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Measurements of visceral adipose tissue cross-sectional area and radiation attenuation from computed tomography (CT) scans provide useful information about risk and mortality. However, scan protocols vary, encompassing differing vertebra levels and utilizing differing phases of contrast enhancement. Furthermore, fat measurements have been extracted from CT using different Hounsfield Unit (HU) ranges. To our knowledge, there have been no large studies of healthy cohorts that reported reference values for visceral fat area and radiation attenuation at multiple vertebra levels, for different contrast phases, and using different fat HU ranges. Two-phase CT scans from 1,677 healthy, adult kidney donors (age 18–65) between 1999 and 2017, previously studied to determine healthy reference values for skeletal muscle measures, were utilized. Visceral adipose tissue cross-sectional area (VFA) and radiation attenuation (VFRA) measures were quantified using axial slices at T10 through L4 vertebra levels. T-tests were used to compare males and females, while paired t-tests were conducted to determine the effect (magnitude and direction) of (a) contrast enhancement and (b) different fat HU ranges on each fat measure at each vertebra level. We report the means, standard deviations, and effect sizes of contrast enhancement and fat HU range. Male and female VFA and VFRA were significantly different at all vertebra levels in both contrast and non-contrast scans. Peak VFA was observed at L4 in females and L2 in males, while peak VFRA was observed at L1 in both females and males. In general, non-contrast scans showed significantly greater VFA and VFRA compared to contrast scans. The average paired difference due to contrast ranged from 1.6 to − 8% (VFA) and 3.2 to − 3.0% (VFRA) of the non-contrast value. HU range showed much greater differences in VFA and VFRA than contrast. The average paired differences due to HU range ranged from − 5.3 to 22.2% (VFA) and − 5.9 to 13.6% (VFRA) in non-contrast scans, and − 4.4 to 20.2% (VFA) and − 4.1 to 12.6% (VFRA) in contrast scans. The − 190 to − 30 HU range showed the largest differences in both VFA (10.8% to 22.2%) and VFRA (7.6% to 13.6%) compared to the reference range (− 205 to − 51 HU). Incidentally, we found that differences in lung inflation result in very large differences in visceral fat measures, particularly in the thoracic region. We assessed the independent effects of contrast presence and fat HU ranges on visceral fat cross-sectional area and mean radiation attenuation, finding significant differences particularly between different fat HU ranges. These results demonstrate that CT measurements of visceral fat area and radiation attenuation are strongly dependent upon contrast presence, fat HU range, sex, breath cycle, and vertebra level of measurement. We quantified contrast and non-contrast reference values separately for males and females, using different fat HU ranges, for lumbar and thoracic CT visceral fat measures at multiple vertebra levels in a healthy adult US population.

BackgroundHematopoietic stem cells are cells that differentiate into all blood cell types. Although the placenta secretes hormones, proteins and other factors important for maternal and fetal health, cross-talk between placental cells and hematopoietic stem cells is poorly understood. Moreover, toxicant impacts on placental-hematopoietic stem cell communication is understudied. The goals of this study were to determine if factors secreted from placental cells alter transcriptomic responses in hematopoietic stem cells and if monoethylhexyl phthalate (MEHP), the bioactive metabolite of the pollutant diethylhexyl phthalate, modifies these effects.MethodsWe used K-562 and BeWo cells asin vitromodels of hematopoietic stem cells and placental syncytiotrophoblasts, respectively. We treated K-562 cells with medium conditioned by incubation with BeWo cells, medium conditioned with BeWo cells treated with 10 μM MEHP for 24 hours, or controls treated with unconditioned medium. We extracted K-562 cell RNA, performed RNA sequencing, then conducted differential gene expression and pathway analysis by treatment group.ResultsRelative to controls, K-562 cells treated with BeWo cell conditioned medium differentially expressed 173 genes (FDR2.0), including 2.4 fold upregulatation ofTPM4and 3.3 fold upregulatation ofS1PR3. Upregulated genes were enriched for pathways including stem cell maintenance, cell proliferation and immune processes. Downregulated genes were enriched for terms involved in protein translation and transcriptional regulation. MEHP treatment differentially expressed eight genes (FDRPLIN2, fold-change: 1.4;CPT1A, fold-change: 1.4).ConclusionK-562 cells, a model of hematopoietic stem cells, are responsive to media conditioned by placental cells, potentially impacting pathways like stem cell maintenance and proliferation.

Chicken coccidiosis is a common and severe parasitic disease caused by infection from Eimeria spp., which affects the integrity of the intestinal mucosa. TGF-β has been shown to play an important role in the healing of intestinal mucosas, immunity, and the maintenance of bowel mucosa integrity. Very little is known about the presence of the components of TGF-β/Smads signaling pathway of chicken at different times following coccidian infection. In the present study, we measured the levels of TGF-β2, 3, 4, receptor TβRI, II, down-stream Smad 2, 3, 7 in cecum and spleen of chicken at different times after inoculation with Eimeria tenella using quantitative real-time PCR. The results showed that the TGF-β/Smads signaling pathway was not activated in cecum in the early stage of infection. However, on the 8th day, the expression of TGF-β2, 4, down-stream protein Smad 2, 7 were significant up-regulated in the spleen, which indicated that the TGF-β/Smads signaling was changed in the E. tenella infection and was differentially expressed in various tissues in the early stages of infection.

