bluuebunny/crossref_metadata_2025 huggingface dataset:
Discovering the determinants of energy intensity of Indian manufacturing firms: a panel data approach
Authors: Sahu Udit Kumar , Pradhan Ashis Kumar
Published: July 2024

Our study pores on evaluating the impact of firm specific and macro level determinants of energy intensity of Indian firms belonging to manufacturing and power sector. We collect a panel dataset of 3316 firms for 10 years ranging from 2010 to 2020. We employ the advanced biased corrected method of moments estimator and the quantile regression estimator for panel data models for our empirical analysis. We find that poor labor efficiency is largely responsible for increasing energy intensity of the sample firms. Energy intensity can be optimized by investing in better plant and machinery. Moreover, machineries that require frequent repairs and maintenance need to be replaced with latest tools. While larger firms are found to be energy intensive, profitable firms are found to be in a better position to enhance their energy efficiency. Under macroeconomic scenario, GDP growth and trade openness lead to boosting up the energy consumption at the firm level whereas, the global energy prices act as a constraint and necessitate careful use of energy. Based on our findings we provide certain policy recommendations and suggestions in order to limit energy intensity and enhance energy efficiency of the Indian manufacturing firms.
Design and experimental analysis of a closed-loop autonomous rotary hydroponics system for revolutionizing fenugreek yield and enhancing food security
Authors: Kadam Sudhir A. , Kadam Payal S. , Mohite Dadaso D.
Published: July 2024

The rotary hydroponics system offers a space-saving and potentially high-yielding solution for soilless cultivation, promoting efficient resource use and automation for sustainable food production. This research investigates a closed-loop rotary hydroponics system designed to revolutionize fenugreek yield and enhance food security through resource-efficient and automated cultivation. Building upon the established benefits of aeroponics, particularly its efficient use of space and resources, rotary hydroponics introduces a groundbreaking, cylindrical design. This innovative approach not only maximizes space efficiency but also paves the way for further automation within the cultivation process. The proposed study delves into the design, development, and experimental analysis of a closed-loop, self-sustaining, and low-maintenance rotary hydroponics system specifically designed for fenugreek cultivation. The system prioritizes minimal human intervention through the integration of software-controlled monitoring and parameter adjustments. The research investigates the effectiveness of the system in promoting plant growth and analyzes the growth stages of fenugreek seedlings transplanted into the system. The experiment yielded promising results, with fenugreek plants reaching full maturity within 30 days and achieving an average height of 15–20 cm. These findings highlight the potential of the rotary hydroponics system to revolutionize fenugreek yield and bolster food security through its resource-efficient and sustainable cultivation approach.
Potential of ChatGPT as a digital language learning assistant: EFL teachers’ and students’ perceptions
Authors: Slamet Joko
Published: July 2024

ChatGPT is one example of an artificial intelligence (AI) tool that is gaining attention in the field of language education due to its potential as a digital language learning assistant. ChatGPT allows for customized interactions and real-time feedback to improve language learning. Yet, there is a study void on English as a Foreign Language (EFL) teachers and students’ use of ChatGPT in language learning. To fill this void, this a cross-sectional survey study investigates the perceptions and preferences of the 80 EFL teachers and the 46 EFL students in East Java, Indonesia. The study’s primary objective is to gain insight into how they perceive about using ChatGPT to improve their language learning. The results revealed possible benefits, such as better language competency and individualized learning experiences, as well as problems, such as language accuracy and technological dependence. The study also highlights the importance of pedagogical support, curricular alignment, user-friendly interfaces, and compelling interactive activities for successful integration. In light of these results, this study suggests ways in which teachers might better include ChatGPT as a digital language learning assistant. This study contributes to the body of knowledge of ChatGPT’s function in EFL instruction and will guide the improvement of other digital tools for language learning.

Graphical Abstract
Optimizing Patient Stratification in Healthcare: A Comparative Analysis of Clustering Algorithms for EHR Data
Authors: Aljohani Abeer
Published: July 2024

Advanced data analytics are increasingly being employed in healthcare research to improve patient classification and personalize medicinal therapies. In this paper, we focus on the critical problem of clustering electronic health record (EHR) data to enable appropriate patient categorization. In the era of personalized medicine, optimizing patient classification is critical to healthcare analytics. This research presents a comparative assessment of different clustering algorithms for Electronic Health Record (EHR) data, with the goal of improving the efficacy and productivity of patient clustering methods. Our study focuses on Fuzzy Technique for Order of Preference by Similarity to Ideal Solution (Fuzzy TOPSIS) as a Multi-Criteria Decision-Making (MCDM) strategy, includes an in-depth assessment of eight clustering algorithms: K-Means, DBSCAN, Hierarchical Clustering, Mean Shift, Affinity Propagation, Spectral Clustering, Gaussian Mixture Models (GMM), as well as Self-Organizing Maps. The evaluation factors used for evaluation in this research are Cluster Quality Metrics, Scalability, Robustness to Noise, Cluster Shape and Density, Interpretability, Cluster Number, Dimensionality, and Consistency and Stability. These criteria and alternatives were chosen after conducting a thorough assessment of the literature and consulting with domain experts. All participated specialists actively engaged in the decision-making process, bringing unique insights into the best clustering algorithms for healthcare data. The results of this study illustrate each algorithm’s strengths and weaknesses in the setting of patient stratification, providing insight into their performance across multiple dimensions. The fuzzy TOPSIS MCDM strategy is a reliable instrument for synthesizing expert opinions and methodically evaluating the found clustering alternatives. This study advances healthcare analytics by giving practitioners and researchers with informative perspectives on the selection of clustering algorithms designed to address the unique problems of patient stratification utilizing EHR data.
Triglyceride-Glucose Index as Predictor for Hypertension, CHD and STROKE Risk among Non-Diabetic Patients: A NHANES Cross-Sectional Study 2001–2020
Authors: Sawaf Bisher , Swed Sarya , Alibrahim Hidar , Bohsas Haidara , Dave Tirth , Nasif Mohamad Nour , Hafez Wael , Tashrifwala Fatema Ali Asgar , Jabban Yazan Khair Eldien , Al-Rassas Safwan , Saleh Heba haj , Zaidi Abdul Rehman Zia , Alghalyini Baraa , Mohamed Shaymaa Abdelmaboud , Mohamed Waleed Farouk , Farwati Amr , Seijari Mohammed Najdat , Battikh Naim , Elnagar Basma , Iqbal Seema , Robles-Velasco Karla , Cherrez-Ojeda Ivan
Published: July 2024

