Chemical and spatial dual-confinement engineering for stable Na-S batteries with approximately 100% capacity retention.

Sodium-sulfur (Na-S) batteries are attracting intensive attention due to the merits like high energy and low cost, while the poor stability of sulfur cathode limits the further development. Here, we report a chemical and spatial dual-confinement approach to improve the stability of Na-S batteries. It refers to covalently bond sulfur to carbon at forms of C-S/N-C=S bonds with high strength for locking sulfur. Meanwhile, sulfur is examined to be S1-S2 small species produced by thermally cutting S8 large molecules followed by sealing in the confined pores of carbon materials. Hence, the sulfur cathode achieves a good stability of maintaining a high-capacity retention of 97.64% after 1000 cycles. Experimental and theoretical results show that Na+ is hosted via a coordination structure (N···Na···S) without breaking the C-S bond, thus impeding the formation and dissolution of sodium polysulfide to ensure a good cycling stability. This work provides a promising method for addressing the S-triggered stability problem of Na-S batteries and other S-based batteries.

The penultimate step of proteasomal ATPase assembly is mediated by a switch dependent on the chaperone Nas2.

The proteasome holoenzyme is a complex molecular machine that degrades most proteins. In the proteasome holoenzyme, six distinct ATPase subunits (Rpt1 through Rpt6) enable protein degradation by injecting protein substrates into it. Individual Rpt subunits assemble into a heterohexameric "Rpt ring" in a stepwise manner, by binding to their cognate chaperones. Completion of the heterohexameric Rpt ring correlates with release of a specific chaperone, Nas2; however, it is unclear whether and how this event may ensure proper Rpt ring assembly. Here, we examined the action of Nas2 by capturing the poorly characterized penultimate step of heterohexameric Rpt ring assembly. For this, we used a heterologous Escherichia coli system coexpressing all Rpt subunits and assembly chaperones as well as Saccharomyces cerevisiae to track Nas2 actions during endogenous Rpt ring assembly. We show that Nas2 uses steric hindrance to block premature progression of the penultimate step into the final step of Rpt ring assembly. Importantly, Nas2 can activate an assembly checkpoint via its steric activity, when the last ATPase subunit, Rpt1, cannot be added in a timely manner. This checkpoint can be relieved via Nas2 release, when Nas2 recognizes proper addition of Rpt1 to one side of its cognate Rpt5, and ATP hydrolysis by Rpt4 on the other side of Rpt5, allowing completion of Rpt ring assembly. Our findings reveal dual criteria for Nas2 release, as a mechanism to ensure both the composition and functional competence of a newly assembled proteasomal ATPase, to generate the proteasome holoenzyme.

A Mott-Schottky Heterojunction with Strong Chemisorption and Fast Conversion Effects for Room-Temperature Na-S Batteries.

The practical application of the room-temperature sodium-sulfur (RT Na-S) batteries is currently limited by low reversible capacity and serious capacity decay due to the sluggish reaction kinetics and shuttle effect. It is necessary to design a suitable sulfur host integrated with electrocatalysts to realize effective chemisorption and catalysis of sodium polysulfides (NaPSs). Herein, under the guidance of theoretical calculation, the Mott-Schottky heterojunction with a built-in electric field composed of iron (Fe) and iron disulfide (FeS2) components anchored on a porous carbon matrix (Fe/FeS2-PC) is designed and prepared. The enhanced chemisorption effect of Fe, the fast electrocatalytic effect of FeS2, and the fast transfer effect of the built-in electric field within the Fe/FeS2 heterojunction in the cathode of RT Na-S batteries work together to effectively improve the electrochemical performance. As a result, the Fe/FeS2-PC@S cathode exhibits high reversible capacity (815 mAh g-1 after 150 cycles at 0.2 A g-1) and excellent stability (516 mAh g-1 after 600 cycles at 5 A g-1, with only 0.07% decay per cycle). The design of the Fe/FeS2 heterojunction electrocatalyst provides a new strategy for the development of highly stable RT Na-S batteries.

Hepatitis B surface antigen loss in chronic hepatitis B patients with low-viral-load.