Background Although imaging, endoscopy, and inflammatory biomarkers are associated with future Crohn disease (CD) outcomes, common laboratory studies may also provide prognostic opportunities. We evaluated machine learning models incorporating routinely collected laboratory studies to predict surgical outcomes in U.S. Veterans with CD. Methods Adults with CD from a Veterans Health Administration, Veterans Integrated Service Networks (VISN) 10 cohort examined between 2001 and 2015 were used for analysis. Patient demographics, medication use, and longitudinal laboratory values were used to model future surgical outcomes within 1 year. Specifically, data at the time of prediction combined with historical laboratory data characteristics, described as slope, distribution statistics, fluctuation, and linear trend of laboratory values, were considered and principal component analysis transformations were performed to reduce the dimensionality. Lasso regularized logistic regression was used to select features and construct prediction models, with performance assessed by area under the receiver operating characteristic using 10-fold cross-validation. Results We included 4950 observations from 2809 unique patients, among whom 256 had surgery, for modeling. Our optimized model achieved a mean area under the receiver operating characteristic of 0.78 (SD, 0.002). Anti-tumor necrosis factor use was associated with a lower probability of surgery within 1 year and was the most influential predictor in the model, and corticosteroid use was associated with a higher probability of surgery. Among the laboratory variables, high platelet counts, high mean cell hemoglobin concentrations, low albumin levels, and low blood urea nitrogen values were identified as having an elevated influence and association with future surgery. Conclusions Using machine learning methods that incorporate current and historical data can predict the future risk of CD surgery.

Measurements of skeletal muscle cross-sectional area (SMA) at the level of the third lumbar (L3) vertebra derived from clinical computed tomography (CT) scans are commonly used in assessments of sarcopenia, the loss of skeletal muscle mass and function associated with aging. As SMA is correlated with height and Body Mass Index (BMI), body size adjustment is necessary to fairly assess sarcopenic low muscle mass in individuals of different height and BMI. The skeletal muscle index, a widely used measure, adjusts for height as $$(SMA/height^2)$$ ( S M A / h e i g h t 2 ) but uses no BMI adjustment. There is no agreed upon standard for body size adjustment. We extracted L3 SMA using non-contrast-enhanced CT scans from healthy adults, split into ‘Under-40’ and ‘Over-40’ cohorts. Sex-specific allometric analysis showed that height to the power of one was the optimal integer coefficient for height adjusted SMA in both males and females. We computed two height-adjusted measures $$SMA_{HT}=SMA/height$$ S M A HT = S M A / h e i g h t and $$SMA_{HT2}=SMA/height^2$$ S M A H T 2 = S M A / h e i g h t 2 , comparing their Pearson correlations versus age, height, weight, and BMI separately by sex and cohort. Finally, in the ‘Under-40’ cohort, we used linear regression to convert each height-adjusted measure into a z-score ($$z(SMA_{HT})$$ z ( S M A HT ) , $$z(SMA_{HT2})$$ z ( S M A H T 2 ) ) adjusted for BMI. $$SMA_{HT}$$ S M A HT was less correlated with height in both males and females ($$r=0.005$$ r = 0.005 , $$p=0.91$$ p = 0.91 and $$r=0.1$$ r = 0.1 , $$p=0.01$$ p = 0.01 ) than $$SMA_{HT2}$$ S M A H T 2 ($$r=-\,0.30$$ r = - 0.30 and $$r=-\,0.21$$ r = - 0.21 , $$p p < 0.001 ). $$z(SMA_{HT})$$ z ( S M A HT ) was uncorrelated with BMI and weight, and minimally correlated with height in males and females ($$r=-\,0.01$$ r = - 0.01 , $$p=0.85$$ p = 0.85 and $$r=0.15$$ r = 0.15 , $$p p < 0.001 ). The final $$z(SMA_{HT})$$ z ( S M A HT ) equation was: $$z = (I - {\widehat{I}}) / SD(I)$$ z = ( I - I ^ ) / S D ( I ) , where $$I = SMA/height$$ I = S M A / h e i g h t , $${\widehat{I}} = 50 + BMI + 13 \times sex + 0.6 \times BMI \times sex$$ I ^ = 50 + B M I + 13 × s e x + 0.6 × B M I × s e x , $$SD(I) = 8.8 + 2.6 \times sex$$ S D ( I ) = 8.8 + 2.6 × s e x , and sex = 1 if male, 0 if female. We propose $$SMA_{HT}$$ S M A HT for optimal height adjustment and the $$z(SMA_{HT})$$ z ( S M A HT ) score for optimal height and BMI adjustment. By minimizing correlations with height and BMI, the $$z(SMA_{HT})$$ z ( S M A HT ) score produces unbiased assessments of relative L3 skeletal muscle area across the full range of body sizes.

BackgroundIn response to the development of highly effective but expensive new medications, policymakers, payors, and health systems are considering novel and pragmatic ways to provide these medications to patients. One approach is to target these treatments to those most likely to benefit. However, to maximize the fairness of these policies, and the acceptance of their implementation, the values and beliefs of patients should be considered. The provision of treatments for chronic hepatitis C (CHC) in the resource-constrained context of the Veterans Health Administration (VHA) offered a real-world example of this situation, providing the opportunity to test the value of using Democratic Deliberation (DD) methods to solicit the informed opinions of laypeople on this complex issue.MethodsWe recruited Veterans (n = 30) from the VHA to attend a DD session. Following educational presentations from content experts, participants engaged in facilitated small group discussions to: 1) identify strategies to overcome CHC treatment barriers and 2) evaluate, vote on, and modify/improve two CHC treatment policies – “first come, first served” (FCFS) and “sickest first” (SF). We used transcripts and facilitators’ notes to identify key themes from the small group discussions. Additionally, participants completed pre- and post-DD surveys.ResultsMost participants endorsed the SF policy over the FCFS policy, emphasizing the ethical and medical appropriateness of treating the sickest first. Concerns about SF centered on the difficulty of implementation (e.g., how is “sickest” determined?) and unfairness to other Veterans. Proposed modifications focused on: 1) the need to consider additional health factors, 2) taking behavior and lifestyle into account, 3) offering education and support, 4) improving access, and 5) facilitating better decision-making.ConclusionsDD offered a robust and useful method for addressing the allocation of the scarce resource of CHC treatment. Participants were able to develop a modified version of the SF policy and offered diverse recommendations to promote fairness and improve quality of care for Veterans. DD is an effective approach for incorporating patient preferences and gaining valuable insights for critical healthcare policy decisions in resource-limited environments.

