bluuebunny/crossref_metadata_2025 huggingface dataset:
Research and experiment on active training of lower limb based on five-bar mechanism of man-machine integration system
Authors: Sun Jianghong , Hu Fuqing , Gao Keke , Gao Feng , Ma Chao , Wang Junjian
Published: March 2024

In view of the fact that the current research on active and passive rehabilitation training of lower limbs is mainly based on the analysis of exoskeleton prototype and the lack of analysis of the actual movement law of limbs, the human-machine coupling dynamic characteristics for active rehabilitation training of lower limbs are studied. In this paper, the forward and inverse kinematics are solved on the basis of innovatively integrating the lower limb and rehabilitation prototype into a human-machine integration system and equivalent to a five-bar mechanism. According to the constraint relationship of hip joint, knee joint and ankle joint, the Lagrange dynamic equation and simulation model of five-bar mechanism under the constraint of human physiological joint motion are constructed, and the simulation problem of closed-loop five-bar mechanism is solved. The joint angle experimental system was built to carry out rehabilitation training experiments to analyze the relationship between lower limb error and height, weight and BMI, and then, a personalized training planning method suitable for people with different lower limb sizes was proposed. The reliability of the method is proved by experiments. Therefore, we can obtain the law of limb movement on the basis of traditional rehabilitation training, appropriately reduce the training speed or reduce the man-machine position distance and reduce the training speed or increase the man-machine distance to reduce the error to obtain the range of motion angle closer to the theory of hip joint and knee joint respectively, so as to achieve better rehabilitation.
Video-mediated collaborative lesson planning in virtual exchange among transnational teams of pre-service language teachers
Authors: Ekin Semih , Balaman Ufuk
Published: March 2024

Virtual exchange (VE) projects in pre-service language teacher education are increasingly being recognized as an innovative practice due to their affordances for providing teacher learning opportunities in technology-rich environments. This study aims to report these opportunities based on results from a VE project consisting of diverse teacher education activities, including lectures, webinars, asynchronous tasks, and synchronous video-mediated interactions. This project provides a medium for pre-service teachers to collaboratively design a lesson to be implemented in hybrid language learning environments. We specifically deal with the video-mediated interactions of the transnational groups of pre-service language teachers using multimodal conversation analysis (CA) as the research methodology and investigate VE phases to explore how their interactions become consequential for the final pedagogical design. The findings show that the pre-service teachers retrospectively orient to shared practices in the earlier phases of the VE project, and the deployment of retrospective orientation as an interactional resource creates interactional space for collaborative decision-making related to their pedagogical designs. We argue that tracking the video-mediated pedagogical interactions of the pre-service teachers using CA is a methodological innovation that allows researchers to collect interactional evidence for the emergent teacher learning opportunities. The findings bring new insights to the role of the technology-mediated settings (e.g. VEs and telecollaboration) in language learning, teaching, and teacher education and in bridging different cultures, curricula, and physical spaces.
Genetic dissection of advanced soybean (Glycine max L.) germplasm for spring season cultivation in Pakistan
Authors: Ghuman Hasham Feroz , Ahmed Zaheer , Sadia Bushra , Awan Faisal Saeed
Published: March 2024

Improvement in genetic gains of crops could be achieved by phenomics' characterization of agronomic, physiological and stress-related traits. Molecular and strategic breeding programmes require broad range of foreground and background phenotypic information for crop improvement. The current experiment was performed on 123 advanced soybean (Glycine max L.) genotypes including seven local lines belongs to four different maturity groups (000-lV) to estimate the endogenous potential of various yield-related traits. The experimental trial was repeated for two cropping seasons. Four traits out of six, yield per plant (YPP), number of seeds per plant, number of pods per plant and plant height (PH), showed maximum variation (CV%) that directly correlate with variability in the subjected population. PH, number of pods, 100-seed weight and YPP showed strong positive correlation in both years. Among the principal components, factors 1 and 2 showed maximum contribution in phenotypic variability ranges from 19 to 48.5% and 26 to 47.7% in the first and second years, respectively. Number of pods showed significant positive correlation with genotypes in both years. Dendrogram showed two distinct groups of soybean genotypes. Genetic variation and association among the accessions is indispensable for effective conservation and utilization of germplasm. Principal component analysis helps to identify the diverse genotypes that will be used as a parent for various breeding programmes. These phenotypic data will be used for detection of heat stress-related quantitative trait loci with genotypic data in genome-wide association studies experiments.
Heitor Villa-Lobos and the Traces of Coloniality in Andrés Segovia's Guitar Repertoire
Authors: Achondo Luis
Published: March 2024

Andrés Segovia's repertoire—the repertorio segoviano—has crucially shaped the guitar canon. Although some guitar scholars argue that these works helped rescue the instrument from the periphery of art music, others contend that, by commissioning music from minor, conservative composers, Segovia missed the chance to request pieces from the most influential twentieth-century modernists. This article questions the conservative homogeneity of the repertorio segoviano. Focusing on Segovia's collaborations with Heitor Villa-Lobos, I argue that it contains traces of coloniality: The perpetuation of colonial domination in Latin America. The relationship between Segovia and Villa-Lobos was more contentious than the official narrative suggests—tensions stemming from their dominant personalities, divergent approaches to guitar composition, and conflicting musical ideologies. Indeed, although Segovia's stance aligned with Francoist and European conservative aesthetics, Villa-Lobos embraced a transcultural approach to music shaped by, a response to, and exertion of the coloniality of power—discrepancies that were engraved in their collaborations and ultimately the repertorio segoviano. This article ultimately foregrounds that elite composers from the periphery played an essential role in the modernization of the guitar in the twentieth century, thereby questioning historiographies that detach the instrument from the social, political, and cultural messiness of colonial difference and the coloniality of power.
Volcanic Ash Classification Through Machine Learning
Authors: Benet Damià , Costa Fidel , Widiwijayanti Christina
Published: March 2024

