bluuebunny/crossref_metadata_2025 huggingface dataset:
Left ventricular concentric remodeling is highly common among veterans previously deployed to Southwest Asia Theater of Military Operations and associated with impaired exercise performance
Authors: Cassady Steven J. , Abitante Thomas J. , Pappas Gregory G. , Alexander Thomas , Falvo Michael J. ,   Post-Deployment Cardiopulmonary Evaluation Network
Published: September 2024

Background

Environmental factors, such as exposure to airborne hazards, contribute to cardiac remodeling through a variety of mechanisms including direct cardiotoxicity. Left ventricular concentric remodeling (LVCR) is a pathological process of adaptive myocardial change that may represent a precursor state for systolic and diastolic dysfunction and left ventricular hypertrophy. Given that potentially cardiotoxic airborne hazards, such as those produced by open burn pits, have been found to occur in excess in active military combat zones, deployed veterans may be at increased risk for adverse cardiac remodeling, but this has not been thoroughly investigated.

Methods

139 veterans of Southwest Asia Theater of Military Operations underwent transthoracic echocardiography, cardiopulmonary exercise testing (CPET), and health questionnaires. Two-dimensional echocardiography was used to quantify relative wall thickness (RWT) to classify left ventricular (LV) geometry as normal, concentric/eccentric hypertrophy, or LVCR. Observed rates of LVCR were compared to those reported in the Framingham Heart Study, and CPET results were compared between those with and without LVCR. We examined the association between RWT and select CPET outcomes via an adjusted multivariate regression model.

Results

The prevalence of LVCR in the veteran sample (30.2%) was elevated compared to the Framingham Heart Study cohort (6–16%). Demographics and risk factors were similar between veterans with LVCR and normal geometry; however, veterans with LVCR had reduced exercise capacity (V̇O2,23.7 vs 26.2 ml/kg/min, p<0.05), more inefficient exercise ventilation (VE/V̇CO2nadir: 26.8 vs 25.2, p<0.05), and increased heart rate (HR) reserve (24.7 vs 17.4, p<0.05). RWT was independently associated only with peak HR attained and HR reserve.

Conclusions

In our sample of deployed veterans without significant risk factors, the observed rates of LVCR are 2- to 5-fold greater than those reported in a historical civilian cohort. Further, veterans with LVCR also had impaired exercise performance relative to those with normal LV geometry despite otherwise appearing similar. These findings underscore the importance of cardiovascular assessments as part of a dyspnea evaluation for deployed veterans with airborne hazards exposure and raise concerns about their long-term cardiovascular health.
Integrating multi-tissue expression and splicing data to prioritise anatomical subsite- and sex-specific colorectal cancer susceptibility genes with therapeutic potential
Authors: Hazelwood Emma , Canson Daffodil M. , Wang Xuemin , Kho Pik Fang , Legge Danny , Constantinescu Andrei-Emil , Lee Matthew A. , Bishop D. Timothy , Chan Andrew T. , Gruber Stephen B. , Hampe Jochen , Marchand Loic Le , Woods Michael O. , Pai Rish K. , Schmit Stephanie L. , Figueiredo Jane C , Zheng Wei , Huyghe Jeroen R. , Murphy Neil , Gunter Marc J. , Richardson Tom G. , Whitehall Vicki L. J. , Vincent Emma E. , Glubb Dylan M. , O’Mara Tracy A.
Published: September 2024

Numerous potential susceptibility genes have been identified for colorectal cancer (CRC). However, it remains unclear which genes have a causal role in CRC risk, whether these genes are associated with specific types of CRC, and if they have potential for therapeutic targeting. We performed a multi-tissue transcriptome-wide association study (TWAS) across six relevant normal tissues (n=187-670) and applied a causal framework (involving Mendelian randomisation and genetic colocalisation) to prioritise causal associations between gene expression or splicing events and CRC risk (52,775 cases; 45,940 controls), incorporating sex- and anatomical subsite-specific analyses. We identified 35 genes with robust evidence for a potential causal role in CRC, including ten genes not previously identified by TWAS. Among these genes,SEMA4Demerged as a significant discovery; it is not located at any established CRC genome-wide association study (GWAS) risk locus and its encoded protein is targeted by an antibody currently being clinically studied for CRC treatment. Several genes showed increased expression associated with CRC risk and evidence of CRC cell dependency in CRISPR screen analyses, highlighting their potential as targets for therapeutic inhibition. A female-specific association with CRC risk was observed forCCM2expression, which is involved in progesterone signalling pathways. Subsite-specific associations were also found, including a link between rectal cancer risk and expression ofLAMC1, which encodes a target for a clinically approved drug. Additionally, we performed a focused analysis of established drug targets to further identify potential therapies for CRC, revealingPDCD1, the product of which (PD-1) is targeted by a clinically approved CRC immunotherapy. In summary, our comprehensive analysis provides valuable insights into the molecular underpinnings of CRC and supports promising avenues for therapeutic intervention.
Enhancing Dietary Supplement Question Answer via Retrieval-Augmented Generation (RAG) with LLM
Authors: Hou Yu , Zhang Rui
Published: September 2024

Objective

To enhance the accuracy and reliability of dietary supplement (DS) question answering by integrating a novel Retrieval-Augmented Generation (RAG) LLM system with an updated and integrated DS knowledge base and providing a user-friendly interface. With.

