bluuebunny/crossref_metadata_2025 huggingface dataset:
Environmentally acquired gut-associated bacteria are not critical for growth and survival in a solitary bee,
Megachile rotundata
Authors: Brar Gagandeep , Floden Madison , McFrederick Quinn , Rajamohan Arun , Yocum George , Bowsher Julia
Published: August 2024

Social bees have been extensively studied for their gut microbial functions, but the significance of the gut microbiota in solitary bees remains less explored. Solitary bee,
Megachile rotundata
females provision their offspring with pollen from various plant species, harboring a diverse microbial community that colonizes larvae guts. The
Apilactobacillus
is the most abundant microbe, but evidence concerning the effects of
Apilactobacillus
and other provision microbes on growth and survival are lacking. We hypothesized that the presence of
Apilactobacillus
in abundance would enhance larval and prepupal development, weight, and survival, while the absence of intact microbial communities was expected to have a negative impact on bee fitness. We reared larvae on pollen provisions with naturally collected microbial communities (Natural pollen) or devoid of microbial communities (Sterile pollen). We also assessed the impact of introducing
Apilactobacillus micheneri
by adding it to both types of pollen provisions. Feeding larvae with sterile pollen +
A. micheneri
led to the highest mortality rate, followed by natural pollen +
A. micheneri
, and sterile pollen. Larval development was significantly delayed in groups fed with sterile pollen. Interestingly, larval and prepupal weights did not significantly differ across treatments compared to natural pollen-fed larvae. 16S rRNA gene sequencing found a dominance of
Sodalis
, when
A. micheneri
was introduced to natural pollen. The presence of
Sodalis
with abundant
A. michene
ri suggests potential crosstalk between both, shaping bee nutrition and health. Hence, this study highlights that the reliance on nonhost-specific environmental bacteria may not impact fitness of
M. rotundata
.

IMPORTANCE

This study investigates the impact of environmentally acquired gut microbes of solitary bee fitness with insights into the microbial ecology of bee and their health. While the symbiotic microbiome is well-studied in social bees, the role of environmental acquired microbiota in solitary bees remains unclear. Assessing this relationship in a solitary pollinator, the leaf-cutting bee,
Megachile rotundata
, we discovered that this bee species does not depend on the diverse environmental bacteria found in pollen for either its larval growth or survival. Surprisingly, high concentrations of the most abundant pollen bacteria
, Apilactobacillus micheneri
did not consistently benefit bee fitness, but caused larval mortality. Our findings also suggest an interaction between
Apilactobacillus
and the
Sodalis
and perhaps their role in bee nutrition. Hence, this study provides significant insights that contribute to understanding the fitness, conservation, and pollination ecology of other solitary bee species in the future.
Comparison of the immunogenicity of mRNA-encoded and protein HIV-1 Env–ferritin nanoparticle designs
Authors: Mu Zekun , Whitley Jill , Martik Diana , Sutherland Laura , Newman Amanda , Barr Maggie , Parks Robert , Wiehe Kevin , Cain Derek W. , Hodges Katrina Z. , Venkatayogi Sravani , Lee Esther M. , Smith Lena , Mansouri Katayoun , Edwards Robert J. , Wang Yunfei , Rountree Wes , Alameh Mohamad-Gabriel , Tam Ying , Barbosa Christopher , Tomai Mark , Lewis Mark G. , Santrai Sampa , Maughan Maureen , Tian Ming , Alt Frederick W. , Weissman Drew , Saunders Kevin O. , Haynes Barton F.
Published: August 2024

Nucleoside-modified mRNA technology has revolutionized vaccine development with the success of mRNA COVID-19 vaccines. We used modified mRNA technology for the design of envelopes (Env) to induce HIV-1 broadly neutralizing antibodies (bnAbs). However, unlike SARS-CoV-2 neutralizing antibodies that are readily made, HIV-1 bnAb induction is disfavored by the immune system because of the rarity of bnAb B cell precursors and the cross-reactivity of bnAbs targeting certain Env epitopes with host molecules, thus requiring optimized immunogen design. The use of protein nanoparticles (NPs) has been reported to enhance B cell germinal center responses to HIV-1 Env. Here, we report our experience with the expression of Env–ferritin NPs compared with membrane-bound Env gp160 when encoded by modified mRNA. We found that well-folded Env–ferritin NPs were a minority of the protein expressed by an mRNA design and were immunogenic at 20 µg but minimally immunogenic in mice at 1 µg dose
in vivo
and were not expressed well in draining lymph nodes (LNs) following intramuscular immunization. In contrast, mRNA encoding gp160 was more immunogenic than mRNA encoding Env–NP at 1 µg dose and was expressed well in draining LN following intramuscular immunization. Thus, analysis of mRNA expression
in vitro
and immunogenicity at low doses
in vivo
are critical for the evaluation of mRNA designs for optimal immunogenicity of HIV-1 immunogens.

