bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evidence for Poleward Migration of the Asian Monsoon During the Paleocene‐Eocene Thermal Maximum
Authors: Teng Xiaohua , Wang Chunlian , Zhang Jingyu , Yan Kai , Yu Xiaocan , Zhang Dawen , Sluijs Appy 
Published: February 2025

AbstractThe Paleocene‐Eocene Thermal Maximum (PETM, ∼56 Ma), was a transient episode of global warming, and caused profound changes in biology and climate. The evolution of the hydroclimate during the PETM in East Asia, which currently is influenced by the Asian Monsoon and hosts ∼20% of the world's population, is crucial to understand the future monsoon and climate changes. However, PETM records in Asia are relatively rare and it remains poorly understood how the hydroclimate responded to climate forcing under extreme atmosphere pCO2. Here we present stable carbon isotope records of bulk carbonate and total organic carbon (δ13Ccarb and δ13CTOC) from lacustrine deposits in the Jianghan Basin, Central China that both record the global carbon isotope excursion (CIE) that marks the PETM. The magnitude of both the CIEs in δ13Ccarb and δ13CTOC are larger than that presumed in the global exogenic carbon pool, as is common for terrestrial and marginal marine records. The particularly large amplitude (∼11.4‰) and unique shape of CIE in δ13Ccarb, which represents authigenic lacustrine carbonates and therefore lake dissolved inorganic carbon δ13C values. Although our evidence against diagenesis is not fully conclusive, this signal implies the local addition of 13C‐depleted carbon in excess of the global input. We consider increased transport rates of organic matter‐derived carbon from the catchment to the lake the most likely source. Combined with the disappearance of evaporitic deposits during the PETM, we attribute this to an increase in precipitation and erosion, possibly linked to a northward extension of the Asian summer monsoon.
Declining Groundwater Storage in the Indus Basin Revealed Using GRACE and GRACE‐FO Data
Authors: Dharpure Jaydeo K. , Howat Ian M. , Kaushik Saurabh 
Published: February 2025

AbstractSnow and glacier melt provide freshwater to millions of people in the Indus basin. However, the unprecedented increase in demand for freshwater and depleting resources due to climate warming has put the region's water resources at risk. Therefore, quantifying water mass variation and anticipating changes in hydrological regimes that affect downstream freshwater supply are of utmost importance. To address this, we used Gravity Recovery and Climate Experiment (GRACE) and GRACE Follow‐On derived terrestrial water storage anomaly (TWSA) data from April 2002 to May 2023 over the Indus basin. Several gaps in these data, totaling 33 months, significantly impact regional trends and predictions of water mass changes. We apply a machine learning‐based MissForest algorithm to fill these gaps and compare our results with four previous studies. Annual TWSA shows a declining trend (−0.65 cm/yr) before 2015/16, with a significantly higher (−2.16 cm/yr) after 2015/16. Based on the estimate for the annual groundwater storage anomaly (GWSA), a major portion (83.7%) of the basin is experiencing a significant declining trend (>−0.15 cm/yr, p < 0.05). Glaciated region has a less severe decreasing trend (−0.78 cm/yr) compared to the non‐glaciated region (−1.44 cm/yr). Among sub‐basins, the upper Indus shows the lowest decline (−0.42 cm/yr), while Panjnad exhibits the highest (−1.70 cm/yr). Annual precipitation and runoff are decreasing, while temperature shows no trend. However, evapotranspiration is increasing might be due to a significant increase in vegetation (0.23%/yr) over the basin. The trends of hydroclimatic variables, vegetation, and anthropogenic factors, indicate a consistently decreasing GWSA in the region.
Community-oriented, hospital level genetics: a new approach to improve access for underserved communities
Authors: Gofin Yoel , Tibi Fadel , Fanous Eliana , Ben-Shachar Shay , Sukenik-Halevy Rivka 
Published: February 2025

Abstract

Background
Certain populations are at increased risk for genetic syndromes but have limited access to genetic testing.

Methods
We founded a community-based, pediatric genetics clinic in the Muslim-Arab city of Tayibe, Israel. Children with suspected genetic conditions of consanguineous parents, or families with two or more affected siblings were referred by local staff. The clinic was staffed by a Meir Medical Center (MMC) clinical geneticist. Blood samples were collected during the initial visit. Tests were publicly funded, with no parental involvement in administrative procedures required. A control group consisted of MMC pediatric genetics clinic patients.