Materials and Methods

We developed iDISK2.0 by integrating updated data from multiple trusted sources, including NMCD, MSKCC, DSLD, and NHPD, and applied advanced integration strategies to reduce noise. We then applied the iDISK2.0 with a RAG system, leveraging the strengths of large language models (LLMs) and a biomedical knowledge graph (BKG) to address the hallucination issues inherent in standalone LLMs. The system enhances answer generation by using LLMs (GPT-4.0) to retrieve contextually relevant subgraphs from the BKG based on identified entities in the query. A user-friendly interface was built to facilitate easy access to DS knowledge through conversational text inputs.

Results

The iDISK2.0 encompasses 174,317 entities across seven types, six types of relationships, and 471,063 attributes. The iDISK2.0-RAG system significantly improved the accuracy of DS-related information retrieval. Our evaluations showed that the system achieved over 95% accuracy in answering True/False and multiple-choice questions, outperforming standalone LLMs. Additionally, the user-friendly interface enabled efficient interaction, allowing users to input free-form text queries and receive accurate, contextually relevant responses. The integration process minimized data noise and ensured the most up-to-date and comprehensive DS information was available to users.

Conclusion

The integration of iDISK2.0 with an RAG system effectively addresses the limitations of LLMs, providing a robust solution for accurate DS information retrieval. This study underscores the importance of combining structured knowledge graphs with advanced language models to enhance the precision and reliability of information retrieval systems, ultimately supporting better-informed decisions in DS-related research and healthcare.
Cognitive and Mental Health Profiles of Binge-Eating Populations with and without Comorbid Addiction
Authors: Jeong Jake , Jang Jungwon , Jeon Giho , Baek Kwangyeol
Published: September 2024

Binge eating disorder (BED) is one of the most prevalent eating disorders and involves an increased risk of mental health problems, obesity and metabolic disease. Recent studies suggest that BED is similar to addictive disorders in its phenomenology and neurobiological mechanisms. Comorbid addiction (e.g., substance use disorders and behavioral addiction) is also very frequent in BED patients. However, it is still unclear whether BED population with comorbid addictions differ in their cognitive and mental health characteristics (e.g., impulsivity, behavioral inhibition, self-control, emotion regulation, mood and anxiety) than those without comorbid addiction. In the present study, we compared various psychometric scales across 30 binge-eating individuals with co-occurring addictive behaviors (i.e., alcohol, nicotine, gambling, and video games), 32 binge-eating individuals without addiction, and 178 healthy control subjects with neither binge-eating nor addiction. Both binge-eating groups showed a significant increase in inhibition motivation (BAS/BIS-inhibition), perceived stress, and state/trait anxiety compared to healthy controls, but there was no difference between the two binge-eating groups. Higher impulsivity and lower self-control were observed in both binge-eating populations to a significantly larger extent in the group with comorbid addiction. Interestingly, significantly increased depression and impaired emotion regulation (less use of cognitive reappraisal) were observed only in the binge-eating group with comorbid addiction when compared to the healthy controls. Our findings demonstrated the commonality and difference in binge-eating populations with and without comorbid addiction. It will help to elucidate cognitive and mental health aspects of comorbid addiction in BED and develop more tailored diagnoses and treatments.
Single-stranded HDR templates with truncated Cas12a binding sequences improve knock-in efficiencies in primary human T cells
Authors: Nitulescu Ana-Maria , Du Weijie , Glaser Viktor , Kath Jonas , Greensmith Robert , Mikkelsen Nanna Steengaard , Stein Maik , Bak Rasmus O. , Kaminski Michael , Wagner Dimitrios L.
Published: September 2024

Non-viral gene editing via CRISPR-Cas12a offers an alternative to Cas9-based methods, providing better targeting of AT-rich regions, simplified guide RNA manufacturing, and high specificity. However, the efficacy of editing outcomes is subject to various factors, with template format playing a crucial role. Currently, the predominant non-viral template format for inducing homology-directed repair (HDR) after nuclease-induced DNA breaks is double-stranded DNA (dsDNA), which is toxic when transfected at high doses. Previous studies have demonstrated that using single-stranded DNA (ssDNA) with flanking double-stranded Cas-target-sequences (CTS) as a repair template for Cas9-mediated gene editing can mitigate this toxicity and increase knock-in efficiency. Here, we investigate CTS design for AsCas12a Ultra by exploring PAM orientation and binding requirements of the Cas12a-crRNA complex. Additionally, we rule outin vitrossDNase activity of AsCas12a Ultra under cell-physiological Mg2+conditions. Finally, we showcase the advantage of using ssDNA with double-stranded CTS end modifications (ssCTS) at high doses for delivering clinically relevant transgenes of varying sizes into three T-cell receptor-CD3 complex genes (TRAC,CD3ζ, CD3ε), achieving up to 90% knock-in rates for a 0.8kb insert at theCD3ε locus. Overall, AsCas12a Ultra and ssCTS donors represent a platform for highly efficient knock-in in primary human T cells with minimal toxicity.
Differential interference with actin-binding protein function by acute Cytochalasin B
Authors: Lambert Christopher , Karger Marius , Steffen Anika , Tang Yubo , Döring Hermann , Stradal Theresia E. B. , Lappalainen Pekka , Faix Jan , Bieling Peter , Rottner Klemens
Published: September 2024

