bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluating the implementation of online research training and mentorship among early-career family physicians in sub-Saharan Africa
Authors: Schouw Darcelle , Mash Robert , Ameh Pius , Fatusin Bolatito B. , Engmann Stephen
Published: January 2025

Background:

Research is needed to improve the performance of primary health care. In Africa, few family physicians conduct research, and therefore an online research training and mentorship programme was developed to build research capacity amongst novice and early career researchers.

Aim:

To evaluate the implementation of the AfriWon Research Collaborative (ARC) training and e-mentorship programme in sub-Saharan Africa.

Methods:

A 10-module online curriculum was supported by peer and faculty e-mentorship, to mentor participants in writing a research protocol. A convergent mixed methods study combined quantitative and qualitative data to evaluate nine implementation outcomes.

Findings:

Fifty-three participants (20 mentees, 19 peer mentors, and 14 faculty mentors), mostly male (70%), participated in the ARC online programme. The programme was seen as an acceptable and appropriate initiative. Mentees were mostly postgraduate students from African countries. Faculty mentors were mostly experienced researchers from outside of Africa. There were issues with team selection, orientation, communication, and role clarification. Only 35% of the mentees completed the programme. Alignment of mentoring in teams and engagement with the online learning materials was an issue. Costs were relatively modest and dependent on donor funds.

Conclusion:

Despite many challenges, the majority of participants supported the sustainability of the programme. The evaluation highlights the strengths and weaknesses of the ARC programme and e-mentoring. The ARC working group needed to ensure better organization and leadership of the teams. Going forward the programme should focus more on developing peer mentors and local supervisory capacity as well as the mentees.
Human Health, Ecosystem Quality, and Resource Scarcity Burdens Inflicted by Livestock Production Across Chinese Regions
Authors: Shao Yixuan , Cao Qilin , Song Junnian , Xing Jiahao , Wu You , Sun Cheng , He Pan , Yang Wei
Published: January 2025

Surge in global population and shift toward animal‐based diets have accelerated expansion of livestock production, posing various environmental challenges. It requires inventorying localized, activity‐specific, and indicator‐extended multidimensional eco‐environmental burdens and revealing their transfers within interregional trade to inform holistic livestock production management from both production and consumption sides. Herein, we construct a life cycle framework covering multiple livestock species, feeding regimes, and activities to evaluate nine environmental impacts ending up as human health, ecosystem quality and resource scarcity burdens in Chinese provincial regions. Multi‐regional input‐output analysis is then conducted to trace transfers of these burdens embedded within trade associated with livestock production. Results indicate that fine particulate matter formation (mainly by livestock housing) and climate change (mainly by enteric fermentation) contribute greater than 60% and 30% to health burdens. Besides for health burdens, for ecosystem burdens primarily caused by housing, and resource burdens mainly aggravated by high on‐farm energy use, poultry results in the highest level. The main production regions Shandong, Henan and Sichuan lead from perspectives of both production and consumption‐based burdens. Whereas regions with the largest export (Inner Mongolia, 3.87 × 104 DALY for health burdens) or import (Guangdong, 3.92 × 104 DALY for health burdens) do not necessarily bear greatest burdens. This work provides policy instructions in mitigating various eco‐environmental burdens imposed by livestock production and promoting sustainable agricultural practices.
Experimental Analyses of Pore‐Size Dependent Biomineralization in Porous Media Under Various Flow Rate and Bacterial Density Scenarios
Authors: Yang Ze , Dou Zhi , Guadagnini Alberto , Li Xiaoteng , Wang Chaoqi , Wang Jinguo
Published: January 2025

We document results of a set of laboratory experiments aimed at exploring impacts of injection rate and bacterial density on biomineralization across water‐saturated porous media. The study relies on a Low‐Field Nuclear Magnetic Resonance technology and the ensuing transverse spin‐spin relaxation time distributions. The latter is documented to provide a robust quantification of temporal histories of pore size distributions during biomineralization. As such, our work explores and quantifies pore‐size dependent biomineralization across the three‐dimensional pore space. The study also provides a quantitative analysis of alterations in porosity and permeability induced by biomineralization, together with a quantification of (time‐averaged) rates of pore volume change. A plugging ratio efficiency index is introduced to quantify the strength of pore‐size‐related biomineralization. Our results reveal that biomineralization induces significant alterations in the pore size distribution within a porous medium, these changes being modulated by bacterial density and injection rate. We find that CaCO3 mainly precipitates in macropores, consistent with the presence of favorable local hydrodynamic conditions and large surface areas therein. Precipitated CaCO3 volume is found to increase with bacterial density. High bacterial densities amplify rate of pore volume change within macropores and adequate plugging ratio of biomineralization and contribute to a significant permeability reduction. Otherwise, a diminished strength of biomineralization in mesopores and micropores is documented for the highest injection rates considered.
Quantifying Dynamic Linkages Between Precipitation, Groundwater Recharge, and Streamflow Using Ensemble Rainfall‐Runoff Analysis
Authors: Gao Huibin , Ju Qin , Zhang Dawei , Wang Zhenlong , Hao Zhenchun , Kirchner James W.
Published: January 2025