Results
During the first year, 30 children were assessed. No patients were lost to follow-up, compared to 8 (28%) in the MMC control group. The average time to test results was shorter in the Tayibe group and the diagnostic rate was higher, with 27.6% receiving a diagnosis (42.9%, excluding autism cases).

Conclusion
Our first-year experience shows the success and promising results of this model, with advantages in almost all parameters, compared to the traditional, hospital-based clinic. Factors such as faster time-to-results, greater family adherence and satisfaction, and zero lost to follow-up rate suggest considering implementing this model for providing genetic services to other underserved populations.

Impact

A community-oriented approach for a pediatric genetics clinic allowed reaching high-risk populations, with increased adherence, faster results and a higher yield.

Our clinic relied solely on available public funding and staff, requiring no additional contributions.

The current dogma of hospital-based genetics services should be reconsidered.
Nitric oxide inhibits ten-eleven translocation DNA demethylases to regulate 5mC and 5hmC across the genome
Authors: Palczewski Marianne B. , Kuschman Hannah Petraitis , Hoffman Brian M. , Kathiresan Venkatesan , Yang Hao , Glynn Sharon A. , Wilson David L. , Kool Eric T. , Montfort William R. , Chang Jenny , Petenkaya Aydolun , Chronis Constantinos , Cundari Thomas R. , Sappa Sushma , Islam Kabirul , McVicar Daniel W. , Fan Yu , Chen Qingrong , Meerzaman Daoud , Sierk Michael , Thomas Douglas D. 
Published: February 2025

Abstract
DNA methylation at cytosine bases (5-methylcytosine, 5mC) is a heritable epigenetic mark regulating gene expression. While enzymes that metabolize 5mC are well-characterized, endogenous signaling molecules that regulate DNA methylation machinery have not been described. We report that physiological nitric oxide (NO) concentrations reversibly inhibit the DNA demethylases TET and ALKBH2 by binding to the mononuclear non-heme iron atom forming a dinitrosyliron complex (DNIC) and preventing cosubstrates from binding. In cancer cells treated with exogenous NO, or endogenously synthesizing NO, 5mC and 5-hydroxymethylcytosine (5hmC) increase, with no changes in DNA methyltransferase activity. 5mC is also significantly increased in NO-producing patient-derived xenograft tumors from mice. Genome-wide methylome analysis of cells chronically treated with NO (10 days) shows enrichment of 5mC and 5hmC at gene-regulatory loci, correlating with altered expression of NO-regulated tumor-associated genes. Regulation of DNA methylation is distinctly different from canonical NO signaling and represents a unique epigenetic role for NO.
Single-molecule live-cell RNA imaging with CRISPR–Csm
Authors: Xia Chenglong , Colognori David , Jiang Xueyang Stephen , Xu Ke , Doudna Jennifer A. 
Published: February 2025

Abstract
Understanding the diverse dynamic behaviors of individual RNA molecules in single cells requires visualizing them at high resolution in real time. However, single-molecule live-cell imaging of unmodified endogenous RNA has not yet been achieved in a generalizable manner. Here, we present single-molecule live-cell fluorescence in situ hybridization (smLiveFISH), a robust approach that combines the programmable RNA-guided, RNA-targeting CRISPR–Csm complex with multiplexed guide RNAs for direct and efficient visualization of single RNA molecules in a range of cell types, including primary cells. Using smLiveFISH, we track individual native NOTCH2 and MAP1B transcripts in living cells and identify two distinct localization mechanisms including the cotranslational translocation of NOTCH2 mRNA at the endoplasmic reticulum and directional transport of MAP1B mRNA toward the cell periphery. This method has the potential to unlock principles governing the spatiotemporal organization of native transcripts in health and disease.
Stress management with HRV following AI, semantic ontology, genetic algorithm and tree explainer
Authors: Chatterjee Ayan , Riegler Michael A. , Ganesh K. , Halvorsen Pål 
Published: February 2025