Volcanic ash provides information that can help understanding the evolution of volcanic activity during the early stages of a crisis and possible transitions toward different eruptive styles. Ash consists of particles from a range of origins within the volcanic system and its analysis can be indicative of the processes driving the eruptive activity. However, classifying ash particles into different types is not straightforward. Diagnostic observations for particle classification are not standardized and vary across samples. Here we explore the use of machine learning (ML) to improve the classification accuracy and reproducibility. We use a curated database of ash particles (VolcAshDB) to optimize and train two ML‐based models: Extreme Gradient Boosting (XGBoost) that uses the measured physical attributes of the particles, from which predictions are interpreted by the SHapley Additive exPlanations (SHAP) method, and a Vision Transformer (ViT) that classifies binocular, multi‐focused, particle images. We find that the XGBoost has an overall classification accuracy of 0.77 (macro F1‐score), and specific features of color (hue_mean) and texture (correlation) are the most discriminant between particle types. Classification using the particle images and the ViT is more accurate (macro F1‐score of 0.93), with performances varying from 0.85 for samples of dome explosions, to 0.95 for phreatic and subplinian events. Notwithstanding the success of the classification algorithms, the training dataset is limited in number of particles, ranges of eruptive styles, and volcanoes. Thus, the algorithms should be tested further with additional samples, and it is likely that classification for a given volcano is more accurate than between volcanoes.
A Comparative Analysis of Gravity Waves in He and Ar Densities in the Martian Thermosphere
Authors: Leelavathi V. , Rao N. V.
Published: March 2024

In this study, we conducted a comparative analysis of gravity waves (GWs) in the Martian upper thermosphere, utilizing He and Ar densities measured by the Neutral Gas and Ion Mass Spectrometer aboard the Mars Atmosphere and Volatile EvolutioN spacecraft. Our investigation revealed that GWs are a persistent phenomenon in Martian thermospheric He densities, akin to their presence in heavier species like Ar and CO2. Intriguingly, we observed that local time and seasonal variations in He GW amplitudes exhibit an almost opposite pattern compared to those in Ar. A significant breakthrough was the identification of a temperature‐dependent transition wavelength distinctly demarcating short and long wavelengths. This transition wavelength, which increases with increasing background temperatures, profoundly influences the dominance of GW amplitudes in He and Ar. In the short‐wavelength limit, GW amplitudes in He prevail, while GW amplitudes in Ar take precedence in the long‐wavelength limit. During periods of lower temperatures during midnight and the dawn terminator, transition wavelengths fall within the observed wavelength range enabling the study of dominance of GWs in He and Ar. Conversely, higher temperatures (>180 K) during daytime and the dusk terminator eliminate transition wavelengths within our observational range. Consequently, the amplitudes of GWs in He dominate over those in Ar. Furthermore, under nominal dust conditions, GWs in both He and Ar exhibit an inverse relationship with their respective background densities. During global dust storm, this inverse relationship is maintained for GWs in He, while GWs in Ar display a slight positive correlation with background Ar densities.
Participation in Organized Physical Activity and Discomfort with Locker Rooms Among Youth Across Sexual, Gender, and Racial Identities
Authors: Parchem Benjamin , Poquiz Jonathan , Rahm-Knigge Ryan L. , Panetta Elizabeth , Watson Ryan J. , Rider G. Nic
Published: March 2024

Objective:

Participation in organized physical activity contributes to well-being and positive youth development. Lesbian, gay, bisexual, transgender and gender diverse, and queer/questioning (LGBTQ+) youth, across racial identities, experience barriers to organized physical activity, including discomfort with locker rooms. The current quantitative analysis expands existing qualitative evidence to understand the relation between discomfort with locker rooms and participation in organized physical activity among youth across diverse sexual, gender, and racial identities.

Method:

High school students ( N = 13,469) in the Midwestern United States completed questions about physical activity and discomfort with locker rooms. Independent sample t tests assessed differences in mean participation in organized physical activity by discomfort with locker rooms across LGBTQ+ and racial identities.

Results:

LGBTQ+ youth endorsed half the participation and eight times the discomfort with locker rooms as cisgender/heterosexual peers. Discomfort with locker rooms was less impactful for LGBTQ+ youth of color than white LGBTQ+ youth. Locker rooms were also less of a concern for white LGBTQ+ youth who were active in organized physical activity relative to white LGBTQ+ youth who were not active in organized physical activity.

Conclusions:

Locker rooms may be a larger barrier to any engagement in organized physical activity rather than frequency of activity, and strategies to promote engagement must consider the intersection of LGBTQ+ and racial identities. Pediatric psychologists can intervene through supporting youth’s problem-solving and self-advocacy skills while also advocating directly with schools and community spaces for the restructuring of the binary nature of gendered locker rooms to be more accessible and inclusive for youth with diverse identities.

