bluuebunny/crossref_metadata_2025 huggingface dataset:
Factors Associated With Onabotulinum Toxin-A Discontinuation in a Diverse Urban Population
Authors: Bergeron Tyler , Harandi Arshia Aalami , Liebeskind Mariel , Abraham Nitya
Published: March 2024

Importance

Although overactive bladder (OAB) is a common condition, affecting 16% of Americans, few patients continue on to advanced therapies. Furthermore, procedural therapies like intravesical onabotulinum toxin-A (BTX-A), which require ongoing repeat treatments, have discontinuation rates ranging from 25% to 51%.

Objectives

This study sought to investigate factors associated with dis-continuation of BTX-A injections for idiopathic OAB among a diverse urban population.

Study Design

This was a retrospective review of adults 18 years and older who underwent BTX-A injection for idiopathic OAB. Patient demographics, past medical history, symptoms, and postprocedural outcomes such as subjective improvement, urinary retention, and incidence of urinary tract infection were compared between groups.

Results

Onabotulinum toxin-A injections were administered to 246 patients who met study criteria, of whom 211 (85.7%) were women. One hundred (40.7%) patients discontinued BTX-A therapy. Patients discontinuing BTX-A therapy were more likely to have developed postprocedural urinary retention (18.4% vs 9.7%, P < 0.05) and had a higher median income by zip code ($59,000 vs $50,000; P < 0.01). Patients were significantly more likely to continue BTX-A therapy if they reported preprocedural nocturia (57.2% vs 36.8%, P < 0.01) or urgency urinary incontinence (UUI) (78.1% vs 64.6%, P < 0.05).

Conclusions

Adverse outcomes, such as postprocedural urinary retention, are associated with discontinuation of BTX-A therapy. Patients who reported nocturia and UUI before injection were more likely to continue BTX-A suggesting more severe OAB is more responsive to this therapy. Given the large proportion (>40%) of patients who discontinued BTX-A treatment, further research is needed to identify barriers to continuation of care.
Exploring the role of cultivar, year and plot age in the incidence of esca and Eutypa dieback: insights from 20 years of regional surveys in France
Authors: Etienne Lucas , Fabre Frédéric , Martinetti Davide , Frank Elise , Michel Lucie , Bonnardot Valérie , Guérin-Dubrana Lucia , Delmas Chloé E. L.
Published: March 2024

Grapevine trunk diseases cause yield losses and vine mortality in vineyards worldwide. However, there have been few quantitative studies evaluating grapevine dieback on a large spatial and temporal scale. Here, we consolidated and standardized databases from the 13 main wine regions of France, compiling records of leaf symptoms associated with esca and Eutypa dieback from 2082 plots and 36 cultivars over a 20-year period. This large dataset was used (a) for quantitative analysis of the prevalence (number of plots with at least one symptomatic plant) and incidence (percentage of symptomatic plants) of esca and Eutypa dieback; and (b) to decipher the effects of cultivar, year and plot age on both the prevalence and incidence of esca leaf symptoms by temporal Bayesian modelling. Esca was present on a mean of 74 ± 2% plots annually, with an incidence of 3.1 ± 0.1%. Eutypa dieback occurred in 41 ± 3% of the plots, with an incidence of 1.4 ± 0.1%. Our modelling approach revealed that the cultivar had a significant impact on the prevalence of esca, but not on its incidence when prevalence is greater than zero. Esca prevalence remained stable, whereas esca incidence was higher than the mean value in six of the years after 2012. We also found a significant non-linear effect of plot age, with 10- to 30-year-old plots significantly more susceptible, depending on the cultivar. This study clearly illustrates the importance of considering extensive and continuous monitoring to improve our understanding of the impact and evolution of crop diseases.
Disruption of Circadian Clock Induces Abnormal Mammary Morphology and Aggressive Basal Tumorigenesis by Enhancing LILRB4 Signaling
Authors: Ogunlusi Olajumoke , Sarkar Mrinmoy , Chakrabarti Arhit , Boland Devon J , Nguyen Tristan , Sampson James , Nguyen Christian , Fails Danielle , Jones-Hall Yava , Fu Loning , Mallick Bani , Keene Alex , Jones Jeff , Sarkar Tapasree Roy
Published: March 2024

Epidemiological studies have shown that circadian rhythm disruption (CRD) is associated with the risk of breast cancer. However, the role of CRD in mammary gland morphology and aggressive basal mammary tumorigenesis and the molecular mechanisms underlying CRD and cancer risk remain unknown. To investigate the effect of CRD on aggressive tumorigenesis, a genetically engineered mouse model that recapitulates the human basal type of breast cancer was used for this study. The effect of CRD on mammary gland morphology was investigated using wild-type mice model. The impact of CRD on the tumor microenvironment was investigated using the tumors from LD12:12 and CRD mice via scRNA seq. ScRNA seq was substantiated by multiplexing immunostaining, flow cytometry, and realtime PCR. The effect of LILRB4 immunotherapy on CRD-induced tumorigenesis was also investigated. Here we identified the impact of CRD on basal tumorigenesis and mammary gland morphology and identified the role of LILRB4 on CRD-induced lung metastasis. We found that chronic CRD disrupted mouse mammary gland morphology and increased tumor burden, and lung metastasis and induced an immunosuppressive tumor microenvironment by enhancing LILRB4a expression. Moreover, CRD increased the M2-macrophage and regulatory T-cell populations but decreased the M1-macrophage, and dendritic cell populations. Furthermore, targeted immunotherapy against LILRB4 reduced CRD-induced immunosuppressive microenvironment and lung metastasis. These findings identify and implicate LILRB4a as a link between CRD and aggressive mammary tumorigenesis. This study also establishes the potential role of the targeted LILRB4a immunotherapy as an inhibitor of CRD-induced lung metastasis.
Forage conservation is a neglected nitrous oxide source
Authors: Yang Seongmin , Mahmood Maheen , Baral Rudra , Wu Hui , Almloff Marc , Stanton Lauren E. , Min Doohong , Smiley Brenda K. , Iiams J. Chris , Yu Jisang , Im Jeongdae
Published: March 2024

