bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mechanoelectronic stimulation of autologous extracellular vesicle biosynthesis implant for gut microbiota modulation
Authors: Wan Shuangshuang , Wang Kepeng , Huang Peihong , Guo Xian , Liu Wurui , Li Yaocheng , Zhang Jingjing , Li Zhiyang , Song Jiacheng , Yang Wenjing , Zhang Xianzheng , Ding Xianguang , Leong David Tai , Wang Lianhui 
Published: April 2024

AbstractPathogenic gut microbiota is responsible for a few debilitating gastrointestinal diseases. While the host immune cells do produce extracellular vesicles to counteract some deleterious effects of the microbiota, the extracellular vesicles are of insufficient doses and at unreliable exposure times. Here we use mechanical stimulation of hydrogel-embedded macrophage in a bioelectronic controller that on demand boost production of up to 20 times of therapeutic extracellular vesicles to ameliorate the microbes’ deleterious effects in vivo. Our miniaturized wireless bioelectronic system termed inducible mechanical activation for in-situ and sustainable generating extracellular vesicles (iMASSAGE), leverages on wireless electronics and responsive hydrogel to impose mechanical forces on macrophages to produce extracellular vesicles that rectify gut microbiome dysbiosis and ameliorate colitis. This in vivo controllable extracellular vesicles-produced system holds promise as platform to treat various other diseases.
LKRSDH-dependent histone modifications of insulin-like peptide sites contribute to age-related circadian rhythm changes
Authors: Lv Pengfei , Yang Xingzhuo , Du Juan 
Published: April 2024

AbstractTo understand aging impact on the circadian rhythm, we screened for factors influencing circadian changes during aging. Our findings reveal thatLKRSDHmutation significantly reduces rhythmicity in aged flies. RNA-seq identifies a significant increase ininsulin-like peptides(dilps) inLKRSDHmutants due to the combined effects of H3R17me2 and H3K27me3 on transcription. Genetic evidence suggests thatLKRSDHregulates age-related circadian rhythm changes throughart4anddilps. ChIP-seq analyzes whole genome changes in H3R17me2 and H3K27me3 histone modifications in young and old flies withLKRSDHmutation and controls. The results reveal a correlation between H3R17me2 and H3K27me3, underscoring the role ofLKRSDHin regulating gene expression and modification levels during aging. Overall, our study demonstrates thatLKRSDH-dependent histone modifications atdilpssites contribute to age-related circadian rhythm changes. This data offers insights and a foundational reference for aging research by unveiling the relationship between LKRSDH and H3R17me2/H3K27me3 histone modifications in aging.
Tumor-infiltrating lymphocytes in HER2-positive breast cancer treated with neoadjuvant chemotherapy and dual HER2-blockade
Authors: Liefaard M. C. , van der Voort A. , van Seijen M. , Thijssen B. , Sanders J. , Vonk S. , Mittempergher L. , Bhaskaran R. , de Munck L. , van Leeuwen-Stok A. E. , Salgado R. , Horlings H. M. , Lips E. H. , Sonke G. S. 
Published: April 2024

AbstractTumor-infiltrating lymphocytes (TILs) have been associated with outcomes in HER2-positive breast cancer patients treated with neoadjuvant chemotherapy and trastuzumab. However, it remains unclear if TILs could be a prognostic and/or predictive biomarker in the context of dual HER2-targeting treatment. In this study, we evaluated the association between TILs and pathological response (pCR) and invasive-disease free survival (IDFS) in 389 patients with stage II-III HER2 positive breast cancer who received neoadjuvant anthracycline-containing or anthracycline-free chemotherapy combined with trastuzumab and pertuzumab in the TRAIN-2 trial. Although no significant association was seen between TILs and pCR, patients with TIL scores ≥60% demonstrated an excellent 3-year IDFS of 100% (95% CI 100–100), regardless of hormone receptor status, nodal stage and attainment of pCR. Additionally, in patients with hormone receptor positive disease, TILs as a continuous variable showed a trend to a positive association with pCR (adjusted Odds Ratio per 10% increase in TILs 1.15, 95% CI 0.99–1.34, p = 0.070) and IDFS (adjusted Hazard Ratio per 10% increase in TILs 0.71, 95% CI 0.50–1.01, p = 0.058). We found no interactions between TILs and anthracycline treatment. Our results suggest that high TIL scores might be able to identify stage II-III HER2-positive breast cancer patients with a favorable prognosis.
Critical assessment of G0W0 calculations for 2D materials: the example of monolayer MoS2
Authors: Rodrigues Pela Ronaldo , Vona Cecilia , Lubeck Sven , Alex Ben , Gonzalez Oliva Ignacio , Draxl Claudia 
Published: April 2024

