bluuebunny/crossref_metadata_2025 huggingface dataset:
Systematic review of the risk of type 2 diabetes post therapy for early-stage breast cancer
Authors: Rathinam Ilampirai , Jin Louise , Nguyen Anna , Chen Juliana , Preda Veronica
Published: June 2024

Aims: The purpose of this systematic review was to examine the risk of developing type 2 diabetes in cancer survivors undergoing adjuvant therapy and to collate and appraise the available evidence to provide clinicians with additional evidence to consider when choosing treatments for breast cancer patients. Methods: MEDLINE, PubMed, EMBASE, and Scopus databases were searched. Articles describing the effects of adjuvant chemotherapy or endocrine therapy and how the treatments affected glucose and/or insulin resistance in women aged 18 years or older with breast cancer were included for analysis. Results: Nine publications were included in this systematic review. No association was found between adjuvant chemotherapy and the use of aromatase inhibitors on the development of type 2 diabetes. In three out of five studies, long-term tamoxifen use was associated with an increased risk of developing type 2 diabetes. Conclusion: There is some indication that long-term tamoxifen use is associated with an increased risk of developing type 2 diabetes in breast cancer patients. However, all studies were observational in nature. Further studies are needed to conclusively establish the relationship between this class of medication, treatment length, and the risk of type 2 diabetes in breast cancer survivors.
Euclidean Relativity Solves the Hubble Constant Tension
Authors: Niemz Markolf H.
Published: June 2024

Special relativity (SR) and general relativity (GR) describe nature in “subjective concepts” (concepts of an observer). Examples of such concepts are space and time—or waves and particles. Despite the Lorentz covariance of SR and the general covariance of GR, the perspectives of observers are always egocentric. Coordinate-free formulations of SR/GR based on a parameterization do not provide a “holistic view of nature” (comprehensive view of nature from all possible perspectives at the same instant in time) because there is no absolute time in SR/GR. Neither does collecting information from egocentric perspectives provide a holistic view. Here I show: Euclidean relativity (ER) describes nature in “objective concepts” (concepts that are immanent in all objects). Space and time are replaced by “pure distance”. Waves and particles are replaced by “pure energy”. Each object’s proper space d1, d2, d3 and its proper time τ span an absolute 4D Euclidean spacetime (ES), where d1, d2, d3 and d4 = cτ are pure distances. The invariant parameter in ER is absolute, cosmic time t. An observer’s reality is created by projecting ES orthogonally to his proper space and to his proper time. ER compares to a “heliocentric model 2.0”, in which the sun is the center of our solar system but not of our galaxy. That model provides a holistic view from “beyond” (outside of) our galaxy. Likewise, ER provides a holistic view from beyond space. The “master reality” ES (described by ER) is beyond each observer’s reality (described by SR/GR). ER solves 15 mysteries geometrically, such as the Hubble constant tension and entanglement. Field equations are not required.
An Eﬀect of Boric Acid on the Structure and Luminescence of Yttrium Orthoborates Doped with Europium Synthesized by Two Different Routines
Authors: Kostova Irena P. , Eftimov Tinko A.
Published: June 2024

In this paper, we present the characteristics of photoluminescent YBO3 successfully synthesized through a solid-state reaction and microwave-assisted method. We used yttrium oxide and boric acid in excess as starting reagents. The synthesis conditions are reflected in fluorescent characteristics and the structure. Excess boric acid causes structural changes, as observed by the FTIR spectroscopy analysis. The FTIR spectra analysis of the structure provided valuable insights into the phase composition and modifications induced by varying amounts of boric acid and synthesis methods. The identified structural features contribute to the understanding of the synthesized samples' characteristics and their potential applications in various fields such as illumination and displays and narrow-band fluorescent smartphone readable markers.
Relationship between Interlimb Asymmetries and Performance Variables in Adolescent Tennis Players
Authors: Villanueva-Guerrero Oscar , Gadea Uribarri Héctor , Villavicencio Álvarez Víctor Emilio , Calero-Morales Santiago , Mainer-Pardos Elena
Published: June 2024

Tennis is an individual sport characterised by high intensity action, including sprints and changes of direction (COD). There is a gap in the knowledge of limb asymmetries in adolescent tennis players and their association with performance. This study aimed to examine the relationship between asymmetry in vertical and horizontal jump tests (CMJ and HJ) and COD with lower limb performance variables in adolescent tennis players. Forty-five adolescent tennis players (age: 13.81 ± 1.08 years; height: 167.64 ± 9.9 cm; body mass: 57.48 ± 10.94 kg; body mass index: 20.27 ± 2.18 kg/m2) performed the CMJ test (unilateral and bilateral), horizontal jumps (unilateral and bilateral), 25 m sprint and 180º COD test. The single-leg countermovement jump showed the greatest asymmetries among the different tests (6.62 ± 9.35%). Significant negative relationships were found between CMJ asymmetry and COD asymmetry with unilateral horizontal jump variables (r = -0.30 to -0.53). In addition, CMJ asymmetry showed significant relationships with CMJR (r=0.49) and COD180R (r=0.29), whereas COD asymmetry showed a significant relationship with COD180L (r=0.40). On the other hand, HJ asymmetry showed no significant relationships with any variable. The main findings of this study indicate that greater imbalances in the CMJ and COD tests are associated with a reduced capacity to perform unilateral horizontal jumps. These results suggest the need to incorporate training protocols that reduce interlimb asymmetries in growing athletes to improve their performance.
Challenges and Trends in Green Finance in the Context of Sustainable Development - A Bibliometric Analysis
Authors: Krastev Biser , Krasteva-Hristova Radosveta
Published: June 2024