Dynamic actin filament remodeling is crucial for a plethora of fundamental cell biological processes, ranging from cell division and migration to cell communication, intracellular trafficking or tissue development. Cytochalasin B and -D are fungal secondary metabolites frequently used for interference with such processes. Although generally assumed to block actin filament polymerization at their rapidly growing barbed ends and compete with regulators at these sites, our molecular understanding of their precise effects in dynamic actin structures is scarce. Here we combine live cell imaging and analysis of fluorescent actin-binding protein dynamics with acute treatment of lamellipodia in migrating cells with cytochalasin B. Our results show that in spite of an abrupt halt of lamellipodium protrusion, cytochalasin B affects various actin filament barbed end-binding proteins in a differential fashion. Cytochalasin B enhances instead of diminishes the accumulation of prominent barbed end-binding factors such as Ena/VASP family proteins and heterodimeric capping protein (CP) in the lamellipodium. Similar results were obtained with cytochalasin D. All these effects are highly specific, as cytochalasin-induced VASP accumulation requires the presence of CP, but notvice versa, and coincides with abrogation of both actin and VASP turnover. Cytochalasin B can also increase apparent barbed end interactions with the actin-binding β-tentacle of CP and partially mimic its Arp2/3 complex-promoting activity in the lamellipodium. In conclusion, our results reveal a new spectrum of cytochalasin activities on barbed end-binding factors, with important implications for the interpretation of their effects on dynamic actin structures.
SusC/D-like proteins inGammaproteobacteriathat utilize fructans
Authors: Zühlke Marie-Katherin , Bahr Alexandra , Bartosik Daniel , Solanki Vipul , Teune Michelle , Unfried Frank , Barbeyron Tristan , Ficko-Blean Elizabeth , Cladière Lionel , Jeudy Alexandra , Susemihl Anne , Hartmann Fabian , Jouanneau Diane , Jam Murielle , Höhne Matthias , Delcea Mihaela , Bornscheuer Uwe T. , Becher Dörte , Hehemann Jan-Hendrik , Czjzek Mirjam , Schweder Thomas
Published: September 2024

SusC/D-like proteins are essential components of glycan utilization machineries inBacteroidota, but remain unknown in other bacterial phyla. The glycan-binding SusD-like protein forms a ‘lid’ on top of the SusC-like TonB-dependent transporter (TBDT) and both are structurally designed to function as a complex in sugar uptake. In comparison,Gammaproteobacteriaimport glycans using ‘classical’ TBDTs without an accessory SusD-like protein. We have now identified a SusD-like protein and a SusC-like TBDT in a fructan polysaccharide utilization locus (PUL) of the marine gammaproteobacteriumPseudoalteromonas distincta, which are tandemly organized as inBacteroidota. Proteome analysis revealed an increased production of PUL-encoded proteins during growth on inulin- and levan-type fructans. However,P. distinctapreferred inulin over plant-derived levan and hardly grew on bacterial levan. Further analysis showed that the SusD-like protein has a weak affinity (Ka43 M-1) for oligosaccharides from inulin. The PUL-encoded glycoside hydrolase from family 32 (GH32) hydrolyzes inulin and plant-derived levan, but also has a low activity on bacterial levan, which confirms the growth experiments. Comparative genomics identified further SusC/D-like proteins inGammaproteobacteriagenomes, most of which (83%) were encoded in fructan PULs.

Significance statement

It is a mystery why the Gram-negativeBacteroidotaandGammaproteobacteriause different transport systems for glycan utilization. In contrast to this observation, we found that the gammaproteobacteriumPseudoalteromonas distinctauses aBacteroidota-like transport complex in fructan uptake, composed of a glycan-binding SusD-like protein and a SusC-like TonB-dependent transporter. Proteome analysis revealed that the SusC/D-like proteins and a fructan-degrading enzyme are produced at high levels in fructan-grown cells. Weak affinity of the SusD-like protein to inulin oligosaccharides and enzyme activity on fructans confirmed their fructan specificity. Further SusC/D-like pairs were detected in otherGammaproteobacteria, mostly associated with fructan-related gene clusters. This study thus describes marine fructan use byGammaproteobacteriaand indicates an exchange of protein functions between phyla.
Complete mitochondrial genomes of riverineLamprologus(Actinopterygii, Cichlidae) with an emphasis on the blind cichlidL. lethops
Authors: Jimenez Sebastian M. , Kurata Naoko P. , Stiassny Melanie L. J. , Alter S. Elizabeth , Chakrabarty Prosanta , Alda Fernando
Published: September 2024

