bluuebunny/crossref_metadata_2025 huggingface dataset:
Problem Recognition as A Discrete Concept for Change Processes in Problematic Alcohol Use
Authors: Morris J. , Richards D. K. , Albery I. P
Published: February 2025

Purpose of review

Alcohol problem recognition reflects the extent to which a person with any level of problematic alcohol use (PAU), including hazardous alcohol use, acknowledges the associated risks/harms as potentially/actually problematic with a relative degree of objectivity. Notably, alcohol problem recognition is typically low amongst people with PAU not engaged in treatment or support. This review evaluates existing PAU problem recognition measures and related concepts such as ambivalence, readiness to change, motivation, cognitive biases and other self-evaluative appraisal processes.

Recent findings

Alcohol problem recognition has been operationalised via various measures but is often conflated with other related but theoretically distinct concepts. Limited conceptual work examines the nature of problem recognition as a discrete concept and its function in relation to behaviour change outcomes and key variables.

Problem recognition is proposed as an important theoretically distinct process that warrants further conceptual development and testing for advancing understanding of change processes across the PAU spectrum.
For a Unified Stakeholder Management Science: How Computational Ontologies Can Mend a Broken Theory
Authors: Agafonow Alejandro , Neesham Cristina , Perez Marybel
Published: February 2025

This research explores how stakeholder scholarship can evolve into a puzzle-solving tool, akin to more advanced scientific fields. Only a unified stakeholder management science can address issues like firms that, despite the looming threat of climate disaster, prioritize profits over environmental concerns. Such unification, however, depends on a computational turn of mind outlined herein. Stakeholder scholarship has failed to progress toward this end, because stakeholder theory has fallen short of shedding light on the inner workings of the firm in search of the mechanisms that govern its relations with stakeholders, instead lingering over the outermost parts of the social phenomena where stakeholder macro dynamics are obvious. This lays open several hurdles that must be overcome for stakeholder scholarship to become a puzzle-solving tool at the service of the environment and society. Thus, a computational fix may be within reach in the next few decades if the following five steps, elaborated upon herein, guide the transition: 1) probe firm-level mechanisms, 2) focus on qualitative institutional data, 3) adopt computational language to reduce ambiguities, 4) develop algorithms for how activities discharge powers or capacities to fulfill functions, and 5) break with peer-review silos that have made stakeholder theory self-referential.
Light-Weight Design of Aerospace Components Using Genetic Algorithm and Dandelion Optimization Algorithm
Authors: Akçay Özlem , İlkılıç Cumali
Published: February 2025

In recent years, weight reduction studies using optimization methods have been increasing, and they are widely used in sectors such as aerospace, automotive, and marine. While there are many research studies on weight reduction using these methods, weight reduction efforts in aircraft landing gear systems are inadequate. Therefore, to address this deficiency, in this study, it is proposed to design a lighter component of the aircraft’s nose landing gear fork part that can withstand the same loading conditions with minimum material using optimization techniques. Genetic algorithm and dandelion optimization algorithm, which are algorithms created with a meta-heuristic approach, were used to obtain the optimum size in shape optimization. According to the results obtained, the initial mass of the nose landing gear fork was 14.25 kg, which decreased to 12.99 kg after topology optimization, resulting in approximately an 8.84% weight reduction. The part is 11.79% lighter compared to the initial model after shape optimization using genetic algorithm. With the dandelion optimization algorithm, a mass gain of 1.77 kg resulted in a 12.42% weight reduction, obtaining optimal dimensions. One of the aims of this study is to demonstrate the effectiveness of metaheuristic algorithms on optimal product development. This study is the first to perform weight reduction using artificial intelligence optimization algorithms in landing gear system components.
Spacecraft Trajectory Optimisation Using Differential Dynamic Programming
Authors: Mondino Pietro , Saladino Vincenzo
Published: February 2025