Green finance in the context of sustainable development sits within the broader discourse of environmental economics and sustainable finance. Their integration has become imperative in addressing global challenges, aiming to understand how financial mechanisms can be aligned with sustainability goals, investigating the role of green finance in promoting environmentally friendly investments and fostering sustainable development. This bibliometric analysis explores the evolution, trends, and challenges in green finance research. It examines 436 articles published between 2016 and 2024, revealing insights into influential publications, authors, journals, institutions, and countries engaged in green finance for sustainability. The study identifies China, the UK, and Pakistan as leaders in research output and citation impact. Furthermore, it highlights the interdisciplinary nature of green finance, reflected in diverse publication outlets spanning environmental, social, and economic domains. The analysis underscores the increasing global interest in green finance, as evidenced by the growing citation rates over time. Key findings include the pivotal role of green finance in energy efficiency, renewable energy development, and the promotion of sustainable economic growth. Overall, this research provides valuable insights for policymakers, researchers, and practitioners, emphasizing the importance of interdisciplinary collaboration and continued research efforts in advancing sustainable finance agendas.
Lactiplantibacillus plantarum Lp20 Alleviates High Fat Diet-Induced Obesity in Mice via Its Bile Salt Hydrolase Activity
Authors: Lu Fangzhou , Wang Hui , Qian Haidong , Zhai Zhengyuan , Hao Yanling
Published: June 2024

Obesity is a highly prevalent chronic disease characterized by excessive weight gain and fat accumulation. There is growing evidence that Lactiplantibacillus plantarum strains with bile salt hydrolase (BSH) activity are effective in preventing and alleviating obesity. However, few of them has confirmed the anti-obesity effect of BSH by gene deletion. In this study, 23 BSH-positive Lp. plantarum strains were screened by bile salt precipitation halo assay. Among these strains, Lp. plantarum Lp20 showed the highest BSH activity with a hydrolysis rate to glycodeoxycholic acid (GDCA) by 91.62%. Genomic sequencing and bioinformatics analysis indicated that gene bsh1 was associated with BSH activity of Lp. plantarum Lp20 and gene deletion of bsh1 confirmed the role of Bsh1 in GDCA hydrolysis. To investigate if the Bsh1 from Lp. plantarum Lp20 could alleviate obesity, the wild type and bsh1 deletion mutant strains were administered daily for 8 weeks to diet-induced obese mice, respectively. Compared with mutant strain, the wild type strain Lp20 significantly reduced body weight gain, inguinal white adipose tissue and mesenteric fat mass in obese mice. In addition, Lp20 also reduced serum total cholesterol levels and LDL-C by 20.8% and 33.3%, respectively. Furthermore, the recovered liver steatosis was only observed in Lp. plantarum Lp20 treated mice. Taken together, the bile salt hydrolase Bsh1 from Lp. plantarum Lp20 was a key functional factor on ameliorating HFD-induced obesity by reducing cholesterol levels and suppressing adipogenesis in mice.
The Role of NtproBNP in Diagnosis and Treatment of Heart Failure with Preserved Ejection Fraction, Its Not Always a Seek and Hide Game
Authors: Chrysochoou Christina , Konstantinou Konstantinos , Tsioufis Kostas
Published: June 2024

Although heart failure with preserved ejection fraction (HFpEF) has become the predominant heart failure subtype, it remains clinically under-recognized. This, has been attributed to the complex pathophysiological mechanisms that accompany individuals with several co-morbidities and symptoms and signs of HFpEF. Natriuretic peptides have been recognized to have important role in the diagnosis and monitoring of patients with heart failure with reduced ejection fraction (HFrEF), but their role in HFpEF remains controversial. Its seems that the role of NtproBNP in the diagnosis of HFpEF, is mainly driven by the pathophysiological characteristics of the patients.
The Urban-Rural Transformation and Its Influencing Mecha-Nisms on Air Pollution in the Yellow River Basin
Authors: Xu Chen , Yin Zhenzhen , Sun Wei , Cao Zhi , Cheng Mingyang
Published: June 2024

