bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessing Radiation Fallout in Public Zones near the Nevada National Security Site (NNSS): A Recent Study
Authors: Nangeelil Krishnakumar Divakar , Searcy Haven , Parker Beverly , Sun Zaijing
Published: September 2024

A comprehensive radiological study was conducted in the surrounding public zones of the Nevada National Security Site to identify traces of resuspended radioactivity and heavy elemental contamination that might have resulted from various activities. The study used passive and active nuclear methods, specifically gamma spectrometry and instrumental neutron activation analysis, respectively. Passive gamma spectra analysis of air filter papers from various Community Environmental Monitoring Program stations conclusively verified the presence of radionuclides exclusively originating from the natural decay series of 238U and 232Th. Furthermore, gamma spectrometry and instrumental neutron activation analysis of plant samples from surrounding areas of the Nevada National Security Site revealed the absence of any unusual elemental contamination in the environment. These results demonstrated that there was no measurable radiological impact on the public zones surrounding the site resulting from the spread of radioactive materials or toxic heavy metals associated with previous or ongoing activities at Nevada National Security Site. Therefore, the safety of public zones concerning retained radioactivity and harmful elemental contamination arising from Nevada National Security Site operations is negligible. The significance of this study is further pronounced in the current geopolitical context, as it establishes the baseline elemental composition for various desert plants for future reference.
Do not forget about transplant patients during disasters
Authors: Hommos Musab S. , Brown Ashlyn , Trollinger Brandon , Sekkarie Mohamed , Alasfar Sami
Published: September 2024

Purpose of review

The frequency of natural disasters and man-made conflicts has risen significantly in the past two decades, coinciding with an increase in kidney transplant recipients globally. This review addresses the critical need for disaster preparedness to mitigate the severe impacts on this vulnerable patient cohort.

Recent findings

Kidney transplant recipients are highly dependent on robust healthcare infrastructures for ongoing care, including specialized medical staff, advanced diagnostics, and a consistent supply of immunosuppressive medications. Disasters disrupt these essential services, leading to increased risks of organ rejection, infections, and other medical complications. Strategies at various levels, from government to individual patients, can help maintain care continuity during such crises.

Effective disaster preparedness plans involving strategic medication stockpiling, emergency communication systems, and patient education are crucial to support kidney transplant recipients. By implementing these measures, healthcare systems can better protect the health and well being of transplant patients during and after disasters.
Current developments in prehabilitation in urologic oncology
Authors: Petersen Erin , Cavanaugh Dana , Psutka Sarah P.
Published: September 2024

Purpose of review

Prehabilitation describes interventions that are undertaken prior to a major surgical or medical intervention with the objective of improving functional capability with the goal of improving candidacy for therapy, bolstering one's ability to withstand treatment-associated toxicity, functional decline, and facilitating accelerated recovery. The objective of this review is to detail the key tenets of prehabilitation, synthesize contemporary advances in prehabilitation science within Urologic Oncology, and discuss key methodologic trial design considerations salient to future prehabilitation investigations.

Recent findings

Contemporary prehabilitation clinical trials have primarily evaluated unimodal interventions aiming to improve functional capacity across the domains of physical exercise, nutrition, and cognition with heightened interest in evaluating multimodal interventions addressing two or more domains. Recent investigations have have demonstrated variable improvements in strength, balance, physical function, and quality of life with preoperative exercise. Although presurgical immunonutrition showed promise in other fields, initial results in uro-oncology have not demonstrated reductions in complications nor improvements in early survival. Emerging data supports the potential of multimodal prehabilitation programs to offer more comprehensive benefits, improving functional outcomes, reducing length of stay, and supporting improved recovery.

To date, early prehabilitation studies in patients undergoing surgery for genitourinary malignancies have demonstrated variable ability to facilitate gains in functional capacity and perioperative outcomes. Key issues have arisen including the need to ensure that interventions are pragmatic, scalable, feasible, and acceptable in these populations that often also have a high prevalence of coincident multimorbidity, frailty, and mental health concerns that can increase risk of adverse outcomes after surgery. The integration of personalized prehabilitation strategies as extensions of perioperative enhanced recovery after surgery protocols, supportive care and survivorship paradigms offers of promise to further engage patients in their care, enhance patient resilience and outcomes, while reducing treatment burden in urologic oncology.
Multilevel Drivers of Congenital Syphilis, Oregon, 2013 to 2021
Authors: Menza Tim W. , Zlot Amy , Gonzalez-Pena Yuritzy , Cicognani Cedric , Pearson Shelley , Li Jennifer , Garai Jillian
Published: September 2024

Background

Despite the availability of curative penicillin treatment for syphilis during pregnancy, congenital syphilis (CS) cases have surged in the United States, including in Oregon.

Methods

We conducted a retrospective analysis of individual- and county-level predictors of CS among pregnant people with syphilis in Oregon from 2013 to 2021. Data were collated from surveillance reports, County Health Rankings, and other sources with upstream county-level data. We used multilevel Poisson regression models to assess associations between CS and individual- and county-level factors.

Results

Among 343 people with syphilis during pregnancy, 95 (27.6%) were associated with a case of CS. At the individual level, a history of injection drug use and a history of corrections involvement were associated with an increased risk of CS, whereas a recent gonorrhea diagnosis was associated with a decreased risk of CS. County-level violent crime rate, unemployment, income inequality, and adverse childhood experiences increased the risk of CS. Higher county-level socioenvironmental challenges exacerbated CS risk, particularly among people with corrections involvement.