Understanding streamflow generation at the catchment scale requires quantifying how different components of the system are linked, and how they respond to meteorological forcing. Here we present a proof‐of‐concept study characterizing and quantifying dynamic linkages between precipitation, groundwater recharge, and streamflow using a data‐driven nonlinear deconvolution and demixing approach, Ensemble Rainfall‐Runoff Analysis (ERRA). Streamflow in our mesoscale, intensively farmed test catchment is flashy, but occurs at time lags that are too long to be plausibly attributed to overland flow. Instead, ERRA's estimates of the impulse responses of groundwater recharge to precipitation, and of streamflow to groundwater recharge, imply that this intermittent streamflow is primarily driven by precipitation infiltrating to recharge groundwater, followed by discharge of groundwater to streamflow. ERRA reveals that streamflow increases nonlinearly with increasing precipitation intensity or groundwater recharge, and exhibits almost no response to precipitation or recharge rates of less than 10 mm d−1. Groundwater recharge is both nonlinear, increasing more‐than‐proportionally with precipitation intensity, and nonstationary, increasing with antecedent wetness. Simulations with the infiltration model Hydrus‐1D can reproduce the observed water table time series reasonably well (NSE = 0.70). However, ERRA shows that the model's impulse response is inconsistent with the real‐world impulse response estimated from measured precipitation and groundwater recharge, illustrating that conventional goodness‐of‐fit statistics can be weak tests of model realism. Thus, our proof‐of‐concept study demonstrates how impulse responses estimated by ERRA can help clarify linkages between precipitation and streamflow at the catchment scale, quantify nonlinearity and nonstationarity in hydrologic processes, and critically evaluate simulation models.
Machine learning assisted plasmonic metascreen for enhanced broadband absorption in ultra-thin silicon films
Authors: Ahmed Waqas W. , Cao Haicheng , Xu Changqing , Farhat Mohamed , Amin Muhammad , Li Xiaohang , Zhang Xiangliang , Wu Ying
Published: January 2025

We propose and demonstrate a data-driven plasmonic metascreen that efficiently absorbs incident light over a wide spectral range in an ultra-thin silicon film. By embedding a double-nanoring silver array within a 20 nm ultrathin amorphous silicon (a-Si) layer, we achieve a significant enhancement of light absorption. This enhancement arises from the interaction between the resonant cavity modes and localized plasmonic modes, requiring precise tuning of plasmon resonances to match the absorption region of the silicon active layer. To facilitate the device design and improve light absorption without increasing the thickness of the active layer, we develop a deep learning framework, which learns to map from the absorption spectra to the design space. This inverse design strategy helps to tune the absorption for selective spectral functionalities. Our optimized design surpasses the bare silicon planar device, exhibiting a remarkable enhancement of over 100%. Experimental validation confirms the broadband enhancement of light absorption in the proposed configuration. The proposed metascreen absorber holds great potential for light harvesting applications and may be leveraged to improve the light conversion efficiency of ultra-thin silicon solar cells, photodetectors, and optical filters.
Re-encountering the phobic cue within days after a reconsolidation intervention is crucial to observe a lasting fear reduction in spider phobia
Authors: Peters Jacqueline , Filmer Anna I. , van Doorn Johnny B. , Metselaar Vivian N. , Visser Renée M. , Kindt Merel
Published: January 2025

