bluuebunny/crossref_metadata_2025 huggingface dataset:
Anti-Aggregative and Protective Effects of Vicenin-2 on Heat and Oxidative Stress-Induced Damage on Protein Structures
Authors: Patanè Giuseppe Tancredi , Lombardo Lisa , Putaggio Stefano , Tellone Ester , Ficarra Silvana , Barreca Davide , Laganà Giuseppina , De Luca Laura , Calderaro Antonella
Published: December 2023

Vicenin-2, a flavonoid categorized as a flavones subclass, exhibits a distinctive and uncommon C-glycosidic linkage. Emerging evidence challenges the notion that deglycosylation is not a prerequisite for the absorption of C-glycosyl flavonoid in the small intestine. Capitalizing on this experimental insight and considering its biological attributes, we conducted different assays to test the anti-aggregative and antioxidant capabilities of vicenin-2 on human serum albumin under stressful conditions. Within the concentration range of 0.1–25.0 μM, vicenin-2 effectively thwarted the heat-induced HSA fibrillation and aggregation of HSA. Furthermore, in this study, we have observed that vicenin-2 demonstrated protective effects against superoxide anion and hydroxyl radicals, but it did not provide defense against active chlorine. To elucidate the underlying mechanisms, behind this biological activity, various spectroscopy techniques were employed. UV-visible spectroscopy revealed an interaction between HSA and vicenin-2. This interaction involves the cinnamoyl system found in vicenin-2, with a peak of absorbance observed at around 338 nm. Further evidence of the interaction comes from circular dichroism spectrum, which shows that the formation of bimolecular complex causes a reduction in α-helix structures. Fluorescence and displacement investigations indicated modifications near Trp214, identifying Sudlow’s site I, similarly to the primary binding site. Molecular modeling revealed that vicenin-2, in nonplanar conformation, generated hydrophobic interactions, Pi-pi stacking, and hydrogen bonds inside Sudlow’s site I. These findings expand our understanding of how flavonoids bind to HSA, demonstrating the potential of the complex to counteract fibrillation and oxidative stress.
Lung Cancer Cell-Derived Exosome Detection Using Electrochemical Approach towards Early Cancer Screening
Authors: Irani Koosha , Siampour Hossein , Allahverdi Abdollah , Moshaii Ahmad , Naderi-Manesh Hossein
Published: December 2023

Lung cancer is one of the deadliest cancers worldwide due to the inability of existing methods for early diagnosis. Tumor-derived exosomes are nano-scale vesicles released from tumor cells to the extracellular environment, and their investigation can be very useful in both biomarkers for early cancer screening and treatment assessment. This research detected the exosomes via an ultrasensitive electrochemical biosensor containing gold nano-islands (Au-NIs) structures. This way, a high surface-area-to-volume ratio of nanostructures was embellished on the FTO electrodes to increase the chance of immobilizing the CD-151 antibody. In this way, a layer of gold was first deposited on the electrode by physical vapor deposition (PVD), followed by thermal annealing to construct primary gold seeds on the surface of the electrode. Then, gold seeds were grown by electrochemical deposition through gold salt. The cell-derived exosomes were successfully immobilized on the FTO electrode through the CD-151 antibody, and cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) methods were used in this research. In the CV method, the change in the current passing through the working electrode is measured so that the connection of exosomes causes the current to decrease. In the EIS method, surface resistance changes were investigated so that the binding of exosomes increased the surface resistance. Various concentrations of exosomes in both cell culture and blood serum samples were measured to test the sensitivity of the biosensor, which makes our biosensor capable of detecting 20 exosomes per milliliter.
Molecular Characterization of Local Walnut (Juglans regia) Genotypes in the North-East Parnon Mountain Region of Greece
Authors: Manthos Ioannis , Sotiropoulos Thomas , Karapetsi Lefkothea , Ganopoulos Ioannis , Pratsinakis Emmanouil D. , Maloupa Eleni , Madesis Panagiotis
Published: December 2023

Walnut is one of the most important nuts regarding their production and consumption. The available but uncharacterized genetic resources of walnut are important for the development and breeding of local varieties. Greece holds an important number of genetically uncharacterized walnut landraces, especially within the area of Parnon, which is considered to play a significant role as an in situ gene bank, due to its unique location traits. However, the genetic characterization and further use of these resources has been insufficient, due to the absence of genetic studies. In this study, we implemented SSR molecular markers, both to genetically characterize the walnut tree genetic diversity of the Parnon area and to identify its unique genetic structure, which will form the starting material for subsequent breeding programs. Overall, high levels of genetic variation were found among the individual walnut accessions that were collected in the Parnon mountain region.
Nicotinamide-Expanded Allogeneic Natural Killer Cells with CD38 Deletion, Expressing an Enhanced CD38 Chimeric Antigen Receptor, Target Multiple Myeloma Cells
Authors: Edri Avishay , Ben-Haim Nimrod , Hailu Astar , Brycman Nurit , Berhani-Zipori Orit , Rifman Julia , Cohen Sherri , Yackoubov Dima , Rosenberg Michael , Simantov Ronit , Teru Hideshima , Kurata Keiji , Anderson Kenneth Carl , Hendel Ayal , Pato Aviad , Geffen Yona
Published: December 2023

