bluuebunny/crossref_metadata_2025 huggingface dataset:
Relationship between intrathrombotic appearance of HSP27 and HSP70 and thrombus ages in a murine model of deep vein thrombosis
Authors: Nosaka Mizuho , Ishida Yuko , Kuninaka Yumi , Ishigami Akiko , Taruya Akira , Shimada Emi , Hashizume Yumiko , Yamamoto Hiroki , Kimura Akihiko , Furukawa Fukumi , Kondo Toshikazu
Published: December 2023

Heat shock proteins (HSPs) are molecular chaperones whose primary function is cytoprotection, supporting cell survival under (sub) lethal conditions. They have been implicated in various diseases such as inflammatory diseases and cancer due to their cytoprotective and immunomodulatory effects, and their biological mechanisms have been studied. Central family members include, HSP27, which is induced by various stimuli such as heat shock, hypoxia, hyperoxia, ultraviolet exposure, and nutritional deficiency, and HSP70, which is homeostatically expressed in many organs such as the gastrointestinal tract and has anti-cell death and anti-inflammatory effects. In this study, HSP27 and HSP70 were investigated during thrombus formation and dissolution in a deep vein thrombosis model by immunohistochemistry to determine their involvement in this process and whether their expression could be used as a forensic marker. In the process of thrombus formation and lysis, HSP27 and HSP70 were found to be expressed by immunohistochemical analysis. The role of inhibitors of HSP27 and HSP70 in the pathogenesis of thrombosis in mice was also investigated. When HSP27 or HSP70 inhibitors were administered, thrombi were significantly smaller than in the control group on day 5 after inferior vena cava ligation, indicating pro-thrombotic effects HSP27 and HSP70. If HSP27- or HSP70-positive cells were clearly visible and easily identifiable in the thrombus sections, the thrombus was presumed to be more than 10 days old. Thus, the detection of intrathrombotic HSP27 and HSP70 could forensically provide useful information for the estimation of thrombus ages. Collectively, our study implied that both HSP27 and HSP70 might be molecular targets for thrombus therapy and that the detection of HSP-related molecules such as HSP27 and HSP70 could be useful for the determination of thrombus ages.
Experimental insights into electrocatalytic [Cp*Rh(bpy)Cl]+ mediated NADH regeneration
Authors: Meyer Jonas , Romero Manuela , Thöming Jorg , Baune Michael , Reimer Nicholas , Dringen Ralf , Bösing Ingmar
Published: December 2023

NADH plays a crucial role in many enzymatically catalysed reactions. Due to the high costs of NADH a regeneration mechanism of this cofactor can enlarge the applications of enzymatic reactions dramatically. This paper gives a thorough system analysis of the mediated electrochemical regeneration of active NADH using cyclic voltammograms and potentiostatic measurements with varying pH, electrode potential, and electrolyte solution, highlighting the system’s limiting conditions, elucidating optimal working parameters for the electrochemical reduction of NAD+, and bringing new insight on the oxidation of inactive reduction products. Using [Cp*Rh(bpy)Cl]+ as an electron mediator dramatically increases the percentage of enzymatically active electrochemically reduced NADH from 15% (direct) to 99% (mediated) with a faradaic efficiency of up to 86%. Furthermore, investigations of the catalytic mechanisms of [Cp*Rh(bpy)Cl]+ clarifies the necessary conditions for its functioning and questions the proposed reaction mechanism by two-step reduction where first the mediator is reduced and then brought in contact with NAD+.
Bayesian posterior density estimation reveals degeneracy in three-dimensional multiple emitter localization
Authors: van Dijk Raymond , Kalisvaart Dylan , Cnossen Jelmer , Smith Carlas S.
Published: December 2023

Single-molecule localization microscopy requires sparse activation of emitters to circumvent the diffraction limit. In densely labeled or thick samples, overlap of emitter images is inevitable. Single-molecule localization of these samples results in a biased parameter estimate with a wrong model of the number of emitters. On the other hand, multiple emitter fitting suffers from point spread function degeneracy, which increases model and parameter uncertainty. To better estimate the model, parameters and uncertainties, a three-dimensional Bayesian multiple emitter fitting algorithm was constructed using Reversible Jump Markov Chain Monte Carlo. It reconstructs the posterior density of both the model and the parameters, namely the three-dimensional position and photon intensity, of overlapping emitters. The ability of the algorithm to separate two emitters at varying distance was evaluated using an astigmatic point spread function. We found that for astigmatic imaging, the posterior distribution of the emitter positions is multimodal when emitters are within two times the in-focus standard deviation of the point spread function. This multimodality describes the ambiguity in position that astigmatism introduces in localization microscopy. Biplane imaging was also tested, proving capable of separating emitters up to 0.75 times the in-focus standard deviation of the point spread function while staying free of multimodality. The posteriors seen in astigmatic and biplane imaging demonstrate how the algorithm can identify point spread function degeneracy and evaluate imaging techniques for three-dimensional multiple-emitter fitting performance.
Gα12 signaling regulates transcriptional and phenotypic responses that promote glioblastoma tumor invasion
Authors: Chaim Olga Meiri , Miki Shunichiro , Prager Briana C. , Ma Jianhui , Jeong Anthony Y. , Lara Jacqueline , Tran Nancy K. , Smith Jeffrey M. , Rich Jeremy N. , Gutkind J. Silvio , Miyamoto Shigeki , Furnari Frank B. , Brown Joan Heller
Published: December 2023

