bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multivariate patterns among multimodal neuroimaging and clinical, cognitive, and daily functioning characteristics in bipolar disorder
Authors: Damgaard Viktoria , Fortea Lydia , Schandorff Johanna M. , Macoveanu Julian , Little Bethany , Gallagher Peter , Knudsen Gitte M. , Kessing Lars V. , Miskowiak Kamilla W. 
Published: January 2025

AbstractIndividuals with bipolar disorder (BD) show heterogeneity in clinical, cognitive, and daily functioning characteristics, which challenges accurate diagnostics and optimal treatment. A key goal is to identify brain-based biomarkers that inform patient stratification and serve as treatment targets. The objective of the present study was to apply a data-driven, multivariate approach to quantify the relationship between multimodal imaging features and behavioral phenotypes in BD. We pooled structural, task and resting-state functional magnetic resonance imaging (MRI), and clinical, cognitive, and functioning data from 167 fully or partly remitted patients with BD from three studies conducted at the same site. We performed canonical correlation analysis (CCA) to investigate multivariate relations among the 56 imaging and 23 behavioral features in patients. Data from 46 matched healthy controls were included for covariate-adjusted standardization of patients’ scores and for group comparisons. The imaging and behavioral data sets showed a strong canonical correlation (r = 0.84, p = .004). Among the behavioral variables, cognitive test scores across psychomotor speed, verbal memory, and verbal fluency were associated with the multimodal imaging variate comprising task activation within the dorsolateral prefrontal cortex and supramarginal gyrus, also when other clinical and daily functioning variables were considered. Task activation within the dorsal prefrontal and parietal cognitive control areas constitutes a potential pro-cognitive treatment target.
Neoadjuvant or concurrent atezolizumab with chemoradiation for locally advanced cervical cancer: a randomized phase I trial
Authors: Mayadev Jyoti , Zamarin Dmitriy , Deng Wei , Lankes Heather A. , Pesci Giulio , Kim Hayeon , Chino Junzo P. , Banbury Barbara , Sherry Ned , Sharon Elad , Ghamande Sharad A. , Ferguson Catherine , Mell Loren , Holman Laura , Mathews Cara , O’Malley David , Olawaiye Alexander , Hopp Elizabeth , Leath Charles , Copeland Larry , Mannel Robert , O’Cearbhaill Roisin , Aghajanian Carol , Schilder Russell J. 
Published: January 2025

AbstractCombined immune checkpoint blockade (ICB) and chemoradiation (CRT) is approved in patients with locally advanced cervical cancer (LACC) but optimal sequencing of CRT and ICB is unknown. NRG-GY017 (NCT03738228) was a randomized phase I trial of atezolizumab (anti-PD-L1) neoadjuvant and concurrent with CRT (Arm A) vs. concurrent with CRT (Arm B) in patients with high-risk node-positive LACC. The primary endpoint was the fraction of expanded tumor-associated T-cell receptor (TCR) clones in blood at day 21 as a surrogate measure of anti-tumor immune response. Secondary objectives were safety and feasibility, 2-year disease-free survival (DFS), and predictive value of PD-L1 expression. Forty patients were randomized, 36 received treatment, and 25 were evaluable for the primary endpoint. After cycle 1, there was peripheral expansion of higher proportion of tumor-associated TCR clones in Arm A than in Arm B (p = 0.0025) that remained higher at day 21, meeting the pre-specified endpoint on two-sample T-test (p = 0.052), but not on sensitivity analysis by Wilcoxon test (p = 0.13). At the median follow up of 25.8 months, 2-year DFS was 76% in Arm A and 56% in Arm B (p = 0.28). There were no new safety signals. In conclusion, neoadjuvant ICB prior to CRT was safe and was associated with immunologically and clinically favorable outcomes, warranting larger confirmatory studies.
Structural insights into isoform-specific RAS-PI3Kα interactions and the role of RAS in PI3Kα activation
Authors: Czyzyk Daniel , Yan Wupeng , Messing Simon , Gillette William , Tsuji Takashi , Yamaguchi Mitsuhiro , Furuzono Shinji , Turner David M. , Esposito Dominic , Nissley Dwight V. , McCormick Frank , Simanshu Dhirendra K. 
Published: January 2025