Spacecraft trajectory optimisation represents a pillar for space mission development, as it allows the design of more cost-effective and high-performance operational concepts. In this context, the Mars exploration race, best epitomised by the Mars Sample Return mission (MSR), has highlighted the need to optimise not only the Keplerian phase trajectory, but also the proximity dynamics and the atmosphere environment one. In this paper, the Differential Dynamic Programming (DDP) optimisation algorithm is initially introduced as a proven second-order technique that relies on Bellman’s Principle of Optimality and successive minimisation of quadratic approximations. Then, a collection of modified DDP methods is presented for the purpose of enhancing the classic DDP weaknesses. Subsequently, a constrained DDP algorithm is implemented and applied to two case studies: a deep-space rendez-vous and a martian soil landing manoeuvre. The choice is to test the algorithm in different environments, showing the influence of gravity and atmosphere on the convergence properties. For both problems, a parametric and a convergence analysis is carried out to identify the best input parameters and the resulting trajectory optimisation process is displayed. Satisfactory results are achieved, proving the validity of the algorithm: order of few centimetres for position and some decimetres per second for velocity errors are reached. Furthermore, its adaptability allows to satisfy diverse requirements depending on the type of manoeuvre performed, extending its application field. Finally, some algorithm’s features are pointed out, investigating the influence of regularisation parameters and time of flight on the convergence process.
Multigoal-oriented dual-weighted-residual error estimation using PINNs
Authors: Chakraborty Ayan , Wick Thomas , Rabczuk Timon , Zhuang Xiaoying
Published: February 2025

Deep learning has shown successful application in visual recognition and certain artificial intelligence tasks. It is mainly considered as a powerful tool with high flexibility to approximate functions. This paper proposes a generalized NURBS based approach to solve nonlinear partial differential equations (PDEs) on arbitrary complex-geometry domains by using physics-informed neural networks (PINNs). Our approach is based on a posteriori error estimation in which the adjoint problem is solved for the error localization to formulate an error estimator within the framework of neural network. An efficient and easy to implement algorithm is developed to obtain a posteriori error estimate for multiple goal functionals by employing the dual-weighted residual approach, which is followed by the computation of both primal and adjoint solutions using the neural network. The present study shows that such a data-driven model based learning has superior approximation of quantities of interest even with relatively less training data. Moreover, we illustrate the versatility of activation functions in achieving better learning capabilities and improving convergence rates, especially at the early training stage, and also in increasing solutions accuracies. The novel algorithmic developments are substantiated with several numerical test examples. It has been demonstrated that deep neural networks have distinct advantages over shallow neural networks, and the techniques for enhancing convergence have also been reviewed.
Acute Iatrogenic Distal Aortic Pseudoaneurysm Caused by Metallic Arm of Displaced Vena Cava Filter—Case Report and Review of the Literature
Authors: Slyško Roman , Vulev Ivan , Smoter Šimon
Published: February 2025

Objectives

We report a case of an 82-year-old female patient admitted with severe abdominal and lumbar pain. She had a history of deep vein thrombosis in the lower extremities, complicated by pulmonary embolism, which led to the placement of a vena cava filter. This manuscript provides also a current literature review.

Methods

CT scans revealed chronic collateralized thrombosis and shrinkage of the inferior vena cava, along with the extramural displacement of the filter's metallic arms. One arm penetrated the ventral wall of the abdominal aorta, causing a pseudoaneurysm (PSA). We describe the successful treatment of the PSA with percutaneous endovascular aneurysm repair (PEVAR) and the ongoing extraction of the cava filter, evacuation of the PSA hematoma, lavage, and drainage performed via an extraperitoneal approach due to persistent inflammatory signs.

Results

The patient remained clinically well during subsequent follow-ups.

Conclusion

(P)EVAR is a safe and justified procedure when the abdominal wall is penetrated due to a displaced cava filter. If there is concomitant penetration of the intestinal wall, open surgery is required, either alone or following endovascular treatment. The authors consider it important to note that, to date, no guidelines have been revealed to objectively recommend a specific approach in patients with caval filter penetration. For this reason, we consider a multidisciplinary approach essential as the mainstay of treatment.
Pragmatism and Historical Representation
Authors: Grigoriev Serge
Published: February 2025

No prominent pragmatist philosopher to date has offered us a fully developed theory of history or historical interpretation. Nevertheless, a number of pivotal arguments and suggestions made by the pragmatists appeared to many both insightful and pertinent enough to offer a distinctive promise of a cohesive and distinctive general pragmatist perspective in historical theory. The present contribution is intended to secure some advances in this direction, focusing on the relationships between objectivity and perspective; between representation as an accurate correspondence to reality and the social, cultural sense of representation as being represented and being representative; as well as the relationship between individualizing comprehension and generalizing abstraction in historical contexts.
Lexical Multidimensional Analysis
Authors: Sardinha Tony Berber , Fitzsimmons-Doolan Shannon
Published: February 2025