Background

Cardiovascular disease (CVD) is a leading cause of global mortality. Early intervention and prevention of CVD depend on accurately predicting the risk of CVD. This study aimed to investigate the association between the TyG index and the risk of coronary heart disease (CHD), congestive heart failure (CHF), heart attack (HA), stroke, and hypertension (HTN) among patients without diabetes in the United States.

Methods

In this retrospective, cross-sectional study, we used data from the National Health and Nutrition Examination Survey (NHANES) from 2001 to 2020. We conducted several regression analysis models and calculated the sensitivity and specificity of (TyG) index for predicting the onset of CHD, CHF, HA, stroke, and HTN.

Results

A total of 10,937 individuals without diabetes participated in our study. Individuals with a TyG index greater than 8.96 displayed significant increasing in various parameters, including BMI, systolic/diastolic blood pressure, total cholesterol, LDL, and Apo-B levels (p < 0.001). Almost all regression models ensured that a higher TyGI value was associated with higher odds of having CHD, CHF, HA, stroke, and HTN, which patients with a TyGI value higher than 8.96 have odds ratios of 2.24–5.58 for CHD, 1.68–4.42 for stroke, 2.45–3.77 for HA and 1.75–3.93 for HTN comparing than patients with a TyGI value lower than 8.11 (p-value < 0.05).We evaluated the predictive value of the TyG index for each endpoint, obtaining the following area under the curve (AUC) values: 54.75% for CHF (95% CI: 0.542–0.614), 52.32% for stroke (95% CI: 0.529–0.584), 55.67% for HA (95% CI: 0.595–0.646), 55.59% for HTN (95% CI: 0.574–0.597), and 50.31% for CHD (95% CI: 0.592–0.646).

Conclusion

The TyG index showed a strong correlation with cardiovascular risk factors in individuals without diabetes, however it was a poor predictor of almost studied cardiovascular diseases.
Design of a power processing unit with integrated telemetry for a vacuum arc thruster as part of the SeRANIS mission
Authors: Forster Roman , Szulc Michal , Schein Jochen
Published: July 2024

In this work the design and development of a power processing unit for a vacuum arc thruster is presented. The thruster is part of the Seamless Radio Access Networks for Internet of Space (SeRANIS) mission of the University of the Bundeswehr Munich, which will work as first multifunctional laboratory in orbit with public access. In addition to the basic functionality of generating a voltage peak for igniting the thruster, the power processing unit is equipped with techniques for controlling the ignition sequence and monitoring desired key values. The ignition procedure starts with generating the first trigger signal up to the point where a full-blown plasma is established. The PPU guarantees reliable performance by blocking every additional incoming signal while the ignition sequence is under way and the separation of the satellite’s power bus before the thruster discharges. The status of the power processing unit is constantly controlled and information is provided whether ignition was successful or not. The functionality of this circuit is based on simulation before assembly and testing. In addition, the presented system was designed to pass a test cycle of mechanical, thermal and electrical tests before being declared ready for the space mission.
Nitrogen-doped biochar derived from corn straw for CO2 adsorption: a new vision on nitrogen sources comparison
Authors: Sun Yuxuan , Jia Jixiu , Liu Zhidan , Liu Ziyun , Huo Lili , Zhao Lixin , Zhao Yanan , Yao Zonglu
Published: July 2024

Biochar as a highly promising CO2 adsorbent is of great significance in addressing global warming and promoting human health. Research has shown that nitrogen doping improves the CO2 adsorption performance of biochar, but selecting chemical nitrogen sources such as urea and melamine to prepare nitrogen-doped biochar is not conducive to green production and environmental protection. Therefore, it is necessary to identify a new nitrogen source to enhance the emission reduction characteristics of this process. This study selected corn straw as the raw material and cow manure as a representative protein-based nitrogen source to explore its potential as a urea substitute and reveal the hydrothermal carbonization doping mechanism of different nitrogen sources. The results indicated that in raw materials with the same C/N ratio, biochar prepared from cow manure as the nitrogen source had a better doping effect and CO2 adsorption performance. Moreover, a moderate amount of cow manure was beneficial for efficient nitrogen doping and the adsorption of CO2 by biochar, with a maximum CO2 adsorption performance improvement of 32.7%. Due to the different carbon-nitrogen bonds of the different nitrogen sources, urea was more likely to retain amino groups, while macromolecular protein nitrogen sources tended to retain structural nitrogen. The results of this study provide new ideas and theoretical support for preparing other nitrogen-doped carbon materials derived from biomass.

