bluuebunny/crossref_metadata_2025 huggingface dataset:
Human IgMhiCD300a+ B Cells Are Circulating Marginal Zone Memory B Cells That Respond to Pneumococcal Polysaccharides and Their Frequency Is Decreased in People Living with HIV
Authors: Vitallé Joana , Zenarruzabeitia Olatz , Merino-Pérez Aitana , Terrén Iñigo , Orrantia Ane , Pacho de Lucas Arantza , Iribarren José A. , García-Fraile Lucio J. , Balsalobre Luz , Amo Laura , de Andrés Belén , Borrego Francisco
Published: September 2023

CD300a is differentially expressed among B cell subsets, although its expression in immunoglobulin (Ig)M+ B cells is not well known. We identified a B cell subset expressing CD300a and high levels of IgM (IgMhiCD300a+). The results showed that IgMhiCD300a+ B cells were CD10−CD27+CD25+IgDloCD21hiCD23−CD38loCD1chi, suggesting that they are circulating marginal zone (MZ) IgM memory B cells. Regarding the immunoglobulin repertoire, IgMhiCD300a+ B cells exhibited a higher mutation rate and usage of the IgH-VDJ genes than the IgM+CD300a− counterpart. Moreover, the shorter complementarity-determining region 3 (CDR3) amino acid (AA) length from IgMhiCD300a+ B cells together with the predicted antigen experience repertoire indicates that this B cell subset has a memory phenotype. IgM memory B cells are important in T cell-independent responses. Accordingly, we demonstrate that this particular subset secretes higher amounts of IgM after stimulation with pneumococcal polysaccharides or a toll-like receptor 9 (TLR9) agonist than IgM+CD300a− cells. Finally, the frequency of IgMhiCD300a+ B cells was lower in people living with HIV-1 (PLWH) and it was inversely correlated with the years with HIV infection. Altogether, these data help to identify a memory B cell subset that contributes to T cell-independent responses to pneumococcal infections and may explain the increase in severe pneumococcal infections and the impaired responses to pneumococcal vaccination in PLWH.
A Multiplexed Urinary Biomarker Panel Has Potential for Alzheimer’s Disease Diagnosis Using Targeted Proteomics and Machine Learning
Authors: Hällqvist Jenny , Pinto Rui C. , Heywood Wendy E. , Cordey Jonjo , Foulkes Alexander J. M. , Slattery Catherine F. , Leckey Claire A. , Murphy Eimear C. , Zetterberg Henrik , Schott Jonathan M. , Mills Kevin , Paterson Ross W.
Published: September 2023

As disease-modifying therapies are now available for Alzheimer’s disease (AD), accessible, accurate and affordable biomarkers to support diagnosis are urgently needed. We sought to develop a mass spectrometry-based urine test as a high-throughput screening tool for diagnosing AD. We collected urine from a discovery cohort (n = 11) of well-characterised individuals with AD (n = 6) and their asymptomatic, CSF biomarker-negative study partners (n = 5) and used untargeted proteomics for biomarker discovery. Protein biomarkers identified were taken forward to develop a high-throughput, multiplexed and targeted proteomic assay which was tested on an independent cohort (n = 21). The panel of proteins identified are known to be involved in AD pathogenesis. In comparing AD and controls, a panel of proteins including MIEN1, TNFB, VCAM1, REG1B and ABCA7 had a classification accuracy of 86%. These proteins have been previously implicated in AD pathogenesis. This suggests that urine-targeted mass spectrometry has potential utility as a diagnostic screening tool in AD.
Effects of Early Exposure to Isoflurane on Susceptibility to Chronic Pain Are Mediated by Increased Neural Activity Due to Actions of the Mammalian Target of the Rapamycin Pathway
Authors: Li Qun , Mathena Reilley Paige , Li Fengying , Dong Xinzhong , Guan Yun , Mintz Cyrus David
Published: September 2023

Patients who have undergone surgery in early life may be at elevated risk for suffering neuropathic pain in later life. The risk factors for this susceptibility are not fully understood. Here, we used a mouse chronic pain model to test the hypothesis that early exposure to the general anesthetic (GA) Isoflurane causes cellular and molecular alterations in dorsal spinal cord (DSC) and dorsal root ganglion (DRG) that produces a predisposition to neuropathic pain via an upregulation of the mammalian target of the rapamycin (mTOR) signaling pathway. Mice were exposed to isoflurane at postnatal day 7 (P7) and underwent spared nerve injury at P28 which causes chronic pain. Selected groups were treated with rapamycin, an mTOR inhibitor, for eight weeks. Behavioral tests showed that early isoflurane exposure enhanced susceptibility to chronic pain, and rapamycin treatment improved outcomes. Immunohistochemistry, Western blotting, and q-PCR indicated that isoflurane upregulated mTOR expression and neural activity in DSC and DRG. Accompanying upregulation of mTOR and rapamycin-reversible changes in chronic pain-associated markers, including N-cadherin, cAMP response element-binding protein (CREB), purinergic P2Y12 receptor, glial fibrillary acidic protein (GFAP) in DSC; and connexin 43, phospho-extracellular signal-regulated kinase (p-ERK), GFAP, Iba1 in DRG, were observed. We concluded that early GA exposure, at least with isoflurane, alters the development of pain circuits such that mice are subsequently more vulnerable to chronic neuropathic pain states.
High Salt Promotes Inflammatory and Fibrotic Response in Peritoneal Cells
Authors: Pap Domonkos , Pajtók Csenge , Veres-Székely Apor , Szebeni Beáta , Szász Csenge , Bokrossy Péter , Zrufkó Réka , Vannay Ádám , Tulassay Tivadar , Szabó Attila J.
Published: September 2023

