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Drawing on research in mathematics and science education that has supported student higher-level thinking in K-12 classrooms, we sought to classify the ways of thinking and reasoning supported by robotics coding tasks. As part of a larger project, we examined coding tasks implemented in elementary school classrooms and analyzed ways of thinking and reasoning about coding supported by these tasks. From this analysis, we developed a framework for analyzing the cognitive demand of coding tasks that can be used to support researchers, curriculum developers, and teachers in supporting students' higher levels of thinking as they learn coding.

The authors developed a free online course that centers learning about identity, power, positionality, and privilege to support inclusive teaching for STEM faculty and future faculty. Instructors across all institution types, including community college and 2-year, regional and comprehensive, and public and private research universities, utilized and valued a free asynchronous online course with an optional local learning community facilitated by project-trained facilitation teams. Participants were highly engaged in the online course content, rated the content positively, and demonstrated increases in awareness, confidence, and intent to apply inclusive teaching strategies. Outcomes demonstrate that the key features of the course (My Inclusivity Framework, Learning Community and Affinity Group discussions, and Embodied Case Studies) were viewed as unique teaching development opportunities that created valuable learning for our participants.

Background: Patients who present to the emergency department (ED) with severe hypertension defined as a systolic blood pressure (SBP) ≥180 millimeters of mercury (mm Hg) or diastolic (DBP) ≥120 (mm Hg) without evidence of acute end-organ damage are often deemed high risk and treated acutely in the ED. However, there is a dearth of evidence from large studies with long-term follow-up for the assessment of major adverse cardiovascular events (MACE). We conducted the largest study to date of patients presenting with severe hypertension to identify predictors of MACE and examine whether blood pressure at discharge is associated with heightened risk. Methods: We enrolled ED patients with a SBP of 180–220 mm Hg but without signs of end-organ damage and followed them for one year. The primary outcome was MACE within one year of discharge. Secondarily, we performed a propensity-matched analysis to test whether SBP ≤160 mm Hg at discharge was associated with reduced MACE at 30 days. Results: A total of 12,044 patients were enrolled. The prevalence of MACE within one year was 1,865 (15.5%). Older age, male gender, history of cardiovascular disease, cerebrovascular disease, diabetes, smoking, presentation with chest pain, altered mental status, dyspnea, treatment with intravenous and oral hydralazine, and oral metoprolol were independent predictors for one-year MACE. Additionally, discharge with an SBP ≤160 mm Hg was not associated with 30-day MACE-free survival after propensity matching (hazard ratio 0.99, 95% confidence interval 0.78–1.25, P = 0.92). Conclusion: One-year MACE was relatively common in our cohort of ED patients with severe hypertension without acute end-organ damage. However, discharge blood pressure was not associated with 30-day or one-year MACE, suggesting that BP reduction in and of itself is not beneficial in such patients.

In this qualitative study, preservice early childhood education teachers created block-based code to control robots and used the robots in field experience at local preschools. The study is grounded in a conceptual framework that weaves together playful programing and resilience, interlocking concepts that can explain sustained engagement during times of challenge. We investigated how and why preservice early childhood teachers exhibit resilience during collaborative programing. We analyzed their debugging processes, reflections, and interviews using a phenomenological lens. We conducted open and axial coding and analysis of discourse and actions during debugging episodes. Results suggest that teachers exhibited resilience due to the following three reasons: through playful coding, preservice early childhood teachers (a) learned that computer science is approachable and fun, (b) engaged in adaptive attribution, and (c) engaged in joint celebration when they observed each other’s successes during collaborative tinkering. These findings provide potential insights for teacher learning of computing but also for novices learning to program.

ABSTRACT In a healthy colon, the stratified mucus layer serves as a crucial innate immune barrier to protect the epithelium from microbes. Mucins are complex glycoproteins that serve as a nutrient source for resident microflora and can be exploited by pathogens. We aimed to understand how the intestinal pathogen, Clostridioides difficile, independently uses or manipulates mucus to its benefit, without contributions from members of the microbiota. Using a 2-D primary human intestinal epithelial cell model to generate physiologic mucus, we assessed C. difficile-mucus interactions through growth assays, RNA-Seq, biophysical characterization of mucus, and contextualized metabolic modeling. We found that host-derived mucus promotes C. difficile growth both in vitro and in an infection model. RNA-Seq revealed significant upregulation of genes related to central metabolism in response to mucus, including genes involved in sugar uptake, the Wood-Ljungdahl pathway, and the glycine cleavage system. In addition, we identified differential expression of genes related to sensing and transcriptional control. Analysis of mutants with deletions in highly upregulated genes reflected the complexity of C. difficile-mucus interactions, with potential interplay between sensing and growth. Mucus also stimulated biofilm formation in vitro, which may in turn alter the viscoelastic properties of mucus. Context-specific metabolic modeling confirmed differential metabolism and the predicted importance of enzymes related to serine and glycine catabolism with mucus. Subsequent growth experiments supported these findings, indicating mucus is an important source of serine. Our results better define responses of C. difficile to human gastrointestinal mucus and highlight flexibility in metabolism that may influence pathogenesis.IMPORTANCEClostridioides difficile results in upward of 250,000 infections and 12,000 deaths annually in the United States. Community-acquired infections continue to rise, and recurrent disease is common, emphasizing a vital need to understand C. difficile pathogenesis. C. difficile undoubtedly interacts with colonic mucus, but the extent to which the pathogen can independently respond to and take advantage of this niche has not been explored extensively. Moreover, the metabolic complexity of C. difficile remains poorly understood but likely impacts its capacity to grow and persist in the host. Here, we demonstrate that C. difficile uses native colonic mucus for growth, indicating C. difficile possesses mechanisms to exploit the mucosal niche. Furthermore, mucus induces metabolic shifts and biofilm formation in C. difficile, which has potential ramifications for intestinal colonization. Overall, our work is crucial to better understand the dynamics of C. difficile-mucus interactions in the context of the human gut.