Conclusions

Injection drug use, corrections involvement, and county-level socioenvironmental challenges increased CS risk among pregnant people with syphilis in Oregon. Urgent interventions are needed, including innovative care models, policy reforms targeting systemic issues, and enhanced collaboration with community services to address the escalating CS crisis.
The complete genome sequence of five pre-2013 Escherichia coli sequence type (ST)1193 strains reveals insights into an emerging pathogen

Authors: White Rhys T. , Ashcroft Melinda A. , Bauer Michelle J. , Bell Jan , Butkiewicz Dominika , Álvarez-Fraga Laura , Gibson Justine S. , Kidsley Amanda K. , Mollinger Joanne L. , Peters Kate M. , Phan Minh-Duy , Roberts Leah W. , Rogers Benjamin A. , Schembri Mark A. , Trott Darren J. , Turnidge John , Forde Brian M. , Beatson Scott A.
Published: September 2024

Fluoroquinolone-resistant Escherichia coli sequence type (ST)1193 is a profound, emerging lineage associated with systemic, urinary tract, and neonatal infections. Humans, companion animals, and the environment are reservoirs for ST1193, which has been disseminated globally. Following its detection in 2007, ST1193 has been identified repeatedly amongst fluoroquinolone-resistant clones in Australia. However, despite the growing importance of ST1193, only three complete genomes are published in the literature, none of which are from Australia. Here we expand on the available ST1193 resources with the complete genomes of five ST1193 strains sequenced using Oxford Nanopore Technologies and Illumina. Using in silico genotyping, we found that all strains were multi-drug resistant, including resistances to fluoroquinolones and cephalosporins. In vitro antibiotic susceptibility testing mostly correlated with individual genotypes. The exception was MS8320, which had additional in vitro resistance to piperacillin/tazobactam, ampicillin/sulbactam, cefazolin and doripenem (carbapenem). Further investigation identified seven additional copies of an IS26 transposable unit carrying a blaTEM-1B beta-lactamase gene, suggesting this tandem amplification is associated with extended resistance phenotypes. Uropathogenicity factors, including three separate siderophore-encoding loci, were conserved in chromosomal and plasmid regions. Using all complete genomes, we further elucidated the recombination events surrounding the previously described K5/K1 capsular loci switch. Phenotypic confirmation of differing capsules in Australian ST1193 strains, coupled with genetic analysis revealing insertions downstream of the capsular locus, underscored the genetic distinctions between K5 and K1 capsule encoding strains. This study provides five new reference ST1193 genomes from Australia. These include the earliest complete K5-capsule ST1193 genomes on record (collected 2007), alongside our reference genome (MS10858); a clinical isolate obtained early during the ST1193 expansion and representative of the predominant K1-associated clade. These findings lay the foundations for further genomic and molecular analyses that may help understand the underlying reasons for the rapid global expansion of ST1193.
IL-23 tunes inflammatory functions of human mucosal-associated invariant T (MAIT) cells
Authors: Camard Laetitia , Stephen Tharshana , Yahia-Cherbal Hanane , Guillemot Vincent , Mella Sébastien , Baillet Victoire , Lopez-Maestre Hélène , Capocefalo Daniele , Cantini Laura , Leloup Claire , Marsande Julie , Sienes-Bailo Juan , Dangien Ambre , Pietrosemoli Natalia , Hasan Milena , Wang Huimeng , Eckle Sidonia B. G. , Fourie Anne M. , Greving Carrie , Shaikh Barbara Joyce , Parker Raphaelle , Cua Daniel J. , Bianchi Elisabetta , Rogge Lars
Published: September 2024

IL-23 signaling plays a key role in the pathogenesis of chronic inflammatory and infectious diseases, yet the cellular targets and signaling pathways affected by this cytokine remain poorly understood. We show that IL-23 receptors are expressed on the large majority of human MAIT, but not of conventional T cells. Protein and transcriptional profiling at the population and single cell level demonstrates that stimulation with IL-23 or the structurally related cytokine IL-12 drives distinct functional profiles, revealing a high level of plasticity of MAIT cells. IL-23, in particular, affects key molecules and pathways related to autoimmunity and cytotoxic functions. Integrated analysis of transcriptomic and chromatin accessibility, supported by CRISPR/Cas9 mediated deletion, shows that AP-1 transcription factors constitute a key regulatory node of the IL-23 pathway in MAIT cells. In conclusion, our findings indicate that MAIT cells are key mediators of IL-23 functions in immunity to infections and chronic inflammatory diseases.
Bone mechano-response is driven by locomotion transitions during vertebrate evolution
Authors: Shimochi Saeka , Brunet Clara , Fontcuberta-Rigo Margalida , Hrovat Katja , Puigbò Pere , Nakamura Miho
Published: September 2024