Recent studies draw attention to how excessive salt (NaCl) intake induces fibrotic alterations in the peritoneum through sodium accumulation and osmotic events. The aim of our study was to better understand the underlying mechanisms. The effects of additional NaCl were investigated on human primary mesothelial cells (HPMC), human primary peritoneal fibroblasts (HPF), endothelial cells (HUVEC), immune cells (PBMC), as well as ex vivo on peritoneal tissue samples. Our results showed that a high-salt environment and the consequently increased osmolarity increase the production of inflammatory cytokines, profibrotic growth factors, and components of the renin–angiotensin–aldosterone system, including IL1B, IL6, MCP1, TGFB1, PDGFB, CTGF, Renin and Ace both in vitro and ex vivo. We also demonstrated that high salt induces mesenchymal transition by decreasing the expression of epithelial marker CDH1 and increasing the expression of mesenchymal marker ACTA2 and SNAIL1 in HPMCs, HUVECs and peritoneal samples. Furthermore, high salt increased extracellular matrix production in HPFs. We demonstrated that excess Na+ and the consequently increased osmolarity induce a comprehensive profibrotic response in the peritoneal cells, thereby facilitating the development of peritoneal fibrosis.
Transcriptomic Analysis of Insulin-Secreting Murine Hepatocytes Transduced with an Integrating Adeno-Associated Viral Vector
Authors: Mahoney Alexandra L. G. , Joshua Sergio , Nassif Najah T. , Simpson Ann M.
Published: September 2023

Type 1 Diabetes (T1D) is a chronic metabolic disorder for which current treatments are unable to prevent the onset of complications. Previously, we used an adeno-associated viral vector (AAV8) to deliver furin-cleavable human insulin (INS-FUR) to the livers of diabetic non-obese diabetic (NOD) mice to reverse T1D. The use of the traditional AAV8-INS-FUR vector could not bring about normoglycemia. However, this vector, coupled with a transposon system in the AAV8/piggyBac-INS-FUR vector, was able to do so. This study aimed to investigate the transcriptomic profiles of the livers of diabetic, AAV8-INS-FUR-transduced, and AAV8/piggyBac-INS-FUR-transduced NOD mice and compare these to the normal liver to identify genetic differences resulting from delivery of the AAV8/piggyBac-INS-FUR vector which produced normoglycemia. Differential gene expression was determined by RNA-Seq analysis and differentially expressed genes from each treatment were mapped onto cellular pathways to determine the treatments’ cell signaling and downstream effects. We observed distinct differences between the piggyBac-transduced and diabetic models, particularly in terms of metabolic function and the upregulation of key pancreatic markers in the liver of piggyBac-transduced animals. The success of the AAV8/piggyBac-INS-FUR vector in achieving normoglycemia through stable transduction was evident. However, further engineering is necessary to achieve complete pancreatic transdifferentiation of liver cells.
Non-Ischemic Myocardial Fibrosis in End-Stage Kidney Disease Patients: A New Perspective
Authors: Nakata Kenji , Joki Nobuhiko
Published: September 2023

Cardiovascular medicine, especially for ischemic heart disease, has evolved and advanced over the past two decades, leading to substantially improved outcomes for patients, even those with chronic kidney disease. However, the prognosis for patients with end-stage kidney disease (ESKD) has not improved so greatly. Recent studies have reported that myocardial fibrosis in chronic kidney disease patients is characterized by patchy and interstitial patterns. Areas of fibrosis have been located in the perivascular space, and severe fibrotic lesions appear to spread into myocardial fiber bundles in the form of pericellular fibrosis. These findings are fully consistent with known characteristics of reactive fibrosis. In hemodialysis patients, a greater extent of myocardial fibrosis is closely associated with a poorer prognosis. In this review, we focus on non-ischemic cardiomyopathy, especially reactive myocardial fibrosis, in ESKD patients.
A Novel Amphoteric Ion-Modified, Styrene-Based Nano-Microsphere and Its Application in Drilling Fluid
Authors: Zhang Xianfa , Liu Jingping , Sun Jinsheng , Wang Zonglun , Dai Zhiwen , Sun Yuanwei , Zhang Taifeng
Published: September 2023

With the gradual depletion of shallow oil and gas, deep oil and gas has become the focus of development. However, deep formations generally face the challenge of high-temperature and high-salinity, and drilling fluid agents are prone to failure, leading to drilling fluid intrusion into the formation that can cause serious drilling accidents such as well bore collapse. For this, a styrene-based nano-microsphere (SSD) modified with amphoteric ions was developed, with a particle size of 228 nm which could resist temperatures up to 200 °C and sodium chloride (NaCl) up to saturation. SSD has significant salt-responsive properties and its aqueous dispersion becomes transparent with increasing salinity. The SSD provided superior plugging performance in solutions containing NaCl, with a core plugging efficiency of 95.2%, and it was significantly better than the anion-modified microspheres. In addition, in drilling fluids under high temperature and high-salinity conditions, the SSD promotes particle gradation of drilling fluids and improves the zeta potential through its own plugging and synergistic effect with clay, which significantly improves the comprehensive performance of drilling fluids, such as stability, rheological performance, and filtration reduction performance. The development of SSD provides a new idea for research of high-temperature and high-salinity-resistant drilling fluid agents.
Diagnostic Roles of Immunohistochemical Markers CK20, CD44, AMACR, and p53 in Urothelial Carcinoma In Situ
Authors: Yoo Daeseon , Min Kyueng-Whan , Pyo Jung-Soo , Kim Nae Yu
Published: September 2023