Air pollution has recently gained much attention from the general population. Despite pollution control being an issue in both urban and rural regions, most of the available research has concentrated on urban districts. Hence, investigations into how urban-rural transition affects PM2.5 are warranted within the framework of urban-rural integration. Using the Yellow River Basin as a case study, this study employed the entropy method and Analytic Hierarchy Process (AHP) to uncover the extent of urban-rural transformation. It then used the spatial autocorrelation method to investigate the spatiotemporal features of PM2.5 and the spatial econometric model to investigate the mechanisms that influence the relationship between urban-rural transformation and PM2.5. The results are as follows: (1) Over time, there was a discernible upward tendency in the change in urban-rural areas. The development has progressed from asymmetrical north-east and south-west elevations to a more balanced pattern of north-east, middle-east, and west-west elevations. (2) The PM2.5 concentration increased steadily, then fluctuated, and finally decreased. Notably, the general pattern has not changed much, and it is high in the east and low in the west. (3) Different subsystems of the urban-rural transformation have different impacts on air pollution at different stages. The influence of industrial transformation (IT) on PM2.5 showed an inverted “N-shaped” curve of negative-positive-negative changes, and the industrial structure played a leading role in the spatiotemporal evolution of PM2.5. Currently, an inverted "U-shaped" curve forms the left side of the impact of population transition (PT) on PM2.5. Land development (LT) has a "U-shaped" curve for its effect on PM2.5. This research provides a new perspective on the topic of PM2.5 and its connection to urban-rural integration, which is crucial to understanding the dynamics of this shift. To achieve its goal of high-quality development, it supports regional initiatives to reduce PM2.5 emissions in the Yellow River Basin. Moreover, it can provide a reference for decision-makers in the world’s densely populated areas that suffer from serious air pollution.
A Systematic Review of Secretome-Based Therapies for Alzheimer's Disease: Bridging the Preclinical and Clinical Gap
Authors: Hambarsari Yetty , Suroto Suroto , Mirawati Diah Kurnia , Soetrisno Soetrisno , Wasita Brian , Widyaningsih Vitri , Pamungkasari Eti Poncorini , Subandi Subandi , Danuaji Rivan , Hamidi Baarid Luqman , Hutabarat Ervina Arta Jayanti , Ristinawati Ira , Tejomukti Teddy , Tedjo Raden Andi Ario , Asaduddin Aiman Hilmi , Hafizhan Muhammad , Putra Stefanus Erdana
Published: June 2024

Background: Alzheimer's Disease (AD) is a progressive neurodegenerative disorder with a rapidly increasing prevalence. Current therapeutic options primarily manage symptoms, not modifying the disease. Secretome-based therapies have emerged as a promising avenue for AD treatment in targeting multiple pathways and promoting neuroprotection and regeneration. This systematic review evaluated the preclinical and clinical evidences for secretome-based therapies in AD.Methods: A systematic search was conducted across Scopus, PubMed, ScienceDirect, and Cochrane Library. The SYRCLE risk of bias (RoB) tool was used for preclinical studies and Cochrane RoB 2.0 for clinical studies. We performed qualitative analysis of study results.Results: Included 21 in vivo studies and 2 clinical trials revealed promising outcomes of treatments involving secretomes, exosomes, and extracellular vesicles from different cell sources. The therapies could reduce amyloid plaque load, reactive gliosis, and enhance neuronal density. These findings suggested the treatments reveal mechanism of action in neuroprotection, neuroregeneration, and inflammation modulation, which are critical in AD pathology. Ongoing trials also supported the safety and efficacy of the treatment strategies. However, translational medical study faces several challenges regarding large-scale production, optimization of protocols, and understanding biomarkers. The heterogeneity in secretome-based therapies administration have complicated the comparison of study outcomes and the translation of preclinical findings into clinical settings. Deeper understanding of the secretome's mechanisms of action, optimal dosing, and delivery methods are needed to maximize therapeutic outcomes.Conclusion: Despite secretome-based therapies hold significant promise for AD treatment, addressing the identified gaps and limitations is crucial for advancing these therapies from preclinical research to clinical practice.
High-Resolution Iodine-enhanced Micro-Computed Tomography of Intact Human Hearts for Detailed Coronary Microvasculature Analysis
Authors: Reifart Joerg , Iaizzo Paul
Published: June 2024

Current Micro-Computed Tomography (Micro-CT) protocols for microvasculature analysis often necessitate organ dissection and non-clearable contrast agents. We describe a non-destructive technique for achieving high-resolution images of the human coronary microvasculature.
Formalin-fixed human hearts were cannulated using venogram catheters designed for balloon occlusion. Catheters were anchored at the aortic root. Hearts were placed in sealable, radiolucent containers filled with insulating polyurethane foam. Iodine potassium iodide (IKI, Lugol's solution;6.3% Potassium Iodide, 4.1% Iodide) was injected into the coronary arteries. Contrast distribution was monitored using a North Star Imaging X3000 Micro-CT scanner with low-radiation settings, followed by high-radiation scans (3600 rad, 60 kV, 900 mA).
We successfully imaged two intact human hearts with chronic total coronary occlusions of the right coronary artery. The scans enabled detailed analysis of the vasa vasorum surrounding stenosed and occluded segments. After imaging, both hearts were cleared of iodine and excess polyurethane foam and then returned to their initial formalin-fixed state for indefinite storage.
Conclusions:
This method allows for the non-destructive, high-resolution micro-CT imaging of coronary microvasculature in intact human hearts, paving the way for 3D microvascular reconstruction in a macrovascular context.
Change Through Play, Rethinking Masculinity: An Intervention to Gun Violence in the United States
Authors: Baffoe Helena
Published: June 2024

This scholarly article introduces the "Change Through Play: Rethinking Masculinity" program, a potential intervention designed to address gun violence in the United States by targeting its societal roots, particularly through the lens of gender socialization. The program focuses on transforming children’s, particularly young boys', perceptions of masculinity away from gun violence by influencing the types of toys they play with. By promoting non-violent play, the initiative aims to foster a future generation less inclined to engage in gun violence. This community-interactive and educational approach emphasizes the importance of evidence-based interventions that respect community values and cultural dynamics. The program employs a mixed-methods approach, combining qualitative and quantitative research to evaluate its effectiveness. The program highlights the necessity of sustained, collective action to transform the entrenched practices and beliefs that perpetuate violence, ultimately striving for a society that prioritizes peace, justice, and safety.
Advancing Lung Cancer Classification through Machine Learning: A Comprehensive Comparative Analysis of Model Performance
Authors: Asghari Ilani Mohsen , Kavei Ashkan , Moftakhar Tehran Saba
Published: June 2024

