bluuebunny/crossref_metadata_2025 huggingface dataset:
Non-Traditional Physical Education Classes Improve High School Students’ Movement Competency and Fitness: A Mixed-Methods Program Evaluation Study
Authors: Heinrich Katie M. , Beattie Cassandra M. , Crawford Derek A. , Stoepker Peter , George Jason
Published: May 2023

Non-traditional physical education (PE) programs may facilitate functional movement patterns and develop fitness and work capacity to facilitate long-term physical activity. This program evaluation study compared changes in body composition, movement competency, work capacity, and fitness for high school students in CrossFit or weight training PE; both classes were hypothesized to improve each area, with greater improvements in the CrossFit class. Students participated in 57 min classes 4 days per week for 9 months. Measures including body composition, movement competencies (squat, lunge, push-up, pull-up, hinge, and brace), work capacity (two CrossFit workouts), and fitness (air squats, push-ups, inverted row, plank hold, horizontal and vertical jumps, 5 rep max back squat and press, 500 m bike, and 12 min run) were taken at baseline, midpoint, and post-test. Focus groups to assess students’ experiences and outcomes were conducted at post-test. Students significantly improved in movement competencies (ps = 0.034 to <0.001), work capacity (ps < 0.001), and all fitness tests (ps = 0.036 to <0.001). The CrossFit class was only superior on the 500 m bike. Four themes were identified from the focus groups: (1) increased self-confidence, (2) health improvements, (3) newfound community, and (4) translational sports improvements. Future research should examine changes using an experimental design.
Research Participant Selection Bias in the Workshop Using Socially Assistive Robots for Older Adults and Its Effect on Population Representativeness
Authors: Igarashi Toshiharu , Sugawara Ikuko , Inoue Takenobu , Nihei Misato
Published: May 2023

Every research participant has their own personality characteristics. For example, older adults assisted by socially assistive robots (SAR) may have their own unique characteristics and may not be representative of the general population of older adults. In this research, we compared the average personality characteristics of participants in a workshop on robotics recruited directly through posting with those of older Japanese adults to examine participant selection bias and group representativeness for future study of SARs. After a one-week recruitment period, the workshop was attended by 20 older participants (nine males and 11 females) aged between 62 and 86 years. Extroversion among workshop participants was 4.38, 0.40 higher than the average for older adults in Japan. The workshop participants’ openness was 4.55, 1.09 higher than the average for the Japanese elderly. Thus, the results indicate a slight selection bias in the personal characteristics of the participants depending on the recruitment method when compared to the Japan national average for older adults. In addition, only one of 20 participants was below the cutoff on the LSNS-6 score and considered to have a tendency toward social isolation. The development and introduction of socially assistive robots is often being considered to support people in social isolation in their daily lives; however, the results of this study showed that it is difficult to recruit people who tend to be socially isolated when gathering research participants by methods such as posting. Therefore, the effectiveness of the method of recruiting participants should be carefully verified in research regarding socially assistive robots.
Citric Acid Confers Broad Antibiotic Tolerance through Alteration of Bacterial Metabolism and Oxidative Stress
Authors: Li Xue-Song , Xue Jun-Ze , Qi Yu , Muhammad Inam , Wang Hao , Li Xuan-Yu , Luo Yi-Jia , Zhu Dao-Mi , Gao Yun-Hang , Kong Ling-Cong , Ma Hong-Xia
Published: May 2023

Antibiotic tolerance has become an increasingly serious crisis that has seriously threatened global public health. However, little is known about the exogenous factors that can trigger the development of antibiotic tolerance, both in vivo and in vitro. Herein, we found that the addition of citric acid, which is used in many fields, obviously weakened the bactericidal activity of antibiotics against various bacterial pathogens. This mechanistic study shows that citric acid activated the glyoxylate cycle by inhibiting ATP production in bacteria, reduced cell respiration levels, and inhibited the bacterial tricarboxylic acid cycle (TCA cycle). In addition, citric acid reduced the oxidative stress ability of bacteria, which led to an imbalance in the bacterial oxidation–antioxidant system. These effects together induced the bacteria to produce antibiotic tolerance. Surprisingly, the addition of succinic acid and xanthine could reverse the antibiotic tolerance induced by citric acid in vitro and in animal infection models. In conclusion, these findings provide new insights into the potential risks of citric acid usage and the relationship between antibiotic tolerance and bacterial metabolism.
Molecular and Genetics-Based Systems for Tracing the Evolution and Exploring the Mechanisms of Human Norovirus Infections
Authors: Lin Sheng-Chieh , Bai Geng-Hao , Lin Pei-Chun , Chen Chung-Yung , Hsu Yi-Hsiang , Lee Yuan-Chang , Chen Shih-Yen
Published: May 2023

Human noroviruses (HuNoV) are major causes of acute gastroenteritis around the world. The high mutation rate and recombination potential of noroviruses are significant challenges in studying the genetic diversity and evolution pattern of novel strains. In this review, we describe recent advances in the development of technologies for not only the detection but also the analysis of complete genome sequences of noroviruses and the future prospects of detection methods for tracing the evolution and genetic diversity of human noroviruses. The mechanisms of HuNoV infection and the development of antiviral drugs have been hampered by failure to develop the infectious virus in a cell model. However, recent studies have demonstrated the potential of reverse genetics for the recovery and generation of infectious viral particles, suggesting the utility of this genetics-based system as an alternative for studying the mechanisms of viral infection, such as cell entry and replication.
Heterocyclic Compounds as Synthetic Tyrosinase Inhibitors: Recent Advances
Authors: Vittorio Serena , Dank Christian , Ielo Laura
Published: May 2023

