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Illuminated bridges have become important assets to navigable aquatic systems. However, if artificial light at night (ALAN) from illuminated bridges reaches aquatic habitats, such as rivers, it can threaten the river's natural heterogeneity and alter the behavioural responses of migratory fish. Here, via a pilot study, we quantified levels of ALAN at illuminated bridges that cross a river and, propose a conceptual model to estimate its potential implications on two migrating fish species with contrasting life histories. Night-time light measurements on the river Spree in Berlin were performed continuously along a transect and in detail at seven illuminated bridges. Photometric data of the pilot study showed rapidly increased and decreased light levels at several illuminated bridges from which we derived several model illumination scenarios. These illumination scenarios and their potential effect on migrating Atlantic salmon smolts (Salmo salar) and European silver eel (Anguilla anguilla) are presented as a conceptual model, considering illuminated bridges as behavioural barriers to fish migration. ALAN's adverse effects on freshwater habitats must be better researched, understood, managed, and properly communicated to develop future sustainable lighting practices and policies that preserve riverscapes and their biodiversity.

Abstract There are epidemiological associations between obesity and type 2 diabetes, cardiovascular disease and Alzheimer’s disease. The role of amyloid beta 42 (Aβ42) in these diverse chronic diseases is obscure. Here we show that adipose tissue releases Aβ42, which is increased from adipose tissue of male mice with obesity and is associated with higher plasma Aβ42. Increasing circulating Aβ42 levels in male mice without obesity has no effect on systemic glucose homeostasis but has obesity-like effects on the heart, including reduced cardiac glucose clearance and impaired cardiac function. The closely related Aβ40 isoform does not have these same effects on the heart. Administration of an Aβ-neutralising antibody prevents obesity-induced cardiac dysfunction and hypertrophy. Furthermore, Aβ-neutralising antibody administration in established obesity prevents further deterioration of cardiac function. Multi-contrast transcriptomic analyses reveal that Aβ42 impacts pathways of mitochondrial metabolism and exposure of cardiomyocytes to Aβ42 inhibits mitochondrial complex I. These data reveal a role for systemic Aβ42 in the development of cardiac disease in obesity and suggest that therapeutics designed for Alzheimer’s disease could be effective in combating obesity-induced heart failure.

The blood-brain barrier (BBB) prevents antibodies from penetrating the CNS and limits conventional antibody-based approaches to brain tumors. We now show that ENT2, a transporter that regulates nucleoside flux at the BBB, may offer an unexpected path to circumventing this barrier to allow targeting of brain tumors with an anti-DNA autoantibody. Deoxymab-1 (DX1) is a DNA-damaging autoantibody that localizes to tumors and is synthetically lethal to cancer cells with defects in the DNA damage response. We found that DX1 penetrated brain endothelial cells and crossed the BBB, and mechanistic studies identify ENT2 as the key transporter. In efficacy studies, DX1 crosses the BBB to suppress orthotopic glioblastoma and breast cancer brain metastases. ENT2-linked transport of autoantibodies across the BBB has potential to be exploited in brain tumor immunotherapy, and its discovery raises hypotheses on actionable mechanisms of CNS penetration by neurotoxic autoantibodies in CNS lupus.

Elasmosaurid plesiosaurian remains have been documented from non-marine to paralic (fluvial to estuarine) sediments of the upper Campanian Dinosaur Park Formation (DPF) of southern Alberta since 1898. Despite this long collection history, this material has received relatively little research attention, largely due to the highly fragmentary nature of most recovered specimens. However, this assemblage is significant, as it constitutes a rare occurrence of plesiosaurian remains in a non-marine depositional environment. This study reports on a recently collected and prepared specimen, which represents the most complete elasmosaurid yet collected from the DPF. This specimen preserves the trunk region, the base of the neck and tail, a partial fore and hind limb, and tooth, and is sufficiently complete to be assigned as the holotype of a new genus and species. This new taxon is diagnosed by a distinctive character state combination including a boomerang-shaped clavicular arch with acute anterior process, convex anterolateral margin, deeply embayed posterior margin, and pronounced ventral keel, together with the presence of 22 dorsal vertebrae, and the anterior dorsal centra bearing a ventral notch. The DPF plesiosaurian fossils were recovered from both estuarine/bay and fluvial palaeochannel sediments. The holotype skeleton represents an osteologically mature individual with an estimated body length of around 5 m, although the largest referred DPF elasmosaurid might have been closer to 7 m, which is considerably larger than other plesiosaurians reported from non-marine deposits. This suggests small-body lengths relative to typical elasmosaurids from marine settings, but is consistent with other plesiosaurians recovered from non-marine sediments. The identification of a distinct elasmosaurid taxon in the DPF might be evidence of niche-partitioning among the predominantly oceanic members of the ubiquitous plesiosaurian clade.

