bluuebunny/crossref_metadata_2025 huggingface dataset:
Cold Collapse and Bounce of a FLRW Cloud
Authors: Pradhan Swaraj , Gabler Michael , Gaztanaga Enrique
Published: October 2024

We study the collapse of spherical cold clouds beyond black hole (BH) formation to investigate the possibility of a bounce in the in-falling matter when a critical density or pressure is reached. As a first step, we analyze the pressureless collapse in general relativity (GR), where an analytic solution exists, and demonstrate that an equivalent Newtonian solution can be derived. Such equivalence also holds for spherically symmetric perfect fluids with uniform density and non-vanishing pressure. We numerically investigate the Newtonian collapse of such clouds with masses of $5$, $20$, and $1000$ M$_\odot$ obeying a polytropic equation of state (EoS). By choosing EoS parameters inspired by typical neutron star conditions, we observe bounces at and above nuclear saturation density. Assuming approximate uniformity, we explore the equivalent GR behaviour of the matter during the bounce. Our findings are: i) A GR bounce occurs around the ground state of the matter, characterized by $P = -\rho$. ii) The GR solution significantly differs from the Newtonian result due to the presence of curvature ($k \neq 0$). iii) Both the curvature and the ground state are crucial factors in allowing a GR bounce to occur.
Standard versus Reduced CDK4/6 Inhibitor Therapy in Elderly Patients with Metastatic Hormone Receptor‐Positive, HER2‐Negative Breast Cancer: An Observational Multicenter Study
Authors: Fedele Palma , Landriscina Matteo , Moraca Lucia , Gadaleta-Caldarola Arianna , Cusmai Antonio , Giuliani Francesco , Chiuri Vincenzo , Giotta Francesco , Pinto Antonello , Mirisola Valentina , Gadaleta-Caldarola Gennaro
Published: October 2024

Background
CDK4/6 inhibitors are the standard of care for HR+/HER2-negative metastatic breast cancer in combination with endocrine therapy. However, the real-world efficacy and safety of standard versus reduced doses in elderly patients remain unclear. This study aims to compare the clinical outcomes of standard versus reduced doses of CDK4/6 inhibitors in elderly patients with metastatic breast cancer.
Methods
This multicenter retrospective cohort study included 158 patients aged ≥70 years diagnosed with HR+/HER2-negative metastatic breast cancer who received either standard or reduced doses of CDK4/6 inhibitors (Ademaciclib, Ribociclib, Palbociclib) as first-line therapy. Progression-free survival (PFS), overall survival (OS), and adverse events (AEs) were evaluated. PFS and OS were estimated using the Kaplan-Meier method, and comparisons between groups were performed using the log-rank test.
Results
Of the total population, 108 patients (68.4%) received the standard dose, and 50 patients (31.6%) received a reduced dose. The standard dose group had significantly longer median PFS compared to the reduced dose group (21.3 vs. 15.2 months, p = 0.014), while median OS did not differ significantly (37.2 vs. 37.2 months, p = 0.103). Subgroup analyses revealed no significant differences in PFS or OS between standard and reduced doses for Ademaciclib and Ribociclib, while Palbociclib at standard dose showed superior PFS (21.9 vs. 12.7 months, p = 0.029) and OS (50.5 vs. 28.6 months, p = 0.026). The incidence of Grade 2-4 AEs was higher in the standard dose group (74.2% vs. 56.8%, p = 0.044).
Conclusions
Dose reduction of CDK4/6 inhibitors, particularly Ademaciclib and Ribociclib, is a viable option in elderly patients, maintaining comparable OS outcomes to standard dosing while reducing the risk of adverse events. Palbociclib at standard dose may offer superior outcomes. These findings support personalized dosing strategies to optimize efficacy and tolerability in frail or elderly patients.
Glycemic Control Efficacy of ‘Avaram Amrit’ in Type 2 Diabetes Mellitus: A 12-Week Open-Label Clinical Trial
Authors: Arivarasan Vishnu Kirthi , Karthik Ramapriya , Gangarapu Kiran , Suman Sangeethalakshmi , P Sathyarajeswaran , M.S. Shree Devi
Published: October 2024

Background: Avaram Amrit, derived from a traditional medicinal plant, has shown potential in diabetes management. This study aimed to evaluate its clinical efficacy in glycemic control. Methods: A 12-week, open-label clinical trial was conducted with 9 type 2 diabetes patients. Participants received Avaram Amrit extract daily. Fasting and postprandial glucose levels were measured bi-weekly, with HbA1c assessed at baseline and week 12. Results: Fasting glucose levels decreased significantly from 252.54 ± 71.99 mg/dL at baseline to 195.50 ± 55.01 mg/dL at week 12 (p<0.001), representing a 22.6% reduction. Mean HbA1c decreased by 1.25 percentage points. Postprandial glucose levels showed consistent improvement across the study period. A strong positive correlation was observed between initial HbA1c and fasting glucose (r=0.89). Conclusion: Avaram Amrit demonstrated significant improvement in glycemic control over 12 weeks. The consistent decrease in both short-term (glucose levels) and long-term (HbA1c) measures indicates a positive response to the intervention. While promising, larger randomized controlled trials are necessary to confirm these findings and establish Avaram Amrit's role in diabetes management.
Physical, Textural and Sensory Properties of Spreadable Processed Whey Cheese as Affected by Addition of Polysaccharides
Authors: Chatziantoniou Soumela E. , Thomareis Apostolos S.
Published: October 2024

