bluuebunny/crossref_metadata_2025_split huggingface dataset:
Spatiotemporal Landscape of Kidney Tubular Responses to Glomerular Proteinuria
Authors: Faivre Anna , Bugarski Milica , Rinaldi Anna , Sakhi Imene B. , Verissimo Thomas , Legouis David , Correia Sara , Kaminska Monika , Dalga Delal , Malpetti Daniele , Cippa Pietro E. , de Seigneux Sophie , Hall Andrew M. 
Published: April 2024

Key Points

Glomerular proteinuria induces large-scale changes in gene expression along the nephron.Increased protein uptake in the proximal tubule results in axial remodeling and injury.Increased protein delivery to the distal tubule causes dedifferentiation of the epithelium.

Background
Large increases in glomerular protein filtration induce major changes in body homeostasis and are associated with a higher risk of kidney functional decline and cardiovascular disease. We investigated how elevated protein exposure modifies the landscape of tubular function along the entire nephron, to understand the cellular changes that mediate these important clinical phenomena.

Methods
We conducted single-nucleus RNA sequencing, functional intravital imaging, and antibody staining to spatially map transport processes along the mouse kidney tubule. We then delineated how these were altered in a transgenic mouse model of inducible glomerular proteinuria (POD-ATTAC) at 7 and 28 days.

Results
Glomerular proteinuria activated large-scale and pleiotropic changes in gene expression in all major nephron sections. Extension of protein uptake from early (S1) to later (S2) parts of the proximal tubule initially triggered dramatic expansion of a hybrid S1/2 population, followed by injury and failed repair, with the cumulative effect of loss of canonical S2 functions. Proteinuria also induced acute injury in S3. Meanwhile, overflow of luminal proteins to the distal tubule caused transcriptional convergence between specialized regions and generalized dedifferentiation.

Conclusions
Proteinuria modulated cell signaling in tubular epithelia and caused distinct patterns of remodeling and injury in a segment-specific manner.
Toward Tectonic-Type and Global 1D Seismic Models of the Upper Mantle Constrained by Broadband Surface Waves
Authors: Civiero Chiara , Lebedev Sergei , Xu Yihe , Bonadio Raffaele , Lavoué François 
Published: April 2024

ABSTRACT
The unprecedentedly dense current sampling of the upper mantle with seismic data offers an opportunity for determining representative seismic velocity models for the Earth’s main tectonic environments. Here, we use over 1.17 million Rayleigh- and 300,000 Love-wave, fundamental-mode, phase-velocity curves measured with multimode waveform inversion of data available since the 1990s, and compute phase-velocity maps in a 17–310 s period range. We then compute phase-velocity curves averaged over the globe and eight tectonic environments, and invert them for 1D seismic velocity profiles of the upper mantle. The averaged curves are smooth and fit by VS models with very small misfits, under 0.1%, at most periods. For phase-velocity curves extending up to 310 s, Rayleigh waves resolve VSV structure down to the shallow lower mantle. Love-wave sampling is shallower, and VSH and, thus, radial anisotropy profiles are resolved down to 375–400 km depth. The uncertainty of the VS models is dominated by the trade-offs of VS at neighboring depths. Using the model-space-projection approach, we quantify the uncertainty of VS in layers of different thickness and at different depths, and show how it decreases with the increasing thickness of the layers. Example 1D VS models that fit the data display the expected increase of the lithospheric seismic velocity with the age of the oceanic lithosphere and with the average age of the continental tectonic type. Radial anisotropy in the global and most tectonic-type models show a flip of the sign from positive (VSH&gt;VSV) to negative at 200–300 km depth. Negative anisotropy is also observed in the shallow mantle lithosphere beneath oceans down to 45–55 km depth. We also compute a global model with the minimal structural complexity, which fits the data worse than the best-fitting one but does not include a sublithospheric low-velocity zone, providing a simple reference for seismic studies.
Unified blended learning environment: the Kazakhstani context
Authors: Bakhisheva S. M. , Tikhonyuk E. V. , Mukhtar Z. G. , Kinzhekova R. S. , Kemeshova A. M. 
Published: April 2024