Implications for Impact Statement

Feeling uncomfortable in locker rooms is a frequently endorsed barrier to engaging in any organized physical activity among lesbian, gay, bisexual, transgender and gender diverse, and queer/questioning (LGBTQ+) youth, who participate at rates nearly half that of their cisgender/heterosexual peers. Pediatric psychologists can help support LGBTQ+ youth explore strategies to navigate binary locker rooms through developing problem-solving skills and self-advocacy skills. Beyond the individual level, pediatric psychologists can also play a role in advocating for restructuring the binary nature of locker rooms given the potential mental and physical health benefits of having more inclusive spaces to access organized physical activity.
Cancer-derived exosomal Alu RNA promotes colorectal cancer progression
Authors: Magliacane Trotta Sara , Adinolfi Antonio , D’Orsi Luca , Panico Sonia , Mercadante Grazia , Mehlen Patrick , Ambati Jayakrishna , De Falco Sandro , Tarallo Valeria
Published: March 2024

Inflammation plays a crucial role in cancer progression, but the relevance of the inflammasome remains unclear. Alu RNA was the first endogenous nucleic acid shown to activate the NLRP3 (nucleotide-binding domain leucine-rich repeat containing 3) inflammasome. Here, we showed that Alu RNA can induce epithelial-to-mesenchymal transition (EMT) through NLRP3 inflammasome activation and IL-1β release in colorectal cancer (CRC) cells. Alu RNA is stored, transported and transferred to CRC cells by exosomes. Exosomal Alu RNA promotes tumorigenesis by inducing invasion, metastasis and EMT via NLRP3 inflammasome activation. Consistent with these data, we found that significantly increased Alu RNA expression correlates with the induction of NLRP3 priming in human CRC patients. Furthermore, the level of Alu RNA in circulating exosomes correlates with CRC progression in a preclinical model. These findings reveal the direct involvement of Alu RNA in cancer pathogenesis, and its presence in CRC cell-derived exosomes could be used as a noninvasive diagnostic biomarker.
Prmt7 regulates the JAK/STAT/Socs3 signaling pathway in postmenopausal cardiomyopathy
Authors: Ahn Byeong-Yun , Zhang Yan , Wei Shibo , Jeong Yideul , Park Dong-Hyun , Lee Sang-Jin , Leem Young-Eun , Kang Jong-Sun
Published: March 2024

Protein arginine methyltransferases (PRMTs) modulate diverse cellular processes, including stress responses. The present study explored the role of Prmt7 in protecting against menopause-associated cardiomyopathy. Mice with cardiac-specific Prmt7 ablation (cKO) exhibited sex-specific cardiomyopathy. Male cKO mice exhibited impaired cardiac function, myocardial hypertrophy, and interstitial fibrosis associated with increased oxidative stress. Interestingly, female cKO mice predominantly exhibited comparable phenotypes only after menopause or ovariectomy (OVX). Prmt7 inhibition in cardiomyocytes exacerbated doxorubicin (DOX)-induced oxidative stress and DNA double-strand breaks, along with apoptosis-related protein expression. Treatment with 17β-estradiol (E2) attenuated the DOX-induced decrease in Prmt7 expression in cardiomyocytes, and Prmt7 depletion abrogated the protective effect of E2 against DOX-induced cardiotoxicity. Transcriptome analysis of ovariectomized wild-type (WT) or cKO hearts and mechanical analysis of Prmt7-deficient cardiomyocytes demonstrated that Prmt7 is required for the control of the JAK/STAT signaling pathway by regulating the expression of suppressor of cytokine signaling 3 (Socs3), which is a negative feedback inhibitor of the JAK/STAT signaling pathway. These data indicate that Prmt7 has a sex-specific cardioprotective effect by regulating the JAK/STAT signaling pathway and, ultimately, may be a potential therapeutic tool for heart failure treatment depending on sex.
Ultrafast atomic-scale scanning tunnelling spectroscopy of a single vacancy in a monolayer crystal
Authors: Roelcke C. , Kastner L. Z. , Graml M. , Biereder A. , Wilhelm J. , Repp J. , Huber R. , Gerasimenko Y. A.
Published: March 2024

Defects in atomically thin semiconductors and their moiré heterostructures have emerged as a unique testbed for quantum science. Strong light–matter coupling, large spin–orbit interaction and enhanced Coulomb correlations facilitate a spin–photon interface for future qubit operations and efficient single-photon quantum emitters. Yet, directly observing the relevant interplay of the electronic structure of a single defect with other microscopic elementary excitations on their intrinsic length, time and energy scales remained a long-held dream. Here we directly resolve in space, time and energy how a spin–orbit-split energy level of an isolated selenium vacancy in a moiré-distorted WSe2 monolayer evolves under the controlled excitation of lattice vibrations, using lightwave scanning tunnelling microscopy and spectroscopy. By locally launching a phonon oscillation and taking ultrafast energy-resolved snapshots of the vacancy’s states faster than the vibration period, we directly measure the impact of electron–phonon coupling in an isolated single-atom defect. The combination of atomic spatial, sub-picosecond temporal and millielectronvolt energy resolution marks a disruptive development towards a comprehensive understanding of complex quantum materials, where the key microscopic elementary interactions can now be disentangled, one by one.
Decay pattern of SARS-CoV-2 RNA surface contamination in real residences
Authors: Lin Nan , Zhang Bo , Shi Rong , Gao Yu , Wang Zixia , Ling Zhiyi , Tian Ying
Published: March 2024