The Coronagraphic Debris Exoplanet Exploring Payload (CDEEP) is a Small-Sat mission concept for high contrast imaging of circumstellar disks. CDEEP is designed to observe disks in scattered light at visible wavelengths at a raw contrast level of 10^-7 per resolution element (10^-8 with post processing). This exceptional sensitivity will allow the imaging of transport dominated debris disks, quantifying the albedo, composition, and morphology of these low-surface brightness disks. CDEEP combines an off-axis telescope, microelectromechanical systems (MEMS) deformable mirror, and a vector vortex coronagraph (VVC). This system will require rigorous testing and characterization in a space environment. We report on the CDEEP mission concept, and the status of the vacuum-compatible CDEEP prototype testbed currently under development at the University of Arizona, including design development and the results of simulations to estimate performance., 17 pages, 12 figures, Published in proceedings of SPIE Astronomical Telescopes + Instrumentation 2020

BACKGROUND: Advances in imaging technology have the potential to transform the early diagnosis and treatment of hepatocellular carcinoma (HCC) through quantitative image analysis. Computational ‘radiomic’ techniques extract biomarker information from images which can be used to improve diagnosis and predict tumor biology. AIMS: We performed a systematic review of literature on radiomic features in HCC diagnosis and prognosis, with a focus on reporting metrics and methodologic standardization. METHODS: A systematic review was performed of all full-text articles published from inception through December 1, 2019. Standardized data extraction and quality assessment metrics were applied to all studies. RESULTS: A total of 54 unique studies were included for analysis. Radiomic features demonstrated good discriminatory performance to differentiate HCC from other solid lesions (c-statistics 0.66–0.95), predict microvascular invasion (c-statistic 0.76–0.92), predict early recurrence after hepatectomy (c-statistics 0.71–0.86), and predict prognosis after locoregional or systemic therapies (c-statistics 0.74–0.81). Common stratifying features for diagnostic and prognostic radiomic tools included analyses of imaging skewness, analysis of the peritumoral region, and feature extraction from the arterial imaging phase. The overall quality of the included studies was low, with common deficiencies in both internal and external validation, standardized imaging segmentation, and lack of comparison to a gold standard. CONCLUSIONS: Quantitative image analysis demonstrates promise as a non-invasive biomarker to improve HCC diagnosis and management. However, standardization of protocols and outcome measurement, sharing of algorithms and analytic methods, and external validation are necessary prior to widespread application of radiomics to HCC diagnosis and prognosis in clinical practice.

(abridged) Context. The origin of hot exozodiacal dust and its connection with outer dust reservoirs remains unclear. Aims. We aim to explore the possible connection between hot exozodiacal dust and warm dust reservoirs (> 100 K) in asteroid belts. Methods. We use precision near-infrared interferometry with VLTI/PIONIER to search for resolved emission at H band around a selected sample of nearby stars. Results. Our observations reveal the presence of resolved near-infrared emission around 17 out of 52 stars, four of which are shown to be due to a previously unknown stellar companion. The 13 other H-band excesses are thought to originate from the thermal emission of hot dust grains. Taking into account earlier PIONIER observations, and after reevaluating the warm dust content of all our PIONIER targets through spectral energy distribution modeling, we find a detection rate of 17.1(+8.1)(-4.6)% for H-band excess around main sequence stars hosting warm dust belts, which is statistically compatible with the occurrence rate of 14.6(+4.3)(-2.8)% found around stars showing no signs of warm dust. After correcting for the sensitivity loss due to partly unresolved hot disks, under the assumption that they are arranged in a thin ring around their sublimation radius, we however find tentative evidence at the 3{\sigma} level that H-band excesses around stars with outer dust reservoirs (warm or cold) could be statistically larger than H-band excesses around stars with no detectable outer dust. Conclusions. Our observations do not suggest a direct connection between warm and hot dust populations, at the sensitivity level of the considered instruments, although they bring to light a possible correlation between the level of H-band excesses and the presence of outer dust reservoirs in general., Comment: Accepted for publication in A&A

Background Indomethacin treatment for patent ductus arteriosus (PDA) is associated with acute kidney injury (AKI). Fenoldopam, a dopamine (DA) DA1-like receptor agonist dilates the renal vasculature and may preserve renal function during indomethacin treatment. However, limited information exists on DA receptor-mediated signaling in the ductus and fenoldopam may prevent ductus closure given its vasodilatory nature. Methods DA receptor expression in CD-1 mouse vessels was analyzed by qPCR and immunohistochemistry. Concentration-response curves were established using pressure myography. Pretreatment with SCH23390 (DA1-like receptor antagonist), phentolamine (α -adrenergic receptor antagonist) or indomethacin addressed mechanisms for DA-induced changes. Fenoldopam's effects on postnatal ductus closure were evaluated in vivo. Results DA1 receptors were expressed equally in ductus and aorta. High-dose DA induced modest vasoconstriction under newborn O2 conditions. Phentolamine inhibited DA-induced constriction, while SCH23390 augmented constriction, consistent with a vasodilatory role for DA1 receptors. Despite this, fenoldopam had little effect on ductus tone nor indomethacin- or O2-induced constriction and did not impair postnatal closure in vivo. Conclusion(s) DA receptors are present in the ductus but have limited physiologic effects. DA-induced ductus vasoconstriction is mediated via α-adrenergic pathways. The absence of DA1-mediated impairment of ductus closure supports the study of potential role for fenoldopam during PDA treatment.