AbstractMutations in RAS and PI3Kα are major drivers of human cancer. Their interaction plays a crucial role in activating PI3Kα and amplifying the PI3K-AKT-mTOR pathway. Disrupting RAS-PI3Kα interaction enhances survival in lung and skin cancer models and reduces tumor growth and angiogenesis, although the structural details of this interaction remain unclear. Here, we present structures of KRAS, RRAS2, and MRAS bound to the catalytic subunit (p110α) of PI3Kα, elucidating the interaction interfaces and local conformational changes upon complex formation. Structural and mutational analyses highlighted key residues in RAS and PI3Kα impacting binding affinity and revealed isoform-specific differences at the interaction interface in RAS and PI3K isoforms, providing a rationale for their differential affinities. Notably, in the RAS-p110α complex structures, RAS interaction with p110α is limited to the RAS-binding domain and does not involve the kinase domain. This study underscores the pivotal role of the RAS-PI3Kα interaction in PI3Kα activation and provides a blueprint for designing PI3Kα isoform-specific inhibitors to disrupt this interaction.
High-impedance microwave resonators with two-photon nonlinear effects
Authors: Andersson S. , Havir H. , Ranni A. , Haldar S. , Maisi V. F. 
Published: January 2025

AbstractNonlinear effects play a central role in photonics as they form the foundation for most of the device functionalities such as amplification and quantum state preparation and detection. Typically the nonlinear effects are weak and emerge only at high photon numbers with strong drive. Here we present an experimental study of a Josephson junction -based high-impedance resonator. We show that by taking the resonator to the limit of consisting effectively only of one junction, results in strong nonlinear effects already for the second photon while maintaining a high impedance of the resonance mode. Our experiment yields thus resonators with strong interactions both between individual resonator photons and from the resonator photons to other electric quantum systems. We also present an energy diagram technique which enables to measure, identify and analyse different multi-photon optics processes along their energy conservation lines.
Thermally driven quantum refrigerator autonomously resets a superconducting qubit
Authors: Aamir Mohammed Ali , Jamet Suria Paul , Marín Guzmán José Antonio , Castillo-Moreno Claudia , Epstein Jeffrey M. , Yunger Halpern Nicole , Gasparinetti Simone 
Published: January 2025

Abstract
Although classical thermal machines power industries and modern living, quantum thermal engines have yet to prove their utility. Here, we demonstrate a useful quantum absorption refrigerator formed from superconducting circuits. We use it to cool a transmon qubit to a temperature lower than that achievable with any one available bath, thereby resetting the qubit to an initial state suitable for quantum computing. The process is driven by a thermal gradient and is autonomous, requiring no external feedback. The refrigerator exploits an engineered three-body interaction between the target qubit and two auxiliary qudits. Each auxiliary qudit is coupled to a physical heat bath, realized with a microwave waveguide populated with synthesized quasithermal radiation. If the target qubit is initially fully excited, its effective temperature reaches a steady-state level of approximately 22 mK, lower than what can be achieved by existing state-of-the-art reset protocols. Our results demonstrate that superconducting circuits with propagating thermal fields can be used to experimentally explore quantum thermodynamics and apply it to quantum information-processing tasks.
A scalable variational inference approach for increased mixed-model association power
Authors: Loya Hrushikesh , Kalantzis Georgios , Cooper Fergus , Palamara Pier Francesco 
Published: January 2025

Abstract
The rapid growth of modern biobanks is creating new opportunities for large-scale genome-wide association studies (GWASs) and the analysis of complex traits. However, performing GWASs on millions of samples often leads to trade-offs between computational efficiency and statistical power, reducing the benefits of large-scale data collection efforts. We developed Quickdraws, a method that increases association power in quantitative and binary traits without sacrificing computational efficiency, leveraging a spike-and-slab prior on variant effects, stochastic variational inference and graphics processing unit acceleration. We applied Quickdraws to 79 quantitative and 50 binary traits in 405,088 UK Biobank samples, identifying 4.97% and 3.25% more associations than REGENIE and 22.71% and 7.07% more than FastGWA. Quickdraws had costs comparable to REGENIE, FastGWA and SAIGE on the UK Biobank Research Analysis Platform service, while being substantially faster than BOLT-LMM. These results highlight the promise of leveraging machine learning techniques for scalable GWASs without sacrificing power or robustness.
Deep sequencing-derived Metagenome Assembled Genomes from the gut microbiome of liver transplant patients
Authors: Banerjee Goutam , Papri Suraya Rahman , Huang Hai , Satapathy Sanjaya Kumar , Banerjee Pratik 
Published: January 2025