The COVID-19 pandemic has provided valuable lessons that deserve deep thought to prepare for the future. The decay pattern of surface contamination by SARS-CoV-2 RNA in the residences of COVID-19 patients is important but still unknown. We collected 2,233 surface samples from 21 categories of objects in 141 residences of COVID-19 patients in Shanghai when attacked by the omicron variant in spring 2022. Several characteristics of the patients and their residences were investigated to identify relevant associations. The decay of contamination was explored to determine the persistence. Approximately 8.7% of the surface samples were tested positive for SARS-CoV-2 RNA. The basin, water tap, and sewer inlet had the highest positive rates, all exceeding 20%. Only time was significantly associated with the level of surface contamination with SARS-CoV-2, showing a negative association. The decrease fit a first-order decay model with a decay rate of 0.77 ± 0.07 day−1, suggesting a 90% reduction in three days. Positive associations between the cumulative number of newly diagnosed patients in the same building and the positive rate of SARS-CoV-2 RNA in the public corridor were significant during the three days. Our results, in conjunction with the likely lower infectivity or viability, demonstrate that fomite transmission played a limited role in COVID-19 spread. The time determined SARS-CoV-2 RNA contamination, which was reduced by three days. This study is the first to show the decay patterns of SARS-CoV-2 contamination in real residential environments, providing insight into the patterns of transmission, as well as community-based prevention and control of similar threats.
Enterobacter asburiae ST229: an emerging carbapenemases producer
Authors: Mattioni Marchetti Vittoria , Kuka Angela , Piazza Aurora , Gaiarsa Stefano , Merla Cristina , Sottosanti Mariangela , Cambieri Patrizia , Migliavacca Roberta , Baldanti Fausto
Published: March 2024

Enterobacter asburiae, member of the Enterobacter cloacae complex (ECC) group, shows an increasing clinical relevance being responsible for infections like pneumonia, urinary tract infections and septicemia. The aim of the present study was the investigation of the genomic features of two XDR E. asburiae ST229 clinical strains co-carrying blaNDM-1 and blaVIM-1 determinants, collected in October 2021 and in June 2022, respectively. Two E. asburiae strains were collected from rectal swabs of as many patients admitted to the cardiopulmonary intensive care unit of Fondazione I.R.C.C.S. “Policlinico San Matteo” in Pavia, Italy. Based on the antibiotic susceptibility profile results, both isolates showed an XDR phenotype, retaining susceptibility only to fluoroquinolones. Both isolates shared identical resistome, virulome, plasmid content, and belonged to ST229, a rarely reported sequence type. They co-harbored blaNDM-1 and blaVIM-1 genes, that resulted located on transferable plasmids by conjugation and transformation. Moreover, both strains differed in 24 SNPs and showed genetic relatedness with E. asburiae ST709 and ST27. We described the first case of ST229 E. asburiae co-harboring blaNDM-1 and blaVIM-1 in Italy. This study points out the emergence of carbapenemases in low-risk pathogens, representing a novel challenge for public health, that should include such types of strains in dedicated surveillance programs. Antimicrobial susceptibility testing was carried out using Thermo Scientific™ Sensititre™ Gram Negative MIC Plates DKMGN. Both strains underwent whole-genome sequencing (WGS) using Illumina Miseq platform. Resistome, plasmidome, virulome, MLST, plasmid MLST and a SNPs-based phylogenetic tree were in silico determined.
Artifact removal by template subtraction enables recordings of the frequency following response in cochlear-implant users
Authors: Gransier Robin , Carlyon Robert P. , Richardson Matthew L. , Middlebrooks John C. , Wouters Jan
Published: March 2024

Electrically evoked frequency-following responses (eFFRs) provide insight in the phase-locking ability of brainstem of cochlear-implant (CI) users. eFFRs can potentially be used to gain insight in the individual differences in the biological limitation on temporal encoding of the electrically stimulated auditory pathway, which can be inherent to the electrical stimulation itself and/or the degenerative processes associated with hearing loss. One of the major challenge of measuring eFFRs in CI users is the process of isolating the stimulation artifact from the neural response, as both the response and the artifact overlap in time and have similar frequency characteristics. Here we introduce a new artifact removal method based on template subtraction that successfully removes the stimulation artifacts from the recordings when CI users are stimulated with pulse trains from 128 to 300 pulses per second in a monopolar configuration. Our results show that, although artifact removal was successful in all CI users, the phase-locking ability of the brainstem to the different pulse rates, as assessed with the eFFR differed substantially across participants. These results show that the eFFR can be measured, free from artifacts, in CI users and that they can be used to gain insight in individual differences in temporal processing of the electrically stimulated auditory pathway.
Topical netarsudil for the treatment of primary corneal endothelial degeneration in dogs
Authors: Casanova M. Isabel , Park Sangwan , Mayes Melaney A. , Roszak Karolina , Ferneding Michelle , Echeverria Nayeli , Bowman Morgan A. W. , Michalak Sarah R. , Ardon Monica , Wong Sydni , Le Sophie M. , Daley Nicole , Leonard Brian C. , Good Kathryn L. , Li Jennifer Y. , Thomasy Sara M.
Published: March 2024