Natural killer (NK) cells are a vital component of cancer immune surveillance. They provide a rapid and potent immune response, including direct cytotoxicity and mobilization of the immune system, without the need for antigen processing and presentation. NK cells may also be better tolerated than T cell therapy approaches and are susceptible to various gene manipulations. Therefore, NK cells have become the focus of extensive translational research. Gamida Cell’s nicotinamide (NAM) platform for cultured NK cells provides an opportunity to enhance the therapeutic potential of NK cells. CD38 is an ectoenzyme ubiquitously expressed on the surface of various hematologic cells, including multiple myeloma (MM). It has been selected as a lead target for numerous monoclonal therapeutic antibodies against MM. Monoclonal antibodies target CD38, resulting in the lysis of MM plasma cells through various antibody-mediated mechanisms such as antibody-dependent cellular cytotoxicity (ADCC), complement-dependent cytotoxicity, and antibody-dependent cellular phagocytosis, significantly improving the outcomes of patients with relapsed or refractory MM. However, this therapeutic strategy has inherent limitations, such as the anti-CD38-induced depletion of CD38-expressing NK cells, thus hindering ADCC. We have developed genetically engineered NK cells tailored to treat MM, in which CD38 was knocked-out using CRISPR-Cas9 technology and an enhanced chimeric antigen receptor (CAR) targeting CD38 was introduced using mRNA electroporation. This combined genetic approach allows for an improved cytotoxic activity directed against CD38-expressing MM cells without self-inflicted NK-cell-mediated fratricide. Preliminary results show near-complete abolition of fratricide with a 24-fold reduction in self-lysis from 19% in mock-transfected and untreated NK cells to 0.8% of self-lysis in CD38 knock-out CAR NK cells. Furthermore, we have observed significant enhancements in CD38-mediated activity in vitro, resulting in increased lysis of MM target cell lines. CD38 knock-out CAR NK cells also demonstrated significantly higher levels of NK activation markers in co-cultures with both untreated and αCD38-treated MM cell lines. These NAM-cultured NK cells with the combined genetic approach of CD38 knockout and addition of CD38 CAR represent a promising immunotherapeutic tool to target MM.
Evaluation of the Antitumor Activity of Quaternary Ammonium Surfactants
Authors: Hyla Kinga , Jama Dominika , Grzywacz Aleksandra , Janek Tomasz
Published: December 2023

Quaternary ammonium surfactants, due to their diverse chemical structure and their biological properties, can be used in medicine as DNA carriers, disinfectants, and antimicrobial and antitumor agents. In this study, using melanoma A375, colon adenocarcinoma HT-29 and normal human dermal fibroblast (NHDF) cells, we tested the hypothesis that the quaternary ammonium surfactants 2-dodecanoyloxyethyl)trimethylammonium bromide (DMM-11), 2-dodecanoyloxypropyl)trimethylammonium bromide (DMPM-11) and 2-pentadecanoyloxymethyl)trimethylammonium bromide (DMGM-14) act selectively against cancer cells. The results showed that these compounds led to the initiation of the apoptotic process of programmed cell death, as evidenced by the ratio of the relative expression of Bax protein to Bcl-2. The encapsulation of surfactants in liposomes allowed lower concentrations to be used. Moreover, encapsulation reduced their toxicity towards non-cancerous cells. The anticancer efficiency and apoptotic effect of the liposomal formulations with surfactants (DMM-11, DMPM-11 and DMGM-14) were higher than those of surfactant-free liposomes. Therefore, quaternary ammonium surfactant-loaded liposomes show significant potential as delivery vehicles for the treatment of melanoma and colon cancers. The use of nano-formulations offers the advantage of optimizing quaternary ammonium surfactant delivery for improved anticancer therapy.
A Configurable 64-Channel ASIC for Cherenkov Radiation Detection from Space
Authors: Di Salvo Andrea , Garbolino Sara , Mignone Marco , Zugravel Stefan Cristi , Rivetti Angelo , Bertaina Mario Edoardo , Palmieri Pietro Antonio
Published: December 2023

This work presents the development of a 64-channel application-specific integrated circuit (ASIC), implemented to detect the optical Cherenkov light from sub-orbital and orbital altitudes. These kinds of signals are generated by ultra-high energy cosmic rays (UHECRs) and cosmic neutrinos (CNs). The purpose of this front-end electronics is to provide a readout unit for a matrix of silicon photo-multipliers (SiPMs) to identify extensive air showers (EASs). Each event can be stored into a configurable array of 256 cells where the on-board digitization can take place with a programmable 12-bits Wilkinson analog-to-digital converter (ADC). The sampling, the conversion process, and the main digital logic of the ASIC run at 200 MHz, while the readout is managed by dedicated serializers operating at 400 MHz in double data rate (DDR). The chip is designed in a commercial 65 nm CMOS technology, ensuring a high configurability by selecting the partition of the channels, the resolution in the interval 8–12 bits, and the source of its trigger. The production and testing of the ASIC is planned for the forthcoming months.
A Comparative Analysis between Flexible Ureteroscopic Lithotripsy and Tubeless Percutaneous Nephrolithotomy in the Treatment of >15 mm Non-Obstructing Proximal Ureteral Stones
Authors: Choi Yong Sun , Sorkhi Samuel Ryan , Cho Hyuk Jin , Kim Kang Sup
Published: December 2023

