bluuebunny/crossref_metadata_2025 huggingface dataset:
Exploring the Effects of Light and Dark on Crime in London
Authors: Erturk Ezgi , Raynham Peter , Teji Jemima Unwin
Published: May 2024

Safety from crime is a fundamental human need. In Maslow’s hierarchy, safety is one of the foundational needs of well-being. The built environment should be safe to use at all times of the day and for all groups of people. After dark, the appearance of the outdoor environment changes dramatically, and this could impact the opportunities for crime. This study investigated the impact of daylight on the rates of different types of crime by comparing the crime rates during selected periods of daylight and darkness. The study used records of crime data from the Metropolitan Police Service. By studying crimes in the week on either side of the twice-yearly clock change, it is possible to compare periods that are dark in one week and light in the other at the same clock time. Where the time at which the crime took place was known, and using the GPS coordinates of the specific crime, the solar altitude was calculated and used to determine if it was light or dark at the time of the crime. A similar calculation was used to see if the crime would have been in the dark or light in the week on the other side of the clock change. The headline result is that there was 4.8% (OR 1.07) more crime in the dark periods than the light ones. However, this increase was not uniform across all crime types, and there were some further complications in some results due to potential changes in the behavior of some victims after dark. For the crimes of theft from a person and robbery of personal property, there was a significant increase during the dark period. The availability of light had an impact on the rate of certain crimes. Whilst this does not provide any information about the impact of street lighting on crime, it does provide some idea of by how much crime could be reduced if better lighting was provided.
Metabolic Regulation of Endothelial Cells: A New Era for Treating Wet Age-Related Macular Degeneration
Authors: Chen Xirui , Xu Yang , Ju Yahan , Gu Ping
Published: May 2024

Wet age-related macular degeneration (wet AMD) is a primary contributor to visual impairment and severe vision loss globally, but the prevailing treatments are often unsatisfactory. The development of conventional treatment strategies has largely been based on the understanding that the angiogenic switch of endothelial cells (ECs) is mainly dictated by angiogenic growth factors. Even though treatments targeting vascular endothelial growth factor (VEGF), like ranibizumab, are widely administered, more than half of patients still exhibit inadequate or null responses, suggesting the involvement of other pathogenic mechanisms. With advances in research in recent years, it has become well recognized that EC metabolic regulation plays an active rather than merely passive responsive role in angiogenesis. Disturbances of these metabolic pathways may lead to excessive neovascularization in angiogenic diseases such as wet AMD, therefore targeted modulation of EC metabolism represents a promising therapeutic strategy for wet AMD. In this review, we comprehensively discuss the potential applications of EC metabolic regulation in wet AMD treatment from multiple perspectives, including the involvement of ECs in wet AMD pathogenesis, the major endothelial metabolic pathways, and novel therapeutic approaches targeting metabolism for wet AMD.
New Polymeric Hydrogels with Cannabidiol and α-Terpineol as Potential Materials for Skin Regeneration—Synthesis and Physicochemical and Biological Characterization
Authors: Zagórska-Dziok Martyna , Nowak Anna , Zgadzaj Anna , Oledzka Ewa , Kędra Karolina , Wiącek Agnieszka Ewa , Sobczak Marcin
Published: May 2024

Dermatology and cosmetology currently prioritize healthy, youthful-looking skin. As a result, research is being conducted worldwide to uncover natural substances and carriers that allow for controlled release, which could aid in the battle against a variety of skin illnesses and slow the aging process. This study examined the biological and physicochemical features of novel hydrogels containing cannabidiol (CBD) and α-terpineol (TER). The hydrogels were obtained from ε-caprolactone (CL) and poly(ethylene glycol) (PEG) copolymers, diethylene glycol (DEG), poly(tetrahydrofuran) (PTHF), 1,6-diisocyanatohexane (HDI), and chitosan (CHT) components, whereas the biodegradable oligomers were synthesized using the enzyme ring-opening polymerization (e-ROP) method. The in vitro release rate of the active compounds from the hydrogels was characterized by mainly first-order kinetics, without a “burst release”. The antimicrobial, anti-inflammatory, cytotoxic, antioxidant, and anti-aging qualities of the designed drug delivery systems (DDSs) were evaluated. The findings indicate that the hydrogel carriers that were developed have the ability to scavenge free radicals and impact the activity of antioxidant enzymes while avoiding any negative effects on keratinocytes and fibroblasts. Furthermore, they have anti-inflammatory qualities by impeding protein denaturation as well as the activity of proteinase and lipoxygenase. Additionally, their ability to reduce the multiplication of pathogenic bacteria and inhibit the activity of collagenase and elastase has been demonstrated. Thus, the developed hydrogel carriers may be effective systems for the controlled delivery of CBD, which may become a valuable tool for cosmetologists and dermatologists.
T Cell Homeostasis Disturbances in a Cohort of Long-Term Elite Controllers of HIV Infection
Authors: Benito José M. , Jiménez-Carretero Daniel , Restrepo Clara , Ligos José M. , Valentín-Quiroga Jaime , Mahillo Ignacio , Cabello Alfonso , López-Collazo Eduardo , Sánchez-Cabo Fátima , Górgolas Miguel , Estrada Vicente , Rallón Norma
Published: May 2024

