bluuebunny/crossref_metadata_2025 huggingface dataset:
Urban Polycentricity and Architectural Heritage: A PROMETHEE-Based Multicriteria Approach
Authors: Sofianou Evina , Papathanasiou Jason , Aretoulis George
Published: August 2024

Polycentricity is a multiscalar concept referring to the interconnections of neighboring spatial areas in search of synergies. More specifically, urban polycentricity has lately gained increasing momentum in academic research and strategic planning as urban polycentric structures could stimulate urban and regional performance in a sustainable way. Architectural heritage, with its connotative meanings, is among the indicators of incorporation in polycentric networking. The present paper investigates the challenges of implementing urban polycentricity methodological approaches to highlight new polycentric networks based on built architectural heritage. In this study, appointed architectural assets are considered as nodes of the potential networks. As a new research strand, the MCDA PROMETHEE method is applied to compile and assemble all indicators (namely, rank size and node hierarchy, accessibility, transportation, and digital promotion). The ultimate research goal is to build a new polycentricity index as an innovative methodological tool to highlight polycentric networking synergies on interurban and intraregional scales. The region of Thrace in Northern Greece is chosen to apply the proposed methodology. Research on ways to couple polycentricity and PROMETHEE methods is limited, and thus, the proposed methodological approach is expected to contribute to the field of urban and regional strategies for researchers and practitioners.
Assessing the Settlement and Deformation of Pile-Supported Embankments Undergoing Groundwater-Level Fluctuations: An Experimental and Simulation Study
Authors: Ye Jiahuan , Wang Kangyu , Qiu Ziliang , Wang Xinquan
Published: August 2024

The intensification of extreme weather phenomena, ranging from torrential downpours to protracted dry spells, which trigger fluctuations at the groundwater level, poses a grave threat to the stability of embankments, giving rise to an array of concerns including cracking and differential settlement. Consequently, it is crucial to embark on research targeted at uncovering the settlement and deformation behaviors of pile-supported embankments amidst changes in water levels. In tackling this dilemma, a series of direct shear tests were carried out across a range of wet–dry cyclic conditions. The results confirmed that the occurrence of wet–dry cycles significantly impacted the resilience of silty clay. Additionally, it was observed that the erosion of cohesion and the angle of internal friction initially diminished sharply, subsequently leveling off, with the first wet–dry cycle exerting the most substantial influence on soil strength. Employing a holistic pile-supported embankment model, simulations revealed that variations in the groundwater level, fluctuations therein, varying descent rates, and periodic shifts in the groundwater level could all prompt alterations in soil settlement between embankment piles and could augment the peak tensile stress applied to geogrids. In summary, the orthogonal experimental method was utilized, indicating that, in terms of impacting embankment settlement under periodic water-level changes, the factors ranked in descending order were the following: pile spacing, pile length, embankment height, and the height of the groundwater table.
Renewable Energy Technology Selection for Hotel Buildings: A Systematic Approach Based on AHP and VIKOR Methods
Authors: Arıkan Kargı Vesile Sinem , Cesur Fatma
Published: August 2024

This study provides an assessment of renewable energy technology utilization in hotel buildings, which are significant structures in terms of energy consumption. The aim of the study is to determine suitable renewable energy technologies (RETs) for hotel buildings by defining criteria for evaluating RETs, assessing the relative importance of these criteria, and proposing a multi-criteria decision-making framework to solve the problem of selecting the most appropriate RETs during the design stage. The alternatives for RETs and the criteria for their evaluation are gathered through a literature review and expert consultations. Eight fundamental RETs used in hotel buildings (such as heat pumps, solar panels, biomass boilers, etc.) are examined, and nine selection criteria are analyzed. According to the weights determined by the Analytic Hierarchy Process (AHP) method, the initial investment cost is the most influential decision criterion, with a weight of 0.314. As a result of applying the AHP and VIKOR (Multi-Criteria Optimization and Compromise Solution) methods for technology selection, photovoltaic panels emerge as the top-ranked choice. This comprehensive evaluation provides stakeholders in the building production process of hotel buildings with detailed analyses and multi-criteria decision-making methods for selecting RETs.
A Real-Time Inverted Velocity Model for Fault Detection in Deep-Buried Hard Rock Tunnels Based on a Microseismic Monitoring System
Authors: Xie Houlin , Chen Bingrui , Liu Qian , Xiao Yaxun , Liu Liu , Zhu Xinhao , Li Pengxiang
Published: August 2024

Microseismic monitoring is an effective and widely used technology for dynamic fault disaster early warning and prevention in deep-buried hard rock tunnels. However, the insufficient understanding of the distribution of native faults poses a major challenge to yielding precise early warnings of disasters using an MS (Microseismic Monitoring System). Velocity field inversion is a reliable means to reflect fault information, and there is an urgent need to establish a real-time velocity field inversion method during tunnel excavation. In this paper, a method based on an MS is proposed to achieve the inversion of the velocity field in the monitoring area using microseismic event and excavation blasting data. The velocity field inversion method integrates the reflected wave ray-tracing method based on PSO (Particle Swarm Optimization) theory and FWI (Full-Waveform Inversion) theory. The accuracy of the proposed velocity inversion method was verified by various classic numerical simulation cases. In numerical simulations, the robustness of our method is evident in its ability to identify anomalous structural surfaces and velocity discontinuities ahead of the tunnel face.
Impact Resistance Performance and Damage Characteristics of Mortise-and-Tenon Joint Prefabricated Bridge Piers
Authors: Li Shukun , Mi Jiahe , Qi Xingjun , Jin Yudong , Guo Yupeng
Published: August 2024