In silico interrogation of glioblastoma (GBM) in The Cancer Genome Atlas (TCGA) revealed upregulation of GNA12 (Gα12), encoding the alpha subunit of the heterotrimeric G-protein G12, concomitant with overexpression of multiple G-protein coupled receptors (GPCRs) that signal through Gα12. Glioma stem cell lines from patient-derived xenografts also showed elevated levels of Gα12. Knockdown (KD) of Gα12 was carried out in two different human GBM stem cell (GSC) lines. Tumors generated in vivo by orthotopic injection of Gα12KD GSC cells showed reduced invasiveness, without apparent changes in tumor size or survival relative to control GSC tumor-bearing mice. Transcriptional profiling of GSC-23 cell tumors revealed significant differences between WT and Gα12KD tumors including reduced expression of genes associated with the extracellular matrix, as well as decreased expression of stem cell genes and increased expression of several proneural genes. Thrombospondin-1 (THBS1), one of the genes most repressed by Gα12 knockdown, was shown to be required for Gα12-mediated cell migration in vitro and for in vivo tumor invasion. Chemogenetic activation of GSC-23 cells harboring a Gα12-coupled DREADD also increased THBS1 expression and in vitro invasion. Collectively, our findings implicate Gα12 signaling in regulation of transcriptional reprogramming that promotes invasiveness, highlighting this as a potential signaling node for therapeutic intervention.
The timing of the initial collision between the South and North China blocks constraining from the sediments in the eastern Sichuan Basin
Authors: Liu Tianjia , Hu Zongquan , Zhang Dianwei , Li Shuangjian , Cheng Chuanjie , Zhou Lingfang , Wang Guanping , Wang Xunlian , Wang Zhentao
Published: December 2023

In this study, detrital zircon U–Pb geochronology, trace element and Hf isotopic compositional data from the Early-Middle Triassic clastic rocks in the eastern Sichuan Basin were obtained to distinguish the sediment provenance and constrain the timing of the initial collision between the South China and North China blocks. Detrital zircons from the Early Triassic Feixianguan Formation clastic rocks yield one major age peak at 2476 Ma and three minor age peaks at 1886, 802 and 304 Ma. These detrital zircons may be derived from the South China Block. Detrital zircons from the Early Triassic Jialingjiang Formation clastic rocks yield multiple age peaks at 979, 856, 392 and 269 Ma, indicating a mixed sediment provenance from the South China Block and Qinling Orogenic Belt. This is the first appearance of the detritus with the Qinling Orogenic Belt affinity in the eastern Sichuan Basin. Detrital zircons from the Middle Triassic Leikoupo Formation clastic rocks yield two centralized age peaks at 447 and ca. 245 Ma. These zircons may mainly be derived from the Qinling Orogenic Belt. The results indicate an abrupt change in the detrital zircon U–Pb provenance from the South China Block to the Qinling Orogenic Belt during the Early-Middle Triassic. Integrating the provenance change and other geological characteristics, we suggest that the initial collision in the eastern Qinling Orogenic Belt occurred in the Early Triassic.
Brain age prediction using combined deep convolutional neural network and multi-layer perceptron algorithms
Authors: Joo Yoonji , Namgung Eun , Jeong Hyeonseok , Kang Ilhyang , Kim Jinsol , Oh Sohyun , Lyoo In Kyoon , Yoon Sujung , Hwang Jaeuk
Published: December 2023

The clinical applications of brain age prediction have expanded, particularly in anticipating the onset and prognosis of various neurodegenerative diseases. In the current study, we proposed a deep learning algorithm that leverages brain structural imaging data and enhances prediction accuracy by integrating biological sex information. Our model for brain age prediction, built on deep neural networks, employed a dataset of 3004 healthy subjects aged 18 and above. The T1-weighted images were minimally preprocessed and analyzed using the convolutional neural network (CNN) algorithm. The categorical sex information was then incorporated using the multi-layer perceptron (MLP) algorithm. We trained and validated both a CNN-only algorithm (utilizing only brain structural imaging data), and a combined CNN-MLP algorithm (using both structural brain imaging data and sex information) for age prediction. By integrating sex information with T1-weighted imaging data, our proposed CNN-MLP algorithm outperformed not only the CNN-only algorithm but also established algorithms, such as brainageR, in prediction accuracy. Notably, this hybrid CNN-MLP algorithm effectively distinguished between mild cognitive impairment and Alzheimer’s disease groups by identifying variances in brain age gaps between them, highlighting the algorithm’s potential for clinical application. Overall, these results underscore the enhanced precision of the CNN-MLP algorithm in brain age prediction, achieved through the integration of sex information.
Surface plasmon coupling between wide-field SPR microscopy and gold nanoparticles
Authors: Al-Bataineh Qais M. , Telfah Ahmad D. , Tavares Carlos J. , Hergenröder Roland
Published: December 2023

