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Abstract Coronavirus disease 2019 (COVID-19) continues to significantly impact the global population, thus countermeasure platforms that enable rapid development of therapeutics against variants of SARS-CoV-2 are essential. We report use of a phage display human antibody library approach to rapidly identify neutralizing antibodies (nAbs) against SARS-CoV-2. We demonstrate the binding and neutralization capability of two nAbs, STI-2020 and STI-5041, against the SARS-CoV-2 WA-1 strain as well as the Alpha and Beta variants. STI-2020 and STI-5041 were protective when administered intravenously or intranasally in the golden (Syrian) hamster model of COVID-19 challenged with the WA-1 strain or Beta variant. The ability to administer nAbs intravenously and intranasally may have important therapeutic implications and Phase 1 healthy subjects clinical trials are ongoing.

Metal/carbon nanocomposites have shown great potential as high-performance, low-cost electrocatalysts owing largely to their unique metal-support interactions. These nanocomposites are typically prepared by conventional pyrolysis that is tedious and energy-intensive. Herein, we report the ultrafast preparation of cobalt/carbon nanocomposites by magnetic induction heating (MIH) of metal organic frameworks within seconds under an inert atmosphere. The resulting samples consist of cobalt nanoparticles encapsulated within defective carbon shells, and effectively catalyze oxygen evolution reaction (OER) in alkaline media. Among the series, the sample prepared at 400 A for 10 s exhibits the best OER performance, needing a low overpotential of +308 mV to reach the current density of 10 mA cm−2, along with excellent stability, and even outperforms commercial RuO2 at high overpotentials. This is ascribed to the charge transfer between the carbon scaffold and metal nanoparticles. Operando X-ray absorption spectroscopy measurements show that the electrochemically produced CoOOH species is responsible for the high electrocatalytic performance. The results highlight the unique potential of MIH in the development of effective nanocomposite catalysts for electrochemical energy technologies.

Gestational diabetes mellitus (GDM) is a growing public health concern for many reasons, and its etiology remains unclear. Due to the similarity of its pathophysiology with type 2 diabetes (T2DM), we evaluated the relationship between published T2DM susceptibility genes and the risk of GDM. A total of 303 SNPs from genes including IRS1, IGF2BP2, CDKAL1, GCK, TCF7L2, KCNQ1, and KCNJ11 and the risk of GDM were examined in a nested case-control study with 321 GDM cases and 316 controls. The odds ratios (ORs) and their 95% confidence interval (95% CI) were estimated by unconditional logistical regression as a measure of the associations between genotypes and GDM in additive, recessive, dominant, and codominant models adjusting for maternal age, maternal BMI, parity, and family history of diabetes. At the gene level, CDKAL1 was associated with GDM risk. SNPs in the CDKAL1 gene including rs4712527, rs7748720, rs9350276, and rs6938256 were associated with reduced GDM risk. However, SNPs including rs9295478, rs6935599, and rs7747752 were associated with elevated GDM risk. After adjusting for multiple comparisons, rs9295478 and rs6935599 were still significant across the additive, recessive, and codominant models; rs7748720 and rs6938256 were significant in dominant and codominant models; and rs4712527 was only significant in the codominant model. Our study provides evidence for an association between the CDKAL1 gene and risk of GDM. However, its role in the GDM pathogenesis still needs to be verified by further studies.