Background: The proper surgical modality for large non-obstructing proximal ureteral stones is disputed. We compare effectiveness and safety of flexible ureteroscopic lithotripsy (FURL) and tubeless percutaneous nephrolithotomy (TPNL) in treatment of upper ureteral stones larger than 1.5 cm. Methods: We reviewed the medical records of patients who performed FURL or TPNL for upper ureteral stones between June 2016 and November 2018. Comparative analysis was conducted regarding demographic parameters, stone free rate, postoperative pain and complications. Results: This study included 58 patients treated with FURL and 60 patients treated with TPNL owing to upper ureteral stones larger than 1.5 cm. Stone size was similar in the FURL and TPNL groups (17.6 ± 2.6 vs. 18.0 ± 2.1 mm, p = 0.194). The overall 3-month stone clearance rate was 95.8% for FURL versus 96.0% for TPNL (p = 0.575). There was no difference between the FURL and TPNL groups for hospital stay (p = 0.280) and postoperative complications. On the other hand, patients treated with FURL had longer operative time (p = 0.012) and less postoperative pain (p = 0.008). Conclusions: Both surgical techniques were considered feasible and effective surgical procedures in the treatment of large upper ureteral stones.
Mesenchymal Stromal Cell Healing Outcomes in Clinical and Pre-Clinical Models to Treat Pressure Ulcers: A Systematic Review
Authors: Torres-Guzman Ricardo A. , Avila Francisco R. , Maita Karla , Garcia John P. , De Sario Gioacchino D. , Borna Sahar , Eldaly Abdullah S. , Quinones-Hinojosa Alfredo , Zubair Abba C. , Ho Olivia A. , Forte Antonio J.
Published: December 2023

Background: Despite numerous measures used to prevent pressure ulcers, their growing prevalence in recent years is expected to continue as the population ages. This review aims to report the outcomes of the regenerative potential of MSCs in treating pressure ulcers, assessing the effectiveness of MSCs in treating pressure ulcers. Methods: A computerized search for articles on animal models that use MSCs as primary therapy to treat pressure ulcers, published from conception to present, was conducted using PubMed, MEDLINE, Embase, and CINAHL. Our search yielded 52 articles, narrowed to 44 after excluding duplicates. Results: Out of 52 articles collected from four databases, 11 met the inclusion criteria. A total of 11 articles published between 2008 and 2020 met the inclusion criteria. Eight studies were observational descriptive papers in animal models, and three were prospective. Six studies used autologous MSCs, while five used allogenic MSCs. Three studies were conducted in humans, and the remaining eight were conducted in animals. The most common method of cell delivery was an intradermal injection in the margins of the ulcer. All studies reported positive results, including improved wound healing, reduced inflammation, and improved tissue regeneration. Conclusions: MSCs have shown promising results in treating pressure ulcers in animal and clinical trials. The combination of MSCs and scaffold materials has also been studied and found to be effective in wound healing. A standardized human wound model has been proposed further to investigate the efficacy of cell-based therapies for chronic wounds. However, more research is needed to determine the best quantity of cells to apply for pressure ulcers and to ensure the safety and efficacy of these treatments in clinical settings.
X-Linked Hypophosphatemia: Does Targeted Therapy Modify Dental Impairment?
Authors: Abdullah Anusha , Wuersching Sabina Noreen , Kollmuss Maximilian , Poxleitner Philipp , Dewenter Ina , Brandenburg Leonard Simon , Steybe David , Fegg Florian Nepomuk , Smolka Wenko , Otto Sven , Obermeier Katharina Theresa
Published: December 2023

X-linked hypophosphatemia is a rare, hereditary disorder that significant influences teeth and alveolar bone. The first clinical sign leading to the diagnosis of X-linked hypophosphatemia is often dental impairment with dental abscesses and dentin mineralization defects. Genetic analysis helped find the responsible gene and therefore opened up new ways of therapeutically managing X-linked hypophosphatemia. The human monoclonal antibody Burosumab represents a milestone in the targeted therapy of this hereditary disease by directly addressing its pathophysiology. Targeted therapy has been shown to improve skeletal impairment, pain, and phosphate metabolism. However, the influence of this new therapy on dental impairment has only been addressed in a few recent studies with varying results. Therefore, in this review, we aim to summarize the dental phenotype and analyze the different treatment modalities with a focus on dental impairment.
The Impact of Hydrogen Peroxide (H2O2) Fumigation on Bacterial Levels in Dental Office Environments: A Randomized Clinical Trial Investigation
Authors: Matys Jacek , Gedrange Tomasz , Dominiak Marzena , Grzech-Leśniak Kinga
Published: December 2023

Background: Fumigation with hydrogen peroxide has proven to be a highly effective approach to maintaining biological safety within dental offices. The main purpose of this research was to investigate the efficacy of hydrogen peroxide (H2O2) fumigation in reducing bacterial levels in dental office environments. Methods: The study involved 30 participants diagnosed with moderate caries decay (ICDAS 3 and 4) in their mandibular molars. Sixty Petri dishes (two per patient) with Columbia Agar and 5% Sheep Blood were opened at the beginning of the caries treatment. After the completion of caries treatment and tooth restoration, 30 plates (G1 group) were closed. Following this, a 20 min fumigation procedure with 6% hydrogen peroxide biosanitizer using a compressed air device was conducted. After the fumigation, the remaining plates were closed (G2 group). The total number of bacteria CFUs (colony-forming units) in the dental office air was determined using the Koch sedimentation method. Results: The total bacterial colony (TBC) level, measured in cfu/m3, demonstrated a significant decrease in the number of bacteria following room environment fumigation (163.1 ± 145.7; G2 group) compared to non-fumigated samples (817.2 ± 208.2; G1 group) (p < 0.001). The predominant bacteria observed in the microbiological plates before fumigation were Micrococcus and Bacillus species, found in 80% (24/30) and 60% (18/30) of the plates, respectively. Application of H2O2 room fumigation resulted in a significant reduction in bacterial numbers: 79.2% (5/30) for Micrococcus species (p < 0.001), 83.3% (3/30) for Bacillus species (p < 0.001), and 100% (0/30) for Staphylococcus arlettae (p < 0.05). Conclusion: Fumigation with 6% H2O2 is an effective method for reducing bacterial counts in a dental office environment.
Structured Light Plethysmography for Non-Invasive Assessment of Respiratory Pattern in Spinal Muscular Atrophy Type 1
Authors: Brolatti Noemi , Trucco Federica , Ferretti Marta , Avanti Chiara , Tacchetti Paola , Panicucci Chiara , Striano Pasquale , Minetti Carlo , Bruno Claudio , Pedemonte Marina
Published: December 2023