AbstractTwo-dimensional (2D) materials combine many fascinating properties that make them more interesting than their three-dimensional counterparts for a variety of applications. For example, 2D materials exhibit stronger electron-phonon and electron-hole interactions, and their energy gaps and effective carrier masses can be easily tuned. Surprisingly, published band gaps of several 2D materials obtained with the GW approach, the state-of-the-art in electronic-structure calculations, are quite scattered. The details of these calculations, such as the underlying geometry, the starting point, the inclusion of spin-orbit coupling, and the treatment of the Coulomb potential can critically determine how accurate the results are. Taking monolayer MoS2 as a representative material, we employ the linearized augmented planewave + local orbital method to systematically investigate how all these aspects affect the quality of G0W0 calculations, and also provide a summary of literature data. We conclude that the best overall agreement with experiments and coupled-cluster calculations is found for G0W0 results with HSE06 as a starting point including spin-orbit coupling, a truncated Coulomb potential, and an analytical treatment of the singularity at q = 0.
The first chromosome-level genome of the stag beetle Dorcus hopei Saunders, 1854 (Coleoptera: Lucanidae)
Authors: Li Xiaolu , Mao Chuyang , He Jinwu , Bin Xiaoyan , Liu Guichun , Dong Zhiwei , Zhao Ruoping , Wan Xia , Li Xueyan 
Published: April 2024

AbstractStag beetles (Coleoptera: Lucanidae) represent a significant saproxylic assemblage in forest ecosystems and are noted for their enlarged mandibles and male polymorphism. Despite their relevance as ideal models for the study of exaggerated mandibles that aid in attracting mates, the regulatory mechanisms associated with these traits remain understudied, and restricted by the lack of high-quality reference genomes for stag beetles. To address this limitation, we successfully assembled the first chromosome-level genome of a representative species Dorcus hopei. The genome was 496.58 Mb in length, with a scaffold N50 size of 54.61 Mb, BUSCO values of 99.8%, and 96.8% of scaffolds anchored to nine pairs of chromosomes. We identified 285.27 Mb (57.45%) of repeat sequences and annotated 11,231 protein-coding genes. This genome will be a valuable resource for further understanding the evolution and ecology of stag beetles, and provides a basis for studying the mechanisms of exaggerated mandibles through comparative analysis.
Exploring the role of apolipoprotein E gene promoter polymorphisms in susceptibility to normal-tension glaucoma in a Korean population
Authors: Park Young Jun , Shin Hye-Young , Kim Jong-Il 
Published: April 2024

AbstractGlaucoma, particularly primary open-angle glaucoma (POAG), poses a significant global health concern. Distinguished by intraocular pressure (IOP), POAG encompasses high-tension glaucoma (HTG) and normal-tension glaucoma (NTG). Apolipoprotein E (APOE) is a multifaceted protein with roles in lipid metabolism, neurobiology, and neurodegenerative diseases. However, controversies persist regarding the impact of APOE single-nucleotide polymorphisms (SNPs) on open-angle glaucoma and NTG. This study aimed to identify APOE-specific SNPs influencing NTG risk. A cohort of 178 patients with NTG recruited from Uijeongbu St. Mary’s Hospital and 32,858 individuals from the Korean Genome and Epidemiology Study (KoGES) cohort were included in the analysis. Genotype and haplotype analyses were performed on three promoter SNPs (rs449647, rs769446, and rs405509) and two exonic SNPs (rs429358 and rs7412) located on chromosome 19. Among the five SNPs, rs769446 genotypes exhibited significant differences between cases and controls. The minor allele C of rs769446 emerged as a protective factor against NTG. Furthermore, haplotype analysis of the five SNPs revealed that the A-T-G-T-T haplotype was a statistically significant risk factor for NTG. This study indicated an association between APOE promoter SNPs and NTG in the Korean population. Further studies are required to understand how APOE promoter SNPs contribute to NTG pathogenesis.
SARS-CoV-2 booster vaccine dose significantly extends humoral immune response half-life beyond the primary series
Authors: Korosec Chapin S. , Dick David W. , Moyles Iain R. , Watmough James 
Published: April 2024

