Depleting myeloid-biased haematopoietic stem cells rejuvenates aged immunity.

Ageing of the immune system is characterized by decreased lymphopoiesis and adaptive immunity, and increased inflammation and myeloid pathologies1,2. Age-related changes in populations of self-renewing haematopoietic stem cells (HSCs) are thought to underlie these phenomena3. During youth, HSCs with balanced output of lymphoid and myeloid cells (bal-HSCs) predominate over HSCs with myeloid-biased output (my-HSCs), thereby promoting the lymphopoiesis required for initiating adaptive immune responses, while limiting the production of myeloid cells, which can be pro-inflammatory4. Ageing is associated with increased proportions of my-HSCs, resulting in decreased lymphopoiesis and increased myelopoiesis3,5,6. Transfer of bal-HSCs results in abundant lymphoid and myeloid cells, a stable phenotype that is retained after secondary transfer; my-HSCs also retain their patterns of production after secondary transfer5. The origin and potential interconversion of these two subsets is still unclear. If they are separate subsets postnatally, it might be possible to reverse the ageing phenotype by eliminating my-HSCs in aged mice. Here we demonstrate that antibody-mediated depletion of my-HSCs in aged mice restores characteristic features of a more youthful immune system, including increasing common lymphocyte progenitors, naive T cells and B cells, while decreasing age-related markers of immune decline. Depletion of my-HSCs in aged mice improves primary and secondary adaptive immune responses to viral infection. These findings may have relevance to the understanding and intervention of diseases exacerbated or caused by dominance of the haematopoietic system by my-HSCs.

Genome-wide DNA methylation changes in human spermatogenesis.

Sperm production and function require the correct establishment of DNA methylation patterns in the germline. Here, we examined the genome-wide DNA methylation changes during human spermatogenesis and its alterations in disturbed spermatogenesis. We found that spermatogenesis is associated with remodeling of the methylome, comprising a global decline in DNA methylation in primary spermatocytes followed by selective remethylation, resulting in a spermatids/sperm-specific methylome. Hypomethylated regions in spermatids/sperm were enriched in specific transcription factor binding sites for DMRT and SOX family members and spermatid-specific genes. Intriguingly, while SINEs displayed differential methylation throughout spermatogenesis, LINEs appeared to be protected from changes in DNA methylation. In disturbed spermatogenesis, germ cells exhibited considerable DNA methylation changes, which were significantly enriched at transposable elements and genes involved in spermatogenesis. We detected hypomethylation in SVA and L1HS in disturbed spermatogenesis, suggesting an association between the abnormal programming of these regions and failure of germ cells progressing beyond meiosis.

Antigenic cartography using variant-specific hamster sera reveals substantial antigenic variation among Omicron subvariants.

Severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) has developed substantial antigenic variability. As the majority of the population now has pre-existing immunity due to infection or vaccination, the use of experimentally generated animal immune sera can be valuable for measuring antigenic differences between virus variants. Here, we immunized Syrian hamsters by two successive infections with one of nine SARS-CoV-2 variants. Their sera were titrated against 16 SARS-CoV-2 variants, and the resulting titers were visualized using antigenic cartography. The antigenic map shows a condensed cluster containing all pre-Omicron variants (D614G, Alpha, Delta, Beta, Mu, and an engineered B.1+E484K variant) and considerably more diversity among a selected panel of Omicron subvariants (BA.1, BA.2, BA.4/BA.5, the BA.5 descendants BF.7 and BQ.1.18, the BA.2.75 descendant BN.1.3.1, the BA.2-derived recombinants XBB.2 and EG.5.1, and the BA.2.86 descendant JN.1). Some Omicron subvariants were as antigenically distinct from each other as the wildtype is from the Omicron BA.1 variant. Compared to titers measured in human sera, titers in hamster sera are of higher magnitude, show less fold change, and result in a more compact antigenic map topology. The results highlight the potential of sera from hamsters for the continued antigenic characterization of SARS-CoV-2.

