bluuebunny/crossref_metadata_2025 huggingface dataset:
The Impact of Pre-analytical Quality Initiatives on Cholangiocarcinoma Diagnostics in Thailand
Authors: Koonmee Supinda , Sangkhamanon Sakkarn , Intarawichian Piyapharom , Aphivatanasiri Chaiwat , Kunprom Waritta , Sa-ngiamwibool Prakasit , Balthaisong Suwit , Phuyao Chitsakul , Prajumwongs Piya , Alaghehbandan Reza , Thanee Malinee
Published: June 2022

Cholangiocarcinoma (CCA) is the most prevalent malignancy in Thailand, with unfortunate late diagnosis and frequent metastatic disease outcomes. An accurate tissue diagnosis is the first and most important step in the treatment of CCA. Tissue quality and preservation during the pre-analytical phase play major roles in the proper histological evaluation and potential biomarker testing. This study evaluated the impact of using the “Cholangiocarcinoma Screening and Care Program (CASCAP)” container, as an innovative tool to address pre-analytical challenges faced by pathology laboratories in Thailand. This is a comparison study examining the quality of CCA specimens using the CASCAP container vs. the conventional method, using hematoxylin and eosin (H&E) and immunohistochemistry (IHC). CCA tissue quality using the CASCAP container significantly reduced artifact deposition while improving the cellular structure and nuclear and cytoplasmic morphologies. The immunohistochemical expression of cytokeratin 19 (CK19), a prognostic marker in CCA, significantly improved in the CASCAP container group in comparison with the conventional method. This innovation is proven to significantly enhance the CCA tissue quality diagnostics and prognostic biomarker testing, hence improving overall cancer care, diagnosis, and treatment in Thailand.
Applying Translational Science Approaches to Protect Workers Exposed to Nanomaterials
Authors: Schulte Paul A. , Guerin Rebecca J. , Cunningham Thomas R. , Hodson Laura , Murashov Vladimir , Rabin Borsika Adrienn
Published: June 2022

Like nanotechnology, translational science is a relatively new and transdisciplinary field. Translational science in occupational safety and health (OSH) focuses on the process of taking scientific knowledge for the protection of workers from the lab to the field (i.e., the worksite/workplace) and back again. Translational science has been conceptualized as having multiple phases of research along a continuum, beyond scientific discovery (T0), to efficacy (T1), to effectiveness (T2), to dissemination and implementation (D&I) (T3), to outcomes and effectiveness research in populations (T4). The translational research process applied to occupational exposure to nanomaterials might involve similar phases. This builds on basic and efficacy research (T0and T1) in the areas of toxicology, epidemiology, industrial hygiene, medicine and engineering. In T2, research and evidence syntheses and guidance and recommendations to protect workers may be developed and assessed for effectiveness. In T3, emphasis is needed on D&I research to explore the multilevel barriers and facilitators to nanotechnology risk control information/research adoption, use, and sustainment in workplaces. D&I research for nanomaterial exposures should focus on assessing sources of information and evidence to be disseminated /implemented in complex and dynamic workplaces, how policy-makers and employers use this information in diverse contexts to protect workers, how stakeholders inform these critical processes, and what barriers impede and facilitate multilevel decision-making for the protection of nanotechnology workers. The T4phase focuses on how effective efforts to prevent occupational exposure to nanomaterials along the research continuum contribute to large-scale impact in terms of worker safety, health and wellbeing (T4). Stakeholder input and engagement is critical to all stages of the translational research process. This paper will provide: (1) an illustration of the translational research continuum for occupational exposure to nanomaterials; and (2) a discussion of opportunities for applying D&I science to increase the effectiveness, uptake, integration, sustainability, and impact of interventions to protect the health and wellbeing of workers in the nanotechnology field.
Vitamin D: A Potential Mitigation Tool for the Endemic Stage of the COVID-19 Pandemic?
Authors: Briceno Noriega Daniela , Savelkoul Huub F. J.
Published: June 2022

The impact of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic and associated development of clinical symptoms of COVID-19 have presented an enormous global impact on our health care systems, public health and economy. To date several observational epidemiological studies consistently found that vitamin D deficiency, measured as low levels of circulating 25-hydroxyvitamin D, is associated with cardiovascular diseases, diabetes, certain cancers, autoimmune diseases and many infectious diseases, including acute respiratory infections. Since vitamin D is not merely immunosuppressive but also acts as an immunomodulator in tolerance and homeostasis, many experts have considered a role of vitamin D in the prevalence and severity of immune mediated inflammatory diseases, such as SARS-CoV-2, adding to the evidence of the importance of vitamin D in the immune response against viral respiratory infections and reinforcing the need for targeted vitamin D supplementation, with a focus on high-risk populations and a high-dose supplementation treatment for COVID-19 hospitalized patients. The expected transition to endemicity of SARS-CoV-2 even further corroborates as a potential of vitamin D as an potential mitigation tool for the prevention of COVID-19. The aim of this paper is to analyse the current evidence regarding vitamin D and present a hypothesis of its potential role in the current COVID-19 pandemic and in the future as a potential preventive measurement in public health.
Configurational Paths to Higher Efficiency in County Hospital: Evidence From Qualitative Comparative Analysis
Authors: Yin Gang , Ning Jie , Peng Yarui , Yue Jingkai , Tao Hongbing
Published: June 2022

Background

The efficient operation of county-level medical institutions is a significant guarantee in constructing Chinese rural tertiary care service networks. However, it is still unclear how to increase the efficiency of county hospitals under the interaction of multiple factors. In this study, 35 county general hospitals in China were selected to explore the configuration paths of county hospitals' high and poor efficiency status under the Environment-Structure-Behavior (ESB) framework and provide evidence-based recommendations for measures to enhance its efficiency.

