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Objective: To assess the value of material density (MD) images generated from a rapid kilovoltage-switching dual-energy CT (rsDECT) in early detection of peritoneal carcinomatosis (PC). Materials and methods: Thirty patients (60 ± 13 years; 24 women) with PC detected on multiple abdominal DECT scans were included. Four separate DECTs with varying findings of PC from each patient were used for qualitative/quantitative analysis, resulting in a total of 120 DECT scans (n = 30 × 4). Three radiologists independently reviewed DECT images (65 keV alone and 65 keV + MD) for diagnosis of PC (diagnostic confidence, lesion conspicuity, sharpness/delineation and image quality) using a 5-point Likert scale. Quantitative estimation of contrast-to-noise ratio (CNR) was done. Wilcoxon signed-rank test and Odds ratio calculation were used to compare between the two protocols. Inter-observer agreement was evaluated using Kappa coefficient analysis. P values < 0.05 were considered statistically significant. Results: 65 keV + MD images showed a slightly higher sensitivity (89%[95%CI:84,92]) for PC detection compared with 65 keV images alone without statistical significance (84%[95%CI:78,88], p = 0.11) with the experienced reader showing significant improvement (98%[95%CI:93,100] vs. 90%[95%CI:83,94], p = 0.02). On a per-patient basis, use of MD images allowed earlier diagnosis for PC in an additional 13–23% of patients. On sub-group analysis, earlier diagnosis of PC was particularly beneficial in patients with BMI ≤ 29.9 kg/m2. 65 keV + MD images showed higher diagnostic confidence, lesion conspicuity, and lesion sharpness for the experienced reader (p < 0.001). CNR was higher in MD images (1.7 ± 0.5) than 65 keV images (0.1 ± 0.02, p < 0.001). All readers showed moderate interobserver agreement for determining PC by both protocols (κ = 0.58 and κ = 0.47). Conclusion: MD images allow earlier and improved detection of PC with the degree of benefit varying based on reader experience and patient body habitus. [ABSTRACT FROM AUTHOR]

Blood velocities measured by Transcranial Doppler (TCD) are dependent on the angle between the incident ultrasound beam and the direction of blood flow (known as the Doppler angle). However, when TCD examinations are performed without imaging the Doppler angle for each vessel segment is not known. We have measured Doppler angles in the basal cerebral arteries examined with TCD using three-dimensional (3D) vessel models generated from computed tomography angiography (CTA) scans. This approach produces angle statistics that are not accessible during non-imaging TCD studies. We created 3D models of the basal cerebral arteries for 24 vasospasm patients. Standard acoustic windows were mapped to the specific anatomy of each patient. Virtual ultrasound transmit beams were generated that originated from the acoustic window and intersected the centerline of each arterial segment. Doppler angle measurements were calculated and compiled for each vessel segment. Doppler angles were smallest for the middle cerebral artery M1 segment (median 24.6°) and ophthalmic artery (median 25.0°), and largest for the anterior cerebral artery A2 segment (median 76.4°) and posterior cerebral artery P2 segment (median 75.8°). The ophthalmic artery had the highest proportion of Doppler angles that were less than 60° (99%) while the anterior cerebral artery A2 segment had the lowest proportion of Doppler angles that were less than 60° (10%). These angle measurements indicate the expected deviation between measured and true velocities in the cerebral arteries, highlighting specific segments that may be prone to underestimation of velocity. [ABSTRACT FROM AUTHOR]

South Pacific archipelagos are central in the biogeographic debate on the relative importance of vicariance and dispersal in shaping the distribution of species. However, each taxonomic group was subject to different processes and histories, and here, we reveal the historical biogeography of the diverse Eumolpinae leaf beetles, widely distributed in the region. Extensive taxon sampling focusing on South Pacific Eumolpinae was used to infer the first molecular phylogeny of the group using three single‐copy protein‐coding nuclear and two mitochondrial markers. Upon assessing the clade of interest for lineage‐specific variation in substitution rates, the age of the most recent common ancestors was estimated using out‐group calibration and multi‐gamma site models (MGSMs). Biogeographic analyses used standard event‐based inferences also incorporating phylogenetic uncertainty. Zealandian Eumolpinae are monophyletic and appear to have split from their global relatives in the transition from the Cretaceous to the Paleogene. Variation in the rates of molecular evolution affected the in‐group stem branch, with a significant drop in the substitution rate, and the MGSM correction recovered the crown age of Zealandian Eumolpinae during the Late Eocene–Oligocene transition. Biogeographic inference resolved the origin of the radiation in New Caledonia, favouring a null model without island age constraints, and repeated dispersal events to the other islands, including three independent but synchronous colonisations of New Zealand during the Miocene. New Caledonia, with a highly diverse Eumolpinae fauna of uncertain origin, acted as a hub and pump of biodiversity of these beetles in the entire South Pacific region, sending migrants to other islands through long‐distance dispersal with lineages establishing when land became available. [ABSTRACT FROM AUTHOR]

