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Abstract Rapid climatic warming of the Antarctic Peninsula is driving regional population declines and distribution shifts of predators and prey. Affected species include Antarctic ice seals and the southern elephant seal, all of which rely on the peninsula region for critical stages of their life cycle. However, data collection is difficult in this remote region, and therefore long-term time series with which to identify and investigate population trends in these species are rare. We present the Cape Shirreff Phocid Census (CS-PHOC) dataset: weekly counts of phocids (crabeater, leopard, southern elephant, and Weddell seals) hauled out at Cape Shirreff, Livingston Island, during most austral summers since 1997. Data from these censuses were cleaned and aggregated, resulting in robust and comparable count data from 284 censuses across 23 field seasons. The CS-PHOC dataset, which is publicly available through the SCAR Biodiversity Portal, will be updated yearly to provide important information about Southern Ocean phocids in the Antarctic Peninsula.

Abstract Background Prior case reports and animal studies have reported on potential ophthalmologic complications of babesiosis, but this issue has not previously been addressed in a cohort of patients with babesiosis. This cross-sectional descriptive pilot study evaluated the retinas of patients with acute babesiosis to determine if retinal abnormalities are a feature of the disease. Methods We screened all patients admitted to Yale New Haven Hospital with laboratory confirmed babesiosis during the summer of 2023 and obtained informed consent. Patients were interviewed and underwent pupil dilation and a retinal examination using an indirect ophthalmoscope. Demographic and clinical information were obtained by questionnaire and through chart review. Results Ten patients underwent retinal eye exams with results that were generally unremarkable. No study patients showed any signs of retinal inflammation, infection, retinal bleeding, retinal tears, or abnormal vessel formation that could be attributed to infection. Conclusion This small study did not find evidence of retinopathy in patients with babesiosis. Further studies with larger populations, repeated exams, and long term follow up will further elucidate the potential small vessel complications of human babesiosis.

Summary: Background: [177Lu]Lu-PSMA-617 (177Lu-PSMA-617) prolonged life in patients with metastatic castration-resistant prostate cancer (mCRPC) in VISION (NCT03511664). However, distinguishing between patients likely and unlikely to respond remains a clinical challenge. We present the first multivariable models of outcomes with 177Lu-PSMA-617 built using data from VISION, a large prospective phase 3 clinical trial powered for overall survival. Methods: Adults with progressive post androgen receptor pathway inhibitor and taxane prostate-specific membrane antigen (PSMA)-positive mCRPC received 177Lu-PSMA-617 plus protocol-permitted standard of care (SoC) or SoC alone. In this post hoc analysis, multivariable Cox proportional hazards models of overall survival (OS) and radiographic progression-free survival (rPFS), and a logistic regression model of prostate-specific antigen response (≥50% decline; PSA50) were constructed and evaluated using C-index or receiver operating characteristic (ROC) analyses with bootstrapping validation. Nomograms were constructed for visualisation. Findings: Patients were randomised between June 2018 and October 2019. Data from all 551 patients in the 177Lu-PSMA-617 arm were analysed in multivariable modelling. The OS nomogram (C-index, 0.73; 95% confidence interval [CI], 0.70–0.76) included whole-body maximum standardised uptake value (SUVmax), time since diagnosis, opioid analgesic use, aspartate aminotransferase, haemoglobin, lymphocyte count, presence of PSMA-positive lesions in lymph nodes, lactate dehydrogenase (LDH), alkaline phosphatase (ALP), and neutrophil count. The rPFS nomogram (C-index, 0.68; 0.65–0.72) included SUVmax, time since diagnosis, opioid analgesic use, lymphocyte count, presence of liver metastases by computed tomography, LDH, and ALP. The PSA50 nomogram (area under ROC curve, 0.72; 95% CI, 0.68–0.77) included SUVmax, lymphocyte count and ALP. Performances of the OS and rPFS models were maintained when they were reconstructed excluding SUVmax. Interpretation: These models of outcomes with 177Lu-PSMA-617 are the first built using prospective phase 3 data. They show that a combination of pretreatment laboratory, clinical, and imaging parameters, reflecting both patient and tumour status, influences outcomes. These models are important for aiding treatment selection, patient management, and clinical trial design. Funding: Novartis.

This work studies mathematical foundations for optimal boundary control of mixers which mix two fluid phases. Existence of optima is proved and the influence of common objective functionals is discussed.

Abstract Background Cost-effective production of biofuels from lignocellulose requires the fermentation of d-xylose. Many yeast species within and closely related to the genera Spathaspora and Scheffersomyces (both of the order Serinales) natively assimilate and ferment xylose. Other species consume xylose inefficiently, leading to extracellular accumulation of xylitol. Xylitol excretion is thought to be due to the different cofactor requirements of the first two steps of xylose metabolism. Xylose reductase (XR) generally uses NADPH to reduce xylose to xylitol, while xylitol dehydrogenase (XDH) generally uses NAD+ to oxidize xylitol to xylulose, creating an imbalanced redox pathway. This imbalance is thought to be particularly consequential in hypoxic or anoxic environments. Results We screened the growth of xylose-fermenting yeast species in high and moderate aeration and identified both ethanol producers and xylitol producers. Selected species were further characterized for their XR and XDH cofactor preferences by enzyme assays and gene expression patterns by RNA-Seq. Our data revealed that xylose metabolism is more redox balanced in some species, but it is strongly affected by oxygen levels. Under high aeration, most species switched from ethanol production to xylitol accumulation, despite the availability of ample oxygen to accept electrons from NADH. This switch was followed by decreases in enzyme activity and the expression of genes related to xylose metabolism, suggesting that bottlenecks in xylose fermentation are not always due to cofactor preferences. Finally, we expressed XYL genes from multiple Scheffersomyces species in a strain of Saccharomyces cerevisiae. Recombinant S. cerevisiae expressing XYL1 from Scheffersomyces xylosifermentans, which encodes an XR without a cofactor preference, showed improved anaerobic growth on xylose as the primary carbon source compared to S. cerevisiae strain expressing XYL genes from Scheffersomyces stipitis. Conclusion Collectively, our data do not support the hypothesis that xylitol accumulation occurs primarily due to differences in cofactor preferences between xylose reductase and xylitol dehydrogenase; instead, gene expression plays a major role in response to oxygen levels. We have also identified the yeast Sc. xylosifermentans as a potential source for genes that can be engineered into S. cerevisiae to improve xylose fermentation and biofuel production.