Lamprologine cichlids are a diverse group of fishes distributed in Lake Tanganyika and the Congo River. Nine species ofLamprologusoccur in the Congo River basin including the only blind cichlidLamprologus lethops, but little is known about the natural history and evolution of this enigmatic species. To alleviate this knowledge gap, we characterized the complete mitochondrial genomes ofL. lethopsand its riverine congeners and provided a phylogenetic hypothesis based on these data. We recovered complete mitochondrial genomes from eleven specimens of eight species ofLamprologus. Mitogenomes were identical in the number and order of genes and similar in size (16,579-16,587 bp). In contrast to previous phylogenomic studies, riverineLamprologuswere recovered in two non-sister mitochondrial lineages that were more closely related to other genera of Lake Tanganyika lamprologines than to each other. In the first lineage, most relationships were not highly supported. In the second lineage,L. lethopswas recovered as the sister species ofL. markerti, L. mocquardiandL. tigripictilis. Interestingly, sequences fromL. mocquardiwere found in the two mitochondrial lineages. Our results hint at multiple events of past introgression and highlight the importance of increasing taxonomic and genomic sampling to study complex evolutionary histories.
Antibiotic-Induced Morphological Changes Enhance Phage Propagation: A Mathematical Model of Plaque Formation in Structured Environments
Authors: Bulssico Julián , Panigrahi Swapnesh , Ginet Nicolas , Ansaldi Mireille
Published: September 2024

A distinctive manifestation of phage infection in solid media is the appearance of lysis plaques, which correspond to the circular thinning of a bacterial lawn. During plaque formation, successive cycles of phage replication generally take place from a single point of infection and spread radially in a matrix of immobilized bacterial hosts. Many different factors affect plaque size, such as the composition and the reticulation of the propagation matrix, the characteristics of the phage, but also parameters related to the physiology of the bacterial host.

Since combined administration of both antibiotics and phages is a common practice during compassionate treatments, our research focuses on the effects of antibiotics on phage predation, which can be of crucial importance for the therapeutic applications of phages.

It has been previously observed that the presence of antibiotics at sublethal concentrations can affect drastically bacterial physiology, allowing phages to spread more rapidly and resulting in better bacterial eradication. Previous experimental work has focused on the phage characteristics that influence plaque size. However, as plaque formation is strongly influenced by host growth dynamics, a comprehensive model integrating both the host growth and phage infection parameters is required.

In this work, we suggest that plaque enlargement is linked to morphological changes of the host that have an impact on the rate of epidemic propagation and certainly on phage diffusion into the matrix. To support this hypothesis, we characterized the growth parameters of two different phages and bacteria in semi-solid media in the presence of various antibiotics. By combining these data, we have produced a mathematical model that accounts for these observations and explains the increase in plaque size when the host morphology is affected.

Significance Statement

This study provides new insights into the phenomenon of Phage-Antibiotic Synergy (PAS) by demonstrating that antibiotic-induced morphological changes in bacterial hosts play a critical role in enhancing phage propagation in structured environments. By linking these morphological alterations—such as cell filamentation and bloating—to increased lysis plaque size, the research underscores the importance of host dynamics in phage therapy. The development of a mathematical model integrating both host growth and phage infection parameters offers a novel framework for understanding and optimizing phage-based treatments in the presence of antibiotics, potentially improving therapeutic outcomes.
Single Distal Mutation Enhances Activity of known PETases via Stabilisation of PET-binding
Authors: Fu Xiaozhi , Gracia I. Carmona Oriol , Abrusan Gyorgy , Jiao Xiang , Diaciuc Alexander , Gautel Mathias , Fraternali Franca , Zelezniak Aleksej
Published: September 2024

As a major source of plastic pollution, PET has attracted significant interest for biodegradation due to its potential in the circular economy. Finding effective enzymes still remains a challenge as screening methods are limited by either the low throughput or dependence on alternative non-PET substrates due to PET’s insolubility. Here, we report a highly active, stable and robust enzyme, Fast_2.9, identified while directly screening for PET-degrading activity in mesophilic conditions using droplet-based encapsulation of PET nanoparticles with the throughput above 1 kHz. We identified a distal S269T mutation that improves activity in the majority of all known PETases with up to 400 times over wildtype, and more than twice of known engineered PETases, as tested on untreated post-consumer plastics. Microsecond time scale molecular dynamics analyses indicate that this distant mutation possibly influences residues near the substrate-binding cleft via a common mechanism across PETases. Compared to the state-of-the-art FastPETase and LCCICCGenzymes, the engineered Fast_2.9 enzyme requires up to 8 and 42 times lower enzyme concentrations to reach the same enzymatic activity, ultimately requiring significantly less enzyme. As such our engineered enzyme degrades multiple post-consumer PET substrates, including polyester textiles, within as least as just 2 days with up to nearly 100% terephthalic acid conversion using as little as 0.72 mgenzyme/gPETat 50℃. Our study presents a universal methodology for direct screening of insoluble substrates at ultra-high-throughput and highlights the techno-economic potential of Fast_2.9 for PET depolymerisation.
PathMHC: a workflow to selectively target pathogen-derived MHC peptides in discovery immunopeptidomics experiments for vaccine target identification
Authors: Leddy Owen , Yuki Yuko , Carrington Mary , Bryson Bryan D. , White Forest M.
Published: September 2024

