bluuebunny/crossref_metadata_2025 huggingface dataset:
Statistical Evaluations and Applications for IER Parameters from Generalized Progressively Type-II Hybrid Censored Data
Authors: Elshahhat Ahmed , Mohammed Heba S. , Abo-Kasem Osama E.
Published: June 2023

Generalized progressively Type-II hybrid strategy has been suggested to save both the duration and cost of a life test when the experimenter aims to score a fixed number of failed units. In this paper, using this mechanism, the maximum likelihood and Bayes inferential problems for unknown model parameters, in addition to both reliability, and hazard functions of the inverted exponentiated Rayleigh model, are acquired. Applying the observed Fisher data and delta method, the normality characteristic of the classical estimates is taken into account to derive confidence intervals for unknown parameters and several indice functions. In Bayes’ viewpoint, through independent gamma priors against both symmetrical and asymmetrical loss functions, the Bayes estimators of the unknown quantities are developed. Because the Bayes estimators are acquired in complicated forms, a hybrid Monte-Carlo Markov-chain technique is offered to carry out the Bayes estimates as well as to create the related highest posterior density interval estimates. The precise behavior of the suggested estimation approaches is assessed using wide Monte Carlo simulation experiments. Two actual applications based on actual data sets from the mechanical and chemical domains are examined to show how the offered methodologies may be used in real current events.
A New Class of Accretive Mappings in Semi-Inner Product Space with an Application to Solve Variational Inclusion
Authors: Gupta Sanjeev , Altaweel Nifeen Hussain
Published: June 2023

This work aims to develop a new class of accretive mappings and investigate its associated class of proximal mappings. This new class of accretive mappings is known as generalized (Hk,φ)-η-accretive mappings. Further, the research work includes a discussion of its application, leading to set-valued variational-like inclusions (SVVLI, in short) in the semi-inner product spaces. The corresponding fixed point problem for SVVLI is given. This fixed point problem is used to provide an iterative scheme for solving SVVLI. Furthermore, we study the convergence analysis of the suggested iterative method. An illustration is built in support of our result.
Thermo-Optical Measurements and Simulation in a Fibre-Optic Circuit Using an Extrinsic Fabry–Pérot Interferometer under Pulsed Laser Heating
Authors: Kotov Artem N. , Starostin Aleksandr A. , Gorbatov Vladimir I. , Skripov Pavel V.
Published: June 2023

Advantages of using an external Fabry–Pérot interferometer (EFPI) as a high-speed local temperature deformation sensor are demonstrated for the fibre-optic circuit combining a powerful laser beam for surface heating with a low-power probing radiation. The difference in the formation of the heating and probing radiation provides a simple basis for varying the gap between the fibre end and the surface in order to change the ratio between the heating and EFPI measuring areas. Using an example of modelling the laser heating by radiation from a standard single-mode fibre, we demonstrate the possibility of employing the EFPI to measure the temperature deformation of the surface on a quasi-isothermal area with the temperature close to the maximum at gap values of more than 100 μm. With the condition of preliminary calibration, the proposed scheme can be used to evaluate the heat treatment of the surface with the speed of the applied photodetector. The practical possibilities of the method are demonstrated on examples of heating some metal and semiconductor samples by laser pulses of microsecond duration.
The Influence of Carious Lesion and Bleeding Time on the Success of Partial Pulpotomy in Permanent Molars with Irreversible Pulpitis: A Prospective Study
Authors: Aldeen Rami Zen , Aljabban Ossama , Almanadili Ahmad , Alkurdi Saleh , Eid Ammar , Mancino Davide , Haikel Youssef , Kharouf Naji
Published: June 2023

This prospective study aimed to evaluate the success rate of partial pulpotomy using mineral trioxide aggregate (MTA), in permanent molars with symptomatic irreversible pulpitis. Moreover, this study aimed to investigate the effect of carious lesion depth and activity and bleeding time on the outcome of partial pulpotomy. Forty permanent molars with deep and extremely deep carious lesions clinically diagnosed with symptomatic irreversible pulpitis were included. The status of the carious lesion was evaluated clinically and radiographically to determine its activity (rapidly or slowly progressing) and depth (deep or extremely deep). A partial pulpotomy was performed and MTA was used. Clinical and radiographic analysis were performed at 3, 6 and 12 months. Chi-square analysis and Fisher’s exact test were used. Scanning electron microscope and energy dispersive X-rays were used to investigate the crystalline structures and their chemical composition onto MTA surfaces after immersion in several conditions. The partial pulpotomy was 88.9% successful, with no significant difference in outcome between deep and extremely deep carious lesions (p = 0.22) or between rapidly and slowly progressing lesions (p = 0.18). Nevertheless, all failed cases were associated with rapidly progressing lesions and extremely deep lesions. All failures occurred when the bleeding time was more than 3 min (p = 0.10). Different crystalline structures were detected on MTA surfaces, with higher calcium percentages in PBS conditions. Within the limitations of the present study, favorable results demonstrated that MTA might be recommended as a suitable agent for partial pulpotomy in permanent molars with irreversible pulpitis. The depth and activity of the carious lesion as well as the bleeding time are important factors in the success of partial pulpotomy treatment. The prolonged bleeding time and the extremely deep rapidly progressing caries could be related with the failure cases in partial pulpotomy treatment of irreversible pulpitis.
Anti-TNF Biologicals Enhance the Anti-Inflammatory Properties of IgG N-Glycome in Crohn’s Disease
Authors: Hanić Maja , Vučković Frano , Deriš Helena , Bewshea Claire , Lin Simeng , Goodhand James R. , Ahmad Tariq , Trbojević-Akmačić Irena , Kennedy Nicholas A. , Lauc Gordan ,   PANTS Consortium
Published: June 2023

