bluuebunny/crossref_metadata_2025 huggingface dataset:
HORNET: Tools to find genes with causal evidence and their regulatory networks using eQTLs
Authors: Lorincz-Comi Noah , Yang Yihe , Ajayakumar Jayakrishnan , Mews Makaela , Bermudez Valentina , Bush William , Zhu Xiaofeng
Published: October 2024

Motivation

Nearly two decades of genome-wide association studies (GWAS) have identify thousands of disease-associated genetic variants, but very few genes with evidence of causality. Recent methodological advances demonstrate that Mendelian Randomization (MR) using expression quantitative loci (eQTLs) as instrumental variables can detect potential causal genes. However, existing MR approaches are not well suited to handle the complexity of eQTL GWAS data structure and so they are subject to bias, inflation, and incorrect inference.

Results

We present a whole-genome regulatory network analysis tool (HORNET), which is a comprehensive set of statistical and computational tools to perform genome-wide searches for causal genes using summary level GWAS data that is robust to biases from multiple sources. Applying HORNET to schizophrenia, we identified differential magnitudes of gene expression causality. Applying HORNET to schizophrenia, we identified differential magnitudes of gene expression causality across different brain tissues.

Availability and Implementation

Freely available athttps://github.com/noahlorinczcomi/HORNETorMac, Windows, and Linux users.

Contact

njl96@case.edu.
Reducing Information and Selection Bias in EHR-Linked Biobanks via Genetics-Informed Multiple Imputation and Sample Weighting
Authors: Salvatore Maxwell , Kundu Ritoban , Du Jiacong , Friese Christopher R , Mondul Alison M , Hanauer David , Lu Haidong , Pearce Celeste Leigh , Mukherjee Bhramar
Published: October 2024

Electronic health records (EHRs) are valuable for public health and clinical research but are prone to many sources of bias, including missing data and non-probability selection. Missing data in EHRs is complex due to potential non-recording, fragmentation, or clinically informative absences. This study explores whether polygenic risk score (PRS)-informed multiple imputation for missing traits, combined with sample weighting, can mitigate missing data and selection biases in estimating disease-exposure associations. Simulations were conducted for missing completely at random (MCAR), missing at random (MAR), and missing not at random (MNAR) conditions under different sampling mechanisms. PRS-informed multiple imputation showed generally lower bias, particularly when combined with sample weighting. For example, in biased samples of 10,000 with exposure and outcome MAR data, PRS-informed imputation had lower percent bias (3.8%) and better coverage rate (0.883) compared to PRS-uninformed (4.5%; 0.877) and complete case analyses (10.3%; 0.784) in covariate-adjusted, weighted, multiple imputation scenarios. In a case study using Michigan Genomics Initiative (n=50,026) data, PRS-informed imputation aligned more closely with a sample-weighted All of Us-derived benchmark than analyses ignoring missing data and selection bias. Researchers should consider leveraging genetic data and sample weighting to address biases from missing data and non-probability sampling in biobanks.
Shared Transcriptomic Signatures Reveal Synaptic Pruning as a Link Between Alzheimer’s Disease and Epilepsy
Authors: Li Huihong , Xie Zhiran , Tian Yuxuan , Lin Bingying , Li Jianwei , Wu Jie , Chen Mingjie , Liu Xueke , Sun Yushan , Chen Si , Deng Zihan , Hong Mengqi , Huang Bing , Wei Naili , Ji Xiaoyu
Published: October 2024

Alzheimer’s disease (AD) and epilepsy (EP) exhibit a complex, bidirectional relationship, however, the molecular mechanisms underlying their comorbidity remain poorly understood. To address this gap, we analyzed large-scale transcriptomic datasets from pilocarpine-induced EP mouse models (n = 200), two AD mouse models expressing human tau (rTg4510) or amyloid precursor protein (J20) (n = 141), and transcriptomic profiles from AD and EP patient cohorts. Differential expression and weighted gene co-expression network analyses identified a highly conserved immune-related module enriched in microglia-specific genes, particularlyTyrobp,Trem2, andC1qcomplement component genes (C1qa,C1qb,C1qc) implicated in the synaptic pruning pathway. Gene regulatory network analysis showed thatTyrobpregulates theseC1qcomponents gene throughTrem2. These hub genes were markedly upregulated in both models and human patient datasets, preserved their regulatory relationship across species, and displayed strong diagnostic value. Cell composition deconvolution and single-cell transcriptomics confirmed their high, cell-type-specific expression in microglia from both animal model and human patient datasets. Moreover, computational modeling indicated that excessive synaptic pruning, particularly of inhibitory synapses, alters the excitation/inhibition (E/I) balance toward excitability that increases neural network synchrony. Collectively, our findings reveal how microglial complement-driven synapse elimination may promote both seizure activity and cognitive decline. We suggest that microglia play a central role in the comorbidity of EP and AD, and further exploration of this synaptic pruning pathway in the context of EP may provide promising insights into the treatment of AD and EP comorbidity.

Graphic abstract

Highlights

Transcriptomic analysis across epilepsy (EP) and Alzheimer’s disease (AD) models and patient datasets revealed a conserved immune gene module.

Shared transcriptomic signatures identified in animal models show strong diagnostic value in both AD and EP patient datasets.

Tyrobp-Trem2-C1qmicroglial synaptic pruning pathway was identified as a central shared molecular mechanism across model and patient datasets.