Graphical Abstract
Pulmonary functions test in asymptomatic rheumatoid lung disease patients: a hospital-based study
Authors: Hassan Asmaa Mohammed , Osman Asim Alaaeldin , Ali Ibrahim Abdelrhim
Published: July 2024

Background

As a common extra-articular symptom of rheumatoid arthritis (RA), pulmonary involvement affects 20–67% of patients and accounts for 10–20% of RA-related deaths. This study aimed to assess the impact of RA on pulmonary function tests (PFTs) in Sudanese RA patients attending the rheumatology clinics of the Omdurman Military Hospital.

Methods

This was an analytical, cross-sectional, hospital-based study of 32 RA patients who met the 2010 Rheumatoid Arthritis Classification Criteria of the American College of Rheumatology (RA ACR/EULAR) and who were nonsmokers and free of known respiratory or chronic diseases. Pulmonary function parameters (PFTs), including forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), the FEV1/FVC ratio, and the peak expiratory flow rate (PEFR), were measured for each participant using a digital spirometer. A control group of Sudanese subjects of similar age, sex, and height was matched, and the results were compared with normal reference values.

Results

A high prevalence of lung function abnormalities (93.8%) was observed in RA patients, and 6.2% of them had normal PFT parameters. Restrictive lung disease was recorded in 78.1% of the patients, and obstructive lung disease was observed in 15.7% of the patients. All measured PFT parameters in the RA patients were significantly lower than the published reference normal values for Sudanese subjects, except for the FEV1/FVC ratio. The mean values of FEV1, FVC, the FEV1/FVC ratio, and the PRFR in RA patients were 1.8 ± 0.3 L/min, 2.1 ± 0.4 L/min, 87.1 ± 12.2%, and 223.6 ± 86.2 L/min, respectively, compared to 2.4 ± 0.1 L/min, 2.7 ± 0.1 L/min, 90.81 ± 2.6%, and 345.4 ± 16.2 L/min, respectively, in the control group (P values of 0.001, 0.001, 0.299, and 0.001, respectively). There was no statistically significant correlation between PFT results and disease duration, age, or BMI.

Conclusions

Regardless of the duration of RA, restrictive lung abnormalities are frequent in asymptomatic RA patients. The PFT can serve as an indicator of RA. Spirometry has been advised as a baseline examination and for follow-up and to promote the early detection and management of pulmonary involvement in RA patients.
Characterizing the Spatial Distribution of Mixing and Transport in the Northern Middle Atmosphere During Winter
Authors: Curbelo J. , Mechoso C. R.
Published: July 2024

A three‐dimensional winter (DJF) climatology of Lagrangian diffusivity characterizing eddy mixing and transport in the northern middle atmosphere is presented. To emphasize aspects other than zonal averages, we use the theory of Lagrangian diffusivity (κyy) hitherto not applied in stratospheric contexts to our knowledge. Our formulation of Lagrangian diffusivity requires the calculation of parcel trajectories, which is made on isentropic surfaces. A Lagrangian descriptor is used to estimate the boundary of the stratospheric polar vortex (SPV). To characterize quasi‐geostrophic motions and their influence on the SPV we apply the wave activity flux (W) and Local Wave Activity . Our data set is the ERA5 reanalysis for the period 1979–2013. Results for κyy show important zonal asymmetries. In the lower and middle stratosphere, κyy is highest at midlatitudes, particularly around the prime meridian. This location is surrounded by manifolds associated with hyperbolic trajectories emanating from the outer SPV boundary. κyy is also high within the SPV, and near the locations where the SPV boundary is open. Zonal asymmetries are also clear in W at midlatitudes. The larger values of are at high latitudes and upstream of the opening of the vortex boundary. The role of quasi‐geostrophic waves on the south‐north shift of the midlatitude westerlies is highlighted. In particular, the waves contribute to open the SPV boundary at around 90W. The interannual variability of κyy is explored by contrasting winters with positive‐negative Northern Annular Mode index, and Sudden Stratospheric Warmings of displacement‐split type.
Present‐Day Three‐Dimensional Crustal Deformation Velocity of the Tibetan Plateau Due to Multi‐Component Land Water Loading
Authors: Jiao Jiashuang , Pan Yuanjin , Ren Ding , Zhang Xiaohong
Published: July 2024

Quantitative understanding of the land water loading is a prerequisite to the construction of reliable tectonic deformation velocity field in the Tibetan Plateau (TP). Here, for the first time, we image the three‐dimensional crustal loading deformation velocity field of each land water component in the TP. Our results reveal that the loading signal strength of the six land water components ranks from largest to smallest as groundwater, glacier, lake, soil water, permafrost, and snow, with the maximum vertical velocity close to ±1.60 mm/yr and the maximum horizontal velocity exceeding 0.40 mm/yr. All land water components can achieve a strong enough vertical loading velocity exceeding the present‐day Global Positioning System (GPS) velocity at some sites. But for horizontal loading, apparent impacts are only from glacier, lake and groundwater, however, are very limited, with the absolute ratio of loading velocity to GPS velocity being smaller than 5% at almost all the sites.
A Statistical Study of the Day‐To‐Day Variability of Diurnal and Semidiurnal Tides in the Ionospheric Dynamo Region From MIGHTI/ICON Observations
Authors: Oberheide J. , Lu X. , Aggarwal D.
Published: July 2024

