bluuebunny/crossref_metadata_2025 huggingface dataset:
The Fourfold Way to Gaussianity: Physical Interactions, Distributional Models and Monadic Transformations
Authors: Giona Massimiliano , Pezzotti Chiara , Procopio Giuseppe
Published: March 2023

The Central Limit Theorem stands as a milestone in probability theory and statistical physics, as the privileged, if not the unique, universal route to normal distributions. This article addresses and describes several other alternative routes to Gaussianity, stemming from physical interactions, related to particle-particle and radiative particle–photon elementary processes. The concept of conservative mixing transformations of random ensembles is addressed, as it represents the other main universal distributional route to Gaussianity in classical low-energy physics. Monadic ensemble transformations are introduced, accounting for radiative particle–photon interactions, and are intimately connected with the theory of random Iterated Function Systems. For Monadic transformations, possessing a thermodynamic constraint, Gaussianity represents the equilibrium condition in two limiting cases: in the low radiative-friction limit in any space dimension, and in the high radiative-friction limit, when the dimension of the physical space tends to infinity.
On the Simulations of Second-Order Oscillatory Problems with Applications to Physical Systems
Authors: Kwari Lydia J. , Sunday Joshua , Ndam Joel N. , Shokri Ali , Wang Yuanheng
Published: March 2023

Second-order oscillatory problems have been found to be applicable in studying various phenomena in science and engineering; this is because these problems have the capabilities of replicating different aspects of the real world. In this research, a new hybrid method shall be formulated for the simulations of second-order oscillatory problems with applications to physical systems. The proposed method shall be formulated using the procedure of interpolation and collocation by adopting power series as basis function. In formulating the method, off-step points were introduced within the interval of integration in order to bypass the Dahlquist barrier, improve the accuracy of the method and also upgrade the order of consistence of the method. The paper further validated the some properties of the hybrid method derived and from the results obtained; the new method was found to be consistent, convergent and stable. The simulation results generated as a result of the application of the new method on some second-order oscillatory differential equations also showed that the new hybrid method is computationally reliable.
Newton-like Normal S-iteration under Weak Conditions
Authors: Singh Manoj K. , Argyros Ioannis K. , Singh Arvind K.
Published: March 2023

In the present paper, we introduced a quadratically convergent Newton-like normal S-iteration method free from the second derivative for the solution of nonlinear equations permitting f′(x)=0 at some points in the neighborhood of the root. Our proposed method works well when the Newton method fails and performs even better than some higher-order converging methods. Numerical results verified that the Newton-like normal S-iteration method converges faster than Fang et al.’s method. We studied different aspects of the normal S-iteration method regarding the faster convergence to the root. Lastly, the dynamic results support the numerical results and explain the convergence, divergence, and stability of the proposed method.
Correction: Vogt et al. Production and Characterisation of Fibre-Reinforced All-Solid-State Electrodes and Separator for the Application in Structural Batteries. Batteries 2022, 8, 55
Authors: Vogt Daniel , Michalowski Peter , Kwade Arno
Published: March 2023

There was an error in the original publication [...]
Biological Activity of Cyclic Peptide Extracted from Sphaeranthus amaranthoides Using De Novo Sequencing Strategy by Mass Spectrometry for Cancer
Authors: Yanamadala Swarnalatha , Shanthirappan Sivakumar , Kannan Sidhika , Chiterasu Narendran , Subramanian Kumaran , Al-Keridis Lamya Ahmed , Upadhyay Tarun Kumar , Alshammari Nawaf , Saeed Mohd , Srinivasan Guru Prasad , Karunakaran Rohini
Published: March 2023

Though there are several advancements and developments in cancer therapy, the treatment remains challenging. In recent years, the antimicrobial peptides (AMPs) from traditional herbs are focused for identifying and developing potential anticancer molecules. In this study, AMPs are identified from Sphaeranthus amaranthoides, a natural medicinal herb widely used as a crucial immune stimulant in Indian medicine. A total of 86 peptide traces were identified using liquid-chromatography–electrospray-ionisation mass spectrometry (LC-ESI-MS). Among them, three peptides were sequenced using the manual de novo sequencing technique. The in-silico prediction revealed that SA923 is a cyclic peptide with C-N terminal interaction of the carbon atom of ASP7 with the nitrogen atom of GLU1 (1ELVFYRD7). Thus, SA923 is presented under the orbitides class of peptides, which lack the disulfide bonds for cyclization. In addition, SA923, steered with the physicochemical properties and support vector machine (SVM) algorithm mentioned for the segment, has the highest in silico anticancer potential. Further, the in vitro cytotoxicity assay revealed the peptide has anti-proliferative activity, and toxicity studies were demonstrated in Danio rerio (zebrafish) embryos.
Whole-Exome Sequencing in Family Trios Reveals De Novo Mutations Associated with Type 1 Diabetes Mellitus
Authors: Mousa Mira , Albarguthi Sara , Albreiki Mohammed , Farooq Zenab , Sajid Sameeha , El Hajj Chehadeh Sarah , ElBait Gihan Daw , Tay Guan , Deeb Asma Al , Alsafar Habiba
Published: March 2023