The mortise-and-tenon joint prefabricated connection combines the assembly form of mortise-and-tenon joints and cast-in-place wet joints. It achieves reliable joint connections through small joint depths and lap-spliced reinforcement lengths. To study the impact resistance and damage characteristics of the assembled pier, a nonlinear finite element analysis was performed on the assembled and monolithic pier model piers to study the effects of mortise-and-tenon joint depths, lap reinforcement, and grout on the response of the piers to vehicle impact. The results showed that, after impact, the damage to the prefabricated pier was similar to that of the monolithic one. The failure mode involved opening of the seam at the impact face-pier bottom junction and localized concrete compression at the back-impact face pier bottom, and damage accumulated from the column base towards the column centerline. The mortise-and-tenon joint provided substantial horizontal constraint for the pier, imparting excellent resistance to lateral stiffness. Consequently, both piers showed nearly identical peak impact forces, yet the prefabricated pier exhibited a lesser degree of bending deformation compared to the monolithic one. The depth of the mortise-and-tenon joints was a critical factor affecting the impact response of the prefabricated bridge pier. When the depth reached 0.4D or more, it ensured good impact resistance and joint connection, enhancing energy absorption capability and reducing pier damage. The length of lap-spliced reinforcement significantly affected the overall integrity of prefabricated component connections. Lap lengths of 10d or more greatly reduced the probability of failure in the connection between pier columns and cap beams, lowering damage to the pier columns, joints, and pier cap beams, thus ensuring good impact resistance. The diameter of the lap-spliced reinforcement and the elastic modulus of the grouting material affected the local stiffness near the joints. Increasing the diameter of the lap-spliced reinforcement appropriately prevented excessive local damage, while altering the elastic modulus had minimal impact on improving pier damage.
Restorative Potential Assessment of Public Open Space in Old Urban Communities in the Context of Aging—A Case Study of Dabeizhuang Community in Maanshan, China
Authors: Huang Jiaxin , Song Yimin , Sheng Ying , Zhang Yuqing , Hu Di
Published: August 2024

Restorative environments have a positive impact on improving the physical and mental health of the elderly. In China, the proportion of elderly residents in aging urban communities is significantly higher than in newly constructed ones, making it essential to understand the restorative potential of public open spaces (POSs) in these settings to promote the development of aging-in-place models. To investigate this issue, we employed the Fuzzy Delphi Method (FDM) and the Analytic Hierarchy Process (AHP) to construct an evaluation system for the restorative potential of public open spaces. Subsequently, we assessed the restorative effects of POSs in the Dabeizhuang community using 320 residents’ questionnaires and the fuzzy comprehension evaluation method. The results indicate that the dimension of safety is the most critical factor in creating restorative environments. In contrast, the dimension of comfort is the primary reason affecting the current evaluation of the community’s restorative environment. By establishing a restorative environment evaluation system, this research will facilitate the creation of more restorative environments in urban areas, thereby promoting active and healthy aging among elderly residents.
Experimental Investigation on the Seismic Performance of Novel Prefabricated Composite RC Shear Walls with Concrete-Filled Steel Tube Frame
Authors: Dou Lijun , Huang Ziheng , Liu Yuxi , Wang Yuhao , Zhao Lei
Published: August 2024

The present study proposed novel prefabricated composite RC shear walls with a concrete-filled steel tube frame (CCRCSW-CFST) because of the superior seismic performance of shear walls incorporating CFSTs as boundary-restrained members. One cast-in-place reinforced concrete shear wall (RCSW) and seven CRCSW-CFSTs, each varying in axial compression ratios, concrete strengths, and shear span ratios, were designed for experimental analysis. Cyclic loading tests were performed on these specimens, yielding the following results: (1) Compared to reinforced concrete shear walls, CCRCSW-CFSTs demonstrated superior seismic performance, with 14.2% increased ductility and 47.5% greater energy dissipation capacity. (2) Elevating the axial compression ratio in CCRCSW-CFSTs resulted in increased yield strength, peak strength, and stiffness. Conversely, this adjustment also expedited the degradation of stiffness with displacement and decreased both ductility and ultimate deformation. (3) The peak displacement and ultimate displacement of CCRCSW-CFSTs were both increased with an increase in concrete strength. Increasing the axial compression ratio enhanced the initial stiffness of CCRCSW-CFSTs and mitigated the rate at which stiffness deteriorated with increasing displacement. (4) The stiffness, peak and ultimate displacements, peak and ultimate loads, and shear span ratio of CCRCSW-CFSTs were significantly reduced as the shear span ratio was increased. (5) The minor slip between the reinforced concrete panel of the precast slab and the encasing C-shaped steel contributed to an increase in early-stage energy dissipation of the CCRCSW-CFSTs.
Recent Treatment Strategies and Molecular Pathways in Resistance Mechanisms of Antiangiogenic Therapies in Glioblastoma
Authors: Rahman Md Ataur , Ali Meser M.
Published: August 2024