Background and Objectives: This study aimed to evaluate the diagnostic roles of various immunohistochemical (IHC) markers in urothelial carcinoma in situ (uCIS) through a meta-analysis and review of diagnostic test accuracy. Materials and Methods: The IHC markers CK20, CD44, AMACR, and p53 were evaluated in the present study. We analyzed the expression rates of the IHC markers and compared their diagnostic accuracies. Results: The estimated expression rates were 0.803 (95% confidence interval [CI]: 0.726–0.862), 0.142 (95% CI: 0.033–0.449), 0.824 (95% CI: 0.720–0.895), and 0.600 (95% CI: 0.510–0.683) for CK20, CD44, AMACR, and p53, respectively. In the comparison between uCIS and reactive/normal urothelium, the expression of CK20, AMACR, and p53 in uCIS was significantly higher than in reactive/normal urothelium. CD44 showed significantly lower expression in uCIS than in the reactive/normal urothelium. Among the markers, AMACR had the highest sensitivity, specificity, and diagnostic odds ratio. The AUC on SROC was the highest for CK20. Conclusions: In conclusion, IHC markers, such as CK20, CD44, AMACR, and p53, can be useful in differentiating uCIS from reactive/normal urothelium.
Nortopsentins as Leads from Marine Organisms for Anticancer and Anti-Inflammatory Agent Development
Authors: Pecoraro Camilla , Terrana Francesca , Panzeca Giovanna , Parrino Barbara , Cascioferro Stella , Diana Patrizia , Giovannetti Elisa , Carbone Daniela
Published: September 2023

The marine environment is an excellent source of molecules that have a wide structural diversity and a variety of biological activities. Many marine natural products (MNPs) have been established as leads for anticancer drug discovery. Most of these compounds are alkaloids, including several chemical subclasses. In this review, we focus on the bis-indolyl alkaloid Nortopsentins and their derivatives with antiproliferative properties. Nortopsentins A–C were found to exhibit in vitro cytotoxicity against the P388 murine leukaemia cell line. Their structural manipulation provided a wide range of derivatives with significant anti-tumour activity against human cell lines derived from different cancer types (bladder, colon, gastric, CNS, liver, lung, breast, melanoma, ovarian, pancreatic, prostate, pleural mesothelioma, renal, sarcoma, and uterus). In vivo assays on animal models also proved that Nortopsentins and related bis-indolyl compounds have potent anti-inflammatory activity. These remarks set the foundation for future investigations into the development of new Nortopsentin derivatives as new anticancer and anti-inflammatory agents.
Development of a Liquid Chromatography–Tandem Mass Spectrometry (LC–MS/MS) Method for Characterizing Linalool Oral Pharmacokinetics in Humans
Authors: Wang Yan-Hong , Mondal Goutam , Stevens Nicole , Bascoul Cécile , Osguthorpe Russell J. , Khan Ikhlas A. , Yates Charles R.
Published: September 2023

Lavender (Lavandula angustifolia Miller or Lavandula officinalis Chaix) is an ethnopharmacological plant commonly known as English lavender. Linalool and linalyl acetate are putative phytoactives in lavender essential oil (LEO) derived from the flower heads. LEO has been used in aroma or massage therapy to reduce sleep disturbance and to mitigate anxiety. Recently, an oral LEO formulation was administered in human clinical trials designed to ascertain its anxiolytic effect. However, human pharmacokinetics and an LC–MS/MS method for the measurement of linalool are lacking. To address this deficiency, a rapid and sensitive liquid chromatography–tandem mass spectrometry (LC–MS/MS) method was developed for the analysis of linalool in human serum. Prior to the analysis, a simple sample preparation protocol including protein precipitation and liquid–liquid extraction of serum samples was created. The prepared samples were analyzed using a C18 reversed-phase column and gradient elution (acetonitrile and water, both containing 0.1% formic acid). A Waters Xevo TQ-S tandem mass spectrometer (positive mode) was used to quantitatively determine linalool and IS according to transitions of m/z 137.1→95.1 (tR 0.79 min) and 205.2→149.1 (tR 1.56 min), respectively. The method was validated for precision, accuracy, selectivity, linearity, sensitivity, matrix effects, and stability, and it was successfully applied to characterize the oral pharmacokinetics of linalool in humans. The newly developed LC–MS/MS-based method and its application in clinical trial serum samples are essential for the characterization of potential pharmacokinetic and pharmacodynamic interactions.
Gut Microbiota Combined with Metabolomics Reveal the Mechanisms of Sika Deer Antler Protein on Cisplatin-Induced Hepatorenal Injury in Mice
Authors: Wang Lulu , Li Lei , Wang Zhenyi , Zhang Pu , Zhang Jing
Published: September 2023