Memory reconsolidation interventions offer an exciting alternative to exposure treatment because they may target fear memories directly, thereby preventing relapse. A previous reconsolidation intervention for spider fear abruptly reduced avoidance behaviour, whereas changes in self-reported fear followed later. In this pre-registered placebo-controlled study, we first aimed to conceptually replicate these effects in spider phobia. Second, we investigated whether re-encountering the phobic cue after the reconsolidation intervention is necessary for changes in self-reported fear to occur. Third, we tested whether the window to trigger such changes is time limited. Individuals with spider phobia (N = 69) were randomized into three groups and underwent a memory reactivation procedure with a tarantula, followed immediately by propranolol (reconsolidation intervention) or placebo. One reconsolidation intervention group and the placebo group re-encountered spiders two days after treatment in behavioural approach tasks, whereas another reconsolidation intervention group re-encountered spiders after four weeks. Changes in spider avoidance behaviour and self-reported fear were followed for one year. In the short term, the reconsolidation intervention was not more effective than placebo: both conditions benefited from the intervention. In the long term, the reconsolidation intervention was more effective than placebo, but only when the phobic stimulus was re-encountered within days after treatment. Specifically, we found less tarantula avoidance behaviour and self-reported fear over the course of one year when spiders were re-encountered two days after the reconsolidation intervention, but not when the behavioural test was conducted four weeks after the intervention. These findings challenge the idea that a reconsolidation-inspired intervention alone is sufficient to treat clinical fears: Experiencing the behavioural change during the re-encounter within days after the reconsolidation window has closed seems crucial to observe a lasting fear reduction.
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

Individuals 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

Combined 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

Mutations 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

Nonlinear 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

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

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

Recurrence 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

Breathing 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

Some 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

Vulvar 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

Automated 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

This 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

The 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.
Excited state dynamics of azanaphthalenes reveal opportunities for the rational design of photoactive molecules
Authors: Garrow Malcolm , Bertram Lauren , Winter Abi , Prentice Andrew W. , Crane Stuart W. , Lane Paul D. , Greaves Stuart J. , Paterson Martin J. , Kirrander Adam , Townsend Dave
Published: January 2025

Various photoactive molecules contain motifs built on aza-aromatic heterocycles, although a detailed understanding of the excited state photophysics and photochemistry in such systems is not fully developed. To help address this issue, the non-adiabatic dynamics operating in azanaphthalenes under hexane solvation was studied following 267 nm excitation using ultrafast transient absorption spectroscopy. Specifically, the species quinoline, isoquinoline, quinazoline, quinoxaline, 1,6-naphthyridine, and 1,8-naphthyridine were investigated, providing a systematic variation in the relative positioning of nitrogen heteroatom centres within a bicyclic aromatic structure. Our results indicate considerable differences in excited state lifetimes, and in the propensity for intersystem crossing vs internal conversion across the molecular series. The overall pattern of behaviour can be explained in terms of potential energy barriers and spin-orbit coupling effects, as demonstrated by extensive quantum chemistry calculations undertaken at the SCS-ADC(2) level of theory. The fact that quantum chemistry calculations can achieve such detailed and nuanced agreement with experimental data across a full set of six molecules exhibiting subtle variations in their composition provides an excellent example of the current state-of-the-art and is indicative of future opportunities for rational design of photoactive molecules.
Dynamic effects of psychiatric vulnerability, loneliness and isolation on distress during the first year of the COVID-19 pandemic
Authors: Atlas Lauren Y. , Farmer Cristan , Shaw Jacob S. , Gibbons Alison , Guinee Emily P. , Lossio-Ventura Juan Antonio , Ballard Elizabeth D. , Ernst Monique , Japee Shruti , Pereira Francisco , Chung Joyce Y.
Published: January 2025

The COVID-19 pandemic’s impact on mental health is challenging to quantify because pre-existing risk, disease burden and public policy varied across individuals, time and regions. Longitudinal, within-person analyses can determine whether pandemic-related changes in social isolation impacted mental health. We analyzed time-varying associations between psychiatric vulnerability, loneliness, psychological distress and social distancing in a US-based study during the first year of the pandemic. We surveyed 3,655 participants about psychological health and COVID-19-related circumstances every 2 weeks for 6 months. We combined self-reports with regional social distancing estimates and a classifier that predicted probability of psychiatric diagnosis at enrollment. Loneliness and psychiatric vulnerability both impacted psychological distress. Loneliness and distress were also linked to social isolation and stress associated with distancing, and psychiatric vulnerability shaped how regional distancing affected loneliness across time. Public health policies should address loneliness when encouraging social distancing, particularly in those at risk for psychiatric conditions.
OTUD6B regulates KIFC1-dependent centrosome clustering and breast cancer cell survival
Authors: Marotta Valeria E , Sabat-Pośpiech Dorota , Fielding Andrew B , Ponsford Amy H , Thomaz Amanda , Querques Francesca , Morgan Mark R , Prior Ian A , Coulson Judy M
Published: January 2025