Malignant gliomas present great difficulties in treatment, with little change over the past 30 years in the median survival time of 15 months. Current treatment options include surgery, radiotherapy (RT), and chemotherapy. New therapies aimed at suppressing the formation of new vasculature (antiangiogenic treatments) or destroying formed tumor vasculature (vascular disrupting agents) show promise. This study summarizes the existing knowledge regarding the processes by which glioblastoma (GBM) tumors acquire resistance to antiangiogenic treatments. The discussion encompasses the activation of redundant proangiogenic pathways, heightened tumor cell invasion and metastasis, resistance induced by hypoxia, creation of vascular mimicry channels, and regulation of the tumor immune microenvironment. Subsequently, we explore potential strategies to overcome this resistance, such as combining antiangiogenic therapies with other treatment methods, personalizing treatments for each patient, focusing on new therapeutic targets, incorporating immunotherapy, and utilizing drug delivery systems based on nanoparticles. Additionally, we would like to discuss the limitations of existing methods and potential future directions to enhance the beneficial effects of antiangiogenic treatments for patients with GBM. Therefore, this review aims to enhance the research outcome for GBM and provide a more promising opportunity by thoroughly exploring the mechanisms of resistance and investigating novel therapeutic strategies.
A Deep Learning-Based Framework for Highly Accelerated Prostate MR Dispersion Imaging
Authors: Zhao Kai , Pang Kaifeng , Hung Alex LingYu , Zheng Haoxin , Yan Ran , Sung Kyunghyun
Published: August 2024

Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) measures microvascular perfusion by capturing the temporal changes of an MRI contrast agent in a target tissue, and it provides valuable information for the diagnosis and prognosis of a wide range of tumors. Quantitative DCE-MRI analysis commonly relies on the nonlinear least square (NLLS) fitting of a pharmacokinetic (PK) model to concentration curves. However, the voxel-wise application of such nonlinear curve fitting is highly time-consuming. The arterial input function (AIF) needs to be utilized in quantitative DCE-MRI analysis. and in practice, a population-based arterial AIF is often used in PK modeling. The contribution of intravascular dispersion to the measured signal enhancement is assumed to be negligible. The MR dispersion imaging (MRDI) model was recently proposed to account for intravascular dispersion, enabling more accurate PK modeling. However, the complexity of the MRDI hinders its practical usability and makes quantitative PK modeling even more time-consuming. In this paper, we propose fast MR dispersion imaging (fMRDI) to effectively represent the intravascular dispersion and highly accelerated PK parameter estimation. We also propose a deep learning-based, two-stage framework to accelerate PK parameter estimation. We used a deep neural network (NN) to estimate PK parameters directly from enhancement curves. The estimation from NN was further refined using several steps of NLLS, which is significantly faster than performing NLLS from random initializations. A data synthesis module is proposed to generate synthetic training data for the NN. Two data-processing modules were introduced to improve the model’s stability against noise and variations. Experiments on our in-house clinical prostate MRI dataset demonstrated that our method significantly reduces the processing time, produces a better distinction between normal and clinically significant prostate cancer (csPCa) lesions, and is more robust against noise than conventional DCE-MRI analysis methods.
Catalysts for Sustainable Hydrogen Production: Preparation, Applications and Process Integration, 2nd Edition
Authors: Ruocco Concetta , Martino Marco
Published: August 2024

The effects of climate change are now evident all over the world [...]
Comparative Study on Ethanol-Based Oxygenate Synthesis via Syngas over Monometallic Rh Catalysts Supported on Different Zr-MOFs
Authors: Yu Ruiqi , Duan Xiangjiang , Yu Xuanwang , Zheng Xiang , Mao Haifang , Yu Jun
Published: August 2024

Three types of Zr-based metal–organic frameworks (Zr-MOFs) were employed as supports to prepare monometallic Rh catalysts by the impregnation method. The effects of the structural properties of Zr-MOFs on their supported monometallic Rh catalysts for syngas conversion were investigated. The results showed that, compared to catalysts with Rh@MOF-808 and Rh@UiO-66, Rh@UiO-67 had higher CO conversion and C2+ oxygenate selectivity. The state of the Rh site is affected by the different structure of the Zr-MOFs, which is responsible for the difference in catalytic performance. The relatively higher Rh dispersion on the UiO-67 support boosted its CO adsorption ability, and Rh@UiO-67 having the best C2+ oxygenate selectivity was mainly attributed to it having the highest Rh+/Rh0 ratio.
Metformin Alleviates Inflammation and Induces Mitophagy in Human Retinal Pigment Epithelium Cells Suffering from Mitochondrial Damage
Authors: Toppila Maija , Ranta-aho Sofia , Kaarniranta Kai , Hytti Maria , Kauppinen Anu
Published: August 2024

Mitochondrial malfunction, excessive production of reactive oxygen species (ROS), deficient autophagy/mitophagy, and chronic inflammation are hallmarks of age-related macular degeneration (AMD). Metformin has been shown to activate mitophagy, alleviate inflammation, and lower the odds of developing AMD. Here, we explored the ability of metformin to activate mitophagy and alleviate inflammation in retinal pigment epithelium (RPE) cells. Human ARPE-19 cells were pre-treated with metformin for 1 h prior to exposure to antimycin A (10 µM), which induced mitochondrial damage. Cell viability, ROS production, and inflammatory cytokine production were measured, while autophagy/mitophagy proteins were studied using Western blotting and immunocytochemistry. Metformin pre-treatment reduced the levels of proinflammatory cytokines IL-6 and IL-8 to 42% and 65% compared to ARPE-19 cells exposed to antimycin A alone. Metformin reduced the accumulation of the autophagy substrate SQSTM1/p62 (43.9%) and the levels of LC3 I and II (51.6% and 48.6%, respectively) after antimycin A exposure. Metformin also increased the colocalization of LC3 with TOM20 1.5-fold, suggesting active mitophagy. Antimycin A exposure increased the production of mitochondrial ROS (226%), which was reduced by the metformin pre-treatment (84.5%). Collectively, metformin showed anti-inflammatory and antioxidative potential with mitophagy induction in human RPE cells suffering from mitochondrial damage.
Exploring the Role of the Gut Microbiota in Modulating Colorectal Cancer Immunity
Authors: Shakhpazyan Nikolay K. , Mikhaleva Liudmila M. , Bedzhanyan Arkady L. , Gioeva Zarina V. , Mikhalev Alexander I. , Midiber Konstantin Y. , Pechnikova Valentina V. , Biryukov Andrey E.
Published: August 2024