Agricultural activities are the major anthropogenic source of nitrous oxide (N2O), an important greenhouse gas and ozone-depleting substance. However, the role of forage conservation as a potential source of N2O has rarely been studied. We investigated N2O production from the simulated silage of the three major crops—maize, alfalfa, and sorghum—used for silage in the US, which comprises over 90% of the total silage production. Our findings revealed a substantial N2O could be generated, which potentially places forage conservation as the third largest N2O source in the agricultural sector. Notably, the application of chlorate as an additive significantly reduced N2O production, but neither acetylene nor intermittent exposure to oxygen showed any impact. Overall, the results highlight that denitrifiers, rather than nitrifiers, are responsible for N2O production from silage, which was confirmed by molecular analyses. Our study reveals a previously unexplored source of N2O and provides a crucial mechanistic understanding for effective mitigation strategies.

Significance Statement

N2O is the third most important greenhouse gas (GHG) and agriculture contributes 80% of the total anthropogenic emissions in the US. The major sources of N2O in the agricultural sector identified by the USEPA include agricultural land management, manure management, and the field burning of agricultural residues. Here, we show that forage conservation could be a significant unaccounted source of N2O, surpassing the field burning by 30. Our study provides a mechanistic understanding of N2O production and a simple and effective remedy for reducing N2O emissions. The findings have substantial implications for mitigating climate change, informing policy-makers, and guiding future research on reducing greenhouse gas emissions from livestock production.
Mapping single-cell developmental potential in health and disease with interpretable deep learning
Authors: Kang Minji , Armenteros Jose Juan Almagro , Gulati Gunsagar S. , Gleyzer Rachel , Avagyan Susanna , Brown Erin L. , Zhang Wubing , Usmani Abul , Earland Noah , Wu Zhenqin , Zou James , Fields Ryan C. , Chen David Y. , Chaudhuri Aadel A. , Newman Aaron M.
Published: March 2024

Single-cell RNA sequencing (scRNA-seq) has transformed our understanding of cell fate in developmental systems. However, identifying the molecular hallmarks of potency – the capacity of a cell to differentiate into other cell types – has remained challenging. Here, we introduce CytoTRACE 2, an interpretable deep learning framework for characterizing potency and differentiation states on an absolute scale from scRNA-seq data. Across 31 human and mouse scRNA-seq datasets encompassing 28 tissue types, CytoTRACE 2 outperformed existing methods for recovering experimentally determined potency levels and differentiation states covering the entire range of cellular ontogeny. Moreover, it reconstructed the temporal hierarchy of mouse embryogenesis across 62 timepoints; identified pan-tissue expression programs that discriminate major potency levels; and facilitated discovery of cellular phenotypes in cancer linked to survival and immunotherapy resistance. Our results illuminate a fundamental feature of cell biology and provide a broadly applicable platform for delineating single-cell differentiation landscapes in health and disease.
When spatial attention cannot be divided: Quadrantic enhancement of early visual processing across task–relevant and irrelevant locations
Authors: Özkan Mert , Störmer Viola
Published: March 2024

Spatial attention enables us to select regions of space and prioritize visual processing at the attended locations. Previous research has shown that spatial attention can be flexibly tuned to broader or narrower regions in space, and in some cases be split amongst multiple locations. Here, we investigate how attentional resources are distributed within a visual quadrant when participants are instructed to either focus attention narrowly, broadly, or split attention among two non-contiguous locations. Using a combination of behavior and steady-state visual-evoked potentials (SSVEP), the oscillatory response of the visual cortex to incoming flickering stimuli, we find clear evidence for ineffective splitting of spatial attention within a visual quadrant. Importantly, by assessing visual-cortical processing across locations at a high spatial resolution (by flickering nearby locations at distinct frequencies), our results reveal that attention was distributed in the exact same manner regardless of whether participants were instructed to attend broadly across a large region of space, or divide attention amongst two non-contiguous locations: In both cases, the intermediate location showed the strongest boost in visual-cortical processing, no matter whether it was the center of the attended region (broad-focus condition), or the uncued, to-be-ignored location (split-focus condition). Thus, the present study provides strong evidence that when trying to attend to multiple separate locations within a visual quadrant, sustained attention inadvertently enhances visual processing at the intermediate location even when it is detrimental to task performance.
Evidence for the key roles of thePseudomonas syringaemobilome in shaping biotic interactions
Authors: Holtappels D. , Rickus G.E.J. , Morgan T. , de Rezende R. R. , Koskella B. , Alfenas-Zerbini P.
Published: March 2024