The coupling behavior of the wide field surface plasmon microscopy (WF-SPRM) with single-, two-, and multiple-gold nanoparticles (AuNPs) with different AuNPs sizes is investigated using theoretical, simulation, and experimental approaches. The signal intensity of a single AuNP increases from 208 a.u. to 583 a.u. as particle size increases from 40 to 80 nm, which evidences the signal-building mechanism of Rayleigh scattering theory. A discrete particle model of SPR is used to understand the interaction between an Au-layer and a single AuNP. The calculated intensity profile of the single AuNP from the discrete particle model is accepted with the experimental data. In addition, the superposition between 2-AuNPs surface plasmon waves is studied using the finite element method as well as experimental data from WF-SPRM. The surface plasmon waves around the two particles generate an interference pattern. Finally, it is demonstrated that plasmonic multiple particles scattering can be represented by an effective media, which is described by Maxwell-Garnet equations.
Experimental study on the gas desorption law in coal affected by dynamic water injection
Authors: Shi Tianwei , Wang Aiwen , Dai Lianpeng , Wang Gang
Published: December 2023

Water from hydraulic technology affects the desorption of gas from coal seams. Gas desorption behavior is critical information for gas control in coal mines. In this study, a designed coal seam water injection simulation experimental device was utilized to conduct dynamic water injection experiments on coal samples at different adsorption equilibrium pressures, analyzing the gas desorption law under dynamic water injection, as well as the role of water replacement, water imbibition and water blockage in gas desorption. The results showed that water altered the gas desorption rate in coal, causing fluctuating attenuation of the desorption rate of a water-injected coal sample (WCS). Under the same adsorption equilibrium pressure, the relationship between the desorption rate of the WCS and the non-water-injected coal samples (NCS) underwent a transition in desorption time. In contrast to the NCS desorption curves, the WCS desorption curves lacked a rapid growth phase and exhibited only a slow growth phase and a stopping phase. Water imbibition and water replacement promoted the desorption of gas in the non-wet area during the water injection process, while it inhibited the desorption of gas in the wet area. Under the effects of water imbibition, water blockage, and water replacement, the discharge rate of WCS is greater than the desorption rate of NCS, indicating that water injection increases the total amount of gas desorption. The study results have significant implications for gas extraction and the prevention and control of coal and gas outbursts.
Decomposing the rural–urban gap in hygienic material use during menstruation among adolescent women in India
Authors: Chakrabarty Mahashweta , Singh Aditya , Let Subhojit , Singh Shivani
Published: December 2023

The use of hygienic materials (sanitary napkins, locally prepared napkins, tampons, and menstrual cups) during menstruation among adolescent women in India has improved over the years, yet a significant rural–urban gap in the usage persists at the national level. This study investigates how this rural-urabn gap varies across different states and union territories (UTs) of India and uses Fairlie decomposition to quantify the contribution of various factors to this gap. The study uses data on 114,805 adolescent women (aged 15–19 years) from the fifith round of National Family Health Survey (2019–21). The utilization of hygienic materials during menstruation among adolescent women in rural India stood at 43%, whereas in urban areas, it was 68%, indicating a significant 25 percentage point (pp) difference between the two. The rural–urban gap in the hygienic material use varied significantly across Indian states and UTs. The gap exceeded 20 pp in Madhya Pradesh (36 pp), Odisha (26 pp), Jammu and Kashmir (25 pp), Assam (25 pp), Uttar Pradesh (23 pp), Jharkhand (22 pp), Chhattisgarh (21 pp), and Rajasthan (21 pp). In contrast, the gap in Tamil Nadu, Himachal Pradesh, and Telangana was less than 10 pp. The decomposition analysis of the rural–urban gap (25 pp) revealed that the variables included in the anlaysis explained about 70% of the gap. The difference in the household wealth between rural and urban areas contributed about 69% of the explained gap. Other significant contributors to the explained gap were ‘transportation to health facility’ (5.6%), ‘mass-media exposure’ (4.9%), and ‘level of education (4.4%). The findings underscore the necessity for state-specific interventions aimed at vulnerable groups, particularly individuals from economically disadvantaged backgrounds, those with lower levels of education, and limited exposure to mass media, in order to reduce the existing rural–urban disparity in hygienic material use among adolescent women.
Hematopoietic and stromal DMP1-Cre labeled cells form a unique niche in the bone marrow
Authors: Root Sierra H. , Matthews Brya G. , Torreggiani Elena , Aguila Hector Leonardo , Kalajzic Ivo
Published: December 2023

Skeletogenesis and hematopoiesis are interdependent. Niches form between cells of both lineages where microenvironmental cues support specific lineage commitment. Because of the complex topography of bone marrow (BM), the identity and function of cells within specialized niches has not been fully elucidated. Dentin Matrix Protein 1 (DMP1)-Cre mice have been utilized in bone studies as mature osteoblasts and osteocytes express DMP1. DMP1 has been identified in CXCL12+ cells and an undefined CD45+ population. We crossed DMP1-Cre with Ai9 reporter mice and analyzed the tdTomato+ (tdT+) population in BM and secondary hematopoietic organs. CD45+tdT+ express myeloid markers including CD11b and are established early in ontogeny. CD45+tdT+ cells phagocytose, respond to LPS and are radioresistant. Depletion of macrophages caused a significant decrease in tdT+CD11b+ myeloid populations. A subset of CD45+tdT+ cells may be erythroid island macrophages (EIM) which are depleted after G-CSF treatment. tdT+CXCL12+ cells are in direct contact with F4/80 macrophages, express RANKL and form a niche with B220+ B cells. A population of resident cells within the thymus are tdT+ and express myeloid markers and RANKL. In conclusion, in addition to targeting osteoblast/osteocytes, DMP1-Cre labels unique cell populations of macrophage and stromal cells within BM and thymus niches and expresses key microenvironmental factors.
Sustainable manufacturing through application of reconfigurable and intelligent systems in production processes: a system perspective
Authors: Todescato Marco , Braholli Orjola , Chaltsev Dmitry , Di Blasio Ilaria , Don Davide , Egger Georg , Emig Julius , Pasetti Monizza Gabriele , Sacco Pasqualina , Siegele Dietmar , Steiner Dieter , Terzer Michael , Riedl Michael , Giusti Andrea , Matt Dominik
Published: December 2023