Recent insights from human induced pluripotent stem cell models into the role of microglia in amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease, primarily leading to the degeneration of motor neurons. The traditional focus on motor neuron-centric mechanisms has recently shifted towards understanding the contribution of non-neuronal cells, such as microglia, in ALS pathophysiology. Advances in induced pluripotent stem cell (iPSC) technology have enabled the generation of iPSC-derived microglia monocultures and co-cultures to investigate their role in ALS pathogenesis. Here, we briefly review the insights gained from these studies into the role of microglia in ALS. While iPSC-derived microglia monocultures have revealed intrinsic cellular dysfunction due to ALS-associated mutations, microglia-motor neuron co-culture studies have demonstrated neurotoxic effects of mutant microglia on motor neurons. Based on these findings, we briefly discuss currently unresolved questions and how they could be addressed in future studies. iPSC models hold promise for uncovering disease-relevant pathways in ALS and identifying potential therapeutic targets.

Ancient Genomes From Bronze Age Remains Reveal Deep Diversity and Recent Adaptive Episodes for Human Oral Pathobionts.

Ancient microbial genomes can illuminate pathobiont evolution across millenia, with teeth providing a rich substrate. However, the characterization of prehistoric oral pathobiont diversity is limited. In Europe, only preagricultural genomes have been subject to phylogenetic analysis, with none compared to more recent archaeological periods. Here, we report well-preserved microbiomes from two 4,000-year-old teeth from an Irish limestone cave. These contained bacteria implicated in periodontitis, as well as Streptococcus mutans, the major cause of caries and rare in the ancient genomic record. Despite deriving from the same individual, these teeth produced divergent Tannerella forsythia genomes, indicating higher levels of strain diversity in prehistoric populations. We find evidence of microbiome dysbiosis, with a disproportionate quantity of S. mutans sequences relative to other oral streptococci. This high abundance allowed for metagenomic assembly, resulting in its first reported ancient genome. Phylogenetic analysis indicates major postmedieval population expansions for both species, highlighting the inordinate impact of recent dietary changes. In T. forsythia, this expansion is associated with the replacement of older lineages, possibly reflecting a genome-wide selective sweep. Accordingly, we see dramatic changes in T. forsythia's virulence repertoire across this period. S. mutans shows a contrasting pattern, with deeply divergent lineages persisting in modern populations. This may be due to its highly recombining nature, allowing for maintenance of diversity through selective episodes. Nonetheless, an explosion in recent coalescences and significantly shorter branch lengths separating bacteriocin-carrying strains indicate major changes in S. mutans demography and function coinciding with sugar popularization during the industrial period.

Inferring Taxonomic Affinities and Genetic Distances Using Morphological Features Extracted from Specimen Images: a Case Study with a Bivalve dataset.

Reconstructing the tree of life and understanding the relationships of taxa are core questions in evolutionary and systematic biology. The main advances in this field in the last decades were derived from molecular phylogenetics; however, for most species, molecular data are not available. Here, we explore the applicability of two deep learning methods - supervised classification approaches and unsupervised similarity learning - to infer organism relationships from specimen images. As a basis, we assembled an image dataset covering 4144 bivalve species belonging to 74 families across all orders and subclasses of the extant Bivalvia, with molecular phylogenetic data being available for all families and a complete taxonomic hierarchy for all species. The suitability of this dataset for deep learning experiments was evidenced by an ablation study resulting in almost 80% accuracy for identifications on the species level. Three sets of experiments were performed using our dataset. First, we included taxonomic hierarchy and genetic distances in a supervised learning approach to obtain predictions on several taxonomic levels simultaneously. Here, we stimulated the model to consider features shared between closely related taxa to be more critical for their classification than features shared with distantly related taxa, imprinting phylogenetic and taxonomic affinities into the architecture and training procedure. Second, we used transfer learning and similarity learning approaches for zero-shot experiments to identify the higher-level taxonomic affinities of test species that the models had not been trained on. The models assigned the unknown species to their respective genera with approximately 48% and 67% accuracy. Lastly, we used unsupervised similarity learning to infer the relatedness of the images without prior knowledge of their taxonomic or phylogenetic affinities. The results clearly showed similarities between visual appearance and genetic relationships at the higher taxonomic levels. The correlation was 0.6 for the most species-rich subclass (Imparidentia), ranging from 0.5 to 0.7 for the orders with the most images. Overall, the correlation between visual similarity and genetic distances at the family level was 0.78. However, fine-grained reconstructions based on these observed correlations, such as sister-taxa relationships, require further work. Overall, our results broaden the applicability of automated taxon identification systems and provide a new avenue for estimating phylogenetic relationships from specimen images.