The skeleton supports the muscles in keeping the body upright against gravity while enduring thousands of daily loads. In this study, we investigated non-collagenous bone matrix proteins using osteoblast cell cultures and phylogenetic analyses to identify the molecular mechanisms involved in mechanical loading. The results indicate that the bone mechano-response is an evolutionary-driven process and that several non-collagenous proteins may significantly regulate the bone’s response to mechanical stress. According to our results, two significant evolutionary transitions in vertebrate locomotion shaped the roles of non-collagenous proteins in humans: the water-to-land transition, which increased mechanical stress on the limbs, and the evolution to bipedalism in humans, which altered the distribution of stress on the lower and upper limbs. Fetuin A, positively selected in both evolutionary transitions, showed the most significant expression change during mechanical stimulation.
The lincRNAPantr1is a FOXG1 target gene conferring site-specific chromatin binding of FOXG1
Authors: Gather Fabian , Rauleac Tudor , Akol Ipek , Arumugam Ganeshkumar , Fullio Camila L. , Müller Teresa , Kleidonas Dimitrios , Fischer Andre , Vlachos Andreas , Backofen Rolf , Vogel Tanja
Published: September 2024

Derailed gene expression programs within the developing nervous system, encompassing both transcriptional and posttranscriptional processes, can cause diverse neurodevelopmental diseases (NDD). The NDD FOXG1-syndrome lacks full understanding of the mechanistic role of its eponymous gene product. While it is known that FOXG1 acts in part at the chromatin by binding to regulative regions, it is unclear what factors control its presence at specific sites. Long non-coding RNAs (lncRNAs) can mediate site-directed transcription factor binding, but their potential role in FOXG1-syndrome has not been described. Here, we show that FOXG1 localisation is regulated at selected loci through the lncRNAPantr1.

We identified FOXG1 as an upstream transcriptional activator ofPantr1in human and mice. Further, we discovered that FOXG1 has the ability to associate with RNAs. Both, transcriptional regulation ofPantr1by FOXG1 and association of both partners, build up a regulative network that impacts the localisation of FOXG1 at selected genomic loci. Specifically,Pantr1facilitates cooperative presence of FOXG1/NEUROD1 at specific sites, andPantr1reduction leads to redistribution of FOXG1 to comparably more generic binding sites. The rescue of impaired dendritic outgrowth upon FOXG1 reduction by simultaneous overexpression ofPantr1underlines the importance of the FOXG1/Pantr1regulative network.

GRAPHICAL ABSTRACT
Robustness Revisited: On the Neutral Evolution of Centrality and Localization
Authors: Sella Yehonatan , Bergman Aviv
Published: September 2024

This study investigates the intricate interplay among neutral landscape structure, mutation rate, recombination rate, and population dynamics in shaping evolutionary robustness. We provide a comprehensive framework that elucidates how different evolutionary forces interact to influence genotypic robustness and localization within haploid and diploid populations. We demonstrate that in haploid populations, high mutation rates relative to recombination typically drive the population toward regions of increased eigencentrality, a graphtheoretic measure of centrality which is correlated while not identical to mutational robustness. On the other hand, recombination increases the localization of the population to a smaller region of genotypic space, while high values of recombination relative to mutation can introduce shifts in distribution away from eigencentrality and toward attractors of the recombination dynamics. Diploid dynamics further complicate these interactions, showing reduced alignment with eigencentrality under both high mutation and recombination rates, with the exception of structured diploid landscapes where dynamics are still aligned with increasing eigencentrality. Our findings underscore the nuanced dependencies of evolutionary outcomes on both local and global landscape structures as well as evolutionary parameters.

Significance Statement

Our work advances the theory of neutral evolution, paying particular attention to the question of how the holistic fitness landscape structure shapes the process of evolution and gives rise to emergent evolutionary phenomena. Since neutral evolution does not depend on direct selection, its ramifications can be both subtle, as they depend on network-wide properties, and ubiquitous, as they are not tied to context-specific adaptations. Our study provides a theoretical framework that connects the structure of neutral fitness landscapes with the dynamics of mutation and recombination rates, and the distinct behaviors of haploid and diploid populations. We establish general heuristic principles regarding the way evolutionary outcomes, such as robustness and localization, are influenced by the interplay of these factors.
A hepatocyte-specific cytochromecoxidase deficiency in mice leads to a lymphopenia owing to deficiencies in bone marrow progenitors
Authors: Pioli KimAnh T. , Ghosh Sampurna , Boulet Aren , Leary Scot C. , Pioli Peter D.
Published: September 2024

Mutations that negatively impact mitochondrial function are highly prevalent in humans and lead to disorders with a wide spectrum of disease phenotypes, including deficiencies in immune cell development and/or function. Previous analyses of mice with a hepatocyte-specific cytochromecoxidase (COX) deficiency revealed an unexpected peripheral blood leukopenia associated with splenic and thymic atrophy. Here, we use mice with a hepatocyte-specific deletion of the COX assembly factorSco1to show that metabolic defects extrinsic to the hematopoietic compartment lead to a pan-lymphopenia represented by severe losses in both B and T cells. We further demonstrate that immune defects in these mice are associated with the loss of bone marrow lymphoid progenitors common to both lineages and early signs of autoantibody-mediated autoimmunity. Our findings collectively point to a significant role for hepatocyte dysfunction as an instigator of immunodeficiency in patients with congenital mitochondrial defects who suffer from chronic or recurrent infections.
Novel method to assess group dynamics in rats reveals deficits in behavioral contagion in KM rats
Authors: Smirnov K. , Starkov I. , Sysoeva O. , Midzyanovskaya I.
Published: September 2024