The statistics of day‐to‐day tidal variability within 35‐day running mean windows is obtained from Michelson Interferometer for Global High‐Resolution Thermospheric Imaging (MIGHTI)/Ionospheric Connection Explorer (ICON) observations in the 90–107 km height region for the year 2020. Temperature standard deviations for 18 diurnal and semidiurnal tidal components, and for four quasi‐stationary planetary waves are presented, as function of latitude, altitude, and day‐of‐year. Our results show that the day‐to‐day variability (DTDV) can be as large as 70% of the monthly mean amplitudes, thus providing a significant source of variability for the ionospheric E‐region dynamo and hence for the F‐region plasma. We further validate our results with COSMIC‐2 ionospheric observations and present an approach to extend the MIGHTI/ICON results to all latitudes using Hough Mode Extension fitting, to produce global tidal fields and their statistical DTDV that are suitable as lower boundary conditions for nudging and ensemble modeling of TIE‐GCM. In the future, this will likely help to establish a data‐driven perspective of space weather variability caused by the tidal weather of the lower atmosphere.
Short‐Term Sea Fog Area Forecast: A New Data Set and Deep Learning Approach
Authors: Chen Keran , Zhou Yuan , Ren Tian , Li Xiaofeng
Published: July 2024

Prompt and precise forecast of sea fog regions ensures maritime navigational safety. This paper establishes a prompt and precise forecast of sea fog regions that ensure maritime navigational safety. This paper establishes a multivariable sea fog forecast (MV‐SFF) data set and proposes a deep learning‐based forecast method named rich‐element aggregated (REA) for short‐term forecasts. The MV‐SFF data set contains 122 sea fog events from 2010 to 2020. Each event in the MV‐SFF data set includes meteorological variables from reanalysis data and geostationary ocean color imager satellite images captured hourly on the day of the sea fog occurrence. This data set aims to comprehensively utilize meteorological elements and remote sensing observations to predict the spatial changes of sea fog areas in the next 7 hours. The proposed REA model can extract and integrate features from historical meteorological elements of different types, times, and spatial locations. In addition, REA utilizes a position‐aware edge detection mechanism to locate the exact position of sea fog. We perform a seven‐hour ahead forecast starting from 09:16 local time and show promising forecasting results, which demonstrate the fog area forecast ability of our model. Compared with existing advanced deep learning networks, the REA model is superior in performance and stability.
The circadian gene ARNTL2 promotes nasopharyngeal carcinoma invasiveness and metastasis through suppressing AMOTL2-LATS-YAP pathway
Authors: Zou Wenqing , Lei Yiming , Ding Cong , Xiao Hongjun , Wang Shunxin , Liang Shaobo , Luo Weijie , Long Zhiqing , He Shiwei , Li Qingjie , Qiao Han , Liu Na , Mao Yanping
Published: July 2024

Metastasis is the major culprit of treatment failure in nasopharyngeal carcinoma (NPC). Aryl hydrocarbon receptor nuclear translocator like 2 (ARNTL2), a core circadian gene, plays a crucial role in the development of various tumors. Nevertheless, the biological role and mechanism of ARNTL2 are not fully elucidated in NPC. In this study, ARNTL2 expression was significantly upregulated in NPC tissues and cells. Overexpression of ARNTL2 facilitated NPC cell migration and invasion abilities, while inhibition of ARNTL2 in similarly treated cells blunted migration and invasion abilities in vitro. Consistently, in vivo xenograft tumor models revealed that ARNTL2 silencing reduced nude mice inguinal lymph node and lung metastases, as well as tumor growth. Mechanistically, ARNTL2 negatively regulated the transcription expression of AMOTL2 by directly binding to the AMOTL2 promoter, thus reducing the recruitment and stabilization of AMOTL2 to LATS1/2 kinases, which strengthened YAP nuclear translocation by suppressing LATS-dependent YAP phosphorylation. Inhibition of AMOTL2 counteracted the effects of ARNTL2 knockdown on NPC cell migration and invasion abilities. These findings suggest that ARNTL2 may be a promising therapeutic target to combat NPC metastasis and further supports the crucial roles of circadian genes in cancer development.
Epithelial cells maintain memory of prior infection with Streptococcus pneumoniae through di-methylation of histone H3
Authors: Chevalier Christine , Chica Claudia , Matheau Justine , Pain Adrien , Connor Michael G. , Hamon Melanie A.
Published: July 2024

Epithelial cells are the first point of contact for bacteria entering the respiratory tract. Streptococcus pneumoniae is an obligate human pathobiont of the nasal mucosa, carried asymptomatically but also the cause of severe pneumoniae. The role of the epithelium in maintaining homeostatic interactions or mounting an inflammatory response to invasive S. pneumoniae is currently poorly understood. However, studies have shown that chromatin modifications, at the histone level, induced by bacterial pathogens interfere with the host transcriptional program and promote infection. Here, we uncover a histone modification induced by S. pneumoniae infection maintained for at least 9 days upon clearance of bacteria with antibiotics. Di-methylation of histone H3 on lysine 4 (H3K4me2) is induced in an active manner by bacterial attachment to host cells. We show that infection establishes a unique epigenetic program affecting the transcriptional response of epithelial cells, rendering them more permissive upon secondary infection. Our results establish H3K4me2 as a unique modification induced by infection, distinct from H3K4me3 or me1, which localizes to enhancer regions genome-wide. Therefore, this study reveals evidence that bacterial infection leaves a memory in epithelial cells after bacterial clearance, in an epigenomic mark, thereby altering cellular responses to subsequent infections and promoting infection.
A chemogenetic approach for dopamine imaging with tunable sensitivity
Authors: Labouesse Marie A. , Wilhelm Maria , Kagiampaki Zacharoula , Yee Andrew G. , Denis Raphaelle , Harada Masaya , Gresch Andrea , Marinescu Alina-Măriuca , Otomo Kanako , Curreli Sebastiano , Serratosa Capdevila Laia , Zhou Xuehan , Cola Reto B. , Ravotto Luca , Glück Chaim , Cherepanov Stanislav , Weber Bruno , Zhou Xin , Katner Jason , Svensson Kjell A. , Fellin Tommaso , Trudeau Louis-Eric , Ford Christopher P. , Sych Yaroslav , Patriarchi Tommaso
Published: July 2024