Tyrosinase is a copper-containing enzyme which is widely distributed in nature (e.g., bacteria, mammals, fungi) and involved in two consecutive steps of melanin biosynthesis. In humans, an excessive production of melanin can determine hyperpigmentation disorders as well as neurodegenerative processes in Parkinson’s disease. The development of molecules able to inhibit the high activity of the enzyme remain a current topic in medicinal chemistry, because the inhibitors reported so far present several side effects. Heterocycle-bearing molecules are largely diffuse in this sense. Due to their importance as biologically active compounds, we decided to report a comprehensive review of synthetic tyrosinase inhibitors possessing heterocyclic moieties reported within the last five years. For the reader’s convenience, we classified them as inhibitors of mushroom tyrosinase (Agaricus bisporus) and human tyrosinase.
Translocation of Methionine Adenosyl Transferase MAT2A and Its Prognostic Relevance for Liver Hepatocellular Carcinoma
Authors: Chu Pei-Yi , Chou Dev-Aur , Chen Po-Ming , Chiang En-Pei Isabel
Published: May 2023

Methionine adenosyl transferases (MATs) catalyze the synthesis of the biological methyl donor adenosylmethionine (SAM). Dysregulation of MATs has been associated with carcinogenesis in humans. We previously found that downregulation of the MAT1A gene enriches the protein-associated translation process and worsens liver hepatocellular carcinoma (LIHC) prognosis. We also discovered that subcellular localization of the MAT2A protein has independently prognostic relevance in breast cancer patients. The present study aimed to examined the clinical relevance of MAT2A translocation in human LIHC. Essential methionine cycle gene expressions in TCGA LIHC datasets were analyzed using Gene Expression Profiling Interactive Analysis 2 (GEPIA2). The protein expression pattern of MAT2A was determined in the tissue array of our own LIHC cohort (n = 261) using immuno-histochemistry, and the prognostic relevance of MAT2A protein’s subcellular localization expression was examined using Kaplan–Meier survival curves. LIHC patients with higher MAT2A mRNA expression had a worse survival rate (p = 0.0083). MAT2A protein immunoreactivity was observed in both cytoplasm and nucleus fractions in the tissue array. Tumor tissues had elevated MAT2A protein expression in both cytoplasm and nucleus compared to their adjacent normal tissues. A higher cytoplasmic to nuclear MAT2A protein expression ratio (C/N) was found in female LIHC patients compared to that of male patients (p = 0.047). Kaplan–Meier survival curves showed that a lower MAT2A C/N correlated with poor overall survival in female LIHC patients (10-year survival rate: 29.2% vs. 68.8%, C/N ≤ 1.0 vs. C/N > 1.0, log-rank p = 0.004). Moreover, we found that specificity protein 1 (SP1) may have a potential interaction with nuclear MAT2A protein, using protein–protein interaction; this we found using the GeneMANIA algorithm. We explored the possible protective effects of the estrogen axis in LIHC using the Human Protein Atlas (HPA), and found evidence supporting a possible protective effect of estrogen-related protein ESSRG in LIHC. The localization of SP1 and MAT2 appeared to be inversely associated with ESRRG expression in LIHC. The present study demonstrated the translocation of MAT2A and its prognostic relevance in female LIHC patients. Our findings suggest the potential of estrogen in SP1 regulation and localization of MAT2A, as therapeutic modalities against in female LIHC patients.
Correlated Target Search by Vaccinia Virus Uracil–DNA Glycosylase, a DNA Repair Enzyme and a Processivity Factor of Viral Replication Machinery
Authors: Diatlova Evgeniia A. , Mechetin Grigory V. , Yudkina Anna V. , Zharkov Vasily D. , Torgasheva Natalia A. , Endutkin Anton V. , Shulenina Olga V. , Konevega Andrey L. , Gileva Irina P. , Shchelkunov Sergei N. , Zharkov Dmitry O.
Published: May 2023

The protein encoded by the vaccinia virus D4R gene has base excision repair uracil–DNA N-glycosylase (vvUNG) activity and also acts as a processivity factor in the viral replication complex. The use of a protein unlike PolN/PCNA sliding clamps is a unique feature of orthopoxviral replication, providing an attractive target for drug design. However, the intrinsic processivity of vvUNG has never been estimated, leaving open the question whether it is sufficient to impart processivity to the viral polymerase. Here, we use the correlated cleavage assay to characterize the translocation of vvUNG along DNA between two uracil residues. The salt dependence of the correlated cleavage, together with the similar affinity of vvUNG for damaged and undamaged DNA, support the one-dimensional diffusion mechanism of lesion search. Unlike short gaps, covalent adducts partly block vvUNG translocation. Kinetic experiments show that once a lesion is found it is excised with a probability ~0.76. Varying the distance between two uracils, we use a random walk model to estimate the mean number of steps per association with DNA at ~4200, which is consistent with vvUNG playing a role as a processivity factor. Finally, we show that inhibitors carrying a tetrahydro-2,4,6-trioxopyrimidinylidene moiety can suppress the processivity of vvUNG.
In-Frame Deletion of Dystrophin Exons 8–50 Results in DMD Phenotype
Authors: Egorova Tatiana V. , Galkin Ivan I. , Velyaev Oleg A. , Vassilieva Svetlana G. , Savchenko Irina M. , Loginov Vyacheslav A. , Dzhenkova Marina A. , Korshunova Diana S. , Kozlova Olga S. , Ivankov Dmitry N. , Polikarpova Anna V.
Published: May 2023