Lexical Multidimensional Analysis (LMDA), an extension of Biber's (1988) Multidimensional Analysis, seeks to identify dimensions (correlated lexical features across texts in a corpus) unveiling underlying patterns of lexical co-occurrence and variation within texts that are operationalized as a variety of latent, macro-level discursive constructs. Initially developed in the 2010s, LMDA has been applied to diverse domains, including education policy, national representations, applied linguistics, music, the infodemic, religion, sustainability, and literary style. This Element introduces LMDA for the identification and analysis of discourses and ideologies, offering insights into how lexis marks discourse formations and ideological alignments. Two case studies demonstrate the application of LMDA: uncovering discourses on climate change within conservative social media and analyzing ideological discourses in migrant education.
Breaking-up and breaking the norm: Intergenerational divorce transmission among two ethnolinguistic groups
Authors: Uggla Caroline , Saarela Jan
Published: February 2025

Individuals who experience divorce in childhood are more likely to divorce themselves as adults. Notably, the magnitude of the intergenerational divorce transmission is stronger for groups among whom divorce is rare. This transmission may reflect differences in mating strategies passed from parent to child, or differences in cultural norms between groups. Sociologists and demographers have struggled to disentangle socioeconomic and cultural factors, because groups that are less wealthy also tend to have higher divorce rates. We use data from Finland, where two native ethnolinguistic groups with comparable socioeconomic characteristics - but different divorce risks - live side by side; Swedish speakers and Finnish speakers. Using register data on the entire Finnish population (N=554,337 couples 1987-2020), we examine separation risk as a function of parental divorce. Data suggest that the intergenerational transmission is greater among Swedish speakers, who have an overall lower separation rate. Group differences in separation risk persist even after controlling for socioeconomic factors and each partner’s experience of parental divorce. Notably, Finnish-speaking couples who reside in Swedish-dominated areas have both somewhat lower separation risk, and higher intergenerational transmission than their peers in Finnish-dominated areas. These results point to a cultural transmission of separation, beyond strong socioeconomic factors.
The Modifiable Areal Unit Problem in Political Science
Authors: Lee Dong Wook , Rogers Melissa , Soifer Hillel David
Published: February 2025

Building on the availability of geospatial data, improvements in mapping software, and innovations in spatial statistics, political scientists are increasingly taking geography seriously. As we adopt the tools of geographers, we must also consider the methodological challenges they have identified. We focus on the modifiable areal unit problem (MAUP)—the idea that the size of aggregate spatial units and the location of their borders affect the empirical results we obtain. We first describe the logic of the MAUP, and then demonstrate the MAUP through simulations, showing MAUP-related inconsistency in regression results in randomly generated and real-world data. We identify MAUP concerns, and best practices, in top journals in political science. We conclude by suggesting how scholars may respond in theoretical and empirical terms to concerns about validity and reliability that arise from the MAUP.
Habsburg in Havana. Outsider Participation in the Spanish Empire: the Slaving Licence of Romberg & Consors of Ghent, 1780–90
Authors: Pannier Stan
Published: February 2025

The history of European overseas expansion has traditionally been studied from a national perspective. However, the rise of Atlantic history, global history, and a revitalized maritime history has prompted scholars to question the rigidity of Early Modern borders assumed by these conventional national or imperial frameworks. In parallel, researchers have contested the state-centric viewpoint by advocating for an actor-focused approach to Atlantic System history, emphasizing the role of private merchants and their informal, international networks. These approaches have uncovered the involvement of entrepreneurs belonging to polities without a formal empire in the colonial ventures of other nations. This paper examines one such trans-imperial enterprise: Romberg & Consors, a firm operating from the Austrian Netherlands. During and after the American War of Independence (1775–83), Romberg & Consors leveraged evolving Spanish attitudes toward the slave trade and the establishment of neutral trade to organize slave trade expeditions to Cuba. By closely analyzing the operations of this Imperial firm, this study illuminates a decisive phase in Spanish imperial history while contributing to the often-overlooked Atlantic history of the Habsburg Monarchy and the Austrian Netherlands.
Multifaceted multilingual experiences modulate neurocognitive mechanisms of task switching
Authors: Zhang Haoyun , Li Defeng , Lei Victoria Lai Cheng , Leong Teng Ieng , Leong Cheok Teng , Li Jiaze , Huang Ruey-Song
Published: February 2025

