bluuebunny/crossref_metadata_2025 huggingface dataset:
Integration of fuzzy inference module using web technologies
Authors: Badanina Natalya Dmitriyevna , Zinchenko Aleksandra Andreevna , Sudakov Vladimir Anatolievich
Published: October 2023

This paper proposes a developed fuzzy computing module and possible ways to integrate it for a web application. As a result of the use of fuzzy calculations, it is possible to improve the quality of decisions made and increase the accuracy of the results, so there was a need to develop software that would be available to the user using web technologies without unnecessary installation steps.
Deformation and Trapping of Cell Nucleus Using Micropillar Substrates Possibly Affect UV Radiation Resistance of DNA
Authors: Nagayama Kazuaki , Sagawa Chiaki , Sato Akiko
Published: October 2023

DNA damage induced by the ultraviolet (UV) light, which affects adversely on genome stability, causes many kinds of diseases. Thus, a biochemical or biomechanical method in DNA damage protection is well required. In the present study, we investigated the effects of mechanical factors, such as deformation of cell nucleus using polydimethylsiloxane (PDMS)-based microfabricated array of micropillars, on UV radiation resistance of DNA in cultured cells. The epithelial-like cells spread normally in the spaces between micropillars and their nuclei showed remarkable deformation and appeared to be “trapped” mechanically on the array of pillars. We found that the UV radiation-induced DNA damage estimated by the fluorescent intensity of the phospho-histone γ-H2AX, was significantly inhibited with the nucleus deformation on the pillars. The result indicates that the inhibition of UV radiation-induced DNA damages might be resulted from structural change of DNA caused by the mechanical stress of the cell nucleus on the micropillars.
Development of a Microfluidic Ion Current Measurement System for Single-Microplastic Detection
Authors: Kishimoto Yuta , Ide Sachiko , Naito Toyohiro , Nakashima Yuta , Nakanishi Yoshitaka , Kaji Noritada
Published: October 2023

Microplastics (MPs) can adsorb heavy metals and metalloids and may cause a potential health hazard. Precise measurements of their size, shape, composition, and concentration at a single-MP level are important to evaluate their potential toxicity and identify their original source. However, current single-MP analytical methods such as micro-Raman spectroscopy and scanning electron microscopy have low throughput. Therefore, in this study, we applied the ion current sensing method, which has been used for single cell analysis, to single-MP analysis and examined whether size measurement and composition analysis of MPs at the single particle level are possible. In single-MP measurements, plastic particles must be mono-dispersed in solution at least within the measurement time. The agglomeration behavior was carefully observed after adding sodium dodecyl sulfate to tris-borate-EDTA buffer at 2–16 mM. Under these conditions, the size of polystyrene beads could be measured using the ion current sensing under the mono-dispersed condition. Next, ion current sensing was performed on four pseudo MPs fabricated from different materials (polyethylene, polyethylene terephthalate, polypropylene, and polyvinyl chloride) that were mechanically grazed and UV-irradiated to imitate real marine MPs. Although significant differences in the ion current signals from different material MPs were not observed, fast (100 MPs within 2 s) and precise measurements in the MPs’ sizes at a single-MP level were successfully achieved.
Visual Emotion Recognition Through Multimodal Cyclic-Label Dequantized Gaussian Process Latent Variable Model
Authors: Saito Naoki , Maeda Keisuke , Ogawa Takahiro , Asamizu Satoshi , Haseyama Miki
Published: October 2023

A multimodal cyclic-label dequantized Gaussian process latent variable model (mCDGP) for visual emotion recognition is presented in this paper. Although the emotion is followed by various emotion models that describe cyclic interactions between them, they should be represented as precise labels respecting the emotions’ continuity. Traditional feature integration approaches, however, are incapable of reflecting circular structures to the common latent space. To address this issue, mCDGP uses the common latent space and the cyclic-label dequantization by maximizing the probability function utilizing the cyclic-label feature as one of the observed features. The likelihood maximization problem provides limits to preserve the emotions’ circular structures. Then mCDGP increases the number of dimensions of the common latent space by translating the rough label to the detailed one by label dequantization, with a focus on emotion continuity. Furthermore, label dequantization improves the ability to express label features by retaining circular structures, making accurate visual emotion recognition possible. The main contribution of this paper is the implementation of feature integration through the use of cyclic-label dequantization.
Experimental Evaluation of Highly Accurate 3D Measurement Using Stereo Camera and Line Laser
Authors: Nonaka Shunya , Pathak Sarthak , Umeda Kazunori
Published: October 2023

This paper proposes a method to improve the accuracy of 3D measurement of a stereo camera by marking a measured object using a line laser. Stereo cameras are commonly used for 3D measurement, but the accuracy of 3D measurement is affected by the amount of texture. Therefore, a new measurement system combining a stereo camera and a line laser is developed. The accuracy of 3D measurement with a stereo camera is improved by using a line laser to mark arbitrary points on the measured object and measuring the marked points, regardless of the amount of texture on the measured object. Because the laser is only used to mark points on the measurement target, calibration is not required with the stereo camera. Experimental evaluation showed that our proposed method can obtain millimeters.
Design and Development of an Interactive Video Player for Supporting Formative Assessment in Online Learning
Authors: BAYAZIT Alper , AKÇAPINAR Gökhan
Published: October 2023

