bluuebunny/crossref_metadata_2025 huggingface dataset:
The REthinking Clinical Trials Program Retreat 2023: Creating Partnerships to Optimize Quality Cancer Care
Authors: Beltran-Bless Ana-Alicia , Clemons Mark , Vandermeer Lisa , El Emam Khaled , Ng Terry L. , McGee Sharon , Awan Arif Ali , Pond Gregory , Renaud Julie , Barton Gwen , Hutton Brian , Savard Marie-France
Published: March 2024

Patients, families, healthcare providers and funders face multiple comparable treatment options without knowing which provides the best quality of care. As a step towards improving this, the REthinking Clinical Trials (REaCT) pragmatic trials program started in 2014 to break down many of the traditional barriers to performing clinical trials. However, until other innovative methodologies become widely used, the impact of this program will remain limited. These innovations include the incorporation of near equivalence analyses and the incorporation of artificial intelligence (AI) into clinical trial design. Near equivalence analyses allow for the comparison of different treatments (drug and non-drug) using quality of life, toxicity, cost-effectiveness, and pharmacokinetic/pharmacodynamic data. AI offers unique opportunities to maximize the information gleaned from clinical trials, reduces sample size estimates, and can potentially “rescue” poorly accruing trials. On 2 May 2023, the first REaCT international symposium took place to connect clinicians and scientists, set goals and identify future avenues for investigator-led clinical trials. Here, we summarize the topics presented at this meeting to promote sharing and support other similarly motivated groups to learn and share their experiences.
Outpatient Embedded Palliative Care for Patients with Advanced Thoracic Malignancy: A Retrospective Cohort Study
Authors: Boulanger Mary C. , Krasne Margaret D. , Gough Ethan K. , Myers Samantha , Browner Ilene S. , Feliciano Josephine L.
Published: March 2024

Although cancer care is often contextualized in terms of survival, there are other important cancer care outcomes, such as quality of life and cost of care. The ASCO Value Framework assesses the value of cancer therapies not only in terms of survival but also with consideration of quality of life and financial cost. Early palliative care for patients with advanced cancer is associated with improved quality of life, mood, symptoms, and overall survival for patients, as well as cost savings. While palliative care has been shown to have numerous benefits, the impact of real-world implementation of outpatient embedded palliative care on value-based metrics is not fully understood. We sought to describe the association between outpatient embedded palliative care in a multidisciplinary thoracic oncology clinic and inpatient value-based metrics. We performed a retrospective cohort study of 215 patients being treated for advanced thoracic malignancies with non-curative intent. We evaluated the association between outpatient embedded palliative care and inpatient clinical outcomes including emergency room visits, hospitalizations, intensive care unit admissions, hospital charges, as well as hospital quality metrics including 30-day readmissions, admissions within 30 days of death, inpatient mortality, and inpatient hospital charges. Outpatient embedded palliative care was associated with lower hospital charges per day (USD 3807 vs. USD 4695, p = 0.024). Furthermore, patients who received outpatient embedded palliative care had lower hospital admissions within 30 days of death (O.R. 0.45; 95% CI 0.29, 0.68; p < 0.001) and a lower inpatient mortality rate (IRR 0.67; 95% CI 0.48, 0.95; p = 0.024). Our study further supports that outpatient palliative care is a high-value intervention and alternative models of palliative care, including one embedded into a multidisciplinary thoracic oncology clinic, is associated with improved value-based metrics.
Spatial Distribution Pattern of the Mesozooplankton Community in Ross Sea Region Marine Protected Area (RSR MPA) during Summer
Authors: Kim Sung Hoon , Son Wuju , Kim Jeong-Hoon , La Hyoung Sul
Published: March 2024

The Ross Sea region Marine Protected Area (RSR MPA) is one of the most productive regions in the Southern Ocean. Mesozooplankton intermediates the primary product to the higher predators, such as penguins and seals, in this ecosystem. In this study, the mesozooplankton community structure and spatial pattern in the RSR MPA in January were investigated by using 505 μm-mesh-size bongo net samples. As a result, 37 mesozooplankton taxa with a total mean abundance of 35.26 ind./m3, ranging from 2.94 to 139.17 ind./m3, were confirmed. Of the 37 taxa, 7 occupied almost 84% of the total abundance, with copepods being the main dominant taxa. As shown by our hierarchical analysis, the mesozooplankton community was divided into four groups, each associated with a specific geographical distribution. Group A was composed of stations around Terra Nova Bay and showed relatively low abundance. Group B included stations around the continental slope region. Group D was composed of the Ross Sea continental shelf stations, while group C consisted of stations geographically located between those of groups B and D. These four groups were influenced by various environmental factors, such as water temperature, salinity, and nutrients. In summary, the mesozooplankton community can be separated according to geographical pattern. This pattern is related to several environmental factors.
Correction: Wang, L.; Guan, C. Improving Security in the Internet of Vehicles: A Blockchain-Based Data Sharing Scheme. Electronics 2024, 13, 714
Authors: Wang Lianhai , Guan Chenxi
Published: March 2024

In the original publication [...]
ComPipe: A Novel Flow Placement and Measurement Algorithm for Programmable Composite Pipelines
Authors: Ran Dengyu , Chen Xiao , Song Lei
Published: March 2024

