bluuebunny/crossref_metadata_2025 huggingface dataset:
Metagenomic analysis during capecitabine therapy reveals microbial chemoprotective mechanisms and predicts drug toxicity in colorectal cancer patients
Authors: Hillege Lars E. , Trepka Kai R. , Ziemons Janine , Aarnoutse Romy , Guthrie Benjamin G. H. , de Vos-Geelen Judith , Iersel Liselot Valkenburg-van , van Hellemond Irene E.G. , Baars Arnold , Vestjens Johanna H.M.J. , Penders John , Deutschbauer Adam , Atreya Chloe E. , Kidder Wesley A. , Turnbaugh Peter J. , Smidt Marjolein L.
Published: October 2024

Purpose

Unpredictable chemotherapy side effects are a major barrier to successful treatment. Cell culture and mouse experiments indicate that the gut microbiota is influenced by and influences anti-cancer drugs. However, metagenomic data from patients paired to careful side effect monitoring remains limited. Herein, we focus on the oral fluoropyrimidine capecitabine (CAP). We investigate CAP-microbiome interactions through metagenomic sequencing of longitudinal stool sampling from a cohort of advanced colorectal cancer (CRC) patients.

Methods

We established a prospective cohort study including 56 patients with advanced CRC treated with CAP monotherapy across 4 centers in the Netherlands. Stool samples and clinical questionnaires were collected at baseline, during cycle 3, and post-treatment. Metagenomic sequencing to assess microbial community structure and gene abundance was paired with transposon mutagenesis, targeted gene deletion, and media supplementation experiments. An independent US cohort was used for model validation.

Results

CAP treatment significantly altered gut microbial composition and pathway abundance, enriching for menaquinol (vitamin K2) biosynthesis genes. Transposon library screens, targeted gene deletions, and media supplementation confirmed that menaquinol biosynthesis protectsEscherichia colifrom drug toxicity. Microbial menaquinol biosynthesis genes were associated with decreased peripheral sensory neuropathy. Machine learning models trained in this cohort predicted hand-foot syndrome and dose reductions in an independent cohort.

Conclusion

These results suggest treatment-associated increases in microbial vitamin biosynthesis serve a chemoprotective role for bacterial and host cells, with implications for toxicities outside the gastrointestinal tract. We provide aproof-of-conceptfor the use of microbiome profiling and machine learning to predict drug toxicities across independent cohorts. These observations provide a foundation for future human intervention studies, more in-depth mechanistic dissection in preclinical models, and extension to other cancer treatments.
Antibiotic-Mediated Plasmonic Resonance on a Novel Nanopillar Metasurface Array
Authors: Waitkus Jacob , Park JaeWoo , Ndukaife Theodore , Yang Sui , Du Ke
Published: October 2024

This study demonstrates a silicon nanopillar metasurface coupled with localized surface plasmon resonance (LSPR) mediated by the presence of cephalexin antibiotics in solution for biosensing applications. A facile fabrication process was developed to create the metasurface on silicon wafers with a unique resonance signature. The resulting metasurface consists of periodic nanopillars approximately 180 nm in diameter, 210 nm deep, and with a controlled edge-to-edge separation of 200 nm. These dimensions were chosen based on a finite element method simulation that was used to investigate the ideal parameters to produce the desired resonance effect in the metasurface reflection spectra. Optimization of the nanopillar surface properties and the sidewall angle allowed for replication of the simulations. This metasurface was coupled with BSA-coated gold nanospheres (BSANS) to mediate the redshift of peak resonance wavelength values, occurring only in the presence of the antibiotic linker. The device fabricated herein exhibits a significant 22 nm wavelength shift resulting from changes to the local refractive index in the presence of the BSANS-antibiotic coupling. Further enhancement of the binding events is promoted by the LSPR hot spots formed between the nanoparticles and the metasurface allowing for sensitive and real-time detection.
Noninvasive Assessment of Temporal Dynamics in Sympathetic and Parasympathetic Baroreflex Responses
Authors: Suarez-Roca Heberto , Mamoun Negmeldeen , Mathew Joseph P , Bortsov Andrey V
Published: October 2024

Background

The baroreflex system is crucial for cardiovascular regulation and autonomic homeostasis. A comprehensive assessment requires understanding the simultaneous temporal dynamics of its multiple functional branches, which traditional methods often overlook.

Objective

To develop and validate a noninvasive method for simultaneously assessing the temporal dynamics of sympathetic and parasympathetic baroreflexes using pulse contour analysis and the sequence method.

Methods

Beat-to-beat blood pressure and ECG recordings were analyzed from 55 preoperative cardiothoracic surgery patients in the supine position and 21 subjects from the EUROBAVAR dataset in both supine and standing positions. Systolic arterial pressure (SAP), interbeat interval (IBI), cardiac output (CO), myocardial contraction (dP/dtmax), and systemic vascular resistance (SVR) were estimated using pulse contour analysis. Baroreflex sensitivity (BRS) was calculated via the sequence method and correlated with hemodynamic and heart rate variability (HRV) parameters.