There is a critical gap in knowledge about how Gram-negative bacterial pathogens, using survival strategies developed for other niches, cause lethal bacteremia. Facultative anaerobic species of the Enterobacterales order are the most common cause of Gram-negative bacteremia, including Escherichia coli, Klebsiella pneumoniae, Serratia marcescens, Citrobacter freundii, and Enterobacter hormaechei. Bacteremia often leads to sepsis, a life-threatening organ dysfunction resulting from unregulated immune responses to infection. Despite a lack of specialization for this host environment, Gram-negative pathogens cause nearly half of bacteremia cases annually. Based on our existing Tn-Seq fitness factor data from a murine model of bacteremia combined with comparative genomics of the five Enterobacterales species above, we prioritized 18 conserved fitness genes or operons for further characterization. Mutants were constructed for all genes in all five species. Each mutant was used to cochallenge C57BL/6 mice via tail vein injection along with each respective wild-type strain to determine competitive indices for each fitness gene. Five fitness factor genes, when mutated, attenuated mutants in four or five species in the spleen and liver (tatC, ruvA, gmhB, wzxE, arcA). Five additional fitness factor genes or operons were validated as outcompeted by wild-type in three, four, or five bacterial species in the spleen (xerC, prc, apaGH, atpG, aroC). Overall, 17 of 18 fitness factor mutants were attenuated in at least one species in the spleen or liver. Together, these findings allow for the development of a model of bacteremia pathogenesis that may include future targets of therapy against bloodstream infections. Author summary: Frequent cases of bacteremia plague our ICUs, bone marrow transplant units, and inpatient facilities. Nearly half of these infections are caused by Gram-negative bacteria. The Enterobacterales order including E. coli, K. pneumoniae, S. marcescens, C. freundii, and E. hormaechei are leading causes of bacteremia. An alarming proportion of these are due to antibiotic-resistant isolates, which are four times more likely to kill than antibiotic-susceptible isolates. Clearly, we need new therapeutic targets to treat cases of bacteremia and sepsis. Previously, it has been unclear what genes contribute to their ability to survive in this hostile host environment. We have previously undertaken unbiased genetic screens to identify genes shared by all five bacterial genera that are required for maintaining bacterial burden in the blood and blood-filtering organs. These include genes that encode proteins that maintain proton motive force, resist antimicrobial peptides and complement, mediate genome maintenance, transport key metabolites and proteins, avoid oxidative stress, acquire iron, and regulate key pathways. Mutants, constructed in these shared genes in the five species, were validated for a high proportion of genes as critical for infection in the mouse model of bacteremia. [ABSTRACT FROM AUTHOR]

Peripheral blood mononuclear cell (PBMC) immunophenotyping is crucial in tracking activation, disease state, and response to therapy in human subjects. Many studies require the shipping of blood from clinical sites to a laboratory for processing to PBMC, which can lead to delays that impact sample quality. We used an extensive cytometry by time-of-flight (CyTOF) immunophenotyping panel to analyze the impacts of delays to processing and distinct storage conditions on cell composition and quality of PBMC from seven adults across a range of ages, including two with rheumatoid arthritis. Two or more days of delay to processing resulted in extensive red blood cell contamination and increased variability of cell counts. While total memory and naïve B- and T-cell populations were maintained, 4-day delays reduced the frequencies of monocytes. Variation across all immune subsets increased with delays of up to 7 days in processing. Unbiased clustering analysis to define more granular subsets confirmed changes in PBMC composition, including decreases of classical and non-classical monocytes, basophils, plasmacytoid dendritic cells, and follicular helper T cells, with each subset impacted at a distinct time of delay. Expression of activation markers and chemokine receptors changed by Day 2, with differential impacts across subsets and markers. Our data support existing recommendations to process PBMC within 36 h of collection but provide guidance on appropriate immunophenotyping experiments with longer delays. Peripheral blood mononuclear cells are key to the analysis of human immunophenotypes but require isolation from whole blood shortly after collection. For multisite clinical trials, this can be logistically complex. We analyzed the impacts of delays of up to 7 days on immunophenotyping by CyTOF and created a decision tree on the usability of samples given a known delay to processing. Graphical Abstract [ABSTRACT FROM AUTHOR]