Abstract
Heart Rate Variability (HRV) serves as a vital marker of stress levels, with lower HRV indicating higher stress. It measures the variation in the time between heartbeats and offers insights into health. Artificial intelligence (AI) research aims to use HRV data for accurate stress level classification, aiding early detection and well-being approaches. This study’s objective is to create a semantic model of HRV features in a knowledge graph and develop an accurate, reliable, explainable, and ethical AI model for predictive HRV analysis. The SWELL-KW dataset, containing labeled HRV data for stress conditions, is examined. Various techniques like feature selection and dimensionality reduction are explored to improve classification accuracy while minimizing bias. Different machine learning (ML) algorithms, including traditional and ensemble methods, are employed for analyzing both imbalanced and balanced HRV datasets. To address imbalances, various data formats and oversampling techniques such as SMOTE and ADASYN are experimented with. Additionally, a Tree-Explainer, specifically SHAP, is used to interpret and explain the models’ classifications. The combination of genetic algorithm-based feature selection and classification using a Random Forest Classifier yields effective results for both imbalanced and balanced datasets, especially in analyzing non-linear HRV features. These optimized features play a crucial role in developing a stress management system within a Semantic framework. Introducing domain ontology enhances data representation and knowledge acquisition. The consistency and reliability of the Ontology model are assessed using Hermit reasoners, with reasoning time as a performance measure. HRV serves as a significant indicator of stress, offering insights into its correlation with mental well-being. While HRV is non-invasive, its interpretation must integrate other stress assessments for a holistic understanding of an individual’s stress response. Monitoring HRV can help evaluate stress management strategies and interventions, aiding individuals in maintaining well-being.
Object detection algorithm based on improved YOLOv8 for drill pipe on coal mines
Authors: Li Xiaojun , Li Miao , Zhao Mingyang 
Published: February 2025

Abstract
Gas extraction is an important measure for coal mine gas disaster control. Its effect is closely correlated to the drilling depth. The existing methods usually determine the drilling depth by manually counting the number of drill pipes, and the number of drill pipes can be automatically counted by object detection and real-time tracking algorithms. An improved object detection model was proposed for the problem of the poor performance of the object detection algorithm due to such interference factors as bright light, low illuminance and heavy dust and mist in coal mines. In terms of data augmentation, the ACE dehazing algorithm is introduced to improve image quality. In order to solve the problem of leak detection caused by the irregular shape that appears due to the interference of bright light, the deformable convolution DCNv2 module was integrated in the C2f module to make the sampling points of the convolution kernel diffuse irregularly, so as to fully extract the shape features of the drill pipe and then improve the detection rate of the model. For the problem of too low confidence of the model in detecting drill pipes due to uneven illumination, the attention paid by the model to the features of the drill pipe could be improved by embedding the SimAM non-parametric attention mechanism module in the backbone network, which can further improve the confidence of the drill pipe. For the problem of low average category detection accuracy caused by the changeable environment of the underground drilling site, the dynamic head was used to improve the ability of the model to extract the features of the drill pipe in scale, space, and channel, and improve the average category detection accuracy of the drill pipe. To address the issue of diverse angle differences between predicted and real boxes, CIoU loss function is replaced with the SIoU loss function. Finally, the improved detection algorithm was verified with the homemade drill pipe dataset. The experimental results showed that: the improved model effectively alleviated the problem of partial leak detection of the original network for scenes such as heavy dust and mist and uneven illumination; the recall rate increased by 4.9%; the mean average precision was improved by 5.3%. At the same time, it maintains a high real-time performance (the FPS is 117), providing the basis of the drill pipe detection model for the application of real-time tracking of the number of drill pipes.
Scalable intracellular delivery via microfluidic vortex shedding enhances the function of chimeric antigen receptor T-cells
Authors: Sytsma Brandon J. , Allain Vincent , Bourke Struan , Faizee Fairuz , Fathi Mohsen , Ferreira Leonardo M. R. , Brewer W. Jared , Li Lian , Pan Fong L. , Rothrock Allison G. , Nyberg William A. , Li Zhongmei , Wilson Leah H. , Berdeaux Rebecca , Eyquem Justin , Pawell Ryan S. 
Published: February 2025