Abstract Background The Health Information Technology for Economic and Clinical Health Act of 2009 introduced the Meaningful Use program to incentivize the adoption of electronic health records (EHRs) in the U.S. This study investigates the disparities in EHR adoption and interoperability between rural and urban physicians in the context of federal programs like the Medicare Access and CHIP Reauthorization Act of 2015 and the 21st Century Cures Act. Methods A cross-sectional analysis was conducted using the 2021 Quality Payment Program Experience Report Public Use File to compare EHR adoption and Promoting Interoperability scores (PISs) between urban and rural physician participants. Data were linked with the Certified Health IT Product List to assess certified EHR adoption and interoperability. Results The study included 209,152 physician participants, 12% of whom practiced in rural communities. EHR adoption was significantly higher in urban (74%) than in rural areas (64%). Epic Systems dominated the market in both settings. Multivariable logistic regression indicated lower odds of EHR adoption among rural physicians (OR: 0.79, CI: 0.76–0.82). Rural physicians also had lower PISs (β: –3.5, CI: –4.1 to –3.0). Factors like extreme hardship, small practitioner status, and location in a health professional shortage area significantly impacted EHR adoption and PISs. Conclusions Significant disparities exist in EHR adoption and interoperability between rural and urban physicians. These disparities highlight the need for targeted interventions to enhance EHR adoption and interoperability in rural settings to ensure equitable access to healthcare technologies and improved patient outcomes across all communities.

Chasmosaurine ceratopsids are well documented from the Upper Cretaceous (Campanian) Dinosaur Park Formation (DPF) of southern Alberta and Saskatchewan, and include Chasmosaurus belli, Chasmosaurus russelli, Mercuriceratops gemini, Vagaceratops irvinensis, and material possibly referable to Spiclypeus shipporum. In this study, we describe three recently prepared chasmosaurine skulls (CMN 8802, CMN 34829, and TMP 2011.053.0046) from the DPF, and age-equivalent sediments, of Alberta. CMN 8802 and CMN 34829 are both referred to Chasmosaurus sp. based on the size and shape of the preserved parietal fenestrae. TMP 2011.053.0046 is referred to Vagaceratops sp. based on the position and orientation of its preserved epiparietals. Each skull is characterized by the presence of an accessory fenestra in either the squamosal (CMN 8802 and TMP 2011.053.0046) or parietal (CMN 34829). Such fenestrae are common occurrences in chasmosaurine squamosals, but are rare in the parietal portion of the frill. The origin of the fenestrae in these three specimens is unknown, but they do not appear to exhibit evidence of pathology, as has been previously interpreted for the accessory fenestrae in most other chasmosaurine frills. These three skulls contribute to a better understanding of the morphological variation, and geographic and stratigraphic distribution, of chasmosaurines within the DPF and age-equivalent sediments in Western Canada.

The?"Urban STEM Collaboratory" is a five-year project sponsored by the National Science Foundation (NSF) that addresses challenges to student success in STEM disciplines through a multi-institutional collaboration via?the?University of Memphis (UofM), University of Colorado Denver (CU Denver), and Indiana University-Purdue University Indianapolis (IUPUI). Study groups, tutoring, peer and faculty mentoring, and career exploration programs are being used across the three campuses to increase the participants' commitment to a STEM field. Innovative features from "CourseNetworking" (CN) software are being deployed to provide scholars with evidence of their learning journey while expanding a meaningful academic cloud-based social network. This paper extends a previous introductory ASEE conference paper titled: "Launching the Urban STEM Collaboratory," (Author, et al., 2020), which outlined the initial efforts of the tri-campus collaboration. The purpose of the present paper is to summarize the impact of the project, including data analysis of effectiveness, for Year 1: 2019-2020 and Year 2: 2020-2021. Although still in progress, with the longitudinal efficacy of several of the project's components undetermined, the project's organizational structure, activities, and findings to date should be of value to others conducting or proposing projects with similar goals.

