bluuebunny/crossref_metadata_2025 huggingface dataset:
The Effect of UV-Vis Radiation on DNA Systems Containing the Photosensitizers Methylene Blue and Acridine Orange
Authors: Pivetta Thais P. , Ribeiro Paulo A. , Raposo Maria
Published: January 2024

As a vital biomolecule, DNA is known as a target of antineoplastic drugs for cancer therapy. These drugs can show different modes of interaction with DNA, with intercalation and groove binding being the most common types. The intercalation of anticancer drugs with DNA can lead to the disruption of its normal function, influencing cell proliferation. Methylene blue (MB) and acridine orange (AO) are examples of DNA-intercalating agents that have been studied for their application against some types of cancer, mainly for photodynamic therapy. In this work, the impact of light irradiation on these compounds in the absence and presence of DNA was analyzed by means of UV-vis spectroscopy. Bathochromic and hypochromic shifts were observed in the absorbance spectra, revealing the intercalation of the dyes with the DNA base pairs. Dyes with and without DNA present different profiles of photodegradation, whereby the dyes alone were more susceptible to degradation. This can be justified by the intercalation of the dyes on the DNA base pairs allowing the DNA molecule to partially hinder the molecules’ exposition and, therefore, reducing their degradation.
Exploring the Interplay of Working Memory, Apathy, and Mood/Emotional Factors
Authors: Thellung di Courtelary Elisa , Scozia Gabriele , Lasaponara Stefano , Aguzzetti Giorgia , Doricchi Fabrizio , Conversi David
Published: January 2024

Background: Previous investigations on healthy humans showed conflicting evidence regarding the impact of mood on working memory performance. A systematic investigation of how mood affects apathy levels in healthy participants is currently missing. Methods: We administered a visuospatial (VS) and a numerical (N) n-back task to a sample of 120 healthy individuals. In these participants, using a series of questionnaires, we also evaluated apathy, mood, working memory, perceived stress, PTSD symptoms caused by the COVID-19 pandemic outbreak, and general psychiatric symptoms. Successively, we investigated their performance in the n-back task as a function of scores to these questionnaires. Results: Participants performed better in the N block than in the VS one. Their accuracy decreased as a function of the n-back difficulty. We reported no differences in working memory performance or apathy as a function of mood, stress, or PTSD symptoms. We found that phobic anxiety negatively predicted accuracy to the numerical n-back task and that subjects with greater anxiety and difficulty in regulating emotions also showed higher levels of withdrawal from the task. Conclusion: The study’s results suggest that while mood did not significantly affect working memory performance, strong associations were found between WMQ scores and working memory capabilities.
Two Stochastic Methods to Model Initial Geometrical Imperfections of Steel Frame Structures
Authors: Jindra Daniel , Kala Zdeněk , Kala Jiří
Published: January 2024

The stochastic modeling of geometrically imperfect steel frame structures requires statistical inputs for imperfection parameters, often with specific mutual correlations. The stochastic input values of geometrical imperfections are derived from European Standard EN 1090-2:2018 tolerance criteria. Two advanced stochastic methods, #RSS (random storey sway) and #RSP (random storey position), are developed based on these criteria. This paper presents a verification study, using random sampling simulations, for these two stochastic methods (#RSS and #RSP) to directly model the initial global geometrical imperfections of steel frame structures. The proposed methods have been verified for structures with equidistant storey heights and for those comprising up to 24 storeys, making them applicable to a wide range standard steel frame structures. It has been found that the performance of the #RSS method is satisfactory. An advantage of #RSS is that the random parameters are statistically independent. On the other hand, the #RSP method requires the definition of these mutual correlations in order to satisfy the criterion that 95 percent of random realizations of initial imperfections fall within the tolerance limits of the corresponding European Standard. The #RSP method, however, might have certain advantages for structures with a larger number of storeys (above 24), as closely discussed in this study. Additionally, this study provides useful provisions for the advanced numerical analyses of multi-storey steel frames of various geometries.
Sustainable Built Environments: Building Information Modeling, Biomaterials, and Regenerative Practices in Mexico
Authors: Colmenero Fonseca Fabiola , Rodríguez Pérez Ramiro , Perlaza Rodríguez Juana , Palomino Bernal Juan Francisco , Cárcel-Carrasco Javier
Published: January 2024

This article explores how the construction sector can significantly contribute to minimizing its environmental impact through reuse and recycling practices, in rehabilitation or new construction projects. This research focuses on implementing BIM methodology alongside biomaterials, 3D modeling, and digitization in compliance with the Green Building Code. Two case studies located in Jalisco and Querétaro (Mexico) are examined through a comparative analysis. The simulations are carried out in different geographical areas with two construction systems that allow us to see the output similarities. The results show the clear advantages of biomaterials over traditional materials such as concrete. The construction materials are shown to determine their operational energy consumption. From an economic point of view, this study supports data regarding lower energy costs, and a significant reduction in CO2 emissions is observed. In conclusion, both the models and simulations, along with the Toolkit, highlight the benefits of biomaterials over conventional industrial materials.
Longitudinal Seismic Response of Metro Tunnels Crossing a Fault with Multi-Slip Surfaces
Authors: Wang Qiyao , Yang Yawu , Teng Hongquan , He Yifei
Published: January 2024