Elite controllers (ECs) are people living with HIV (PLWH) able to control HIV replication without antiretroviral therapy and have been proposed as a model of a functional HIV cure. Much evidence suggests that this spontaneous control of HIV has a cost in terms of T cell homeostasis alterations. We performed a deep phenotypic study to obtain insight into T cell homeostasis disturbances in ECs maintaining long-term virologic and immunologic control of HIV (long-term elite controllers; LTECs). Forty-seven PLWH were included: 22 LTECs, 15 non-controllers under successful antiretroviral therapy (onART), and 10 non-controllers not receiving ART (offART). Twenty uninfected participants (UCs) were included as a reference. T cell homeostasis was analyzed by spectral flow cytometry and data were analyzed using dimensionality reduction and clustering using R software v3.3.2. Dimensionality reduction and clustering yielded 57 and 54 different CD4 and CD8 T cell clusters, respectively. The offART group showed the highest perturbation of T cell homeostasis, with 18 CD4 clusters and 15 CD8 clusters significantly different from those of UCs. Most of these alterations were reverted in the onART group. Interestingly, LTECs presented several disturbances of T cell homeostasis with 15 CD4 clusters and 13 CD8 clusters different from UC. Moreover, there was a specific profile of T cell homeostasis alterations associated with LTECs, characterized by increases in clusters of naïve T cells, increases in clusters of non-senescent effector CD8 cells, and increases in clusters of central memory CD4 cells. These results demonstrate that, compared to ART-mediated control of HIV, the spontaneous control of HIV is associated with several disturbances in CD4 and CD8 T cell homeostasis. These alterations could be related to the existence of a potent and efficient virus-specific T cell response, and to the ability to halt disease progression by maintaining an adequate pool of CD4 T cells.
Biological Characterization and Genomic Analysis of Three Novel Serratia- and Enterobacter-Specific Virulent Phages
Authors: Shymialevich Dziyana , Błażejak Stanisław , Średnicka Paulina , Cieślak Hanna , Ostrowska Agnieszka , Sokołowska Barbara , Wójcicki Michał
Published: May 2024

Due to the high microbiological contamination of raw food materials and the increase in the incidence of multidrug-resistant bacteria, new methods of ensuring microbiological food safety are being sought. One solution may be to use bacteriophages (so-called phages) as natural bacterial enemies. Therefore, the aim of this study was the biological and genomic characterization of three newly isolated Serratia- and Enterobacter-specific virulent bacteriophages as potential candidates for food biocontrol. Serratia phage KKP_3708 (vB_Sli-IAFB_3708), Serratia phage KKP_3709 (vB_Sma-IAFB_3709), and Enterobacter phage KKP_3711 (vB_Ecl-IAFB_3711) were isolated from municipal sewage against Serratia liquefaciens strain KKP 3654, Serratia marcescens strain KKP 3687, and Enterobacter cloacae strain KKP 3684, respectively. The effect of phage addition at different multiplicity of infection (MOI) rates on the growth kinetics of the bacterial hosts was determined using a Bioscreen C Pro growth analyzer. The phages retained high activity in a wide temperature range (from −20 °C to 60 °C) and active acidity values (pH from 3 to 12). Based on transmission electron microscopy (TEM) imaging and whole-genome sequencing (WGS), the isolated bacteriophages belong to the tailed bacteriophages from the Caudoviricetes class. Genomic analysis revealed that the phages have linear double-stranded DNA of size 40,461 bp (Serratia phage KKP_3708), 67,890 bp (Serratia phage KKP_3709), and 113,711 bp (Enterobacter phage KKP_3711). No virulence, toxins, or antibiotic resistance genes were detected in the phage genomes. The lack of lysogenic markers indicates that all three bacteriophages may be potential candidates for food biocontrol.
Developmental Programming of the Fetal Immune System by Maternal Western-Style Diet: Mechanisms and Implications for Disease Pathways in the Offspring
Authors: Nelson Benjamin N. , Friedman Jacob E.
Published: May 2024

Maternal obesity and over/undernutrition can have a long-lasting impact on offspring health during critical periods in the first 1000 days of life. Children born to mothers with obesity have reduced immune responses to stimuli which increase susceptibility to infections. Recently, maternal western-style diets (WSDs), high in fat and simple sugars, have been associated with skewing neonatal immune cell development, and recent evidence suggests that dysregulation of innate immunity in early life has long-term consequences on metabolic diseases and behavioral disorders in later life. Several factors contribute to abnormal innate immune tolerance or trained immunity, including changes in gut microbiota, metabolites, and epigenetic modifications. Critical knowledge gaps remain regarding the mechanisms whereby these factors impact fetal and postnatal immune cell development, especially in precursor stem cells in bone marrow and fetal liver. Components of the maternal microbiota that are transferred from mothers consuming a WSD to their offspring are understudied and identifying cause and effect on neonatal innate and adaptive immune development needs to be refined. Tools including single-cell RNA-sequencing, epigenetic analysis, and spatial location of specific immune cells in liver and bone marrow are critical for understanding immune system programming. Considering the vital role immune function plays in offspring health, it will be important to understand how maternal diets can control developmental programming of innate and adaptive immunity.
Towards Clinical Development of Scandium Radioisotope Complexes for Use in Nuclear Medicine: Encouraging Prospects with the Chelator 1,4,7,10-Tetraazacyclododecane-1,4,7,10-tetraacetic Acid (DOTA) and Its Analogues
Authors: Ioannidis Ioannis , Lefkaritis George , Georgiades Savvas N. , Pashalidis Ioannis , Kontoghiorghes George J.
Published: May 2024