Type 1 diabetes mellitus (T1DM) is a chronic autoimmune disease characterized by insulin deficiency and loss of pancreatic islet β-cells. The objective of this study is to identify de novo mutations in 13 trios from singleton families that contribute to the genetic basis of T1DM through the application of whole-exome sequencing (WES). Of the 13 families sampled for this project, 12 had de novo variants, with Family 7 having the highest number (nine) of variants linked to T1DM/autoimmune pathways, whilst Family 4 did not have any variants past the filtering steps. There were 10 variants of 7 genes reportedly associated with T1DM (MST1; TDG; TYRO3; IFIHI; GLIS3; VEGFA; TYK2). There were 20 variants of 13 genes that were linked to endocrine, metabolic, or autoimmune diseases. Our findings demonstrate that trio-based WES is a powerful approach for identifying new candidate genes for the pathogenesis of T1D. Genotyping and functional annotation of the discovered de novo variants in a large cohort is recommended to ascertain their association with disease pathogenesis.
The Impact of Flavonoid-Loaded Nanoparticles in the UV Protection and Safety Profile of Topical Sunscreens
Authors: Fonseca Magda , Rehman Mubashar , Soares Raquel , Fonte Pedro
Published: March 2023

Excessive UV radiation exposure is harmful to skin cells since sunburn is accompanied by oxidative burst, leading to a rapid increase in skin cancer. However, the insufficient UV photoprotection of approved sunscreens and the negative impact of their compositions on ecosystems and human health makes the utility of sunscreen a questionable recommendation. Therefore, discovering UV filters with significant antioxidant activity and improved topical performance and photostability is an urgent need. Recently, the use of nanosized natural molecules incorporated in sunscreens has been a scientific hot topic, as it has been suggested that they provide a synergistic effect with synthetic UV filters, improving overall SPF and antioxidant activity, higher retention on the epidermis, and less toxicity. The aim of this review was to verify the usefulness of sunscreens incorporating flavonoid-loaded nanoparticles. A literature review was performed, where original and review articles published in the last 6 years were analyzed. Formulations containing nanosized flavonoids with improved UVA photoprotection and safer toxicological profiles, associated or not with synthetic filters, are promising sunscreens and more clinical investigation must be performed to validate these findings.
The Pancreatic Beta Cell: Editorial
Authors: Bartolomé Alberto
Published: March 2023

Pancreatic beta cells play a critical role in maintaining glucose homeostasis by serving as the primary source of insulin [...]
The Use of Sensors in Blood-Brain Barrier-on-a-Chip Devices: Current Practice and Future Directions
Authors: Kincses András , Vigh Judit P. , Petrovszki Dániel , Valkai Sándor , Kocsis Anna E. , Walter Fruzsina R. , Lin Hung-Yin , Jan Jeng-Shiung , Deli Mária A. , Dér András
Published: March 2023

The application of lab-on-a-chip technologies in in vitro cell culturing swiftly resulted in improved models of human organs compared to static culture insert-based ones. These chip devices provide controlled cell culture environments to mimic physiological functions and properties. Models of the blood-brain barrier (BBB) especially profited from this advanced technological approach. The BBB represents the tightest endothelial barrier within the vasculature with high electric resistance and low passive permeability, providing a controlled interface between the circulation and the brain. The multi-cell type dynamic BBB-on-chip models are in demand in several fields as alternatives to expensive animal studies or static culture inserts methods. Their combination with integrated biosensors provides real-time and noninvasive monitoring of the integrity of the BBB and of the presence and concentration of agents contributing to the physiological and metabolic functions and pathologies. In this review, we describe built-in sensors to characterize BBB models via quasi-direct current and electrical impedance measurements, as well as the different types of biosensors for the detection of metabolites, drugs, or toxic agents. We also give an outlook on the future of the field, with potential combinations of existing methods and possible improvements of current techniques.
Investigating Students’ Pre-University Admission Requirements and Their Correlation with Academic Performance for Medical Students: An Educational Data Mining Approach
Authors: Qahmash Ayman , Ahmad Naim , Algarni Abdulmohsen
Published: March 2023

Medical education is one of the most sought-after disciplines for its prestigious and noble status. Institutions endeavor to identify admissions criteria to register bright students who can handle the complexity of medical training and become competent clinicians. This study aims to apply statistical and educational data mining approaches to study the relationship between pre-admission criteria and student performance in medical programs at a public university in Saudi Arabia. The present study is a retrospective cohort study conducted at the College of Computer Science, King Khalid University, Abha, Kingdom of Saudi Arabia between February and November 2022. The current pre-admission criterion is the admission score taken as the weighted average of high school percentage (HSP), general aptitude test (GAT) and standard achievement admission test (SAAT), with respective weights of 0.3, 0.3 and 0.4. Regression and optimization techniques have been applied to identify weightages that better fit the data. Five classification techniques—Decision Tree, Neural Network, Random Forest, Naïve Bayes and K-Nearest Neighbors—are employed to develop models to predict student performance. The regression and optimization analyses show that optimized weights of HSP, GAT and SAAT are 0.3, 0.2 and 0.5, respectively. The results depict that the performance of the models improves with admission scores based on optimized weightages. Further, the Neural Network and Naïve Bayes techniques outperform other techniques. Firstly, this study proposes to revise the weights of HSP, GAT and SAAT to 0.3, 0.2 and 0.5, respectively. Secondly, as the evaluation metrics of models remain less than 0.75, this study proposes to identify additional student features for calculating admission scores to select ideal candidates for medical programs.
Experimental Loading of Staircase Made from Cement Fiber Boards with Cellulose Fibers Using Full-Scale Model
Authors: Nespěšný Ondřej , Bečkovský David , Vystrčil Jan , Vaněk Vojtěch , Novotný Miloslav , Pěnčík Jan
Published: March 2023