Relationship between Androgens and Vascular and Placental Function during Pre-eclampsia.

Hypertensive disorders of pregnancy (HDP) represent a substantial risk to maternal and fetal health. Emerging evidence suggests an association between testosterone and pre-eclampsia (PE), potentially mediated through androgen receptors (AR). Nevertheless, the mechanism driving this association is yet to be elucidated. On the other hand, reports of transgender men's pregnancies offer a limited and insightful opportunity to understand the role of high androgen levels in the development of HDP. In this sense, a literature review was performed from a little over 2 decades (1998-2022) to address the association of testosterone levels with the development of HDP. Furthermore, this review addresses the case of transgender men for the first time. The main in vitro outcomes reveal placenta samples with greater AR mRNA expression. Moreover, ex vivo studies show that testosterone-induced vasorelaxation impairment promotes hypertension. Epidemiological data point to greater testosterone levels in blood samples during PE. Studies with transgender men allow us to infer that exogenous testosterone administration can be considered a risk factor for PE and that the administration of testosterone does not affect fetal development. Overall, all studies analyzed suggested that high testosterone levels are associated with PE.

BDNF-dependent signaling in the olfactory bulb modulates social recognition memory in mice.

An operative olfactory bulb (OB) is critical to social recognition memory (SRM) in rodents, which involves identifying conspecifics. Furthermore, OB also allocates synaptic plasticity events related to olfactory memories in their intricate neural circuit. Here, we asked whether the OB is a target for brain-derived neurotrophic factor (BDNF), a well-known mediator of plasticity and memory. Adult ICR-CD1 male mice had their SRM evaluated under the inhibition of BDNF-dependent signaling directly in the OB. We also quantified the expression of BDNF in the OB, after SRM acquisition. Our results presented an amnesic effect of anti-BDNF administered 12 h post-training. Although the western blot showed no statistical difference in pro-BDNF and BDNF expression, the analysis of fluorescence intensity in slices suggests SRM acquisition decreases BDNF in the granular cell layer of the OB. Next, to test the ability of BDNF to rescue SRM deficit, we administered the human recombinant BDNF (rBDNF) directly in the OB of socially isolated (SI) mice. Unexpectedly, rBDNF did not rescue SRM in SI mice. Furthermore, BDNF and pro-BDNF expression in the OB was unchanged by SI. Our study reinforces the OB as a plasticity locus in memory-related events. It also adds SRM as another type of memory sensitive to BDNF-dependent signaling.

Team Science Approaches to Unravel Monogenic Parkinson's Disease on a Global Scale.

BACKGROUND: Until recently, about three-quarters of all monogenic Parkinson's disease (PD) studies were performed in European/White ancestry, thereby severely limiting our insights into genotype-phenotype relationships at a global scale. OBJECTIVE: To identify the multi-ancestry spectrum of monogenic PD. METHODS: The first systematic approach to embrace monogenic PD worldwide, The Michael J. Fox Foundation Global Monogenic PD Project, contacted authors of publications reporting individuals carrying pathogenic variants in known PD-causing genes. In contrast, the Global Parkinson's Genetics Program's Monogenic Network took a different approach by targeting PD centers underrepresented or not yet represented in the medical literature. RESULTS: In this article, we describe combining both efforts in a merger project resulting in a global monogenic PD cohort with the buildup of a sustainable infrastructure to identify the multi-ancestry spectrum of monogenic PD and enable studies of factors modifying penetrance and expressivity of monogenic PD. CONCLUSIONS: This effort demonstrates the value of future research based on team science approaches to generate comprehensive and globally relevant results. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Clinical Validation of Digitally Acquired Clinical Data and Machine Learning Models for Remote Measurement of Psoriasis and Psoriatic Arthritis: A Proof-of-Concept Study.