IMPORTANCE

An effective HIV-1 vaccine that induces protective antibody responses remains elusive. We have used mRNA technology for designs of HIV-1 immunogens in the forms of membrane-bound full-length envelope gp160 and envelope ferritin nanoparticle. Here, we demonstrated in a mouse model that the membrane-bound form induced a better response than envelope ferritin nanoparticle because of higher
in vivo
protein expression. The significance of our research is in highlighting the importance of analysis of mRNA design expression and low-dose immunogenicity studies for HIV-1 immunogens before moving to vaccine clinical trials.
The Rab6 post-Golgi secretory pathway contributes to herpes simplex virus 1 (HSV-1) egress
Authors: Bergeman Melissa H. , Velarde Kimberly , Hargis Hailee L. , Glenn Honor L. , Hogue Ian B.
Published: August 2024

Herpes simplex virus 1 (HSV-1) is an alpha herpesvirus that infects a majority of the world population. The mechanisms and cellular host factors involved in the intracellular transport and exocytosis of HSV-1 particles are not fully understood. To elucidate these late steps in the replication cycle, we developed a live-cell fluorescence microscopy assay of HSV-1 virion intracellular trafficking and exocytosis. This method allows us to track individual virus particles and identify the precise moment and location of particle exocytosis using a pH-sensitive reporter. We show that HSV-1 uses the host cell’s post-Golgi secretory pathway during egress. The small GTPase, Rab6, binds to nascent secretory vesicles at the
trans
-Golgi network and plays important, but non-essential, roles in vesicle traffic and exocytosis at the plasma membrane, therefore making it a useful marker of the Golgi and post-Golgi secretory pathway. We show that HSV-1 particles colocalize with Rab6a in the region of the Golgi, cotraffic with Rab6a to the cell periphery, and undergo exocytosis from Rab6a vesicles. Consistent with previous reports, we find that HSV-1 particles accumulate at preferential egress sites in infected cells. The secretory pathway mediates this preferential/polarized egress, since Rab6a vesicles accumulate near the plasma membrane similarly in uninfected cells. These data suggest that, following particle envelopment, HSV-1 egress follows a pre-existing cellular secretory pathway to exit infected cells rather than novel, virus-induced mechanisms.

IMPORTANCE

Herpes simplex virus 1 (HSV-1) infects a majority of people. It establishes a life-long latent infection and occasionally reactivates, typically causing characteristic oral or genital lesions. Rarely in healthy natural hosts, but more commonly in zoonotic infections and in elderly, newborn, or immunocompromised patients, HSV-1 can cause severe herpes encephalitis. The precise cellular mechanisms used by HSV-1 remain an important area of research. In particular, the egress pathways that newly assembled virus particles use to exit from infected cells are unclear. In this study, we used fluorescence microscopy to visualize individual virus particles exiting from cells and found that HSV-1 particles use the pre-existing cellular secretory pathway.
Probing Gag-Env dynamics at HIV-1 assembly sites using live-cell microscopy
Authors: Muecksch Frauke , Klaus Severina , Laketa Vibor , Müller Barbara , Kräusslich Hans-Georg
Published: August 2024

Human immunodeficiency virus (HIV)-1 assembly is initiated by Gag binding to the inner leaflet of the plasma membrane (PM). Gag targeting is mediated by its N-terminally myristoylated matrix (MA) domain and PM phosphatidylinositol 4,5-bisphosphate [PI(4,5)P
2
]. Upon Gag assembly, envelope (Env) glycoproteins are recruited to assembly sites; this process depends on the MA domain of Gag and the Env cytoplasmic tail. To investigate the dynamics of Env recruitment, we applied a chemical dimerizer system to manipulate HIV-1 assembly by reversible PI(4,5)P
2
depletion in combination with super resolution and live-cell microscopy. This approach enabled us to control and synchronize HIV-1 assembly and track Env recruitment to individual nascent assembly sites in real time. Single virion tracking revealed that Gag and Env are accumulating at HIV-1 assembly sites with similar kinetics. PI(4,5)P
2
depletion prevented Gag PM targeting and Env cluster formation, confirming Gag dependence of Env recruitment. In cells displaying pre-assembled Gag lattices, PI(4,5)P
2
depletion resulted in the disintegration of the complete assembly domain, as not only Gag but also Env clusters were rapidly lost from the PM. These results argue for the existence of a Gag-induced and -maintained membrane micro-environment, which attracts Env. Gag cluster dissociation by PI(4,5)P
2
depletion apparently disrupts this micro-environment, resulting in the loss of Env from the former assembly domain.

IMPORTANCE

Human immunodeficiency virus (HIV)-1 assembles at the plasma membrane of infected cells, resulting in the budding of membrane-enveloped virions. HIV-1 assembly is a complex process initiated by the main structural protein of HIV-1, Gag. Interestingly, HIV-1 incorporates only a few envelope (Env) glycoproteins into budding virions, although large Env accumulations surrounding nascent Gag assemblies are detected at the plasma membrane of HIV-expressing cells. The matrix domain of Gag and the Env cytoplasmatic tail play a role in Env recruitment to HIV-1 assembly sites and its incorporation into nascent virions. However, the regulation of these processes is incompletely understood. By combining a chemical dimerizer system to manipulate HIV-1 assembly with super resolution and live-cell microscopy, our study provides new insights into the interplay between Gag, Env, and host cell membranes during viral assembly and into Env incorporation into HIV-1 virions.
Intestinal tissue response to Shiga toxin exposure
Authors: Hanson Kendal L. , Weiss Alison Ann
Published: August 2024

Shiga toxin (Stx) is produced by some pathogenic strains of
Escherichia coli
. To study the impact of Stx on the human intestine, we utilized human intestinal organoids and human intestinal enteroids grown as human intestinal enteroid monolayers (HIEMs) in transwells. To establish optimal experimental conditions, HIEMs were grown with or without mesenchymal cells added to the basolateral wells to recapitulate the interactions between the intestinal epithelium and the underlying mesenchyme. Monolayer barrier integrity was determined through transepithelial electrical resistance (TEER) readings. Apical saline was used on the apical surface since growth medium caused uneven development of the TEER. The medium used for epithelial cells contains added growth factors, while the mesenchymal medium lacks these growth factors. We have shown that mesenchymal cells can maintain the epithelial monolayer in the medium lacking growth factors, suggesting they produce these factors. Furthermore, growth factors produced by mesenchymal cells need to build up in the medium over time, since daily medium changes were not as effective as medium changes performed every 3 days. We have also shown that addition of growth factors is toxic to mesenchymal cells. Epithelial cells were more resistant to Stx2 than the mesenchymal cells, and mesenchymal cells contributed to epithelial cell death. Epithelial cells tolerated luminal exposure better than basolateral exposure. These studies demonstrate the importance of understanding tissue interactions in a disease state when using
in vitro
and
in vitro
models.