ABSTRACT The airway milieu of individuals with muco-obstructive airway diseases (MADs) is defined by the accumulation of dehydrated mucus due to hyperabsorption of airway surface liquid and defective mucociliary clearance. Pathological mucus becomes progressively more viscous with age and disease severity due to the concentration and overproduction of mucin and accumulation of host-derived extracellular DNA (eDNA). Respiratory mucus of MADs provides a niche for recurrent and persistent colonization by respiratory pathogens, including Pseudomonas aeruginosa, which is responsible for the majority of morbidity and mortality in MADs. Despite high concentration inhaled antibiotic therapies and the absence of antibiotic resistance, antipseudomonal treatment failure in MADs remains a significant clinical challenge. Understanding the drivers of antibiotic tolerance is essential for developing more effective treatments that eradicate persistent infections. The complex and dynamic environment of diseased airways makes it difficult to model antibiotic efficacy in vitro. We aimed to understand how mucin and eDNA concentrations, the two dominant polymers in respiratory mucus, alter the antibiotic tolerance of P. aeruginosa. Our results demonstrate that polymer concentration and molecular weight affect P. aeruginosa survival post antibiotic challenge. Polymer-driven antibiotic tolerance was not explicitly associated with reduced antibiotic diffusion. Lastly, we established a robust and standardized in vitro model for recapitulating the ex vivo antibiotic tolerance of P. aeruginosa observed in expectorated sputum across age, underlying MAD etiology, and disease severity, which revealed the inherent variability in intrinsic antibiotic tolerance of host-evolved P. aeruginosa populations.IMPORTANCEAntibiotic treatment failure in Pseudomonas aeruginosa chronic lung infections is associated with increased morbidity and mortality, illustrating the clinical challenge of bacterial infection control. Understanding the underlying infection environment, as well as the host and bacterial factors driving antibiotic tolerance and the ability to accurately recapitulate these factors in vitro, is crucial for improving antibiotic treatment outcomes. Here, we demonstrate that increasing concentration and molecular weight of mucin and host eDNA drive increased antibiotic tolerance to tobramycin. Through systematic testing and modeling, we identified a biologically relevant in vitro condition that recapitulates antibiotic tolerance observed in ex vivo treated sputum. Ultimately, this study revealed a dominant effect of in vivo evolved bacterial populations in defining inter-subject ex vivo antibiotic tolerance and establishes a robust and translatable in vitro model for therapeutic development.

Abstract Background Diet is among the most influential lifestyle factors impacting chronic disease risk. Nutrimetabolomics, the application of metabolomics to nutrition research, allows for the detection of food-specific compounds (FSCs) that can be used to connect dietary patterns, such as a Mediterranean-style (MED) diet, to health. This validation study is based upon analyses from a controlled feeding MED intervention, where our team identified FSCs from eight foods that can be detected in biospecimens after consumption and may therefore serve as food intake biomarkers. Methods Individuals with overweight/obesity who do not habitually consume a MED dietary pattern will complete a 16-week randomized, multi-intervention, semi-controlled feeding study of isocaloric dietary interventions: (1) MED-amplified dietary pattern, containing 500 kcal/day from eight MED target foods: avocado, basil, cherry, chickpea, oat, red bell pepper, walnut, and a protein source (alternating between salmon or unprocessed, lean beef), and (2) habitual/Western dietary pattern, containing 500 kcal/day from six non-MED target foods: cheesecake, chocolate frozen yogurt, refined grain bread, sour cream, white potato, and unprocessed, lean beef. After a 2-week washout, participants complete four, 4-week intervention periods, with biospecimen sampling and outcome assessments at baseline and at intervention weeks 4, 8, 12, and 16. The primary outcome is change in the relative abundance of FSCs from the eight MED target foods in participant biospecimens from baseline to the end of each intervention period. Secondary outcomes include mean change in cardiometabolic health indicators, inflammatory markers, and adipokines. Exploratory outcomes include change in diversity and community composition of the gut microbiota. Discussion Our stepwise strategy, beginning with identification of FSCs in whole diets and biospecimens, followed by relating these to health indicators will lead to improved methodology for assessment of dietary patterns and a better understanding of the relationship between food and health. This study will serve as a first step toward validating candidate food intake biomarkers and allow for assessment of relationships with cardiometabolic health. The identification of food intake biomarkers is critical to future research and has implications spanning health promotion and disease prevention for many chronic conditions. Trial registration Registered at ClinicalTrials.gov: NCT05500976 ; Date of registration: August 15, 2022.

Abstract This study explores the sphingolipid class of oligohexosylceramides (OHCs), a rarely studied group, in barley (Hordeum vulgare L.) through a new lipidomics approach. Profiling identified 45 OHCs in barley (Hordeum vulgare L.), elucidating their fatty acid (FA), long-chain base (LCB) and sugar residue compositions; and was accomplished by monophasic extraction followed by reverse-phased high performance liquid chromatography electrospray ionisation quadrupole-time-of-flight tandem mass spectrometry (HPLC–ESI–QqTOF–MS/MS) employing parallel reaction monitoring (PRM). Results revealed unknown ceramide species and highlighted distinctive FA and LCB compositions when compared to other sphingolipid classes. Structurally, the OHCs featured predominantly trihydroxy LCBs associated with hydroxylated FAs and oligohexosyl residues consisting of two–five glucose units in a linear 1 → 4 linkage. A survey found OHCs in tissues of major cereal crops while noting their absence in conventional dicot model plants. This study found salinity stress had only minor effects on the OHC profile in barley roots, leaving questions about their precise functions in plant biology unanswered.