Methods

Data envelopment analysis with the bootstrapping procedure was used to estimate the technical efficiency value of case hospitals. A fuzzy-set qualitative comparative analysis approach was carried out to explore the configuration of conditions to the efficiency status.

Results

Antecedent configurations affecting the efficiency status of county hospitals were identified based on the ESB analytical framework. Three high-efficiency configuration paths can be summarized as structural optimization, capacity enhancement, and government support. Another three types of paths, namely insufficient capacity, aggressive expansion, and poor decision-making, will lead to inefficient configurations.

Conclusion

Qualitative comparative analysis is necessary when exploring complex causality. The efficiency situation of county hospitals results from a combination of influencing factors instead of the effect of a single one. There is no solitary configuration for high efficiency that applies to all healthcare units. Any measures aimed at efficiency promotion should be discussed within the framework of a case-specific analysis.
Nudging Sustainable Consumption: A Large-Scale Data Analysis of Sustainability Labels for Fashion in German Online Retail
Authors: Gossen Maike , Jäger Sebastian , Hoffmann Marja Lena , Bießmann Felix , Korenke Ruben , Santarius Tilman
Published: June 2022

A transition toward a sustainable way of living is more pressing than ever. One link to achieving this transition is to increase the currently low level of sustainable consumption, and sustainability labeling has been shown to directly influence sustainable purchasing decisions. E-commerce retailers have recently picked up on a means to inform online shoppers about sustainable alternatives by introducing on their websites third-party and private sustainability labels as nudging instruments. However, despite its increasing relevance in practice, research lacks evidence about the availability and credibility of sustainability labeling in online retail. Our study is guided by the question of how online retailers use sustainability labels to communicate information on the sustainability of products to consumers. Our empirical research is based on a large-scale dataset containing sustainability information of nearly 17,000 fashion products of the leading online retailers in Germany Zalando and Otto. The results show that a large number of fashion products are tagged as sustainable, with two-thirds carrying a private label and one-third a third-party verified label. Only 14% of the tagged products, however, present credible third-party verified sustainability labels. This low percentage makes it challenging for consumers to comprehend to what degree a product is sustainable. The wide distribution of private labels indicates that most of the available sustainability information in the selected online shops addresses only single sustainability issues, preventing comparability. Furthermore, label heterogeneity can add to the confusion and uncertainty among consumers. Our practical recommendations support political initiatives that tackle the risk of greenwashing resulting from uncertified and weak sustainability information.
Case Report: Rectal Perforation Secondary to a Toothbrush in an Elderly Man
Authors: Aimanan Karthigesu , Lim Soon Yee , Ahmad Hamidi Ahmad Junaidi , Chieng Tiong How , Hayati Firdaus
Published: June 2022

Rectal foreign bodies often constitute an arduous diagnosis and perplexing management. A 72-year-old gentleman who is mentally sound was brought to the emergency department for severe epigastric pain of a 1-week duration. On examination, he was pyrexial and in sepsis. The abdomen was guarded. A digital rectal examination was normal. Erect chest radiography revealed air under the diaphragm and abdominal radiography showed neither dilated bowel nor foreign body. A diagnostic laparoscopy was performed which revealed a yellow hard rod-shaped foreign body at the pelvis. Upon conversion to midline laparotomy, the foreign body was found to be a toothbrush with intraperitoneal rectal perforation of 1 cm in length. The brush was removed and the perforation was repaired primarily. A diverting transverse loop colostomy was created. Rectal foreign bodies may cause life-threatening rectal injuries including lacerations, bleeding, perforation, and obstruction. It is deemed crucial that any patient with rectal foreign body demands an orderly approach with the intention of diagnosis, management, and post-extraction evaluation.
Development of an Indirect ELISA for the Detection of SARS-CoV-2 Antibodies in Cats
Authors: Bold Dashzeveg , Roman-Sosa Gleyder , Gaudreault Natasha N. , Zayat Batsukh , Pogranichniy Roman M. , Richt Juergen A.
Published: June 2022