IMPORTANCE

These studies have cemented the need for complex cell culture models when studying host-pathogen interactions. Common animal models such as mice are resistant to
E. coli
O157:H7 infections and intestinal delivery of Stx2, while humans appear to be sensitive to both. It has been proposed that in humans, shiga toxin-producing
E. coli
-mediated intestinal damage destroys the intestinal barrier and allows basolateral access to Stx2. In mice, there is no epithelial damage; therefore, they are resistant to epithelial delivery of Stx2 while remaining sensitive to Stx2 injection. Our studies show that like mice, the human epithelial layer is quite resistant to Stx2, and it is the sensitivity of the mesenchymal cells that kills the epithelial cells. We have shown that Stx2 is transported through the intact epithelium without causing damage to the resistant epithelial layer. Understanding tissue interactions during infections is therefore critical in determining the effects of pathogens on human tissues.
Differential processing of VesB by two rhomboid proteases in
Vibrio cholerae
Authors: Roberts Cameron S. , Shannon Austin B. , Korotkov Konstantin V. , Sandkvist Maria
Published: August 2024

Rhomboid proteases are universally conserved and facilitate the proteolysis of peptide bonds within or adjacent to cell membranes. While eukaryotic rhomboid proteases have been demonstrated to harbor unique cellular roles, prokaryotic members have been far less characterized. For the first time, we demonstrate that
Vibrio cholerae
expresses two active rhomboid proteases that cleave a shared substrate at distinct sites, resulting in differential localization of the processed protein. The rhomboid protease rhombosortase (RssP) was previously found to process a novel C-terminal domain called GlyGly-CTERM, as demonstrated by its effect on the extracellular serine protease VesB during its transport through the
V. cholerae
cell envelope. Here, we characterize the substrate specificity of RssP and GlpG, the universally conserved bacterial rhomboid proteases. We show that RssP has distinct cleavage specificity from GlpG, and specific residues within the GlyGly-CTERM of VesB target it to RssP over GlpG, allowing for efficient proteolysis. RssP cleaves VesB within its transmembrane domain, whereas GlpG cleaves outside the membrane in a disordered loop that precedes the GlyGly-CTERM. Cleavage of VesB by RssP initially targets VesB to the bacterial cell surface and, subsequently, to outer membrane vesicles, while GlpG cleavage results in secreted, fully soluble VesB. Collectively, this work builds on the molecular understanding of rhomboid proteolysis and provides the basis for additional rhomboid substrate recognition while also demonstrating a unique role of RssP in the maturation of proteins containing a GlyGly-CTERM.

IMPORTANCE

Despite a great deal of insight into the eukaryotic homologs, bacterial rhomboid proteases have been relatively understudied. Our research aims to understand the function of two rhomboid proteases in
Vibrio cholerae
. This work is significant because it will help us better understand the catalytic mechanism of rhomboid proteases as a whole and assign a specific role to a unique subfamily whose function is to process a subset of effector molecules secreted by
V. cholerae
and other pathogenic bacteria.
Post-Devonian re-emergence and demise of stromatoporoids as major reef-builders on a Carboniferous Panthalassan seamount
Authors: Ezaki Yoichi , Masui Mitsuru , Nagai Koichi , Webb Gregory E. , Shimizu Koki , Sugama Shota , Adachi Natsuko , Sugiyama Tetsuo
Published: August 2024

Stromatoporoids were major reef-builders during the middle Paleozoic; however, no Carboniferous stromatoporoid reefs have been reported. The Akiyoshi Limestone Group of southwest Japan formed on a seamount in the Panthalassa Ocean from the Mississippian (Visean) to the middle Permian (Capitanian). The Early Pennsylvanian (Bashkirian) reef-core setting was well developed and laterally differentiated into several reef environments. Laminated skeletons made up of cystose or flat laminae and pillar-like vertical structures were abundant and, together with Chaetetes, contributed greatly to reef construction in most reef-core environments. The morphology of the laminated skeletons clearly indicates a stromatoporoid, probably labechiid, affinity. Thus, a lineage of reef-building stromatoporoids reappeared on a Panthalassan seamount in a locally warm-water tropical setting after the Late Devonian extinctions. Ongoing global glaciation may have resulted in enhanced ocean circulation, upwelling, and nutrient supply, especially around shallow-water seamounts, culminating in elevated carbonate saturation, which should have favored hypercalcified stromatoporoids and Chaetetes. The Chaetetes–stromatoporoid reefs remained in the Moscovian, but probably died out during the Kasimovian with intensive global cooling and frequent subaerial exposure, to be replaced by Palaeoaplysina–phylloid algal reefs. The occurrence of Bashkirian reef-building stromatoporoids indicates that Paleozoic stromatoporoids continued as reef-builders long after the Late Devonian extinction, at least in Panthalassa. This occurrence emphasizes the significance of rarely preserved open, but isolated oceanic settings like Akiyoshi for global biogeography and evolution.
Cortical inexcitability in ALS: correlating a clinical phenotype
Authors: Pavey Nathan , Hannaford Andrew , Higashihara Mana , van den Bos Mehdi , Geevasinga Nimeshan , Vucic Steve , Menon Parvathi
Published: August 2024

Background

Cortical inexcitability, a less studied feature of upper motor neuron (UMN) dysfunction in amyotrophic lateral sclerosis (ALS), was identified in a large cross-sectional cohort of ALS patients and their demographic and clinical characteristics were contrasted with normal or hyperexcitable ALS cohorts to assess the impact of cortical inexcitability on ALS phenotype and survival.

