bluuebunny/crossref_metadata_2025 huggingface dataset:
Habituation of vestibular‐evoked balance responses after repeated exposure to a postural threat
Authors: Zaback Martin , Villemer Solenne , Missen Kyle J. , Inglis J. Timothy , Carpenter Mark G.
Published: February 2025

Vestibular‐evoked balance responses are facilitated when faced with threats to stability. However, the extent to which these sensorimotor adaptations covary with changes in emotional and autonomic state remains unclear. This study repeatedly exposed individuals to the same postural threat while vestibular‐motor responses were probed using stochastic vestibular stimulation (SVS; 2–25 Hz). This allowed emotional and autonomic state to be manipulated within the same threat environment to determine if vestibular‐evoked balance responses are coupled with the emotional/autonomic changes induced by the threat or are facilitated in a strictly context‐dependent manner. Twenty‐three young adults stood with their head turned 90° while receiving SVS at LOW (0.8 m above ground, away from edge) and HIGH (3.2 m above ground, at edge) conditions. LOW trials were completed before and after a block of 10 HIGH trials. Ground reaction forces (GRFs) and plantar flexor (soleus and medial gastrocnemius (MG)) EMG were recorded. Vestibular‐evoked responses recorded from GRFs and EMG were quantified in terms of signal coupling (coherence and cumulant density) and gain, and emotional and autonomic state were assessed from self‐reports and electrodermal activity. Vestibular‐evoked balance responses were facilitated with initial threat exposure. After repeated exposure, there was significant habituation of the emotional response to threat, which was accompanied by reductions in vestibular‐evoked balance responses, most notably for GRFs and MG‐EMG. This suggests that threat‐related changes in vestibular‐motor function are tightly coupled with the emotional and autonomic changes induced by the threat, and not an invariant response to context‐specific features of the threat.

image

Key points

Balance corrective responses mediated through vestibular‐motor pathways are facilitated when stability is threatened; however, the extent to which these sensorimotor adaptations covary with changes in emotional state remains unclear.

By having young adults repeatedly stand at the edge of an elevated surface, this study examined how vestibular‐evoked balance responses, probed using stochastic vestibular stimulation and recorded from ground reaction forces and plantar flexor EMG, changed alongside estimates of emotional state.

Vestibular‐evoked responses were facilitated when individuals were first exposed to the postural threat, but demonstrated marked habituation alongside estimates of emotional state after repeated exposure.

This suggests that threat‐related changes in vestibular‐motor function are coupled to the emotional response to threat, and are not an invariant response to context‐specific features of the threat.

These changes in vestibular‐motor function are likely part of a multisensory adaptation process that primes the nervous system to respond to sudden destabilizing forces when fearful of falling.
HETEROGENEOUS MULTI-SOURCE DATA FUSION THROUGH INPUT MAPPING AND LATENT VARIABLE GAUSSIAN PROCESS
Authors: Comlek Yigitcan , Ravi Sandipp Krishnan , Pandita Piyush , Ghosh Sayan , Wang Liping , Chen Wei
Published: February 2025

Artificial intelligence and machine learning frameworks have become powerful tools for establishing computationally efficient mappings between inputs and outputs in engineering problems. These mappings have enabled optimization and analysis routines, leading to innovative designs, advanced material systems, and optimized manufacturing processes. In such modeling efforts, it is common to encounter multiple information (data) sources, each varying in specifications. Data fusion frameworks offer the capability to integrate these diverse sources into unified models, enhancing predictive accuracy and enabling knowledge transfer. However, challenges arise when these sources are heterogeneous, i.e., they do not share the same input parameter space. Such scenarios occur when domains differentiated by complexity such as fidelity, operating conditions, experimental setup, and scale, require distinct parametrizations. To address this challenge, a heterogeneous multi-source data fusion framework based on input mapping calibration (IMC) and latent variable Gaussian process (LVGP) is proposed. In the first stage, the IMC algorithm transforms the heterogeneous input parameter spaces into a unified reference parameter space. In the second stage, an LVGP-enabled multi-source data fusion model constructs a single source-aware surrogate model on the unified space. The framework is demonstrated and analyzed through three engineering case studies: the design of a cantilever beam, the design of ellipsoidal voids, and the modeling of Ti6Al4V alloy properties. The results demonstrate that the framework achieves higher predictive accuracy compared to both single-source models and source-unaware models on the transformed space.
Bidirectional Asymmetric Accordion-type Soft Robot for Respiratory Assistance
Authors: Zhou Sipeng , Pu Zihan , Yuan Shaoke , Fei Yanqiong
Published: February 2025