Here, we introduce the Tabulae Paralytica—a compilation of four atlases of spinal cord injury (SCI) comprising a single-nucleus transcriptome atlas of half a million cells, a multiome atlas pairing transcriptomic and epigenomic measurements within the same nuclei, and two spatial transcriptomic atlases of the injured spinal cord spanning four spatial and temporal dimensions. We integrated these atlases into a common framework to dissect the molecular logic that governs the responses to injury within the spinal cord1. The Tabulae Paralytica uncovered new biological principles that dictate the consequences of SCI, including conserved and divergent neuronal responses to injury; the priming of specific neuronal subpopulations to upregulate circuit-reorganizing programs after injury; an inverse relationship between neuronal stress responses and the activation of circuit reorganization programs; the necessity of re-establishing a tripartite neuroprotective barrier between immune-privileged and extra-neural environments after SCI and a failure to form this barrier in old mice. We leveraged the Tabulae Paralytica to develop a rejuvenative gene therapy that re-established this tripartite barrier, and restored the natural recovery of walking after paralysis in old mice. The Tabulae Paralytica provides a window into the pathobiology of SCI, while establishing a framework for integrating multimodal, genome-scale measurements in four dimensions to study biology and medicine.The Tabulae Paralytica, a compilation of four molecular atlases of spinal cord injury, provides a window into the pathobiology of spinal cord injury, establishing a framework for integrating multimodal, genome-scale measurements in four dimensions to study biology and medicine. [ABSTRACT FROM AUTHOR]

Background People with HIV (PWH) who are coinfected with hepatitis B virus (HBV) have a higher risk of mortality compared with PWH alone. Populations such as people who inject drugs (PWID) and men who have sex with men (MSM) are particularly at high risk for HBV acquisition; yet, limited epidemiological data from these populations exist on HBV prevalence from low- and middle-income country settings (LMICs). Methods We characterized the prevalence and correlates of HBV serological markers in a sample of PWID and MSM with HIV recruited across 15 Indian cities using hepatitis B surface antigen (HBsAg), hepatitis B core antibody (anti-HBc), and hepatitis B surface antibody (anti-HBs). Testing of stored specimens for the presence of these markers was performed on the Abbott ARCHITECT i1000 as per the manufacturer's instructions. Correlates of ever being infected with HBV (reactive for anti-HBc and/or HBsAg) and chronic HBV (reactive for HBsAg) among those ever infected were assessed using univariable and multivariable multilevel logistic regression models accounting for site-level clustering. Results A total of 2198 (95%) of the 2314 participants recruited for the trial were screened for HBV markers. The median age among the PWID and MSM participants was 30 and 32 years, respectively. The prevalence of ever being infected with HBV was 75.6% vs 46.9% in PWID vs MSM, respectively (P <.01); prevalence of chronic infection was also higher in PWID vs MSM (14.1% vs 9.5%; P <.01). Correlates of ever being infected with HBV among PWID included unstable housing (adjusted odds ratio [aOR], 5.02) and sharing injection paraphernalia (aOR, 2.70), and among MSM, correlates included history of injection drug use (aOR, 4.87) and gender identity. The prevalence of isolated core (anti-HBc in the absence of anti-HBs) was 34.7% vs 29.4% in PWID vs MSM (P <.05). Vaccination serostatus was <10% in both populations. Conclusions In this large sample of PWID and MSM with HIV, we observed a high prevalence of serology consistent with HBV infection and low vaccination, highlighting the need for routine screening and catch-up vaccination. The high prevalence of isolated anti-HBc reactivity highlights the need to understand the risk of reactivation with this serological pattern. [ABSTRACT FROM AUTHOR]