Vaccine-elicited T cell responses can contribute to immune protection against emerging infectious disease risks such as antimicrobials-resistant (AMR) microbial pathogens and viruses with pandemic potential, but rapidly identifying appropriate targets for T cell priming vaccines remains challenging. Mass spectrometry (MS) analysis of peptides presented on major histocompatibility complexes (MHCs) can identify potential targets for protective T cell responses in a proteome-wide manner. However, pathogen-derived peptides are outnumbered by self peptides in the MHC repertoire and may be missed in untargeted MS analyses. Here we present a novel approach, termed PathMHC, that uses computational analysis of untargeted MS data followed by targeted MS to discover novel pathogen-derived MHC peptides more efficiently than untargeted methods alone. We applied this workflow to identify MHC peptides derived from multiple microbes, including potential vaccine targets presented on MHC-I by human dendritic cells infected withMycobacterium tuberculosis. PathMHC will facilitate antigen discovery campaigns for vaccine development.
The transcriptome of playfulness is sex-biased in the juvenile rat medial amygdala: a role for inhibitory neurons
Authors: Marquardt Ashley E. , Basu Mahashweta , VanRyzin Jonathan W. , Ament Seth A. , McCarthy Margaret M.
Published: September 2024

Social play is a dynamic behavior known to be sexually differentiated; in most species, males play more than females, a sex difference driven in large part by the medial amygdala (MeA). Despite the well-conserved nature of this sex difference and the importance of social play for appropriate maturation of brain and behavior, the full mechanism establishing the sex bias in play is unknown. Here, we explore “the transcriptome of playfulness” in the juvenile rat MeA, assessing differences in gene expression between high- and low-playing animals of both sexes via bulk RNA-sequencing. Using weighted gene co-expression network analysis (WGCNA) to identify gene modules combined with analysis of differentially expressed genes (DEGs), we demonstrate that the transcriptomic profile in the juvenile rat MeA associated with playfulness is largely distinct in males compared to females. Of the 13 play-associated WGCNA networks identified, only two were associated with play in both sexes, and very few DEGs associated with playfulness were shared between males and females. Data from our parallel single-cell RNA-sequencing experiments using amygdala samples from newborn male and female rats suggests that inhibitory neurons drive this sex difference, as the majority of sex-biased DEGs in the neonatal amygdala are enriched within this population. Supporting this notion, we demonstrate that inhibitory neurons comprise the majority of play-active cells in the juvenile MeA, with males having a greater number of play-active cells than females, of which a larger proportion are GABAergic. Through integrative bioinformatic analyses, we further explore the expression, function, and cell-type specificity of key play-associated modules and the regulator “hub genes” predicted to drive them, providing valuable insight into the sex-biased mechanisms underlying this fundamental social behavior.
The transmembrane glycoprotein Gpnmb is required for the immune and fibrotic responses during zebrafish heart regeneration
Authors: Gupta Savita , Bajwa Gursimran Kaur , El-Sammak Hadil , Mattonet Kenny , Günther Stefan , Looso Mario , Stainier Didier Y. R. , Marín-Juez Rubén
Published: September 2024

Myocardial infarction occurs when coronary supply of oxygen and nutrients to part of the heart is interrupted. In contrast to adult mammals, adult zebrafish have a unique ability to regenerate their heart after cardiac injury. Several processes are involved in this regenerative response including inflammation, coronary endothelial cell proliferation and revascularization, endocardial expansion, cardiomyocyte repopulation, and transient scar formation. To identify potential regulators of zebrafish cardiac regeneration, we profiled the transcriptome of regenerating coronary endothelial cells at 7 days post cryoinjury (dpci) and observed the significant upregulation of dozens of genes includinggpnmb. Gpnmb (glycoprotein non-metastatic melanoma protein B) is a transmembrane glycoprotein implicated in inflammation resolution and tissue regeneration. Transcriptomic profiling data of cryoinjured zebrafish hearts reveal thatgpnmbis mostly expressed by macrophages. To investigategpnmbfunction during zebrafish cardiac regeneration, we generated a full locus deletion (FLD) allele. We find that after cardiac cryoinjury, animals lackinggpnmbexhibit neutrophil retention and decreased macrophage recruitment as well as reduced myofibroblast numbers. Moreover, loss ofgpnmbimpairs coronary endothelial cell regeneration and cardiomyocyte dedifferentiation. Transcriptomic analyses of cryoinjuredgpnmbmutant hearts identified enhanced collagen gene expression and the activation of extracellular matrix (ECM) related pathways. Furthermore,gpnmbmutant hearts exhibit larger fibrotic scars revealing additional defects in cardiac regeneration. Altogether, these data indicate thatgpnmbexpressing macrophages modulate inflammation and ECM deposition after cardiac cryoinjury in zebrafish and further highlight the importance of this subset of immune cells to support a regenerative response.
From peas to people - using quantitative traits to aid genetic discovery in depression
Authors: Hall Lynsey S , Adams Mark J , Zeng Yanni , Gibson Jude , Wigmore Ella M , Fernandez-Pujals Ana Maria , Whalley Heather C , Haley Chris S , McIntosh Andrew M
Published: September 2024