BACKGROUND AND AIM: Among low viral load (DNA of hepatitis B virus (HBV) was < 2000 IU/mL), the factor of the loss of hepatitis B surface antigen (HBsAg) remained elusive. METHODS: The retrospective study recruited patients with chronic hepatitis B (CHB) who were negative low for hepatitis B e-antigen (HBeAg), had a low viral load, and experienced HBsAg loss during follow-up. CHB patients with low-viral load but without consequent HBsAg loss were also enrolled at the ratio of 1:4. The factors contributing to HBsAg loss were analyzed. RESULTS: A total of 80 patients were recruited for the current study, with a mean age of 63.9 years and 61.3% being male. Among them, 62.5% patients (50/80) were treated with potent nucleoside/nucleotide analogues (NAs) during the follow-up period. Additionally, 12.5% patients (10/80) had a prior history of NAs treatment before enrolment. During the follow-up, HBsAg loss occurred in 17 patients (21.3%). Compared with patients without HBsAg loss, those with HBsAg loss were younger (57.9 years vs 65.5 years; P = 0.01), had lower HBV DNA levels (1.3 log10 IU/mL vs 2.3 log10 IU/mL; P = 0.003), and higher proportion of prior NAs-treated history. Logistic regression analysis revealed that the factors associated with factors associated with HBsAg loss were age < 60 years (OR/CI: 3.95/1.15-13.60, P = 0.03), prior NAs-treated history (OR/CI: 7.59/1.42-40.51, P = 0.01) and current NAs-treated (OR/CI: 0.19/0.05-0.71, P = 0.01). CONCLUSIONS: In the study, older age and prior NAs were positively associated with HBsAg loss, and current NAs was negatively associated with HBsAg loss. Additionally, some patients experienced HBsAg loss during the NAs therapy.

Short communication: An alternative pathway for melatonin synthesis in the skin of European flounder (Platichthys flesus).

The classic melatonin biosynthesis pathway (Mel; N-acetyl-5-methoxytryptamine) involves two consecutive enzymatic steps that are decisive in hormone production: conversion of serotonin (5-hydroxytryptamine; 5-HT) to N-acetylserotonin (NAS) and the methylation of the last compound to Mel. This pathway requires the activity of the enzymes: the first is of the category of N-acetyltransferases (AANAT, SNAT, or NAT) and the second is N-acetylserotonin O-methyltransferase (ASMT; also known as HIOMT). However, quite recently, new information has been provided on the possibility of an alternative Mel synthesis pathway; it would include a two-step action by these enzymes, but in reverse order, where ASMT (or ASMTL, the enzyme related to ASMT) methylates 5-HT to 5-methoxytryptamine (5-MT), and then the last compound is acetylated by an enzyme of the category of N-acetyltransferases to Mel. In our study on the activity of enzymes in the Mel biosynthesis pathway in flounder skin, we have found an increase in 5-MT level, as a result of the increase in 5-HT concentration, which is followed by a growing concentration of Mel. However, we have not found any increase in Mel concentration, despite an increase in NAS in the samples. Our data strongly suggest an alternative way of Mel production in flounder skin in which 5-HT is first methylated to 5-MT, which is then acetylated to Mel.

Protein intrinsically disordered region prediction by combining neural architecture search and multi-objective genetic algorithm.

BACKGROUND: Intrinsically disordered regions (IDRs) are widely distributed in proteins and related to many important biological functions. Accurately identifying IDRs is of great significance for protein structure and function analysis. Because the long disordered regions (LDRs) and short disordered regions (SDRs) share different characteristics, the existing predictors fail to achieve better and more stable performance on datasets with different ratios between LDRs and SDRs. There are two main reasons. First, the existing predictors construct network structures based on their own experiences such as convolutional neural network (CNN) which is used to extract the feature of neighboring residues in protein, and long short-term memory (LSTM) is used to extract the long-distance dependencies feature of protein residues. But these networks cannot capture the hidden feature associated with the length-dependent between residues. Second, many algorithms based on deep learning have been proposed but the complementarity of the existing predictors is not fully explored and used. RESULTS: In this study, the neural architecture search (NAS) algorithm was employed to automatically construct the network structures so as to capture the hidden features in protein sequences. In order to stably predict both the LDRs and SDRs, the model constructed by NAS was combined with length-dependent models for capturing the unique features of SDRs or LDRs and general models for capturing the common features between LDRs and SDRs. A new predictor called IDP-Fusion was proposed. CONCLUSIONS: Experimental results showed that IDP-Fusion can achieve more stable performance than the other existing predictors on independent test sets with different ratios between SDRs and LDRs.