In this study, the aim was to design a video player with embedded quizzes to enhance students' interactions with video learning materials and enable them to derive maximum benefit from these materials. The developed tool is integrated into the Moodle learning management system and presents questions from a question bank to students at predetermined time intervals set by the instructor. Additionally, it records interactions between the student and embedded quizzes, such as the number of attempts and the number of correct or incorrect answers. Furthermore, students' video interactions, encompassing actions like play, pause, and seek, are also stored in the database. The tool allows instructors to export 15 features related to students' videos and embedded quiz interactions. Consequently, students can assess their comprehension of the content they are viewing and receive immediate feedback, while instructors can access summary reports for all students. This enables them to find out how many students have watched the videos and their responses to the questions before or after the class. This paper explains the development process of the tool and presents findings from a pilot study utilizing the tool. The results of the pilot study revealed that students' video-watching behaviors in interactive videos differed from those in non-interactive videos. An interactive video player that allows embedding quiz questions to support formative assessment in online learning environments, can be advantageous for researchers, instructors, and learners.
Investigation into the Multistage Mechanical Damage Behavior of Columnar Jointed Basalts with Different Meso-Constitutive Relations and Model Sizes
Authors: Wang Yongyi , Gong Bin , Yang Xiaoyu , Tang Chun’an
Published: October 2023

The mechanical characteristics of columnar jointed basalts (CJBs) are generally considered to be subject to size effects. They display complex mechanical behaviors under lateral pressure, which may be related to the variation in the rock's mesoproperties. In this study, many nonuniform CJB models with various rock meso-constitutive relations and model sizes were established, and their influences on the strength and deformation properties, multistage mechanical damage behavior, and acoustic emission characteristics of CJBs were investigated. The results show that, as the residual strength coefficient increases, the compressive strength of CJBs rises, and the equivalent deformation modulus of CJBs decreases or increases slightly; with an increase in the model size, the compressive strength slightly decreases at first and then varies moderately, and the equivalent deformation modulus shows a fluctuating trend. Furthermore, the macro stress–strain relationships can be divided into different stages according to the corresponding damage behaviors. The strains and energy accumulations before peak stress was reached were further analyzed. The results greatly improve our understanding of the collapse process of CJBs and the instability precursors of related structures.
Biostratigraphy, Lithology and Geochemistry of the Lower and Middle Cambrian Rocks in the Kyulenke River Basin: First Results of Borehole Core Study
Authors: Korovnikov I.V. , Varaksina I.V. , Kontorovich A.E. , Parfenova T.M.
Published: October 2023

—We have studied biostratigraphy, lithology and geochemistry of drill cores from the Kyulenke River basin. The study of fossil remains and rock compositions, the analysis of trilobite distributions and changes in the lithological and geochemical characteristics of the sediments made it possible to identify structural features of the marker horizons, to correlate borehole sections and outcrops, to compare individual Cambrian intervals and the regional zones of the Yudoma–Olenek facies region of the Siberian Platform. The study has shown rocks of the Kuonamka Fomation to be enriched in uranium (U) and revealed a direct relationship between the contents of U and organic carbon (Corg) in the analyzed rocks, typical for the lower and middle Cambrian black shale deposits sampled from the outcrops in the eastern parts of the Siberian Platform. For the first time, a relationship of rock radioactivity by gamma-ray logging with the contents of U and Corg in Cambrian rocks was established.
Insights from a 3-Year Genomic Evolution of SARS-CoV-2 Shows a Predominance of Variants from Developing Countries
Authors: Abdelmounim ESSABBAR , Safae EL MAZOURI , Azeddine IBRAHIMI
Published: October 2023

Introduction: In nearly 3 years of circulation among the human population, SARS-CoV-2 underwent a complex evolution, shaping its genetics and adaptation to humans. Our study highlights varying prevalence, distribution across regions, and pandemic timeline.
Methodology: In this study we used a dataset of 14,759 SARS-CoV-2 genomes collected between December 2019 and January 2023 from 214 countries. The sequences were analyzed comparatively to explore how SARS-CoV-2 variant mutation patterns varied across time and geographic locations.
Results: We identified a total of 801 lineages harboring 17,360 nucleic mutations, with an average annual evolution rate of 26.07 substitutions per sample. The lifespan of these variants significantly shortened over time, as dominant virus strains were successively replaced by more adapted variants. SARS-CoV-2 variants' lifespan notably decreased as the pandemic progressed. Dominant virus strains were replaced by more fit variants carrying mutations associated with neutralizing antibodies and potential immune escape. Importantly, we identified a significant proportion of new SARS-CoV-2 variants emerging from developing countries, particularly in sub-Saharan Africa, South America, and South Asia, in spite of the overall homogenization of the SARS-CoV-2 genomic landscape since January 2021.
Conclusions: Our analysis underscores the dynamic evolution of SARS-CoV-2, with variants rapidly emerging, adapting, and spreading globally, particularly from specific geographic regions of the world which shaped the course of the pandemic.
Direct regeneration and morpho-histological study of de novo shoot development from leaf explants of Rhododendron mucronulatum Turcz.
Authors: Zaytseva Yulianna
Published: October 2023