A key component of Mendels work is what we now refer to as pleiotropy - when variation in one gene gives rise to variation in multiple phenotypes. This study focuses on aiding genetic discovery in depression by revisiting the depressed phenotype and developing a quantitative trait in a large mixed family and population study, using analyses built upon the theory which underpins Mendels pleiotropic observations - the relationship between phenotypic variation and genetic variation. Measures of genetic covariation were used to evaluate and rank ten measures of mood, personality, and cognitive ability as endophenotypes for depression. The highest-ranking traits were subjected to principal component analysis, and the first principal component used to create multivariate measures of depression. Four traits fulfilled most endophenotype criteria, however, only two traits (neuroticism and the general health questionnaire) consistently ranked highest across all measures of covariation. As such, three composite traits were derived incorporating two, three, or four traits. Composite traits were compared to the binary classification of depression and to their constituent univariate traits in terms of their coheritability, their ability to identify risk loci in a genome-wide association analysis, and phenotypic variance explained by polygenic profile scores for depression. Association analyses of binary depression, univariate traits, and composite traits yielded no genome-wide significant results. However, composite traits were more heritable and more highly correlated with depression than their constituent traits, suggesting that analysing candidate endophenotypes in combination captures more of the heritable component of depression and may in part be limited by sample size in the current study.
Inverse magnetic catalysis and energy loss in a holographic QCD model
Authors: Zhu Zhou-Run , Hou Defu
Published: September 2024

In this paper, we consider the Einstein-Maxwell-dilaton holographic model for light quarks with nonzero magnetic field and chemical potential. First, we study the phase diagrams in T−μ and T−B planes. We observe inverse magnetic catalysis which is consistent with the lattice QCD results. We discuss the influence of the magnetic field and chemical potential on the location of the critical end point (CEP). It is found that the magnetic field increases the critical μCEP of the CEP in the T−μ plane and the chemical potential increases the critical BCEP of the CEP in the T−B plane. Second, we discuss the equations of state (EOS) with nonzero magnetic field and chemical potential. We observe that the EOS near the phase transition temperature are nonmonotonic. Then we study the energy loss with a nonzero magnetic field and chemical potential. It is found that the drag force of the heavy quark and jet quenching parameter q^ show an enhancement near the phase transition temperature. The peak values of drag force and q^ are pushed toward lower temperature with increasing B or μ. This phenomenon is consistent with the phase transition temperature decrease with increasing B or μ in this holographic model. Moreover, we find that the heavy quark may lose more energy when it is perpendicular to a magnetic field, which is consistent with the results of the jet quenching parameter.

Published by the American Physical Society
2024
Model for efficient dynamical ranking in networks
Authors: Della Vecchia Andrea , Neocosmos Kibidi , Larremore Daniel B. , Moore Cristopher , De Bacco Caterina
Published: September 2024

We present a physics-inspired method for inferring dynamic rankings in directed temporal networks—networks in which each directed and timestamped edge reflects the outcome and timing of a pairwise interaction. The inferred ranking of each node is real-valued and varies in time as each new edge, encoding an outcome like a win or loss, raises or lowers the node's estimated strength or prestige, as is often observed in real scenarios including sequences of games, tournaments, or interactions in animal hierarchies. Our method works by solving a linear system of equations and requires only one parameter to be tuned. As a result, the corresponding algorithm is scalable and efficient. We test our method by evaluating its ability to predict interactions (edges' existence) and their outcomes (edges' directions) in a variety of applications, including both synthetic and real data. Our analysis shows that in many cases our method's performance is better than existing methods for predicting dynamic rankings and interaction outcomes.

Published by the American Physical Society
2024
How women and lesbian, gay, bisexual, transgender, and queer physics doctoral students navigate graduate education: The roles of professional environments and social networks
Authors: Gutzwa Justin A. , Barthelemy Ramón S. , Amaral Camila , Swirtz Madison , Traxler Adrienne , Henderson Charles
Published: September 2024

Despite knowing physics and astronomy doctoral programs are laden with identity-based inequities, they continue to push minoritized students to the margins. This qualitative social network analysis of 100 women and/or lesbian, gay, bisexual, transgender, queer, and more (LGBT+) physics and astronomy Ph.D.’s explores how minoritized physics and astronomy students utilize social networks to navigate departmental exclusion. Our findings indicate that many of the participants’ identities were often unacknowledged or negatively addressed within their graduate education, with only four participants reporting a positive or favorable experience during this period of their career. Direct support from peers, faculty, and identity-based affinity groups was necessary for participants to navigate their educations. This study demonstrated that generic best practices often cannot fully support the diverse range of persons who come to physics and that identity-neutral values in physics further isolate students by insinuating that their own minoritized experiences are not valid.

Published by the American Physical Society
2024
Protocols for trainable and differentiable quantum generative modeling
Authors: Kyriienko Oleksandr , Paine Annie E. , Elfving Vincent E.
Published: September 2024

We propose an approach for learning probability distributions as differentiable quantum circuits (DQC) that enable efficient quantum generative modeling (QGM) and synthetic data generation. Contrary to existing QGM approaches, we perform training of a DQC-based model, where data is encoded in a latent space with the proposed phase feature map of exponential capacity. This is followed by a trainable quantum circuit, forming the model. We then map the trained model to the bit basis using a fixed unitary transformation, in this case corresponding to a quantum Fourier transform circuit. It allows fast sampling from parametrized distributions using a single-shot readout. Importantly, latent space training provides models that are automatically differentiable, and we show how samples from solutions of stochastic differential equations (SDEs) can be accessed by solving stationary and time-dependent Fokker-Planck equations with a quantum protocol. Our approach opens a route to multidimensional generative modeling with qubit registers explicitly correlated via a (fixed) entangling layer. In this case quantum computers can offer advantage as efficient samplers, which perform complex inverse transform sampling enabled by the fundamental laws of quantum mechanics. On a technical side the advances are multiple, as we introduce the phase feature map, analyze its properties, and develop frequency-taming techniques that include qubitwise training and feature map sparsification.