Lung cancer remains a pervasive global health challenge, necessitating precise and efficient classification methods to inform optimal treatment strategies. In this study, we investigate the potential of machine learning algorithms in developing a computer-aided diagnostic tool for early and accurate lung cancer classification, leveraging essential protein biomarkers as predictive features. Our investigation reveals the superiority of Deep Neural Networks (DNNs) in lung cancer classification, achieving an impressive accuracy of 96.91%. This highlights the transformative potential of DNNs in facilitating real-world clinical applications, offering clinicians a powerful tool for accurate diagnosis and prognosis. Additionally, we analyze the performance of Ensemble Methods, including Voting (91.75%) and Bagging (93.81%), as viable alternatives to DNNs. These ensemble techniques demonstrate robust performance, further underlining their utility in lung cancer classification tasks. Furthermore, our study underscores the critical role of hyperparameter tuning, particularly in adjusting parameters such as min child weights and learning rates, in mitigating overfitting and enhancing the generalizability of diverse machine learning models. For instance, Support Vector Machines (SVM) exhibit varying accuracies ranging from 74.23% to 95.88% across different hyperparameter configurations, emphasizing the importance of hyperparameter optimization in maximizing model performance. In summary, our comprehensive comparative analysis sheds light on the efficacy of different machine learning approaches in lung cancer classification. By leveraging advanced algorithms and optimizing model parameters, researchers and clinicians can harness the power of machine learning to advance early detection and personalized treatment strategies for lung cancer patients.
New Amphiphilic Terpolymers of N-Vinylpyrrolidone with Acrylic Acid and Triethylene Glycol Dimethacrylate: Design, Synthesis and Biomedical Applications
Authors: Kurmaz Svetlana V. , Komendant Roman I. , Perepelitsina Evgenia O. , Kurmaz Vladimir A. , Emelyanova Nina S. , Filatova Natalia V. , Amozova Vera I. , Balakina Anastasia A. , Terentyev Alexey A.
Published: June 2024

The terpolymers of N-vinylpyrrolidone (VP) with acrylic acid and triethylene glycol methacrylate were synthesized with more than 90% yield by radical copolymerization in ethanol from monomeric mixtures of different composition (98 : 2 : 2, 95 : 5: 2 and 98 : 2: 5). Their physical and chemical characteristics such as monomer composition, absolute molecular masses and hy-drodynamic radii in aqueous media at different temperature were determined. The temperature effect on the behavior of terpolymers in water and aqueous saline buffer solution with pH 7.4 has been studied and the ability of a copolymer enriched with dimethacrylates units was discovered to respond to a temperature change in these media. On the basis of terpolymers and linear polyvi-nylpyrrolidone (PVP), polymer compositions of hydrophobic dye methyl pheophorbide a, MPP, that is fluorescent in the red region of the spectrum, were obtained; the sizes of the polymer nanostructures of MPP in water were determined. The structures based on terpolymers were demonstrated to be more stable than MPP-PVP ones. It was carried out the quantum-chemical modelling of the possible structures of MPP-copolymer that formed as a result of intermolecular interaction between MPP and terpolymer’s chains; the possibility of the formation of hydrogen bonds between the donors of the electrons of terpolymer units and the proton donors of the MPP molecule was shown. Using the MTT test, it was established that copolymers of various compositions are low toxic for non-tumor Vero cells and HeLa tumor cells. It was shown that the cytotoxicity of polymer particles loaded with MPP for FetMSC and HeLa cells increased. Using fluorescence microscopy, the accumulation and distribution of polymer particles in non-tumor (FetMSC) and tumor (HeLa) cells was studied and an increase in the accumulation of MPP with both types of particles was shown.
Detecting Near-Surface Sub-millimeter Voids in Additively Manufactured Ti-5V-5Al-5Mo-3Cr Alloy Using a Transmit-Receive Eddy Current Probe
Authors: Halliday Brendan Sungjin , Eastmure Allyson , Underhill P. Ross , Krause Thomas Walter
Published: June 2024

Additive Manufacturing (AM) Direct Laser Fabrication (DLF) of Ti-5Al-5V-5Mo-3Cr (Ti5553) is being developed as a method for producing aircraft components. The additive manufacturing process can produce flaws near the surface, such as porosity and material voids, which act as stress raisers, leading to potential component failure. Eddy current testing was investigated to detect flaws on or near the surface of DLF Ti5553 bar samples. For this application, the objective was to develop an eddy current probe capable of detecting flaws 500 µm in diameter, located 1 mm below the component's surface. Two initial sets of coil parameters were chosen: The first, based on successful experiments that demonstrated detection of a near surface flaw in Ti5553 using a transmit-receive array probe, and the second, derived from simulation by Finite Element Method (FEM). An optimized transmit receive coil design, based on the FEM simulations, was constructed. The probe was evaluated on Ti5553 samples containing sub-surface voids of the target size, as well as samples with side-drilled holes and samples with holes drilled from the opposing inspection surface. The probe was able to effectively detect 80% of the sub-surface voids. Limitations included the probe’s inability to detect sub-surface voids near sample edges and a sensitivity to surface roughness, which produces local changes in lift-off. Multifrequency mixing improved signal-to-noise ratio when surface roughness was present on average by 22%. A probe based on that described in this paper could benefit quality assurance of additively manufactured aircraft components.
Location Problem in Relativistic Positioning: Relative Formulation
Authors: Montesinos Ramón Serrano , Ferrando Joan Josep , Morales-Lladosa Juan Antonio
Published: June 2024