Determinants of increased nursing workload in the COVID-era: A retrospective analysis of prospectively collected data.

BACKGROUND: COVID-19 is associated with increased nursing workload, therefore a high nurse-to-patient ratio would be required. AIM: To analyse difference in nursing workload, as expressed with the Nursing Activities Score (NAS), between COVID-19 patients versus control patients without COVID-19 disease (NCOVID-19 group) in an Italian Extracorporeal Membrane Oxygenation (ECMO) centre. STUDY DESIGN: Retrospective analysis of prospectively collected data, enrolling consecutive patients admitted to a general Intensive Care Unit, between 1st May 2019 and 28th February 2021. A multivariate analysis was then performed to assess if COVID-19 disease was an independent predictor of higher NAS and to assess which other factors and procedures are independently associated with increased workload. RESULTS: We enrolled 574 patients, of which 135 (24%) were in the COVID-19 group and 439 (76%) in the NCOVID-19 group. The average NAS was higher in the COVID-19 group (79 ± 11 vs. 65 ± 15, T = -10.026; p < 0.001). Prone positioning, continuous renal replacement therapy (CRRT) and ECMO were used more frequently in the COVID-19 group. A higher fraction of patients in the COVID group showed colonization from multidrug resistant bacteria. COVID-19 group had a higher duration of mechanical ventilation and longer ICU stay. The COVID-19 diagnosis was independently associated with a higher NAS. Other independent predictors of higher NAS were the use of prone positioning and continuous renal replacement therapy (CRRT). Colonization from multidrug resistant bacteria and ECMO support were not independently associated with higher NAS. CONCLUSIONS: The higher nursing workload in COVID-19 patients is mainly due to specific procedures required to treat the most hypoxemic patients, such as prone positioning. Colonization with multidrug resistant bacteria and ECMO support were not independently associated with a higher NAS. RELEVANCE TO CLINICAL PRACTICE: Higher workload in COVID-19 patients was due to specific interventions, such as prone positioning and CRRT, with the related nursing activities, as continuous presence at patient's bed, mobilization, positioning and complex hygienic procedures.

Root-to-shoot iron partitioning in Arabidopsis requires IRON-REGULATED TRANSPORTER1 (IRT1) protein but not its iron(II) transport function.

IRON-REGULATED TRANSPORTER1 (IRT1) is the root high-affinity ferrous iron (Fe) uptake system and indispensable for the completion of the life cycle of Arabidopsis thaliana without vigorous Fe supplementation. Here we provide evidence supporting a second role of IRT1 in root-to-shoot partitioning of Fe. We show that irt1 mutants overaccumulate Fe in roots, most prominently in the cortex of the differentiation zone in irt1-2, compared to the wild type. Shoots of irt1-2 are severely Fe-deficient according to Fe content and marker transcripts, as expected. We generated irt1-2 lines producing IRT1 mutant variants carrying single amino-acid substitutions of key residues in transmembrane helices IV and V, Ser206 and His232, which are required for transport activity in yeast. Root short-term 55 Fe uptake rates were uninformative concerning IRT1-mediated transport. Overall irt1-like concentrations of the secondary substrate Mn suggested that the transgenic Arabidopsis lines also remain incapable of IRT1-mediated root Fe uptake. Yet, IRT1S206A partially complements rosette dwarfing and leaf chlorosis of irt1-2, as well as root-to-shoot Fe partitioning and gene expression defects of irt1-2, all of which are fully complemented by wild-type IRT1. Taken together, these results suggest a regulatory function for IRT1 in root-to-shoot Fe partitioning that does not require Fe transport activity of IRT1. Among the genes of which transcript levels are partially dependent on IRT1, we identify MYB DOMAIN PROTEIN10, MYB DOMAIN PROTEIN72 and NICOTIANAMINE SYNTHASE4 as candidates for effecting IRT1-dependent Fe mobilization in roots. Understanding the biological functions of IRT1 will help to improve Fe nutrition and the nutritional quality of agricultural crops.