Abstract The Black Summer fire season of 2019–2020 in southeastern Australia contributed to an intense ‘super outbreak’ of fire-induced and smoke-infused thunderstorms, known as pyrocumulonimbus (pyroCb). More than half of the 38 observed pyroCbs injected smoke particles directly into the stratosphere, producing two of the three largest smoke plumes observed at such altitudes to date. Over the course of 3 months, these plumes encircled a large swath of the Southern Hemisphere while continuing to rise, in a manner consistent with existing nuclear winter theory. We connect cause and effect of this event by quantifying the fire characteristics, fuel consumption, and meteorology contributing to the pyroCb spatiotemporal evolution. Emphasis is placed on the unusually long duration of sustained pyroCb activity and anomalous persistence during nighttime hours. The ensuing stratospheric smoke plumes are compared with plumes injected by significant volcanic eruptions over the last decade. As the second record-setting stratospheric pyroCb event in the last 4 years, the Australian super outbreak offers new clues on the potential scale and intensity of this increasingly extreme fire-weather phenomenon in a warming climate.

Abstract Objective To analyse data from 2016–17 from a hospital-based antimicrobial resistance surveillance with national coverage in a network of hospitals Viet Nam. Methods We analysed data from 13 hospitals, 3 less than the dataset from the 2012–13 period. Identification and antimicrobial susceptibility testing data from the clinical microbiology laboratories from samples sent in for routine diagnostics were used. Clinical and Laboratory Standards Institute 2018 guidelines were used for antimicrobial susceptibility testing interpretation. WHONET was used for data entry, management and analysis. Results 42,553 deduplicated isolates were included in this analysis; including 30,222 (71%) Gram-negative and 12,331 (29%) Gram-positive bacteria. 8,793 (21%) were from ICUs and 7,439 (18%) isolates were from invasive infections. Escherichia coli and Staphylococcus aureus were the most frequently detected species with 9,092 (21%) and 4,833 isolates (11%), respectively; followed by Klebsiella pneumoniae (3,858 isolates – 9.1%) and Acinetobacter baumannii (3,870 isolates – 9%). Bacteria were mainly isolated from sputum (8,798 isolates – 21%), blood (7,118 isolates – 17%) and urine (5,202 isolates – 12%). Among Gram-positives 3,302/4,515 isolates (73%) of S. aureus were MRSA; 99/290 (34%) of Enterococcus faecium were resistant to vancomycin; and 58% (663/1,136) of Streptococcus pneumoniae proportion were reduced susceptible to penicillin. Among Gram-negatives 59% (4,085/6,953) and 40% (1,186/2,958) of E. coli and K. pneumoniae produced ESBL and 29% (376/1,298) and 11% (961/8,830) were resistant to carbapenems, respectively. 79% (2855/3622) and 45% (1,514/3,376) of Acinetobacter spp. and Pseudomonas aeruginosa were carbapenem resistant, respectively. 88% (804/911) of Haemophilus influenzae were ampicillin resistant and 18/253 (7%) of Salmonella spp. and 7/46 (15%) of Shigella spp. were resistant to fluoroquinolones. The number of isolates from which data were submitted in the 2016–2017 period was twice as high as in 2012–2013. AMR proportions were higher in 2016–2017 for most pathogen-antimicrobial combinations of interest including imipenem-resistant A. baumannii, P. aeruginosa and Enterobacterales. Conclusions The data show alarmingly high and increasing resistant proportions among important organisms in Viet Nam. AMR proportions varied across hospital types and should be interpreted with caution because existing sampling bias and missing information on whether isolates were community or hospital acquired. Affordable and scalable ways to adopt a sample- or case-based approach across the network should be explored and clinical data should be integrated to help provide more accurate inferences of the surveillance data.