AbstractRecurrence of metabolic dysfunction-associated steatotic liver disease (MASLD) after liver transplantation (LT) is a continuing concern. The role of gut microbiome dysbiosis in MASLD initiation and progression has been well established. However, there is a lack of comprehensive gut microbiome shotgun sequence data for patients experiencing MASLD recurrence after LT. In this data descriptor, we describe a dataset of deep metagenomic sequences of a well-defined LT recipient population. Community-based analysis revealed a high abundance of Akkermansia muciniphila, consistently observed in most patient samples with a low (0–2) MASLD Activity Score (NAS). We constructed 357 metagenome-assembled genomes (MAGs), including 220 high-quality MAGs (>90% completion). The abundance of different species of Bacteroides MAGs dominated in patient samples with NAS > 5 (“definite MASH”). In contrast, the MAGs of A. muciniphila, Akkermansia sp., and Blutia sp. dominated in samples from patients without MASH (NAS = 0–2). In addition, the phylogenetic analysis of A. muciniphila and Akkermansia sp. MAGs identified two new phylogroups of Akkermansia that are distinct from the previously reported three phylogroups.
Usability, acceptance, and the role of realism in virtual humans for breathing exercise training
Authors: Dar Sanobar , Ekart Aniko , Bernardet Ulysses 
Published: January 2025

AbstractBreathing exercises are used to address a multitude of issues ranging from mental health to physical well-being. While they are recommended for various health conditions, access to professional support is often limited due to time and cost constraints. Virtual Reality technology offers a promising solution for enhancing mindfulness and relaxation practices, including breathing exercises. In our study, we explored the effectiveness of a computer-generated “virtual breathing coach”. Our virtual coach has a human appearance, speaks in a human voice, and displays breathing physiology while guiding the participants through a set of breathing exercises of different cycle lengths. The agent exhibits breathing behaviour with the aim of augmenting the influence the agent exerts through the mechanisms of physiological entrainment known from human-to-human interaction. Our empirical, exploratory study with 20 participants, was conducted using non-immersive VR where the system ran on a web browser. On the one hand, we investigated the perception of the virtual human coach, and on the other hand, we evaluated the usability, acceptability, and adherence of the system. We also evaluated the role of realism in acceptance of and adherence to the virtual coach. Participants’ responses were recorded using questionnaires. Participants were influenced by the virtual coach and adhered to it if they perceived the virtual coach as more realistic. The participants reported that the system ran well, and they would be willing to continue using the system in the future. Although the virtual human-to-human interaction experience provided by our system is not on par with the naturalistic human-to-human interaction, the results indicate that people are willing to replace a real human coach with a virtual coach. Systems like this are a step towards improving the affordability and on-demand access to another human, such as a coach in our system, especially where access and affordability are limited such as in healthcare. The qualities such as trust and likeability in an embodied interaction can make this interaction more efficient and effective.
Clinical characteristics of anti-myelin oligodendrocyte glycoprotein antibody among aquaporin-4 negative neuromyelitis optica spectrum disorders in Egyptian patients
Authors: Taha Sara I. , Bakr Salwa I. , Fouad Nermeen T. , Zamzam Dina , Mohamed Yasmine A. 
Published: January 2025

AbstractSome patients with neuromyelitis optica spectrum disorder (NMOSD)-like symptoms test negative for anti-aquaporin-4 (anti-AQP4) antibodies. Among them, a subset has antibodies targeting myelin oligodendrocyte glycoprotein (MOG), a condition now termed MOG antibody-associated disease (MOGAD). MOGAD shares features with NMOSD, like optic neuritis and myelitis, but differs in pathophysiology, clinical presentation, imaging findings, and biomarkers. The present study investigated the prevalence of anti-myelin oligodendrocyte glycoprotein (anti-MOG) antibodies in anti-AQP4 seronegative Egyptian patients initially diagnosed with NMOSD and the link between their presence and clinical characteristics and disease-induced disability to gain insights into MOGAD. This pilot cross-sectional study included 40 anti-AQP4 antibody-negative patients initially diagnosed with NMOSD, six children and 34 adults. They were screened for anti-MOG antibodies by the indirect immunofluorescence cell-based assay. Of all included patients, only 7.5% (n = 3) were positive for anti-MOG antibodies and had significantly higher disability scores than seronegative patients (p = 0.021). The presence of anti-MOG antibodies was not significantly associated with age (p = 0.696), gender (p = 0.232), type of relapse (p = 0.488), number of attacks (p = 0.968), family history of consanguinity (p = 0.211), family history of autoimmune disease (p = 0.608), nor with smoking (p = 0.608). Detecting anti-MOG antibodies in anti-AQP4-negative NMOSD patients is essential for accurate diagnosis and personalized treatment, as MOGAD is now recognized as a separate clinical entity.
Pathological variants in HPV-independent vulvar tumours
Authors: Farkas Sanja A. , Qvick Alvida , Helenius Gisela , Lillsunde-Larsson Gabriella 
Published: January 2025