Sustainable production aims at creating products from processes that minimize environmental impact, energy consumption and natural resources. Customers and markets are ever more leaning towards digital, custom, and flexible solutions with lower environmental impact. Hence, Industry 4.0 (I4.0) solutions are increasingly including social and environmental sustainability aspects. We focus on the realization of an infrastructure integrating industrially relevant application modules by combining system reconfigurability and artificial intelligence, towards sustainable production. To meet the final goal of sustainable production, we address four challenges considering flexibility and sustainability in production in a holistic way: (1) developing infrastructural and methodological tools to support companies to explore the potential of I4.0 towards sustainable production; (2) managing the configurability and customization possibilities of products; (3) effectively handling the flexibility provided by a production system with rapid reconfiguration capabilities; (4) integrating hardware and software flexibility by using reconfigurable robotics and machine learning methods. By developing and connecting different application modules, we obtain a physical demonstrator which represents on the one hand an exemplary scenario of reconfigurable and flexible production system; on the other, it enables new research activities and insights with a see, touch & feel approach for industrial and research realities.
New polyvinyl alcohol/gellan gum-based bioplastics with guava and chickpea extracts for food packaging
Authors: Elsaeed Shaimaa , Zaki Elsayed , Diab Ayman , Tarek Menna-Alla , Omar Walaa A. E.
Published: December 2023

Plastic is a fossil-based synthetic polymer that has become an essential material in our daily life. Plastic pollution resulting from the accumulation of plastic objects has become problematic for our environment. Bioplastic can be a biodegradable environmentally friendly alternative for the synthetic plastic. In this paper, bioplastics based on polyvinyl alcohol (PVA)/gellan gum (GG) blend have been produced in three different compositions and their chemical structure, mechanical, morphological and thermal properties have been studied. Glycerol has been used as a plasticizer. To add extra features to the PVA/GG bioplastic, Psidium guajava (guava) leaves, GL, and chickpea, CP, extracts have been added to the PVA/GG (30/70) blend. Water and aqueous ethanol have been used in the extraction of GL and CP, respectively. The addition of the plant’s extracts enhanced the tensile properties of the PVA/GG bioplastic. Weathering acceleration tests have been carried out to examine the degradation of the prepared bioplastics. Cytotoxicity studies revealed that the prepared bioplastic is safe to be used in food packaging applications. Water and oxygen permeability for the new PVA/GG bioplastic have also been studied. The addition of the plant extracts (GL and CP extracts) increased the oxygen and water permeability to different extents. Bioplastic life cycle assessment (LCA) and CO2 emissions in comparison to fossil-based plastic have been investigated. From all the results, PVA/GG based bioplastic proved to be a degradable, safe and effective alternative for fossil-based plastics in food packaging applications.
Evolving information complexity of coarsening materials microstructures
Authors: Rickman J. M. , Barmak K. , Chen B. Y. , Patrick Matthew
Published: December 2023

The temporal evolution of microstructural features in metals and ceramics has been the subject of intense investigation over many years because deviations from normal grain growth behavior are ubiquitous and strongly dictate observed mechanical and magnetic properties. To distinguish among different grain growth scenarios, we examine the time evolution of the information content of both synthetic and experimental coarsening microstructures as quantified by both a computable information density (CID) and a spectral entropy along with selected metrics and measures of shared information and interaction strength. In these approaches, microstructural evolution is described in terms of two time series representations, namely: (1) strings and their compressed counterparts that reflect the information contained in the configuration of a system over time, and (2) the spectra of graph Laplacians that embody the information contained in a coarsening grain network. These approaches permit one to characterize dynamically evolving microstructures and to identify correlation times associated with different coarsening scenarios. Moreover, as the information content of a system is a proxy for the entropy, a thermodynamic description of grain growth is also described.
Identification of black plastics with terahertz time-domain spectroscopy and machine learning
Authors: Cielecki Paweł Piotr , Hardenberg Michel , Amariei Georgiana , Henriksen Martin Lahn , Hinge Mogens , Klarskov Pernille
Published: December 2023

Several optical spectroscopy and imaging techniques have already proven their ability to identify different plastic types found in household waste. However, most common optical techniques feasible for plastic sorting, struggle to measure black plastic objects due to the high absorption at visible and near-infrared wavelengths. In this study, 12 black samples of nine different materials have been characterized with Fourier-transform infrared spectroscopy (FTIR), hyperspectral imaging, and terahertz time-domain spectroscopy (THz-TDS). While FTIR validated the plastic types of the samples, the hyperspectral camera using visible and near-infrared wavelengths was challenged to measure the samples. The THz-TDS technique was successfully able to measure the samples without direct sample contact under ambient conditions. From the recorded terahertz waveforms the refractive index and absorption coefficient are extracted for all samples in the range from 0.4 to 1.0 THz. Subsequently, the obtained values were projected onto a two-dimensional map to discriminate the materials using the classifiers k-Nearest Neighbours, Bayes, and Support Vector Machines. A classification accuracy equal to unity was obtained, which proves the ability of THz-TDS to discriminate common black plastics.
TWAS revealed significant causal loci for milk production and its composition in Murrah buffaloes
Authors: Chhotaray Supriya , Vohra Vikas , Uttam Vishakha , Santhosh Ameya , Saxena Punjika , Gahlyan Rajesh Kumar , Gowane Gopal
Published: December 2023