Genetically-encoded dopamine (DA) sensors enable high-resolution imaging of DA release, but their ability to detect a wide range of extracellular DA levels, especially tonic versus phasic DA release, is limited by their intrinsic affinity. Here we show that a human-selective dopamine receptor positive allosteric modulator (PAM) can be used to boost sensor affinity on-demand. The PAM enhances DA detection sensitivity across experimental preparations (in vitro, ex vivo and in vivo) via one-photon or two-photon imaging. In vivo photometry-based detection of optogenetically-evoked DA release revealed that DETQ administration produces a stable 31 minutes window of potentiation without effects on animal behavior. The use of the PAM revealed region-specific and metabolic state-dependent differences in tonic DA levels and enhanced single-trial detection of behavior-evoked phasic DA release in cortex and striatum. Our chemogenetic strategy can potently and flexibly tune DA imaging sensitivity and reveal multi-modal (tonic/phasic) DA signaling across preparations and imaging approaches.
Enhancing sorption kinetics by oriented and single crystalline array-structured ZSM-5 film on monoliths
Authors: Weng Junfei , Zhu Chunxiang , Zhao Binchao , Tang Wenxiang , Lu Xingxu , Liu Fangyuan , Wu Mudi , Ding Yong , Gao Pu-Xian
Published: July 2024

To enhance the reaction kinetics without sacrificing activity in porous materials, one potential solution is to utilize the anisotropic distribution of pores and channels besides enriching active centers at the reactive surfaces. Herein, by designing a unique distribution of oriented pores and single crystalline array structures in the presence of abundant acid sites as demonstrated in the ZSM-5 nanorod arrays grown on monoliths, both enhanced dynamics and improved capacity are exhibited simultaneously in propene capture at low temperature within a short duration. Meanwhile, the ZSM-5 array also helps mitigate the long-chain HCs and coking formation due to the enhanced diffusion of reactants in and reaction products out of the array structures. Further integrating the ZSM-5 array with Co3O4 nanoarray enables comprehensive propene removal throughout a wider temperature range. The array structured film design could offer energy-efficient solutions to overcome both sorption and reaction kinetic restrictions in various solid porous materials for various energy and chemical transformation applications.
Maternal mRNA deadenylation is defective in in vitro matured mouse and human oocytes
Authors: Liu Yusheng , Tao Wenrong , Wu Shuang , Zhang Yiwei , Nie Hu , Hou Zhenzhen , Zhang Jingye , Yang Zhen , Chen Zi-Jiang , Wang Jiaqiang , Lu Falong , Wu Keliang
Published: July 2024

Oocyte in vitro maturation is a technique in assisted reproductive technology. Thousands of genes show abnormally high expression in in vitro maturated metaphase II (MII) oocytes compared to those matured in vivo in bovines, mice, and humans. The mechanisms underlying this phenomenon are poorly understood. Here, we use poly(A) inclusive RNA isoform sequencing (PAIso-seq) for profiling the transcriptome-wide poly(A) tails in both in vivo and in vitro matured mouse and human oocytes. Our results demonstrate that the observed increase in maternal mRNA abundance is caused by impaired deadenylation in in vitro MII oocytes. Moreover, the cytoplasmic polyadenylation of dormant Btg4 and Cnot7 mRNAs, which encode key components of deadenylation machinery, is impaired in in vitro MII oocytes, contributing to reduced translation of these deadenylase machinery components and subsequently impaired global maternal mRNA deadenylation. Our findings highlight impaired maternal mRNA deadenylation as a distinct molecular defect in in vitro MII oocytes.
Whole-exome sequencing identifies protein-coding variants associated with brain iron in 29,828 individuals
Authors: Gong Weikang , Fu Yan , Wu Bang-Sheng , Du Jingnan , Yang Liu , Zhang Ya-Ru , Chen Shi-Dong , Kang JuJiao , Mao Ying , Dong Qiang , Tan Lan , Feng Jianfeng , Cheng Wei , Yu Jin-Tai
Published: July 2024

Iron plays a fundamental role in multiple brain disorders. However, the genetic underpinnings of brain iron and its implications for these disorders are still lacking. Here, we conduct an exome-wide association analysis of brain iron, measured by quantitative susceptibility mapping technique, across 26 brain regions among 26,789 UK Biobank participants. We find 36 genes linked to brain iron, with 29 not being previously reported, and 16 of them can be replicated in an independent dataset with 3,039 subjects. Many of these genes are involved in iron transport and homeostasis, such as FTH1 and MLX. Several genes, while not previously connected to brain iron, are associated with iron-related brain disorders like Parkinson’s (STAB1, KCNA10), Alzheimer’s (SHANK1), and depression (GFAP). Mendelian randomization analysis reveals six causal relationships from regional brain iron to brain disorders, such as from the hippocampus to depression and from the substantia nigra to Parkinson’s. These insights advance our understanding of the genetic architecture of brain iron and offer potential therapeutic targets for brain disorders.
Experimental demonstration of tunable hybrid improper ferroelectricity in double-perovskite superlattice films
Authors: Jiang Yaoxiang , Niu Jianguo , Wang Cong , Xue Donglai , Shi Xiaohui , Gao Weibo , Zhao Shifeng
Published: July 2024

