bluuebunny/crossref_metadata_2025 huggingface dataset:
Molecular Docking and Intracellular Translocation of Extracellular Vesicles for Efficient Drug Delivery
Authors: Matsuzaka Yasunari , Yashiro Ryu
Published: October 2022

Extracellular vesicles (EVs), including exosomes, mediate intercellular communication by delivering their contents, such as nucleic acids, proteins, and lipids, to distant target cells. EVs play a role in the progression of several diseases. In particular, programmed death-ligand 1 (PD-L1) levels in exosomes are associated with cancer progression. Furthermore, exosomes are being used for new drug-delivery systems by modifying their membrane peptides to promote their intracellular transduction via micropinocytosis. In this review, we aim to show that an efficient drug-delivery system and a useful therapeutic strategy can be established by controlling the molecular docking and intracellular translocation of exosomes. We summarise the mechanisms of molecular docking of exosomes, the biological effects of exosomes transmitted into target cells, and the current state of exosomes as drug delivery systems.
Hypusinated eIF5A Promotes Ribosomal Frameshifting during Decoding of ODC Antizyme mRNA in Saccharomyces cerevisiae
Authors: Halwas Kai , Döring Lennard-Maximilian , Oehlert Franziska Valentina , Dohmen R. Jürgen
Published: October 2022

Polyamines are essential biogenic poly-cations with important roles in many cellular processes and diseases such as cancer. A rate-limiting step early in the biosynthesis of polyamines is the conversion of ornithine to putrescine by the homodimeric enzyme ornithine decarboxylase (ODC). In a conserved mechanism of posttranslational regulation, ODC antizyme (OAZ) binds to ODC monomers promoting their ubiquitin-independent degradation by the proteasome. Decoding of OAZ mRNA is unusual in that it involves polyamine-regulated bypassing of an internal translation termination (STOP) codon by a ribosomal frameshift (RFS) event. Using Saccharomyces cerevisiae, we earlier showed that high polyamine concentrations lead to increased efficiency of OAZ1 mRNA translation by binding to nascent Oaz1 polypeptide. The binding of polyamines prevents stalling of the ribosomes on OAZ1 mRNA caused by nascent Oaz1 polypeptide thereby promoting synthesis of full-length Oaz1. Polyamine depletion, however, also inhibits RFS during the decoding of constructs bearing the OAZ1 shift site lacking sequences encoding the Oaz1 parts implicated in polyamine binding. Polyamine depletion is known to impair hypusine modification of translation factor eIF5A. Using a novel set of conditional mutants impaired in the function of eIF5A/Hyp2 or its hypusination, we show here that hypusinated eIF5A is required for efficient translation across the OAZ1 RFS site. These findings identify eIF5A as a part of Oaz1 regulation, and thereby of polyamine synthesis. Additional experiments with DFMO, however, show that depletion of polyamines inhibits translation across the OAZ1 RFS site not only by reducing Hyp2 hypusination, but in addition, and even earlier, by affecting RFS more directly.
Patches as Polymeric Systems for Improved Delivery of Topical Corticosteroids: Advances and Future Perspectives
Authors: Dubashynskaya Natallia V. , Skorik Yury A.
Published: October 2022

Mucoadhesive polymer patches are a promising alternative for prolonged and controlled delivery of topical corticosteroids (CS) to improve their biopharmaceutical properties (mainly increasing local bioavailability and reducing systemic toxicity). The main biopharmaceutical advantages of patches compared to traditional oral dosage forms are their excellent bioadhesive properties and their increased drug residence time, modified and unidirectional drug release, improved local bioavailability and safety profile, additional pain receptor protection, and patient friendliness. This review describes the main approaches that can be used for the pharmaceutical R&D of oromucosal patches with improved physicochemical, mechanical, and pharmacological properties. The review mainly focuses on ways to increase the bioadhesion of oromucosal patches and to modify drug release, as well as ways to improve local bioavailability and safety by developing unidirectional -release poly-layer patches. Various techniques for obtaining patches and their influence on the structure and properties of the resulting dosage forms are also presented.
Valdecoxib Protects against Cell Apoptosis Induced by Endoplasmic Reticulum Stress via the Inhibition of PERK-ATF4-CHOP Pathway in Experimental Glaucoma
Authors: Gao Zhaolin , Li Min , Yao Fei , Xia Xiaobo , Duan Tianqi , Meng Jingzhuo , Huang Yanxia , He Ye , Saro Adonira , Huang Jufang
Published: October 2022

The purpose of this study was to investigate the effects of valdecoxib on the retina in retinal ischemia-reperfusion injury (IRI) and R28 cells following oxygen-glucose deprivation/recovery (OGD/R) injury, as well as the underlying mechanisms. Immunofluorescence and Cell Counting Kit-8 (CCK-8) analyses were used to identify the proper timepoint and concentration of valdecoxib’s protective effect on the R28 cells in the OGD/R model. Hematoxylin-eosin (HE) staining and immunofluorescence were used to explore valdecoxib’s effect on the retina and retina ganglion cell (RGC) in IRI. Cell apoptosis was determined by a TUNEL Apoptosis Detection Kit and Annexin V-FITC/PI flow cytometry. The expression levels of p-PERK, transcription factor 4 (ATF4), GRP78, CHOP, cleaved caspase 3, bax and bcl-2 were measured by Western blot analyses. The valdecoxib protected the R28 cells from OGD/R injury by decreasing the cell apoptosis rate, and it exerted a protective effect on retinas in I/R injury by inhibiting RGC apoptosis. The valdecoxib pretreatment reversed the expression of p-PERK, ATF4, CHOP, GRP78, cleaved caspase 3 and bax induced by the glaucomatous model. Meanwhile, the CCT020312 reversed the valdecoxib’s anti-apoptosis effect by activating PERK-ATF4-CHOP pathway-mediated endoplasmic reticulum (ER) stress. These findings suggest that valdecoxib protects against glaucomatous injury by inhibiting ER stress-induced apoptosis via the inhibition of the PERK-ATF4-CHOP pathway.
In Vitro/In Vivo Translation of Synergistic Combination of MDM2 and MEK Inhibitors in Melanoma Using PBPK/PD Modelling: Part I
Authors: Witkowski Jakub , Polak Sebastian , Rogulski Zbigniew , Pawelec Dariusz
Published: October 2022