Milk yield is the most complex trait in dairy animals, and mapping all causal variants even with smallest effect sizes has been difficult with the genome-wide association study (GWAS) sample sizes available in geographical regions with small livestock holdings such as Indian sub-continent. However, Transcriptome-wide association studies (TWAS) could serve as an alternate for fine mapping of expression quantitative trait loci (eQTLs). This is a maiden attempt to identify milk production and its composition related genes using TWAS in Murrah buffaloes (Bubalus bubalis). TWAS was conducted on a test (N = 136) set of Murrah buffaloes genotyped through ddRAD sequencing. Their gene expression level was predicted using reference (N = 8) animals having both genotype and mammary epithelial cell (MEC) transcriptome information. Gene expression prediction was performed using Elastic-Net and Dirichlet Process Regression (DPR) model with fivefold cross-validation and without any cross-validation. DPR model without cross-validation predicted 80.92% of the total genes in the test group of Murrah buffaloes which was highest compared to other methods. TWAS in test individuals based on predicted gene expression, identified a significant association of one unique gene for Fat%, and two for SNF% at Bonferroni corrected threshold. The false discovery rates (FDR) corrected P-values of the top ten SNPs identified through GWAS were comparatively higher than TWAS. Gene ontology of TWAS-identified genes was performed to understand the function of these genes, it was revealed that milk production and composition genes were mainly involved in Relaxin, AMPK, and JAK-STAT signaling pathway, along with CCRI, and several key metabolic processes. The present study indicates that TWAS offers a lower false discovery rate and higher significant hits than GWAS for milk production and its composition traits. Hence, it is concluded that TWAS can be effectively used to identify genes and cis-SNPs in a population, which can be used for fabricating a low-density genomic chip for predicting milk production in Murrah buffaloes.
A theoretical stability of mixed convection 3D Sutterby nanofluid flow due to bidirectional stretching surface
Authors: Yasmin Humaira , Zeeshan Zeeshan , Alshehry Azzh Saad , Ganie Abdul Hamid , Shah Rasool
Published: December 2023

Host (base) fluids are unable to deliver efficient heating and cooling processes in industrial applications due to their limited heat transfer rates. Nanofluids, owing to their distinctive and adaptable thermo-physical characteristics, find a widespread range of practical applications in various disciplines of nanotechnology and heat transfer equipment. The novel effect of this study is to determine the effects of mixed convection, and activation energy on 3D Sutterby nanofluid across a bi-directional extended surface under the impact of thermophoresis diffusion and convective heat dissipation. The flow equations are simplified in terms of partial differential equations (PDEs) and altered to non-dimensional ODEs by implementing classical scaling invariants. Numerical results have been obtained via the bvp4c approach. The physical insights of crucial and relevant parameters on flow and energy profiles are analysed through plotted visuals. Some factors have multiple solutions due to shrinking sheets. So stability analysis has been adapted to analyses stable solutions. Graphical representations demonstrate the reliability and accuracy of the numerical algorithm across a variety of pertinent parameters and conditions. A comparison between existing results and previously published data shows a high degree of compatibility between the two datasets. The present study extensively explored a multitude of practical applications across a diverse spectrum of fields, including but not limited to gas turbine technology, power generation, glass manufacturing, polymer production, wire coating, chemical production, heat exchangers, geothermal engineering, and food processing.
A clinical assessment of portable point-of-care testing for quick cortisol assay during adrenal vein sampling
Authors: Aiga Ko , Kometani Mitsuhiro , Karashima Shigehiro , Konishi Seigo , Higashitani Takuya , Aono Daisuke , Mai Xurong , Usukura Mikiya , Asano Takahiro , Wakayama Ayako , Noda Yuko , Koda Wataru , Minami Tetsuya , Kobayashi Satoshi , Murayama Toshinori , Yoneda Takashi
Published: December 2023

This study assessed the clinical performance of point-of-care testing (POCT) for quick cortisol assay (QCA) during adrenal vein sampling (AVS) using a newly invented portable quantitative assay instrument. An observational study was conducted prospectively at two centres in Japan. Forty-eight patients with primary aldosteronism considered for adrenalectomy were enrolled in this study and underwent AVS. Three basal adrenal vein samples from each adrenal vein and two from the inferior vena cava were collected sequentially. The cortisol concentration of adrenal vein samples was measured by routine method and QCA. A total of 338 adrenal vein samples were analysed from 250 sites to determine AVS success or failure. The distribution of turnaround time of the QCA for AVS success or failure followed a normal distribution with an average of 20.5 min. A positive correlation between the routine method and QCA was observed regarding cortisol concentration or selectivity index. No significant difference between the two methods was observed regarding the success rate of AVS. Using the routine method as a reference, the sensitivity and specificity of AVS success or failure were 99.1% (210/212) and 81.6% (31/38), respectively. Easy, quick, portable, and precise POCT-QCA demonstrated its compatibility with routine methods regarding clinical performance.
Unveiling the molecular basis of lobeline's allosteric regulation of NMDAR: insights from molecular modeling
Authors: Remya Chandran , Variyar E. J. , Omkumar R. V. , Sadasivan C. , Dileep K. V.
Published: December 2023