AbstractSARS-CoV-2 lipid nanoparticle mRNA vaccines continue to be administered as the predominant prophylactic measure to reduce COVID-19 disease pathogenesis. Quantifying the kinetics of the secondary immune response from subsequent doses beyond the primary series and understanding how dose-dependent immune waning kinetics vary as a function of age, sex, and various comorbidities remains an important question. We study anti-spike IgG waning kinetics in 152 individuals who received an mRNA-based primary series (first two doses) and a subset of 137 individuals who then received an mRNA-based booster dose. We find the booster dose elicits a 71–84% increase in the median Anti-S half life over that of the primary series. We find the Anti-S half life for both primary series and booster doses decreases with age. However, we stress that although chronological age continues to be a good proxy for vaccine-induced humoral waning, immunosenescence is likely not the mechanism, rather, more likely the mechanism is related to the presence of noncommunicable diseases, which also accumulate with age, that affect immune regulation. We are able to independently reproduce recent observations that those with pre-existing asthma exhibit a stronger primary series humoral response to vaccination than compared to those that do not, and further, we find this result is sustained for the booster dose. Finally, via a single-variate Kruskal-Wallis test we find no difference between male and female humoral decay kinetics, however, a multivariate approach utilizing Least Absolute Shrinkage and Selection Operator (LASSO) regression for feature selection reveals a statistically significant (p$$<1\times 10^{-3}$$

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), albeit small, bias in favour of longer-lasting humoral immunity amongst males.
Perceptual (but not acoustic) features predict singing voice preferences
Authors: Bruder Camila , Poeppel David , Larrouy-Maestri Pauline 
Published: April 2024

AbstractWhy do we prefer some singers to others? We investigated how much singing voice preferences can be traced back to objective features of the stimuli. To do so, we asked participants to rate short excerpts of singing performances in terms of how much they liked them as well as in terms of 10 perceptual attributes (e.g.: pitch accuracy, tempo, breathiness). We modeled liking ratings based on these perceptual ratings, as well as based on acoustic features and low-level features derived from Music Information Retrieval (MIR). Mean liking ratings for each stimulus were highly correlated between Experiments 1 (online, US-based participants) and 2 (in the lab, German participants), suggesting a role for attributes of the stimuli in grounding average preferences. We show that acoustic and MIR features barely explain any variance in liking ratings; in contrast, perceptual features of the voices achieved around 43% of prediction. Inter-rater agreement in liking and perceptual ratings was low, indicating substantial (and unsurprising) individual differences in participants’ preferences and perception of the stimuli. Our results indicate that singing voice preferences are not grounded in acoustic attributes of the voices per se, but in how these features are perceptually interpreted by listeners.
Hemodynamic study of the ICA aneurysm evolution to attain the cerebral aneurysm rupture risk
Authors: Huo Huaying , Chang Yigang 
Published: April 2024

AbstractThe influence of the aneurysm evolution on the hemodynamic characteristic of the blood flow inside the sac region is comprehensively investigated. By using the computational method, the blood flow through the vessel and aneurysm of the sac region is examined to find the role of aneurysm evolution on the wall shear stress, pressure, and risk of aneurysm rupture. Three different models of ICA aneurysms are chosen for the investigation of the aneurysm evolution at risk of rupture. Obtained data shows that the evolution of the aneurysm decreases the wall shear stress and pressure on the sac surface while an oscillatory index of blood increases on the aneurysm wall.
Analysis of plasma metabolomes from 11 309 subjects in five population-based cohorts
Authors: Ghosh Nilanjana , Lejonberg Carl , Czuba Tomasz , Dekkers Koen , Robinson Richard , Ärnlöv Johan , Melander Olle , Smith Maya Landenhed , Evans Anne M. , Gidlöf Olof , Gerszten Robert E. , Lind Lars , Engström Gunnar , Fall Tove , Smith J. Gustav 
Published: April 2024