The mobilome, defined as the collection of mobile genetic elements within a bacterial genome, plays a critical role in the adaptation of bacteria to abiotic and biotic drivers. In particular, prophages have been reported to contribute to bacterial resistance to virulent bacteriophages, the competitive interaction of bacterial hosts within microbial communities, and in pathogenicity and virulence. It is therefore critical to better understand the role of prophages in distributing genes and functions within and among bacterial species to predict how bacteria adapt to their biotic environment.Pseudomonas syringaeoffers an ideal study system to ask these questions both because of its broad range of lifestyles (spanning from environmental growth to plant pathogens) and its high intraspecies diversity. To examine the role of the mobilome in this species complex, we compared 590 genomes available from public databases and annotated the defense mechanisms, effectors, and prophages in the genomes. We found that this species complex has an elaborate phage pandefensome consisting of 139 defense mechanisms. Host-associatedP. syringaeisolates were found to have both elaborate phage defensomes and effectoromes. Assessing taxonomical signatures of the observed prophages uncovered broad differences in the types and numbers of genes encoded by different phage families, emphasizing how the evolutionary advantages conferred to hosts will depend on the prophage composition and offering insight to how these genes might disperse within a community. Our study highlights the intimate association of phage families with their hosts and uncovers their key role in shaping ecology for this widespread species complex.

Significance statement

The bacterial accessory genome, including the mobilome and prophages, plays a critical role in shaping bacterial adaptation to abiotic and biotic drivers. These prophages are widespread across bacterial taxa and likely maintained because of their evolutionary advantage. Our ability to predict how a bacterial population will evolve over time requires a better understanding of where key functional traits arrive. To address this question, we assessed prophage-encoded phage defenses and effector acrossPseudomonas syringae. We show that prophages carrying these genes belong to specific phage taxa with differences in the types of genes encoded. This emphasizes the evolutionary advantage of these prophages, offering a framework to uncover how these genes disperse within microbial communities and their role in pathogen evolution.
Anti-JOVI.1 antibody to detect clonal T cell populations: implementation into a diagnostic flow cytometry laboratory and correlation with clinical findings
Authors: Reardon Benjamin , Hsu Jennifer , Smith Sandy , van der Linde Riana , Brown David A. , Tegg Elizabeth , Sasson Sarah C.
Published: March 2024

The development of a high through-put flow cytometric assay for the identification of clonal T cells has proved challenging. We assessed the surface expression of a specific T Cell Receptor β-chain constant region using conjugated anti-JOV1.1 monoclonal antibodies to identify clonal T cell populations in a large diagnostic flow cytometry laboratory within a quaternary referral hospital. 37 cases were analysed. We identified 15 cases of clonal JOVI.1 expression, 7 of which had a consensus diagnosis of T-cell lymphoproliferative disease (TLPD). The remaining 22 cases had polyclonal JOVI.1 expression, none of which had a consensus diagnosis of TLPD, resulting in a sensitivity of 100% and specificity of 73%. When clonal NK-T cells were excluded, specificity further improves to 97%. These results provide real-world data and support the widespread adoption of this assay into diagnostic use.
Large Language Model in Medical Information Extraction from Titles and Abstracts with Prompt Engineering Strategies: A Comparative Study of GPT-3.5 and GPT-4
Authors: Tang Yiyi , Xiao Ziyan , Li Xue , Fang Qiwen , Zhang Qingpeng , Fong Daniel Yee Tak , Lai Francisco Tsz Tsun , Chui Celine Sze Ling , Chan Esther Wai Yin , Wong Ian Chi Kei ,   Research Data Collaboration Task Force
Published: March 2024

Background

While it is believed that large language models (LLMs) have the potential to facilitate the review of medical literature, their accuracy, stability and prompt strategies in complex settings have not been adequately investigated. Our study assessed the capabilities of GPT-3.5 and GPT-4.0 in extracting information from publication abstracts. We also validated the impact of prompt engineering strategies and the effectiveness of evaluating metrics.

Methodology

We adopted a stratified sampling method to select 100 publications from nineteen departments in the LKS Faculty of Medicine, The University of Hong Kong, published between 2015 and 2023. GPT-3.5 and GPT-4.0 were instructed to extract seven pieces of information – study design, sample size, data source, patient, intervention, comparison, and outcomes – from titles and abstracts. The experiment incorporated three prompt engineering strategies: persona, chain-of-thought and few-shot prompting. Three metrics were employed to assess the alignment between the GPT output and the ground truth: ROUGE-1, BERTScore and a self-developed LLM Evaluator with improved capability of semantic understanding. Finally, we evaluated the proportion of appropriate answers among different GPT versions and prompt engineering strategies.

Results

The average accuracy of GPT-4.0, when paired with the optimal prompt engineering strategy, ranged from 0.736 to 0.978 among the seven items measured by the LLM evaluator.

Sensitivity of GPT is higher than the specificity, with an average sensiti ity score of 0.8550 while scoring only 0.7353 in specificity. The GPT version was shown to be a statistically significant factor impacting accuracy, while prompt engineering strategies did not exhibit cumulative effects. Additionally, the LLM evaluator outperformed the ROUGE-1 and BERTScore in assessing the alignment of information.