Neurological and psychiatric disorders contribute significantly to the global disease burden, adversely affecting the quality of life for both patients and their families. Impaired glutamatergic signaling is considered to be a major cause for most of the neurological and psychiatric disorders. Glutamate receptors are over activated in excitotoxic conditions, leading to dysregulation of Ca2+ homeostasis, triggering the production of free radicals and oxidative stress, mitochondrial dysfunction and eventually cell death. Excitotoxicity primarily results from the overactivity of NMDARs, a subtype of ionotropic glutamate receptors, due to their pronounced Ca2+ permeability and conductance characteristics. NMDAR antagonists are suggested to have therapeutic use as they can prevent excitotoxicity. Our previous studies demonstrated lobeline, an alkaloid, exerts neuroprotective action in excitotoxic conditions by blocking NMDAR. However, the atomic level interactions of lobeline with NMDAR was not characterized yet. Structural comparison of lobeline with a known NMDAR antagonist ifenprodil, followed by molecular docking and dynamics simulations revealed that lobeline could bind to the ifenprodil binding site i.e., in the heterodimer interface of GluN1-GluN2B subunits and exert ifenprodil like activities. By in silico structure guided modifications on lobeline and subsequent free energy calculations, we propose putative NMDAR antagonists derived from lobeline.
Molecular forms of BMP15 and GDF9 in mammalian species that differ in litter size
Authors: Swinerd Gene W. , Alhussini Abdulaziz A. , Sczelecki Sarah , Heath Derek , Mueller Thomas D. , McNatty Kenneth P. , Pitman Janet L.
Published: December 2023

Bone morphogenetic protein (BMP15) and growth differentiation factor (GDF9) are critical for ovarian follicular development and fertility and are associated with litter size in mammals. These proteins initially exist as pre-pro-mature proteins, that are subsequently cleaved into biologically active forms. Thus, the molecular forms of GDF9 and BMP15 may provide the key to understanding the differences in litter size determination in mammals. Herein, we compared GDF9 and BMP15 forms in mammals with high (pigs) and low to moderate (sheep) and low (red deer) ovulation-rate. In all species, oocyte lysates and secretions contained both promature and mature forms of BMP15 and GDF9. Whilst promature and mature GDF9 levels were similar between species, deer produced more BMP15 and exhibited, together with sheep, a higher promature:mature BMP15 ratio. N-linked glycosylation was prominant in proregion and mature GDF9 and in proregion BMP15 of pigs, and present in proregion GDF9 of sheep. There was no evidence of secreted native homo- or hetero-dimers although a GDF9 dimer in red deer oocyte lysate was detected. In summary, GDF9 appeared to be equally important in all species regardless of litter size, whilst BMP15 levels were highest in strict monovulatory species.
Clinical manifestations and associated factors of uveitis in patients with pulmonary sarcoidosis: a case control study
Authors: Lee Jang Ho , Han Ye Eun , Yang Jiyoul , Kim Ho Cheol , Lee Junyeop
Published: December 2023

Sarcoidosis, an idiopathic and inflammatory disease, affects various organs and can manifest as uveitis. Due to limited evidence, researchers investigated the risk factors associated with uveitis in patients with pulmonary sarcoidosis. A retrospective study was conducted on 71 pulmonary sarcoidosis patients, including 19 with uveitis and 52 without. Data on involved organs, imaging findings, spirometry, and analyses from blood and bronchoalveolar lavage fluid were collected. Logistic regression models were used for multivariate analysis. Among the 71 newly diagnosed pulmonary sarcoidosis patients, uveitis was observed in 19 patients (26.8%). No significant differences were found in clinical characteristics between patients with and without uveitis. Fewer patients with uveitis presented lung parenchymal lesions (P = 0.043). In multivariate analysis, skin lesions (aOR 7.619, 95% CI 1.277–45.472, P = 0.026) and ophthalmic symptoms (aOR 4.065, 95% CI 1.192–13.863, P = 0.025) were associated with uveitis. Absence of uveitis was related to lung parenchymal lesions (aOR 0.233, 95% CI 0.062–0.883, P = 0.032). Approximately one-quarter of patients with an initial diagnosis of pulmonary sarcoidosis were diagnosed with uveitis. Presence of skin lesions, ophthalmic symptoms, and absence of lung parenchymal lesions were related to uveitis. These results need to be clarified by further studies to confirm the clinical role of early ophthalmologic screening for pulmonary sarcoidosis patients with these factors.
A comparative analysis of linear regression, neural networks and random forest regression for predicting air ozone employing soft sensor models
Authors: Zhou Zheng , Qiu Cheng , Zhang Yufan
Published: December 2023