Respiratory assistance is of significant importance for achieving pulmonary rehabilitation in individuals with weakened respiratory muscles. Soft actuators has great potential in rehabilitation application, yet there is little research on soft respiratory rehabilitation robots. This paper presents a novel bidirectional asymmetric accordion-type soft robot capable of generating chest expansion and contraction actions, designed for respiratory assistance in patients with respiratory muscle weakness. The robot consists of two bidirectional asymmetric accordion-type pneumatic actuators (APA), each composed of a primary accordion-type pneumatic actuator (PAPA) and a subordinate accordion-type pneumatic actuator (SAPA), capable of providing torque to human body to facilitate auxiliary expansion and contraction of the chest. A kinematic motion model is developed to couple the movements of the human arm with the actuator by analyzing their angular relationships. By modeling the airbags as compressed spheres and simplifying the contact areas, the angle can be calculated at the specified pressure and torque, thereby selecting the optimal geometric parameters of PAPA and SAPA to ensure the desired angle is achieved. Experimental validation confirmed the accuracy of the kinematic coupled motion model and output torque of PAPA. The robot's efficacy in respiratory assistance was assessed by comparing volume flow rate (VFR) and moving air volume (MAV) between ten participants with and without robot assistance. Results show the average improvement rates of exhalation VFR, inhalation VFR, and MAV of the participants are 154.4%, 147.94%, and 155.26%, which demonstrated the robot's capability to enhance respiratory function.
Modelling Particulate Deposition in Gas Turbines Part I: a Non-Spherical Bounce Stick Model
Authors: Gaskell Jack , McGilvray Matthew , Gillespie David R.H.
Published: February 2025

The secondary air system and cooling passages of gas turbine components are prone to blockage from sand and dust. Prediction of deposition requires accurate models of particle transport and thermo-mechanical interaction with walls. Bounce stick models predict whether a particle will bounce or stick upon impact and calculate rebound trajectories if applicable. This paper proposes a bounce stick model that uses analytical solutions of adhesion, plastic deformation and viscoelasticity to time-resolve collision physics. The Discrete-Element Methods (DEM) model shows good agreement when compared to experimental studies and FEA simulations, requiring minimal parametric fitting. Further comparison is made to the best resolved and industry standard models available. In addition to coefficients of restitution, other variables crucial to modelling rebound, for example angular velocity, are predicted. The time-stepping explicit approach allows coupling between internal processes during contact and shows that viscoelasticity plays a significant role in adhesion. Modelling time-dependent internal variables like wall-normal force allow the modelling of non-spherical particles, the physics of which has been shown by previous work to differ significantly from that of spheres. These effects have not been captured well, if at all, by other models. The spherical version of this model has previously been shown to produce good predictions of deposition distribution in CFD. The developments presented here allow the inclusion of more complex collision physics which will improve numerical predictions of deposition. The accompanying second part to this paper demonstrates this with the addition of surface roughness modelling.
Influence of morphology and surface properties on the antibacterial action of GaOOH microparticles
Authors: Johnson D. A. , Ahluwalia P. , Brannon J. H. , Jodhka P. , Wayman V. , Rabine Z. , Strzhemechny Y. M.
Published: February 2025

The growing threat of antibiotic-resistant bacteria necessitates the development of alternative antimicrobial agents. Gallium oxyhydroxide (GaOOH) is a promising candidate, though its direct antibacterial efficacy is unexplored. This study provides the first direct evidence of GaOOH microparticles exhibiting cytotoxic effects against both Gram-positive Staphylococcus aureus (S.aureus) and Gram-negative Escherichia coli (E. coli). Orthorhombic GaOOH particles were synthesized hydrothermally, with their morphology influenced by the pH of the synthesis process, as confirmed by scanning electron microscopy and x-ray diffraction analysis. Antibacterial assays revealed that cytotoxicity against E. coli increases with a higher synthesis pH, a trend we demonstrate to be associated with the enhanced defect density in particles, as supported by photoluminescence spectra and FTIR analysis. The study underscores the significant influence of synthesis conditions on the morphology and crystallinity of the resulting GaOOH microparticles, highlighting the influence of surface characteristics on antibacterial agents.
Effect of the microscale of the nanofiber membranes on their sound absorption performance
Authors: Liu Chuang , Sun Wenhao , Xu Jingjian , Zhou Jie , Sui Dan
Published: February 2025

Nanofiber membranes (NMs), fabricated via electrospinning of poly(vinylidene fluoride-co-hexafluoropropylene) solution, can effectively enhance the sound absorption coefficient (SAC) of porous materials with minimal mass and space requirements, making them appealing for aircraft noise reduction. The macroscopic property of a material is inherently influenced by its microscale, and therefore, this study investigates the effect of NM microscale on sound absorption and utilizes the transfer matrix method to reveal the effect of fiber diameter on the sound absorption of the membranes. The impact of the polymer concentration and solvent composition on the fiber diameter of these membranes is discussed. Experimental results demonstrate that alterations in solution parameters yield diverse fiber diameters and acoustic properties. An optimized polymer concentration and solvent composition for enhanced sound absorption are given through controlled experiments under specific stirring and electrospinning parameters. Notably, in the 1–2 kHz range, NM for melamine foam exhibits a 25% average increase in SAC, with 0.15% thickness and 0.02% weight increments. The Knudsen number and specific surface area are introduced to explain the variations in the SACs among NMs. This study provides insights into membrane acoustic properties at the microscopic level and offers guidance for producing high-performance NMs for sound absorption.
A link between aging and persistence
Authors: Proenca A. M. , Rang C. U. , Chao L.
Published: February 2025