Translation of the synergy between the Siremadlin (MDM2 inhibitor) and Trametinib (MEK inhibitor) combination observed in vitro into in vivo synergistic efficacy in melanoma requires estimation of the interaction between these molecules at the pharmacokinetic (PK) and pharmacodynamic (PD) levels. The cytotoxicity of the Siremadlin and Trametinib combination was evaluated in vitro in melanoma A375 cells with MTS and RealTime-Glo assays. Analysis of the drug combination matrix was performed using Synergy and Synergyfinder packages. Calculated drug interaction metrics showed high synergy between Siremadlin and Trametinib: 23.12%, or a 7.48% increase of combined drug efficacy (concentration-independent parameter β from Synergy package analysis and concentration-dependent δ parameter from Synergyfinder analysis, respectively). In order to select the optimal PD interaction parameter which may translate observed in vitro synergy metrics into the in vivo setting, further PK/PD studies on cancer xenograft animal models coupled with PBPK/PD modelling are needed.
Poor Compliance of Diabetic Patients with AI-Enabled E-Health Self-Care Management in Saudi Arabia
Authors: Alanazi Fuhid , Gay Valerie , Alturki Ryan
Published: October 2022

Still in its nascent stage, the Kingdom of Saudi Arabia’s self-care system lacks most features of a state-of-the-art e-health care system. With the Industrial Revolution 4.0 and the expanding use of artificial intelligence (AI), e-health initiatives in Saudi Arabia are increasing, which is compelling academics, clinicians, and policymakers to develop a better understanding of e-health trends, their efficacy, and their high impact areas. An increase in the number of diabetic patients in the Kingdom demands improvements to the current e-health care system, where the capability to manage diabetic patients is still in its infancy. In this survey, a total of 210 valid responses were obtained for analysis. SPSS version 27.0 was used for the quantitative analysis. The main technique used to address the aims of the data analysis was Spearman’s correlation analysis. This study indicated that the compliance rate with prescribed medication, blood glucose monitoring, and insulin injections from hospitals is increasing, with the highest rates found for Jeddah City. However, diet control and physical activity compliance levels were found to be poorly combined, predominantly due to the lower number of registered patients in the e-health care system. This non-compliance trends with selected variables (education and income) and highlights the dire need for improvement to the current health system by the inclusion of the latest technology, including big data, cloud computing, and the Internet of Things (IoT). Hence, this study suggests the implementation of government-regulated e-health care systems on mobile-based policies. The study revealed the experience of patients using e-health systems, which could be used to improve their efficacy and durability. More research needs to be conducted to address the deficiencies in the current e-health care system regarding diabetes care, and how it can be integrated into the healthcare system in general.
Addressing Vehicle Sharing through Behavioral Analysis: A Solution to User Clustering Using Recency-Frequency-Monetary and Vehicle Relocation Based on Neighborhood Splits
Authors: Brandizzi Nicolo’ , Russo Samuele , Galati Gaspare , Napoli Christian
Published: October 2022

In many developed cities around the world, vehicle sharing is becoming an increasingly popular form of green transportation. While such services are associated with lower emissions and easier mobility, their management poses a significant challenge. In this paper, we examine a dataset collected in Barcelona during the months of august and september 2020 in order to investigate relocation strategies and user clustering. By proposing a neighborhood area split and relating it to user demand, we propose two different areas based on majority demand and users’ requests and provide interpretations of both. We then aim to identify groups of similar users using a variant of Recency Frequency Monetary/Duration (RFM or RFD) clustering that extends to GPS coordinates of voyages in order to differentiate scores based on economic and geographical factors; furthermore, a user-based clustering approach was used to maximize client preferences. As a result of our analysis, the sharing company may be able to make more informed decisions regarding where to focus its resources. In fact, we find that the majority of the demand is concentrated in an area that represents 7.47 percent of the city’s area. Additionally, we propose a discount-based approach in order to influence the user’s behavior in parking the vehicle where it is most needed.
Physical Model of Shallow Foundation under Dynamic Loads on Sands
Authors: Gil Diego F. , Mendoza Cristhian C. , Vásquez-Varela Luis R. , Cano Santiago
Published: October 2022