Computational modeling revealed that excessive synaptic pruning, particularly of inhibitory synapses, alters E/I balance toward excitability and increases synchrony in neural network.
WAVE1 and WAVE2 facilitate human papillomavirus-driven actin polymerization during cellular entry
Authors: Fernandez DJ , Cheng Stephanie , Prins Ruben , Hamm-Alvarez Sarah F , Kast W Martin
Published: October 2024

Human Papillomavirus Type 16 (HPV16) is an etiological agent of human cancers that requires endocytosis to initiate infection. HPV16 entry into epithelial cells occurs through a non-canonical endocytic pathway that is actin-driven, but it is not well understood how HPV16-cell surface interactions trigger actin reorganization in a way that facilitates entry. This study provides evidence that Wiskott-Aldrich syndrome protein family verprolin-homologous proteins 1 and 2 (WAVE1 and WAVE2) are molecular mediators of the actin polymerization that facilitates HPV endocytosis and intracellular trafficking. We demonstrate through post-transcriptional gene silencing and genome editing that WAVE1 and WAVE2 are critical for efficient HPV16 infection, and that restoration of each in knockout cells rescues HPV16 infection. Cells lacking WAVE1, WAVE2, or both, internalize HPV16 at a significantly reduced rate. Analysis of fluorescently labeled cells exposed to HPV16 and acquired by confocal fluorescence microscopy revealed that HPV16, WAVE1, WAVE2, and actin are all colocalized at the cellular dorsal surface. We also found that HPV16 stimulates WAVE1 and WAVE2-mediated cellular dorsal surface filopodia formation during the viral endocytic process. Taken together, this study provides evidence that the HPV endocytic process needed for infection is controlled by actin reorganization into filopodial protrusions and that this process is mediated by WAVE1 and WAVE2.

Author Summary

Human Papillomavirus (HPV) is the most common sexually transmitted infection in the United States. While its mode of entry into cells has yet to be fully described, extensive studies indicate HPV entry occurs via a macropinocytosis-like pathway. Interestingly, more than 10 viruses enter cells via macropinocytosis-like entry, with no two viruses utilizing identical factors for entry. It is unclear whether these viruses are entering cells via the same pathway, or if the term “macropinocytosis” describes a subset of endocytic pathways. One unifying feature of entry for each of these viruses is their requirement of actin polymerization. In this study, we identify the cellular factors necessary for actin polymerization to participate in HPV endocytosis. The findings of this study are of importance to the field of virology as they may extend to the infection of other viruses. It is also of interest in cancer studies as macropinocytosis has been associated with the scavenging of nutrients and methuosis, a form of cell death in cancer cells that occurs from over- scavenging. Nanoparticle delivery can also occur via macropinocytosis. Therefore, the contribution of WAVE proteins to macropinocytosis and macropinocytosis-like endocytic events is informative to a broad audience.
Cross-Species Analysis Reveals No Universal Programmed Aging Mechanism: Insights from Single-Cell Transcriptomics in Zebrafish, Fruit Fly, and Nematode
Authors: Niu Yunhui , Wu Dongzhi , Zhang Sen , Zheng Hong , Wu Xing , Chen Jiansong , Zhang Yunze , Zhang Tao , He Wenhui , Chen Li
Published: October 2024

The question of whether aging follows a universal programmed process has been a topic of debate for a long time. Previous arguments, either supporting or refuting programmed aging, were mainly based on different evolutionary biology theories. In this study, we analysed single-cell RNA sequencing data from zebrafish, fruit fly, and nematode at various stages of development to explore gene co-expression modules across these species. We successfully identified a co-expression module related to ribosomal protein genes that is shared across the early development stages in multiple tissues of all three species. However, we did not find any cross-species shared gene co-expression modules related to aging. Further analysis of gene regulatory networks (GRNs) demonstrated that although certain aging-related genes are conserved, their regulatory mechanisms vary significantly between species. These findings suggest that aging is not governed by a conserved universal program but rather by species-specific adaptations to damage and environmental conditions.
A mitochondrial redox switch licenses the onset of morphogenesis in animals
Authors: Kahlon Updip , Ricca Francesco Dalla , Pillai Saraswathi J. , Olivetta Marine , Tharp Kevin M. , Jao Li-En , Dudin Omaya , McDonald Kent , Aydogan Mustafa G.
Published: October 2024

Embryos undergo pre-gastrulation cleavage cycles to generate a critical cell mass before transitioning to morphogenesis. The molecular underpinnings of this transition have traditionally centered on zygotic chromatin remodeling and genome activation1,2, as their repression can prevent downstream processes of differentiation and organogenesis. Despite precedents that oxygen depletion can similarly suspend development in early embryos3–6, hinting at a pivotal role for oxygen metabolism in this transition, whether there is abona fidechemical switch that licenses the onset of morphogenesis remains unknown. Here we discover that a mitochondrial oxidant acts as a metabolic switch to license the onset of animal morphogenesis. Concomitant with the instatement of mitochondrial membrane potential, we found a burst-like accumulation of mitochondrial superoxide (O2-) during fly blastoderm formation.In vivochemistry experiments revealed that an electron leak from site IIIQoat ETC Complex III is responsible for O2-production. Importantly, depleting mitochondrial O2-fully mimics anoxic conditions and, like anoxia, induces suspended animation prior to morphogenesis, but not after. Specifically, H2O2, and not ONOO-, NO, or HO•, can single-handedly account for this mtROS-based response. We demonstrate that depleting mitochondrial O2-similarly prevents the onset of morphogenetic events in vertebrate embryos and ichthyosporea, close relatives of animals. We postulate that such redox-based metabolic licensing of morphogenesis is an ancient trait of holozoans that couples the availability of oxygen to development, conserved from early-diverging animal relatives to vertebrates.
Structure, dynamics and evolution of theCandida albicansmulti-drug resistance ABC transporter CDR1
Authors: Shin Jeeeun , Jin Ruitao , Gall Barnabas , Jobichen Chacko , Jackson Colin , Rug Melanie , Corry Ben , Brock Joseph
Published: October 2024