Despite the various strategies that microorganisms have evolved to resist antibiotics, survival to drug treatments can be driven by subpopulations of susceptible bacteria in a transient state of dormancy. This phenotype, known as bacterial persistence, arises due to a natural and ubiquitous heterogeneity of growth states in bacterial populations. Nonetheless, the unifying mechanism of persistence remains unknown, with several pathways being able to trigger the phenotype. Here, we show that asymmetric damage partitioning, a form of cellular aging, produces the underlying phenotypic heterogeneity upon which persistence is triggered. Using single-cell microscopy and microfluidic devices, we demonstrate that deterministic asymmetry in exponential phase populations leads to a state of growth stability, which prevents the spontaneous formation of persisters. However, as populations approach stationary phase, aging bacteria—those inheriting more damage upon division—exhibit a sharper growth rate decline, increased probability of growth arrest, and higher persistence rates. These results indicate that persistence triggers are biased by bacterial asymmetry, thus acting upon the deterministic heterogeneity produced by cellular aging. This work suggests unifying mechanisms for persistence and offers new perspectives on the treatment of recalcitrant infections.
mSphere of Influence: Fungal behavior as a framework for the evolution of emergent traits
Authors: Swafford Andrew J. M.
Published: February 2025

Andrew Swafford works in the field of evolutionary cell biology. In this mSphere of Influence article, he reflects on how the simultaneous introduction to the evolution of vision, the sensory biology of chytrid fungi, and a classic paper by Vrba and Gould helped shape his thinking about sensory evolution.
Bifidobacterium longum
increases serum vitamin D metabolite levels and modulates intestinal flora to alleviate osteoporosis in mice
Authors: Wang Hongchao , Tian Gao , Pei Zhangming , Yu Xihua , Wang Yi , Xu Fuchun , Zhao Jianxin , Lu Shourong , Lu Wenwei
Published: February 2025

The elderly population is prone to osteoporosis, owing to the deterioration of the skin, liver, and kidney functions. Vitamin D (VD) supplementation has a limited effect, and VD deficiency is mostly treated with medication. Several studies have shown that the gut microbiota alters intestinal VD metabolism and that probiotic supplements can influence circulating VD levels. Therefore, in the present study, we screened a strain of
Bifidobacterium longum
FSHHK13M1 that can increase the level of VD metabolites in the fermented supernatant species
in vitro
by modeling fecal bacterial fermentation. The results showed that FSHHK13M1 intervention significantly increased the serum levels of 1,25-dihydroxy VD and osteocalcin. It activated the expression of the VDR, OPG, Wnt10b/β-catenin, and Runx2/Osterix pathways and inhibited the expression of RANKL/RANK pathway. Furthermore, there was an enhancement in the quantity of bone trabeculae and the proportion of bone volume. Concurrently, the gut microbiota in mice with osteoporosis exhibited signs of imbalance. FSHHK13M1 intervention increased the relative abundance of specific bacteria, such as
Faecalibaculum rodentium
,
Limosilactobacillus fermentum
,
Bifidobacterium pseudolongum
, and
Akkermansia muciniphila
. These results suggest that
B. longum
FSHHK13M1 alleviates retinoic acid-induced osteoporosis symptoms by modulating related genes, regulating the intestinal flora and increasing the level of active VD.

IMPORTANCE

Osteoporosis is a systemic metabolic disease in which the patient’s bone mass decreases for a variety of reasons, and the microstructure of the bone tissue is altered, leading to an increase in bone brittleness and susceptibility to fracture. Osteoporosis is almost always present in the elderly population, and fractures from falls are an important predisposing factor for mortality risk in the elderly population. Supplementation is quite limited for them as they are not able to utilize vitamin D well due to declining liver, kidney, and skin functions. In the present study, a strain of
Bifidobacterium longum
probiotic was found to increase the levels of the active form of vitamin D and ameliorate osteoporosis. This may play an important role in preventing osteoporosis and reducing fracture risk in the elderly.
Effects of human immunoglobulin A on
Cryptococcus neoformans
morphology and gene expression
Authors: Trevijano-Contador Nuria , de Oliveira Haroldo C. , Malacatus-Bravo Claudia , Sarai Varona , Cuesta Isabel , Rodrigues Marcio L. , Zaragoza Óscar , Pirofski Liise-anne
Published: February 2025

Human IgM was previously shown to inhibit Titan-like cell formation of
Cryptococcus neoformans
, whereas IgG did not. Here, we conducted an in-depth analysis of the effect of normal human IgA on
C. neoformans
biology (strain H99) and compared it to that of IgG and IgM. We found that like IgM, IgA affected H99 cell size and morphology. The total size of cells cultured with IgA was significantly smaller at 24 h than cells cultured with IgM and IgG and comparable to IgM but smaller than IgG at 72 h. We also examined extracellular vesicle (EV) production and found that it was significantly reduced in cells cultured with IgA than the control, but the EVs were larger. To further probe the effect of IgA on H99, we performed expression profiling by RNAseq of H99 cells cultured with each immunoglobulin isotype and compared the results with IgA to those with IgM, IgG, and a control (PBS). These comparisons showed that cells cultured with IgA overexpressed genes related to cell rescue, defense, virulence, energy conservation, adapation to stress with CNAG_00735 (aldehyde dehydrogenase family seven member A1) being the most overexpressed, and repressed some genes related to vesicular transport, including CNAG_04306 (vesicle transporter SFT2B) and CNG_00063 (histone H3). Collectively, our findings suggest that the effects of IgA on cryptococcal biology deserve further investigation, as they reveal new insights into human host–
C. neoformans
interaction, which suggest that antibody responses may affect gene expression in
C. neoformans
.