Structures built on sands worldwide, with shallow foundations, have experienced damage and collapse during and after earthquakes. Two phenomena triggered the collapse: the liquefaction phenomenon and the P-Δ effects. However, current research and practice do not fully understand granular soil behavior during liquefaction and P-Δ effects, as proven by the sum of investigations on physical models, constitutive models, and laboratory testing proposals about these topics. A question appears at this point: what is the relationship between excitation frequency, displacement amplitude, and the triggering of overturning? To cope with this issue, the authors propose to create a physical 1-g model composed of a single-degree-of-freedom oscillator (SDOFO) capable of transmitting cyclic loadings to the soil in rocking vibration mode. The measurement methodology was based on computer vision using OpenCV by Python, which allowed the “free movement” of the SDOFO. The authors use computer vision as a suitable way to obtain displacements and times without sensors placed directly in the physical model. According to the results, it was possible to define an inversely non-linear relationship between frequency, displacement amplitude, and the total cycles required to reach overturning for different effective grain-size (D10).
Data-Driven Prediction of Stability of Rock Tunnel Heading: An Application of Machine Learning Models
Authors: Ngamkhanong Chayut , Keawsawasvong Suraparb , Jearsiripongkul Thira , Cabangon Lowell Tan , Payan Meghdad , Sangjinda Kongtawan , Banyong Rungkhun , Thongchom Chanachai
Published: October 2022

In this paper, Artificial Neural Networks (ANN) have been utilized to predict the stability of a planar tunnel heading in rock mass based on the well-defined Hoek-Brown (HB) yield criterion. The HB model was developed to capture the failure criterion of rock masses. To provide the datasets for an ANN model, the numerical upper bound (UB) and lower bound (LB) solutions obtained from the finite element limit analysis (FELA) with the HB failure criterion for the problem of tunnel headings are derived. The sensitivity analysis of all influencing parameters on the stability of rock tunnel heading is then performed on the developed ANN model. The proposed solutions will enhance the dependability and preciseness of predicting the stability of rock tunnel heading. Note that the effect of the unlined length ratio has not been explored previously but has been found to be of critical importance and significantly contributes to the failure of rock tunnel heading. By utilizing the machine learning-aided prediction capability of the ANN approach, the numerical solutions of the stability of tunnel heading can be accurately predicted, which is better than the use of the classic linear regression approach. Thus, providing a better and much safer assessment of mining or relatively long-wall tunnels in rock masses.
Development of Detailed Mix Design Methodology for Low Calcium Fly Ash Based Geopolymer Concrete Incorporating OPC and Crumb Rubber
Authors: Gill Parmender , Parveen
Published: October 2022

This experimental study proposes a systematic mix-design procedure to develop rubberized geopolymer concrete (RGPC). The developed method is meant to identify the mix ratios for the production of high-strength, low-calcium fly ash-based geopolymer concrete, with OPC as a supplementary binder and crumb rubber as a partial replacement for the fine aggregates. The binder (80% fly ash + 20% OPC) content (350, 375, and 400 kg/m3), crumb rubber percentage (0, 5, 10, and 15%), and NaOH molarity (8, 10, and 12 M) are identified as key variables, with the focus on attaining the targeted compressive strength and workability under heat curing (60 °C). Thirty-six mix designs were tested for their compressive strength after 7 and 28 days, and their graphical relationship with the chosen variables is presented (CR-GPC graphs). A trial experiment with an example is performed to establish the validity of the developed mix-design procedure. It was found that the targeted compressive strength and slump of the rubberized GPC can be achieved with conviction.
Novel Enrofloxacin Schiff Base Metal Complexes: Synthesis, Spectroscopic Characterization, Computational Simulation and Antimicrobial Investigation against Some Food and Phyto-Pathogens
Authors: Mohamed Amira A. , Ahmed Fatma M. , Zordok Wael A. , El-Shwiniy Walaa H. , Sadeek Sadeek A. , Elshafie Hazem S.
Published: October 2022

Condensation of the reaction between enrofloxacin and ethylenediamine in the existence of glacial acetic acid produced a new N,N-ethylene (bis 1-cyclopropyl-7-(4-ethylpiperazin-1-yl)-6-fluoro-1,4-dihydroquinoline-3-carboxylic acid Schiff base (H2Erx-en). H2Erx-en was used as a tetra-dentate ligand to produce novel complexes by interacting with metal ions iron(III), yttrium(III), zirconium(IV), and lanthanum(III). The synthetic H2Erx-en and its chelates had been detected with elemental analysis, spectroscopic methods, mass spectrometry, thermal studies, conductometric and magnetic measurements experiments. The calculated molar conductance of the complexes in 1 × 10−3 M DMF solution shows that iron(III), yttrium(III) and lanthanum(III) are 1:1 electrolytes, however the zirconium(IV) complex is non-electrolyte. The infrared spectra of H2Erx-en chelates indicated that the carboxylic group is deprotonated and H2Erx-en is associated with metals as a tetra-dentate through nitrogen and oxygen atoms. The disappearance of the carboxylic proton in all complexes corroborated information concerning H2Erx-en deprotonation and complexation with metal ions, according to 1H NMR data. Thermal analysis revealed the abundance of H2O particles in the chelates’ entrance and outlet spheres, indicating the disintegration pattern of H2Erx-en and their chelates. The Coats–Redfern and Horowitz–Metzeger approaches were utilized to calculate the thermodynamic items (Ea, ΔS *, ΔH *, and ΔG *) at n = 1 and n ≠ 1. The resulting data reveal better organized chelate building activation. Density functional theory (DFT) was created to properly grasp the optimal architecture of the molecules. The chelates are softer than H2Erx-en, with estimates varying between 95.23 eV to 400.00 eV, compared to 31.47 eV for H2Erx-en. The disc diffusion technique was utilized to assess H2Erx-en and their chelates in an antimicrobial assay against various food and phytopathogens. The zirconium(IV) chelate has the most potent antibacterial action and is particularly efficient against Salmonella typhi.
Molecular and Supramolecular Structure of a New Luminescent Hybrid Compound: (C5N2H14)2[BiBr6]Br·H2O
Authors: Bykov Andrey V. , Shestimerova Tatiana A. , Bykov Mikhail A. , Lyssenko Konstantin A. , Korshunov Vladislav M. , Metlin Mikhail T. , Taydakov Ilya V. , Shevelkov Andrei V.
Published: October 2022