Defining the serum proteomic signature of hepatic steatosis, inflammation, ballooning and fibrosis in non-alcoholic fatty liver disease.

BACKGROUND & AIMS: Despite recent progress, non-invasive tests for the diagnostic assessment and monitoring of non-alcoholic fatty liver disease (NAFLD) remain an unmet need. Herein, we aimed to identify diagnostic signatures of the key histological features of NAFLD. METHODS: Using modified-aptamer proteomics, we assayed 5,220 proteins in each of 2,852 single serum samples from 636 individuals with histologically confirmed NAFLD. We developed and validated dichotomized protein-phenotype models to identify clinically relevant severities of steatosis (grade 0 vs. 1-3), hepatocellular ballooning (0 vs. 1 or 2), lobular inflammation (0-1 vs. 2-3) and fibrosis (stages 0-1 vs. 2-4). RESULTS: The AUCs of the four protein models, based on 37 analytes (18 not previously linked to NAFLD), for the diagnosis of their respective components (at a clinically relevant severity) in training/paired validation sets were: fibrosis (AUC 0.92/0.85); steatosis (AUC 0.95/0.79), inflammation (AUC 0.83/0.72), and ballooning (AUC 0.87/0.83). An additional outcome, at-risk NASH, defined as steatohepatitis with NAFLD activity score ≥4 (with a score of at least 1 for each of its components) and fibrosis stage ≥2, was predicted by multiplying the outputs of each individual component model (AUC 0.93/0.85). We further evaluated their ability to detect change in histology following treatment with placebo, pioglitazone, vitamin E or obeticholic acid. Component model scores significantly improved in the active therapies vs. placebo, and differential effects of vitamin E, pioglitazone, and obeticholic acid were identified. CONCLUSIONS: Serum protein scanning identified signatures corresponding to the key components of liver biopsy in NAFLD. The models developed were sufficiently sensitive to characterize the longitudinal change for three different drug interventions. These data support continued validation of these proteomic models to enable a "liquid biopsy"-based assessment of NAFLD. CLINICAL TRIAL NUMBER: Not applicable. IMPACT AND IMPLICATIONS: An aptamer-based protein scan of serum proteins was performed to identify diagnostic signatures of the key histological features of non-alcoholic fatty liver disease (NAFLD), for which no approved non-invasive diagnostic tools are currently available. We also identified specific protein signatures related to the presence and severity of NAFLD and its histological components that were also sensitive to change over time. These are fundamental initial steps in establishing a serum proteome-based diagnostic signature of NASH and provide the rationale for using these signatures to test treatment response and to identify several novel targets for evaluation in the pathogenesis of NAFLD.

Core-Shell Tandem Catalysis Coupled with Interface Engineering For High-Performance Room-Temperature Na-S Batteries.

The sluggish redox kinetics and shuttle effect seriously impede the large application of room-temperature sodium-sulfur (RT Na-S) batteries. Designing effective catalysts into cathode material is a promising approach to overcome the above issues. However, considering the multistep and multiphase transformations of sulfur redox process, it is impractical to achieve the effective catalysis of the entire S8 →Na2 Sx →Na2 S conversion through applying a single catalyst. Herein, this work fabricates a nitrogen-doped core-shell carbon nanosphere integrated with two different catalysts (ZnS-NC@Ni-N4 ), where isolated Ni-N4 sites and ZnS nanocrystals are distributed in the shell and core, respectively. ZnS nanocrystals ensure the rapid reduction of S8 into Na2 Sx (4 < x ≤ 8), while Ni-N4 sites realize the efficient conversion of Na2 Sx into Na2 S, bridged by the diffusion of Na2 Sx from the core to shell. Besides, Ni-N4 sites on the shell can also induce an inorganic-rich cathode-electrolyte interface (CEI) on ZnS-NC@Ni-N4 to further inhibit the shuttle effect. As a result, ZnS-NC@Ni-N4 /S cathode exhibits an excellent rate-performance (650 mAh g-1 at 5 A g-1 ) and ultralong cycling stability for 2000 cycles with a low capacity-decay rate of 0.011% per cycle. This work will guide the rational design of multicatalysts for high-performance RT Na-S batteries.