Rhododendron mucronulatum Turcz., a rare medicinal and ornamental deciduous multi-branched shrub native to northern parts of East Asia, is a valuable genetic resource for breeding and biotechnological producing bioactive metabolites. To create propagation system of R. mucronulatum, an efficient method of direct shoot regeneration from leaf explants based on thidiazuron (TDZ) and dark treatment was developed, and detailed histological analysis for revealing localization of cell competent to morphogenesis was carried out for the first time. The highest regeneration rate (75%) and number of shoots per explant (an average of 51.7) were achieved under 0.5 µM TDZ and dark treatment. The dark treatment was found to increase the regeneration rate more than two-fold compared to culturing under light conditions. The histological analysis showed direct organogenesis pathway. The competent to morphogenesis cells were located in epidermal tissue of leaf explants on adaxial side of petiole next to main vein. Two sites of beginning of TDZ-induced adventitious shoot formation were revealed: the shoot formation directly from epidermal tissues and shoot formation from de novoepidermis-derived protrusions. The formation of embryo-like structures was observed on the late morphogenesis stages. It was discovered that parenchymal and epidermal tissues of embryo-like structures were separated from explant tissue but its vascular bundle was connected with vascular bundle of explant. These structures gave rise to development of adventitious shoots. The result obtained can promote further establishment of efficient and stable systems for genetic transformation and biomass production of R. mucronulatum.
Field evaluation of a simple and rapid diagnostic test, RLDT to detect Shigella and enterotoxigenic E. coli in Indian children
Authors: Chowdhury Goutam , Ghosh Debjani , Zhou YiYi , Deb Alok K. , Mukhopadhyay Asish Kumar , Dutta Shanta , Chakraborty Subhra
Published: October 2023

The diagnostic assays currently used to detect Shigella spp. (Shigella) and enterotoxigenic Escherichia coli (ETEC) are complex or elaborate which make them difficult to apply in resource poor settings where these diseases are endemic. The simple and rapid nucleic acid amplification-based assay "Rapid LAMP-based Diagnostic Test (RLDT)" was evaluated to detect Shigella spp (Shigella) and enterotoxigenic Escherichia coli (ETEC) and determine the epidemiology of these pathogens in Kolkata, India. Stool samples (n = 405) from children under five years old with diarrhea seeking care at the hospitals were tested, and 85(21%) and 68(17%) by RLDT, 91(23%) and 58(14%) by quantitative PCR (qPCR) and 35(9%) and 15(4%) by culture, were positive for Shigella and ETEC, respectively. The RLDT showed almost perfect agreement with qPCR, Kappa 0.96 and 0.89; sensitivity 93% and 98%; specificity 100% and 97% for Shigella and ETEC, respectively. While RLDT detected 12% more Shigella and 13% more ETEC than culture, all culture positives for Shigella and ETEC except one each were also positive by the RLDT, sensitivity 97% and 93% respectively. RLDT is a simple, sensitive, and rapid assay that could be implemented with minimum training in the endemic regions to strengthen the disease surveillance system and rapid outbreak detection.
Analysis of the physical-mechanical behavior of the polymer composite reinforced with silicon flotation residue
Authors: Banna Wassim El , Xavier Wendel de Jesus da Cruz , Costa Deibson Silva da , Pinheiro Darllan do Rosário
Published: October 2023

The use of composite materials has seen a significant increase for economic, performance, and environmental reasons. Consequently, improperly discarded industrial waste has been employed as particles in composite materials. Thus, this study addresses the fabrication of polyester matrix composites reinforced with in natura silicon residue particles. In this regard, the manual hand lay-up method was used in the fabrication process, employing rectangular metal molds. Silicon residue was incorporated at mass fractions of 5%, 10%, and 15%. The manufactured composites were analyzed for mechanical properties (tensile and flexural) and physical properties (density, apparent density, water absorption, and apparent porosity). The results showed that the mechanical characteristics of the materials changed with varying mass fractions. X-ray Diffraction (XRD) analysis provided insights into certain material properties based on the identified materials. The studied composite achieved a flammability classification according to established standards. Furthermore, it exhibited tensile strength (37.28 ± 4.87 MPa) and flexural strength (114.17 ± 12.09 MPa).
Assessing Genetic Diversity in Critically Endangered Chieniodendron hainanense Populations within Fragmented Habitats in Hainan
Authors: Chen Yukai , Zhang Hai-Li , Zhang Li , Wu Tingtian , Liu Tingting , Zhou Qin , Nizamani Mir Muhammad
Published: October 2023

Habitat fragmentation engenders a reduction in the geographic distribution of species, thereby rendering diminutive populations susceptible to extinction due to environmental, demographic, and genetic factors. Chieniodendron hainanense (henceforth C. hainanense) exemplifies a wild plant with extremely small populations (WPESP) and faces endangerment, necessitating urgent national conservation efforts. Elucidating the genetic diversity of C. hainanense is crucial for uncovering underlying mechanisms and devising protective strategies. In the present study, 35 specimens from six distinct cohort groups were genotyped utilizing genotyping-by-sequencing (GBS) and single nucleotide polymorphism (SNP) methodologies. The results indicated that C. hainanense exhibits limited genetic diversity. Observed heterozygosity within C. hainanensepopulations spanned from 10.79% to 14.55%, with an average value of 13.15%. The six C. hainanense populations can be categorized into two distinct groups: (1) Diaoluoshan and Baishaling, and (2) Wuzhishan, Huishan, Bawangling, and Jianfengling. The degree of genetic differentiation among C. hainanensepopulations is relatively weak. The observed loss of diversity can be attributed to the effects of natural selection.
Macroscopic inhibition of DNA damage repair pathways by targeting TFAP2A with LEI110 eradicates hepatocellular carcinoma
Authors: Wang Chenchen , Zhao Zhenjun , Zhao Yudon , Xia Lei , Qiang Xia
Published: October 2023