Cisplatin is a widely used antineoplastic drug, though its adverse effects, particularly its hepatorenal toxicity, limit its long-term application. Sika deer antler is a valuable traditional Chinese medicine (TCM) documented to possess the capacity for tonifying the kidney and regulating the liver, of which the sika deer antler protein is an important active ingredient. In this study, two protein fractions, SVPr1 and SVPr2, of sika deer antler were purified and administered to mice treated with cisplatin, and serum metabolome and fecal microbiota were measured using ultrahigh-performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) and 16S rRNA gene sequencing. SVPr1 and SVPr2 significantly ameliorated cisplatin-induced liver and kidney injury and reduced mitochondrial dysfunction, oxidative stress, inflammatory response, and apoptosis. In addition, SVPr1 and SVPr2 impacted the gut microbiota structure of mice, significantly increasing the relative abundances of Lactobacillus, which deserves to be scrutinized. Moreover, SVPr1 and SVPr2 antagonism of cisplatin-induced hepatorenal injury may be related to the regulation of lysine degradation, tryptophan metabolism, and riboflavin metabolism pathways, significantly altering the levels of L-saccharopine, L-lysine, L-kynurenine, 3-methylindole, xanthurenic acid, riboflavin, and D-ribulose-5-phosphate. A correlation between the differential metabolites and Lactobacillus was identified. These findings increased the knowledge of the gut microbiota–metabolites axis mediated by SVPr1 and SVPr2, and may be able to contribute to the development of new therapeutic strategies for the simultaneous prevention and treatment of liver and kidney injury from cisplatin treatment.
Bismuth-Antimony Alloy Nanoparticles Embedded in 3D Hierarchical Porous Carbon Skeleton Film for Superior Sodium Storage
Authors: Wang Jiafan , Lin Yonghui , Lv Wei , Yuan Yongfeng , Guo Shaoyi , Yan Weiwei
Published: September 2023

A composite film that features bismuth–antimony alloy nanoparticles uniformly embedded in a 3D hierarchical porous carbon skeleton is synthesized by the polyacrylonitrile-spreading method. The dissolved polystyrene is used as a soft template. The average diameter of the bismuth–antimony alloy nanoparticles is ~34.5 nm. The content of the Bi-Sb alloy has an impact on the electrochemical performance of the composite film. When the content of the bismuth–antimony alloy is 45.27%, the reversible capacity and cycling stability of the composite film are the best. Importantly, the composite film outperforms the bismuth–antimony alloy nanoparticles embedded in dense carbon film and the cube carbon nanobox in terms of specific capacity, cycling stability, and rate capability. The composite film can provide a discharge capacity of 322 mAh g−1 after 500 cycles at 0.5 A g−1, 292 mAh g−1 after 500 cycles at 1 A g−1, and 185 mAh g−1 after 2000 cycles at 10 A g−1. The carbon film prepared by the spreading method presents a unique integrated composite structure that significantly improves the structural stability and electronic conductivity of Bi-Sb alloy nanoparticles. The 3D hierarchical porous carbon skeleton structure further enhances electrolyte accessibility, promotes Na+ transport, increases reaction kinetics, and buffers internal stress.
Ebselen Inhibits the Growth of Lung Cancer Cells via Cell Cycle Arrest and Cell Death Accompanied by Glutathione Depletion
Authors: Park Woo Hyun
Published: September 2023

Ebselen is a glutathione (GSH) peroxidase (GPx) mimic originally developed to reduce reactive oxygen species (ROS). However, little is known about its cytotoxicological effects on lung cells. Therefore, this study aimed to investigate the effects of Ebselen on the cell growth and cell death of A549 lung cancer cells, Calu-6 lung cancer cells, and primary normal human pulmonary fibroblast (HPF) cells in relation to redox status. The results showed that Ebselen inhibited the growth of A549, Calu-6, and HPF cells with IC50 values of approximately 12.5 μM, 10 μM, and 20 μM, respectively, at 24 h. After exposure to 15 μM Ebselen, the proportions of annexin V-positive cells were approximately 25%, 65%, and 10% in A549, Calu-6, and HPF cells, respectively. In addition, Ebselen induced arrest at the S phase of the cell cycle in A549 cells and induced G2/M phase arrest in Calu-6 cells. Treatment with Ebselen induced mitochondrial membrane potential (MMP; ΔΨm) loss in A549 and Calu-6 cells. Z-VAD, a pan-caspase inhibitor, did not decrease the number of annexin V-positive cells in Ebselen-treated A549 and Calu-6 cells. Intracellular ROS levels were not significantly changed in the Ebselen-treated cancer cells at 24 h, but GSH depletion was efficiently induced in these cells. Z-VAD did not affect ROS levels or GSH depletion in Ebselen-treated A549 or Ebselen-treated Calu-6 cells. In conclusion, Ebselen inhibited the growth of lung cancer and normal fibroblast cells and induced cell cycle arrest and cell death in lung cancer cells with GSH depletion.
Rapid Limit Test of Eight Quinolone Residues in Food Based on TLC-SERS, a New Limit Test Method
Authors: Zhang Honglian , Zhang Min , Li Li , Dong Wei , Ren Qiyong , Xu Feng , Wang Yuanrui , Xu Tao , Liu Jicheng
Published: September 2023