Methods

Threshold-tracking transcranial magnetic stimulation (TMS) technique with measurement of mean short interval intracortical inhibition (SICI) differentiated ALS patients into three groups (1) inexcitable (no TMS response at maximal stimulator output in the setting of preserved lower motor neuron (LMN) function), (2) hyperexcitable (SICI≤5.5%) and (3) normal cortical excitability (SICI>5.5%). Clinical phenotyping and neurophysiological assessment of LMN function were undertaken, and survival was recorded in the entire cohort.

Results

417 ALS patients were recruited, of whom 26.4% exhibited cortical inexcitability. Cortical inexcitability was associated with a younger age of disease onset (p<0.05), advanced Awaji criteria (p<0.01) and Kings stage (p<0.01) scores. Additionally, patients with cortical inexcitability had higher UMN score (p<0.01), lower revised ALS Functional Rating Scale score (p<0.01) and reduced upper limb strength score (MRC UL, p<0.01). Patient survival (p=0.398) was comparable across the groups, despite lower riluzole use in the cortical inexcitability patient group (p<0.05).

Conclusion

The present study established that cortical inexcitability was associated with a phenotype characterised by prominent UMN signs, greater motor and functional decline, and a younger age of onset. The present findings inform patient management and could improve patient stratification in clinical trials.
Translational approach to establish the cardiometabolic health effects and mechanisms of action of fish nutrients–it takes a village
Authors: Mitchell Patricia L. , Pilon Geneviève , Bazinet Laurent , Gagnon Claudia , Weisnagel S. John , Jacques Hélène , Vohl Marie-Claude , Marette André
Published: August 2024

People use dietary supplements to offset nutritional deficiencies and manage metabolic dysfunction. While the beneficial effect of fish proteins on glucose homeostasis is well established, the ability of fish peptides to replicate the protein findings is less clear. With financial support from a programmatic Canadian Institutes of Health Research (CIHR) Team grant, we aimed to identify salmon peptide fractions (SPFs) with the potential to mitigate metabolic dysfunction. Additionally, the grant aims included assessing whether vitamin D, a nutrient commonly found in salmon, could potentiate the beneficial effects of salmon peptides. In parallel, technologies were developed to separate and filter the isolated peptides. We employed an integrative approach that combined nutritional interventions in animal models and human subjects to identify metabolic pathways regulated by salmon peptides and other fish nutrients. This combination of interdisciplinary expertise revealed that a SPF could be a therapeutic tool used in the prevention and management of cardiometabolic diseases. Herein, we present a perspective of our CIHR funded grant that utilized a translational approach to establish the cardiometabolic health effects and mechanisms of action of fish nutrients: from animal models to clinical trials.
An improved small-scale test setup for assessing backward erosion piping
Authors: Ramezanifouladi Sina , Côté Jean
Published: August 2024

Backward erosion piping is one of the erosion mechanisms that lead to embankment dam incidents, whereby foundation granular materials are transported to the downstream toe leaving a shallow pipe in place. Most previous studies have focused on secondary erosion as the responsible process for the pipe progression. On the other hand, a few experimental investigations have considered primary erosion by restricting the pipe pathway within a confined channel for easier monitoring of local gradients. This paper presents a modified small-scale setup with the hole-type exit configuration to capture local hydraulic conditions associated with the progression of the pipe in a realistic and unconstrained pathway. Horizontal compaction and a more accurate measurement and acquisition system are other improvements added to this setup. The test outcomes of the two fine sands have revealed that the scale factor of Sellmeijer’s model can be used to predict the critical global hydraulic gradient for the specific geometry of the small-scale setup with the hole-type exit. Moreover, the progression of the pipe remains unaffected by loading history. Results also confirm the previous findings regarding the mutual influence of local gradient and pipe tip progression.
Existence of non-singular stellar solutions within the context of electromagnetic field: a comparison between minimal and non-minimal gravity models
Authors: Naseer Tayyab , Said Jackson Levi
Published: August 2024

In this paper, we explore the existence of various non-singular compact stellar solutions influenced by the Maxwell field within the matter-geometry coupling based modified gravity. We start this analysis by considering a static spherically symmetric spacetime which is associated with the isotropic matter distribution. We then determine the field equations corresponding to two specific functions of this modified theory. Along with these models, we also adopt different forms of the matter Lagrangian. We observe several unknowns in these equations such as the metric potentials, charge and fluid parameters. Thus, the embedding class-one condition and a particular realistic equation of state is used to construct their corresponding solutions. The former condition provides the metric components possessing three constants, and we calculate them through junction conditions. Further, four developed models are graphically analyzed under different parametric values. Finally, we find all our developed solutions well-agreeing with the physical requirements, offering valuable insights for future explorations of the stellar compositions in this theory.
ARTIFICIAL INTELLIGENCE FOR INNOVATION: A BIBLIOMETRIC ANALYSIS AND STRUCTURAL VARIATION APPROACH
Authors: JABEUR SAMI BEN , STEF NICOLAE , ARFI WISSAL BEN
Published: August 2024