Different polysaccharides, namely xanthan gum, guar gum, locust bean gum and κ-carrageenan were used as stabilizers, individually or in mixtures (50:50), in order to prepare nine (9) spreadable processed whey cheese (PWC) samples: X, G, L, C, X/G, X/L, C/X, C/G, and C/L. The pH and chemical composition of samples were constant. The impact of polysaccharides on the physical, textural, and sensory characteristics of PWC samples was examined, revealing significant differences (P<0.05) in all assessed properties among the samples. PWC samples had an off-white color with a slight yellowish hue. All samples were stable emulsion gels, with free oil formation values ​​ranging between 4% (X/L) and 12% (C/G). Textural properties, as determined by texture profile analysis, highly correlated with physical and sensory attributes. The PWC samples X, G, L, X/G and C/X were less hard, while they were rated by panelists as having increased fattiness, stickiness, as well as texture and overall acceptability. Sample X was the softest and the most cohesive, adhesive, springy, stringy and gummy, in comparison to the other PWC samples. In contrast, brittleness and increased hardness were exhibited by the samples C, C/G, C/L and X/L, which were judged unsuitable for spreading by the panelists. In conclusion, the development of such cheeses aims not only at the production of tasty and nutritious products, but also at sustainability, as it utilizes whey, which is a by-product of cheese making.
Towards Precision Sports Nutrition: A Scoping Review of Systems Biology Approaches in Endurance Athletes
Authors: Bedrač Leon , Deutsch Leon , Terzić Sanja , Červek Matej , Šelb Julij , Ašič Urška , Verstraeten Laure M G , Kuščer Enej , Cvetko Filip
Published: October 2024

Background: Endurance athletes require personalized nutrition strategies to optimize performance, recovery, and training adaptations. While traditional sports nutrition guidelines provide a foundation for personalization, individual variability in metabolic responses underscores the need for precision nutrition, tailored to genetic, biological, and environmental factors. This scoping review evaluates the application of systems biology-driven sports nutrition for endurance athletes, focusing on ‘omics’ and wearable technologies. Methods: A scoping review of the literature was conducted following PRISMA guidelines across PubMed, Scopus, and Web of Science with the following inclusion criteria: original research in English, involving endurance athletes, systems biology approaches, and nutritional interventions or continuous glucose monitoring (CGM). Relevant data were extracted in a systematic way. Results: Forty-eight reports were included with running as most studied sport. Eleven reports used metabolomics, ten nutrigenetics, nine metagenomics, nine CGM, six multi-omics, one proteomics, one epigenomics, and one lipidomics. Over half (62%) were randomized controlled trials (RCTs). Most studies were proof-of-concept investigations aimed at assessing biomarkers; however, the evidence linking these biomarkers to performance, recovery, and long-term health outcomes in endurance athletes remains insufficient. Significant inter-individual variability in responses to exercise and nutritional interventions was observed. Furthermore, many studies were constrained by small sample sizes and inadequate reporting of training status. Conclusions: While evidence is limited, some of the reviewed papers suggest a potential utility of systems biology-driven nutritional recommendations for endurance athletes. Future research should focus on well-powered replicated crossover RCTs, 360-degree systems-wide approaches, and validation of genetic impacts on nutritional interventions to refine dietary guidelines.
Influence of Soil Ecological Stoichiometry on aboveground biomass Under Fertilizer Application and Mixed Sowing Treatments
Authors: Zhou Juanjuan , Xia Fei , Cao Wenxia , Wei Wei
Published: October 2024

The construction of artificial grasslands using native species is an effective measure to restore degraded grassland. In this study, three native grass species, Elymus nutans, Elymus tangutorum and Poa litwinowiana, domesticated in the northern Tibetan Plateau, were used as test subjects. Three monocultures El. N, El. T and Po. L and four mixed combinations El. N+El. T, El. N+Po. L, El. T+Po. L and El. N + El. T + Po. L were set up, with 7 sowing combinations as the main zones, and nested fertilization and non-fertilization as the secondary zones. The optimal sowing combinations were selected to clarify the community growth dynamics of different grass pasture, and to investigate the transgressive overyielding and diversity effects of artificial grassland and the response of soil chemometrics to fertilizer application, with a view to providing a scientific basis for ecological restoration of degraded grassland in the northern Tibetan Plateau. The results show that the different sowing combinations of grassland all exhibit significant growth, with aboveground biomass peaking on 20 September. The type of El. N is the dominant community of the mixed combinations. The forage yield was highest in the combination, and the fertilization treatment significantly increased the forage yield. El. N + El. T + Po. L mixed sowing with fertilizer application is the recommended methodology to establish artificial grassland in the northern Tibetan Plateau. The relative yield totals of the mixed combinations were all greater than 1, and all were transgressive overyielding. Combined with the analysis of the distribution of soil ecological stoichiometric characteristics under fertilizer and non-fertilizer treatments, it was found that aboveground biomass and transgressive overyielding coefficients responded to soil ecological stoichiometry in completely different ways. Under the unfertilized treatment, soil C, N and P are regulated primarily through microbial stoichiometry under the resource dependence of soil dissolved nutrient stoichiometry, which affected aboveground of artificial grassland. Under the fertilizer treatment, microbially mediated extracellular enzyme stoichiometry was dynamically changing to regulate the new substrate environmental supply and demand balance derived from fertilizer application. Future research should further explore the long-term effects of these combinations under different environmental conditions and integrate other ecological restoration techniques to enhance the sustainability and ecological benefits of artificial grasslands. This will help achieve ecological balance and efficient utilization of forage resources in the Tibetan Plateau region, providing a more comprehensive scientific basis for regional environmental protection.
Theoretical Study of Electron-Surface Optical Phonon Interaction in Monolayer Transition Metal Dichalcogenides Deposited on SiC and Hexagonal BN Dielectric Substrates in the Vicinity of the Points K+ K- of the Brillouin Zone
Authors: Mahdouani Mounira , Bourguiga Ramzi , Gardelis Spiros
Published: October 2024