Results

Parasympathetic BRS for IBI was correlated with the root mean square of successive differences of ECG RR intervals (RMSSD-HRV) at 0-beat delay. Sympathetic BRS for SVR strongly correlated with SVR, CO, and RMSSD-HRV, particularly at 3-beat delay, and was uniquely associated with SAP at 1-beat delay. Sympathetic BRS for dP/dtmaxcorrelated with dP/dtmaxat 1-beat delay. In contrast, BRS for CO correlated with CO and SVR at 0- and 3-beat delays. Postural changes mainly affected parasympathetically-mediated BRS for IBI and, to a lesser extent, the sympathetic vascular and myocardial branches.

Conclusions

This method effectively captures multiple baroreflex responses and their temporal dynamics, revealing distinct autonomic mechanisms and the impact of postural changes. Further validation is warranted.
A European clinical practice guideline on pain, agitation, delirium, and iatrogenic withdrawal syndrome management in critically ill children: A protocol
Authors: MacDonald Ibo , Cavin-Trombert Alexia , Jaques Cécile , Amigoni Angela , Ramelet Anne-Sylvie
Published: October 2024

Introduction

In pediatric intensive care units, pain, sedation, delirium, and iatrogenic withdrawal syndrome must be managed as interrelated conditions. Existing clinical practice guidelines have some methodological limitations and are not readily transferrable to the European context without adaptation. This protocol describes the methods for developing a high-quality, and the first patient- and family-informed European guideline for managing pain, sedation, delirium and iatrogenic withdrawal syndrome.

Methods

The guideline will be developed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) - ADOLOPEMENT approach, engaging clinical experts and patients and families in the development process. It will consist of seven phases: 1) Set-up – establishing three groups for guideline development: i) steering committee, ii) development panel (experts and patient/family partners from across Europe), and iii) patient and family advisory panel, and scoping to determine population, conditions, purpose, and users of the guideline; 2) Preparation – voting on summary recommendations, prioritizing research questions and outcomes, and matching research questions with existing recommendations; 3) Search and retrieval of evidence – using three search approaches to develop search strategies to find evidence, conducting individualized searches for each summary recommendation and new research question, selecting evidence, study appraisal, and initial data extraction; 4) Evidence synthesis – summarizing evidence in evidence profiles and summary of evidence tables, and conducting panel surveys of current practice when evidence is absent; 5) Development – drafting recommendations, voting on and approving them, and developing accompanying materials; 6) Review – conducting internal, society-level, and external international expert reviews; and 7) Issue – publishing the guideline.

Discussion

This protocol ensures a transparent process follows the GRADE approach for guideline development, leading to a high-quality, trustworthy, and credible guideline for managing pain, sedation, delirium and iatrogenic withdrawal syndrome in critically ill children. Tailored to the European context for healthcare professionals.

Registration:Practice guideline REgistration for transPAREncy (PREPARE) registration number PREPARE-2024CN859
Cross-species vs species-specific models for protein melting temperature prediction
Authors: López Sebastián García , Salomon Jesper , Boomsma Wouter
Published: October 2024

Abstract

Protein melting temperatures are important proxies for stability, and frequently probed in protein engineering campaigns, including enzyme discovery, protein optimization, and de novo protein design. With the emergence of large datasets of melting temperatures for diverse natural proteins, it has become possible to train models to predict this quantity, and the literature has reported impressive performance values in terms of Spearman rho. The high correlation scores suggest that it should be possible to reliably predict melting temperature changes in engineered variants, to design de novo thermostable proteins, and identifying naturally thermostable proteins. However, in practice, results in this setting are often disappointing. In this paper, we explore the discrepancy between these two settings. We show that Spearman rho over cross-species data gives an overly optimistic impression of prediction performance, and that models trained on species-specific data often outperform larger cross-species models. Finally, we explore a number of strategies for improving performance, demonstrating a performance boost of 1.5 degree RMSE with fairly simple means.
Invasive mammals disrupt native dung beetle community coexistence
Authors: Akashi Ryo , Yamaguchi Ryo , Nakaoka Shinji
Published: October 2024

Biological invasions are among the major drivers of biodiversity and are increasing worldwide. Among the invasive species, mammals have a particularly profound impact on native ecosystems. As primary decomposers of mammalian feces, dung beetles are critical in ecosystem functioning, and their community structure is closely linked to their services. However, the introduction of invasive mammals threatens these beetles and potentially disrupts their ecosystem services. Therefore, it is necessary to understand the resulting changes in communities. We developed a novel population dynamics model focusing on the interactions among mammals, feces, and dung beetles. Our results indicate that such invasions increase the risk of extinction of specialist dung beetles that cannot utilize the feces of invasive mammals. The risk of extinction is particularly high when generalist dung beetles show a preference for native feces, leading to intensified interspecific competition for resources. Additionally, the extinction risk of specialist dung beetles increases when invasive mammals display irruptive population dynamics. In conclusion, our findings demonstrated that non-native mammalian invasions disrupt the coexistence of native dung beetle communities, potentially leading to losses in biodiversity and ecosystem function. These risks should be considered in future empirical studies to evaluate the impact of invasive mammals on dung beetle communities.
Green synthesized silver nanoparticles fromMoringa: Potential for preventative treatment of SARS-CoV-2 contaminated water
Authors: Bello Adebayo J. , Ebunoluwa Omorilewa B. , Ayorinde Rukayat O. , Onyepeju Nneka , Shaibu Joseph O. , Adewole Adeniyi R. , Adewole Abeebat O. , Adedeji Olusegun , Akinnusi Ololade O. , Oladapo Olajumoke B. , Popoola Temitope S. , Arotiba Oluwamodupe M. , Minari Joseph B. , Adams Luqman A. , Okpuzor Joy , Shittu Mujeeb O.
Published: October 2024