Artificial intelligence (AI) has gained significant popularity in recent years. This study critically examines the existing literature on the role and potential of AI, machine learning (ML) and big data in driving innovation. To the best of our knowledge, no existing survey has provided a comprehensive overview of this topic. The aim of this paper is thus to provide a coherent overview of theoretical cornerstones as well as recent trends in research on AI and data analytics for innovation. Using various bibliometric analyses of themes including publication counts and trends, co-citations, co-authorship, and keyword co-occurrence, we infer the thematic structure of AI research in innovation for the period from 1991 to 2021. The publications are grouped into three major clusters, with Cluster 1 remaining a constantly dominant theme in the digital innovation publication landscape. Cluster 2 includes published studies on big data, which also received much research attention. Cluster 3, which is the most prominent, includes business performance, business analytics, and information systems. We also analyse publication citation counts in the literature using Poisson and negative binomial regressions. The results show that the structural variation approach provides a new method for tracking and evaluating the potential of freshly published studies in context. The findings of the current study will be significant in identifying new areas of research of potential interest to scholars and practitioners in the field of AI for innovation worldwide. We conclude this review with limitations and theoretical and practical orientations.
Room-Temperature Superconductivity Heats Up
Authors: Greengard Samuel
Published: August 2024

Workable technology could all but eliminate energy losses while significantly advancing neuromorphic AI computing.
FASDSA: A Flexible Adaptive and Secure Data Sharing Architecture
Authors: Wang ZiXuan , Wang Pan , Sun Zhixin , Zhou Xiaokang , Fu MengYi , Liu MinYao , Wang XinTong , Chen Lu
Published: August 2024

With the development of Web 3.0 and Metaverse technologies, the ability of autonomous vehicles has been dramatically improved. These technologies have decentralized features that break the traditional data-sharing mode, grant users control over their data, and achieve benefits through data sharing, promoting the widespread circulation of data. To ensure data exchange security, flexibility, and reliability, this paper proposes FASDSA: A Flexible, Adaptive, and Secure Data Sharing Architecture for CAVs with Web 3.0 and Metaverse. This architecture has three advantages: First, it adopts a decentralized, federated learning and CAV role division method, which allows different computational power CAVs to participate in data sharing according to their roles, achieving flexible data privacy protection. Second, it has the ability of tampered model detection based on interpretable analysis, which can effectively ensure that the model is not tampered with. Third, it has a reward mechanism based on work contribution and trust assessment, which uses blockchain technology to ensure the continuous security operation of this architecture. To verify the performance of FASDSA, we used the UNSW-NB15 dataset to conduct three experiments. The experimental results indicate that compared to traditional methods, FASDSA possesses greater flexibility and security while maintaining similar or even superior model performance.
Designing Heterogeneous LLM Agents for Financial Sentiment Analysis
Authors: Xing Frank
Published: August 2024

Large language models (LLMs) have drastically changed the possible ways to design intelligent systems, shifting the focus from massive data acquisition and new model training to human alignment and strategic elicitation of the full potential of existing pre-trained models. This paradigm shift, however, is not fully realized in financial sentiment analysis (FSA) due to the discriminative nature of this task and a lack of prescriptive knowledge of how to leverage existing generative models in such a context. This study investigates the effectiveness of the new paradigm, that is, using LLMs without fine-tuning for FSA. Rooted in Minsky’s theory of mind and emotions, a design framework with heterogeneous LLM agents is proposed and applied to FSA. The framework instantiates specialized agents using prior guiding knowledge from both linguistics and finance. Then, a summative agent reasons on the aggregated agent discussions. Comprehensive evaluations using six FSA datasets show that the framework yields better accuracies compared to many alternative multi-LLM agent settings, especially when the discussion contents are substantial. This study contributes to the design foundations and paves new avenues for LLMs-based FSA and potentially other tasks. Implications for business and management have also been discussed.
Update on PI-RADS Version 2.1 Diagnostic Performance Benchmarks for Prostate MRI: Systematic Review and Meta-Analysis
Authors: Oerther Benedict , Nedelcu Andrea , Engel Hannes , Schmucker Christine , Schwarzer Guido , Brugger Timo , Schoots Ivo G. , Eisenblaetter Michel , Sigle August , Gratzke Christian , Bamberg Fabian , Benndorf Matthias
Published: August 2024

This systematic review and meta-analysis provides an evidence synthesis of prostate MRI diagnostic performance based on PI-RADS version 2.1 for benchmarking different diagnostic metrics and outcome thresholds.
Bio-Based Materials for Electrochemical Detection of Bisphenol A
Authors: Sefari Wassila , Zazoua Ali , Rabiaa Helim , Korri-Youssoufi Hafsa
Published: August 2024

Bisphenol A is a widely used endocrine disruptor known for its toxicity and prevalence in the environment. It contaminates drinking water, especially when plastic bottles are exposed to Sunlight. Rapid, on-site detection of BPA in drinking water is crucial for protecting human health and the environment. Herein, we developed an electrochemical sensor for detecting and monitoring bisphenol A in water bodies utilizing biobased materials. The device uses a biopolymeric membrane with agarose and gelified green tea tannins (GT/Agar). A sensitive part was made using this natural composite due to its high ability to attach bisphenol A to tannin monomers. Green tea tannins were purified and characterized through HPLC, FTIR, SEM, and AFM. The electrochemical activity of the GT-Agar/Au sensor is also evaluated by electrochemical impedance spectroscopy, cyclic voltammetry, square wave voltammetry and scan rate. Based on its redox signal under the optimal experimental conditions, this sensor has a detection range of 10−16 M to 10−4 M, a limit of detection of 1.52 to 10−17 M and very high selectivity. The proposed sensor successfully determined BPA levels from ultra-trace concentrations in bottled water samples, achieving satisfactory recovery rates. Compared to the results obtained using HPLC, it demonstrates high reliability.
Electrochemical Dissolution Behavior of ZCuPb10Sn10 Alloy in NaNO3 Solution
Authors: Zhang Qingliang , Qu Ningsong
Published: August 2024