The pleiotropic drug resistance transporter Cdr1 fromCandida albicansplays a crucial role in antifungal resistance. Here, we present high-resolution cryo-electron microscopy structures ofC. albicansCdr1 in multiple functional states: nucleotide-bound, substrate-bound, and apo forms. The 3.5 Å resolution structure of Cdr1 in complex with ATP and ADP reveals the molecular details of its asymmetric nucleotide-binding sites (NBS), with ATP bound to the deviant NBS1 and ADP to the canonical NBS2. Structures of Cdr1 bound to rhodamine 6G (3.4 Å) and Oregon Green 488 (3.5 Å) in complex with these nucleotides elucidate the pleiotropic substrate-binding pocket and highlight how nucleotide exchange drives conformational change required for transport. Additionally, we determined a 3.7 Å resolution structure of Cdr1 in the detergent LMNG without nucleotides, as well as a 3.5 Å resolution structure with nucleotides but no substrate, representing an apo state. We complemented these structural insights with molecular dynamics simulations to understand substrate binding dynamics, ancestral sequence reconstruction to trace the evolution of key functional motifs, and analysis of clinical isolates from sequence databases to identify potential resistance-associated variations. Comparison of these structures provides new insights into the conformational changes associated with the transport cycle of this asymmetric ABC transporter, revealing how ATP binding at the deviant NBS1 allosterically regulates the canonical NBS2, driving ATPase activity. This work significantly advances our understanding of the molecular mechanisms underlying multidrug resistance in pathogenic fungi and provides a structural and evolutionary framework for the rational design of Cdr1 inhibitors to combat antifungal resistance.
Socio-Demographic Biases in Medical Decision-Making by Large Language Models: A Large-Scale Multi-Model Analysis
Authors: Omar Mahmud , Soffer Shelly , Agbareia Reem , Bragazzi Nicola Luigi , Apakama Donald U. , Horowitz Carol R , Charney Alexander W , Freeman Robert , Kummer Benjamin , Glicksberg Benjamin S , Nadkarni Girish N , Klang Eyal
Published: October 2024

Large language models (LLMs) are increasingly integrated into healthcare but concerns about potential socio-demographic biases persist. We aimed to assess biases in decision-making by evaluating LLMs’ responses to clinical scenarios across varied socio-demographic profiles. We utilized 500 emergency department vignettes, each representing the same clinical scenario with differing socio-demographic identifiers across 23 groups—including gender identity, race/ethnicity, socioeconomic status, and sexual orientation—and a control version without socio-demographic identifiers. We then used Nine LLMs (8 open source and 1 proprietary) to answer clinical questions regarding triage priority, further testing, treatment approach, and mental health assessment, resulting in 432,000 total responses. We performed statistical analyses to evaluate biases across socio-demographic groups, with results normalized and compared to control groups. We find that marginalized groups—including Black, unhoused, and LGBTQIA+ individuals—are more likely to receive recommendations for urgent care, invasive procedures, or mental health assessments compared to the control group (p < 0.05 for all comparisons). High-income patients were more often recommended advanced diagnostic tests such as CT scans or MRI, while low-income patients were more frequently advised to undergo no further testing. We observed significant biases across all models, both proprietary and open source regardless of the model’s size. The most pronounced biases emerged in mental health assessment recommendations. LLMs used in medical decision-making exhibit significant biases in clinical recommendations, perpetuating existing healthcare disparities. Neither model type nor size affects these biases. These findings underscore the need for careful evaluation, monitoring, and mitigation of biases in LLMs to ensure equitable patient care.
Cortical iron-related markers are elevated in mild Traumatic Brain Injury: An individual-level quantitative susceptibility mapping study
Authors: Essex Christi A. , Overson Devon K. , Merenstein Jenna L. , Truong Trong-Kha , Madden David J. , Bedggood Mayan J. , Morgan Catherine , Murray Helen , Holdsworth Samantha J. , Stewart Ashley W. , Faull Richard L. M. , Hume Patria , Theadom Alice , Pedersen Mangor
Published: October 2024