Introduction. The present work investigates the issues related to technological and administrative support for the blended learning process in higher education in Kazakhstan.Aim. This article aims to develop an author’s conceptual model of a unified system for managing the blended learning process by defining the evaluation criteria for an optimal educational environment.Methodology and research methods. The research was conducted in four stages using mixed methods. The first stage involved conducting surveys with participants in the educational process to identify the challenges they encountered while working in a digital educational environment and explore potential solutions. The second stage involved developing evaluation criteria for an optimal educational environment for blended learning. The third stage entailed empirical testing of existing educational platforms that are utilised by 33 leading Kazakh universities. The fourth stage witnessed the development of a pilot conceptual model for a unified environment for blended learning.Results. Based on the integration of Learning Activity Management System (LAMS), Learning Management System (LMS), and Education Content Management System (ECMS), a conceptual model of a unified environment for blended learning was developed. The criteria for the optimal educational environment of blended learning were developed to evaluate the technical, functional, and didactic capabilities of educational platforms.Scientific novelty. The study resulted in the development of a conceptual model for a unified environment for managing the blended learning process.Practical significance. The proposed model can be employed by the administrations of top Kazakhstani universities to implement a student-centred approach to the educational process.
Analysis of the Work Experience of the Expert Commission of the Section “Mathematics and its Applications in Information Technology and Economics” of the International Forum of Scientific Youth “Step into the Future”
Authors: Журавлева Е.В. , Студеникина Л.И. 
Published: April 2024

Рассмотрены особенности работ, присылаемых для участия в секции 3F молодежного форума «Шаг в будущее» «Математика и ее приложения в информационных технологиях и экономике». Изучена динамика изменений качества конкурсных работ, сформулированы рекомендации по формированию направлений исследований обучающихся средних общеобразовательных и средних профессиональных образовательных организаций.
The features of works sent for participation in section 3F of the youth forum “Step into the Future” “Mathematics and its applications in information technology and economics” are considered. The dynamics of changes in the quality of competitive works have been studied, recommendations have been formulated on the formation of areas of research for students of secondary general education and secondary vocational educational organizations.
Seismic events in the Vorkuta coal industrial district in 2023
Authors: Noskova N. , Verkholantsev F. , Asming Vladimir , Vaganova Natalia , Popov I. 
Published: April 2024

In 2023, regional seismic stations recorded 25 seismic events in the Vorkuta coal industrial district of the Komi Republic, with a local magnitude ML from 1.8 to 2.8. A significant contribution to the detection of weak, ML ≤ 2, events was made by data obtained from the temporary seismic station of the IG FRC Komi SC UB RAS, installed as part of expeditionary work in the summer of 2023 in the Polar Urals.
Among them the seismic event on August 1, 2023, which had a macroseismic effect, is of particular interest. Residents of several districts of Vorkuta felt tremors similar to an earthquake. Seismic records from 5 stations with epicentral distances from 40 to 1070 km were processed. The following parameters of the epicenter were obtained: t0 = 18:39:07, 67.529N, 64.001E, h = 0 km, Rminor = 3.9 km, Rmajor = 6.7 km, AzMajor = 90°, Kp = 9.0, ML = 2.8, Ms = 2.35. The instrumental epicenter of the event is located in Vorkuta, near the mine field of the Vorkuta mine. We classified the seismic event as a rock burst. Macroseismic intensity calculated in accordance with the Seismic intensity scale-2017 using 57 questionnaires and 163 definitions of sensor categories was I0 = 4.73 ± 0.02. The calculated value of the macroseismic depth of the source was H = 0.5 ± 0.4 km, which corresponds to the instrumental definition and to the range of depths of mine workings of the Vorkuta coal deposit.
TERRITORIALIDADES QUILOMBOLAS E JUDICIÁRIO: ANÁLISE DOS VOTOS DOS MINISTROS DO STF NA AÇÃO DIRETA DE INCONSTITUCIONALIDADE N. 3239-DF
Authors: Aires Alves Freitas Ana Beatriz , Martins Lemes João Vitor 
Published: April 2024