Crohn’s disease (CD) is a chronic inflammation of the digestive tract that significantly impairs patients’ quality of life and well-being. Anti-TNF biologicals revolutionised the treatment of CD, yet many patients do not adequately respond to such therapy. Previous studies have demonstrated a pro-inflammatory pattern in the composition of CD patients’ immunoglobulin G (IgG) N-glycome compared to healthy individuals. Here, we utilised the high-throughput UHPLC method for N-glycan analysis to explore the longitudinal effect of the anti-TNF drugs infliximab and adalimumab on N-glycome composition of total serum IgG in 198 patients, as well as the predictive potential of IgG N-glycans at baseline to detect primary non-responders to anti-TNF therapy in 1315 patients. We discovered a significant decrease in IgG agalactosylation and an increase in monogalactosylation, digalactosylation and sialylation during the 14 weeks of anti-TNF treatment, regardless of therapy response, all of which suggested a diminished inflammatory environment in CD patients treated with anti-TNF therapy. Furthermore, we observed that IgG N-glycome might contain certain information regarding the anti-TNF therapy outcome before initiating the treatment. However, it is impossible to predict future primary non-responders to anti-TNF therapy based solely on IgG N-glycome composition at baseline.
In Silico Identification of Potential Inhibitors of the SARS-CoV-2 Main Protease among a PubChem Database of Avian Infectious Bronchitis Virus 3CLPro Inhibitors
Authors: Soulère Laurent , Barbier Thibaut , Queneau Yves
Published: June 2023

Remarkable structural homologies between the main proteases of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the avian infectious bronchitis virus (IBV) were revealed by comparative amino-acid sequence and 3D structural alignment. Assessing whether reported IBV 3CLPro inhibitors could also interact with SARS-CoV-2 has been undertaken in silico using a PubChem BioAssay database of 388 compounds active on the avian infectious bronchitis virus 3C-like protease. Docking studies of this database on the SARS-CoV-2 protease resulted in the identification of four covalent inhibitors targeting the catalytic cysteine residue and five non-covalent inhibitors for which the binding was further investigated by molecular dynamics (MD) simulations. Predictive ADMET calculations on the nine compounds suggest promising pharmacokinetic properties.
Molecular Biophysics of Class A G Protein Coupled Receptors–Lipids Interactome at a Glance—Highlights from the A2A Adenosine Receptor
Authors: Tzortzini Efpraxia , Kolocouris Antonios
Published: June 2023

G protein-coupled receptors (GPCRs) are embedded in phospholipid membrane bilayers with cholesterol representing 34% of the total lipid content in mammalian plasma membranes. Membrane lipids interact with GPCRs structures and modulate their function and drug-stimulated signaling through conformational selection. It has been shown that anionic phospholipids form strong interactions between positively charged residues in the G protein and the TM5-TM6-TM 7 cytoplasmic interface of class A GPCRs stabilizing the signaling GPCR-G complex. Cholesterol with a high content in plasma membranes can be identified in more specific sites in the transmembrane region of GPCRs, such as the Cholesterol Consensus Motif (CCM) and Cholesterol Recognition Amino Acid Consensus (CRAC) motifs and other receptor dependent and receptor state dependent sites. Experimental biophysical methods, atomistic (AA) MD simulations and coarse-grained (CG) molecular dynamics simulations have been applied to investigate these interactions. We emphasized here the impact of phosphatidyl inositol-4,5-bisphosphate (PtdIns(4,5)P2 or PIP2), a minor phospholipid component and of cholesterol on the function-related conformational equilibria of the human A2A adenosine receptor (A2AR), a representative receptor in class A GPCR. Several GPCRs of class A interacted with PIP2 and cholesterol and in many cases the mechanism of the modulation of their function remains unknown. This review provides a helpful comprehensive overview for biophysics that enter the field of GPCRs-lipid systems.
Engineering Siderophore Biosynthesis and Regulation Pathways to Increase Diversity and Availability
Authors: Puja Hélène , Mislin Gaëtan L. A. , Rigouin Coraline
Published: June 2023

Siderophores are small metal chelators synthesized by numerous organisms to access iron. These secondary metabolites are ubiquitously present on Earth, and because their production represents the main strategy to assimilate iron, they play an important role in both positive and negative interactions between organisms. In addition, siderophores are used in biotechnology for diverse applications in medicine, agriculture and the environment. The generation of non-natural siderophore analogs provides a new opportunity to create new-to-nature chelating biomolecules that can offer new properties to expand applications. This review summarizes the main strategies of combinatorial biosynthesis that have been used to generate siderophore analogs. We first provide a brief overview of siderophore biosynthesis, followed by a description of the strategies, namely, precursor-directed biosynthesis, the design of synthetic or heterologous pathways and enzyme engineering, used in siderophore biosynthetic pathways to create diversity. In addition, this review highlights the engineering strategies that have been used to improve the production of siderophores by cells to facilitate their downstream utilization.
Immune Phenotype as a Biomarker for Systemic Lupus Erythematosus
Authors: Nakayamada Shingo , Tanaka Yoshiya
Published: June 2023

