bluuebunny/crossref_metadata_2025 huggingface dataset:
A physics-based modeling method for DC characteristics of GaN HEMTs with conventional, dual-, and tri-gate
Authors: Wang Ashu , Zeng Lingyan
Published: February 2025

In this study, we have developed a physics-based modeling approach to accurately characterize the DC properties of GaN high electron mobility transistors (HEMTs) featuring conventional, dual-, and tri-gate architectures. Our methodology begins with the derivation of analytical expressions for the intrinsic drain current of these three device types, omitting the effects of source and drain access resistances. For dual-gate HEMTs, we employ an approximation of depletion within a rectangular region to depict the channel modulation achieved by the sidewall gate. Building upon this, we dissect the combined influence of the top and sidewall gates in tri-gate HEMTs into two distinct control mechanisms. This involves initially calculating the two-dimensional electron gas (2DEG) density under sole top gate control, followed by determining the 2DEG depletion width governed by the sidewall gate. Incorporating access resistances, the DC characteristics of all three devices are computed through numerical iteration. To validate the channel control model directly, we exclude the self-heating effect and conduct comparative TCAD simulations. Furthermore, our modeling results, which encompass the self-heating effect, are corroborated by experimental data, thereby ensuring the reliability and accuracy of our approach.
Explainable multiscale temporal convolutional neural network model for sleep stage detection based on electroencephalogram activities
Authors: Phang Chun-Ren , Hirata Akimasa
Published: February 2025

Objective: Humans spend a significant portion of their lives in sleep (an essential driver of body metabolism). Moreover, as sleep deprivation could cause various health complications, it is crucial to develop an automatic sleep stage detection model to facilitate the tedious manual labeling process. Notably, recently proposed sleep staging algorithms lack model explainability and still require performance improvement. Approach: We implemented multiscale neurophysiology-mimicking kernels to capture sleep-related electroencephalogram (EEG) activities at varying frequencies and temporal lengths; the implemented model was named “Multiscale Temporal Convolutional Neural Network (MTCNN).” Further, we evaluated its performance using an open-source dataset (Sleep-EDF Database Expanded comprising 153 days of polysomnogram data). Main results: By investigating the learned kernel weights, we observed that MTCNN detected the EEG activities specific to each sleep stage, such as the frequencies, K-complexes, and sawtooth waves. Furthermore, regarding the characterization of these neurophysiologically significant features, MTCNN demonstrated an overall accuracy (OAcc) of 91.12% and a Cohen kappa coefficient of 0.86 in the cross-subject paradigm. Notably, it demonstrated an OAcc of 88.24% and a Cohen kappa coefficient of 0.80 in the leave-few-days-out analysis. Our MTCNN model also outperformed the existing deep learning models in sleep stage classification even when it was trained with only 16% of the total EEG data, achieving an OAcc of 85.62% and a Cohen kappa coefficient of 0.75 on the remaining 84% of testing data. Significance: The proposed MTCNN enables model explainability and it can be trained with lesser amount of data, which is beneficial to its application in the real-world because large amounts of training data are not often and readily available.
Impacts of climate change on groundwater quality: a systematic literature review of analytical models and machine learning techniques
Authors: Chowdhury Tahmida Naher Naher , Battamo Ashenafi Yohannes , Nag Rajat , Zekker Ivar , Salauddin Md
Published: February 2025

The increasing impact of global climate change on hydrogeological and hydrological systems presents substantial challenges to the sustainable management of groundwater quality. Changes in precipitation regimes, temperature fluctuations, and the frequency of extreme hydro-climatic events driven by climate change accelerate the deterioration of groundwater quality (GWQ), thereby threatening ecosystems and human health. In response to these challenges, recent research has increasingly focused on developing and refining analytical models (AM) and machine learning (ML) techniques to understand better and predict the impacts of climate change on GWQ. This systematic literature review critically examines the current state of knowledge on applying AM and ML models in the context of GWQ assessment under climate-induced stressors. By synthesizing findings from a comprehensive review of existing studies, this paper discusses the capabilities, limitations, and future directions of hybrid ML and traditional AM in GWQ prediction, vulnerability, and threshold estimation. The review reveals that while ML approaches significantly enhance predictive accuracy and model robustness, there remain substantial challenges in their application due to the complexity of climate-induced variables and the scarcity of high-resolution data. This paper aims to provide GWQ researchers, water resource managers, and policymakers with an advanced understanding of the interactions between climate change and GWQ and the innovative AM and ML modelling approaches available to address these challenges. By highlighting the potential and limitations of current models, this review offers insights into developing more effective and adaptive management strategies for safeguarding groundwater quality in an era of rapid climatic change.
Massless conformal fields in ten dimensions , minimal unitary representation of E
7(-25) and exceptional supergravity
Authors: Gunaydin Murat
Published: February 2025

