bluuebunny/crossref_metadata_2025 huggingface dataset:
Adaptive Attentional Network for Few-Shot Relational Learning of Knowledge Graphs
Authors: Ma Ruixin , Li Zeyang , Ma Yunlong , Wu Hao , Yu Mengfei , Zhao Liang
Published: April 2022

Few-shot knowledge graph reasoning is a research focus in the field of knowledge graph reasoning. At present, in order to expand the application scope of knowledge graphs, a large number of researchers are devoted to the study of the multi-shot knowledge graph model. However, as far as we know, the knowledge graph contains a large number of missing relations and entities, and there are not many reference examples at the time of training. In this paper, our goal is to be able to infer the correct entity given a few training instances, or even only one training instance is available. Therefore, we propose an adaptive attentional network for few-shot relational learning of knowledge graphs, extracting knowledge based on traditional embedding methods, using the Transformer mechanism and hierarchical attention mechanism to obtain hidden attributes of entities, and then using a noise checker to filter out unreasonable candidate entities. Our model produces large performance improvements on the NELL-One dataset.
Chronological Evaluation of Gait Ability and Posture Balance after Adult Spinal Deformity Surgery
Authors: Sakaguchi Tomoyoshi , Tanaka Masato , Suthar Hardik , Fujiwara Yoshihiro , Uotani Koji , Arataki Shinya , Yamauchi Taro , Sugyo Atsushi , Takamatsu Kazuhiko , Yasuda Yosuke , Nakagawa Masami , Takahashi Nana
Published: April 2022

Adult spinal deformity (ASD) is highly prevalent in persons older than 65 years, affecting more than 30% of the total population. There are many important reports that describe excellent postoperative results for ASD surgery. However, there is no report that describes a chronological evaluation of gait ability and spinal balance after ASD surgery. The present prospective study aimed to determine the recovery time of gait and spinal balance ability after adult spinal deformity (ASD) surgery. Patients with ASD (n = 25: mean age, 73.0 years) who underwent corrective surgery and preoperative and postoperative gait and spinal balance ability evaluation. Spinal radiographs and gait analysis data (static balance; single-leg standing, dynamic balance; time-up and go test, gait ability; 10 m walk velocity) were acquired preoperatively, 1 month, 6 months, and 12 months after surgery. The radiographic parameters of the spine and pelvis (lumbar lordosis; LL, pelvic tilt; PT, sagittal vertical axis; SVA, pelvic incidence; PI) were measured. The mean postoperative SVA, LL, PT, and PI-LL became 30.0 mm, 50.1 degrees, 14.1 degrees, and 0.35 degrees, respectively. Preoperatively, all spinal balance and gait ability were worse than the normal threshold (one-leg standing; 14.2 s vs. 15.0 s, time-up and go test; 13.9 s vs. 13.5 s, 10-m walk speed; 0.91 m/s vs. 1.00 m/s). At 12 months after surgery, all spinal balance and gait ability became normal or improved (single-leg standing; 14.7 s, time-up and go test; 11.0 s, 10-m walk speed; 1.09 m/s). The ODI at one-year follow-up improved from 46.8 ± 12.6% to 27.8 ± 18.1%. In conclusion, gait and spinal balance analysis revealed that ASD patients could not recover gait and spinal balance ability one month after surgery. At 12 months after surgery, gait ability and dynamic spinal balance became better than preoperative levels. However, the static spinal balance was at the same level as that of preoperative status.
Design and Implementation of Anatomically Inspired Mesenteric and Intestinal Vascular Patterns for Personalized 3D Bioprinting
Authors: Cadle Rachel , Rogozea Dan , Moldovan Leni , Moldovan Nicanor I.
Published: April 2022

Recent progress in bioprinting has made possible the creation of complex 3D intestinal constructs, including vascularized villi. However, for their integration into functional units useful for experimentation or implantation, the next challenge is to endow them with a larger-scale, anatomically realistic vasculature. In general, the perfusion of bioprinted constructs has remained difficult, and the current solution is to provide them with mostly linear and simply branched channels. To address this limitation, here we demonstrated an image analysis-based workflow leading through computer-assisted design from anatomic images of rodent mesentery and colon to the actual printing of such patterns with paste and hydrogel bioinks. Moreover, we reverse-engineered the 2D intestinal image-derived designs into cylindrical objects, and 3D-printed them in a support hydrogel. These results open the path towards generation of more realistically vascularized tissue constructs for a variety of personalized medicine applications.
Autologous Blood Doping Induced Changes in Red Blood Cell Rheologic Parameters, RBC Age Distribution, and Performance
Authors: Grau Marijke , Zollmann Emily , Bros Janina , Seeger Benedikt , Dietz Thomas , Noriega Ureña Javier Antonio , Grolle Andreas , Zacher Jonas , Notbohm Hannah L. , Suck Garnet , Bloch Wilhelm , Schumann Moritz
Published: April 2022