There are multiple seismic fault zones near Xi’an in China, among which the Li Piedmont Fault has multiple slip surfaces. A 3D finite element dynamic Soil–Fault–Tunnel model was established based on the engineering background of the Xi’an Metro tunnel orthogonally crossing the Li Piedmont Fault. The input seismic loads used the Chi-Chi, El-Centro, and artificial seismic waves, and the latter was artificially synthesized based on seismic conditions and site conditions of actual engineering. The Chi-Chi seismic wave with larger PGV/PGA and wider acceleration-sensitive area is a near-field seismic wave, while the others are far-field seismic waves. The seismic loads were transformed into the equivalent nodal force on the boundary nodes of the model, and nonlinear dynamic calculation was carried out to obtain the longitudinal seismic response of the structure. The main results show that the fault amplifies the seismic response of the tunnel, and the tunnel at the position of the fault slip surfaces is more vulnerable to failure, especially near the slip surface between the hanging wall and the fault, where the maximum acceleration, soil pressure, and internal force of the tunnel structure occur. In addition, the seismic response of the tunnel and soil caused by near-field seismic motion is significantly stronger than that caused by far-field seismic motion.
Thrombomodulin Serum Levels—A Predictable Biomarker for the Acute Onset of Ischemic Stroke
Authors: Zaharia Andrei-Lucian , Tutunaru Dana , Oprea Violeta Diana , Tănase Claudiu Elisei , Croitoru Ana , Stan Bianca , Voinescu Doina Carina , Ionescu Ana-Maria , Coadǎ Camelia Alexandra , Lungu Mihaiela
Published: January 2024

The early diagnosis of acute ischemic stroke (AIS) can be challenging in cases presenting with a scarcity of clinical signs, normal cerebral imaging in early stages and a lack of specific serum markers. Thrombomodulin has been shown to be associated with cerebrovascular ischemic events and can be considered an important biomarker for the acute onset of ischemic stroke. In our study, we compared the serum levels of thrombomodulin (sTM) between a relevant patient group of 70 AIS patients and a control group of patients without AIS admitted into the neurology department between June 2022 and May 2023. sTM levels were measured at 24 h and 48 h after patients’ admissions into the hospital. There was a significant difference between the two groups (AIS: 23.2 ± 9.17 ng/mL vs. controls: 3.64 ± 1.72 ng/mL; p-value < 0.001). sTM values were correlated with the score of neurological deficits, with gender and dyslipidemia. The association of sTM values with the acute onset of AIS as an end point was significant, which allows rapid therapeutic interventions, even in the absence of a well-defined clinical syndrome (AUC = 0.99). Reanalysis of the patients after propensity score matching increased the power of sTM as a biomarker (AUC = 1). sTM represents a potentially useful biomarker to diagnose the onset of an AIS, even in scarce clinical presentations, which makes thrombomodulin a valuable indicator for early treatment initiation.
The Identification of New c-FLIP Inhibitors for Restoring Apoptosis in TRAIL-Resistant Cancer Cells
Authors: Yaacoub Katherine , Pedeux Rémy , Lafite Pierre , Jarry Ulrich , Aci-Sèche Samia , Bonnet Pascal , Daniellou Richard , Guillaudeux Thierry
Published: January 2024

The catalytically inactive caspase-8-homologous protein, c-FLIP, is a potent antiapoptotic protein highly expressed in various types of cancers. c-FLIP competes with caspase-8 for binding to the adaptor protein FADD (Fas-Associated Death Domain) following death receptors’ (DRs) activation via the ligands of the TNF-R family. As a consequence, the extrinsic apoptotic signaling pathway involving DRs is inhibited. The inhibition of c-FLIP activity in tumor cells might enhance DR-mediated apoptosis and overcome immune and anticancer drug resistance. Based on an in silico approach, the aim of this work was to identify new small inhibitory molecules able to bind selectively to c-FLIP and block its anti-apoptotic activity. Using a homology 3D model of c-FLIP, an in silico screening of 1880 compounds from the NCI database (National Cancer Institute) was performed. Nine molecules were selected for in vitro assays, based on their binding affinity to c-FLIP and their high selectivity compared to caspase-8. These molecules selectively bind to the Death Effector Domain 2 (DED2) of c-FLIP. We have tested in vitro the inhibitory effect of these nine molecules using the human lung cancer cell line H1703, overexpressing c-FLIP. Our results showed that six of these newly identified compounds efficiently prevent FADD/c-FLIP interactions in a molecular pull-down assay, as well as in a DISC immunoprecipitation assay. The overexpression of c-FLIP in H1703 prevents TRAIL-mediated apoptosis; however, a combination of TRAIL with these selected molecules significantly restored TRAIL-induced cell death by rescuing caspase cleavage and activation. Altogether, our findings indicate that new inhibitory chemical molecules efficiently prevent c-FLIP recruitment into the DISC complex, thus restoring the caspase-8-dependent apoptotic cascade. These results pave the way to design new c-FLIP inhibitory molecules that may serve as anticancer agents in tumors overexpressing c-FLIP.
Development of a Carotenoid-Rich Microalgae Colorant by Microencapsulation
Authors: Nunes Ana N. , Monte Joana , Rodríguez-Rojo Soraya , Nogueira Isabel D. , Gouveia Luís F. , Brazinha Carla , Matias Ana A.
Published: January 2024