The gut microbiota plays an essential role in maintaining immune homeostasis and influencing the immune landscape within the tumor microenvironment. This review aims to elucidate the interactions between gut microbiota and tumor immune dynamics, with a focus on colorectal cancer (CRC). The review spans foundational concepts of immuno-microbial interplay, factors influencing microbiome composition, and evidence linking gut microbiota to cancer immunotherapy outcomes. Gut microbiota modulates anti-cancer immunity through several mechanisms, including enhancement of immune surveillance and modulation of inflammatory responses. Specific microbial species and their metabolic byproducts can significantly influence the efficacy of cancer immunotherapies. Furthermore, microbial diversity within the gut microbiota correlates with clinical outcomes in CRC, suggesting potential as a valuable biomarker for predicting response to immunotherapy. Conclusions: Understanding the relationship between gut microbiota and tumor immune responses offers potential for novel therapeutic strategies and biomarker development. The gut microbiota not only influences the natural history and treatment response of CRC but also serves as a critical modulator of immune homeostasis and anti-cancer activity. Further exploration into the microbiome’s role could enhance the effectiveness of existing treatments and guide the development of new therapeutic modalities.
Helicobacter pylori HP0018 Has a Potential Role in the Maintenance of the Cell Envelope
Authors: Rosinke Kyle , Starai Vincent J. , Hoover Timothy R.
Published: August 2024

Helicobacter pylori is a bacterial pathogen that colonizes the human stomach, where it can cause a variety of diseases. H. pylori uses a cluster of sheathed flagella for motility, which is required for host colonization in animal models. The flagellar sheath is continuous with the outer membrane and is found in most Helicobacter species identified to date. HP0018 is a predicted lipoprotein of unknown function that is conserved in Helicobacter species that have flagellar sheaths but is absent in Helicobacter species that have sheath-less flagella. Deletion of hp0018 in H. pylori B128 resulted in the formation of long chains of outer membrane vesicles, which were most evident in an aflagellated variant of the Δhp0018 mutant that had a frameshift mutation in fliP. Flagellated cells of the Δhp0018 mutant possessed what appeared to be a normal flagellar sheath, suggesting that HP0018 is not required for sheath formation. Cells of the Δhp0018 mutant were also less helical in shape compared to wild-type cells. A HP0018-superfolder green fluorescent fusion protein expressed in the H. pylori Δhp0018 mutant formed fluorescent foci at the cell poles and lateral sites. Co-immunoprecipitation assays with HP0018 identified two enzymes involved in the modification of the cell wall peptidoglycan, AmiA and MltD, as potential HP0018 interaction partners. HP0018 may modulate the activity of AmiA or MltD, and in the absence of HP0018, the unregulated activity of these enzymes may alter the peptidoglycan layer in a manner that results in an altered cell shape and hypervesiculation.
Ruthenium-p-Cymene Complexes Incorporating Substituted Pyridine–Quinoline Ligands with –Br (Br-Qpy) and –Phenoxy (OH-Ph-Qpy) Groups for Cytotoxicity and Catalytic Transfer Hydrogenation Studies: Synthesis and Characterization
Authors: Dritsopoulos Alexandros , Zacharopoulos Nikolaos , Peyret Aigli-Eleonora , Karampella Eftychia , Tsoureas Nikolaos , Cheilari Antigoni , Machalia Christina , Emmanouilidou Evangelia , Andreopoulou Aikaterini K. , Kallitsis Joannis K. , Philippopoulos Athanassios I.
Published: August 2024

Organometallic ruthenium complexes with p-cymene = 1-methyl-4-(1-methylethyl)-benzene and N^N = bidentate polypyridyl ligands constitute interesting candidates with biological and catalytic properties. Towards this aim, we have synthesized four ruthenium(II)–arene complexes of the type [Ru(η6-p-cymene)(N^N)Cl][X] (N^N = Br-Qpy = 6-bromo-4-phenyl-2-pyridin-2-yl-quinoline, X = Cl− (1a); PF6− (1b); N^N = OH-Ph-Qpy = 4-(4-phenyl-2-(pyridin-2-yl)quinolin-6-yl)phenol, X = Cl− (2a); PF6− (2b)). This is the first report of ruthenium(II) p-cymene complexes incorporating substituted pyridine–quinoline ligands, with –Br and –C6H4OH groups in the 6-position of quinoline. We also refer to the cytotoxicity of the ligands and their possible effect of modulating the activity of the ruthenium(II) complexes. These were characterized by a combination of spectroscopic methods (ATR-IR, UV–Vis, multinuclear NMR), elemental analysis, and conductivity measurements. The solid-state structure of 2b, determined by single-crystal X-ray diffraction, reveals a three-legged piano-stool geometry. The in vitro cytotoxic activities of the new complexes were evaluated in HEK293T (human embryonic kidney cells) and in HeLa cells (cervical cancer cells), via the MTT assay. Poor in vitro anticancer activities were observed for the HeLa cancer cell line, with 2a being the most potent (IC50 = 75 μΜ). The cytotoxicity of Br-Qpy in HEK293T is comparable to that of cisplatin. Both complexes 1a and 1b successfully catalyze the transfer hydrogenation of benzophenone to benzhydrol by 2-propanol at 82 °C. The catalytic performance of 1a in the ratio of S:Cat:B = 400:1:40 (S = substrate, Cat = catalyst, B = base = KOiPr) leads to a conversion of 94%, within 3 h of reaction. Presumably, catalytic transformation takes place via ruthenium(II) hydride species being the active catalyst.
Are Adolescent Athletes Sleeping Enough? An Observational Study of Sleep Parameters during Schooldays and Holidays
Authors: Souabni Mehdi J. , Souabni Maher , Hammouda Omar , Driss Tarak
Published: August 2024