This study evaluated the tolerability and efficacy of the topical rho-kinase inhibitor netarsudil for canine primary corneal endothelial degeneration (PCED). Twenty-six eyes of 21 client-owned dogs with PCED were enrolled in a prospective, randomized, vehicle control clinical trial and received topical netarsudil 0.02% (Rhopressa®) or vehicle control twice daily (BID) for the first 4 months. Then, all patients received netarsudil for the next 4 or 8 months. Complete ophthalmic examination, ultrasonic pachymetry, Fourier-domain optical coherence tomography, and in vivo confocal microscopy were performed at baseline and 1, 2, 4, 6, 8 and 12 months. Effect of netarsudil on central corneal thickness (CCT), percentage of cornea with edema, and endothelial cell density (ECD) were evaluated by repeated measures ANOVA. Kaplan–Meier curves and log-rank test were used to compare corneal edema and clinical progression of eyes in netarsudil versus vehicle control groups. All dogs developed conjunctival hyperemia in at least one eye while receiving netarsudil. Unilateral transient reticulated intraepithelial bullae and stromal hemorrhage were observed respectively in 2 dogs in the netarsudil group. Two dogs showed persistently decreased tear production while receiving netarsudil, requiring topical immunomodulatory treatment. No significant differences in CCT, ECD, corneal edema or clinical progression were observed between netarsudil or vehicle treated eyes. When comparing efficacy of topical netarsudil BID and topical ripasudil 0.4% administered four times daily from our previous study, dogs receiving ripasudil had significantly less progression than those receiving netarsudil.
An emergent constraint on the thermal sensitivity of photosynthesis and greenness in the high latitude northern forests
Authors: Liu Junjie , Wennberg Paul O.
Published: March 2024

Despite the general consensus that the warming over the high latitudes northern forests (HLNF) has led to enhanced photosynthetic activity and contributed to the greening trend, isolating the impact of temperature increase on photosynthesis and greenness has been difficult due to the concurring influence of the CO2 fertilization effect. Here, using an ensemble of simulations from biogeochemical models that have contributed to the Trends in Net Land Atmosphere Carbon Exchange project (TRENDY), we identify an emergent relationship between the simulation of the climate-driven temporal changes in both gross primary productivity (GPP) and greenness (Leaf Area Index, LAI) and the model’s spatial sensitivity of these quantities to growing-season (GS) temperature. Combined with spatially-resolved observations of LAI and GPP, we estimate that GS-LAI and GS-GPP increase by 17.0 ± 2.4% and 24.0 ± 3.0% per degree of warming, respectively. The observationally-derived sensitivities of LAI and GPP to temperature are about 40% and 71% higher, respectively, than the mean of the ensemble of simulations from TRENDY, primarily due to the model underestimation of the sensitivity of light use efficiency to temperature. We estimate that the regional mean GS-GPP increased 28.2 ± 5.1% between 1983–1986 and 2013–2016, much larger than the 5.8 ± 1.4% increase from the CO2 fertilization effect implied by Wenzel et al. This suggests that warming, not CO2 fertilization, is primarily responsible for the observed dramatic changes in the HLNF biosphere over the last century.
Three-dimensional choroidal contour mapping in healthy population
Authors: Arora Supriya , Singh Sumit Randhir , Rosario Brian , Ibrahim Mohammed Nasar , Selvam Amrish , Zarnegar Arman , Harihar Sanjana , Sant Vinisha , Sahel Jose Alain , Vupparaboina Kiran Kumar , Chhablani Jay
Published: March 2024

Purpose was to study 3-dimensional choroidal contour at choroidal inner boundary (CIB) and choroidal outer boundary (COB) in healthy eyes. Healthy eyes imaged on wide field swept-source optical coherence tomography were included. Delineation of CIB and COB was done based on our previously reported methods. Quantitative analysis of the surfaces of CIB and COB was based on analyzing best fit spherical radius (R) (overall and sectoral). One hundred and seven eyes of 74 subjects with a mean age of 46.4 ± 19.3 years were evaluated. Overall, R COB (mean ± SD: 22.5 ± 4.8 mm) < R CIB (32.4 ± 9.4 mm). Central sector had the least R at COB (7.2 ± 5.9 mm) as well as CIB (25.1 ± 14.3 mm) across all age groups. Regression analysis between R (CIB) and age (r = −0.31, r2 = 0.09) showed negative correlation (P < 0.001) and that between R (COB) and age was positive (r = 0.26, r2 = 0.07) (P = 0.01). To conclude, central sector is the steepest sector in comparison to all the other sectors. This is indicative of a prolate shape of choroidal contour at CIB and COB. Outer boundary of choroid is steeper than inner boundary across all age groups. However, with ageing, outer boundary becomes flatter and inner boundary becomes steeper.
Genetic and molecular characterization of metabolic pathway-based clusters in esophageal squamous cell carcinoma
Authors: Wang Ze , Zhang Yuan , Yang Xiaorong , Zhang Tongchao , Li Zhen , Zhong Yang , Fang Yuan , Chong Wei , Chen Hao , Lu Ming
Published: March 2024