Cancer cells often display centrosome amplification, requiring the kinesin KIFC1/HSET for centrosome clustering to prevent multipolar spindles and cell death. In parallel siRNA screens of deubiquitinase enzymes, we identify OTUD6B as a positive regulator of KIFC1 expression that is required for centrosome clustering in triple-negative breast cancer (TNBC) cells. OTUD6B can localise to centrosomes and the mitotic spindle and interacts with KIFC1. In OTUD6B-deficient cells, we see increased KIFC1 polyubiquitination and premature KIFC1 degradation during mitosis. Depletion of OTUD6B increases multipolar spindles without inducing centrosome amplification. Phenotypic rescue is dependent on OTUD6B catalytic activity and evident upon KIFC1 overexpression. OTUD6B is commonly overexpressed in breast cancer, correlating with KIFC1 protein expression and worse patient survival. TNBC cells with centrosome amplification, but not normal breast epithelial cells, depend on OTUD6B to proliferate. Indeed CRISPR-Cas9 editing results in only OTUD6B

-/+
TNBC cells which fail to divide and die. As a deubiquitinase that supports KIFC1 expression, allowing pseudo-bipolar cell division and survival of cancer cells with centrosome amplification, OTUD6B has potential as a novel target for cancer-specific therapies.
Point-of-care testing of methotrexate using a controlled release sensor based on a personal glucose meter
Authors: Yang Liyu , Yang Siyi , Zhang Ting , Zhao Langyi , Fa Huanbao , Wang Yongzhong , Huo Danqun , Hou Changjun , Yang Mei
Published: January 2025

A controlled-release sensor used a PGM for rapid MTX detection. HP-UiO-66-NH2 stored glucose, and aptamer-conjugated AuNPs acted as gates. It achieved 30 min detection, leveraging the PGM's versatility.
Photoredox cobalt dual catalysis toward C3-functionalization of quinoxalinones with alkenes and alkynes
Authors: Mondal Karunamayee , Pilania Mahima , Jayabalan Karthikeyan , Baidya Mahiuddin
Published: January 2025

A site-selective coupling involving quinoxalin-2-ones with alkenes and alkynes has been developed through synergistic visible-light photoredox cobalt catalysis.
Natural hematite-derived NiFe2O4 as a separator modification material for improved Li–S battery performance
Authors: Zhang Lei , Cui Jiawen , Zhu Haoxian , Yang Kun , Li Wei , Sun Li
Published: January 2025

Utilizing NiFe2O4 from natural hematite as a coating material innovatively enhances lithium–sulfur battery performance and sustainability.
A systematic study on the use of biogenic acids in directing the hyperbranched growth of Au nanocorals
Authors: Ende Christian Paul Y. , Ramos Rufus Mart Ceasar R. , Pangilinan Phil Justin A. , Bautista Rogie I. , Escosio John Rae Louis , Regulacio Michelle D.
Published: January 2025

Hyperbranched Au nanocorals can be readily produced with the right combination of biogenic acids.
Classification of crystal structures of extended aromatic hydrocarbons and the systematic relations
Authors: Mori Takehiko
Published: January 2025

Crystal structures of extended aromatic hydrocarbons are systematically classified starting from the orientation of the non-parallel interaction.
Flux through membrane channel: linear transport vs. single-molecule approaches
Authors: Berezhkovskii Alexander M. , Bezrukov Sergey M.
Published: January 2025

Describing molecule’s motion in the membrane channel by the one-dimensional Smoluchowski equation, one recovers classical results given by the linear transport theory by imposing the radiation boundary conditions at the channel openings.
Tailored on-surface fabrication of mesoporous metallic composites by direct pyrolysis of metal ion-accumulated micellar films for enhanced electrocatalytic water splitting
Authors: Wang Jingchun , Sun Yan , Cui Yan , Qiu Huibin
Published: January 2025

A micellar film system was employed to direct the formation of highly tailored mesoporous metallic composites on eletrode.
pH-Independent lead sequestration and light management enable sustainable and efficient perovskite photovoltaics
Authors: Jin Xi , Li Jun , Zhu Siyuan , Tan Wenyan , Tang Jiahong , Gong Xueyuan , Liu Xingyu , Zhang Yu , Zhou Chao , Tang Zhaoheng , Nyamori Vincent O. , Martincigh Bice S. , Davies Matthew L. , Li Minghua , Chen Tongsheng , Chen Qi , Hu Jinsong , Liang Qijie , Chen Weiqiang , Jiang Yan
Published: January 2025

Textured phosphate-buffered functionalized polymer films are designed to mitigate the lead leakage and optical loss challenges of perovskite solar cells.
Construction of bimetallic oxy-hydroxides based on Ni(OH)2 nanosheets for sensitive non-enzymatic glucose detection via electrochemical oxidation and incorporation
Authors: Dai Weiji , Wu Bing , Zhang Fan , Huang Yuxi , Zhao Cuijiao , Zhang Yudong , Cui Can , Guo Jing , Huang Saifang
Published: January 2025