Quantitative susceptibility mapping (QSM) has been applied to map brain iron distribution after mild traumatic brain in-jury (mTBI), to understand properties of neural tissue which may be related to microstructural damage. However, mTBI is a heterogeneous injury associated with microstructural brain changes, and ‘traditional’ group-wise statistical approaches may lead to a loss of clinically relevant information, as subtle individual-level changes can be obscured by averages and confounded by within-group variability. More precise and individualised approaches are needed to characterise mTBI better and elucidate potential cellular mechanisms to improve intervention and rehabilitation. To address this issue, we build individualised profiles of regional positive (iron-related) magnetic susceptibility across 34 bilateral cortical regions of interest (ROIs) following mTBI. Healthy population templates were constructed for each cortical area using standardised z-scores derived from 25 age-matched male controls, serving as a reference against which z-scores of 35 males with acute (< 14 days) sports-related mTBI (sr-mTBI) were compared. Secondary analyses sensitive to cortical depth and curvature were also generated to approximate the location of iron accumulation in the cortical laminae and the effect of gyrification. Our primary analyses indicated that approximately one-third (11/35; 31%) of mTBI participants exhibited elevated positive sus-ceptibility indicative of abnormal iron profiles relative to the healthy control population, a finding that was mainly concentrated in ROIs within the temporal lobe. Injury severity was significantly higher (p < 0.01) for these mTBI participants than their iron-normal counterparts, suggesting a link between injury severity, symptom burden, and elevated cortical iron. Secondary analyses of cortical depth and curvature profiles revealed abnormal iron accumulation in 83% (29/35) of mTBI participants, enabling better localisation of mTBI-related changes in iron content to specific loci within each ROI and identifying effects that may be more subtle and lost in ROI-wise averaging. Our findings suggest that individualised approaches can further elucidate the clinical relevance of iron in mTBI. Differences in injury severity between iron-normal and iron-abnormal mTBI participants highlight not only why precise investigation is required to understand the link between objective changes in the brain and subjective symptomatology, but also identify iron as a candidate biomarker for tissue damage after mTBI.
Antibiotic lethality dictates mycobacterial infection outcomes
Authors: Jovanovic Alexander , Bright Frederick K. , Sadeghi Ahmad , Wicki Basil , Muñiz Santiago E. Caño , Toprak Sara , Sauteur Loïc , Rodoni Anna , Wüst Andreas , Lupien Andréanne , Borrell Sonia , Grogono Dorothy M. , Wheeler Nicole , Dehio Philippe , Nemeth Johannes , Pargger Hans , Thomson Rachel , Bell Scott C. , Gagneux Sebastien , Bryant Josephine M. , Peng Tingying , Diacon Andreas , Floto R. Andres , Abanto Michael , Boeck Lucas
Published: October 2024

Antibiotic development and treatment focus on bacterial growth inhibition, often with limited success. Here, we introduce Antimicrobial Single-Cell Testing (ASCT), an advanced imaging strategy to assess bacterial killing in real-time. By tracking 140 million bacteria and generating over 20,000in vitrotime-kill curves, we can predictMycobacterium tuberculosistreatment outcomes in mice and humans and link strain-specific survival (drug tolerance) inMycobacterium abscessusto clinical responses. Using ASCT, we reveal drug tolerance as a distinct genetically encoded bacterial trait conserved across drugs with similar targets and, via genome-wide associations, uncover molecular mechanisms that govern bacterial killing. This study establishes the technical framework andin vivovalidation for large-scale bacterial killing assessments to advance our understanding of bacterial survival, antibiotic development and clinical decision-making.
Sequence determinants of intron-mediated enhancement learned from thousands of random introns
Authors: Kowal Emma J. K. , Sakai Yuta , McGurk Michael P. , Pasetsky Zoe J. , Burge Christopher B.
Published: October 2024

Spliceosomal introns are a ubiquitous feature of eukaryotic genes, whose presence often boosts the expression of their host gene, a phenomenon known as intron-mediated enhancement (IME). IME has been noted across diverse genes and organisms, but remains mysterious in many respects. For example, how does intron sequence affect the magnitude of IME? In this study, we performed a massively parallel reporter assay (MPRA) to assess the effect of varying intron sequence on gene expression in a high-throughput manner, in human cells, using tens of thousands of synthetic introns with natural splice sites and randomized internal sequence. We observe that most random introns splice efficiently and enhance gene expression as well as or better than fully natural introns. Nearly all introns stimulate gene expression ∼eight-fold above an intronless control, at both mRNA and protein levels, suggesting that the primary mechanism acts to increase mRNA levels. IME strength is positively associated with splicing efficiency and with the intronic content of poly-uridine stretches, which we confirm using reporter experiments. Together, this work elucidates sequence determinants of IME from tens of thousands of random introns, and confirms that enhancement of gene expression is a general property of splicing.
Phytochemical characterization and antimicrobial properties ofAzadirachtin indicaagainst selected bacterial human pathogens
Authors: Eka Idorenyin Idorenyin , Wilson Idongesit Udo , Ibuot Aniefon Alphonsus
Published: October 2024

The study was conducted to assess the phytochemical and antibacterial potentials ofAzadirechtin indicaagainstSalmonella typhi, Staphylococcus aureusandPseudomonas aeruginosausing microbiological techniques. Ethanol and water were used to extract the active components from theAzadirechtin indicaleaves.Salmonella typhishowed range of inhibition zone from 11mm to 16mm at 50% to 90% concentrations of the plant ethanolic extract.Staphylococcus aureushad a range of inhibition zone from 10mm to 13mm at 50% to 90 % concentrations of the plant ethanolic extract andPseudomonas aeruginosahad a range of inhibition zone from 10mm to 12mm at 50% to 90% concentrations of the plant ethanolic extract. Ethanol extract showed greater antibacterial activity against the test organisms when compared with the aqueous extract. Preliminary screening of phytochemicals in the leaf extract ofAzadirechtin indicarevealed the presence of alkaloids (7.376mg/100g), saponins (12.041mg/100g), flavonoids (2.641mg/100g), tannins (3.431mg/100g) and cyannogenic glycosides (0.952 mg/100g). This result provides scientific support forAzadirechtin indicato be further investigated and used as drug.
Structural enzymological studies of the long chain fatty acyl-CoA synthetase FadD5 from themce1operon ofMycobacterium tuberculosis
Authors: Rahman Mohammad Asadur , Dalwani Subhadra , Venkatesan Rajaram
Published: October 2024