Behavioral copying is a key process in group actions, but it is challenging for individuals with Autism Spectrum Disorder (ASD). We investigated behavioral contagion, or instinctual replication of behaviors, in Krushinky-Molodkina (KM) rats (n=16), a new rodent model for ASD, compared to control Wistar rats (n=15). A randomly chosen healthy Wistar male (“demonstrator rat”) was introduced to the homecage of experimental rats (“observers”) 10-14 days before the experiments to become a member of the group. For the implementation of the behavioral contagion experiment, we used the IntelliCage system, where rats can live in a group of 5-6 rats and their water visits can be fully controlled. During the experiment, the demonstrator was taken out of IntelliCage for 24 hours of water deprivation and then placed back. As a result, a drinking behavior of the water-deprived demonstrator rat prompted activated behaviors in the whole group. Unlike the Wistar controls, KM observers showed fewer visits to the drinking bottles, particularly lacking inspection visits. The control group, in contrast, exhibited a dynamic, cascade-like visiting of the water corners. The proportion of activated observers in KM rats was significantly lower, as compared to Wistar ones, and they did not mimic other observer rats. KM rats, therefore, displayed an attenuated pattern of behavioral contagion, highlighting social deficits in this ASD model. This study suggests that measuring group dynamics of behavioral contagion in an automated, non-invasive setup offers valuable insights into social behavior in rodents, particularly for studying social deficits in ASD models.

Highlights

Thirsty demonstrators triggered an avalanche of observers’ visits to the water corners

The contaged behavior was attenuated in observer KM rats

Behavioral contagion test provides a new tool for objective, automated phenotyping in rodent models of social deficits
Application of cryo-FIB-SEM for investigating organelle ultrastructure in guard cells of higher plants
Authors: Franzisky Bastian Leander , Zhang Xudong , Burkhardt Claus Jakob , Majorovits Endre , Hummel Eric , Schertel Andreas , Geilfus Christoph-Martin , Zörb Christian
Published: September 2024

Stomata are vital for CO2 and water vapor exchange, with guard cells’ aperture and ultrastructure highly responsive to environmental cues. However, traditional methods for studying guard cell ultrastructure, which rely on chemical fixation and embedding, often distort cell morphology and compromise membrane integrity, leaving no suitable methodology until now. In contrast, plunge-freezing in liquid ethane rapidly preserves cells in a near-native vitreous state for cryogenic electron microscopy. Using this approach, we applied Cryo-Focused Ion Beam-Scanning Electron Microscopy (cryo- FIB-SEM) to study the guard cell ultrastructure ofVicia faba, a higher plant model chosen for its sensitivity to external factors and ease of epidermis isolation, advancing beyond previous cryo-FIB-SEM applications in lower plant algae. The results firstly introduced cryo-FIB-SEM volume imaging, enabling subcellular ultrastructure visualization of higher plants likeV. fabain a vitrified, unaltered state. 3D models of organelles such as stromules, chloroplast protrusions, chloroplasts, starch granules, mitochondria, and vacuoles were reconstructed from cryo-FIB-SEM volumetric data, with their surface area and volume initially determined using manual segmentation. Future studies using this near-native volume imaging technique hold promise for investigating how environmental factors like drought or salinity influence stomatal behavior and the morphology of guard cells and their organelles.
Full-season spring migration counts reveal seasonal contrasts in raptor migration through the eastern Black Sea flyway
Authors: Tal Tohar , Jansen Diego , Jansen Erik , Green Arthur W. , Hoekstra Elien , Heetkamp Marc , T’jollyn Filiep , Engelen Dries , Hoekstra Bart , Kaasiku Triin , Vansteelant Wouter M.G.
Published: September 2024

The extent to which geographical features like coastlines and mountain ranges funnel migrating birds depends on the seasonal context and direction of migration. Near Batumi, in the Republic of Georgia, the eastern Black Sea coast and Lesser Caucasus funnel over one million raptors through a 10-20 km wide coastal strip every autumn. The funnelling effect of the Lesser Caucasus appears much less evident for northbound migrants. Yet historical data suggest tens of thousands of raptors pass through the region in spring. To elucidate the composition and timing of spring raptor migration we conducted full-season migration surveys near Batumi in 2019, 2020 and 2022. In total, we recorded 33 species and, on average, counted 542,161 raptors (min. 455,799 - max. 618,848) annually. The bulk of the spring passage consisted of Black KiteMilvus migrans(239,649 ± 22,547) and Steppe BuzzardButeo buteo vulpinus(194,029 ± 102,702). The most diverse and intense spring migration occurred from late March through mid-April, when the median passage date of 12 of 15 common species (>100 ind. y-1) occurred. Species with longer autumn migration periods tended to have longer spring migration periods, and most species had a longer migration period in spring than in autumn, likely due to larger age differences in timing during spring. Species’ abundance was up to an order of magnitude lower in spring than in autumn, consistent with a weaker bottleneck-effect in spring. Nevertheless, our results confirm the eastern Black Sea coast as a principal spring flyway and help redraw the map of East African-Eurasian migration for several Palearctic raptors. While we will not continue annual spring migration surveys, our data provides a baseline for detecting changes in raptor migration through short-term surveys and can help plan migration-based conservation and research at Batumi in spring.
Selective killing of plasma cell clones using splice-switching oligonucleotides targeting immunoglobulin variable exons
Authors: Lambert Jean-Marie , Praité Antoine , Contini Marion , Ashi Mohamad Omar , Marchalot Anne , Pennec Soazig Le , Sirac Christophe , Al Hayek Sandy , Delpy Laurent
Published: September 2024