Biogenic silver nanoparticles have been reported as good antimicrobial candidates. Thus, this study investigated the antiviral activity of silver nanoparticles synthesized against SARS-CoV-2. The silver nanoparticle was biosynthesized using leave extracts ofMoringa oleifera(AgNPmo) and characterized using UV-Vis spectroscopy, Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy, and X-ray diffractometry (XRD). The AgNPmo was first tested on clinical bacterial isolates,Pseudomonas aeruginosa(ATTC 154423) andStaphylococcus aureus(ATTC 209233), to ascertain its antimicrobial potential. In-vitro studies were also conducted to determine the cytotoxicity effect of AgNPmo on Vero cells. The efficacy and concentration of AgNPmo against SARS-CoV-2 were evaluated using a qPCR assay in a dose-dependent manner. The results demonstrated the successful biosynthesis and characterization of AgNPmo and its efficacy against the bacterial isolates. The AgNPmo showed low toxicity on the Vero cells. The IC50from the cytotoxicity assay demonstrated the antiviral activity of the AgNPmo on the SARS-CoV-2 virus, leading to an increase in the Cycle threshold values, notably at 48 hours of incubation and at low concentrations. The results showed that the biogenic AgNPmo synthesized was cost-effective and showed both antimicrobial and antiviral potentials. These findings suggest that the nanoparticles could be a promising alternative for combating SARS-CoV-2, especially for water purification and preventing transmission.
Real-time high-resolution microscopy reveals how single-cell lysis shapes biofilm matrix morphogenesis
Authors: Squyres Georgia R. , Newman Dianne K.
Published: October 2024

During development, multiscale patterning requires that cells organize their behavior in space and time. Bacteria in biofilms must similarly dynamically pattern their behavior with a simpler toolkit. Like in eukaryotes, morphogenesis of the extracellular matrix is essential for biofilm development, but how it is patterned has remained unclear. Here, we explain how the architecture of eDNA, a key matrix component, is controlled by single cell lysis events duringPseudomonas aeruginosabiofilm development. We extend single-cell imaging methods to capture complete biofilm development, characterizing the stages of biofilm development and visualizing eDNA matrix morphogenesis. Mapping the spatiotemporal distribution of single cell lysis events reveals that cell lysis is restricted to a specific biofilm zone. Simulations indicate that this patterning couples cell lysis to growth, more uniformly distributing eDNA throughout the biofilm. Finally, we find that patterning of cell lysis is organized by nutrient gradients that act as positioning cues.
A systematic review of aperiodic neural activity in clinical investigations
Authors: Donoghue Thomas
Published: October 2024

In the study of neuro-electrophysiological recordings, aperiodic neural activity – activity with no characteristic frequency – has increasingly become a common feature of study. This interest has rapidly extended to clinical work, with many reports investigating aperiodic activity from patients from a broad range of clinical disorders. This work typically seeks to evaluate aperiodic activity as a putative biomarker relating to diagnosis or treatment response, and/or as a potential marker of underlying physiological activity. There is thus far no clear consensus on if and how aperiodic neural activity relates to clinical disorders, nor on the best practices for how to study it in clinical research. To address this, this systematic literature review, following PRISMA guidelines, examines reports of aperiodic activity in electrophysiological recordings with human patients with psychiatric and/or neurological disorders, finding 143 reports across 35 distinct disorders. Reports within and across disorders are summarized to evaluate current findings and examine what can be learned as pertains to the analysis, interpretations, and overall utility of aperiodic neural activity in clinical investigations. Aperiodic activity is commonly reported to relate to clinical diagnoses, with 31 of 35 disorders reporting a significant effect in diagnostic and/or treatment related studies. However, there is variation in the consistency of results across disorders, with the heterogeneity of patient groups, disease etiologies, and treatment status arising as common themes across different disorders. Overall, the current variability of results, potentially confounding covariates, and limitations in current understanding of aperiodic activity suggests further work is needed before aperiodic activity can be established as a potential biomarker and/or marker of underlying pathological physiology. Finally, a series of recommendations are proposed, based on the findings, limitations, and key discussion topics of the current literature to assist with guiding productive future work on the clinical utility of studying aperiodic neural activity.