Dunaliella salina has been recognized as an excellent biomass source of carotenoid, which can be used as a natural orange coloring agent for food products. The most eco-friendly approach for extracting carotenoid is through supercritical carbon dioxide extraction, as it yields highly concentrated extracts while preventing pigment thermal degradation. However, there are limitations when a lipophilic extract is considered a food ingredient, in particular very difficult handling and low solubility in water-based products. The aim of this study was to develop a hydrosoluble form of a natural carotenoid-rich extract recovered from algae biomass within a biorefinery concept to be incorporated in aqueous-based food products. A two-step process was developed, starting with the emulsification of the supercritical extract into a mixture of maltodextrin and gum arabic, using soy lecithin as an emulsifier. The emulsification was followed by a spray-drying step. The impact of process variables on the encapsulation yield, efficiency, emulsion properties, and particle characteristics was studied. The resulting particles exhibited an intense orange color and good water dispersibility, facilitating uniform yellow coloring when incorporated into an aqueous-based product. Overall, spray-drying emulsions containing carotenoids derived from Dunaliella salina prove to be a promising strategy for the global market demand for natural colorants.
Improving the EAR Index for Flexible Pavement and a Preliminary Definition of an Environmental Index (ECR) for Rigid Pavement
Authors: Tozzo Cristina , Chiola Davide , Pierani Matteo , Urbano Leonardo , Ricci Riccardo , Susani Stefano
Published: January 2024

Nowadays, roadway infrastructures are designed in order to satisfy technical and economical requirements, as well as to guarantee advanced environmental performance. Focusing on that, this paper deals with an innovative procedure for the characterization of pavement materials, both asphalt and cement-bound mixtures. The methodology takes its cue from a previous study in which the so-called Environmental Asphalt Rating (EAR) was firstly introduced as a reference parameter for asphalt pavements to evaluate technical offers and for the assignment of scores, in terms of environmental impacts, during the tender phase. In this work, the EAR methodology is revised with a focus on the main variations and improvements related to the new version of the ISO standard. By applying the same approach to rigid or concrete pavements, a preliminary version of the Environmental Concrete Rating (ECR) is presented. For ECR, a correction is provided regarding functionality through a fatigue-related parameter and the surface characteristics related to the IRI value. Despite its strong applicability to the pavement sector, the strength of the proposed method is its ability to be fine-tuned to different fields by varying the associated performance coefficients.
Real-World Treatment Patterns, Clinical Outcomes, and Healthcare Resource Utilization in Early-Stage Non-Small-Cell Lung Cancer
Authors: O’Sullivan Dylan E. , Boyne Devon J. , Ford-Sahibzada Chelsea , Inskip Jessica A. , Smith Christopher J. , Sripada Kaushik , Brenner Darren R. , Cheung Winson Y.
Published: January 2024

The prognosis of early non-small-cell lung cancer (eNSCLC) remains poor. An understanding of current therapies and outcomes can provide insights into how novel therapies can be integrated into clinics. We conducted a large, retrospective, population-based cohort study of patients with de novo eNSCLC (stages IB, IIA, IIB, and IIIA) diagnosed in Alberta, Canada, between 2010 and 2019. The primary objectives were to describe treatment patterns and survival outcomes among patients with eNSCLC. A total of 5126 patients with eNSCLC were included. A total of 45.3% of patients were referred to a medical oncologist, ranging from 23.7% in stage IB to 58.3% in IIIA. A total of 23.6% of patients initiated systemic therapy (ST), ranging from 3.5% in stage IB to 38.5% in IIIA. For stage IIB and IIIA individuals who received surgery, adjuvant ST was associated with a decreased likelihood of death (hazard ratios (HR) of 0.77 (95% CI: 0.56–1.07) and 0.69 (95% CI: 0.54–0.89), respectively). In a Canadian real-world setting, stage IIB and IIIA patients who received adjuvant ST tended to have better survival than patients who did not, but future studies that provide adjustment of additional confounders are warranted. Examining referral pathways that account for disparities based on age, sex, and comorbidities in the real world would also provide further insights.
An Analysis of the Use of Systemic Antifungals (Fluconazole, Itraconazole, and Terbinafine) in Galicia, Spain, between 2019 and 2022
Authors: Vázquez-Prieto Severo , Vaamonde Antonio , Paniagua Esperanza
Published: January 2024

In the present work, we examined the consumption of systemic antifungals (fluconazole, itraconazole, and terbinafine) in outpatients in the four provinces of Galicia, Spain, between 2019 and 2022. We also described the variability in the use of these types of drugs between these provinces. In addition, we detected any deviation in consumption at a seasonal level and analyzed possible changes during the study period. A descriptive, cross-sectional, and retrospective study of the use of antifungals, expressed in terms of a defined daily dose per 1000 inhabitants per day, was carried out. The results obtained revealed statistically significant differences between provinces and by the active principle consumed in the four Galician provinces (p < 0.001), which can be explained by multiple factors. This study also revealed that there was stable consumption during the study period, with no significant seasonal differences observed. This study represents a contribution to the knowledge about the consumption of antifungals for systemic use in Galicia and serves as a basis for subsequent studies. This will allow us to understand the consumption patterns of these types of drugs and, ultimately, will help to establish stewardship strategies and prevent the development of resistance.
Energy Efficiency in Petroleum Supply Chain Optimization: Push Segment Coordination
Authors: Redutskiy Yury , Balycheva Marina
Published: January 2024