Programmable networks comprise heterogeneous network devices based on both hardware and software. Hardware devices provide superior bandwidth and low latency but encounter challenges in managing large table entries. Conversely, software devices offer abundant flow tables but have a limited forwarding capacity. To overcome this limitation, some commercial switches offer implementations that combine both hardware and software devices. In this context, this paper presents the Composite Pipeline (ComPipe), an algorithm for high-performance and high-precision flow placement and measurement. ComPipe utilizes a multi-level hashing algorithm for the real-time identification of heavy hitters, incorporates a unique flow eviction strategy, and is implemented on commercial programmable hardware. For non-heavy flows, ComPipe employs sketch structures to accomplish a high-performance flow synopsis within limited memory constraints. This design allows to replace flow rules entirely in the data plane, ensuring the timely detection and offloading of heavy-hitter flows, and offering a unified interface to the controller. The ComPipe prototype has been implemented in both testbed and simulation environments. The results indicate that ComPipe is an effective solution for dynamic flow placement in programmable networks, distinguished by its low cost, high performance, and high accuracy.
Beyond Reality: Exploring User Experiences in the Metaverse Art Exhibition Platform from an Integrated Perspective
Authors: Xu Junping , Liu Sixuan , Yang Wei , Fang Meichen , Pan Younghwan
Published: March 2024

With the rise of the metaverse, digital transformation is profoundly affecting the field of art exhibitions. Museums and galleries are actively adopting metaverse technologies to present artworks through virtual platforms, providing audiences with novel opportunities for immersive engagement and art experiences and shaping high-quality user experiences. However, the factors influencing user engagement in the metaverse art exhibition platform (MeAEP) remain unclear in the current research. This research combines the information systems success model (ISSM) and the hedonic motivation system adoption model (HMSAM) to construct a theoretical model that provides insights into the factors influencing MeAEP users’ intention to engage and their immersion behavior, with a focus on the sustainability of the art exhibition. We quantitatively analyzed 370 users that experienced MeAEP and analyzed the data and measurement model using SPSS 27 and partial least squares structural equation modeling (PLS-SEM). The results showed that information quality (IQ), system quality (SQ), and perceived ease of use (PEOU) significantly and positively influenced perceived usefulness (PU), curiosity (CUR), joy (JOY), and control (CON). PU, JOY, and CON have a positive and significant effect on Immersion (IM). Finally, PU, CUR, JOY, and CON had a positive effect on behavioral intention (BI). In conclusion, only one of the twenty hypotheses was not supported. The research findings not only enrich the academic and managerial theories related to the metaverse and art exhibition platforms, but also provide practical insights for administrators, developers, and MeAEP designers to create higher-quality and more immersive art content, as well as provide constructive ideas for the sustainability of art exhibitions to further enhance user experience.
Sewage Sludge-Derived Biochar and Its Potential for Removal of Ammonium Nitrogen and Phosphorus from Filtrate Generated during Dewatering of Digested Sludge
Authors: Wystalska Katarzyna , Grosser Anna
Published: March 2024

Utilizing waste, such as sewage sludge, into biochar fits the circular economy concept. It maximizes the reuse and recycling of waste materials in the wastewater treatment plant. The experiments were conducted to assess: (1) the impact of the temperature on the properties of biochar from sewage sludge (400 °C, 500 °C, 600 °C, 700 °C); (2) how the physical activation (CO2, hot water) or chemical modification using (MgCl2, KOH) could affect the removal of ammonia nitrogen and phosphorus from filtrate collected from sludge dewatering filter belts or synthetic solution, wherein the concentration of ammonium nitrogen and phosphorus were similar to the filtrate. Based on the Brunner–Emmett–Teller (BET) surface and the type and concentration of surface functional groups for the second stage, biochar was selected and produced at 500 °C. The modification of biochar had a statistically significant effect on removing nitrogen and phosphorus from the media. The best results were obtained for biochar modified with potassium hydroxide. For this trial, 15%/17% (filtrate/synthetic model solution) and 72%/86% nitrogen and phosphorus removal, respectively, were achieved.
A Qualitative Analysis Using Thermography for Characterization of the Built Environment
Authors: Ferreira Ana Teresa Vaz , Ferreira Pedro , Santos Michael M.
Published: March 2024

The revised Energy Performance of Buildings Directive (EPBD) recognizes nearly zero-energy buildings (nZEB) and building renovation as essential steps in the decarbonization of the built environment. A thorough understanding of existing buildings is a prerequisite for improving their thermal performance and ensuring that interventions are based on pre-existing conditions. This study investigates the use of thermography as a tool for identifying construction solutions and assessing the thermal performance of buildings. Initially, it addresses the benefits and limitations of this technique, as well as some results of a qualitative analysis and standard application of this technology. Specific conditions for capturing images on-site were identified, along with the relevant factors for interpreting thermograms under natural conditions. These images enabled the identification of previous works, changes in buildings, and the use of different materials and construction techniques, thereby contributing to the characterization of buildings. Consequently, they can be used in the diagnostic phase to enhance the accuracy of intervention solutions based on a better understanding of existing conditions.
The Influence of Different Forest Landscapes on Physiological and Psychological Recovery
Authors: Shi Hui , Luo Han , Wei Yawei , Shin Won-Sop
Published: March 2024