A relativistic positioning system is a set of four emitters broadcasting their proper times by means of light signals. The four emitter times received at an event constitute the emission coordinates of the event. Covariant quantities associated with relativistic positioning systems are analysed relatively to an observer in Minkowski space-time by splitting them in their relative space-like and time-like components. The location of a user in inertial coordinates from a standard set of emission data (emitted times and satellite trajectories) is solved in the underlying 3+1 formalism. The analytical location solution obtained by Kleusberg for the GPS system is recovered and interpreted in a Minkowskian context.
Upper Airway Alarmin Cytokine Expression in Asthma of Different Severities
Authors: Marriott Hazel , Duchesne Marc , Moitra Subhabrata , Okoye Isobel , Gerla Luke , Mayers Irvin , Moolji Jalal , Adatia Adil , Lacy Paige
Published: June 2024

Background: The secretion of alarmin cytokines by epithelial cells, including thymic stromal lymphopoietin (TSLP), interleukin (IL)-25, and IL-33, heralds the onset of the inflammatory cascade and immune effector infiltration in asthma. However, alarmin cytokine expression in the upper airways in asthma remains largely unknown.
Methods: We recruited 40 participants with asthma who were categorized into four severity groups as per the Global Initiative for Asthma (GINA) classifications (10 in each group of GINA-1/2, -3, -4, and -5). Cells were derived from buccal, nasal and throat brushings, and intracellular alarmin cytokine expression (TSLP, IL-25, and IL-33) was assessed in cytokeratin 8+ (Ck8+) epithelial cells immediately after collection using flow cytometry with fluorescence minus one (FMO) controls. We assessed differences in alarmin cytokine expressions across asthma severity using quantile regression adjusted for age and sex.
Results: Of all patients, 24 (60%) were females with a mean (standard deviation [SD]) age of 41 (16) years. TSLP levels in Ck8+ epithelial cells in nasal samples of GINA-5 patients were significantly (p=0.03) higher than other GINA groups after adjusting for age and sex but did not differ between patients with and without nasal comorbidities. However, we did not find any significant changes in TSLP levels in Ck8+ epithelial cells in buccal and throat samples across GINA groups. IL-25 or IL-33 (obtained from nasal, buccal, and throat epithelial cell samples) were not significantly different across GINA groups.
Conclusions: Our study demonstrates for the first time that Ck8+ nasal epithelial cells from GINA-5 asthmatics express elevated levels of TSLP.
Synergistic Enhancement of Antitumor Effects by Combining Abemaciclib With Desipramine
Authors: Li Yan , Sung Yeojin , Choi Young Eun , Choi Yongdoo , Goh Sung-Ho
Published: June 2024

Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors, including abemaciclib, have been approved for the treatment of hormone receptor-positive, HER2-negative advanced, and metastatic breast cancer. Despite the high therapeutic efficacy of CDK4/6 inhibitors, they are associated with various adverse effects, including potentially fatal interstitial lung disease. Therefore, a combination of CDK4/6 inhibitors with letrozole or fulvestrant has been attempted but has demonstrated limitations in reducing adverse effects, highlighting the need to develop new combination therapies. This study proposes a combination strategy using CDK4/6 inhibitors and tricyclic antidepressants to enhance the therapeutic outcomes of these inhibitors while reducing their side effects. The therapeutic efficacies of abemaciclib and desipramine were tested in different cancer cell lines (H460, MCF7, and HCT-116). The antitumor effects of the combined abemaciclib and desipramine treatment were evaluated in a xenograft colon tumor model. In vitro cell studies have showed the synergistic anticancer effects of combination therapy in the HCT-116 cell line. The combination treatment significantly reduced tumor size compared with control or single treatment without causing apparent toxicity to normal tissues. The combination of abemaciclib and desipramine may be a promising therapeutic strategy as they could reduce side effects and enhance tumor suppression.
Development of a versatile Nanostructured Lipid Carrier (NLC) using Design of Experiments (DoE) – Part II: Incorporation and stability of butamben with different surfactants
Authors: Matarazzo Ananda Pulini , Rios Carlos Alberto , Gerônimo Gabriela , Ondei Roberta , de Paula Eneida , Breitkreitz Márcia Cristina
Published: June 2024

Nanostructured lipid carriers (NLC) are typically composed of liquid lipids, solid lipids, and surfactants, enabling the encapsulation of lipophilic drugs. Butamben is a Class II anesthetic drug according to the Biopharmaceutical Classification System (BCS), it has a log P 2.87 and is considered a 'brick dust' (poorly water-soluble and poorly lipid-soluble) drug. This characteristic poses a challenge for the development of NLCs, as they are not soluble in the liquid lipid present in the NLC core. In a previous study [1] we have developed a NLC core consisting of solid lipid (CrodamolTM CP), liquid lipid of medium polarity (SRTM Lauryl lactate), and a hydrophilic excipient (SRTM DMI) that allowed the solubilization of 'brick dust' type of drugs including butamben. In this study, starting from the NLC core formulation previously developed we carried out the optimization of the surfactant system and evaluated their performance in aqueous medium. Three different surfactants (CrodasolTM HS HP, SynperonicTM PE/F68, and CroduretTM 40) were studied and, for each of them, a 2³ factorial design was stablished, with total lipids, % surfactant, and sonication time (min) as the input variables and particle size (nm), polydispersity index (PDI) and zeta potential (mV) as the response variables. Stable NLCs were obtained using CrodasolTM HS HP and SynperonicTM PE/F68 as surfactants. Through a comparison between NLCs developed with and without SRTM DMI, it was observed that besides helping the solubilization of butamben in the NLC core, this excipient helped stabilizing the system and decreasing particle size NLCs containing CrodasolTM HS HP and SynperonicTM PE/F68 presented particle size values in the nanometric scale, PDI lower than 0.3 and zeta potential above |10|mV. Concerning NLCs stability, SBTB-NLC with SynperonicTM PE/F68 and butamben demonstrated stability over a 3-month period in aqueous medium. The remaining NLCs showed phase separation or precipitation during the 3-month analysis. Nevertheless, these formulations could be freeze-dried after preparation, which would avoid precipitation in aqueous medium.
Human Upper Limb Movement Classification using Machine Learning on Sensor Data
Authors: Gulrez Sabahat , Rehman Azizur , Kabir Ashad
Published: June 2024