The study presents a possible innovative use of cement fiber boards (CFBs) reinforced with cellulose fibers for construction of an interior prefabricated staircase. Regarding the unusual use of traditional material that was used in all bearing elements of the staircase, a numerical simulation with the use of a material model SBETA was carried out and, subsequently, multiple experimental static loading was applied. In order to carry out experimental testing of static load capacity, a full-scale experiment method was chosen and performed on a real staircase structure for family houses. The full-scale experiment is considered the most precise method to test structures or material behavior. The obtained results show that the designed and tested staircase structure of CFBs is able to meet the requirements of technical standards related to static loading of staircases. The load test confirmed the potential use of cement fiber boards produced by the Hatschek process for real bearing structures under static loading.
Study on the Performance of Active Embedded Steel Wire Knot Form in Silicone Graphene Composite Thermal Insulation Structure Integrated System
Authors: Zhao Xiaoxia , Geng Dajiang , Cheng Zhiqiang , Bai Zhicheng , Long Mingjian , Chen Yang , Lu Qingqing , Ying Wei
Published: March 2023

Based on the advantages of the silicone graphene composite thermal insulation board, it was used to replace traditional plywood in the external wall formwork system, and the active embedded steel wire knot form in silicone graphene composite thermal insulation structure integrated system was designed. Firstly, the theoretical model of steel wire drawing resistance was established by theoretical analysis method, and the rationality of the theoretical model was verified by combining relevant experimental data. The relationship between multiple variables and steel wire pull-out resistance was analyzed. Then, combined with the theory of wind pressure strength of the exterior wall of a building structure, the layout form and the corresponding number of embedded steel wires of thermal insulation board under different building heights were analyzed. Finally, the silicone graphene composite thermal insulation board and ordinary plywood were compared and analyzed from the force of perspective of external wall formwork. The results showed that the pull-out resistance of steel wire was directly proportional to the diameter of steel wire, embedded depth, and embedded deflection angle. With the increase of building height, the number of steel wires to be arranged also increased. When the thickness of the silicone graphene composite thermal insulation board is not less than 80 mm, the anti-deformation effect is close to that of the ordinary plywood, which can meet the construction requirements of the external wall formwork. It can ensure the energy conservation and thermal insulation of the external wall, integrate the building’s exterior wall and thermal insulation structure of the building, and achieve the purpose of exemption from formwork removal.
Effects of Large-Diameter Rebar Replacement on Seismic Behavior of Precast Concrete Columns with Grouted Sleeve Connections
Authors: Wang Qiang , Qin Weiyang , Lu Chunling
Published: March 2023

Congested reinforcement may lead to difficulties with compacting concrete and reduce the connection efficiency. To overcome this problem, using large-diameter longitudinal rebar to replace medium-diameter longitudinal rebar to reduce the number of longitudinal rebars may be a useful mean. However, the seismic behavior of precast concrete (PC) columns with different-diameter longitudinal rebars was still unclear. In order to evaluate the influence of large-diameter longitudinal rebar replacement on the seismic behavior of PC columns, a series of large-scale reinforced concrete (RC) columns adopting similar concrete strength, longitudinal rebar ratio, and transverse rebar ratio was fabricated and tested. Six of the columns were prefabricated with grouted sleeve connections and the remaining two were cast in place (CIP) for reference. The longitudinal rebar diameter varied from 18 mm to 32 mm. A low-cycle reversed horizontal load was applied to study their seismic performance, including failure modes, load-bearing capacity, hysteresis behavior, stiffness degeneration, and energy-dissipation capacity. The test results showed that the PC column with large-diameter longitudinal rebar replacement performed similarly to CIP columns in general. The column with large-diameter longitudinal rebar suffered significant bond-slip between longitudinal rebar and concrete, especially for columns with a high axial compressive ratio of 0.6. It may be of detriment to the seismic behavior of the columns to some extent. Additionally, with the increase in the diameter of longitudinal rebar, the ductility and energy-dissipation capacity of PC columns were reduced slightly. In the grouted sleeve region, a local rigid zone was formed, making its overall lateral stiffness higher than that of corresponding CIP columns. It is recommended to extend the strengthening zone, with closer transverse reinforcement, to two times the column depth of the PC columns with grouted sleeve connections, as the plastic hinges may be shifted upward.
Experimental and Numerical Analysis of Reinforced Concrete Columns under Lateral Impact Loading
Authors: Chen Airong , Liu Yanjie , Ma Rujin , Zhou Xiaoyu
Published: March 2023

Reinforced concrete bridge columns (RCCs) are vulnerable to collisions with vehicles or vessels. To assess the performance of RCCs under lateral impact loading and to guide the impact-resistant design of RCCs, scaled model tests and numerical simulations were carried out in this study. An experimental facility was designed, and three sets of RCC specimens were tested. The specimens were available in three sizes: 60 cm × 14 cm × 14 cm, 80 cm × 14 cm × 14 cm, and 80 cm × 20 cm × 20 cm. Finite element models of RCCs were created in LS-DYNA, and parametric studies were carried out to investigate the variables influencing the impact resistance of RCCs. According to the findings, the impact mass and velocity had a positive correlation with the extreme value of dynamic strain. When the mass of a model car increased by 22.8% and 45.6% during the impact test, the extreme concrete strain at the same position increased by 22.5% and 42.3%, respectively. In addition, as the longitudinal reinforcement ratio increased, RCCs exhibited significantly less plastic deformation and damage. The findings of this study aided in the formulation of several recommendations for future research.
Evaluating the Effectiveness of Visuospatial Memory Stimulation Using Virtual Reality in Head and Neck Cancer Patients—Pilot Study
Authors: Serweta-Pawlik Anna , Lachowicz Maciej , Żurek Alina , Rosen Bill , Żurek Grzegorz
Published: March 2023