Deregulated proliferation of a plasma cell (PC) clone is accompanied by an excess production of a monoclonal immunoglobulin (mo-Ig) component with unique V(D)J rearrangement features. In systemic Ig light chain (AL) amyloidosis, organ dysfunction is due to the deposition of amyloid fibrils composed of mo-Ig light chains in target tissues. Recent advances in exon skipping therapy using splice-switching antisense oligonucleotides (ASO) prompted us to examine a new antisense strategy targeting the variable (V) exon in myeloma cells. Indeed, we previously observed that the production of truncated Ig light chains, encoded by alternatively spliced mRNAs lacking V exon, heightened endoplasmic reticulum (ER) stress and triggered apoptosis of antibody-secreting plasma cells. We designed ASO hybridizing donor or acceptor V exon splice sites on mo-Ig pre-mRNAs. These compounds were very potent alternative splicing inducers and increased the production of V-domain-less truncated Ig chains. Remarkably,in vitroexperiments and tumor xenograft models revealed that myeloma cells were highly sensitive to specific ASO treatment, compared to an irrelevant control-ASO. RNA-seq experiments further confirmed that the production of truncated Ig induced upon ASO treatment provoked a massive myeloma cell death through ER stress-associated apoptosis. In addition, high throughput sequencing of Ig repertoire demonstrated that ASO targeting JH2 or Jκ1 donor splice site induced massive elimination of VDJH2- or VJκ1-rearranged clones respectively, while sparing the others. Collectively, these data provide evidence that ASO targeting V exon on mo-Ig pre-mRNAs can emerge as new weapons to induce selective killing of plasma cell clones.
Richness and composition of phyllosphereMethylobacteriumcommunities cause variation inArabidopsis thalianagrowth
Authors: Lauzon Jocelyn , Pelletier Jérémie , Favron Élanore , Wang Zihui , Kembel Steven W.
Published: September 2024

The phyllosphere – the aerial parts of plants – forms a vast microbial habitat that harbors diverse bacterial communities playing key roles in ecosystem function. The foliar surface is thus a promising study system to investigate biodiversity-ecosystem function relationships. Researchers have found a positive correlation between leaf bacterial diversity and ecosystem productivity, but the causality of this relationship has yet to be demonstrated. To understand how the diversity and composition of phyllosphere bacterial communities could cause variation in the growth of their host plants, we assembled synthetic communities composed of different diversity and compositions ofMethylobacteriumstrains – a plant growth-promoting bacterial genus ubiquitous in the phyllosphere – that we inoculated onArabidopsis thalianagrown in gnotobiotic conditions. We hypothesized that (1) increasingMethylobacteriumdiversity should cause an increase in host growth; (2) strains should differ in their impact on host growth; and (3) the relationship between bacterial diversity and plant productivity should be strain-dependent. Our results supported our three hypotheses but revealed unpredicted patterns in howA. thalianaleaf biomass varied according to inoculatedMethylobacteriumstrain richness and identity. Increasing bacterial richness induced a higher host leaf biomass, but only after an initial reduction in biomass, suggesting competition alleviation by multispecies interactions. TwoMethylobacteriumstrains showed beneficial effects onA. thalianagrowth, and one strain was detrimental for the plant. Community composition shaped the relationship between diversity and productivity, highlighting the importance of community mutualistic and antagonistic interactions. Furthermore, niche complementarity was likely the main ecological mechanism driving the diversity-productivity relationship in our study system. By demonstrating the causal effects ofMethylobacteriumcommunity diversity and composition on host plant growth, our experiment shed light on the importance of phyllosphere bacteria in terrestrial ecosystem functioning.
The over-activated peritoneal immune environment in endometriosis is characterised by a lack of PD-1 inhibition
Authors: Tresso Anna , Thota Niharika , James Chloe , Borash Natasha , Brennan Emily , Bayat Shima , Vollenhoven Beverley , Tapmeier Thomas
Published: September 2024

Background

Endometriosis is characterised by chronic inflammation in the peritoneal cavity causing acute and chronic pelvic pain, largely explained by dysregulation in the immune environment within peritoneal fluid. The activation status of the peritoneal immune cells is unclear. In addition, a comparison with the status of the systemic immune system is desirable to explore avenues of diagnosis and treatment of endometriosis-related inflammation and pain.

Objective(s)

To investigate the immune environment in endometriosis in peritoneal fluid and blood by full-spectrum flow cytometry with a focus on activation and inhibition of immune cells.

Study Design

This was an observational study in patients undergoing laparoscopy for diagnosis or treatment of peritoneal endometriosis or for unrelated conditions; PF was collected from n=5 endometriosis patients and n=4 controls, blood from n=4 endometriosis patients and n=3 controls. Data were analysed for statistical significance using ANOVA, the Kruskal-Wallis or Mann-Whitney U test, with a p-value below 0.05 considered significant.

Results

We observed a prevailing of myeloid immune cells in the peritoneal fluid as opposed to lymphoid cells in the blood. The main differences between endometriosis and control samples, however, were found in the smaller compartments, i.e., in lymphoid populations in peritoneal fluid and myeloid populations in blood. PD-1 levels in peritoneal fluid endometriosis samples were significantly lower than in controls (p<0.05).

Conclusion(s)

The immune checkpoint PD-1 could be a new angle of treating endometriosis-related inflammation and pain in women suffering from this chronic and intractable condition.

Tweetable

Lack of PD-1 plays a role in endometriosis-related inflammation.