Esophageal squamous cell carcinoma (ESCC) is one of the most aggressive types of squamous cell carcinoma and represents a significant proportion of esophageal cancer. Metabolic reprogramming plays a key role in the occurrence and development of ESCC. Unsupervised clustering analysis was employed to stratify ESCC samples into three clusters: MPC1-lipid type, MPC2-amino acid type, and MPC3-energy type, based on the enrichment scores of metabolic pathways extracted from the Reactome database. The MPC3 cluster exhibited characteristics of energy metabolism, with heightened glycolysis, cofactors, and nucleotide metabolism, showing a trend toward increased aggressiveness and poorer survival rates. On the other hand, MPC1 and MPC2 primarily involved lipid and amino acid metabolism, respectively. In addition, liquid chromatography‒mass spectrometry-based metabolite profiles and potential therapeutic agents were explored and compared among ESCC cell lines with different MPCs. MPC3 amplified energy metabolism markers, especially carnitines. In contrast, MPC1 and MPC2 predominantly had elevated levels of lipids (primarily triacylglycerol) and amino acids, respectively. Furthermore, MPC3 demonstrated a suboptimal clinical response to PD-L1 immunotherapy but showed increased sensitivity to the doramapimod chemotherapy regimen, as evident from drug sensitivity evaluations. These insights pave the way for a more personalized therapeutic approach, potentially enhancing treatment precision for ESCC patients.
Driving forces of digital transformation in chinese enterprises based on machine learning
Authors: Chen Qi-an , Zhao Xu , Zhang Xinyi , Jiang Zizhe , Wang Yuxuan
Published: March 2024

With advanced science and digital technology, digital transformation has become an important way to promote the sustainable development of enterprises. However, the existing research only focuses on the linear relationship between a single characteristic and digital transformation. In this study, we select the data of Chinese A-share listed companies from 2010 to 2020, innovatively use the machine learning method and explore the differences in the predictive effects of multi-dimensional features on the digital transformation of enterprises based on the Technology-Organization-Environment (TOE) theory, thus identifying the main drivers affecting digital transformation and the fitting models with stronger predictive effect. The study found that: first, by comparing machine learning and traditional linear regression models, it is found that the prediction ability of ensemble earning method is generally higher than that of tradition measurement method. For the sample data selected in this research, XGBoost and LightGBM have strong explanatory ability and high prediction accuracy. Second, compared with the technical driving force and environmental driving force, the organizational driving force has a greater impact. Third, among these characteristics, equity concentration and executives’ knowledge level in organizational dimension have the greatest impact on digital transformation. Therefore, enterprise managers should always pay attention to the decision-making role of equity concentration and executives’ knowledge level. This study further enriches the literature on digital transformation in enterprises, expands the application of machine learning in economics, and provides a theoretical basis for enterprises to enhance digital transformation.
Identification of kidney stones in KUB X-ray images using VGG16 empowered with explainable artificial intelligence
Authors: Ahmed Fahad , Abbas Sagheer , Athar Atifa , Shahzad Tariq , Khan Wasim Ahmad , Alharbi Meshal , Khan Muhammad Adnan , Ahmed Arfan
Published: March 2024

A kidney stone is a solid formation that can lead to kidney failure, severe pain, and reduced quality of life from urinary system blockages. While medical experts can interpret kidney-ureter-bladder (KUB) X-ray images, specific images pose challenges for human detection, requiring significant analysis time. Consequently, developing a detection system becomes crucial for accurately classifying KUB X-ray images. This article applies a transfer learning (TL) model with a pre-trained VGG16 empowered with explainable artificial intelligence (XAI) to establish a system that takes KUB X-ray images and accurately categorizes them as kidney stones or normal cases. The findings demonstrate that the model achieves a testing accuracy of 97.41% in identifying kidney stones or normal KUB X-rays in the dataset used. VGG16 model delivers highly accurate predictions but lacks fairness and explainability in their decision-making process. This study incorporates the Layer-Wise Relevance Propagation (LRP) technique, an explainable artificial intelligence (XAI) technique, to enhance the transparency and effectiveness of the model to address this concern. The XAI technique, specifically LRP, increases the model's fairness and transparency, facilitating human comprehension of the predictions. Consequently, XAI can play an important role in assisting doctors with the accurate identification of kidney stones, thereby facilitating the execution of effective treatment strategies.
Discovering therapeutic possibilities for polycystic ovary syndrome by targeting XIST and its associated ceRNA network through the analysis of transcriptome data
Authors: Berenji Elahe , Valipour Motlagh Ali , Fathi Marziyeh , Esmaeili Maryam , Izadi Tayebeh , Rezvanian Parsa , Zanjirband Maryam , Safaeinejad Zahra , Nasr-Esfahani Mohammad Hossein
Published: March 2024