Autologous blood doping (ABD) refers to the transfusion of one’s own blood after it has been stored. Although its application is prohibited in sports, it is assumed that ABD is applied by a variety of athletes because of its benefits on exercise performance and the fact that it is not detectable so far. Therefore, this study aims at identifying changes in hematological and hemorheological parameters during the whole course of ABD procedure and to relate those changes to exercise performance. Eight healthy men conducted a 31-week ABD protocol including two blood donations and the transfusion of their own stored RBC volume corresponding to 7.7% of total blood volume. Longitudinal blood and rheological parameter measurements and analyses of RBC membrane proteins and electrolyte levels were performed. Thereby, responses of RBC sub-populations—young to old RBC—were detected. Finally, exercise tests were carried out before and after transfusion. Results indicate a higher percentage of young RBC, altered RBC deformability and electrolyte concentration due to ABD. In contrast, RBC membrane proteins remained unaffected. Running economy improved after blood transfusion. Thus, close analysis of RBC variables related to ABD detection seems feasible but should be verified in further more-detailed studies.
Cas14a1-Mediated Nucleic Acid Diagnostics for Spinal Muscular Atrophy
Authors: Hu Zhiqing , Chen Miaomiao , Zhang Chunhua , Li Zhuo , Feng Mai , Wu Lingqian , Zhou Miaojin , Liang Desheng
Published: April 2022

Spinal muscular atrophy (SMA) is the main genetic cause of infant death. In >95% of the patients with SMA, the disease is caused by a single hotspot pathogenic mutation: homozygous deletion of exon 7 of the survival motor neuron 1 gene (SMN1). Recently, clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR associated protein (Cas)-based assays have been developed as a promising new option for nucleic acid detection. Here, we developed a Cas14a1-based assay combined with asymmetric PCR to establish a method for detection of the homozygous deletion of SMN1 exon 7 in SMA patients. The minimum detectable concentration of genomic DNA reached 5.26 aM with our method, and the assessment of its detection performance in 33 clinical samples revealed that the results were completely consistent with those of multiple ligation-dependent probe amplification and quantitative PCR. Thus, our novel nucleic acid diagnostics combining CRISPR/Cas14a1 and asymmetric PCR not only provides specific and sensitive testing of the deletion of SMN1 exon 7, but also holds promise for an accurate detection platform of genetic diseases and pathogens in multiple sample types.
Early Diagnosis of Cerebral Palsy in Low- and Middle-Income Countries
Authors: King Arrabella R. , Al Imam Mahmudul Hassan , McIntyre Sarah , Morgan Catherine , Khandaker Gulam , Badawi Nadia , Malhotra Atul
Published: April 2022

Cerebral palsy describes a group of permanent disorders of movement, motor function and posture that occur due to non-progressive insults to the developing brain. Most of the information concerning the early diagnosis of cerebral palsy originates from studies conducted in high-income countries. In this scoping review, we aimed to explore the tools used in low- and middle-income countries for the early diagnosis of cerebral palsy. A systematic search was conducted using OVID Medline and PubMed databases. “Early diagnosis” was defined as diagnosis prior to 12 months of age, and low- and middle-income countries were classified according to the World Bank classification system. We identified nine studies on the early diagnosis of cerebral palsy from low- and middle-income countries. The tools featured (n = number of studies) were: General Movement Assessment (6), neonatal magnetic resonance imaging (3), Hammersmith Neonatal Neurological Examination (2), Hammersmith Infant Neurological Examination (1) and cranial ultrasound (1). We found a paucity of published literature on the early diagnosis of cerebral palsy from low- and middle-income countries. Further research is needed to determine the tools that are accurate and feasible for use in low-resource settings, particularly since cerebral palsy is more prevalent in these areas.
Automated Classification of Cognitive Workload Levels Based on Psychophysiological and Behavioural Variables of Ex-Gaussian Distributional Features
Authors: Kaczorowska Monika , Plechawska-Wójcik Małgorzata , Tokovarov Mikhail , Krukow Paweł
Published: April 2022

The study is focused on applying ex-Gaussian parameters of eye-tracking and cognitive measures in the classification process of cognitive workload level. A computerised version of the digit symbol substitution test has been developed in order to perform the case study. The dataset applied in the study is a collection of variables related to eye-tracking: saccades, fixations and blinks, as well as test-related variables including response time and correct response number. The application of ex-Gaussian modelling to all collected data was beneficial in the context of detection of dissimilarity in groups. An independent classification approach has been applied in the study. Several classical classification methods have been invoked in the process. The overall classification accuracy reached almost 96%. Furthermore, the interpretable machine learning model based on logistic regression was adapted in order to calculate the ranking of the most valuable features, which allowed us to examine their importance.
MicroRNA Expression Profiling Predicts Nodal Status and Disease Recurrence in Patients Treated with Curative Intent for Colorectal Cancer
Authors: Davey Matthew G. , Feeney Gerard , Annuk Heidi , Paganga Maxwell , Holian Emma , Lowery Aoife J. , Kerin Michael J. , Miller Nicola
Published: April 2022

