insecurities of the traditional communication and networking technologies; however, the IIoT requires further effort to customize the available security solutions with more focus on critical industrial control systems. Several proposals discuss the issue of security, privacy, and trust in IIoT systems, but comprehensive literature considering the several aspects (e.g., users, devices, applications, cascading services, or the emergence of resources) of an IIoT system is missing in the present state of the art IIoT research. In other words, the need for considering a vision for securing an IIoT system with broader security analysis and its potential countermeasures is missing in recent times. To address this issue, in this paper, we provide a comparative analysis of the available security issues present in an IIoT system. We identify a list of security issues comprising logical, technological, and architectural points of view and consider the different IIoT security requirements. We also discuss the available IIoT architectures to examine these security concerns in a systematic way. We show how the functioning of different layers of an IIoT architecture is affected by various security issues and report a list of potential countermeasures against them. This study also presents a list of future research directions towards the development of a large-scale, secure, and trustworthy IIoT system. The study helps understand the various security issues by indicating various threats and attacks present in an IIoT system.
Novel Service Efficiency Evaluation and Management Model
Authors: Li Mingyuan , Lin Lung-Yu , Chen Kuen-Suan , Hsu Ting-Hsin
Published: October 2021

Numerous scholars have invested in the research of service innovation management, hoping to find a more objective and scientific service efficiency evaluation and management model so as to stride forward towards the goal of smart innovation management. In the service operating system, the multi-workstation service operation is one of the common service operation models. Some studies have pointed out: apart from a good service attitude, the service operation time of each workstation is a key factor which measures the performance of the workstation’s service operation. Therefore, this paper proposed a standardized concept with a service operation efficiency evaluation index. This index is not only convenient and easy-to-use, but it also has a one-to-one mathematical relationship with the performance achievement rate. Next, the radar evaluation chart was employed to evaluate the service efficiency of each workstation. First, according to the upper confidence limit and the required value of the index, the minimum value (MV) of the index estimator was derived and marked on each radar line; at the same time, all MVs were connected to form a control block. When the point estimate of the index does not fall into the control block of the radar chart, it represents that the service operation efficiency of the workstation has not reached the required level, so it needs to be improved. Because this model can directly compare the point estimate of the index with the MV, it can judge whether the service operation efficiency reaches the required level. In this way, the advantage of simple and easy-to-use point estimate can be maintained, and the risk of misjudgment caused by sampling errors can be reduced as well, which is helpful for the service industry to move towards the goal of intelligent innovation management. This method is not only applied to the performance evaluation of the multi-workstation service operation process but also applicable to the performance evaluations of other service operations.
Direct Rating Estimation of Enlarged Perivascular Spaces (EPVS) in Brain MRI Using Deep Neural Network
Authors: Yang Ehwa , Gonuguntla Venkateswarlu , Moon Won-Jin , Moon Yeonsil , Kim Hee-Jin , Park Mina , Kim Jae-Hun
Published: October 2021

In this article, we propose a deep-learning-based estimation model for rating enlarged perivascular spaces (EPVS) in the brain’s basal ganglia region using T2-weighted magnetic resonance imaging (MRI) images. The proposed method estimates the EPVS rating directly from the T2-weighted MRI without using either the detection or the segmentation of EVPS. The model uses the cropped basal ganglia region on the T2-weighted MRI. We formulated the rating of EPVS as a multi-class classification problem. Model performance was evaluated using 96 subjects’ T2-weighted MRI data that were collected from two hospitals. The results show that the proposed method can automatically rate EPVS—demonstrating great potential to be used as a risk indicator of dementia to aid early diagnosis.
Analysis of the Major Probiotics in Healthy Women’s Breast Milk by Realtime PCR. Factors Affecting the Presence of Those Bacteria
Authors: Nikolopoulou Georgia , Tsironi Theofania , Halvatsiotis Panagiotis , Petropoulou Ekaterini , Genaris Nikolaos , Vougiouklaki Despina , Antonopoulos Dionyssios , Thomas Apollon , Tsilia Anastasia , Batrinou Anthimia , Tsakali Efstathia , Van Impe Jan F. M. , Houhoula Dimitra
Published: October 2021