As territorialidades quilombolas são objeto de disputa frequente no judiciário brasileiro, sendo a Ação Direta de Inconstitucionalidade n. 3229-DF, ajuizada pelo, à época, Partido da Frente Liberal (PFL), a ação judicial que define os contornos dos direitos territoriais quilombolas a partir da discussão da constitucionalidade do Decreto n. 4.887/2003, que trata de regulamentar o art. 68 do Ato das Disposições Constitucionais Transitórias. Tendo sido ajuizada em 2004 e pautada para julgamento pela primeira vez em 2012, a ação foi julgada improcedente em 2018, assegurando os direitos das comunidades quilombolas aos seus territórios. Dessa forma, por meio de pesquisa quali-quantitativa e com uso da técnica de estudo de decisões judiciais, a presente pesquisa objetiva compreender as categorias em disputa quando se analisa os direitos territoriais quilombolas e quais os fundamentos prevalecem a partir do julgamento da referida ação. Tal levantamento foi realizado a partir do cotejamento entre as divergências apresentadas pelos ministros em suas decisões, destacados, sobremaneira, os votos dos ministros Cezar Peluso, Rosa Weber e Dias Toffoli, que estabeleceram três linhas distintas quanto à constitucionalidade do decreto impugnado.
Fear and Climate Change: How natural disasters and environmental fears shape American climate attitudes across political orientation
Authors: Garneau Christopher , Bedle Heather , Stanfield Rory 
Published: April 2024

Abstract

Climate change remains a polarizing issue along partisan lines in the United States, with conservatives expressing greater skepticism about its risks. This research investigates how fear shapes climate change attitudes across political orientations. From a 2023 national survey, results support hypotheses that conservatives demonstrate lower climate concern relative to liberals (H1), and that fear of natural and environmental disasters increase climate concern. While evidence for the hypothesis that the effect is more pronounced among conservatives is mixed (H3), the findings suggest that fear of anthropogenic environmental disasters elicit climate attitude shifts among conservatives, consistent with threat perception literature. When respondents noted heightened ecological fear, the political divisions in attitudes diminish, as trends converge on acknowledging the climate risks and causes. This relationship highlights messaging opportunities by focusing on locally relevant environmental threats that can aid in influencing conservative climate actions, which could build collective climate action support across political divides.
Evaluating the Discriminative Capacity of a Random Forest Predictive Model for Deep Vein Thrombosis in Tibial Plateau Fracture Patients
Authors: Liu Hao , Xing Fei , Jiang Jiabao , Chen Zhao , Xiang Zhou , Duan Xin 
Published: April 2024

Abstract

Introduction: This study aims to construct an efficient random forest predictive model to address the knowledge limitations in predicting deep vein thrombosis (DVT) among tibial plateau fracture (TPF) patients. DVT, being a critical and potentially life-threatening consequence, often necessitates intricate clinical management. Materials and Methods This investigation retrospectively examined adult patients who underwent surgical intervention for tibial plateau fractures in our institution from June 2020 to December 2023. Among the 562 patients who underwent surgical intervention, 231 were included in the study cohort, subsequently divided into training and testing cohorts in a 70:30 ratio. The training cohort utilized the R software to construct a random forest predictive model, which was then validated in the testing group. Furthermore, logistic regression analysis was conducted in this study to acquire feature selection variables and the area under the curve (AUC), evaluating the credibility and discriminative capacity of the random forest algorithm. Results As for the discriminative capacity of the random forest predictive model, in the training cohort, the 95% confidence interval (CI), area under the curve (AUC), sensitivity, specificity, F1, and Balanced Accuracy were respectively (0.9775, 1), 1.0000, 1.0000, 1.0000, 1.0000, and 1.0000. Correspondingly, in the testing cohort, these metrics were (0.7326, 0.9176), 0.901, 0.8696, 0.8261, 0.7843, and 0.8478. Conclusion Utilizing the discerningly chosen " important " variables, this study employed the random forest algorithm to craft a predictive model, demonstrating exceptional discriminative prowess. These identified " important " variables, serving as predictive factors, aid clinicians in the identification of high-risk DVT patients. This, in turn, facilitates timely intervention, fortification of care, and enhancement of prognostic outcomes for patients with fractures.
Metformin's Effect on Non-Alcoholic Fatty Liver Disease through the miR-200a-5p and AMPK/SERCA2b Pathway
Authors: Chen Hang , Huang Minshan , Wang Hui , Zhang Dan , Wang Da , Li Mengwei , Wang Xianmei , Zhu Rui , Liu Jianjun , Ma Lanqing 
Published: April 2024