IMPORTANCE

Profound CD4 T cell deficiency is associated with the development of cryptococcosis in HIV-infected individuals. However, perturbations in antibody immunity, including reduced levels of plasma IgA and IgM, have also been associated with cryptococcal disease status. While IgM has been studied in some detail, IgA has not. Here, we evaluated the effect of normal human IgA on
Cryptococcus neoformans
biology and morphology to expand knowledge of the role that it may play in cryptococcal pathogenesis.
Protocol for a national intervention programme aimed to reduce unwarranted variation and overuse of shoulder arthroscopy in Norway
Authors: Tjomsland Ole , Bertilsson Helena Maria , Bjerkan Geir , Blomquist Per Jesper , Brox Jens Ivar , Bøe Berte Marie , Jøsendal Ola , Major Daniel , Panchakulasingam Kandiah , Stensland Eva , Strehle Michael , Valdimarsson Kristjan , Thoresen Christian
Published: February 2025

Several advice-based approaches have aimed to reduce the overuse of procedures characterised as low-value healthcare services but have so far shown marginal impact on utilisation rates. Differences in utilisation rates tend to be associated with type of healthcare provider. Commercial providers have a tendency to have higher utilisations rates compared with non-profit providers. Norway has a publicly funded universal health coverage system where healthcare services are mainly provided by publicly owned hospitals in addition to a small number of non-profit hospitals and commercial hospitals reimbursed by the regional health authorities. According to previous experiences, unwarranted variation in utilisation rates can be associated with the type of healthcare provider. The aim of the present study is to evaluate the impact of tailoring the interventions on reducing overuse of low-value care based on an analysis of the clinical pathways and the various types of healthcare providers. The National Decision Forum in Norway has decided that acromion resection in patients with impingement symptoms and repair of non-traumatic cuff rupture should not be offered as standard treatment. The present protocol describes the planned intervention to reduce the overuse of these procedures.
Abstracts from international emergency medicine journals
Authors: Production EMJ
Published: February 2025

Editor’s note:EMJhas partnered with the journals of multiple international emergency medicine societies to share from each a highlighted research study, as selected by their editors. This edition will feature an abstract from each publication.
Clinical indications and Z-score-assisted NIPT testing: a new perspective in prenatal screening
Authors: Zhang Runling , Zhang Haiying , Zhang Lin , Kong Xiangsha , Wang Wei , Jia Yuyuan , Ren Meihong , Liu Yan , Zhu Ling , Chen Hongsong , Rao Huiying
Published: February 2025

Objective

We aim to explore positive predictive value (PPV) in non-invasive prenatal testing (NIPT)-positive cases and investigate the impact of diverse clinical indications and Z-scores on PPV performance.

Methods

From January 2021 to June 2024, 37 891 pregnant women underwent NIPT screening for fetal trisomy 21 (T21), trisomy 18 (T18) and trisomy 13 (T13) at our laboratory using the NextSeq CN500 platform. Positive results were verified through prenatal diagnostic karyotype analysis and fluorescence in situ hybridisation (FISH) techniques.

Results

The sensitivity, specificity and PPV were 95.24%, 99.95%, 67.80% for T21; 100%, 99.97%, 56.00% for T18; and 100%, 99.97%, 16.67% for T13. Across clinical indications, PPV ranged from 0% to 100% for T21 and T18 and 0% to 28.57% for T13. In the T21 group, the predominant proportion of pregnant women (45.76%) exhibited Z-scores between 5 and 10, accompanied by a PPV of 77.78%. For those with Z-scores above 10 (23.73%), the PPV was 85.71%. Pregnant women with Z-scores between 3 and 5 exhibited a PPV of 16.67%. In the T18 group, the majority of women (52.00%) exhibited Z-scores ranging from 3 to 5, with a PPV of 33.85%. In the T13 group, all women had Z-scores between 5 and 10, with a PPV of 40.00%.

Conclusions

NIPT exhibits elevated PPVs for T21 and T18. Moreover, the detection efficacy of NIPT differs across several clinical indication categories. The PPV performance of NIPT for T21/T18/T13 is associated with Z-scores. These results provide valuable guidance for clinicians in prenatal consultation and interpretation of NIPT results.
Skin mutation burden drives adaptive immunity and response to immunotherapy
Authors: Looney Timothy
Published: February 2025

Numerous studies over the past century have reported an inverse correlation between lifetime solar ultraviolet radiation (UV) exposure and all-cancer incidence and mortality. For decades, this relationship was hypothesized to reflect the action of photosynthesized vitamin D, though subsequent clinical trials have failed to demonstrate the expected anti-cancer properties. Rather than a consequence of vitamin D, I hypothesize that this inverse correlation reflects the immune stimulatory action of UV-derived skin neoantigens. Over time, such UV-mediated immune education drives immune repertoire diversification and superior adaptive immune responses to infectious disease and cancer. This hypothesis would explain the strong positive selection for light skin pigmentation following the out-of-Africa migration among humans inhabiting northerly latitude regions, and the longstanding racial disparities in cancer and infectious disease observed in North America. It suggests that the skin comprises an important reservoir of anti-cancer T cells that may be harnessed for anti-cancer therapy, and that skin mutation burden (SMB) may serve as a predictive biomarker of immunotherapy response. I propose a novel, non-invasive method for quantifying SMB as a biomarker.
EPAuto: Efficient Privacy-Preserving Machine Learning on AI-powered Autonomous Driving Systems using Multi-Party Computation
Authors: Zeng Chenkai , He Debiao , Feng Qi , Yang Xiaolin , Luo Qingcai
Published: February 2025