The reaction of homopiperazine, C5N2H12, with BiBr3 in strong hydrobromic acid affords a new organic-inorganic hybrid (C5N2H14)2[BiBr6]Br·H2O. It crystallizes in the orthorhombic space group, Pbca, with unit cell dimensions of a = 15.0775 (2), b = 15.7569 (2), and c = 20.7881 (4) Å, and eight formula units per unit cell. The crystal structure features slightly distorted octahedral BiBr63− and monoatomic Br− anions in the inorganic substructure and C5N2H142+ dications and adjacent water molecules in the organic substructure. Various weak interactions that include (N)H···Br, (N)H···O, and (O)H···Br hydrogen bonds ensure the assembling of the structural moieties into a 3D supramolecular structure. (C5N2H14)2[BiBr6]Br·H2O shows two emission bands in the photoluminescence spectrum, a rather narrow deep-blue PL at 432 nm, and a broadband red PL centered at 650 nm. Their nature and relations to the crystal structure are discussed in this paper.
On the Mechanism of Heterogeneous Water Oxidation Catalysis: A Theoretical Perspective
Authors: Patra Shanti Gopal , Meyerstein Dan
Published: October 2022

Earth abundant transition metal oxides are low-cost promising catalysts for the oxygen evolution reaction (OER). Many transition metal oxides have shown higher OER activity than the noble metal oxides (RuO2 and IrO2). Many experimental and theoretical studies have been performed to understand the mechanism of OER. In this review article we have considered four earth abundant transition metal oxides, namely, titanium oxide (TiO2), manganese oxide/hydroxide (MnOx/MnOOH), cobalt oxide/hydroxide (CoOx/CoOOH), and nickel oxide/hydroxide (NiOx/NiOOH). The OER mechanism on three polymorphs of TiO2: TiO2 rutile (110), anatase (101), and brookite (210) are summarized. It is discussed that the surface peroxo O* intermediates formation required a smaller activation barrier compared to the dangling O* intermediates. Manganese-based oxide material CaMn4O5 is the active site of photosystem II where OER takes place in nature. The commonly known polymorphs of MnO2; α-(tetragonal), β-(tetragonal), and δ-(triclinic) are discussed for their OER activity. The electrochemical activity of electrochemically synthesized induced layer δ-MnO2 (EI-δ-MnO2) materials is discussed in comparison to precious metal oxides (Ir/RuOx). Hydrothermally synthesized α-MnO2 shows higher activity than δ-MnO2. The OER activity of different bulk oxide phases: (a) Mn3O4(001), (b) Mn2O3(110), and (c) MnO2(110) are comparatively discussed. Different crystalline phases of CoOOH and NiOOH are discussed considering different surfaces for the catalytic activity. In some cases, the effects of doping with other metals (e.g., doping of Fe to NiOOH) are discussed.
Activated Plasma Albumin Gel (APAG) in Transalveolar Technique for Maxillary Sinus Lift: A Case Series
Authors: Leonida Alessandro , Caccianiga Paolo , Bader Ayt Alla , Rosi Stefano , Ceraulo Saverio , Caccianiga Gianluigi
Published: October 2022

Over the past 20 years, transalveolar techniques have progressively improved. They have become increasingly predictable and reliable, with the additional advantage of simplified procedures that are less operator dependent. The aim of this study is to evaluate the effectiveness of a new technique to lift the maxillary sinus through a transalveolar approach, Simple Minimal Safe (SMS), with use of activated plasma albumin gel (APAG). A total of 33 patients (22 female and 11 male), aged between 36 and 79, were consecutively operated on, with 44 implants positioned using the SMS technique. All were placed in the premolar or molar areas of the maxillary bone. No implant was lost during the follow-up period (6 months) and all implants were then prosthetically loaded. The average bone gain was 4.43 mm. In the first quadrant, sites 15, 16 and 17 were involved with an average bone gain of 3.5 mm, 4.6 mm and 4.5 mm, respectively. In the second quadrant the sites 24, 25, 26 and 27 were involved with an average bone gain of 4.25 mm, 4.5 mm, 4.4 mm and 4.5 mm, respectively. Analyzing the data considering the sex, implants in women had an average gain of 4.66 mm, while in men the average gain was 3.83 mm. With the SMS technique, we achieved a reduction in post-operatory morbidity and in the frequency of Schneiderian membrane perforation. In conclusion, maxillary sinus augmentation via the transalveolar approach has become a more predictable surgical procedure and an easier technique due to less operator-dependent processes.
A Holistic Overview of the Internet of Things Ecosystem
Authors: Paolone Gaetanino , Iachetti Danilo , Paesani Romolo , Pilotti Francesco , Marinelli Martina , Di Felice Paolino
Published: October 2022