SARS-CoV-2 infection activates CREB/CBP in cellular cyclic AMP-dependent pathways.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global coronavirus disease 2019 (COVID-19) pandemic that has affected the lives of billions of individuals. However, the host-virus interactions still need further investigation to reveal the underling mechanism of SARS-CoV-2 pathogenesis. Here, transcriptomics analysis of SARS-CoV-2 infection highlighted possible correlation between host-associated signaling pathway and virus. In detail, cAMP-protein kinase (PKA) pathway has an essential role in SARS-CoV-2 infection, followed by the interaction between cyclic AMP response element binding protein (CREB) and CREB-binding protein (CBP) could be induced and leading to the enhancement of CREB/CBP transcriptional activity. The replication of Delta and Omicron BA.5 were inhibited by about 49.4% and 44.7% after knockdown of CREB and CBP with small interfering RNAs, respectively. Furthermore, a small organic molecule naphthol AS-E (nAS-E), which targets on the interaction between CREB and CBP, potently inhibited SARS-CoV-2 wild-type (WT) infection with comparable the half-maximal effective concentration (EC50 ) 1.04 µM to Remdesivir 0.57 µM. Compared with WT virus, EC50 in Calu-3 cells against Delta, Omicron BA.2, and Omicron BA.5 were, on average, 1.5-fold, 1.1-fold, and 1.5-fold higher, respectively, nAS-E had a satisfied antiviral effect against Omicron variants. Taken together, our study demonstrated the importance of CREB/CBP induced by cAMP-PKA pathway during SARS-CoV-2 infection, and further provided a novel CREB/CBP interaction therapeutic drug targets for COVID-19.

Distribution of morphine and methadone to the brain in a developmental chicken embryo model.

The use and/or misuse of opioids by pregnant women would expose the fetuses to these drugs during critical stages of development with serious effects for the newborn, like the neonatal abstinence syndrome (NAS). We have revisited an established chicken model for NAS to describe the distribution of morphine and methadone to the brain and explore its validity as a valuable alternative to rodent models. For this purpose, chicken eggs were injected with a single dose of 10 mg/kg or 20 mg/kg morphine or 20 mg/kg methadone onto the chorioallantoic membrane (CAM) on embryonal day 13. Whole brains and lungs were harvested and the concentrations of morphine, methadone and their subsequent metabolites (morphine-3-glucuronide and EDDP, respectively) determined in the brain and lungs at different time points using LC-MS/MS. Morphine and methadone, as well as their metabolites, were detected both in the brain and lungs, with significantly higher concentrations in the lungs. Pharmacokinetic modelling showed that the distribution of morphine to the brain followed a first-order absorption with transit compartments and linear elimination, with concentrations linearly dependent on dose. Moreover, methadone, but not morphine, reduced µ receptor (the main morphine receptor) binding, which can be of relevance for opioid tolerance. The present study is the first to report the brain distribution of morphine, which can be described by standard pharmacokinetic processes, and methadone in the developing chicken embryo. The present findings supplement the already established model and support the use of this chicken model to study NAS.

P-doped porous carbon from camellia shell for high-performance room temperature sodium-sulfur batteries.