Hybrid improper ferroelectricity can effectively avoid the intrinsic chemical incompatibility of electronic mechanism for multiferroics. Perovskite superlattices, as theoretically proposed hybrid improper ferroelectrics with simple structure and high technological compatibility, are conducive to device integration and miniaturization, but the experimental realization remains elusive. Here, we report a strain-driven oxygen octahedral distortion strategy for hybrid improper ferroelectricity in La2NiMnO6/La2CoMnO6 double-perovskite superlattices. The epitaxial growth mode with mixed crystalline orientations maintains a large strain transfer distance more than 90 nm in the superlattice films with lattice mismatch less than 1%. Such epitaxial strain permits sustainable long-range modulation of oxygen octahedral rotation and tilting, thereby inducing and regulating hybrid improper ferroelectricity. A robust room-temperature ferroelectricity with remnant polarization of ~ 0.16 μC cm−2 and piezoelectric coefficient of 2.0 pm V−1 is obtained, and the density functional theory calculations and Landau-Ginsburg-Devonshire theory reveal the constitutive correlations between ferroelectricity, octahedral distortions, and strain. This work addresses the gap in experimental studies of hybrid improper ferroelectricity for perovskite superlattices and provides a promising research platform and idea for designing and exploring hybrid improper ferroelectricity.
Identification of unique cell type responses in pancreatic islets to stress
Authors: Maestas Marlie M. , Ishahak Matthew , Augsornworawat Punn , Veronese-Paniagua Daniel A. , Maxwell Kristina G. , Velazco-Cruz Leonardo , Marquez Erica , Sun Jiameng , Shunkarova Mira , Gale Sarah E. , Urano Fumihiko , Millman Jeffrey R.
Published: July 2024

Diabetes involves the death or dysfunction of pancreatic β-cells. Analysis of bulk sequencing from human samples and studies using in vitro and in vivo models suggest that endoplasmic reticulum and inflammatory signaling play an important role in diabetes progression. To better characterize cell type-specific stress response, we perform multiplexed single-cell RNA sequencing to define the transcriptional signature of primary human islet cells exposed to endoplasmic reticulum and inflammatory stress. Through comprehensive pair-wise analysis of stress responses across pancreatic endocrine and exocrine cell types, we define changes in gene expression for each cell type under different diabetes-associated stressors. We find that β-, α-, and ductal cells have the greatest transcriptional response. We utilize stem cell-derived islets to study islet health through the candidate gene CIB1, which was upregulated under stress in primary human islets. Our findings provide insights into cell type-specific responses to diabetes-associated stress and establish a resource to identify targets for diabetes therapeutics.
X chromosome dosage drives statin-induced dysglycemia and mitochondrial dysfunction
Authors: Zhang Peixiang , Munier Joseph J. , Wiese Carrie B. , Vergnes Laurent , Link Jenny C. , Abbasi Fahim , Ronquillo Emilio , Scheker Katherine , Muñoz Antonio , Kuang Yu-Lin , Theusch Elizabeth , Lu Meng , Sanchez Gabriela , Oni-Orisan Akinyemi , Iribarren Carlos , McPhaul Michael J. , Nomura Daniel K. , Knowles Joshua W. , Krauss Ronald M. , Medina Marisa W. , Reue Karen
Published: July 2024

Statin drugs lower blood cholesterol levels for cardiovascular disease prevention. Women are more likely than men to experience adverse statin effects, particularly new-onset diabetes (NOD) and muscle weakness. Here we find that impaired glucose homeostasis and muscle weakness in statin-treated female mice are associated with reduced levels of the omega-3 fatty acid, docosahexaenoic acid (DHA), impaired redox tone, and reduced mitochondrial respiration. Statin adverse effects are prevented in females by administering fish oil as a source of DHA, by reducing dosage of the X chromosome or the Kdm5c gene, which escapes X chromosome inactivation and is normally expressed at higher levels in females than males. As seen in female mice, we find that women experience more severe reductions than men in DHA levels after statin administration, and that DHA levels are inversely correlated with glucose levels. Furthermore, induced pluripotent stem cells from women who developed NOD exhibit impaired mitochondrial function when treated with statin, whereas cells from men do not. These studies identify X chromosome dosage as a genetic risk factor for statin adverse effects and suggest DHA supplementation as a preventive co-therapy.
Epigenetic-based differentiation therapy for Acute Myeloid Leukemia
Authors: San José-Enériz Edurne , Gimenez-Camino Naroa , Rabal Obdulia , Garate Leire , Miranda Estibaliz , Gómez-Echarte Nahia , García Fernando , Charalampopoulou Stella , Sáez Elena , Vilas-Zornoza Amaia , San Martín-Uriz Patxi , Valcárcel Luis V. , Barrena Naroa , Alignani Diego , Tamariz-Amador Luis Esteban , Pérez-Ruiz Ana , Hilscher Sebastian , Schutkowski Mike , Alfonso-Pierola Ana , Martinez-Calle Nicolás , Larrayoz María José , Paiva Bruno , Calasanz María José , Muñoz Javier , Isasa Marta , Martin-Subero José Ignacio , Pineda-Lucena Antonio , Oyarzabal Julen , Agirre Xabier , Prósper Felipe
Published: July 2024