OBJECTIVE: Psoriatic disease remains underdiagnosed and undertreated. We developed and validated a suite of novel, sensor-based smartphone assessments (Psorcast app) that can be self-administered to measure cutaneous and musculoskeletal signs and symptoms of psoriatic disease. METHODS: Participants with psoriasis (PsO) or psoriatic arthritis (PsA) and healthy controls were recruited between June 5, 2019, and November 10, 2021, at 2 academic medical centers. Concordance and accuracy of digital measures and image-based machine learning models were compared to their analogous clinical measures from trained rheumatologists and dermatologists. RESULTS: Of 104 study participants, 51 (49%) were female and 53 (51%) were male, with a mean age of 42.3 years (SD 12.6). Seventy-nine (76%) participants had PsA, 16 (15.4%) had PsO, and 9 (8.7%) were healthy controls. Digital patient assessment of percent body surface area (BSA) affected with PsO demonstrated very strong concordance (Lin concordance correlation coefficient [CCC] 0.94 [95% CI 0.91-0.96]) with physician-assessed BSA. The in-clinic and remote target plaque physician global assessments showed fair-to-moderate concordance (CCCerythema 0.72 [0.59-0.85]; CCCinduration 0.72 [0.62-0.82]; CCCscaling 0.60 [0.48-0.72]). Machine learning models of hand photos taken by patients accurately identified clinically diagnosed nail PsO with an accuracy of 0.76. The Digital Jar Open assessment categorized physician-assessed upper extremity involvement, considering joint tenderness or enthesitis (AUROC 0.68 [0.47-0.85]). CONCLUSION: The Psorcast digital assessments achieved significant clinical validity, although they require further validation in larger cohorts before use in evidence-based medicine or clinical trial settings. The smartphone software and analysis pipelines from the Psorcast suite are open source and freely available.

Prediction of post-hemorrhagic ventricular dilatation trajectory using a growth mixture model in preterm infants.

BACKGROUND: Early intervention for post-hemorrhagic ventricular dilatation (PHVD), guided by ventricular size measurements from cranial ultrasound (cUS), is associated with improved neurodevelopmental outcomes in preterm infants but benefits must be balanced against intervention risks. METHODS: Anterior horn width (AHW) and ventricular index (VI) were measured from cUS for preterm infants (<29 weeks) with intraventricular hemorrhage admitted from 2010-2018. PHVD was defined as AHW > 6 mm or VI >97th percentile for postmenstrual age. Individual ventricular size trajectories were plotted, and a growth mixture model (GMM) used to identify latent trajectory classes and compare these to predetermined outcome of neurosurgical intervention. RESULTS: Measurements were obtained from 1543 cUS in 249 infants, of whom 39 had PHVD without and 17 PHVD with neurosurgical intervention based on signs of raised intracranial pressure. The GMM predicted trajectory identified: 93.3% of infants without PHVD, 88.2% and 30.8% of infants with PHVD with and without intervention using AHW; 100% of infants without PHVD, 52.9% and 59.0% of infants with PHVD with and without intervention using VI. CONCLUSIONS: The AHW GMM identified a significant proportion of infants with severe PHVD. Model refinement offers a promising approach for identifying differences in PHVD trajectory at an early stage to guide management. IMPACT: It is difficult to distinguish the trajectory of PHVD in the early stage of development, in particular PHVD that spontaneously arrests from slowly progressive PHVD which eventually requires intervention. We report the first modeling-based evaluation of PHVD trajectory for the prediction of short-term outcome of PHVD progression and neurosurgical intervention. With additional clinical validation and optimization to increase accuracy, predictive modeling has the potential to identify important differences in PHVD trajectory at an early stage in the clinical course, allowing for more individualized data-driven risk-benefit assessments to guide decisions on early intervention.

Methodological considerations on diffusion MRI tractography in infants aged 0-2 years: a scoping review.