Project Repository

The project repository contains code & data related to this project:https://github.com/TomDonoghue/AperiodicClinical
Reversing Immunosenescence with Senolytics to Enhance Tumor Immunotherapy
Authors: Liu Niu , Wu Jiaying , Deng Enze , Zhong Jianglong , Wei Bin , Cai Tingting , Duan Xiaohui , Fu Sha , Osei-Hwedieh David O. , Sha Ou , Chen Yunsheng , Lv Xiaobin , Zhu Yingying , Zhang Lizao , Lin Hsinyu , Li Qunxing , Lu Peichia , Miao Jiahao , Yamada Teppei , Cai Lei , Du Hongwei , Baca Sylvan C. , Huang Qingpei , Ferrone Soldano , Wang Xinhui , Xu Fang , Fan Xiaoying , Fan Song
Published: October 2024

Recent advancements in cancer immunotherapy have improved patient outcomes, yet responses to immunotherapy remain moderate. We conducted a Phase II clinical trial (NCT04718415) involving 51 cancer patients undergoing neoadjuvant chemoimmunotherapy and applied single-cell RNA and T/BCR sequencing on tumor and blood samples to elucidate the immune cell perturbations. Our findings associate poor response with reduced levels of CCR7+CD4 Naïve T cells and CD27+Memory B cells, as well as higher expression of immunosenescence-related genes in T and B cell subsets. Using naturally aged andErcc1+/-transgenic aging mouse models, we found that senolytics enhance the therapeutic efficacy of immunotherapy in multiple solid tumors by mitigating tumor immunosenescence. Notably, we launched a Phase II clinical trial, COIS-01 (NCT05724329), which pioneers the combination of senolytics with anti-PD-1 therapy. The clinical results demonstrate that this therapeutic strategy is associated with a favorable safety profile and therapeutic efficacy, significantly mitigating adverse effects and alleviating immunosenescence. These findings underscore the pivotal role of immunosenescence characteristics in influencing the effectiveness of immunotherapy and suggest a promising therapeutic efficacy along with a beneficial safety assessment for the combination of senolytics with anti-PD-1 therapy.
CT-derived Body Composition Associated with Pulmonary Nodule Malignancy and Growth
Authors: Yu Tong , Zhao Xiaoyan , Kokenberger Grant , Leader Joseph K , Wang Jing , Xiao David , Meng Xin , Kammer Michael N , Grogan Eric L , Herman James , Wilson David , Pu Jiantao
Published: October 2024

Background: Body composition may be a valuable biomarker for assessing pulmonary nodule malignancy. However, its relationship with nodule malignancy remains unexplored. Objective: This study investigated the association between body composition and pulmonary nodule malignancy and growth. Methods: A dataset of subjects with indeterminate pulmonary nodules (IPNs) was created from internal (n=216) and external (n=162) cohorts. Five different tissues were automatically segmented and quantified from baseline and follow-up chest low-dose computed tomography (LDCT) scans using artificial intelligence (AI) algorithms. Logistic regression, t-tests, and Person correlation analyses were performed to study the association between body tissues and malignancy, as well as nodule changes in density, size, and shape. Gender differences were investigated. The area under the receiver operating characteristic curve (ROC-AUC) assessed classifier performance. Feature importance was evaluated using several machine learning models. Causal relationships were analyzed and visualized using a novel graph method. Results: Univariate analysis revealed a significant association between Skeletal muscle density and nodule malignancy in both genders (p<0.001). The body composition model yielded AUCs of 0.77 (95% CI: 0.71-0.84) and 0.63 (95% CI: 0.54-0.72) on the internal and external datasets, respectively. The composite model combining body composition and nodule features yielded AUCs of 0.87 (95% CI: 0.82-0.91) and 0.62 (95% CI: 0.53-0.72) on the internal and external datasets, respectively. Skeletal muscle and intermuscular adipose tissue features were highly ranked among tissue features, with skeletal muscle density retaining its highest rank even after adjusting for clinical and nodule features. The causal graph identified two nodule features and skeletal muscle density as directly linked to malignancy. Skeletal muscle density and intramuscular adipose tissue density were identified as nodule growth indicators in both genders. Conclusions: Body composition could be a potential biomarker for assessing nodule malignancy and evaluating nodule growth in both genders.
A novel prediction model for immunotherapy induced pneumonitis prediction based on Chest CT and electronic health record
Authors: Lyu Qing , Yuan Hongyu , Lin Zhen , Ponnatapura Janardhana , Whitlow Christopher T
Published: October 2024

Immune checkpoint inhibitors (ICIs) have been extensively used for the treatment of non-small cell lung cancer patients in recent years, providing a significant survival benefit. However, a major drawback of ICIs-related immunotherapy is the risk of developing post-surgical pneumonitis. In this study, we propose a deep learning-embedded, multi-modality prediction approach to assess whether patients will develop ICI-pneumonitis after receiving ICIs-based immunotherapy. This approach utilizes multi-modal data, including clinical data and pre-treatment lung screening computed tomography (CT) images. We extracted three types of features: 1) deep learning features from CT scans using a pretrained vision transformer, 2) radiomic features from CT scans using predefined radiomic algorithms, and 3) clinical features from patients’ clinical records. We then compared multiple machine learning algorithms for prediction based on these extracted features. Our results demonstrated a prediction accuracy of 0.823 and an area under the receiver operating characteristic curve of 0.895.
Does smoking during pregnancy influence offspring handedness? Extending gene-by-environment Mendelian randomisation to include polygenic risk scores
Authors: Crick Daisy CP , Medland Sarah , Davey Smith George , Evans David
Published: October 2024