The Internet of Things (IoT) is a complex ecosystem of connected devices that exchange data over a wired or wireless network and whose final aim is to provide services either to humans or machines. The IoT has seen rapid development over the past decade. The total number of installed connected devices is expected to grow exponentially in the near future, since more and more domains are looking for IoT solutions. As a consequence, an increasing number of developers are approaching IoT technology for the first time. Unfortunately, the number of IoT-related studies published every year is becoming huge, with the obvious consequence that it would be impossible for anyone to predict the time that could be necessary to find a paper talking about a given problem at hand. This is the reason why IoT-related discussions have become predominant in various practitioners’ forums, which moderate thousands of posts each month. The present paper’s contribution is twofold. First, it aims at providing a holistic overview of the heterogeneous IoT world by taking into account a technology perspective and a business perspective. For each topic taken into account, a tutorial introduction (deliberately devoid of technical content to make this document within the reach of non-technical readers as well) is provided. Then, a table of very recent review papers is given for each topic, as the result of a systematic mapping study.
Cardio-Ankle Vascular Index as an Arterial Stiffness Marker Improves the Prediction of Cardiovascular Events in Patients without Cardiovascular Diseases
Authors: Okamoto Yuko , Miyoshi Toru , Ichikawa Keishi , Takaya Yoichi , Nakamura Kazufumi , Ito Hiroshi
Published: October 2022

Several studies have reported that the cardio-ankle vascular index (CAVI), a non-invasive measurement of arterial stiffness, is associated with the incidence of cardiovascular events. We investigated whether adding CAVI to a risk score improves the prediction of cardiovascular events in the setting of primary prevention. This retrospective observational study included consecutive 554 outpatients with cardiovascular disease risk factors but without known cardiovascular disease (68 ± 9 years, 64% men). The CAVI was measured using the VaSera vascular screening system. Major adverse cardiovascular events (MACE) included cardiovascular death, myocardial infarction, stroke, hospitalization for heart failure, and coronary revascularization. During a median follow-up of 4.3 years, cardiovascular events occurred in 65 patients (11.7%). Multivariate Cox analysis showed that abnormal CAVI (>9.0) was significantly associated with the incidence of MACE (hazard ratio 2.31, 95% confidence interval 1.27–4.18). The addition of CAVI to the Suita score, a conventional risk score for coronary heart disease in Japan, significantly improved the C statics from 0.642 to 0.713 (p = 0.04). In addition to a conventional risk score, CAVI improved the prediction of cardiovascular events in patients with cardiovascular disease risk factors but without known cardiovascular diseases.
Early Stages of Age-Related Macular Degeneration: Racial/Ethnic Differences and Proposal of a New Classification Incorporating Emerging Concept of Choroidal Pathology
Authors: Sasaki Mariko , Kawasaki Ryo , Yanagi Yasuo
Published: October 2022

The progression of age-related macular degeneration (AMD) is determined by environmental and genetic factors, and phenotypic or molecular risk factors have been investigated extensively. Interestingly, risk factor profiles for advanced AMD differ among individuals, and one of the causes of variation may be explained by their ethnic background. Recent advances in retinal imaging technology have led to the identification of previously unrecognized risk factors for advanced AMD on optical coherence tomography (OCT) and OCT angiography, which expands the concept of traditional imaging risk factors such as drusen and pigmentary abnormalities visible on color fundus photographs. This OCT imaging modality has identified novel pathognomonic changes for early AMD, including the associated photoreceptor, retinal pigment epithelium, and underlying choroidal changes. Regarding features of multimodal imaging associated with the presence or progression of geographic atrophy, there is an international expert consensus classification system; however, features associated with the progression of macular neovascularization (MNV) are still obscure. To make a consensus towards understanding features associated with the risk of MNV, this review focuses on the early stages of AMD by summarizing imaging characteristics and early signs and classifications in view of advanced multimodal imaging technology. Recent evidence suggests that neovascular AMD is not a single disease entity but a heterogeneous disease characterized by MNV. Besides drusen, OCT features associated with pigment abnormalities, such as shallow irregular RPE elevation (SIRE, also known as double-layer sign), pachychoroid pigment epitheliopathy, and choriocapillaris ischemia, seem to confer a high risk of MNV developing, especially for Asian populations.
Optimum Post-Discharge Care of Acute Kidney Injury (AKI) Survivors
Authors: Alwagdani Abdulrahman , Awad Alaa S. , Abdel-Rahman Emaad M.
Published: October 2022

Acute kidney injury (AKI) is a serious problem, affecting multiple organs, and is associated with a high mortality. The severe consequences of AKI extend beyond hospital discharge to the outpatient setting. While a plethora of literature exists guiding the management of AKI in the hospital setting, currently, there are no guidelines for the best care of AKI patients post-hospital discharge. In this review, we address the burden of AKI on patients and the importance of optimal coordinated care of these patients post-hospital discharge. We review the care of patients with or without dialysis requirements at the time of discharge and thereafter.
Acute Kidney Injury and Blood Purification Techniques in Severe COVID-19 Patients
Authors: Napoli Marianna , Provenzano Michele , Hu Lilio , Bini Claudia , Abenavoli Chiara , La Manna Gaetano , Comai Giorgia
Published: October 2022

Although most patients with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) experience respiratory manifestations, multi-organ dysfunction is frequent. Almost 20% of hospitalized patients with SARS-CoV-2 infection develop acute kidney injury (AKI). The pathophysiology of AKI is a result of both the direct and indirect effects of SARS-CoV-2 infection, including systemic inflammatory responses, the activation of the renin-angiotensin-aldosterone system (RAAS), and endothelial and coagulative dysfunction. Underlying SARS-CoV-2 infection-associated AKI, an immunological hyper-response with an unbalanced innate and adaptative response defined as a “cytokine storm” has emerged. Numerous agents have been tested in an effort to mitigate the cytokine storm, and a range of extracorporeal cytokine removal techniques have been proposed as potential therapeutic options. In the present review, we summarize the main pathogenetic mechanisms underlying COVID-19-related AKI in order to provide an appropriate individual therapeutic strategy to improve clinical outcomes and limit the progression of early disease.
Pathological Findings in COVID-19 and Non-COVID-19 Vaccine-Associated Lymphadenopathy: A Systematic Review
Authors: Chua Tzy Harn , Takano Angela
Published: October 2022