Minimal unitary representation of $SO(d,2)$ and its deformations describe all the conformally massless fields in $d$ dimensional Minkowskian spacetimes. In critical dimensions these spacetimes admit extensions with twistorial coordinates plus a dilatonic coordinate to causal spacetimes coordinatized by Jordan algebras $J_3^{\mathbb{A}}$ of degree three over the four division algebras $\mathbb{A}=\mathbb{R} , \mathbb{C} , \mathbb{H} , \mathbb{O} $. We study the minimal unitary representation (minrep) of the conformal group $E_{7(-25)}$ of the spacetime coordinatized by the exceptional Jordan algebra $J_3^{\mathbb{O}}$ defined over octonions $\mathbb{O}$. We show that the minrep of $E_{7(-25)}$ decomposes into infinitely many massless representations of the ten dimensional conformal group $SO(10,2)$. Corresponding conformal fields transform as symmetric tensors in spinor indices of $SO(9,1)$ subject to certain constraints. Even and odd tensorial fields describe bosonic and fermionic conformal fields , respectively. Each irrep of $SO(10,2)$ comes with infinite multiplicity and fall into a unitary representation of an $SU(1,1)$ subgroup that commutes with $SO(10,2)$. The noncompact generators transforming in spinor representation $16 $ of $SO(10)$ interpolate between the bosonic and fermionic representations and hence act like "bosonic supersymmetry" generators. These results truncate to similar results in the lower critical space-time dimensions. We also give the decomposition of the minrep of $E_{7(-25)}$ with respect to the subgroup $SO^*(12)\times SU(2)$ with $SO^*(12) $ acting as the conformal group of the spacetime coordinatized by the $J_3^{\mathbb{H}}$ defined over quaternions $\mathbb{H}$. Group $E_{7(-25)}$ is also the U-duality group of the exceptional $N=2$ Maxwell-Einstein supergravity in four dimensions. We discuss the relevance of our results to the composite scenario that was proposed for the exceptional supergravity so as to accommodate the families of quarks and leptons of the standard model as well as to the proposal that $E_{7(-25)}$ acts as spectrum generating symmetry group of the $5d$ exceptional supergravity.
Invasion of perennial sagebrush steppe by shallow-rooted exotic cheatgrass reduces stable forms of soil carbon in a warmer but not cooler ecoregion.
Authors: Katz Sydney , Maxwell Toby , de Graaff Marie Anne , Germino Matthew
Published: February 2025

Soil organic carbon (“SOC”) in drylands comprises nearly a third of the global SOC pool and has relatively rapid turnover and thus is a key driver of variability in the global carbon cycle. SOC is also a sensitive indicator of longer-term directional change and disturbance-responses of ecosystem C storage. Biome-scale disruption of the dryland carbon cycle by exotic annual grass invasions (mainly Bromus tectorum, “Cheatgrass”) threatens carbon storage and corresponding benefits to soil hydrology and nutrient retention. Past studies on cheatgrass impacts mainly focused on total C, and of the few that evaluated SOC, none compared the very different fractions of SOC, such as relatively unstable particulate organic carbon (POC) or relatively stable, mineral-associated organic carbon (MAOC). We measured SOC and its POC and MAOC constituents in the surface soils of sites that had sagebrush canopies but differed in whether their understories had been invaded by cheatgrass or not, in both warm and relatively colder ecoregions of the western USA. MAOC stocks were 36.1% less in the 0-10 cm depth and 46.1% less in the 10-20 cm depth in the cheatgrass-invaded stands compared to the uninvaded stands of the warmer Colorado Plateau, but not in the cooler and more carbon-rich Wyoming Basin ecoregion. In plots where cheatgrass increased SOC, it was via unstable POC. These findings indicate that cheatgrass effects on the distribution of soil carbon among POC and MAOC fractions may vary among ecoregions, and that cheatgrass can reduce forms of carbon that are otherwise considered stable and ‘secure’, i.e. sequestered.
Prediction of rotary seal leakage rate under the influence of stress relaxation based on G A-PSO-BP hybrid algorithm
Authors: Zhang Yi , He Wei , Hu Ling , Lou Zicheng , Zhang Daqin , Wang Zheng
Published: February 2025

Rotary combination seals of composite impactors are susceptible to failure and relaxation in high-pressure, high-temperature deep-well environments. The aim of this study is to analyze the effect of stress relaxation on the performance of the seals and to assess their performance under different operating conditions. The study adopts GA-PSO-BP algorithm to predict the leakage, simulates the contact pressure change of the sealing surface before and after stress relaxation by Abqus software, and calculates the leakage rate by using MATLAB software in combination with the thermoelastic flow lubrication model and the finite element analysis data, to establish the prediction model dataset. The study also optimised the neural network prediction model and verified the accuracy of the model experimentally. The results show that increasing pressure leads to an increase in contact pressure, but relaxation increases contact length and decreases maximum pressure, and increasing compression increases and then decreases contact pressure and increases the peak value, but relaxation decreases the peak value and increases the risk of leakage. The increase in speed and temperature both lead to an increase in leakage rate, and the GA-PSO-BP model predicts more accurately the rotary combination seals with a higher leakage rate after considering the stress relaxation.
Towards virtual painting recolouring using vision transformer on X-ray fluorescence datacubes
Authors: Bombini Alessandro , Bofı́as Fernando Garcı́a-Avello , Giambi Francesca , Ruberto Chiara
Published: February 2025

In this contribution, we define (and test) a pipeline to perform virtual painting recolouring using raw data of X-Ray Fluorescence (XRF) analysis on pictorial artworks. To circumvent the small dataset size, we generate a synthetic dataset, starting from a database of XRF spectra; furthermore, to ensure a better generalisation capacity (and to tackle the issue of in-memory size and inference time), we define a Deep Variational Embedding network to embed the XRF spectra into a lower dimensional, K-Means friendly, metric space. We thus train a set of models to assign coloured images to embedded XRF images. We report here the devised pipeline performances in terms of visual quality metrics, and we close on a discussion on the results.
Democratisation and franchise extension: the literature
Authors: Aidt Toke S , Franck Raphaël
Published: February 2025