We investigated theoretically the electron-surface optical phonon interaction across the long-range Fröhlich coupling in monolayer transition metal dichalcogenides such as WS2, WSe2, MoS2, and MoSe2 monolayers on SiC and hexagonal BN dielectric substrates. We employed the effective Hamiltonian in the 〖K_(+ ) (K〗_-) valley of the hexagonal Brillouin zone, to assess electronic energy shifts induced by the interaction between electronic states and surface polar optical phonons. Our results indicate that the interaction between electron and surface optical phonon depends upon the polar nature of the substrate. We have also calculated the polaronic oscillator strength as well as the polaronic scattering rate of the lower polaron state in monolayer WS2, WSe2, MoS2, and MoSe2 on SiC and hexagonal BN dielectric substrates. As a result, we have proved theoretically; firstly, the enhancement of polaronic scattering rate with temperature, and secondly, the notable influence of the careful selection of surrounding dielectrics on both Polaronic oscillator strength and polaronic scattering rate. Thus, the optimal dielectrics would be those exhibiting both elevated optical phonon energy and a high static dielectric constant.
Developmental Origins of Non-Communicable Chronic Diseases: Role of Fetal Undernutrition and Gut Dysbiosis in Infancy
Authors: Chandra Manju m
Published: October 2024

Globally, there is increasing prevalence of non- communicable chronic diseases (NCCD) like obesity, metabolic syndrome, type2 diabetes mellitus (T2DM), hypertension, allergic asthma and neuro-developmental/psychiatric problems making NCCD a leading cause of disability, morbidity and mortality . Some of these NCCD are presenting at a younger age especially in the socio-economically disadvantaged communities of affluent countries, and in low and middle -income countries undergoing industrialization and socioeconomic transition.to more economic prosperity. NCCD are often attributed to unhealthy personal lifestyles, but there may be more at play.
Through a case report-based discussion, I will illustrate how environmental exposures during the critical window of life, including in utero and early infancy, can significantly influence health as an adult . I will discuss how establishment of a rich and diverse symbiotic gut microbiota in the first three years of life promotes health while a loss of diversity and abundance of beneficial symbiotic gut microbes can predispose to aforementioned NCCD , and the best practices to establish a symbiotic gut.
Methylglyoxal: A Key Factor for Diabetic Retinopathy and Its Effects on Retinal Damage
Authors: Klochkov Vladlen , Chan Chi-Ming , Lin Wan-Wan
Published: October 2024

Diabetic retinopathy is the most common retinal vascular disease, affecting the retina's blood vessels and causing chronic inflammation, oxidative stress, and ultimately, vision loss. Diabetes-induced elevated glucose levels increase glycolysis, the main pathway for methylglyoxal (MGO) formation. MGO is a highly reactive dicarbonyl and the most rapid glycation compound to form endogenous advanced glycation end products (AGEs). MGO can act both intra- and extracellularly by glycating molecules and activating the RAGE pathway. This review summarizes the sources of MGO formation and its actions on various cell pathways in retinal cells such as oxidative stress, glycation, autophagy, ER stress, and mitochondrial dysfunction. Finally, the detoxification of MGO by glyoxalases is discussed.
Evaluation of the Influence of Surface Roughness Parameters on Ultrasonic Rayleigh Waveforms
Authors: Grochalski Karol , Kowalczyk Jakub , Jósko Marian , Wieczorowski Michal
Published: October 2024

Ultrasonic nondestructive testing is widely used not only in the laboratory, but also in industry. The tests use various types of ultrasonic waves, diverse measurement techniques and different apparatus. One of the problems encountered is the high susceptibility of the surface wave to interference. Some of the interference is random in nature and can be minimized (e.g., contamination of the surface, resting a finger on the surface under study). Some of the interference is permanent in nature, such as variable surface roughness. The aim of the conducted research was to evaluate the influence of roughness on ultrasonic wave propagation. The study used samples with surface roughness Sa from 0.28 to 219µm, and ultrasonic surface wave probes with frequencies from 1.41 to 8.02 MHz. It was observed that roughness significantly affects the attenuation of the ultrasonic wave, and the differences in signal amplification reached more than 15dB. Similarly, the effect of the ultrasonic wave's transit time through surfaces of different roughness was noted. It was found that the difference in the ultrasonic wave transition time was more than 50 µs. The results of the study can be helpful, for ultrasonic testing of materials with different surface conditions.
Changes in Composition and Diversity of the Intestinal Microbiota, Associated with Carbohydrate Consumption in Type 2 Diabetes Mellitus Patients
Authors: Martinez-Carrillo Beatriz Elina , De Sales-Millán Amapola , Aguirre-Garrido José Félix , Valdes-Ramos Roxana , Cruz-Estrada Flor de María , Castillo-Cardiel Arturo
Published: October 2024