Abstract

Objectives: Metformin, a primary treatment for type 2 diabetes due to its insulin-sensitizing capabilities, has been widely recognized for its efficacy in improving or mitigating non-alcoholic fatty liver disease (NAFLD). Recent investigations have highlighted the potential involvement of miRNAs in the pathogenesis of NAFLD, yet the precise mechanisms remain elusive. This study aims to explore the role of miR-200a-5p in regulating AMPK/SERCA2b to diminish liver fat accumulation and endoplasmic reticulum (ER) stress in metformin-treated NAFLD, thereby shedding light on novel therapeutic strategies.
Methods: The PA cell model, induced by mixing oleic and palmitic acid solutions in a 2:1 ratio, was utilized to simulate lipid accumulation, which was assessed using oil red O and Nile red staining. RT-PCR measured the mRNA levels of miR-200a-5p and key lipid metabolism genes (Acc1, Fasn, Cpt1, Scd1, Cd36, and Serbp1). Western blotting determined the protein expression of AMPK, phosphorylated AMPK (p-AMPK) and SERCA2b. The interaction between miR-200a-5p and AMPK was investigated via a luciferase reporter assay, and the effect of miR-200a-5p overexpression on AMPK and SERCA2b proteins was also assessed. A high-fat diet-induced NAFLD mouse model was developed to evaluate the impact of metformin on liver steatosis and lipid deposition through HE and oil red O staining. Additionally, liver lipid profiles (TG, TC, LDL-C, and HDL-C) were quantified, and RT-PCR analyzed the mRNA levels of miR-200a-5p and lipid metabolism genes. The expression of AMPK, p-AMPK, and SERCA2b proteins were examined, alongside the mRNA levels of miR-200a-5p in the serum of NAFLD patients.
Results: Elevated mRNA levels of miR-200a-5p and lipid metabolism genes were observed in the PA cell model, while AMPK and SERCA2b had lower protein expression levels. Luciferase reporter assays confirmed miR-200a-5p's interaction with AMPK. The miR-200a-5p mimic group exhibited decreased AMPK and SERCA2b expression levels. Animal studies demonstrated metformin's capacity to lessen liver steatosis and lipid deposition, improving lipid profiles (TG, TC, LDL-C, and HDL-C). Metformin treatment adjusted the mRNA levels of miR-200a-5p and lipid metabolism genes back to normal, as well as the protein expression levels of AMPK, p-AMPK, and SERCA2b. Elevated miR-200a-5p mRNA levels were detected in the serum of NAFLD patients.
Conclusion: Our findings indicate that metformin may alleviate lipid deposition and ER stress in the livers of NAFLD mice by modulating the AMPK/SERCA2b pathway through miR-200a-5p. This study introduces a novel perspective on the mechanism of metformin's therapeutic effects in NAFLD treatment.
Exploring the protective effect and potential mechanism of acutumidine on myocardial ischemia based on “compound-target-pathway” network
Authors: Shao Jia , Yu Yingying , Zheng Rongrong , Luo Ling , Wang Yuanyuan , Zheng Yanxue , Wei Jinxia 
Published: April 2024

Abstract

Background
Menispermi Rhizoma is a traditional Chinese medicine with significant anti-myocardial ischemia (MI) effects. Acutumidine is a major alkaloid component of Menispermi Rhizoma. However, the effect and mechanism of acutumidine on MI remain unknown. This research aims to explore the effect and potential mechanism of acutumidine in treating myocardial ischemia (MI).
Methods
The oxygen glucose deprivation (OGD) model of H9c2 cardiomyocytes was established to simulate MI in vitro. The protective effect of acutumidine against MI was evaluated by MTT assay, Hoechst/PI staining, lactate dehydrogenase (LDH), creatine kinase (CK) release, the levels of superoxide dismutase (SOD), glutathione (GSH) and malondialdehyde (MDA) and cell apoptosis rate. Based on network pharmacology, the potential the anti-MI mechanism of acutumidine is explored by constructing a "compound-target-pathway" network. GO and KEGG enrichment analysis were performed via metascape database. Finally, the key targets of acutumidine were validated by molecular docking.
Results
The experiment results showed that acutumidine could protect H9c2 cardiomyocytes against OGD injury by increasing the levels of SOD and GSH, and decreasing the release of LDH, CK and MDA significantly. The apoptosis rate of OGD H9c2 cells were reduced. All research results suggested that acutumidine could inhibit oxidative stress and cell apoptosis. Network pharmacology showed that the protective effect of acutumidine on MI was related to PI3K/AKT, HIF-1, and Ras signaling pathways. Molecular docking studies further showed that MAPK1, IGF1, EGFR, and KDR are the core targets of acutumidine in the treatment of MI.
Conclusions
Acutumidine was shown to have notable effects to inhibit oxidative stress and cell apoptosis in H9c2 cells through PI3K/AKT, HIF-1 and Ras signaling pathway. This study not only provides new insights into the anti-MI effect and mechanism of acutumidine, but also offers a promising candidate drug for the treatment of MI.
Study on the mechanism of miR-361-5p regulation of androgen receptor in castration-resistant transformation of prostate cancer
Authors: Zhang Peng , Yin Xin , Li Xinzhao , Zang Mingyi , Liang Qing , Zhang Zhiguo , Liu Lin , Han Conghui , He Jie , Liu Dachuang 
Published: April 2024