Breast milk has been reported as a bacteria source that affects infant gut microbiota development. The present study utilizes a realtime PCR method to identify Lactobacillus and Bifidobacterium spp. in the breast milk of healthy women and attempts to identify factors affecting those human milk bacteria. Breast milk samples—both colostrum and mature milk—of 100 healthy women, were collected in Greece along with data about the demographic factors and nutritional habits of the volunteers. The colostrum samples were found to have higher percentages of either Bifidobacterium or Lactobacillus (76.9% and 48.6%, respectively) compared to the mature milk samples. For younger women, aged from 18 to 29 years, and women from rural areas, bacteria were detected in higher incidence than for older groups and women in urban areas, respectively. Moreover, for high-BMI women, bacteria were detected in lower incidence than for those with normal BMI. Probiotic supplements did not affect the composition of the breast milk-identified bacteria. Various factors such as lactation stage, maternal age, maternal weight, and residential location may contribute to the presence of those species in human milk. RT PCR has significant potential for the microbiological analysis of human milk.
Impact of Dredged Material Disposal on Heavy Metal Concentrations and Benthic Communities in Huangmao Island Marine Dumping Area near Pearl River Estuary
Authors: Tao Wei , Jiang Zhongchen , Peng Xiaojuan , Yang Zhenxiong , Cai Weixu , Yu Huili , Ye Jianjun
Published: October 2021

The Huangmao Island dumping area is adjacent to the Pearl River Estuary in the South China Sea. From its first dumping activity in 1986 to 2017, 6750 × 104 m3 dredged materials were dumped in this dumping area. Sediment pollution levels, ecological risk, and benthic communities in 2011–2017 were evaluated; the results showed that the concentrations of the heavy metals (HMs; except Hg) in surface sediments of the dumping area met the class I standard of marine sediment quality (GB 18668-2002). HMs in the surface sediments were relatively high in the northern and central areas but relatively low in the south of the dumping area. Speculation was that the spatial variation in HM concentrations might be caused by dumping activities. The Nemerow index implied that the contaminated area was mainly in the north of the dumping area (S1, S2, and S3), where the dumping amount was the largest. The potential ecological risk (Eir) indices of Zn, As, Cu, and Pb indicate that these metals posed a low risk to the ecosystem of the dumping area, whereas Cd and Hg posed a high risk at some stations. The geoaccumulation indices (Igeo) of Zn, As, Cu, and Pb specified no pollution or light pollution in the study area, whereas those of Cd and Hg in most years indicated mild contamination levels. Benthic organisms in the study area were arthropods, chordates, annelids, mollusks, echinoderms, nemertinean, coelenterate, and echiuran, among which arthropods were the most abundant. The abundance of taxa and density of benthic organisms had a little difference among the stations within the dumping area, but were significantly lower than those of the stations outside the dumping area. In addition, non-metric multidimensional scaling analysis confirmed that the observed patterns separated the stations within the dumping area from stations outside the dumping area. The evaluation results of the HMs revealed that the dumping area with a large dumping amount was more severely polluted. Dumping dredged materials seemed to have a negative impact on the benthic community in the dumping area.
The Readiness Index for Climate Change Adaptation in Africa: The Role of Climate and Adaptive Capacity Proxies
Authors: Epule Terence Epule , Chehbouni Abdelghani , Dhiba Driss , Moto Mirielle Wase
Published: October 2021

As global changes continue, the repercussions in Africa remain profound. This is reflected notably in food and water crises across Africa. This work examines the readiness of Africa to climate change adaptation through a newly developed readiness index (ClimAdaptCap Index). In fact, this work shifts the readiness debate from emotional descriptions that currently flood academic scholarship to a more pragmatic evidence-based approach in assessing readiness. Readiness for climate change adaptation is driven by the intensity of climate forcing and adaptive capacity. The historical climate score data or precipitation and temperature for the period 1991–2016 were culled from the World Bank Climate Portal. The historical adaptive capacity score data included proxies such as poverty and literacy rates from 1991 to 2016 were collected from the World Bank and Macrotrends. The climate data were normalized using the normalization function to enhance interpretation, comparison, and fusion into the index. Missing poverty and literacy rate data were estimated by linear interpolation of the poverty and literacy rate data. The ClimAdaptCap Index was developed to compute readiness. This index is the first of its kind and will serve as a flagship for assessing readiness for climate change adaptation as it is highly adaptable to different contexts. This work’s first-ever maps of readiness show that North and Southern Africa are the readiest for climate change adaptation under historical climate and literacy and poverty conditions. West Africa is the least ready while Middle and East Africa are in the middle. Consistent is that readiness has a positive correlation with literacy rates and an inverse one with poverty rates. In addition, with readiness scores of between 0.35 and 0.39 for all the regions with a maximum potential score of 1, this work has shown that the level of readiness in Africa is generally low, and there is a very small variation between the different regions. In addition, climate change adaptation will highly be influenced by both climatic and non-climatic indicators. The developed readiness index adequately simulates readiness to climate change adaptation in Africa and complements previous frameworks of adaptation preparedness.
Very Fast RP–UHPLC–PDA Method for Identification and Quantification of the Cannabinoids from Hemp Oil
Authors: Blebea Nicoleta Mirela , Rambu Dan , Costache Teodor , Negreș Simona
Published: October 2021