Type 2 diabetes mellitus (T2DM) is a multifactorial disease, influenced by dietary and environmental factors that can modify the intestinal microbiota. The aim was to evaluate changes in composition and diversity of the intestinal microbiota, associated with carbohydrate (CH) consumption in T2DM patients. Forty patients participated, with and without T2DM. Feces samples were collected for the characterization of microbial diversity from the massive sequencing of the 16S rRNA gene. Carbohydrate consumption was quantified from the FCF, the groups were categorized according to BMI and BMI + CH consumption. The group without T2DM showed normal biochemical and anthropometric parameters, although it had high carbohydrate consumption compared to the group with T2DM. At the Phylum level, there were differences in relative abundance, Control overweight group (CL–OW>CH) and T2DM-Normal Weight > CH patients, had increased Bacteroides and decreased Firmicutes. In contrast, CL–OW>CH and T2DM-OW<CH, showed reduced Bacteroidetes and elevated Firmicutes amount. At the genus level, the differences were in the relative abundance of Roseburia, Clostridium_IV, Prevotella, and Sporobacter, associated with the consumption of carbohydrate. The groups that consumed high amounts of carbohydrates, regardless of whether they had diabetes mellitus and overweight, had a significantly reduced proportion of Faecalibacterium, an altered proportion of Bacteroides. The high consumption of carbohydrate showed considerable modifications in the composition and diversity of the bacterial communities.
A Guide to the Multidimensional Nature of Biological Information: Of Maxwell’s and Other Demons
Authors: Srinivasan Bharath
Published: October 2024

The intricate orchestration of molecular events that constitutes life, as we know it, is oftentimes ascribed to an intelligent design motive. It is portrayed as if a paranormal watch maker has engineered the assemblage of parts and events that eventually manifests as the clockwork precision with which ontogeny and evolution operate within the boundary conditions imposed by what we know as life. The debate between those who advocate evolution versus intelligent design as the shaping force for modern life forms persists. However, that is not the motive for this essay. Though there has been several studies and scholarly articles that aspire to decipher and present the complexity of the molecular events that constitutes life in an insular fashion, there is a paucity of resources for undergraduates that summarizes the complexity cogently, as parts of a whole, for appreciating the enormity of the multidimensional nature of biological information and the inherent contradictions that are embedded therein. The fluidity inherent in the way information flows through signalling networks, the way biomolecular architectures maintain homeostasis in the ying-yang of life and the way multicellular complexity evolves through precise cell-cycle control is inherent in the evolution, maintenance and reproduction of biological systems. The matrix of events that encode information at the sequential and structural level across different macromolecules is a fascinating jungle of information. Combining these with how small-molecule metabolites interact with macromolecules in a spatially and temporally coordinated manner to evolve signal over random noise generates a staggering picture of informational organization and relays that, most often, defies human comprehension. This perspective is an attempt to array the various sources of information and put them together in context to appreciate the nuances of how information is stored and relayed within the biological systems. Further, it speculates on how these multitiered organization of biological information could be adapted to guide synthetic biology approaches and the future of information storage and organization.
Importance Sampling for Cost-Optimized Estimation of Burn-Probability Maps in Wildfire Monte Carlo Simulations
Authors: Waeselynck Valentin , Saah David
Published: October 2024

Background: wildfire modelers rely on Monte-Carlo simulations of wildland fire to produce burn-probability maps. These simulations are computationally expensive. Methods: we study the application of Importance Sampling to accelerating the estimation of burn probability maps, using L2 distance as the metric of deviation. Results: assuming a large area of interest, we prove that the optimal proposal distribution re-weights the probability of ignitions by the square root of expected burned area divided by expected computational cost, then generalize these results to assets-weighted L2 distance. We also propose a practical approach to searching for a good proposal distribution. Conclusion: these findings contribute quantitative methods for optimizing the precision/computation ratio of wildfire Monte Carlo simulations without biasing results, offer a principled conceptual framework for justifying and reasoning about other computational shortcuts, and can be readily generalized to a broader spectrum of simulation-based risk modeling.
Optically Stimulated Luminescence (OSL) Dating of Alluvial Deposits from the Cahuachi Archaeological Site (South Peru)
Authors: Delle Rose Marco , Orefici Giuseppe , Panzeri Laura , Galli Anna , Taussi Marco , Quarta Gianluca , Calcagnile Lucio , Renzulli Alberto
Published: October 2024

Cahuachi (Nazca River Valley, South Peru) was the major ceremonial center of the Nasca civilization. According to previous studies, it was struck and destroyed by three El Niño-Southern Oscillation events, which would have occurred around 100 BCE, 600 CE and 1000 CE, respectively. At the end of the series of events, the ceremonial center would have been buried by a cap of conglomerates. Despite this hypothesis raised well-founded doubts regarding its geochronological and paleoenvironmental implications, it is uncritically used as a reference in geoarchaeological research. In the present study, optically stimulated luminescence (OSL) dating results of some samples taken from alluvial deposits at Cahuachi are reported, with the aim to evaluate the literature’s hypothesis. Since the obtained ages are older than the Holocene epoch, such a hypothesis must be rejected. A number of field evidences corroborate this result. Finally, the advancement in fluvial geomorphology knowledge of the Nazca River Valley is briefly discussed.
Lidocaine Modulates Cytokine Production and Enhances Anti-Tumor Immune Response in Gastric Cancer: Dual Effects on Normal Peripheral Blood Mononuclear Cells and Primary Gastric Tumor-Infiltrating Immune Cells
Authors: Wu Yi-Ying , Chen Ming-Shan , Chen I-Chun , Wu Feng-Hsu , Liao Tsai-Ling , Wen Hsiao-Wei , Nielsen Brent L. , Liu Hung-Jen
Published: October 2024