Identification of modifiable dietary factors, which are involved in the development of gestational diabetes mellitus (GDM), could inform strategies to prevent GDM. Therefore, we examined the dietary nutrient patterns and evaluated their relationship with GDM risk in a Chinese population using a case control study design. A total of 1,464 GDM cases and 8,092 non-GDM controls were included in the final analysis. Dietary intake was assessed using a 33-item food frequency questionnaire, and nutrients were estimated using the Chinese Standard Tables of Food Consumption. Dietary nutrient patterns were identified using factor analysis, and their associations with GDM risk were evaluated using unconditional logistic regression models adjusting for total energy intake, maternal age, high blood pressure, education, maternal body mass index (BMI), parity, and family history of diabetes. A “vitamin” nutrient pattern was characterized as the consumption of diet rich in vitamin A, carotene, vitamin B2, vitamin B6, vitamin C, dietary fiber, folate, calcium, and potassium. For every quartile increase in the vitamin factor score during one year prior to conception, the first trimester, and the second trimester of pregnancy, the GDM risk decreased by 9% (OR: 0.91, 95%CI: 0.86-0.96), 9% (OR: 0.91, 95%CI: 0.86-0.96), and 10% (OR: 0.90, 95%CI: 0.85-0.95), respectively. The significant reduced GDM risk was seen in women regardless of age and parity, and slightly stronger effect was found in women whose age≤30 and women who are nulliparous across the three time periods. The significant association was also found in women whose BMI≤24 with similar effect size across the three time periods. Our study suggests that the vitamin nutrient pattern diet is associated with decreased GDM risk. Additional studies are necessary to explore the underlying mechanism of this relationship.

Abstract Background Oxidative injury occurs in septic people, but the role of oxidative stress and antioxidants has rarely been evaluated in foals. Objectives/Hypothesis To measure reactive oxygen species (ROS), biomarkers of oxidative injury, and antioxidants in neonatal foals. We hypothesized that ill foals would have higher blood concentrations of ROS and biomarkers of oxidative injury and lower concentrations of antioxidants compared to healthy foals. Animals Seventy‐two hospitalized and 21 healthy neonatal foals. Methods Prospective cohort study. Reactive oxygen species (hydrogen peroxide [H2O2]), biomarkers of oxidative injury (malondialdehyde [MDA], protein carbonyl), and antioxidants (superoxide dismutase [SOD], catalase [CAT], glutathione, and glutathione reductase [GR] and peroxidase [GPx]) were measured from foals at admission. Measured variables were compared between healthy and ill foals using a 1‐way ANOVA by Tukey's multiple comparisons test. Results Ill foals (n = 51) had significantly higher mean concentrations of H2O2 (healthy 2.6 ± 1.4 nmol/mL, ill 6.8 ± 4.6 L nmol/mL; 95% CI), MDA (healthy 31.2 ± 14.4 nmol/mL, ill 114.3 ± 94.0 nmol/mL; 95% CI), and protein carbonyl (healthy 0.07 ± 0.01 nmol/mg protein, ill 0.12 ± 0.02 nmol/mg protein, 95% CI). Significant lower CAT (healthy 0.4 ± 0.3 mU/mg protein, ill 0.02 ± 0.02 mU/mg protein, 95% CI), glutathione (healthy 238.5 ± 101.9 μg/mL, ill 110.7 ± 37.8 μg/mL, 95% CI; P

Introduction: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, acquired, non-malignant hematologic disease characterized by complement-mediated hemolysis (with or without hemoglobinuria), fatigue, increased susceptibility to thrombosis, and bone marrow dysfunction. The development of complement inhibitors has transformed outcomes for patients with PNH, but patients may still experience pharmacodynamic breakthrough hemolysis (BTH), which can be caused by exposure to a complement amplifying condition (CAC), such as vaccination, infection, or surgery.Materials and methods: A 13-member expert panel used a validated methodology (a RAND/UCLA modified Delphi panel) to develop consensus on how to classify pharmacodynamic BTH in patients with complement-inhibitor treated PNH. Physicians reviewed literature, rated the appropriateness of over 400 scenarios, and discussed the ratings at an in-person meeting.Results: After the meeting, the panel agreed on 77% of scenarios. Here, we present the group’s agreed-upon recommendations on how to manage BTH caused by a CAC, as well as provide a severity classification system for BTH and strategies to mitigate risk of BTH in special circumstances (e.g. vaccination, planned or unplanned surgery, and pregnancy).Discussion: In general, as severity of BTH increased, experts agreed more interventions to manage the BTH were appropriate. These recommendations are based on clinical experience and opinion. Without clear data from randomized trials to guide the management of BTH, expert opinion can be useful to support patient care.