Companion animals are susceptible to a variety of coronaviruses, and recent studies show that felines are highly susceptible to SARS-CoV-2 infection. RT-PCR diagnostic is currently the method of choice to detect the presence of SARS-CoV-2-specific viral nucleic acids in animal samples during an active infection; however, serological assays are critical to determine whether animals were exposed to the virus and to determine the seroprevalence of SARS-CoV-2-specific antibodies in a defined population. In this study, we utilized recombinant nucleocapsid (N) protein and the receptor-binding domain (RBD) of the spike protein of SARS-CoV-2 expressed in E. coli (N) and mammalian cells (N, RBD) to develop indirect ELISA (iELISA) tests using well-characterized SARS-CoV-2-positive and -negative cat serum panels from previous experimental cat challenge studies. The optimal conditions for the iELISA tests were established based on checkerboard dilutions of antigens and antibodies. The diagnostic sensitivity for the detection of feline antibodies specific for the N or RBD proteins of the iELISA tests was between 93.3 and 97.8%, respectively, and the diagnostic specificity 95.5%. The iELISAs developed here can be used for high-throughput screening of cat sera for both antigens. The presence of SARS-CoV-2-specific antibodies in a BSL-2 biocontainment environment, unlike virus neutralization tests with live virus which have to be performed in BSL-3 laboratories.
Effects of Selenium Supplementation on the Ion Homeostasis in the Reproductive Organs and Eggs of Laying Hens Fed With the Diet Contaminated With Cadmium, Lead, Mercury, and Chromium
Authors: Wu Caimei , Li L. , Jiang Y. X. , Kim Woo Kyun , Wu B. , Liu G. M. , Wang Jianping , Lin Y. , Zhang K. Y. , Song J. P. , Zhang R. N. , Wu F. L. , Liang K. H. , Bai Shiping
Published: June 2022

The objective of this study was to explore the toxic effects of different heavy metals in combination with their deposition and ion homeostasis in the reproductive organs and eggs of laying hens, as well as the alleviating action of selenized yeast. A total of 160 Lohmann pink-shell laying hens (63-week-old) were randomly allocated into four treatments with 10 replicates of four hens each. The four dietary treatments were the corn-soybean meal basal dietary (control; CON); the CON dietary supplemented with 0.4 mg/kg selenium from selenized yeast (Se); the CON dietary supplemented with 5 mg/kg Cd + 50 mg/kg Pb +3 mg/kg Hg + 5 mg/kg Cr (HEM), and the HEM dietary supplemented with 0.4 mg/kg selenium from selenized yeast (HEM+Se). The dietary HEM significantly increased Cd, Pb, and Hg deposition in the egg yolk and ovary, and Cd and Hg deposition in the oviduct and in the follicular wall (p < 0.05). The HEM elevated Fe concentration in the egg yolk, ovary, and oviduct (p < 0.05). The HEM decreased Mn concentration in the egg yolk, Fe, Mn, and Zn concentrations in the egg white, Cu concentration in the ovary, Mg concentration in the oviduct, as well as Ca, Cu, Zn, and Mg concentrations in the follicular walls (p < 0.05). Dietary Se addition elevated Se concentration in the egg yolk, oviduct, and follicular walls and Mg concentration (p < 0.05) in the oviduct, whereas it reduced Fe concentration in the oviduct compared with the HEM-treated hens. Some positive or negative correlations among these elements were observed. Canonical Correlation Analysis showed that the concentrations of Pb and Hg in the egg yolk were positively correlated with those in the ovary. The concentration of Cd in the egg white was positively correlated with that in the oviduct. In summary, dietary Cd, Pb, Hg, and Cr in combination caused ion loss and deposition of HEM in reproductive organs of laying hens. Dietary Se addition at 0.4 mg/kg from selenized yeast alleviated the negative effects of HEM on Fe and Mg ion disorder in the oviduct and follicle wall of hens.
A Prognostic and Health Management Framework for Aero-Engines Based on a Dynamic Probability Model and LSTM Network
Authors: Huang Yufeng , Tao Jun , Sun Gang , Zhang Hao , Hu Yan
Published: June 2022

In this study, a prognostics and health management (PHM) framework is proposed for aero-engines, which combines a dynamic probability (DP) model and a long short-term memory neural network (LSTM). A DP model based on Gaussian mixture model-adaptive density peaks clustering algorithm, which has the advantages of an extremely short training time and high enough precision, is employed for modelling engine fault development from the beginning of engine service, and principal component analysis is introduced to convert complex high-dimensional raw data into low-dimensional data. The model can be updated from time to time according to the accumulation of engine data to capture the occurrence and evolution process of engine faults. In order to address the problems with the commonly used data driven methods, the DP + LSTM model is employed to estimate the remaining useful life (RUL) of the engine. Finally, the proposed PHM framework is validated experimentally using NASA’s commercial modular aero-propulsion system simulation dataset, and the results indicate that the DP model has higher stability than the classical artificial neural network method in fault diagnosis, whereas the DP + LSTM model has higher accuracy in RUL estimation than other classical deep learning methods.
A Platform Approach to Smart Farm Information Processing
Authors: Amiri-Zarandi Mohammad , Hazrati Fard Mehdi , Yousefinaghani Samira , Kaviani Mitra , Dara Rozita
Published: June 2022