The cell wall ofMycobacterium tuberculosis(Mtb), the causative agent of tuberculosis, is rich in complex lipids. During intracellular stage, Mtb depends on lipids for its survival. Mammalian cell-entry (Mce) 1 complex encoded by themce1operon is a mycolic/fatty acid importer.mce1operon also encodes a putative fatty acyl-CoA synthetase (FadD5; Rv0166), potentially responsible for the activation of fatty acids imported through the Mce1 complex by conjugating them to Coenzyme A. Here we report that FadD5 is associated to membrane although it can be purified as a soluble dimeric protein. ATP and CoA binding influence FadD5’s stability and conformation. Enzymatic studies with fatty acids of varying chain lengths show that FadD5 prefers long chain fatty acids as substrates. X-ray crystallographic studies on FadD5 and its variant reveal that the C-terminal domain (∼100 residues) is cleaved off during crystallization. Noteworthy, deletion of this domain renders FadD5 completely inactive. SAXS studies, however, confirm the presence of full length FadD5 as a dimer in solution. Further structural analysis and comparisons with homologs provide insights on the possible mode of membrane association and fatty acyl tail binding.
Improved limits on
n→n′
transformation from the Spallation Neutron Source
Authors: Gonzalez Francisco M. , Rock Cary , Broussard Leah J. , DeBeer-Schmitt Lisa , Frost Matthew J. , Heilbronn Lawrence , Iverson Erik B. , Kamyshkov Yuri , Kline Michael , Milstead David , Powers Devyn , Rogers James , Santoro Valentina , Vavra Shaun
Published: October 2024

Conversions between neutrons n and dark matter candidate sterile neutrons n′ have been proposed as a mechanism for baryon number B violation. In the case that there is a small mass difference Δm between the n and the n′ states, oscillations can be induced by compensating for Δm with a magnetic field. A search for such neutron oscillations was performed at the Spallation Neutron Source by looking for anomalous neutron transmission through a strongly absorbing cadmium wafer inside of a 6.6 T magnet. The approach described here saw no regenerated neutrons above background, which provides an improved limit for neutron–sterile neutron transformations for a range of Δm between 0.1 and 1000 neV.

Published by the American Physical Society
2024
Dirac spectral density in
Nf=2+1
QCD at
T=230  MeV
Authors: Alexandru Andrei , Bonanno Claudio , D’Elia Massimo , Horváth Ivan
Published: October 2024

We compute the renormalized Dirac spectral density in Nf=2+1 QCD at physical quark masses, temperature T=230  MeV, and system size Ls=3.4  fm. To that end, we perform a pointwise continuum limit of the staggered density in lattice QCD with staggered quarks. We find, for the first time, that a clear infrared structure (IR peak) emerges in the density of the Dirac operator describing dynamical quarks. We also provide numerical evidence that a component of this peak, which becomes dominant in the thermodynamic limit, is due to a nontrivial accumulation of near-zero modes. Features of this structure are consistent with those previously attributed to the recently proposed IR phase of thermal QCD. Our results (i) provide the only complete first-principles evidence that these IR features exist and are physical, (ii) improve the upper bound for IR phase transition temperature TIR so that the new window is 200<TIR<230  MeV, and (iii) are consistent with the nonrestoration of anomalous UA(1) symmetry (chiral limit) below T=230  MeV.

Published by the American Physical Society
2024
Kagome Hubbard model from a functional renormalization group perspective
Authors: Profe Jonas B. , Klebl Lennart , Grandi Francesco , Hohmann Hendrik , Dürrnagel Matteo , Schwemmer Tilman , Thomale Ronny , Kennes Dante M.
Published: October 2024

The recent discovery of a variety of intricate electronic order in kagome metals has sprouted significant theoretical and experimental interest. From an electronic perspective on the potential microscopic origin of these phases, the most basic model is given by a Hubbard model on the kagome lattice. We employ a functional renormalization group (FRG) to analyze the kagome Hubbard model. Through our methodological refinement of FRG both within its N-patch and truncated unity formulation, we resolve previous discrepancies of different FRG approaches [Wang , vs Kiesel , ], and analyze both the pure (p-type) and mixed (m-type) van Hove fillings of the kagome lattice.

Published by the American Physical Society
2024
Tensor product random matrix theory
Authors: Altland Alexander , Telles de Miranda Joaquim , Micklitz Tobias
Published: October 2024

The evolution of complex correlated quantum systems such as random circuit networks is governed by the dynamical buildup of both entanglement and entropy. We here introduce a real-time field theory approach—essentially a fusion of the GΣ functional of the SYK model and the field theory of disordered systems—engineered to microscopically describe the full range of such crossover dynamics: from initial product states to a maximum entropy ergodic state. To showcase this approach in the simplest nontrivial setting, we consider a tensor product of coupled random matrices, and compare to exact diagonalization.