Abstract
Adoptive chimeric antigen receptor T-cell (CAR-T) therapy is transformative and approved for hematologic malignancies. It is also being developed for the treatment of solid tumors, autoimmune disorders, heart disease, and aging. Despite unprecedented clinical outcomes, CAR-T and other engineered cell therapies face a variety of manufacturing and safety challenges. Traditional methods, such as lentivirus transduction and electroporation, result in random integration or cause significant cellular damage, which can limit the safety and efficacy of engineered cell therapies. We present hydroporation as a gentle and effective alternative for intracellular delivery. Hydroporation resulted in 1.7- to 2-fold higher CAR-T yields compared to electroporation with superior cell viability and recovery. Hydroporated cells exhibited rapid proliferation, robust target cell lysis, and increased pro-inflammatory and regulatory cytokine secretion in addition to improved CAR-T yield by day 5 post-transfection. We demonstrate that scaled-up hydroporation can process 5 × 108 cells in less than 10 s, showcasing the platform as a viable solution for high-yield CAR-T manufacturing with the potential for improved therapeutic outcomes.
Discovery of rhynchophylline and mitraphylline in two Thai Mitragyna species and the investigation of their biological activity via opioid gene expression analysis
Authors: Sudmoon Runglawan , Tanee Tawatchai , Wonok Warin , Ameamsri Unchaleeporn , Liehr Thomas , Daduang Sakda , Siripiyasing Pornnarong , Chaveerach Arunrat 
Published: February 2025

Abstract

Mitragyna speciosa (Ms), M. diversifolia (Md), M. hirsuta (Mh) and M. rotundifolia (Mr) were investigated for phytochemicals by GC-MS and GC-FID, cytotoxicity and genotoxicity testing by MTT and comet assay, and biological activity examination through gene expression of human µ, δ, κ, and nociceptin opioid receptors by qRT-PCR. The opioid substances mitragynine, 7-hydroxymitragynine, and mitraphylline were found in all studied species, and, for first time, rhynchophylline was found in Mr, and mitraphylline in Md, Mh and Mr. The MTT and comet assays of the ethanol and hexane leaf extracts on PBMCs revealed no cytotoxicity and no significant genotoxicity compared to the negative control, except for the hexane leaf extract of Mh, which caused significant DNA damage. The biological activity of the ethanolic extract of the four species showed a binding affinity to the µ (MOR) receptor revealing a relative gene expression of 89.54 and 50.41 by Ms and Md at 1.92 and 1.133 mg/ml, 32.42 and 19.97 mg/ml by Md and Ms at 3.77 and 1.76 mg/ml. Mr contained the three opioids mentioned plus rhynchophylline and showed low relative µ (MOR) gene expression of 16.89 at 0.189 mg/ml, while as an additional species, Ipomoea aquatica (Ia) showed higher relative µ (MOR) gene expression of 37.75 and 59.76 at 2.878, and 5.813 mg/ml. A combination of Mr and Ia at 1.227, 2.907 and 0.0123, 0.0291 mg/ml extract showed high relative µ (MOR) gene expression at 71.01 and 21.71. These Mitragyna species and the combination (formula details are patent registered), substances and their biological activities can be used for the innovative production of new medicines and further clinical investigation.
Sex-specific asymmetry in lumbar paraspinal muscles among chronic low back pain patients: correlation with pain duration and intensity
Authors: Liu Sihai , Becker Luis , Hoehl Bernhard , Reitmaier Sandra , Mödl Lukas , Yang Daishui , Zhang Tianwei , Pumberger Matthias , Schmidt Hendrik 
Published: February 2025

Abstract
Chronic low back pain (cLBP) is a multifactorial condition, including paraspinal muscle asymmetry. Understanding the relationship between muscle asymmetry and cLBP and how this varies by sex is crucial for targeted interventions. From January 2022 to December 2023, 250 participants were enrolled: 117 without back pain (no-BP) (61 females, 56 males) and 133 with cLBP (69 females, 64 males). MRI assessed the cross-sectional area (CSA), functional CSA (FCSA), and fat infiltration (FI) of the paraspinal muscles, including the psoas major (PM), quadratus lumborum (QL), erector spinae (ES), and multifidus (MF), at all lumbar levels. Asymmetry indices were calculated for CSA (CAI), FCSA (FCAI), and FI (FIAI). Data were analyzed using multiple linear and logistic regression. Muscle asymmetries were observed in both sexes and groups, with significant differences in the CSA and FCSA of the QL in males and notable FI asymmetries in the cLBP group. In women with cLBP, higher ES CAI and FCAI at L5/S1 (p < 0.05) and lower PM FCAI at L4/5 (OR 0.869, 95% CI 1.008–1.150, p = 0.03) were observed. FIAI was significantly higher in cLBP for ES at L2/3 and PM, MF, and ES at L4/5 (p < 0.05). Men with cLBP had lower PM CAI and FCAI at L1/2 and L4/5 (p < 0.05), with varying FIAI levels. FIAI correlated with cLBP duration and intensity in both sexes (p < 0.05). Paraspinal muscle asymmetry, particularly in fat infiltration, is associated with cLBP and varies by sex. These findings support sex-specific approaches to managing cLBP.
A robust strategy for overexpression of DNA polymerase from Thermus aquaticus using an IPTG-independent autoinduction system in a benchtop bioreactor
Authors: Laksmi Fina Amreta , Lischer Kenny , Nugraha Yudhi , Violando Wiga Alif , Helbert  , Nuryana Isa , Khasna Firyal Nida , Nur Naswandi , Ramadhan Kharisma Panji , Tobing Destrianti Adelina Lumban , Hariyatun  , Hidayat Iman 
Published: February 2025