Despite the development of novel therapies for acute myeloid leukemia, outcomes remain poor for most patients, and therapeutic improvements are an urgent unmet need. Although treatment regimens promoting differentiation have succeeded in the treatment of acute promyelocytic leukemia, their role in other acute myeloid leukemia subtypes needs to be explored. Here we identify and characterize two lysine deacetylase inhibitors, CM-444 and CM-1758, exhibiting the capacity to promote myeloid differentiation in all acute myeloid leukemia subtypes at low non-cytotoxic doses, unlike other commercial histone deacetylase inhibitors. Analyzing the acetylome after CM-444 and CM-1758 treatment reveals modulation of non-histone proteins involved in the enhancer–promoter chromatin regulatory complex, including bromodomain proteins. This acetylation is essential for enhancing the expression of key transcription factors directly involved in the differentiation therapy induced by CM-444/CM-1758 in acute myeloid leukemia. In summary, these compounds may represent effective differentiation-based therapeutic agents across acute myeloid leukemia subtypes with a potential mechanism for the treatment of acute myeloid leukemia.
Shifts in attention drive context-dependent subspace encoding in anterior cingulate cortex in mice during decision making
Authors: Hajnal Márton Albert , Tran Duy , Szabó Zsombor , Albert Andrea , Safaryan Karen , Einstein Michael , Vallejo Martelo Mauricio , Polack Pierre-Olivier , Golshani Peyman , Orbán Gergő
Published: July 2024

Attention supports decision making by selecting the features that are relevant for decisions. Selective enhancement of the relevant features and inhibition of distractors has been proposed as potential neural mechanisms driving this selection process. Yet, how attention operates when relevance cannot be directly determined, and the attention signal needs to be internally constructed is less understood. Here we recorded from populations of neurons in the anterior cingulate cortex (ACC) of mice in an attention-shifting task where relevance of stimulus modalities changed across blocks of trials. In contrast with V1 recordings, decoding of the irrelevant modality gradually declined in ACC after an initial transient. Our analytical proof and a recurrent neural network model of the task revealed mutually inhibiting connections that produced context-gated suppression as observed in mice. Using this RNN model we predicted a correlation between contextual modulation of individual neurons and their stimulus drive, which we confirmed in ACC but not in V1.
Environmental circadian disruption re-writes liver circadian proteomes
Authors: Duong Hao A. , Baba Kenkichi , DeBruyne Jason P. , Davidson Alec J. , Ehlen Christopher , Powell Michael , Tosini Gianluca
Published: July 2024

Circadian gene expression is fundamental to the establishment and functions of the circadian clock, a cell-autonomous and evolutionary-conserved timing system. Yet, how it is affected by environmental-circadian disruption (ECD) such as shiftwork and jetlag are ill-defined. Here, we provided a comprehensive and comparative description of male liver circadian gene expression, encompassing transcriptomes, whole-cell proteomes and nuclear proteomes, under normal and after ECD conditions. Under both conditions, post-translation, rather than transcription, is the dominant contributor to circadian functional outputs. After ECD, post-transcriptional and post-translational processes are the major contributors to whole-cell or nuclear circadian proteome, respectively. Furthermore, ECD re-writes the rhythmicity of 64% transcriptome, 98% whole-cell proteome and 95% nuclear proteome. The re-writing, which is associated with changes of circadian regulatory cis-elements, RNA-processing and protein localization, diminishes circadian regulation of fat and carbohydrate metabolism and persists after one week of ECD-recovery.
HiTE: a fast and accurate dynamic boundary adjustment approach for full-length transposable element detection and annotation
Authors: Hu Kang , Ni Peng , Xu Minghua , Zou You , Chang Jianye , Gao Xin , Li Yaohang , Ruan Jue , Hu Bin , Wang Jianxin
Published: July 2024

Recent advancements in genome assembly have greatly improved the prospects for comprehensive annotation of Transposable Elements (TEs). However, existing methods for TE annotation using genome assemblies suffer from limited accuracy and robustness, requiring extensive manual editing. In addition, the currently available gold-standard TE databases are not comprehensive, even for extensively studied species, highlighting the critical need for an automated TE detection method to supplement existing repositories. In this study, we introduce HiTE, a fast and accurate dynamic boundary adjustment approach designed to detect full-length TEs. The experimental results demonstrate that HiTE outperforms RepeatModeler2, the state-of-the-art tool, across various species. Furthermore, HiTE has identified numerous novel transposons with well-defined structures containing protein-coding domains, some of which are directly inserted within crucial genes, leading to direct alterations in gene expression. A Nextflow version of HiTE is also available, with enhanced parallelism, reproducibility, and portability.
Neutrophil extracellular traps-inspired DNA hydrogel for wound hemostatic adjuvant
Authors: Ye Rui , Zhu Ziyu , Gu Tianyi , Cao Dengjie , Jiang Kai , Dai Qiang , Xing Kuoran , Jiang Yifan , Zhou Siyi , Cai Ping , Leong David Tai , Yu Mengfei , Song Jie
Published: July 2024

Severe traumatic bleeding may lead to extremely high mortality rates, and early intervention to stop bleeding plays as a critical role in saving lives. However, rapid hemostasis in deep non-compressible trauma using a highly water-absorbent hydrogel, combined with strong tissue adhesion and bionic procoagulant mechanism, remains a challenge. In this study, a DNA hydrogel (DNAgel) network composed of natural nucleic acids with rapid water absorption, high swelling and instant tissue adhesion is reported, like a band-aid to physically stop bleeding. The excellent swelling behavior and robust mechanical performance, meanwhile, enable the DNAgel band-aid to fill the defect cavity and exert pressure on the bleeding vessels, thereby achieving compression hemostasis for deep tissue bleeding sites. The neutrophil extracellular traps (NETs)-inspired DNAgel network also acts as an artificial DNA scaffold for erythrocytes to adhere and aggregate, and activates platelets, promoting coagulation cascade in a bionic way. The DNAgel achieves lower blood loss than commercial gelatin sponge (GS) in male rat trauma models. In vivo evaluation in a full-thickness skin incision model also demonstrates the ability of DNAgel for promoting wound healing. Overall, the DNAgel band-aid with great hemostatic capacity is a promising candidate for rapid hemostasis and wound healing.
Predictors of reflux persistence after endoscopic dextranomer/hyaluronic Acid copolymer injection in pediatric patients with Vesicoureteral reflux: short-term results
Authors: Yilmaz Ismail Onder , Akdogan Nebil , Deger Mutlu , Aridogan Ibrahim Atilla , Izol Volkan , Satar Nihat
Published: July 2024