Scandium (Sc) isotopes have recently attracted significant attention in the search for new radionuclides with potential uses in personalized medicine, especially in the treatment of specific cancer patient categories. In particular, Sc-43 and Sc-44, as positron emitters with a satisfactory half-life (3.9 and 4.0 h, respectively), are ideal for cancer diagnosis via Positron Emission Tomography (PET). On the other hand, Sc-47, as an emitter of beta particles and low gamma radiation, may be used as a therapeutic radionuclide, which also allows Single-Photon Emission Computed Tomography (SPECT) imaging. As these scandium isotopes follow the same biological pathway and chemical reactivity, they appear to fit perfectly into the “theranostic pair” concept. A step-by-step description, initiating from the moment of scandium isotope production and leading up to their preclinical and clinical trial applications, is presented. Recent developments related to the nuclear reactions selected and employed to produce the radionuclides Sc-43, Sc-44, and Sc-47, the chemical processing of these isotopes and the main target recovery methods are also included. Furthermore, the radiolabeling of the leading chelator, 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA), and its structural analogues with scandium is also discussed and the advantages and disadvantages of scandium complexation are evaluated. Finally, a review of the preclinical studies and clinical trials involving scandium, as well as future challenges for its clinical uses and applications, are presented.
The Influence of Oxidized Imino-Allantoin in the Presence of OXOG on Double Helix Charge Transfer: A Theoretical Approach
Authors: Karwowski Boleslaw T.
Published: May 2024

The genome is continuously exposed to a variety of harmful factors that result in a significant amount of DNA damage. This article examines the influence of a multi-damage site containing oxidized imino-allantoin (OXIa) and 7,8-dihydro-8-oxo-2′-deoxyguanosine (OXOdG) on the spatial geometry, electronic properties, and ds-DNA charge transfer. The ground stage of a d[A1OXIa2A3OXOG4A5]*d[T5C4T3C2T1] structure was obtained at the M06-2X/6-D95**//M06-2X/sto-3G level of theory in the condensed phase, with the energies obtained at the M06-2X/6-31++G** level. The non-equilibrated and equilibrated solvent-solute interactions were also considered. Theoretical studies reveal that the radical cation prefers to settle on the OXOG moiety, irrespective of the presence of OXIa in a ds-oligo. The lowest vertical and adiabatic ionization potential values were found for the OXOG:::C base pair (5.94 and 5.52 [eV], respectively). Conversely, the highest vertical and adiabatic electron affinity was assigned for OXIaC as follows: 3.15 and 3.49 [eV]. The charge transfers were analyzed according to Marcus’ theory. The highest value of charge transfer rate constant for hole and excess electron migration was found for the process towards the OXOGC moiety. Surprisingly, the values obtained for the driving force and activation energy of electro-transfer towards OXIa2C4 located this process in the Marcus inverted region, which is thermodynamically unfavorable. Therefore, the presence of OXIa can slow down the recognition and removal processes of other DNA lesions. However, with regard to anticancer therapy (radio/chemo), the presence of OXIa in the structure of clustered DNA damage can result in improved cancer treatment outcomes.
Predicting Non-Alcoholic Steatohepatitis: A Lipidomics-Driven Machine Learning Approach
Authors: Mouskeftara Thomai , Kalopitas Georgios , Liapikos Theodoros , Arvanitakis Konstantinos , Germanidis Georgios , Gika Helen
Published: May 2024

Nonalcoholic fatty liver disease (NAFLD), nowadays the most prevalent chronic liver disease in Western countries, is characterized by a variable phenotype ranging from steatosis to nonalcoholic steatohepatitis (NASH). Intracellular lipid accumulation is considered the hallmark of NAFLD and is associated with lipotoxicity and inflammation, as well as increased oxidative stress levels. In this study, a lipidomic approach was used to investigate the plasma lipidome of 12 NASH patients, 10 Nonalcoholic Fatty Liver (NAFL) patients, and 15 healthy controls, revealing significant alterations in lipid classes, such as glycerolipids and glycerophospholipids, as well as fatty acid compositions in the context of steatosis and steatohepatitis. A machine learning XGBoost algorithm identified a panel of 15 plasma biomarkers, including HOMA-IR, BMI, platelets count, LDL-c, ferritin, AST, FA 12:0, FA 18:3 ω3, FA 20:4 ω6/FA 20:5 ω3, CAR 4:0, LPC 20:4, LPC O-16:1, LPE 18:0, DG 18:1_18:2, and CE 20:4 for predicting steatohepatitis. This research offers insights into the connection between imbalanced lipid metabolism and the formation and progression of NAFL D, while also supporting previous research findings. Future studies on lipid metabolism could lead to new therapeutic approaches and enhanced risk assessment methods, as the shift from isolated steatosis to NASH is currently poorly understood.
The Antifungal Potential of Niclosamide and Structurally Related Salicylanilides
Authors: Biersack Bernhard
Published: May 2024

Human mycoses cover a diverse field of fungal diseases from skin disorders to systemic invasive infections and pose an increasing global health problem based on ineffective treatment options, the hampered development of new efficient drugs, and the emergence of resistant fungal strains. Niclosamide is currently applied for the treatment of worm infections. Its mechanisms of action, which include the suppression of mitochondrial oxidative phosphorylation (also known as mitochondrial uncoupling), among others, has led to a repurposing of this promising anthelmintic drug for the therapy of further human diseases such as cancer, diabetes, and microbial infections. Given the urgent need to develop new drugs against fungal infections, the considerable antifungal properties of niclosamide are highlighted in this review. Its chemical and pharmacological properties relevant for drug development are also briefly mentioned, and the described mitochondria-targeting mechanisms of action add to the current arsenal of approved antifungal drugs. In addition, the activities of further salicylanilide-based niclosamide analogs against fungal pathogens, including agents applied in veterinary medicine for many years, are described and discussed for their feasibility as new antifungals for humans. Preliminary structure–activity relationships are determined and discussed. Various salicylanilide derivatives with antifungal activities showed increased oral bioavailabilities when compared with niclosamide. The simple synthesis of salicylanilide-based drugs also vouchsafes a broad and cost-effective availability for poorer patient groups. Pertinent literature is covered until 2024.
Synthesis and Photovoltaic Performance of β-Amino-Substituted Porphyrin Derivatives
Authors: Cerqueira Ana F. R. , Pinto Ana Lucia , Malta Gabriela , Neves Maria G. P. M. S. , Parola A. Jorge , Tomé Augusto C.
Published: May 2024