Conclusion

Our result confirms the effectiveness and stability of LLMs in extracting medical information, suggesting their potential as efficient tools for literature review. We recommend utilizing an advanced version of LLMs and the prompt should be tailored to specific tasks. Additionally, LLMs show promise as an evaluation tool related for complex information.
Socio-ecological heterogeneity and uncertainty in the elimination of human schistosomiasis
Authors: Neves M. Inês , Milne Gregory C , Webster Joanne P. , Walker Martin
Published: March 2024

Schistosomiasis is a neglected tropical disease caused by parasitic flatworms which infect approximately 240 million people worldwide living in poverty, mostly in sub-Saharan Africa. The World Health Organization (WHO) aims to eliminate schistosomiasis by 2030, predominantly relying on a strategy of mass drug administration (MDA) using praziquantel. The effectiveness of MDA can vary widely among disease foci. Mathematical modelling is increasingly being used to understand the transmission dynamics of schistosomiasis and for predicting the effectiveness of MDA and time frames to elimination. Due to the highly focal nature of schistosomiasis, many key parameters influencing its transmission are likely highly geographically variable. Yet typically models do not fully integrate this uncertainty into predictions. This can lead to unrealistic expectations on the prospects for elimination. Here, we present a schistosomiasis transmission model to evaluate how uncertainty in parameters relating to local socio-ecological conditions influence resilience of the parasite population to intervention and the effectiveness of MDA. We discuss the growing importance of incorporating uncertainty in mathematical models for this and other NTDs to enable transparent communication of predictions as we move towards the 2030 elimination goals.
Trans-ancestral Genome Wide Association Study of Sporadic and Recurrent Miscarriage
Authors: Reynoso Alexandra , Nandakumar Priyanka , Shi Jingchunzi , Bielenberg Jessica ,   23andMe Research Team, Holmes Michael V. , Aslibekyan Stella
Published: March 2024

Miscarriage is a common adverse pregnancy outcome, impacting approximately 15% of pregnancies. Herein, we present results of the largest trans-ancestral genome wide association study for miscarriage to date, based on 334,593 cases of sporadic, and 52,087 cases of recurrent miscarriage in the 23andMe, Inc. Research Cohort. We identified 10 novel genome-wide significant associations for sporadic miscarriage, and one for recurrent miscarriage. These loci mapped to genes with roles in neural development and telomere length, and to developmental disorders including autism spectrum disorder. Three variants, with similar directionality and magnitude of effect, replicated in a previously published GWAS. Using Mendelian randomization and triangulation, robust evidence was found for smoking causally increasing the risk of sporadic (genetic liability to ever vs never smoking: OR 1.13; 95%CI: 1.11-1.15; P=2.61e-42) and recurrent (OR 1.25; 95%CI: 1.21-1.30; P=5.47e-34) miscarriage, with moderate, yet triangulating, evidence identified for a potential etiological role of caffeine consumption.
Exposing Vulnerabilities in Clinical LLMs Through Data Poisoning Attacks: Case Study in Breast Cancer
Authors: Das Avisha , Tariq Amara , Batalini Felipe , Dhara Boddhisattwa , Banerjee Imon
Published: March 2024

Training Large Language Models (LLMs) with billions of parameters on a dataset and publishing the model for public access is the standard practice currently. Despite their transformative impact on natural language processing, public LLMs present notable vulnerabilities given the source of training data is often web-based or crowdsourced, and hence can be manipulated by perpetrators. We delve into the vulnerabilities of clinical LLMs, particularly BioGPT which is trained on publicly available biomedical literature and clinical notes from MIMIC-III, in the realm of data poisoning attacks. Exploring susceptibility to data poisoning-based attacks on de-identified breast cancer clinical notes, our approach is the first one to assess the extent of such attacks and our findings reveal successful manipulation of LLM outputs. Through this work, we emphasize on the urgency of comprehending these vulnerabilities in LLMs, and encourage the mindful and responsible usage of LLMs in the clinical domain.
A T6SS in the coral pathogenVibrio coralliilyticussecretes an arsenal of anti-eukaryotic effectors and contributes to virulence
Authors: Mass Shir , Cohen Hadar , Gerlic Motti , Ushijima Blake , van Kessel Julia C. , Bosis Eran , Salomon Dor
Published: March 2024

Vibrio coralliilyticus(Vcor) is a pathogen of coral and shellfish, leading to devastating economic and ecological consequences worldwide. Although rising ocean temperatures correlate with increasedVcorpathogenicity, the specific molecular mechanisms and determinants contributing to virulence remain poorly understood. Here, we systematically analyzed the type VI secretion system (T6SS), a contact-dependent toxin delivery apparatus, inVcor. We identified two omnipresent T6SSs that are activated at temperatures in whichVcorbecomes virulent; T6SS1 is an antibacterial system mediating interbacterial competition, whereas T6SS2 mediates anti-eukaryotic toxicity and contributes to mortality during infection of an aquatic model organism,Artemia salina. Using comparative proteomics, we identified the T6SS1 and T6SS2 toxin arsenals of threeVcorstrains with distinct disease etiologies. Remarkably, T6SS2 secretes at least nine novel anti-eukaryotic toxins comprising core and accessory repertoires. We propose that T6SSs differently contribute toVcor’s virulence: T6SS2 plays a direct role by targeting the host, while T6SS1 plays an indirect role by eliminating competitors.