COVID-19 vaccine-associated lymphadenopathy (C19-VAL) is increasingly encountered with the widespread use of the vaccine in controlling the outbreak. We aim to characterize the pathological findings of COVID-19 and non-COVID-19 vaccine-associated lymphadenopathy (NC19-VAL). A search for studies that reported pathological findings in vaccine-associated lymphadenopathy on PubMed and Google Scholar was performed on 11 December 2021. C19-VAL studies were pooled for analysis. These studies were split into clinical lymphadenopathy (CL) and subclinical lymphadenopathy detected on imaging (SLDI) for subgroup analysis. A total of 25 studies were related to COVID-19 vaccines, and 21 studies were included in the pooled analysis. The pooled analysis included 37 patients with a mean age of 47.8 ± 19.1 years old, and 62.2% were females. The mean duration from last vaccination to development of CL/SLDI was 14.5 ± 11.0 days. Most were diagnosed as reactive or negative for malignancy (28/37, 75.5%), followed by Kikuchi–Fujimoto disease (KFD) (3/37, 8.1%), florid lymphoid hyperplasia (2/37, 5.4%), and granulomatous inflammation (2/37, 5.4%). Metastases were reported in two patients with a history of malignancy (2/37, 5.4%). Cases with florid lymphoid hyperplasia and KFD were younger than those with reactive changes. A total of 14 studies were related to non-COVID-19 vaccines. Caseating granulomatous inflammation was reported in BCG vaccine-associated lymphadenopathy, while other vaccines were associated with reactive lymphoid hyperplasia, florid post-vaccinal reactions, and KFD. Although most C19-VAL cases were reported as reactive or negative for malignancy, other diagnoses included florid lymphoid hyperplasia, KFD, and granulomatous inflammation. Metastases were reported in lymphadenopathy of patients with a history of malignancy, who had been incidentally vaccinated. In conclusion, C19-VAL can yield different histopathological diagnoses when sampled, most of which require clinical and radiological correlation for optimal patient management.
Utilizing Three-Dimensional Head-Lesser Trochanter Distance Could Further Reduce Leg Length Inequality in Primary Bipolar Hemiarthroplasty
Authors: Oh Seungbae , Kim Yong-Sik , Kwon Soon-Yong , Lim Young-Wook , Park Hyunwoo , Park Jongwoo , Song Joo-Hyoun
Published: October 2022

Background: The aim of this study was to investigate whether the use of three-dimensional (3-D) computed tomography (CT)-based head-lesser trochanter distance (HLD) could reduce leg length discrepancy (LLD) more than the use of a two-dimensional (2-D) plain film method in primary bipolar hemiarthroplasty. Methods: Propensity score matching (PSM) analysis was used to adjust the confounding factors. A retrospective comparative analysis of 128 patients was performed. In the control group, the leg length was equalized using the 2-D, plain film-based HLD. In the study group, primary bipolar hemiarthroplasty was performed using the 3-D CT-based HLD method. Postoperative LLDs were compared between the two groups using the method of Ranawat. In addition, the Harris hip score (HHS) was evaluated and compared at one year after surgery. Results: A significant difference was observed in mean postoperative LLD between the 2-D HLD group and the 3-D CT HLD group: 1.6 ± 1.2 mm (range, 0.1–6.0 mm) and 1.1 ± 1.2 mm (range, 0.1–5.1 mm), respectively (p < 0.05). Additionally, a higher percentage of patients in the 3-D CT HLD group had an LLD of less than 2 mm. The mean HHS at one year after surgery showed no significant difference between the two groups. Conclusions: To minimize the occurrence of LLD, HLD measurement from a CT scanner may be more accurate than an X-ray. The 2-D and 3-D HLD differences in the 3-D CT HLD group were statistically significant. Using a 3-D, CT-based HLD method might decrease the possibility of an LLD over 2 mm.
Clinical Advances in Cystic Fibrosis
Authors: Imperlini Esther , Papa Rosanna
Published: October 2022

Over recent decades, significant advances have been achieved in ameliorating clinical outcomes for patients with cystic fibrosis (CF) [...]
Association between Lower-to-Upper Ratio of Appendicular Skeletal Muscle and Metabolic Syndrome
Authors: Moon Hyun Eui , Lee Tae Sic , Chung Tae-Ha
Published: October 2022