Previous studies have reported that exposure to forest landscapes has many benefits on human physiological and psychological health, as well as effectiveness in reducing stress and improving mood depending on different types of landscape. This study examined the effects of different types of forest landscapes for indirect visual experiences on the physical and mental health of college students (N = 33). Three types of landscape images were selected, in which forest landscapes included vegetated landscapes and water features, and as a control, we set up images of urban landscapes without natural elements. Physiological and psychological assessment was performed before the experiment for each student, followed by each student being exposed consecutively to nine landscape images for 3 min (each type) and assessed after each exposure. The results showed that both forest landscapes decreased stress (p < 0.05 for all) and improved mood and self-esteem (p < 0.01 for all). In contrast, water landscapes showed a slightly higher impact on physical and mental health than vegetated landscapes, but there was no significant difference. Conversely, only for self-esteem, the response after viewing vegetated landscapes (VL, SD = 29.06 ± 3.38) was better than after water views (WL, SD = 28.21 ± 2.48). Despite significant differences between the two types of forest landscapes not being found in our findings, the benefits of forest landscapes were observed through understanding the health-promoting capacities of different forest landscapes.
Aerial Biomass Estimation in the Cerrado Biome Using Canopy Height Data
Authors: Toneli Carlos Augusto Zangrando , Scardua Fernando Paiva , Martins Rosana de Carvalho Cristo , Matricardi Eraldo Aparecido Trondoli , Ribeiro Andressa , Ferraz Filho Antonio Carlos
Published: March 2024

Adaptations to climate change rely on understanding the dynamics of plant biomass stocks on the planet. The high levels of deforestation in Cerrado have transformed this biome into the second-largest Brazilian source of carbon emissions. The objective of this study was to develop a method to accurately estimate aboveground and total biomass values among shrublands, savannas, and forests located in the Cerrado biome using an allometric equation adjusted from canopy height obtained through optical and laser sensors. The results show similarity between the estimates employed by our method and the data found in the literature review for different phytophysiognomies in the Cerrado biome. Shrubland formations showed higher biomass estimation uncertainties due to the discontinuity of isolated trees and the lower canopy height when compared to more clustered tree canopies in savannas and taller canopies in forests. Aboveground biomass estimates are related to expansion factors, and specific maps were developed for each compartment by root, litter, and necromass. The sum of these compartments is presented in the aboveground and below forest biomass map. This study presents, for the first time, the mapping of total biomass in 10 m pixels of all regions of the Cerrado biome.
Detection of Escherichia coli O157:H7 in Ground Beef Using Long-Read Sequencing
Authors: Counihan Katrina L. , Kanrar Siddhartha , Tilman Shannon , Capobianco Joseph , Armstrong Cheryl M. , Gehring Andrew
Published: March 2024

Foodborne pathogens are a significant cause of illness, and infection with Shiga toxin-producing Escherichia coli (STEC) may lead to life-threatening complications. The current methods to identify STEC in meat involve culture-based, molecular, and proteomic assays and take at least four days to complete. This time could be reduced by using long-read whole-genome sequencing to identify foodborne pathogens. Therefore, the goal of this project was to evaluate the use of long-read sequencing to detect STEC in ground beef. The objectives of the project included establishing optimal sequencing parameters, determining the limit of detection of all STEC virulence genes of interest in pure cultures and spiked ground beef, and evaluating selective sequencing to enhance STEC detection in ground beef. Sequencing libraries were run on the Oxford Nanopore Technologies’ MinION sequencer. Optimal sequencing output was obtained using the default parameters in MinKNOW, except for setting the minimum read length to 1 kb. All genes of interest (eae, stx1, stx2, fliC, wzx, wzy, and rrsC) were detected in DNA extracted from STEC pure cultures within 1 h of sequencing, and 30× coverage was obtained within 2 h. All virulence genes were confidently detected in STEC DNA quantities as low as 12.5 ng. In STEC-inoculated ground beef, software-controlled selective sequencing improved virulence gene detection; however, several virulence genes were not detected due to high bovine DNA concentrations in the samples. The growth enrichment of inoculated meat samples in mTSB resulted in a 100-fold increase in virulence gene detection as compared to the unenriched samples. The results of this project suggest that further development of long-read sequencing protocols may result in a faster, less labor-intensive method to detect STEC in ground beef.
The Effects of Jet-Milling and Pulsed Electric Fields on the Preservation of Spinach Juice Lutein Contents during Storage
Authors: Kim Si-Yeon , Lee Yeong-Geol , Ju Hye-In , Jeon Ji-Hee , Jeong Se-Ho , Lee Dong-Un
Published: March 2024