Purpose: To investigate features and outcomes of circumscribed choroidal hemangioma by patient age. Methods: Retrospective review of circumscribed choroidal hemangioma from 3/29/1967–6/4/2018 based on age at presentation (≤20 vs. >20–50 vs. >50 years). Results: There were 458 circumscribed choroidal hemangiomas diagnosed at mean age (13 vs. 41 vs. 64 years, p

The young (50-400 Myr) A3V star $\beta$ Leo is a primary target to study the formation history and evolution of extrasolar planetary systems as one of the few stars with known hot ($\sim$1600$^\circ$K), warm ($\sim$600$^\circ$K), and cold ($\sim$120$^\circ$K) dust belt components. In this paper, we present deep mid-infrared measurements of the warm dust brightness obtained with the Large Binocular Telescope Interferometer (LBTI) as part of its exozodiacal dust survey (HOSTS). The measured excess is 0.47\%$\pm$0.050\% within the central 1.5 au, rising to 0.81\%$\pm$0.026\% within 4.5 au, outside the habitable zone of $\beta$~Leo. This dust level is 50 $\pm$ 10 times greater than in the solar system's zodiacal cloud. Poynting-Robertson drag on the cold dust detected by Spitzer and Herschel under-predicts the dust present in the habitable zone of $\beta$~Leo, suggesting an additional delivery mechanism (e.g.,~comets) or an additional belt at $\sim$5.5 au. A model of these dust components is provided which implies the absence of planets more than a few Saturn masses between $\sim$5 au and the outer belt at $\sim$40 au. We also observationally constrain giant planets with the LBTI imaging channel at 3.8~$\mu$m wavelength. Assuming an age of 50 Myr, any planet in the system between approximately 5 au to 50 au must be less than a few Jupiter masses, consistent with our dust model. Taken together, these observations showcase the deep contrasts and detection capabilities attainable by the LBTI for both warm exozodiacal dust and giant exoplanets in or near the habitable zone of nearby stars., Comment: 11 pages, 9 figures, accepted for publication in Astronomical Journal

Debris disks are tenuous, dusty belts surrounding main sequence stars generated by collisions between planetesimals. HD 206893 is one of only two stars known to host a directly imaged brown dwarf orbiting interior to its debris ring, in this case at a projected separation of 10.4 au. Here we resolve structure in the debris disk around HD 206893 at an angular resolution of 0.6" (24 au) and wavelength of 1.3 mm with the Atacama Large Millimeter/submillimeter Array (ALMA). We observe a broad disk extending from a radius of, 24 pages, 12 figures, Accepted for publication in ApJ

There is a growing recognition of the role of particle-attached (PA) and free-living (FL) microorganisms in marine carbon cycle. However, current understanding of PA and FL microbial communities is largely focused on those in the upper photic zone, and relatively fewer studies have focused on microbial communities of the deep ocean. Moreover, archaeal populations receive even less attention. In this study, we determined bacterial and archaeal community structures of both the PA and FL assemblages at different depths, from the surface to the bathypelagic zone along two water column profiles in the South China Sea. Our results suggest that environmental parameters including depth, seawater age, salinity, particulate organic carbon (POC), dissolved organic carbon (DOC), dissolved oxygen (DO) and silicate play a role in structuring these microbial communities. Generally, the PA microbial communities had relatively low abundance and diversity compared with the FL microbial communities at most depths. Further microbial community analysis revealed that PA and FL fractions generally accommodate significantly divergent microbial compositions at each depth. The PA bacterial communities mainly comprise members of Alphaproteobacteria and Gammaproteobacteria, together with some from Planctomycetes and Deltaproteobacteria, while the FL bacterial lineages are also mostly distributed within Alphaproteobacteria and Gammaproteobacteria, along with other abundant members chiefly from Actinobacteria, Cyanobacteria, Bacteroidetes, Marinimicrobia and Deltaproteobacteria. Moreover, there was an obvious shifting in the dominant PA and FL bacterial compositions along the depth profiles from the surface to the bathypelagic deep. By contrast, both PA and FL archaeal communities dominantly consisted of euryarchaeotal Marine Group II (MGII) and thaumarchaeotal Nitrosopumilales, together with variable amounts of Marine Group III (MGIII), Methanosarcinales, Marine Benthic Group A (MBG-A) and Woesearchaeota. However, the pronounced distinction of archaeal community compositions between PA and FL fractions was observed at a finer taxonomic level. A high proportion of overlap of microbial compositions between PA and FL fractions implies that most microorganisms are potentially generalists with PA and FL dual lifestyles for versatile metabolic flexibility. In addition, microbial distribution along the depth profile indicates a potential vertical connectivity between the surface-specific microbial lineages and those in the deep ocean, likely through microbial attachment to sinking particles.

The Origins Space Telescope will trace the history of our origins from the time dust and heavy elements permanently altered the cosmic landscape to present-day life. How did galaxies evolve from the earliest galactic systems to those found in the Universe today? How do habitable planets form? How common are life-bearing worlds? To answer these alluring questions, Origins will operate at mid- and far-infrared (IR) wavelengths and offer powerful spectroscopic instruments and sensitivity three orders of magnitude better than that of the Herschel Space Observatory, the largest telescope flown in space to date. We describe the baseline concept for Origins recommended to the 2020 US Decadal Survey in Astronomy and Astrophysics. The baseline design includes a 5.9-m diameter telescope cryocooled to 4.5 K and equipped with three scientific instruments. A mid-infrared instrument (Mid-Infrared Spectrometer and Camera Transit spectrometer) will measure the spectra of transiting exoplanets in the 2.8 to 20 μm wavelength range and offer unprecedented spectrophotometric precision, enabling definitive exoplanet biosignature detections. The far-IR imager polarimeter will be able to survey thousands of square degrees with broadband imaging at 50 and 250 μm. The Origins Survey Spectrometer will cover wavelengths from 25 to 588 μm, making wide-area and deep spectroscopic surveys with spectral resolving power R ∼ 300, and pointed observations at R ∼ 40,000 and 300,000 with selectable instrument modes. Origins was designed to minimize complexity. The architecture is similar to that of the Spitzer Space Telescope and requires very few deployments after launch, while the cryothermal system design leverages James Webb Space Telescope technology and experience. A combination of current-state-of-the-art cryocoolers and next-generation detector technology will enable Origins’ natural background-limited sensitivity.