Graduate Teaching Assistants (GTAs) are doctoral researchers who are paid to teach. Building on work exploring identity construction in doctoral education and in the GTA context, this study uses role identity theory (McCall and Simmons 1978) as a theoretical framework to explore the factors influencing GTAs' teacher identity development. Role identity theory emphasises the importance of social interaction and negotiation of identity with those in similar and opposing roles. Semi-structured interviews were conducted with nine GTAs from a variety of STEMM disciplines. From a role identity perspective, we found that the development of GTA teacher identities was strongly influenced by the behaviours and values of others, whilst maintaining the autonomy of the individual. We conclude with a set of recommendations for academic leadership and practice that consider the institutional cultures within which teaching and learning are situated to suggest how GTAs can be supported to develop their identities as teachers. [ABSTRACT FROM AUTHOR]

Neuroendocrine neoplasms (NENs) are a diverse group of tumors with varying clinical behaviors. Their incidence has risen due to increased awareness, improved diagnostics, and aging populations. The 2019 World Health Organization classification emphasizes integrating radiology and histopathology to characterize NENs and create personalized treatment plans. Imaging methods like CT, MRI, and PET/CT are crucial for detection, staging, treatment planning, and monitoring, but each of them poses different interpretative challenges and none are immune to pitfalls. Treatment options include surgery, targeted therapies, and chemotherapy, based on the tumor type, stage, and patient-specific factors. This review aims to provide insights into the latest developments and challenges in NEN imaging, diagnosis, and management. [ABSTRACT FROM AUTHOR]

During NASA X-59 quiet supersonic aircraft community response tests, low-boom recordings will contain contaminating noise from instrumentation and ambient acoustical sources. This noise can inflate sonic boom perception metrics by several decibels. This paper discusses the development and comparison of robust lowpass filtering techniques for removing contaminating noise effects from low-boom recordings. The two filters are a time-domain Butterworth-magnitude filter and a frequency-domain Brick Wall filter. Both filters successfully reduce noise contamination in metric calculations for simulated data with real-world contaminating noise and demonstrate comparable performance to a modified ISO 11204 correction. The Brick Wall filter's success indicates that further attempts to match boom spectrum high-frequency roll-off beyond the contaminating noise floor are unnecessary and have marginal improvements on final metric calculations. Additionally, the Butterworth filter removes statistical correlation between ambient and boom levels for a real-world flight campaign, adding evidence that these techniques also work on other boom shapes. Overall, both filters can produce accurate metric calculations with only a few hundred hertz of positive signal-to-noise ratio. This work describes methods for accurate metric calculations in the presence of moderate noise contamination that should benefit X-59 and future low-boom supersonic aircraft testing. [ABSTRACT FROM AUTHOR]

(Soliman, The Accounting Review 83:823–853, 2008) finds that separating return on net operating assets (RNOA) into DuPont components—profit margin and asset turnover—improves prediction of future RNOA. (Dickinson, The Accounting Review 86:1969–1994, 2011) finds that a firm's life-cycle stage explains changes in future RNOA. (Vorst and Yohn, The Accounting Review 93:357–381, 2018) find that life-cycle calibration improves prediction more than industry grouping in prediction models that do not include the DuPont components. We unite and extend the above studies by using data updated since the early 2000s and performing out-of-sample tests. We show that the DuPont components continue to improve prediction of one-year-ahead RNOA. Industry grouping and life-cycle calibration using the components improve prediction further. The improvement by life-cycle calibration is stronger for mature companies, more R&D-intensive companies, less capital-intensive companies, and companies in less concentrated industries. Sell-side equity analysts and investors appear to initially rely more on basic prediction models than the expanded models that include DuPont components, industry grouping, and life-cycle calibration. While there is some evidence of investor surprise associated with the expanded models, hedge portfolios formed based on the expanded model predictions do not produce abnormal returns. [ABSTRACT FROM AUTHOR]