Hepatocellular carcinoma (HCC) is one of the world’s leading causes of cancer-related death and DNA damage repair-related genes were closed related to the progression of HCC. Combining the copy number variation and the expression profile of DNA damage repair-related genes, we observed a unique cluster of “deletion-up” genes in HCC, which strongly correlated with the prognosis of liver cancer. Binding motif analysis and further validation with ChIP-qPCR/dual luciferase assay unveiled that the TFAP2A could modulate the transcription of critical DNA repair genes including TOP2A, NUDT1, POLD1, and PARP1, which eventually facilitated the sanitation of oxidized DNA lesions in cells. Structural analysis and the following validation identified LEI110 as a potent TFAP2A inhibitor. We demonstrated that LEI110 could stabilize TFAP2A and sensitize HCC cells towards different DNA damaging reagents in liver cancer cells. Together, we identified TFAP2A as a crucial transcription modulator for a unique cluster of “deletion-up” genes in HCC and identified LEI110 as a potential inhibitor of TFAP2A which sensitized HCC to DNA-damaging reagents. Our study provide insights into a concept of macroscopic inhibition of DNA damage repair-related genes in the cancer treatment.
Uni-pKa: An Accurate and Physically Consistent pKa Prediction through Protonation Ensemble Modeling
Authors: Zheng Hang , Luo Weiliang , Zhou Gengmo , Zhu Zhengdan , Yuan Yannan , Ke Guolin , Wei Zhewei , Gao Zhifeng
Published: October 2023

Predicting pKa values of small molecules has key applications in drug discovery and molecular simulation. However, current methods face challenges in rigorously interpreting experimental data and ensuring thermodynamic consistency between successive pKa values. To address these limitations, we present Uni-pKa, an accurate and reliable pKa prediction framework. Uni-pKa is based on comprehensive free energy modeling of possible molecules in protonation equilibrium. Within this framework, a structural enumerator recovers underlying structures in pKa datapoints, and a neural network serves as a free energy predictor, learning from data rigorously while inherently preserving thermodynamic consistency. Through a pretraining-finetuning strategy utilizing predicted and experimental pKa data, Uni-pKa achieves state-of-the-art accuracy among chemoinformatic methods. Uni-pKa provides a good example of combining chemical principles and machine learning to solve scientific problems.
Sowing Seeds of Purpose: How Green HRM Practices Elevate Employee Experience
Authors: Sidique Nazif , Pereira Leandro , Dias Alvaro
Published: October 2023

Green Human Resource Management (GHRM) merges environmental and HR practices, promoting green behavior across organizations. This quantitative study examines the effects of GHRM on employees' experiences and perceptions. Results indicate that a higher inclination to adopt GHRM correlates with an enhanced sense of purpose in work, leading to a positive work ambiance. This motivation also ties to greater job satisfaction, emphasizing the significance of aligning individual values with organizational objectives. Notably, organizations with robust GHRM leadership foster greater employee loyalty, underscoring GHRM's role in boosting commitment and cohesion. These insights shed light on GHRM's profound influence on employee welfare and organizational dynamics. Future research should investigate the long-term effects of GHRM on employee behavior.
Property Deterioration in Reactive Elastomeric Terpolymer Modified Binders During Storage at Elevated Temperatures
Authors: Sharma Alok , Pandey Akanksha , R.N GD Ransinchung , Ravindrananth Sham S.
Published: October 2023

Polymer-modified binders are often stored and transported at elevated temperatures, where their properties may deteriorate if mishandled. This study investigates the effect of storage temperature, storage time, base binder, and PPA concentration on the conventional and rheological properties of commercial-grade reactive elastomeric terpolymer-modified binders (RET-MBs). To mimic practical storage conditions, RET-MB was contained in sealed metal tubes and stored in a forced convection oven at temperatures of 120, 135, 150, and 165°C for up to 14 days. The results show that the deterioration in conventional and rheological properties of RET-MB was noticeable even at a low storage temperature of 135°C. At temperatures of 150 and 165°C, significant erosion in properties was observed within the first three days of storage. After 7 days of storage at 150°C, the softening point, Tu, and % elastic recovery values decrease by 4°C, 3.5°C, and 46%, respectively. One PG-grade drop can occur after 3–7 days of storage at 150 and 165°C. FTIR analysis of the solution-cast films of RET polymer reveals a strong interaction of the epoxy ring with PPA molecules to form phosphate ester linkage during storage, due to which the interaction between RET polymer and binder molecules reduces, resulting in property erosion during storage. The results show that RET-MBs should be stored and transported at temperatures < 135°C.
NK Receptors Replace CD28 As the Dominant Source of Signal 2 for Cognate Recognition of Cancer Cells by TAA-specific Effector CD8+ T Cells
Authors: Kalinski Pawel , Dong Bowen , Obermajer Natasa , Tsuji Takemasa , Matsuzaki Junko , Bonura Cindy , Withers Henry , Long Mark , Chavel Colin , Olejniczak Scott , Minderman Hans , Edwards Robert , Storkus Walter , Romero Pedro
Published: October 2023