Lidocaine, a commonly used local anesthetic, has demonstrated modulatory effects in various cells. This study investigates the impact of lidocaine on cytokine production in peripheral blood mononuclear cells (PBMCs) from healthy donors and tumor-infiltrating immune cells (TIICs) from gastric cancer patients. Flow cytometry and cytokine assays revealed that lidocaine inhibited IFN-γ and IL-12 production in CD8+ and CD14+ PBMCs, respectively, while enhancing anti-inflammatory cytokines IL-10, TGF-β, and IL-35 in CD4+CD25+ and CD14+ PBMCs. In contrast, lidocaine promoted the secretion of pro-inflammatory IFN-γ and IL-12 in CD8+ and CD14+ TIICs, while reducing IL-10, TGF-β, and IL-35 levels, thus shifting CD14+ macrophages toward an M1-like phenotype. Additionally, lidocaine decreased PD-1 expression and increased IFN-γ production in CD8+ TIICs via NF-κB activation, enhancing their cytotoxicity against primary gastric cancer cells (PGCCs). Importantly, lidocaine did not affect the viability of normal PBMCs, TIICs, or PGCCs at concentrations up to 1.5 mM. These findings suggest that lidocaine reprograms the tumor immune microenvironment, supporting its potential as an adjunct therapy in gastric cancer by enhancing anti-tumor immunity.
Modelling Lifetime Data and Athletes Red Cells Counts
Using the New Topp-Leone-Lomax Poisson Distribution
Authors: Pararai Mavis , Chipepa Fastel
Published: October 2024

A new compounded distribution called the Topp-Leone-Lomax Poisson
is developed. The statistical properties of this model are derived. The
model parameters are estimated via the maximum likelihood technique.
The performance of the estimation techniques was assessed by means
of simulation studies. The new model was exposed to three data sets
and compared to other models within the same class and the evidence
supports the importance of the new model in data modelling.
Advancing towards Higher Contrast, Energy‐Efficient Screens with Advanced Anti‐Glare Manufacturing Technology
Authors: van der Heijden Danielle , Casimiro Anna , ter Meulen Jan Matthijs , Keskinbora Kahraman , Ercan Erhan
Published: October 2024

The pervasive use of screens, averaging nearly 7 hours per day globally across mobile phones, computers, notebooks and TVs, has sparked a growing desire to minimize reflections from ambient lighting and enhance readability in harsh lighting conditions, without the need to increase screen brightness. This demand highlights a significant need for advanced anti-glare (AG) technologies, to increase comfort and eventually reduce energy consumption of the devices. Currently used production technologies are limited in their texture designs, which can lead to suboptimal performance of the anti-glare texture. To overcome this design limitation and improve performance of the anti-glare feature, this work reports a new, cost-effective high-volume production method that enables the much needed design freedom on a large area. This is achieved by combining mastering via large-area Laser Beam Lithography (LBL) and replication by Nanoimprint Lithography (NIL) processes. The environmental impact of the production method, such as material consumption, are considered and the full cycle from design to final imprint is discussed.
Diospyros kaki Alcoholic Extract Induces Mitochondrial Dysfunction in Colorectal Cancer Cell Lines
Authors: Bianchini Stefano , Bovio Federica , Negri Stefano , Bisson Leonardo , Piccinelli Anna Lisa , Rastrelli Luca , Forcella Matilde , Fusi Paola
Published: October 2024

Diospyros kaki, the most widely cultivated species of persimmon, has been long used in traditional medicine since its leaves extracts contain high amounts of flavonoids and terpenoids, endowed with potential antioxidant, anti-inflammatory, anticancer, antidiabetic and antimicrobial effects. Re-cently, many in vitro and in vivo studies have assessed different potential health benefits of per-simmon leaves; however, its anticancer activity towards colorectal cancer (CRC), the second deadliest cancer in Western countries, has not been investigated in depth. Since CRC current therapies are associated with serious side effects and show no efficacy towards patients carrying RAS/BRAF mutations, the search for new and more effective therapies has turned to plant extracts, which could help reduce conventional drugs dosages and toxicity. The effect of Diospyros kaki al-coholic extract has been investigated on E705 CRC cell line, representative of most CRC patients, and on SW480 cells, carrying a KRAS activating mutation. This extract is effective in reducing tumor cells viability, without affecting the healthy mucosa cell line CCD 841, and it triggers apoptosis in CRC cells, by disrupting mitochondrial functionality and increasing oxidative stress.
A Neuroprotective Peptide Modulates Retinal cAMP Response Element-Binding Protein (CREB), Synapsin I (SYN1), and Growth-Associated Protein 43 (GAP43) in Rats with Silicone Oil-Induced Ocular Hypertension.
Authors: Johnson Gretchen , Krishnamoorthy Raghu , Nagaraj Ram , Stankowska Dorota
Published: October 2024