Abstract Background Continuous glucose monitoring systems have been validated for eu‐ and hyperglycemic cats. The FreeStyle Libre 2 (FSL2) is sufficiently accurate in people during hypoglycemia to guide critical treatment decisions without confirmation of blood glucose concentration (BG). Objectives Assess FSL2 accuracy in cats with hypoglycemia. Animals Nine healthy, purpose‐bred cats. Methods Hyperinsulinemic‐hypoglycemic clamps were performed by IV infusion of regular insulin (constant rate) and glucose (variable rate). Interstitial glucose concentration (IG), measured by FSL2, was compared to BG measured by AlphaTrak2. Data were analyzed for all paired measurements (n = 364) and separately during stable BG (≤1 mg/dL/min change over 10 minutes). Pearson's r test, Bland‐Altman test, and Parkes Error Grid analysis respectively were used to determine correlation, bias, and clinical accuracy (P

Abstract Background Two loop diuretics, torsemide and frusemide, can affect the urinary system and consequently the cardiordiovascular haemodynamics in different ways. Objectives This study compared a number of echocardiographic parameters and systemic arterial blood pressure (ABP) changes following administration of furosemide or torsemide. Methods Five shelter dogs underwent transthoracic two‐dimensional M‐mode echocardiography to obtain the following measurements: left ventricular internal dimension at end‐systole (LVIDs), left ventricular internal dimension at end‐diastole (LVIDd), fractional shortening (FS), heart rate (HR) and the distance between the mitral valve socket and the ventricle wall (septal to E Point, SEP). Arterial blood pressure was measured using the oscillometric method. Measurements recorded before treatment (baseline data) were compared to those after the dogs received furosemide (5 mg/kg) or torsemide (0.5 mg/kg). Results Torsemide significantly reduced blood pressure 1 h after administration, but this was not seen with furosemide. Fractional shortening, LVIDd and SEP decreased following both treatments, but there were no significant differences between the treatment groups. Torsemide increased heart rate above that seen in the furosemide groups. Conclusions The results of this study indicate that 1 h after administration, torsemide increases heart rate and decreases blood pressure when compared to furosemide, but both drugs have similar effects on measured cardiovascular indices.

People with muco-obstructive pulmonary diseases such as cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD) often have acute or chronic respiratory infections that are difficult to treat due in part to the accumulation of hyperconcentrated mucus within the airway. Mucus accumulation and obstruction promote chronic inflammation and infection and reduce therapeutic efficacy. Bacterial aggregates in the form of biofilms exhibit increased resistance to mechanical stressors from the immune response (e.g., phagocytosis) and chemical treatments including antibiotics. Herein, combination treatments designed to disrupt the mechanical properties of biofilms and potentiate antibiotic efficacy are investigated against mucus-grown Pseudomonas aeruginosa biofilms and optimized to 1) alter biofilm viscoelastic properties, 2) increase mucociliary transport rates, and 3) reduce bacterial viability. A disulfide bond reducing agent (tris(2-carboxyethyl)phosphine, TCEP), a surfactant (NP40), a biopolymer (hyaluronic acid, HA), a DNA degradation enzyme (DNase), and an antibiotic (tobramycin) are tested in various combinations to maximize biofilm disruption. The viscoelastic properties of biofilms are quantified with particle tracking microrheology and transport rates are quantified in a mucociliary transport device comprised of fully differentiated primary human bronchial epithelial cells. The combination of the NP40 with hyaluronic acid and tobramycin was the most effective at increasing mucociliary transport rates, decreasing the viscoelastic properties of mucus, and reducing bacterial viability. Multimechanistic targeting of biofilm infections may ultimately result in improved clinical outcomes, and the results of this study may be translated into future in vivo infection models.

AimAssess whether school-based teacher-led screening is effective at identifying children with motor difficulties.MethodsTeachers tested 217 children aged between 5 and 11 years old, after a one hour training session, using a freely available tool (FUNMOVES). Four classes (n = 91) were scored by both researchers and teachers to evaluate inter-rater reliability. Researchers assessed 22 children using the Movement Assessment Battery for Children (MABC-2; considered to be the 'gold standard' in Europe for use as part of the diagnostic process for Developmental Coordination Disorder) to assess concurrent and predictive validity.ResultsInter-rater reliability for all individual activities within FUNMOVES ranged from 0.85-0.97 (unweighted Kappa; with 95%CI ranging from 0.77-1). For total score this was lower (κ = 0.76, 95%CI = 0.68-0.84), however when incorporating linear weighting, this improved (κ = 0.94, 95%CI = 0.89-0.99). When evaluating FUNMOVES total score against the MABC-2 total score, the specificity (1, 95%CI = 0.63-1) and positive predictive value (1; 95%CI = 0.68-1) of FUNMOVES were high, whereas sensitivity (0.57, 95%CI = 0.29-0.82) and negative predictive values (0.57, 95%CI = 0.42-0.71) were moderate. Evaluating only MABC-2 subscales which are directly related to fundamental movement skills (Aiming & Catching, and Balance) improved these values to 0.89 (95%CI = 0.52-1) and 0.93 (95%CI = 0.67-0.99) respectively.InterpretationTeacher-led screening of fundamental movement skills (via FUNMOVES) is an effective method of identifying children with motor difficulties. Such universal screening in schools has the potential to identify movement difficulties and enable earlier intervention than the current norm.