New β-amino-substituted porphyrin derivatives bearing carboxy groups were synthesized and their performance as sensitizers in dye-sensitized solar cells (DSSC) was evaluated. The new compounds were obtained in good yields (63–74%) through nucleophilic aromatic substitution reactions with 3-sulfanyl- and 4-sulfanylbenzoic acids. Although the electrochemical studies indicated suitable HOMO and LUMO energy levels for use in DSSC, the devices fabricated with these compounds revealed a low power conversion efficiency (PCE) that is primarily due to the low open-circuit voltage (Voc) and short-circuit current density (Jsc) values.
Molecular Evolution of SNAREs in Vitis vinifera and Expression Analysis under Phytohormones and Abiotic Stress
Authors: Zeng Bao-zhen , Zhou Xue-ting , Gou Hui-min , Che Li-li , Lu Shi-xiong , Yang Juan-bo , Cheng Yong-juan , Liang Guo-ping , Mao Juan
Published: May 2024

SNARE proteins (soluble N-ethylmaleimide-sensitive factor attachment protein receptors) play a key role in mediating a variety of plant biological processes. Currently, the function of the SNARE gene family in phytohormonal and abiotic stress treatments in grapevine is currently unknown, making it worthwhile to characterize and analyze the function and expression of this family in grapevine. In the present study, 52 VvSNARE genes were identified and predominantly distributed on 18 chromosomes. Secondary structures showed that the VvSNARE genes family irregular random coils and α-helices. The promoter regions of the VvSNARE genes were enriched for light-, abiotic-stress-, and hormone-responsive elements. Intraspecific collinearity analysis identified 10 pairs collinear genes within the VvSNARE family and unveiled a greater number of collinear genes between grapevine and apple, as well as Arabidopsis thaliana, but less associations with Oryza sativa. Quantitative real-time PCR (qRT-PCR) analyses showed that the VvSNARE genes have response to treatments with ABA, NaCl, PEG, and 4 °C. Notably, VvSNARE2, VvSNARE14, VvSNARE15, and VvSNARE17 showed up-regulation in response to ABA treatment. VvSNARE2, VvSNARE15, VvSNARE18, VvSNARE19, VvSNARE20, VvSNARE24, VvSNARE25, and VvSNARE29 exhibited significant up-regulation when exposed to NaCl treatment. The PEG treatment led to significant down-regulation of VvSNARE1, VvSNARE8, VvSNARE23, VvSNARE25, VvSNARE26, VvSNARE31, and VvSNARE49 gene expression. The expression levels of VvSNARE37, VvSNARE44, and VvSNARE46 were significantly enhanced after exposure to 4 °C treatment. Furthermore, subcellular localization assays certified that VvSNARE37, VvSNARE44, and VvSNARE46 were specifically localized at the cell membrane. Overall, this study showed the critical role of the VvSNARE genes family in the abiotic stress response of grapevines, thereby providing novel candidate genes such as VvSNARE37, VvSNARE44, and VvSNARE46 for further exploration in grapevine stress tolerance research.
The Improved Antigen Uptake and Presentation of Dendritic Cells Using Cell-Penetrating D-octaarginine-Linked PNVA-co-AA as a Novel Dendritic Cell-Based Vaccine
Authors: Fujioka Yuri , Ueki Hideto , A Ruhan , Sasajima Akari , Tomono Takumi , Ukawa Masami , Yagi Haruya , Sakuma Shinji , Kitagawa Koichi , Shirakawa Toshiro
Published: May 2024

Cancer immunotherapy using antigen-pulsed dendritic cells can induce strong cellular immune responses by priming cytotoxic T lymphocytes. In this study, we pulsed tumor cell lysates with VP-R8, a cell-penetrating D-octaarginine-linked co-polymer of N-vinylacetamide and acrylic acid (PNVA-co-AA), into the DC2.4 murine dendritic cell line to improve antigen uptake and then determined the anti-tumor effect in tumor-bearing mice. DC2.4 cells were pulsed with the cell lysate of EL4, a murine lymphoma cell line, and VP-R8 to generate the DC2.4 vaccine. For the in vivo study, DC2.4 cells pulsed with EL4 lysate and VP-R8 were subcutaneously injected into the inguinal lymph node to investigate the anti-tumor effect against EL4 and EL4-specific T cell immune responses. VP-R8 significantly improved antigen uptake into DC2.4 compared to conventional keyhole limpet hemocyanin (p < 0.05). The expression of MHC class I, MHC class II, and CD86 in DC2.4 cells significantly increased after pulsing tumor lysates with VP-R8 compared to other treatments (p < 0.05). The intra-lymph node injection of DC2.4 pulsed with both VP-R8 and EL4 lysate significantly decreased tumor growth compared to DC2.4 pulsed with KLH and lysates (p < 0.05) and induced tumor-infiltrating CD8T cells. The DC2.4 vaccine also remarkably increased the population of IFN-gamma-producing T cells and CTL activity against EL4 cells. In conclusion, we demonstrated that VP-R8 markedly enhances the efficiency of dendritic cell-based vaccines in priming robust anti-tumor immunity, suggesting its potential as a beneficial additive for dendritic cell-based immunotherapy.
Exploring the Neuroprotective Potential of N-Methylpyridinium against LPS-Induced Neuroinflammation: Insights from Molecular Mechanisms
Authors: Giannotti Laura , Di Chiara Stanca Benedetta , Spedicato Francesco , Stanca Eleonora , Damiano Fabrizio , Quarta Stefano , Massaro Marika , Siculella Luisa
Published: May 2024