International audience; The Origins Space Telescope will trace the history of our origins from the time dust and heavy elements permanently altered the cosmic landscape to present-day life. How did galaxies evolve from the earliest galactic systems to those found in the universe today? How do habitable planets form? How common are life-bearing worlds? We describe how Origins was designed to answer these alluring questions. We discuss the key decisions taken by the Origins mission concept study team, the rationale for those choices, and how they led through an exploratory design process to the Origins baseline mission concept. To understand the concept solution space, we studied two distinct mission concepts and descoped the second concept, aiming to maximize science per dollar and hit a self-imposed cost target. We report on the study approach and describe the concept evolution. The resulting baseline design includes a 5.9-m diameter telescope cryocooled to 4.5 K and equipped with three scientific instruments. The chosen architecture is similar to that of the Spitzer Space Telescope and requires very few deployments after launch. The cryo-thermal system design leverages James Webb Space Telescope technology and experience.

Cerebral cavernous malformations (CCMs) are neurovascular abnormalities characterized by thin, leaky blood vessels resulting in lesions that predispose to haemorrhages, stroke, epilepsy and focal neurological deficits. CCMs arise due to loss-of-function mutations in genes encoding one of three CCM complex proteins, KRIT1, CCM2 or CCM3. These widely expressed, multi-functional adaptor proteins can assemble into a CCM protein complex and (either alone or in complex) modulate signalling pathways that influence cell adhesion, cell contractility, cytoskeletal reorganization and gene expression. Recent advances, including analysis of the structures and interactions of CCM proteins, have allowed substantial progress towards understanding the molecular bases for CCM protein function and how their disruption leads to disease. Here, we review current knowledge of CCM protein signalling with a focus on three pathways which have generated the most interest—the RhoA–ROCK, MEKK3–MEK5–ERK5–KLF2/4 and cell junctional signalling pathways—but also consider ICAP1-β1 integrin and cdc42 signalling. We discuss emerging links between these pathways and the processes that drive disease pathology and highlight important open questions—key among them is the role of subcellular localization in the control of CCM protein activity.

Key Points Question Can deep learning recurrent neural network (RNN) models using raw longitudinal data extracted directly from electronic health records outperform conventional regression models in predicting the risk of developing hepatocellular carcinoma (HCC)? Findings This prognostic study included 48 151 patients with hepatitis C virus (HCV)–related cirrhosis in the national Veterans Health Administration who had at least 3 years of follow-up after the diagnosis of cirrhosis. Deep learning RNN models outperformed conventional linear regression models and could be used to identify patients with HCV-related cirrhosis at high risk of developing HCC. Meaning The findings of this study suggest that RNN models could have multiple applications in clinical practice and could be applied to HCC outreach and surveillance strategies., This prognostic study examines whether deep learning recurrent neural network (RNN) models that use raw longitudinal data extracted directly from electronic health records outperform conventional regression models in predicting the risk of developing hepatocellular carcinoma (HCC)., Importance Deep learning, a family of machine learning models that use artificial neural networks, has achieved great success at predicting outcomes in nonmedical domains. Objective To examine whether deep learning recurrent neural network (RNN) models that use raw longitudinal data extracted directly from electronic health records outperform conventional regression models in predicting the risk of developing hepatocellular carcinoma (HCC). Design, Setting, and Participants This prognostic study included 48 151 patients with hepatitis C virus (HCV)–related cirrhosis in the national Veterans Health Administration who had at least 3 years of follow-up after the diagnosis of cirrhosis. Patients were identified by having at least 1 positive HCV RNA test between January 1, 2000, to January 1, 2016, and were followed up from the diagnosis of cirrhosis to January 1, 2019, for the development of incident HCC. A total of 3 models predicting HCC during a 3-year period were developed and compared, as follows: (1) logistic regression (LR) with cross-sectional inputs (cross-sectional LR); (2) LR with longitudinal inputs (longitudinal LR); and (3) RNN with longitudinal inputs. Data analysis was conducted from April 2018 to August 2020. Exposures Development of HCC. Main Outcomes and Measures Area under the receiver operating characteristic curve, area under the precision-recall curve, and Brier score. Results During a mean (SD) follow-up of 11.6 (5.0) years, 10 741 of 48 151 patients (22.3%) developed HCC (annual incidence, 3.1%), and a total of 52 983 samples (51 948 [98.0%] from men) were collected. Patients who developed HCC within 3 years were older than patients who did not (mean [SD] age, 58.2 [6.6] years vs 56.9 [6.9] years). RNN models had superior mean (SD) area under the receiver operating characteristic curve (0.759 [0.009]) and mean (SD) Brier score (0.136 [0.003]) than cross-sectional LR (0.689 [0.009] and 0.149 [0.003], respectively) and longitudinal LR (0.682 [0.007] and 0.150 [0.003], respectively) models. Using the RNN model, the samples with the mean (SD) highest 51% (1.5%) of HCC risk, in which 80% of all HCCs occurred, or the mean (SD) highest 66% (1.2%) of HCC risk, in which 90% of all HCCs occurred, could potentially be targeted. Among samples from patients who achieved sustained virologic response, the performance of the RNN models was even better (mean [SD] area under receiver operating characteristic curve, 0.806 [0.025]; mean [SD] Brier score, 0.117 [0.007]). Conclusions and Relevance In this study, deep learning RNN models outperformed conventional LR models, suggesting that RNN models could be used to identify patients with HCV-related cirrhosis with a high risk of developing HCC for risk-based HCC outreach and surveillance strategies.