The treatment of rheumatoid arthritis was revolutionized with the use of molecular-targeted drugs that target immunoregulatory molecules. The success of treatment with these drugs prompted the development of molecular-targeted drugs for systemic lupus erythematosus. However, systemic lupus erythematosus is a disease with high heterogeneous immune abnormalities, and diverse cells or molecules can be treatment targets. Thus, the identification of subpopulations based on immune abnormalities is essential for the development of effective treatment. One analytical method used to identify subpopulations is the immunophenotyping of peripheral blood samples of patients. This analysis evaluates the validity of target molecules for peripheral blood immune cell subsets, which are expected to be developed as biomarkers for precision medicine in which appropriate treatment targets are set for each subpopulation.
Intravitreal Neuroglobin Mitigates Primate Experimental Glaucomatous Structural Damage in Association with Reduced Optic Nerve Microglial and Complement 3-Astrocyte Activation
Authors: Chan Anita S. Y. , Tun Sai B. B. , Lynn Myoe N. , Ho Candice , Tun Tin A. , Girard Michaël J. A. , Sultana Rehena , Barathi Veluchamy A. , Aung Tin , Aihara Makoto
Published: June 2023

Current management of glaucomatous optic neuropathy is limited to intraocular pressure control. Neuroglobin (Ngb) is an endogenous neuroprotectant expressed in neurons and astrocytes. We recently showed that exogenous intravitreal Ngb reduced inflammatory cytokines and microglial activation in a rodent model of hypoxia. We thus hypothesised that IVT-Ngb may also be neuroprotective in experimental glaucoma (EG) by mitigating optic nerve (ON) astrogliosis and microgliosis as well as structural damage. In this study using a microbead-induced model of EG in six Cynomolgus primates, optical coherence imaging showed that Ngb-treated EG eyes had significantly less thinning of the peripapillary minimum rim width, retinal nerve fibre layer thickness, and ON head cupping than untreated EG eyes. Immunohistochemistry confirmed that ON astrocytes overexpressed Ngb following Ngb treatment. A reduction in complement 3 and cleaved-caspase 3 activated microglia and astrocytes was also noted. Our findings in higher-order primates recapitulate the effects of neuroprotection by Ngb treatment in rodent EG studies and suggest that Ngb may be a potential candidate for glaucoma neuroprotection in humans.
Human IGF2 Gene Epigenetic and Transcriptional Regulation: At the Core of Developmental Growth and Tumorigenic Behavior
Authors: Scalia Pierluigi , Williams Stephen J. , Fujita-Yamaguchi Yoko
Published: June 2023

Regulation of the human IGF2 gene displays multiple layers of control, which secures a genetically and epigenetically predetermined gene expression pattern throughout embryonal growth and postnatal life. These predominantly nuclear regulatory mechanisms converge on the function of the IGF2-H19 gene cluster on Chromosome 11 and ultimately affect IGF2 gene expression. Deregulation of such control checkpoints leads to the enhancement of IGF2 gene transcription and/or transcript stabilization, ultimately leading to IGF-II peptide overproduction. This type of anomaly is responsible for the effects observed in terms of both abnormal fetal growth and increased cell proliferation, typically observed in pediatric overgrowth syndromes and cancer. We performed a review of relevant experimental work on the mechanisms affecting the human IGF2 gene at the epigenetic, transcriptional and transcript regulatory levels. The result of our work, indeed, provides a wider and diversified scenario for IGF2 gene activation than previously envisioned by shedding new light on its extended regulation. Overall, we focused on the functional integration between the epigenetic and genetic machinery driving its overexpression in overgrowth syndromes and malignancy, independently of the underlying presence of loss of imprinting (LOI). The molecular landscape provided at last strengthens the role of IGF2 in cancer initiation, progression and malignant phenotype maintenance. Finally, this review suggests potential actionable targets for IGF2 gene- and regulatory protein target-degradation therapies.
SmartPill™ Administration to Assess Gastrointestinal Function after Spinal Cord Injury in a Porcine Model—A Preliminary Study
Authors: Knibbe Chase A. , Ahmed Rakib Uddin , Wilkins Felicia , Sharma Mayur , Ethridge Jay , Morgan Monique , Gibson Destiny , Cooper Kimberly B. , Howland Dena R. , Vadhanam Manicka V. , Barve Shirish S. , Davison Steven , Sherwood Leslie C. , Semler Jack , Abell Thomas , Boakye Maxwell
Published: June 2023

Gastrointestinal (GI) complications, including motility disorders, metabolic deficiencies, and changes in gut microbiota following spinal cord injury (SCI), are associated with poor outcomes. After SCI, the autonomic nervous system becomes unbalanced below the level of injury and can lead to severe GI dysfunction. The SmartPill™ is a non-invasive capsule that, when ingested, transmits pH, temperature, and pressure readings that can be used to assess effects in GI function post-injury. Our minipig model allows us to assess these post-injury changes to optimize interventions and ultimately improve GI function. The aim of this study was to compare pre-injury to post-injury transit times, pH, and pressures in sections of GI tract by utilizing the SmartPill™ in three pigs after SCI at 2 and 6 weeks. Tributyrin was administered to two pigs to assess the influences on their gut microenvironment. We observed prolonged GET (Gastric Emptying Time) and CTT (Colon Transit Time), decreases in contraction frequencies (Con freq) in the antrum of the stomach, colon, and decreases in duodenal pressures post-injury. We noted increases in Sum amp generated at 2 weeks post-injury in the colon, with corresponding decreases in Con freq. We found transient changes in pH in the colon and small intestine at 2 weeks post-injury, with minimal effect on stomach pH post-injury. Prolonged GETs and CTTs can influence the absorptive profile in the gut and contribute to pathology development. This is the first pilot study to administer the SmartPill™ in minipigs in the context of SCI. Further investigations will elucidate these trends and characterize post-SCI GI function.
Factors Influencing Receipt and Type of Therapy Services in the NICU
Authors: Butera Christiana D. , Brown Shaaron E. , Burnsed Jennifer , Darring Jodi , Harper Amy D. , Hendricks-Muñoz Karen D. , Hyde Megan , Kane Audrey E. , Miller Meagan R. , Stevenson Richard D. , Spence Christine M. , Thacker Leroy R. , Dusing Stacey C.
Published: June 2023