Abstract NEMO is a ubiquitin-binding protein which regulates canonical NF-κB pathway activation in innate immune signaling, cell death regulation and host-pathogen interactions. Here we identify an NF-κB-independent function of NEMO in proteostasis regulation by promoting autophagosomal clearance of protein aggregates. NEMO-deficient cells accumulate misfolded proteins upon proteotoxic stress and are vulnerable to proteostasis challenges. Moreover, a patient with a mutation in the NEMO-encoding IKBKG gene resulting in defective binding of NEMO to linear ubiquitin chains, developed a widespread mixed brain proteinopathy, including α-synuclein, tau and TDP-43 pathology. NEMO amplifies linear ubiquitylation at α-synuclein aggregates and promotes the local concentration of p62 into foci. In vitro, NEMO lowers the threshold concentrations required for ubiquitin-dependent phase transition of p62. In summary, NEMO reshapes the aggregate surface for efficient autophagosomal clearance by providing a mobile phase at the aggregate interphase favoring co-condensation with p62.

BackgroundBabesiosis is a worldwide emerging protozoan infection that is associated with a spectrum of disease severity from asymptomatic infection to severe organ damage and death. While effective treatment strategies are available, some immunocompromised patients experience severe acute and prolonged/relapsing illness due in part to an impaired host antibody response. Intravenous immunoglobulin (IVIG) has been used as an adjunctive therapy in some immunocompromised babesiosis patients, but its therapeutic effect is uncertain. We evaluated the presence of Babesia microti antibodies in commercial samples of IVIG.Methods/principle findingsThe presence of B. microti antibodies in commercial samples of IVIG were tested using an immunofluorescence assay. A subset of samples was then tested for B. microti antibodies using an enzyme linked immunosorbent assay. Out of 57 commercial IVIG samples tested using IFA, and 52 samples tested using ELISA, none were positive for B. microti antibodies.ConclusionsCommercially available IVIG may not be of therapeutic benefit for babesiosis patients. Additional sampling of IVIG for B. microti antibody and a clinical trial of babesiosis patients given IVIG compared with controls would provide further insight into the use of IVIG for the treatment of babesiosis.

Babesiosis is a globally distributed parasitic infection caused by intraerythrocytic protozoa. The full spectrum of neurologic symptoms, the underlying neuropathophysiology, and neurologic risk factors are poorly understood. Our study sought to describe the type and frequency of neurologic complications of babesiosis in a group of hospitalized patients and assess risk factors that might predispose patients to neurologic complications. We reviewed medical records of adult patients who were admitted to Yale-New Haven Hospital, New Haven, Connecticut, USA, during January 2011–October 2021 with laboratory-confirmed babesiosis. More than half of the 163 patients experienced >1 neurologic symptoms during their hospital admissions. The most frequent symptoms were headache, confusion/delirium, and impaired consciousness. Neurologic symptoms were associated with high-grade parasitemia, renal failure, and history of diabetes mellitus. Clinicians working in endemic areas should recognize the range of symptoms associated with babesiosis, including neurologic.

The pervasive presence of plastic in the environment has reached a concerning scale, being identified in many ecosystems. Bioremediation is the cheapest and most eco-friendly alternative to remove this polymer from affected areas. Recent work described that a novel cold-active esterase enzyme extracted from the bacteria Kaistella jeonii could promiscuously degrade PET. Compared to the well-known PETase from Ideonella sakaiensis, this novel esterase presents a low sequence identity yet has a remarkably similar folding. However, enzymatic assays demonstrated a lower catalytic efficiency. In this work, we employed a strict computational approach to investigate the binding mechanism between the esterase and PET. Understanding the underlying mechanism of binding can shed light on the evolutive mechanism of how enzymes have been evolving to degrade these artificial molecules and help develop rational engineering approaches to improve PETase-like enzymes. Our results indicate that this esterase misses a disulfide bridge, keeping the catalytic residues closer and possibly influencing its catalytic efficiency. Moreover, we describe the structural response to the interaction between enzyme and PET, indicating local and global effects. Our results aid in deepening the knowledge behind the mechanism of biological catalysis of PET degradation and as a base for the engineering of novel PETases.

Summary: Chaperone-mediated autophagy (CMA) and endosomal microautophagy (eMI) are pathways for selective degradation of cytosolic proteins in lysosomes and late endosomes, respectively. These autophagic processes share as a first step the recognition of the same five-amino-acid motif in substrate proteins by the Hsc70 chaperone, raising the possibility of coordinated activity of both pathways. In this work, we show the existence of a compensatory relationship between CMA and eMI and identify a role for the chaperone protein Bag6 in triage and internalization of eMI substrates into late endosomes. Association and dynamics of Bag6 at the late endosome membrane change during starvation, a stressor that, contrary to other autophagic pathways, causes a decline in eMI activity. Collectively, these results show a coordinated function of eMI with CMA, identify the interchangeable subproteome degraded by these pathways, and start to elucidate the molecular mechanisms that facilitate the switch between them.

Background: Non-melanoma skin cancers (NMSCs) are responsible for up to one-third of all human malignancies. Surgery is usually the treatment of choice, but patients often experience pain during the procedure. Topical rhenium-188 resin skin cancer treatment (RSCT) may be a valid therapeutic alternative. Methods: In this monocentric pilot study, 19 patients suffering from NMSC were treated with RSCT. Most of these patients had also experienced surgery, either because they developed a new NMSC in aftercare, or they had suffered previously from NMSC. Three RSCT-treated patients, who had no exposure to surgery so far, were paired with three matched patients, who had received surgery. We sought to evaluate and compare the patients’ experience with both treatments. A questionnaire assessed patients’ perceptions regarding side effects, aesthetic outcomes, wound care, fear of complications, and personal treatment preferences. Patients evaluated the different parameters of their either RSCT- or surgery-treated lesions on a scale from 0–10. Results: Patients were more afraid of complications before surgery than before RSCT (p = 0.04). Treatment with RSCT caused significantly less pain on treatment day (mean 0.56) than surgery (mean 2.32) (0 no pain, 10 maximum pain) (p = 0.02) and 14 days after the procedure (mean 0.89 versus mean 2.47) (p = 0.02). On day 14, RSCT-treated lesions were also significantly less itchy (mean 0.34) than after surgery (mean 1.50). Most patients were very satisfied with the aesthetic outcome after both RSCT (mean 8.42) and surgery (mean 8.31) (p = 0.89). In the case of a new NMSC, the majority of patients who experienced both treatments would rather be treated primarily with RSCT (44%) or would consider both options (31%); only 19% preferred surgery. Conclusion: Patients evaluated RSCT as less painful than surgery. The aesthetic outcomes of both treatments were comparable. For pain-sensitive patients, RSCT might be a preferable treatment option.