The proposed methodology presents a comprehensive analysis of soft sensor modeling techniques for air ozone prediction. We compare the performance of three different modeling techniques: LR (linear regression), NN (neural networks), and RFR (random forest regression). Additionally, we evaluate the impact of different variable sets on prediction performance. Our findings indicate that neural network models, particularly the RNN (recurrent neural networks), outperform the other modeling techniques in terms of prediction accuracy. The proposed methodology evaluates the impact of different variable sets on prediction performance, finding that variable set E demonstrates exceptional performance and achieves the highest average prediction accuracy among various software sensor models. In comparing variable set E and A, B, C, D, it is observed that the inclusion of an additional input feature, PM10, in the latter sets does not improve overall performance, potentially due to multicollinearity between PM10 and PM2.5 variables. The proposed methodology provides valuable insights into soft sensor modeling for air ozone prediction.Among the 72 sensors, sensor NNR[Y]C outperforms all other evaluated sensors, demonstrating exceptional predictive performance with an impressive R2 of 0.8902, low RMSE of 24.91, and remarkable MAE of 19.16. With a prediction accuracy of 81.44%, sensor NNR[Y]C is reliable and suitable for various technological applications.
CFD microscale modelling of flow behavior in different parts of a rotating packed bed
Authors: Alatyar Ahmed M. , Berrouk Abdallah S. , AlShehhi Mohamed S.
Published: December 2023

Process intensification (PI) is playing a key role in alleviating the challenge of reducing carbon footprint of many chemical processes and bringing down their development costs. Over the years, many PI technologies have been investigated with rotating packed bed (RPB) technology receiving much of the attention for its potential of significant intensification in terms of capital expenditure, operating costs, and hardware size. In this study, microscale CFD simulations of a rotating packed bed were conducted, and the results were validated with experimental data. The results show the strong relation between the reverse flow at the packing outer periphery and the gas maldistribution factor. The latter is mainly caused by the accelerating flow in the outer cavity. Inside the wire mesh packing, the gas flow is found to be almost fully uniform for nearly half of the total packing depth. Also, turbulent kinetic energy (TKE) levels at the packing outer edge are strongly linked to the slip tangential velocity component, while at its inner edge, they depend mainly on the radial packing velocity. The so-called gas end effect zone is detected by observing the TKE profiles near the packing outer edge. The latter accounts for less than 10% of the total packing depth. The validity of the widely used porous media model in RPBs’ packing for both radial and tangential directions is confirmed by the obtained results, but this excludes the packing inner and outer edges. In the inner cavity region, gas exhibits two distinctive behaviors and transits from free vortex flow to swirling flow as the flow becomes close to the vortex core. As a result of this transition, the increase in shear stress accelerates the decrease in the gas tangential velocity in the vortex core and help speed up the favorable pressure gradient and flow establishment beyond the vortex core.
Artesunate acts through cytochrome c to inhibit growth of pediatric AML cells
Authors: Hill Kristen S. , Schuler Erin E. , Ellingson Sally R. , Kolesar Jill M.
Published: December 2023

Artesunate is a derivative of artemisinin, an active compound isolated from Artemisia annua which has been used in Traditional Chinese Medicine and to treat malaria worldwide. Artemisinin derivatives have exhibited anti-cancer activity against both solid tumors and leukemia. The direct target(s) of artesunate are controversial; although, heme-bound proteins in the mitochondria have been implicated. We utilized computational modeling to calculate the predicted binding score of artesunate with heme-bound mitochondrial proteins and identified cytochrome c as potential artesunate target. UV–visible spectroscopy showed changes in the absorbance spectrum, and thus protein structure, when cytochrome c was incubated with artesunate. Artesunate induces apoptosis, disrupts mitochondrial membrane potential, and is antagonized by methazolamide in pediatric AML cells indicating a probable mechanism of action involving cytochrome c. We utilized a multi-disciplinary approach to show that artesunate can interact with and is dependent on cytochrome c release to induce cell death in pediatric AML cell lines.
Risk factors of diffuse alveolar hemorrhage in Chinese patients with systemic lupus erythematosus
Authors: Xu Lishan , Yang Rong , Cao Yingping , Wang Meihua , Yang Xuwei
Published: December 2023

This study aimed to investigate the frequency and features of diffuse alveolar hemorrhage (DAH) in Chinese patients with systemic lupus erythematosus (SLE) and evaluate the association of DAH with the features. A total of 943 patients with SLE were categorized into two groups: 896 patients without DAH and 47 patients with DAH. The demographic data, clinical and laboratory findings, and SLE disease activity index 2000 of all patients were statistically analyzed. The DAH frequency in patients with SLE was 4.98%, and the mortality rate of DAH was 42.55%. The clinical features with statistical differences between the two groups were analyzed by multivariate logistic regression, and the results suggested that shorter disease duration [odds ratio (OR): 0.972, 95% confidence interval (CI) 0.946, 0.998], younger age (OR: 0.867, 95% CI 0.764, 0.984), moderate (OR: 25.949, 95% CI 3.316, 203.065) or severe (OR: 24.904, 95% CI 2.675, 231.859) anemia, abnormally elevated levels of urine protein (OR: 10.839, 95% CI 1.351, 86.938) and serum creatinine (OR: 14.534, 95% CI 5.012, 42.142), interstitial lung disease (OR: 6.569, 95% CI 2.053, 21.021), and infection (OR: 8.890, 95% CI 3.580, 22.077) were independent risk factors for the occurrence of DAH in patients with SLE. Moderate or severe anemia was highly suggestive of DAH.
Construction and validation of a prognostic signature based on seven endoplasmic reticulum stress-related lncRNAs for patients with head and neck squamous cell carcinoma
Authors: Zhou Mingzhu , Li Huihui , Hu Juanjuan , Zhou Tao , Zhou Liuqing , Li Yuncheng
Published: December 2023