The prevalence of Cancer-related Cognitive Impairment (CRCI) in cancer patients necessitates the search for methods to help stimulate cognitive function. An innovative and repeatedly used method in oncology departments is virtual reality (VR). To date, no one has used VR for head and neck cancer patients in an attempt to stimulate their working memory. The goal of our research is to intervene with off-the-shelf VR applications in HNC patients to lower the risk of CRCI. Twenty-two patients with head and neck cancer were enrolled in this pilot study to characterize their visuospatial memory capacity, a form of working memory. During the oncological treatment, the patient had 30 min sessions, three times a week, using publicly available applications of VR. No significant changes were observed in the pre- and post-study. The individual patient results present a favorable trend of changes in their working memory after the intervention: despite oncological treatment, visual-spatial memory did not deteriorate in 88% of patients, including 28% of patients with higher scores than before the intervention. In this pilot study, VR was safely used in patients with head and neck cancer with no negative side effects. The use of VR may prevent CRCI in most HNC patients and, in some, VR may improve their cognitive functioning. A more rigorous study with larger numbers and controls is advised.
Mucins as Potential Biomarkers for Early Detection of Cancer
Authors: Gautam Shailendra K. , Khan Parvez , Natarajan Gopalakrishnan , Atri Pranita , Aithal Abhijit , Ganti Apar K. , Batra Surinder K. , Nasser Mohd W. , Jain Maneesh
Published: March 2023

Early detection significantly correlates with improved survival in cancer patients. So far, a limited number of biomarkers have been validated to diagnose cancers at an early stage. Considering the leading cancer types that contribute to more than 50% of deaths in the USA, we discuss the ongoing endeavors toward early detection of lung, breast, ovarian, colon, prostate, liver, and pancreatic cancers to highlight the significance of mucin glycoproteins in cancer diagnosis. As mucin deregulation is one of the earliest events in most epithelial malignancies following oncogenic transformation, these high-molecular-weight glycoproteins are considered potential candidates for biomarker development. The diagnostic potential of mucins is mainly attributed to their deregulated expression, altered glycosylation, splicing, and ability to induce autoantibodies. Secretory and shed mucins are commonly detected in patients’ sera, body fluids, and tumor biopsies. For instance, CA125, also called MUC16, is one of the biomarkers implemented for the diagnosis of ovarian cancer and is currently being investigated for other malignancies. Similarly, MUC5AC, a secretory mucin, is a potential biomarker for pancreatic cancer. Moreover, anti-mucin autoantibodies and mucin-packaged exosomes have opened new avenues of biomarker development for early cancer diagnosis. In this review, we discuss the diagnostic potential of mucins in epithelial cancers and provide evidence and a rationale for developing a mucin-based biomarker panel for early cancer detection.
Immunotherapy for Soft Tissue Sarcomas: Anti-PD1/PDL1 and Beyond
Authors: Fazel Mina , Dufresne Armelle , Vanacker Hélène , Waissi Waisse , Blay Jean-Yves , Brahmi Mehdi
Published: March 2023

Sarcomas gather a heterogeneous group of mesenchymal malignant tumors including more than 150 different subtypes. Most of them represent aggressive tumors with poor prognosis at the advanced stage, despite the better molecular characterization of these tumors and the development of molecular-driven therapeutic strategies. During the last decade, immunotherapy has been developed to treat advanced cancers, mainly thanks to immune checkpoint inhibitors (ICI) such as anti-PD1/PDL1 and later to adoptive immune cell therapies. In this review, we aim to summarize the state of the art of immunotherapy in soft tissue sarcomas (STS). Overall, the clinical trials of ICI that included a wide diversity of STS subtypes reported limited efficacy with some outlying responders. Both emerging biomarkers are of interest in selecting good candidates and in the development of combination therapies. Finally, the recent breakthroughs of innovative adoptive therapies in STS seem highly promising.
The First-In-Class Anti-AXL×CD3ε Pronectin™-Based Bispecific T-Cell Engager Is Active in Preclinical Models of Human Soft Tissue and Bone Sarcomas
Authors: Polerà Nicoletta , Mancuso Antonia , Riillo Caterina , Caracciolo Daniele , Signorelli Stefania , Grillone Katia , Ascrizzi Serena , Hokanson Craig A. , Conforti Francesco , Staropoli Nicoletta , Gervasi Luigia , Di Martino Maria Teresa , Arbitrio Mariamena , Nisticò Giuseppe , Crea Roberto , Tagliaferri Pierosandro , Juli Giada , Tassone Pierfrancesco
Published: March 2023