This study explored the relationship between multifaceted multilingualism and cognitive shifting through a task-switching paradigm using fMRI. Multilingualism was modeled from both convergent (i.e., integrated multilingual index) and divergent (i.e., L2 proficiency, interpreting training, language entropy) perspectives. Participants identified letters or numbers based on task cues, with Repeat trials maintaining the same task and Switch trials requiring a different task. Switch cost (Switch–Repeat) was used to reflect shifting demands. Better task-switching performance was associated with a higher integrated multilingual index and interpreting training. Neuroimaging indicated that multilinguals predominantly engaged left-hemisphere regions for switching, with extensive multilingual experience requiring fewer neural resources for switch cost (i.e., more efficient processing for cognitive control). During task switching, brain connectivity was regulated locally by L2 proficiency, and globally by interpreting training. These findings underscore the importance of considering multifaceted multilingual experience to understand its impact on cognitive function and brain activity.
Erfassung der numerischen Kompetenzen im Kindergartenalter
Authors: Gloor Noemi , Kucian Karin , Bruns Julia , Gasteiger Hedwig , Moser Opitz Elisabeth
Published: February 2025

Zusammenfassung: Studien haben gezeigt, dass frühe numerische Kompetenzen einen Einfluss auf die spätere mathematische Entwicklung haben. Vor diesem Hintergrund ist es wichtig, die numerischen Kompetenzen bereits im Kindergartenalter zu erfassen, um Kinder, denen wichtige Kompetenzen für die mathematische Entwicklung fehlen, und für die das Risiko der Entwicklung von Rechenschwierigkeiten besteht, frühzeitig und praxistauglich zu identifizieren. In der Studie wird ein Screening zur Erfassung der numerischen Kompetenzen im Kindergartenalter präsentiert, bei dem ausgewählte Aufgaben in einem Gruppensetting durchgeführt werden können. An der Validierung nahmen Kinder im Alter von vier bis sechs Jahren aus der Schweiz ( n = 431) und aus Deutschland ( n = 325) teil. Die Ergebnisse zeigen, dass mit dem Screening in verschiedenen Gruppen (Schweiz, Deutschland) mit wenigen Ausnahmen dieselben Eigenschaften gemessen werden. Die prognostische Validität für den Zeitpunkt kurz vor Schuleintritt ist zufriedenstellend. Der Testwert auf Basis des Gruppensettings lässt sich valide interpretieren, da sich keine Unterschiede zwischen Kindern, die die Aufgaben einzeln gelöst haben und Kindern, die die Aufgaben in Gruppen bearbeitet haben, gezeigt haben. Zusammenfassend lässt sich sagen, dass das Screening durch die Kombination von Einzel- und Kleingruppentests die Erfassung numerischer Fähigkeiten im Kindergarten in kurzer Zeit zuverlässig und valide ermöglicht.
Past and Future Modulation of the ENSO Teleconnection to Southeast Asian Rainfall by Interbasin Interactions
Authors: Le Roy Emmie J. , Ummenhofer Caroline C.
Published: February 2025

Decadal variations in the El Niño‐Southern Oscillation (ENSO)'s influence on Southeast Asian rainfall are modulated by variability in the mean state of atmospheric circulation and moisture anomalies in the Indo‐Pacific Warm Pool (IPWP). Variations in the mean state are characterized by a tripolar pattern in sea surface temperatures (SST) spanning the Indian Ocean, central IPWP, and western Pacific regions. Due to ENSO teleconnection asymmetry, Southeast Asian rainfall is more sensitive to La Niña than El Niño. During positive phases of the tripole pattern, the mean state is drier, with reduced vertical motion over mainland Southeast Asia suppressing La Niña anomalies. In negative phases, the mean state is wetter, with enhanced vertical motion amplifying La Niña anomalies. From 1980 to 2015, relative SST trends show a negative tripole pattern, strengthening the ENSO ‐ Southeast Asian rainfall relationship. However, future projections for 2050–2100 suggest a positive tripole pattern, predicting a weakening of this relationship by 2100.
Two Decades of Dust Radiative Forcing on Snow Cover Across the Great Salt Lake Basin
Authors: Lang Otto I. , Naple Patrick , Mallia Derek , Hosler Ty , Adams Bradley , McKenzie Skiles S.
Published: February 2025