Residual quinolones in food that exceed their maximum residue limit (MRL) are harmful to human health. However, the existing methods used for testing these residues have limitations; so, we developed a new limit test method called TLC-SERS to rapidly determine the levels of residues of the following: enrofloxacin (A), ciprofloxacin (B), ofloxacin (C), fleroxacin (D), sparfloxacin (E), enoxacin (F), gatifloxacin (G), and nadifloxacin (H). The residues ware preliminarily separated via TLC. The tested compounds’ position on a thin-layer plate were labeled using their relative Rf under 254 nm ultraviolet light, and an appropriate amount of nanometer silver solution was added to the position. The silver on the plate was irradiated with a 532 nm laser to obtain the SERSs of the compounds. The results show significant differences in the SERS of the eight quinolones: the LODs of H, A, D, E, C, G, F, and B were 9.0, 12.6, 8.9, 19.0, 8.0, 8.7, 19.0, and 12.6 ng/mL, respectively; and the RSD was ≤4.9% for the SERS of each quinolone. The limit test results of 20 samples are consistent with those obtained via UPLC–MS/MS. The results indicate that TLC-SERS is a specific, sensitive, stable, and accurate method, providing a new reference for the rapid limit test of harmful residues in foods.
Contribution of Dynamic Rheology Coupled to FTIR and Raman Spectroscopies to the Real-Time Shaping Ability of a Hyperbranched Polycarbosilane
Authors: Dhondoo Nilesh , Cornette Julie , Foucaud Sylvie , Colas Maggy , Lucas-Roper Romain
Published: September 2023

In the field of non-oxide ceramics, the polymer-derived ceramic (PDC) approach appears to be very promising, especially for obtaining easily shaped and homogeneous materials in terms of structure and composition. However, in order to reach a suitable form during the process, it is often necessary to study the rheology of preceramic polymers while they are modified during polymerisation or crosslinking reactions. Given this need in the understanding of the real-time rheology of macromolecules during their synthesis, a rheometer coupled with both an infrared spectrometer and a Raman probe is described as a powerful tool for monitoring in situ synthesised polycarbosilanes. Indeed, this original device allows one to control the viscosity of a hyberbranched polycarbosilane from defined difunctional and tetrafunctional monomers. Meanwhile, it links this evolution to structural modifications in the macromolecular structure (molar masses, dispersity and conformation), based on SEC-MALS analyses, synchronised by the monomer conversion determined by using Raman and infrared spectroscopies, a common denominator of the aforementioned instrumental platform.
Antigingivitis and Antiplaque Effects of Oral Probiotic Containing the Streptococcus salivarius M18 Strain: A Randomized Clinical Trial
Authors: Babina Ksenia , Salikhova Dilara , Doroshina Vladlena , Makeeva Irina , Zaytsev Alexandr , Uvarichev Matvey , Polyakova Maria , Novozhilova Nina
Published: September 2023

We aimed to assess the effect of oral probiotic containing the Streptococcus salivarius M18 strain on gingival inflammation, bleeding on probing, and oral biofilm. Sixty-one consenting participants aged between 18 and 25 with gingivitis were recruited in this double-blind, parallel-group study and randomly divided into the probiotic group (n = 31) and the placebo group (n = 30). Fifty-seven participants completed the entire study protocol, 27 in the probiotic group and 30 in the placebo group. The outcomes were assessed after 4 weeks of intervention and 4 weeks of follow-up. There was a significant decrease in the Gingival Index, with the effect size of 0.58 [95%CI 0.05–1.10], and Turesky modification of the Quigley and Hein Plaque Index, with the effect size of 0.55 [95%CI: 0.02–1.07], in the probiotic group after the intervention. However, after a 4-week follow-up, the only significant treatment outcome was improved gingival condition according to the Gingival Index. The Gingival Bleeding Index also decreased significantly in the probiotic group after the intervention period; after the follow-up, this parameter did not differ significantly in both groups from the baseline values. In the placebo group, there were no significant improvements in the assessed parameters throughout this study. No serious side effects were registered. Within the limitations of this study, we conclude that the use of oral probiotic containing the Streptococcus salivarius M18 strain resulted in a significant improvement in gingival condition and oral hygiene level in young adults with gingivitis. Trial registration NCT05727436. Funding: none.
The Development and Potential of a Digital out of Home Food Environment Monitoring Platform
Authors: Hetz Kathrin , Weerasinghe Nuwan , Rippin Holly , Wickramasinghe Kremlin , Zhiteneva Olga , Usman Muhammad Arslan , Politis Christos , Galea Gauden
Published: September 2023

The rapidly growing field of digital meal delivery platforms has transformed the out of home (OOH) food environment, presenting both opportunities and challenges for public health. This paper introduces the development and potential of a novel digital platform designed for monitoring the OOH food environment. Drawing on publicly available data from meal delivery applications, this platform provides valuable insights into the landscape of digital food offerings, such as the most common restaurants per region, average caloric content per meal type, and energy value per monetary unit. This research addresses the current void in regulations for this digital environment, particularly around food labeling and provision of nutrition information. Even though the platform has significantly improved our understanding of the digital food ecosystem, it highlights gaps, primarily due to the lack of publicly available individual data and inconsistencies in provided information. Despite these challenges, the proposed digital platform holds considerable promise for better understanding the digital food environment, supporting healthier food choices, and informing future policy interventions aimed at regulating the online food environment. This research advocates for mandatory regulations in the digital food sector to ensure comprehensive, comparable, and transparent nutrition information and equality in access to nutritious foods.
Niraparib and Advanced Ovarian Cancer: A Beacon in the Non-BRCA Mutated Setting
Authors: Maiorano Mauro Francesco Pio , Maiorano Brigida Anna , Biancofiore Annalucia , Cormio Gennaro , Maiello Evaristo
Published: September 2023