Today, the world is transitioning from traditional energy to clean, renewable sources. The petroleum sector is to play a role in this transition by supporting material and energy needs related to developing new energy systems. It is, therefore, vital that in upcoming years, the petroleum sector runs in a smart and efficient way, which can be achieved by coordination and the meaningful integration of decision-making issues in petroleum supply chains (PSCs). The existing literature on PSC optimization reveals a research gap; specifically, there is an insufficient level of technological detail considered while planning capacities of new infrastructures and its impact on the efficiency of further operations, specifically in the push segment of the PSC. This paper proposes a mixed-integer nonlinear programming model for planning capacities and coordinating activities within the mentioned PSC segment. The infrastructure capacity planning model covers technological details such as hydraulics and pump systems’ operational efficiency. The results reveal that the proposed model and its technological decision-making criterion of minimizing energy consumption drive infrastructural choices and operational modes to achieve machinery performance close to the best efficiency point. Also, the computational results demonstrate how traditional (minimum-cost) approaches lead to inefficient energy use while producing and transporting hydrocarbons. The proposed framework aims to facilitate the preliminary design stage of projects undertaken by engineering contractors in the energy sector.
Dynamic of H2NG in Distribution Systems
Authors: Eparu Cristian Nicolae , Stoica Doru Bogdan , Neacsa Adrian , Radulescu Renata , Chiritescu Dragos , Prundurel Alina Petronela , Ionete Bogdan
Published: January 2024

The reduction in GHG emissions has become one of the most important objectives in Europe. One of these clean technologies in the quest for large-scale decarbonisation is the blending of hydrogen and natural gas (H2NG). The significance of this article lies in conducting a technical–economic analysis that relies on simulating annual consumption patterns. This study focuses on the utilization of H2NG at different proportions within a distribution network in Bucharest, Romania’s largest city. The paper is a fallow up of another paper and presents a case study for the injection through all four entry points in the city of different percentages of hydrogen and the dynamic of the mix through the gas distribution network. The study found that the variation in H2 in the network is high and depends on the entry point levels and consumption. An economic analysis was conducted on seasonal real consumption, which confirmed the investment’s profitability.
A Journey to Hear: The Evolution of Cochlear Implants
Authors: Athanasopoulos Michail , Samara Pinelopi , Athanasopoulos Ioannis
Published: January 2024

Cochlear implants (CIs), a revolutionary breakthrough in auditory technology, have profoundly impacted the lives of individuals with severe hearing impairment. Surgically implanted behind the ear and within the delicate cochlea, these devices represent a direct pathway to restoring the sense of hearing. Implanting hope alongside innovation, their captivating history unfolds through pivotal dates and transformative milestones. From the first human implantation by Drs. William House and John Doyle in 1961 to FDA approval in 1984, each step in their evolution mirrors a triumph of human ingenuity. The 1990s witnessed significant miniaturization, enhancing accessibility, while the 21st century brought about improvements in speech processing and electrode technology. These strides have elevated CIs beyond functional devices to life-changing instruments, enriching both auditory experiences and communication skills. This entry delves into the captivating history of CIs, spotlighting key dates that paint a vivid picture of challenges overcome and remarkable progress achieved. It explores the people and moments that defined their development, ultimately shaping these implants into indispensable tools that continually redefine the landscape of hearing assistance.
Co-Creation
Authors: Ertz Myriam
Published: January 2024

Co-creation has gained traction in recent years and various fields, including marketing, product development, and innovation studies, as it leverages the collective expertise and insights of multiple parties to enhance outcomes. Broadly, co-creation refers to the collaborative process of involving stakeholders, such as customers, suppliers, employees, or the public, in creating or improving products, services, or experiences.
Long-Term Patterns in Forest Soil CO2 Flux in a Pacific Northwest Temperate Rainforest
Authors: Fischer Dylan G. , Chamberlain Zoe R. , Cook Claire E. , Martin Randall Adam , Mueller Liam O.
Published: January 2024