AI-powered autonomous driving systems are being increasingly adopted by automobile manufacturers, while training autonomous driving models using machine learning technique requires vast amounts of driving data. Manufacturers tend to collaborate through ecosystem partnerships to jointly advance the development of autonomous driving algorithms such as Huawei has established partnerships with multiple collaborators sharing intelligent automotive solutions. However, concerns about data privacy naturally arise among automobile manufacturers. This paper proposes a privacy-preserving framework, EPAuto, for collaborative machine learning among automobile manufacturers. EPAuto leverages secure multi-party computation (MPC) to enable efficient privacy-preserving machine learning (PPML). We propose our improved bit-wise comparison and most significant bit (MSB) extraction protocols, leveraging the random permutation matrix as the core technique. Additionally, we design fundamental building blocks for privacy-preserving machine learning (PPML), including DReLU, ReLU, and Maxpool protocols. The security of EPAuto is formally proven under the static semi-honest adversary model in the dishonest-majority setting. We implement our protocols within 2 to 120 parties in both LAN and WAN environments. Our results demonstrate nanosecond-level online response over LAN in multi-party settings, and our PPML implementations achieve up to a 907× performance improvement compared to state-of-the-art works in the same setting.
Image Cropping with Content and Composition Attribute-aware Global Relation Reasoning
Authors: Zhu Hancheng , Yan Li , Zhou Yong , Yao Rui , Shao Zhiwen , Zhao Jiaqi , Li Leida
Published: February 2025

Image cropping aims to find visually pleasing content in an image, which will enhance its aesthetic quality. Existing image cropping approaches mainly emphasize the geometric properties of images, such as composition and layout, neglecting the rich aesthetic information available from the physical attributes (e.g., content and themes), and background information beyond the foreground in images. Consequently, this paper proposes an image cropping method based on the content and composition attribute-aware global relation reasoning, which aims at guiding the generation of cropped sub-images by exploring critical attributes based on content and composition as well as global object correlations that affect aesthetics in images. Particularly, to comprehensively introduce aesthetic information into image cropping, we capture feature representations reinforced by content and composition attributes simultaneously. The feature representations can strengthen the visual aesthetics of cropped sub-images. To make the cropped sub-images amply contain more global information, we introduce a global relation reasoning branch in the proposed cropping module, which can fully exploit the dependency relationship between the foreground and background in images. Extensive experiments on image cropping benchmarks demonstrate that our approach is superior to state-of-the-art image cropping methods.
Methylseq, Single-nuclei RNAseq, and Discovery Proteomics Identifies Pathways Associated with Nephron Deficit CKD in the HSRA Rat Model
Authors: Milner Andrew R. , Johnson Ashley C. , Attipoe Esinam M. , Wu Wenjie , Challagundla Lavanya , Garrett Michael R.
Published: February 2025

Low nephron numbers are associated with increased risk of developing chronic kidney disease (CKD) and hypertension, both significant global health problems. To investigate the impact of nephron deficiency, our lab developed a novel inbred rat model (HSRA rat). In this model, approximately 75% of offspring are born with a single kidney (HSRA-S), compared to two-kidney littermates (HSRA-C). HSRA-S rats show impaired kidney development, resulting in ~20% fewer nephrons. Our previous data and current findings demonstrate nephron deficit (failure of one kidney to form and altered development in the remaining kidney) predispose HSRA-S to CKD late in life (increased proteinuria by 18 months of age in HSRA-S=51± 3.4 versus HSRA-C = 8± 1.5 mg/24hours). To understand early molecular mechanisms contributing to the increased predisposition to CKD, Methylseq using reduced representation bisulfite sequencing, single nuclei (sn)RNAseq, and discovery proteomics were performed in kidneys of 4-week-old HSRA rats. Methylation analysis revealed a small number of differences, including 5 differentially methylated cytosines and 6 differentially methylated regions between groups. The snRNAseq analysis identified differentially expressed genes in most kidney cell types, with several hundred genes dysregulated depending on the analysis method (Seurat vs DESeq2). Notably, many genes are involved in kidney development. Discovery proteomic analysis identified 366 differentially expressed proteins. A key finding was dysregulation of Deptor/DEPTOR and Amdhd2/AMDHD2 across omics layers, suggesting a potential role in compensatory mechanisms or the genetic basis of altered kidney development. Further understanding of these mechanisms may guide interventions to preserve nephron health and slow kidney disease progression.
Exploring Potential Drug Targets in Multiple Cardiovascular Diseases: A Study Based on Proteome‐Wide Mendelian Randomization and Colocalization Analysis
Authors: Fan Maoxia , Li Na , Huang Libin , Chen Chen , Dong Xueyan , Gao Wulin
Published: February 2025

Background: Cardiovascular diseases (CVDs) encompass a group of diseases that affect the heart and/or blood vessels, making them the leading cause of global mortality. In our study, we performed proteome‐wide Mendelian randomization (MR) and colocalization analyses to identify novel therapeutic protein targets for CVDs and evaluate the potential drug‐related protein side effects.