Diffusion MRI (dMRI) enables studying the complex architectural organization of the brain's white matter (WM) through virtual reconstruction of WM fiber tracts (tractography). Despite the anticipated clinical importance of applying tractography to study structural connectivity and tract development during the critical period of rapid infant brain maturation, detailed descriptions on how to approach tractography in young infants are limited. Over the past two decades, tractography from infant dMRI has mainly been applied in research settings and focused on diffusion tensor imaging (DTI). Only few studies used techniques superior to DTI in terms of disentangling information on the brain's organizational complexity, including crossing fibers. While more advanced techniques may enhance our understanding of the intricate processes of normal and abnormal brain development and extensive knowledge has been gained from application on adult scans, their applicability in infants has remained underexplored. This may partially be due to the higher technical requirements versus the need to limit scan time in young infants. We review various previously described methodological practices for tractography in the infant brain (0-2 years-of-age) and provide recommendations to optimize advanced tractography approaches to enable more accurate reconstructions of the brain WM's complexity. IMPACT: Diffusion tensor imaging is the technique most frequently used for fiber tracking in the developing infant brain but is limited in capability to disentangle the complex white matter organization. Advanced tractography techniques allow for reconstruction of crossing fiber bundles to better reflect the brain's complex organization. Yet, they pose practical and technical challenges in the fast developing young infant's brain. Methods on how to approach advanced tractography in the young infant's brain have hardly been described. Based on a literature review, recommendations are provided to optimize tractography for the developing infant brain, aiming to advance early diagnosis and neuroprotective strategies.

Allometric relationships and trade-offs in 11 common Mediterranean-climate grasses.

Biomass allocation in plants is the foundation for understanding dynamics in ecosystem carbon balance, species competition, and plant-environment interactions. However, existing work on plant allometry has mainly focused on trees, with fewer studies having developed allometric equations for grasses. Grasses with different life histories can vary in their carbon investment by prioritizing the growth of specific organs to survive, outcompete co-occurring plants, and ensure population persistence. Further, because grasses are important fuels for wildfire, the lack of grass allocation data adds uncertainty to process-based models that relate plant physiology to wildfire dynamics. To fill this gap, we conducted a greenhouse experiment with 11 common California grasses varying in photosynthetic pathway and growth form. We measured plant sizes and harvested above- and belowground biomass throughout the life cycle of annual species, while for the establishment stage of perennial grasses to quantify allometric relationships for leaf, stem, and root biomass, as well as plant height and canopy area. We used basal diameter as a reference measure of plant size. Overall, basal diameter is the best predictor for leaf and stem biomass, height, and canopy area. Including height as another predictor can improve model accuracy in predicting leaf and stem biomass and canopy area. Fine root biomass is a function of leaf biomass alone. Species vary in their allometric relationships, with most variation occurring for plant height, canopy area, and stem biomass. We further explored potential trade-offs in biomass allocation across species between leaf and fine root, leaf and stem, and allocation to reproduction. Consistent with our expectation, we found that fast-growing plants allocated a greater fraction to reproduction. Additionally, plant height and specific leaf area negatively influenced the leaf-to-stem ratio. However, contrary to our hypothesis, there were no differences in root-to-leaf ratio between perennial and annual or C4 and C3 plants. Our study provides species-specific and functional-type-specific allometry equations for both above- and belowground organs of 11 common California grass species, enabling nondestructive biomass assessment in California grasslands. These allometric relationships and trade-offs in carbon allocation across species can improve ecosystem model predictions of grassland species interactions and environmental responses through differences in morphology.

Recurrence of fusocellular subtype GIST with SDHB mutation: A case of SDHB-loss and therapeutic challenges.

Gastrointestinal stromal tumors (GISTs) are sarcomas affecting the stomach and small intestine, with a rare subtype characterized by succinate dehydrogenase B (SDHB)-loss posing significant diagnostic and therapeutic challenges. A 62-year-old man with weight loss and abdominal pain was diagnosed with a gastric GIST showing SDHB-loss. Initial treatment with Imatinib reduced the tumor size, but surgery revealed no residual tumor. Despite adjuvant Imatinib, recurrence occurred, necessitating further surgical intervention. While GISTs typically benefit from surgery and tyrosine kinase inhibitors (TKIs), those with SDHB-loss are resistant to TKIs, requiring a different management approach. This case emphasizes the importance of surgical intervention for SDHB-deficient GISTs and the need for ongoing research into effective treatments for this subtype.