This chapter surveys theories from the political economics literature on franchise extension that seeks to explain the logic of democratisation during the long nineteenth century, and it evaluates the empirical literature in economics and political science that confront the competing theories with historical and contemporaneous data. It classifies these theories into two categories. Bottom-up theories emphasise that the members of the incumbent elite share power with others to avoid losing power entirely or because they become persuaded of the merits of doing so. Conversely, top-down theories emphasise that the ruling elite, or some part thereof, can directly benefit from democratisation. Based on this survey, the chapter develops three hypotheses of suffrage reform—the threat of revolution hypothesis, the social movement hypothesis, and the political expedience hypothesis—which are tested in the subsequent chapters in the context of the Great Reform Act of 1832 using the new process-focused approach.
A Comprehensive Bioinformatic Evaluation of the NTRK Family's Potential as Prognostic Biomarkers In Breast Cancer
Authors: Mohammadi Ramtin , Ghiasi Mohsen , Mehdizadeh Saber , Mohammadi Javad , Mohammad Ganji Shahla
Published: February 2025

Motivation

Breast cancer (BC), with its rising prevalence and mortality rate, is one of the most significant human health issues. The family of transmembrane tyrosine kinases that promote neuronal growth includes the Neurotrophic Tyrosine Kinase Receptors (NTRK). NTRK1–3 genes encode the members of this family. Alterations of NTRK genes can induce carcinogenesis both in neurogenic and non-neurogenic cells. The prevalence of NTRK gene fusion is under 1% in solid tumours but is highly encountered in rare tumours. Since the prognostic values of NTRK families’ expression in various types of cancer are becoming increasingly evident, we aimed to conduct a comprehensive bioinformatics study evaluating the prognostic significance of the NTRK family in BC. online Bioinformatic databases including TCGA, UALCAN, Kaplan–Meier plotter, bc-GenExMiner, cBioPortal, STRING, Enrichr, and TIMER were utilized for analysis.

Results

High levels of NTRK2 and 3 demonstrated better associations with overall survival (OS) and recurrence-free survival (RFS) in BC patients (P < 0.05), while high levels of NTRK1 showed an applicable correlation with RFS in BC patients (P < 0.001). Our findings provide a new outlook that might aid in the field of personalized medicine and therapeutic use of NTRK as a prognostic biomarker in BC.
Investigating surgeon performance metrics as key predictors of robotic herniorrhaphy outcomes using iterative machine learning models: retrospective study
Authors: Shin Thomas H , Fanta Abeselom , Shields Mallory , Kaoukabani Georges , Gokcal Fahri , Liu Xi , Tavakkoli Ali , Kudsi O Yusef
Published: February 2025

Background

Robotic data streams allow for capture of objective performance indicators, providing the ability to quantify and analyse operator technique and movement in optimizing postoperative outcomes. This study provided proof-of-concept demonstration of how intraoperative surgeon-factors could influence post-robotic herniorrhaphy complications via machine learning analyses of objective performance indicators.

Study design

Data on robotic-assisted ventral hernia repair were retrospectively reviewed between February 2013 and November 2022 at a single academic centre. Machine learning modelling on systematic chart review data correlated perioperative patient factors, intraoperative objective performance indicators, and postoperative outcomes. Complications were classified with the Clavien–Dindo scale. Endpoints of interest included postoperative complications at discharge, at postoperative day 30, and at the last follow-up. Machine learning models employed included linear, k-nearest neighbours, support vector, decision tree, random forest, adaptive boosting, and extreme gradient boosting regression algorithms.

Results

Some 520 patients undergoing robotic ventral hernia were included. Median age of patients was 56 years with 52.7% male and median body mass index 31.9 kg/m2. 92.7% of patients had at least one medical comorbidity peoperatively. Complications occurred in 33 (6.3%) patients at time of discharge. Machine learning models demonstrated an accuracy 0.95, a precision 0.92, a recall 0.95, and a F1 0.92 of objective performance indicator predicting complications and an accuracy 0.95, a precision 0.95, a recall 0.95, and a F1 0.94 by Clavien–Dindo grade at time of discharge. Thematic analyses of top ranked factors included operator-specific objective performance indicators alongside patient factors canonically associated with hernia complications.