Copper alloys, such as ZCuPb10Sn10, have been widely applied to friction pairs in various products. Surface texture, such as micro-dimple array has attracted significant attention from researchers worldwide to improve tribological performance. To generate micro-dimple array on ZCuPb10Sn10 alloy by electrochemical machining, it is essential to investigate the electrochemical dissolution behavior of ZCuPb10Sn10 in NaNO3 solution. In this paper, the electrochemical dissolution behavior of ZCuPb10Sn10 alloy in NaNO3 solution is investigated through experimental tests. Anodic polarization, Tafel polarization, and electrochemical impedance spectroscopy were conducted to investigate its passive and corrosion behavior. The microstructure and composition of the dissolved surfaces were analyzed under various conditions. Additionally, a model was proposed to explain the electrochemical dissolution process of ZCuPb10Sn10 alloy in NaNO3 solution under high pressure hydrostatic conditions. Ultimately, a NaNO3 solution with 10% in concentration and 20 °C in temperature was selected as the electrolyte and a micro-dimple array with an average diameter of 119.7 μm and a depth of 7.4 μm was successfully generated with through-mask electrochemical micromachining on the surface of ZCuPb10Sn10 alloy.
Thermodynamic Equilibrium between Non-Stoichiometric Na-β-Alumina and α-Alumina
Authors: Näfe Helfried , Wang Yude
Published: August 2024

A solid-state electrochemical technique based on a potentiometric oxygen concentration cell has been used to characterize the thermodynamic stability of the phase mixture α-Al2O3 + Na-β-Al2O3 by determining its Na2O activity. In combination with phase analysis based on Rietveld refinement of X-ray diffraction patterns the magnitude and variability of the stoichiometric composition of the β-phase have been quantified. Upon variation of the Na2O content of the phase mixture, the Na2O activity resulting from the α/β-equilibrium has proved to be stable because both phases are readily inter-convertible. This behaviour guarantees that the material is eminently suitable as a stable sodium electrode, while simultaneously functioning as a sodium-ion conducting solid electrolyte. The temperature dependence of the logarithm of the Na2O activity has been found to be two-part. This is in line with the trend of the majority of critically assessed literature data thus demonstrating that former apprehension about the prevalence of a possible methodical flaw due to electronic conduction was unsubstantiated. As a conclusion, the knowledge about electronic conduction through Na-β-Al2O3 is advanced. The findings are the prerequisite for putting a straightforward solid-state CO2 sensor and sodium ion battery into practice.
Citrullination, a novel posttranslational modification of elastin, is involved in COPD pathogenesis
Authors: Murphy Mark P. , Zieger Marina , Henry Michael , Meleady Paula , Mueller Christian , McElvaney Noel G. , Reeves Emer P.
Published: August 2024

This study provides evidence for the impact of peptidyl arginine deiminase (PAD) enzymes on lung function decline, indicating promising potential for the future development of PAD-based therapeutics for preserving lung function in patients with COPD.
Psychosocial Trauma History Negatively Impacts Liver Transplant Access in Women with Chronic Liver Disease
Authors: Cooper Katherine M. , Colletta Alessandro , Amin Dhruval , Herscovici Darya M. , Devuni Deepika
Published: August 2024

Introduction. Few studies have evaluated the impact of psychological trauma (mental, emotional, or physical) on liver transplant (LT) candidacy and outcomes. Methods. We performed a single center retrospective analysis of patients who completed routine LT evaluation between October 2017 and June 2021. We identified the prevalence of psychological trauma history in men and women LT candidates and evaluated the association between trauma history and LT access. The primary outcome measure was listing for LT. Results. A total of 463 patients completed LT evaluation, of which 17% (n = 79) reported a history of trauma: 49 of 159 women and 30 of 304 men. Trauma history was significantly more common in women than in men (31% vs. 10%, p < 0.001). Women with trauma history were less likely to be listed for LT (80% vs. 93%, p = 0.016). Women with trauma history were also more likely to be removed from the LT waitlist (26% vs. 12%, p = 0.045); this persists when excluding patients removed for transfer to another center or for medical improvement (22% vs. 7%, p = 0.020). In contrast, listing for LT (87% vs. 86%, p = 0.973) and waitlist removal (12% vs. 10%, p = 0.766) did not differ in men with and without trauma history. In those that received a LT (n = 107), post‐LT relapse, rejection, readmissions, and death did not differ in patients with (n=13)and without (n=94) trauma history. Conclusions. Trauma history is associated with reduced access to LT in women but not men with chronic liver disease. Further studies are needed to understand the impact of psychological trauma on LT access and post‐LT outcomes.
Digital Self‐Management Intervention Paths for Early Breast Cancer Patients: Results of a Pilot Study
Authors: Poikonen-Saksela Paula , Karademas Evangelos , Vehmanen Leena , Utriainen Meri , Kondylakis Haridimos , Kourou Konstadina , Manikis Georgios C. , Kolokotroni Eleni , Argyropaidas Panagiotis , Sousa Berta , Pat Horenczyk Ruth , Mazzocco Ketti , Mattson Johanna
Published: August 2024