Mutations that prevent the production of proteins in the DMD gene cause Duchenne muscular dystrophy. Most frequently, these are deletions leading to reading-frame shift. The “reading-frame rule” states that deletions that preserve ORF result in a milder Becker muscular dystrophy. By removing several exons, new genome editing tools enable reading-frame restoration in DMD with the production of BMD-like dystrophins. However, not every truncated dystrophin with a significant internal loss functions properly. To determine the effectiveness of potential genome editing, each variant should be carefully studied in vitro or in vivo. In this study, we focused on the deletion of exons 8–50 as a potential reading-frame restoration option. Using the CRISPR-Cas9 tool, we created the novel mouse model DMDdel8-50, which has an in-frame deletion in the DMD gene. We compared DMDdel8-50 mice to C57Bl6/CBA background control mice and previously generated DMDdel8-34 KO mice. We discovered that the shortened protein was expressed and correctly localized on the sarcolemma. The truncated protein, on the other hand, was unable to function like a full-length dystrophin and prevent disease progression. On the basis of protein expression, histological examination, and physical assessment of the mice, we concluded that the deletion of exons 8–50 is an exception to the reading-frame rule.
Inducible and Conditional Activation of Adult Neurogenesis Rescues Cadmium-Induced Hippocampus-Dependent Memory Deficits in ApoE4-KI Mice
Authors: Matsushita Megumi T. , Wang Hao , Abel Glen M. , Xia Zhengui
Published: May 2023

The apolipoprotein E (ApoE) gene is a genetic risk factor for late-onset Alzheimer’s disease, in which ε4 allele carriers have increased risk compared to the common ε3 carriers. Cadmium (Cd) is a toxic heavy metal and a potential neurotoxicant. We previously reported a gene–environment interaction (GxE) effect between ApoE4 and Cd that accelerates or increases the severity of the cognitive decline in ApoE4-knockin (ApoE4-KI) mice exposed to 0.6 mg/L CdCl2 through drinking water compared to control ApoE3-KI mice. However, the mechanisms underlying this GxE effect are not yet defined. Because Cd impairs adult neurogenesis, we investigated whether genetic and conditional stimulation of adult neurogenesis can functionally rescue Cd-induced cognitive impairment in ApoE4-KI mice. We crossed either ApoE4-KI or ApoE3-KI to an inducible Cre mouse strain, Nestin-CreERTM:caMEK5-eGFPloxP/loxP (designated as caMEK5), to generate ApoE4-KI:caMEK5 and ApoE3-KI:caMEK5. Tamoxifen administration in these mice genetically and conditionally induces the expression of caMEK5 in adult neural stem/progenitor cells, enabling the stimulation of adult neurogenesis in the brain. Male ApoE4-KI:caMEK5 and ApoE3-KI:caMEK5 mice were exposed to 0.6 mg/L CdCl2 throughout the experiment, and tamoxifen was administered once Cd-induced impairment in spatial working memory was consistently observed. Cd exposure impaired spatial working memory earlier in ApoE4-KI:caMEK5 than in ApoE3-KI:caMEK5 mice. In both strains, these deficits were rescued after tamoxifen treatment. Consistent with these behavioral findings, tamoxifen treatment enhanced adult neurogenesis by increasing the morphological complexity of adult-born immature neurons. These results provide evidence for a direct link between impaired spatial memory and adult neurogenesis in this GxE model.
Genetic Diversity of a Heat Activated Channel—TRPV1 in Two Desert Gerbil Species with Different Heat Sensitivity
Authors: Wang Bing , Zhang Xue-Ying , Yuan Shuai , Fu He-Ping , Wang Chen-Zhu , Wang De-Hua
Published: May 2023

Heat sensation and tolerance are crucial for determining species’ survival and distribution range of small mammals. As a member of the transmembrane proteins, transient receptor potential vanniloid 1 (TRPV1) is involved in the sensation and thermoregulation of heat stimuli; however, the associations between animal’s heat sensitivity and TRPV1 in wild rodents are less studied. Here, we found that Mongolian gerbils (Meriones unguiculatus), a rodent species living in Mongolia grassland, showed an attenuated sensitivity to heat compared with sympatrically distributed mid-day gerbils (M. meridianus) based on a temperature preference test. To explain this phenotypical difference, we measured the TRPV1 mRNA expression of two gerbil species in the hypothalamus, brown adipose tissue, and liver, and no statistical difference was detected between two species. However, according to the bioinformatics analysis of TRPV1 gene, we identified two single amino acid mutations on two TRPV1 orthologs in these two species. Further Swiss-model analyses of two TRPV1 protein sequences indicated the disparate conformations at amino acid mutation sites. Additionally, we confirmed the haplotype diversity of TRPV1 in both species by expressing TRPV1 genes ectopicly in Escherichia coli system. Taken together, our findings supplemented genetic cues to the association between the discrepancy of heat sensitivity and the functional differentiation of TRPV1 using two wild congener gerbils, promoting the comprehension of the evolutionary mechanisms of the TRPV1 gene for heat sensitivity in small mammals.
Structure-Guided Design of N-Methylpropargylamino-Quinazoline Derivatives as Multipotent Agents for the Treatment of Alzheimer’s Disease
Authors: Svobodova Barbora , Pulkrabkova Lenka , Panek Dawid , Misiachna Anna , Kolcheva Marharyta , Andrys Rudolf , Handl Jiri , Capek Jan , Nyvltova Pavlina , Rousar Tomas , Prchal Lukas , Hepnarova Vendula , Hrabinova Martina , Muckova Lubica , Tosnerova Daniela , Karabanovich Galina , Finger Vladimir , Soukup Ondrej , Horak Martin , Korabecny Jan
Published: May 2023