CD28-driven “signal 2” is critical for naïve CD8+ T cell responses to dendritic cell (DC)-presented weak antigens, including non-mutated tumor-associated antigens (TAAs). However, it is unclear how DC-primed cytotoxic T lymphocytes (CTLs) respond to the same TAAs presented by cancer cells which lack CD28 ligands. Here, we show that NK receptors (NKRs) DNAM-1 and NKG2D replace CD28 during CTL re-activation by cancer cells presenting low levels of MHC I/TAA complexes, leading to enhanced proximal TCR signaling, immune synapse formation, CTL polyfunctionality, release of cytolytic granules and antigen-specific cancer cell killing. Double-transduction of T cells with recombinant TCR and NKR constructs or upregulation of NKR-ligand expression on cancer cells by chemotherapy enabled effective recognition and killing of poorly immunogenic tumor cells by CTLs. Operational synergy between TCR and NKRs in CTL recognition explains the ability of cancer-expressed self-antigens to serve as tumor rejection antigens, helping to develop more effective therapies.
Reference interval proposal for fasting insulin and HOMA-IR measurement based on access to an extensive big Brazilian laboratory database.
Authors: Schrank Yolanda , Fontes Rosita , Perozo Andrea Faria Dutra Fragoso , Araújo Paula Bruna , Pinheiro Maria Fernanda Miguens Castelar , Gomes Dalva Margareth Valente , Vieira Luisane Maria Falci
Published: October 2023

Objectives: Fasting insulin and the homeostatic model assessment of insulin resistance (HOMA-IR) index are relatively simple and reliable noninvasive markers of insulin resistance (IR). Given the relevance of correctly diagnosing IR, we emphasize the importance of establishing reliable reference intervals (RIs) for these markers.
This study aimed to determine the reference RIs of fasting insulin and HOMA-IR index in adults living in Rio de Janeiro – Brazil, and, secondarily, to verify if there was any difference in RIs between sexes.
Methods: Fasting serum insulin levels of 146497 (20 to 60 years old) subjects submitted to blood sampling from January to December of 2019 in Rio de Janeiro were obtained retrospectively through access to an extensive laboratory database. Insulin was determined by the electrochemiluminescence immunoassay (ECLIA) method, using Roche Diagnostics kits. After applying exclusion criteria 21684 subjects [18576 (86%) women] were included (average 36 ± 3.66 years). Reference interval was established using a validated mining algorithm named Laboratory Reference Interval (LabRI).
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Results: Overall, 95% RIs for fasting insulin levels were, respectively, 2.54-13.30, 2.43-11.89, and 2.52-13.14 μU/mL (15.3-80.12, 14.6-71.7, and 15.2-79.2 pmol/L) in women, men, and the total population. HOMA-IR index RIs were 0.39-2.86, 0.38-2.81, and 0.39-2.86 in women, men, and the total population. Although the difference in insulin levels and HOMA-IR index between men and women were statistically significant, it does not justify using sex-specific RIs.
Conclusion: We conclude that RIs of fasting insulin and HOMA-IR index found in the total population can be applied to both sexes. Thus, we suggest the following RIs for our population: fasting Insulin: 2.52-13.14 μU/mL (15.1-78.8 pmol/L) and HOMA-IR index: 0.39-2.86.
Spontaneous creation of muons and destruction of protons in ultra- dense hydrogen H(0)
Authors: Holmlid Leif
Published: October 2023

A patented laser-induced muon generator (Holmlid 2017) is here used to observe also the spontaneous formation of muons from ultra-dense hydrogen H(0). The muons are detected by their interaction with converters and scintillators both inside and outside the vacuum apparatus containing the muon generator. This interaction creates x-ray radiation which then gives beta e+e- pairs with a zero energy cutoff of 510 ± 10 keV. The e+e- energy distributions are matched by a statistical model. It is concluded that muons are formed by spontaneous annihilation nuclear processes in H(0) primarily creating mesons. The lifetime before the spontaneous proton destruction by annihilation is estimated from the results to be of the order of 1011 years, thus much shorter than theoretical proton lifetimes.
Effects of Metformin on Transcriptomic and Metabolomic Profiles in Breast Cancer Survivors Enrolled in the Randomized Placebo-Controlled MetBreCS Trial
Authors: Strømland Pouda Panahandeh , Bertelsen Bjørn-Erik , Viste Kristin , Chatziioannou Anastasia Chrysovalantou , Bellerba Federica , Robinot Nivonirina , Trolat Amarine , Flågeng Marianne Hauglid , Scalbert Augustin , Keski-Rahkonen Pekka , Sears Dorothy D. , Bonanni Bernardo , Gandini Sara , Johansson Harriet , Mellgren Gunnar
Published: October 2023