Room-temperature sodium-sulfur batteries are still hampered by severe shuttle effects and sluggish kinetics. Most of the sulfur hosts require high cost and complex synthesis process. Herein, a facile method is proposed to prepare a phosphorous doped porous carbon (CSBP) with abundant defect sites from camellia shell by oxidation pretreatment combined with H3PO4activation. The pretreatment can introduce pores and adjust the structure of biochar precursor, which facilitates the further activation of H3PO4and effectively avoids the occurrence of large agglomeration. Profiting from the synergistic effects of physical confinement and doping effect, the prepared CSBP/S cathode delivers a high reversible capacity of 804 mAh g-1after 100 cycles at 0.1 C and still maintains an outstanding capacity of 458 mAh g-1after 500 cycles at 0.5 C (1 C = 1675 mA g-1). This work provides new insights into the rational design of the microstructures of carbon hosts for high-performance room temperature sodium-sulfur batteries.

Prognostic Factors for Non-anastomotic Biliary Strictures Following Adult Liver Transplantation: A Systematic Review and Meta-Analysis.

INTRODUCTION: The development of non-anastomotic biliary strictures (NAS) following orthotopic adult liver transplantation (OLT) is associated with significant morbidity. We performed a systematic review and meta-analysis to identify all prognostic factors for the development of NAS. METHODS: A systematic review was conducted following preferred reporting items for systematic reviews and meta-analyses (PRISMA) and the meta-analysis of observational studies in epidemiology (MOOSE) guidelines. We used the Newcastle-Ottawa scale to assess the quality of the included studies. Using the random-effects model, we calculated the weighted pooled odds ratios (OR), mean differences (MD), hazard ratios (HR), and 95% confidence intervals (CI) of the risk factors. RESULTS: Based on 19 international studies that included a total of 8269 adult LT patients, we calculated an 8% overall incidence of NAS. In this study, 7 potential prognostic factors were associated with a statistically significant hazard ratio for NAS in pooled analyses including (1) DCD donors compared to DBD donors (2) PSC as an indication for a liver transplant (3) Roux-en-Y bile duct reconstruction compared to duct-to-duct reconstruction (4) hepatic artery thrombosis (5) longer cold ischemia time (6) longer warm ischemia time (7) and total operative times. CONCLUSION: In this systematic review and meta-analysis, we identified 7 prognostic factors for the development of NAS following OLT. These findings might lay the groundwork for development of diagnostic algorithms to better risk stratify patients at risk for development of NAS.

Neonatal opioid toxicity: opioid withdrawal (abstinence) syndrome with emphasis on pharmacogenomics and respiratory depression.

The increasing use of opioids in pregnant women has led to an alarming rise in the number of cases of neonates with drug-induced withdrawal symptoms known as neonatal opioid withdrawal syndrome (NOWS). NOWS is a toxic heterogeneous condition with many neurologic, autonomic, and gastrointestinal symptoms including poor feeding, irritability, tachycardia, hypertension, respiratory defects, tremors, hyperthermia, and weight loss. Paradoxically, for the management of NOWS, low doses of morphine, methadone, or buprenorphine are administered. NOWS is a polygenic disorder supported by studies of genomic variation in opioid-related genes. Single-nucleotide polymorphisms (SNPs) in CYP2B6 are associated with variations in NOWS infant responses to methadone and SNPs in the OPRM1, ABCB1, and COMT genes are associated with need for treatment and length of hospital stay. Epigenetic gene changes showing higher methylation levels in infants and mothers have been associated with more pharmacologic treatment in the case of newborns, and for mothers, longer infant hospital stays. Respiratory disturbances associated with NOWS are not well characterized. Little is known about the effects of opioids on developing neonatal respiratory control and respiratory distress (RD), a potential problem for survival of the neonate. In a rat model to test the effect of maternal opioids on the developing respiratory network and neonatal breathing, maternal-derived methadone increased apneas and lessened RD in neonates at postnatal (P) days P0 and P1. From P3, breathing normalized with age suggesting reorganization of respiratory rhythm-generating circuits at a time when the preBötC becomes the dominant inspiratory rhythm generator. In medullary slices containing the preBötC, maternal opioid treatment plus exposure to exogenous opioids showed respiratory activity was maintained in younger but not older neonates. Thus, maternal opioids blunt centrally controlled respiratory frequency responses to exogenous opioids in an age-dependent manner. In the absence of maternal opioid treatment, exogenous opioids abolished burst frequencies at all ages. Prenatal opioid exposure in children stunts growth rate and development while studies of behavior and cognitive ability reveal poor performances. In adults, high rates of attention deficit disorder, hyperactivity, substance abuse, and poor performances in intelligence and memory tests have been reported.