Alzheimer’s disease (AD) is a complex disease with an unknown etiology. Available treatments, limited to cholinesterase inhibitors and N-methyl-d-aspartate receptor (NMDAR) antagonists, provide symptomatic relief only. As single-target therapies have not proven effective, rational specific-targeted combination into a single molecule represents a more promising approach for treating AD, and is expected to yield greater benefits in alleviating symptoms and slowing disease progression. In the present study, we designed, synthesized, and biologically evaluated 24 novel N-methylpropargylamino-quinazoline derivatives. Initially, compounds were thoroughly inspected by in silico techniques determining their oral and CNS availabilities. We tested, in vitro, the compounds’ effects on cholinesterases and monoamine oxidase A/B (MAO-A/B), as well as their impacts on NMDAR antagonism, dehydrogenase activity, and glutathione levels. In addition, we inspected selected compounds for their cytotoxicity on undifferentiated and differentiated neuroblastoma SH-SY5Y cells. We collectively highlighted II-6h as the best candidate endowed with a selective MAO-B inhibition profile, NMDAR antagonism, an acceptable cytotoxicity profile, and the potential to permeate through BBB. The structure-guided drug design strategy applied in this study imposed a novel concept for rational drug discovery and enhances our understanding on the development of novel therapeutic agents for treating AD.
DNA Methylation Biomarkers for Young Children with Idiopathic Autism Spectrum Disorder: A Systematic Review
Authors: Stoccoro Andrea , Conti Eugenia , Scaffei Elena , Calderoni Sara , Coppedè Fabio , Migliore Lucia , Battini Roberta
Published: May 2023

Autism spectrum disorder (ASD) is a complex neurodevelopmental condition, the underlying pathological mechanisms of which are not yet completely understood. Although several genetic and genomic alterations have been linked to ASD, for the majority of ASD patients, the cause remains unknown, and the condition likely arises due to complex interactions between low-risk genes and environmental factors. There is increasing evidence that epigenetic mechanisms that are highly sensitive to environmental factors and influence gene function without altering the DNA sequence, particularly aberrant DNA methylation, are involved in ASD pathogenesis. This systematic review aimed to update the clinical application of DNA methylation investigations in children with idiopathic ASD, investigating its potential application in clinical settings. To this end, a literature search was performed on different scientific databases using a combination of terms related to the association between peripheral DNA methylation and young children with idiopathic ASD; this search led to the identification of 18 articles. In the selected studies, DNA methylation is investigated in peripheral blood or saliva samples, at both gene-specific and genome-wide levels. The results obtained suggest that peripheral DNA methylation could represent a promising methodology in ASD biomarker research, although further studies are needed to develop DNA-methylation-based clinical applications.
A Novel Time-Resolved Fluorescence Resonance Energy Transfer Assay for the Discovery of Small-Molecule Inhibitors of HIV-1 Tat-Regulated Transcription
Authors: Shin Young Hyun , Kim Dong-Eun , Yu Kyung Lee , Park Chul Min , Kim Hong Gi , Kim Kyung-Chang , Bae Songmee , Yoon Cheol-Hee
Published: May 2023

Human immunodeficiency virus-1 (HIV-1) transactivator (Tat)-mediated transcription is essential for HIV-1 replication. It is determined by the interaction between Tat and transactivation response (TAR) RNA, a highly conserved process representing a prominent therapeutic target against HIV-1 replication. However, owing to the limitations of current high-throughput screening (HTS) assays, no drug that disrupts the Tat-TAR RNA interaction has been uncovered yet. We designed a homogenous (mix-and-read) time-resolved fluorescence resonance energy transfer (TR-FRET) assay using europium cryptate as a fluorescence donor. It was optimized by evaluating different probing systems for Tat-derived peptides or TAR RNA. The specificity of the optimal assay was validated by mutants of the Tat-derived peptides and TAR RNA fragment, individually and by competitive inhibition with known TAR RNA-binding peptides. The assay generated a constant Tat-TAR RNA interaction signal, discriminating the compounds that disrupted the interaction. Combined with a functional assay, the TR-FRET assay identified two small molecules (460-G06 and 463-H08) capable of inhibiting Tat activity and HIV-1 infection from a large-scale compound library. The simplicity, ease of operation, and rapidity of our assay render it suitable for HTS to identify Tat-TAR RNA interaction inhibitors. The identified compounds may also act as potent molecular scaffolds for developing a new HIV-1 drug class.
Epigenetic Histone Methylation of PPARγ and CPT1A Signaling Contributes to Betahistine Preventing Olanzapine-Induced Dyslipidemia
Authors: Su Yueqing , Deng Chao , Liu Xuemei , Lian Jiamei
Published: May 2023