Soil CO2 efflux (Fs) plays an important role in forest carbon cycling yet estimates of Fs can remain unconstrained in many systems due to the difficulty in measuring Fs over long time scales in natural systems. It is important to quantify seasonal patterns in Fs through long-term datasets because individual years may show patterns that are not reflective of long-term averages. Additionally, determining predictability of net patterns in soil carbon flux based on environmental factors, such as moisture and temperature, is critical for appropriately modeling forest carbon flux. Ecosystems in moderate climates may have strong CO2 efflux even during winter, and so continuous quantification of annual variability is especially important. Here, we used a 2008–2023 dataset in a lowland temperate forest ecosystem to address two main questions: (1) What are the seasonal patterns in Fs in a highly productive temperate rainforest? (2) How is average Fs across our study area predicted by average coincident temperature, soil moisture and precipitation totals? Data showed clear seasonality where Fs values are higher in summer. We also find Fs across our measurement network was predicted by variation in abiotic factors, but the interaction between precipitation/moisture and temperature resulted in greater complexity. Specifically, in spring a relatively strong relationship between air temperature and Fs was present, while in summer the relationship between temperature and Fs was flat. Winter and autumn seasons showed weak positive relationships. Meanwhile, a negative relationship between precipitation and Fs was present in only some seasons because most precipitation falls outside the normal growing season in our study system. Our data help constrain estimates of soil CO2 fluxes in a temperate rainforest ecosystem at ~14–20 kg C ha−1 day−1 in summer and autumn, and 6.5–10.5 kg C ha−1 day−1 in winter and spring seasons. Together, estimates suggest this highly productive temperate rainforest has annual soil-to-atmosphere fluxes of CO2 that amount to greater than 4.5 Mg C ha−1 year−1. Sensitivity of such fluxes to regional climate change will depend on the balance of Fs determined by autotrophic phenological responses versus heterotrophic temperature and moisture sensitivity. Relatively strong seasonal variation coupled with comparatively weak responses to abiotic variables suggest Fs may be driven largely by seasonal trends in autotrophic respiration. Accordingly, plant and tree responses to climate may have a stronger effect on Fs in the context of climate change than temperature or moisture changes alone.
Three Censuses of a Mapped Plot in Coastal California Mixed-Evergreen and Redwood Forest
Authors: Gilbert Gregory S. , Carvill Sarah G. , Krohn Alexander R. , Jones Alexander S.
Published: January 2024

Large, mapped forest research plots are important sources of data to understand spatial and temporal changes in forest communities in the context of global change. Here, we describe the data from the first three censuses of the 16-ha UC Santa Cruz Forest Ecology Research Plot, located in the Mediterranean-climate forest on the central coast of California, USA. The forest includes both mixed-evergreen forest and redwood-dominated forest and is recovering from significant logging disturbances in the early 20th century. Each woody stem with a diameter ≥ 1 cm at 1.3 m was mapped, tagged, identified, and measured, with censuses performed at ~5-year intervals. The first census included just 6 ha (previously described), and the area was then expanded to 16 ha in the second census. We describe the temporal dynamics of the forest in the original 6 ha, as well as the structure and temporal dynamics of the full 16 ha. The community includes 34 woody species, including 4 gymnosperm and 9 angiosperm tree species, 18 species of shrubs, and 3 species of lianas. The community includes eight non-native species, representing less than 0.5% of the stems. More than half the species show greater rates of mortality than recruitments, reflective of a dynamic forest community. Over a decade, the number of living woody stems has declined, but the basal area has increased, reflecting a self-thinning process.
Studies on the Inhibition Mechanism of Linalyl Alcohol against the Spoilage Microorganism Brochothrix thermosphacta
Authors: Wang Longteng , Liu Xing , Chen Wenxue , Sun Zhichang
Published: January 2024

The aim of this study was to investigate the bacterial inhibitory ability and mechanism of action of linalyl alcohol against B. thermosphacta. Linalyl alcohol causes the leakage of intracellular material by disrupting the cell wall and exposing the hydrophobic phospholipid bilayer, which binds to bacterial membrane proteins and alters their structure. In addition, linalyl alcohol causes cell membrane damage by affecting fatty acids and proteins in the cell membrane. By inhibiting the synthesis of macromolecular proteins, the normal physiological functions of the bacteria are altered. Linalyl alcohol binds to DNA in both grooved and embedded modes, affecting the normal functioning of B. thermosphacta, as demonstrated through a DNA interaction analysis.
Diversity of ‘Cabernet Sauvignon’ Grape Epidermis and Environmental Bacteria in Wineries from Different Sub-Regions of the Eastern Foothills of Helan Mountain, Ningxia
Authors: Yang Hui , Wang Zheng , Zhang Zhong , Shu Chao , Zhu Jiaqi , Li Ying , Zhang Junxiang
Published: January 2024

Understanding the composition of the bacterial community on the epidermis of wine grapes and in winery environments, as well as the response of grape epidermal bacteria to climatic factors, plays a significant role in ensuring grape health and promoting grape conversion into wine. This study utilized high-throughput sequencing to explore the composition of the bacterial community on the wine grape epidermis and representative wineries of three sub-regions of the Eastern Foothills of Helan Mountain, Ningxia. The results showed that the bacterial diversity and richness in the Yongning (YN) sub-region were the highest, with Qingtongxia (QTX) having the lowest levels of grape epidermal bacteria. The bacterial diversity and richness were the highest in Yinchuan (YC) and the lowest in YN in the winery environment (p < 0.05). The composition of dominant bacteria on the grape epidermis and in winery environments of the three sub-regions was not different at the phylum and genus level, but the levels of these dominant bacteria were different among the sub-regions. There was a correlation between grape epidermal bacteria and climatic factors. Approximately 93% of the bacterial genera on the grape epidermal genera in the three sub-regions are present in the winery environment and contain all the dominant bacterial genera on the epidermis.
Stability in the Sense of Hyers–Ulam–Rassias for the Impulsive Volterra Equation
Authors: El-hady El-sayed , Öğrekçi Süleyman , Lazăr Tania A. , Lazăr Vasile L.
Published: January 2024

This article aims to use various fixed-point techniques to study the stability issue of the impulsive Volterra integral equation in the sense of Ulam–Hyers (sometimes known as Hyers–Ulam) and Hyers–Ulam–Rassias. By eliminating key assumptions, we are able to expand upon and enhance some recent findings.
A Mixed Finite Element Method for the Multi-Term Time-Fractional Reaction–Diffusion Equations
Authors: Zhao Jie , Dong Shubin , Fang Zhichao
Published: January 2024