With the rapid growth of population and the increasing demand for food worldwide, improving productivity in farming procedures is essential. Smart farming is a concept that emphasizes the use of modern technologies such as the Internet of Things (IoT) and artificial intelligence (AI) to enhance productivity in farming practices. In a smart farming scenario, large amounts of data are collected from diverse sources such as wireless sensor networks, network-connected weather stations, monitoring cameras, and smartphones. These data are valuable resources to be used in data-driven services and decision support systems (DSS) in farming applications. However, one of the major challenges with these large amounts of agriculture data is their immense diversity in terms of format and meaning. Moreover, the different services and technologies in a smart farming ecosystem have limited capability to work together due to the lack of standardized practices for data and system integration. These issues create a significant challenge in cooperative service provision, data and technology integration, and data-sharing practices. To address these issues, in this paper, we propose the platform approach, a design approach intended to guide building effective, reliable, and robust smart farming systems. The proposed platform approach considers six requirements for seamless integration, processing, and use of farm data. These requirements in a smart farming platform include interoperability, reliability, scalability, real-time data processing, end-to-end security and privacy, and standardized regulations and policies. A smart farming platform that considers these requirements leads to increased productivity, profitability, and performance of connected smart farms. In this paper, we aim at introducing the platform approach concept for smart farming and reviewing the requirements for this approach.
The Dynamics of Antimicrobial Resistance among Enterobacteriaceae Isolates in Russia: Results of the 2012–2018 INFORM and ATLAS International Program Studies
Authors: Kozlov Roman , Kuzmenkov Alexey
Published: June 2022

Background: The increasing prevalence of multidrug-resistant Enterobacteriaceae limits the range of active antimicrobial agents, thus worsening clinical outcomes. The objective of this study was to identify the trends in antimicrobial resistance for Enterobacteriaceae in Russia using the databases for the International Network for Optimal Resistance Monitoring (INFORM) and Antimicrobial Testing Leadership and Surveillance (ATLAS) studies between 2012 and 2018. Methods: This subanalysis was performed for 3811 non-duplicate clinical isolates of Enterobacteriaceae to evaluate the in vitro activity of the main classes of antibiotics against relevant clinical isolates from hospitalized patients with complicated infections of different anatomical locations. Results: The lowest susceptibility was observed for colistin (0%), ampicillin (16.4%), and ampicillin/sulbactam (31.1%), whereas the best susceptibility was observed for all combinations containing avibactam (>96%). Among individual antimicrobials, doripenem (3.2%), tigecycline (1.6%), and meropenem (5.9%) exhibited the lowest resistance. Important trends included the decreasing resistance of Enterobacteriaceae to glycylcyclines and the increasing resistance to aminoglycosides and carbapenems. K. pneumoniae strains were most aggressive in terms of the percentage of strains having multidrug resistance (8.3–18.3%, depending on location) and the percentage of ESBL-positive strains (44.8–86.8%). Conclusions: The current patterns and trends of antimicrobial resistance in different bacterial species should be taken into consideration for timely updating of clinical guidelines and local treatment protocols to ensure effective antimicrobial therapy.
Selenium Status in Diet Affects Nephrotoxicity Induced by Cisplatin in Mice
Authors: Liu Shuang , Wen Xing , Huang Qihan , Zhu Minghui , Lu Jun
Published: June 2022

Cisplatin is one of the most active chemotherapy drugs to treat solid tumors. However, it also causes various side effects, especially nephrotoxicity, in which oxidative stress plays critical roles. Our previous studies found that cisplatin selectively inhibited selenoenzyme thioredoxin reductase1 (TrxR1) in the kidney at an early stage and, subsequently, induced the activation of Nrf2. However, the effects of selenium on cisplatin-induced nephrotoxicity are still unclear. In this study, we established mice models with different selenium intake levels to explore the effects of selenoenzyme activity changes on cisplatin-induced nephrotoxicity. Results showed that feeding with a selenium-deficient diet sensitize the mice to cisplatin-induced damage, whereas selenium supplementation increased the activities of selenoenzymes TrxR and glutathione peroxidase (GPx), changed the renal cellular redox environment to a reduced state, and exhibited protective effects. These results demonstrated the correlation of selenoenzymes with cisplatin-induced side effects and provided a basis for the potential approach to alleviate cisplatin-induced renal injury.
Advanced Analysis of 3D Kinect Data: Supervised Classification of Facial Nerve Function via Parallel Convolutional Neural Networks
Authors: Shayestegan Mohsen , Kohout Jan , Štícha Karel , Mareš Jan
Published: June 2022

In this paper, we designed a methodology to classify facial nerve function after head and neck surgery. It is important to be able to observe the rehabilitation process objectively after a specific brain surgery, when patients are often affected by face palsy. The dataset that is used for classification problems in this study only contains 236 measurements of 127 patients of complex observations using the most commonly used House–Brackmann (HB) scale, which is based on the subjective opinion of the physician. Although there are several traditional evaluation methods for measuring facial paralysis, they still suffer from ignoring facial movement information. This plays an important role in the analysis of facial paralysis and limits the selection of useful facial features for the evaluation of facial paralysis. In this paper, we present a triple-path convolutional neural network (TPCNN) to evaluate the problem of mimetic muscle rehabilitation, which is observed by a Kinect stereovision camera. A system consisting of three modules for facial landmark measure computation and facial paralysis classification based on a parallel convolutional neural network structure is used to quantitatively assess the classification of facial nerve paralysis by considering facial features based on the region and the temporal variation of facial landmark sequences. The proposed deep network analyzes both the global and local facial movement features of a patient’s face. These extracted high-level representations are then fused for the final evaluation of facial paralysis. The experimental results have verified the better performance of TPCNN compared to state-of-the-art deep learning networks.
Sparse Data-Extended Fusion Method for Sea Surface Temperature Prediction on the East China Sea
Authors: Wang Xiaoliang , Wang Lei , Zhang Zhiwei , Chen Kuo , Jin Yingying , Yan Yijun , Liu Jingjing
Published: June 2022