Background: Inconsistent sleep schedules, frequent awakening after sleep onset (WASO), and decreased sleep efficiency (SE) are common issues among adolescent team sports athletes. Moreover, research indicates that sleep problems are enhanced across schooldays. The aim of the present study was to assess sleep patterns of adolescent athletes and compare sleep parameters between schooldays and holidays. Methods: The chronotype and sleep quality of twelve adolescent basketball players (mean age: 15.58 ± 0.67 years) were assessed. Objective sleep parameters were then analyzed using actigraphy over a 12-day period, which included six days during the school period and six days during holidays. Results: Data showed that total sleep time (TST), SE, and WASO (382.48 min, 81.81%, and 66.70 min, respectively) did not meet international recommendations for sleep quantity and quality. During school weekdays, time in bed (TIB), TST, and SE significantly decreased compared to weekends (p < 0.001, d = −1.49; p < 0.001, d = −1.64; and p = 0.01, d = −0.89, respectively). On weekdays, TIB, TST, and WASO were significantly lower on schooldays compared to holidays (p < 0.001, d = −1.83; p < 0.01, d = −1.01; and p = 0.02, d = −0.77, respectively). While no significant difference was observed in social jetlag, the mid-point of sleep was significantly later on holiday weekdays compared to school weekdays (p < 0.05, d = 0.65). Conclusions: Adolescent athletes experience insufficient sleep, especially on school weekdays, which is partially improved during weekends and holidays. Although sleep duration was longer during holidays, our results suggest that adolescent athletes’ sleep was more fragmented. Consequently, it remains crucial to implement strategies to enhance their sleep health (e.g., napping).
The Role of Extracellular Vesicles in Bone Regeneration and Associated Bone Diseases
Authors: Wan Xinyue , Zhang Wenjie , Dai Lingyan , Chen Liang
Published: August 2024

Extracellular vesicles (EVs) are nanoscale particles with a lipid bilayer membrane structure secreted by various cell types. Nearly all human cells secrete EVs, primarily mediating intercellular communication. In recent years, scientists have discovered that EVs can carry multiple biological cargos, such as DNA, non-coding RNAs (ncRNAs), proteins, cytokines, and lipids, and mediate intercellular signal transduction. Bone is a connective tissue with a nerve supply and high vascularization. The repair process after injury is highly complex, involving interactions among multiple cell types and biological signaling pathways. Bone regeneration consists of a series of coordinated osteoconductive and osteoinductive biological processes. As mediators of intercellular communication, EVs can promote bone regeneration by regulating osteoblast-mediated bone formation, osteoclast-mediated bone resorption, and other pathways. This review summarizes the biogenesis of EVs and the mechanisms by which EV-mediated intercellular communication promotes bone regeneration. Additionally, we focus on the research progress of EVs in various diseases related to bone regeneration. Finally, based on the above research, we explore the clinical applications of engineered EVs in the diagnosis and treatment of bone regeneration-related diseases.
Role of Nutrients Regulating Myeloid Derived Suppressor Cells in Cancer: A Scoping Review
Authors: Pérez-Peláez Beatriz , Jiménez-Cortegana Carlos , de la Cruz-Merino Luis , Sánchez-Margalet Víctor
Published: August 2024

Myeloid-derived suppressor cells (MDSCs) are immature cells with an immunosuppressive function. MDSCs have been related to inflammation in many settings, including infections, transplantation, obesity, aging, or cancer. In oncological settings, MDSCs participate in tumor immunoescape, growth, and metastasis. Certain nutrients can modify chronic inflammation by their interaction with MDSCs. Therefore, the possible influence of certain nutrients on immune surveillance by their actions on MDSCs and how this may affect the prognosis of cancer patients were evaluated in this scoping review. We identified seven papers, six of which were murine model studies and only one was a human clinical trial. Globally, a significant reduction in cancer growth and progression was observed after achieving a reduction in both MDSCs and their immunosuppressive ability with nutrients such as selected vegetables, icaritin, retinoic acid, curdlan, active vitamin D, soy isoflavones, and green tea. In conclusion, the consumption of certain nutrients may have effects on MDSCs, with beneficial results not only in the prevention of tumor development and growth but also in improving patients’ response.
Molecular Analysis of High-Grade Serous Ovarian Carcinoma Exhibiting Low-Grade Serous Carcinoma and Serous Borderline Tumor
Authors: Kanno Kosuke , Nakayama Kentaro , Razia Sultana , Islam Sohel Hasibul , Farzana Zahan Umme , Sonia Shahataj Begum , Sasamori Hiroki , Yamashita Hitomi , Ishibashi Tomoka , Ishikawa Masako , Imamura Kayo , Ishikawa Noriyoshi , Kyo Satoru
Published: August 2024