Conclusions

This study showed the novel application of machine learning modelling to bridge objective performance indicators and clinical patient factors to postoperative clinical outcomes, demonstrating the relevance of dynamic intraoperative surgeon factors on clinical outcomes.
When the whole is greater than the sum of its parts: why machine learning and conventional statistics are complementary for predicting future health outcomes
Authors: Janse Roemer J , Abu-Hanna Ameen , Vagliano Iacopo , Stel Vianda S , Jager Kitty J , Tripepi Giovanni , Zoccali Carmine , Dekker Friedo W , van Diepen Merel
Published: February 2025

An artificial intelligence boom is currently ongoing, mainly due to large language models, leading to significant interest in artificial intelligence and subsequently also in machine learning (ML). One area where ML is often applied, prediction modelling, has also long been a focus of conventional statistics. As a result, multiple studies have aimed to prove superiority of one of the two scientific disciplines over the other. However, we argue that ML and conventional statistics should not be competing fields. Instead, both fields are intertwined and complementary to each other. In order to illustrate this, we discuss some essentials of prediction modelling, elaborate on prediction modelling using techniques from conventional statistics, and explain prediction modelling using common ML techniques such as support vector machines, random forests, and artificial neural networks. We then showcase that conventional statistics and ML are in fact quite similar in many aspects, including underlying statistical concepts and methods used in model development and validation. Finally, we argue that conventional statistics and ML can and should be seen as a single integrated field. This integration can further improve prediction modelling for both disciplines (e.g. regarding fairness and reporting standards) and will support the ultimate goal: developing the best performing prediction models for the patient and healthcare provider.
Relevant determinants of Dutch patients’ informed decision-making and use of online access to medical records
Authors: Thielmann Rosa R L C , Hoving Ciska , Cals Jochen W L , Crutzen Rik
Published: February 2025

Patient online access to medical records can foster patient empowerment and advance patient-centered healthcare. Despite high patient interest, user rates often remain low. While previous research has identified determinants influencing the adoption of online access, this study assessed the relevance of these determinants. By doing so, this study aimed to point towards measures to improve adoption efficiently. Furthermore, supporting patient-informed decision-making about using online access might facilitate sustained use. Therefore, conducting a nationwide online survey study among Dutch adults, we examined the relevance of 22 psychological determinants for the use of online access (N = 1888) and decisional conflict (as an indicator of uninformed decision-making) regarding use (N = 3403). Analyses concerned visualization of univariate distributions of determinants and their associations with (i) use and (ii) decisional conflict regarding use. Greater relevance was indicated by lower means and stronger associations. Results showed that secured data privacy and feeling sufficiently instructed were most relevant for use. Concerning decisional conflict regarding the use, additionally, patients’ beliefs about the effects of online access on their ability to participate in their healthcare process and on the patient–provider relationship were most relevant. Overall explained variance was low (R2 = 0.17 for use and R2 = 0.19 for decisional conflict). Efficiently supporting the use of online access and informed decision-making about use might be achieved by addressing data privacy, providing clear instructions and communicating potential effects. The low explained variance indicates the need for additional measures, such as facilitating easy opportunities and understanding individual patient preferences.
Comparison of eco-directed and health-focused brief awareness-raising interventions for enhancing active participation of community residents in drug take-back program
Authors: Wu Shuzhe , Liu Qinghua , Li Qin , Wang Jun
Published: February 2025

Drug take-back system provides a legal, safe and eco-friendly avenue to appropriately dispose of unwanted medicines, contributing to both environmental sustainability and reducing medication misuse. This study designed and implemented a brief educational intervention, which took <1 min on average, to enhance awareness of community residents regarding the dangers of hoarding and improperly disposing of expired and unused medication at home. In a Chinese urban community, 104 eligible households were evenly assigned into 2 groups receiving leaflet-based awareness-raising interventions. Messages about risks of unwanted medicines delivered to the two groups focused on either environmental concerns of pharmaceutical emerging contaminants (eco-directed) or health hazards associated with misuse or overuse (health-focused). Compared with those in a health-focused intervention, significantly more households participating in an eco-directed awareness-raising activity returned unwanted medicines, supported community-level drug take-back program and agreed that drug take-back program should be mandatory and paid for by consumers. Data suggested that the eco-directed awareness-raising intervention might be an attractive approach to enhance the public’s active participation in drug take-back program.
A scoping review of visual communication of written patient health information preferences including a Māori perspective
Authors: Caisip A , Kremer L , Edmonds L , Young A
Published: February 2025

This scoping review examines the visual design elements of written patient information (WPI), specifically focusing on imagery, colour, layout and content presentation, and their impact on health information communication, understanding, behaviour and preferences among patients. Understanding patient preferences allows for patient-informed WPI design, which is important for Māori (Indigenous peoples of Aotearoa New Zealand) living in a colonial society. Nine studies were analysed, primarily investigating the integration of visual illustrations within WPI. Participants generally favoured the inclusion of images alongside text, finding them instrumental in enhancing comprehension and making health information more approachable. The preference for simpler and less detailed visuals, such as cartoons, was highlighted, although there was variability depending on literacy levels and cultural backgrounds. The use of colour, layout features (e.g. font type and white space) and content framing (e.g. positive versus negative framing of risk information) were explored for their effects on information reception and behavioural outcomes. Currently, there is a paucity of literature on Māori preferences and requires further research. Overall, this scoping review highlights the importance of designing WPIs with visual elements that cater to diverse literacy levels and cultural preferences to optimize communication effectiveness and patient engagement.
Emerging β-lactam non-susceptibility in Group A Streptococcus: implications for Ethiopia’s healthcare system
Authors: Geteneh Alene , Biset Sirak , Reta Melese Abate
Published: February 2025