In recent years, hemp oils have become ubiquitous in health products on the European market. As the trend continues to grow and more cannabinoids are researched for their therapeutic benefits, more academic and industrial interests are drawn to this direction. Cannabidiol, Δ9-tetrahydrocannabinol, and their acidic forms remain the most examined cannabinoids in hemp and cannabis oils, in the case of cannabidiol due to its proven health implications in numerous articles, and in the case of Δ9-tetrahydrocannabinol, due to the legislation in the European area. These oils sold on the internet contain a wide range of cannabinoids that could demonstrate their effects and benefits. As a result of these claims, we developed a robust and rapid method that can identify and quantify 10 of the most common cannabinoids found in hemp oils: cannabivarin, cannabidiolic acid, cannabigerolic acid, cannabigerol, cannabidiol, cannabinol, Δ9-tetrahydrocannabinol, Δ8-tetrahydrocannabinol, cannabichromene, and tetrahydrocannabinolic acid in less than 11 min, with reverse-phase–high-performance liquid chromatography–photodiode matrix system (RP–UHPLC–PDA) equipped with C18 column, eluting in a gradient using water and acetonitrile with formic acid as mobile phases. The quantification of 9 sample products presented in different matrixes was performed using a calibration curve obtained by analyzing standard solutions from a 10-cannabinoid-mix-certified reference standard. The developed method demonstrated the ability to identify and quantify the main cannabinoids in hemp oil and is a useful tool for pharmaceutical professionals.
Blind Image Separation Method Based on Cascade Generative Adversarial Networks
Authors: Jia Fei , Xu Jindong , Sun Xiao , Ma Yongli , Ni Mengying
Published: October 2021

To solve the challenge of single-channel blind image separation (BIS) caused by unknown prior knowledge during the separation process, we propose a BIS method based on cascaded generative adversarial networks (GANs). To ensure that the proposed method can perform well in different scenarios and to address the problem of an insufficient number of training samples, a synthetic network is added to the separation network. This method is composed of two GANs: a U-shaped GAN (UGAN), which is used to learn image synthesis, and a pixel-to-attention GAN (PAGAN), which is used to learn image separation. The two networks jointly complete the task of image separation. UGAN uses the unpaired mixed image and the unmixed image to learn the mixing style, thereby generating an image with the “true” mixing characteristics which addresses the problem of an insufficient number of training samples for the PAGAN. A self-attention mechanism is added to the PAGAN to quickly extract important features from the image data. The experimental results show that the proposed method achieves good results on both synthetic image datasets and real remote sensing image datasets. Moreover, it can be used for image separation in different scenarios which lack prior knowledge and training samples.
Systematic Nomination of COVID-19 Quarantine Facilities
Authors: Sorooshian Shahryar
Published: October 2021

This short communication explains the need for a clear method for the selection of COVID-19 quarantine hotels. It also lists available systematic methods that are usable for this aim.
Triply Differential Positron and Electron Impact Ionization of Argon: Systematic Features and Scaling
Authors: DuBois R. D. , de Lucio O. G.
Published: October 2021