Background: Spinal muscular atrophy (SMA) type 1 is a severe condition leading to early respiratory failure. Treatment options have become available, yet respiratory outcome measures in SMA type 1 are limited. The aim of this study was to assess the respiratory pattern in SMA type 1 patients via structured light plethysmography (SLP). SLP measures the thoraco-abdominal movements by projecting a light grid onto the anterior thoraco-abdominal surface. Methods: Cross-sectional study of consecutive children with SMA type 1. All children underwent motor assessment (CHOP-INTEND) and one-minute tidal breathing recording by SLP in supine position while self-ventilating in room air. The Respiratory rate, the abdominal vs. chest contribution to breath (Relative Expired Abdomen%, Relative Expired Chest%) and the severity of thoraco-abdominal paradox (Phase Angle) were acquired. Results: Nineteen patients were included, median (IQR) age 2.3 years (1.4–7.9). Their respiratory pattern captured via SLP showed a raised median (IQR) respiratory rate per age of 33.5 bpm (26.6–41.7), a prevalent abdominal contribution to tidal breathing with median (IQR) Relative Expired Abdomen 77% (68–90) vs. Chest 23% (10–32). Thoracoabdominal paradox was detected (median Phase Angle 48.70°) and its severity correlated negatively with CHOP-INTEND (r −0.8, p < 0.01). Conclusions: SLP captured and quantified the respiratory features of infants and children with SMA type 1.
Does Far Cortical Locking Improve Fracture Healing in Distal Femur Fractures: A Randomised, Controlled, Prospective Multicentre Study
Authors: England Thomas , Khan Humza , Moniz Sheldon , Mitchell David , Kuster Markus S.
Published: December 2023

(1) Background: Bone healing is influenced by various mechanical factors, such as stability, interfragmentary motion, strain rate, and direction of loading. Far cortical locking (FCL) is a novel screw design that promotes bone healing through controlled fracture motion. (2) Methods: This study compared the outcome of distal femur fractures treated with FCL or SL (standard locking) screws and an NCB plate in a randomised controlled prospective multicentre trial. The radiographic union scale (RUST) and healing time was used to quantify bone healing on follow-up imaging. (3) Results: The study included 21 patients with distal femur fractures, 7 treated with SL and 14 treated with FCL screws. The mean working length for patients with SL screws was 6.1, whereas for FCL screws, it was 3.9. The mean RUST score at 6 months post fracture was 8.0 for patients with SL plates and 7.3 for patients with FCL plates (p value > 0.05). The mean healing time was 6.5 months for patients with SL plates and 9.9 months for patients with FCL plates (p value < 0.05). (4) Conclusions: Fractures fixed with SL plates had longer working lengths and faster healing times when compared to FCL constructs, suggesting that an adequate working length is important for fracture healing regardless of screw choice.
Electrochemical Oxidation of Phenol Released from Spent Coordination Polymer Impregnated with Ionic Liquid
Authors: Plesu Nicoleta , Maranescu Bianca , Tara-Lunga Mihali Milica , Visa Aurelia
Published: December 2023

Coordination polymer (CP)-type adsorbents impregnated with ionic liquids that are used to remove phenol from wastewater must be regenerated. A simple washing of the adsorbent releases about 70% from the spent adsorbent. In order to increase and study the phenol release, an electrochemical method was used. For this purpose, an electrochemical commercial graphite electrode was used as the working electrode, and the electrolyte support was a 3% NaCl solution. During the electrochemical investigation, the spent CP was immersed in a saline solution. The PH content in the electrolyte affected the direct electrooxidation (EO); the formation of BQ appeared to be accelerated by a lower concentration and a slower release of PH. After 90 min, an efficiency of PH electrooxidation (EOPH) of 36.22% from Cu-PA and EOPH of 42.14% from Cu-PA-IL, respectively, was achieved. These results were significantly higher than the EOPH of the solution resulting from washing the wasted adsorbent with a saline solution (22.58%). This work highlights the potential for the simultaneous electrooxidation of desorbed PH and the recovery of spent adsorbent in this situation. The number of cycles in which the adsorbent can be used without losing its absorbance ability is three.
The Role of Macrophages in Cardiac Function and Disease
Authors: Prevete Nella , Sorriento Daniela
Published: December 2023