In this work, a fully discrete mixed finite element (MFE) scheme is designed to solve the multi-term time-fractional reaction–diffusion equations with variable coefficients by using the well-known L1 formula and the Raviart–Thomas MFE space. The existence and uniqueness of the discrete solution is proved by using the matrix theory, and the unconditional stability is also discussed in detail. By introducing the mixed elliptic projection, the error estimates for the unknown variable u in the discrete L∞(L2(Ω)) norm and for the auxiliary variable λ in the discrete L∞((L2(Ω))2) and L∞(H(div,Ω)) norms are obtained. Finally, three numerical examples are given to demonstrate the theoretical results.
Hereditary Angioedema: Novel Molecules for Treatment of Acute Attacks and Long-Term Prophylaxis
Authors: Covella Bianca , Giliberti Marica , Montinaro Adriano , Rossi Luigi , Montinaro Vincenzo
Published: January 2024

Hereditary angioedema (HAE) is a rare disease caused by a genetic alteration of the SERPING1 gene and characterized by recurrent attacks of angioedema that involve the skin, and the mucosae of the gastrointestinal tract and upper airways, which significantly affect the quality of life of patients. Nowadays there are effective drugs for both 1. treating acute attacks and 2. preventing attacks with a long-term prophylaxis. However, there are some unmet needs for HAE treatment, and therefore several novel molecules are under active testing for this clinical condition. Novel drugs will simplify the mode of administration (oral versus parenteral for both on demand treatment or long-term prophylaxis), prolong the interval between administrations (up to 3–6 months of efficacy with a single administration), target more specifically the central enzymes involved in the generation of bradykinin, the ultimate mediator of angioedema (prekallikrein, activated plasma kallikrein or activated factor XII), and potentially determine a definitive cure for the disease by genetic manipulation of the altered gene (SERPING1) or other downstream genes (KLKB1). In this review we provide a panoramic view of all new medications that are under active experimentation and will probably transform and enrich all of the therapeutic armamentarium for treating this disease.
Effect of Policies to Accelerate the Adoption of Battery Electric Vehicles in Finland—A Delphi Study
Authors: Nair Sheba , Viri Riku , Mäkinen Johanna , Pöllänen Markus , Liimatainen Heikki , O’Hern Steve
Published: January 2024

Greenhouse gas (GHG) emissions from transport contribute significantly to climate change. Some of the transport policies with the greatest potential to mitigate climate change are related to zero-emission vehicles. This study aimed to analyse the different factors, and their importance, influencing purchase decisions for battery electric vehicles (BEV). Experts’ perceptions were collected with a Delphi study consisting of a two-round survey to assess factors that would increase the probability of a petrol- or diesel-car owner purchasing a BEV in Finland in the year 2025. Increasing the possibilities for home charging and the provision of a purchase subsidy were seen as the most important factors. Public fast charging and the difference in use costs between current technology vehicles and BEVs were also recognised as important factors. Existing systems of financial instruments and policies must be constantly evaluated and updated due to the evolving BEV industry.
Sex and Ethnic Disparities during COVID-19 Pandemic among Acute Coronary Syndrome Patients
Authors: Alharbi Abdulmajeed , Elzanaty Ahmed , Safi Mohammad , Shah Momin , Alfatlawi Halah , Holtzapple Zachary , Jabr Abed , Eltahawy Ehab
Published: January 2024

Introduction: The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) caused a global pandemic that emerged in 2019. During this period, a significant disparity in hospitalization and mortality rates emerged, particularly in terms of Ethnicity and sex. Notably, this study aims to examine the influence of sex and Ethnicity on acute coronary syndrome outcomes, specifically during the global SARS-CoV-2 pandemic. Methods: This retrospective observational study analyzed adult patients hospitalized with a primary diagnosis of acute coronary syndrome in the United States in 2020. Primary outcomes included inpatient mortality and the time from admission to percutaneous coronary intervention (PCI). Secondary outcomes encompassed the length of stay and hospital costs. The National Inpatient Sample (NIS) database was utilized to identify and study patients in our test group. Results: A total of 779,895 patients hospitalized with a primary diagnosis of acute coronary syndrome in the year 2020 and 935,975 patients in 2019 were included in this study. Baseline findings revealed that inpatient mortality was significantly higher in 2020 compared to 2019, regardless of sex and Ethnicity (adjusted odds ratio (aOR) 1.20, 95% confidence interval (CI) 1.12–1.23, p-value < 0.001). Concerning primary outcomes, there was no difference in inpatient mortality for hospitalized patients of different sexes between 2019 and 2020 (STEMI: aOR 1.05, 95% CI 0.96–1.14, p-value 0.22; NSTEMI/UA aOR 1.08, 95% CI 0.98–1.19, p-value 0.13). Regarding time to admission for PCI, NSTEMI/UA cases were found to be statistically significant in female patients compared to males (mean difference 0.06 days, 95% CI 0.02–0.10, p-value < 0.01) and African Americans compared to Caucasians (mean difference 0.13 days, 95% CI 0.06–0.19, p < 0.001). In terms of the length of stay, female patients had a shorter length of stay compared to males (mean difference −0.22, 95% CI −0.27 to −0.16, p-value < 0.01). Conclusions: As acute coronary syndrome is an urgent diagnosis, a global pandemic has the potential to exacerbate existing healthcare disparities related to sex and Ethnicity. This study did not reveal any difference in inpatient mortality, aligning with studies conducted prior to the pandemic. However, it highlighted significantly longer treatment times (admission to PCI) for NSTEMI/UA management in female and African American populations. These findings suggest that some disparities may have diminished during the pandemic year, warranting further research to confirm these trends in the years to come.
Historical Use of Travertine in the Tuscan Architecture (Italy)
Authors: Rescic Silvia , Fratini Fabio , Cuzman Oana Adriana , Sacchi Barbara
Published: January 2024