The viscoelastic properties of biofilms are correlated with their susceptibility to mechanical and chemical stress, and the airway environment in muco-obstructive pulmonary diseases (MOPD) facilitates robust biofilm formation. Hyperconcentrated, viscoelastic mucus promotes chronic inflammation and infection, resulting in increased mucin and DNA concentrations. The viscoelastic properties of biofilms are regulated by biopolymers, including polysaccharides and DNA, and influence responses to antibiotics and phagocytosis. We hypothesize that targeted modulation of biofilm rheology will compromise structural integrity and increase antibiotic susceptibility and mucociliary transport. We evaluate biofilm rheology on the macro, micro, and nano scale as a function of treatment with a reducing agent, a biopolymer, and/or tobramycin to define the relationship between the viscoelastic properties of biofilms and susceptibility. Disruption of the biofilm architecture is associated with altered macroscopic and microscopic moduli, rapid vector permeability, increased antibiotic susceptibility, and improved mucociliary transport, suggesting that biofilm modulating therapeutics will improve the treatment of chronic respiratory infections in MOPD.

Abstract Background Real-world evidence for digitally-supported asthma programs among Medicaid-enrolled children remains limited. Using data from a collaborative quality improvement program, we evaluated the impact of a digital intervention on asthma inhaler use among children in southwest Detroit. Methods Children (6–13 years) enrolled with Kids Health Connection (KHC), a program involving home visits with an asthma educator, were invited to participate in a digital self-management asthma program (Propeller Health). Patients were provided with a sensor to capture short-acting beta-agonist (SABA) medication use, and given access to a paired mobile app to track usage. Patients’ healthcare providers and caregivers (“followers”) were invited to view data as well. Retrospective paired t-tests assessed change in mean SABA use and SABA-free days (SFD) over time, and regressions explored the relationship between followers and medication use. Results Fifty-one patients were assessed. Mean program participation was nine months, and patients had on average 3 followers. From the first to last participation month, mean SABA use decreased from 0.68 to 0.25 puffs/day (p

We describe a method for calculating the probability that a distal geographic location is impacted by a pyroclastic density current (PDC) of a given size, considering the key related uncertainties. Specifically, we evaluate the minimum volume and mass of a PDC generated at the Aso caldera (Japan) that might affect each of five distal infrastructure (marker) sites, with model input parameter uncertainties derived from expert judgment. The 5 marker sites are all located 115–145 km from the caldera; as these lie in well-separated directions, we can test the effects of the different topographic shielding effects in each case. To inform our probabilistic analysis, we apply alternative kinetic energy assessment approaches, i.e., rock avalanche and density current dynamics. In the latter formulation, the minimum mass needed to reach the markers ranges between median values of ∼153×1012 and ∼465×1012 kg (M 7.2–7.7), depending on the site. Rock avalanche dynamics modeling indicates that a ∼3-times greater mass would be required to reach the marker sites with 50 % probability, while the hypothetical scenario of a relatively dilute distal ash cloud would require ∼3-times less mass. We compare our results with the largest recorded Aso eruption, showing that a catastrophic eruption, similar to Aso-4, ≈ M8, would present a significant conditional probability of PDCs reaching the marker sites, in the density current formulation and contingent on uncertainty in the erupted mass and on marker site direction.

Plant breeding is used to develop crops with host resistance to aphids, however, virulent biotypes often develop that overcome host resistance genes. We tested whether the symbionts, Arsenophonus (A) and Wolbachia (W), affect virulence and fecundity in soybean aphid biotypes Bt1 and Bt3 cultured on whole plants and detached leaves of three resistant, Rag1, Rag2 and Rag1 + 2, and one susceptible, W82, soybean genotypes. Whole plants and individual aphid experiments of A. glycines with and without Arsenophonus and Wolbachia did not show differences in overall fecundity. Differences were observed in peak fecundity, first day of deposition, and day of maximum nymph deposition of individual aphids on detached leaves. Bt3 had higher fecundity than Bt1 on detached leaves of all plant genotypes regardless of bacterial profile. Symbionts did not affect peak fecundity of Bt1 but increased it in Bt3 (A+W+) and all Bt3 strains began to deposit nymphs earlier than the Bt1 (A+W−). Arsenophonus in Bt1 delayed the first day of nymph deposition in comparison to aposymbiotic Bt1 except when reared on Rag1 + 2. For the Bt1 and Bt3 strains, symbionts did not result in a significant difference in the day they deposited the maximum number of nymphs nor was there a difference in survival or variability in number of nymphs deposited. Variability of number of aphids deposited was higher in aphids feeding on resistant plant genotypes. The impact of Arsenophonus on soybean aphid patterns of fecundity was dependent on the aphid biotype and plant genotype. Wolbachia alone had no detectable impact but may have contributed to the increased fecundity of Bt3 (A+W+). An individual based model, using data from the detached leaves experiment and with intraspecific competition removed, found patterns similar to those observed in the greenhouse and growth chamber experiments including a significant interaction between soybean genotype and aphid strain. Combining individual data with the individual based model of population growth isolated the impact of fecundity and host resistance from intraspecific competition and host health. Changes to patterns of fecundity, influenced by the composition and concentration of symbionts, may contribute to competitive interactions among aphid genotypes and influence selection on virulent aphid populations.