Sarcomas are heterogeneous malignancies with limited therapeutic options and a poor prognosis. We developed an innovative immunotherapeutic agent, a first-in-class Pronectin™-based Bispecific T-Cell Engager (pAXL×CD3ε), for the targeting of AXL, a TAM family tyrosine kinase receptor highly expressed in sarcomas. AXL expression was first analyzed by flow cytometry, qRT-PCR, and Western blot on a panel of sarcoma cell lines. The T-cell-mediated pAXL×CD3ε cytotoxicity against sarcoma cells was investigated by flow cytometry, luminescence assay, and fluorescent microscopy imaging. The activation and degranulation of T cells induced by pAXL×CD3ε were evaluated by flow cytometry. The antitumor activity induced by pAXL×CD3ε in combination with trabectedin was also investigated. In vivo activity studies of pAXL×CD3ε were performed in immunocompromised mice (NSG), engrafted with human sarcoma cells and reconstituted with human peripheral blood mononuclear cells from healthy donors. Most sarcoma cells showed high expression of AXL. pAXL×CD3ε triggered T-lymphocyte activation and induced dose-dependent T-cell-mediated cytotoxicity. The combination of pAXL×CD3ε with trabectedin increased cytotoxicity. pAXL×CD3ε inhibited the in vivo growth of human sarcoma xenografts, increasing the survival of treated mice. Our data demonstrate the antitumor efficacy of pAXL×CD3ε against sarcoma cells, providing a translational framework for the clinical development of pAXL×CD3ε in the treatment of human sarcomas, aggressive and still-incurable malignancies.
Comparison of Survival Outcomes of Single- and Five-Fraction Schedules of Stereotactic Body Radiation Therapy for Early-Stage Central or Peripheral NSCLC
Authors: Huang Karen , Prasad Sharan , Ma Sung Jun , Iovoli Austin J. , Farrugia Mark K. , Malik Nadia K. , Singh Anurag K.
Published: March 2023

Background: The treatment of early-stage non-small cell lung cancer (NSCLC) with stereotactic body radiation therapy (SBRT) frequently involves different fractionation schemes for peripheral and central tumors due to concerns with toxicity. We performed an observational cohort study to determine survival outcomes for patients with peripheral and central NSCLC treated with SBRT. Methods: A single-institutional database of patients with early-stage NSCLC treated with SBRT from September 2008 to December 2018 was evaluated. Outcomes were progression-free survival (PFS), overall survival (OS), local failure (LF), nodal failure (NF), and distant failure (DF). Cox multivariable analysis (MVA), Kaplan–Meier plotting, Fine–Gray competing risk MVA, and propensity score matching were performed. Results: A total of 265 patients were included with a median follow-up of 44.2 months. There were 191 (72%) and 74 (28%) patients with peripheral and central tumors treated with single-fraction SBRT to a dose of 27 Gy and five-fraction SBRT to a dose of 50 Gy, respectively. On Cox MVA, there was no difference in OS (adjusted hazards ratio (aHR) of 1.04, 95% CI of 0.74–1.46) or PFS (aHR of 1.05, 95% CI of 0.76–1.45). On Fine–Gray competing risk MVA, there were no differences in LF, NF, or DF. Propensity matching confirmed these findings. Conclusion: The survival outcomes of patients treated with SBRT for early-stage NSCLC were equivalent for central and peripheral tumors.
Survival in People Living with HIV with or without Recurrence of Hepatocellular Carcinoma after Invasive Therapy
Authors: Bertoni Costanza , Galli Laura , Lolatto Riccardo , Hasson Hamid , Siribelli Alessia , Messina Emanuela , Castagna Antonella , Uberti Foppa Caterina , Morsica Giulia
Published: March 2023

Background and Aims: To address the overall survival (OS) and recurrence (RE) in people living with HIV (PLWH) treated with invasive therapy (IT) for hepatocellular carcinoma (HCC). Methods: This is a retrospective cohort study on 41 PLWH with HCC receiving IT, defined as liver resection (LR), orthotopic liver transplantation (OLT), radiofrequency thermo-ablation (RFTA) trans arterial chemo, or radioembolization (CRE). OS and RE were investigated by Kaplan–Meier curves. The Cox proportional hazard regression model was used for multivariate analyses. Results: Recurrence occurred in 46.3% PLWH; in 36.7% of participants at 2 years and in 52% at 5 years from HCC diagnosis; it was less frequent in males, p = 0.036. Overall, 2- and 5-year survival after HCC diagnosis was 72% and 48%, respectively. Two-and five-year survival was 100% and 90.9%, respectively, in PLWH receiving OLT, compared to other IT (60.9% and 30.6%, respectively) log-rank p = 0.0006. Two- and five-year survival in participants with no-RE was 70.5% and 54.6%, respectively, and 73.7% and 42.1% among RE, respectively, log-rank p = 0.7772. By multivariate analysis, AFP at values < 28.8 ng/mL, at HCC diagnosis, was the only factor predicting survival. Conclusions: Fifty percent of PLWH survived five years after HCC diagnosis; 90.9% among OLT patients. Recurrence after IT was observed in 46% of HCC/PLWH. AFP cut-off levels of 28.8 ng/mL were the only independent variable associated with survival.
Pyruvate Dehydrogenase Kinase 4 Deficiency Increases Tumorigenesis in a Murine Model of Bladder Cancer
Authors: Woolbright Benjamin L. , Rajendran Ganeshkumar , Abbott Erika , Martin Austin , Didde Ryan , Dennis Katie , Harris Robert A. , Taylor John A.
Published: March 2023