Insulin is a central autoantigen in the pathogenesis of T1D, and thymic epithelial cell expression of insulin under the control of the Autoimmune Regulator (Aire) is thought to be a key component of maintaining tolerance to insulin. In spite of this general working model, direct detection of this thymic selection on insulin-specific T cells has been somewhat elusive. Here, we used a combination of highly sensitive T cell receptor transgenic models for detecting thymic selection and sorting and sequencing of Insulin-specific CD4+ T cells from Aire-deficient mice as a strategy to further define their selection. This analysis revealed a number of unique t cell receptor (TCR) clones in Aire-deficient hosts with high affinity for insulin/major histocompatibility complex (MHC) ligands. We then modeled the thymic selection of one of these clones in Aire-deficient versus wild-type hosts and found that this model clone could escape thymic negative selection in the absence of thymic Aire. Together, these results suggest that thymic expression of insulin plays a key role in trimming and removing high-affinity insulin-specific T cells from the repertoire to help promote tolerance. [ABSTRACT FROM AUTHOR]

Clade I monkeypox virus (MPXV), which can cause severe illness in more people than clade II MPXVs, is endemic in the Democratic Republic of the Congo (DRC), but the country has experienced an increase in suspected cases during 2023-2024. In light of the 2022 global outbreak of clade II mpox, the increase in suspected clade I cases in DRC raises concerns that the virus could spread to other countries and underscores the importance of coordinated, urgent global action to support DRC's efforts to contain the virus. To date, no cases of clade I mpox have been detected outside of countries in Central Africa where the virus is endemic. CDC and other partners are working to support DRC's response. In addition, CDC is enhancing U.S. preparedness by raising awareness, strengthening surveillance, expanding diagnostic testing capacity for clade I MPXV, ensuring appropriate specimen handling and waste management, emphasizing the importance of appropriate medical treatment, and communicating guidance on the recommended contact tracing, containment, behavior modification, and vaccination strategies. [ABSTRACT FROM AUTHOR]

Simple Summary: Checkpoint-inhibitor-associated diabetes mellitus is a severely morbid immune-related adverse event that occurs from immunotherapy treatment during cancer therapy. Many patients and clinicians opt to discontinue therapy after this adverse event occurs while others choose to resume treatment. There are currently no data to inform this decision in terms of risks and benefits to the patient. This study aims to determine future risk for immune-related adverse events and cancer outcomes in patients who make this decision after experiencing diabetes mellitus. Immune checkpoint inhibitor (CPI)-induced diabetes mellitus (CPI-DM) is a rare immune-related adverse event (irAE). Patients and providers fear that continuing CPIs puts patients at risk for additional irAEs and thus may discontinue therapy. Currently, there are little data to inform this decision. Therefore, this study aims to elucidate whether discontinuing CPIs after diagnosis of CPI-DM impacts the development of future irAEs and cancer outcomes such as progression and death. Patients who developed CPI-DM during cancer treatment at UCSF from 1 July 2015 to 5 July 2023 were analyzed for cancer outcomes and irAE development. Fisher's exact tests, Student t-tests, Kaplan–Meier methods, and Cox regression were used as appropriate. Of the 43 patients with CPI-DM, 20 (47%) resumed CPIs within 90 days of the irAE, 4 (9%) patients restarted after 90 days, and 19 (44%) patients never restarted. Subsequent irAEs were diagnosed in 9 of 24 (38%) who resumed CPIs and 3 of 19 (16%) who discontinued CPIs (p = 0.17). There was no significant difference in death (p = 0.74) or cancer progression (p = 0.55) between these two groups. While our single-institution study did not show worse cancer outcomes after discontinuing CPIs, many variables can impact outcomes, which our study was not adequately powered to evaluate. A nuanced approach is needed to decide whether to continue CPI treatment after a severe irAE like CPI-DM. [ABSTRACT FROM AUTHOR]

We report the first case of imatinib use in an adolescent with diabetes and suggest that it impacts the natural course of disease. A 14-year-old male patient presented in diabetic ketoacidosis (DKA) and was diagnosed with presumed autoantibody-negative type 1 diabetes (T1D) as well as myeloid neoplasm with platelet-derived growth factor receptor beta (PDGFRB) rearrangement. After starting exogenous insulin and imatinib, he experienced a 1.7-point reduction in glycated hemoglobin (HbA1c) and a 71% reduction in insulin requirement with sustained partial diabetes remission. Our case suggests imatinib as a potential therapeutic agent for pediatric T1D. [ABSTRACT FROM AUTHOR]