This study aimed to investigate the effects of jet-milling on the lutein extraction contents of spinach powder (SP), as well as the effects of pulsed electric field (PEF), as a non-thermal pasteurization technology, on the preservation of spinach juice (SJ) lutein contents. SP particles were divided into SP-coarse (Dv50 = 315.2 μm), SP-fine (Dv50 = 125.20 μm), and SP-superfine (Dv50 = 5.59 μm) fractions, and SP-superfine was added to SJ due to its having the highest contents of lutein extract. PEFs and thermal treatment were applied to evaluate the effects of preserving the lutein content of PEF during storage (25 days). The juice was then designated as untreated (no pasteurization), PEF-1,2 (SJ treated with PEF 20 kV/cm 110 kJ/L, 150 kJ/L), or Thermal-1,2 (SJ treated with 90 °C, 10 min and 121 °C, 15 min). The sizes and surface shapes of the superfine SP particles were more homogeneous and smoother than those of the other samples. SJ made with SP-superfine and treated with PEF had the highest lutein content and antioxidant activities among the group during storage. A complex of jet-milling and PEF could have great potential as a method to improve the lutein contents of lutein-enriched juice in the food industry.
Characterization of Nanovesicles Isolated from Olive Vegetation Water
Authors: Buratta Sandra , Latella Raffaella , Chiaradia Elisabetta , Salzano Anna Maria , Tancini Brunella , Pellegrino Roberto Maria , Urbanelli Lorena , Cerrotti Giada , Calzoni Eleonora , Alabed Husam B. R. , De Pascale Sabrina , Lugini Luana , Federici Cristina , Scaloni Andrea , Emiliani Carla
Published: March 2024

Edible plant and fruit-derived nanovesicles (NVs) are membrane-enclosed particles with round-shape morphology and signaling functions, which resemble mammalian cell-derived extracellular vesicles. These NVs can transmit cross-kingdom signals as they contain bioactive molecules and exert biological effects on mammalian cells. Their properties and stability in the gastrointestinal tract suggest NVs as a promising nutraceutical tool. In this study, we have demonstrated for the first time the presence of NVs in olive vegetation water (OVW), a waste by-product generated during olive oil production. Biophysical characterization by scanning electron microscopy, cryo-transmission electron microscopy, and nanoparticle tracking analysis revealed the presence in OVW of NVs having size and morphology similar to that of vesicles isolated from edible plants. Integrated lipidomic, metabolomic, and proteomic analyses showed that OVW-NVs carry a set of lipids, metabolites and proteins which have recognized antioxidant and anti-inflammatory activities. The nature of biomolecules identified in OVW-NVs suggests that these vesicles could exert beneficial effects on mammalian cells and could be used in the nutraceutical and food industries. The successful isolation of OVW-NVs and the characterization of their features strengthen the idea that agricultural waste might represent a source of NVs having features similar to NVs isolated from edible plants/fruits.
A Composite Tool for Forecasting El Niño: The Case of the 2023–2024 Event
Authors: Varotsos Costas , Sarlis Nicholas V. , Mazei Yuri , Saldaev Damir , Efstathiou Maria
Published: March 2024

Remotely sensed data play a crucial role in monitoring the El Niño/La Niña Southern Oscillation (ENSO), which is an oceanic-atmospheric phenomenon occurring quasi-periodically with several impacts worldwide, such as specific biological and global climate responses. Since 1980, Earth has witnessed three strong ENSO events (1982–1983, 1997–1998, 2015–2016). In September 2022, La Niña entered its third year and was unlikely to continue through 2024. Instead, since 2022, forecasts have pointed to a transition from La Niña to a Neutral phase in the summer or late 2023. The onset of El Niño occurred around April 2023, and it is anticipated by sophisticated models to be a strong event through the Northern Hemisphere winter (December 2023–February 2024). The aim of this study is to demonstrate the ability of the combination of two new methods to improve the accuracy of the above claim because El Niño apart from climate anomalies, significantly impacts Earth’s ecosystems and human societies, regulating the spread of diseases by insects (e.g., malaria and dengue fever), and influencing nutrients, phytoplankton biomass, and primary productivity. This is done by exploring first the previous major El Niño events in the period January 1876–July 2023. Our calculations show that the ongoing 2023–2024 El Niño will not be the strongest.
Spray-Dried Chitosan Hydrogel Particles as a Potential Delivery System for Benzydamine Hydrochloride
Authors: Milenkova Sofia , Ambrus Rita , Mukhtar Mahwash , Pilicheva Bissera , Marudova Maria
Published: March 2024

Chitosan, being a biocompatible and mucoadhesive polysaccharide, is one of the most preferred hydrogel-forming materials for drug delivery. The objectives of the present study are to obtain spray-dried microparticles based on low-molecular-weight chitosan and study their potential application as cargo systems for the orally active drug benzydamine hydrochloride. Three types of particles are obtained: raw chitosan particles (at three different concentrations), cross-linked with sodium tripolyphosphate (NaTPP) particles (at three different chitosan:NaTPP ratios), and particles coated with mannitol (at three different chitosan:mannitol ratios), all of them in the size range between 1 and 10 µm. Based on the loading efficiency and the yields of the formulated hydrogel particles, one model of each type is chosen for further investigation of the effect of the cross-linker or the excipient on the properties of the gel structures. The morphology of both empty and benzydamine hydrochloride-loaded chitosan particles was examined by scanning electron microscopy, and it was quite regular and spherical. Interactions and composition in the samples are investigated by Fourier-transformed infrared spectroscopy. The thermal stability and phase state of the drug and drug-containing polymer matrixes were tested by differential scanning calorimetry and X-ray powdered diffraction, revealing that the drug underwent a phase transition. A drug release kinetics study of the chosen gel-based structures in simulated saliva buffer (pH = 6.8) and mathematical modeling of the process were performed, indicating the Weibull model as the most appropriate one.
Arrival Infrastructures: Segregation of Displaced Migrants and Processes of Urban Change in Athens
Authors: Arapoglou Vassilis P. , Spyrellis Stavros Nikiforos
Published: March 2024