AbstractVulvar cancer is a rare gynaecological disease that can be caused by infection with human papillomavirus (HPV). The mutational frequencies and landscape for HPV-associated and HPV-independent vulvar tumor development are supposedly two distinctly different pathways and more detailed knowledge on target biological mechanisms for individualized future treatments is needed. The study included formalin-fixed paraffin-embedded (FFPE) samples from 32 cancer patients (16 HPV-negative and 16 HPV-associated), treated in Örebro, Sweden from 1988 to 2008. The Oncomine™ Comprehensive Assay v3 was used to detect variants across 161 different tumor relevant genes. Data analysis included quality assessment followed by variant analysis of DNA with the Oncomine Comprehensive v3 workflow and with a custom filter using the VarSome Clinical software. The RNA-analysis was performed with the Oncomine Comprehensive v3 workflow. Totally, 94% of DNA libraries and 81% of RNA libraries were of adequate quality for further downstream analysis. With the Oncomine™ filter chain there was an increased number of variants in the HPV-negative group (2.5 variants) compared to the HPV-associated group (1.5 variants). Using custom filter and the Varsome Clinical software; additional single nucleotide variants (SNV) were detected where the vast majority were classified as likely benign/benign. HPV-negative tumors had a larger fraction of variants of unknown significance (VUS), and likely pathogenic/pathogenic compared to the HPV-associated tumours. The top 10 frequently mutated genes in HPV-indepentent tumors were TP53, POLE, PTCH1, BRCA2, CREBBP, NOTCH2, ARID1A, CDKN2A, MSH2, and NOTCH1. Three fusion genes were detected; TBL1XR1(1)::PIK3CA(2) (n = 2) and NF1(5)::PSMD11(2) (n = 1). Copy number variations (CNV) were more common in HPV-associated tumors (n = 13/16, 81%) compared to HPV-negative tumors (n = 9/14, 64%). The most frequent CNV was found in the cMYC gene, followed by CDK2 (n = 5) and CDK4 (n = 4). The main outcome of this study show that vulvar cancer harbour genetic variations of different types and specifically, HPV-independent tumours are molecularly very heterogeneous and harboured more SNVs while HPV-associated tumors more frequently presented with gene amplifications. The PI3K/AKT/mTOR1 pathway was affected in both the groups as well as the cell cycle regulation pathway. Similarly, the DNA repair gene POLE was found mutated in both vulvar cancer groups.
Comparing multi-texture fibrosis analysis versus binary opacity-based abnormality detection for quantitative assessment of idiopathic pulmonary fibrosis
Authors: Nowak Sebastian , Creuzberg Dominik , Theis Maike , Pizarro Carmen , Isaak Alexander , Pieper Claus C. , Luetkens Julian A. , Skowasch Dirk , Sprinkart Alois M. , Kütting Daniel 
Published: January 2025