As a partial histamine H1 receptor agonist and H3 antagonist, betahistine has been reported to partially prevent olanzapine-induced dyslipidemia and obesity through a combination therapy, although the underlying epigenetic mechanisms are still not known. Recent studies have revealed that histone regulation of key genes for lipogenesis and adipogenesis in the liver is one of the crucial mechanisms for olanzapine-induced metabolic disorders. This study investigated the role of epigenetic histone regulation in betahistine co-treatment preventing dyslipidemia and fatty liver caused by chronic olanzapine treatment in a rat model. In addition to abnormal lipid metabolism, the upregulation of peroxisome proliferator-activated receptor γ (PPARγ) and CCAAT/enhancer binding protein (C/EBPα), as well as the downregulation of carnitine palmitoyltransferase 1A (CPT1A) in the liver induced by olanzapine, were significantly attenuated by betahistine co-treatment. In addition, betahistine co-treatment significantly enhanced the global expression of H3K4me and the enrichment of H3K4me binding on the promoter of Cpt1a gene as revealed by ChIP-qPCR, but inhibited the expression of one of its site-specific demethylases, lysine (K)-specific demethylase 1A (KDM1A). Betahistine co-treatment also significantly enhanced the global expression of H3K9me and the enrichment of H3K9me binding on the promoter of the Pparg gene, but inhibited the expression of two of its site-specific demethylases, lysine demethylase 4B (KDM4B) and PHD finger protein 2 (PHF2). These results suggest that betahistine attenuates abnormal adipogenesis and lipogenesis triggered by olanzapine through modulating hepatic histone methylation, and thus inhibiting the PPARγ pathway-mediated lipid storage, while at the same time promoting CP1A-mediated fatty acid oxidation.
Microglia and the Blood–Brain Barrier: An External Player in Acute and Chronic Neuroinflammatory Conditions
Authors: Gullotta Giorgia Serena , Costantino Giuseppe , Sortino Maria Angela , Spampinato Simona Federica
Published: May 2023

Microglia are the resident immune cells of the central nervous system that guarantee immune surveillance and exert also a modulating role on neuronal synaptic development and function. Upon injury, microglia get activated and modify their morphology acquiring an ameboid phenotype and pro- or anti-inflammatory features. The active role of microglia in blood–brain barrier (BBB) function and their interaction with different cellular components of the BBB—endothelial cells, astrocytes and pericytes—are described. Here, we report the specific crosstalk of microglia with all the BBB cell types focusing in particular on the involvement of microglia in the modulation of BBB function in neuroinflammatory conditions that occur in conjunction with an acute event, such as a stroke, or in a slow neurodegenerative disease, such as Alzheimer’s disease. The potential of microglia to exert a dual role, either protective or detrimental, depending on disease stages and environmental conditioning factors is also discussed.
Nuclear Receptors in Health and Diseases
Authors: Xu Pengfei
Published: May 2023

Nuclear receptors (NRs) are a vital superfamily of transcription factors that play crucial roles in physiology and pharmacology [...]
Recent Advances in Urinary Peptide and Proteomic Biomarkers in Chronic Kidney Disease: A Systematic Review
Authors: Catanese Lorenzo , Siwy Justyna , Mischak Harald , Wendt Ralph , Beige Joachim , Rupprecht Harald
Published: May 2023

Biomarker development, improvement, and clinical implementation in the context of kidney disease have been a central focus of biomedical research for decades. To this point, only serum creatinine and urinary albumin excretion are well-accepted biomarkers in kidney disease. With their known blind spot in the early stages of kidney impairment and their diagnostic limitations, there is a need for better and more specific biomarkers. With the rise in large-scale analyses of the thousands of peptides in serum or urine samples using mass spectrometry techniques, hopes for biomarker development are high. Advances in proteomic research have led to the discovery of an increasing amount of potential proteomic biomarkers and the identification of candidate biomarkers for clinical implementation in the context of kidney disease management. In this review that strictly follows the PRISMA guidelines, we focus on urinary peptide and especially peptidomic biomarkers emerging from recent research and underline the role of those with the highest potential for clinical implementation. The Web of Science database (all databases) was searched on 17 October 2022, using the search terms “marker *” OR biomarker * AND “renal disease” OR “kidney disease” AND “proteome *” OR “peptid *” AND “urin *”. English, full-text, original articles on humans published within the last 5 years were included, which had been cited at least five times per year. Studies based on animal models, renal transplant studies, metabolite studies, studies on miRNA, and studies on exosomal vesicles were excluded, focusing on urinary peptide biomarkers. The described search led to the identification of 3668 articles and the application of inclusion and exclusion criteria, as well as abstract and consecutive full-text analyses of three independent authors to reach a final number of 62 studies for this manuscript. The 62 manuscripts encompassed eight established single peptide biomarkers and several proteomic classifiers, including CKD273 and IgAN237. This review provides a summary of the recent evidence on single peptide urinary biomarkers in CKD, while emphasizing the increasing role of proteomic biomarker research with new research on established and new proteomic biomarkers. Lessons learned from the last 5 years in this review might encourage future studies, hopefully resulting in the routine clinical applicability of new biomarkers.
Evaluation of the Novel Sepsis Biomarker Host-Derived Delta-like Canonical Notch Ligand 1—A Secondary Analysis of 405 Patients Suffering from Inflammatory or Infectious Diseases
Authors: Hölle Tobias , Rehn Patrick , Leventogiannis Konstantinos , Kotsaki Antigone , Kanni Theodora , Antonakos Nikolaos , Psarrakis Christos , Damoraki Georgia , Schenz Judith , Schmitt Felix C. F. , Uhle Florian , Weigand Markus A. , Giamarellos-Bourboulis Evangelos J. , Dietrich Maximilian
Published: May 2023