Recent treatment of accommodation and arrival infrastructures for asylum seekers and refugees has fuelled international research on refugee reception policies in urban environments and on the consequences of related initiatives of the European Union and international organizations such as the UNHCR. Using Athens as a case study, this article provides empirical evidence to revive the theoretical treatment of the importance of arrival and accommodation infrastructures in urban areas in transition. We collected and compiled data from four sources: the 2011 population census, the 2018 ESTIA accommodation program and the UNHCR Site Management Support (SMS) Reports of Temporary Accommodation Sites and Reception and Identification Centres (RICs), and a primary survey of services for asylum seekers and refugees. After the geocoding of data, we calculate indices for key dimensions of the segregation of accommodated asylum seekers and foreign nationals. We discuss the findings, seeking to highlight how the location and the composition of accommodation infrastructures has been influenced by a wider process of urban change and adaptations to global forces, leading not only to the transformation of inner-city zones but also suburban and peri-urban areas.
A Comparative Study of Embedded Wall Displacements Using Small-Strain Hardening Soil Model
Authors: Eilat Tzuri , Mitelman Amichai , McQuillan Alison , Elmo Davide
Published: March 2024

Traditional analysis of embedded earth-retaining walls relies on simplistic lateral earth pressure theory methods, which do not allow for direct computation of wall displacements. Contemporary numerical models rely on the Mohr–Coulomb model, which generally falls short of accurate wall displacement prediction. The advanced constitutive small-strain hardening soil model (SS-HSM), effectively captures complex nonlinear soil behavior. However, its application is currently limited, as SS-HSM requires multiple input parameters, rendering numerical modeling a challenging and time-consuming task. This study presents an extensive numerical investigation, where wall displacements from numerical models are compared to empirical findings from a large and reliable database. A novel automated computational scheme is created for model generation and advanced data analysis is undertaken for this objective. The main findings indicate that the SS-HSM can provide realistic predictions of wall displacements. Ultimately, a range of input parameters for the utilization of SS-HSM in earth-retaining wall analysis is established, providing a good starting point for engineers and researchers seeking to model more complex scenarios of embedded walls with the SS-HSM.
An Integrated Sample Referral System for HIV Viral Load and Early Infant Diagnosis in North-Western Province, Zambia—A Retrospective Cross-Sectional Study
Authors: Shempela Doreen Mainza , Sikalima Jay , Mwandia Jim , Mwila Ernest , Chilyabanyama Rodgers , Masona Mike , Kasonde Cynthia Banda , Mwandila Andrew , Kamalamba Hector , Kasanga Maisa , Mutanekelwa Imukusi , Mudenda Steward , Kandama Franco Jordan , Cham Fatim , Njuguna Michael , McCarrick Paul , Morrison Linden , Daka Victor , Sichinga Karen
Published: March 2024

Zambia’s adult HIV prevalence is high at 11% and faces challenges in achieving UNAIDS 95-95-95 targets for HIV, with a national viral load suppression of 86.2% falling short of the required 95%. North-Western Province has the lowest viral load suppression at 77.5%. Our study investigated the role of an integrated sample referral system in optimizing HIV viral load coverage and Early Infant Diagnosis turnaround time in the province. Using electronic data from the DISA Laboratory Information System and Smartcare, a retrospective cross-sectional analysis was conducted, involving 160,922 viral load and Early Infant Diagnosis results. The chi-square test and multiple linear regression were used for analysis. Following the implementation of the integrated sample referral system, viral load coverage consistently increased monthly (p < 0.001), Early Infant Diagnosis turnaround time improved by 47.7%, and sample volume increased by 25%. The study identifies associations between various factors and testing outcomes. These findings demonstrate improvements in viral load coverage and the Early Infant Diagnosis turnaround time and suggest targeting modifiable factors to further optimize the referral system. We recommend continued strengthening of the referral system and more deliberate demand-creation implementation strategies.
Natural Radioactivity in Raw Building Materials for Underground Parking Lots and Assessment of Radiological Health Risk for the Population
Authors: Caridi Francesco , Paladini Giuseppe , Mottese Antonio Francesco , Praticò Filippo Giammaria , Faggio Giuliana , Messina Giacomo , Belvedere Alberto , Marguccio Santina , D’Agostino Maurizio , Majolino Domenico , Venuti Valentina
Published: March 2024