AbstractAutomated tools for quantification of idiopathic pulmonary fibrosis (IPF) can aid in ensuring reproducibility, however their complexity and costs can differ substantially. In this retrospective study, two automated tools were compared in 45 patients with biopsy proven (12/45) and imaging-based (33/45) IPF diagnosis (mean age 74 ± 9 years, 37 male) for quantification of pulmonary fibrosis in CT. First, a tool that identifies multiple characteristic lung texture features was applied to measure multi-texture fibrotic lung (MTFL) by combining the amount of ground glass, reticulation, and honeycombing. Opacity-based fibrotic lung (OFL) was measured by a second tool that performs a simpler binary classification of tissue into either normal or opacified lung and was originally developed for quantifying pneumonia. Differences in quantification of MTFL and OFL were assessed by Mann-Whitney U-test and Pearson correlation (r). Also, correlation with spirometry parameters (percent predicted total lung capacity (TLC), percent predicted vital capacity (VC), percent predicted forced expiratory volume in 1 s (FEV1), diffusing capacity of the lungs for carbon monoxide (DLCO), partial pressure of oxygen (PO2) and carbon dioxide (PCO2)) were assessed by r. The prognostic values for 3-year patient survival of OFL, LSS and MTFL were investigated by multivariable Cox-proportional-hazards (CPH) models including sex, age and TLC and including sex, age and VC. Also, Kaplan-Meier analysis with log rank test between subgroups separated by median OFL and MTFL were conducted. No significant difference between OFL and MTFL was observed (median and interquartile range: OFL = 29% [20-38%], MTFL = 31% [19-45%]; P = 0.44). For OFL significant correlation was observed to MTFL (r = 0.93, P < 0.01) and VC (r=-0.50, P = 0.03). For MTFL no significant correlation to spirometry parameters was found. The total time for one analysis was lower for the automated MTFL (MTFL: 313 ± 25s vs. OFL: 612 ± 61s, P < 0.001). Both analyses were significant predictors in the multivariable CPH analysis including TLC (hazard-ratios: MTFL 1.03 [1.01–1.06], P = 0.02; OFL 1.03 [1.00-1.06], P = 0.03). No parameter was a significant predictor in the CPH models including VC (hazard-ratios: MTFL 1.01 [0.98–1.04], P = 1; OFL 1.01 [0.97–1.05], P = 1). OFL showed significance in Kaplan-Meier analysis (MTFL: P = 0.17; OFL: P = 0.03). Using a simple opacity-based quantification of pulmonary fibrosis in IPF patients displayed similar results and prognostic value compared to a more complex multi-texture based analysis.
Optimization of parallel coiled cavities of different depths in microperforated panel sound absorbers
Authors: Min Hequn , Lou Huading , Zhao Yuchen 
Published: January 2025

AbstractThis paper presents a microperforated panel (MPP) sound absorber with parallel coiled-up-cavities of different-depths (PCD) and the corresponding optimization on their cavities. In this study, an analytical model is initially proposed for estimating the cavity depths of the PCD-MPP absorber upon normal incidence absorption coefficient evaluation at given resonance frequencies. Cavity effective depths and normal incidence absorption coefficient are evaluated after coiling up cavities for a compact structure. Numerical simulations with the finite element method and experiments are conducted for validations. Subsequently, a design process is suggested on the basis of the proposed model for sound absorption optimization. Results show that, absorption coefficient from the proposed analytical model agrees well with finite element simulations and experiments. It is also shown that, for the effective depth evaluation of the coiled-up cavities of PCD-MPP absorbers, the diagonal lines of subchannels of coiled-up cavities with a coiled-up angle of 180° can accurately represent the effective depths, while the combination of centerlines of subchannels and quarter arc inside the coiled-up area is more suitable for those with a coiled-up angle of 90°. Optimization investigation shows that, PCD-MPP absorbers can have high absorption performance with the averaged and maximum absorption coefficient of 0.91 and 0.98 within the target bandwidth of 400–1600 Hz, where the absorber thickness can stay below 65 mm. This work can provide valuable guidelines for the design of sound absorbers for broadband absorption.
Engineering performance and environmental assessment of sustainable concrete incorporating nano silica and metakaolin as cementitious materials
Authors: Raveendran Namitha , Krishnan Vasugi 
Published: January 2025

AbstractThe carbon footprint associated with cement production, coupled with depletion of natural resources and climate change, underscores the need for sustainable alternatives. This study explores the effect of metakaolin (MK) and nano-silica (NS) on concrete’s engineering performance and environmental impact. Initially, compressive, tensile, and flexural strength tests, along with durability assessments like water absorption, sorptivity, rapid chloride permeability, and resistance to acid and sulphate attacks, were conducted. Later, X-ray Diffraction spectroscopy and Field-emission scanning electron microscopy were employed for microstructural analysis. Subsequently, the environmental impact of micro and nano materials was assessed using embodied carbon emissions and eco-strength efficiency. The results revealed that the hybrid mixes of 12.50% MK and 2% NS (M7) showed superior performance, demonstrating significant strength enhancements and eco-efficiency, achieving 0.15 MPa/kg CO2/m3 at 28th day. Meanwhile, the MK-only mix (M6) yielded the lowest embodied CO2 emissions at 330 kg CO2/m3. MK and NS effectively reduce porosity and enhance durability against environmental factors while lowering clinker content, contributing to sustainability. Furthermore, the microstructural behaviour showed early hydration, dense microstructure and additional Calcium Silicate Hydrate formation, leading to improved properties. The outcomes reveal that the concrete configuration has altered at micro and nano levels by the inclusion of MK and NS, demonstrating their substantial contribution to producing environmentally friendly, effective, and beneficial concrete.