(1) Background: Metabolic syndrome (MetS) is a cluster-based disorder comprising several pre-disease or pre-clinical statuses for diabetes, hypertension, dyslipidemia, cardiovascular risk, and mortality. Appendicular skeletal muscle (ASM), or lean mass, is considered the main site of insulin-mediated glucose utilization. Therefore, we aimed to reveal the association between lower appendicular skeletal muscle mass to upper appendicular skeletal muscle mass ratio (LUR) and risk for MetS. (2) Methods: We analyzed the 2008–2011 Korean National Health Examination and Nutrition Survey (KNHANES) data. Quintiles of lower ASM to upper ASM ratio (LUR) were categorized as follows: Q1: ≤2.65, Q2: 2.66–2.80, Q3: 2.81–2.94, Q4: 2.95–3.11, and Q5: ≥3.12 in men and Q1: ≤3.00, Q2: 3.01–3.18, Q3: 3.19–3.36, Q4: 3.37–3.60, and Q5: ≥3.61 in women. Multivariate logistic regression models were used after setting MetS and the LUR quintiles as the independent and dependent variables and adjusting for covariates. (3) Result: In men, MetS in accordance with the LUR quintiles exhibits a reverse J-curve. All groups from Q2 to Q5 had a lower odds ratio (OR) (95% CI) for MetS compared to the Q1 group. The lowest OR (95% CI) of 0.85 (0.80–0.91) was observed in Q4. However, in women, the figure shows a sine curve. Compared to the Q1 group, the Q2 and Q3 groups had a higher OR, while the Q4 and Q5 groups presented a lower OR. Among them, the OR (95% CI) in the Q4 group was lowest, at 0.83 (0.76–0.91). (4) Conclusions: While total appendicular skeletal muscle mass is important to prevent MetS, it is necessary to maintain an optimal ratio of muscle mass between the upper and lower appendicular skeletal muscle mass.
Development of the Sphenoid Sinus in Japanese Children: A Retrospective Longitudinal Study Using Three-Dimensional Computed Tomography
Authors: Higashino Masaaki , Abe Susumu , Sawada Masaki , Yamada Hiroshi , Ayani Yusuke , Haginomori Shin-Ichi , Kawata Ryo , Matsuoka Toshihiro , Nakai Go , Osuga Keigo , Tanaka Eiji
Published: October 2022

Background: The sphenoid sinus (SS) is located close to vital structures, such as the pituitary gland, and it has significant clinical relevance. This study aimed to clarify the growth pattern of the SS in Japanese children using three-dimensional computed tomography (CT). Methods: Seventy-eight participants with congenital, acquired, or external auditory canal cholesteatoma were recruited and underwent CT more than twice during their treatment. Using the volume-rendered images, the size and volume of the SS were measured. Furthermore, on the scout image, the morphological measurements of the cranial base were determined. Results: The size and volume of the SS increased with age, and peaked at the mean age of 15 years. For males, the volume of the SS was smaller than that of females aged <5 years. The growth rate of the SS was significantly higher in males than in females. The maximum growth rate was detected at the age of 12 years for males and 10 years for females. For females, the increase in the length of the anterior cranial base ceased at approximately 10 years of age and remained constant thereafter. In contrast, for males, the length of the anterior cranial base increased gradually until 15 years of age. Conclusions: Considering the similarity of the periods between the adolescent growth spurt and the maximum growth rate of the SS, changes in the size of the SS may be used as an indicator of the physical growth spurt.
Clinical Pharmacology of Factor XI Inhibitors: New Therapeutic Approaches for Prevention of Venous and Arterial Thrombotic Disorders
Authors: Campello Elena , Simioni Paolo , Prandoni Paolo , Ferri Nicola
Published: October 2022

Bleeding is the dominant adverse event of anticoagulation and often discourages many patients and physicians from starting treatment with anticoagulant drugs. The fact that factor (F)XI deficiency is associated with a mild bleeding phenotype and that FXI knockdown or inhibition in different animal models reduced the occurrence of thrombotic events in response to injury suggests that FXI is more important for the coagulation propagation and thrombotic process than for the overall hemostasis. The aim of this review is to summarize clinical pharmacology and evidence from phase 2 clinical trials on efficacy and safety of drugs directed against FXI for the treatment and prevention of thrombosis. Inhibition of FXI or FXIa has been proven to be effective in phase 2 studies at preventing venous thromboembolism (VTE) in patients undergoing total knee arthroplasty, or for prevention of major adverse vascular events in patients with end-stage kidney disease undergoing hemodialysis or as adjuncts to antiplatelet therapy for prevention of recurrent ischemic events in patients with acute myocardial infarction or non-cardioembolic stroke. Should the efficacy of FXI inhibitors as anticoagulant without impairing the hemostasis be proven in phase 3 randomized clinical trials, it would provide an innovative therapeutic option.
State of the Art in Lung Nodule Localization
Authors: Alicuben Evan T. , Levesque Renee L. , Ashraf Syed F. , Christie Neil A. , Awais Omar , Sarkaria Inderpal S. , Dhupar Rajeev
Published: October 2022

Lung nodule and ground-glass opacity localization for diagnostic and therapeutic purposes is often a challenge for thoracic surgeons. While there are several adjuncts and techniques in the surgeon’s armamentarium that can be helpful, accurate localization persists as a problem without a perfect solution. The last several decades have seen tremendous improvement in our ability to perform major operations with minimally invasive procedures and resulting lower morbidity. However, technological advances have not been as widely realized for lung nodule localization to complement minimally invasive surgery. This review describes the latest advances in lung nodule localization technology while also demonstrating that more efforts in this area are needed.
Guillain–Barré Syndrome in Northern China: A Retrospective Analysis of 294 Patients from 2015 to 2020
Authors: Zhai Qiongqiong , Guo Cheng , Xue Fang , Qiang Jing , Li Chaonan , Guo Li
Published: October 2022