Sepsis is defined as organ failure caused by dysregulated host response to infection. While early antibiotic treatment in patients with acute infection is essential, treating non-infectious patients must be avoided. Current guidelines recommend procalcitonin (PCT) to guide discontinuation of antibiotic treatment. For initiation of therapy, there is currently no recommended biomarker. In this study, we evaluated Host-Derived Delta-like Canonical Notch Ligand 1 (DLL1), a monocyte membrane ligand that has shown promising results in differentiating infectious from non-infectious critically ill patients. Soluble DLL1 levels were measured in plasma samples of six different cohorts. The six cohorts comprise two cohorts with non-infectious inflammatory auto-immune diseases (Hidradenitis Suppurativa, Inflammatory Bowel Disease), one cohort of bacterial skin infection, and three cohorts of suspected systemic infection or sepsis. In total, soluble DLL1 plasma levels of 405 patients were analyzed. Patients were divided into three groups: inflammatory disease, infection, and sepsis (defined according to the Sepsis-3 definition), followed by the evaluation of its diagnostic performance via Area Under the Receiver Operating Characteristics (AUROC) analyses. Patients of the sepsis group showed significantly elevated plasma DLL1 levels compared to patients with uncomplicated infections and sterile inflammation. However, patients with infections had significantly higher DLL1 levels than patients with inflammatory diseases. Diagnostic performance was evaluated and showed better performance for DLL1 for the recognition of sepsis (AUC: 0.823; CI 0.731–0.914) than C-reactive protein (AUC 0.758; CI 0.658–0.857), PCT (AUC 0.593; CI 0.474–0.711) and White Blood Cell count (AUC 0.577; CI 0.46–0.694). DLL1 demonstrated promising results for diagnosing sepsis and was able to differentiate sepsis from other infectious and inflammatory diseases.
Reinforcement Learning-Based Hybrid Multi-Objective Optimization Algorithm Design
Authors: Palm Herbert , Arndt Lorin
Published: May 2023

The multi-objective optimization (MOO) of complex systems remains a challenging task in engineering domains. The methodological approach of applying MOO algorithms to simulation-enabled models has established itself as a standard. Despite increasing in computational power, the effectiveness and efficiency of such algorithms, i.e., their ability to identify as many Pareto-optimal solutions as possible with as few simulation samples as possible, plays a decisive role. However, the question of which class of MOO algorithms is most effective or efficient with respect to which class of problems has not yet been resolved. To tackle this performance problem, hybrid optimization algorithms that combine multiple elementary search strategies have been proposed. Despite their potential, no systematic approach for selecting and combining elementary Pareto search strategies has yet been suggested. In this paper, we propose an approach for designing hybrid MOO algorithms that uses reinforcement learning (RL) techniques to train an intelligent agent for dynamically selecting and combining elementary MOO search strategies. We present both the fundamental RL-Based Hybrid MOO (RLhybMOO) methodology and an exemplary implementation applied to mathematical test functions. The results indicate a significant performance gain of intelligent agents over elementary and static hybrid search strategies, highlighting their ability to effectively and efficiently select algorithms.
A Web-Based Docker Image Assistant Generation Tool for User-PC Computing System
Authors: Aung Lynn Htet , Funabiki Nobuo , Aung Soe Thandar , Zhou Xudong , Xiang Xu , Kao Wen-Chung
Published: May 2023

Currently, we are developing the user-PC computing (UPC) system based on the master-worker model as a scalable, low-cost, and high-performance computing platform. To run various application programs on personal computers (PCs) with different environments for workers, it adopts Docker technology to bundle every necessary software as one image file. Unfortunately, the Docker file/image are manually generated through multiple steps by a user, which can be the bottleneck. In this paper, we present a web-based Docker image assistant generation (DIAG) tool in the UPC system to assist or reduce these process steps. It adopts Angular JavaScript for offering user interfaces, PHP Laravel for handling logic using RestAPI, MySQL database for storing data, and Shell scripting for speedily running the whole program. In addition, the worker-side code modification function is implemented so that a user can modify the source code of the running job and update the Docker image at a worker to speed up them. For evaluations, we collected 30 Docker files and 10 OpenFOAM jobs through reverse processing from Docker images in Github and generated the Docker images using the tool. Moreover, we modified source codes for network simulations and generated the Docker images in a worker five times. The results confirmed the validity of the proposal.
Early and Long-Term Clinical and Echocardiographic Outcomes of Sutureless vs. Sutured Bioprosthesis for Aortic Valve Replacement
Authors: Dokollari Aleksander , Torregrossa Gianluca , Bisleri Gianluigi , Hassanabad Ali Fatehi , Sa Michel Pompeu , Sicouri Serge , Veshti Altin , Prifti Edvin , Bacchi Beatrice , Cabrucci Francesco , Ramlawi Basel , Bonacchi Massimo
Published: May 2023

Objective: The goal of this manuscript is to compare clinical and echocardiographic outcomes of patients undergoing aortic valve replacement (AVR) with Perceval sutureless bioprosthesis (SU-AVR) and sutured bioprosthesis (SB). Methods: Following the PRISMA statement, data were extracted from studies published after August 2022 and found in PubMed/MEDLINE, EMBASE, CENTRAL/CCTR, ClinicalTrials.gov, SciELO, LILACS, and Google Scholar. The primary outcome of interest was post-procedural permanent pacemaker implantation, and the secondary outcomes were new left bundle branch block (LBBB), moderate/severe paravalvular leak (PVL), valve dislocation (pop-out), need for a second transcatheter heart valve, 30-day mortality, stroke, and echocardiographic outcomes. Results: Twenty-one studies were included in the analysis. When SU-AVR was compared to other SB, mortality ranged from 0 to 6.4% for Perceval and 0 to 5.9% for SB. Incidence of PVL (Perceval 1–19.4% vs. SB 0–1%), PPI (Perceval 2–10.7% vs. SB 1.8–8.5%), and MI (Perceval 0–7.8% vs. SB 0–4.3%) were comparable. In addition, the stroke rate was lower in the SU-AVR group when compared to SB (Perceval 0–3.7% vs. SB 1.8–7.3%). In patients with a bicuspid aortic valve, the mortality rate was 0–4% and PVL incidence was 0–2.3%. Long-term survival ranged between 96.7 and 98.6%. Valve cost analysis was lower for the Perceval valve and higher for sutured bioprosthesis. Conclusions: Compared to SB valves, Perceval bioprosthesis has proved to be a reliable prosthesis for surgical aortic valve replacement due to its non-inferior hemodynamics, implantation speed, reduced cardiopulmonary bypass time, reduced aortic cross-clamp time, and shorter length of stay.
Balloon Dilatation in the Management of Congenital Obstructive Lesions of the Heart: Review of Author’s Experiences and Observations—Part I
Authors: Rao P. Syamasundar
Published: May 2023