The landscape of an area is not only made up of natural elements but also of man-made elements represented by civil and agricultural artefacts and much more. These elements used to blend aesthetically and harmoniously with the landscape itself thanks to the use of local building materials. Particularly, this contribution examines the use of the travertine in the architecture of the Tuscany region from the Etruscan time to the contemporary age. In Tuscany, travertine is a remarkable example of an identity stone of the territory, so rich in thermal springs that favoured the formation of large deposits of this stone widely used in public and private buildings both in interior design and urban furnishing. The work was carried out through a survey in the Tuscan territory and collection of bibliographic information on the architectural web sites. The survey made it possible to collect a photographic documentation and to assess the state of conservation through the empirical observation of the morphologies of decay when present. Indeed, this stone material in the Mediterranean climate, which characterises Tuscany, shows a good durability against atmospheric agents but may be affected by a chromatic alteration that tends to give the surfaces a greyish appearance. This aesthetic issue is more evident in the Tuscan travertine due to is classic whitish colour.
How Is Telehealth Currently Being Utilized to Help in Hypertension Management within Primary Healthcare Settings? A Scoping Review
Authors: Idris Haerawati , Nugraheni Wahyu Pudji , Rachmawati Tety , Kusnali Asep , Yulianti Anni , Purwatiningsih Yuni , Nuraini Syarifah , Susianti Novia , Faisal Debri Rizki , Arifin Hidayat , Maharani Asri
Published: January 2024

Telehealth has improved patient access to healthcare services and has been shown to have a positive impact in various healthcare settings. In any case, little is understood regarding the utilization of telehealth in hypertension management in primary healthcare (PHC) settings. This study aimed to identify and classify information about the types of interventions and types of telehealth technology in hypertension management in primary healthcare. A scoping review based on PRISMA-ScR was used in this study. We searched for articles in four databases: Pubmed, Scopus, Science Direct, and Embase in English. The selected articles were published in 2013–2023. The data were extracted, categorized, and analyzed using thematic analysis. There were 1142 articles identified and 42 articles included in this study. Regarding the proportions of studies showing varying trends in the last ten years, most studies came from the United States (US) (23.8%), were conducted in urban locations (33.3%), and had a quantitative study approach (69%). Telehealth interventions in hypertension management are dominated by telemonitoring followed by teleconsultation. Asynchronous telehealth is becoming the most widely used technology in managing hypertension in primary care settings. Telehealth in primary care hypertension management involves the use of telecommunications technology to monitor and manage blood pressure and provide medical advice and counselling remotely.
NSD3 in Cancer: Unraveling Methyltransferase-Dependent and Isoform-Specific Functions
Authors: Nuñez Yanara , Vera Sebastian , Baeza Victor , Gonzalez-Pecchi Valentina
Published: January 2024

NSD3 (nuclear receptor-binding SET domain protein 3) is a member of the NSD histone methyltransferase family of proteins. In recent years, it has been identified as a potential oncogene in certain types of cancer. The NSD3 gene encodes three isoforms, the long version (NSD3L), a short version (NSD3S) and the WHISTLE isoforms. Importantly, the NSD3S isoform corresponds to the N-terminal region of the full-length protein, lacking the methyltransferase domain. The chromosomal location of NSD3 is frequently amplified across cancer types, such as breast, lung, and colon, among others. Recently, this amplification has been correlated to a chromothripsis event, that could explain the different NSD3 alterations found in cancer. The fusion proteins containing NSD3 have also been reported in leukemia (NSD3-NUP98), and in NUT (nuclear protein of the testis) midline carcinoma (NSD3-NUT). Its role as an oncogene has been described by modulating different cancer pathways through its methyltransferase activity, or the short isoform of the protein, through protein interactions. Specifically, in this review we will focus on the functions that have been characterized as methyltransferase dependent, and those that have been correlated with the expression of the NSD3S isoform. There is evidence that both the NSD3L and NSD3S isoforms are relevant for cancer progression, establishing NSD3 as a therapeutic target. However, further functional studies are needed to differentiate NSD3 oncogenic activity as dependent or independent of the catalytic domain of the protein, as well as the contribution of each isoform and its clinical significance in cancer progression.
KCNQ1 p.D446E Variant as a Risk Allele for Arrhythmogenic Phenotypes: Electrophysiological Characterization Reveals a Complex Phenotype Affecting the Slow Delayed Rectifier Potassium Current (IKs) Voltage Dependence by Causing a Hyperpolarizing Shift and a Lack of Response to Protein Kinase A Activation
Authors: González-Garrido Antonia , López-Ramírez Omar , Cerda-Mireles Abel , Navarrete-Miranda Thania , Flores-Arenas Aranza Iztanami , Rojo-Domínguez Arturo , Arregui Leticia , Iturralde Pedro , Antúnez-Argüelles Erika , Domínguez-Pérez Mayra , Jacobo-Albavera Leonor , Carnevale Alessandra , Villarreal-Molina Teresa
Published: January 2024