Triply differential data are presented for the 200 eV positron and electron impact ionization of argon. Six electron emission energies between 2.6 and 19 eV, and for scattering angles of 2, 3, and 4 degrees cover a momentum transfer range of 0.16 to 0.31 a.u. The binary and recoil intensities are fitted using a double peak structure in both regions, which, for the present kinematic conditions, are unresolved. The fitted peak intensities and angular positions are shown to have systematic dependences as a function of the momentum transfer and kinematic emission angle, respectively, and illustrate projectile charge effects. A comparison with available theories is made where it is seen that the most notable differences include the fact that for the binary lobe, the observed intensity for emission angles around 100° is absent in the theories, and the theoretical predications overestimate the importance of recoil interactions.
Antibiotic Resistance of Staphylococci from Bulk-Tank Milk of Sheep Flocks: Prevalence, Patterns, Association with Biofilm Formation, Effects on Milk Quality, and Risk Factors
Authors: Lianou Daphne T. , Petinaki Efthymia , Cripps Peter J. , Gougoulis Dimitris A. , Michael Charalambia K. , Tsilipounidaki Katerina , Skoulakis Anargyros , Katsafadou Angeliki I. , Vasileiou Natalia G. C. , Giannoulis Themis , Voidarou Chrysoula , Mavrogianni Vasia S. , Caroprese Mariangela , Fthenakis George C.
Published: October 2021

The objectives of this work were to study prevalence and characteristics of resistance to antibiotics of staphylococcal isolates from the bulk-tank milk of sheep flocks across Greece, to assess possible associations of the presence of antibiotic resistance with the quality of milk in these flocks and to evaluate flock-related factors potentially associated with antibiotic resistance among these isolates. A cross-sectional study was performed in 325 sheep flocks in Greece. Bulk-tank milk samples were collected for bacteriological examination; staphylococcal isolates were evaluated for resistance to 20 antibiotics. Oxacillin-resistant staphylococcal isolates, isolates resistant to any antibiotic, and multi-resistant isolates were recovered from 8.0%, 30.5%, and 12.0% of flocks, respectively. Of 232 isolates, 11.6% were resistant to oxacillin, 46.1% were resistant to at least one antibiotic, and 16.4% were multi-resistant. Resistance was seen more frequently among coagulase-negative (50.6%) than among Staphylococcus aureus (31.5%) isolates. Resistance was more frequent against penicillin and ampicillin (34.1% of isolates), clindamycin (17.7%), and fosfomycin (14.2%). An association was found between biofilm formation by staphylococci and resistance to fosfomycin. For recovery of oxacillin-resistant isolates, the lack of experience by farmers emerged as a significant factor; respective factors for the isolation of staphylococci resistant to any antibiotic or multi-resistant isolates were the early stage of the lactation period (0th–1st month) and the intensive management system applied in the flocks, respectively.
Extracellular Matrix Components as Diagnostic Tools in Inflammatory Bowel Disease
Authors: Golusda Laura , Kühl Anja A. , Siegmund Britta , Paclik Daniela
Published: October 2021

Work from the last years indicates that the extracellular matrix (ECM) plays a direct role in various cellular processes, including proliferation, migration and differentiation. Besides homeostatic processes, its regulatory function in inflammation becomes more and more evident. In inflammation, such as inflammatory bowel disease, the ECM composition is constantly remodeled, and this can result in a structuring of fistulizing disease course. Thus, tracking early ECM changes might bear the potential to predict the disease course. In this review, we provide an overview of relevant diagnostic methods, focusing on ECM changes.
DNA End Joining: G0-ing to the Core
Authors: Frock Richard L. , Sadeghi Cheyenne , Meng Jodie , Wang Jing L.
Published: October 2021

Humans have evolved a series of DNA double-strand break (DSB) repair pathways to efficiently and accurately rejoin nascently formed pairs of double-stranded DNA ends (DSEs). In G0/G1-phase cells, non-homologous end joining (NHEJ) and alternative end joining (A-EJ) operate to support covalent rejoining of DSEs. While NHEJ is predominantly utilized and collaborates extensively with the DNA damage response (DDR) to support pairing of DSEs, much less is known about A-EJ collaboration with DDR factors when NHEJ is absent. Non-cycling lymphocyte progenitor cells use NHEJ to complete V(D)J recombination of antigen receptor genes, initiated by the RAG1/2 endonuclease which holds its pair of targeted DSBs in a synapse until each specified pair of DSEs is handed off to the NHEJ DSB sensor complex, Ku. Similar to designer endonuclease DSBs, the absence of Ku allows for A-EJ to access RAG1/2 DSEs but with random pairing to complete their repair. Here, we describe recent insights into the major phases of DSB end joining, with an emphasis on synapsis and tethering mechanisms, and bring together new and old concepts of NHEJ vs. A-EJ and on RAG2-mediated repair pathway choice.
Degradation of Poly(ε-caprolactone) by a Thermophilic Community and Brevibacillus thermoruber Strain 7 Isolated from Bulgarian Hot Spring
Authors: Atanasova Nikolina , Paunova-Krasteva Tsvetelina , Stoitsova Stoyanka , Radchenkova Nadja , Boyadzhieva Ivanka , Petrov Kaloyan , Kambourova Margarita
Published: October 2021