Ovarian cancer is classified as type 1 or 2, representing low- and high-grade serous carcinoma (LGSC and HGSC), respectively. LGSC arises from serous borderline tumor (SBT) in a stepwise manner, while HGSC develops from serous tubal intraepithelial carcinoma (STIC). Rarely, HGSC develops from SBT and LGSC. Herein, we describe the case of a patient with HGSC who presented with SBT and LGSC, and in whom we analyzed the molecular mechanisms of carcinogenesis. We performed primary debulking surgery, resulting in a suboptimal simple total hysterectomy and bilateral salpingo-oophorectomy due to strong adhesions. The diagnosis was stage IIIC HGSC, pT3bcN0cM0, but the tumor contained SBT and LGSC lesions. After surgery, TC (Paclitaxel + Carbopratin) + bevacizumab therapy was administered as adjuvant chemotherapy followed by bevacizumab as maintenance therapy. The tumor was chemo-resistant and caused ileus, and bevacizumab therapy was conducted only twice. Next-Generation Sequencing revealed KRAS (p.G12V) and NF2 (p.W184*) mutations in all lesions. Interestingly, the TP53 mutation was not detected in every lesion, and immunohistochemistry showed those lesions with wild-type p53. MDM2 was amplified in the HGSC lesions. DNA methylation analysis did not show differentially methylated regions. This case suggests that SBT and LGSC may transform into HGSC via p53 dysfunction due to MDM2 amplification.
Promising Support Coming from Nature: Antioxidant and Anti-Inflammatory Potential of Castanea sativa Wood Distillate on Skin Cells
Authors: Filippelli Arianna , Ciccone Valerio , Loppi Stefano , Morbidelli Lucia
Published: August 2024

Tissue homeostasis, function recovery, and protection mechanisms are boosted by the balanced and timely control of inflammation and oxidative stress. Nowadays, many natural products and bio-derivates exhibit antioxidant and anti-inflammatory activity, supporting medical care and tissue wellness against inflammation, oxidative stress, and inflammaging. Castanea sativa wood distillate (WD) is a bio-derivative used as a corroborant and biofertilizer in agriculture. Based on the safety profile of low concentrations of WD on human cells, the present study aims to assess the anti-inflammatory and antioxidant activity of WD on different cell types in the integumentary system. Human keratinocytes, mucosal epithelium, dermal fibroblasts, and endothelial cells were exposed to WD, and the concentrations devoid of pro-apoptotic potential were profiled. Then, the effect of nontoxic doses of WD revealed an anti-inflammatory effect, observed through the immunodetection of prostanoid cascade markers in experimentally induced inflammation. A reduction in endothelial hyperpermeability was evidenced by the immunofluorescence analysis of cell–cell adhesion proteins, VE-cadherin and ZO-1. In addition, WD buffered the exogenously produced oxidative stress. On the whole, WD showed both anti-inflammatory and antioxidant activities on the various cell types, preserving endothelial barrier integrity. Overall, this study supports the involvement of this bio-derivative in novel exploitable fields, such as therapeutic dermatological applications for human and animal medical care.
A Theoretical Study of the Interaction of PARP-1 with Natural and Synthetic Inhibitors: Advances in the Therapy of Triple-Negative Breast Cancer
Authors: Turpo-Peqqueña Albert Gabriel , Leiva-Flores Emily Katherine , Luna-Prado Sebastián , Gómez Badhin
Published: August 2024

In the current study, we have investigated the secondary metabolites present in ethnomedical plants used for medicinal purposes—Astilbe chinensis (EK1), Scutellaria barbata D. Don (EK2), Uncaria rhynchophylla (EK3), Fallugia paradoxa (EK4), and Curcuma zedoaria (Christm.) Thread (EK5)—and we have compared them with five compounds of synthetic origin for the inhibition of PARP-1, which is linked to abnormal DNA replication, generating carcinogenic cells. We have studied these interactions through molecular dynamics simulations of each interacting system under physiological conditions (pH, temperature, and pressure) and determined that the compounds of natural origin have a capacity to inhibit PARP-1 (Poly(ADP-ribose) Polymerase 1) in all the cases inspected in this investigation. However, it is essential to mention that their interaction energy is relatively lower compared to that of compounds of synthetic origin. Given that binding energy is mandatory for the generation of a scale or classification of which is the best interacting agent, we can say that we assume that compounds of natural origin, having a complexation affinity with PARP-1, induce cell apoptosis, a potential route for the prevention of the proliferation of carcinogenic cells.
Artificial Neural Networks for Drought Forecasting in the Central Region of the State of Zacatecas, Mexico
Authors: Esquivel-Saenz Pedro Jose , Ortiz-Gómez Ruperto , Zavala Manuel , Flowers-Cano Roberto S.
Published: August 2024