The emergence of β-lactam non-susceptibility in Group A Streptococcus (GAS) or Streptococcus pyogenes represents a major challenge for the global public health, particularly in resource-limited settings like Ethiopia. GAS, a primary cause of pharyngitis and invasive infections, is conventionally treated with β-lactam antibiotics such as penicillin. However, the recent evidence raises concerns about the treatment efficacy with reduced susceptibility, the diagnostic limitations, and the potential for complications such as acute rheumatic fever. This commentary calls for attention to the antimicrobial resistance trends in Ethiopian GAS isolates, underscoring the need for routine susceptibility testing, advanced molecular diagnostics, and strengthened laboratory capacities to guide effective treatment strategies and mitigate the antibiotic resistance-associated risks.
Transcriptional analysis provides molecular insights into degeneration of the edible fungus Flammulina filiformis
Authors: Wang Caiyi , Sun Yu , Yang Xinyu , Wang Zehao , Xiang Shibo , Huang Zhuqing , Liang Yue
Published: February 2025

Aims

Flammulina filiformis, a widely cultivated edible fungus, frequently suffers from strain degeneration, leading to reduce yield and quality, and causing significant economic losses in large-scale production. This study aimed to better understand degeneration mechanisms and to develop an assay for predicting degeneration.

Methods and Results

This study investigates strain degeneration by comparing a cultivated strain (F1) and its subcultured derivative (F7). Although both strains display similar mycelial growth, F7 shows impaired fruiting body production, indicating that degeneration occurs prior to visible changes in mycelial growth. To uncover the molecular mechanisms underlying degeneration, transcriptome analysis was carried out. A total of 352 down-regulated and 280 up-regulated differentially expressed genes (DEGs) were identified in F7 compared to F1. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses revealed significant enrichment of DEGs in functional categories related to oxidoreductase activities and peroxisome pathway. Quantitative PCR further validated the regulation of certain DEGs associated with these enriched functions. A stress tolerance assay was developed to detect degeneration in strains with unchanged mycelial growth but reduced fruiting body production.

Conclusions

Results suggested that strain degeneration in F. filiformis is closely linked to oxidative stress regulation and occurs prior to observable mycelial impairment.
TDAP flap in reconstruction of a severe postburn contracture of the axillary region—a case report
Authors: Eljuga Domagoj , Muzar Rhea Marie , Jaman Josip , Eljuga Ksenija , Rafaj Goranka , Vlajcic Zlatko
Published: February 2025

Herein we report a case of a male patient who was burned with hot oil and as a consequence developed a severe axillary contracture with limited abduction and elevation of his left arm. Due to the restriction in the range of movements, our patient reported limitations in everyday activities with decreased quality of life. For this patient we proposed a reconstructive plan that required a combination of multiple techniques of scar release and reconstruction of the defect with thoracodorsal artery perforator (TDAP)-based flap. One year postoperatively, we achieved a significant improvement in range of motion. We showed that TDAP flap provides a thin and pliable tissue coverage with a safe vascular supply. Furthermore, we eliminated the need for prolonged splinting which enabled early postoperative rehabilitation. To conclude, TDAP flap proved to be an ideal flap for this scenario and when used in combination with other techniques, optimal end result can be achieved.
Distribution functions for the modelling of accretion remnants in Milky Way-like galaxies: Insights from IllustrisTNG
Authors: Lane James M M , Bovy Jo
Published: February 2025

We study accretion remnants around Milky Way analogs in the IllustrisTNG simulations to determine how well commonly used distribution functions (DFs) describe their phase-space distributions. We identify 30 Milky Way analogs and 116 remnants from mergers with stellar mass ratios greater than 1:20. Two-power density profiles, as well as rotating constant-anisotropy and Osipkov-Merritt DFs are fit to the remnants. We determine that the remnants are suitable for equilibrium modelling by assessing them in the context of the Jeans equation. Each of the models we consider are reasonably able to fit the stellar remnant energy and angular momentum distribution, as well as the magnitude and shape of velocity dispersion profiles. Case studies matched to two well-known merger remnants in the stellar halo – Gaia-Sausage/Enceladus (GS/E) and Sequoia – are explored in more depth. We find good evidence that remnants with high anisotropy β, such as GS/E, are better modelled with a superposition of two Osipkov-Merritt DFs than either a constant-anisotropy model or a single Osipkov-Merritt DF. We estimate an Osipkov-Merritt profile with scale radius between 2–4 kpc would be a good first-order representation of GS/E, and comment on existing observational evidence for this as well as studies which could demonstrate it. Overall, we find that DF-based models work well for describing the kinematics of large merger remnants. Our results will be an important reference for future studies which seek to constrain both the spatial and kinematic properties of merger remnants in the Milky Way stellar halo.
Estimating Gene Conversion Tract Length and Rate From PacBio HiFi Data
Authors: Charmouh Anders Poulsen , Porsborg Peter Sørud , Hansen Lasse Thorup , Besenbacher Søren , Boeg Winge Sofia , Almstrup Kristian , Hobolth Asger , Bataillon Thomas , Schierup Mikkel Heide
Published: February 2025