Background. Despite excellent prognosis of early breast cancer, the patients face problems related to decreased quality of life and mental health. There is a need for easily available interventions targeting modifiable factors related to these problems. The aim of this study was to test the use of a new digital supportive intervention platform for early breast cancer patients. Material and Methods. Ninety‐seven early breast cancer patients answered questions on wellbeing, exercise, and sociodemographic factors before systemic adjuvant treatment at the Helsinki University Hospital. Based on these answers and predictive algorithms for anxiety and depression, they were guided onto one or several digital intervention paths. Patients under 56 years of age were guided onto a nutrition path, those who exercised less than the current guideline recommendations onto an exercise path, and those at risk of mental health deterioration onto an empowerment path. Information on compliance was collected at 3 months on the amount of exercise and quality of life using EORTC‐C30 scale, anxiety and depression using HADS scale at baseline and 12 months, and log‐in information at 3 and 12 months. Results. Thirty‐two patients followed the empowerment path, 43 the nutrition path, and 75 the exercise path. On a scale of 1–5, most of the participants (mean = 3.4; SD 0.815) found the interventions helpful and would have recommended testing and supportive interventions to their peers (mean = 3.70; SD 0.961). During the 10‐week intervention period, the mean number of log‐ins to the empowerment path was 3.69 (SD = 4.24); the nutrition path, 4.32 (SD = 2.891); and the exercise path, 8.33 (SD = 6.293). The higher number of log‐ins to the empowerment (rho = 0.531, P = 0.008, and n = 24) and exercise paths (rho = 0.330, P = 0.01, and n = 59) was related to better global quality of life at one year. The number of log‐ins correlated to the weekly amount of exercise in the exercise path (cc 0.740, P value <0.001, and n = 20). Conclusion. Patients’ attitudes towards the interventions were positive, but they used them far less than was recommended. A randomized trial would be needed to test the effect of interventions on patients’ QoL and mental health.
H3K18 Lactylation Potentiates Immune Escape of Non–Small Cell Lung Cancer
Authors: Zhang Cai , Zhou Lijie , Zhang Mingyuan , Du Yue , Li Cai , Ren Huijun , Zheng Lu
Published: August 2024

Recently discovered epigenetic modification lysine lactylation contributes to tumor development and progression in several types of cancer. In addition to the tumor-intrinsic effects, histone lactylation may mediate tumor microenvironment remodeling and immune evasion. In this study, we observed elevated pan–lysine lactylation and histone H3 lysine 18 lactylation (H3K18la) levels in non–small cell lung cancer (NSCLC) tissues, which was positively correlated with poor patient prognosis. Interruption of glycolysis by 2-deoxy-D-glucose and oxamate treatment and silencing of lactate dehydrogenase A and lactate dehydrogenase B reduced H3K18la levels and circumvented immune evasion of NSCLC cells by enhancing CD8+ T-cell cytotoxicity. Mechanistically, H3K18la directly activated the transcription of pore membrane protein 121 (POM121), which enhanced MYC nuclear transport and direct binding to the CD274 promoter to induce PD-L1 expression. In a mouse NSCLC xenograft model, combination therapy with a glycolysis inhibitor and an anti-PD-1 antibody induced intratumoral CD8+ T-cell function and exhibited strong antitumor efficacy. Overall, this work revealed that H3K18la potentiates the immune escape of NSCLC cells by activating the POM121/MYC/PD-L1 pathway, which offers insights into the role of posttranslational modifications in carcinogenesis and provides a rationale for developing an epigenetic-targeted strategy for treating NSCLC.

Significance: H3K18 lactylation supports immunosuppression in non-small cell lung cancer by inducing POM121 to increase MYC activity and PD-L1 expression, which can be reversed by metabolic reprogramming and immunotherapy treatment.
The Neurodevelopmental Protein POGZ Suppresses Metastasis in Triple-Negative Breast Cancer by Attenuating TGFβ Signaling
Authors: Heath John , Mirabelli Caitlynn , Annis Matthew G. , Sabourin Valerie , Hebert Steven , Findlay Steven , Kim HaEun , Witcher Michael , Kleinman Claudia L. , Siegel Peter M. , Orthwein Alexandre , Ursini-Siegel Josie
Published: August 2024

The pogo transposable element–derived zinc finger protein, POGZ, is notably associated with neurodevelopmental disorders through its role in gene transcription. Many proteins involved in neurological development are often dysregulated in cancer, suggesting a potential role for POGZ in tumor biology. Here, we provided experimental evidence that POGZ influences the growth and metastatic spread of triple-negative breast cancers (TNBC). In well-characterized models of TNBC, POGZ exerted a dual role, both as a tumor promoter and metastasis suppressor. Mechanistically, loss of POGZ potentiated TGFβ pathway activation to exert cytostatic effects while simultaneously increasing the mesenchymal and migratory properties of breast tumors. Although POGZ levels are elevated in human breast cancers, the most aggressive forms of TNBC tumors, including those with increased mesenchymal and metastatic properties, exhibit dampened POGZ levels, and low POGZ expression was associated with inferior clinical outcomes in these tumor types. Taken together, these data suggest that POGZ is a critical suppressor of the early stages of the metastatic cascade.