Understanding the type and frequency of current neonatal intensive care unit (NICU) therapy services and predictors of referral for therapy services is a crucial first step to supporting positive long-term outcomes in very preterm infants. This study enrolled 83 very preterm infants (<32 weeks, gestational age mean 26.5 ± 2.0 weeks; 38 male) from a longitudinal clinical trial. Race, neonatal medical index, neuroimaging, and frequency of therapy sessions were extracted from medical records. The Test of Infant Motor Performance and the General Movement Assessment were administered. Average weekly sessions of occupational therapy, physical therapy, and speech therapy were significantly different by type, but the magnitude and direction of the difference depended upon the discharge week. Infants at high risk for cerebral palsy based on their baseline General Movements Assessment scores received more therapy sessions than infants at low risk for cerebral palsy. Baseline General Movements Assessment was related to the mean number of occupational therapy sessions but not physical therapy or speech therapy sessions. Neonatal Medical Index scores and Test of Infant Motor Performance scores were not predictive of combined therapy services. Medical and developmental risk factors, as well as outcomes from therapy assessments, should be the basis for referral for therapy services in the neonatal intensive care unit.
The Effect of Follower Identity on Followership: The Mediating Role of Self-Efficacy
Authors: Zeng Weixi , Xu Zheming , Zhao Lixia
Published: June 2023

Followership is as crucial as leadership for organizational success. Significant efforts have been made by numerous researchers to examine how leadership influences followership; however, not enough attention has been paid to the influence of internal factors of followers on followership from the followers’ perspective. This study relies on identity theory to understand the relationship between the influence of followers’ perceived self-following traits (FTP) and followership prototype (FP) on followership, and the mediation role of self-efficacy in the relationship between FTP-FP consistency and followership. In order to avoid common method bias and ensure good discriminant validity of the variables, a two-wave time-lagged data collection design was used to collect 276 valid questionnaires from front-line business staff and junior supervisors in private and public sector organizations of China. Polynomial regression and response surface analysis were used to investigate the effect of FTP-FP consistency on followership. The empirical findings indicated that (1) the more consistent FTP-FP, the stronger the followership; (2) compared to the ‘low FTP-low FP’, employees with ‘high FTP-high FP’ had stronger followership; (3) employees with ‘high FTP-low FP’ had stronger followership than ‘low FTP-high FP’; (4) self-efficacy played a mediating role between FTP-FP consistency and followership. These findings contribute to management practice by revealing antecedents to followership from the perspective follower identity and the effect of follower identity on followership.
Creative Performance and Conflict through the Lens of Humble Leadership: Testing a Moderated Mediation Model
Authors: Liu Haiou , Ahmed Syed Jameel , Kakar Abdul Samad , Durrani Dilawar Khan
Published: June 2023

This study developed and tested a moderated mediation model by examining the relationships between humble leadership (HL), emotional intelligence, employee conflict (EC), and creative performance (CP), using resource-based theory as the theoretical foundation. We conducted a cross-sectional survey of 322 employees and their immediate supervisors (n = 53) from the telecom sector in Pakistan. The data was analyzed using AMOS 21 and SPSS 26. The results demonstrate that HL has a positive effect on creative performance and a negative relationship with employee conflict. Furthermore, employee conflict has a negative impact on CP and mediates the impact of HL on CP. Moreover, a leader’s emotional intelligence moderates the negative relationship between HL and EC. Finally, this study reveals that EI moderates the indirect effects of HL on CP. The conclusions and implications are discussed at the end of this paper.
Evidence for Using ACQUIRE Therapy in the Clinical Application of Intensive Therapy: A Framework to Guide Therapeutic Interactions
Authors: DeLuca Stephanie C. , Trucks Mary Rebekah , Wallace Dorian , Ramey Sharon Landesman
Published: June 2023

Intensive therapies have become increasingly popular for children with hemiparesis in the last two decades and are specifically recommended because of high levels of scientific evidence associated with them, including multiple randomized controlled trials and systematic reviews. Common features of most intensive therapies that have documented efficacy include: high dosages of therapy hours; active engagement of the child; individualized goal-directed activities; and the systematic application of operant conditioning techniques to elicit and progress skills with an emphasis on success-oriented play. However, the scientific protocols have not resulted in guiding principles designed to aid clinicians with understanding the complexity of applying these principles to a heterogeneous clinical population, nor have we gathered sufficient clinical data using intensive therapies to justify their widespread clinical use beyond hemiparesis. We define a framework for describing moment-by-moment therapeutic interactions that we have used to train therapists across multiple clinical trials in implementing intensive therapy protocols. We also document outcomes from the use of this framework during intensive therapies provided clinically to children (7 months–20 years) from a wide array of diagnoses that present with motor impairments, including hemiparesis and quadriparesis. Results indicate that children from a wide array of diagnostic categories demonstrated functional improvements.
Effect of Viroc Conduct under Compression on the Mechanical Characteristics of Sustainable Materials
Authors: Albadrani Mohammed Aqeel
Published: June 2023