Background
Metformin reduces the incidence of breast cancer in patients with type 2 diabetes and obesity. However, our knowledge about the effects of metformin on cancer recurrence in breast tissue is limited. Therefore, in this study, we examined the breast tissue gene expression changes by metformin in breast cancer survivors.
Methods
Within the randomized placebo-controlled MetBreCS trial, baseline and one-year post-treatment fasting plasma and serum as well as breast tissue biopsies were collected. Breast cancer survivors with BMI >25 kg/m2 were randomly assigned to metformin (n=27), or placebo (n=13). We analyzed the transcriptomic profiles of the tissue biopsies by RNA sequencing. We also performed high-throughput metabolomics and sex steroid hormone analyses on the plasma and serum samples, respectively. To identify the metformin-associated signaling pathways in breast tissues, we integrated the gene expression and metabolomics and steroid hormone profiles using bivariate and functional analysis.
Results
Comparing breast tissue transcriptomic data, we identified MS4A1, HBA2, MT-RNR1 and MT-RNR2 expression to be differentially expressed in breast tissues from pre- and postmenopausal women. We also found significant metformin-associated down-regulation of EGFL6 and FDCSP in postmenopausal women. Long-term metformin treatment was significantly associated with decreased plasma levels of citrulline, arginine, PC ae C36:5, PC ae C38:6, caffeine, and 4-methyl-2-oxovalerate. The integration of transcriptomic and metabolomic profiles using bivariate correlation analysis followed by functional analysis revealed a down-regulation of immune response associated with the reduced plasma levels of arginine and citrulline in the pre- and postmenopausal metformin-treated group. The correlation between two steroid hormones (17β-estradiol, estrone) and global gene expression also showed an enrichment of steroid hormone biosynthesis and metabolism pathway with highly negatively correlated CYP11A1 and CYP1B1 expression in breast tissue from postmenopausal metformin-treated women.
Conclusions
Our results indicate that breast cancer survivors treated with metformin have specific changes in breast tissue gene expression that may prevent the development of new tumors. Reduced levels of circulating arginine, citrulline, and estrogens in metformin-treated breast cancer survivors may also contribute to reducing recurrence risk in obesity-associated breast cancer.
Trial registration
MetBreCs trial was started in 2015 and is registered at European Union Clinical Trials Register (EudraCT Protocol #: 2015-001001-14) on 7 October 2015.
The Perennial Logistical Challenges during Nigerian Elections: The Unmanned Aircraft System (UAS) Solution
Authors: Ehimare Ehinomen , Orikpete Ochuko , Ewim Daniel Raphael Ejike
Published: October 2023

The Independent National Electoral Commission (INEC) in Nigeria continues to grapple with recurrent logistical issues during elections. To address these challenges, this research focused on the potential deployment of a hybrid Vertical Take-off and Landing (VTOL) fixed-wing Unmanned Aircraft System (UAS), employing Commercial-off-the-Shelf (COTS) components and subsystems, as a conduit for efficient transmission of election results from remote polling units to nationwide collation centers. The study used a mixed-methods approach, combining technical evaluation, economic analysis, and a consideration of political and environmental contexts. Additionally, the research considered the practicalities of component sourcing and the economic implications of importing necessary equipment into Nigeria. Findings underscored the paramountcy of cost-effectiveness, component reliability, weight, and system criticality in the selection of COTS components that would best fulfill the project's objectives. Importantly, the results highlighted the potential political barriers to UAS deployment in this context. The study concludes that while the proposed UAS solution holds promise, it must contend with significant political hurdles and practical considerations concerning component sourcing and importation. The study recommends further exploration of these issues to optimally implement this technological solution to address Nigeria's election logistics challenges.
Irritable bowel syndrome associated with B. hominis or without relationship of it? A case control study and minireview
Authors: Maghsood Amir Hossein , Kayedimajd Shaghayegh , Motavallihaghi Seyedmousa , Abedian Rohallah , Kordi Shirafkan , Davoodi Lotfollah , Faizi Fariba , Soleymani Eissa
Published: October 2023

Background: Blastocystis hominis (B. hominis) is a protozoan parasite that is found worldwide distribution. some studies have suggested a link between B. hominis and the development of irritable bowel syndrome (IBS). The objective of this study was to determine the prevalence of B. hominis in patients with IBS compared to healthy individuals.
Material and methods: A total of 65 stool samples from patients with IBS and 65 samples from healthy individuals in northern Iran were examined, the samples were tested using various methods including direct smear, formalin ether sedimentation and culture to detect the presence of B. hominis. Additionally, polymerase chain reaction (PCR) was performed on all culture-positive isolates to confirm the results and identify the genotype.
Results: B. hominis was detected in 15.38% of IBS patients and 9.2% of the healthy group. The culture in RPMI1640 was found to be better than the formalin ether and direct smear methods. Positive samples were confirmed using the molecular method. No significant difference was observed in the order of B. hominisinfection between the two groups.
Conclusions: The results of our study indicate that no significant difference was observed in the order of B. hominisinfection between IBS patients and healthy groups. Therefore, firthet, study is necessary to determine the potential pathogenic effects of this parasite and its role in causing IBS.
Synergistic neuroprotective action of prolactin and 17β-estradiol on kainic acid-induced hippocampal injury and long-term memory deficit in ovariectomized rats.
Authors: Torre Karen De la , Cerbón Marco Antonio , Molina-Salinas Gladys , Suárez-Santiago José Eduardo , Morin Jean Pascal , Roldán-Roldán Gabriel , Picazo Ofir
Published: October 2023