The Vega planetary system hosts the archetype of extrasolar Kuiper belts, and is rich in dust from the sub-au region out to 100's of au, suggesting intense dynamical activity. We present ALMA mm observations that detect and resolve the outer dust belt from the star for the first time. The interferometric visibilities show that the belt can be fit by a Gaussian model or by power-law models with a steep inner edge (at 60-80 au). The belt is very broad, extending out to at least 150-200 au. We strongly detect the star and set a stringent upper limit to warm dust emission previously detected in the infrared. We discuss three scenarios that could explain the architecture of Vega's planetary system, including the new {ALMA} constraints: no outer planets, a chain of low-mass planets, and a single giant planet. The planet-less scenario is only feasible if the outer belt was born with the observed sharp inner edge. If instead the inner edge is currently being truncated by a planet, then the planet must be $\gtrsim$6 M$_{\oplus}$ and at $\lesssim71$ au to have cleared its chaotic zone within the system age. In the planet chain scenario, outward planet migration and inward scattering of planetesimals could produce the hot and warm dust observed in the inner regions of the system. In the single giant planet scenario, an asteroid belt could be responsible for the warm dust, and mean motion resonances with the planet could put asteroids on star-grazing orbits, producing the hot dust., 18 pages, 3 figures, Accepted for publication in ApJ

There remain unanswered questions concerning mother‐to‐child‐transmission (MTCT) of SARS‐CoV‐2. Despite reports of neonatal COVID‐19, SARS‐CoV‐2 has not been consistently isolated in perinatal samples thus, definitive proof of transplacental infection is still lacking. To address these questions, we assessed investigative tools used to confirm maternal‐fetal infection and known protective mechanisms of the placental barrier that prevent transplacental pathogen migration. Forty studies of COVID‐19 pregnancies reviewed suggest a lack of consensus on diagnostic strategy for congenital infection. While RT‐PCR of neonatal swabs was universally performed, a wide range of clinical samples was screened including vaginal secretions (22.5%), amniotic fluid (35%), breast milk (22.5%) and umbilical cord blood. Neonatal COVID‐19 was reported in eight studies, two of which were based on the detection of SARS‐CoV‐2 IgM in neonatal blood. Histological examination demonstrated sparse viral particles, vascular malperfusion and inflammation in the placenta from pregnant women with COVID‐19. The paucity of placental co‐expression of ACE‐2 and TMPRSS2, two receptors involved in cytoplasmic entry of SARS‐CoV‐2, may explain its relative insensitivity to transplacental infection. Viral interactions may utilise membrane receptors other than ACE‐2 thus, tissue susceptibility may be broader than currently known. Further spatial‐temporal studies are needed to determine the true potential for transplacental migration. This article is protected by copyright. All rights reserved.

The Large Binocular Telescope Interferometer (LBTI) enables nulling interferometric observations across the N band (8 to 13 um) to suppress a star's bright light and probe for faint circumstellar emission. We present and statistically analyze the results from the LBTI/HOSTS (Hunt for Observable Signatures of Terrestrial Systems) survey for exozodiacal dust. By comparing our measurements to model predictions based on the Solar zodiacal dust in the N band, we estimate a 1 sigma median sensitivity of 23 zodis for early type stars and 48 zodis for Sun-like stars, where 1 zodi is the surface density of habitable zone (HZ) dust in the Solar system. Of the 38 stars observed, 10 show significant excess. A clear correlation of our detections with the presence of cold dust in the systems was found, but none with the stellar spectral type or age. The majority of Sun-like stars have relatively low HZ dust levels (best-fit median: 3 zodis, 1 sigma upper limit: 9 zodis, 95% confidence: 27 zodis based on our N band measurements), while ~20% are significantly more dusty. The Solar system's HZ dust content is consistent with being typical. Our median HZ dust level would not be a major limitation to the direct imaging search for Earth-like exoplanets, but more precise constraints are still required, in particular to evaluate the impact of exozodiacal dust for the spectroscopic characterization of imaged exo-Earth candidates., Comment: accepted for publication in AJ

An updated version of the Weather Research and Forecast model coupled with Chemistry (WRF-Chem) was applied to quantify and investigate the full effects of dust on the meteorological field over East Asia during March and April 2012. The performances of the model in simulating the shortwave and longwave radiation, surface temperature, and precipitation over East Asia are improved by incorporating the effects of dust in the simulations. The radiative forcing induced by the direct radiative effect of dust is greater than that by the dust-enhanced cloud radiative effect. The indirect effects of dust result in a substantial increase in ice clouds at the middle to upper troposphere and a reduction in liquid clouds at the low to mid-troposphere. The radiative forcing combined with the redistribution of atmospheric water vapor results in an overall decrease in near-surface temperature and an increase in temperature at the middle to upper troposphere over East Asia, leading to an inhibition of atmospheric instability over most land areas, but an enhancement of atmospheric instability over south China. Upon considering the effects of dust, convective precipitation exhibits an inhibition over areas from central to east China and an enhancement over south China. Meanwhile, the locations of non-convective precipitation are shifted due to the perturbation of cloud water path. The total amount of precipitation over East Asia remains unchanged; however, the precipitation locations are shifted. The precipitation can be enhanced or inhibited by up to 20 % at particular areas.