Methods: We conducted a comprehensive proteome‐wide MR study to assess the causal relationship between plasma proteins and the risk of CVDs. Summary‐level data for 4907 circulating protein levels were extracted from a large‐scale protein quantitative trait loci (pQTL) study involving 35,559 individuals. Additionally, genome‐wide association study (GWAS) data for CVDs were extracted from the UK Biobank and the Finnish database. Colocalization analysis was utilized to identify causal variants shared between plasma proteins and CVDs. Finally, we conducted a comprehensive phenome‐wide association study (PheWAS) using the R10 version of the Finnish database. This study was aimed at examining the potential drug‐related protein side effects in the treatment of CVDs. A total of 2408 phenotypes were included in the analysis, categorized into 44 groups.

Results: The research findings indicate the following associations: (1) In coronary artery disease (CAD), the plasma proteins A4GNT, COL6A3, KLC1, CALB2, KPNA2, MSMP, and ADH1B showed a positive causal relationship (p‐fdr < 0.05). LAYN and GCKR exhibited a negative causal relationship (p‐fdr < 0.05). (2) In chronic heart failure (CHF), PLG demonstrated a positive causal relationship (p‐fdr < 0.05), while AZGP1 displayed a negative causal relationship (p‐fdr < 0.05). (3) In ischemic stroke (IS), ALDH2 exhibited a positive causal relationship (p‐fdr < 0.05), while PELO showed a negative causal relationship (p‐fdr < 0.05). (4) In Type 2 diabetes (T2DM), the plasma proteins MCL1, SVEP1, PIP4K2A, RFK, HEXIM2, ALDH2, RAB1A, APOE, ANGPTL4, JAG1, FGFR1, and MLN demonstrated a positive causal relationship (p‐fdr < 0.05). PTPN9, SNUPN, VAT1, COMT, CCL27, BMP7, and MSMP displayed a negative causal relationship (p‐fdr < 0.05). Colocalization analysis conclusively identified that AZGP1, ALDH2, APOE, JAG1, MCL1, PTPN9, PIP4K2A, SNUPN, and RAB1A share a single causal variant with CVDs (PPH3 + PPH4 > 0.8). Further phenotype‐wide association studies have shown some potential side effects of these nine targets (p‐fdr < 0.05).

Conclusions: This study identifies plasma proteins with significant causal associations with CVDs, providing a more comprehensive understanding of potential therapeutic targets. These findings contribute to our knowledge of the underlying mechanisms and offer insights into potential avenues for treatment.
Genetic Parameters, Correlation, and Multivariate Analysis of Yield and Yield Components in 30 Promising Wheat (Triticum aestivum L.) Genotypes
Authors: K. C. Bigyan , Pandit Rishav , Maharjan Binju , Adhikari Nav Raj , Poudel Mukti Ram , Thapa Dhruba Bahadur , Poudel Sudeep
Published: February 2025

An experiment with the aim to assess genetic variability and heritability and to examine the degree of association between yield and yield‐attributing traits among the 30 wheat genotypes was performed in alpha lattice design at Golbhatta, Lalitpur. The genotypes were replicated twice with six blocks per replication and each block consisted of five genotypes. The research was carried out in farmer’s fields under irrigated conditions. The result revealed the presence of variance among different genotypes for all traits which can be exploited for improvement of the existing genotypes under irrigated conditions. Characters such as plant height, spike length, number of spikelets per spike, grain number per spike, thousand grain weight, spikes’ number per meter square, and grain yield showed higher heritability along with high genetic advance as percent of mean which are highly desirable for selection as they are governed by additive gene action. The correlation study revealed that parameters such as plant height, number of spikelets per spike, grain number per spike, and spikes’ number per meter square had positive and significant correlations with the grain yield. Among the 10 principal components, three principal components were considered on the basis of eigenvalue accounting for 75.2% of the total variation. Thirty wheat genotypes were classified into five clusters with the help of a dendrogram. Cluster 2 was found to be superior for yield and yield‐attributing traits. Fifteen genotypes including two checks yielded more than the mean yield, where WK3599 (4539 kg/ha) recorded the highest yield, while WK3516 (1657 kg/ha) recorded the lowest among the genotypes. Tested genotypes revealed the presence of genetic diversity among them; hence, indirect selection of traits such as number of spikelets per spike, grain number per spike, spikes’ number per meter square and thousand grain weight will ultimately provide higher yield in these genotypes.
Supplementary Table 1 from A Phase 2 Study of Sotigalimab, a CD40 Agonist Antibody, plus Concurrent Chemoradiation as Neoadjuvant Therapy for Esophageal and Gastroesophageal Junction Cancers
Authors: Ko Andrew H. , Chao Joseph , Noel Marcus S. , Shankaran Veena , Sohal Davendra , Crow Mary , Oberstein Paul E. , Scott Aaron J. , McRee Autumn J. , Rocha Lima Caio Max Sao Pedro , Fong Lawrence , Keenan Bridget P. , Soto Maira , Filbert Erin L. , Hsu Frank J. , Yang Xiaodong
Published: February 2025

Representativeness of Study Participants Table
Figure 1 from A Phase 2 Study of Sotigalimab, a CD40 Agonist Antibody, plus Concurrent Chemoradiation as Neoadjuvant Therapy for Esophageal and Gastroesophageal Junction Cancers
Authors: Ko Andrew H. , Chao Joseph , Noel Marcus S. , Shankaran Veena , Sohal Davendra , Crow Mary , Oberstein Paul E. , Scott Aaron J. , McRee Autumn J. , Rocha Lima Caio Max Sao Pedro , Fong Lawrence , Keenan Bridget P. , Soto Maira , Filbert Erin L. , Hsu Frank J. , Yang Xiaodong
Published: February 2025