Background: Obesity during pregnancy is related to adverse maternal and neonatal outcomes. Factors involved in these outcomes may include increased maternal insulin resistance, inflammation, oxidative stress, and nutrient mishandling. The placenta is the primary determinant of fetal outcomes, and its function can be impacted by maternal obesity. The aim of this study on mice was to determine the effect of obesity on maternal lipid handling, inflammatory and redox state, and placental oxidative stress, inflammatory signaling, and gene expression relative to female and male fetal growth. Methods: Female mice were fed control or obesogenic high-fat/high-sugar diet (HFHS) from 9 weeks prior to, and during, pregnancy. On day 18.5 of pregnancy, maternal plasma, and liver, placenta, and fetal serum were collected to examine the immune and redox states. The placental labyrinth zone (Lz) was dissected for RNA-sequencing analysis of gene expression changes. Results: the HFHS diet induced, in the dams, hepatic steatosis, oxidative stress (reduced catalase, elevated protein oxidation) and the activation of pro-inflammatory pathways (p38-MAPK), along with imbalanced circulating cytokine concentrations (increased IL-6 and decreased IL-5 and IL-17A). HFHS fetuses were asymmetrically growth-restricted, showing sex-specific changes in circulating cytokines (GM-CSF, TNF-α, IL-6 and IFN-γ). The morphology of the placenta Lz was modified by an HFHS diet, in association with sex-specific alterations in the expression of genes and proteins implicated in oxidative stress, inflammation, and stress signaling. Placental gene expression changes were comparable to that seen in models of intrauterine inflammation and were related to a transcriptional network involving transcription factors, LYL1 and PLAG1. Conclusion: This study shows that fetal growth restriction with maternal obesity is related to elevated oxidative stress, inflammatory pathways, and sex-specific placental changes. Our data are important, given the marked consequences and the rising rates of obesity worldwide.

BackgroundAgricultural interventions are often recommended to address undernutrition in subsistence farming communities. However, intensified agriculture exposure can increase soil transmitted helminth (STH) infections, which are linked with poor child growth. This study examined impacts of the VERASAN public health and agricultural intervention program on preschool child growth attainment (HAZ and WAZ) and relative growth velocity over 7 months [change in height-for-age (∆HAD) and weight-for-age (∆WAD) difference].MethodsVERASAN was initiated in 15 subsistence farming communities in rural Panama experiencing chronic undernutrition. Activities targeted improved household food security, preschool child diets and growth by intensifying and diversifying household agriculture. Our objectives were to explore the relationship between VERASAN and preschool child growth attainment (HAZ and WAZ) and velocity (∆HAD and ∆WAD) during one agricultural cycle in 238 households. We compared those new to VERASAN with those involved for 1 or 5 years, and identified if agricultural practices, food security, diet diversity and treatment of pre-existing STH infection were associated with growth attainment or velocity.ResultsPrior participation in VERASAN did not directly influence WAZ, HAZ or ΔHAD but VERASAN-related benefits had an indirect influence. ΔHAD was positively associated with VERASAN-associated improvements in diet diversity and food security. HAZ and WAZ during land preparation were positively associated with diet diversity and HAZ with food security during harvest. HAZ was negatively associated with children visiting the agricultural plot, consuming leafy green vegetables and pre-existing hookworm infections. Both agricultural season and STH influenced ΔWAD. Children in VERASAN for 1 or 5 years experienced growth faltering between land preparation and growing season, but not those new to VERASAN. In contrast, between growing and harvest, ∆WAD declined in children new to VERASAN compared to children in VERASAN for longer. ΔWAD from land preparation to harvest was higher with pre-existing Ascaris infection whereas it was lower between growing season and harvest for pre-existing hookworm infection.ConclusionIn a context of preschool child growth faltering, malnutrition and STH infections, improved food security, agricultural production and diet diversity associated with VERASAN were associated with improved growth. In contrast, STH infections were negatively associated with some, but not all, growth outcomes.

Striped marlin use a dynamic prey division method when hunting as a group, taking turns to feed but without doing so equally.

Abstract The utility of amyloid positron emission tomography (PET) for the etiological diagnosis of dementia and its impact on functional status of patients in routine care are currently unclear. Here, we describe the design of ENABLE, a randomized controlled two‐armed coverage with evidence development (CED) study in Germany. Approximately 1126 patients with mild to moderate dementia of unclear etiology will be randomly assigned to either an amyloid PET or a no amyloid PET group. Patients will be followed‐up for 24 months. The study has been registered at the German Clinical Trials Register (https://drks.de/search/de/trial/DRKS00030839) with the registration code DRKS00030839. The primary endpoint of ENABLE is the ability to perform functional activities of daily living at 18 months. Secondary endpoints include change in diagnosis, diagnostic confidence, and cognitive and clinical outcomes of patients. We expect that the CED study ENABLE will inform about patient relevant effects of amyloid PET in routine care. Furthermore, we anticipate that ENABLE will support physicians’ and payers’ decisions on provision of health care for patients with dementia. Highlights Study design focuses on the usefulness of amyloid positron emission tomography (PET) in routine care. Study design addresses the patient‐relevant effect of amyloid PET. Patient representatives were involved in the creation of the study design. The study will help improve routine care for people with dementia.

Evaluating physiological responses in the context of a species’ life history, demographics, and ecology is essential to understanding the health of individuals and populations. Here, we measured the main mammalian glucocorticoid, cortisol, in an elusive Antarctic apex predator, the leopard seal (Hydrurga leptonyx). We also examined intraspecific variation in cortisol based on life history (sex), morphometrics (body mass, body condition), and ecological traits (δ15N, δ13C). To do this, blood samples, life history traits, and morphometric data were collected from 19 individual leopard seals off the Western Antarctic Peninsula. We found that adult leopard seals have remarkably high cortisol concentrations (100.35 ± 16.72 μg/dL), showing the highest circulating cortisol concentration ever reported for a pinniped: 147 μg/dL in an adult male. Leopard seal cortisol concentrations varied with sex, body mass, and diet. Large adult females had significantly lower cortisol (94.49 ± 10.12 μg/dL) than adult males (120.85 ± 6.20 μg/dL). Similarly, leopard seals with higher isotope values (i.e., adult females, δ15N: 11.35 ± 0.69‰) had lower cortisol concentrations than seals with lower isotope values (i.e., adult males, δ15N: 10.14 ± 1.65‰). Furthermore, we compared cortisol concentrations across 26 closely related Arctoid taxa (i.e., mustelids, bears, and pinnipeds) with comparable data. Leopard seals had the highest mean cortisol concentrations that were 1.25 to 50 times higher than other Arctoids. More broadly, Antarctic ice seals (Lobodontini: leopard seal, Ross seal, Weddell seal, crabeater seal) had higher cortisol concentrations compared to other pinnipeds and Arctoid species. Therefore, high cortisol is a characteristic of all lobodontines and may be a specialized adaptation within this Antarctic-dwelling clade. Together, our results highlight exceptionally high cortisol concentrations in leopard seals (and across lobodontines) and reveal high variability in cortisol concentrations among individuals from a single location. This information provides the context for understanding how leopard seal physiology changes with life history, ecology, and morphology and sets the foundation for assessing their physiology in the context of a rapidly changing Antarctic environment.