This article reports the results of an investigation into the activity concentration of natural radionuclides in raw building materials for underground parking lots, together with the assessment of the radiation hazard for the public related to exposure to ionizing radiations. To this purpose, high-purity germanium (HPGe) γ-ray spectrometry was employed in order to quantify the average specific activity of 226Ra, 232Th, and 40K natural radioisotopes. With the aim to assess any possible radiological health risk for the population, the absorbed γ-dose rate (D), the annual effective dose equivalent outdoor (AEDEout) and indoor (AEDEin), the activity concentration index (I), and the alpha index (Iα) were also estimated, resulting in values that were lower than the maximum recommended ones for humans. Finally, the extent of the correlations existing between the observed radioactivity and radiological parameters and of these parameters with the analyzed samples was quantified through statistical analyses, including Pearson’s correlation, a principal component analysis (PCA), and a hierarchical cluster analysis (HCA). As a result, three clusters of the investigated samples were recognized based on their chemical composition and mineralogical nature. Noteworthily, this paper covers a certain gap in science since its topic does not appear in literature in this form. Thus, the authors underline the importance of this work to global knowledge in the environmental research and public health fields.
Modeling Shallow Landslide Runout Distance in Eocene Flysch Facies Using Empirical–Statistical Models (Western Black Sea Region of Türkiye)
Authors: Komu Muge Pinar , Nefeslioglu Hakan Ahmet , Gokceoglu Candan
Published: March 2024

Uncertainties related to runout distances in shallow landslide analyses may not only affect lives but may also result in economic losses. Owing to the increase in shallow landslides, which are especially triggered by heavy rainfall, runout distances have been investigated to decipher whether applications of a functional runout distance are feasible. This paper aims to give insights into the modeling of the shallow landslide runout probability in Eocene flysch facies in the Western Black Sea region of Türkiye. There are two main stages in this study—which are dominated by empirical models, the detection of initiation points, and propagation—which help us to understand and visualize the possible runout distances in the study area. Shallow landslide initiation point determination using machine learning has a critical role in the ordered tasks in this study. Modified Holmgren and simplified friction-limited model (SFLM) parameters were applied to provide a good approximation of runout distances during the propagation stage using Flow-R software. The empirical model parameters suggested for debris flows and shallow landslides were investigated comparatively. The runout distance models had approximately the same performance depending on the debris flow and shallow landslide parameters. While the impacted total runout areas for the debris flow parameters were predicted to amount to approximately 146 km2, the impacted total runout areas for the shallow landslide parameters were estimated to be about 101 km2. Considering the inclusion of the RCP 4.5 and RCP 8.5 precipitation scenarios in the analyses, this also shows that the shallow landslide and debris flow runout distance impact areas will decrease. The investigation of runout distance analyses and the inclusion of the RCP scenarios in the runout analyses are highly intriguing for landslide researchers.
Highways and Detours in the Realm of Photodynamic Therapy
Authors: Kessel David , Peng Qian
Published: March 2024

Photodynamic therapy (PDT) has been a topic of interest since the first report in 1900 but has yet to become a ‘mainstream’ treatment protocol in the medical field. There are clear indications for which PDT might be the ‘method of choice’, but it is unlikely that there will be protocols for the treatment of systemic disease. This report discusses recent developments for promoting PDT efficacy, in the context of what is already known. Factors that can limit the scope of these applications are also indicated. Among the more interesting of these developments is the use of formulation techniques to target specific organelles for photodamage. This can enhance responses to PDT and circumvent situations where an impaired death pathway interferes with PDT efficacy.
Extracellular Vesicles from Cerebrospinal Fluid of Leptomeningeal Metastasis Patients Deliver MiR-21 and Induce Methotrexate Resistance in Lung Cancer Cells
Authors: Im Ji Hye , Lee Kyue-Yim , Seo Yoona , Rhim Jiho , Dho Yun-Sik , Yoo Byong Chul , Park Jong Bae , Shin Sang Hoon , Yoo Heon , Kim Jong Heon , Gwak Ho-Shin
Published: March 2024

Leptomeningeal metastasis (LM) is a common and fatal complication of advanced non-small cell lung cancer (NSCLC) caused by the spread of malignant cells to the leptomeninges and cerebrospinal fluid (CSF). While intra-CSF methotrexate (MTX) chemotherapy can improve prognosis, eventual MTX resistance deters continued chemotherapy. Recent studies have shown that increased miRNA-21 (miR-21) expression in the CSF of patients with LM after intraventricular MTX-chemotherapy is associated with poor overall survival; however, the molecular mechanisms underlying this resistance are poorly understood. Here, we confirm, in 36 patients with NSCLC-LM, that elevated miR-21 expression prior to treatment correlates with poor prognosis. MiR-21 overexpression or sponging results in a corresponding increase or decrease in MTX resistance, demonstrating that cellular miR-21 expression correlates with drug resistance. MiR-21-monitoring sensor and fluorescent extracellular vesicle (EV) staining revealed that EV-mediated delivery of miR-21 could modulate MTX resistance. Moreover, EVs isolated from the CSF of LM patients containing miR-21 could enhance the cell proliferation and MTX resistance of recipient cells. These results indicate that miR-21 can be transferred from cell-to-cell via EVs and potentially modulate MTX sensitivity, suggesting that miR-21 in CSF EVs may be a prognostic and therapeutic target for overcoming MTX resistance in patients with NSCLC-LM.
Biomaterials in Drug Delivery: Advancements in Cancer and Diverse Therapies—Review
Authors: Drabczyk Anna , Kudłacik-Kramarczyk Sonia , Jamroży Mateusz , Krzan Marcel
Published: March 2024