Published by the American Physical Society
2024
Squeezing-induced quantum-enhanced multiphase estimation
Authors: Ho Le Bin
Published: September 2024

We investigate how squeezing techniques can improve the measurement precision in multiphase quantum metrology. While these methods are well studied and effectively used in single-phase estimations, their usage in multiphase situations has yet to be examined. We fill this gap by investigating the mechanism of quantum enhancement in the multiphase scenarios. Our analysis provides theoretical and numerical insights into the optimal condition for achieving the quantum Cramér-Rao bound, helping us understand the potential and mechanism for quantum-enhanced multiphase estimations with squeezing. In this paper, we open possibilities for advancements in quantum metrology and sensing technologies.

Published by the American Physical Society
2024
Guiding Diffusion Models for Antibody Sequence and Structure Co-design with Developability Properties
Authors: Villegas-Morcillo Amelia , Weber Jana M. , Reinders Marcel J. T.
Published: September 2024

Recent advances in deep generative methods have allowed antibody sequence and structure co-design. This study addresses the challenge of tailoring the highly variable complementarity-determining regions (CDRs) in antibodies to fulfill developability requirements. We introduce a guidance approach that integrates property information into the antibody design process using diffusion probabilistic models. This approach allows us to simultaneously design CDRs conditioned on antigen structures while considering critical properties like solubility and folding stability. Our property-guided diffusion model offers versatility by accommodating diverse property constraints, presenting a promising avenue for computational antibody design in therapeutic applications.

Published by the American Physical Society
2024
Crystal structure, Hirshfeld surface analysis, DFT optimized molecular structure and the molecular docking studies of 1-[2-(cyanosulfanyl)acetyl]-3-methyl-2,6-bis(4-methylphenyl)piperidin-4-one
Authors: Karthiga A. R. , Divyabharathi S. , Shalo R. Reshwen , Rajeswari K. , Vidhyasagar T. , Selvanayagam S.
Published: September 2024

The two molecules in the asymmetric unit of the title compound, C23H24N2O2S, have a structural overlap with an r.m.s. deviation of 0.82 Å. The piperidine rings adopt a distorted boat conformation. Intra- and intermolecular C—H...O hydrogen bonds are responsible for the cohesion of the crystal packing. The intermolecular interactions were quantified and analysed using Hirshfeld surface analysis. The molecular structure optimized by density functional theory (DFT) at the B3LYP/6–311++G(d,p)level is compared with the experimentally determined molecular structure in the solid state.
Synthesis, crystal structure and Hirshfeld surface analysis of 4′-cyano-[1,1′-biphenyl]-4-yl 3-(benzyloxy)benzoate
Authors: Harish Kumar M. , Vinduvahini M. , Devarajegowda H. C. , Srinivasa H. T. , Palakshamurthy B. S.
Published: September 2024

In the title compound, C27H19O3N, the dihedral angle between the aromatic rings of the biphenyl unit is 38.14 (2)° and the C—O—C—C torsion angle in the benzyloxy benzene fragment is 179.1 (2)°. In the crystal, the molecules are linked by weak C—H...O interactions forming S(9) chains propagating along [010]. The most important contributions to the Hirshfeld surface arise from H...H (32.4%) and C...H/H...C (37.0%) contacts.
Green supply chain management and sustainable performance: exploring the role of circular economy capability and green ambidexterity innovation
Authors: Martínez-Falcó Javier , Sánchez-García Eduardo , Marco-Lajara Bartolomé , Andreu Rosario
Published: September 2024

Purpose

The present research aims to analyze the influence of Green Supply Chain Management (GSCM) on the Sustainable Performance (SP) of Spanish wineries, examining the intermediary roles of Circular Economy Capability (CEC) and Green Ambidexterity Innovation (GAI) within this primary relationship. In particular, the study seeks to answer the following Research Questions (RQs): (RQ1), does GSCM exert a positive impact on wineries’ SP? (RQ2), does CEC play a mediating role in the interconnection between GSCM and wineries’ SP? And (RQ3), does GAI function as a mediator in the interplay between GSCM and wineries’ SP?

Design/methodology/approach

The research utilizes Partial Least Squares Structural Equation Modeling (PLS-SEM) to evaluate the hypothesized theoretical model using primary data collected from 196 Spanish wineries from September 2022 to January 2023.

Findings

The results reveal a positive relationship between GSCM and SP in Spanish wineries, as well as the existence of positive partial mediations of CEC and GAI in this main linkage, which allows an affirmative answer to the three RQs formulated.