Absence seizures—generalized rhythmic spike-and-wave discharges (SWDs) are the defining property of childhood (CAE) and juvenile (JAE) absence epilepsies. Such seizures are the most compelling examples of pathological neuronal hypersynchrony. All the absence detection algorithms proposed so far have been derived from the properties of individual SWDs. In this work, we investigate EEG phase synchronization in patients with CAE/JAE and healthy subjects to explore the possibility of using the wavelet phase synchronization index to detect seizures and quantify their disorganization (fragmentation). The overlap of the ictal and interictal probability density functions was high enough to preclude effective seizure detection based solely on changes in EEG synchronization. We used a machine learning classifier with the phase synchronization index (calculated for 1 s data segments with 0.5 s overlap) and the normalized amplitude as features to detect generalized SWDs. Using 19 channels (10-20 setup), we identified 99.2% of absences. However, the overlap of the segments classified as ictal with seizures was only 83%. The analysis showed that seizures were disorganized in approximately half of the 65 subjects. On average, generalized SWDs lasted about 80% of the duration of abnormal EEG activity. The disruption of the ictal rhythm can manifest itself as the disappearance of epileptic spikes (with high-amplitude delta waves persisting), transient cessation of epileptic discharges, or loss of global synchronization. The detector can analyze a real-time data stream. Its performance is good for a six-channel setup (Fp1, Fp2, F7, F8, O1, O2), which can be implemented as an unobtrusive EEG headband. False detections are rare for controls and young adults (0.03% and 0.02%, respectively). In patients, they are more frequent (0.5%), but in approximately 82% cases, classification errors are caused by short epileptiform discharges. Most importantly, the proposed detector can be applied to parts of EEG with abnormal EEG activity to quantitatively determine seizure fragmentation. This property is important because a previous study reported that the probability of disorganized discharges is eight times higher in JAE than in CAE. Future research must establish whether seizure properties (frequency, length, fragmentation, etc.) and clinical characteristics can help distinguish CAE and JAE.

The present state of research in computational fluid dynamics (CFD) is marked by an ongoing process of refining numerical methods and algorithms with the goal of achieving accurate modeling and analysis of fluid flow and heat transfer phenomena. Remarkable progress has been achieved in the domains of turbulence modeling, parallel computing, and mesh generation, resulting in heightened simulation precision when it comes to capturing complex flow behaviors. Nevertheless, CFD faces a significant challenge due to the time and expertise needed for a meticulous simulation setup and intricate numerical techniques. To surmount this challenge, we introduce paint2sim—an innovative mobile application designed to enable on-the-fly 2D fluid simulations using a device’s camera. Seamlessly integrated with OpenLB, a high-performance Lattice Boltzmann-based library, paint2sim offers accurate simulations. The application leverages the capabilities of the Lattice Boltzmann Method (LBM) to model fluid behaviors accurately. Through a symbiotic interaction with the open-source OpenCV library, paint2sim can scan and extract hand-drawn simulation domains, affording the capability for instant simulation and visualization. Notably, paint2sim can also be regarded as a digital twin, facilitating just-in-time representation and analysis of 2D fluid systems. The implications of this technology extend significantly to both fluid dynamics education and industrial applications, effectively lowering barriers and rendering fluid simulations more accessible. Encouragingly, the outcomes of simulations conducted with paint2sim showcase promising qualitative and quantitative results. Overall, paint2sim offers a groundbreaking approach to mobile 2D fluid simulations, providing users with just-in-time visualization and accurate results, while simultaneously serving as a digital twin for fluid systems.

Zw 049.057 is a moderate-mass, dusty, early-type galaxy that hosts a powerful compact obscured nucleus (CON, L _FIR,CON ≥ 10 ^11 L _⊙ ). The resolution of the Hubble Space Telescope enabled measurements of the stellar light distribution and characterization of dust features. Zw 049.057 is inclined with a prominent three-zone disk; the R ≈ 1 kpc star-forming inner dusty disk contains molecular gas, a main disk with less dust and an older stellar population, and a newly detected outer stellar region at R > 6 kpc with circular isophotes. Previously unknown polar dust lanes are signatures of a past minor merger that could have warped the outer disk to near face-on. Dust transmission measurements provide lower limit gas mass estimates for dust features. An extended region with moderate optical depth and M ≥ 2 × 10 ^8 M _⊙ obscures the central 2 kpc. Optical spectra show strong interstellar Na D absorption with a constant velocity across the main disk, likely arising in this extraplanar medium. Opacity measurements of the two linear dust features, pillars, give a total mass of ≥10 ^6 M _⊙ , flow rates of ≥2 M _⊙ yr ^−1 , and few Myr flow times. Dust pillars are associated with the CON and are visible signs of its role in driving large-scale feedback. Our assessments of feedback processes suggest gas recycling sustains the CON. However, radiation pressure driven mass loss and efficient star formation must be avoided for the active galactic nucleus to retain sufficient gas over its lifespan to produce substantial mass growth of the central black hole.

This data brief presents leachate disposal and management data for 43 active or closed municipal solid waste (MSW) landfills and planar surface areas for 40 of those landfills in Ohio, USA. Data were extracted from publicly available Annual Operational Reports from the Ohio Environmental Protection Agency (Ohio EPA) and consolidated into a digital dataset of two delimited text files. A total of 9,985 data points represent monthly leachate disposal totals, arranged by management type and by landfill. Leachate management data for some landfills extend from 1988-2020 but are mostly limited to 2010-2020. Annual planar surface areas were identified from topographic maps in the annual reports. A total of 610 data points were created for the annual surface area dataset. This dataset aggregates and organizes the information, allowing for accessibility and increased application to engineering analysis and research projects.