Abstract
The DNA polymerase derived from Thermus aquaticus is the most widely utilized among various DNA polymerases, indicating its significant economic importance. Consequently, efforts to achieve a substantial yield of Taq DNA polymerase (Taq-pol) are ongoing. The expression of recombinant protein using T7-induced promoters presents challenges in cost-effectiveness, primarily due to the reliance on traditional induction method. Our study aims to enhance cost-efficiency, and scalability of our method for overproducing Taq-pol, particularly in comparison to traditional IPTG-induced techniques, which remain underreported in the current literature. To achieve those purposes, this work integrated the use of (1) a high copy number vector; (2) an optimized chemically defined medium; and (3) optimized fermentation conditions in a 5 L bioreactor. A total of 83.5 mg/L of pure Taq-pol was successfully synthesized in its active form, leading to a 9.7-fold enhancement in protein yield. This was achieved by incorporating glucose, glycerol, and lactose into a defined medium at concentrations of 0.1, 0.6, and 1%, respectively, under specific production conditions in a 5 L bioreactor: 300 rpm, 2 vvm, and 10% inoculant. The data collectively suggest that the strategy serves as a significant foundation for the future advancement of large-scale production of Taq-pol.
A taguchi neural network–based optimization of a dual-port, dual-band MIMO antenna encompassing the 28/34 GHz millimeter wave regime
Authors: Dwivedi Ajay Kumar , Singh Vivek , Alzahrani Yazeed , Chaitanya R Krishna , Singh Suyash Kumar , Singh Subhav , Parashar Komal , Tolani Manoj 
Published: February 2025

Abstract
This study presents a novel printed antenna design that operates at the millimeter-wave frequencies of 28 and 34 GHz, which are crucial for the current and upcoming mobile communication generations. The radiating component in the antenna is a slot-etched rectangular ring that is fed through a stepped impedance microstrip line feed. Using advanced machine learning techniques, the design parameters of the suggested antenna have been fine-tuned to ensure optimal impedance matching at 28 GHz within the frequency range of 27.61–28.49 GHz. Additionally, the antenna also provides excellent impedance matching at 34.5 GHz within the frequency range of 33.61–34.27 GHz. Using the designated antenna, a Multiple Input Multiple Output (MIMO) system with two ports is constructed. The MIMO system’s performance is evaluated by analyzing channel capacity loss (CCL), diversity gain (DG), and envelope correlation coefficient (ECC), which showcases outstanding outcomes. The study further explores the optimization of a antenna’s structure using a Taguchi-based Neural Network (Taguchi NN) approach to predict the reflection coefficient (|S11|) across a frequency range of 27–35 GHz. By systematically varying the gap width (∆w) and shift (∆t), a dataset was generated and used to train the network. The optimal model configuration achieved a validation Mean Square Error (MSE) of 2.244 and an R² of 0.848 enabling reliable prediction of the reflection coefficient (|S11|) without extensive simulations. The findings further highlight the construction and experimental assessment of a single-element antenna and MIMO system, which exhibit excellent impedance matching across both lower and higher frequency bands. The antenna displays a maximum gain of 8.75 and 5.5 dBi at frequencies of 28 and 34 GHz, respectively. The recommended antenna exhibits excellent radiation efficiency across both lower and higher frequency bands, with rates of 98.46% and 99.17%, respectively. In addition, the experimental measurements of the coupling coefficients between the MIMO antenna systems indicate extremely low coupling values. This results in an efficient MIMO system that is well-suited for future millimeter-wave (mm-wave) applications.