Author Summary

Coral reefs are diverse ecosystems providing habitats for various fish, invertebrates, and microorganisms. Climate change, leading to rising ocean water temperatures, correlates with coral bleaching and mass mortality events. An implicated causal agent of coral disease outbreaks is the marine bacteriumVibrio coralliilyticus. Here, we found that two toxin injection systems present in allVibrio coralliilyticusstrains are regulated by temperature; we revealed the toxins that they secrete and their function in competition against rival bacteria and in the intoxication of an animal host. Our findings implicate these systems as previously unappreciated contributors toVibrio coralliilyticusvirulence, illuminating possible targets to treat or prevent coral infection.
Interplay of IGF1R and estrogen signaling regulates hematopoietic stem and progenitor cells
Authors: Xie Ying , Xiang Dongxi , Hu Xin , Pakula Hubert , Park Eun-Sil , Chi Jiadong , Linn Douglas E. , Tao Luwei , Li Zhe
Published: March 2024

Tissue stem cells often exhibit developmental stage-specific and sexually dimorphic properties, but the underlying mechanism remains largely elusive. By characterizing IGF1R signaling in hematopoietic cells, here we report that its disruption exerts sex-specific effects in adult hematopoietic stem and progenitor cells (HSPCs). Loss of IGF1R decreases the HSPC population in females but not in males, in part due to a reduction in HSPC proliferation induced by estrogen. In addition, the adult female microenvironment enhances engraftment of wild-type but notIgf1r-null HSPCs. In contrast, during gestation, when both female and male fetuses are exposed to placental estrogens, loss of IGF1R reduces the numbers of their fetal liver HSPCs regardless of sex. Collectively, these data support the interplay of IGF1R and estrogen pathways in HSPCs and suggest that the proliferation-promoting effect of estrogen on HSPCs is in part mediated via IGF1R signaling.
MAP4 kinase-regulated reduced CLSTN1 expression in medulloblastoma is associated with increased invasiveness
Authors: Sönmez Ece , Yan Shen , Lin Meng-Syuan , Baumgartner Martin
Published: March 2024

De-regulated protein expression contributes to tumor growth and progression in medulloblastoma (MB), the most common malignant brain tumor in children. MB is associated with impaired differentiation of specific neural progenitors, suggesting that the deregulation of proteins involved in neural physiology could contribute to the transformed phenotype in MB.

Calsynthenin 1 (CLSTN1) is a neuronal protein involved in cell-cell interaction, vesicle trafficking, and synaptic signaling. We previously identified CLSTN1 as a putative target of the pro-invasive kinase MAP4K4, which we found to reduce CLSTN1 surface expression. Herein, we explored the expression and functional significance of CLSTN1 in MB. We found thatCLSTN1expression is decreased in primary MB tumors compared to tumor-free cerebellum or brain tissues. CLSTN1 is expressed in laboratory-established MB cell lines, where it localized to the plasma membrane, intracellular vesicular structures, and regions of cell-cell contact. The reduction of CLSTN1 expression significantly increased growth factor-driven invasiveness. Pharmacological inhibition of MAP4 kinases caused increased CLSTN1 expression and CLSTN1 accumulation in cell-cell contacts. Co-culture of tumor cells with astrocytes increased CLSTN1 localization in cell-cell contacts, which was further enhanced by MAP4K inhibition.

Our study revealed a repressive function of CLSTN1 in growth-factor-driven invasiveness in MB and its potential implication in homologous and heterologous interactions of the tumor cells with cells in their microenvironment.
Non-peroxide antibacterial activity of Meliponula (Axestotrigona) ferruginea honey from Tanzania
Authors: Mduda Christopher Alphonce
Published: March 2024

Honey serves as a medicinal food that is utilized for both preventative care and the treatment of various ailments. Amidst the contemporary challenge of antibiotic resistance, honey emerges as a promising natural antimicrobial solution. The efficacy of honey in therapy hinges on its mechanisms of antimicrobial action. Thus, this study investigated the non-peroxide antibacterial properties of honey sources from a stingless bee species, Meliponula (Axestotrigona) ferruginea, that is commonly managed in Tanzania. The findings reveal that honey from stingless bees exhibits remarkable antibacterial efficacy against both resistant and susceptible bacterial strains. Notably, the studied honey samples retained a substantial portion of their antibacterial potency (89.9 - 98.7%) even after the removal of hydrogen peroxide. Interestingly, the antibacterial activity of honey did not correlate with its total phenolic and flavonoid content, suggesting the influence of specific bioactive compounds rather than overall phytochemical content. Stingless bee honey was most effective against gram-positive bacterial strains, particularly Staphylococcus aureus. These results underscore the therapeutic potential of stingless bee honey for the management of pathogenic bacteria. Future investigations should focus on elucidating the specific bioactive compounds present in stingless bee honey to bolster its clinical applications.
Deciphering the Role of Aggrecan in Parvalbumin Interneurons: Unexpected Outcomes from a Conditional ACAN Knockout That Eliminates WFA+ Perineuronal Nets
Authors: Grødem Sverre , Thompson Elise H. , Røe Malin B. , Vatne Guro H. , Nymoen Ingeborg , Buccino Alessio , Madland Tarjei , Hafting Torkel , Fyhn Marianne , Lensjø Kristian K.
Published: March 2024

The transition from juvenile to adult is accompanied by the maturation of inhibitory parvalbumin-positive (PV+) neurons and reduced plasticity. This transition involves the formation of perineuronal nets (PNNs), a dense configuration of the extracellular matrix that predominantly envelops parvalbumin-positive (PV+) neurons. Aggrecan, a proteoglycan encoded by the ACAN gene, has been shown to have a key role in the PNNs as knock-out of ACAN in the adult brain reactivates juvenile plasticity, but the contribution of different cell populations is unknown

Here, we establish and characterize a mouse model in which ACAN is selectively knocked out (KO) in PV+ neurons (ACANflx/PVcre). Moreover, we develop a viral tool to perform similar cell-type directed KO in adult mice. Both models are compared with the traditional method of PNN removal, namely enzymatic degradation of PNNs with Chondroitinase ABC (chABC).