Nano-sized biomaterials are innovative drug carriers with nanometric dimensions. Designed with biocompatibility in mind, they enable precise drug delivery while minimizing side effects. Controlled release of therapeutic substances enhances efficacy, opening new possibilities for treating neurological and oncological diseases. Integrated diagnostic-therapeutic nanosystems allow real-time monitoring of treatment effectiveness, which is crucial for therapy personalization. Utilizing biomaterials as nano-sized carriers in conjunction with drugs represents a promising direction that could revolutionize the field of pharmaceutical therapy. Such carriers represent groundbreaking drug delivery systems on a nanometric scale, designed with biocompatibility in mind, enabling precise drug delivery while minimizing side effects. Using biomaterials in synergy with drugs demonstrates significant potential for a revolutionary impact on pharmaceutical therapy. Conclusions drawn from the review indicate that nano-sized biomaterials constitute an innovative tool that can significantly improve therapy effectiveness and safety, especially in treating neurological and oncological diseases. These findings should guide researchers towards further studies to refine nano-sized biomaterials, assess their effectiveness under various pathological conditions, and explore diagnostic-therapeutic applications. Ultimately, these results underscore the promising nature of nano-sized biomaterials as advanced drug carriers, ushering in a new era in nanomedical therapy.
Correlation of Presynaptic and Postsynaptic Proteins with Pathology in Alzheimer’s Disease
Authors: Serrano Geidy E. , Walker Jessica , Nelson Courtney , Glass Michael , Arce Richard , Intorcia Anthony , Cline Madison P. , Nabaty Natalie , Acuña Amanda , Huppert Steed Ashton , Sue Lucia I. , Belden Christine , Choudhury Parichita , Reiman Eric , Atri Alireza , Beach Thomas G.
Published: March 2024

Synaptic transmission is essential for nervous system function and the loss of synapses is a known major contributor to dementia. Alzheimer’s disease dementia (ADD) is characterized by synaptic loss in the mesial temporal lobe and cerebral neocortex, both of which are brain areas associated with memory and cognition. The association of synaptic loss and ADD was established in the late 1980s, and it has been estimated that 30–50% of neocortical synaptic protein is lost in ADD, but there has not yet been a quantitative profiling of different synaptic proteins in different brain regions in ADD from the same individuals. Very recently, positron emission tomography (PET) imaging of synapses is being developed, accelerating the focus on the role of synaptic loss in ADD and other conditions. In this study, we quantified the densities of two synaptic proteins, the presynaptic protein Synaptosome Associated Protein 25 (SNAP25) and the postsynaptic protein postsynaptic density protein 95 (PSD95) in the human brain, using enzyme-linked immunosorbent assays (ELISA). Protein was extracted from the cingulate gyrus, hippocampus, frontal, primary visual, and entorhinal cortex from cognitively unimpaired controls, subjects with mild cognitive impairment (MCI), and subjects with dementia that have different levels of Alzheimer’s pathology. SNAP25 is significantly reduced in ADD when compared to controls in the frontal cortex, visual cortex, and cingulate, while the hippocampus showed a smaller, non-significant reduction, and entorhinal cortex concentrations were not different. In contrast, all brain areas showed lower PSD95 concentrations in ADD when compared to controls without dementia, although in the hippocampus, this failed to reach significance. Interestingly, cognitively unimpaired cases with high levels of AD pathology had higher levels of both synaptic proteins in all brain regions. SNAP25 and PSD95 concentrations significantly correlated with densities of neurofibrillary tangles, amyloid plaques, and Mini Mental State Examination (MMSE) scores. Our results suggest that synaptic transmission is affected by ADD in multiple brain regions. The differences were less marked in the entorhinal cortex and the hippocampus, most likely due to a ceiling effect imposed by the very early development of neurofibrillary tangles in older people in these brain regions.
Membrane Interaction Characteristics of the RTX Toxins and the Cholesterol-Dependence of Their Cytolytic/Cytotoxic Activity
Authors: Ostolaza Helena , Amuategi Jone
Published: March 2024

RTX toxins are important virulence factors produced by a wide range of Gram-negative bacteria. They are secreted as water-soluble proteins that are able to bind to the host cell membrane and insert hydrophobic segments into the lipid bilayer that ultimately contribute to the formation of transmembrane pores. Ion diffusion through these pores leads then to cytotoxic and cytolytic effects on the hosts. Several reports have evidenced that the binding of several RTX toxins to the target cell membrane may take place through a high-affinity interaction with integrins of the β2 family that is highly expressed in immune cells of the myeloid lineage. However, at higher toxin doses, cytotoxicity by most RTX toxins has been observed also on β2-deficient cells in which toxin binding to the cell membrane has been proposed to occur through interaction with glycans of glycosylated lipids or proteins present in the membrane. More recently, cumulative pieces of evidence show that membrane cholesterol is essential for the mechanism of action of several RTX toxins. Here, we summarize the most important aspects of the RTX toxin interaction with the target cell membrane, including the cholesterol dependence, the recent identification in the sequences of several RTX toxins of linear motifs coined as the Cholesterol Recognition/interaction Amino acid Consensus (CRAC), and the reverse or mirror CARC motif, which is involved in the toxin–cholesterol interaction.
Two-Photon Absorbing Dendrimers and Their Properties—An Overview
Authors: Maraval Valérie , Caminade Anne-Marie
Published: March 2024