AJOG at a glance

The inflammatoru immune environment in endometriosis needs investigating as it iis causative of the pain, i.e., the predominant symptom.

We found a lack of PD-1 expression on peritoneal fluid cells in endometriosis compared to controls.

This could explain the persistent inflammation and open avenues of treatment.
The interaction between abiotic and biotic soil factors drive heterosis expression in maize
Authors: Clouse Kayla M. , Ellis Martel L. , Ford Natalie E. , Hostetler Rachel , Balint-Kurti Peter J. , Kleiner Manuel , Wagner Maggie R.
Published: September 2024

Heterosis or hybrid vigor refers to the superior phenotypes of hybrids relative to their parental inbred lines. Recently, soil microbes were identified as an environmental driver of maize heterosis. While manipulation of the soil microbial community consistently altered heterosis, the direction of the effect appeared to be dependent on the microbiome composition, environment, or both. Abiotic factors are well-known modifiers of heterosis expression, however, how the interactive effects between the soil microbial community and abiotic factors contribute to heterosis are poorly understood. To disentangle the proposed mechanisms by which microbes influence heterosis, we characterize the variation in heterosis expression when maize was grown in soil inocula derived from active maize farms or prairies. While we did not observe consistent differences in heterosis among plants grown in these inocula, our observations reaffirm that microbial effects on heterosis are likely specific to the local microbial community. The introduction of a nutrient amendment resulted in greater heterosis expression in the presence of an agricultural inoculum but not a prairie inoculum. We also observed an effect of soil inocula and nutrient treatment on the composition of bacterial and fungal communities in the root endosphere. In addition, the interaction between soil and nutrient treatment significantly affected bacterial community composition, whereas fungal community composition was only marginally affected by this interaction. These results further suggest that the soil microbial community plays a role in maize heterosis expression but that the abiotic environment is likely a larger driver.
Model uncertainty estimates for deep learning mammographic density prediction using ordinal and classification approaches
Authors: Squires Steven , Kuling Grey , Evans D. Gareth , Martel Anne L. , Astley Susan M.
Published: September 2024

Purpose

Mammographic density is associated with the risk of developing breast cancer and can be predicted using deep learning methods. Model uncertainty estimates are not produced by standard regression approaches but would be valuable for clinical and research purposes. Our objective is to produce deep learning models with in-built uncertainty estimates without degrading predictive performance.

Approach

We analyse data from over 150,000 mammogram images with associated continuous density scores from expert readers in the Predicting Risk Of Cancer At Screening (PROCAS) study. We re-designate the continuous density scores to 100 density classes then train classification and ordinal deep learning models. Distributions and distribution-free methods are applied to extract predictions and uncertainties. A deep learning regression model is trained on the continuous density scores to act as a direct comparison.

Results

The root mean squared error (RMSE) between expert assigned density labels and predictions of the standard regression model are 8.42 (8.34-8.51) while the RMSE for the classification and ordinal classification are 8.37 (8.28-8.46) and 8.44 (8.35-8.53) respectively. The average uncertainties produced by the models are higher when the density scores from pairs of expert readers density scores differ more, are higher when different mammogram views of the same views are more variable and when two separately trained models show higher variation.

Conclusions

Using either a classification or ordinal approach we can produce model uncertainty estimates without loss of predictive performance.
Efficacy and safety of neoadjuvant stereotactic body radiation therapy plus dalpiciclib and exemestane for hormone receptor-positive, HER2-negative breast cancer: A prospective pilot study
Authors: Zhang Yu , Cao Shuo , Niu Nan , Shan Huilian , Xue Jinqi , Chen Guanglei , Xu Yongqing , Yin Jianqiao , Liu Chao , Sun Lisha , Jiang Xiaofan , Tang Meiyue , Xu Qianshi , Jia Mingxuan , Zhang Xu , Zhang Zhenyong , Zhang Qingfu , Wang Jianfei , Li Ailin , Yang Yongliang , Liu Caigang
Published: September 2024

Background

Both neoadjuvant chemotherapy and endocrine therapy only result in trivial pathological complete response rates and moderate objective response rates (ORR) in hormone receptor (HR)-positive, human epidermal growth factor receptor-2 (HER2)-negative breast cancer, more promising alternatives are urgently needed. With proven synergistic effect of cyclin dependent kinase 4/6 (CDK4/6) inhibitor and radiotherapy in preclinical studies, this pilot study aimed to explore the efficacy and safety of neoadjuvant stereotactic body radiation therapy (SBRT) followed by dalpiciclib and exemestane in HR-positive, HER2-negative breast cancer.

Methods

This was a single-arm, non-controlled prospective pilot study. Treatment-naïve patients with unilateral HR-positive, HER2-negative breast cancer received neoadjuvant radiotherapy (24Gy/3F) followed by dalpiciclib and exemestane for 6 cycles. The primary endpoint was the proportion of patients with residual cancer burden (RCB) score of 0-I. Key secondary endpoints included ORR, breast-conservation rate, biomarker analysis, and safety.

Results

All 12 enrolled patients completed the study treatment and surgery. Two (16.7%) of them achieved the RCB 0-I with the ORR of 91.7% (11/12). Analyses of tumor specimens showed significant increase of infiltrating T cells rather than alteration of PD-L1 positive immune cells. The most common grade 3 adverse events (AEs) were neutropenia (66.7%) and leukopenia (25.0%), but no grade 4-5 AE or death occurred.