AbstractPlasma metabolomics holds potential for precision medicine, but limited information is available to compare the performance of such methods across multiple cohorts. We compared plasma metabolite profiles after an overnight fast in 11,309 participants of five population-based Swedish cohorts (50–80 years, 52% women). Metabolite profiles were uniformly generated at a core laboratory (Metabolon Inc.) with untargeted liquid chromatography mass spectrometry and a comprehensive reference library. Analysis of a second sample obtained one year later was conducted in a subset. Of 1629 detected metabolites, 1074 (66%) were detected in all cohorts while only 10% were unique to one cohort, most of which were xenobiotics or uncharacterized. The major classes were lipids (28%), xenobiotics (22%), amino acids (14%), and uncharacterized (19%). The most abundant plasma metabolome components were the major dietary fatty acids and amino acids, glucose, lactate and creatinine. Most metabolites displayed a log-normal distribution. Temporal variability was generally similar to clinical chemistry analytes but more pronounced for xenobiotics. Extensive metabolite-metabolite correlations were observed but mainly restricted to within each class. Metabolites were broadly associated with clinical factors, particularly body mass index, sex and renal function. Collectively, our findings inform the conduct and interpretation of metabolite association and precision medicine studies.
Affinity chromatography reveals direct binding of the GATA4–NKX2-5 interaction inhibitor (3i-1000) with GATA4
Authors: Jumppanen Mikael , Kinnunen Sini M. , Zore Matej , Välimäki Mika J. , Talman Virpi , Gennäs Gustav Boije af , Ruskoaho Heikki J. , Yli-Kauhaluoma Jari 
Published: April 2024

AbstractHeart failure is a serious medical condition with a poor prognosis. Current treatments can only help manage the symptoms and slow the progression of heart failure. However, there is currently no cure to prevent and reverse cardiac remodeling. Transcription factors are in a central role in various cellular processes, and in the heart, GATA4 and NKX2-5 transcription factors mediate hypertrophic responses and remodeling. We have identified compounds that modulate the synergistic interaction of GATA4 and NKX2-5 and shown that the most promising compound (1, 3i-1000) is cardioprotective in vitro and in vivo. However, direct evidence of its binding site and mechanism of action has not been available. Due to the disordered nature of transcription factors, classical target engagement approaches cannot be utilized. Here, we synthesized a small-molecule ligand-binding pulldown probe of compound 1 to utilize affinity chromatography alongside CETSA, AlphaScreen, and molecular modeling to study ligand binding. These results provide the first evidence of direct physical binding of compound 1 selectively to GATA4. While developing drugs that target transcription factors presents challenges, advances in technologies and knowledge of intrinsically disordered proteins enable the identification of small molecules that can selectively target transcription factors.
Association between social dominance hierarchy and PACAP expression in the extended amygdala, corticosterone, and behavior in C57BL/6 male mice
Authors: Meloni Edward G. , Carlezon William A. , Bolshakov Vadim Y. 
Published: April 2024

AbstractThe natural alignment of animals into social dominance hierarchies produces adaptive, and potentially maladaptive, changes in the brain that influence health and behavior. Aggressive and submissive behaviors assumed by animals through dominance interactions engage stress-dependent neural and hormonal systems that have been shown to correspond with social rank. Here, we examined the association between social dominance hierarchy status established within cages of group-housed mice and the expression of the stress peptide PACAP in the bed nucleus of the stria terminalis (BNST) and central nucleus of the amygdala (CeA). We also examined the relationship between social dominance rank and blood corticosterone (CORT) levels, body weight, motor coordination (rotorod) and acoustic startle. Male C57BL/6 mice were ranked as either Dominant, Submissive, or Intermediate based on counts of aggressive/submissive encounters assessed at 12 weeks-old following a change in homecage conditions. PACAP expression was significantly higher in the BNST, but not the CeA, of Submissive mice compared to the other groups. CORT levels were lowest in Submissive mice and appeared to reflect a blunted response following events where dominance status is recapitulated. Together, these data reveal changes in specific neural/neuroendocrine systems that are predominant in animals of lowest social dominance rank, and implicate PACAP in brain adaptations that occur through the development of social dominance hierarchies.
The Fur-like regulatory protein MAP3773c modulates key metabolic pathways in Mycobacterium avium subsp. paratuberculosis under in-vitro iron starvation
Authors: Thapa Sajani , Rathnaiah Govardhan , Zinniel Denise K. , Barletta Raul G. , Bannantine John P. , Huebner Marianne , Sreevatsan Srinand 
Published: April 2024