Drought is, among natural hazards, one of the most harmful to humanity. The forecasting of droughts is essential to reduce their impact on the economy, agriculture, tourism and water resource systems. In this study, drought forecast in the central region of the state of Zacatecas, a semi-arid region of Mexico, is explored by means of artificial neural networks (ANNs), forecasting numerical values of three drought indices—the standardized precipitation index (SPI), the standardized precipitation and evapotranspiration index (SPEI) and the reconnaissance drought index (RDI)—in an effort to establish the most suitable index for drought forecasting with ANNs in semi-arid regions. Records of 52 years of monthly precipitation and temperature were used. The indices were calculated in three different time scales: 3, 6 and 12 months. The analyzed models showed great capacity to forecast the values of the three drought indices, and it was found that for the trial set, the RDI was the drought index that was best fitted by the models, with the evaluation metrics R2 (determination coefficient), RMSE (root mean square error), MAE (mean absolute error) and MBE (Mean Bias Error) showing ranges of 0.834–0.988, 0.099–0.402, 0.072–0.343 and 0.017–0.095, respectively. For the validation set, the evaluation metrics were slightly better.
Individuals with Tinnitus Report More Positive Experiences following Internet-Based Cognitive Behavioral Therapy
Authors: Manchaiah Vinaya , Beukes Eldré W. , Andersson Gerhard , Bateman Emily , Swanepoel De Wet , Uhler Kristin , Vinay
Published: August 2024

Background: This study aimed to examine whether individuals with chronic tinnitus report more positive experiences following internet-based cognitive behavioral therapy (CBT). Methods: A mixed-methods design was used, nested in clinical trials evaluating internet interventions for tinnitus. Participants (n = 164) completed online questionnaires (both structured and open-ended) providing demographic information as well as health variables (e.g., tinnitus distress, anxiety, depression, insomnia). An open-ended question listing positive effects or outcomes related to having tinnitus was also included. Responses to the open-ended questions were analyzed using qualitative content analysis. Results: Of the 164 eligible participants, 32.3% (n = 53) provided at least 1 positive experience both at pre- and post-intervention, with 9.1% (n = 19) providing positive experiences only at pre-intervention, 49 (29.9%) providing positive experiences only at post-intervention, and 28.7% (n = 47) of the participants did not provide any positive experiences on either measurement occasion. Significantly more positive experiences were reported following the intervention in the overall sample (p < 0.0001, paired sample t-test). In addition, participants who reported positive experiences in both pre- and post-intervention also reported more positive experiences following intervention (p = 0.008, paired sample t-test). Conclusions: Internet-based CBT can help individuals with tinnitus to think more positively by changing unhelpful thought patterns. Open-ended questions can supplement structured questionnaires to measure treatment outcomes.
Assessment of the Validity and Quality of Polycystic Ovarian Syndrome (PCOS) Screening Tools Available for Women Globally: A Systematic Review
Authors: Sacca Lea , Lobaina Diana , Knopf Elisheva , Burgoa Sara , Jimenez Samantha , Okwaraji Goodness , Etzel Madison , Vardanyan Vartiter , Tharp Madison , Rao Meera , Jhumkhawala Vama , Sohmer Joshua , Densley Sebastian , Linzer Niko , Meka Pranav , Diaz Daniella , Knecht Michelle , Hopkins Dawn Kimberly , Kitsantas Panagiota , Mejia Maria , Wilson Candy
Published: August 2024

Background: This systematic review has the following aims: (1) to identify measurement tools used globally by healthcare providers to diagnose PCOS in women at elevated risk; (2) to assess the comprehensiveness of these tools regarding mental health and chronic pain; (3) to list strategies for validating, disseminating, and implementing these tools; and (4) to provide future recommendations for experts in healthcare settings. Methods: This review utilized the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) and the Arksey and O’Malley York methodology. Studies were sourced from the PubMed, Embase, and Cochrane Library databases, with inclusion criteria focusing on peer-reviewed articles addressing PCOS diagnosis and associated comorbidities. Data extraction and analysis followed the Joanna Briggs Institute (JBI) recommendations. Results: A total of 63 studies met the inclusion criteria. Findings indicate that current screening tools for PCOS often lack comprehensive integration of mental health and chronic pain assessments. Tools like the PCOSQ and its updated version, PCOSQ-50, inadequately address pain-related symptoms, highlighting a gap in holistic patient evaluation. This review identified significant associations between PCOS and mental health disorders, including anxiety and depression, emphasizing the need for mental health screenings as part of PCOS management. Conclusions: There is a critical need for validated PCOS screening tools that encompass both physical and psychological aspects of the condition. Educating healthcare providers on the cultural and social determinants influencing PCOS can improve diagnosis and patient outcomes. Future research should focus on developing holistic screening tools and culturally relevant educational resources, aiming to enhance the overall quality of life for women with PCOS.
Assessing the Role of Adalimumab in Treating Hidradenitis Suppurativa: Findings from a Retrospective Study at a Reference Center
Authors: Šakaitytė Austėja , Česnavičiūtė Inga , Raudonis Tadas
Published: August 2024