Background: Approximately one-third of colorectal cancer (CRC) patients will suffer recurrence. MiRNAs are small non-coding RNAs that play important roles in gene expression. We aimed to correlate miRNA expression with aggressive clinicopathological characteristics and survival outcomes in CRC. Methods: Tumour samples were extracted from 74 CRC patients. MiRNAs were quantified using real-time reverse transcriptase polymerase chain reaction. Descriptive statistics and Cox regression analyses were performed to correlate miRNA targets with clinicopathological and outcome data. Results: Aberrant miR-21 and miR-135b expression correlate with increased nodal stage (p = 0.039, p = 0.022). Using univariable Cox regression analyses, reduced miR-135b (β-coefficient −1.126, hazard ratio 0.324, standard error (SE) 0.4698, p = 0.017) and increased miR-195 (β-coefficient 1.442, hazard ratio 4.229, SE 0.446, p = 0.001) predicted time to disease recurrence. Survival regression trees analysis illustrated a relative cut-off of ≤0.488 for miR-195 and a relative cut-off of >−0.218 for miR-135b; both were associated with improved disease recurrence (p < 0.001, p = 0.015). Using multivariable analysis with all targets as predictors, miR-195 (β-coefficient 3.187, SE 1.419, p = 0.025) was the sole significant independent predictor of recurrence. Conclusion: MiR-195 has strong value in predicting time to recurrence in CRC patients. Additionally, miR-21 and miR-135b predict the degree nodal burden. Future studies may include these findings to personalize therapeutic and surgical decision making.
Schwann Cells Promote Myogenic Differentiation of Myoblasts and Adipogenic Mesenchymal Stromal Cells on Poly-ɛ-Caprolactone-Collagen I-Nanofibers
Authors: Cai Aijia , Zheng Zeng-Ming , Himmler Marcus , Schubert Dirk W. , Fuchsluger Thomas A. , Weisbach Volker , Horch Raymund E. , Arkudas Andreas
Published: April 2022

For the purpose of skeletal muscle tissue engineering, different cell types have been investigated regarding their myogenic differentiation potential, including co-cultured myoblasts and adipogenic mesenchymal stromal cells (Mb/ADSC). As neural cells enhance synaptic junction formation, the aim of this study was to co-culture Schwann cells (SCs) with Mb/ADSC on biocompatible electrospun aligned poly-ε-polycaprolacton (PCL)-collagen I-nanofibers. It was hypothesized that SCs, as part of the peripheral nervous system, promote the myogenic differentiation of Mb/ADSC co-cultures. Mb/ADSC were compared to Mb/ADSC/SC regarding their capacity for myogenic differentiation via immunofluorescent staining and gene expression of myogenic markers. Mb/ADSC/SC showed more myotubes after 28 days of differentiation (p ≤ 0.05). After 28 days of differentiation on electrospun aligned PCL-collagen I-nanofibers, gene expression of myosin heavy chains (MYH2) and myogenin (MYOG) was upregulated in Mb/ADSC/SC compared to Mb/ADSC (p ≤ 0.01 and p ≤ 0.05, respectively). Immunofluorescent staining for MHC showed highly aligned multinucleated cells as possible myotube formation in Mb/ADSC/SC. In conclusion, SCs promote myogenic differentiation of Mb/ADSC. The co-culture of primary Mb/ADSC/SC on PCL-collagen I-nanofibers serves as a physiological model for skeletal muscle tissue engineering, applicable to future clinical applications.
Effect of Low-Angle Boundaries on the Microstructures and Tensile Properties of the Third-Generation Single-Crystal Superalloy DD9
Authors: Yang Wanpeng , Li Jiarong , Liu Shizhong , Wang Xiaoguang , Zhao Jinqian , Shi Zhenxue
Published: April 2022

The microstructure of low-angle boundaries (LABs) of thethird-generation single-crystal superalloy DD9 and its effect on the tensile properties at 1100 °C were investigated. Double seed crystals techniques were used to obtain the specimens of DD9 alloy with LABs. The results show thatthe as-cast LABs of DD9 alloy are composed of strip-like and bulk γ′ phases with γ matrix, while no γ′ phases were foundat the LABs after the heat treatment. The LABs had little effect on the tensile strength of DD9 alloy, but hadan obvious effect on the tensile plasticity, and the fracture surfaces of tensile-ruptured DD9 alloy with LABs of 3.7°~11.4° exhibited intergranular fracture features at 1100 °C.
Detection of Unknown and Rare Pathogenic Variants in Antithrombin, Protein C and Protein S Deficiency Using High-Throughput Targeted Sequencing
Authors: Vrtel Petr , Slavik Ludek , Vodicka Radek , Stellmachova Julia , Prochazka Martin , Prochazkova Jana , Ulehlova Jana , Rohon Peter , Simurda Tomas , Stasko Jan , Martinkova Ivana , Vrtel Radek
Published: April 2022

The deficiency of natural anticoagulants—antithrombin (AT), protein C (PC), and protein S (PS)—is a highly predisposing factor for thrombosis, which is still underdiagnosed at the genetic level. We aimed to establish and evaluate an optimal diagnostic approach based on a high-throughput sequencing platform suitable for testing a small number of genes. A fast, flexible, and efficient method involving automated amplicon library preparation and target sequencing on the Ion Torrent platform was optimized. The cohort consisted of a group of 31 unrelated patients selected for sequencing due to repeatedly low levels of one of the anticoagulant proteins (11 AT-deficient, 13 PC-deficient, and 7 PS-deficient patients). The overall mutation detection rate was 67.7%, highest in PC deficiency (76.9%), and six variants were newly detected—SERPINC1 c.398A > T (p.Gln133Leu), PROC c.450C > A (p.Tyr150Ter), c.715G > C (p.Gly239Arg) and c.866C > G (p.Pro289Arg), and PROS1 c.1468delA (p.Ile490fs) and c.1931T > A (p.Ile644Asn). Our data are consistent with those of previous studies, which mostly used time-consuming Sanger sequencing for genotyping, and the indication criteria for molecular genetic testing were adapted to this process in the past. Our promising results allow for a wider application of the described methodology in clinical practice, which will enable a suitable expansion of the group of indicated patients to include individuals with severe clinical findings of thrombosis at a young age. Moreover, this approach is flexible and applicable to other oligogenic panels.
A Multi-Colony Social Learning Approach for the Self-Organization of a Swarm of UAVs
Authors: Shafiq Muhammad , Ali Zain Anwar , Israr Amber , Alkhammash Eman H. , Hadjouni Myriam
Published: April 2022