The Alberta Neonatal Abstinence Syndrome Mother-Baby Care ImprovEmeNT (NASCENT) program: protocol for a stepped wedge cluster randomized trial of a hospital-level Neonatal Abstinence Syndrome rooming-in intervention.

BACKGROUND: Neonatal Abstinence Syndrome (NAS), a problem common in newborns exposed to substances in-utero, is an emerging health concern. In traditional models of care, infants with NAS are routinely separated from their mothers and admitted to the Neonatal Intensive Care Unit (NICU) with long, expensive length of stay (LOS). Research shows a rooming-in approach (keeping mothers and infants together in hospital) with referral support is a safe and effective model of care in managing NAS. The model's key components are facilitating 24-h care by mothers on post-partum or pediatric units with support for breastfeeding, transition home, and access to Opioid Dependency Programs (ODP). This study will implement the rooming-in approach at eight hospitals across one Canadian Province; support practice and culture shift; identify and test the essential elements for effective implementation; and assess the implementation's impact/outcomes. METHODS: A stepped wedge cluster randomized trial will be used to evaluate the implementation of an evidence-based rooming-in approach in the postpartum period for infants born to mothers who report opioid use during pregnancy. Baseline data will be collected and compared to post-implementation data. Six-month assessment of maternal and child health and an economic evaluation of cost savings will be conducted. Additionally, barriers and facilitators of the rooming-in model of care within the unique context of each site and across sites will be explored pre-, during, and post-implementation using theory-informed surveys, interviews, and focus groups with care teams and parents. A formative evaluation will examine the complex contextual factors and conditions that influence readiness and sustainability and inform the design of tailored interventions to facilitate capacity building for effective implementation. DISCUSSION: The primary expected outcome is reduced NICU LOS. Secondary expected outcomes include decreased rates of pharmacological management of NAS and child apprehension, increased maternal ODP participation, and improved 6-month outcomes for mothers and infants. Moreover, the NASCENT program will generate the detailed, multi-site evidence needed to accelerate the uptake, scale, and spread of this evidence-based intervention throughout Alberta, leading to more appropriate and effective care and use of healthcare resources. TRIAL REGISTRATION: ClinicalTrials.gov, NCT0522662. Registered February 4th, 2022.

Positive allosteric modulation of indoleamine 2,3-dioxygenase 1 restrains neuroinflammation.

l-tryptophan (Trp), an essential amino acid for mammals, is the precursor of a wide array of immunomodulatory metabolites produced by the kynurenine and serotonin pathways. The kynurenine pathway is a paramount source of several immunoregulatory metabolites, including l-kynurenine (Kyn), the main product of indoleamine 2,3-dioxygenase 1 (IDO1) that catalyzes the rate-limiting step of the pathway. In the serotonin pathway, the metabolite N-acetylserotonin (NAS) has been shown to possess antioxidant, antiinflammatory, and neuroprotective properties in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). However, little is known about the exact mode of action of the serotonin metabolite and the possible interplay between the 2 Trp metabolic pathways. Prompted by the discovery that NAS neuroprotective effects in EAE are abrogated in mice lacking IDO1 expression, we investigated the NAS mode of action in neuroinflammation. We found that NAS directly binds IDO1 and acts as a positive allosteric modulator (PAM) of the IDO1 enzyme in vitro and in vivo. As a result, increased Kyn will activate the ligand-activated transcription factor aryl hydrocarbon receptor and, consequently, antiinflammatory and immunoregulatory effects. Because NAS also increased IDO1 activity in peripheral blood mononuclear cells of a significant proportion of MS patients, our data may set the basis for the development of IDO1 PAMs as first-in-class drugs in autoimmune/neuroinflammatory diseases.