Ovarian cancer (OC) is the eighth most common cancer among the female population and the most lethal of all the female reproductive system malignancies. Poly (ADP-ribose) polymerase inhibitors (PARPis) have reshaped the treatment scenario of metastatic OC in the maintenance setting post platinum-based chemotherapy. Niraparib is the first Food and Drug Administration (FDA)- and European Medical Agency (EMA)-approved PARPi as maintenance therapy for platinum-sensitive OC, regardless of BReast CAncer gene (BRCA) status, in first-line patients, with a recent restriction to germline BRCA mutations in second-line patients. In this review, we comprehensively summarized the pharmacological properties of niraparib, alongside the efficacy and safety data of the main trials leading to the current approvals, and discussed the future development of this agent.
Exploring Proteus mirabilis Methionine tRNA Synthetase Active Site: Homology Model Construction, Molecular Dynamics, Pharmacophore and Docking Validation
Authors: Elbaramawi Samar S. , Eissa Ahmed G. , Noureldin Nada A. , Simons Claire
Published: September 2023

Currently, the treatment of Proteus mirabilis infections is considered to be complicated as the organism has become resistant to numerous antibiotic classes. Therefore, new inhibitors should be developed, targeting bacterial molecular functions. Methionine tRNA synthetase (MetRS), a member of the aminoacyl-tRNA synthetase family, is essential for protein biosynthesis offering a promising target for novel antibiotics discovery. In the context of computer-aided drug design (CADD), the current research presents the construction and analysis of a comparative homology model for P. mirabilis MetRS, enabling development of novel inhibitors with greater selectivity. Molecular Operating Environment (MOE) software was used to build a homology model for P. mirabilis MetRS using Escherichia coli MetRS as a template. The model was evaluated, and the active site of the target protein predicted from its sequence using conservation analysis. Molecular dynamic simulations were performed to evaluate the stability of the modeled protein structure. In order to evaluate the predicted active site interactions, methionine (the natural substrate of MetRS) and several inhibitors of bacterial MetRS were docked into the constructed model using MOE. After validation of the model, pharmacophore-based virtual screening for a systemically prepared dataset of compounds was performed to prove the feasibility of the proposed model, identifying possible parent compounds for further development of MetRS inhibitors against P. mirabilis.
Graphene-Based Nanomaterials for Photothermal Therapy in Cancer Treatment
Authors: Báez Daniela F.
Published: September 2023

Graphene-based nanomaterials (GBNMs), specifically graphene oxide (GO) and reduced graphene oxide (rGO), have shown great potential in cancer therapy owing to their physicochemical properties. As GO and rGO strongly absorb light in the near-infrared (NIR) region, they are useful in photothermal therapy (PTT) for cancer treatment. However, despite the structural similarities of GO and rGO, they exhibit different influences on anticancer treatment due to their different photothermal capacities. In this review, various characterization techniques used to compare the structural features of GO and rGO are first outlined. Then, a comprehensive summary and discussion of the applicability of GBNMs in the context of PTT for diverse cancer types are presented. This discussion includes the integration of PTT with secondary therapeutic strategies, with a particular focus on the photothermal capacity achieved through near-infrared irradiation parameters and the modifications implemented. Furthermore, a dedicated section is devoted to studies on hybrid magnetic-GBNMs. Finally, the challenges and prospects associated with the utilization of GBNM in PTT, with a primary emphasis on the potential for clinical translation, are addressed.
Storage Stability of Atheroglitatide, an Echogenic Liposomal Formulation of Pioglitazone Targeted to Advanced Atheroma with a Fibrin-Binding Peptide
Authors: Klegerman Melvin E. , Peng Tao , Huang Shao-Ling , Frierson Brion , Moody Melanie R. , Kim Hyunggun , McPherson David D.
Published: September 2023

We have conducted a stability study of a complex liposomal pharmaceutical product, Atheroglitatide (AGT), stored at three temperatures, 4, 24, and 37 °C, for up to six months. The six parameters measured were functions of liposomal integrity (size and number), drug payload (loading efficiency), targeting peptide integrity (conjugation efficiency and specific avidity), and echogenicity (ultrasound-dependent controlled drug release), which were considered most relevant to the product’s intended use. At 4 °C, liposome diameter trended upward, indicative of aggregation, while liposome number per mg lipid and echogenicity trended downward. At 24 °C, peptide conjugation efficiency (CE) and targeting efficiency (TE, specific avidity) trended downward. At 37 °C, CE and drug (pioglitazone) loading efficiency trended downward. At 4 °C, the intended storage temperature, echogenicity, and liposome size reached their practical tolerance limits at 6 months, fixing the product expiration at that point. Arrhenius analysis of targeting peptide CE and drug loading efficiency decay at the higher temperatures indicated complete stability of these characteristics at 4 °C. The results of this study underscore the storage stability challenges presented by complex nanopharmaceutical formulations.
Impact of Implant Diameter on Success and Survival of Dental Implants: An Observational Cohort Study
Authors: Romanos Georgios E. , Schesni Aigerim , Nentwig Georg-Hubertus , Winter Anna , Sader Robert , Brandt Silvia
Published: September 2023

Narrow-diameter implants (NDIs) can be inserted instead of standard dental implants (SDIs) in sites with limited space and bone availability. The aim of this study was to evaluate the effect of implant diameter on peri-implant bone, attached mucosa, and on the associated probability of implant success and survival. The implants with progressive thread design and platform switching (Ankylos®, Dentsply Sirona; Mannheim, Germany) investigated were identified retrospectively and assigned to two groups based on their diameter: 3.5 mm (NDIs) and 4.5 mm (SDIs). Peri-implant bone loss was analyzed based on available radiographs. Descriptive and implant-associated factors were gathered from patient files. Data were statistically analyzed using the Kolmogorov–Smirnov–Lilliefors test and regression analyses. The level of significance was p ≤ 0.05. Results: In total, data for 415 implants in 194 patients were included in the study. Ten-year survival was 95.8% (NDIs) and 91.1% (SDIs). Implant diameter had no significant effect on peri-implant crestal bone loss (p = 0.098) or on the width of the attached gingiva (p = 0.052). Survival and success rates of NDIs were like or slightly better than those of SDIs. Because implant diameter had no effect on peri-implant tissue, NDIs can be recommended in selected cases.
Modeling Landslide Susceptibility in Forest-Covered Areas in Lin’an, China, Using Logistical Regression, a Decision Tree, and Random Forests
Authors: Chen Chongzhi , Shen Zhangquan , Weng Yuhui , You Shixue , Lin Jingya , Li Sinan , Wang Ke
Published: September 2023