Published by the American Physical Society
2024
Effects of Sn addition in W-doped Ag paste against electrochemical corrosion and sulfurization
Authors: Shih Huei-Jyun , Lee Ying-Chieh , Pan Jing-Ru , Chung Claire
Published: October 2024

Purpose

This study aims to address these challenges by enhancing the resistance of Ag-based pastes to corrosion and sulfurization, thereby improving their performance and weatherability in high-power and high-frequency electronic applications.

Design/methodology/approach

This study investigates the influence of Sn doping in W-doped Ag paste to enhance resistance against electrochemical corrosion and sulfurization. A systematic examination was conducted using transient liquid phase sintering and solid–liquid inter-diffusion techniques to understand the microstructural and electrochemical properties.

Findings

This study found that Sn addition in W-doped Ag paste significantly improves its resistance to electrochemical corrosion and sulfurization. The sintering process at 600°C led to the formation of an Ag2WO4 phase at the grain boundaries, which, along with the presence of Sn, effectively inhibited the growth of Ag2WO4 grains. The 0.5% Sn-doped samples exhibited optimal anti-corrosion properties, demonstrating a longer grain boundary length and a passivation effect that significantly reduced the corrosion rate. No Ag2S phase was detected in the weatherability tests, confirming the enhanced durability of the doped samples.

Originality/value

The findings of this study highlight the potential of Sn-doped Ag-W composites as a promising material for electronic components, particularly in environments prone to sulfurization and corrosion. By improving the anti-corrosion properties and reducing the grain size, this study offers a new approach to extending the lifespan and reliability of electronic devices, making a significant contribution to the development of advanced materials for high-power and high-frequency applications.
Beyond the myth: understanding women's impulsive retail footwear shopping
Authors: Duarte Paulo , Silva Susana C. , Magro Margarida , Dias Joana Carmo
Published: October 2024

Purpose

This research focuses on common misconceptions about the factors driving women to purchase footwear impulsively. Its primary objective is to explore how emotional and social triggers specifically influence women's purchasing decisions, contrasting with the traditionally rational consumer models.

Design/methodology/approach

An online questionnaire was administered to a sample of women, yielding 199 useable responses.

Findings

The findings reveal the key determinants of women's impulsive retail footwear purchases, which include self-regulation, hedonic motivations and the influence of the retail store environment. This research challenges the prevailing assumption that women's passion for shopping is driven solely by inherent characteristics and suggests that external factors substantially shape their impulsive buying behaviour. In summary, the stereotypical portrayal of women as compulsive retail footwear shoppers may result more from external stimuli and environmental factors rather than an intrinsic trait.

Originality/value

This study improves the existing knowledge of women’s impulsive buying behaviour by unveiling the determinants of women's impulsive footwear purchases and assessing whether prevailing stereotypes hold true.
The future of tourism: an interview with Leslie Vella about the future of tourism in Malta
Authors: Yeoman Ian Seymour , Vella Leslie
Published: October 2024

Purpose

As the Journal of Tourism Futures celebrates its 10th Anniversary, Dr Ian Yeoman (Hotel Management School Leeuwarden) interviews Leslie Vella (Malta Tourism Authority) about the future of tourism in Malta, drawing upon a series of scenarios as a reflective learning tool.

Design/methodology/approach

A personal interview.

Findings

The interview discusses the future of tourism in Malta raising issues and reflections, through four scenarios that portray the Mediterranean island: Scenario 1: A Regenerative Future – Reposition, Realignment and Refocus (Transformation), Scenario 2: A Sustainable Pathway – Adaption and Innovative Growth (Growth), Scenario 3: Europe’s Second Class – Second Choice Destination (Stagnation) and Scenario 4: No Tourism (Collapse).

Originality/value

Upon critical reflection, scenarios can be seen as a powerful learning device to frame, surface and discuss issues associated with tourism, in this case in Malta.
The expensive son hypothesis
Authors: Invernizzi Lucas , Lemaître Jean‐François , Douhard Mathieu
Published: October 2024

In its initial form, the expensive son hypothesis postulates that sons from male‐biased sexually dimorphic species require more food during growth than daughters, which ultimately incur fitness costs for mothers predominantly producing and rearing sons.

We first dissect the evolutionary framework in which the expensive son hypothesis is rooted, and we provide a critical reappraisal of its differences from other evolutionary theories proposed in the field of sex allocation. Then, we synthesize the current (and absence of) support for the costs of producing and rearing sons on maternal fitness components (future reproduction and survival).

Regarding the consequences in terms of future reproduction, we highlight that species with pronounced sexual size dimorphism display a higher cost of sons than of daughters on subsequent reproductive performance, at least in mammals. However, in most studies, the relative fitness costs of producing and rearing sons and daughters can be due to sex‐biased maternal allocation strategies rather than differences in energetic demands of offspring, which constitutes an alternative mechanism to the expensive son hypothesis stricto sensu.

We observe that empirical studies investigating the differential costs of sons and daughters on maternal survival in non‐human animals remain rare, especially for long‐term survival. Indeed, most studies have investigated the influence of offspring sex (or litter sex ratio) at year T on survival at year T + 1, and they rarely provide a support to the expensive son hypothesis. On the contrary, in humans, most studies have focused on the relationship between proportion of sons and maternal lifespan, but these results are inconsistent.