This research offers an improved method for the self-organization of a swarm of UAVs based on a social learning approach. To start, we use three different colonies and three best members i.e., unmanned aerial vehicles (UAVs) randomly placed in the colonies. This study uses max-min ant colony optimization (MMACO) in conjunction with social learning mechanism to plan the optimized path for an individual colony. Hereinafter, the multi-agent system (MAS) chooses the most optimal UAV as the leader of each colony and the remaining UAVs as agents, which helps to organize the randomly positioned UAVs into three different formations. Afterward, the algorithm synchronizes and connects the three colonies into a swarm and controls it using dynamic leader selection. The major contribution of this study is to hybridize two different approaches to produce a more optimized, efficient, and effective strategy. The results verify that the proposed algorithm completes the given objectives. This study also compares the designed method with the Non-Dominated Sorting Genetic Algorithm II (NSGA-II) to prove that our method offers better convergence and reaches the target using a shorter route than NSGA-II.
EmSM: Ensemble Mixed Sampling Method for Classifying Imbalanced Intrusion Detection Data
Authors: Jung Ilok , Ji Jaewon , Cho Changseob
Published: April 2022

Research on the application of machine learning to the field of intrusion detection is attracting great interest. However, depending on the application, it is difficult to collect the data needed for training and testing, as the least frequent data type reflects the most serious threats, resulting in imbalanced data, which leads to overfitting and hinders precise classification. To solve this problem, in this study, we propose a mixed resampling method using a hybrid synthetic minority oversampling technique with an edited neural network that increases the minority class and removes noisy data to generate a balanced dataset. A bagging ensemble algorithm is then used to optimize the model with the new data. We performed verification using two public intrusion detection datasets: PKDD2007 (balanced) and CSIC2012 (imbalanced). The proposed technique yields improved performance over state-of-the-art techniques. Furthermore, the proposed technique enables improved true positive identification and classification of serious threats that rarely occur, representing a major functional innovation.
A Unified Forensic Model Applicable to the Database Forensics Field
Authors: Alhussan Amel Ali , Al-Dhaqm Arafat , Yafooz Wael M. S. , Emara Abdel-Hamid M. , Bin Abd Razak Shukor , Khafaga Doaa Sami
Published: April 2022

The Database Forensics Investigation (DBFI) field is focused on capturing and investigating database incidents. DBFI is a subdomain of the digital forensics domain, which deals with database files and dictionaries to identify, acquire, preserve, examine, analyze, reconstruct, present, and document database incidents. Several frameworks and models have been offered for the DBFI field in the literature. However, these specific models and frameworks have redundant investigation processes and activities. Therefore, this study has two aims: (i) conducting a compressive survey to discover the challenges and issues of the DBFI field and (ii) developing a Unified forensic model for the database forensics field. To this end, the design science research (DSR) method was used in this study. The results showed that the DBFI field suffers from many issues such as the lack of standardization, multidimensional nature, heterogeneity, and ambiguity, making it complex for those working in this domain. In addition, a model was proposed in this paper, called the Unified Forensic Model (UFM), which consists of five main stages: initialization stage, acquiring stage, investigation stage, restoring and recovering stage, and evaluation stage. Each stage has several processes and activities. The applicability of UFM was evaluated from two perspectives: completeness and implementation perspectives. UFM is a novel model covering all existing DBFI models and comprises two new stages: the recovering and restoring stage and the evaluation stage. The proposed UFM is so flexible that any forensic investigator could employ it easily when investigating database incidents.
Application of the Reformulated Gash Analytical Model for Rainfall Interception Loss to Unmanaged High-Density Coniferous Plantations Laden with Dead Branches
Authors: Jeong Seonghun , Kume Tomonori , Shinohara Yoshinori , Farahnak Moein , Otsuki Kyoichi
Published: April 2022

Interception loss (IL) by the forest canopy removes a substantial quantity of rainwater within forested ecosystems. The large-scale unmanaged Japanese coniferous plantations with high stand density (SD) in Japan raise concerns about an additional increasing IL as a result of a new influential factor of dead branches under canopies. Thus, evaluating the usage of IL estimation models is vital to regulating the water and environment in such coniferous plantations. This study aimed to examine the applicability of the reformulated Gash analytical model (RGAM) to unmanaged coniferous plantations with high SD laden with dead branches. We established two plots (P1 and P2) laden with dead branches under the same SD of 2250 stems ha−1 but with different numbers of dead branches (56 vs. 47 branches per tree) in an unmanaged Japanese coniferous plantation. Results demonstrated that a large difference was found in canopy storage capacity (S) in P1 and P2 (3.94 vs. 3.25 mm), which was influenced by the different number of dead branches; therefore, the IL ratio to gross rainfall differed considerably (32.7% in P1 and 26.7% in P2) regardless of the SD being the same. The difference in S enables the RGAM to reflect the influence of dead branch structures on IL, leading to an acceptable RGAM performance for both P1 and P2 (“fair” IL relative errors: −20.2% vs. −16.1%) in the present study of unmanaged coniferous plantations with high SD laden with dead branches.
Promoting Caregiver Early Childhood Development Behaviors through Social and Behavioral Change Communication Program in Tanzania
Authors: Broadbent Eliza , McConkie McKayla , Aleson Emily , Kim Lily , Stewart Rebekah , Mulokozi Generose , Dearden Kirk A. , Linehan Mary , Cherian Dennis , Torres Scott , Crookston Ben T. , Hall Parley C. , West Joshua H.
Published: April 2022