To meet energy-saving requirements, in recent years, Saudi Arabia’s construction industry has focused on researching the use of naturally available resources as raw materials. This study looks at the behavior of Viroc, specifically using pinewood and its compression properties in eco-friendly concrete. The study demonstrates the feasibility of adding pinewood to concrete and provides a theoretical basis for the promotion of dry pinewood particles and Portland cement composite materials. The Viroc specimens used in the study are 18 mm long, 12 mm wide, and 12 mm deep. The mechanical properties of the specimens were tested and compared by using a universal testing machine (UTM) and the Ansys software program 2022. The test results show that Viroc can increase the compression strength and modulus of the construction material as well as increase its brittleness and toughness (mechanical properties). The results show that it is feasible to incorporate wood and cement, resulting in a new type of Viroc composite material in an eco-friendly environment.
Current Status and Future Research Trends of Construction Labor Productivity Monitoring: A Bibliometric Review
Authors: Lee Tsu Yian , Ahmad Faridahanim , Sarijari Mohd Adib
Published: June 2023

Construction labor productivity (CLP) is a critical measure of efficiency in the construction industry. This bibliometric review comprehensively analyzes global research trends in CLP monitoring over the past 56 years. The review identifies the top journals, authors, and nations contributing to this field and highlights a significant increase in publications since 2000. The co-authorship bibliometric map illustrates how different nations collaborate in research, with Europe and Asia being the most engaged regions in the study of CLP monitoring. The author keyword co-occurrence analysis indicated the need for more consistent and reliable measurements of CLP in the field. Furthermore, the review highlights the importance of factors such as occupational health and safety, change orders, and the adoption of lean construction principles and innovative technologies for monitoring and improving CLP. Finally, we evaluated the characteristics of different modeling approaches utilized in CLP monitoring studies, considering factors such as data availability, the complexity of relationships, and the required expertise. This study highlights the need for real-time and transparent CLP monitoring methods. Overall, this study contributes to the research field by offering insightful information on the current state of CLP monitoring and proposing potential future directions for research.
Immuno-Contexture and Immune Checkpoint Molecule Expression in Mismatch Repair Proficient Colorectal Carcinoma
Authors: Giacomelli Mauro , Monti Matilde , Pezzola Diego Cesare , Lonardi Silvia , Bugatti Mattia , Missale Francesco , Cioncada Rossella , Melocchi Laura , Giustini Viviana , Villanacci Vincenzo , Baronchelli Carla , Manenti Stefania , Imberti Luisa , Giurisato Emanuele , Vermi William
Published: June 2023

Colorectal carcinoma (CRC) represents a lethal disease with heterogeneous outcomes. Only patients with mismatch repair (MMR) deficient CRC showing microsatellite instability and hyper-mutated tumors can obtain clinical benefits from current immune checkpoint blockades; on the other hand, immune- or target-based therapeutic strategies are very limited for subjects with mismatch repair proficient CRC (CRCpMMR). Here, we report a comprehensive typing of immune infiltrating cells in CRCpMMR. We also tested the expression and interferon-γ-modulation of PD-L1/CD274. Relevant findings were subsequently validated by immunohistochemistry on fixed materials. CRCpMMR contain a significantly increased fraction of CD163+ macrophages (TAMs) expressing TREM2 and CD66+ neutrophils (TANs) together with decrease in CD4−CD8−CD3+ double negative T lymphocytes (DNTs); no differences were revealed by the analysis of conventional and plasmacytoid dendritic cell populations. A fraction of tumor-infiltrating T-cells displays an exhausted phenotype, co-expressing PD-1 and TIM-3. Remarkably, expression of PD-L1 on fresh tumor cells and TAMs was undetectable even after in vitro stimulation with interferon-γ. These findings confirm the immune suppressive microenvironment of CRCpMMR characterized by dense infiltration of TAMs, occurrence of TANs, lack of DNTs, T-cell exhaustion, and interferon-γ unresponsiveness by host and tumor cells. Appropriate bypass strategies should consider these combinations of immune escape mechanisms in CRCpMMR.
Intolerance of Uncertainty and Cognition in Breast Cancer Survivors: The Mediating Role of Anxiety
Authors: Yang Yesol , Gorka Stephanie M. , Pennell Michael L. , Weinhold Kellie , Orchard Tonya
Published: June 2023

Cancer-related cognitive impairment (CRCI) is one of the most prevalent symptoms that breast cancer survivors experience. While cancer treatments are established contributors to CRCI, inter-individual differences in CRCI are not well understood. Individual differences in sensitivity to uncertainty are potential contributors to CRCI; however, no prior studies have attempted to examine this link in the context of breast cancer. To address the gap, we used preliminary findings from an ongoing cross-sectional study. A total of 38 women with stage I–III breast cancer (1–4 years post-treatment) were included in this study. Intolerance of uncertainty (IU) was assessed using the Intolerance of Uncertainty Scale. Self-reported cognitive function was assessed with the Neuro-QoL questionnaire. Anxiety was assessed using the Patient-Reported Outcomes Measurement System Bank. From this study, we found that anxiety mediates the association between IU and cognitive function of survivors. In other words, among post-menopausal breast cancer survivors, those with higher IU showed higher anxiety and consequently had lower cognitive function. This finding suggests that assessing IU may help predict the risk of CRCI. This study expands the current knowledge that addresses the importance of IU as a factor associated with cognitive health.
Enzyme–Iron Oxide Nanoassemblies: A Review of Immobilization and Biocatalytic Applications
Authors: Valls-Chivas Ángeles , Gómez Javier , Garcia-Peiro Jose I. , Hornos Felipe , Hueso Jose L.
Published: June 2023