People living with HIV (PWH) have been shown to bear a higher burden of hepatitis B virus (HBV) due to shared routes and risk factors for transmission. Populations such as men who have sex with men (MSM) are at an increased risk of both being infected with HBV and HIV, that places them at higher risk of hepatocellular carcinoma. Using weighted and adjusted multilevel logistic regression, we characterized the prevalence and correlates of hepatitis B surface antigen (HBsAg) among MSM living with HIV across 12 Indian cities from 2012 to 2013. Overall, the prevalence of HBsAg was 8% (range across cities: 0.5%–19%). Being between the ages of 25–34, and 35–44 increased the odds of having chronic HBV infection compared to MSM 24 years or younger. Daily or seasonal employment and being unemployed increased the odds of HBsAg prevalence compared to those with monthly or weekly wages. Sexual risk behaviours such as having had sex with both men and women in the prior 6 months and history of sex work increased the odds of having HBV. Ever having insertive sex with a man or hijra (assigned male at birth, currently identifies as female/nonbinary) was negatively associated with HBV. Despite the existence of efficacious vaccines, HBV continues to have high prevalence among PWHs. Programmes to increase early screening, vaccinations and HBV literacy are urgently needed. Integrating HBV and HIV programmes for MSM populations could be critical in addressing this dual burden and improving outcomes for both infections. [ABSTRACT FROM AUTHOR]

Background The 2022 outbreak of the clade IIb monkeypox virus and subsequent global spread lead to an urgent need for the development of high-throughput, sensitive, and reproducible diagnostic tests. Methods We developed 3 assays to detect monkeypox virus, 2 (MPXV+ and MPXV) for m2000 RealTime and 1 (MPXV) for Alinity m platforms. Dual targets in E9L and B6R (MPXV+) and J2L and B7R (MPXV) increased mutation resistance. In silico prediction indicates MPXV+ cross-reactivity with orthopox viruses and specific monkeypox virus detection with MPXV. Results m2000 RealTime MPXV+ and MPXV assay sensitivity was determined to be 3.2 plaque-forming units/mL using a reference virus culture diluted into universal transport medium (UTM). Alinity m MPXV lower limit of detection was 200 copies/mL using monkeypox virus plasmids in pooled UTM matrix. m2000 RealTime MPXV+ and MPXV assays were validated with lesion swabs in UTM and 1:1 saliva to UTM mixtures. Commercially available and remnant clinical lesion specimens in UTM were tested with RealTime MPXV+, RealTime MPXV and Alinity m MPXV assays and demonstrated high agreement to known mpox (MPX)-positive specimens. Conclusions RealTime MPXV+, RealTime MPXV, and Alinity MPXV are high throughput and sensitive assays used for the detection of monkeypox virus. These assays maybe useful during MPX outbreaks. [ABSTRACT FROM AUTHOR]

Deciding where to implement actions for biodiversity conservation remains challenging for many reasons, including the increase in maps aimed at prioritizing locations for conservation efforts. Although a growing numbers of maps can create the perception of uncertainty and competing science, a shared set of principles underlie many mapping initiatives. We overlaid the priority areas identified by a subset of maps to assess the extent to which they agree. The comparison suggests that when maps are used without understanding their origin, confusion seems justified: The union of all maps covers 73% of the contiguous United States, whereas the intersection of all maps is at least 3.5%. Our findings support the need to place a strong focus on the principles and premises underpinning the maps and the end users' intentions. We recommend developing a science-based guidance to aid scientists, policymakers, and managers in selecting and applying maps for supporting on-the-ground decisions addressing biodiversity loss and its interconnected crises. [ABSTRACT FROM AUTHOR]

The role of the autoimmune regulator (Aire) in central immune tolerance and thymic self-representation was first described more than 20 years ago, but fascinating new insights into its biology continue to emerge, particularly in the era of advanced single-cell genomics. We briefly describe the role of human genetics in the discovery of Aire, as well as insights into its function gained from genotype–phenotype correlations and the spectrum of Aire-associated autoimmunity—including insights from patients with Aire mutations with broad and diverse implications for human health. We then highlight emerging trends in Aire biology, focusing on three topic areas. First, we discuss medullary thymic epithelial diversity and the role of Aire in thymic epithelial development. Second, we highlight recent developments regarding the molecular mechanisms of Aire and its binding partners. Finally, we describe the rapidly evolving biology of the identity and function of extrathymic Aire-expressing cells (eTACs), and a novel eTAC subset called Janus cells, as well as their potential roles in immune homeostasis. [ABSTRACT FROM AUTHOR]