Treatment schema demonstrating changes in timing and dosing intervals of sotigalimab relative to the administration of neoadjuvant chemoradiation and surgery, based on sequential protocol amendments. Number of patients treated in each cohort: cohort A (n = 3); cohort B (n = 10); and cohort C (n = 20).
Safety and anti-tumor activity of a novel aCD25 Treg depleter RG6292 as a single agent and in combination with atezolizumab in patients with solid tumors
Authors: Gambardella Valentina , Ong Michael , Rodriguez-Ruiz Maria E. , Machiels Jean-Pascal , Sanmamed Miguel F. , Galvao Vladimir , Spreafico Anna , Renouf Daniel J. , Luen Stephen J. , Galot Rachel , Doger de Speville Bernard , Calvo Emiliano , Naing Aung , Curdt Samira , Kolben Theresa Maria. , Rossmann Eva , Tanos Tamara , Smart Kevin , Amann Maria , Xie Yuying , Xu Linxinyu , Gomez Alcaide Enrique , Städler Nicolas , Justies Nicole , Boetsch Christophe , Karanikas Vaios , Schnetzler Gabriel , Rohrberg Kristoffer S.
Published: February 2025

Purpose: Therapeutic depletion of immunosuppressive regulatory T cells (Tregs) may overcome resistance to cancer immunotherapies. RG6292 is an anti-CD25 antibody that preferentially depletes Tregs while preserving effector T cell functions in preclinical models. The safety, pharmacokinetics, pharmacodynamics, and anti-tumor efficacy of selective Treg depletion by RG6292 administered as monotherapy or in combination with atezolizumab was evaluated in two Phase I studies. Materials and Methods: Adult patients with advanced solid tumors were administered intravenous RG6292 given every 3 weeks (Q3W) alone (Study 1: NCT04158583, N=76) or with 1200 mg atezolizumab Q3W (Study 2: NCT04642365, N=49). Both studies included dose escalation and expansion parts to determine the maximum tolerated dose (MTD) and recommended phase 2 dose (R2PD). Results: RG6292 was well-tolerated. Pruritus and rash were most frequent AEs and were manageable with supportive treatment. Serum RG6292 levels increased dose-proportionally, independent of atezolizumab combination. RG6292 induced a sustained dose-dependent depletion of peripheral Tregs with no apparent effect on other immune cells. Evidence of intratumoral Treg cell reduction (≥50% vs baseline) was observed at RG6292 doses of 35 to 100 mg. The MTD was 165 mg Q3W and the RP2D was proposed as 70 mg Q3W. Objective responses were limited to three partial responses in patients receiving RG6292 combined with atezolizumab. Conclusions: RG6292 induced a dose-dependent peripheral blood and measurable intratumoral Treg depletion in concordance with the proposed mode of action; however, clinical efficacy as single agent or combined with atezolizumab was insufficient to warrant further exploration in this population.
O jogo e o diálogo: compondo com aparelhos
Authors: Chagas Paulo C.
Published: February 2025

Este artigo examina a criação musical no contexto das novas formas de informação e comunicação da sociedade contemporânea, com base na minha experiência profissional no histórico Estúdio de Música Eletrônica da Rádio de Colônia, Alemanha (1990-99). O texto investiga os processos de produção de música eletrônica (ou eletroacústica), desde o início da era analógica até a transição para a era digital, com foco na realidade dos aparelhos. O conceito de "aparelho", proposto por Flusser, é central para a compreensão da nova complexidade comunicativa da sociedade telemática, baseada na automatização dos aparelhos e da mídia. Os aparelhos oferecem um universo de símbolos, por meio dos quais projetamos nossos pensamentos, emoções e desejos. Eles programam os seres humanos para determinados comportamentos, automatizam o pensamento e bloqueiam, assim, a crítica. Os métodos de produção desenvolvidos no Estúdio de Colônia, baseados na colaboração entre compositores, técnicos e artistas, são analisados como exemplo de "criação dialógica", capaz de despertar a consciência crítica para a realidade dos aparelhos. O ensaio demonstra como a música eletrônica explora os aparelhos de maneira não ortodoxa – como um jogo. Esse jogo pode subverter a função alienante dos aparelhos e promover o diálogo, criando novas informações e conceitos que ajudem a sociedade a decifrar os programas dos aparelhos.
Postural behavior of wild aye-ayes in Madagascar’s Ihofa Forest
Authors: Sefczek Timothy M. , Louis Edward E. , McGraw W. Scott
Published: February 2025

We studied an adult female and a juvenile male aye-aye (Daubentonia madagascariensis) in Madagascar’s Ihofa forest from May to December 2017 to investigate whether the postural diversity of this lemur varied with age, maintenance activity, and habitat use. We used bout sampling (female N = 488, male N = 355) to record postures during feeding and resting and tested for differences using . For both individuals, bimanual and unimanual cling were the most common postures used during feeding (78.4% and 82.9%) and these behaviors were strongly associated with the use of vertical supports – trunks and bamboo – in the main canopy. When feeding on branches and boughs, pronograde postures such as tri-pedal crouch and crouch were most common. Most rest occurred on horizontal branches using primarily pronograde postures. Our data indicate that although aye-ayes exploit multiple forest strata, the great majority of feeding is accomplished using orthograde postures from vertical supports, even in forest strata dominated by horizontal supports. These findings support recent arguments about the significance of vertically oriented behaviors in the evolution of early mammalian arboreal quadrupeds.
Can Plurilaterals Solve the WTO’s National Security Crisis?
Authors: Pahis Stratos
Published: February 2025