The continual plastic accumulation in the environment and the hazardous consequences determine the interest in thermophiles as possible effective plastic degraders, due to their unique metabolic mechanisms and change of plastic properties at elevated temperatures. PCL is one of major biodegradable plastics with promising application to replace existing non-biodegradable polymers. Metagenomic analysis of the phylogenetic diversity in plastic contaminated area of Marikostinovo hot spring, Bulgaria revealed a higher number taxonomic groups (11) in the sample enriched without plastic (Marikostinovo community, control sample, MKC-C) than in that enriched in the presence of poly-ε-caprolactone (PCL) (MKC-P), (7). A strong domination of the phylum Proteobacteria was observed for MKC-C, while the dominant phyla in MKC-P were Deinococcus-Thermus and Firmicutes. Among the strains isolated from MKC-P, the highest esterase activity was registered for Brevibacillus thermoruber strain 7 at 55 °C. Its co-cultivation with another isolate resulted in ~10% increase in enzyme activity. During a 28-day biodegradation process, a decrease in PCL molecular weight and weight loss were established resulting in 100% degradation by MKC-P and 63.6% by strain 7. PCL degradation intermediate profiles for MKC-P and pure strain were similar. Broken plastic pieces from PCL surface and formation of a biofilm by MKC-P were observed by SEM, while the pure strain caused significant deformation of PCL probes without biofilm formation.
Perfusion Patterns in Patients with Chronic Limb-Threatening Ischemia versus Control Patients Using Near-Infrared Fluorescence Imaging with Indocyanine Green
Authors: Van Den Hoven Pim , Goncalves Lauren N. , Quax Paulus H. A. , Van Rijswijk Catharina S. P. , Van Schaik Jan , Schepers Abbey , Vahrmeijer Alexander L. , Hamming Jaap F. , Van Der Vorst Joost R.
Published: October 2021

In assessing the severity of lower extremity arterial disease (LEAD), physicians rely on clinical judgements supported by conventional measurements of macrovascular blood flow. However, current diagnostic techniques provide no information about regional tissue perfusion and are of limited value in patients with chronic limb-threatening ischemia (CLTI). Near-infrared (NIR) fluorescence imaging using indocyanine green (ICG) has been used extensively in perfusion studies and is a possible modality for tissue perfusion measurement in patients with CLTI. In this prospective cohort study, ICG NIR fluorescence imaging was performed in patients with CLTI and control patients using the Quest Spectrum Platform® (Middenmeer, The Netherlands). The time–intensity curves were analyzed using the Quest Research Framework. Fourteen parameters were extracted. Successful ICG NIR fluorescence imaging was performed in 19 patients with CLTI and in 16 control patients. The time to maximum intensity (seconds) was lower for CLTI patients (90.5 vs. 143.3, p = 0.002). For the inflow parameters, the maximum slope, the normalized maximum slope and the ingress rate were all significantly higher in the CLTI group. The inflow parameters observed in patients with CLTI were superior to the control group. Possible explanations for the increased inflow include damage to the regulatory mechanisms of the microcirculation, arterial stiffness, and transcapillary leakage.
The Morphological Spectrum of Papillary Renal Cell Carcinoma and Prevalence of Provisional/Emerging Renal Tumor Entities with Papillary Growth
Authors: Lobo João , Ohashi Riuko , Helmchen Birgit M. , Rupp Niels J. , Rüschoff Jan H. , Moch Holger
Published: October 2021