Abstract Background The hypothalamic‐pituitary‐adrenocortical axis (HPAA) response to sepsis can be impaired in critical illness. Corticotropin‐releasing hormone (CRH) stimulation test might assess HPAA function in foals. Objective To evaluate plasma cortisol, ACTH, arginine vasopressin (AVP), and endogenous CRH (eCRH) response to different doses of ovine CRH (oCRH). Animals Healthy (n = 14) and hospitalized (n = 15) foals

IntroductionCytogenetic analysis is important for stratifying patients with various neoplasms. We explored the use of targeted next generation sequencing (NGS) in detecting chromosomal structural abnormalities or copy number variations (CNVs) in patients with myeloid neoplasms.MethodsPlasma cell-free DNA (cfDNA) from 2821 myeloid or lymphoid neoplasm patients were collected. cfDNA was sequenced using a 275 gene panel. CNVkit software was used for analyzing and visualizing CNVs. Cytogenetic data from corresponding bone marrow (BM) samples was available on 89 myeloid samples.ResultsOf the 2821 samples, 1539 (54.5%) showed evidence of mutations consistent with the presence of neoplastic clones in circulation. Of these 1539 samples, 906 (59%) showed abnormalities associated with myeloid neoplasms and 633 (41%) with lymphoid neoplasms. Chromosomal structural abnormalities in cfDNA were detected in 146 (16%) myeloid samples and 76 (12%) lymphoid samples. Upon comparison of the myeloid samples with 89 BM patients, NGS testing was able to reliably detect chromosomal gain or loss, except for fusion abnormalities. When cytogenetic abnormalities were classified according to prognostic classes, there was a complete (100%) concordance between cfDNA NGS data and cytogenetic data.ConclusionsThis data shows that liquid biopsy using targeted NGS is reliable in detecting chromosomal structural abnormalities in myeloid neoplasms. In specific circumstances, targeted NGS may be reliable and efficient to provide adequate information without the need for BM biopsy considering broad mutation profiling can be obtained through adequate sequencing within the same test. Overall, this study supports the use of liquid biopsy for early diagnosis and monitoring of patients with myeloid neoplasms.

Inflammatory bowel diseases (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), are complex, multifactorial disorders that lead to chronic and relapsing intestinal inflammation. The exact etiology remains unknown, however multiple factors including the environment, genetic, dietary, mucosal immunity, and altered microbiome structure and function play important roles in disease onset and progression. Supporting this notion that the gut microbiota plays a pivotal role in IBD pathogenesis, studies in gnotobiotic mice have shown that mouse models of intestinal inflammation require a microbial community to develop colitis. Additionally, antimicrobial therapy in some IBD patients will temporarily induce remission further demonstrating an association between gut microbes and intestinal inflammation. Finally, a dysfunctional intestinal epithelial barrier is also recognized as a key pathogenic factor in IBD. The intestinal epithelium serves as a barrier between the luminal environment and the mucosal immune system and guards against harmful molecules and microorganisms while being permeable to essential nutrients and solutes. Beneficial (i.e., mutualists) bacteria promote mucosal health by strengthening barrier integrity, increasing local defenses (mucin and IgA production) and inhibiting pro-inflammatory immune responses and apoptosis to promote mucosal homeostasis. In contrast, pathogenic bacteria and pathobionts suppress expression and localization of tight junction proteins, cause dysregulation of apoptosis/proliferation and increase pro-inflammatory signaling that directly damages the intestinal mucosa. This review article will focus on the role of intestinal epithelial cells (IECs) and the luminal environment acting as mediators of barrier function in IBD. We will also share some of our translational observations of interactions between IECs, immune cells, and environmental factors contributing to maintenance of mucosal homeostasis, as it relates to GI inflammation and IBD in different animal models.