AbstractJohne’s disease (JD) is a chronic enteric infection of dairy cattle worldwide. Mycobacterium avium subsp. paratuberculosis (MAP), the causative agent of JD, is fastidious often requiring eight to sixteen weeks to produce colonies in culture—a major hurdle in the diagnosis and therefore in implementation of optimal JD control measures. A significant gap in knowledge is the comprehensive understanding of the metabolic networks deployed by MAP to regulate iron both in-vitro and in-vivo. The genome of MAP carries MAP3773c, a putative metal regulator, which is absent in all other mycobacteria. The role of MAP3773c in intracellular iron regulation is poorly understood. In the current study, a field isolate (K-10) and an in-frame MAP3773c deletion mutant (ΔMAP3773c) derived from K-10, were exposed to iron starvation for 5, 30, 60, and 90 min and RNA-Seq was performed. A comparison of transcriptional profiles between K-10 and ΔMAP3773c showed 425 differentially expressed genes (DEGs) at 30 min time post-iron restriction. Functional analysis of DEGs in ΔMAP3773c revealed that pantothenate (Pan) biosynthesis, polysaccharide biosynthesis and sugar metabolism genes were downregulated at 30 min post-iron starvation whereas ATP-binding cassette (ABC) type metal transporters, putative siderophore biosynthesis, PPE and PE family genes were upregulated. Pathway analysis revealed that the MAP3773c knockout has an impairment in Pan and Coenzyme A (CoA) biosynthesis pathways suggesting that the absence of those pathways likely affect overall metabolic processes and cellular functions, which have consequences on MAP survival and pathogenesis.
A meta-analysis on the potency of foot-and-mouth disease vaccines in different animal models
Authors: Jiao Jiao , Wu Peng 
Published: April 2024

AbstractWhether mice can be used as a foot-and-mouth disease (FMD) model has been debated for a long time. However, the major histocompatibility complex between pigs and mice is very different. In this study, the protective effects of FMD vaccines in different animal models were analyzed by a meta-analysis. The databases PubMed, China Knowledge Infrastructure, EMBASE, and Baidu Academic were searched. For this purpose, we evaluated evidence from 14 studies that included 869 animals with FMD vaccines. A random effects model was used to combine effects using Review Manager 5.4 software. A forest plot showed that the protective effects in pigs were statistically non-significant from those in mice [MH = 0.56, 90% CI (0.20, 1.53), P = 0.26]. The protective effects in pigs were also statistically non-significant from those in guinea pigs [MH = 0.67, 95% CI (0.37, 1.21), P = 0.18] and suckling mice [MH = 1.70, 95% CI (0.10, 28.08), P = 0.71]. Non-inferiority test could provide a hypothesis that the models (mice, suckling mice and guinea pigs) could replace pigs as FMDV vaccine models to test the protective effect of the vaccine. Strict standard procedures should be established to promote the assumption that mice and guinea pigs should replace pigs in vaccine evaluation.
Maximizing solar power generation through conventional and digital MPPT techniques: a comparative analysis
Authors: Sarang Shahjahan Alias , Raza Muhammad Amir , Panhwar Madeeha , Khan Malhar , Abbas Ghulam , Touti Ezzeddine , Altamimi Abdullah , Wijaya Andika Aji 
Published: April 2024

AbstractA substantial level of significance has been placed on renewable energy systems, especially photovoltaic (PV) systems, given the urgent global apprehensions regarding climate change and the need to cut carbon emissions. One of the main concerns in the field of PV is the ability to track power effectively over a range of factors. In the context of solar power extraction, this research paper performs a thorough comparative examination of ten controllers, including both conventional maximum power point tracking (MPPT) controllers and artificial intelligence (AI) controllers. Various factors, such as voltage, current, power, weather dependence, cost, complexity, response time, periodic tuning, stability, partial shading, and accuracy, are all intended to be evaluated by the study. It is aimed to provide insight into how well each controller performs in various circumstances by carefully examining these broad parameters. The main goal is to identify and recommend the best controller based on their performance. It is notified that, conventional techniques like INC, P&O, INC-PSO, P&O-PSO, achieved accuracies of 94.3, 97.6, 98.4, 99.6 respectively while AI based techniques Fuzzy-PSO, ANN, ANFIS, ANN-PSO, PSO, and FLC achieved accuracies of 98.6, 98, 98.6, 98.8, 98.2, 98 respectively. The results of this study add significantly to our knowledge of the applicability and effectiveness of both AI and traditional MPPT controllers, which will help the solar industry make well-informed choices when implementing solar energy systems.