N-methylpyridinium (NMP) is produced through the pyrolysis of trigonelline during the coffee bean roasting process. Preliminary studies suggest that NMP may have health benefits, thanks to its antioxidant properties. Based on this background, the aim of this study was to evaluate whether NMP could have a protective effect against LPS-induced neuroinflammation in human glioblastoma cells (U87MG). With this aim, U87MG cells were pre-treated with NMP (0.5 μM) for 1 h and then exposed to LPS (1 μg/mL) for 24 h. Our findings show that NMP attenuates LPS-induced neuroinflammation by reducing the expression of pro-inflammatory cytokines, such as IL-1β, TNF-α and IL-6, through the inhibition of the NF-κB signaling pathway, which is critical in regulating inflammatory responses. NMP is able to suppress the activation of the NF-κB signaling pathway, suggesting its potential in preventing neuroinflammatory conditions. These outcomes support the notion that regular consumption of NMP, possibly through coffee consumption, may offer protection against neuroinflammatory states implicated in neurological disorders.
CAFs-Associated Genes (CAFGs) in Pancreatic Ductal Adenocarcinoma (PDAC) and Novel Therapeutic Strategy
Authors: Yamashita Keishi , Kumamoto Yusuke
Published: May 2024

Pancreatic ductal adenocarcinoma (PDAC) is the most aggressive cancer with striking fibrosis, and its mortality rate is ranked second across human cancers. Cancer-associated fibroblasts (CAFs) play a critical role in PDAC progression, and we reviewed the molecular understanding of PDAC CAFs and novel therapeutic potential at present. CAFs-associated genes (CAFGs) were tentatively classified into three categories by stroma specificity representing stroma/epithelia expression ratios (SE ratios). The recent classification using single cell transcriptome technology clarified that CAFs were composed of myofibroblasts (myCAFs), inflammatory CAFs (iCAFs), and other minor ones (e.g., POSTN-CAFs and antigen presenting CAFs, apCAFs). LRRC15 is a myCAFs marker, and myCAFs depletion by diphtheria toxin induces the rapid accumulation of cytotoxic T lymphocytes (CTLs) and therefore augment PDL1 antibody treatments. This finding proposes that myCAFs may be a critical regulator of tumor immunity in terms of PDAC progression. myCAFs are located in CAFs adjacent to tumor cells, while iCAFs marked by PDPN and/or COL14A1 are distant from tumor cells, where hypoxic and acidic environments being located in iCAFs putatively due to poor blood supply is consistent with HIF1A and GPR68 expressions. iCAFs may be shared with SASP (secretion-associated phenotypes) in senescent CAFs. myCAFs are classically characterized by CAFGs induced by TGFB1, while chemoresistant CAFs with SASP may dependent on IL6 expression and accompanied by STAT3 activation. Recently, it was found that the unique metabolism of CAFs can be targeted to prevent PDAC progression, where PDAC cells utilize glucose, whereas CAFs in turn utilize lactate, which may be epigenetically regulated, mediated by its target genes including CXCR4. In summary, CAFs have unique molecular characteristics, which have been rigorously clarified as novel therapeutic targets of PDAC progression.
In Silico Assessment of Chemical Disinfectants on Surface Proteins Unveiled Dissimilarity in Antiviral Efficacy and Suitability towards Pathogenic Viruses
Authors: Zure Diaiti , Sung Meng-Hau , Rahim Abdul , Kuo Hsion-Wen
Published: May 2024

Viral pathogens pose a substantial threat to public health and necessitate the development of effective remediation and antiviral strategies. This short communication aimed to investigate the antiviral efficacy of disinfectants on the surface proteins of human pathogenic viruses. Using in silico modeling, the ligand-binding energies (LBEs) of selected disinfectants were predicted and combined with their environmental impacts and costs through an eco-pharmaco-economic analysis (EPEA). The results revealed that the binding affinities of chemical disinfectants to viral proteins varied significantly (p < 0.005). Rutin demonstrated promising broad-spectrum antiviral efficacy with an LBE of −8.49 ± 0.92 kcal/mol across all tested proteins. Additionally, rutin showed a superior eco-pharmaco-economic profile compared to the other chemicals, effectively balancing high antiviral effectiveness, moderate environmental impact, and affordability. These findings highlight rutin as a key phytochemical for use in remediating viral contaminants.
Cold Acclimation and Deacclimation of Winter Oilseed Rape, with Special Attention Being Paid to the Role of Brassinosteroids
Authors: Stachurska Julia , Sadura Iwona , Jurczyk Barbara , Rudolphi-Szydło Elżbieta , Dyba Barbara , Pociecha Ewa , Ostrowska Agnieszka , Rys Magdalena , Kvasnica Miroslav , Oklestkova Jana , Janeczko Anna
Published: May 2024