Objectives: Stunting remains a prevalent issue in Tanzania. The consequences of stunting include reduced height, greater susceptibility to disease, and diminished cognitive ability throughout the lifespan. Lack of psychosocial stimulation is associated with increased stunting, particularly in terms of its cognitive impact. The Addressing Stunting in Tanzania Early (ASTUTE) program was a large social and behavior change communication (SBCC) intervention that aimed to reduce childhood stunting in the region by targeting early childhood development (ECD) behaviors. The purpose of this study is to report on the extent to which exposure to ASTUTE might be related to ECD behaviors. Methods: ASTUTE disseminated program messages via a mass media campaign and interpersonal communication (IPC). Logistic regression models were used to explore the relationship between exposure to TV, radio, IPC messages, and key ECD behaviors of female primary caregivers and male heads of household. Results: Among primary caregivers, IPC was positively associated with all ECD behaviors measured. Radio was associated with all behaviors except drawing with their child. TV was associated with all behaviors except playing with their child. Among heads of household, only the radio was positively associated with the ECD behaviors measured. Conclusions for practice: Findings indicate that SBCC interventions that include mass media and IPC components may be effective at promoting parental engagement in ECD behaviors. Significance: We know that ECD is important for a child’s development. We know that parents play a critical role in promoting ECD behaviors. We are still exploring ways to influence parents so that they are more involved in ECD behaviors. The results presented here provide evidence for successful mass media and IPC efforts to improve parents’ ECD behaviors. We hope this study will add more evidence for large interventions such as these to the literature, and we are very hopeful that governments and large international NGOs will prioritize SBCC approaches in the future, especially in locations where face-to-face interventions may be challenging.
A Systematic Review of Scientific Studies on the Effects of Music in People with or at Risk for Autism Spectrum Disorder
Authors: Applewhite Briana , Cankaya Zeynep , Heiderscheit Annie , Himmerich Hubertus
Published: April 2022

The prevalence of autism spectrum disorders (ASD) is globally increasing, and the current available interventions show variable success. Thus, there is a growing interest in additional interventions such as music therapy (MT). Therefore, we aimed to provide a comprehensive and systematic review of music and people with, or at risk of, ASD. We used the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines and used PubMed, PsycINFO, and Web of Science as databases, with “music”, “music therapy”, “autism spectrum disorder”, and “ASD” as search terms. Among the identified and screened articles, 81 out of 621 qualified as scientific studies involving a total of 43,353 participants. These studies investigated the peculiarities of music perception in people with ASD, as well as the effects of music and MT in this patient group. Most of the music-based interventions were beneficial in improving social, emotional, and behavioural problems. However, the availability of studies utilizing a rigorous randomized controlled trial (RCT) design was scarce. Most of the studies had a small sample size, and the applied therapeutic and scientific research methods were heterogeneous.
DBSCAN Spatial Clustering Analysis of Urban “Production–Living–Ecological” Space Based on POI Data: A Case Study of Central Urban Wuhan, China
Authors: Tu Xiaoqiang , Fu Chun , Huang An , Chen Hailian , Ding Xing
Published: April 2022

As urban spatial patterns are the prerequisite and foundation of urban planning, spatial pattern research will enable its improvement. The formation mechanism and definition of an urban “production–living–ecological” space is used here to construct a classification system for POI (points of interests) data, crawl POI data in Python, and DBSCAN (density-based spatial clustering of application with noise) to perform cluster analysis. This mechanism helps to determine the cluster density and to study the overall and component spatial patterns of the “production–living–ecological” space in the central urban area of Wuhan. The research results are as follows. (1) The spatial patterns of “production–living–ecological” space have significant spatial hierarchical characteristics. Among them, the spatial polarizations of “living” and “production” are significant, while the “ecological” spatial distribution is more balanced. (2) The “living” space and “production” space noise points account for a small proportion of the total and are locally clustered to easily become areas with development potential. The “ecological” space noise points account for a large proportion of the total. (3) The traffic accessibility has an important influence on the spatial patterns of “production–living–ecological” space. (4) The important spatial nodes of each element are consistent with the overall plan of Wuhan, but the distribution of the nodes for some elements is inconsistent. The research results show that the POI big data can accurately reveal the characteristics of urban spatial patterns, which is scientific and practical and provides a useful reference for the sustainable development of territorial and spatial planning.
A Compositional Analysis of Physical Activity, Sedentary Time, and Sleep and Associated Health Outcomes in Children and Adults with Cystic Fibrosis
Authors: Bianchim Mayara S. , McNarry Melitta A. , Holland Anne , Cox Narelle S. , Dreger Julianna , Barker Alan R. , Williams Craig A. , Denford Sarah , Mackintosh Kelly A.
Published: April 2022