A tight association between inflammation and cardiac damage has been extensively recognized. In this review, we will focus on macrophages as key players in the physiology and pathology of the heart and on their role in the functional crosstalk between inflammation and heart disease. In the steady state, macrophages contribute to the homeostasis of cardiac tissue. Indeed, cardiac resident macrophages promote coronary development and tissue homeostasis, favor electric conduction in cardiomyocytes, and contribute to mitochondrial quality control. However, macrophages also take part in adverse cardiac events contributing to the development or the progression of several pathologic conditions. Infiltrating cells derived from circulating monocytes contribute to tissue injury through the release of inflammatory cytokines and catecholamines. In particular, the present review will discuss the role of macrophages in heart failure, atherosclerosis, and anthracycline-dependent cardiotoxicity. Prolonged inflammatory response and increased apoptotic cell death sustained by chronic activation of the transcription factor NFκB are the basis of heart failure pathogenesis. Here, we will discuss the involvement of NFκB signaling in macrophage-dependent cardiac damage and its use as a therapeutic target in the treatment of cardiovascular pathologies.
Adaptive Sampling Path Planning for a 3D Marine Observation Platform Based on Evolutionary Deep Reinforcement Learning
Authors: Zhang Jingjing , Liu Yanlong , Zhou Weidong
Published: December 2023

Adaptive sampling of the marine environment may improve the accuracy of marine numerical prediction models. This study considered adaptive sampling path optimization for a three-dimensional (3D) marine observation platform, leading to a path-planning strategy based on evolutionary deep reinforcement learning. The low sampling efficiency of the reinforcement learning algorithm is improved by evolutionary learning. The combination of these two components as a new algorithm has become a current research trend. We first combined the evolutionary algorithm with different reinforcement learning algorithms to verify the effectiveness of the combination of algorithms with different strategies. Experimental results indicate that the fusion of the two algorithms based on a maximum-entropy strategy is more effective for adaptive sampling using a 3D marine observation platform. Data assimilation experiments indicate that adaptive sampling data from a 3D mobile observation platform based on evolutionary deep reinforcement learning improves the accuracy of marine environment numerical prediction systems.
Acceleration of Morphodynamic Simulations Based on Local Trends in the Bed Evolution
Authors: Newell Ellie , Maldonado Sergio
Published: December 2023

Due to the significant mismatch in timescales associated with morphological and hydrodynamic processes in coastal environments, modellers typically resort to various techniques for speeding up the bed evolution in morphodynamic simulations. In this paper, we propose a novel method that differs from existing ones in several aspects. For example, unlike previous approaches that apply a global measure (such as a constant acceleration factor that uniformly amplifies the bed evolution everywhere), we track and extrapolate local trends in morphological changes. The present algorithm requires the setting of four different parameters, values for which we set through an extensive calibration process. The proposed method is compared against the simple acceleration technique built into the popular software XBeach (wherein it is called morfac) for eight different beach profiles (including linear, Dean, and measured profiles). While the accuracy of both methods is generally similar, the proposed algorithm consistently shows a greater reduction in computational time relative to morfac, with our algorithm-accelerated simulations being on average 2.6 times faster than morfac. In light of these results, and considering the algorithm’s potential for easy generalisation to address arbitrary coastal morphodynamic problems, we believe that this method represents an important addition to the toolbox available to the community interested in coastal modelling.
New Immunological Markers in Chromoblastomycosis—The Importance of PD-1 and PD-L1 Molecules in Human Infection
Authors: Cavallone Italo N. , Belda Walter , de Carvalho Caroline Heleno C. , Laurenti Marcia D. , Passero Luiz Felipe D.
Published: December 2023

The pathogenesis of chromoblastomycosis (CBM) is associated with Th2 and/or T regulatory immune responses, while resistance is associated with a Th1 response. However, even in the presence of IFN-γ, fungi persist in the lesions, and the reason for this persistence is unknown. To clarify the factors associated with pathogenesis, this study aimed to determine the polarization of the cellular immune response and the densities of cells that express markers of exhaustion in the skin of CBM patients. In the skin of patients with CBM, a moderate inflammatory infiltrate was observed, characterized primarily by the occurrence of histiocytes. Analysis of fungal density allowed us to divide patients into groups that exhibited low and high fungal densities; however, the intensity of the inflammatory response was not related to mycotic loads. Furthermore, patients with CBM exhibited a significant increase in the number of CD4+ and CD8+ cells associated with a high density of IL-10-, IL-17-, and IFN-γ-producing cells, indicating the presence of a chronic and mixed cellular immune response, which was also independent of fungal load. A significant increase in the number of PD-1+ and PD-L1+ cells was observed, which may be associated with the maintenance of the fungus in the skin and the progression of the disease.
Changes in the Bacterial Communities of Biocomposites with Different Flame Retardants
Authors: Vasiliauskienė Dovilė , Lukša Juliana , Servienė Elena , Urbonavičius Jaunius
Published: December 2023

In today’s world, the use of environmentally friendly materials is strongly encouraged. These materials derive from primary raw materials of plant origin, like fibrous hemp, flax, and bamboo, or recycled materials, such as textiles or residual paper, making them suitable for the growth of microorganisms. Here, we investigate changes in bacterial communities in biocomposites made of hemp shives, corn starch, and either expandable graphite or a Flovan compound as flame retardants. Using Next Generation Sequencing (NGS), we found that after 12 months of incubation at 22 °C with a relative humidity of 65%, Proteobacteria accounted for >99.7% of the microbiome in composites with either flame retardant. By contrast, in the absence of flame retardants, the abundance of Proteobacteria decreased to 32.1%, while Bacteroidetes (36.6%), Actinobacteria (8.4%), and Saccharobacteria (TM7, 14.51%) appeared. Using the increasing concentrations of either expandable graphite or a Flovan compound in an LB medium, we were able to achieve up to a 5-log reduction in the viability of Bacillus subtilis, Pseudomonas aeruginosa, representatives of the Bacillus and Pseudomonas genera, the abundance of which varied in the biocomposites tested. Our results demonstrate that flame retardants act on both Gram-positive and Gram-negative bacteria and suggest that their antimicrobial activities also have to be tested when producing new compounds.
Sibjotang Protects against Cardiac Hypertrophy In Vitro and In Vivo
Authors: Son Chan-Ok , Hong Mi-Hyeon , Kim Hye-Yoom , Han Byung-Hyuk , Seo Chang-Seob , Lee Ho-Sub , Yoon Jung-Joo , Kang Dae-Gill
Published: December 2023