The accurate temperature background field plays a vital role in the numerical prediction of sea surface temperature (SST). At present, the SST background field is mainly derived from multi-source data fusion, including satellite SST data and in situ data from marine stations, buoys, and voluntary observing ships. The characteristics of satellite SST data are wide coverage but low accuracy, whereas the in situ data have high accuracy but sparse distribution. For obtaining a more accurate temperature background field and realizing the fusion of measured data with satellite data as much as possible, we propose a sparse data-extended fusion method to predict SST in this paper. By using this method, the actual observed sites and buoys data in the East China Sea area are fused with Advanced Very High Resolution Radiometer (AVHRR) Pathfinder Version 5.0 SST data. Furthermore, the temperature field in the study area were predicted by using Long Short-Term Memory (LSTM) and Gate Recurrent Unit (GRU) deep learning methods, respectively. Finally, we obtained the results by traditional prediction methods to verify them. The experimental results show that the method we proposed in this paper can obtain more accurate prediction results, and effectively compensate for the uncertainty caused by the parameterization of ocean dynamic process, the discrete method, and the error of initial conditions.
Advanced Technologies in Data and Information Security
Authors: Drosatos George , Rantos Konstantinos , Demertzis Konstantinos
Published: June 2022

The protection of personal data and privacy is a timeless challenge which has intensified in the modern era [...]
Prediction Method of Water Absorption of Soft Rock Considering the Influence of Composition, Porosity, and Solute Quantitatively
Authors: Cui Guangjun , Zhou Cuiying , Liu Zhen
Published: June 2022

The study of water absorption of soft rock is of great significance to the prevention engineering disasters. However, the research on the prediction method of water absorption of soft rock considering the influence of composition, porosity, and solute is insufficient. Aiming to solve the above problem, water absorption tests are carried out by synthesizing soft rocks and water solutions. Then, the prediction model of water absorption of soft rock is established through quantitative analysis of water absorption data and compared with the water absorption characteristics of natural rock to verify the reliability of the model. The results show that the changes in water content and water absorption velocity of soft rock with time obey the second-order exponential attenuation function and the linear function (double logarithmic coordinates axis), respectively. The types of cations and anions and the type and content of clay minerals have the greatest influence on the process of rock water absorption. In addition, the water absorption prediction model could better predict the water absorption process of natural rock. The research results solve the problem of insufficient research on the soft rock water absorption prediction method considering the influence of composition, porosity and solute.
Observed Changes in Climate Conditions and Weather-Related Risks in Fruit and Grape Production in Serbia
Authors: Vujadinović Mandić Mirjam , Vuković Vimić Ana , Ranković-Vasić Zorica , Đurović Dejan , Ćosić Marija , Sotonica Dunja , Nikolić Dragan , Đurđević Vladimir
Published: June 2022

Climate change, through changes in temperature, precipitation, and frequency of extreme events, has influenced agricultural production and food security over the past several decades. In order to assess climate and weather-related risks to fruit and grape production in Serbia, changes in bioclimatic indices and frequency of the occurrence of unfavourable weather events are spatially analysed for the past two decades (1998–2017) and the standard climatological period 1961–1990. Between the two periods, the Winkler and Huglin indices changed into a warmer category in most of the viticultural regions of Serbia. The average change shift was about 200 m towards higher elevations. Regarding the frequency of spring frost, high summer temperatures and water deficit, the most vulnerable regions in terms of fruit and grape production are found alongside large rivers (Danube, Sava, Great and South Morava), as well as in the northern part of the country. Regions below 300 m are under increased risk of high summer temperatures, as the number and duration of occurrences increased significantly over the studied periods. The high-resolution spatial analysis presented here gives an assessment of the climate change influence on the fruit and grapes production. The presented approach may be used in regional impact assessments and national planning of adaptation measures, and it may help increase resilience of agricultural production to climate change.
New Inequalities and Generalizations for Symmetric Means Induced by Majorization Theory
Authors: Shi Huan-Nan , Du Wei-Shih
Published: June 2022

In this paper, the authors study new inequalities and generalizations for symmetric means and give new proofs for some known results by applying majorization theory.
Biodegradable and Biocompatible Adhesives for the Effective Stabilisation, Repair and Regeneration of Bone
Authors: Tzagiollari Antzela , McCarthy Helen O. , Levingstone Tanya J. , Dunne Nicholas J.
Published: June 2022

Bone defects and complex fractures present significant challenges for orthopaedic surgeons. Current surgical procedures involve the reconstruction and mechanical stabilisation of complex fractures using metal hardware (i.e., wires, plates and screws). However, these procedures often result in poor healing. An injectable, biocompatible, biodegradable bone adhesive that could glue bone fragments back together would present a highly attractive solution. A bone adhesive that meets the many clinical requirements for such an application has yet to be developed. While synthetic and biological polymer-based adhesives (e.g., cyanoacrylates, PMMA, fibrin, etc.) have been used effectively as bone void fillers, these materials lack biomechanical integrity and demonstrate poor injectability, which limits the clinical effectiveness and potential for minimally invasive delivery. This systematic review summarises conventional approaches and recent developments in the area of bone adhesives for orthopaedic applications. The required properties for successful bone repair adhesives, which include suitable injectability, setting characteristics, mechanical properties, biocompatibility and an ability to promote new bone formation, are highlighted. Finally, the potential to achieve repair of challenging bone voids and fractures as well as the potential of new bioinspired adhesives and the future directions relating to their clinical development are discussed.
Nisin Variants Generated by Protein Engineering and Their Properties
Authors: Zheng Yue , Du Yuhui , Qiu Zekai , Liu Ziming , Qiao Jianjun , Li Yanni , Caiyin Qinggele
Published: June 2022