During winter 2015/2016, the Arctic stratosphere was characterized by extraordinarily low temperatures in connection with a very strong polar vortex and with the occurrence of extensive polar stratospheric clouds. From mid-December 2015 until mid-March 2016, the German research aircraft HALO (High Altitude and Long-Range Research Aircraft) was deployed to probe the lowermost stratosphere in the Arctic region within the POLSTRACC (Polar Stratosphere in a Changing Climate) mission. More than 20 flights have been conducted out of Kiruna, Sweden, and Oberpfaffenhofen, Germany, covering the whole winter period. Besides total reactive nitrogen (NOy), observations of nitrous oxide, nitric acid, ozone, and water were used for this study. Total reactive nitrogen and its partitioning between the gas and particle phases are key parameters for understanding processes controlling the ozone budget in the polar winter stratosphere. The vertical redistribution of total reactive nitrogen was evaluated by using tracer–tracer correlations (NOy–N2O and NOy–O3). The trace gases are well correlated as long as the NOy distribution is controlled by its gas-phase production from N2O. Deviations of the observed NOy from this correlation indicate the influence of heterogeneous processes. In early winter no such deviations have been observed. In January, however, air masses with extensive nitrification were encountered at altitudes between 12 and 15 km. The excess NOy amounted to about 6 ppb. During several flights, along with gas-phase nitrification, indications for extensive occurrence of nitric acid containing particles at flight altitude were found. These observations support the assumption of sedimentation and subsequent evaporation of nitric acid-containing particles, leading to redistribution of total reactive nitrogen at lower altitudes. Remnants of nitrified air masses have been observed until mid-March. Between the end of February and mid-March, denitrified air masses have also been observed in connection with high potential temperatures. This indicates the downward transport of air masses that have been denitrified during the earlier winter phase. Using tracer–tracer correlations, missing total reactive nitrogen was estimated to amount to 6 ppb. Further, indications of transport and mixing of these processed air masses outside the vortex have been found, contributing to the chemical budget of the winter lowermost stratosphere. Observations within POLSTRACC, at the bottom of the vortex, reflect heterogeneous processes from the overlying Arctic winter stratosphere. The comparison of the observations with CLaMS model simulations confirm and complete the picture arising from the present measurements. The simulations confirm that the ensemble of all observations is representative of the vortex-wide vertical NOy redistribution.

PIEZO1 is a mechanosensitive cation channel implicated in shear stress-mediated endothelial-dependent vasorelaxation. Since altered shear stress patterns induce a pro-inflammatory endothelial environment, we analyzed transcriptional profiles of human endothelial cells to determine the effect of altered shear stress patterns and subsequent prooxidant and inflammatory conditions on PIEZO1 and mechanosensitive-related genes (MRG). In silico analyses were validated in vitro by assessing PIEZO1 transcript levels in both the umbilical artery (HUAEC) and vein (HUVEC) endothelium. Transcriptional profiling showed that PIEZO1 and some MRG associated with the inflammatory response were upregulated in response to high (15 dyn/cm2) and extremely high shear stress (30 dyn/cm2) in HUVEC. Changes in PIEZO1 and inflammatory MRG were paralleled by p65 but not KLF or YAP1 transcription factors. Similarly, PIEZO1 transcript levels were upregulated by TNF-alpha (TNF-α) in diverse endothelial cell types, and pre-treatment with agents that prevent p65 translocation to the nucleus abolished PIEZO1 induction. ChIP-seq analysis revealed that p65 bonded to the PIEZO1 promoter region, an effect increased by the stimulation with TNF-α. Altogether this data showed that NF-kappa B activation via p65 signaling regulates PIEZO1 expression, providing a new molecular link for prooxidant and inflammatory responses and mechanosensitive pathways in the endothelium.

Babesia spp. are tickborne parasites that cause the clinical infection babesiosis, which has an increasing incidence in the United States. We performed an analysis of hospitalizations in the United States during 2010–2016 in which babesiosis was listed as a diagnosis. We used the National Inpatient Sample database to characterize the epidemiology of Babesia–associated admissions, reflecting severe Babesia-related disease. Over a 7-year period, a total of 7,818 hospitalizations listed babesiosis as a primary or secondary admitting diagnosis. Hospitalizations were seasonal (71.2% occurred during June–August) and situated overwhelmingly in the Northeast and Midwest. The patients were predominantly male and of advanced age, which is consistent with the expected epidemiology. Despite a higher severity of illness in more than (58.5%), the mortality rate was low (1.6%). Comparison with state reporting data suggests that the number of hospitalized persons with babesiosis increased modestly during the observation period.

BackgroundBabesiosis is an emerging infectious disease caused by intraerythrocytic Babesia parasites that can cause severe disease and death. While blood type is known to affect the mortality of Plasmodium falciparum malaria patients, associations between red blood cell (RBC) antigens and Babesia microti infection and disease severity are lacking.MethodsWe evaluated RhD and ABO blood types of Babesia-infected (18S rRNA reactive) blood donors in 10 endemic states in the Northeastern and northern Midwestern United States. We also assessed possible associations between RhD and ABO blood types and disease severity among hospitalized babesiosis patients in Connecticut.ResultsA total of 768 Babesia-infected blood donors were analyzed, of which 750 (97.7%) had detectable B. microti-specific antibodies. B. microti-infected blood donors were more likely to be RhD- (OR of 1.22, p-value 0.024) than RhD+ donors. Hospitalized RhD- babesiosis patients were more likely than RhD+ patients to have high peak parasitemia (p-value 0.017), which is a marker for disease severity. No differences in RhD+ blood type were noted between residents of the Northeast (OR of 0.82, p-value 0.033) and the Midwest (OR of 0.74, p-value 0.23). Overall, ABO blood type was not associated with blood donor B. microti infection, however, B. microti-infected donors in Maine and New Jersey were more likely to be blood type B compared to non-type B (OR 2.49 [p = 0.008] and 2.07 [p = 0.009], respectively), while infected donors from Pennsylvania were less likely to be type B compared to non-type B (OR 0.32 [p = 0.02]).ConclusionsPeople expressing RhD antigen may have a decreased risk of B. microti infection and babesiosis severity. The association of B antigen with B. microti infection is less clear because the antigen appeared to be less prevalent in infected Pennsylvania blood donors but more prevalent in Maine and New Jersey infected donors. Future studies should quantify associations between B. microti genotypes, RBC antigens, and the frequency and severity of B. microti infection to increase our understanding of human Babesia pathogenesis and improve antibody, vaccine, and RBC exchange transfusion strategies.