Gene conversions are broadly defined as the transfer of genetic material from a “donor” to an “acceptor” sequence and can happen both in meiosis and mitosis. They are a subset of noncrossover (NCO) events and, like crossover (CO) events, gene conversion can generate new combinations of alleles and counteract mutation load by reverting germline mutations through GC-biased gene conversion. Estimating gene conversion rate and the distribution of gene conversion tract lengths remains challenging. We present a new method for estimating tract length, rate, and detection probability of NCO events directly in HiFi PacBio long read data. The method can be used to make inference from sequencing of gametes from a single individual. The method is unbiased even under low single nucleotide variant (SNV) densities and does not necessitate any demographic or evolutionary assumptions. We test the accuracy and robustness of our method using simulated datasets where we vary length of tracts, number of tracts, the genomic SNV density, and levels of correlation between SNV density and NCO event position. Our simulations show that under low SNV densities, like those found in humans, only a minute fraction (∼2%) of NCO events are expected to become visible as gene conversions by moving at least 1 SNV. We finally illustrate our method by applying it to PacBio sequencing data from human sperm.
The impact of the new WHO Classification of renal cell carcinoma on the diagnosis of hereditary leiomyomatosis and renal cell carcinoma
Authors: Degenhardt Jan , Tolkach Yuri , Amin Mahul B , Mosiello Giovanni , Baydar Dilek Ertoy , Gall Emilie Cornec-Le , DiCola Jason , Elhag Dean , Frezza Christian , Halbritter Jan , Guillermo Ignacio Blanco , Jewett Michael A S , Lattouf Jean-Baptise , Lovitt Graham , Lundgren Per-Olof , Maher Eamonn R , Mulders Peter , Shuch Brian , Hartmann Arndt , Müller Roman-Ulrich ,   the HLRCC Alliance in collaboration with the ERA Working Group “Genes&Kidney”, the European Reference Networks ERKNet, eUROGEN and GENTURIS, the Uropathology Working Group of the European Society of Pathology and the IKCC, Agaimy A , Beck B , Bonn S E , Bissler J J , Colecchia M , Erger F , Giles R H , Hokamp N Grosse , Jahn A , Kuismin O , La Rosa S , Linehan W M , Lovitt G , Mallett A J , Rajan N , Siemer S , Tran M , Uimari O , Weller A
Published: February 2025

Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) syndrome is caused by heterozygous germline variants in the fumarate hydratase (FH) gene [1,2]. Inheritance follows an autosomal dominant pattern. Loss of FH confers a predisposition for various benign and malignant neoplasms, including cutaneous leiomyomas, uterine fibroids and FH-deficient renal cell carcinoma [3]. While benign, cutaneous and uterine manifestations have a relevant impact on quality of life and risk for complications [4]. The vast majority of FH-deficient RCC exhibit an aggressive behavior with invasive growth and potential for early metastatic spread [5]. Additionally, pathogenic germline FH variants have been associated with other neoplasms, such as adrenal gland [10] and Leydig cell tumors [28, 29].

The aggressive behavior of FH-deficient RCC challenges nephron-sparing resection strategies, as a wide margin is recommended. Even after early nephrectomy for surgical removal of FH-deficient renal cell carcinomas, there is a relevant risk for distant metastasis as well as the remaining predisposition for de novo primary renal tumors in the other kidney. Active screening is central to HLRCC care since no preventative HLRCC-specific treatment exists. VEGF/EGFR directed treatment regimes, such as Erlotinib/Bevacizumab demonstrate efficacy against HLRCC-associated RCC [6]. This emphasizes the importance of establishing the correct diagnosis in HLRCC early on to guide therapeutic decisions.

Morphologic criteria as well as specific immunohistochemical (IHC) staining and molecular genetics allow the identification of FH-deficient RCC. Changes made in the recent 2022 WHO classification impact the diagnosis of HLRCC in multiple ways. This commentary aims to point out this impact and to raise awareness among pathologists as well as clinicians involved in the care of patients with HLRCC.
A Predicting Tool for Kidney Function Recovery after Drug-Induced Acute Interstitial Nephritis
Authors: Caravaca-Fontán Fernando , Alonso-Riaño Marina , Shabaka Amir , Villacorta Javier , de Lorenzo Alberto , Quintana Luis F , Rodríguez Eva , Gadola Liliana , Cobo María Ángeles , Oliet Aniana , Sierra-Carpio Milagros , Cobelo Carmen , Iglesias Elena , Cordón Alfredo , Praga Manuel , Fernández-Juárez Gema
Published: February 2025

Background

Drug-induced acute interstitial nephritis (DI-AIN) represents a common cause of acute kidney injury. Early withdrawal of the culprit drug and corticosteroid therapy remains the mainstay of treatment.

This study aimed to develop and validate a predictive nomogram to assess the probability of recovery of kidney function at 6 months after treatment.

Methods

Multicenter, retrospective, observational study in 13 nephrology departments. Patients with biopsy proven DI-AIN treated with corticosteroids between 1996-2023 were included. Dataset was randomly divided into training (n=164) and validation sets (n=60). Least absolute shrinkage and selection operator regression was used to screen the main predictors of complete (creatinine increase <25% of the last value before DI-AIN) or no recovery of kidney function (serum creatinine ≥75% or need for dialysis).

Results

The study group comprised 224 patients with DI-AIN: 51 (31%) in the training group and 19 (32%) in the validation set, achieved complete recovery at 6 months. Conversely, 33 (20%) and 8 (13%) patients in each set showed no recovery at 6 months. Clinical characteristics were well balanced between training and validation sets. The selected variables were age (under/above 65 years), gender, degree of interstitial fibrosis and time to corticosteroids initiation (under/above 7 days). Based on multivariable logistic regression model, a nomogram was developed. The area under the curve (AUC) of the nomogram was 0.79 (95% confidence interval: 0.71–0.88) indicating a good discriminative power. Bootstrap self-sampling was performed 1000 times for validation of the model. Calibration plot revealed that the predicted outcomes aligned well with the observations. Decision curve analysis suggested that the model had clinical benefit.