Seasonal snowpacks in mountain drainages of the Great Salt Lake Basin (GSLB), western United States, are the primary surface water supply to regional agriculture, the metropolitan Wasatch Front, and the terminal Great Salt Lake. Spring dust emissions from the eastern Great Basin result in a dust‐darkened GSLB snowpack, locally accelerating snowmelt relative to dust‐free conditions. Such acceleration has been linked to streamflow forecasting errors in the adjacent Colorado River Basin, but snow darkening impacts within the GSLB are largely uninvestigated. To quantify the dust impact, we analyzed patterns in dust radiative forcing (RFdust) over the MODIS record (2001–2023) using spatially and temporally complete RFdust and fractional snow‐covered area products. For validation, retrievals were cross‐referenced with in situ RFdust observations. Results showed that RFdust was present every year and had no significant trend over the record. Spatially, RFdust was similar across all three subbasins. Temporally, RFdust exhibited high interannual variability (−30 to +40 Wm−2 from record means) and has declined slightly in regions of the eastern GSLB. Controls of RFdust may be linked to seasonal meteorology and drought conditions, but drivers remain uncertain. Further understanding of the distribution and controls of RFdust in the GSLB during changing climate and weather patterns may allow us to predict snowmelt more accurately.
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

The 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

Snow 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

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

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

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

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

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

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

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

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

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

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.
Premature ageing of lung alveoli and bone marrow cells from Terc deficient mice with different telomere lengths
Authors: Guerrero-López Rosa , Manguán-García Cristina , Carrascoso-Rubio Carlos , Lozano M. Luz , Toldos-Torres Marta , García-Castro Laura , Sánchez-Dominguez Rebeca , Alberquilla Omaira , Sánchez-Pérez Isabel , Molina-Molina Maria , Bueren Juan A. , Guenechea Guillermo , Perona Rosario , Sastre Leandro
Published: February 2025

Telomeres are terminal protective chromosome structures. Genetic variants in genes coding for proteins required for telomere maintenance cause rare, life-threatening Telomere Biology Disorders (TBDs) such as dyskeratosis congenita, aplastic anemia or pulmonary fibrosis. The more frequently used mice strains have telomeres much longer than the human ones which question their use as in vivo models for TBDs. One mice model with shorter telomeres based on the CAST/EiJ mouse strain carrying a mutation in the Terc gene, coding for the telomerase RNA component, has been studied in comparison with C57BL/6J mice, carrying the same mutation and long telomeres. The possible alterations produced in lungs and the haematopoietic system, frequently affected in TBD patients, were determined at different ages of the mice. Homozygous mutant mice presented a very shortened life span, more notorious in the short-telomeres CAST/EiJ strain. The lungs of mutant mice presented a transitory increase in fibrosis and a significant decrease in the relative amount of the alveolar epithelial type 2 cells from six months of age. This decrease was larger in mutant homozygous animals but was also observed in heterozygous animals. On the contrary the expression of the senescence-related protein P21 increased from six months of age in mutant mice of both strains. The analysis of the haematopoietic system indicated a decrease in the number of megakaryocyte-erythroid progenitors in homozygous mutants and an increase in the clonogenic potential of bone marrow and LSK cells. Bone marrow cells from homozygous mutant animals presented decreasing in vitro expansion capacity. The alterations observed are compatible with precocious ageing of lung alveolar cells and the bone marrow cells that correlate with the alterations observed in TBD patients. The alterations seem to be more related to the genotype of the animals that to the basal telomere length of the strains although they are more pronounced in the short-telomere CAST/EiJ-derived strain than in C57BL/6J animals. Therefore, both animal models, at ages over 6–8 months, could represent valuable and convenient models for the study of TBDs and for the assay of new therapeutic products.