Measurements of skeletal muscle cross-sectional area, index, and radiation attenuation utilizing clinical computed tomography (CT) scans are used in assessments of sarcopenia, the loss of skeletal muscle mass and function associated with aging. To classify individuals as sarcopenic, sex-specific cutoffs for ‘low’ values are used. Conventionally, cutoffs for skeletal muscle measurements at the level of the third lumbar (L3) vertebra are used, however L3 is not included in several clinical CT protocols. Non-contrast-enhanced CT scans from healthy kidney donor candidates (age 18–40) at Michigan Medicine were utilized. Skeletal muscle area (SMA), index (SMI), and mean attenuation (SMRA) were measured at each vertebral level between the tenth thoracic (T10) and the fifth lumbar (L5) vertebra. Sex-specific means, standard deviations (s.d.), and sarcopenia cutoffs (mean-2 s.d.) at each vertebral level were computed. Associations between vertebral levels were assessed using Pearson correlations and Tukey’s difference test. Classification agreement between different vertebral level cutoffs was assessed using overall accuracy, specificity, and sensitivity. SMA, SMI, and SMRA L3 cutoffs for sarcopenia were 92.2 cm2, 34.4 cm2/m2, and 34.3 HU in females, and 144.3 cm2, 45.4 cm2/m2, and 38.5 HU in males, consistent with previously reported cutoffs. Correlations between all level pairs were statistically significant and high, ranging from 0.65 to 0.95 (SMA), 0.64 to 0.95 (SMI), and 0.63 to 0.95 (SMRA). SMA peaks at L3, supporting its use as the primary site for CT sarcopenia measurements. However, when L3 is not available alternative levels (in order of preference) are L2, L4, L5, L1, T12, T11, and T10. Healthy reference values reported here enable sarcopenia assessment and sex-specific standardization of SMA, SMI, and SMRA in clinical populations, including those whose CT protocols do not include L3.

Grace L Su,1 Douglas M Baughman,2 Qinqin Zhang,3 Kasra Rezaei,2 Aaron Y Lee,2 Cecilia S Lee2 1Lewis Katz School of Medicine, Temple University, Philadelphia, PA, 2Department of Ophthalmology, 3Department of Bioengineering, University of Washington, Seattle, WA, USA Purpose: The aim of this study was to compare physician preferences regarding the commercially available spectral-domain (SD) optical coherence tomography angiography (OCTA) and swept-source (SS) OCTA prototype device.Design: Comparative analysis of diagnostic instruments was performed.Patients and methods: Subjects at the University of Washington Eye Institute and Harborview Medical Center were prospectively recruited and imaged with the Zeiss SD OCTA (HD-5000, Angioplex) and Zeiss SS OCTA (Plex Elite, Everest) devices on the same day. The study included 10 eyes from 10 subjects diagnosed with a retinal/choroidal disease. Deidentified images were compiled into a survey and sent to retina specialists in various countries. The survey presented masked SD and SS images of each eye for each retinal sublayer side by side. Respondents were asked about their image preference and impact on clinical management. A priori and post hoc preferences for SD vs SS were collected.Results: Fifty-four retina specialists responded to the survey. Median years in practice was3.00 (interquartile range [IQR] 1.50–17.00). At baseline, 23 (48%) physicians owned an OCTA machine. The majority of physician responses showed a preference for the SS over SD OCTA, independent of the retinal pathology shown (n=454 overall responses, 74%). Nevertheless, themajority indicated that both SD and SS would be equally valuable in informing clinical decisions (n=374 overall responses, 61%).Conclusion: These findings indicate that the majority of retina specialists surveyed prefer SS over SD OCTA based on image quality, regardless of the retinal pathology shown. Regarding the clinical utility of each modality, the majority of physicians perceive SD and SS as equallyeffective. Keywords: swept-source optical coherence tomography angiography, spectral-domain optical coherence tomography angiography, physician preference

Background & Aims Body composition, particularly sarcopenia, is associated with mortality in patients with decompensated cirrhosis undergoing transplant evaluation. Similar data are limited for non-transplant eligible or compensated patients. Methods A total of 274 patients with cirrhosis were followed prospectively for ≤5 years after a CT scan. We utilized Analytic Morphomics® to measure body composition (fat, muscle, and bone) which was rendered into relative values (percentiles) in relation to a reference population. The model for end-stage liver disease (MELD) score was used as a reference model for survival prediction. We validated our models in a separate cohort. Results Our cohort had a mean Child-Pugh score of 7.0 and a mean MELD of 11.3. The median follow-up time was 5.05 years. The proportion of patients alive at 1, 3 and 5 years was 86.5%, 68.0%, and 54.3%; 13 (4.6%) underwent liver transplantation. Child-Pugh B/C (vs. A) cirrhosis was associated with decreased muscle, subcutaneous, and visceral fat area but increased subcutaneous/visceral fat density. Decreased normal density muscle mass was associated with mortality (hazard ratio [HR] 0.984, p, Graphical abstract, Highlights • Features of body composition can predict clinical outcomes in patients with cirrhosis awaiting liver transplantation. • Data are lacking regarding long-term outcomes among patients with compensated disease. • We show that features of muscle and fat are associated with decompensation and risk of death across the spectrum of cirrhosis. • CT scans obtained for unrelated clinical purposes can be analyzed as a digital risk biomarker for patients with compensated cirrhosis.