Abstract Background Initial evidence have shown the short-term efficacy of sTMS in the acute and preventive treatment of migraine. It is unknown whether this treatment approach in the long-term is effective and well tolerated in difficult-to-treat migraine. Methods This is a prospective, single centre, open-label, real-world analysis conducted in difficult-to-treat patients with high-frequency episodic migraine (HFEM) and chronic migraine (CM) with and without medication overuse headache (MOH), who were exposed to sTMS therapy. Patients responding to a three-month sTMS treatment, continued the treatment and were assessed again at month 12. The cut-off outcome for treatment continuation was reduction in the monthly moderate to severe headache days (MHD) of at least 30% (headache frequency responders) and/or a ≥ 4-point reduction in headache disability using the Headache Impact test-6 (HIT-6) (headache disability responders). Results One hundred fifty-three patients were included in the analysis (F:M = 126:27, median age 43, IQR 32.3–56.8). At month 3, 93 out of 153 patients (60%) were responders to treatment. Compared to baseline, the median reduction in monthly headache days (MHD) for all patients at month 3 was 5.0 days, from 18.0 (IQR: 12.0–26.0) to 13.0 days (IQR: 5.75–24.0) (P = 0.002, r = − 0.29) and the median reduction in monthly migraine days (MMD) was 4.0 days, from 13.0 (IQR: 8.75–22.0) to 9.0 (IQR: 4.0–15.25) (P = 0.002, r = − 0.29). Sixty-nine out of 153 patients (45%) reported a sustained response to sTMS treatment at month 12. The percentage of patients with MOH was reduced from 52% (N = 79/153) at baseline to 19% (N = 29/153) at month 3, to 8% (N = 7/87) at month 12. There was an overall median 4-point reduction in HIT-6 score, from 66 (IQR: 64–69) at baseline to 62 at month 3 (IQR: 56–65) (P

Background The American Heart Association defines ideal cardiovascular health based on 8 risk factors (Life's Essential 8 [LE8]); a high LE8 score (range 0–100) reflects greater adherence to their recommendations. Weight status influences cardiovascular health, yet individuals may use detrimental diet and weight loss strategies to improve weight status. We assessed differences in LE8 adherence, diet quality, and weight loss strategies between those with and without a recent history of clinically significant weight loss (CSWL). Methods and Results Data from 2007 to 2016 National Health and Nutrition Examination Survey questionnaires, clinical measures, and 24‐hour dietary recalls were assessed to determine LE8 adherence, diet quality (Healthy Eating Index), and weight loss strategies between adults with: (1) intentional CSWL ≥5%; and (2) non‐CSWL

Across the globe, millions of people are affected by muco-obstructive pulmonary diseases like cystic fibrosis, asthma, and chronic obstructive pulmonary disease. In MOPDs, the airway mucus becomes hyperconcentrated, increasing viscoelasticity and impairing mucus clearance. Research focused on treatment of MOPDs requires relevant sources of airway mucus both as a control sample type and as a basis for manipulation to study the effects of additional hyperconcentration, inflammatory milieu, and biofilm growth on the biochemical and biophysical properties of mucus. Endotracheal tube mucus has been identified as a prospective source of native airway mucus given its several advantages over sputum and airway cell culture mucus such as ease of access and in vivo production that includes surface airway and submucosal gland secretions. Still, many ETT samples suffer from altered tonicity and composition from either dehydration, salivary dilution, or other contamination. Herein, the biochemical compositions of ETT mucus from healthy human subjects were determined. Samples were characterized in terms of tonicity, pooled, and restored to normal tonicity. Salt-normalized ETT mucus exhibited similar concentration-dependent rheologic properties as originally isotonic mucus. This rheology agreed across spatial scales and with previous reports of the biophysics of ETT mucus. This work affirms previous reports of the importance of salt concentration on mucus rheology and presents methodology to increase yield native airway mucus samples for laboratory use and manipulation.

IntroductionDietary intake of whole grains and legumes and adequate physical activity (PA) have been associated with reduced colorectal cancer (CRC) risk. A single-blinded, two-arm, randomized, placebo-controlled pilot trial was implemented to evaluate the impact of a 12-week dietary intervention of rice bran + navy bean supplementation and PA education on metabolite profiles and the gut microbiome among individuals at high risk of CRC.MethodsAdults (n=20) were randomized 1:1 to dietary intervention or control. All participants received PA education at baseline. Sixteen study foods were prepared with either heat-stabilized rice bran + navy bean powder or Fibersol®-2 as a placebo. Intervention participants consumed 30 g rice bran + 30 g navy bean powder daily; those in the control group consumed 10 g placebo daily. Non-targeted metabolite profiling was performed by UPLC-MS/MS to evaluate plasma, urine, and stool at 0, 6, and 12 weeks. Stool was also analyzed for primary and secondary bile acids (BAs) and short chain fatty acids (SCFAs) by UPLC-MS/MS and microbial community structure via 16S amplicon sequencing. Two-way ANOVA was used to compare differences between groups for metabolites, and mixed models were used to compare differences between groups for BAs, SCFAs, and alpha and beta diversity measures of microbial community structure.ResultsAcross biological matrices, the intervention resulted in changes to several amino acid and lipid metabolites, compared to control. There was a 2.33-fold difference in plasma (p

CMV, a ubiquitous herpesvirus, elicits an extraordinarily large T cell response that is sustained or increases over time, a phenomenon termed 'memory inflation.' Remarkably, even latent, non-productive infection can drive memory inflation. Despite intense research on this phenomenon, the infected cell type(s) involved are unknown. To identify the responsible cell type(s), we designed a Cre-lox murine CMV (MCMV) system, where a spread-deficient (ΔgL) virus expresses recombinant SIINFEKL only in Cre+ host cells. We found that latent infection of endothelial cells (ECs), but not dendritic cells (DCs) or hepatocytes, was sufficient to drive CD8 T cell memory inflation. Infection of Lyve-1-Cre and Prox1-CreERT2 mice revealed that amongst EC subsets, infection of lymphatic ECs was sufficient. Genetic ablation of β2m on lymphatic ECs did not prevent inflation, suggesting another unidentified cell type can also present antigen to CD8 T cells during latency. This novel system definitively shows that antigen presentation by lymphatic ECs drives robust CD8 T cell memory inflation.