Hand preference first appearsin utero, yet twin studies and GWAS show that the majority of variance in hand preference is explained by environmental factors. Using UK Biobank data and multivariable logistic regression to test associations between potential causes of handedness and offspring hand preference, we found maternal smoking during pregnancy increased the probability of being right-handed after adjustment for covariates. Using a proxy gene-by-environment (GxE) Mendelian randomization design we investigated the potential causal effect of maternal smoking during pregnancy on offspring handedness. We used rs16969968 in theCHRNA5gene and a polygenic risk score of genome-wide significant smoking-heaviness variants to proxy smoking behaviour. We stratified based on reported maternal smoking during pregnancy because, regardless of genotype, any causal effect of maternal smoking on offspring handedness should only manifest in individuals whose mothers smoked during pregnancy. The GxE MR analyses found no causal effect of maternal smoking during pregnancy on offspring hand-preference. Our study contributes to the understanding of hand preference and its potential early-life determinants. However, the main factors contributing to variation in hand preference remain unresolved.
Structure of the turnip yellows virus particles. How is the readthrough domain exposed on the capsid surface?
Authors: Lai-Kee-Him Joséphine , Trapani Stefano , Boissinot Sylvaine , Reinbold Catherine , Fallet Chloé , Ancelin Aurélie , Lecorre François , Hoh François , Ziegler-Graff Véronique , Brault Véronique , Bron Patrick
Published: October 2024

Turnip yellows virus (TuYV) is a plant virus infecting important crops such as oilseed rape. TuYV is phloem-restricted and transmitted by aphids. The capsid contains two subunit types: the major capsid protein (CP) and a minor component (RTP*) which arises from the C-terminal cleavage of a readthrough product (RTP). RTP* contains the CP sequence fused with a structured domain (denotedNRTD) which is a key determinant of virus transmission. Though both CP and RTP* are involved in virus movement and aphid transmission, how RTP* is incorporated into the capsid is poorly understood. We present here the structural characterisation (by immunogold labelling and 3D cryo-EM) of the wild-type TuYV and a mutant whose capsid contains the CP only. We show that incorporation of RTP* does not impair the capsid structure, and theNRTD does not adopt well-defined positions at the capsid surface. The number of incorporated RTP*s suggests a random insertion.
Most L1CAM is not associated with extracellular vesicles in human biofluids and iPSC–derived neurons
Authors: Kadam Vaibhavi , Wacker Madeleine , Oeckl Patrick , Korneck Milena , Dannenmann Benjamin , Skokowa Julia , Hauser Stefan , Otto Markus , Synofzik Matthis , Mengel David
Published: October 2024

Transmembrane L1 cell adhesion molecule (L1CAM) is widely used as a marker to enrich for neuron-derived extracellular vesicles (EVs), especially in plasma. However, this approach lacks sufficient robust validation. This study aimed to assess whether human biofluids are indeed enriched for EVs, particularly neuron-derived EVs, by L1CAM immunoaffinity, utilizing multiple sources (plasma, CSF, conditioned media from iPSC-derived neurons [iNCM]) and different methods (mass spectrometry [MS], nanoparticle tracking analysis [NTA]).

Following a systematic multi-step validation approach, we confirmed isolation of generic EV populations using size-exclusion chromatography (SEC) and polymer-aided precipitation (PPT) – two most commonly applied EV isolation methods – from all sources. Neurofilament light (NfL) was detected in both CSF and blood-derived EVs, indicating their neuronal origin. However, L1CAM immunoprecipitation did not yield enrichment of L1CAM in EV fractions. Instead, it was predominantly found in its free-floating form. Additionally, MS-based proteomic analysis of CSF-derived EVs also did not show L1CAM enrichment.

Our study validates EV isolation from diverse biofluid sources by several isolation approaches and confirms that some EV subpopulations in human biofluids are of neuronal origin. Thorough testing across multiple sources by different orthogonal methods, however, does not support L1CAM as a marker to reliably enrich for a specific subpopulation of EVs, particularly of neuronal origin.
PWAS Hub for exploring gene-based associations of common complex diseases
Authors: Kelman Guy , Zucker Roei , Brandes Nadav , Linial Michal
Published: October 2024