Conclusions

Our results suggested neoadjuvant SBRT followed by dalpiciclib and exemestane are effective and tolerable, and provides novel insights for the neoadjuvant treatment of HR+/HER2-breast cancer, which may be considered as a feasible option for patients with HR-positive, HER2-negative breast cancer.
Effect of fumarate and live yeast on methane emissions, rumen fermentation, blood metabolites, and lactation performance in dairy goats
Authors: Dong Huixin , Tan Jinlei , Li Shuaishuai , Ma Jingbo , Tang Guangfu , Dai Jiake , Yao Junhu , Li Zongjun
Published: September 2024

The objective of this study was to evaluate the effects and combined effects of fumarate (32 g/d) and active dry yeast (ADY) (1.5 g/d) on methane emissions, rumen fermentation, microbial community and function, apparent total tract digestibility, blood metabolites, and lactation performance in 28 lactating goats using a randomized complete block design with a 2 × 2 factorial arrangement. Fumarate supplementation inhibited methane emission rates for 3 h post-feeding, while ADY increased the methane emission rates for 2 h pre-feeding, without combined effects between them. Fumarate increased the rumen pH and reduced total VFA concentration without changing the VFA profiles before feeding. Based on two custom dataset of 4,674 metagenome-assembled genomes and 7,758,615 nonredundant genes, neither fumarate nor live yeast influenced the rumen microbial community and function. The addition of fumarate reduced the concentrations of glucose, serum malondialdehyde (MDA), and ammonia in the serum, as well as the activity of insulin, while increasing the activity of serum malate dehydrogenase (MDH) and the levels of urea in both serum and milk. The addition of live yeast reduced serum glucose levels and increased serum MDA concentrations and MUN levels. There was a negative interaction between fumaric acid and live yeast on the levels of urea nitrogen in serum and milk.

Conclusions

The methane inhibition effect of fumaric acid persists for 3 h post-feeding, reflecting its retention or metabolism time in the rumen. Fumaric acid enhances the TCA cycle and the urea cycle in dairy goats, thereby improving energy utilization efficiency and reducing the risk of ammonia toxicity.
Developing simple DNA extraction and PCR-RFLP forMALE STERILITY 4(MS4) gene inCryptomeria japonicaD. Don: Toward an environmentally friendly protocol
Authors: Ueno Saneyoshi , Ito Yukiko , Hasegawa Yoichi , Moriguchi Yoshinari
Published: September 2024

This study presents the development of a simple DNA extraction method and a novel PCR-RFLP protocol for genotyping theMALE STERILITY 4(MS4) gene inCryptomeria japonicaas a proof of concept. Traditional CTAB-based DNA extraction methods, while effective, involve hazardous chemicals and require high-speed centrifugation, which are impractical in many field settings. Our approach utilizes a household dish detergent-based buffer, sodium chloride, and polyvinylpyrrolidone K-30 to extract DNA fromC. japonicaneedle leaf tissues—without the need for liquid nitrogen. The simplicity of this method makes it more accessible and environmentally friendly. The extracted DNA was successfully used in PCR-RFLP analysis, targeting a single nucleotide polymorphism in theMS4gene, demonstrating its efficacy for genotyping. The PCR-RFLP markers reliably discriminated between individual genotypes, confirming the practical application of our simple extraction method, even for conifers containing inhibitory substances. This technique is particularly advantageous for use in arboretums and field stations, where the use of hazardous chemicals, specialized equipment, and a draft chamber is limited. Our study contributes to genetic resource management by providing an easy, reliable, and safer method for DNA extraction and genetic analysis.
Evolution of lateralized gustation in nematodes
Authors: Mackie Marisa , Le Vivian Vy , Carstensen Heather R. , Kushnir Nicole R. , Castro Dylan L. , Dimov Ivan M. , Quach Kathleen T. , Cook Steven J. , Hobert Oliver , Chalasani Sreekanth H. , Hong Ray L.
Published: September 2024

Animals with small nervous systems have a limited number of sensory neurons that must encode information from a changing environment. This problem is particularly exacerbated in nematodes that populate a wide variety of distinct ecological niches but only have a few sensory neurons available to encode multiple modalities. How does sensory diversity prevail within this neuronal constraint? To identify the genetic basis for patterning different nervous systems, we demonstrate that sensory neurons in thePristionchus pacificusrespond to various salt sensory cues in a manner that is partially distinct from that of the distantly related nematodeC. elegans. By visualizing neuronal activity patterns, we show that contrary to previous expectations based on its genome sequence, the salt responses ofP. pacificusare encoded in a left/right asymmetric manner in the bilateral ASE neuron pair. Our study illustrates patterns of evolutionary stability and change in the gustatory system of nematodes.
Translation components in adultDrosophila melanogasteradipocytes regulate the ovarian germline stem cell lineage
Authors: Sahu Subhshri , Armstrong Alissa Richmond
Published: September 2024