Conversion of char from pyrolysis of plastic wastes into alternative activated carbons for heavy metal removal.

The valorization of post-consumer mixed plastics in pyrolysis processes represents an abundant reservoir of carbon that can be effectively converted into useful chars. This process not only holds appeal in terms of improving plastic waste concerns but also contributes to the reduction of greenhouse gas emissions, thus aligning with the principles of a circular economy paradigm. In this study, the char produced from the pyrolysis of post-consumer mixed plastic waste has been activated with Na2CO3, KOH, NaOH, and K2CO3 to improve the textural, structural, and composition characteristics, leading to improved adsorption capability. These characteristics were studied by N2 adsorption-desorption isotherms, scanning electron microscopy, elemental and immediate analysis, and X-ray photoelectron spectroscopy. The developed surface area (SBET) was 573, 939, 704 and 592 m2 g-1 for Na2CO3, KOH, NaOH and K2CO3 activated carbons, respectively. These activated chars (ACs) were tested for the adsorption of heavy metals in both synthetic waters containing Pb, Cd, and Cu and industrial wastewater collected at an agrochemical production plant. Na2CO3-AC was the best performing material. The metal uptake in synthetic waters using a batch set-up was 40, 13 and 12 mg g-1 for Pb, Cd and Cu. Experiments in a column set-up using Na2CO3-AC resulted in a saturation time of 290, 16, and 80 min for Pb, Cd, and Cu synthetic waters, respectively, and metal uptakes of 26.8, 4.1, and 7.9 mg g-1, respectively. The agrochemical effluents, containing mainly Cr, Cu, Mn, and Zn were tested in a plug-flow column. The metal uptake notably decreased compared to synthetic water due to a competition effect for active sites.

Endobronchial Ultrasound Guided Transbronchial Needle Aspiration and PD-L1 Yields.

PURPOSE: Immunotherapy is a leading approach for treating advanced non-small cell lung cancer (NSCLC) by targeting the PD-1/PD-L1 checkpoint signaling pathway, particularly in tumors expressing high levels of PD-L1 (Jug et al. in J Am Soc Cytopathol 9:485-493, 2020; Perrotta et al. in Chest 158: 1230-1239, 2020). Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a minimally invasive method to obtain tissue for molecular studies, including PD-L1 analysis, in unresectable tumors (Genova et al. in Front Immunol 12: 799455, 2021; Wang et al. in Ann Oncol 29: 1417-1422, 2018). This study aimed to assess the adequacy of PD-L1 assessment in EBUS-TBNA cytology specimens. METHODS: Data was collected retrospectively from patients who underwent EBUS-TBNA between 2017 and 2021 for suspected lung cancer biopsy. Samples positive for NSCLC were examined for PD-L1 expression. EBUS was performed by experienced practitioners, following institutional guidelines of a minimum of five aspirations from positively identified lesions. Sample adequacy for molecular testing was determined by the pathology department. RESULTS: The analysis involved 387 NSCLC cases (149 squamous cell, 191 adenocarcinoma, 47 unspecified). Of the 263 EBUS-TBNA specimens tested for PD-L1, 237 (90.1%) were deemed adequate. While 84% adhered to the protocol, adherence did not yield better results. Significantly higher PD-L1 adequacy was observed in squamous cell carcinomas (93.2%) compared to adenocarcinoma (87.6%). The number of aspirations and sedation type did not correlate with PD-L1 adequacy in either cancer type, but lesion size and location had a significant impact in adenocarcinomas. Adenocarcinoma exhibited higher PD-L1 expression (68%) compared to squamous cell carcinoma (48%). CONCLUSION: EBUS-TBNA offers high yields for assessing immunotherapy markers like PD-L1, with satisfactory adequacy regardless of NSCLC subtype, lesion size, or location.