Pyruvate dehydrogenase kinase 4 (PDK4) is a mitochondrial isozyme in the PDK family (PDK1-4) partially responsible for phosphorylation of pyruvate dehydrogenase (PDH). Phosphorylation of PDH is thought to result in a pro-proliferative shift in metabolism that sustains growth of cancer cells. Previous data from our lab indicate the pan-PDK inhibitor dichloroacetate (DCA) or acute genetic knockdown of PDK4 blocks proliferation of bladder cancer (BCa) cells. The goal of this study was to determine the role of PDK4 in an in vivo BCa model, with the hypothesis that genetic depletion of PDK4 would impair formation of BCa. PDK4−/− or WT animals were exposed to N-Butyl-N-(4-hydroxybutyl) nitrosamine (BBN) for 16 weeks, and tumors were allowed to develop for up to 7 additional weeks. PDK4−/− mice had significantly larger tumors at later time points. When animals were treated with cisplatin, PDK4−/− animals still had larger tumors than WT mice. PDK4 expression was assessed in human tissue and in mice. WT mice lost expression of PDK4 as tumors became muscle-invasive. Similar results were observed in human samples, wherein tumors had less expression of PDK4 than benign tissue. In summary, PDK4 has a complex, multifunctional role in BCa and may represent an underrecognized tumor suppressor.
Preparation of High-Performance Zn-Based Catalysts Using Printing and Dyeing Wastewater and Petroleum Coke as a Carrier in Acetylene Acetoxylation
Authors: Chen Yuhao , Li Mengli , Xu Zhuang , Shen Guowang , Wang Xugeng , Dai Bin
Published: March 2023

In this study, novel Zn catalysts were prepared by the wet impregnation method using printing and dyeing wastewater (PDW)-modified petroleum coke (petcoke) as a carrier, and they were applied to the acetylene acetoxylation. The pretreated petroleum coke has a high specific surface area which provides sufficient space for the loading of Zn. Calcination further increases catalyst activity, but when calcination temperatures exceed 1000 °C, a significant loss of Zn occurs, resulting in a dramatic decrease in catalyst activity. This enables the conversion of acetic acid up to 85%. X-ray photoelectron spectroscopy confirmed that a large amount of N is introduced into PC from PDW, which changes the electron transfer around Zn. Temperature-programmed desorption (TPD) analysis revealed that the nitrogen-doped Zn(OAc)2 catalyst enhanced the catalytic activity by modulating the intensity of the catalyzed adsorption of acetic acid and acetylene. This study provides a new way to reuse petroleum coke and printing and dyeing wastewater to support the sustainable development of the vinyl acetate industry.
FGF-2 Differentially Regulates Lens Epithelial Cell Behaviour during TGF-β-Induced EMT
Authors: Flokis Mary , Lovicu Frank J.
Published: March 2023

Fibroblast growth factor (FGF) and transforming growth factor-beta (TGF-β) can regulate and/or dysregulate lens epithelial cell (LEC) behaviour, including proliferation, fibre differentiation, and epithelial–mesenchymal transition (EMT). Earlier studies have investigated the crosstalk between FGF and TGF-β in dictating lens cell fate, that appears to be dose dependent. Here, we tested the hypothesis that a fibre-differentiating dose of FGF differentially regulates the behaviour of lens epithelial cells undergoing TGF-β-induced EMT. Postnatal 21-day-old rat lens epithelial explants were treated with a fibre-differentiating dose of FGF-2 (200 ng/mL) and/or TGF-β2 (50 pg/mL) over a 7-day culture period. We compared central LECs (CLECs) and peripheral LECs (PLECs) using immunolabelling for changes in markers for EMT (α-SMA), lens fibre differentiation (β-crystallin), epithelial cell adhesion (β-catenin), and the cytoskeleton (alpha-tropomyosin), as well as Smad2/3- and MAPK/ERK1/2-signalling. Lens epithelial explants cotreated with FGF-2 and TGF-β2 exhibited a differential response, with CLECs undergoing EMT while PLECs favoured more of a lens fibre differentiation response, compared to the TGF-β-only-treated explants where all cells in the explants underwent EMT. The CLECs cotreated with FGF and TGF-β immunolabelled for α-SMA, with minimal β-crystallin, whereas the PLECs demonstrated strong β-crystallin reactivity and little α-SMA. Interestingly, compared to the TGF-β-only-treated explants, α-SMA was significantly decreased in the CLECs cotreated with FGF/TGF-β. Smad-dependent and independent signalling was increased in the FGF-2/TGF-β2 co-treated CLECs, that had a heightened number of cells with nuclear localisation of Smad2/3 compared to the PLECs, that in contrast had more pronounced ERK1/2-signalling over Smad2/3 activation. The current study has confirmed that FGF-2 is influential in differentially regulating the behaviour of LECs during TGF-β-induced EMT, leading to a heterogenous cell population, typical of that observed in the development of post-surgical, posterior capsular opacification (PCO). This highlights the cooperative relationship between FGF and TGF-β leading to lens pathology, providing a different perspective when considering preventative measures for controlling PCO.
iProm-Sigma54: A CNN Base Prediction Tool for σ54 Promoters
Authors: Shujaat Muhammad , Kim Hoonjoo , Tayara Hilal , Chong Kil To
Published: March 2023