PWAS (proteome-wide association study) is an innovative genetic association approach that complements widely used methods like GWAS (genome-wide association study). The PWAS approach involves consecutive phases. Initially, machine learning modeling and probabilistic considerations quantify the impact of genetic variants on protein-coding genes’ biochemical functions. Secondly, for each individual, aggregating the variants per gene determines a gene-damaging score. Finally, standard statistical tests are activated in the case-control setting to yield statistically significant genes per phenotype. The PWAS Hub offers a user-friendly interface for an in-depth exploration of gene–disease associations from the UK Biobank (UKB). Results from PWAS cover 99 common diseases and conditions, each with over 10,000 diagnosed individuals per phenotype. Users can explore genes associated with these diseases, with separate analyses conducted for males and females. For each phenotype, the analyses account for sex-based genetic effects, inheritance modes (dominant and recessive), and the pleiotropic nature of associated genes. The PWAS Hub showcases its usefulness for asthma by navigating through proteomic-genetic analyses. Inspecting PWAS asthma-listed genes (a total of 27) provide insights into the underlying cellular and molecular mechanisms. Comparison of PWAS-statistically significant genes for common diseases to the Open Targets benchmark shows partial but significant overlap in gene associations for most phenotypes. Graphical tools facilitate comparing genetic effects between PWAS and coding GWAS results, aiding in understanding the sex-specific genetic impact on common diseases. This adaptable platform is attractive to clinicians, researchers, and individuals interested in delving into gene–disease associations and sex-specific genetic effects.
Generation of Antibody Libraries for Phage Display: Human Fab Format
Authors: Peng Haiyong , Rader Christoph
Published: October 2024

Phage display is a powerful method for the de novo generation and affinity maturation of human monoclonal antibodies from naive, immune, and synthetic antibody repertoires. The pComb3 phagemid family of phage display vectors facilitates the selection of human monoclonal antibody libraries in the monovalent Fab format, which consists of human variable domains VHand VL(Vκor Vλ), fused to the human constant domains CH1 of IgG1 and CL(Cκor Cλ), respectively. Here, we describe the use of a pComb3 derivative, phagemid pC3C, for the generation of human Fab libraries with randomly combined human variable domains (VH, Vκ, and Vλ) of high sequence diversity, starting from the preparation of mononuclear cells from blood and bone marrow. Depending on the complexity of the parental antibody repertoire, the protocol can be scaled for yielding a library size of 108–1011independent human Fab clones. As such, it can be used, for instance, for the generation of a large naive human Fab library from healthy individuals or for the generation of a specialized immune human Fab library from individuals with an endogenous antibody response of interest.
Generation of Antibody Libraries for Phage Display: Library Reamplification
Authors: Peng Haiyong , Rader Christoph
Published: October 2024

Phage display of Fab libraries enables the de novo discovery and in vitro evolution of monoclonal antibodies. Fab libraries are collections of millions to billions of different antibodies that collectively cover a large antigen or epitope binding space. To preserve the diversity of the Fab library for repeated selection campaigns, it is recommended to use the original phage from the Fab library generation rather than reamplified phage, if practically possible. This is because reamplification will bias the Fab library for clones that are expressed at higher rates. Fab-phage, however, should only be used if they have been prepared on the same day, to avoid proteolytic cleavage of the physical linkage of phenotype (phage-displayed Fab protein) and genotype (phage-encapsulated Fab DNA). Thus, in practice, reamplification of a Fab-phage library cannot usually be avoided. Here, we describe the steps for the reamplification of an original Fab-phage library prior to its selection. The protocol can also be used to reamplify Fab-phage from the third or later panning rounds when enriched clones are unlikely to be lost by reamplification biases.
Phage Display Selection of Antibody Libraries: Screening of Selected Binders
Authors: Peng Haiyong , Rader Christoph
Published: October 2024

Phage display selection of antibody libraries is a powerful method for generating and evolving monoclonal antibodies. The pComb3 phagemid family of phage display vectors facilitates the mining of antibody libraries in Fab format from human and nonhuman antibody repertoires. Here, we describe the screening for monoclonal Fab binders after selection of a polyclonal pool of Fab binders to an antigen of interest, with the goal of identifying and sequencing monoclonal antibodies that bind the antigen with high affinity and specificity. The screening cascade involves a phage ELISA, followed by a crude Fab ELISA and DNA fingerprinting and sequencing. The protocol outlines phage and crude Fab ELISAs using purified antigen immobilized on microplates, native antigen expressed on eukaryotic cells, or both.
Global tensor polarization of spin
3/2
hadrons and quark spin correlations in relativistic heavy ion collisions
Authors: Zhang Zhe , Lv Ji-peng , Yu Zi-han , Liang Zuo-tang
Published: October 2024

We study the global polarization of spin-3/2 hadrons in relativistic heavy ion collisions. We show in particular that the global tensor polarizations of rank two or three for spin-3/2 hadrons are sensitive to the local two or three quark spin correlations respectively in the quark gluon plasma produced in the collision processes. We present the relationships between these measurable tensor polarizations and quark spin correlations in the quark matter system.

Published by the American Physical Society
2024
Likelihood analysis of the newly observed
f0(2020)
,
f0(2330)
, and
f0(2470)
in
J/ψ→γη′η′
as high-lying unflavored scalar mesons
Authors: Liu Cheng-Xi , Wang Li-Ming , Li Ting-Yan , Liu Xiang
Published: October 2024

Inspired by the newly observed three scalar states f0(2020), f0(2330), and f0(2470) by the BESIII collaboration in J/ψ→γη′η′, we carried out the study of spectroscopic behavior of these high-lying unflavored scalar mesonic states. In this work, using the phenomenological description of radial

(

n

,

M

2

)

trajectory and the quark pair creation model, we discussed the assignments of the f0(2020), f0(2330), and f0(2470) associated with the f0(2200) as the isoscalar high-lying scalar mesonic states and predicted the spectroscopic properties of their high-lying partners. The present study may provide valuable information for the construction of the scalar meson family.