In this paper, a seamless connection between sensor technology and machine learning (ML) has been presented which has wide applicability in rehabilitation and physical medicine. The intent is to identify an ML algorithm which has a better performance, easy to deploy, and has less training time and consumes less computational resources. In short, we propose an algorithm which maximizes the synergy between a sensor and ML by maximizing classification performance and easy to do implementation, which is robust in computational power and lower in resource consumption. The premise of the work is to show the important considerations for evaluating ML algorithms for Upper-limb activity recognition for Physical medicine and rehabilitation field.
Near-Infrared Phosphorescence of the Raman Photogenerated Singlet Oxygen
Authors: Marcano Olaizola Aristides
Published: June 2024

We report on the phosphorescence of singlet oxygen photogenerated through a stimulated Raman process. Nanosecond radiation in the green spectral region focused on hexane induces a Raman transition of the dissolved in the solvent oxygen molecules toward the singlet oxygen state producing a Stokes signal in the near infrared. The excited oxygen relaxes to ground emitting an infrared photon at 1269 nm. While the Stokes signal’s wavelength changes with the pumping light’s wavelength, the wavelength of the phosphorescent photon remains unaltered. The result confirms previously reports on stimulated Raman excitation of singlet oxygen.
Remote active monitoring of patients after myocardial infarction: are there any advantages over standard outpatient monitoring?
Authors: Sedykh D. Yu. , Alkhimova T. S. , Kashtalap V. V. , Barbarash O. L.
Published: June 2024

Aim. To compare the clinical effectiveness of two patient management programs for 12 months after myocardial infarction (MI) (standard outpatient monitoring and office- based management with additional active remote medical supervision).

Material and methods. 150 patients with non-fatal MI aged 35 to 70 years were included. At discharge, patients were randomized into groups with different followup programs for 12 months after MI (standard outpatient follow-up (n=75) or its combination with active remote patient monitoring (n=75)). One year after MI, the following parameters were was assessed: vital status, frequency of emergency cardiovascular hospitalizations due to coronary insufficiency, actual adherence to therapy and regular outpatient follow-up, achieving target parameters of cardiovascular health, and dynamics of behavioral risk factors.

Results. In the group of patients with MI who spent 12 months in a combined program, compared with patients with standard monitoring, 4.8 times fewer combined ischemic events were registered (p<0.001); the proportion of emergency hospitalizations for cardiovascular reasons was 4.7 times lower (p<0.001). It was shown that patients observed in a combined program throughout the year were 1.7 times more likely to make regular visits to the clinic (p<0.001). Over a year, patients with active remote monitoring were more likely to achieve behavioral changes: the proportion of patients reporting an increase in weekly physical activity (p=0.013) and a decrease in the number of periods of monthly stress or their complete absence from work and/or home was 1.6 times higher (p=0.020), who were 1.8 times more likely to indicate a decrease in the frequency of monthly alcohol consumption and a decrease in the number of servings (p=0.001), as well as changes in dietary patterns. Patients who underwent additional remote patient monitoring were 1.2 times more likely to indicate a decrease in daily consumption of table salt (p = 0.011), 1.3 times more likely to note the addition of dietary meat to the diet (p=0.003), 1.1 times more likely to more often — fresh and cooked vegetables (>300 g per week) (p=0.032), 1.4 times more often — fresh fruits and berries (>300 g per week) (p=0.003), 1.2 times more often reported about reducing the consumption of complex carbohydrates to > ¼ of the plate per day (p=0.036).

Conclusion. An original program of combined standard outpatient monitoring of patients and their active remote monitoring for 12 months after MI demonstrated advantages in secondary prevention of cardiovascular events and modification of cardiovascular risk factors.
Risk factors of ventricular arrhythmias in non-syndromic mitral valve prolapse
Authors: Trisvetova E. L.
Published: June 2024