This review describes the two-photon absorption properties of dendrimers, which are arborescent three-dimensional macromolecules differing from polymers by their perfectly defined structure. The two-photon absorption process is a third order non-linear optical property that is attractive because it can be used in a wide range of applications. In this review, dendrimers that were studied for their two-photon absorption properties are first described. Then, the use of dendritic TPA chromophores for light harvesting, photopolymerization, optical power limitation, cell imaging, singlet oxygen generation, and photodynamic therapy is described. This review thus proposes an overview of the properties and possible applications of two-photon absorbing dendrimers.
The Role of Metabolomics and Microbiology in Urinary Tract Infection
Authors: Zheng Haoyu , Wang Chao , Yu Xiao , Zheng Wenxue , An Yiming , Zhang Jiaqi , Zhang Yuhan , Wang Guoqiang , Qi Mingran , Lin Hongqiang , Wang Fang
Published: March 2024

One of the common illnesses that affect women’s physical and mental health is urinary tract infection (UTI). The disappointing results of empirical anti-infective treatment and the lengthy time required for urine bacterial culture are two issues. Antibiotic misuse is common, especially in females who experience recurrent UTI (rUTI). This leads to a higher prevalence of antibiotic resistance in the microorganisms that cause the infection. Antibiotic therapy will face major challenges in the future, prompting clinicians to update their practices. New testing techniques are making the potential association between the urogenital microbiota and UTIs increasingly apparent. Monitoring changes in female urinary tract (UT) microbiota, as well as metabolites, may be useful in exploring newer preventive treatments for UTIs. This review focuses on advances in urogenital microbiology and organismal metabolites relevant to the identification and handling of UTIs in an attempt to provide novel methods for the identification and management of infections of the UT. Particular attention is paid to the microbiota and metabolites in the patient’s urine in relation to their role in supporting host health.
Exploring the Link between Hydrodynamic Size and Immunoglobulins of Circulating Immune Complexes in Rheumatoid Arthritis Patients
Authors: Djukić Tamara , Drvenica Ivana , Kovačić Marijana , Milanović Sladjan , Majerič Dragana , Šefik-Bukilica Mirjana , Miletić Maja , Bugarski Branko , Ilić Vesna
Published: March 2024

The function of immune complexes in rheumatoid arthritis (RA) is related to their composition and size. Using dynamic light scattering (DLS), we investigated the link between the RA circulating immune complex (CIC) particles’ size and the CIC immunoglobulin level. In this study, 30 RA patients and 30 healthy individuals were included. IgA, IgG, and IgM were found in all analyzed CICs, but more IgA and IgG were found in RA than in control CICs. In both control and RA CICs, DLS detected 50 particles that differed in size and clustered around two size groups: with a 7.5–164 nm radius and with a 342–1718 nm radius. An increased level of IgA in RA CICs, compared to control ones, was associated with more than 50% of CIC particles. In RA, compared to the control, a higher number of CICs with 28.2 nm, 531 nm, 712 nm, and 1718 nm particles and a lower number of CICs with 78.8 nm particles were detected. This particle distribution pattern did not reflect the changes in the CIC immunoglobulin level. Thus, RA elevated CIC IgA was linked with all these particles (except the 1718 nm particle), the IgM increase was linked with 43.8 nm and 712 nm particles, and the IgG increase was linked with the 712 nm particle only. This study provides the very first data on the association between CIC particles’ size, CIC immunoglobulin level, and RA. It opens the possibility that the size of CICs determined by DLS can be used as a criterion in RA diagnosis or monitoring after a large-scale study confirmation.
Role of CD44 in Chemotherapy Treatment Outcome: A Scoping Review of Clinical Studies
Authors: Wu Zihao , Lu Jillian , Loo Andrew , Ho Nathan , Nguyen Danny , Cheng Po Yueh , Mohammed Ali I. , Cirillo Nicola
Published: March 2024

Cluster of differentiation 44 (CD44), a cell surface adhesion molecule overexpressed in cancer stem cells, has been implicated in chemoresistance. This scoping review, following PRISMA-ScR guidelines, systematically identified and evaluated clinical studies on the impact of CD44 expression on chemotherapy treatment outcomes across various cancer types. The search encompassed PubMed (1985–2023) and SCOPUS (1936–2023) databases, yielding a total of 12,659 articles, of which 40 met the inclusion criteria and were included in the qualitative synthesis using a predefined data extraction table. Data collected included the cancer type, sample size, interventions, control, treatment outcome, study type, expression of CD44 variants and isoforms, and effect of CD44 on chemotherapy outcome. Most of the studies demonstrated an association between increased CD44 expression and negative chemotherapeutic outcomes such as shorter overall survival, increased tumor recurrence, and resistance to chemotherapy, indicating a potential role of CD44 upregulation in chemoresistance in cancer patients. However, a subset of studies also reported non-significant relationships or conflicting results. In summary, this scoping review highlighted the breadth of the available literature investigating the clinical association between CD44 and chemotherapeutic outcomes. Further research is required to elucidate this relationship to aid clinicians in managing CD44-positive cancer patients.