Babesiosis developed in a 62-year-old immunocompetent physician, who had an uneventful recovery after receiving atovaquone and azithromycin. Three years later, babesiosis developed again, and he was again successfully given treatment. Clinical and laboratory evidence were highly supportive of Babesia reinfection. Healthcare professionals should be aware that reinfection might occur in babesiosis.

Abstract Background Cardiotoxicity resulting in heart failure (HF) is among the most dreaded complications of cancer therapy and can significantly impact morbidity and mortality. Leading professional societies in cardiology and oncology recommend improved access to hospice and palliative care (PC) for patients with cancer and advanced HF. However, there is a paucity of published literature on the use of PC in cardio-oncology, particularly in patients with HF and a concurrent diagnosis of cancer. Aims To identify existing criteria for referral to and early integration of PC in the management of cases of patients with cancer and patients with HF, and to identify assessments of outcomes of PC intervention that overlap between patients with cancer and patients with HF. Design Systematic literature review on PC in patients with HF and in patients with cancer. Data sources Databases including Ovid Medline, Ovid Embase, Cochrane Library, and Web of Science from January 2009 to September 2020. Results Sixteen studies of PC in cancer and 14 studies of PC in HF were identified after screening of the 8647 retrieved citations. Cancer and HF share similarities in their patient-reported symptoms, quality of life, symptom burden, social support needs, readmission rates, and mortality. Conclusion The literature supports the integration of PC into oncology and cardiology practices, which has shown significant benefit to patients, caregivers, and the healthcare system alike. Incorporating PC in cardio-oncology, particularly in the management of HF in patients with cancer, as early as at diagnosis, will enable patients, family members, and healthcare professionals to make informed decisions about various treatments and end-of-life care and provide an opportunity for patients to participate in the decisions about how they will spend their final days.

CD47-SIRPα interaction acts as a “don’t eat me” signal and is exploited by cancer to downregulate innate and adaptive immune surveillance. There has been intense interest to develop a mechanism of blockade, and we aimed to analyze the emerging data from early clinical trials. We performed a systematic review and meta-analysis of relevant databases and conference abstracts including clinical trials using CD47 and/or SIRPα inhibitors in cancer treatment. Nonlinear mixed models were applied for comparison of response and toxicity. We retrieved 317 articles, 24 of which were eligible. These included 771 response-evaluable patients with hematologic (47.1%) and solid tumors (52.9%). Of these, 6.4% experienced complete response, 10.4% partial response, and 26.1% stable disease for a 16.7% objective response rate (ORR), 42.8% disease control rate, and 4.8-month median duration of response. ORR was significantly higher for hematologic cancers (25.3%) than solid cancers (9.1%, p=0.042). Comparing by mechanism, seven CD47 monoclonal antibodies (mAbs) and six selective SIRPα blockers were given alone or combined with checkpoint inhibitors, targeted therapy, and/or chemotherapy. In solid cancers, selective SIRPα blockade showed a higher ORR (16.2%) than anti-CD47 mAbs (2.8%, p=0.079), which was significant for combination therapies (ORR 28.3% vs 3.0%, respectively, p=0.010). Responses were seen in head and neck, colorectal, endometrial, ovarian, hepatocellular, non-small cell lung, and HER2+gastroesophageal cancers. Dose-limiting toxicity (DLT) was seen in 3.3% of patients (5.4% anti-CD47 mAbs, 1.4% selective SIRPα blockers; p=0.01). The frequency of treatment-related adverse events (TRAEs) ≥grade 3 was 18.0%, similar between the two groups (p=0.082), and mostly laboratory abnormalities. For anti-CD47 mAbs, the most common toxicities included grade 1-2 fatigue (27.2%), headache (21.0%), and anemia (20.5%). For selective SIRPα blockers, these included grade 1-2 infusion reaction (23.1%) and fatigue (15.8%). Anti-CD47 mAbs were significantly more likely than selective SIRPα blockers to cause grade 1-2 fever, chills, nausea/vomiting, headache, and anemia. In conclusion, combination therapies using selective SIRPα blockade had higher response rates in solid tumors than anti-CD47 mAb combinations. Hematologic changes were the main TRAEs, and selective SIRPα blockers seemed to have a better grade 1-2 toxicity profile. Treatment was well-tolerated with minimal DLTs.

Wall-flow filters are applied in the exhaust treatment of internal combustion engines for the removal of particulate matter (PM). Over time, the pressure drop inside those filters increases due to the continuously introduced solid material, which forms PM deposition layers on the filter substrate. This leads to the necessity of regenerating the filter. During such a regeneration process, fragments of the PM layers can potentially rearrange inside single filter channels. This may lead to the formation of specific deposition patterns, which affect a filter’s pressure drop, its loading capacity and the separation efficiency. The dynamic formation process can still not consistently be attributed to specific influence factors, and appropriate calculation models that enable a quantification of respective factors do not exist. In the present work, the dynamic rearrangement process during the regeneration of a wall-flow filter channel is investigated. As a direct sequel to the investigation of a static deposition layer in a previous work, the present one additionally investigates the dynamic behaviour following the detachment of individual layer fragments as well as the formation of channel plugs. The goal of this work is the extension of the resolved particle methodology used in the previous work via a discrete method to treat particle–particle and particle–wall interactions in order to evaluate the influence of the deposition layer topology, PM properties and operating conditions on dynamic rearrangement events. It can be shown that a simple mean density methodology represents a reproducible way of determining a channel plug’s extent and its average density, which agrees well with values reported in literature. The sensitivities of relevant influence factors are revealed and their impact on the rearrangement process is quantified. This work contributes to the formulation of predictions on the formation of specific deposition patterns, which impact engine performance, fuel consumption and service life of wall-flow filters.