Non-syndromic mitral valve prolapse (MVP) is a common disease. In most cases, its benign course is noted, however, a connection between MVP and ventricular arrhythmias is reported, as well as sudden cardiac death. Clinical signs (chest pain, syncope/lipotymia, mid-systolic click), results of instrumental studies (electrocardiographic, echocardiographic, magnetic resonance imaging) allow us to identify known ("old") risk factors and new phenomena encountered in rhythm and conduction disturbances during MVP. Signs of "arrhythmic" MVP, often detected in young women, include prolapse of thickened both mitral valve leaflets, T wave inversion in the inferior basal leads on the electrocardiogram, annulus fibrosus disjunction, fibrosis of the papillary muscles and myocardium in the inferior basal wall of the left ventricle, determined by magnetic resonance imaging. resonance tomography and myocardial biopsies. In 2022, the European Heart Rhythm Association Expert Consensus presented risk stratification and treatment principles for patients with arrhythmic MVP, identifying low, intermediate and high-risk groups, and in 2024, the first meta-analysis of studies was performed to identify prognostic risk factors of arrhythmic MVP. The most significant predictors of arrhythmias included late gadolinium enhancement on magnetic resonance imaging, T-wave inversion on the electrocardiogram, prolapse of both mitral valve leaflets, and mitral annulus disjunction. When choosing treatment for patients with arrhythmic MVP, clinical characteristics are taken into account and a personalized approach is used to prevent sudden cardiac death and severe ventricular arrhythmias. As a rule, to prevent sudden cardiac death in patients with arrhythmic MVP, four treatment options are considered: medications (beta-blockers or non-dihydropyridine slow calcium channel blockers, a combination of a beta-blocker and flecainide, or amiodarone), radiofrequency ablation, surgical treatment of the mitral valve, implantable cardioverter — defibrillator (for primary or secondary prevention of sudden cardiac death).

The rationale for surgical, electrophysiological, and/or therapeutic treatments depends on the specific rhythm disorder.
The phenomenon of complete treatment refusal in patients with acute cerebrovascular accident (according to the LIS-2 registry)
Authors: Lukina Yu. V. , Kutishenko N. P. , Zagrebelny A. V. , Ginzburg M. L. , Martsevich S. Yu. , Drapkina O. M.
Published: June 2024

Aim. To describe and analyze a series of cases of absolute non-adherence to treatment (ANA), as well as to study the relationship of the phenomenon of refusal of treatment with long-term adverse outcomes in patients with acute cerebrovascular accident (ACVA), according to the LIS-2 registry (Lyubertsy Mortality Study 2).

Material and methods. The study analyzed the results of two stages of prospective follow-up of patients with acute cerebrovascular accident included in the  LIS-2 registry (n=960). After 2.8 [2.1; 3.5] years, an examination, a survey, and an assessment of treatment adherence according to the original questionnaire were conducted in 370 patients. After 6.9 [6.1;7.7] years, the outcomes of these patients were evaluated. The survival analysis included death from all causes, nonfatal myocardial infarctions and repeated ACVA, and emergency hospitalization for cardiovascular diseases also. These are the components of the primary combined endpoint.

Results. According to the results of the questionnaire, 23 (6,2%) patients replied that they did not take prescribed medications, i.e. they were absolutely not adherent to treatment. Absolutely non-adherent patients smoked more often (p=0.004), were less comorbid, and had statistically significant difference in hypertension and coronary heart disease (CHD) (p<0.001 and p=0.03, respectively). The most common reason for ANA was unwillingness to take medications for a long time (n=12, 52,2%), the second most common reason was fear of drugs side effects and harm to health during long-term treatment (n=5, 21.7%). The components of the primary combined endpoint were registered in 10 (43.5%) absolutely non-adherent patients and in 104 (30.0%) people of the rest of the group. There was a discrepancy in the Kaplan-M ayer survival curves for the groups of absolutely non-adherent and all other patients, which did not reach statistical significance (p=0.12), as well as an increased risk of adverse long-term outcomes (hazard ratio, HR) in patients who completely refused treatment: HR=1.68, 95% confidence interval (CI) 0.87-3.21, p=0.12 (univariate Cox analysis). According to the results of multivariate Cox regression analysis, the predictors significantly associated with an increase in the risk of endpoints were ANA (HR=2.66, 95% CI 1.06;6.68, p=0.037); presence of coronary heart disease (HR=2.18, 95% CI 1.13;4.24, p=0.021); increase in age for each year (HR=1.08, 95%CI 1.04;1.12, p<0.0001).

Conclusion. The phenomenon of complete treatment refusal or ANA was noted in 6% of cases in patients with ACVA. Its leading cause was the reluctance of patients to take medications for a long time. In patients with ACVA it has been shown that the presence of CHD and complete refusal of recommended treatment increases the risk of adverse long-term outcomes by more than two times.
Clinical and prognostic value of the MELD-XI score in hospitalized patients with chronic heart failure
Authors: Dragomiretskaya N. A. , Podzolkov V. I. , Tolmacheva A. V. , Shvedov I. I. , Vetluzhskaya M. V. , Chistyakova V. D.
Published: June 2024

Aim: to evaluate the diagnostic and prognostic role of the MELD-XI index in hospitalized patients with CHF.

Material and methods: The prospective study included 182 patients (92 men and 90 women), age 72.3±12.1 years, hospitalized at Clinical Hospital No. 4 of the First Moscow State Medical University with the CHF class II-IV. All patients signed the informed consent and underwent a standard examination with determination of NTproBNP and calculation of the MELD-XI index = 5.11 (ln [total bilirubin, mg/dl]) + 11.76 (ln [creatinine, mg/dl]) + 9.44. The primary endpoint was death from all causes within 36±3 months.

Results: Based on the median MELD-XI index, 2 groups of patients were identified - high MELD-XI index>11.4 points (n=85 (47%)) and low - MELD-XI<11.4 points (n=97 (53 %)). Patients in the groups were comparable in age, comorbid diseases, and main classes of drug therapy received. Patients with a high MELD-XI index were characterized by a more severe course of stage IIB-III CHF and low LVEF (42.5[37; 50]% vs 52 [40; 60], p=0.0005).