Winter plants acclimate to frost mainly during the autumn months, through the process of cold acclimation. Global climate change is causing changes in weather patterns such as the occurrence of warmer periods during late autumn or in winter. An increase in temperature after cold acclimation can decrease frost tolerance, which is particularly dangerous for winter crops. The aim of this study was to investigate the role of brassinosteroids (BRs) and BR analogues as protective agents against the negative results of deacclimation. Plants were cold-acclimated (3 weeks, 4 °C) and deacclimated (1 week, 16/9 °C d/n). Deacclimation generally reversed the cold-induced changes in the level of the putative brassinosteroid receptor protein (BRI1), the expression of BR-induced COR, and the expression of SERK1, which is involved in BR signal transduction. The deacclimation-induced decrease in frost tolerance in oilseed rape could to some extent be limited by applying steroid regulators. The deacclimation in plants could be detected using non-invasive measurements such as leaf reflectance, chlorophyll a fluorescence, and gas exchange monitoring.
PvdL Orchestrates the Assembly of the Nonribosomal Peptide Synthetases Involved in Pyoverdine Biosynthesis in Pseudomonas aeruginosa
Authors: Manko Hanna , Steffan Tania , Gasser Véronique , Mély Yves , Schalk Isabelle , Godet Julien
Published: May 2024

The pyoverdine siderophore is produced by Pseudomonas aeruginosa to access iron. Its synthesis involves the complex coordination of four nonribosomal peptide synthetases (NRPSs), which are responsible for assembling the pyoverdine peptide backbone. The precise cellular organization of these NRPSs and their mechanisms of interaction remain unclear. Here, we used a combination of several single-molecule microscopy techniques to elucidate the spatial arrangement of NRPSs within pyoverdine-producing cells. Our findings reveal that PvdL differs from the three other NRPSs in terms of localization and mobility patterns. PvdL is predominantly located in the inner membrane, while the others also explore the cytoplasmic compartment. Leveraging the power of multicolor single-molecule localization, we further reveal co-localization between PvdL and the other NRPSs, suggesting a pivotal role for PvdL in orchestrating the intricate biosynthetic pathway. Our observations strongly indicates that PvdL serves as a central orchestrator in the assembly of NRPSs involved in pyoverdine biosynthesis, assuming a critical regulatory function.
Osteoarthritis as a Systemic Disease Promoted Prostate Cancer In Vivo and In Vitro
Authors: Rosas Samuel , Kwok Andy , Moore Joseph , Shi Lihong , Smith Thomas L. , Tallant E. Ann , Kerr Bethany A. , Willey Jeffrey S.
Published: May 2024

Osteoarthritis (OA) is increasing worldwide, and previous work found that OA increases systemic cartilage oligomeric matrix protein (COMP), which has also been implicated in prostate cancer (PCa). As such, we sought to investigate whether OA augments PCa progression. Cellular proliferation and migration of RM1 murine PCa cells treated with interleukin (IL)-1α, COMP, IL-1α + COMP, or conditioned media from cartilage explants treated with IL-1α (representing OA media) and with inhibitors of COMP were assessed. A validated murine model was used for tumor growth and marker expression analysis. Both proliferation and migration were greater in PCa cells treated with OA media compared to controls (p < 0.001), which was not seen with direct application of the stimulants. Migration and proliferation were not negatively affected when OA media was mixed with downstream and COMP inhibitors compared to controls (p > 0.05 for all). Mice with OA developed tumors 100% of the time, whereas mice without OA only 83.4% (p = 0.478). Tumor weight correlated with OA severity (Pearson correlation = 0.813, p = 0.002). Moreover, tumors from mice with OA demonstrated increased Ki-67 expression compared to controls (mean 24.56% vs. 6.91%, p = 0.004) but no difference in CD31, PSMA, or COMP expression (p > 0.05). OA appears to promote prostate cancer in vitro and in vivo.
Food Insecurity in Hispanic Populations Is Associated with an Increased Risk of Hepatic Steatosis: A Nationally Representative Study
Authors: Niezen Sebastian , Goyes Daniela , Vipani Aarshi , Yang Ju Dong , Ayoub Walid S. , Kuo Alexander , Long Michelle T. , Trivedi Hirsh D.
Published: May 2024

Introduction: The Hispanic population in the US faces a higher risk of nonalcoholic fatty liver disease (NAFLD). Multiple factors influence this risk, including genetics, environmental factors, and socioeconomic statuses. Inadequate access to nutritious foods, or food insecurity, is prevalent among Hispanic individuals and poses a metabolic risk for both the onset and development of NAFLD. Materials and Methods: We utilized the National Health and Nutrition Examination Survey (NHANES) 2017–2020 pre-pandemic data to analyze the association between Hispanic ethnicity, hepatic steatosis, fibrosis, and food insecurity. Vibration-controlled transient elastography (VCTE) was employed to assess liver stiffness (LSM) and controlled attenuation parameter (CAP) scores to determine fibrosis and steatosis, respectively. Linear and ordinal logistic regression models were applied to their continuous, log-transformed, and categorical forms, adjusting for demographics, metabolic comorbidities, and socioeconomic factors. Models were subsequently stratified based on food security statuses. Results: A total of 7396 Hispanic participants were included in the study. Under multivariable analysis, Hispanic individuals had higher CAP scores (Beta-coefficient: 10.2 dB/m, 95% CI: 6.1–14.4 dB/m, p = 0.001)) vs. non-Hispanic individuals, without statistically significant differences in fibrosis. Food-insecure participants exhibited higher CAP scores than their food-secure counterparts. After stratification, a stronger association between Hispanic ethnicity and CAP scores was evident in the food-insecure group (Beta-coefficient: 11.8 dB/m, 95% CI: 4.4–19.3 dB/m, p = 0.003). Discussion: This study demonstrates the heightened risk of hepatic steatosis among individuals with Hispanic ancestry in the US. The risk is exacerbated by food insecurity, particularly for Hispanic individuals. The contribution is linked to the dietary habits in this population that lead to metabolic risk factors associated with hepatic steatosis. Considering the rising prevalence of NAFLD and food insecurity, interventions focusing on nutritional support and healthcare access among this population could mitigate these burdens.
Association between Physical Function, Mental Function and Frailty in Community-Dwelling Older Adults: A Cross-Sectional Study
Authors: Park Hye-Jin , Thapa Ngeemasara , Bae Seongryu , Yang Ja-Gyeong , Choi Jaewon , Noh Eun-Seon , Park Hyuntae
Published: May 2024