Low-resource individuals are at increased risk of obesity and cardiovascular disease (CVD), partially attributable to poor dietary patterns and dysfunctional microbiota. Dietary patterns in childhood play critical roles in physiological development and are shaped by caregivers, making caregiver-child dyads attractive targets for dietary interventions to reduce metabolic disease risk. Herein, we targeted low-resource caregiver-child dyads for a 10-week, randomized, controlled, multifaceted lifestyle intervention including: nutrition and physical activity education, produce harvesting, cooking demonstrations, nutrition counseling, and kinetic activites; to evaluate its effects on dietary patterns, CVD risk factors, and microbiome composition. Subjects in the lifestyle intervention group improved total diet quality, increased whole grain intake, decreased energy intake, and enhanced fecal elimination of the microbe-derived metabolite lithocholic acid (LCA) in contrast to control subjects. Microbiomes were highly personalized, similar within dyads, and altered by lifestyle intervention. Differential modeling of microbiome composition identified taxa associated with total diet quality, whole grain intake, and LCA elimination including recognized fiber-degrading bacteria such as Subdoligranulum, and bile acid metabolizing organisms like Bifidobacterium. Inclusion of taxa identified in diet and metabolite modeling within blood pressure models improved prediction accuracy of microbiome-blood pressure associations. Importantly, microbiota-blood pressure relationships were shared between dyads, implying shared host-microbiota responses to lifestyle intervention. Overall, these outcomes provide insight into mechanisms by which dietary interventions impact the gut-cardiovascular axis to reduce future CVD risk. Registered at clinicaltrials.gov: NCT05367674

Radiological imaging techniques, including magnetic resonance imaging (MRI) and positron emission tomography (PET), are the standard-of-care non-invasive diagnostic approaches widely applied in neuro-oncology. Unfortunately, accurate interpretation of radiological imaging data is constantly challenged by the indistinguishable radiological image features shared by different pathological changes associated with tumor progression and/or various therapeutic interventions. In recent years, machine learning (ML)-based artificial intelligence (AI) technology has been widely applied in medical image processing and bioinformatics due to its advantages in implicit image feature extraction and integrative data analysis. Despite its recent rapid development, ML technology still faces many hurdles for its broader applications in neuro-oncological radiomic analysis, such as lack of large accessible standardized real patient radiomic brain tumor data of all kinds and reliable predictions on tumor response upon various treatments. Therefore, understanding ML-based AI technologies is critically important to help us address the skyrocketing demands of neuro-oncology clinical deployments. Here, we provide an overview on the latest advancements in ML techniques for brain tumor radiomic analysis, emphasizing proprietary and public dataset preparation and state-of-the-art ML models for brain tumor diagnosis, classifications (e.g., primary and secondary tumors), discriminations between treatment effects (pseudoprogression, radiation necrosis) and true progression, survival prediction, inflammation, and identification of brain tumor biomarkers. We also compare the key features of ML models in the realm of neuroradiology with ML models employed in other medical imaging fields and discuss open research challenges and directions for future work in this nascent precision medicine area.

ABSTRACT The pathological properties of airway mucus in cystic fibrosis (CF) are dictated by mucus concentration and composition, with mucins and DNA being responsible for mucus viscoelastic properties. As CF pulmonary disease progresses, the concentrations of mucins and DNA increase and are associated with increased mucus viscoelasticity and decreased transport. Similarly, the biophysical properties of bacterial biofilms are heavily influenced by the composition of their extracellular polymeric substances (EPS). While the roles of polymer concentration and composition in mucus and biofilm mechanical properties have been evaluated independently, the relationship between mucus concentration and composition and the biophysical properties of biofilms grown therein remains unknown. Pseudomonas aeruginosa biofilms were grown in airway mucus as a function of overall concentration and DNA concentration to mimic healthy, and CF pathophysiology and biophysical properties were evaluated with macro- and microrheology. Biofilms were also characterized after exposure to DNase or DTT to examine the effects of DNA and mucin degradation, respectively. Identifying critical targets in biofilms for disrupting mechanical stability in highly concentrated mucus may lead to the development of efficacious biofilm therapies and ultimately improve CF patient outcomes. Overall mucus concentration was the predominant contributor to biofilm viscoelasticity and both DNA degradation and mucin reduction resulted in compromised biofilm mechanical strength. IMPORTANCE Pathological mucus in cystic fibrosis (CF) is highly concentrated and insufficiently cleared from the airway, causing chronic inflammation and infection. Pseudomonas aeruginosa establishes chronic infection in the form of biofilms within mucus, and this study determined that biofilms formed in more concentrated mucus were more robust and less susceptible to mechanical and chemical challenges compared to biofilms grown in lower concentrated mucus. Neither DNA degradation nor disulfide bond reduction was sufficient to fully degrade biofilms. Mucus rehydration should remain a priority for treating CF pulmonary disease with concomitant multimechanistic biofilm degradation agents and antibiotics to clear chronic infection.