Nisin, a typical lantibiotic, has robust antimicrobial activity combined with limited cytotoxicity, and the development of resistance to it is slow. These properties make nisin a promising antimicrobial agent to control pathogenic microorganisms in dairy foods. However, its low solubility, poor stability and short half-life at neutral pH limit its application within the dairy industry. Protein engineering technology has revealed the potential of modifying nisin to improve its properties, and many valuable variants have emerged. This review summarizes progress in the generation of nisin variants for the dairy industry and for other purposes. These nisin variants with additional modification have improved properties and can even expand the inhibition spectrum range of nisin. Nisin, as the most thoroughly studied lantibiotic, and its variants can also guide the modification of other lantibiotics.
Confirmation of the Applicability of Skeletochronology and Estimating the Age Structure of Kaloula borealis (Microhylidae: Anura) at Lake Sihwa, South Korea
Authors: Rahman Md Mizanur , Lee Yu-Young , Park Seung-Min , Ham Choong-Ho , Sung Ha-Cheol
Published: June 2022

Despite having some limitations, the use of skeletochronology—age determination by counting lines of arrested growth (LAGs)—in amphibians is increasing. The main limitation of using skeletochronology is identifying the innermost visible line (IVL) and counting the exact number of LAGs. Thus, we tested its applicability to Kaloula borealis, a class II endangered amphibian in South Korea. We reared juveniles in the lab to investigate the process of bone formation. This confirmed the development of one LAG each year. Hence, our study validates skeletochronology for the age determination of this species and recommends it for others that show similar growth patterns. Furthermore, the comparison of threshold diameters with the IVL of wild individuals confirmed no LAG1 resorption. The average age of males and females in this population was 2.75 ± 1.05 and 3.64 ± 3 years, respectively. We estimated sexual maturity at 2 years with rapid growth up to that stage in both sexes. We found a female-dominated sexual size dimorphism. This study offers accurate information on the life history traits and age structure of K. borealis that may help to evaluate population dynamics in other areas, identify vulnerable life stages and sites, assess the causes of population decline, and set conservation priorities.
Flow Cytometric Detection of Malignant Blasts in Cerebrospinal Fluid: A Biomarker of Central Nervous System Involvement in Childhood Acute Lymphoblastic Leukemia
Authors: Thastrup Maria , Marquart Hanne Vibeke , Schmiegelow Kjeld
Published: June 2022

Despite the excellent prognosis for children and adolescents with acute lymphoblastic lymphoma (ALL), the involvement of the central nervous system (CNS) represents a major therapeutic challenge. Patients who develop CNS relapse have a very poor prognosis, and since current methods cannot reliably identify patients with CNS involvement or patients at high risk of CNS relapse, all children with ALL receive CNS-directed treatment. The current golden standard for detecting CNS involvement is the assessment of cytomorphology on cytospin slides of cerebrospinal fluid (CSF). This technique is inadequate due to low sensitivity and reproducibility. Flow cytometric analysis of CSF represent a novel, highly specific and sensitive technique for the detection of leukemic cells in the CNS. In prospective studies, CSF flow cytometry demonstrated two to three times higher rates of CNS involvement at diagnosis of childhood ALL than conventional cytospin, and especially demonstrated superior sensitivity in detecting low-level CNS disease. CNS involvement determined via flow cytometry has been linked to a higher risk of CNS relapse and poor outcomes in several studies. In this review, we discuss the central analytical concepts of CSF flow cytometry and summarize the current evidence supporting the use of flow cytometric detection of malignant blasts as a biomarker of CNS involvement in childhood ALL.
An Integrative Analysis of DNA Methylation Pattern in Myotonic Dystrophy Type 1 Samples Reveals a Distinct DNA Methylation Profile between Tissues and a Novel Muscle-Associated Epigenetic Dysregulation
Authors: Koehorst Emma , Odria Renato , Capó Júlia , Núñez-Manchón Judit , Arbex Andrea , Almendrote Miriam , Linares-Pardo Ian , Natera-de Benito Daniel , Saez Verónica , Nascimento Andrés , Ortez Carlos , Rubio Miguel Ángel , Díaz-Manera Jordi , Alonso-Pérez Jorge , Lucente Giuseppe , Rodriguez-Palmero Agustín , Ramos-Fransi Alba , Martínez-Piñeiro Alicia , Nogales-Gadea Gisela , Suelves Mònica
Published: June 2022