Published by the American Physical Society
2024
Causal fermion states in magnetic field in a relativistic rotating frame and electromagnetic radiation by a rapidly rotating charge
Authors: Buzzegoli Matteo , Tuchin Kirill
Published: October 2024

We consider the Dirac field uniformly rotating with angular velocity Ω and also subject to the constant magnetic field B directed along the rotation axis. The causal states are constrained to the interior of the light cylinder of radius c/Ω. When this radius is smaller than the system size, as in the quark-gluon plasma, the effect of the boundary on the fermion spectrum is critical. We derive the fermion spectrum and study its properties. We compute the intensity of the electromagnetic radiation emitted due to transitions between the fermion states. We study its dependence on energy and angular momentum for different values of the angular velocity and the magnetic field. Rotation has enormous impact on the electromagnetic radiation by the quark-gluon plasma with or without the magnetic field.

Published by the American Physical Society
2024
Spatial electron-photon entanglement
Authors: Kazakevich Eitan , Aharon Hadar , Kfir Ofer
Published: October 2024

Free electron beams and their quantum coupling with photons are attracting a rising interest due to the basic questions they address and the innovative technology these particles are involved in, such as microscopy, spectroscopy, and quantum computation. This work proposes spatially encoded coupling, where a dual-rail-like electron (e−) state is entangled to a dual-rail photonic qubit. Thus, it complements the leading current concept of the coupling, which links photonic Fock states with the e− energy. Importantly, we show that a spatial electron-photon pair can reach maximal entanglement and propose mutually unbiased bases for verifying the entanglement in a realistic experimental apparatus. Although the energy-level coupling of an e− beam with photonic excitations is well understood, we show that a naïve approach for extending such interaction from a single to a double path results in a retrocausal paradox. In the future, the atomic scale precision of electron microscopes can harness such position-encoded free-e− entangled qubits for novel quantum sensing and quantum transduction.

Published by the American Physical Society
2024
Self-sustained optomechanical state destruction triggered by the Kerr nonlinearity
Authors: Delattre A. , Golokolenov I. , Pedurand R. , Zhou X. , Fefferman A. , Collin E.
Published: October 2024

Cavity optomechanics implements a unique platform where moving objects can be probed by quantum fields, either laser light or microwave signals. With a pump tone driving at a frequency above the cavity resonance, self-sustained oscillations can be triggered at large injected powers. These limit-cycle dynamics are particularly rich, presenting hysteretic behaviors, broad comb signals, and especially large motion amplitudes. All of these features can be exploited for both fundamental quantum research and engineering. Here we present low-temperature microwave experiments performed on a high-Q cavity resonance capacitively coupled to the flexure of a beam resonator. We study the limit-cycle dynamics parameter space as a function of pump parameters (detuning, power). Unexpectedly, we find that in a region of this parameter space the microwave resonance is irremediably destroyed: Only a dramatic power reset can restore the dynamics to its original state. The phenomenon can be understood as an optical instability linked to the Kerr nonlinearity of the cavity. A theory supporting this claim is presented, reproducing almost quantitatively the measurement. This remarkable feature might be further optimized and represents a new resource for quantum microwave circuits.

Published by the American Physical Society
2024
Accurate optimal quantum error correction thresholds from coherent information
Authors: Colmenarez Luis , Huang Ze-Min , Diehl Sebastian , Müller Markus
Published: October 2024

Quantum error correcting (QEC) codes protect quantum information from decoherence as long as error rates fall below critical error thresholds. In general, obtaining thresholds implies simulating the QEC procedure using, in general, suboptimal decoding strategies. In a few cases and for sufficiently simple noise models, optimal decoding of QEC codes can be framed as a phase transition in disordered classical spin models. In both situations, accurate estimation of thresholds demands intensive computational resources. Here we use the coherent information of the mixed state of noisy QEC codes to accurately estimate the associated optimal QEC thresholds already from small-distance codes at moderate computational cost. We show the effectiveness and versatility of our method by applying it first to the topological surface and color code under bit-flip and depolarizing noise. We then extend the coherent information based methodology to phenomenological and quantum circuit level noise settings. For all examples considered, we obtain highly accurate estimates of optimal error thresholds from small, low-distance instances of the codes, in close agreement with threshold values reported in the literature. Our findings establish the coherent information as a reliable competitive tool for the calculation of optimal thresholds of state-of-the-art QEC codes under realistic noise models.