There exists significant heterogeneity in the 'freshness' of consumer marine- and plant-derived omega-3 (Ω3) supplements. Fears of rancidity, or the oxidation of consumer Ω3 supplements, has been debated in the literature with several prior authors reporting contradictory findings. We report the peroxide value (PV), para-anisidine value (p-AV) and total oxidation values (TOTOX) associated with 72 consumer Ω3 supplements sold in the United States sampled from 2014–2020. The effect of flavoring on the oxidation of the supplements was examined in an adjusted fixed effects model controlling for type of delivery system (enteric, liquid, animal- and vegetable-derived gelatin softgel, spray), source (algae, calamari, fish, krill, mussels), and certifications assigned by third-party organizations (e.g. USP). Overall, our results revealed that 68% (23/34) of flavored and 13% (5/38) unflavored consumer Ω3 supplements exceeded the TOTOX upper limit set by the Global Organization for EPA and DHA (GOED) voluntary monograph standard of ≤ 26, with 65% (22/34) flavored supplements and 32% (12/38) unflavored supplements failing the PV upper limit of ≤ 5 and 62% (21/34) flavored supplements exceeding the p-AV upper limit of ≤ 20. To our knowledge, no prior authors have modeled the impact of flavoring on oxidative status in 72 marine- and plant-derived Ω3 products sold in the U.S. We present our findings in this context and discuss the clinical implications related to the consumption of oxidized consumer fish oils and their effects on human health. [ABSTRACT FROM AUTHOR]

This work introduces the Queen's University Agent-Based Outbreak Outcome Model (QUABOOM). This tool is an agent-based Monte Carlo simulation for modelling epidemics and informing public health policy. We illustrate the use of the model by examining capacity restrictions during a lockdown. We find that public health measures should focus on the few locations where many people interact, such as grocery stores, rather than the many locations where few people interact, such as small businesses. We also discuss a case where the results of the simulation can be scaled to larger population sizes, thereby improving computational efficiency. [ABSTRACT FROM AUTHOR]

Thymic epithelial cells are indispensable for T cell maturation and selection and the induction of central immune tolerance. The self-peptide repertoire expressed by medullary thymic epithelial cells is in part regulated by the transcriptional regulator Aire (Autoimmune regulator) and the transcription factor Fezf2. Due to the high complexity of mTEC maturation stages (i.e., post-Aire, Krt10+ mTECs, and Dclk1+ Tuft mTECs) and the heterogeneity in their gene expression profiles (i.e., mosaic expression patterns), it has been challenging to identify the additional factors complementing the transcriptional regulation. We aimed to identify the transcriptional regulators involved in the regulation of mTEC development and self-peptide expression in an unbiased and genomewide manner. We used ATAC footprinting analysis as an indirect approach to identify transcription factors involved in the gene expression regulation in mTECs, which we validated by ChIP sequencing. This study identifies Fezf2 as a regulator of the recently described thymic Tuft cells (i.e., Tuft mTECs). Furthermore, we identify that transcriptional regulators of the ELF, ESE, ERF, and PEA3 subfamily of the ETS transcription factor family and members of the Krüppel-like family of transcription factors play a role in the transcriptional regulation of genes involved in late mTEC development and promiscuous gene expression. [ABSTRACT FROM AUTHOR]