In the search for new biotechnological advances, increasing attention is currently being paid to the development of magnetic nanoplatforms loaded with enzymes, since, on the one hand, they can be recovered and reused, and on the other hand, they improve their catalytic activity and increase their stability, avoiding processes such as aggregation or autolysis. In this review, we evaluate a series of key parameters governing the enzyme–nanoparticle immobilization phenomena from a thermodynamic and kinetic point of view. We also focus on the use of magnetite nanoparticles (MNPs) as multifunctional vectors able to anchor enzymes, summarize the most relevant aspects of functionalization and immobilization and, finally, describe some recent and relevant applications of the enzyme–MNP hybrids as biocatalysts with especial emphasis on cancer therapy.
Synthesis of a Novel Photocatalyst Based on Silicotitanate Nanoparticles for the Removal of Some Organic Matter from Polluted Water
Authors: Alahl Amr A. Sayed , Ezzeldin Hesham A. , Al-Kahtani Abdullah A. , Pandey Sadanand , Kotp Yousra H.
Published: June 2023

The use of waste from various agricultural sectors has recently drawn increased interest from the scientific, technological, ecological, economic, and social fields. As such, in this study, a novel production of an affordable and environmentally friendly photocatalyst of silicotitanate (S1, S2, and S3) made from silica solution (extracted from rice husk ash) and various molar ratios of titanium (IV) 2-ethylhexyl-oxide is reported. Following that, chitosan/silicotitanate (CHMix) nanocomposite material was created through a crosslinking reaction between chitosan and fabricated silicotitanate (S2). Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), scanning electron microscopy (SEM-EDX), as well as N2 adsorption-desorption isotherm and zeta potential measurements were used to characterize each of the fabricated samples. Additionally, in comparison to neat chitosan, the newly fabricated material’s (CHMix) photocatalytic reactivity was investigated using two synthetic anionic dyes, reactive blue and Congo red, with decolorization rates of up to 95.76% and 99.9%, respectively. The decolorization results showed that CHMix is the most efficient photocatalyst for the degradation of reactive blue and Congo red. Reactive blue and Congo red’s molecular structures were almost completely broken when equilibrium was reached using sunlight, and the decolorization rate for both dyes was close to 100%. As a result, the combination of chitosan and silicotitanate, or CHMix, has an effective photocatalytic capability for dye degradation in both natural and concentrated sunlight.
Comparative Analysis of Two Candida parapsilosis Isolates Originating from the Same Patient Harbouring the Y132F and R398I Mutations in the ERG11 Gene
Authors: Štefánek Matúš , Garaiová Martina , Valček Adam , Jordao Luisa , Bujdáková Helena
Published: June 2023

This work presents a comparative analysis of two clinical isolates of C. parapsilosis, isolated from haemoculture (HC) and central venous catheter (CVC). Both strains harboured Y132F and R398I mutations in the gene ERG11 associated with resistance to fluconazole (FLC). Differences between the HC and CVC isolates were addressed in terms of virulence, resistance to FLC, and lipid distribution. Expression of the ERG6 and ERG9 genes, lipid analysis, fatty acid composition, and lipase activity were assessed via qPCR, thin-layer chromatography/high-performance liquid chromatography, gas chromatography, and spectrophotometry, respectively. Regulation of the ERG6 and ERG9 genes did not prove any impact on FLC resistance. Analysis of lipid metabolism showed a higher accumulation of lanosterol in both the isolates regardless of FLC presence. Additionally, a decreased level of triacylglycerols (TAG) with an impact on the composition of total fatty acids (FA) was observed for both isolates. The direct impact of the ERG11 mutations on lipid/FA analysis has not been confirmed. The higher lipase activity observed for C. parapsilosis HC isolate could be correlated with the significantly decreased level of TAG. The very close relatedness between both the isolates suggests that one isolate was derived from another after the initial infection of the host.
Circadian Disruption Primes Myofibroblasts for Accelerated Activation as a Mechanism Underpinning Fibrotic Progression in Non-Alcoholic Fatty Liver Disease
Authors: Jokl Elliot , Llewellyn Jessica , Simpson Kara , Adegboye Oluwatobi , Pritchett James , Zeef Leo , Donaldson Ian , Athwal Varinder S. , Purssell Huw , Street Oliver , Bennett Lucy , Guha Indra Neil , Hanley Neil A. , Meng Qing-Jun , Piper Hanley Karen
Published: June 2023