This study sought to investigate the association of light physical activity (LPA), moderate-to-vigorous physical activity (MVPA), sedentary time (SED), and sleep with lung function in children and adults with CF. In total, 86 children (41 females; 13.6 ± 2.8 years; FEV1%predicted: 86 ± 1%) and 43 adults (21 females; 24.6 ± 4.7 years; FEV1%predicted: 63 ± 21%) with CF participated in this study. Wrist-worn accelerometery was used to assess PA, SED and sleep. Compositional linear regression models were conducted following normalisation via isometric log-ratio transformations. Sequential binary partitioning was applied to investigate the impact of reallocating 10 to 30 min between each behaviour on FEV1%predicted. A decline in FEV1%predicted was predicted with the reallocation of 30 min from MVPA to SED or LPA or sleep to any other behaviour in children (−3.04–−0.005%) and adults (−3.58–−0.005%). Conversely, improvements in FEV1%predicted were predicted when 30 min was reallocated to MVPA from LPA or SED in children (0.12–1.59%) and adults (0.77–2.10%), or when 30 min was reallocated to sleep from any other behaviour in both children (0.23–2.56%) and adults (1.08–3.58%). This study supports the importance of MVPA and sleep for maintaining and promoting lung function in people with CF.
The Relationship between Anxiety and Depression Levels and General Health Status before and 12 Months after SUI Treatment in Postmenopausal Women from the Lower Silesian Population
Authors: Zalewski Maciej , Kołodyńska Gabriela , Fink-Lwow Felicja , Mucha Anna , Andrzejewski Waldemar
Published: April 2022

Menopause is often the cut-off point from which most cases of stress urinary incontinence (SUI) in women begin. This dysfunction affects not only the physical experience of the patient, but is also related to the psychological aspects, leading to a reduced quality of life. Despite the large number of patients with SUI and the frequent use of surgical treatment for this condition, there are few scientific reports evaluating the effectiveness of the procedure in terms of reducing depressive symptoms or improving overall health. The aim of this study was to evaluate the relationship between anxiety and depression and general health status before and 12 months after surgical treatment for SUI in postmenopausal women. Seventy-five patients qualified for the study, but due to the long study duration, both sets of questionnaires were eventually obtained from 60 postmenopausal patients. All patients that qualified for the study had a trans obturator tape (TOT) procedure. All patients enrolled in the project were given the Hospital Anxiety and Depression Scale (hAdS) and King’s Health Questionnaire (KHQ). After 12 months of surgery with midurethral slings, symptoms of depression were present in only a small number of subjects, 11.7%, and anxiety was present in 13.3% of the entire group. The study confirms that patients with a general poor health condition may suffer from depression or anxiety, and therefore may also need psychological treatment. Patients with SUI should therefore receive therapeutic care from a multidisciplinary team, in which therapeutic activities are divided between doctors, nurses, physiotherapists and psychologists. As a result of the treatment, after 12 months, we confirmed a significant improvement in patients with depression and anxiety disorders.
Endocytosis at the Crossroad of Polarity and Signaling Regulation: Learning from Drosophila melanogaster and Beyond
Authors: Papagiannouli Fani
Published: April 2022

Cellular trafficking through the endosomal–lysosomal system is essential for the transport of cargo proteins, receptors and lipids from the plasma membrane inside the cells and across membranous organelles. By acting as sorting stations, vesicle compartments direct the fate of their content for degradation, recycling to the membrane or transport to the trans-Golgi network. To effectively communicate with their neighbors, cells need to regulate their compartmentation and guide their signaling machineries to cortical membranes underlying these contact sites. Endosomal trafficking is indispensable for the polarized distribution of fate determinants, adaptors and junctional proteins. Conversely, endocytic machineries cooperate with polarity and scaffolding components to internalize receptors and target them to discrete membrane domains. Depending on the cell and tissue context, receptor endocytosis can terminate signaling responses but can also activate them within endosomes that act as signaling platforms. Therefore, cell homeostasis and responses to environmental cues rely on the dynamic cooperation of endosomal–lysosomal machineries with polarity and signaling cues. This review aims to address advances and emerging concepts on the cooperative regulation of endocytosis, polarity and signaling, primarily in Drosophila melanogaster and discuss some of the open questions across the different cell and tissue types that have not yet been fully explored.
Oncostatin M Induces Lipolysis and Suppresses Insulin Response in 3T3-L1 Adipocytes
Authors: Bailey Jennifer L. , Hang Hardy , Boudreau Anik , Elks Carrie M.
Published: April 2022