Cardiac hypertrophy is developed by various diseases such as myocardial infarction, valve diseases, hypertension, and aortic stenosis. Sibjotang (十棗湯, Shizaotang, SJT), a classic formula in Korean traditional medicine, has been shown to modulate the equilibrium of body fluids and blood pressure. This research study sought to explore the impact and underlying process of Sibjotang on cardiotoxicity induced by DOX in H9c2 cells. In vitro, H9c2 cells were induced by DOX (1 μM) in the presence or absence of SJT (1–5 μg/mL) and incubated for 24 h. In vivo, SJT was administrated to isoproterenol (ISO)-induced cardiac hypertrophy mice (n = 8) at 100 mg/kg/day concentrations. Immunofluorescence staining revealed that SJT mitigated the enlargement of H9c2 cells caused by DOX in a dose-dependent way. Using SJT as a pretreatment notably suppressed the rise in cardiac hypertrophic marker levels induced by DOX. SJT inhibited the DOX-induced ERK1/2 and p38 MAPK signaling pathways. In addition, SJT significantly decreased the expression of the hypertrophy-associated transcription factor GATA binding factor 4 (GATA 4) induced by DOX. SJT also decreased hypertrophy-associated calcineurin and NFAT protein levels. Pretreatment with SJT significantly attenuated DOX-induced apoptosis-associated proteins such as Bax, caspase-3, and caspase-9 without affecting cell viability. In addition, the results of the in vivo study indicated that SJT significantly reduced the left ventricle/body weight ratio level. Administration of SJT reduced the expression of hypertrophy markers, such as ANP and BNP. These results suggest that SJT attenuates cardiac hypertrophy and heart failure induced by DOX or ISO through the inhibition of the calcineurin/NFAT/GATA4 pathway. Therefore, SJT may be a potential treatment for the prevention and treatment of cardiac hypertrophy that leads to heart failure.
Hierarchical and Bidirectional Joint Multi-Task Classifiers for Natural Language Understanding
Authors: Ji Xiaoyu , Hu Wanyang , Liang Yanyan
Published: December 2023

The MASSIVE dataset is a spoken-language comprehension resource package for slot filling, intent classification, and virtual assistant evaluation tasks. It contains multi-language utterances from human beings communicating with a virtual assistant. In this paper, we exploited the relationship between intent classification and slot filling to improve the exact match accuracy by proposing five models with hierarchical and bidirectional architectures. There are two variants for hierarchical architectures and three variants for bidirectional architectures. These are the hierarchical concatenation model, the hierarchical attention-based model, the bidirectional max-pooling model, the bidirectional LSTM model, and the bidirectional attention-based model. The results of our models showed a significant improvement in the averaged exact match accuracy. The hierarchical attention-based model improved the accuracy by 1.01 points for the full training dataset. As for the zero-shot setup, we observed that the exact match accuracy increased from 53.43 to 53.91. In this study, we observed that, for multi-task problems, utilizing the relevance between different tasks can help in improving the model’s overall performance.
Asymptotic Properties for Cumulative Probability Models for Continuous Outcomes
Authors: Li Chun , Tian Yuqi , Zeng Donglin , Shepherd Bryan E.
Published: December 2023

Regression models for continuous outcomes frequently require a transformation of the outcome, which is often specified a priori or estimated from a parametric family. Cumulative probability models (CPMs) nonparametrically estimate the transformation by treating the continuous outcome as if it is ordered categorically. They thus represent a flexible analysis approach for continuous outcomes. However, it is difficult to establish asymptotic properties for CPMs due to the potentially unbounded range of the transformation. Here we show asymptotic properties for CPMs when applied to slightly modified data where bounds, one lower and one upper, are chosen and the outcomes outside the bounds are set as two ordinal categories. We prove the uniform consistency of the estimated regression coefficients and of the estimated transformation function between the bounds. We also describe their joint asymptotic distribution, and show that the estimated regression coefficients attain the semiparametric efficiency bound. We show with simulations that results from this approach and those from using the CPM on the original data are very similar when a small fraction of the data are modified. We reanalyze a dataset of HIV-positive patients with CPMs to illustrate and compare the approaches.
Optimal Shipping Route under the Designation of the Mediterranean Sulfur Emission Control Area: Mathematical Models and Applications
Authors: Wang Haoqing , Liu Yuan , Yang Ying , Yan Ran , Wang Shuaian
Published: December 2023