Abstract Background Immunofluorescent confocal microscopy uses labeled antibodies as probes against specific macromolecules to discriminate between multiple cell types. For images of the developmental mouse lung, these cells are themselves organized into densely packed higher-level anatomical structures. These types of images can be challenging to segment automatically for several reasons, including the relevance of biomedical context, dependence on the specific set of probes used, prohibitive cost of generating labeled training data, as well as the complexity and dense packing of anatomical structures in the image. The use of an application ontology helps surmount these challenges by combining image data with its metadata to provide a meaningful biological context, modeled after how a human expert would make use of contextual information to identify histological structures, that constrains and simplifies the process of segmentation and object identification. Results We propose an innovative approach for the semi-supervised analysis of complex and densely packed anatomical structures from immunofluorescent images that utilizes an application ontology to provide a simplified context for image segmentation and object identification. We describe how the logical organization of biological facts in the form of an ontology can provide useful constraints that facilitate automatic processing of complex images. We demonstrate the results of ontology-guided segmentation and object identification in mouse developmental lung images from the Bioinformatics REsource ATlas for the Healthy lung database of the Molecular Atlas of Lung Development (LungMAP1) program Conclusion We describe a novel ontology-guided approach to segmentation and classification of complex immunofluorescence images of the developing mouse lung. The ontology is used to automatically generate constraints for each image based on its biomedical context, which facilitates image segmentation and classification.

IntroductionAsthma is the most common chronic disease in children. Children with asthma are at high risk for complications from influenza; however annual influenza vaccination rates for this population are suboptimal. The overall aim of this study was to describe the characteristics of a high-risk population of children with asthma presenting to an urban pediatric emergency department according to influenza vaccination status.MethodsThe study was a retrospective chart review of 4355 patients aged 2 to 18 years evaluated in a Michigan pediatric emergency department (PED) between November 1, 2017 and April 30, 2018 with an ICD-10-CM code for asthma (J45.x). Eligible patient PED records were matched with influenza vaccination records for the 2017-2018 influenza season from the Michigan Care Improvement Registry. Geospatial analysis was employed to examine the distribution of influenza vaccination status.Results1049 patients (30.9%) with asthma seen in the PED had received an influenza vaccine. Influenza vaccination coverage varied by Census Tract, ranging from 10% to >99%. Most vaccines were administered in a primary care setting (84.3%) and were covered by public insurance (76.8%). The influenza vaccination rate was lowest for children aged 5-11 years (30.0%) and vaccination status was associated with race (pConclusionsIdentification of neighborhood Census Tract and demographic groups with suboptimal influenza vaccination could guide development of targeted public health interventions to improve vaccination rates in high-risk patients. Given the morbidity and mortality associated with pediatric asthma, a data-driven approach may improve outcomes and reduce healthcare-associated costs for this pediatric population.

We describe a new catalog of accelerating star candidates with Gaia G ≤ 17.5 mag and distances d ≤ 100 pc. Designated as the Gaia Nearby Accelerating Star Catalog (GNASC), it contains 29,684 members identified using a supervised machine-learning algorithm trained on the Hipparcos–Gaia Catalog of Accelerations (HGCA), Gaia Data Release 2, and Gaia Early Data Release 3. We take advantage of the difference in observation timelines between the two Gaia catalogs and information about the quality of the astrometric modeling based on the premise that acceleration will correlate with astrometric uncertainties. Catalog membership is based on whether constant proper motion over three decades can be ruled out at high confidence (greater than 99.9%). Test data suggest that catalog members each have a 68% likelihood of true astrometric acceleration; subsets of the catalog perform even better, with the likelihood exceeding 85%. We compare the GNASC with Gaia Data Release 3 and its table of stars for which acceleration is detected at high confidence based on precise astrometric fits. Our catalog, derived without this information, captures over 96% of the sources in the table that meet our selection criteria. In addition, the GNASC contains bright, nearby candidates that were not in the original Hipparcos survey, including members of known binary systems as well as stars with companions yet to be identified. It thus extends the HGCA and demonstrates the potential of the machine-learning approach for discovering hidden partners of nearby stars in future astrometric surveys.

Objectives COVIDTrach is a UK multicentre prospective cohort study project that aims to evaluate the outcomes of tracheostomy in patients with COVID-19 receiving mechanical ventilation and record the incidence of SARS-CoV-2 infection among healthcare workers involved in the procedure.Design Data on patient demographic, clinical history and outcomes were entered prospectively and updated over time via an online database (REDCap). Clinical variables were compared with outcomes, with logistic regression used to develop a model for mortality. Participants recorded whether any operators tested positive for SARS-CoV-2 within 2 weeks of the procedure.Setting UK National Health Service departments involved in treating patients with COVID-19 receiving mechanical ventilation.Participants The cohort comprised 1605 tracheostomy cases from 126 UK hospitals collected between 6 April and 26 August 2020.Main outcome measures Mortality following tracheostomy, successful wean from mechanical ventilation and length of time from tracheostomy to wean, discharge from hospital, complications from tracheostomy, reported SARS-CoV-2 infection among operators.Results The median time from intubation to tracheostomy was 15 days (IQR 11, 21). 285 (18%) patients died following the procedure. 1229 (93%) of the survivors had been successfully weaned from mechanical ventilation at censoring and 1049 (81%) had been discharged from hospital. Age, inspired oxygen concentration, positive end-expiratory pressure setting, fever, number of days of ventilation before tracheostomy, C reactive protein and the use of anticoagulation and inotropic support independently predicted mortality. Six reports were received of operators testing positive for SARS-CoV-2 within 2 weeks of the procedure.Conclusions Tracheostomy appears to be safe in mechanically ventilated patients with COVID-19 and to operators performing the procedure and we identified clinical parameters that are predictive of mortality.Trial registration number The study is registered with ClinicalTrials.Gov (NCT04572438).