Long non-coding RNA (lncRNA) regulates many physiological processes by acting as competitive endogenous RNA (ceRNA). The dysregulation of lncRNA X-inactive specific transcript (XIST) has been shown in various human disorders. However, its role in the pathogenesis of polycystic ovary syndrome (PCOS) is yet to be explored. This study aimed to explore the underlying mechanism of XIST in the pathogenesis of PCOS, specifically through dataset functional analysis. GEO PCOS datasets including RNA-seq, microarray, and miRNA-seq in granulosa cells (GCs) and blood, were examined and comprehensively analyzed. Enrichment analysis, ROC curve constructions, lncRNA-miRNA-mRNA interaction network analyses, and qRT-PCR validation were performed followed by a series of drug signature screenings. Our results revealed significant dysregulation in the expression of 1131 mRNAs, 30 miRNAs, and XIST in GCs of PCOS patients compared to healthy individuals. Of the120 XIST-correlated upregulated genes, 25 were enriched in inflammation-related pathways. Additionally, 5 miRNAs were identified as negative regulators of XIST-correlated genes. Accordingly, a ceRNA network containing XIST-miRNAs-mRNAs interactions was constructed. Furthermore, 6 genes, including AQP9, ETS2, PLAU, PLEK, SOCS3, and TNFRSF1B served as both GCs and blood-based biomarkers. By analyzing the number of interactions among XIST, miRNAs, and mRNAs, we pinpointed ETS2 as the pivotal gene within the ceRNA network. Our findings reveal a novel XIST- hsa-miR-146a-5p, hsa-miR-144-3p, and hsa-miR-1271-5p-ETS2 axis that comprehensively elucidates the XIST-associated mechanism underlying PCOS onset. qRT-PCR analysis further confirmed the, overexpression of both XIST and ETS2 . Furthermore, our results demonstrated that XIST and ETS2 were correlated with some assisted reproductive technologies outcomes. Finally, we identified two novel compounds including, methotrexate/folate and threonine using drug–gene interaction databases for PCOS management. These findings provide novel insights into the molecular etiology, diagnosis, and potential therapeutic interventions for PCOS.
Prognostic mutation signature would serve as a potential prognostic predictor in patients with diffuse large B-cell lymphoma
Authors: Cho Shih-Feng , Yeh Tsung-Jang , Wang Hui-Ching , Du Jeng-Shiun , Gau Yuh-Ching , Lin Yu-Yin , Chuang Tzer-Ming , Liu Yi-Chang , Hsiao Hui-Hua , Moi Sin-Hua
Published: March 2024

The present study aimed to elucidate the prognostic mutation signature (PMS) associated with long-term survival in a diffuse large B-cell lymphoma (DLBCL) cohort. All data including derivation and validation cohorts were retrospectively retrieved from The Cancer Genome Atlas (TCGA) database and whole-exome sequencing (WES) data. The Lasso Cox regression analysis was used to construct the PMS based on WES data, and the PMS was determined using the area under the receiver operating curve (AUC). The predictive performance of eligible PMS was analyzed by time-dependent receiver operating curve (ROC) analyses. After the initial evaluation, a PMS composed of 94 PFS-related genes was constructed. Notably, this constructed PMS accurately predicted the 12-, 36-, and 60-month PFS, with AUC values of 0.982, 0.983, and 0.987, respectively. A higher level of PMS was closely linked to a significantly worse PFS, regardless of the molecular subtype. Further evaluation by forest plot revealed incorporation of international prognostic index or tumor mutational burden into PMS increased the prediction capability for PFS. The drug-gene interaction and pathway exploration revealed the PFS-related genes were associated with DNA damage, TP53, apoptosis, and immune cell functions. In conclusion, this study utilizing a high throughput genetic approach demonstrated that the PMS could serve as a prognostic predictor in DLBCL patients. Furthermore, the identification of the key signaling pathways for disease progression also provides information for further investigation to gain more insight into novel drug-resistant mechanisms.
Assessing the impact of post-mortem damage and contamination on imputation performance in ancient DNA
Authors: Garrido Marques Antonio , Rubinacci Simone , Malaspinas Anna-Sapfo , Delaneau Olivier , Sousa da Mota Bárbara
Published: March 2024

Low-coverage imputation is becoming ever more present in ancient DNA (aDNA) studies. Imputation pipelines commonly used for present-day genomes have been shown to yield accurate results when applied to ancient genomes. However, post-mortem damage (PMD), in the form of C-to-T substitutions at the reads termini, and contamination with DNA from closely related species can potentially affect imputation performance in aDNA. In this study, we evaluated imputation performance (i) when using a genotype caller designed for aDNA, ATLAS, compared to bcftools, and (ii) when contamination is present. We evaluated imputation performance with principal component analyses and by calculating imputation error rates. With a particular focus on differently imputed sites, we found that using ATLAS prior to imputation substantially improved imputed genotypes for a very damaged ancient genome (42% PMD). Trimming the ends of the sequencing reads led to similar improvements in imputation accuracy. For the remaining genomes, ATLAS brought limited gains. Finally, to examine the effect of contamination on imputation, we added various amounts of reads from two present-day genomes to a previously downsampled high-coverage ancient genome. We observed that imputation accuracy drastically decreased for contamination rates above 5%. In conclusion, we recommend (i) accounting for PMD by either trimming sequencing reads or using a genotype caller such as ATLAS before imputing highly damaged genomes and (ii) only imputing genomes containing up to 5% of contamination.
Solubility of α-synuclein species in the L62 mouse model of synucleinopathy
Authors: Schwab Karima , Magbagbeolu Mandy , Theuring Franz , Harrington Charles R. , Wischik Claude M. , Riedel Gernot
Published: March 2024