Renal cell carcinoma (RCC) represents a heterogeneous disease, encompassing an increasing number of tumor subtypes. Post-2016, the World Health Organization (WHO) classification recognized that the spectrum of papillary renal cell carcinoma is evolving and has long surpassed the dichotomic simplistic “type 1 versus type 2” classification. The differential diagnosis of pRCC includes several new provisional/emerging entities with papillary growth. Type 2 tumors have been cleared out of several confounding entities, now regarded as independent tumors with specific clinical and molecular backgrounds. In this work we describe the prevalence and characteristics of emerging papillary tumor entities in two renal tumor cohorts (one consisting of consecutive papillary tumors from a single institute, the other consisting of consultation cases from several centers). After a review of 154 consecutive pRCC cases, 58% remained type 1 pRCC, and 34% type 2 pRCC. Papillary renal neoplasm with reversed polarity (1.3%), biphasic hyalinizing psammomatous RCC (1.3%), and biphasic squamoid/alveolar RCC (4.5%) were rare. Among 281 consultation cases, 121 (43%) tumors had a dominant papillary growth (most frequently MiT family translocation RCCs, mucinous tubular and spindle cell carcinoma and clear cell papillary RCC). Our data confirm that the spectrum of RCCs with papillary growth represents a major diagnostical challenge, frequently requiring a second expert opinion. Papillary renal neoplasm with reversed polarity, biphasic hyalinizing psammomatous RCC, and biphasic squamoid/alveolar RCC are rarely sent out for a second opinion, but correct classification and knowledge of these variants will improve our understanding of the clinical behavior of renal tumors with papillary growth.
Initial Biological Assessment of Upconversion Nanohybrids
Authors: Ferrera-González Juan , Francés-Soriano Laura , Galiana-Roselló Cristina , González-Garcia Jorge , González-Béjar María , Fröhlich Eleonore , Pérez-Prieto Julia
Published: October 2021

Nanoparticles for medical use should be non-cytotoxic and free of bacterial contamination. Upconversion nanoparticles (UCNPs) coated with cucurbit[7]uril (CB[7]) made by combining UCNPs free of oleic acid, here termed bare UCNPs (UCn), and CB[7], i.e., UC@CB[7] nanohybrids, could be used as photoactive inorganic-organic hybrid scaffolds for biological applications. UCNPs, in general, are not considered to be highly toxic materials, but the release of fluorides and lanthanides upon their dissolution may cause cytotoxicity. To identify potential adverse effects of the nanoparticles, dehydrogenase activity of endothelial cells, exposed to various concentrations of the UCNPs, was determined. Data were verified by measuring lactate dehydrogenase release as the indicator of loss of plasma membrane integrity, which indicates necrotic cell death. This assay, in combination with calcein AM/Ethidium homodimer-1 staining, identified induction of apoptosis as main mode of cell death for both particles. The data showed that the UCNPs are not cytotoxic to endothelial cells, and the samples did not contain endotoxin contamination. Higher cytotoxicity, however, was seen in HeLa and RAW 264.7 cells. This may be explained by differences in lysosome content and particle uptake rate. Internalization of UCn and UC@CB[7] nanohybrids by cells was demonstrated by NIR laser scanning microscopy.
Shared Patterns of Brain Functional Connectivity for the Comorbidity between Migraine and Insomnia
Authors: Chou Kun-Hsien , Kuo Chen-Yuan , Liang Chih-Sung , Lee Pei-Lin , Tsai Chia-Kuang , Tsai Chia-Lin , Huang Ming-Hao , Hsu Yi-Chih , Lin Guan-Yu , Lin Yu-Kai , Lin Ching-Po , Yang Fu-Chi
Published: October 2021

Migraine is commonly comorbid with insomnia; both disorders are linked to functional disturbance of the default mode network (DMN). Evidence suggests that DMN could be segregated into multiple subnetworks with specific roles that underline different cognitive processes. However, the relative contributions of DMN subnetworks in the comorbidity of migraine and insomnia remain largely unknown. This study sought to identify altered functional connectivity (FC) profiles of DMN subnetworks in the comorbidity of migraine and insomnia. Direct group comparisons with healthy controls, followed by conjunction analyses, were used to identify shared FC alterations of DMN subnetworks. The shared FC changes of the DMN subnetworks in the migraine and insomnia groups were identified in the dorsomedial prefrontal and posteromedial cortex subnetworks. These shared FC changes were primarily associated with motor and somatosensory systems, and consistently found in patients with comorbid migraine and insomnia. Additionally, the magnitude of FC between the posteromedial cortex and postcentral gyrus correlated with insomnia duration in patients with comorbid migraine and insomnia. Our findings point to specific FC alterations of the DMN subnetwork in migraine and insomnia. The shared patterns of FC disturbance may be associated with the underlying mechanisms of the comorbidity of the two disorders.
Plague Prevention and Therapy: Perspectives on Current and Future Strategies
Authors: Rosario-Acevedo Raysa , Biryukov Sergei S. , Bozue Joel A. , Cote Christopher K.
Published: October 2021