Objectives: Acute motor axonal neuropathy (AMAN) was first reported to be the main subtype of Guillain–Barré syndrome (GBS) in northern China in the 1990s. About 30 years has passed, and it is unknown whether the disease spectrum has changed over time in northern China. We aimed to study the epidemiological, clinical, and electrophysiological features of GBS in northern China in recent years. Methods: We retrospectively analyzed the medical records of GBS patients admitted to the Second Hospital of Hebei Medical University in northern China from 2015 to 2020. Results: A total of 294 patients with GBS were enrolled, with median age 53 years and 60.5% of participants being male, and a high incidence in summer and autumn. AMAN was still the predominant subtype in northern China (40.1%). The AMAN patients had shorter time to nadir, longer hospitalization time, and a more severe HFGS score at discharge than acute inflammatory demyelinating polyneuropathies (AIDP) (p < 0.05). With SPSS multivariable logistic regression analysis, we found the GBS disability score (at admission), dysphagia, and dysautonomia were independent risk factors for GBS patients requiring MV (p < 0.05). In comparison with other regions, the proportion of AMAN in northern China (40.1%) was higher than in eastern (35%) and southern (19%) China. Conclusions: AMAN is still the predominant subtype in northern China after 30 years, but there have been changes over time in the GBS spectrum since the 1990s. There are regional differences in GBS in China.
China Rose/Hibiscus rosa-sinensis Pollen-Mediated Phytosynthesis of Silver Nanoparticles and Their Catalytic Activity
Authors: Kumar Brajesh , Smita Kumari , Angulo Yolanda , Debut Alexis , Cumbal Luis
Published: October 2022

We reported an ecofriendly method for the phytosynthesis of silver nanoparticles (AgNPs) using the pollen of double-petal China rose/Hibiscus rosa-sinensis as a natural reducing and stabilizing agent. The phytosynthesized AgNPs were preliminary characterized by their optical properties by UV–vis spectroscopy and showed their corresponding surface plasmonic resonance (SPR) at 405 nm. The distribution pattern and morphology of the synthesized AgNPs were confirmed by dynamic light scattering and transmission electron microscopy whereas X-ray diffraction and Fourier transform infrared spectroscopy depicts their surface properties and crystalline nature. The phytosynthesized AgNPs were spherical, well dispersed, 10–50 nm in size, and crystalline. It also showed moderate photocatalytic activity for the degradation (>30%, 2.5 h) of Thioflavin T dye in direct sunlight. Thus, this work highlights the importance of China rose pollen in green nanoscience and supports the cleanliness of nature by naturally available materials.
Processing, Mechanical Characterization, and Electric Discharge Machining of Stir Cast and Spray Forming-Based Al-Si Alloy Reinforced with ZrO2 Particulate Composites
Authors: Shetty Raviraj , Gurupur Prakash Rao , Hindi Jamaluddin , Hegde Adithya , Naik Nithesh , Ali Mohammed Sabraz Sabir , Patil Ishwargouda S. , Nayak Madhukar
Published: October 2022

High performance lightweight structures made of metal matrix composites (MMCs) are in demand for application in variety of industries such as aircraft, spacecraft, automobile, marine, sports equipment, etc. However, uniform distribution of the reinforcement phase to improve the mechanical properties and quality of MMCs has been the challenge for the manufacturing industries. Hence, researchers are focusing on the development of traditional low-cost method of producing metal matrix composites. In the view of above facts, an attempt is made to study the processing and characterization of Si-Al alloy reinforced with zirconium dioxide particulate composites in this paper. Hence, this paper concentrates on experimentally identifying the effect of stir cast and spray forming processing techniques followed by hot pressing on micro hardness, compressive strength, and tensile strength using Taguchi’s design of experiments for aluminum silicon matrix alloy reinforced with zirconium dioxide particulates. From the extensive experimentation on aluminum and silicon reinforced with the ZrO2 powder particulates, it was observed that there was an improvement in selected mechanical properties as the percentage of ZrO2 increased with 13 wt.% of silicon under spray forming processing technique compared to stir cast composites. This may be due to uniform distribution homogenous dispersion, larger work hardening rate, and structure of dislocation tangles around the ZrO2 particulates that occurred during spray forming processing technique. Further, results obtained from the interaction plot, contour plot, main effects plot, and analysis of variance (ANOVA) proved to be successful for identifying the optimum processing parameters for Si-Al alloy reinforced with zirconium dioxide particulate composites. Further, this paper also discusses wear study using pin on disc wear testing apparatus on spray forming processed aluminum and silicon (13.0 wt.%) alloy reinforced with the ZrO2 powder particulates based on Taguchi’s design of experiments followed by second order model generation for wear using response surface methodology. Finally, electrode wear study of spray forming processed aluminum and silicon alloy reinforced with the ZrO2 powder particulates using electric discharge machining by varying peak current (A), pulse on time (μs), and pulse off time (μs) using brass, copper, and graphite as electrode material based on L27orthogonal array. The understanding gained from the design of experiments in this paper can be used to develop future guidelines for processing and characterization of Si-Al alloy reinforced with zirconium dioxide particulate composites.
4-Band Multispectral Images Demosaicking Combining LMMSE and Adaptive Kernel Regression Methods
Authors: Hounsou Norbert , Mahama Amadou T. Sanda , Gouton Pierre
Published: October 2022

In recent years, multispectral imaging systems are considerably expanding with a variety of multispectral demosaicking algorithms. The most crucial task is setting up an optimal multispectral demosaicking algorithm in order to reconstruct the image with less error from the raw image of a single sensor. In this paper, we presented a four-band multispectral filter array (MSFA) with the dominant blue band and a multispectral demosaicking algorithm that combines the linear minimum mean square error (LMMSE) and the adaptive kernel regression methods. To estimate the missing blue bands, we used the LMMSE algorithm and for the other spectral bands, the directional gradient method, which relies on the estimated blue bands. The adaptive kernel regression is then applied to each spectral band for their update without persistent artifacts. The experiment results demonstrate that our proposed method outperforms other existing approaches both visually and quantitatively in terms of peak signal-to-noise-ratio (PSNR), structural similarity index (SSIM) and root mean square error (RMSE).