National security poses an existential threat to the WTO and trade multilateralism. The accommodation reached between trade and security under the GATT is no longer sufficient, and the United States has taken the WTO hostage until a new accommodation is reached. This article explores whether plurilateral agreements between a subset of WTO members can help resolve the crisis. It begins by explaining why national security poses such a challenge to multilateral trade. It analyzes how the prevailing interpretation of the existing GATT security exception addresses some but not all dimensions of the challenge. And it proposes how plurilateral agreements may do so instead, including by supporting a multilateral agreement to broaden the current GATT security exception or by creating a parallel dispute settlement mechanism for disputes not involving national security. It suggests that such agreements should be encouraged within the WTO to preserve the institution’s relevance in this new geopolitical era.
What and Where on Earth Is Waqwaq?
Authors: Toorawa Shawkat M.
Published: February 2025

For well over a century, Indian Ocean Arabists, using primarily linguistic (and biological) arguments, have posited that Waqwaq is one place or another, one life-form or another. It is now Madagascar, now Sumatra; now a milkweed, now a pandanus; now a bird, now a woman-fruit. It is now a tree, now an island … I myself have not been immune to this need to identify, categorize, classify, locate, and domesticate Waqwaq. The impulse is a dangerous one: it arises out of a notion implicit in the colonial and philological enterprise that to be able to name something, to know how it got its name, and to put it on one’s map, is the better to be able to control it. Recent scholarship has been less constrained by potential philological and interpretive tyrannies and Waqwaq has accordingly benefited from re-sitings and re-readings. In this paper, I ask: What are the roots of Waqwaq and what routes has it taken as it traveled from the Abbasid court to China, from Japan to the Mascarenes, from India to the Philippines, from Istanbul to the New World, and even to Hell (and back).
Scribal Habits of the Aramaic Qumran Texts
Authors: Tov Emanuel
Published: February 2025

In the description of the scribal habits of the Qumran corpus, usually no distinction is made between its constituent groups. Indeed, the Aramaic corpus shares the major scribal practices with the Hebrew corpus (Table 1) as well as some specific ones (Table 2). The two corpora reflect the same systems that were practiced in the last three pre-Christian centuries and the first century CE in Palestine. Further, quite unexpectedly from the angle of the scribal practices, the scribes of two scrolls may be linked to Qumran sectarian scrolls, 4QpapToba ar (4Q196) and 4QPsDana ar (4Q243).
Solomon b. Buyāʿā (Scribe of the Aleppo Codex) and St. Petersburg EVR II B 61+
Authors: Beiler Vincent D.
Published: February 2025

The article provides an introduction to RNL St. Petersburg Ms. EVR II B 61+, a 10th century Masoretic codex containing the Latter Prophets that is nearly entirely extant. There is considerable evidence that Solomon b. Buyāʿā, the scribe of the Aleppo Codex and RNL St. Petersburg Ms. EVR II B 17, wrote the consonantal text and most of the Masorah magna of Ms. EVR II B 61+. The identity of the scribe that provided the Masorah parva, vocalisation, and cantillation is also considered. Cantillation symbol and Masorah parva similarity between II B 17/L1 and the present codex suggest that these were added by Solomon’s brother Ephraim, the masran and naqdan of L1.
Unrealistic Career Optimism Among Korean Adolescents: A Discrepancy Between Career Aspirations and Career Preparation Behaviors
Authors: Lee Bo Hyun , Lee Sang Min , Lee J. Hannah
Published: February 2025

The present study aims to identify unrealistic career optimism among Korean high school students and to examine its characteristics. Cluster analysis was conducted to identify the number of groups classified by the reported levels of career aspirations and career preparation behaviors among 420 Korean high school students, and each group’s characteristic was investigated using a series of one-way covariance (ANCOVA). Three clusters were identified: (a) Doer (30.3%), (b) Bystander (35%), and (c) Unrealistic Career Optimist (UCO; 34.7%). Clusters Doer and Bystander were characterized by high/low scores on both career aspirations and career preparation behaviors, respectively, while the cluster UCO endorsed high levels of career aspirations despite low levels of career preparation behaviors. Significant differences in optimism, subjective well-being, and career maturity between groups were documented, suggesting implications for both research and practice.
Bitcoin as Tool for Financial Inclusion in El Salvador: The Perils of Authoritarian Governance
Authors: Meijering Titus , Rosales Antulio
Published: February 2025

In 2021, El Salvador declared bitcoin legal tender. According to President Nayib Bukele, the measure was intended to expand access to financial services in a country with a high proportion of unbanked people and to cheapen and ease remittance flows for migrants and their families. In this article, we inquire about the use of bitcoin as a tool for financial inclusion and contend that this policy needs to be seen in the broader context of democratic backsliding. We show that bitcoin has not translated into financial inclusion, but instead, the bitcoin law serves as a public relations tool to capture new support from like-minded constituencies, build closer relations with them, and empower international “crypto-bros.” On the other hand, this is a tool to benefit a close circle close to the president with the use of public funds, as part of a broader historical shift of elites in El Salvador.