Bimetallic oxy-hydroxides based on Ni(OH)2 nanosheets ((CoNi)Ox/Ni(OH)2@NF) were prepared by an electrochemical oxidation and incorporation method as high performance non-enzymatic sensors for glucose detection.
Mitochondria-targeting nanostructures from enzymatically degradable fluorescent amphiphilic polyesters
Authors: Biswas Subhendu , Rajdev Priya , Banerjee Ankita , Das Anindita
Published: January 2025

pH-responsive aqueous nanoassembly from a fluorescent neutral polyester selectively targets mitochondria in cancer cells over non-cancerous cells due to positive charge gain, while similar assemblies from cationic polyesters show no such selectivity.
Lignan–phloroglucinol hybrids with an unprecedented beadlike core from the leaves of Melicope chunii
Authors: Fan Shi-Ying , Hong Li-Hong , Wang Yu-Xia , Zhu Jiang-Min , Feng Zi-Tong , Vu Van-Tuan , Kong Ling-Yi , Luo Jian-Guang
Published: January 2025

(±)-Melichuniiones A and B (1 and 2), two novel enantiomeric pairs of lignan–phloroglucinol hybrids with an unprecedented beadlike core were isolated from the leaves of Melicope chunii, together with four new analogues 3–6.
Photoresponsive polymers for carbodiimide-fueled transient hydrogels
Authors: Raji Ibrahim O. , Wilcox Torin C. , Hartley C. Scott , Konkolewicz Dominik
Published: January 2025

Light and fuel responsive polymers were developed. Transient hydrogels could be formed only after exposure to both photochemical and fuel stimuli.
Computational study on Pd-catalyzed ipso,meta-dimethylation of ortho-substituted iodoarenes: mechanisms and the role of the base
Authors: Lv Kang , Zhou Yihang , Meng Zitong , Zhang Jing , Liu Tao
Published: January 2025

The detailed mechanisms of Pd-catalyzed ipso,meta-dimethylation reactions of ortho-substituted iodoarenes and the origin of base-controlled chemoselectivity were investigated by DFT calculations.
Terpene polymerization via a binary neodymium-based catalytic system with di-n-butylmagnesium as a co-catalyst
Authors: Córdova Teresa , Enriquez-Medrano Francisco Javier , Magaña Ilse , García-Zamora Maricela , Jimenéz-Reyes Nelson A. , Mata-Padilla José M. , Cabrera-Álvarez Edgar E. , Valencia Luis , Díaz de León Ramón
Published: January 2025

The Nd-based catalytic system with Mg(n-Bu)2 efficiently polymerizes β-myrcene and β-farnesene, yielding polyterpenes with high controlled microstructures, offering a sustainable strategy for elastomer synthesis from renewable resources.
The influential IPr: 25 years after its discovery
Authors: Voloshkin Vladislav A. , Zorba Leandros P. , Nolan Steven P.
Published: January 2025

25 Years after the discovery of the most influential NHC ligand, we revisit and highlight studies involving IPr that have shaped the field of NHC-transition metal catalysis.
Effect of the molar concentration ratio of copper cobalt phosphate in supercapacitor application
Authors: Sutar Pratik , Deshmukh Puja , Jadhav Amar , Kadam Anamika V.
Published: January 2025

Effect of the molar concentration ratio of copper cobalt phosphate in supercapacitor.
Enhancing the performance and safety of quasi-solid-state zinc ion batteries through advanced electrolyte and material design
Authors: Dou Qianqian , Tan Huiyun , Feng Wenhao , Wu Mengfei , Sun Tianci , Deng Shuolei , Liu Ao , Dong Yifan
Published: January 2025

Schematic diagram of ion transport.
α-Synuclein interaction with POPC/POPS vesicles
Authors: Dubackic Marija , Lattanzi Veronica , Liu Yun , Haertlein Michael , Devos Juliette M. , Sparr Emma , Linse Sara , Olsson Ulf
Published: January 2025

We have investigated the adsorption of α-Synuclein (αSyn) onto small unilamellar vesicles composed of zwitterionic POPC and anionic POPS lipids, as well as the impact αSyn fibril formation has on vesicle stability.
Calcination-driven enhancement of LAGP for high-performance solid-state lithium metal batteries
Authors: Jung Seo In , Nasir Mohammad , Park Hee Jung
Published: January 2025

Tailored calcination and sintering processes influence the microstructure and ionic conductivity of LAGP electrolytes. Optimized LAGP_700 shows improved conductivity and cycling performance.