Published by the American Physical Society
2024
Contrasting conformational behaviors of molecules XXXI and XXXII in the seventh blind test of crystal structure prediction
Authors: Beran Gregory J. O. , Cook Cameron J. , Unzueta Pablo A.
Published: October 2024

Accurate modeling of conformational energies is key to the crystal structure prediction of conformational polymorphs. Focusing on molecules XXXI and XXXII from the seventh blind test of crystal structure prediction, this study employs various electronic structure methods up to the level of domain-local pair natural orbital coupled cluster singles and doubles with perturbative triples [DLPNO-CCSD(T1)] to benchmark the conformational energies and to assess their impact on the crystal energy landscapes. Molecule XXXI proves to be a relatively straightforward case, with the conformational energies from generalized gradient approximation (GGA) functional B86bPBE-XDM changing only modestly when using more advanced density functionals such as PBE0-D4, ωB97M-V, and revDSD-PBEP86-D4, dispersion-corrected second-order Møller–Plesset perturbation theory (SCS-MP2D), or DLPNO-CCSD(T1). In contrast, the conformational energies of molecule XXXII prove difficult to determine reliably, and variations in the computed conformational energies appreciably impact the crystal energy landscape. Even high-level methods such as revDSD-PBEP86-D4 and SCS-MP2D exhibit significant disagreements with the DLPNO-CCSD(T1) benchmarks for molecule XXXII, highlighting the difficulty of predicting conformational energies for complex, drug-like molecules. The best-converged predicted crystal energy landscape obtained here for molecule XXXII disagrees significantly with what has been inferred about the solid-form landscape experimentally. The identified limitations of the calculations are probably insufficient to account for the discrepancies between theory and experiment on molecule XXXII, and further investigation of the experimental solid-form landscape would be valuable. Finally, assessment of several semi-empirical methods finds r
2SCAN-3c to be the most promising, with conformational energy accuracy intermediate between the GGA and hybrid functionals and a low computational cost.
Crystal structure of the incommensurate modulated high-pressure phase of the potassium guaninate monohydrate
Authors: Gaydamaka A. A. , Rashchenko S. V.
Published: October 2024

The crystal structure of the incommensurate modulated phase of potassium guaninate monohydrate has been solved on the basis of high-pressure single-crystal X-ray diffraction data. The modulated structure was described as a `mosaic' sequence of three different local configurations of two neighbouring guaninate rings. In contrast to known examples of incommensurate modulated organic compounds, the modulation functions of all atoms are discontinuous. This is the first example of the experimental detection of an incommensurate modulated crystal structure that can be modelled using the special `soliton mode' modulation function proposed by Aramburu et al. [(1995), J. Phys. Condens. Matter, 7, 6187–6196].
Factors influencing consumers' purchase behavior toward indigenous chicken: insights from a cognitive affect behavior model
Authors: Abbasi Iffat Abbas , Shamim Amjad , Ashari Hasbullah
Published: October 2024

Purpose

This study addresses a critical gap in understanding consumer behavior toward indigenous chicken, investigating the interaction between cognitive factors and purchase decisions. The current research offers a valuable contribution to the field of sustainable food marketing by shedding light on these dynamics.

Design/methodology/approach

The research employed a quantitative survey method to gather data from consumers of indigenous chicken in Malaysia and analyzed it using structural equation modeling.

Findings

Health and price consciousness, along with effort expectancy, significantly influence consumer attitudes toward indigenous chicken. However, environmental consciousness and availability do not directly impact attitude. Similarly, attitude mediates the relationship between health consciousness, price consciousness, effort expectancy and purchase behavior, while attitude does not mediate the relationship between environmental consciousness, availability and purchase behavior of indigenous chicken.

Originality/value

This study is one of the pioneering works to apply the cognitive affect behavior (CAB) model to examine the factors influencing consumer attitudes and purchase behavior toward indigenous chicken. It investigates how constructs such as health consciousness, environmental consciousness, price consciousness, effort expectancy and availability affect these attitudes and behaviors, offering novel insights into the purchase intentions of younger and educated individuals.
Winners and losers in Africa: a longitudinal examination of market-share gains by advanced and emerging market multinationals versus local firms
Authors: Khan Huda , Ozkan Kubilay S.L. , Cavusgil Erin
Published: October 2024

Purpose

Market share gain is one of the key objectives for all firms for seeking growth. It is also a fundamental aspect of competitive rivalry. The extant review of the literature points to a gap among market share performances of emerging market multinationals (EMNEs) firms, advanced economy multinationals (AMNEs) and local firms. The purpose of this study is to delineate and contrast the market share performance of EMNEs, AMNEs and local firms in Africa.

Design/methodology/approach

The study used available longitudinal data (2013–2022) of six industries across four African countries from Euromonitor Passport, a rich, proprietary database.

Findings

Applying contingency theory, the study shows that, over time, there is no clear-cut winner in all markets and industries. Rather, market share gain is contingent on country and industry settings in Africa. Empirical analysis demonstrates that high-tech EMNE firms operating in Africa will exceed those of high-tech AMNEs and local firms. The findings also show that local firms generally performed better during the pandemic.

Originality/value

As Africa is a region of interest for scholars and practitioners, critical international business (IB) research contributions in Africa have predominantly focused on foreign investments from a particular nation. The present study enriches the literature by comparing the market share performance of AMNEs, EMNEs and local firms in this important region – during and prepandemic. The study offers theoretical and managerial implications for understanding the long-term performance of these three types of firms.