This study aims to investigate the factors effective in predicting the persistence of reflux after the first subureteric transurethral injection (STING) of dextranomer/hyaluronic acid copolymer in pediatric patients with vesicoureteral reflux. The data of patients without a previous history of surgery to treat vesicoureteral reflux and who underwent STING for the first time between September 2011 and November 2020 were investigated retrospectively. After considering exclusion criteria, of 199 patients, 127 patients and 180 renal units were suitable for inclusion. A renal unit-based evaluation was made. Age < 61 months (univariate: p = 0.001, multivariate: p = 0.015, HR: 2.352 (1.181–4.686), OR (95% CI)), moderate reflux level (grade 3) (univariate: p < 0.001, multivariate: p = 0.019, HR: 2.703 (1.177–6.209), OR (95% CI)), DRF (differential renal function) < 45 (univariate: p = 0.020, multivariate: p = 0.047, HR: 1.992 (1.009–3.935), OR (95% CI)), and UDR (ureteral diameter ratio) > 0.15 (univariate: p < 0.001, multivariate: p = 0.005, HR: 2.786 (1.368–5.672), OR (95% CI)) were found predictors of reflux persistence after STING surgery both univariate and multivariate analysis. High reflux level (grade 4–5) was statistically significant in univariate analysis (p < 0.001) but not statistically significant in multivariate analysis (p = 0.215). In our study, UDR and DRF were found to be factors affecting reflux persistence. UDR and DRF should be considered in order to predict reflux resolution in patients who will undergo STING.
An automatic deep reinforcement learning bolus calculator for automated insulin delivery systems
Authors: Ahmad Sayyar , Beneyto Aleix , Zhu Taiyu , Contreras Ivan , Georgiou Pantelis , Vehi Josep
Published: July 2024

In hybrid automatic insulin delivery (HAID) systems, meal disturbance is compensated by feedforward control, which requires the announcement of the meal by the patient with type 1 diabetes (DM1) to achieve the desired glycemic control performance. The calculation of insulin bolus in the HAID system is based on the amount of carbohydrates (CHO) in the meal and patient-specific parameters, i.e. carbohydrate-to-insulin ratio (CR) and insulin sensitivity-related correction factor (CF). The estimation of CHO in a meal is prone to errors and is burdensome for patients. This study proposes a fully automatic insulin delivery (FAID) system that eliminates patient intervention by compensating for unannounced meals. This study exploits the deep reinforcement learning (DRL) algorithm to calculate insulin bolus for unannounced meals without utilizing the information on CHO content. The DRL bolus calculator is integrated with a closed-loop controller and a meal detector (both previously developed by our group) to implement the FAID system. An adult cohort of 68 virtual patients based on the modified UVa/Padova simulator was used for in-silico trials. The percentage of the overall duration spent in the target range of 70–180 mg/dL was $$71.2\%$$

71.2
%

and $$76.2\%$$

76.2
%

, $$<70$$

<
70

mg/dL was $$0.9\%$$

0.9
%

and $$0.1\%$$

0.1
%

, and $$>180$$

>
180

mg/dL was $$26.7\%$$

26.7
%

and $$21.1\%$$

21.1
%

, respectively, for the FAID system and HAID system utilizing a standard bolus calculator (SBC) including CHO misestimation. The proposed algorithm can be exploited to realize FAID systems in the future.
The effect of pollen monodiets on fat body morphology parameters and energy substrate levels in the fat body and hemolymph of Apis mellifera L. workers
Authors: Bryś Maciej Sylwester , Staniec Bernard , Strachecka Aneta
Published: July 2024

Human activities associated with large-scale farms and the monocultures expose honey bees to one type of food. Moreover, there is an ongoing decline of plant species producing pollen and nectar in Europe. A poorly balanced diet affects a number of processes occurring in a bee’s body. The fat body and hemolymph are the tissues that participate in all of them. Therefore, the aim of our study was to determine the effect of hazel, pine, rapeseed, buckwheat, phacelia and goldenrod pollen on the morphological parameters of fat body trophocytes, the diameters of cell nuclei in oenocytes and the concentrations of compounds involved in energy metabolism (glucose, glycogen, triglycerides and protein). In the cage tests, the bees were fed from the first day of life with sugar candy (control group) or candy with a 10% addition of one of the 6 pollen types. Hemolymph and fat body from various locations were collected from 1-, 7- and 14-day-old workers. Pollen produced by plant species such as hazel and pine increased glucose concentrations in the bee tissues, especially in the hemolymph. It can therefore be concluded that they are valuable sources of energy (in the form of simple carbohydrates) which are quickly used by bees. Pollen from plants blooming in the summer and autumn increased the concentrations of proteins, glycogen and triglycerides in the fat body, especially that from the third tergite. The accumulation of these compounds was associated with an increased the length and width of trophocytes as well as with enhanced metabolic activity, which was evidenced in the increasing diameter of oenocyte cell nuclei. It seems a balanced multi-pollen diet is more valuable for bees, but it is important to understand the effects of the particular pollen types in the context of a mono-diet. In the future, this will make it possible to produce mixtures that can ensure homeostasis in the apian body.