Endoplasmic reticulum stress (ERS) occurs when misfolded or unfolded proteins accumulate in the endoplasmic reticulum (ER), and it is often observed in tumors, including head and neck squamous cell carcinoma (HNSCC). Relevant studies have demonstrated the prognostic significance of ERS-related long non-coding RNAs (lncRNAs) in various cancers. However, the relationship between ERS and lncRNAs in HNSCC has received limited attention in previous studies. In this study, we aimed to develop an ERS-related lncRNAs prognostic model using correlation analysis, Cox regression analysis, least absolute shrinkage, and selection operator (LASSO) regression analysis based on data from The Cancer Genome Atlas (TCGA) database. The survival and predictive ability of this model were evaluated using Kaplan–Meier analysis and time-dependent receiver operating characteristics (ROC), while nomograms and calibration curves were constructed. Then, functional enrichment analyses, tumor mutation burden (TMB), tumor infiltration of immune cells, single sample Gene Set Enrichment Analysis (ssGSEA), and drug sensitivity analysis were performed. Additionally, we conducted a consensus cluster analysis to compare differences between subtypes of tumors. Finally, we validated the expression of the ERS-related lncRNAs that constructed prognostic risk score model in HNSCC tissues through quantitative real-time PCR (qRT-PCR). We developed a prognostic signature based on seven ERS-related lncRNAs, which showed better predictive performance than other clinicopathological features. The high-risk poor prognosis group had a poorer prognosis in comparison to the low-risk good prognosis. The area under the ROC curve (AUC) predicted by this model for 3-year survival rates of HNSCC patients was 0.805. Enrichment analysis revealed that the differentially expressed genes were primarily enriched in pathways related to immune responses and signal transduction. Low-risk patients had lower TMB, more immune cell infiltrations, and enhanced anti-tumor immunity. Cluster analysis indicated that cluster 3 may have a better prognosis and immunotherapy effect. In addition, the result of qRT-PCR was consistent with our analysis. This prognostic model based on seven ERS-related lncRNAs is a promising tool for risk stratification, survival prediction, and immune cell infiltration status assessment.
Sex differences in risk factors for coronary heart disease events: a prospective cohort study in Iran
Authors: Ramezankhani Azra , Azizi Fereidoun , Hadaegh Farzad
Published: December 2023

We investigated sex-specific associations and their differences between major cardiovascular risk factors and the risk of incident coronary heart disease (CHD) and hard CHD (defined as nonfatal myocardial infarction and CHD death). A total of 7518 (3377 men) participants from the Tehran Lipid and Glucose Study were included. Cox models were used to estimate the hazard ratios (HRs) and women-to-men ratios of HRs for CHD events associated with each risk factor. During 20 years of follow-up (1999–2018), 1068 (631 men) and 345 (238 men) new cases of CHD and hard CHD, respectively, were documented. In total population, the incidence rates per 1000 person-years were 9.5 (9.0–10.1) and 2.9 (2.6–3.2) for CHD and hard CHD, respectively. Hypertension, diabetes, pre-diabetes, and a high waist-to-hip ratio (WHR) were associated with a greater HR of hard CHD in women than men; the women-to-men HRs were 2.85 [1.36–5.98], 1.92 [1.11–3.31], 2.04 [1.09–3.80] and 1.42 [1.10–1.82], respectively. Diabetes was associated with a higher HR of CHD in women than men (ratio of HRs 1.49 (1.10–2.01). In conclusion, we found that hypertension, diabetes, pre-diabetes, and high WHR conferred a greater excess risk of CHD events in women than in men, suggesting that Iranian women may require greater attention for the prevention of CHD events.
Polystyrene nanoparticles induce concerted response of plant defense mechanisms in plant cells
Authors: Adamczyk Sylwia , Chojak-Koźniewska Joanna , Oleszczuk Sylwia , Michalski Krzysztof , Velmala Sannakajsa , Zantis Laura J. , Bosker Thijs , Zimny Janusz , Adamczyk Bartosz , Sowa Slawomir
Published: December 2023

Recent advances in knowledge suggest that micro- and nanoplastics pose a threat to plant health, however, the responses of plants to this stressor are not well-known. Here we examined the response of plant cell defence mechanisms to nanoparticles of commonly used plastic, polystyrene. We used plant cell cultures of widely cultivated plants, the monocots wheat and barley (Triticum aestivum L., Hordeum vulgare L.) and the dicots carrot and tomato (Daucus carota L., Solanum lycopersicum L.). We measured the activities of enzymes involved in the scavenging of reactive oxygen species and nonenzymatic antioxidants and we estimated potential damages in plant cell structures and functioning via lipid peroxidation and DNA methylation levels. Our results demonstrate that the mode of action of polystyrene nanoparticles on plant cells involves oxidative stress. However, the changes in plant defence mechanisms are dependent on plant species, exposure time and nanoplastic concentrations. In general, both monocots showed similar responses to nanoplastics, but the carrot followed more the response of monocots than a second dicot, a tomato. Higher H2O2, lipid peroxidation and lower enzyme activities scavenging H2O2 suggest that tomato cells may be more susceptible to polystyrene-induced stress. In conclusion, polystyrene nanoplastics induce oxidative stress and the response of the plant defense mechanisms involving several chain reactions leading to oxidoreductive homeostasis.