Background: This study examines the relationship between physical and mental function and frailty, independently and in conjunction with polypharmacy, among older adults. Methods: This cross-sectional study consisted of 368 participants aged ≥60 years. The participants were categorized into either robust or frail groups using Fried’s frailty phenotype. Physical functions were assessed using grip strength, gait speed, Timed Up and Go (TUG), the Five Chair Sit to Stand Test (FCSST) and the Six-Minute Walk Test (SMWT). Mental functions were assessed using cognitive function and depression. Cognitive function was measured using Mini-Mental State Examination (MMSE). Depression was assessed with the Korean version of the Short Geriatric Depression Scale (SGDS). Results: The mean age of study population was 75.4 years. In this population, we identified 78.8% (n = 290) robust participants and 21.2% (n = 78) frail participants. The study examined frailty status (frail vs. non-frail) and frailty with and without polypharmacy using multivariate logistic regressions, adjusting for age and sex. In the logistic regression model estimating the risk of frailty, after adjustments for age, sex, BMI, and number of medications, individuals with low SMWT showed a significantly increased risk of frailty, with an odds ratio (OR) of 8.66 and a 95% confidence interval (CI) of 4.55–16.48. Additionally, global cognitive function was associated with a 1.97-fold increase in frailty risk (95% CI: 1.02–3.67). Moreover, in models adjusted for age, sex, and BMI to assess frailty risk linked to polypharmacy, the TUG, SMWT, and SGDS all showed increased risks, with ORs of 3.65 (95% CI: 1.07–12.47), 5.06 (95% CI: 1.40–18.32), and 5.71 (95% CI: 1.79–18.18), respectively. Conclusions: Physical function (SMWT, FCSST, TUG) and mental function (depression, cognition) were associated with frailty. By comprehensively examining these factors, we will gain valuable insights into frailty and enable more precise strategies for intervention and prevention.
Examination of the Vitreolenticular Interface in Relation to Uneventful Phacoemulsification over One-Year Postoperative Period
Authors: Elekes Ágnes , Németh Gábor , Lauter Dóra , Edelmayer Márton , Rupnik Zsófia , Vámosi Péter
Published: May 2024

Background: Swept-source anterior segment optical coherence tomography (SS-AS-OCT) is a suitable examination for the vitreolenticular interface. Methods: In a prospective study using Anterion (Heidelberg Engineering, Heidelberg, Germany), 102 eyes of 102 patients were examined in pupil dilation, preoperatively and 6 times over 1-year follow-up. Preoperatively anterior hyaloid membrane (AHM) visibility was determined with Imaging App with high reliability. Postoperatively capsular bag–AHM distance was measured on six points by using Metrics App. Results: The AHM was visible in 18.6% preoperatively and postoperatively as well (Group 1), 49% of the preoperatively adherent AHMs became visible (Group 2A), 32.4% remained attached (Group 2B). Group 1: the average deepest point on the first day was 782.5 ± 324.1 microns, and it significantly differed from the later follow-up values. Group 2A: the average deepest value was 184.1 ± 220.1 microns, and there was no statistically significant difference between the postoperative visit values. The difference between the groups was statistically significant at every location and at each time point. Conclusions: AS-SS-OCT can be used to check BS both preoperatively (with limitations) and postoperatively.
Energy Loss Index and Dimensionless Index Outperform Direct Valve Planimetry in Low-Gradient Aortic Stenosis
Authors: Hugelshofer Sarah , de Brito Diana , Antiochos Panagiotis , Tzimas Georgios , Rotzinger David C. , Auberson Denise , Vella Agnese , Fournier Stephane , Kirsch Matthias , Muller Olivier , Monney Pierre
Published: May 2024

Background/Objectives: Among patients with suspected severe aortic stenosis (AS), discordance between effective orifice area (EOA) and transvalvular gradients is frequent and requires a multiparametric workup including flow assessment and calcium-scoring to confirm true severe AS. The aim of this study was to assess direct planimetry, energy loss index (Eli) and dimensionless index (DI) as stand-alone parameters to identify non-severe AS in discordant cases. Methods: In this prospective cohort study, we included consecutive AS patients > 70 years with EOA < 1.0 cm2 referred for valve replacement between 2014 and 2017. AS severity was retrospectively reassessed using the multiparametric work-up recommended in the 2021 ESC/EACTS guidelines. DI and ELi were calculated, and valve area was measured by direct planimetry on transesophageal echocardiography. Results: A total of 101 patients (mean age 82 y; 57% male) were included. Discordance between EOA and gradients was observed in 46% and non-severe AS found in 24% despite an EOA < 1 cm2. Valve planimetry performed poorly, with an area under the ROC curve (AUC) of 0.64. At a cut-off value of >0.82 cm2, sensitivity and specificity to identify non-severe AS were 67 and 66%, respectively. DI and ELi showed a higher diagnostic accuracy, with an AUC of 0.77 and 0.76, respectively. Cut-off values of >0.24 and >0.6 cm2/m2 identified non-severe AS, with a high specificity of 79% and 91%, respectively. Conclusions: Almost one in four patients with EOA < 1 cm2 had non-severe AS according to guideline-recommended multiparametric assessment. Direct valve planimetry revealed poor diagnostic accuracy and should be interpreted with caution. Usual prognostic cut-off values for DI > 0.24 and ELI > 0.6 cm2/m2 identified non-severe AS with high specificity and should therefore be included in the assessment of low-gradient AS.
Syncope in the Emergency Department: A Practical Approach
Authors: Furlan Ludovico , Jacobitti Esposito Giulia , Gianni Francesca , Solbiati Monica , Mancusi Costantino , Costantino Giorgio
Published: May 2024