We show that PV+ neurons in adult ACANflx/PVcre mice do not produce PNNs that are labeled byWisteria floribunda agglutinin(WFA), the most commonly used PNN marker. Surprisingly, electrophysiological properties of PV+ interneurons in the visual cortex (V1) and ocular dominance plasticity of adult ACANflx/PVcre mice were similar to controls. In contrast, AAV-mediated ACAN knockout in adult mice increased ocular dominance plasticity. Moreover, in vivo chABC treatment of KO mice resulted in reduced firing rate of PV+ cells and increased frequency of spontaneous excitatory postsynaptic currents (sEPSC), a phenotype associated with chABC treatment of WT animals. This suggests compensatory mechanisms in the germline KO. Indeed, qPCR of bulk tissue indicates that other PNN components are expressed at higher levels in the KO animals. Finally, we perform memory-and behavioral testing to see if the lack of ACAN from PV+ neurons throughout development affected stereotypic behaviors and memory processing. ACANflx/PVcre mice have learning and memory abilities similar to controls, but use bold search strategies during navigation in the Morris water maze. The low level of anxiety-related behavior is confirmed in an open field and zero maze, where they spent nearly twice the time in open areas.
Loss of prohibitin 2 in Schwann cells dysregulates key transcription factors controlling developmental myelination
Authors: Wilson Emma R. , Nunes Gustavo Della-Flora , Shen Shichen , Moore Seth , Gawron Joseph , Maxwell Jessica , Syed Umair , Hurley Edward , Lanka Meghana , Qu Jun , Desaubry Laurent , Wrabetz Lawrence , Poitelon Yannick , Feltri M. Laura
Published: March 2024

Schwann cells are critical for the proper development and function of the peripheral nervous system, where they form a mutually beneficial relationship with axons. Past studies have highlighted that a pair of proteins called the prohibitins play major roles in Schwann cell biology. Prohibitins are ubiquitously expressed and versatile proteins. We have previously shown that while prohibitins play a crucial role in Schwann cell mitochondria for long-term myelin maintenance and axon health, they may also be present at the Schwann cell-axon interface during development. Here, we expand on this work, showing that drug-mediated modulation of prohibitinsin vitrodisrupts myelination and confirming that Schwann cell-specific ablation of prohibitin 2 (Phb2)in vivoresults in early and severe defects in peripheral nerve development. Using a proteomic approachin vitro, we identify a pool of candidate PHB2 interactors that change their interaction with PHB2 depending on the presence of axonal signals. Furthermore, we showin vivothat loss ofPhb2in mouse Schwann cells causes ineffective proliferation and dysregulation of transcription factors EGR2 (KROX20), POU3F1 (OCT6) and POU3F2 (BRN2) that are necessary for proper Schwann cell maturation. Schwann cell-specific deletion ofJun, a transcription factor associated with negative regulation of myelination, confers partial rescue of the development defect seen in mice lacking Schwann cellPhb2. This work develops our understanding of Schwann cell biology, revealing thatPhb2may directly or indirectly modulate the timely expression of transcription factors necessary for proper peripheral nervous system development, and proposing candidates that may play a role in PHB2-mediated integration of axon signals in the Schwann cell.
Systemic coordination of whole-body tissue remodeling in sea anemone local regeneration
Authors: Cheung Stephanie , Bredikhin Danila , Gerber Tobias , Steenbergen Petrus J. , Basu Soham , Bailleul Richard , Hansen Pauline , Paix Alexandre , Benton Matthew A. , Korswagen Hendrik C. , Arendt Detlev , Stegle Oliver , Ikmi Aissam
Published: March 2024

The complexity of regeneration extends beyond local wound responses (1,2), eliciting systemic processes that engage the entire organism. However, their functional relevance, and the spatial and temporal orchestration of the underlying molecular processes distant from the injury site remain unknown. Here, we demonstrate that local regeneration in the cnidarianNematostella vectensisinvolves a systemic homeostatic response, leading to coordinated whole-body remodeling. Leveraging spatial transcriptomics, endogenous protein tagging, and live imaging, we comprehensively dissect this systemic response at the organismal scale. We identify proteolysis as a critical process driven by both local and systemic upregulation of metalloproteases. We show that metalloproteinase expression levels and activity scale with the extent of tissue loss, leading to proportional long-range movement of tissue and its associated extracellular matrix. Our findings illuminate the adaptive nature of the systematic response in regeneration. We propose that this integrated regenerative mechanism, shifting the system from a steady to a dynamic homeostatic state, allows the organism to cope with a wide range of injuries.
Analysis and culturing of the prototypic crAssphage reveals a phage-plasmid lifestyle
Authors: Schmidtke Danica T. , Hickey Angela S. , Liachko Ivan , Sherlock Gavin , Bhatt Ami S.
Published: March 2024