In order to tackle sulfur oxides (SOx) emissions from maritime activities, both local governmental bodies and the International Maritime Organization (IMO) have implemented a range of regulations with the establishment of sulfur emission control areas (SECAs) being one crucial measure. Recently, the IMO made the significant decision to designate the Mediterranean as an SECA, aiming to promote environmental conservation as well as sustainable development in the maritime industry and mitigate the adverse health effects caused by air pollutants emitted from ships in Mediterranean regions. While this policy signifies significant progress in the reduction of sulfur emissions, it simultaneously presents intricate challenges for maritime enterprises. Notably, under the Mediterranean SECA designation, shipping companies may opt to bypass this region and choose routes through the Cape of Good Hope as a means of minimizing the overall costs, resulting in a potential increase in global carbon emissions. To support shipping companies in formulating optimal strategies within the framework of this new policy, the research introduces advanced techniques to make the optimal decisions concerning route selection, sailing speeds, and the appropriate number of ships for both SECAs and non-SECAs. Furthermore, we elucidate how these optimal decisions can be dynamically adapted in response to the dynamic fluctuations in fuel prices and the weekly operational expenditures incurred by maritime fleets. In the experimental results, taking into account factors like route distance and fuel costs, shipping companies select routes through the Mediterranean region in both eastward and westward directions. The total cost amounts to $6,558,766.78, utilizing eight vessels. Regarding ship speeds, vessels sail at reduced speeds in SECAs compared to non-SECAs. Furthermore, longer voyage distances require deploying a greater number of ships to maintain a weekly service frequency. This research exhibits robust timeliness and practicality, which is in line with practice. It not only timely supplements and enhances the extant body of knowledge concerning SECAs but also serves as a valuable point of reference and emulation for shipping companies seeking to optimize their operations within the framework of the new policy landscape. Furthermore, it offers pertinent insights for the IMO in formulating policies related to SECAs.
A Multi-Point Geostatistical Modeling Method Based on 2D Training Image Partition Simulation
Authors: Zhao Yifei , Chen Jianhong , Yang Shan , He Kang , Shimada Hideki , Sasaoka Takashi
Published: December 2023

In this paper, a multi-point geostatistical (MPS) method based on variational function partition simulation is proposed to solve the key problem of MPS 3D modeling using 2D training images. The new method uses the FILTERSIM algorithm framework, and the variational function is used to construct simulation partitions and training image sequences, and only a small number of training images close to the unknown nodes are used in the partition simulation to participate in the MPS simulation. To enhance the reliability, a new covariance filter is also designed to capture the diverse features of the training patterns and allow the filter to downsize the training patterns from any direction; in addition, an information entropy method is used to reconstruct the whole 3D space by selecting the global optimal solution from several locally similar training patterns. The stability and applicability of the new method in complex geological modeling are demonstrated by analyzing the parameter sensitivity and algorithm performance. A geological model of a uranium deposit is simulated to test the pumping of five reserved drill holes, and the results show that the accuracy of the simulation results of the new method is improved by 11.36% compared with the traditional MPS method.
Pregnancy Outcomes in Patients with Urosepsis and Uncomplicated Urinary Tract Infections—A Retrospective Study
Authors: Radu Viorel-Dragos , Vicoveanu Petronela , Cărăuleanu Alexandru , Adam Ana-Maria , Melinte-Popescu Alina-Sinziana , Adam Gigi , Onofrei Pavel , Socolov Demetra , Vasilache Ingrid-Andrada , Harabor AnaMaria , Melinte-Popescu Marian , Scripcariu Ioana Sadiye , Mihalceanu Elena , Stuparu-Cretu Mariana , Harabor Valeriu
Published: December 2023

Background and Objectives: Urinary tract infections (UTIs) are an important cause of perinatal and maternal morbidity and mortality. The aim of this study was to describe and compare the main pregnancy outcomes among pregnant patients with complicated and uncomplicated UTIs; Materials and Methods: This retrospective study included 183 pregnant patients who were evaluated for uncomplicated UTIs and urosepsis in the Urology Department of ‘C.I. Parhon’ University Hospital, and who were followed up at a tertiary maternity hospital—‘Cuza-voda’ from Romania between January 2014 and October 2023. The control group (183 patients) was randomly selected from the patient’s cohort who gave birth in the same time frame at the maternity hospital without urinary pathology. Clinical and paraclinical data were examined. Descriptive statistics and a conditional logistic regression model were used to analyze our data. Results: Our results indicated that patients with urosepsis had increased risk of premature rupture of membranes (aOR: 5.59, 95%CI: 2.02–15.40, p < 0.001) and preterm birth (aOR: 2.47, 95%CI: 1.15–5.33, p = 0.02). We could not demonstrate a statistically significant association between intrauterine growth restriction and pre-eclampsia with the studied urological pathologies. Conclusions: Careful UTI screening during pregnancy is needed for preventing maternal–fetal complications.
Exploring Sleep in Caregivers of Children with Autism Spectrum Disorder (ASD) and the Relationship to Health-Related Quality of Life (HRQoL) and Family Quality of Life (FQoL)
Authors: Russell Maureen , Baldwin Carol M. , Quan Stuart F.
Published: December 2023

Background and Objectives: To investigate (1) the prevalence of sleep disorder symptoms in caregivers of children with autism spectrum disorder (ASD) and (2) the relationships between caregiver sleep problems and their health-related quality of life and family quality of life. Materials and Methods: Descriptive cross-sectional study of caregivers (N = 62) of children aged 6 to 11 years old diagnosed with ASD and receiving care at a regional autism research and resource center. Results: Participants completed the Sleep Habits Questionnaire (SHQ), the Medical Outcomes Study (MOS) SF-12, and the Beach Center Family Quality of Life Scale (FQoL). Caregivers with longer sleep duration reported better mental health and better family quality of life. Caregivers who reported insomnia symptoms, non-restorative sleep, and insufficient sleep were more likely to report poorer mental health than caregivers who did not report these sleep disorder symptoms. Caregivers with obstructive sleep apnea and restless legs syndrome experienced worse physical quality of life. Conclusions: The physical and mental health of the primary caregiver is essential to the support of the child with ASD and to the functioning of the family. The study findings point to the importance of future research and interventions to enhance sleep health in order to improve quality of life for caregivers of children with ASD.
CanStoc: A Hybrid Stochastic–GCM System for Monthly, Seasonal and Interannual Predictions
Authors: Lovejoy Shaun , Del Rio Amador Lenin
Published: December 2023