Conclusions

We developed and validated a nomogram to predict kidney recovery at 6 months in DI-AIN patients treated with corticosteroids. This tool helps clinicians estimate prognosis and optimize corticosteroid therapy's intensity and duration for better treatment outcomes.
An Interview with Professor Vincent Dousset: Psychoradiology is a Pioneering Field, Our Aspiration is to Unite Psychiatrists with Radiologists in France
Authors: Cui Longbiao
Published: February 2025

From July 20th to 22nd, 2024, the ISMRM Endorsed Workshop on MR for Psychiatry was held in Chengdu City, China. This prestigious event attracted numerous academic elites worldwide.

Vincent Dousset is a professor of medicine and radiology at the University of Bordeaux, and the chairman of Medical Imaging at the University Hospital of Bordeaux. The hospital is running a completed new project dedicated to applying MRI technology in the field of psychiatry, and Professor Dousset will manage the project. However, this is an entirely new domain for the radiologists and technicians in the hospital. Therefore, Professor Dousset attended the ISMRM-endorsed Workshop on MR for Psychiatry in Chengdu to gain insight into the latest advancements in psychoradiology and hoped to apply valuable experience to their project.
Micro MPCs and Macro Counterfactuals: The Case of the 2008 Rebates
Authors: Orchard Jacob D , Ramey Valerie A , Wieland Johannes F
Published: February 2025

We present evidence that the high estimated MPCs from the leading household studies result in implausible macroeconomic counterfactuals. Using the 2008 tax rebate as a case study, we calibrate a standard macro model with the estimated micro MPCs to construct counterfactual macroeconomic consumption paths in the absence of a rebate. The counterfactual paths imply that consumption expenditures would have plummeted in spring and summer 2008 and then mostly recovered in September 2008. We use narratives and forecasts to argue that these paths are implausible. We then show that standard two-way fixed effect estimates of the micro MPCs are upward biased. When we correct for the biases, we estimate smaller micro MPCs using the CEX data than the previous literature. We also show that realistic modifications of the model result in general equilibrium forces that dampen rather than amplify micro MPCs. The combination of smaller micro MPCs and dampening general equilibrium forces implies general equilibrium consumption multipliers that are below 0.2.
EGFR in Placental Health and Disease: Pathways, Dysfunction, and Chemical Disruption
Authors: Waye Anita A , Moeller Jacob , Veiga-Lopez Almudena
Published: February 2025

Formation of the placenta during gestation is required to support fetal growth and development. Derived from the placenta, trophoblast cells express nuclear and membrane-bound receptors. Among these receptors is the epidermal growth factor receptor (EGFR) which plays a key role in placental development. Activation of EGFR-mediated signaling in trophoblast cells regulates critical processes, such as proliferation, differentiation, invasion, and fusion during pregnancy, making it essential for normal placental formation. Dysfunction of EGFR in placental trophoblast cells has been associated with adverse pregnancy outcomes, including intrauterine growth restriction, preeclampsia, and preterm birth. Ubiquitous environmental chemicals, like polycyclic aromatic hydrocarbons, polychlorinated biphenyls, organochlorine pesticides, and bisphenols, have been reported to modulate EGFR signaling pathways, potentially contributing to placental dysfunction. This review explores the pivotal role of EGFR signaling in placental development and function, with a focus on how environmental chemicals interfere with EGFR-mediated pathways and placental cell functions as well as their implications for pregnancy outcomes. Findings presented herein underscore the need for further research into the effects of exposure to environmental chemicals on modulating EGFR signaling pathways in the context of placental health.
Circ‐Sirt6 promotes the stability and expression of m6A modified Sirt6mRNA by recruiting IGF2BP2
Authors: Zhang Chuanfeng , Wang Jianing , Kong Peng , Sun Guangbin , Sun Hongfang , Yu Yuan
Published: February 2025

Coronary artery disease (CAD) is the leading cause of death worldwide. Even though numerous circRNAs have been linked to the formation and progression of CAD, more circular RNA regulators still need to be uncovered in order to enhance the knowledge of the CAD regulatory networks. Microarray analysis was employed to identify aberrantly expressed circRNAs in vascular pathology, and the level of circ‐Sirt6 in abnormally proliferated vascular smooth muscle cells (VSMCs) was detected by qRT‐PCR. The effects of circ‐Sirt6, IGF2BP2, and Sirt6 on the proliferation and migration of VSMCs were examined by EdU incorporation assay and migration assays. The interaction between circ‐Sirt6, IGF2BP2, and Sirt6 was verified by RNA pull‐down assay, RIP, FISH, and immunofluorescent staining. Dot blot assay and m6A‐methylated RNA immunoprecipitation‐qPCR were performed to confirm that circ‐Sirt6 promoted m6A modification and stabilization of Sirt6 mRNA. According to our research, circ‐Sirt6 expression was markedly downregulated in VSMCs treated with PDGF‐BB and carotid artery balloon injury. The in vitro and in vivo proliferation and migration of VSMCs were inhibited by overexpression of circ‐Sirt6. Mechanistically, circ‐Sirt6 specifically binds to IGF2BP2 and promotes the stability and expression of Sirt6 mRNA by enhancing its m6A modification. Our findings highlight the importance of circ‐Sirt6‐mediated m6A in VSMC phenotype switching. Circ‐Sirt6 may be a novel biological target for CAD.
Dolutegravir induces endoplasmic reticulum stress at the blood–brain barrier
Authors: Huang Chang , Qu Qing Rui , Hoque Md. Tozammel , Bendayan Reina
Published: February 2025