Circadian rhythm governs many aspects of liver physiology and its disruption exacerbates chronic disease. CLOCKΔ19 mice disrupted circadian rhythm and spontaneously developed obesity and metabolic syndrome, a phenotype that parallels the progression of non-alcoholic fatty liver disease (NAFLD). NAFLD represents an increasing health burden with an estimated incidence of around 25% and is associated with an increased risk of progression towards inflammation, fibrosis and carcinomas. Excessive extracellular matrix deposition (fibrosis) is the key driver of chronic disease progression. However, little attention was paid to the impact of disrupted circadian rhythm in hepatic stellate cells (HSCs) which are the primary mediator of fibrotic ECM deposition. Here, we showed in vitro and in vivo that liver fibrosis is significantly increased when circadian rhythm is disrupted by CLOCK mutation. Quiescent HSCs from CLOCKΔ19 mice showed higher expression of RhoGDI pathway components and accelerated activation. Genes altered in this primed CLOCKΔ19 qHSC state may provide biomarkers for early liver disease detection, and include AOC3, which correlated with disease severity in patient serum samples. Integration of CLOCKΔ19 microarray data with ATAC-seq data from WT qHSCs suggested a potential CLOCK regulome promoting a quiescent state and downregulating genes involved in cell projection assembly. CLOCKΔ19 mice showed higher baseline COL1 deposition and significantly worse fibrotic injury after CCl4 treatment. Our data demonstrate that disruption to circadian rhythm primes HSCs towards an accelerated fibrotic response which worsens liver disease.
Unraveling White Adipose Tissue Heterogeneity and Obesity by Adipose Stem/Stromal Cell Biology and 3D Culture Models
Authors: Baptista Leandra S. , Silva Karina R. , Jobeili Lara , Guillot Lucile , Sigaudo-Roussel Dominique
Published: June 2023

The immune and endocrine dysfunctions of white adipose tissue are a hallmark of metabolic disorders such as obesity and type 2 diabetes. In humans, white adipose tissue comprises distinct depots broadly distributed under the skin (hypodermis) and as internal depots (visceral). Depot-specific ASCs could account for visceral and subcutaneous adipose tissue properties, by regulating adipogenesis and immunomodulation. More importantly, visceral and subcutaneous depots account for distinct contributions to obesity and its metabolic comorbidities. Recently, distinct ASCs subpopulations were also described in subcutaneous adipose tissue. Interestingly, the superficial layer closer to the dermis shows hyperplastic and angiogenic capacities, whereas the deep layer is considered as having inflammatory properties similar to visceral. The aim of this focus review is to bring the light of recent discoveries into white adipose tissue heterogeneity together with the biology of distinct ASCs subpopulations and to explore adipose tissue 3D models revealing their advantages, disadvantages, and contributions to elucidate the role of ASCs in obesity development. Recent advances in adipose tissue organoids opened an avenue of possibilities to recreate the main cellular and molecular events of obesity leading to a deep understanding of this inflammatory disease besides contributing to drug discovery. Furthermore, 3D organ-on-a-chip will add reproducibility to these adipose tissue models contributing to their translation to the pharmaceutical industry.
USP10 Contributes to Colon Carcinogenesis via mTOR/S6K Mediated HIF-1α but Not HIF-2α Protein Synthesis
Authors: Kubaichuk Kateryna , Kietzmann Thomas
Published: June 2023

Colorectal cancer ranks among the third most common human malignant diseases and is one of the leading causes of cancer-related deaths globally. Colon cancer cells are hypoxic and display disturbed protein homeostasis. Ubiquitin-ligase-initiated proteasomal degradation as well as its prevention by deubiquitinases (DUBs) are supposed to contribute to the above-mentioned disturbances. However, not much is known about the involvement of ubiquitinating and deubiquitinating enzymes in colon cancer and their effect on the hypoxia response. Here, we identify the DUB ubiquitin-specific protease 10 (USP10) as an important player in the control of colon cancer progression and a new modifier of the hypoxia response. Mechanistically, we show that knockout of USP10 in different colon cancer cells causes an elevation in HIF-1α but not HIF-2α protein levels under both normoxic and hypoxic conditions. In addition, the lack of USP10 increased cellular migration, reduced cell adhesion, and switched the energy phenotype towards increased glycolysis and enhanced extracellular acidification. These changes were at least partially caused by HIF-1α, as the knockdown of HIF-1α rescued the cellular phenotype caused by USP10 deficiency. Interestingly, the USP10-dependent increase in HIF-1 α was neither caused by enhanced transcription nor prolonged half-life but via mTOR/S6K mediated HIF-1α protein synthesis. Together, the current findings indicate that USP10 is able to participate in colon carcinogenesis by modulating the hypoxia response and may therefore represent a new therapeutic target.
An Electrochemical Sensor for Trimethoprim Based on a Magnetic Molecularly Imprinted Carbon Paste Electrode
Authors: Liu Peng , Zhang Ruiying , Zheng Liyan , Cao Qiue
Published: June 2023

In order to achieve simple, rapid, and highly sensitive detection of trimethoprim (TMP), a magnetic molecularly imprinted carbon paste electrode (MCPE) was prepared by drop-coating magnetic molecularly imprinted polymer (MIP@Fe3O4@MWNTs) on the surface of reduction graphene oxide (rGO)/MCPE doped with Fe3O4@MWNTs. The introduction of multi-walled carbon nanotubes (MWNTs) and rGO served as dual signal-amplification materials, which can improve the response sensitivity of the sensor. In addition, the magnetic interaction between the substrate electrode and the molecularly imprinted material was beneficial to increasing the stability of the sensor. As expected, the electrochemical sensor not only showed sensitivity and selectivity for the detection of TMP, but it also possessed good stability. The detection range for TMP was 4.0 × 10−9~5.0 × 10−4 mol/L, and the detection limit was 1.2 × 10−9 mol/L. The response performance varied within 10% when the sensor was placed for more than 2 months and used more than 60 times. The spiked recoveries of TMP in environmental water samples, urine samples, and pharmaceuticals (drugs) were between 91% and 110%, and the relative standard deviation (RSD) was within 5%.
Correlation between the Rheological Properties of Asphalt Mortar and the High-Temperature Performance of Asphalt Mixture
Authors: Li Song , Shi Xingxing , Si Chundi , Bao Binshuo , Hu Mengmeng
Published: June 2023