Genetic testing is crucial in inherited arrhythmogenic channelopathies; however, the clinical interpretation of genetic variants remains challenging. Incomplete penetrance, oligogenic, polygenic or multifactorial forms of channelopathies further complicate variant interpretation. We identified the KCNQ1/p.D446E variant in 2/63 patients with long QT syndrome, 30-fold more frequent than in public databases. We thus characterized the biophysical phenotypes of wildtype and mutant IKs co-expressing these alleles with the β-subunit minK in HEK293 cells. KCNQ1 p.446E homozygosity significantly shifted IKs voltage dependence to hyperpolarizing potentials in basal conditions (gain of function) but failed to shift voltage dependence to hyperpolarizing potentials (loss of function) in the presence of 8Br-cAMP, a protein kinase A activator. Basal IKs activation kinetics did not differ among genotypes, but in response to 8Br-cAMP, IKs 446 E/E (homozygous) activation kinetics were slower at the most positive potentials. Protein modeling predicted a slower transition of the 446E Kv7.1 tetrameric channel to the stabilized open state. In conclusion, biophysical and modelling evidence shows that the KCNQ1 p.D446E variant has complex functional consequences including both gain and loss of function, suggesting a contribution to the pathogenesis of arrhythmogenic phenotypes as a functional risk allele.
Natural-Origin Betaine Surfactants as Promising Components for the Stabilization of Lipid Carriers
Authors: Pucek-Kaczmarek Agata , Celary Dominika , Bazylińska Urszula
Published: January 2024

In the present work, we demonstrate studies involving the influence of the formulation composition on the physicochemical properties of nanocarriers: solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs). Novel lipid-origin platforms were prepared using two “green” betaine-based surfactants, cocamidopropyl betaine (ROKAmina K30) and coco betaine (ROKAmina K30B), in combination with three different solid lipids, cetyl palmitate (CRODAMOL CP), trimyristin (Dynasan 114), and tristearin (Dynasan 118). Extensive optimization studies included the selection of the most appropriate lipid and surfactant concentration for effective SLN and NLC stabilization. The control parameters involving the hydrodynamic diameters of the obtained nanocarriers along with the size distribution (polydispersity index) were determined by dynamic light scattering (DLS), while shape and morphology were evaluated by atomic force microscopy (AFM) and transmission electron microscopy (TEM). Electrophoretic light scattering (ELS) and turbidimetric method (backscattering profiles) were used to assess colloidal stability. The studied results revealed that both betaine-stabilized SLN and NLC formulations containing CRODAMOL CP as lipid matrix are the most monodisperse and colloidally stable regardless of the other components and their concentrations used, indicating them as the most promising candidates for drug delivery nanosystems with a diverse range of potential uses.
PAMPs and DAMPs in Sepsis: A Review of Their Molecular Features and Potential Clinical Implications
Authors: Cicchinelli Sara , Pignataro Giulia , Gemma Stefania , Piccioni Andrea , Picozzi Domitilla , Ojetti Veronica , Franceschi Francesco , Candelli Marcello
Published: January 2024

Sepsis is a serious organ dysfunction caused by a dysregulated immune host reaction to a pathogen. The innate immunity is programmed to react immediately to conserved molecules, released by the pathogens (PAMPs), and the host (DAMPs). We aimed to review the molecular mechanisms of the early phases of sepsis, focusing on PAMPs, DAMPs, and their related pathways, to identify potential biomarkers. We included studies published in English and searched on PubMed® and Cochrane®. After a detailed discussion on the actual knowledge of PAMPs/DAMPs, we analyzed their role in the different organs affected by sepsis, trying to elucidate the molecular basis of some of the most-used prognostic scores for sepsis. Furthermore, we described a chronological trend for the release of PAMPs/DAMPs that may be useful to identify different subsets of septic patients, who may benefit from targeted therapies. These findings are preliminary since these pathways seem to be strongly influenced by the peculiar characteristics of different pathogens and host features. Due to these reasons, while initial findings are promising, additional studies are necessary to clarify the potential involvement of these molecular patterns in the natural evolution of sepsis and to facilitate their transition into the clinical setting.
From Synaptic Physiology to Synaptic Pathology: The Enigma of α-Synuclein
Authors: Nordengen Kaja , Morland Cecilie
Published: January 2024

Alpha-synuclein (α-syn) has gained significant attention due to its involvement in neurodegenerative diseases, particularly Parkinson’s disease. However, its normal function in the human brain is equally fascinating. The α-syn protein is highly dynamic and can adapt to various conformational stages, which differ in their interaction with synaptic elements, their propensity to drive pathological aggregation, and their toxicity. This review will delve into the multifaceted role of α-syn in different types of synapses, shedding light on contributions to neurotransmission and overall brain function. We describe the physiological role of α-syn at central synapses, including the bidirectional interaction between α-syn and neurotransmitter systems.