Background: Hidradenitis suppurativa (HS) is a chronic inflammatory skin condition characterized by inflammatory lesions, often leading to scarring. Managing HS can be difficult, requiring biological therapy, specifically adalimumab. Methods: A retrospective study was conducted on patients diagnosed with HS and treated with the TNF-α inhibitor adalimumab. Data from 21 patients were included in this study. International Hidradenitis Suppurativa Severity Score System (IHS4); Dermatology Life Quality Index (DLQI); pain intensity according to the Visual Analogue Scale (VAS); and number of nodules, abscesses, and fistulas were assessed. Results: Notably, 47.62% of patients achieved Hidradenitis Suppurativa Clinical Response. The mean number of inflamed nodules decreased from 5.62 ± 4.12 to 3 ± 3.46, abscesses decreased from 1.76 ± 2.63 to 0.81 ± 1.4, and fistulas decreased from 2.62 ± 1.86 to 2 ± 1.9 (p < 0.05). The IHS4 score decreased from 19 ± 10.78 to 12.62 ± 11.13 (p = 0.001), DLQI from 15.76 ± 7.73 to 7.43 ± 7.76 (p < 0.001), and VAS from 6.69 ± 1.56 to 3.64 ± 2.65 (p < 0.001). There was a significant difference in the baseline IHS4 scores between patients who had prior surgery with a mean score of 23.86 ± 9.4 versus non-surgical patients with a mean IHS4 score of 9.29 ± 5.53 (p = 0.001). Conclusions: About half of HS patients responded positively to adalimumab treatment; the use of the drug reduces inflammatory lesions, and pain, and improves quality of life.
State Contexts for a Public Health Emergency: The Divergence of Politics and Administration in COVID-19 Vaccination Rates
Authors: Janousek Christian L. , Noh Shihyun
Published: August 2024

Amid the array of challenges prompted by the COVID-19 pandemic, the policy response of governments proved vital. Different states in the U.S. pursued varied policy approaches that demonstrated distinct divergences in impact. Particularly, contrasting state contexts produced markedly assorted frameworks for the delivery of public health services, which indicate potential effects for COVID-19 policy implementation. Using the rates of COVID-19 vaccination as a measure of policy execution, the purpose of this study is to examine the political and administrative influences contributing to differences in COVID-19 public health policy outcomes among the states in the U.S. Ordinary least squares (OLS) regression models included data sources of nationally representative information pertaining to state public health attributes of politics and administration during the height of the pandemic and vaccine campaign. The findings suggest that state political leadership and fiscal capacity display significant associations with COVID-19 vaccination disparities, while other administrative indicators did not. The results signal important policy implications for the politics–administration dynamic within the COVID-19 pandemic and offer further understanding toward the roles of federalism and governance in future public health emergencies.
The Role of Intestinal Epithelial Permeability in Multisystem Inflammatory Syndrome in Children: A Case–Control Study
Authors: Roarty Cathal , Mills Clare , Tonry Claire , Groves Helen E. , Watson Chris , Waterfield Thomas
Published: August 2024

Background: Multisystem inflammatory syndrome in children (MIS-C) occurs after SARS-CoV-2 infection, with gastrointestinal symptoms a prominent feature. This syndrome has been proposed to be triggered by persistent SARS-CoV-2 antigenemia due to increased intestinal epithelial permeability. We obtained evidence for this in this study. Methods: In a single-centre study, we recruited 83 children and analysed blood samples to quantify the circulating markers of increased intestinal permeability following SARS-CoV-2 infection. Publicly available proteomics MIS-C datasets were also accessed to assess the evidence for increased intestinal permeability. We further quantified SARS-CoV-2 antigenemia and the humoral response to SARS-CoV-2 spike protein. Results: Following SARS-CoV-2 infection, healthy children demonstrated no dysregulation of the intestinal epithelial barrier. In MIS-C, considerable increases in markers of epithelial dysfunction were observed, with similar increases noted in febrile controls. Furthermore, we found little evidence of persistent SARS-CoV-2 antigenemia in MIS-C. Conclusions: Our results suggest that although increased intestinal epithelial permeability is a feature of MIS-C, it is not unique to the condition, and persistent SARS-CoV-2 antigenemia does not occur.
Challenges and Opportunities in Developing an Oncology Clinical Trial Network in the United States Veterans Affairs Health Care System: The VA STARPORT Experience
Authors: Solanki Abhishek A. , Zheng Kevin , Skipworth Alicia N. , Robin Lisa M. , Leparski Ryan F. , Henry Elizabeth , Rettig Matthew , Salama Joseph K. , Ritter Timothy , Jones Jeffrey , Quek Marcus , Chang Michael , Block Alec M. , Welsh James S. , Kumar Aryavarta , Chao Hann-Hsiang , Chen Albert C. , Shapiro Ronald , Bitting Rhonda L. , Kwon Robert , Stross William , Puckett Lindsay , Wong Yu-Ning , Nickols Nicholas G. , Carlson Kimberly
Published: August 2024

The United States Veterans Affairs (VA) Health Care System has a strong history of conducting impactful oncology randomized clinical trials (RCTs). We developed a phase II/III RCT to test the use of metastasis-directed therapy in Veterans with oligometastatic prostate cancer (OMPC)—the first VA RCT in OMPC that leverages novel imaging and advanced radiotherapy techniques. To accomplish this, we developed a clinical trial network to conduct the study. In this manuscript, we describe several challenges we encountered in study development/conduct and our strategies to address them, with the goal of helping investigators establish robust study networks to conduct clinical trials. In the study start-up, we encountered challenges in timely site activation, and leveraged project management to maximize efficiency. Additionally, there were several changes in the clinical paradigms in imaging and treatment that led to protocol amendments to ensure maximum equipoise, recruitment, and impact of the study. Specifically, we amended the trial to add de novo OMPC patients (from initially only recurrent OMPC) and expanded the study to allow up to 10 metastases (from initially five). Finally, in order to maintain local study team engagement, we developed initiatives to maximize collaboration and add value to the overall clinical program through study participation.