Abstract Background The vascular endothelium has important endocrine and paracrine roles, particularly in the regulation of vascular tone and immune function, and it has been implicated in the pathophysiology of a range of cardiovascular and inflammatory conditions. This study uses a series of transgenic murine models to explore for the first time the role of the hypoxia-inducible factors, HIF-1α and HIF-2α in the pulmonary and systemic circulations as potential regulators of systemic vascular function in normoxic or hypoxic conditions and in response to inflammatory stress. We developed a series of transgenic mouse models, the HIF-1α Tie2Cre, deficient in HIF1-α in the systemic and pulmonary vascular endothelium and the L1Cre, a pulmonary endothelium specific knockout of HIF-1α or HIF-2α. In vivo, arterial blood pressure and metabolic activity were monitored continuously in normal atmospheric conditions and following an acute stimulus with hypoxia (10%) or lipopolysaccharide (LPS). Ex vivo, femoral artery reactivity was assessed using wire myography. Results Under normoxia, the HIF-1α Tie2Cre mouse had increased systolic and diastolic arterial pressure compared to litter mate controls over the day–night cycle under normal environmental conditions. VO2 and VCO2 were also increased. Femoral arteries displayed impaired endothelial relaxation in response to acetylcholine mediated by a reduction in the nitric oxide dependent portion of the response. HIF-1α L1Cre mice displayed a similar pattern of increased systemic blood pressure, metabolic rate and impaired vascular relaxation without features of pulmonary hypertension, polycythaemia or renal dysfunction under normal conditions. In response to acute hypoxia, deficiency of HIF-1α was associated with faster resolution of hypoxia-induced haemodynamic and metabolic compromise. In addition, systemic haemodynamics were less compromised by LPS treatment. Conclusions These data show that deficiency of HIF-1α in the systemic or pulmonary endothelium is associated with increased systemic blood pressure and metabolic rate, a pattern that persists in both normoxic conditions and in response to acute stress with potential implications for our understanding of the pathophysiology of vascular dysfunction in acute and chronic disease.

Epithelial cells of human breast glands are exposed to various mechanical ECM stresses that regulate tissue development and homeostasis. Mechanoadaptation of breast gland tissue to ECM-transmitted shear stress remained poorly investigated due to the lack of valid experimental approaches. Therefore, we created a magnetic shear strain device that enabled, for the first time, to analyze the instant shear strain response of human breast gland cells. MCF10A-derived breast acini with basement membranes (BM) of defined maturation state and basoapical polarization were used to resemble breast gland morphogenesis in vitro. The novel biophysical tool was used to apply cyclic shear strain with defined amplitudes (≤15%, 0.2 Hz) over 22 h on living spheroids embedded in an ultrasoft matrix (

Borrelia miyamotoi is an emerging pathogen that causes a febrile illness and is transmitted by the same hard-bodied (ixodid) ticks that transmit several other pathogens, including Borrelia species that cause Lyme disease. B. miyamotoi was discovered in 1994 in Ixodes persulcatus ticks in Japan. It was first reported in humans in 2011 in Russia. It has subsequently been reported in North America, Europe, and Asia. B. miyamotoi infection is widespread in Ixodes ticks in the northeastern, northern Midwestern, and far western United States and in Canada. In endemic areas, human B. miyamotoi seroprevalence averages from 1 to 3% of the population, compared with 15 to 20% for B. burgdorferi. The most common clinical manifestations of B. miyamotoi infection are fever, fatigue, headache, chills, myalgia, arthralgia, and nausea. Complications include relapsing fever and rarely, meningoencephalitis. Because clinical manifestations are nonspecific, diagnosis requires laboratory confirmation by PCR or blood smear examination. Antibiotics are effective in clearing infection and are the same as those used for Lyme disease, including doxycycline, tetracycline, erythromycin, penicillin, and ceftriaxone. Preventive measures include avoiding areas where B. miyamotoi-infected ticks are found, landscape management, and personal protective strategies such as protective clothing, use of acaricides, and tick checks with rapid removal of embedded ticks.

Rearrangement events in wall-flow filters lead to the formation of specific deposition patterns, which affect a filter’s pressure drop, its loading capacity and the separation efficiency. A universal and consistent formulation of probable causes and influence factors does not exist and appropriate calculation models that enable a quantification of respective influence factors are missing. In this work, a previously developed lattice Boltzmann method, which has been used with inflow velocities of up to 2 m s−1, is applied to elevated velocities of up to 60 m s−1. The particle-free flow, a single layer fragment and a deposition layer during break-up are investigated as three different scenarios. One goal of this work is a comprehensive quantification of the stability and accuracy of both particle-free and particle-including flows, considering static, impermeable deposition-layer fragments. A second goal is the determination of the hydrodynamic surface forces and the deduction of the local detachment likelihood of individual layer fragments. Satisfactory stability and accuracy can be shown for fluid velocity, fluid pressure and the hydrodynamic forces. When considering layer fragments, the parameter domain turns out to be limited to inflow velocities of 28 m s−1. It is shown that fragment detachment rather occurs consecutively and regions of no possible detachment are identified. The work contributes to an understanding of rearrangement events and respective deposition pattern predictions and enables potential optimizations in engine performance, fuel consumption and the service life of wall-flow filters.

Ever since the pioneering studies of George Mendenhall, Klaus Baltzer, Dennis McCarthy, and Moshe Weinfeld, the structural analogies between Deuteronomy and ancient Near Eastern treaties have been a key issue in the scholarly study of the book. More recently, the hypothesis that Deuteronomy 13* and 28* could even represent a Hebrew rendering of the Neo-Assyrian Succession Treaties of Esarhaddon has prompted a yet intensified investigation of the matter. Yielding nuanced models to account for the traditio-historical pluriformity of features in Deuteronomy vis-à-vis the various strands of tradition found in late Hittite and Neo-Assyrian, as well as Aramaic comparative evidence, this latter discussion has arguably once again broadened the horizon. In any case, it only emphasizes that reading Deuteronomy against the background of the ancient Near Eastern treaty tradition more broadly provides an indispensable perspective when it comes to the literary genesis of Deuteronomy as we have it. What is more, it also opens a window on its interpretation. At the same time, however, it can also lead to certain misconceptions, for as much as major parts of Deuteronomy are modeled on a treaty, Deuteronomy is no treaty. The comparative perspective thus requires one to heed both commonalities and differences. This article focuses on one such difference, namely the constellation of agents. It is typical of ancient Near Eastern treaties that the contracting parties agree to delegate the task of safeguarding the treaty to a third party constituted by deities. It is these gods who figure as “witnesses” of the curses that the contracting parties call upon themselves if they should act contrary to the treaty, the term “witness” also denoting, according to the semantics of ancient Near Eastern treaty discourse, “agent of the sanctions.” Hence, the agreed upon sanctions are conceived of as coming into effect without the further involvement of the contracting parties. In fact, this particular feature is the operating principle which makes an ancient Near Eastern treaty work. In Deuteronomy, however, it does not apply. While intriguingly enough there are certain entities in the close context of the curse sections which are called “witnesses,” none of them can truly figure as a witness in the sense described above, for none of them is a deity; neither is there an attempt made to charge these “witnesses” with putting into effect the curse sanctions. Often overlooked, this aspect has significant ramifications for the understanding of the curses in Deuteronomy and the treaty style structure in general.