This study evaluated the neuroprotective potential of peptain-1 conjugated to a cell-penetrating peptide (CPP-P1) in an ocular hypertension model of glaucoma. Brown Norway (BN) rats were subjected to intraocular pressure (IOP) elevation via intracameral injection of silicone oil (SO), with concurrent intravitreal injections of either CPP-P1 or a vehicle. Retinal cross-sections were analyzed for markers of neuroprotection, including cAMP Response Element-Binding Protein (CREB), phosphorylated CREB (p-CREB), growth-associated protein-43 (GAP43), synapsin-1 (SYN1), and superoxide dismutase 2 (SOD2). Hematoxylin and eosin staining was used to assess retinal layer thickness. SO-treated rats exhibited significant reductions in the thickness of the inner nuclear layer (INL, 41%, p=0.016), inner plexiform layer (IPL, 52%, p=0.0002), and ganglion cell layer (GCL, 57%, p=0.001). CPP-P1 treatment mitigated these reductions, preserving INL thickness by 32% (p=0.059), IPL by 19% (p=0.119), and GCL by 31% (p=0.057). Increased levels of CREB and p-CREB were observed in IOP-elevated, CPP-P1-treated retinas compared to IOP-elevated vehicle-treated retinas. Although overall GAP43 levels were low, there was a modest increase in expression within the IPL and GCL in SO- and CPP-P1-treated retinas (p=0.15 and p=0.09, respectively) compared to SO- and vehicle-treated retinas. SO injection reduced SYN1 expression in both IPL and GCL (p=0.01), whereas CPP-P1 treatment significantly increased SYN1 levels in the IPL (p=0.03) and GCL (p=0.002). While SOD2 expression in the GCL was minimal across all groups, a trend toward increased expression was observed in CPP-P1-treated animals (p=0.16). The SO model was replicated with SO removal after 7 days and monitored for 21 days followed by retinal flat-mount preparation to assess retinal ganglion cell (RGC) survival. A 42% loss in RGCs (p=0.009) was observed in SO-injected eyes, which was reduced by approximately 37% (p=0.03) with CPP-P1 treatment. These findings suggest that CPP-P1 is a promising neuroprotective agent that promotes retinal ganglion cell survival and the preservation of other retinal neurons, potentially through enhanced CREB signaling in a rat model of SO-induced ocular hypertension.
Effects of the Quantum Vacuum at a Cosmic Scale and Dark Energy
Authors: Santos Emilio
Published: October 2024

Einstein equation approximated to second order in Newton constant G is quantized and applied to a large region of the universe. The two-point correlations of the vacuum energy density and pressure are included and the resulting metric agrees with the one derived from the $\Lambda CDM$ cosmological model plus an additional contribution of the quantum vacuum. The conclusion is that at least a part of the acceleration in the expansion of the universe is due to the vacuum fluctuations.
Minimum and Stable Coefficient of Thermal Expansion by Three-Step Heat Treatment of Invar 36
Authors: Kul Mehmet , Akgül Bekir , Karabay Yusuf Ziya , Hitzler Leonhard , Sert Enes , Merkel Markus
Published: October 2024

The low coefficient of thermal expansion of Invar 36 represents a significant consideration in light of its potential effects, particularly in industrial applications where thermal stability is of paramount importance. In light of this, a three-step heat treatment was employed, to reduce the thermal expansion coefficient, and enhance the thermal dimensional stability. The ingots produced by vacuum induction melting were subjected to a warm rolling process at 900 °C, followed by a three-step heat treatment consisting of water quenching at 850 °C, tempering at 350 °C with a holding time of 1 hour, and aging at 100 °C for 24 hours. This process enabled the coefficient of thermal expansion to remain almost unchanged, exhibiting values between 0.5 and 0.6 x10-6/°C up to 150 °C. Following the heat treatment, the total elongation increased up to 40% as a natural consequence of the reduction of residual stresses, while a slight decrease in tensile strength was observed. The implementation of a three-step heat treatment process has facilitated an enhancement of the soft magnetic property, which has exhibited a decline in coercivity and an increase in saturation magnetization. As a consequence, three-step heat-treated invar 36 alloys are emerging as a potential candidate for utilization in the aerospace and precision electronics industries, given their satisfactory physical and mechanical characteristics.
From Fields to Microclimate: Assessing the Influence of Agricultural Landscape Structure on Vegetation Cover and Local Climate in Central Europe
Authors: Kuntzman Jan , Brom Jakub
Published: October 2024

Agricultural intensification through simplification and specialisation has homogenised diverse landscapes, reducing their heterogeneity and complexity. While the negative impact of large, simplified fields on biodiversity is well-documented, the role of landscape structure in mitigating and stabilising climate is becoming increasingly important. Despite considerable knowledge of landscape cover types, the understanding of how landscape structure influences climatic characteristics remains limited. To explore this further, we studied an area along the Czech-Austrian border, where socio-political factors have created stark contrasts in landscape structure, despite similar topography. Using Land Parcel Information System (LPIS) data, we analysed the landscape structure on both sides, and processed eight Landsat 8 and 9 OLI/TIRS scenes from the 2022 vegetation season to calculate vegetation indices (NDVI, NDMI) and microclimatic features (surface temperature, albedo, and energy fluxes). Our findings reveal significant differences between the two regions. Czech fields, with their larger, simpler structure and lower edge density, experience more extreme temperatures and fluctuating energy fluxes, while Austrian fields exhibit greater stability. These patterns are consistent across landscape classes, with Austria’s finer landscape structure providing higher stability throughout the vegetation season. In light of climate change and biodiversity conservation, these results emphasise the need to protect and restore landscape complexity to enhance resilience and environmental stability.
Ramsey Approach to Quantum Mechanics
Authors: Bormashenko Edward , Shvalb Nir
Published: October 2024