Oncostatin M (OSM) is an immune cell-derived cytokine that is upregulated in adipose tissue in obesity. Upon binding its receptor (OSMR), OSM induces the phosphorylation of the p66 subunit of Src homology 2 domain-containing transforming protein 1 (SHC1), called p66Shc, and activates the extracellular signal-related kinase (ERK) pathway. Mice with adipocyte-specific OSMR deletion (OsmrFKO) are insulin resistant and exhibit adipose tissue inflammation, suggesting that intact adipocyte OSM–OSMR signaling is necessary for maintaining adipose tissue health. How OSM affects specific adipocyte functions is still unclear. Here, we examined the effects of OSM on adipocyte lipolysis. We treated 3T3-L1 adipocytes with OSM, insulin, and/or inhibitors of SHC1 and ERK and measured glycerol release. We also measured phosphorylation of p66Shc, ERK, and insulin receptor substrate-1 (IRS1) and the expression of lipolysis-associated genes in OSM-exposed 3T3-L1 adipocytes and primary adipocytes from control and OsmrFKO mice. We found that OSM induces adipocyte lipolysis via a p66Shc-ERK pathway and inhibits the suppression of lipolysis by insulin. Further, OSM induces phosphorylation of inhibitory IRS1 residues. We conclude that OSM is a stimulator of lipolysis and inhibits adipocyte insulin response. Future studies will determine how these roles of OSM affect adipose tissue function in health and disease.
Does Intracellular Metabolism Render Gemcitabine Uptake Undetectable in Mass Spectrometry?
Authors: Müller Julian Peter , Gründemann Dirk
Published: April 2022

The ergothioneine transporter ETT (formerly OCTN1; human gene symbol SLC22A4) is a powerful and highly specific transporter for the uptake of ergothioneine (ET). Recently, Sparreboom et al. reported that the ETT would transport nucleosides and nucleoside analogues such as cytarabine and gemcitabine with the highest efficiency. In our assay system, we could not detect any such transport. Subsequently, Sparreboom suggested that the intracellular metabolization of the nucleosides occurs so fast that the original compounds cannot be detected by LC–MS/MS after inward transport. Our current experiments with 293 cells disprove this hypothesis. Uptake of gemcitabine was easily detected by LC–MS/MS measurements when we expressed the Na+/nucleoside cotransporter CNT3 (SLC28A3). Inward transport was 1280 times faster than the intracellular production of gemcitabine triphosphate. The deoxycytidine kinase inhibitor 2-thio-2′-deoxycytidine markedly blocked the production of gemcitabine triphosphate. There was no concomitant surge in intracellular gemcitabine, however. This does not fit the rapid phosphorylation of gemcitabine. Uptake of cytarabine was very slow, but detection by MS was still possible. When the ETT was expressed and incubated with gemcitabine, there was no increase in intracellular gemcitabine triphosphate. We conclude that the ETT does not transport nucleosides.
Effect of Long-Term Supplementation with Acetic Acid on the Skeletal Muscle of Aging Sprague Dawley Rats
Authors: Maruta Hitomi , Abe Reina , Yamashita Hiromi
Published: April 2022

Mitochondrial function in skeletal muscle, which plays an essential role in oxidative capacity and physical activity, declines with aging. Acetic acid activates AMP-activated protein kinase (AMPK), which plays a key role in the regulation of whole-body energy by phosphorylating key metabolic enzymes in both biosynthetic and oxidative pathways and stimulates gene expression associated with slow-twitch fibers and mitochondria in skeletal muscle cells. In this study, we investigate whether long-term supplementation with acetic acid improves age-related changes in the skeletal muscle of aging rats in association with the activation of AMPK. Male Sprague Dawley (SD) rats were administered acetic acid orally from 37 to 56 weeks of age. Long-term supplementation with acetic acid decreased the expression of atrophy-related genes, such as atrogin-1, muscle RING-finger protein-1 (MuRF1), and transforming growth factor beta (TGF-β), activated AMPK, and affected the proliferation of mitochondria and type I fiber-related molecules in muscles. The findings suggest that acetic acid exhibits an anti-aging function in the skeletal muscles of aging rats.
Comparison of Physicochemical, Mechanical, and (Micro-)Biological Properties of Sintered Scaffolds Based on Natural- and Synthetic Hydroxyapatite Supplemented with Selected Dopants
Authors: Hudecki Andrzej , Łyko-Morawska Dorota , Kasprzycka Anna , Kazek-Kęsik Alicja , Likus Wirginia , Hybiak Jolanta , Jankowska Kornelia , Kolano-Burian Aleksandra , Włodarczyk Patryk , Wolany Weronika , Markowski Jarosław , Maziarz Wojciech , Niedzielska Iwona , Pakieła Wojciech , Nowak Mariusz , Łos Marek J.
Published: April 2022

The specific combinations of materials and dopants presented in this work have not been previously described. The main goal of the presented work was to prepare and compare the different properties of newly developed composite materials manufactured by sintering. The synthetic- (SHAP) or natural- (NHAP) hydroxyapatite serves as a matrix and was doped with: (i) organic: multiwalled carbon nanotubes (MWCNT), fullerenes C60, (ii) inorganic: Cu nanowires. Research undertaken was aimed at seeking novel candidates for bone replacement biomaterials based on hydroxyapatite—the main inorganic component of bone, because bone reconstructive surgery is currently mostly carried out with the use of autografts; titanium or other non-hydroxyapatite -based materials. The physicomechanical properties of the developed biomaterials were tested by Scanning Electron Microscopy (SEM), Dielectric Spectroscopy (BSD), Nuclear Magnetic Resonance (NMR), and Differential Scanning Calorimetry (DSC), as well as microhardness using Vickers method. The results showed that despite obtaining porous sinters. The highest microhardness was achieved for composite materials based on NHAP. Based on NMR spectroscopy, residue organic substances could be observed in NHAP composites, probably due to the organic structures that make up the tooth. Microbiology investigations showed that the selected samples exhibit bacteriostatic properties against Gram-positive reference bacterial strain S. epidermidis (ATCC 12228); however, the property was much less pronounced against Gram-negative reference strain E. coli (ATCC 25922). Both NHAP and SHAP, as well as their doped derivates, displayed in good general compatibility, with the exception of Cu-nanowire doped derivates.
Connection between Mesenchymal Stem Cells Therapy and Osteoclasts in Osteoarthritis
Authors: Ibáñez Lidia , Guillem-Llobat Paloma , Marín Marta , Guillén María Isabel
Published: April 2022