Landslides are a common geodynamic phenomenon that cause substantial life and property damage worldwide. In the present study, we developed models to evaluate landslide susceptibility in forest-covered areas in Lin’an, southeastern China using logistic regression (LR), decision tree (DT), and random forest (RF) techniques. In addition to conventional landslide-related natural and human disturbance factors, factors describing forest cover, including forest type (two plantations (hickory and bamboo) and four natural forests (conifer, hardwood, shrub, and moso bamboo) and understory vegetation conditions, were included as predictors. Model performance was evaluated based on true-positive rate, Kappa value, and area under the ROC curve using a 10-fold cross-validation method. All models exhibited good performance with measures of ≥0.70, although the LR model was relatively inferior. The key predictors were forest type, understory vegetation height (UVH), normalized differential vegetation index (NDVI) in summer, distance to road (DTRD), and maximum daily rainfall (MDR). Hickory plantations yielded the highest landslide probability, while conifer and hardwood forests had the lowest values. Bamboo plantations had probability results comparable to those of natural forests. Using the RF model, areas with a shorter UVH (<1.2 m), a lower NDVI (<0.70), a heavier MDR (>115 mm), or a shorter DTRD (<500 m) were predicted to be landslide-prone. Information on forest cover is essential for predicting landslides in areas with rich forest cover, and conversion from natural forests to plantations could increase landslide risk. Across the study areas, the northwestern part was the most landslide-prone. In terms of landslide prevention, the RF model-based map produced the most accurate predictions for the “very high” category of landslide. These results will help us better understand landslide occurrences in forest-covered areas and provide valuable information for governments in designing disaster mitigation.
Implications for Validation of IMERG Satellite Precipitation in a Complex Mountainous Region
Authors: Li Luhan , Chen Xuelong , Ma Yaoming , Zhao Wenqing , Zuo Hongchao , Liu Yajing , Cao Dianbin , Xu Xin
Published: September 2023

Satellite-based precipitation retrievals such as the Integrated Multi-satellite Retrievals for Global Precipitation Measurement (IMERG), provide alternative data in mountainous regions. In this study, we evaluated IMERG in the Yarlung Tsangbo Grand Canyon (YGC) using ground observations. It was found that IMERG underestimated the total rainfall primarily due to under-detection of rainfall events, with misses being more prevalent than false alarms. We analyzed the relationships between the probability of detection (POD), false alarm ratio (FAR), bias in detection (BID), and Heidke skill score (HSS) and terrain factors. It was found that the POD decreased with elevation, leading to increased underestimation of rainfall events at higher elevations, and the FAR was higher in valley sites. In terms of the hit events, IMERG overestimated the light rainfall events and underestimated the heavy rainfall events and the negative bias in the hit events decreased with elevation. IMERG could capture the early morning peak precipitation in the YGC region but underestimated the amplitude of the diurnal variation. This bias was inherent at the sensor level, and the Global Precipitation Climatology Center (GPCC) calibration partially improved the underestimation. However, this improvement was not sufficient for the YGC region. This study fills the gap in IMERG validation in a complex mountainous region and has implications for users and developers.
Accumulation and Cross-Shelf Transport of Coastal Waters by Submesoscale Cyclones in the Black Sea
Authors: Kubryakov Arseny , Aleskerova Anna , Plotnikov Evgeniy , Mizyuk Artem , Medvedeva Alesya , Stanichny Sergey
Published: September 2023

High- and medium-resolution satellite optical imagery show that submesoscale cyclonic eddies (SCEs) trap coastal waters and induce their rapid cross-shelf transport. Due to the presence of a rigid boundary, the convergence is observed in the coastal part of SCEs. It causes accumulation of suspended matter, which spins inward in a spiral motion toward the SCE core. Small SCEs with a radius of 1–10 km transport waters with local anomalies in the concentration of chlorophyll, total suspended matter and temperature to a distance of up to 150 km and are observed for more than 10 days. Lagrangian calculations based on realistic NEMO numerical model are used to estimate the fate of the coastal waters in such SCEs. The eddy entrains the largest number of particles during its separation from the coast when its vorticity reaches the maximum. Then, the SCE weakens, which is accompanied by the flattening of initially risen isopycnals and deepening of the trapped coastal waters. The described mechanism shows that coastal SCEs may cause intense short-period cross-shelf transport of the biological and chemical characteristics, and is another process affecting the functioning of the marine ecosystems.
Rover Attitude and Camera Parameter: Rock Measurements on Mars Surface Based on Rover Attitude and Camera Parameter for Tianwen-1 Mission
Authors: Zheng Dian , Wei Linhui , Lv Weikun , Liu Yu , Wang Yumei
Published: September 2023