Rust fungi (Pucciniales, Basidiomycota) are a species-rich (ca. 8000 species), globally distributed order of obligate plant pathogens. Rust species are host-specific, and as a group they cause disease on many of our most economically and/or ecologically significant plants. As such, the ability to accurately and rapidly identify these fungi is of particular interest to mycologists, botanists, agricultural scientists, farmers, quarantine officials, and associated stakeholders. However, the complexities of the rust life cycle, which may include production of up to five different spore types and alternation between two unrelated host species, have made standard identifications, especially of less-documented spore states or alternate hosts, extremely difficult. The Arthur Fungarium (PUR) at Purdue University is home to one of the most comprehensive collections of rust fungi in the world. Using material vouchered in PUR supplemented with fresh collections we generated DNA barcodes of the 28S ribosomal repeat from > 3700 rust fungal specimens. Barcoded material spans 120 genera and > 1100 species, most represented by several replicate sequences. Barcodes and associated metadata are hosted in a publicly accessible, BLAST searchable database called Rust HUBB (Herbarium-based Universal Barcode Blast) and will be continuously updated. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the recently reported relative diagnostic accuracy of US, CT, MRI, and cholescintigraphy for diagnosing acute cholecystitis. Methods: 2 radiologists independently performed systematic electronic searches for articles published between 2000 and 2021 and applied inclusion/exclusion criteria. 2 different radiologists extracted data from the articles and scored each with a methodological quality tool. Pooled estimates of sensitivity and specificity were calculated with a bivariate linear mixed model. A second analysis made head-to-head comparisons (US vs. CT, US vs. cholescintigraphy). Factors were also analyzed for potential confounding effects on diagnostic accuracy. Results: Of 6121 initial titles, 22 were included. The prevalence of cholecystitis varied widely across studies (9.4–98%). Pooled sensitivity and specificity estimates were 69% (confidence limit [CL] 62–76%) and 79% (CL 71–86%) for US, 91% (CL 86–94%) and 63% (CL 51–74%) for cholescintigraphy, 78% (CL 69–84%) and 81% (CL 71–88%) for CT, and 91% (CL 78–97%) and 93% (CL 70–99%) for MRI. Regarding head-to-head comparisons, the sensitivity of CT (87.6%, CL 70–96%) was significantly higher than US (66.8%, CL 43–84%), while specificities (81.7% with CL 54–95% for US, 91.9% with CL 67–99% for CT) were similar. The sensitivity of cholescintigraphy (87.4%, CL 76–94%) was significantly greater than US (61.6%, CL 44–77%), while the specificity of US (82%, CL 65–92%) was significantly higher than cholescintigraphy (68%, CL 47–84%). Conclusion: Recent data suggests that CT may have a higher sensitivity than US for diagnosing acute cholecystitis, with similar specificity. Cholescintigraphy remains a highly sensitive modality with lower specificity than previously reported. MRI remains under studied, but with promising results. [ABSTRACT FROM AUTHOR]

Purpose: To compare outcomes of robotic and open repair for uncomplicated, moderate-sized, midline ventral hernias. Methods: From 2017 to 2021, patient characteristics and 30 day outcomes for all ventral hernias at our center were prospectively collected. We studied hernias potentially suitable for robotic repair: elective, midline, 3–10 cm rectus separation, no prior mesh, and no need for concomitant procedure. Robotic or open repair was performed by surgeon or patient preference. The primary outcome was any complication using Clavien–Dindo scoring. Secondary outcomes were operative time, length-of-stay, and readmissions. Regression identified predictors of complications. Results: Of 648 hernias repaired, 70 robotic and 52 open repairs met inclusion criteria. The groups had similar patient demographics, co-morbidities, and hernia size, except that there were more immunosuppressed patients in the open group (11 versus 5 patients, p = 0.031). Complications occurred after 7 (13%) open repairs versus 2 (3%) robotic repairs, p = 0.036. Surgical site infection occurred after four open repairs but no robotic repair, p = 0.004. Length-of-stay averaged almost 3 days longer after open repair (4.3 ± 2.7 days versus 1.5 ± 1.4 days, p = 0.031). Readmission occurred after 6 (12%) oppen repairs but only 1 (1%) robotic repair. A long-term survey (61% response rate after mean follow-up of 2.8 years) showed that the HerQLes QOL score was better after robotic repair (46 ± 15 versus 40 ± 17, = 0.049). In regression models, only open technique predicted complications. Conclusions: Robotic techniques were associated with fewer complications, shorter hospitalization, fewer infections, and fewer readmissions compared to open techniques. Open surgical technique was the only predictor of complications. [ABSTRACT FROM AUTHOR]

Intellectual property safeguards should be more widely incorporated into the bilateral contracts that underpin the translational R&D process to preserve the public interest, especially where public funds and resources have spearheaded the innovation process. [ABSTRACT FROM AUTHOR]