Balloon dilatation techniques became available to treat congenital obstructive lesions of the heart in the early/mid-1980s. The purpose of this review is to present the author’s experiences and observations on the techniques and outcomes of balloon dilatation of pulmonary stenosis (PS), aortic stenosis (AS) and aortic coarctation (AC), both native and postsurgical re-coarctations. Balloon dilatation resulted in a reduction of peak pressure gradient across the obstructive lesion at the time of the procedure as well as at short-term and long-term follow-ups. Complications such as recurrence of stenosis, valvar insufficiency (for PS and AS cases) and aneurysm formation (for AC cases) have been reported, but infrequently. It was recommended that strategies be developed to prevent the reported complications.
A Retrospective Study of the Functional Outcomes in Patients with Proximal Humeral Bone Defect after Shoulder Fusion or Prosthetic Replacement
Authors: Pan Zhen , Cheng Dongdong , Guo Hua , Li Zhaohui , Fei Xiang , Yuan Ting , Yang Qingcheng
Published: May 2023

Aims: The reconstruction of proximal humeral defects resulting from tumor resection is challenging. The purpose of this work was to retrospectively study the functional outcomes in patients with large bone defects after the resection of proximal humeral tumors. Methods: We performed a retrospective analysis of 49 patients with malignant or aggressive benign tumors in the proximal humerus at our institution between 2010 and 2021. Forty-nine patients were included in the study (prosthetic replacement, n = 27; shoulder arthrodesis, n = 22). The mean follow-up was 52.8 months (range, 14–129 months). The factors evaluated included the Musculoskeletal Tumor Society (MSTS) functional score, Constant Murley Score (CMS), and complications. Results: Of the 49 patients enrolled in the study, 35 were disease-free by the time of the latest follow-up, and 14 died because of the disease. Adjuvant therapies and medical comorbidities were similar between the two groups. Osteosarcoma was the most common abnormality among all the patients. The mean MSTS scores for surviving patients in the prosthesis and arthrodesis groups were 57.4% and 80.9%, respectively. The mean CMS score for the surviving patients in the prosthesis group was 43.47, and it was 61.44 for arthrodesis cases. Patients with shoulder arthrodesis demonstrated evidence of bony union at a mean of 4.5 months. Conclusions: Shoulder arthrodesis is a reliable reconstructive procedure in patients with large bone defects after the resection of proximal humeral tumors for pediatric osteosarcoma patients. Moreover, prosthetic replacement with anatomical implants results in poor function in older metastasis patients with large bone defects and resection of the deltoid muscle.
Changes in Choroidal Thickness and Retinal Activity with a Myopia Control Contact Lens
Authors: Amorim-de-Sousa Ana , Pauné Jaume , Silva-Leite Sara , Fernandes Paulo , Gozález-Méijome José Manuel , Queirós António
Published: May 2023

Purpose: The axial elongation in myopia is associated with some structural and functional retinal changes. The purpose of this study was to investigate the effect of a contact lens (CL) intended for myopia control on the choroidal thickness (ChT) and the retinal electrical response. Methods: Ten myopic eyes (10 subjects, 18–35 years of age) with spherical equivalents from −0.75 to −6.00 diopters (D) were enrolled. The ChT at different eccentricities (3 mm temporal, 1.5 mm temporal, sub-foveal ChT, 1.5 mm nasal, and 3 mm nasal), the photopic 3.0 b-wave of ffERG and the PERG were recorded and compared with two material-matched contact lenses following 30 min of wear: a single-vision CL (SV) and a radial power gradient CL with +1.50 D addition (PG). Results: Compared with the SV, the PG increased the ChT at all eccentricities, with statistically significant differences at 3.0 mm temporal (10.30 ± 11.51 µm, p = 0.020), in sub-foveal ChT (17.00 ± 20.01 µm, p = 0.025), and at 1.5 mm nasal (10.70 ± 14.50 µm, p = 0.044). The PG decreased significantly the SV amplitude of the ffERG photopic b-wave (11.80 (30.55) µV, p = 0.047), N35-P50 (0.90 (0.96) µV, p = 0.017), and P50-N95 (0.46 (2.50) µV, p = 0.047). The amplitude of the a-wave was negatively correlated with the ChT at 3.0T (r = −0.606, p = 0.038) and 1.5T (r = −0.748, p = 0.013), and the amplitude of the b-wave showed a negative correlation with the ChT at 1.5T (r = −0.693, p = 0.026). Conclusions: The PG increased the ChT in a similar magnitude observed in previous studies. These CLs attenuated the amplitude of the retinal response, possibly due to the combined effect of the induced peripheral defocus high-order aberrations impacting the central retinal image. The decrease in the response of bipolar and ganglion cells suggests a potential retrograde feedback signaling effect from the inner to outer retinal layers observed in previous studies.
Magnetoelectric Properties of Lead-Free Three-Layer Structure Barium–Titanate–Piezoceramic Nickel
Authors: Laletin Vladimir , Kudybin Mikhail , Poddubnaya Natallia , Filippov Dmitry
Published: May 2023