Beyond their deterministic predictability limits of ≈10 days and 6 months, the atmosphere and ocean become effectively stochastic. This has led to the development of stochastic models specifically for this macroweather regime. A particularly promising approach is based on the Fractional Energy Balance Equation (FEBE), an update of the classical Budyko–Sellers energy balance approach. The FEBE has scaling symmetries that imply long memories, and these are exploited in the Stochastic Seasonal and Interannual Prediction System (StocSIPS). Whereas classical long-range forecast systems are initial value problems based on spatial information, StocSIPS is a past value problem based on (long) series at each pixel. We show how to combine StocSIPS with a classical coupled GCM system (CanSIPS) into a hybrid system (CanStoc), the skill of which is better than either. We show that for one-month lead times, CanStoc’s skill is particularly enhanced over either CanSIPS or StocSIPS, whereas for 2–3-month lead times, CanSIPS provides little extra skill. As expected, the CanStoc skill is higher over ocean than over land with some seasonal dependence. From the classical point of view, CanStoc could be regarded as a post-processing technique. From the stochastic point of view, CanStoc could be regarded as a way of harnessing extra skill at the submonthly scales in which StocSIPS is not expected to apply.
Adenoviral Vector Codifying for TNF as a Co-Adjuvant Therapy against Multi-Drug-Resistant Tuberculosis
Authors: Hernández-Bazán Sujhey , Mata-Espinosa Dulce , Ramos-Espinosa Octavio , Lozano-Ordaz Vasti , Barrios-Payán Jorge , López-Casillas Fernando , Hernández-Pando Rogelio
Published: December 2023

Mycobacterium tuberculosis is the main causal agent of pulmonary tuberculosis (TB); the treatment of this disease is long and involves a mix of at least four different antibiotics that frequently lead to abandonment, favoring the surge of drug-resistant mycobacteria (MDR-TB), whose treatment becomes more aggressive, being longer and more toxic. Thus, the search for novel strategies for treatment that improves time or efficiency is of relevance. In this work, we used a murine model of pulmonary TB produced by the MDR-TB strain to test the efficiency of gene therapy with adenoviral vectors codifying TNF (AdTNF), a pro-inflammatory cytokine that has protective functions in TB by inducing apoptosis, granuloma formation and expression of other Th1-like cytokines. When compared to the control group that received an adenoviral vector that codifies for the green fluorescent protein (AdGFP), a single dose of AdTNF at the chronic active stage of the disease produced total survival, decreasing bacterial load and tissue damage (pneumonia), which correlated with an increase in cells expressing IFN-γ, iNOS and TNF in pneumonic areas and larger granulomas that efficiently contain and eliminate mycobacteria. Second-line antibiotic treatment against MDR-TB plus AdTNF gene therapy reduced bacterial load faster within a week of treatment compared to empty vector plus antibiotics or antibiotics alone, suggesting that AdTNF is a new potential type of treatment against MDR-TB that can shorten second-line chemotherapy but which requires further experimentation in other animal models (non-human primates) that develop a more similar disease to human pulmonary TB.
Predominance of Multidrug-Resistant Gram-Negative Bacteria Isolated from Supermarket Retail Seafood in Japan
Authors: Xedzro Christian , Shimamoto Toshi , Shimamoto Tadashi
Published: December 2023

Reports have documented antimicrobial usage in aquaculture, and the aquatic ecosystem can be considered a genetic storage site for antibiotic-resistant bacteria. This study assessed the prevalence of antimicrobial resistance (AMR) among Gram-negative bacteria recovered from retail seafood in Hiroshima, Japan. A total of 412 bacteria were isolated and screened for the presence of β-lactamases, acquired carbapenemases, and mobile colistin-resistance (mcr) genes. Forty-five (10.9%) isolates were dominated by Morganella (28%), Proteus (22%), Aeromonas (14%), Citrobacter (8%), and Escherichia (8%) and carried AMR genes. The identified AMR genes included those encoded in integrons (19), aac(6՛)-Ib (11), blaTEM-1 (7), blaCTX-M-like (12), blaCTX-M-65 (2), blaSHV-12 (1), blaSHV-27 (1), blaOXA-10 (1), blaOXA-2 (1), and mcr (2). The most common clinical resistances were against ampicillin, colistin, sulfamethoxazole/trimethoprim, tetracycline, and ciprofloxacin. Multidrug resistance (MDR) occurred in 27 (60%) AMR isolates, and multiple antibiotic resistance indices ranged from 0.2 to 0.8. A conjugation experiment showed that 10 of the 11 selected MDR strains harbored conjugable plasmids, although PCR-based replicon typing described seven strains as untypable. IncF replicon was identified in MDR extended-spectrum β-lactamase-producing Escherichia coli of the pathogenic B2 phylogroup. Our findings suggest that retail seafood harbors MDR bacteria of human interest that require strict resistance surveillance in the seafood production continuum.