To investigate the hypothesis that APS can attenuate E. coli-induced microvascular dysfunction in chicken intestine, 60 0-day old male chickens were divided into three groups with 5 replications of 4 chicks. Chicken in the APS group were treated with 15 mg APS daily while the others were given 0 mg APS for 6 days. Then all 7-day old chicken were injected intraperitoneally by E. coli, except for the chicken in the control group. After 4 h, all chicken’s intestinal samples were collected to detect gene expressions involved in inflammatory factors and adhesion molecules. Results showed that APS attenuated the signs of edema and hemorrhage in 7-day old chicken intestinal mucosa which were induced by E. coli injection. Consistently, APS significantly reduced the increasing mRNA levels of inflammatory factors such as Tumor necrosis factor-a (TNF-a), interleukin (IL) -1β and inducible nitric oxide synthase (iNOS) (p

The Origins Space Telescope will trace the history of our origins from the time dust and heavy elements permanently altered the cosmic landscape to present-day life. How did galaxies evolve from the earliest galactic systems to those found in the universe today? How do habitable planets form? How common are life-bearing worlds? To answer these alluring questions, Origins will operate at mid- and far-infrared wavelengths and offer powerful spectroscopic instruments and sensitivity three orders of magnitude better than that of Herschel, the largest telescope flown in space to date. After a 3 ½ year study, the Origins Science and Technology Definition Team will recommend to the Decadal Survey a concept for Origins with a 5.9-m diameter telescope cryocooled to 4.5 K and equipped with three scientific instruments. A mid-infrared instrument (MISC-T) will measure the spectra of transiting exoplanets in the 2.8 – 20 μm wavelength range and offer unprecedented sensitivity, enabling definitive biosignature detections. The Far-IR Imager Polarimeter (FIP) will be able to survey thousands of square degrees with broadband imaging at 50 and 250 μm. The Origins Survey Spectrometer (OSS) will cover wavelengths from 25 – 588 μm, make wide-area and deep spectroscopic surveys with spectral resolving power R ~ 300, and pointed observations at R ~ 40,000 and 300,000 with selectable instrument modes. Origins was designed to minimize complexity. The telescope has a Spitzer-like architecture and requires very few deployments after launch. The cryo-thermal system design leverages JWST technology and experience. A combination of current-state-of-the-art cryocoolers and next-generation detector technology will enable Origins’ natural backgroundlimited sensitivity.

We compile a sample of 341 binary and multiple star systems with the aim of searching for and characterising Kuiper belt-like debris discs. The sample is assembled by combining several smaller samples studied in previously published work with targets from two unpublished Herschel surveys. We find that 38 systems show excess emission at 70 or 100 $\mu$m suggestive of a debris disc. While nine of the discs appear to be unstable to perturbations from their host binary based on a simple analysis of their inferred radii, we argue that the evidence for genuine instability is not strong, primarily because of uncertainty in the true disc radii, uncertainty in the boundaries of the unstable regions, and orbital projection effects. The binary separation distributions of the disc-bearing and disc-free systems are different at a confidence level of $99.4\%$, indicating that binary separation strongly influences the presence of detectable levels of debris. No discs are detected for separations between $\sim$25 and 135 au; this is likely a result of binaries whose separations are comparable with typical disc radii clearing out their primordial circumstellar or circumbinary material via dynamical perturbations. The disc detection rate is $19^{+5}_{-3}\%$ for binaries wider than 135 au, similar to published results for single stars. Only $8^{+2}_{-1}\%$ of systems with separations below 25 au host a detectable disc, which may suggest that planetesimal formation is inhibited in binaries closer than a few tens of au, similar to the conclusions of studies of known planet-hosting binaries., Comment: MNRAS, in press; updated publication year

The most dramatic phases of terrestrial planet formation are thought to be oligarchic and chaotic growth, on timescales of up to 100-200 Myr, when violent impacts occur between large planetesimals of sizes up to proto-planets. Such events are marked by the production of large amounts of debris as has been observed in some exceptionally bright and young debris disks (termed extreme debris disks). Here we report five years of Spitzer measurements of such systems around two young solar-type stars: ID8 and P1121. The short-term (weekly to monthly) and long-term (yearly) disk variability is consistent with the aftermaths of large impacts involving large asteroid-size bodies. We demonstrate that an impact-produced clump of optically thick dust, under the influence of the dynamical and viewing geometry effects, can produce short-term modulation in the disk light curves. The long-term disk flux variation is related to the collisional evolution within the impact-produced fragments once released into a circumstellar orbit. The time-variable behavior observed in the P1121 system is consistent with a hypervelocity impact prior to 2012 that produced vapor condensates as the dominant impact product. Two distinct short-term modulations in the ID8 system argue for two violent impacts at different times and locations. Its long-term variation is consistent with the collisional evolution of two different populations of impact-produced debris dominated by either vapor condensates or escaping boulders. The bright, variable emission from the dust produced in large impacts from extreme debris disks provides a unique opportunity to study violent events during the era of terrestrial planet formation., accepted for publication in AJ. typos and latex referencing fixed

One of the defining properties of debris discs compared to protoplanetary discs used to be their lack of gas, yet small amounts of gas have been found around an increasing number of debris discs in recent years. These debris discs found to have gas tend to be both young and bright. In this paper we conduct a deep search for CO gas in the system HD 95086 - a 17 Myr old, known planet host that also has a debris disc with a high fractional luminosity of $1.5\times10^{-3}$. Using the Atacama Large Millimeter/submillimeter Array (ALMA) we search for CO emission lines in bands 3, 6 and 7. By implementing a spectro-spatial filtering technique, we find tentative evidence for CO $J$=2-1 emission in the disc located at a velocity, 8.5$\pm$0.2 km s$^{-1}$, consistent with the radial velocity of the star. The tentative detection suggests that the gas on the East side of the disc is moving towards us. In the same region where continuum emission is detected, we find an integrated line flux of 9.5$\pm$3.6 mJy km s$^{-1}$, corresponding to a CO mass of (1.4-13)$\times10^{-6}$ M$_\oplus$. Our analysis confirms that the level of gas present in the disc is inconsistent with the presence of primordial gas in the system and is consistent with second generation production through the collisional cascade., 11 pages, 7 figures, accepted to MNRAS