The results of the comprehensive magnetoelectric interaction research in three-layer structure Ni–piezoceramic BaTiO3–Ni are presented. It has been theoretically shown and experimentally confirmed that, in the general case, the dependence of the magnetoelectric response has non-linear character. At low bias magnetic field, a quadratic dependence magnetoelectric response from an AC magnetic field is observed then there is a linear section, as well as at high values of the field magnetoelectric response has saturation. The obtained values of the magnetoelectric characteristics (αEmax = 32 V(cmOe) for resonance and 437 mV/(cmOe) for field dependence) for lead-free three-layer structure barium–titanate–piezoceramic nickel are comparable with the magnetoelectric characteristics for similar structures, based on lead-containing ceramics.
Combining CNNs and Markov-like Models for Facial Landmark Detection with Spatial Consistency Estimates
Authors: Gdoura Ahmed , Degünther Markus , Lorenz Birgit , Effland Alexander
Published: May 2023

The accurate localization of facial landmarks is essential for several tasks, including face recognition, head pose estimation, facial region extraction, and emotion detection. Although the number of required landmarks is task-specific, models are typically trained on all available landmarks in the datasets, limiting efficiency. Furthermore, model performance is strongly influenced by scale-dependent local appearance information around landmarks and the global shape information generated by them. To account for this, we propose a lightweight hybrid model for facial landmark detection designed specifically for pupil region extraction. Our design combines a convolutional neural network (CNN) with a Markov random field (MRF)-like process trained on only 17 carefully selected landmarks. The advantage of our model is the ability to run different image scales on the same convolutional layers, resulting in a significant reduction in model size. In addition, we employ an approximation of the MRF that is run on a subset of landmarks to validate the spatial consistency of the generated shape. This validation process is performed against a learned conditional distribution, expressing the location of one landmark relative to its neighbor. Experimental results on popular facial landmark localization datasets such as 300 w, WFLW, and HELEN demonstrate the accuracy of our proposed model. Furthermore, our model achieves state-of-the-art performance on a well-defined robustness metric. In conclusion, the results demonstrate the ability of our lightweight model to filter out spatially inconsistent predictions, even with significantly fewer training landmarks.
Moderating Role of Creative Mindset in the Effect of Metacognitive Experience on Insight Problem Solving
Authors: Jia Xiaoyu , Li Ping , Chen Qunlin , Li Weijian
Published: May 2023

Metacognitive experience, measured by processing fluency, contributes to divergent thinking performance; however, whether it exhibits varying effects on insight problem-solving remains unknown. Additionally, as individuals’ interpretation of metacognitive experience is influenced by their creative mindset, whether creative mindset plays a role in the relationship between metacognitive experience and insight problem-solving is another issue. In Experiment 1, a Chinese logogriph task was used to investigate insight problem-solving performance. The font style of logogriphs (easy versus difficult) was used to alter the ease of processing. The results showed that individuals had lower performance accuracy for logogriphs presented in difficult font styles, suggesting the negative effect of metacognitive disfluency experience on logogriph solving. In Experiment 2, different creative mindsets (entity versus incremental) were activated in individuals via prime manipulation. Individuals with an incremental creative mindset had a significantly higher performance accuracy and longer reaction time for logogriphs presented in difficult font styles than individuals with an entity creative mindset, suggesting that an incremental creative mindset might counteract the negative effect of metacognitive disfluency experience on logogriphs solving. These findings suggest that metacognitive disfluency experience has a negative effect on insight problem-solving and that a creative mindset moderated this effect.
AMA: An Ageing Task Migration Aware for High-Performance Computing
Authors: Ofori-Attah Emmanuel , Agyeman Michael Opoku
Published: May 2023

The dark-silicon challenge poses a design problem for future many-core systems. As a result of this, several techniques have been introduced to improve the number of processing elements that can be powered on. One of the techniques employed by many is Task Migration. In this paper, an Ageing Task Migration Aware for High-Performance Computing (AMA) is proposed to improve the lifetime of nodes. The proposed method determines which clusters applications are mapped to and migrates high-demand tasks amongst nodes to improve the lifetime at every epoch. Experimental results show that the proposed method outperforms state-of-the-art techniques by more than 10%.
Investigation of the Shape and Detectability of Pores with X-ray Computed Tomography
Authors: Baumgärtner Benjamin , Hussein Juan , Hausotte Tino
Published: May 2023

Component porosity is a quality attribute in additive manufacturing (AM). One possibility for the non-destructive three-dimensional determination of porosity or pore shape is X-ray computed tomography (CT), which enables an investigation of the influence of AM process parameters on the appearance and characteristics of the pores. Since there is no porosity standard for CT, a traceable determination of the measurement uncertainty is not possible. Using a digital twin of the CT system, an estimation of the CT measurement uncertainty is in principle possible. In this contribution, experimental CT analyses of powder bed fusion samples made of Ti64 and PA12 are compared with CT simulations. The results show a size-dependent influence on the shape and detectability of the pores. Using the CT model, a simulated shape- and material-dependent probability of detection (POD) is calculated.