Dolutegravir (DTG)‐based antiretroviral therapy is the contemporary first‐line therapy to treat HIV infection. Despite its efficacy, mounting evidence has suggested a higher risk of neuropsychiatric adverse effect (NPAE) associated with DTG use, with a limited understanding of the underlying mechanisms. Our laboratory has previously reported a toxic effect of DTG but not bictegravir (BTG) in disrupting the blood–brain barrier (BBB) integrity. The current study aimed to investigate the underlying mechanism of DTG toxicity. Primary cultures of mouse brain microvascular endothelial cells were treated with DTG and BTG at therapeutically relevant concentrations. RNA sequencing, qPCR, western blot analysis, and cell stress assays (Ca2+ flux, H2DCFDA, TMRE, MTT) were applied to assess the results. The gene ontology (GO) analysis revealed an enriched transcriptome signature of endoplasmic reticulum (ER) stress following DTG treatment. We demonstrated that therapeutic concentrations of DTG but not BTG activated the ER stress sensor proteins (PERK, IRE1, p‐IRE1) and downstream ER stress markers (eIF2α, p‐eIF2α, Hspa5, Atf4, Ddit3, Ppp1r15a, Xbp1, spliced‐Xbp1). In addition, DTG treatment resulted in a transient Ca2+ flux, an aberrant mitochondrial membrane potential, and a significant increase in reactive oxygen species in treated cells. Furthermore, we found that prior treatment with ER sensor or ER stress inhibitors significantly mitigated the DTG‐induced downregulation of tight junction proteins (Zo‐1, Ocln, Cldn5) and elevation of pro‐inflammatory cytokines and chemokines (Il6, Il23a, Il12b, Cxcl1, Cxcl2). The current study provides valuable insights into DTG‐mediated cellular toxicity mechanisms, which may serve as a potential explanation for DTG‐associated NPAEs in the clinic.
Focal Oral Elastosis: Case Series, Proposed Nomenclature, and Literature Review
Authors: Alabdulaaly Lama , Chung Dahee , Woo Sook-Bin
Published: February 2025

Late-onset focal dermal elastosis is an uncommon elastic disorder seen in older individuals and biopsies demonstrate an increase in elastic fibers. Elastosis of the oral cavity is reported uncommonly. The aim of this study is to describe oral biopsies with similar histopathologic features to late-onset focal dermal elastosis and to introduce the term “focal oral elastosis.” We included oral biopsies that showed increased elastic fibers confirmed by Verhoeff-van Gieson histochemical stain. We identified 6 oral biopsies with prominent elastosis. There were 4 men, and the median age was 64.5 years. Elastosis was present in 5 nodular lesions and 1 papule. Lesions occurred on the gingiva (33.3%), palatal mucosa (33.3%), buccal mucosa (16.7%), and upper lip (16.7%). Deposition of amorphic bluish/amphophilic material in the subepithelial areas was seen in all cases confirmed with the Verhoeff-van Gieson stain. Our case series demonstrates the presence of elastic fibers in reactive lesions such as oral fibromas.
Late Recurrent Spitz Melanoma With a TMEM106B::BRAF Fusion
Authors: Koga Shunsuke , Karakousis Giorgos C. , Yang Guang , Elder David E.
Published: February 2025

Melanoma is a clinically and genetically heterogeneous malignancy that can recur long after initial treatment. We report the case of a 70-year-old man who presented with metastatic cutaneous melanoma 36 years after the initial diagnosis. Initially diagnosed with nodular melanoma on the left heel at age 34 years, the patient experienced metastatic spread to the left groin lymph nodes by age 36 years, followed by various systemic therapies, including interferon and cytokine therapy, and subsequent observation, over 15 years. Two years before his current presentation, the patient noted a growing mass in his right thigh and an enlarged left inguinal lymph node. Fine-needle aspiration biopsy of the lymph node confirmed the recurrence of melanoma. He subsequently underwent inguinofemoral lymph node dissection and resection of the right thigh mass. Histopathological evaluation revealed melanoma characterized by tumorigenic proliferation of pleomorphic epithelioid and spindle cells with abundant eosinophilic cytoplasm, large nuclei with prominent nucleoli, sparse lymphocyte infiltration, and minimal necrosis, consistent with an initial diagnosis of Spitzoid melanoma. Genetic profiling using targeted next-generation sequencing identified a novel TMEM106B::BRAF fusion, along with CHEK2 and MUTYH mutations. The BRAF fusion supports the diagnosis of Spitz melanoma, a genetically defined subset of Spitzoid melanoma. This case represents the first report of a TMEM106B::BRAF fusion in melanoma, emphasizing the critical role of molecular profiling in diagnosing and managing this malignancy, and suggesting a potential avenue for future therapeutic exploration.