Syncope is a common condition encountered in the emergency department (ED), accounting for about 0.6–3% of all ED visits. Despite its high frequency, a widely accepted management strategy for patients with syncope in the ED is still missing. Since syncope can be the presenting condition of many diseases, both severe and benign, most research efforts have focused on strategies to obtain a definitive etiologic diagnosis. Nevertheless, in everyday clinical practice, a definitive diagnosis is rarely reached after the first evaluation. It is thus troublesome to aid clinicians’ reasoning by simply focusing on differential diagnoses. With the current review, we would like to propose a management strategy that guides clinicians both in the identification of conditions that warrant immediate treatment and in the management of patients for whom a diagnosis is not immediately reached, differentiating those that can be safely discharged from those that should be admitted to the hospital or monitored before a final decision. We propose the mnemonic acronym RED-SOS: Recognize syncope; Exclude life-threatening conditions; Diagnose; Stratify the risk of adverse events; Observe; decide on the Setting of care. Based on this acronym, in the different sections of the review, we discuss all the elements that clinicians should consider when assessing patients with syncope.
SCORE2 Screening Tool for Cardiovascular Risk Assessment in Psoriasis—A Case–Control Study
Authors: Kampe Tomáš , Baloghová Janette , Kolarčik Peter , Rimárová Kvetoslava , Dorko Erik
Published: May 2024

Background: Psoriasis is a common, T-cell-mediated inflammatory and immune-mediated skin disease. Numerous studies confirmed that patients with psoriasis have a significant frequency of cardiovascular (CV) risk factors and CV diseases (CVDs). Risk stratification is helpful in light of the elevated risk of CVD in psoriasis patients. SCORE2 and SCORE2-OP, a new algorithm derived, calibrated and validated to predict the 10-year risk of first-onset CVD in European populations, enhances the identification of individuals at higher risk of developing CVD across Europe. Objective: Using the SCORE2 and SCORE2-OP scoring systems, the current study objective was to evaluate CV risk in Slovak psoriasis patients and the relationship between CV risk and psoriasis features in a real-world setting. Results: A case–control study was conducted involving 115 outpatients with plaque psoriasis and 66 age- and gender-matched controls with skin conditions other than psoriasis. Patients with psoriasis had significantly higher mean SCORE2 values. In the age group up to 50 years, more psoriasis patients were classified as moderate risk than controls (33.8% vs. 13.6%, p = 0.010); the high-risk category was dominated by psoriasis patients. Analysing the relationship between CV risk and selected variables, we determined, using linear regression, the dependence of the SCORE2 risk score on gender in the age group up to 50 years, on age in both age groups, on waist circumference (WC) in the category up to 50 years and on the duration and severity of psoriasis in both age groups using linear regression. For individuals older than 70, we estimated the SCORE2-OP risk score, with the average risk score being 19.5 ± 4.95. We did not observe controls with a high risk score. Psoriasis patients were more likely to be smokers and had significantly higher mean values for body mass index (BMI), WC, total cholesterol (TC), low-density lipoprotein (LDL) and systolic blood pressure (BP). Conclusions: Because CV risk factors and psoriasis are strongly related, the importance of CV risk stratification is growing, and initiating preventive lifestyle changes or therapeutic interventions in patients with psoriasis is warranted.
Mechanisms of Component Degradation and Multi-Scale Strategies for Predicting Composite Durability: Present and Future Perspectives
Authors: Ferreira Rocha Paulo Ricardo , Fonseca Gonçalves Guilherme , dos Reis Guillaume , Guedes Rui Miranda
Published: May 2024

Composite materials, valued for their adaptability, face challenges associated with degradation over time. Characterising their durability through traditional experimental methods has shown limitations, highlighting the need for accelerated testing and computational modelling to reduce time and costs. This study presents an overview of the current landscape and future prospects of multi-scale modelling for predicting the long-term durability of composite materials under different environmental conditions. These models offer detailed insights into complex degradation phenomena, including hydrolytic, thermo-oxidative, and mechano-chemical processes. Recent research trends indicate a focus on hygromechanical models across various materials, with future directions aiming to explore less-studied environmental factors, integrate multiple stressors, investigate emerging materials, and advance computational techniques for improved predictive capabilities. The importance of the synergistic relationship between experimental testing and modelling is emphasised as essential for a comprehensive understanding of composite material behaviour in diverse environments. Ultimately, multi-scale modelling is seen as a vital contributor to accurate predictions of environmental effects on composite materials, offering valuable insights for sustainable development across industries.
Metaheuristic Optimization of Functionally Graded 2D and 3D Discrete Structures Using the Red Fox Algorithm
Authors: Gaspar J. S. D. , Loja M. A. R. , Barbosa J. I.
Published: May 2024

The growing applicability of functionally graded materials is justified by their ability to contribute to the development of advanced solutions characterized by the material customization, through the selection of the best parameters that will confer the best mechanical behaviour for a given structure under specific operating conditions. The present work aims to attain the optimal design solutions for a set of illustrative 2D and 3D discrete structures built from functionally graded materials using the Red Fox Optimization Algorithm, where the design variables are material parameters. From the results achieved one concludes that the optimal selection and distribution of the different materials’ mixture and the different exponents associated with the volume fraction law significantly influence the optimal responses found. To note additionally the good performance of the coupling between this optimization technique and the finite element method used for the linear static and free vibration analyses.