Originality/value

Distinguished by its innovative exploration, this research marks a pioneering effort in the uncharted field of scrutinizing CEC and GAI as mediating factors in the GSCM-SP nexus, thereby enriching the existing body of knowledge and opening new avenues for future academic research on sustainability in the wine industry.
Framing effects in non-GMO labels: an empirical study of the impact of non-GMO label frames on consumers' food preferences
Authors: Chen Zhouhai , Wang Hong , Hu Jiahao
Published: September 2024

Purpose

Food labels are increasingly used to provide information to consumers. As a common design strategy used for food package labels globally, label frame is often used to expand the perceived breadth of a brand and create a broader brand image. We evaluated the effect of the presence or absence of a non-genetically modified organism (non-GMO) label frame on consumers' preferences for non-GMO foods.

Design/methodology/approach

This study collected data from 120 MBA students at a university in Sichuan, China, and 126 foreign volunteers in a shopping mall in Chengdu, Sichuan Province. The study investigates the effect of the presence or absence of non-GMO label frame (i.e. label with or without an outline) on non-GMO food preferences through a field survey and two controlled experiments. To empirically analyse the psychological mechanisms by which non-GMO label frames affect consumers' preferences for non-GMO food, we set up the mediating variable of food association of safety.

Findings

For ordinary consumers, a framed non-GMO label is more likely to evoke food association of safety and further enhance consumer preference for non-GMO foods. It facilitates consumers' choice of healthier foods. This finding did not otherwise vary across demographic characteristics.

Originality/value

This study is the first to examine the influence of non-GMO label frames on consumers' non-GMO food preferences, which is an innovative research question. The findings of this study are instructive for food manufacturers and policymakers to better design and use non-GMO label frames to attract more consumers to choose non-GMO foods.
Technological and market sensing capabilities as drivers of SME participation in public procurement: an empirical test of the moderating role of financial capability
Authors: Israel Baraka , Mwenda Beny
Published: September 2024

Purpose

Public procurement presents substantial market opportunities for small- and medium-sized enterprises (SMEs), which can contribute to their economic growth. However, limited dynamic capabilities often pose challenges for SMEs to participate effectively in public procurement markets. Drawing on dynamic capability (DC) theory, this study explores whether financial capability (FNCP) influences SMEs’ ability to leverage their technological capability (TECC) and marketing sensing capability (MKSC) and actively engage in public procurement.

Design/methodology/approach

Data for this study were collected from 248 SME managers in the Ilala District, Tanzania, using a cross-sectional questionnaire survey and stratified random sampling technique. The proposed hypotheses were tested empirically through confirmatory factor analysis (CFA) and the Hayes PROCESS macro.

Findings

TECC and MKSC demonstrated significant positive associations with SME participation in public procurement (SMPP). Moreover, the interaction between TECC and FNCP as well as the interaction between MKSC and FNCP demonstrate a significant positive effect, suggesting that FNCP strengthens the impact of TECC and MKSC on SMPP.

Research limitations/implications

The scope of this study was limited to SMEs in the Ilala District of Tanzania, hence affecting the generalizability of the findings to other contexts. More importantly, the study findings enrich the understanding of DC theory, signifying that the integration and reconfiguration of MKSC, TECC and FNCP add significant value to SMPP.

Practical implications

The findings suggest that policymakers, support institutions and SME managers should focus on enhancing SMEs' MKSC and TECC to improve their participation in public procurement. In addition, improving SMEs' access to financial resources can further strengthen these effects, enabling more inclusive participation in public procurement.

Originality/value

The study contributes to the literature on SMPP by highlighting the critical roles of MKSC and TECC. It also underscores the importance of FNCP as a moderator in these relationships, which has not been addressed in the existing literature. By integrating these factors, the study offers a comprehensive framework for understanding the dynamics that influence SMPP from financial, technological and marketing perspectives, particularly in developing economies like Tanzania.
Influence of customer intention on patronizing halal logo in the food premises of Malaysia
Authors: Pauzi Norhidayah , Razali Asbah , Man Saadan , Syed Jaafar Syed Mohd Jeffri , Jamaludin Mohd Hafiz
Published: September 2024

Purpose

This study aims to examine attitude, perceived behavioral and religiosity that influence Muslim consumers’ intention in patronizing at food premises with halal logo.

Design/methodology/approach

The data were collected from 450 respondents on random sampling basis. Quantitative analysis was conducted using SEM SMARTPLS version 3.3.

Findings

Based on the findings gathered using PLS analysis with n = 450, it was indicated that attitude, perceived behavioral control and religiosity significantly influence Muslim consumers’ intention on patronizing at food premise with halal logo.

Research limitations/implications

The data collection for the present study was limited to the respondents in Kuala Lumpur among Muslim consumers, and limited to 450 sample sizes.

Practical implications

The presence of halal logo should be crucial in attracting consumers due to the comprehensive meaning it brings.

Social implications

In the context of food premises, the results of the research suggest that the halal logo shown by the food premise seems to operate significantly in attracting Muslim consumers toward the food premises. Muslim consumers need to be nourished by proper Islamic teachings and have a good understanding of halal principle.

Originality/value

The halal logo of food premise concerns the Muslims. Muslim consumers are relying on surrogates in selecting the alternatives for packaged goods in Islamic marketing literature. However, it is little known how Muslims use indicators to select food premises when there is no halal logo.