Rocks, prominent features on the surface of Mars, are a primary focus of Mars exploration missions. The accuracy of recognizing rock information, including size and position, deeply affects the path planning for rovers on Mars and the geological exploration of Mars. In this paper, we present a rock measurement method for the Mars surface based on a Rover Attitude and Camera Parameter (RACP). We analyze the imaging process of the Navigation and Terrain Camera (NaTeCam) on the Zhurong rover, which involves utilizing a semi-spherical model (SSM) to characterize the camera’s attitude, a projection model (PM) to connect the image data with the three-dimensional (3D) environment, and then estimating the distance and size of rocks. We conduct a test on NaTeCam images and find that the method is effective in measuring the distance and size to Martian rocks and identifying rocks at specific locations. Furthermore, an analysis of the impact of uncertain factors is conducted. The proposed RACP method offers a reliable solution for automatically analyzing the rocks on Mars, which provides a possible solution for the route planning in similar tasks.
A Generative Adversarial Network with Spatial Attention Mechanism for Building Structure Inference Based on Unmanned Aerial Vehicle Remote Sensing Images
Authors: Chen Hao , Guo Zhixiang , Meng Xing , He Fachuan
Published: September 2023

The acquisition of building structures has broad applications across various fields. However, existing methods for inferring building structures predominantly depend on manual expertise, lacking sufficient automation. To tackle this challenge, we propose a building structure inference network that utilizes UAV remote sensing images, with the PIX2PIX network serving as the foundational framework. We enhance the generator by incorporating an additive attention module that performs multi-scale feature fusion, enabling the combination of features from diverse spatial resolutions of the feature map. This modification enhances the model’s capability to emphasize global relationships during the mapping process. To ensure the completeness of line elements in the generator’s output, we design a novel loss function based on the Hough transform. A line penalty term is introduced that transforms the output of the generator and ground truth to the Hough domain due to the original loss function’s inability to effectively constrain the completeness of straight-line elements in the generated results in the spatial domain. A dataset of the appearance features obtained from UAV remote sensing images and the internal floor plan structure is made. Using UAV remote sensing images of multi-story residential buildings, high-rise residential buildings, and office buildings as test collections, the experimental results show that our method has better performance in inferring a room’s layout and the locations of load-bearing columns, achieving an average improvement of 11.2% and 21.1% over PIX2PIX in terms of the IoU and RMSE, respectively.
Non-Contact Face Temperature Measurement by Thermopile-Based Data Fusion
Authors: Bhatti Faraz , Engel Grischan , Hampel Joachim , Khalil Chaimae , Reber Andreas , Kray Stefan , Greiner Thomas
Published: September 2023

Thermal imaging cameras and infrared (IR) temperature measurement devices act as state-of-the-art techniques for non-contact temperature determination of the skin surface. The former is cost-intensive in many cases for widespread application, and the latter requires manual alignment to the measuring point. Due to this background, this paper proposes a new method for automated, non-contact, and area-specific temperature measurement of the facial skin surface. It is based on the combined use of a low-cost thermopile sensor matrix and a 2D image sensor. The temperature values as well as the 2D image data are fused using a parametric affine transformation. Based on face recognition, this allows temperature values to be assigned to selected facial regions and used specifically to determine the skin surface temperature. The advantages of the proposed method are described. It is demonstrated by means of a participant study that the temperature absolute values, which are achieved without manual alignment in an automated manner, are comparable to a commercially available IR-based forehead thermometer.
Compression Performance Analysis of Experimental Holographic Data Coding Systems
Authors: Dong Tianyu , Oh Kwan-Jung , Park Joongki , Jang Euee S.
Published: September 2023

It is challenging to find a proper way to compress computer-generated holography (CGH) data owing to their huge data requirements and characteristics. This study proposes CGH data coding systems with high-efficiency video coding (HEVC), three-dimensional extensions of HEVC (3D-HEVC), and video-based point cloud compression (V-PCC) codecs. In the proposed system, we implemented a procedure for codec usage and format conversion and evaluated the objective and subjective results to analyze the performance of the three coding systems. We discuss the relative advantages and disadvantages of the three coding systems with respect to their coding efficiency and reconstruction results. Our analysis concluded that 3D-HEVC and V-PCC are potential solutions for compressing red, green, blue, and depth (RGBD)-sourced CGH data.
Predictability of Fall Risk Assessments in Community-Dwelling Older Adults: A Scoping Review
Authors: Waterval N. F. J. , Claassen C. M. , van der Helm F. C. T. , van der Kruk E.
Published: September 2023

Fall risk increases with age, and one-third of adults over 65 years old experience a fall annually. Due to the aging population, the number of falls and related medical costs will progressively increase. Correct prediction of who will fall in the future is necessary to timely intervene in order to prevent falls. Therefore, the aim of this scoping review is to determine the predictive value of fall risk assessments in community-dwelling older adults using prospective studies. A total of 37 studies were included that evaluated clinical assessments (questionnaires, physical assessments, or a combination), sensor-based clinical assessments, or sensor- based daily life assessments using prospective study designs. The posttest probability of falling or not falling was calculated. In general, fallers were better classified than non-fallers. Questionnaires had a lower predictive capability compared to the other assessment types. Contrary to conclusions drawn in reviews that include retrospective studies, the predictive value of physical tests evaluated in prospective studies varies largely, with only smaller-sampled studies showing good predictive capabilities. Sensor-based fall risk assessments are promising and improve with task complexity, although they have only been evaluated in relatively small samples. In conclusion, fall risk prediction using sensor data seems to outperform conventional tests, but the method’s validity needs to be confirmed by large prospective studies.