Ramsey theory enables re-shaping of the basic ideas of the quantum mechanics. Quantum observables, represented by linear Hermitian operators are seen as the vertices of the graph. Relation of commutation define coloring of the edges linking the vertices: if the operators commute, they are connected with the red link; if they do not commute they are connected with the green link. Thus, a bi-colored, complete, Ramsey graph emerges. According to the Ramsey theorem, complete, bi-colored graph built of six vertices, will inevitably contain at least one monochromatic triangle; in other words, the Ramsey number R(3,3)=6. In our interpretation, this triangle represents the triad of observables, which could or, alternatively, could not be established simultaneously in a given quantum system. The Ramsey approach to the quantum mechanics is illustrated with the numerous examples, including the motion of a particle in a centrally symmetrical field.
Potential CRISPR/Cas9 Gene Editing Applications in Reversing Acquired Resistance to EGFR-TKIs due to Secondary and Tertiary Mutations to EGFR in NSCLC
Authors: Nishida Malia , Dang Quang , Landry Markita
Published: October 2024

Lung cancer treatment has long been a major field of study in research due to the com-plexity and variability of cancer. Because drug resistance is a major hurdle for lung cancer treat-ment, in this article, we will review the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) used for the treatment of Non Small Cell Lung Cancer (NSCLC) and the EGFR mutations that cause resistance to them. Then, we will discuss the applications of clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR associated protein 9 (Cas9) genome ed-iting in medical treatment. The proposed treatment is specifically for NSCLC patients who have acquired resistance to EGFR TKIs due to mutations to EGFR such as T790M and C797S and would make these TKIs become effective once again. Currently, there is no treatment targeting C797S on the market, but fourth-generation EGFR-TKIs are currently in trial [1,2]. (Figure 1) This proposal will review the potential steps and options available as well as some challenges that may complicate the process.
Comparison of Full-Arch Intraoral Scans Immediately After Implant Insertion versus Healed Tissue: A Multicentric Clinical Study
Authors: Bagnasco Francesco , Menini Maria , Pesce Paolo , Crupi Armando , Gibello Umberto , Delucchi Francesca , Carossa Massimo , Pera Francesco
Published: October 2024

Objectives: The purpose of this clinical study is to compare full-arch intraoral scans taken immediately after implant placement with those obtained after tissue healing in patients rehabilitated with implant-supported fixed prosthesis. Methods: Between September 2023 and March 2024, a total of 19 patients with compromised residual dentition (6 women, 13 men) were rehabilitated using 4 to 6 immediately loaded post-extraction implants. These implants supported fixed full-arch screw-retained prostheses in the lower jaw (9 patients) or upper jaw (10 patients). Intraoral scans were taken immediately after implant placement (termed ‘immediate scan’). After a healing period of four months, the provisional prosthesis was removed and a second intraoral scan was performed using the same scan bodies and scan pattern as the initial scan (termed ‘delayed scan’). The two scans were overlaid and discrepancies between them were measured. Results: The average discrepancy between the immediate and delayed scans was 0.1905 mm. Statistical analysis revealed larger discrepancies for implants placed in the posterior areas, with the implant in site 1.6 ( implant 1 ) showing a discrepancy of 0.2326 mm and the implant in site 2.6 (implant 4) showing 0.2124 mm (P = 0.05). No statistically significant difference was observed when comparing patients treated in the upper and lower jaws. Conclusions: Within the limitations of this study, overlapping digital scans of post-surgical and healed tissues revealed discrepancies that could be attributed to the more difficult conditions present in the post-surgical scenario or operator factors. Further studies are needed to assess the accuracy of post-surgical scans from a clinical point of view.
Research Trends of Thermogravimetric Pyrolysis of carnauba (Copernicia prunifera) and Thermokinetic Models Based on the Bibliometric Analysis
Authors: Ribeiro Filho Manoel , Medeiros Samuel , Lopes Ada , Cruz Glauber , Rios and Maria
Published: October 2024

This study presents a bibliometric analysis of thermogravimetric pyrolysis of carnauba biomass (Copernicia prunifera), a palm tree native to northeastern Brazil, belonging to the Arecaceae family. The objective was to analyze the scientific production and methods used to evaluate the kinetic parameters of biomass pyrolysis. A bibliographic survey was conducted using the Scopus, ScienceDirect, and Web of Science databases. The results were analyzed using VOSviewer and Bibliometrix software, which facilitated the generation of clusters and tables of scientific production. The analyses covered a range of variables, including authors, co-authors, countries of affiliation, academic institutions, journals, and keywords. The search yielded 1,983 articles, and after the application of exclusion criteria, 919 articles were retained, forming the basis for the bibliometric analysis. The data provided a more detailed and accurate overview of thermogravimetric pyrolysis of carnauba research and identified areas for further study. Furthermore, it was possible to ascertain which universities and researchers have devoted the most effort to this line of research, the principal findings, and areas that require further investment to complement existing research. Additionally, the study indicated the suitability of the Friedman kinetic method for determining kinetic parameters in biomass pyrolysis.
Double – Gold/Nitrogen – Nanosecond-Laser Doping of Gold-Coated Silicon Wafer Surface in Liquid Nitrogen
Authors: Kudryashov Sergey , Nastulyavichus Alena , Pryakhina Victoria , Ulturgasheva Evgenia , Kovalev Michael , Podlesnykh Ivan , Stsepuro Nikita , Shakhnov Vadim
Published: October 2024