Abstract The infiltration of chronic lymphocytic leukemia (CLL) cells into lymphoid organs correlates with disease severity. CXCL12 is a key chemotactic factor for the trafficking of CLL. Tissue factor pathway inhibitor (TFPI) is a serine protease inhibitor and plays a role in CXCL12-mediated hematopoietic stem cell homing. We aim to explore the role of TFPI in CXCL12-mediated migration of CLL cells. In this study, plasma TFPI concentrations were measured by ELISA. CLL cells were isolated from patients and used for trans-endothelial migration (TEM) assays. Quantitative RT-PCR and Western blotting were used to detect the expression of CXCR7, CXCR4 and β-catenin. Immunofluorescence and co-immunoprecipitation was used to detect the binding of TFPI and glypican-3 (GPC3). We found that plasma TFPI levels in CLL patients were higher than in healthy controls, particularly in the patients with advanced disease. TFPI enhanced CXCL12-mediated TEM of CLL cells by increasing the expression of the CXCL12 receptor CXCR7, but not of the CXCL12 receptor CXCR4. The effect of TFPI on TEM was abolished by the CXCR7 inhibitor, CCX771, while the CXCR4 inhibitor AMD3100 strongly increased TEM. TFPI co-localized with GPC3 on the cell surface. An antibody to GPC3, HS20, decreased CXCR7 expression and abolished the effect of TFPI on TEM. TFPI activated β-catenin and the Wnt/β-catenin inhibitor IWP4 repressed the effect of TFPI on CXCR7 expression and TEM. We conclude that TFPI may contribute to organ infiltration in CLL patients.

Abstract Background Diarrhoeagenic Escherichia coli (DEC) infections are common in children in low-middle income countries (LMICs). However, detecting the various DEC pathotypes is complex as they cannot be differentiated by classical microbiology. We developed four multiplex real-time PCR assays were to detect virulence markers of six DEC pathotypes; specificity was tested using DEC controls and other enteric pathogens. PCR amplicons from the six E. coli pathotypes were purified and amplified to be used to optimize PCR reactions and to calculate reproducibility. After validation, these assays were applied to clinical samples from healthy and diarrhoeal Vietnamese children and associated with clinical data. Results The multiplex real-time PCRs were found to be reproducible, and specific. At least one DEC variant was detected in 34.7% (978/2815) of the faecal samples from diarrhoeal children; EAEC, EIEC and atypical EPEC were most frequent Notably, 41.2% (205/498) of samples from non-diarrhoeal children was positive with a DEC pathotype. In this population, only EIEC, which was detected in 34.3% (99/289) of diarrhoeal samples vs. 0.8% (4/498) non-diarrhoeal samples (p

Cancer associated fibroblasts (CAFs) have been suggested to regulate cancer cell metabolism, but the mechanisms are not completely elucidated. Here, the authors show that low FAK expression in stromal cells correlates with poor prognosis in breast and pancreatic cancer patients and that FAK-silencing in CAFs promotes tumourigenesis by the paracrine regulation of cancer cell metabolism.

Summary: Pregnancy represents a unique tolerogenic immune state which may alter susceptibility to infection and vaccine response. Here, we characterized humoral immunity to seasonal influenza vaccine strains in pregnant and non-pregnant women. Although serological responses to influenza remained largely intact during late pregnancy, distinct modifications were observed. Pregnant women had reduced hemagglutinin subtype-1 (H1)- IgG, IgG1, IgG2, and IgG3, hemagglutination inhibition, and group 1 and 2 stem IgG titers. Intriguingly, H1-specific avidity and FcγR1 binding increased, and influenza antibodies had distinct Fc and Fab glycans characterized by increased di-galactosylation and di-sialylation. H1-specific Fc-functionality (i.e. monocyte phagocytosis and complement deposition) was moderately reduced in pregnancy. Multivariate antibody analysis revealed two distinct populations (pregnant vs. non-pregnant) segregated by H1 FcγR1 binding, H1-IgG levels, and Fab and Fc glycosylation. Our results demonstrated a structural and functional modulation of influenza humoral immunity during pregnancy that was antigen-specific and consistent with reduced inflammation and efficient placental transport