Endobronchial Ultrasound Guided Transbronchial Needle Aspiration and Next Generation Sequencing Yields.

PURPOSE: The use of endobronchial ultrasound (EBUS) is standard practice for lung cancer diagnosis and staging. Next generation sequencing (NGS) for detection of genetic alterations is recommended in advanced, non-squamous, non-small-cell lung cancer (NSCLC). Existing protocols for NGS testing are minimal and reported yields vary. This study aimed to determine the yield of EBUS samples obtained for NGS using a sampling protocol at our institution and assess predictive factors to form collection protocols. METHODS: We reviewed EBUS bronchoscopies from 2016 to 2021 with non-squamous NSCLC diagnoses. For target lesions suspected to be malignant, the sampling protocol was: (a) two slides for on-site evaluation, (b) three to five fine needle aspirations rinsed into saline for immunohistochemical staining and in-house molecular markers, and (c) additional three to five rinses for NGS. Sufficiency for NGS processing was determined by the pathology department. RESULTS: Two hundred and seventy-eight non-squamous NSCLC samples were obtained by EBUS (205 adenocarcinoma; 73 not otherwise specified). EBUS was performed under general anesthesia in 75.5% of cases. The overall sample adequacy for NGS testing was 57.5%. Higher adequacy rates were observed when protocol was adhered to 66.0% versus 37.2% (p < 0.001). There was no statistically significant difference based on the size of the lesion or location of the sample. CONCLUSION: When a protocol of three to five dedicated needle rinses for NGS was followed, we nearly doubled our sample adequacy rate for NSG as compared to standard care. Studies are needed to determine the ideal collection and processing modality to preserve tissue samples for genetic sequencing.

The impact of relationship factors on antenatal depression in the context of the COVID-19 pandemic.

BACKGROUND: Antenatal depression is the most prevalent pregnancy-associated mental health disorder. Previous studies have identified several risk factors for antenatal depression, including partner support. However, during the COVID-19 pandemic, many relationship dynamics changed. This study examined the extent to which relationship factors had an impact on antenatal depression in comparison with other well-researched factors in the context of the pandemic. METHODS: A secondary analysis was conducted using data from the P3 Cohort in Calgary, a longitudinal cohort study based in Alberta, Canada. Pregnant people (n = 872) completed self-report questionnaires and validated scales about sociodemographic, psychological, and relationship characteristics. Antenatal depression was assessed using the Edinburgh Postnatal Depression Scale (EPDS). Logistic regression was used to assess the impact of reported characteristics on antenatal depression. Tests of model fit were used to examine whether the inclusion of variables related to relationship quality improved model fit after accounting for other known risk factors. RESULTS: Overall, 18.23% of participants experienced antenatal depression. Relationship factors including relationship unhappiness (OR = 1.98 [95% CI: 1.06-3.69]), having an upsetting partner (OR = 2.00 [95% CI: 1.17-3.40]), and having a lower quality of relationships with close friends and family (OR = 1.76 [95% CI: 1.14-2.73]) were associated with antenatal depression; however, inclusion of these relationship factors did not improve model fit after accounting for other known predictors. CONCLUSION: Overall, relationship factors were not associated with antenatal depression during the pandemic after accounting for other known risk factors. Stress and anxiety caused by the pandemic may have overshadowed the impact of relationship factors, or relationship factors may have contributed to higher levels of stress and anxiety more generally within our sample.

Humoral immune escape by current SARS-CoV-2 variants BA.2.86 and JN.1, December 2023.

Variant BA.2.86 and its descendant, JN.1, of SARS-CoV-2 are rising in incidence across Europe and globally. We isolated recent JN.1, BA.2.86, EG.5, XBB.1.5 and earlier variants. We tested live virus neutralisation of sera taken in September 2023 from vaccinated and exposed healthy persons (n = 39). We found clear neutralisation escape against recent variants but no specific pronounced escape for BA.2.86 or JN.1. Neutralisation escape corresponds to recent variant predominance but may not be causative of the recent upsurge in JN.1 incidence.