The sigma (σ) factor of RNA holoenzymes is essential for identifying and binding to promoter regions during gene transcription in prokaryotes. σ54 promoters carried out various ancillary methods and environmentally responsive procedures; therefore, it is crucial to accurately identify σ54 promoter sequences to comprehend the underlying process of gene regulation. Herein, we come up with a convolutional neural network (CNN) based prediction tool named “iProm-Sigma54” for the prediction of σ54 promoters. The CNN consists of two one-dimensional convolutional layers, which are followed by max pooling layers and dropout layers. A one-hot encoding scheme was used to extract the input matrix. To determine the prediction performance of iProm-Sigma54, we employed four assessment metrics and five-fold cross-validation; performance was measured using a benchmark and test dataset. According to the findings of this comparison, iProm-Sigma54 outperformed existing methodologies for identifying σ54 promoters. Additionally, a publicly accessible web server was constructed.
Prognostic Role of Soluble and Extracellular Vesicle-Associated PD-L1, B7-H3 and B7-H4 in Non-Small Cell Lung Cancer Patients Treated with Immune Checkpoint Inhibitors
Authors: Genova Carlo , Tasso Roberta , Rosa Alessandra , Rossi Giovanni , Reverberi Daniele , Fontana Vincenzo , Marconi Silvia , Croce Michela , Dal Bello Maria Giovanna , Dellepiane Chiara , Tagliamento Marco , Ciferri Maria Chiara , Zullo Lodovica , Fedeli Alessandro , Alama Angela , Cortese Katia , Gentili Chiara , Cella Eugenia , Anselmi Giorgia , Mora Marco , Barletta Giulia , Rijavec Erika , Grossi Francesco , Pronzato Paolo , Coco Simona
Published: March 2023

The treatment of non-small cell lung cancer (NSCLC) has changed dramatically with the advent of immune checkpoint inhibitors (ICIs). Despite encouraging results, their efficacy remains limited to a subgroup of patients. Circulating immune checkpoints in soluble (s) form and associated with extracellular vesicles (EVs) represent promising markers, especially in ICI-based therapeutic settings. We evaluated the prognostic role of PD-L1 and of two B7 family members (B7-H3, B7-H4), both soluble and EV-associated, in a cohort of advanced NSCLC patients treated with first- (n = 56) or second-line (n = 126) ICIs. In treatment-naïve patients, high baseline concentrations of sPD-L1 (>24.2 pg/mL) were linked to worse survival, whereas high levels of sB7-H3 (>0.5 ng/mL) and sB7-H4 (>63.9 pg/mL) were associated with better outcomes. EV characterization confirmed the presence of EVs positive for PD-L1 and B7-H3, while only a small portion of EVs expressed B7-H4. The comparison between biomarker levels at the baseline and in the first radiological assessment under ICI-based treatment showed a significant decrease in EV-PD-L1 and an increase in EV-B7H3 in patients in the disease response to ICIs. Our study shows that sPD-L1, sB7-H3 and sB7-H4 levels are emerging prognostic markers in patients with advanced NSCLC treated with ICIs and suggests potential EV involvement in the disease response to ICIs.
Metabolomic Analysis of Respiratory Epithelial Lining Fluid in Patients with Chronic Obstructive Pulmonary Disease—A Systematic Review
Authors: Pulik Kaja , Mycroft Katarzyna , Korczyński Piotr , Ciechanowicz Andrzej K. , Górska Katarzyna
Published: March 2023

Chronic obstructive pulmonary disease (COPD), as the third leading cause of death among adults, is a significant public health problem around the world. However, about 75% of smokers do not develop the disease despite the severe smoking burden. COPD is a heterogeneous disease, and several phenotypes, with differences in their clinical picture and response to treatment, have been distinguished. Metabolomic studies provide information on metabolic pathways, and therefore are a promising tool for understanding disease etiopathogenesis and the development of effective causal treatment. The aim of this systematic review was to analyze the metabolome of the respiratory epithelial lining fluid of patients with COPD, compared to healthy volunteers, refractory smokers, and subjects with other lung diseases. We included observational human studies. Sphingolipids, phosphatidylethanolamines, and sphingomyelins distinguished COPD from non-smokers; volatile organic compounds, lipids, and amino acids distinguished COPD from smokers without the disease. Five volatile organic compounds were correlated with eosinophilia and four were associated with a phenotype with frequent exacerbations. Fatty acids and ornithine metabolism were correlated with the severity of COPD. Metabolomics, by searching for biomarkers and distinguishing metabolic pathways, can allow us to understand the pathophysiology of COPD and the development of its phenotypes.
Degradation of Epoxy–Particles Composites Exposed to UV and Gamma Radiation
Authors: Torres Mauricio , Burdin Louise , Rentería-Rodríguez A. Victoria , Franco-Urquiza Edgar A.
Published: March 2023

In the design and fabrication of any structural system for space application, balance between mass, stiffness and strength is crucial. Structures in space environments are exposed to high radiation levels and thermal shock, due to the sun irradiance and rotation around Earth. Therefore, accurate determination of the thermal and radiation properties is a key issue for the materials used in such applications. This study reports the thermal and mechanical performance of particle composites (epoxy resin and ZnO particles) after gamma and UV radiation. Composites are exposed to gamma and UV radiation at rates of 1 kGy and 10 kGy and characterized after exposure. For the evaluation, DMA, TGA and three-point bending mechanical test are performed to determine thermal properties and possible material degradation after radiation exposure. The incorporation of the filler in the thermal, radiation and mechanical response of the epoxy system improves as a function of its concentration. Then, epoxy resin reinforced with ZnO particles can be a potential candidate as a polymeric matrix for fiber-reinforced composites for nanosatellites.
Advances in Ion Channel, Non-Desmosomal Variants and Autophagic Mechanisms Implicated in Arrhythmogenic Cardiomyopathy
Authors: Li Kexin , Jiang Yufeng , Zeng Yiyao , Zhou Yafeng
Published: March 2023