The prototypic crAssphage (Carjivirus communis) is one of the most abundant, prevalent, and persistent gut bacteriophages, yet it remains uncultured and its lifestyle uncharacterized. For the last decade, crAssphage has escaped plaque-dependent culturing efforts, leading us to investigate alternative lifestyles that might explain its widespread success. Through genomic analyses and culturing, we find that crAssphage uses a phage-plasmid lifestyle to persist extrachromosomally. Plasmid-related genes are more highly expressed than those implicated in phage maintenance. Leveraging this finding, we use a plaque-free culturing approach to measure crAssphage replication in culture withPhocaeicola vulgatus, Phocaeicola dorei,andBacteroides stercoris, revealing a broad host range. We demonstrate that crAssphage persists with its hosts in culture without causing major cell lysis events or integrating into host chromosomes. The ability to switch between phage and plasmid lifestyles within a wide range of hosts contributes to the prolific nature of crAssphage in the human gut microbiome.
Thermal equation of state of rhodium to 191 GPa and 2700 K using double-sided flash laser heating in a diamond anvil cell
Authors: McHardy J. D. , Storm C. V. , Duff M. J. , Lonsdale C. M. , Woolman G. A. , McMahon M. I. , Giordano N. , MacLeod S. G.
Published: March 2024

The phase behavior of rhodium (Rh) metal has been studied to 191 GPa and 2700 K using a combination of room-temperature isothermal compression and double-sided flash laser heating experiments. The isothermal compression data have been fitted with a second-order adapted polynomial of order L equation of state (EoS) with best-fitting parameters of V0=13.764(2)Å3/atom, K0=258(3)GPa, and K′=5.36(9). Two-dimensional maps of the uniaxial stress component t are presented for Rh at different pressures showing the spatial distribution of the local stress state of a relatively high-yield strength material encased in a Bi pressure medium. In addition, a simple, thermal pressure equation-of-state model, based on a single Einstein temperature, has been fitted to the high-pressure-temperature data up to 2700 K at 148 GPa and ambient-pressure thermal expansion data up to 1982 K. Also determined are the best-fitting parameters to reproduce the thermal EoS within the two-dimensional integration software. The optimized parameters are V0=13.764Å3/atom, K0=260.54GPa, K′=5.114, αT=2.99×10−5 K−1, ∂αT/∂T=1.27×10−9

K

−

2

, ∂K0/∂T=−6.43×10−5GPa/K, and ∂K′/∂T=−9.3×10−10K−1.

Published by the American Physical Society
2024
Dynamics of the antiferromagnetic spin ice phase in pyrochlore spinels
Authors: Szabó Attila , Nilsen Gøran J.
Published: March 2024

Motivated by the classical spin-nematic state observed in the breathing pyrochlore spinel LiGa0.95In0.05Cr4O8, we theoretically discuss spin dynamics in models of spin-lattice coupling in these materials. Semiclassical dynamical simulations successfully recover the key features of inelastic neutron-scattering experiments on LiGa0.95In0.05Cr4O8: a broad finite-energy peak alongside a continuum of scattering near the (200) wave vector that extends from the elastic line to high energies. To interpret this result, we generalize linear-spin-wave theory for conventionally ordered magnets to the disordered spin-ice-like ground states expected for moderate spin-lattice coupling, which reproduces the numerical simulation results quantitatively. In particular, we find that the inelastic peak is well explained by collective modes confined to ferromagnetic loops of the underlying nematic order. In addition, we find a sharp, linearly dispersing mode in the dynamic structure factor, which originates in long-wavelength fluctuations of the nematic director. We believe identifying this mode will be an interesting target for future experiments on these materials. We also outline potential future applications of our methods to both pyrochlore spinels and other spin-nematic systems.

Published by the American Physical Society
2024
Phenomenological study of a gauged
Lμ−Lτ
model with a scalar leptoquark
Authors: Chen Chuan-Hung , Chiang Cheng-Wei , Su Chun-Wei
Published: March 2024

A Z′ gauge boson with sub-GeV mass has acquired a significant interest in phenomenology, particularly in view of the muon g−2 anomaly and coherent elastic neutrino-nucleon scattering. The latter is challenged by the nuclear recoil energy of a few tens of keV but has been observed by the COHERENT experiment. To further reconcile the observed excesses in R(D(*)) from semileptonic charmful B decays and in the W boson mass, we investigate a model with a gauged U(1)Lμ−Lτ symmetry and a scalar leptoquark. In contrast to the mechanism that involves kinetic mixing between the gauge bosons of U(1)em and U(1)Lμ−Lτ, we adopt a dynamical symmetry breaking of U(1)Lμ−Lτ by incorporating an additional Higgs doublet. Through mixing with the U(1)Lμ−Lτ-charged Higgs doublet, new Higgs decay channels h→Z1Z1/Z1Z2 occur at percent-level branching ratios, which could be accessible at the LHC. The W-mass anomaly observed by CDF II can be potentially resolved through the enhancement in the oblique parameter T. Due to the flavored gauge symmetry, the introduced scalar leptoquark S13=(3¯,1,2/3) exhibits a unique coupling to the τ lepton, offering an explanation for the excesses observed in R(D(*)). Moreover, τ→μ(Z1→)e−e+ via the resonant light gauge boson decay can reach the sensitivity of Belle II at an integrated luminosity of 50  ab−1.