Abstract

Prostate cancer has become one of the most common tumors endangering men's health. At present, the main clinical treatments for prostate tumors are surgery, radiotherapy, endocrine therapy, chemotherapy, etc. However, due to drug resistance, the treatment effect of prostate cancer is not good, and the expression of androgen receptor (AR) and its protein structure changes play a crucial role in the resistance of prostate cancer. The expression of androgen receptor (AR) and changes in its protein structure play a crucial role in prostate cancer drug resistance. Non-coding RNAs, especially miRNAs, are involved in post-transcriptional regulation of genes and play an important role in the development of tumor cells, and may be used as specific substances to assist in the treatment of cancer. Our previous study showed that miR-361-5p expression was down-regulated in prostate cancer and that overexpression of miR-361-5p inhibited the proliferation, migration and promoted apoptosis of castration-resistant prostate cancer cells, DU145 and PC3, however, the mechanism through which miR-361-5p affects the progression of prostate cancer is unknown. We found that miR-361-5p could target binding to androgen receptor (AR) and play a role in the transformation of hormone-sensitive prostate cancer cells (LNCAP) to castration-resistant prostate cancer cells (LNCAP-AI), which inhibited proliferation, migration and promoted apoptosis of prostate cancer cells. Therefore, we suggest that miR-361-5p can target AR and inhibit the rapid growth of AR in the early stage of transformation, thus inhibiting the transformation of prostate cancer cells to castration-resistant.
Albendazole resistance evidence in Teladorsagia circumcincta in Iranian sheepby allele-specific PCR
Authors: Mirzaei Yousef , Yakhchali Mohammad , Mardani Karim 
Published: April 2024

Abstract

Globally, gastrointestinal nematodes (GIN) have a considerable impact on the livestock husbandry and health conditions in Iran and throughout the world. The infected animals with gastrointestinal nematodes mostly need anthelmintic therapy which leads to the development of anthelmintic drug resistance. The main objective of the current study was to determine the frequency of β-tubulin isotype 1 gene polymorphism to albendazole (Alb) in Teladorsagia circumcincta isolated from sheep abomasum in Urmia city, Iran. A total number of 140 sheep abomasa were randomly collected and 157 infected abomasa with T. circumcincta were found. Alb resistance in T. circumcincta determined using Allele-Specific PCR (ASP) technique. The frequency of the homozygous susceptible (SS), homozygous resistant (rr) and heterozygous susceptible (Sr) to Alb were 51.7%, 6.9% and 41.4% in the examined T. circumcincta, respectively. It was concluded that Alb-resistance alleles were widespread in examined T. circumcincta which prevention control program should be lunched in the region.
Divergent mechanisms of steroid inhibition in the human ρ1 GABAA receptor
Authors: Lindahl Erik , Fan Chen , Cowgill John , Howard Rebecca 
Published: April 2024

Abstract

ρ-type γ-aminobutyric acid-A (GABAA) receptors are widely distributed in the retina and brain, and are potential drug targets for the treatment of visual, sleep and cognitive disorders. Endogenous neuroactive steroids including β-estradiol and pregnenolone sulfate negatively modulate the function of ρ1 GABAA receptors, but their inhibitory mechanisms are not clear. By combining four new cryo-EM structures with electrophysiology and molecular dynamics simulations, we characterize binding sites and negative modulation mechanisms of β-estradiol and pregnenolone sulfate at the human ρ1 GABAA receptor. β-estradiol binds in a pocket at the interface between extracellular and transmembrane domains, apparently specific to the ρ subfamily, and disturbs allosteric conformational transitions linking GABA binding to pore opening. In contrast, pregnenolone sulfate binds inside the pore to block ion permeation, with a preference for activated structures. These results illuminate contrasting mechanisms of ρ1 inhibition by two different neuroactive steroids, with potential implications for subtype-specific gating and pharmacological design.