Purpose
The neuroprotective actions of the ovarian hormone 17β-estradiol (E2) against different brain lesions have been continuously confirmed in a variety of models including kainic acid (KA) lesions. In the same line, the pituitary hormone prolactin (PRL), traditionally associated to lactogenesis, has recently been linked to a great diversity of functions, including neurogenesis, neuroprotection, and cognitive processes. While the mechanisms of actions of E2 regarding its neuroprotective and behavioral effects have been extensively explored, the molecular mechanisms of PRL related to these roles remain under investigation. The aim of the current study was to explore if the simultaneous administration of PRL and a low dose of E2 prevents the KA-induced cognitive deficit and if this action is associated to changes in hippocampal neuronal density.
Methods
Ovariectomized (OVX) rats were treated with saline, PRL and/or E2 in the presence or absence of KA. Neuroprotection was assessed by Nissl staining and neuron counting. Evaluation of memory was carried out by means of the novel object recognition test (NOR).
Results
These findings indicate that both PRL and E2 prevent short- and long-term memory deficits in lesioned animals. In addition, both hormones exert neuroprotection against KA-induced excitotoxicity in the hippocampus. Interestingly, the combined hormonal treatment was superior at improving the behavioral performance of rats in the NOR and neuronal survival than either treatment administered separately.
Conclusion
Taken together, these results suggest that these hormones act in different ways at the hippocampus to produce their behavioral, proliferative, and neuroprotective effects.
Alkalosis in Regional Citrate Anticoagulation during Continuous Renal Replacement Therapy—— A single-center retrospective study
Authors: Tang Hanqi , Cui Qinghong , Xu Shengyong , Wu Yao , Shi Jing , Zhu Huadong , Yu Xuezhong , Xu Jun
Published: October 2023

Background:
Metabolic alkalosis has raised concerns in patients receiving continuous renal replacement therapy (CRRT) via regional citrate anticoagulation (RCA). This study searched for alkalosis-related factors and mechanisms.
Measurements:
We conducted a retrospective cross-sectional study of alkalosis in patients who received CRRT for at least 12 hours with RCA at an emergency department in a tertiary hospital between April 2017 and April 2020.
Main Results:
The 59 patients meeting the inclusion criteria were 49% male, with a mean age of 55 ± 18 years old, and 42% had alkalosis by 12 hours after CRRT. Patients were divided into 4 groups based on whether they received NaHCO3 and alkalosis after 12 hours of CRRT. No significant differences in demographic features or laboratory results were observed among the groups. CRRT metrics, including blood flow rate, PBP rate, replacement fluid rate and total effluent rate, were significantly different among groups (p < 0.01). Multivariable logistic regression analysis indicated that the citrate rate was a risk factor for alkalosis (OR 1.088, 95% CI 1.020–1.161, p = 0.010). In patients receiving no NaHCO3 and without alkalosis, the linear regression analysis described the relationships of citrate with replacement fluid rate (citrate rate = 0.090 × replacement fluid rate + 56.581; R2 = 0.6918) and total effluent rate (citrate rate = 0.099 × total effluent rate + 2.449).
Conclusions:
This retrospective observational study demonstrated that CRRT metrics are highly associated with alkalosis after 12 hours of CRRT. Without NaHCO3 infusion, a 10-fold linear correlation was observed between citrate and total effluent rate in patients without metabolic alkalosis.
Retromer stabilization using a pharmacological chaperone protects in an α-synuclein based mouse model of Parkinson’s
Authors: Eleuteri Simona , Fang Tracy Shi Zhang , Cutillo Gianni , Persico Michele , Simon David K
Published: October 2023

Background In the present study we assessed the protective effects of a pharmacological approach to stabilize the retromer complex in a PD mouse model. Missense mutations in the VPS35 gene are a rare cause of familial PD. The VPS35 protein is a subunit of the retromer cargo recognition complex and has a variety of functions within neurons, many of which are potentially relevant for the pathophysiology of PD. Prior studies have revealed a role for the retromer complex in controlling accumulation and clearance of α-synuclein aggregates. We previously identified an aminoguanidine hydrazone, 1,3 phenyl bis guanylhydrazone (compound 2a), as a pharmacological stabilizer of the retromer complex that increases retromer subunit protein levels and function.
Methods Here, we validate the efficacy of 2a in protecting against αSynuclein pathology and dopaminergic neuronal degeneration in a PD mouse model generated by unilateral injection of AAV-A53T-αSynuclein in the substantia nigra.
Results Daily intraperitoneal administration of 2a at 10 mg/Kg for 100 days led to robust protection against behavioral deficits, dopaminergic neuronal loss and loss of striatal dopaminergic fibers and striatal monoamines. Treatment with 2a activated αSynuclein degradation pathways in the SN and led to significant reductions in aggregates and pathological αSynuclein.
Conclusion These data suggest retromer stabilization as a promising therapeutic strategy for Parkinson’s disease leading to neuroprotection of dopaminergic neurons and rescue in the accumulation of pathological and aggregates αSynuclein. We identified 2a compound as potential clinical drug candidate for future testing in Parkinson’s disease patients.
Prevention Messaging Concerning Safe Storage of Firearms in Media Reports of Pediatric Unintentional Firearm Deaths.
Authors: Hammig Bart , Bordelon Abigail , Chandler Corinne
Published: October 2023