Plague, caused by the bacterial pathogen Yersinia pestis, is a vector-borne disease that has caused millions of human deaths over several centuries. Presently, human plague infections continue throughout the world. Transmission from one host to another relies mainly on infected flea bites, which can cause enlarged lymph nodes called buboes, followed by septicemic dissemination of the pathogen. Additionally, droplet inhalation after close contact with infected mammals can result in primary pneumonic plague. Here, we review research advances in the areas of vaccines and therapeutics for plague in context of Y. pestis virulence factors and disease pathogenesis. Plague continues to be both a public health threat and a biodefense concern and we highlight research that is important for infection mitigation and disease treatment.
A Perspective on the Development of c-Jun N-terminal Kinase Inhibitors as Therapeutics for Alzheimer’s Disease: Investigating Structure through Docking Studies
Authors: Cho Hyunwook , Hah Jung-Mi
Published: October 2021

c-Jun N-terminal kinase (JNK) plays an important role in cell death caused by various stimuli. Because the isoform JNK3 is mainly expressed in the brain, it is believed to play a pivotal role in various neurodegenerative diseases, including Alzheimer’s disease (AD) and Parkinson’s disease (PD), which still lack plausible therapeutics. To develop a novel and selective JNK3 inhibitor, we conducted a decadal review (2011 to 2021) of published articles on JNK inhibitors, particularly those focusing on a structural perspective and docking insights. We observed the structures of three isoforms of JNK, namely holo-proteins and co-crystal structures, with JNK3 inhibitors and summarized the significant structural aspects of selective JNK3 inhibitors as AD therapeutics.
Nanostructures as Targeted Therapeutics for Combating Oral Bacterial Diseases
Authors: Afrasiabi Shima , Chiniforush Nasim , Barikani Hamid Reza , Partoazar Alireza , Goudarzi Ramin
Published: October 2021

Pathogenic oral biofilms are now recognized as a key virulence factor in many microorganisms that cause the heavy burden of oral infectious diseases. Recently, new investigations in the nanotechnology field have propelled the development of novel biomaterials and approaches to control bacterial biofilms, either independently or in combination with other substances such as drugs, bioactive molecules, and photosensitizers used in antimicrobial photodynamic therapy (aPDT) to target different cells. Moreover, nanoparticles (NPs) showed some interesting capacity to reverse microbial dysbiosis, which is a major problem in oral biofilm formation. This review provides a perspective on oral bacterial biofilms targeted with NP-mediated treatment approaches. The first section aims to investigate the effect of NPs targeting oral bacterial biofilms. The second part of this review focuses on the application of NPs in aPDT and drug delivery systems.
Microbiome Modulation as a Therapeutic Approach in Chronic Skin Diseases
Authors: Polak Karina , Jobbágy Antal , Muszyński Tomasz , Wojciechowska Kamila , Frątczak Aleksandra , Bánvölgyi András , Bergler-Czop Beata , Kiss Norbert
Published: October 2021

There is a growing quantity of evidence on how skin and gut microbiome composition impacts the course of various dermatological diseases. The strategies involving the modulation of bacterial composition are increasingly in the focus of research attention. The aim of the present review was to analyze the literature available in PubMed (MEDLINE) and EMBASE databases on the topic of microbiome modulation in skin diseases. The effects and possible mechanisms of action of probiotics, prebiotics and synbiotics in dermatological conditions including atopic dermatitis (AD), psoriasis, chronic ulcers, seborrheic dermatitis, burns and acne were analyzed. Due to the very limited number of studies available regarding the topic of microbiome modulation in all skin diseases except for AD, the authors decided to also include case reports and original studies concerning oral administration and topical application of the pro-, pre- and synbiotics in the final analysis. The evaluated studies mostly reported significant health benefits to the patients or show promising results in animal or ex vivo studies. However, due to a limited amount of research and unambiguous results, the topic of microbiome modulation as a therapeutic approach in skin diseases still warrants further investigation.
Viscous Cervical Environment-on-a-Chip for Selecting High-Quality Sperm from Human Semen
Authors: Lee Manhee , Park Jin Woo , Kim Dongwon , Kwon Hyojeong , Cho Min Jeong , Lee Eun Ji , Shin Tai Eun , Kim Dae Keun , Lee Seungki , Byeun Do Gyeung , Ko Jung Jae , Lee Jae Ho , Choi Jung Kyu
Published: October 2021