Our study highlights new avenues for future research that should provide a comprehensive view of the expensive son hypothesis, by notably disentangling the effects of offspring behaviour from the effect of sex‐specific maternal allocation. Moreover, we emphasize that future studies should also embrace the mechanistic side of the expensive son hypothesis, largely neglected so far, by deciphering the physiological pathways linking son's production to maternal health and fitness.
Influence of different calcium‐chelating salts on the colloidal structure of skimmed milk under simulated heat treatment conditions
Authors: Campos Nathalia da Silva , Dias Biany Aparecida de Castro , Desiderio Eduarda Coelho Gaudard , Alves Natalia Maria Germano , Perrone Ítalo Tuler , Wolfschoon Pombo Alan , Stephani Rodrigo
Published: October 2024

Research objective was to study the influence of calcium‐chelating salts on colloidal properties of skimmed milk, which best meets the Brazilian regulation for UHT milk production. Citrate and different ortho‐ and polyphosphate sodium salts were added to milk at 5 concentrations (0.00 up to 0.20% w/w). Samples were heat‐treated (oil bath, 155°C, F0 = 1.43 min), cooled down and analysed. The main changes were caused by tetrasodium diphosphate and sodium triphosphate at 0.15% and 0.20% w/w, as they increased the pH, sequestering capacity and altered the particle size distribution, showing that the impacts on the colloidal structure are influenced by the salt concentration.
Microbial dysbiosis in the gut–mammary axis as a mechanism for mastitis in dairy cows
Authors: Wang Zhiwei , Ma Zheng , Tian Zhichen , Jia Haoran , Zhang Lei , Mao Yongjiang , Yang Zhangping , Liu Xu , Li Mingxun
Published: October 2024

Mastitis is a significant and costly disease in dairy cows, reducing milk production and affecting herd health. Recent research highlights the role of gastrointestinal microbial dysbiosis in the development of mastitis. This review focuses on how microbial imbalances in the rumen and intestines can compromise the integrity of the gastrointestinal barriers, allowing harmful bacteria and endotoxins, such as lipopolysaccharide, to enter the bloodstream and reach the mammary gland, triggering inflammation. This process links gastrointestinal health to mammary gland inflammation through the gut–mammary axis. Furthermore, disruptions in glucose metabolism and immune responses are implicated in the progression of mastitis. This review underscores the potential for non‐antibiotic interventions aimed at restoring microbial balance to reduce mastitis incidence, providing new insights into improving dairy cow health and farm productivity. Our findings emphasise the critical need to explore preventive measures targeting the rumen and intestinal microbiota for effective mastitis control.
Patient controlled epidural analgesia during labor: Protocol for a scoping review
Authors: Henriksen Magnus Grønbæk , Svensson Nikoline , Møller Ann Merete
Published: October 2024

Background

Childbirth remains one of the most painful experiences for women. Patient‐controlled epidural analgesia provides the women in labor with self‐control and thereby a shorter time interval between onset of pain and administration of analgesia, thus potentially improving the childbirth experience. This scoping review aims to investigate PCEA during labor involving maternal satisfaction, risks of adverse effects and obstetric interventions by mapping the evidence and identifying gaps in the current evidence base.

Methods

The forthcoming review will adhere to the Preferred Reporting Items for Systematic reviews and Meta‐Analysis extension for Scoping Reviews (PRISMA‐ScR) and the JBI methodology for scoping reviews. A systematic search will be carried out across major peer‐reviewed databases and gray literature will be sought. All study types involving women in labor receiving PCEA will be eligible for inclusion. The extracted data will be charted regarding trial characteristics, population/participation characteristics, interventions, outcomes, and key findings.

Results

The results will be presented through relevant tables, figures, and graphs when appropriate. Alongside this, we present the data descriptively to explain how the results align with the objectives of the review.

Conclusion

PCEA offers women greater autonomy during childbirth, making it essential to examine its effects and potential risks. By mapping current evidence regarding PCEA, this review aims to identify knowledge gaps and provide insights to enhance maternal care and improve childbirth experiences.
Impact of childhood psoriasis on children and parents during transition to adolescence: An interpretative phenomenological analysis
Authors: Day Marianne , Heapy Connor , Norman Paul , Emerson Lisa‐Marie , Murphy Ruth , Hughes Olivia , Thompson Andrew R.
Published: October 2024

Objectives

Psoriasis is a chronic skin condition that can develop at any age. Childhood psoriasis can lead to stigmatization and reduced quality of life in children and parents. This study aimed to gather a detailed family‐level understanding of the experience of childhood psoriasis during the time of transition to adolescence.

Design

A multi‐perspectival interpretative phenomenological analysis (IPA) was used.

Methods

Sixteen semi‐structured interviews with eight parent–child dyads were conducted and analysed in accordance with IPA principles.

Results

Three superordinate themes and three sub‐themes were identified: 1. ‘Transition and transaction’ including: 1.1 ‘Shifting responsibilities and self‐efficacy’; 2. ‘Stigma and social impact’; and 3. ‘The treatment journey’ including: 3.1 ‘Finding an effective treatment’, 3.2 ‘Coping with on‐going management’. Uncertainties surrounding treatment options were an initial focus of difficulty for families. In adolescence, the difficulty shifted to be more identity focussed as the responsibility for disease management and the increased awareness on body image posed added challenges. Both parents and children described visibility and stigma as the most distressing aspects of living with psoriasis and experienced negative emotions that resurfaced during adolescence.