Background: To examine the use of prevention messaging on the safe storage of firearms among media outlets when reporting on unintentional firearm deaths among children aged 0-11.
Methods: The Gun Violence Archive collects information from media sources regarding firearm injuries and deaths. We analyzed data from 2021-2022 to analyze prevention messaging incorporated into the media reports. We then examined if media reporting of events that occurred in States with CAP laws had a higher likelihood of including prevention messaging compared to those events occurring in States without CAP laws.
Results: There were 223 deaths reported that were attributed to unintentional firearm discharge among children aged 0-11. Prevention messages were delivered in 61 of the 223 incidents. Specific messages which included the word “lock” when referring to firearm storage were included in 21.9% of all incidents. An analysis examining State CAP laws and the presence of any prevention message per event did not yield any discernable relationship.
Conclusion: Inclusion of prevention messaging stating that firearms should be stored locked and unloaded when reporting on unintentional firearm deaths among children is lacking. When specific prevention messaging was included, the source was often law enforcement. Public health officials may play an important role in educating the journalistic and law enforcement communities about the inclusion of safe storage messages when reporting on firearm deaths.
Elucidating the Link Between Hypovitaminosis D and Sarcopenia: New Insights into Mechanisms and Threshold from the Evidence of NHANES 2011-2018
Authors: He Yuwei , Li Yuguang , Liu Yining , Zhao Yixin , Li Fangqi , Chen Xinqiao , Song Jia , Ji Wei , Liu XiangLiang , Cui JiuWei
Published: October 2023

Background:
Sarcopenia is most common in older adults and is defined as a decrease in skeletal muscle muscle mass, which can cause impaired mobility and increased risk of physical disability. The role of Vitamin D is well known for its classical effects on bone health, and growing evidence also suggests its beneficial effects on muscle function and metabolism. Our study aimed to explore the association between vitamin D and sarcopenia/low muscle mass by using statistic approaches.
Methods:
In this study, 7217 participants aged 18–60 years in the nationally National Health and Nutrition Examination Survey (NHANES)2011–2018 were included finally. Multivariable logistic regression was used to assess the the potential and deeper connection of vitamin D and sarcopenia/low muscle mass. Restricted cubic splines (RCS) was used to explore their potential dose-response relationships and interactions. Mediation analysis was used to explore their potential mediated effects of neutrophils and calcium and phosphate product between vitamin D and sarcopenia/low muscle mass.
Results:
With increasing vitamin D, both the risk of sarcopenia and low muscle mass decreased significantly. The RCS showed the similar results. Mediation analysis suggested that neutrophils can be affected by mediations from vitamin D to sarcopenia/low muscle mass. Additionally, vitamin D may lead to low muscle mass by stimulating mechanisms calcium and phosphate product.
Conclusions:
Decreased serum vitamin D may be strongly associated with occurrence of sarcopenia/low muscle mass. This study provided important evidence for elucidating the relationships between vitamin D and skeletal muscle mass.
Biological features of the rarest narrow-range plant species Potentilla porphyrantha Juz. (Rosaceae)
Authors: Fayvush George , Ghukasyan Anahit , Janjughazyan Karine , Aleksanyan Alla , Khachatryan Lilit , Hovhannisyan Hripsime , Hovakimyan Zhanna
Published: October 2023

Potentilla porphyranthaJuz. (Rosaceae)is a very rare stenotopic species, which area of distribution includes small subpopulations in Armenia, Nakhichevan and North Iran. It was assessed and listed in the Red Data Book of Armenia in the category Critically Endangered Species. The main threats for this species could be anthropogenic factors (mainly mining industry) and forecasted climate change. The purpose of this work was to identify the adaptive potential of the studied species and the possibility of its conservation in ex situ conditions as well reintroduction into nature, and to assess the threat to natural populations from predicted climate change. It was shown that in Armenia there is only one species from the sectionPersicaewith pink flowers. In the first time karyology and palynology of this species were investigated, number of chromosomes and karyotype were find, as well in the first time pollen morphology was described and their fertility was estimated. Eco-physiological investigations allowed to estimate potential of species adaptation to new environmental conditions. Special attention was paid to possible adaptation of this species to forecasted climate change. All these investigations allowed us to elaborate methods for conservation, reproduction and reintroduction ofPotentilla porphyranthaback to the nature.
Late myocardial infarction due to coronary embolism after mechanical aortic valve replacement: A case report
Authors: Kus Mukan Kagan , Karaagac Anil , Bozkurt Burak , Ceylan Ufuk Sadik , Kaplan Mehmet
Published: October 2023

Prosthetic valve thrombosis in aortic valve and its complication coronary embolism is a very rare condition. Diagnosis and treatment process is challenging. We present a young patient with acute myocardial infarction who underwent mechanical aortic valve replacement operation one month earlier. Primary coronary intervention was performed and it was succesful. Transeasophageal ecocardiography was performed. Thrombus was seen on the mechanical aortic valve and thrombolytic therapy was initiated. Control TEE was performed and there was no signs of thrombi. The patient was discharged.