All-causes death over 3 years of follow-up was 39.6%. In patients who reached the end point, regardless of their initial LVEF, MELD-XI index values ​​were significantly higher (12.2 [9.7; 15.2] points) compared to survivors (10,6 [8,2;12,8] points (p<0.001)). According to ROC analysis, the threshold value of the MELD-XI index for high risk of death was 11.4 points (sensitivity 62.73%, specificity 59.15% (AUC 0.634; p=0.03)). Regression analysis showed that MELD-XI index values ​​>11.4 points increase the risk of death by 2.3 times (OR: 2.345, 95% CI: 1.274-4.315, p = 0.006) and are independent significant predictors of poor prognosis, along with LVEF <40%, NT-proBNP and sST2 levels and community-acquired pneumonia. Each subsequent 1-point increase in MELD-XI score increases the odds of death by 1.157 times (OR: 1.157, 95% CI: 1.0616-1.261, p<0.01)

Conclusion: The MELD-XI score is a simple and reliable method for diagnosing multiple organ dysfunction in patients with CHF. MELD-XI index>11.4 points is a predictor of poor long-term prognosis in hospitalized patients with CHF.
Effective Etch Times of Fossil Fission Tracks in Geological Apatite Samples and Impact on Temperature-Time Modeling
Authors: Trilsch Florian , Fu Hongyang , Jonckheere Raymond , Ratschbacher Lothar
Published: June 2024

Apatite fission-track modeling reconstructs the low-temperature histories of geological samples based on measurements of the lengths of etched confined fission tracks and counted surface tracks. The duration for which each confined track was etched can be calculated from its width given the apatite etch-rate νR. We measured νR as a function of crystallographic orientation for fourteen samples from the igneous and metasedimentary basement of Tian Shan, Central Asia, to optimize the track-length distribution for modeling the thermal histories of apatites with varying chemical compositions. To first order, νR scales with the size of the track intersections with the mineral surface in the range of Dpar = 1.4–2.6 µm. We use νR for calculating the effective etch time tE of confined tracks measured after 20–60 seconds of immersion in 5.5 M HNO3 at 21°C. Considering only tracks within a predetermined etch-time window improves the reproducibility of the track-length distributions. Because an etch-time window allows excluding under- and over-etched tracks, sample immersion times can be optimized to increase the number of confined tracks suitable for modeling. Longer immersion times also allow the longest-etched tracks to develop a clear geometrical outline from which the orientation of the apatite c-axis can be inferred. We finish by comparing thermal histories obtained with a conventional 20-second immersion protocol, without tE selection, with those using the length of tracks within the range of tE = 15–30 seconds. Overall, the alternative models fit better to independent AHe data than the conventional ones.
Tectonic–Hydrothermal Processes and their Relationship with the Petroleum Potential of the Bazhenov-Abalak Complex of Western Siberia
Authors: Zubkov M.Yu.
Published: June 2024

—The main types of reservoir rocks have been identified within the Bazhenov-Abalak complex. To assess the geological resources of hydrocarbons, it is proposed to formally divide the entire set of lithological rock types comprising the Bazhenov-Abalak complex into two main varieties: fluid seals and reservoirs. We argue that it is possibile to distinguish between potentially productive and productive rocks, represented by siliceous and carbonate varieties, according to logging data. A possible mechanism for the formation of reservoir rocks within the Bazhenov-Abalak complex as a result of the tectonic-hydrothermal impact on these deposits has been reconstructed. An original methodology for identifying perspective zones of various categories of hydrocarbon accumulation in the Bazhenov-Abalak complex through integrating seismic data and tectonophysical modeling carried out on their basis has been proposed. For example, an assessment of the predicted geological resources of hydrocarbons contained in the Bazhenov-Abalak complex within the limits of 3D seismic exploration of the Yem-Yegovskaya area has been carried out. The necessity of assessing the prospects for oil content and calculating the predicted geological resources of hydrocarbons in the whole Bazhenov-Abalak complex, and not only in the Bazhenov Formation, is substantiated, based on a single mechanism of formation of reservoir rocks of tectonic-hydrothermal origin in them.
Evolution of Intrusive Magmatism in West Sayan
Authors: Rudnev S.N. , Babin G.A. , Semenova D.V. , Travin A.V.
Published: June 2024

—We summarize the results of geological, geochronological and petrochemical studies of the intrusive complexes of West Sayan, and on their basis analyze the scales, formation sequence, petrochemical characteristics and geodynamic environments of the formation of granitoid and gabbroid complexes. Geochronological data indicate that the formation of intrusive complexes (granitoids and gabbroids) of West Sayan ranged within 580–370 Ma at several age levels and in various geodynamic environments: island-arc – 580–570, 550–520 Ma, accretion-collision – 505–450 Ma, transform-shear of continental margins – 440–430 Ma, and active continental margin – 425–370 Ma. According to petrochemical characteristics, we distinguish the rocks of tholeiitic, calc-alkali and subalkaline series among the studied granitoid complexes. The study of xenogenic zircons from granitoid and gabbroid complexes indicate the age range of 650–440 Ma. Several age clusters are distinguished (~ 645, ~ 570, 555–520, 505–475, 455–440 Ma); this indicates heterogeneous composition of the West Sayan crust and participation of the Late Riphean, Vendian – Early Cambrian and Ordovician crust sources in granite formation.