Stress granules (SGs) are dynamic, reversible biomolecular condensates, which assemble in the cytoplasm of eukaryotic cells under various stress conditions. Formation of SGs typically occurs upon stress-induced translational arrest and polysome disassembly. The increase in cytoplasmic mRNAs triggers the formation of a protein-RNA network that undergoes liquid-liquid phase separation when a critical interaction threshold has been reached. This adaptive stress response allows a transient shutdown of several cellular processes until the stress is removed. During the recovery from stress, SGs disassemble to re-establish cellular activities. Persistent stress and disease-related mutations in SG components favor the formation of aberrant SGs that are impaired in disassembly and prone to aggregation. Recently, posttranslational modifications of SG components have been identified as major regulators of SG dynamics. Here, we summarize new insights into the role of ubiquitination in affecting SG dynamics and clearance and discuss implications for neurodegenerative diseases linked to aberrant SG formation.

Abstract Background Strong line of evidence suggests that the increased risk to develop AD may at least be partly mediated by cholesterol metabolism. A key regulator of cholesterol transport is the Apolipoprotein E4 (ApoE4), which plays a fundamental role in neuronal maintenance and repair. Impaired function of ApoE4 may contribute to altered cerebral metabolism leading to higher susceptibility to neurodegeneration. Methods To determine a possible link between ApoE function and alterations in AD in the brain of Apolipoprotein E-deficient mice (ApoE−/−) in a longitudinal manner metabolic and neurochemical parameters were analyzed. Cortical metabolism was measured by 2-deoxy-2-[18F]fluoroglucose ([18F]FDG)-PET/CT and proton magnetic resonance spectroscopy (1H-MRS) served to record neurochemical status. Results By using [18F]FDG-PET/CT, we showed that brain metabolism declined significantly stronger with age in ApoE−/− versus wild type (wt) mice. This difference was particularly evident at the age of 41 weeks in almost each analyzed brain region. In contrast, the 1H-MRS-measured N-acetylaspartate to creatine ratio, a marker of neuronal viability, did not decline with age and did not differ between ApoE−/− and wt mice. Conclusion In summary, this longitudinal in vivo study shows for the first time that ApoE−/− mice depict cerebral hypometabolism without neurochemical alterations.

Abstract Background Suicide risk of psychiatric patients has proven to be strongly increased in the months after discharge from a psychiatric hospital. Despite this high risk, there is a lack of systematic research on the causes of this elevated suicide risk as well as a lack of treatment and intervention for patients at high risk after discharge. The main objective of this pilot study is, firstly, to examine the factors contributing to the elevated suicide risk and, secondly, to investigate whether an additional setting of care starting at discharge may reduce suicidality. Methods In this multi-centre pilot study, treatment as usual is complemented by an additional 18-month post-discharge setting of care for psychiatric patients at high risk for suicide. Two groups of patients differing in the amount of post-discharge personal contacts will be compared. One group of patients will be offered continuous personal contacts after discharge (months 1–6: monthly contacts; months 6–18: every 2 months) while another group of patients will receive contacts only at months 6, 12, and 18 after discharge. Data on suicidality, as well as associated with other symptoms, treatment, and significant events, will be collected. In the case of health-related severe events, the setting of care allows the patient to have the opportunity to connect with the doctor or therapist treating the patient. Discussion The results of this study will contribute to identifying critical factors raising suicide risk after discharge and will demonstrate the potential influence on suicide prevention of a setting of care with regular personal contact after discharge. Trial registration ZMVI1-2517FSB135 – funded by the German Federal Ministry of Health.

Abstract Background Resolving the preferred prey items and dietary proportions of leopard seals is central to understanding food-web dynamics in the rapidly-warming Antarctic Peninsula region. Previous studies have identified a wide range of prey items; however, due to anecdotal or otherwise limited information, leopard seal diets remain unresolved by seal sex, individual, body size, region, and season. Over the 2013, 2014, and 2017 field seasons we collected scat, tissue samples (red blood cells and plasma; n = 23) for stable isotope analyses, and previously-reported animal-borne video from 19 adult leopard seals foraging near mesopredator breeding colonies at Cape Shirreff, Livingston Island. We summarized a priori diet information from scat and video analysis and applied a three-isotope (δ 13C, δ 15N, δ 34S), four-source (fish, fur seal, krill, penguin) Bayesian mixing model to examine temporal variability in both prey sources and leopard seal tissues. Results The austral spring diets of males and females focused on Antarctic krill (31.7–38.0%), notothen fish (31.6–36.5%), and penguin (24.4–26.9%) and were consistent across all 3 years. Several lines of evidence suggest the transition to summer foraging was distinct for males and females. Female diets transitioned rapidly to higher δ 15N values (+2.1‰), indicating increased consumption of penguin (29.5–46.2%) and energy-dense Antarctic fur seal pup (21.3–37.6%). Conclusions The seasonal increase in leopard seal δ 15N values, and thus fur seal in their diet, was predictably related to larger body size; it may also be forcing reductions to the largest Antarctic fur seal colony in the Antarctic Peninsula. Our ensemble sampling approach reduces historical biases in monitoring marine apex predator diets. Further, our results are necessary to best inform regional fisheries management planning.

Abstract Babesia microti is an intraerythrocytic parasite and the primary causative agent of human babesiosis. It is transmitted by Ixodes ticks, transfusion of blood and blood products, organ donation, and perinatally. Despite its global public health impact, limited progress has been made to identify and characterize immunodominant B. microti antigens for diagnostic and vaccine use. Using genome-wide immunoscreening, we identified 56 B. microti antigens, including some previously uncharacterized antigens. Thirty of the most immunodominant B. microti antigens were expressed as recombinant proteins in E. coli. Among these, the combined use of two novel antigens and one previously described antigen provided 96% sensitivity and 100% specificity in identifying B. microti antibody containing sera in an ELISA. Using extensive computational sequence and bioinformatics analyses and cellular localization studies, we have clarified the domain architectures, potential biological functions, and evolutionary relationships of the most immunodominant B. microti antigens. Notably, we found that the BMN-family antigens are not monophyletic as currently annotated, but rather can be categorized into two evolutionary unrelated groups of BMN proteins respectively defined by two structurally distinct classes of extracellular domains. Our studies have enhanced the repertoire of immunodominant B. microti antigens, and assigned potential biological function to these antigens, which can be evaluated to develop novel assays and candidate vaccines.