The accumulation of α-synuclein (α-Syn) into Lewy bodies is a hallmark of synucleinopathies, a group of neurological disorders that include Parkinson’s disease (PD) and dementia with Lewy bodies (DLB). Small oligomers as well as larger fibrils of α-Syn have been suggested to induce cell toxicity leading to a degenerative loss of neurones. A richer understanding of α-Syn aggregation in disease, however, requires the identification of the different α-Syn species and the characterisation of their biochemical properties. We here aimed at a more in-depth characterisation of the α-Syn transgenic mice, Line 62 (L62), and examined the deposition pattern and solubility of human and murine α-Syn in these mice using immunohistochemical and biochemical methods. Application of multiple antibodies confirmed mAb syn204 as the most discriminatory antibody for human α-Syn in L62. Syn204 revealed an intense and widespread immunohistochemical α-Syn labelling in parietal cortex and hippocampus, and to a lower level in basal forebrain and hindbrain regions. The labelled α-Syn represented somatic inclusions as well as processes and synaptic endings. Biochemical analysis revealed a Triton-resistant human α-Syn pool of large oligomers, a second pool of small oligomers that was not resistant to solubilization with urea/Triton. A third SDS-soluble pool of intermediate sized aggregates containing a mixture of both, human and mouse α-Syn was also present. These data suggest that several pools of α-Syn can exist in neurones, most likely in different cellular compartments. Information about these different pools is important for the development of novel disease modifying therapies aimed at α-Syn.
Imeglimin mitigates the accumulation of dysfunctional mitochondria to restore insulin secretion and suppress apoptosis of pancreatic β-cells from db/db mice
Authors: Aoyagi Kyota , Nishiwaki Chiyono , Nakamichi Yoko , Yamashita Shun-ichi , Kanki Tomotake , Ohara-Imaizumi Mica
Published: March 2024

Mitochondrial dysfunction in pancreatic β-cells leads to impaired glucose-stimulated insulin secretion (GSIS) and type 2 diabetes (T2D), highlighting the importance of autophagic elimination of dysfunctional mitochondria (mitophagy) in mitochondrial quality control (mQC). Imeglimin, a new oral anti-diabetic drug that improves hyperglycemia and GSIS, may enhance mitochondrial activity. However, chronic imeglimin treatment’s effects on mQC in diabetic β-cells are unknown. Here, we compared imeglimin, structurally similar anti-diabetic drug metformin, and insulin for their effects on clearance of dysfunctional mitochondria through mitophagy in pancreatic β-cells from diabetic model db/db mice and mitophagy reporter (CMMR) mice. Pancreatic islets from db/db mice showed aberrant accumulation of dysfunctional mitochondria and excessive production of reactive oxygen species (ROS) along with markedly elevated mitophagy, suggesting that the generation of dysfunctional mitochondria overwhelmed the mitophagic capacity in db/db β-cells. Treatment with imeglimin or insulin, but not metformin, reduced ROS production and the numbers of dysfunctional mitochondria, and normalized mitophagic activity in db/db β-cells. Concomitantly, imeglimin and insulin, but not metformin, restored the secreted insulin level and reduced β-cell apoptosis in db/db mice. In conclusion, imeglimin mitigated accumulation of dysfunctional mitochondria through mitophagy in diabetic mice, and may contribute to preserving β-cell function and effective glycemic control in T2D.
Immediate angiographic control after intra-arterial nimodipine administration underestimates the vasodilatory effect
Authors: Zaeske Charlotte , Zopfs David , Laukamp Kai , Lennartz Simon , Kottlors Jonathan , Goertz Lukas , Stetefeld Henning , Hof Marion , Abdullayev Nuran , Kabbasch Christoph , Schlamann Marc , Schönfeld Michael
Published: March 2024

Intra-arterial nimodipine administration is a widely used rescue therapy for cerebral vasospasm. Although it is known that its effect sets in with delay, there is little evidence in current literature. Our aim was to prove that the maximal vasodilatory effect is underestimated in direct angiographic controls. We reviewed all cases of intra-arterial nimodipine treatment for subarachnoid hemorrhage-related cerebral vasospasm between January 2021 and December 2022. Inclusion criteria were availability of digital subtraction angiography runs before and after nimodipine administration and a delayed run for the most affected vessel at the end of the procedure to decide on further escalation of therapy. We evaluated nimodipine dose, timing of administration and vessel diameters. Delayed runs were performed in 32 cases (19 patients) with a mean delay of 37.6 (± 16.6) min after nimodipine administration and a mean total nimodipine dose of 4.7 (± 1.2) mg. Vessel dilation was more pronounced in delayed vs. immediate controls, with greater changes in spastic vessel segments (n = 31: 113.5 (± 78.5%) vs. 32.2% (± 27.9%), p < 0.0001) vs. non-spastic vessel segments (n = 32: 23.1% (± 13.5%) vs. 13.3% (± 10.7%), p < 0.0001). In conclusion intra-arterially administered nimodipine seems to exert a delayed vasodilatory effect, which should be considered before escalation of therapy.
Identifying microRNAs associated with tumor immunotherapy response using an interpretable machine learning model
Authors: Nam Dong-Yeon , Rhee Je-Keun
Published: March 2024

Predicting clinical responses to tumor immunotherapy is essential to reduce side effects and the potential for sustained clinical responses. Nevertheless, preselecting patients who are likely to respond to such treatments remains highly challenging. Here, we explored the potential of microRNAs (miRNAs) as predictors of immune checkpoint blockade responses using a machine learning approach. First, we constructed random forest models to predict the response to tumor ICB therapy using miRNA expression profiles across 19 cancer types. The contribution of individual miRNAs to each prediction process was determined by employing SHapley Additive exPlanations (SHAP) for model interpretation. Remarkably, the predictive performance achieved by using a small number of miRNAs with high feature importance was similar to that achieved by using the entire miRNA set. Additionally, the genes targeted by these miRNAs were closely associated with tumor- and immune-related pathways. In conclusion, this study demonstrates the potential of miRNA expression data for assessing tumor immunotherapy responses. Furthermore, we confirmed the potential of informative miRNAs as biomarkers for the prediction of immunotherapy response, which will advance our understanding of tumor immunotherapy mechanisms.