Significance: The POGZ neurodevelopmental protein plays dual functions in triple-negative breast cancers as a tumor promoter and metastasis suppressor, inhibiting TGFβ-regulated EMT to limit breast cancer metastatic progression.
Supplementary Data file 2 from Systemic Blockade of Clever-1 Elicits Lymphocyte Activation Alongside Checkpoint Molecule Downregulation in Patients with Solid Tumors: Results from a Phase I/II Clinical Trial
Authors: Virtakoivu Reetta , Rannikko Jenna H. , Viitala Miro , Vaura Felix , Takeda Akira , Lönnberg Tapio , Koivunen Jussi , Jaakkola Panu , Pasanen Annika , Shetty Shishir , de Jonge Maja J.A. , Robbrecht Debbie , Ma Yuk Ting , Skyttä Tanja , Minchom Anna , Jalkanen Sirpa , Karvonen Matti K. , Mandelin Jami , Bono Petri , Hollmén Maija
Published: August 2024

Excel spreadsheet of differentially expressed genes in CD14+ monocytes
Table 1 from BRCA Status Dictates Wnt Responsiveness in Epithelial Ovarian Cancer
Authors: Chehade Hussein , Gogoi Radhika , Adzibolosu Nicholas K. , Galoforo Sandra , Fehmi Rouba-Ali , Kheil Mira , Fox Alexandra , Kim Seongho , Rattan Ramandeep , Hou Zhanjun , Morris Robert T. , Matherly Larry H. , Mor Gil , Alvero Ayesha B.
Published: August 2024

Patient characteristics
Figure S6 from BRCA Status Dictates Wnt Responsiveness in Epithelial Ovarian Cancer
Authors: Chehade Hussein , Gogoi Radhika , Adzibolosu Nicholas K. , Galoforo Sandra , Fehmi Rouba-Ali , Kheil Mira , Fox Alexandra , Kim Seongho , Rattan Ramandeep , Hou Zhanjun , Morris Robert T. , Matherly Larry H. , Mor Gil , Alvero Ayesha B.
Published: August 2024

Nuclear and cytoplasmic green fluorescence were measured in all cells from cultures represented in Figure 3C using image J. Nuclear (left panel) and cytoplasmic (right panel) quantifications are reported separately for each cell line. Statistical significance between control and treated cultures was not achieved.
Supplementary Table S1 from mTORC1-Driven Protein Translation Correlates with Clinical Benefit of Capivasertib within a Genetically Preselected Cohort of PIK3CA-Altered Tumors
Authors: Sobsey Constance A. , Froehlich Bjoern C. , Mitsa Georgia , Ibrahim Sahar , Popp Robert , Zahedi Rene P. , de Bruin Elza C. , Borchers Christoph H. , Batist Gerald
Published: August 2024

Detailed results of the label-free quantitation
Supplementary Methods S1 from mTORC1-Driven Protein Translation Correlates with Clinical Benefit of Capivasertib within a Genetically Preselected Cohort of PIK3CA-Altered Tumors
Authors: Sobsey Constance A. , Froehlich Bjoern C. , Mitsa Georgia , Ibrahim Sahar , Popp Robert , Zahedi Rene P. , de Bruin Elza C. , Borchers Christoph H. , Batist Gerald
Published: August 2024

Supplemental Materials and Methods concerning patient samples, cell lines, tissue culture, iMALDI-MS, Nano-LC-Orbitrap-MS, LC-MRM-MS
Figure S1 from BRCA Status Dictates Wnt Responsiveness in Epithelial Ovarian Cancer
Authors: Chehade Hussein , Gogoi Radhika , Adzibolosu Nicholas K. , Galoforo Sandra , Fehmi Rouba-Ali , Kheil Mira , Fox Alexandra , Kim Seongho , Rattan Ramandeep , Hou Zhanjun , Morris Robert T. , Matherly Larry H. , Mor Gil , Alvero Ayesha B.
Published: August 2024

Chord diagrams of top 10 differentially regulated Pathways and involved DEGs in BRCA2mt vs BRCA1mt
Supplementary Figure S1 from mTORC1-Driven Protein Translation Correlates with Clinical Benefit of Capivasertib within a Genetically Preselected Cohort of PIK3CA-Altered Tumors
Authors: Sobsey Constance A. , Froehlich Bjoern C. , Mitsa Georgia , Ibrahim Sahar , Popp Robert , Zahedi Rene P. , de Bruin Elza C. , Borchers Christoph H. , Batist Gerald
Published: August 2024

Individual protein concentrations measured by iMALDI-MS for each sample, comparison of measured PTEN concentration to IHC H-score
Figure 4 from BRCA Status Dictates Wnt Responsiveness in Epithelial Ovarian Cancer
Authors: Chehade Hussein , Gogoi Radhika , Adzibolosu Nicholas K. , Galoforo Sandra , Fehmi Rouba-Ali , Kheil Mira , Fox Alexandra , Kim Seongho , Rattan Ramandeep , Hou Zhanjun , Morris Robert T. , Matherly Larry H. , Mor Gil , Alvero Ayesha B.
Published: August 2024

β-Catenin is stabilized upon loss of BRCA2. A, ID8 mouse ovarian cancer cells were treated with 10 µg/mL cycloheximide at designated time points, and levels of β-catenin were determined by Western blot analysis. B, Quantification of A. C, ID8 mouse ovarian cancer cells were treated with 50 µmol/L MG132, and levels of phosphorylated and total β-catenin were determined by Western blot analysis. D, Figures depicting components of the β-catenin destruction complex. E, Basal levels of phosphorylated and total GSK3β were determined by Western blot analysis. NT, no treatment. (Created with Biorender.com.)