Arrhythmogenic cardiomyopathy (ACM) is a heterogeneous disorder characterized by the replacement of cardiac myocytes with fibro-fatty tissues, leading to abnormal excitation-contraction (EC) coupling and a range of malignant events, such as ventricular tachycardia (VT), sudden cardiac death/arrest (SCD/A) and heart failure (HF). The concept of ACM has recently been ex-tended to include right ventricular cardiomyopathy (ARVC), left ventricular cardiomyopathy (ALVC) and biventricular cardiomyopathy. ARVC is generally seen as the most common type of ACM. The pathogenesis of ACM involves mutation variants in desmosomal or non-desmosomal gene loci, as well as various external factors, such as intense exercise, stress and infections. Ion channel alterations, autophagy and non-desmosomal variants are also important components in the development of ACM. As clinical practice enters the era of precision therapy, it is important to review recent studies on these topics to better diagnose and treat the molecular phase of ACM.
Whole-Genome Analysis of Antimicrobial-Resistant Salmonella enterica Isolated from Duck Carcasses in Hanoi, Vietnam
Authors: Nguyen Trung Thanh , Le Hoa Vinh , Vu Thi Hai Ha , Nguyen Tuan Thanh , Nguyen Huong Minh , Pham Xuan Da , Tran Thi Thanh Huyen , Le Thi Hao Hong
Published: March 2023

Salmonella enterica is one of the most dangerous foodborne pathogens listed by the World Health Organization. In this study, whole-duck samples were collected at wet markets in five districts in Hanoi, Vietnam, in October 2019 to assess their Salmonella infection rates and evaluate the susceptibility of the isolated strains to antibiotics currently used in the prophylaxis and treatment of Salmonella infection. Based on the antibiotic resistance profiles, eight multidrug resistance strains were whole-genome-sequenced, and their antibiotic resistance genes, genotypes, multi-locus sequence-based typing (MLST), virulence factors, and plasmids were analyzed. The results of the antibiotic susceptibility test indicate that phenotypic resistance to tetracycline and cefazolin was the most common (82.4%, 28/34 samples). However, all isolates were susceptible to cefoxitin and meropenem. Among the eight sequenced strains, we identified 43 genes associated with resistance to multiple classes of antibiotics such as aminoglycoside, beta-lactam, chloramphenicol, lincosamide, quinolone, and tetracycline. Notably, all strains carried the blaCTX-M-55 gene, which confers resistance to third-generation antibiotics including cefotaxime, cefoperazone, ceftizoxime, and ceftazidime, as well as resistance genes of other broad-spectrum antibiotics used in clinical treatment such as gentamicin, tetracycline, chloramphenicol, and ampicillin. Forty-three different antibiotic resistance genes were predicted to be present in the isolated Salmonella strains’ genomes. In addition, three plasmids were predicted in two strains, 43_S11 and 60_S17. The sequenced genomes also indicated that all strains carried SPI-1, SPI-2, and SPI-3. These SPIs are composed of antimicrobial resistance gene clusters and thus represent a potential threat to public health management. Taken together, this study highlights the extent of multidrug-resistant Salmonella contamination in duck meat in Vietnam.
Laser Cladding of NiCrBSi/WC + W2C Composite Coatings
Authors: Lisiecki Aleksander , Kurc-Lisiecka Agnieszka
Published: March 2023

This article presents the results of a study on the laser cladding of metal matrix composite coatings using an experimental custom-made powder composed of NiCrBSi matrix with 65 wt.% reinforcing hard particles of eutectic WC + W2C. The chemical and phase composition of the powder was designed to ensure high hardness, abrasion wear resistance at moderate dynamic loads and corrosion resistance at high temperature of the coatings. The influence of the basic processing parameters of the laser cladding, especially energy input, on the quality and single bead geometry, the dilution, share of the massive carbides in the matrix, and the fraction share of reinforcing carbides particles on cross-section of the clads, as well as hardness profiles and abrasive wear resistance, were analysed and presented. The microstructure of test coatings, chemical and phase composition were analysed by optical and scanning electron microscopes (OM, SEM), EDS and XRD spectrometers. It was found that the differences in the wear resistance of the coatings produced at different energy inputs of laser cladding were directly related to the share of the massive carbides WC + W2C in the metal matrix NiCrBSi. The tribological characteristics of the coatings were also studied and described. The test results indicate that the coefficient of friction for carbides is slightly higher than for the metal matrix, and therefore the greater the share of carbides, the higher the value of the coefficient of friction of the coating.
Liquid–Solid Impact Mechanism, Liquid Impingement Erosion, and Erosion-Resistant Surface Engineering: A Review
Authors: Marzbali Mason , Yeganehdoust Firoozeh , Ibrahim Mohamed , Tarasi Fariba , Jadidi Mehdi
Published: March 2023

Liquid impingement erosion has been known as mechanical degradation, where the original material is removed progressively from a solid surface due to continued exposure to impacts by high-speed liquid droplets. This is a major issue in many industries, including aerospace and aviation and power generation, particularly gas and steam turbines, nuclear power plants, and wind energy. Tremendous numerical and experimental studies have been performed so far to understand the physical phenomena involved in this process and to improve the erosion resistance of different surfaces. In this review paper, first, the liquid–solid impact in a wide range of relative velocities is reviewed fundamentally. Then, the liquid impingement erosion of metals, including damage regimes and damage accumulation mechanisms, as well as the role of solid properties on erosion performance are explained. Finally, promising water droplet erosion-resistant materials and surface treatments are discussed. This review paper is intended to summarize the present knowledge of the different mechanisms involved in the liquid impingement erosion process.