Conclusions

This study suggests that childhood psoriasis can have a significant impact on children, particularly as they begin to transition to adolescence. Findings also highlight the burden of psoriasis for parents. As such, psychological interventions (such as adapted forms of mindfulness‐based Cognitive‐Behavioural‐Therapy) are needed to target and reduce stress. Such interventions are likely to require a systemic focus and support validation of the real impact and fear of stigmatization.
Daily effects of a brief compassion‐focused intervention for self‐compassion
Authors: Varley Deanna , Sherwell Chase S. , Kirby James N.
Published: October 2024

Interventions for increasing self‐compassion are typically assessed through retrospective reports, which may not accurately capture everyday self‐compassionate behaviour. Our study addresses this using experience sampling to evaluate a brief compassion‐focused intervention's effects on needs for self‐compassion, awareness of opportunities for self‐compassion, self‐compassionate behaviour and emotional responses to one's distress in daily life. Results indicated that the intervention was associated with less likelihood of reporting needs and opportunities for self‐compassion but with no difference in self‐compassionate actions or emotional experience. When participants acted self‐compassionately, they reported more positive emotional experiences after needing self‐compassion. This underscores the disparity between retrospective and ecological assessments, emphasizing the need for interventions to be evaluated in real‐life contexts.
Pharmacokinetics and cardioprotective efficacy of intravenous miR‐125b* microRNA mimic in a mouse model of acute myocardial infarction
Authors: Szabados Tamara , Makkos András , Ágg Bence , Benczik Bettina , Brenner Gábor G. , Szabó Márta , Váradi Barnabás , Vörös Imre , Gömöri Kamilla , Varga Zoltán V. , Görbe Anikó , Bencsik Péter , Ferdinandy Péter
Published: October 2024

Background and purpose

MicroRNA (miRNA) therapy is a promising approach to induce cardioprotection. We have previously identified cardiac microRNA‐125b* (microRNA‐125b‐2‐3p; miR‐125b*) as a potential cardioprotective miRNA, termed ProtectomiR. We aimed to characterize the pharmacokinetics and pharmacodynamics, and the effect of miR‐125b* mimic on infarct size using an in vivo mouse model.

Experimental approach

To characterize the pharmacokinetics properties of miR‐125b* mimic, a single injection of 10‐μg miR‐125b* mimic or its scramble miRNA control, or vehicle i.v. was given to C57BL/6 mice. MiR‐125b* expression was measured from plasma, heart, kidney and liver samples. Effect of miR‐125b* on area at risk and infarct size was assessed after 45‐min coronary occlusion, followed by 24‐h reperfusion; 10‐μg miR‐125b* mimic or 10‐μg non‐targeting miRNA mimic control or vehicle were administered via the right jugular vein at 10th mins of coronary occlusion. To assess molecular mechanism involved in cardioprotection, expression of mRNA targets of miR‐125b* were measured from ventricular myocardium at 1, 2, 4, 8 or 24 h post‐treatment using quantitative real time polymerase chain reaction.

Key results

MiR‐125b* expression was markedly increased in plasma and myocardium 1 h, and in the liver 2h after treatment. Infarct size was significantly reduced after miR‐125b* mimic treatment when compared to the vehicle. The expression of Ccna2, Eef2k and Cacnb2 target mRNAs was significantly reduced 8 h after injection of miR‐125b* mimic.

Conclusion and implications

This is the first demonstration of pharmacokinetic and molecular pharmacodynamic properties as well as the cardioprotective effect of miR‐125b* mimic in vivo.

LINKED ARTICLES

This article is part of a themed issue Non‐coding RNA Therapeutics. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v182.2/issuetoc
MISNeR: Medical Implicit Shape Neural Representation for Image Volume Visualisation
Authors: Jin G. , Jung Y. , Bi L. , Kim J.
Published: October 2024

Three‐dimensional visualisation of mesh reconstruction of the medical images is commonly used for various clinical applications including pre / post‐surgical planning. Such meshes are conventionally generated by extracting the surface from volumetric segmentation masks. Therefore, they have inherent limitations of staircase artefacts due to their anisotropic voxel dimensions. The time‐consuming process for manual refinement to remove artefacts and/or the isolated regions further adds to these limitations. Methods for directly generating meshes from volumetric data by template deformation are often limited to simple topological structures, and methods that use implicit functions for continuous surfaces, do not achieve the level of mesh reconstruction accuracy when compared to segmentation‐based methods. In this study, we address these limitations by combining the implicit function representation with a multi‐level deep learning architecture. We introduce a novel multi‐level local feature sampling component which leverages the spatial features for the implicit function regression to enhance the segmentation result. We further introduce a shape boundary estimator that accelerates the explicit mesh reconstruction by minimising the number of the signed distance queries during model inference. The result is a multi‐level deep learning network that directly regresses the implicit function from medical image volumes to a continuous surface model, which can be used for mesh reconstruction from arbitrary high volume resolution to minimise staircase artefacts. We evaluated our method using pelvic computed tomography (CT) dataset from two public sources with varying z‐axis resolutions. We show that our method minimised the staircase artefacts while achieving comparable results in surface accuracy when compared to the state‐of‐the‐art segmentation algorithms. Furthermore, our method was 9 times faster in volume reconstruction than comparable implicit shape representation networks.