Novel double-impurity doping process for silicon (Si) surfaces was developed, utilizing nanosecond-laser melting of a top 11-nm thick gold (Au) film and a Si wafer substrate in a laser plasma-activated liquid-nitrogen (LN) environment. Scanning electron microscopy revealed the fluence- and exposure-independent surface micro-spike topography, while energy-dispersive x-ray spectroscopy identified minor Au (0.05 at. %) and major N (1-2 at. %) dopants, localized within a 0.5-m thick surface layer, and slight surface post-oxidation of the micro-relief (oxygen (O), 1.5-2.5 at. %). X-ray photoelectron spectroscopy identified bound surface (SiNx) and bulk doping chemical states of the introduced nitrogen (10 at. %), metallic (<0.01 at. %) and cluster (<0.1 at. %) forms of gold dopant, and evaluated their depth distributions, strongly affected by the competition between gold dopant in its marginal local concentrations and other more abundant dopants (N, O). 532-nm Raman micro-spectroscopy indicated the slight reduction of the crystalline order revealed in the second-order Si phonon band, nanoscale dimensions of the resolidified Si nano-crystallites envisioned by the main Si optical-phonon peak, negligible a-Si abundance and a low-wavenumber peak of Si3N4 structure. In contrast, Fourier-transform infrared (FT-IR) 2D-mapping exhibited the only broad structureless absorption bands in the range of 600-5500 cm-1 related to dopant absorption and light-trapping in the surface micro-relief. The room-temperature electrical characteristics of the laser-double-doped Si layer – carrier mobility of 1050 cm2/Vs and background carrier sheet concentration 21010 cm-2 (bulk concentration 1014-1015 cm-3) – are superior regarding previously reported parameters of nitrogen-implanted/annealed Si samples. This novel facile double-element laser-doping procedure paves the way toward local mask-less on-demand introduction of multiple intra-gap intermediate donor and acceptor bands in Si, providing its related multi-wavelength IR photoconductivity for optoelectronic applications.
Photocatalytic Reactions over TiO2-Based Interfacial Charge Transfer Complexes
Authors: Lazić Vesna , Nedeljković Jovan M.
Published: October 2024

The present review is related to the novel approach for improvement of the optical properties of wide bandgap metal oxides, in particular TiO2, based on the formation of the inorganic-organic hybrids that display absorption in the visible spectral range due to the formation of interfacial charge transfer (ICT) complexes. We outlined the property requirements of TiO2-based ICT complexes for efficient photo-induced catalytic reactions, emphasizing the simplicity of the synthetic procedure, the possibility of the fine-tuning of the optical properties supported by the density functional theory (DFT) calculations, and the formation of a covalent linkage between inorganic and organic components of hybrids, i.e., the nature of the interface. In addition, this study provides a comprehensive insight into potential applications of TiO2-based ICT complexes in photo-driven catalytic reactions (water splitting and degradation of organic molecules), including the identification of reactive species that participate in photocatalytic reactions by the spin-trapping electron paramagnetic resonance (EPR) technique. Considering the practically limitless number of combinations between inorganic and organic components capable of forming oxide-based ICT complexes and with the knowledge that this research area is unexplored, we are confident it is worth studying, and we emphasized some further perspectives.
Crystal Structures of Antigen-Binding Fragment (Fab) of Anti-Osteocalcin Antibody KTM219: Structural Basis for Quenchbody (Q-body)
Authors: Yazaki Shuma , Komatsu Misaki , Dong Jinhua , Ueda Hiroshi , Arai Ryoichi
Published: October 2024

Quenchbody (Q-body), a new type of fluorescent immunosensor, is an antibody fragment labeled with a fluorescent dye. When Q-body binds to its antigen, the fluorescence intensity increases. Highly sensitive detection of antigens by changes in fluorescence intensity is performed in a single step by mixing sample and reagent. In this study, to reveal the structural basis for Q-body, we solved the crystal structures of antigen-binding fragment (Fab) of an anti-osteocalcin antibody KTM219, which is applicable to Q-body, and its complex with the antigen osteocalcin C-terminal peptide (BGP-C7). Also, we solved the structure of a KTM219 Fab crystal grown in the presence of a fluorescent dye 5(6)-carboxytetramethylrhodamine (TAMRA), however, a tightly bound TAMRA was not found in the electron density map. We predicted the binding site of TAMRA by docking simulations. These results support the structural basis for the Q-body mechanism as follows. In the absence of the antigen, the fluorophore located near tryptophan residues is quenched in the hydrophobic pocket of the antigen binding site between VH and VL. In association with the competitive binding of the antigen, the fluorophore is released from the antigen binding pocket and emits fluorescence. The crystal structures of KTM219 Fab and the structural basis of Q-body would be useful for further development and improvement of Q-body fluorescent immunosensors.