Myotonic dystrophy type 1 (DM1) is a progressive, non-treatable, multi-systemic disorder. To investigate the contribution of epigenetics to the complexity of DM1, we compared DNA methylation profiles of four annotated CpG islands (CpGis) in the DMPK locus and neighbouring genes, in distinct DM1 tissues and derived cells, representing six DM1 subtypes, by bisulphite sequencing. In blood, we found no differences in CpGi 74, 43 and 36 in DNA methylation profile. In contrast, a CTCF1 DNA methylation gradient was found with 100% methylation in congenital cases, 50% in childhood cases and 13% in juvenile cases. CTCF1 methylation correlated to disease severity and CTG expansion size. Notably, 50% of CTCF1 methylated cases showed methylation in the CTCF2 regions. Additionally, methylation was associated with maternal transmission. Interestingly, the evaluation of seven families showed that unmethylated mothers passed on an expansion of the CTG repeat, whereas the methylated mothers transmitted a contraction. The analysis of patient-derived cells showed that DNA methylation profiles were highly preserved, validating their use as faithful DM1 cellular models. Importantly, the comparison of DNA methylation levels of distinct DM1 tissues revealed a novel muscle-specific epigenetic signature with methylation of the CTCF1 region accompanied by demethylation of CpGi 43, a region containing an alternative DMPK promoter, which may decrease the canonical promoter activity. Altogether, our results showed a distinct DNA methylation profile across DM1 tissues and uncovered a novel and dual epigenetic signature in DM1 muscle samples, providing novel insights into the epigenetic changes associated with DM1.
Mitochondrial Quality Control in the Heart: The Balance between Physiological and Pathological Stress
Authors: Fajardo Giovanni , Coronado Michael , Matthews Melia , Bernstein Daniel
Published: June 2022

Alterations in mitochondrial function and morphology are critical adaptations to cardiovascular stress, working in concert in an attempt to restore organelle-level and cellular-level homeostasis. Processes that alter mitochondrial morphology include fission, fusion, mitophagy, and biogenesis, and these interact to maintain mitochondrial quality control. Not all cardiovascular stress is pathologic (e.g., ischemia, pressure overload, cardiotoxins), despite a wealth of studies to this effect. Physiological stress, such as that induced by aerobic exercise, can induce morphologic adaptations that share many common pathways with pathological stress, but in this case result in improved mitochondrial health. Developing a better understanding of the mechanisms underlying alterations in mitochondrial quality control under diverse cardiovascular stressors will aid in the development of pharmacologic interventions aimed at restoring cellular homeostasis.
Molecular Mechanisms and Potential Rationale of Immunotherapy in Peritoneal Metastasis of Advanced Gastric Cancer
Authors: Kang Donghoon , Kim In-Ho
Published: June 2022

Peritoneal metastasis (PM) is one of the most frequent metastasis patterns of gastric cancer (GC), and the prognosis of patients with PM is very dismal. According to Paget’s theory, disseminated free cancer cells are seeded and survive in the abdominal cavity, adhere to the peritoneum, invade the subperitoneal tissue, and proliferate through angiogenesis. In these sequential processes, several key molecules are involved. From a therapeutic point of view, immunotherapy with chemotherapy combination has become the standard of care for advanced GC. Several clinical trials of newer immunotherapy agents are ongoing. Understanding of the molecular process of PM and the potential rationale of immunotherapy for PM treatment is necessary. Beyond understanding of the molecular aspect of PM, many studies have been conducted on the modality of treatment of PM. Notably, intraperitoneal approaches, including chemotherapy or immunotherapy, have been conducted, because systemic treatment of PM has limitations. In this study, we reviewed the molecular mechanisms and immunologic aspects of PM, and intraperitoneal approaches under investigation for treating PM.
Male Knock-in Mice Expressing an Arachidonic Acid Lipoxygenase 15B (Alox15B) with Humanized Reaction Specificity Are Prematurely Growth Arrested When Aging
Authors: Schäfer Marjann , Kakularam Kumar R. , Reisch Florian , Rothe Michael , Stehling Sabine , Heydeck Dagmar , Püschel Gerhard P. , Kuhn Hartmut
Published: June 2022

Mammalian arachidonic acid lipoxygenases (ALOXs) have been implicated in cell differentiation and in the pathogenesis of inflammation. The mouse genome involves seven functional Alox genes and the encoded enzymes share a high degree of amino acid conservation with their human orthologs. There are, however, functional differences between mouse and human ALOX orthologs. Human ALOX15B oxygenates arachidonic acid exclusively to its 15-hydroperoxy derivative (15S-HpETE), whereas 8S-HpETE is dominantly formed by mouse Alox15b. The structural basis for this functional difference has been explored and in vitro mutagenesis humanized the reaction specificity of the mouse enzyme. To explore whether this mutagenesis strategy may also humanize the reaction specificity of mouse Alox15b in vivo, we created Alox15b knock-in mice expressing the arachidonic acid 15-lipoxygenating Tyr603Asp+His604Val double mutant instead of the 8-lipoxygenating wildtype enzyme. These mice are fertile, display slightly modified plasma oxylipidomes and develop normally up to an age of 24 weeks. At later developmental stages, male Alox15b-KI mice gain significantly less body weight than outbred wildtype controls, but this effect was not observed for female individuals. To explore the possible reasons for the observed gender-specific growth arrest, we determined the basic hematological parameters and found that aged male Alox15b-KI mice exhibited significantly attenuated red blood cell parameters (erythrocyte counts, hematocrit, hemoglobin). Here again, these differences were not observed in female individuals. These data suggest that humanization of the reaction specificity of mouse Alox15b impairs the functionality of the hematopoietic system in males, which is paralleled by a premature growth arrest.
Nomogram to Predict Cognitive State Improvement after Deep Brain Stimulation for Parkinson’s Disease
Authors: Chang Bowen , Ni Chen , Zhang Weiwen , Mei Jiaming , Xiong Chi , Chen Peng , Jiang Manli , Niu Chaoshi
Published: June 2022