Published by the American Physical Society
2024
Quantum coherence enables hybrid multitask and multisource regimes in autonomous thermal machines
Authors: Hammam Kenza , Manzano Gonzalo , De Chiara Gabriele
Published: March 2024

Nonequilibrium effects may have a profound impact on the performance of thermal devices performing thermodynamic tasks such as refrigeration or heat pumping. The possibility of enhancing the performance of thermodynamic operations by means of quantum coherence is of particular interest but requires an adequate characterization of heat and work at the quantum level. In this work, we demonstrate that the presence of even small amounts of coherence in the thermal reservoirs powering a three-terminal machine, enables the appearance of combined, and hybrid modes of operation, where either different resources are combined to perform a single thermodynamic task, or more than one task is performed at the same time. We determine the performance of such coherence-enabled modes of operation obtaining their power and efficiency. In the case of hybrid regimes, the presence of coherence in the hot bath allows for an increase in power while maintaining high efficiencies. On the other hand, in combined regimes, a contrasting behavior emerges whereby coherence has a detrimental impact on power output and efficiency.

Published by the American Physical Society
2024
Stabilization of discrete time-crystalline response on a superconducting quantum computer by increasing the interaction range
Authors: Solfanelli Andrea , Ruffo Stefano , Succi Sauro , Defenu Nicolò
Published: March 2024

The simulation of complex quantum many-body systems is a promising short-term goal of noisy intermediate-scale quantum (NISQ) devices. However, the limited connectivity of native qubits hinders the implementation of quantum algorithms that require long-range interactions. We present the outcomes of a digital quantum simulation where we overcome the limitations of the qubit connectivity in NISQ devices. Utilizing the universality of quantum processor native gates, we demonstrate how to implement couplings among physically disconnected qubits at the cost of increasing the circuit depth. We apply this method to simulate a Floquet-driven quantum spin chain featuring interactions beyond nearest neighbors. Specifically, we benchmark the prethermal stabilization of the discrete Floquet time-crystalline response as the interaction range increases, a phenomenon never observed experimentally. Our quantum simulation addresses one of the significant limitations of superconducting quantum processors, namely, device connectivity. It reveals that nontrivial physics involving couplings beyond nearest neighbors can be extracted after the impact of noise is properly taken into account in the theoretical model and consequently mitigated from the experimental data.

Published by the American Physical Society
2024
Guided quantum walk
Authors: Schulz Sebastian , Willsch Dennis , Michielsen Kristel
Published: March 2024

We utilize the theory of local amplitude transfer (LAT) to gain insights into quantum walks (QWs) and quantum annealing (QA) beyond the adiabatic theorem. By representing the eigenspace of the problem Hamiltonian as a hypercube graph, we demonstrate that probability amplitude traverses the search space through a series of local Rabi oscillations. We argue that the amplitude movement can be systematically guided towards the ground state using a time-dependent hopping rate based solely on the problem's energy spectrum. Building upon these insights, we extend the concept of multistage QW by introducing the guided quantum walk (GQW) as a bridge between QW-like and QA-like procedures. We assess the performance of the GQW on exact cover, traveling salesperson, and garden optimization problems with 9 to 30 qubits. Our results provide evidence for the existence of optimal annealing schedules, beyond the requirement of adiabatic time evolutions. These schedules might be capable of solving large-scale combinatorial optimization problems within evolution times that scale linearly in the problem size.

Published by the American Physical Society
2024
Steady-state quantum thermodynamics with synthetic negative temperatures
Authors: Bera Mohit Lal , Pandit Tanmoy , Chatterjee Kaustav , Singh Varinder , Lewenstein Maciej , Bhattacharya Utso , Bera Manabendra Nath
Published: March 2024

A bath with a negative temperature is a subject of intense debate in recent times. It raises fundamental questions not only on our understanding of negative temperature of a bath in connection with thermodynamics but also on the possibilities of constructing devices using such baths. In this work, we study steady-state quantum thermodynamics involving baths with negative temperatures. A bath with a negative temperature is created synthetically using two baths of positive temperatures and weakly coupling these with a qutrit system. These baths are then coupled to each other via a working system. At steady state, the laws of thermodynamics are analyzed. We find that whenever the temperatures of these synthetic baths are identical, there is no heat flow, which reaffirms the zeroth law. There is always a spontaneous heat flow for different temperatures. In particular, heat flows from a bath with a negative temperature to a bath with a positive temperature which, in turn, implies that a bath with a negative temperature is “hotter” than a bath with a positive temperature. This warrants an amendment in the Kelvin-Planck statement of the second law, as suggested in earlier studies. In all these processes, the overall entropy production is positive, as required by the Clausius statement of the second law. We construct continuous heat engines operating between positive and negative temperature baths. These engines yield maximum possible heat-to-work conversion efficiency, that is, unity. We also study the thermodynamic nature of heat from a bath with a negative temperature and find that it is thermodynamic work but with negative entropy.

Published by the American Physical Society
2024
Observations of specimen morphology effects on near-zone-axis convergent-beam electron diffraction patterns
Authors: Tan Xiaofen , Bourgeois Laure , Nakashima Philip N. H.
Published: March 2024

This work presents observations of symmetry breakages in the intensity distributions of near-zone-axis convergent-beam electron diffraction (CBED) patterns that can only be explained by the symmetry of the specimen and not the symmetry of the unit cell describing the atomic structure of the material. The specimen is an aluminium–copper–tin alloy containing voids many tens of nanometres in size within continuous single crystals of the aluminium host matrix. Several CBED patterns where the incident beam enters and exits parallel void facets without the incident beam being perpendicular to these facets are examined. The symmetries in their intensity distributions are explained by the specimen morphology alone using a geometric argument based on the multislice theory. This work shows that it is possible to deduce nanoscale morphological information about the specimen in the direction of the electron beam – the elusive third dimension in transmission electron microscopy – from the inspection of CBED patterns.