The use of mesenchymal stem cells constitutes a promising therapeutic approach, as it has shown beneficial effects in different pathologies. Numerous in vitro, pre-clinical, and, to a lesser extent, clinical trials have been published for osteoarthritis. Osteoarthritis is a type of arthritis that affects diarthritic joints in which the most common and studied effect is cartilage degradation. Nowadays, it is known that osteoarthritis is a disease with a very powerful inflammatory component that affects the subchondral bone and the rest of the tissues that make up the joint. This inflammatory component may induce the differentiation of osteoclasts, the bone-resorbing cells. Subchondral bone degradation has been suggested as a key process in the pathogenesis of osteoarthritis. However, very few published studies directly focus on the activity of mesenchymal stem cells on osteoclasts, contrary to what happens with other cell types of the joint, such as chondrocytes, synoviocytes, and osteoblasts. In this review, we try to gather the published bibliography in relation to the effects of mesenchymal stem cells on osteoclastogenesis. Although we find promising results, we point out the need for further studies that can support mesenchymal stem cells as a therapeutic tool for osteoclasts and their consequences on the osteoarthritic joint.
Mutated KIT Tyrosine Kinase as a Novel Molecular Target in Acute Myeloid Leukemia
Authors: Katagiri Seiichiro , Chi SungGi , Minami Yosuke , Fukushima Kentaro , Shibayama Hirohiko , Hosono Naoko , Yamauchi Takahiro , Morishita Takanobu , Kondo Takeshi , Yanada Masamitsu , Yamamoto Kazuhito , Kuroda Junya , Usuki Kensuke , Akahane Daigo , Gotoh Akihiko
Published: April 2022

KIT is a type-III receptor tyrosine kinase that contributes to cell signaling in various cells. Since KIT is activated by overexpression or mutation and plays an important role in the development of some cancers, such as gastrointestinal stromal tumors and mast cell disease, molecular therapies targeting KIT mutations are being developed. In acute myeloid leukemia (AML), genome profiling via next-generation sequencing has shown that several genes that are mutated in patients with AML impact patients’ prognosis. Moreover, it was suggested that precision-medicine-based treatment using genomic data will improve treatment outcomes for AML patients. This paper presents (1) previous studies regarding the role of KIT mutations in AML, (2) the data in AML with KIT mutations from the HM-SCREEN-Japan-01 study, a genome profiling study for patients newly diagnosed with AML who are unsuitable for the standard first-line treatment (unfit) or have relapsed/refractory AML, and (3) new therapies targeting KIT mutations, such as tyrosine kinase inhibitors and heat shock protein 90 inhibitors. In this era when genome profiling via next-generation sequencing is becoming more common, KIT mutations are attractive novel molecular targets in AML.
Cardiovascular Diseases—A Focus on Atherosclerosis, Its Prophylaxis, Complications and Recent Advancements in Therapies
Authors: Bułdak Łukasz
Published: April 2022

Long-term consequences of atherosclerosis remain the major culprit of mortality in developed and developing countries [...]
Localization of BDNF and Calretinin in Olfactory Epithelium and Taste Buds of Zebrafish (Danio rerio)
Authors: Aragona Marialuisa , Porcino Caterina , Guerrera Maria Cristina , Montalbano Giuseppe , Laurà Rosaria , Levanti Maria , Abbate Francesco , Cobo Teresa , Capitelli Gabriel , Calapai Fabrizio , Vega José A , Germanà Antonino
Published: April 2022

Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin family and it is involved in several fundamental functions in the central and peripheral nervous systems, and in sensory organs. BDNF regulates the chemosensory systems of mammals and is consistently expressed in those organs. In zebrafish, the key role of BDNF in the biology of the hair cells of the inner ear and lateral line system has recently been demonstrated. However, only some information is available about its occurrence in the olfactory epithelium, taste buds, and cutaneous isolated chemosensory cells. Therefore, this study was undertaken to analyze the involvement of BDNF in the chemosensory organs of zebrafish during the larval and adult stages. To identify cells displaying BDNF, we compared the cellular pattern of BDNF-displaying cells with those immunoreactive for calretinin and S100 protein. Our results demonstrate the localization of BDNF in the sensory part of the olfactory epithelium, mainly in the ciliated olfactory sensory neurons in larvae and adult zebrafish. Intense immunoreaction for BDNF was also observed in the chemosensory cells of oral and cutaneous taste buds. Moreover, a subpopulation of olfactory sensory neurons and chemosensory cells of olfactory rosette and taste bud, respectively, showed marked immunopositivity for calcium-binding protein S100 and calretinin. These results demonstrate the possible role of BDNF in the development and maintenance of olfactory sensory neurons and sensory cells in the olfactory epithelium and taste organs of zebrafish during all stages of development.