Purpose: Parkinson’s disease (PD) is a common neurodegenerative disease, for which cognitive impairment is a non-motor symptom (NMS). Bilateral subthalamic nucleus deep brain stimulation (STN-DBS) is an effective treatment for PD. This study established a nomogram to predict cognitive improvement rate after STN-DBS in PD patients. Methods: We retrospectively analyzed 103 PD patients who underwent STN-DBS. Patients were followed up to measure improvement in MoCA scores one year after surgery. Univariate and multivariate logistic regression analyses were used to identify factors affecting improvement in cognitive status. A nomogram was developed to predict this factor. The discrimination and fitting performance were evaluated by receiver operating characteristics (ROC) analysis, calibration diagram, and decision curve analysis (DCA). Results: Among 103 patients, the mean improvement rate of the MoCA score was 37.3% and the median improvement rate was 27.3%, of which 64% improved cognition, 27% worsened cognition, and 8.7% remained unchanged. Logistic multivariate regression analysis showed that years of education, UPDRSIII drug use, MoCA Preop, and MMSE Preop scores were independent factors affecting the cognitive improvement rate. A nomogram model was subsequently developed. The C-index of the nomogram was 0.98 (95%CI, 0.97–1.00), and the area under the ROC was 0.98 (95%CI 0.97–1.00). The calibration plot and DCA demonstrated the goodness-of-fit between nomogram predictions and actual observations. Conclusion: Our nomogram could effectively predict the possibility of achieving good cognitive improvement one year after STN-DBS in patients with PD. This model has value in judging the expected cognitive improvement of patients with PD undergoing STN-DBS.
PTPRN Serves as a Prognostic Biomarker and Correlated with Immune Infiltrates in Low Grade Glioma
Authors: Li Peng , Chen Fanfan , Yao Chen , Zhu Kezhou , Zhang Bei , Zheng Zelong
Published: June 2022

Background: Glioma is one of the most common malignant tumors of the central nervous system. Immune infiltration of tumor microenvironment was associated with overall survival in low grade glioma (LGG). However, effects of Tyrosine phosphatase receptor type N (PTPRN) on the progress of LGG and its correlation with tumor infiltration are unclear. Methods: Here, datasets of LGG were from The Cancer Genome Atlas (TCGA) and normal samples were from GTEx dataset. Gepia website and Human Protein Atlas (HPA) Database were used to analyze the mRNA and protein expression of PTPRN. We evaluated the influence of PTPRN on survival of LGG patients. MethSurv was used to explore the expression and prognostic patterns of single CpG methylation of PTPRN gene in LGG. The correlations between the clinical information and PTPRN expression were analyzed using logistic regression and Multivariate Cox regression. We also explored the correlation between PTPRN expression and cancer immune infiltration by TIMER. Gene set enrichment analysis (GSEA) was formed using TCGA RNA-seq datasets. Results: PTPRN mRNA and protein expression decreased in LGG compared to normal brain tissue in TCGA and HPA database. Kaplan-Meier analysis showed that the high expression level of PTPRN correlated with a good overall survival (OS) of patients with LGG. The Multivariate Cox analysis demonstrated that PTPRN expression and other clinical-pathological factors (age, WHO grade, IDH status, and primary therapy outcome) significantly correlated with OS of LGG patients. The DNA methylation pattern of PTPRN with significant prognostic value were confirmed, including cg00672332, cg06971096, cg01382864, cg03970036, cg10140638, cg16166796, cg03545227, and cg25569248. Interestingly, PTPRN expression level significantly negatively correlated with infiltrating level of B cell, CD4+ T cells, Macrophages, Neutrophils, and DCs in LGG. Finally, GSEA showed that signaling pathways, mainly associated with tumor microenvironment and immune cells, were significantly enriched in PTPRN high expression. Conclusion: PTPRN is a potential biomarker and correlates with tumor immune infiltration in LGG.
Electroporation and Immunotherapy—Unleashing the Abscopal Effect
Authors: Justesen Tobias Freyberg , Orhan Adile , Raskov Hans , Nolsoe Christian , Gögenur Ismail
Published: June 2022

The discovery of electroporation in 1968 has led to the development of electrochemotherapy (ECT) and irreversible electroporation (IRE). ECT and IRE have been established as treatments of cutaneous and subcutaneous tumors and locally advanced pancreatic cancer, respectively. Interestingly, the treatment modalities have been shown to elicit immunogenic cell death, which in turn can induce an immune response towards the tumor cells. With the dawn of the immunotherapy era, the potential of combining ECT and IRE with immunotherapy has led to the launch of numerous studies. Data from the first clinical trials are promising, and new combination regimes might change the way we treat tumors characterized by low immunogenicity and high levels of immunosuppression, such as melanoma and pancreatic cancer. In this review we will give an introduction to ECT and IRE and discuss the impact on the immune system. Additionally, we will present the results of clinical and preclinical trials, investigating the combination of electroporation modalities and immunotherapy.