The performance of an asphalt mixture is significantly affected by the properties of its asphalt mortar, which consists of an asphalt binder, mineral fillers, fine aggregates and air voids. The aim of this work was to evaluate the correlations between the high-temperature performance of an asphalt mixture and the rheological properties of its corresponding asphalt mortar. The multisequence repeated loading (MSRL) test was used to estimate the high-temperature performance of the asphalt mixture. Six different gradations, AC-13, SMA-13, SUP-13, AC-20, SUP-20 and AC-25, and two styrene–butadiene–styrene (SBS)-modified asphalt binders were considered and used to prepare the asphalt mixture specimens. The gradations and asphalt types of asphalt mortars were consistent with their asphalt mixtures. A modified multiple-stress creep–recovery (MSCR) test was proposed for evaluating the rheological properties of asphalt mortar with a dynamic shear rheometer (DSR). Based on the basic form of the Hirsh model, a multiple regression model was established, and its coefficient of determination (R-square) was 0.96. The rheological response of the asphalt mortar presented great correlation with the high-temperature behaviour of the asphalt mixture. In addition, the MSCR indicators (nonrecoverable compliance and percent recovery) obtained at 12.8 kPa creep stress represented the rheological status of asphalt mortar in asphalt mixture well. Therefore, the mechanical behaviours of asphalt mixture at high temperature could be accurately predicted by the MSCR indicators of asphalt mortar and its coarse aggregate parameters.
Hybrid Coating of Polystyrene–ZrO2 for Corrosion Protection of AM Magnesium Alloys
Authors: Chávez Luis , Veleva Lucien , Sánchez-Ahumada Diana , Ramírez-Bon Rafael
Published: June 2023

A hybrid material of polystyrene (PS)–ZrO2 was developed by the sol–gel technique and deposited by spin-coating on AM60 and AM60–AlN nanocomposite surfaces to enhance corrosion resistance in marine environments. PS–ZrO2 with an average thickness of ≈305 ± 20 nm was dispersed homogeneously, presenting isolated micro–nano-structure defects with air trapped inside, which led to an increase in roughness (≈4 times). The wettability of the coated substrates was close to the hydrophobic border (θCA=90°–94°). The coated samples were exposed for 30 days to SME solution, simulating the marine–coastal ambience. The initial pH = 7.94 of the SME shifted to more alkaline pH ≈ 8.54, suggesting the corrosion of the Mg matrix through the coating defects. In the meantime, the release of Mg2+ from the PS–ZrO2-coated alloy surfaces was reduced by ≈90% compared to that of non-coated. Localized pitting attacks occurred in the vicinity of Al–Mn and β–Mg17Al12 cathodic particles characteristic of the Mg matrix. The depth of penetration (≈23 µm) was reduced by ≈85% compared to that of non-coated substrates. The protective effect against Cl ions, attributed to the hybrid PS–ZrO2-coated AM60 and AM60–AlN surfaces, was confirmed by the increase in their polarization resistance (Rp) in 37% and 22%, respectively, calculated from EIS data.
Influence of Feedstock in the Formation Mechanism of Cold-Sprayed Copper Coatings
Authors: Liang Jui-Ting , Chang Shao-Fu , Wu Cheng-Han , Chen Shih-Hsun , Tsai Che-Wei , Cheng Kuei-Chung , Hsu Kim
Published: June 2023

The aim of this article is to investigate the characterizations and formation mechanisms of cold-sprayed coatings using gas-atomized and electrolytic powders. The study highlights the importance of reaching the particles’ critical velocity for optimal deposition. The main findings reveal that the morphology and stacking conditions of the coatings have a significant impact on their mechanical properties. Coatings made with gas-atomized powders exhibited noticeable pores and higher plastic deformation, while electrolytic powder coatings had greater density and smoother interfaces with the substrate. Adhesion strength relied on the physical bonding resulting from the plastic deformation energy between the spraying powders and the substrate. Gas-atomized powders showed higher adhesion compared to electrolytic powders, with dendritic powders resulting in lower adhesion due to dispersed impact force. The interaction between thermal and kinetic energy during the cold spraying process facilitated plastic deformation and particle deposition by softening and eroding the substrate surface. Insufficient plastic deformation with dendritic powders led to incomplete overlap, pore formation at the interface, and the persistence of the oxide layer along powder boundaries. Overall, these findings provide valuable insights into the influence of powder properties on coating morphology, adhesion strength, and overall performance, contributing to the understanding and optimization of cold spray processes.
Mathematical Modeling of Multi-Phase Filtration in a Deformable Porous Medium
Authors: Burnashev V. F. , Viswanathan K. K. , Kaytarov Z. D.
Published: June 2023

In this paper, a mathematical model of multiphase filtration in a deformable porous medium is presented. Based on the proposed model, the influence of the deformation of a porous medium on the filtration processes is studied. Numerical calculations are performed and the characteristics of the process are determined. This paper shows that an increase in the compressibility coefficient leads to a sharp decrease in porosity, absolute permeability and internal pressure of the medium near the well, and a decrease in the distance between wells leads to a sharp decrease in hydrodynamic parameters in the inter-well zone.