Abstract This paper summarizes the presentations submitted for publication of the 12th AIST National Congress (Associazione Italiana Studio Tosse/Italian Association for Cough Study) entitled “The thousand facets of cough. A clinical and therapeutic update”, which occurred last February 2nd-3rd, 2018 in Bologna (Italy). It summarizes the contributions from leading experts of the sector, who, as in the previous editions, also this year have analyzed a problem too often underestimated which still has many dark sides as regards both the diagnosis and the therapy of cough. The Scientific Committee has chosen topics that had less space in previous editions and these are topical subjects representing a concrete opportunity for learning and comparison of opinions, as well as indispensable elements for the correct management of the symptoms. Hereby we report the abstracts of the works submitted for publication in this Meeting report. The main topics have covered Cough relationship with nerve vagus, ATP, air pollution, GERD, imaging, COPD, pediatric and therapy. Of particular interest it is the preliminary data on cough hydration ratio that shows a highly significant correlation between dehydration and cough.

The expansion of RN-to-BSN (registered nurse to Bachelor of Science in Nursing) education is addressing the need for nursing workforce development. However, little is known about what RNs expect from their RN-to-BSN education experience. Lack of understanding of student expectations could lead to student-perceived gaps in service quality. The aim of this study was to explore students’ expectations of the RN-to-BSN program compared with the faculty’s perceptions of what students expect. A descriptive qualitative research study using structured interviews was conducted at a school of nursing in the Midwest region of the United States. Student and faculty reports revealed the common themes of workload, flexibility, coursework, and support. Congruencies were noted in the areas of workload and coursework, and differences were identified in the areas of flexibility and support. Conducting a gap analysis can be a worthwhile endeavor for educators seeking to understand the needs of their student population. Acknowledging RN-to-BSN student expectations and addressing gaps between their expectations and reality early in the program could improve student perceptions of program quality.

OBJECTIVES/SPECIFIC AIMS: A mimic of congenital infections and a rare genetic cause of interferon overproduction, Aicardi Goutières Syndrome (AGS) results in significant neurologic disability. AGS is caused by pathogenic changes in the intracellular nucleic acid sensing machinery (TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, ADAR1, and IFIH1). All affected individuals exhibit neurologic impairment: from mild spastic paraparesis to severe tetraparesis and global developmental delay. We hypothesize that genotype influences the heterogeneous developmental trajectory found in AGS. METHODS/STUDY POPULATION: To characterize this spectrum, age and symptoms at presentation and longitudinal developmental skill acquisition was collected from an international cohort of children (n=88) with genetically confirmed AGS. RESULTS/ANTICIPATED RESULTS: We found that individuals present at variable ages, with the largest range in SAMHD1, ADAR, and IFIH1. There are 3 clusters of symptoms at presentation: altered mental status (irritability or lethargy), systemic inflammatory symptoms, and acute neurologic symptoms, with variability across all genotypes. By creating Kaplan-Meier curves for developmental milestones, we were able to create genotype-based developmental trajectories for the children affected by the 5 most common genotypes: TREX1, IFIH1, SAMHD1, ADAR, and RNASEH2B. Individuals with AGS secondary to TREX1 were the most severely affected, significantly less likely to reach milestones compared to the other genotypes, including head control, sitting, and nonspecific mama/dada (p-value

This paper argues that comparative education researchers – and education researchers generally – should pay more attention to how they conceptualize the Context(s) of schools and education systems. The construction of «the research context» is caught up in the mobilization of norms, power relations, regulative principles, technologies and strategies. Ascriptions of Context can operate as externally imposed categories that enclose, disable, and deny access to resources, opportunities, agency, and subject positions. In like measure, inscriptions of Context can sometimes enable, increase access and generally privilege particular cultural groups or particular social settings. This paper offers methodological strategies for analytically approaching the problem of Context in educational research. We propose that challenge is to understand how Context is part of an interweaving process with an object/objects within an assemblage that is ever changing. The «entangled analysis» approach (Sobe, forthcoming) advanced here attends to the constructed and constructing quality of Context. And it necessarily brings the researcher into the problematic, as she too is continually within the power/knowledge relations that make Contexts meaningful and consequential. We are argue that «contextualizing» a study should not be merely a preparatory activity but should carry across the entirety of a research project. Rather than beginning with standardized Contextual categories researchers should seek to understand the confluence of practices and objects that are coming together as well as constantly flowing and changing.