Adult stem cells, which support tissue homeostasis and damage repair, are influenced by whole organism physiology. Dietary input has a major impact on the stem cell supported ovary inDrosophila melanogasterfemales, appropriately matching reproductive output to nutrient availability. Previous work has shown that inter-organ communication plays a role in modulating the ovarian response to diet. Specifically, amino acid sensing by the adipose tissue remotely controls germline stem cells and their progeny. While we have shown that activation of the amino acid response pathway, a part of the integrated stress response, and mTOR signaling in adipocytes impacts germline stem cell maintenance and ovulation, it is unclear how downstream signaling mediates these responses. Here, using a combination of genetic and cell biological tools, we show that regulation of translation in adult adipocytes impacts the ovarian germline stem cell lineage, from stem cell maintenance to ovulation of mature oocytes. This work strongly suggests that the adipose tissue produces specific factors to control stem cell activity in the ovary and highlights how inter-organ communication underlies organismal physiological responses to diet.
Inter- and intra-specific variation in the pelagic larval duration of four Tropical Eastern Pacific damselfishes (Pomacentridae:Stegastes) with contrasting distribution patterns
Authors: Lozano-Cortés D. F. , Rodríguez-Moreno M. , Zapata F. A.
Published: September 2024

Abstract

Dispersal is a key ecological function in marine populations that are naturally fragmented and sometimes isolated. Pelagic larval duration (PLD) is thought to approximate the dispersal potential of coral reef fishes and may reflect the extent of connectivity in reef fish populations. Inter- and intra-specific variation in PLD of four damselfish species was investigated in the Colombian Pacific at four locations (two on the mainland coast, one at a continental island and one at an oceanic island) at multiple spatial scales (between localities and between sites within a single locality). Two of the species (Stegastes acapulcoensisandS. flavilatus) are broadly distributed on the continental coast while the other two (S. beebeiandS. arcifrons) are largely restricted to oceanic islands. Nonetheless, individuals of continental species sporadically colonize oceanic habitats, and vice- versa. The PLD was estimated using counts of otolith growth increments from juveniles collected at all localities. Species with an oceanic distribution had longer PLDs than their congeners with continental distributions. Differences in PLD between the two continental species varied between localities and significant intra- specific spatial variability was observed between localities but not within a single locality. Although the species studied have the necessary PLD to reach all available habitat, there are no apparent colonization events between mainland and oceanic islands suggesting that their distribution is not limited by dispersal but by other processes. We discuss the possible underlying causes of the observed variability, and suggest the need to consider spatial variability in the development of dispersal models and connectivity patterns for better management of coral reef fish populations.
Reciprocal regulation of m6A modification and miRNA production machineries via phase separation-dependent and -independent mechanisms
Authors: Zhong Songxiao , Li Xindi , Li Changhao , Bai Haiyan , Chen Jingjing , Gan Lu , Zhu Jiyun , Oh Taerin , Yan Xingxing , Zhu Jiaying , Li Niankui , Koiwa Hisashi , Meek Thomas , Peng Xu , Yu Bin , Zhang Zhonghui , Zhang Xiuren
Published: September 2024

Methyltransferase complex (MTC) depositsN6-adenosine (m6A) onto RNA, whereas microprocessor produces miRNA. Whether and how these two distinct complexes cross-regulate each other has been poorly studied. Here we report that the MTC subunit B (MTB) tends to form insoluble condensates with poor activity, with its level monitored by 20S proteasome. Conversely, the microprocessor component SERRATE (SE) forms liquid-like condensates, which in turn promotes solubility and stability of MTB, leading to increased MTC activity. Consistently, the hypomorphic lines expressing SE variants, defective in MTC interaction or liquid-like phase behavior, exhibit reduced m6A level. Reciprocally, MTC can recruit microprocessor toMIRNAloci, prompting co-transcriptional cleavage of primary miRNA (pri-miRNAs) substrates. Additionally, pri-miRNAs carrying m6A modifications at their single-stranded basal regions are enriched by m6A readers, which retain microprocessor in the nucleoplasm for continuing processing. This reveals an unappreciated mechanism of phase separation in RNA modification and processing through MTC and microprocessor coordination.
Analytic validation of anFGFR-focused cell-free DNA liquid biopsy assay (FGFR-Dx)
Authors: Reeser Julie W. , Wing Michele R. , Samorodnitsky Eric , Dao Thuy , Smith Amy , Stein Leah , Paruchuri Anoosha , Miya Jharna , Bonneville Russell , Chang Yi-Seok , Avenarius Matthew , Freud Aharon G. , Yu Lianbo , Roychowdhury Sameek
Published: September 2024

Commercial liquid biopsy assays are routinely used by oncologists to monitor disease response and resistance to therapy. Additionally, in cases where tumor tissue is not available, clinicians may rely on cell-free DNA (cfDNA) testing as a surrogate for comprehensive tumor testing. While some gene rearrangements are well detected, current commercial liquid biopsy assays exhibit low sensitivity for fibroblast growth factor receptor (FGFR) rearrangements.FGFRsare altered in ∼2.5% of all cancers, includingFGFR2rearrangements in 10% of intrahepatic cholangiocarcinoma andFGFR3point mutations and rearrangements in 10-15% of urothelial carcinoma. Therefore, we developed and analytically validated FGFR-Dx, anFGFR-focused cfDNA assay with improved sensitivity forFGFRrearrangements. FGFR-Dx comprehensively targets the introns inFGFR1-3previously shown to be involved in gene fusions as well as all coding exons. CustomFGFRsynthetic reference standards representing both single nucleotide variants (SNVs) and gene rearrangements were utilized at a range of variant frequencies and revealed a detection limit of 0.5% with sensitivities of 97.2% and 92.9% for SNVs and rearrangements, respectively. Furthermore, FGFR-Dx detected rearrangements and identified the intronic breakpoints from cfDNA collected from 13 of 15 patients with known FGFR fusions.