Strain diversity and infection durations of Staphylococcus spp. and Streptococcus spp. causing intramammary infections in dairy cows.

To effectively prevent and control bovine mastitis, farmers and their advisors need to take infection pathways and durations into account. Still, studies exploring both aspects through molecular epidemiology with sampling of entire dairy cow herds over longer periods are scarce. Therefore, quarter foremilk samples were collected at 14-d intervals from all lactating dairy cows (n = 263) over 18 wk in one commercial dairy herd. Quarters were considered infected with Staphylococcus aureus, Streptococcus uberis, or Streptococcus dysgalactiae when ≥100 cfu/mL of the respective pathogen was detected, or with Staphylococcus epidermidis or Staphylococcus haemolyticus when ≥500 cfu/mL of the respective pathogen was detected. All isolates of the mentioned species underwent randomly amplified polymorphic DNA (RAPD)-PCR to explore strain diversity and to distinguish ongoing from new infections. Survival analysis was used to estimate infection durations. Five different strains of Staph. aureus were isolated, and the most prevalent strain caused more than 80% of all Staph. aureus infections (n = 46). In contrast, 46 Staph. epidermidis and 69 Staph. haemolyticus strains were isolated, and none of these caused infections in more than 2 different quarters. The 3 most dominant strains of Strep. dysgalactiae (7 strains) and Strep. uberis (18 strains) caused 81% of 33 and 49% of 37 infections in total, respectively. The estimated median infection duration for Staph. aureus was 80 d, and that for Staph. epidermidis and Staph. haemolyticus was 28 and 22 d, respectively. The probability of remaining infected with Strep. dysgalactiae or Strep. uberis for more than 84 and 70 d was 58.7 and 53.5%, respectively. Staphylococcus epidermidis and Staph. haemolyticus were not transmitted contagiously and the average infection durations were short, which brings into question whether antimicrobial treatment of intramammary infections with these organisms is justified. In contrast, infections with the other 3 pathogens lasted longer and largely originated from contagious transmission.

Obstacle Detection System for Navigation Assistance of Visually Impaired People Based on Deep Learning Techniques.

Visually impaired people seek social integration, yet their mobility is restricted. They need a personal navigation system that can provide privacy and increase their confidence for better life quality. In this paper, based on deep learning and neural architecture search (NAS), we propose an intelligent navigation assistance system for visually impaired people. The deep learning model has achieved significant success through well-designed architecture. Subsequently, NAS has proved to be a promising technique for automatically searching for the optimal architecture and reducing human efforts for architecture design. However, this new technique requires extensive computation, limiting its wide use. Due to its high computation requirement, NAS has been less investigated for computer vision tasks, especially object detection. Therefore, we propose a fast NAS to search for an object detection framework by considering efficiency. The NAS will be used to explore the feature pyramid network and the prediction stage for an anchor-free object detection model. The proposed NAS is based on a tailored reinforcement learning technique. The searched model was evaluated on a combination of the Coco dataset and the Indoor Object Detection and Recognition (IODR) dataset. The resulting model outperformed the original model by 2.6% in average precision (AP) with acceptable computation complexity. The achieved results proved the efficiency of the proposed NAS for custom object detection.

Neural Architecture Search Survey: A Computer Vision Perspective.

In recent years, deep learning (DL) has been widely studied using various methods across the globe, especially with respect to training methods and network structures, proving highly effective in a wide range of tasks and applications, including image, speech, and text recognition. One important aspect of this advancement is involved in the effort of designing and upgrading neural architectures, which has been consistently attempted thus far. However, designing such architectures requires the combined knowledge and know-how of experts from each relevant discipline and a series of trial-and-error steps. In this light, automated neural architecture search (NAS) methods are increasingly at the center of attention; this paper aimed at summarizing the basic concepts of NAS while providing an overview of recent studies on the applications of NAS. It is worth noting that most previous survey studies on NAS have been focused on perspectives of hardware or search strategies. To the best knowledge of the present authors, this study is the first to look at NAS from a computer vision perspective. In the present study, computer vision areas were categorized by task, and recent trends found in each study on NAS were analyzed in detail.