When ejaculated sperm travels through the vagina to the uterus, mucus secreted by the cervical canal generally filters out sperm having low motility and poor morphology. To investigate this selection principle in vivo, we developed a microfluidic sperm-sorting chip with a viscous medium (polyvinylpyrrolidone: PVP) to imitate the biophysical environment mimic system of the human cervical canal. The material property of the PVP solution was tuned to the range of viscosities of cervical mucus using micro-viscometry. The selection of high-quality human sperm was experimentally evaluated in vitro and theoretically analyzed by the convection-diffusion mechanism. The convection flow is shown to be dominant at low viscosity of the medium used in the sperm-sorting chip when seeded with raw semen; hence, the raw semen containing sperm and debris convectively flow together with suppressed relative dispersions. Also, it was observed that the sperm selected via the chip not only had high motilities but also normal morphologies and high DNA integrity. Therefore, the biomimetic sperm-sorting chip with PVP medium is expected to improve male fertility by enabling the selection of high-quality sperm as well as uncovering pathways and regulatory mechanisms involved in sperm transport through the female reproductive tract for egg fertilization.
Combined Metabolic Activators Decrease Liver Steatosis by Activating Mitochondrial Metabolism in Hamsters Fed with a High-Fat Diet
Authors: Yang Hong , Mayneris-Perxachs Jordi , Boqué Noemí , del Bas Josep M. , Arola Lluís , Yuan Meng , Türkez Hasan , Uhlén Mathias , Borén Jan , Zhang Cheng , Mardinoglu Adil , Caimari Antoni
Published: October 2021

Although the prevalence of non-alcoholic fatty liver disease (NAFLD) continues to increase, there is no effective treatment approved for this condition. We previously showed, in high-fat diet (HFD)-fed mice, that the supplementation of combined metabolic activators (CMA), including nicotinamide riboside (NAD+ precursor) and the potent glutathione precursors serine and N-acetyl-l-cysteine (NAC), significantly decreased fatty liver by promoting fat oxidation in mitochondria. Afterwards, in a one-day proof-of-concept human supplementation study, we observed that this CMA, including also L-carnitine tartrate (LCT), resulted in increased fatty acid oxidation and de novo glutathione synthesis. However, the underlying molecular mechanisms associated with supplementation of CMA have not been fully elucidated. Here, we demonstrated in hamsters that the chronic supplementation of this CMA (changing serine for betaine) at two doses significantly decreased hepatic steatosis. We further generated liver transcriptomics data and integrated these data using a liver-specific genome-scale metabolic model of liver tissue. We systemically determined the molecular changes after the supplementation of CMA and found that it activates mitochondria in the liver tissue by modulating global lipid, amino acid, antioxidant and folate metabolism. Our findings provide extra evidence about the beneficial effects of a treatment based on this CMA against NAFLD.
Relationships of Ischemic Stroke Occurrence and Outcome with Gene Variants Encoding Enzymes of Tryptophan Metabolism
Authors: Boros Fanni Annamária , Maszlag-Török Rita , Szűcs Mónika , Annus Ádám , Klivényi Péter , Vécsei László
Published: October 2021

Ischemic stroke is among the leading causes of mortality and long-term disability worldwide. Among stroke risk factors the importance of genetic background is gaining interest. There is a growing body of evidence of changes of metabolite levels and enzyme activities involved in the conversion of Trp during the course of cerebral ischemia. We compared the frequencies of ten SNPs of five genes related to Trp metabolism between groups of 122 ischemic stroke patients and 120 control individuals. Furthermore, we examined the mRNA levels of TPH1, IDO1 and KYAT1 genes in peripheral venous blood with the aim of assessing (i) whether there are changes in their expression during the course of stroke and (ii) does any of their investigated SNPs have an impact on gene expression. In seven cases out of ten studied polymorphisms we detected significant differences in frequencies in relation to ischemic stroke occurrence, etiology, and clinical parameters. We also detected changes in the expression of TPH1 and IDO1 genes during the course of the disease. We found that those IDO1 variants which show a trend towards elevated mRNA level are more frequent in stroke patients than in controls. Our results are important novel observations which suggest a causal relationship between elevated IDO1 expression and stroke etiology.