Detecting animals by identifying their DNA in water is a valuable tool for locating and monitoring species that are difficult to detect through other survey techniques. We developed a test for detecting the endangered Gouldian finch Erythrura gouldiae, a small bird endemic to northern Australia. Only 1 previous study has reported an environmental DNA (eDNA) test that unequivocally identifies a bird species using the water bodies from which they drink. In controlled aviary trials with a pair of Gouldian finches, first detection in 200 ml of water occurred after as little as 6 h, but the detection rate was higher at 30 h. DNA persisted in water exposed to the sun for

Abstract Background Born in Bradford (BiB) is a prospective multi-ethnic pregnancy and birth cohort study that was established to examine determinants of health and development during childhood and, subsequently, adult life in a deprived multi-ethnic population in the north of England. Between 2007 and 2010, the BiB cohort recruited 12,453 women who experienced 13,776 pregnancies and 13,858 births, along with 3353 of their partners. Forty five percent of the cohort are of Pakistani origin. Now that children are at primary school, the first full follow-up of the cohort is taking place. The aims of the follow-up are to investigate the determinants of children’s pre-pubertal health and development, including through understanding parents’ health and wellbeing, and to obtain data on exposures in childhood that might influence future health. Methods We are employing a multi-method approach across three data collection arms (community-based family visits, school based physical assessment, and whole classroom cognitive, motor function and wellbeing measures) to follow-up over 9000 BiB children aged 7–11 years and their families between 2017 and 2021. We are collecting detailed parent and child questionnaires, cognitive and sensorimotor assessments, blood pressure, anthropometry and blood samples from parents and children. Dual x-ray absorptiometry body scans, accelerometry and urine samples are collected on subsamples. Informed consent is collected for continued routine data linkage to health, social care and education records. A range of engagement activities are being used to raise the profile of BiB and to disseminate findings. Discussion Our multi-method approach to recruitment and assessment provides an efficient method of collecting rich data on all family members. Data collected will enhance BiB as a resource for the international research community to study the interplay between ethnicity, socioeconomic circumstances and biology in relation to cardiometabolic health, mental health, education, cognitive and sensorimotor development and wellbeing.

The promoter variant rs35705950 confers a gain of function to the MUC5B gene and is the dominant risk factor for idiopathic pulmonary fibrosis. Here the authors show that mice overexpressing Muc5b in distal airspaces show impaired mucociliary clearance and increased susceptibility to bleomycin-induced lung fibrosis, and that both characteristics are reduced by treatment with a mucolytic agent.

Objective: to comprehensively study the presidential rhetoric as crime control theater.Methods: dialectical approach to the cognition of social phenomena, enabling to analyze them in their historical development and functioning in the context of a set of objective and subjective factors, which determined the choice of the following research methods: formal-logical, comparative-legal, and sociological.Results: Presidents have increasingly made criminal justice a part of their public agenda. Much of their political speech on crime and violence focuses on creating the impression of action, even when none is taken. Moreover, if actions are taken, they are ineffective and do not result in significant policy shifts. When presidents give the impression that they are fighting crime, it is often called crime control theater. This is characterized by the use of mythic narratives, a reliance on moral panic, little public dissent, and the ineffectiveness of the policy itself. While many previous studies have demonstrated the importance of crime control theater regarding different criminal justice topics, none have focused on the emerging problems of cybercrime. Scientific novelty: for the first time, the article analyzes the issue of the presidential rhetoric as crime control theater, examines the patterns and trends in presidential rhetoric on cybercrime. The authors use a qualitative content analysis to test the hypothesis that presidents rely on the techniques that comprise crime control theater when discussing cybercrime, in particular, mythic narrative and moral panic. As a result, public fears of cybercrime are allayed but at the same time, any significant action is postponed. The research results have confirmed the proposed hypothesis. Practical significance: the main provisions and conclusions of the article can be used in scientific and pedagogical activity when considering the issues related to the presidential rhetoric as crime control theater.

BackgroundA large proportion of children are not able to perform age-appropriate fundamental movement skills (FMS). Thus, it is important to assess FMS so that children needing additional support can be identified in a timely fashion. There is great potential for universal screening of FMS in schools, but research has established that current assessment tools are not fit for purpose.ObjectiveTo develop and validate the psychometric properties of a FMS assessment tool designed specifically to meet the demands of universal screening in schools.MethodsA working group consisting of academics from developmental psychology, public health and behavioural epidemiology developed an assessment tool (FUNMOVES) based on theory and prior evidence. Over three studies, 814 children aged 4 to 11 years were assessed in school using FUNMOVES. Rasch analysis was used to evaluate structural validity and modifications were then made to FUNMOVES activities after each study based on Rasch results and implementation fidelity.ResultsThe initial Rasch analysis found numerous psychometric problems including multidimensionality, disordered thresholds, local dependency, and misfitting items. Study 2 showed a unidimensional measure, with acceptable internal consistency and no local dependency, but that did not fit the Rasch model. Performance on a jumping task was misfitting, and there were issues with disordered thresholds (for jumping, hopping and balance tasks). Study 3 revealed a unidimensional assessment tool with good fit to the Rasch model, and no further issues, once jumping and hopping scoring were modified.ImplicationsThe finalised version of FUNMOVES (after three iterations) meets standards for accurate measurement, is free and able to assess a whole class in under an hour using resources available in schools. Thus FUNMOVES has the potential to allow schools to efficiently screen FMS to ensure that targeted support can be provided and disability barriers removed.

This article describes our experience developing a novel mobile health unit (MHU) program in the Detroit, Michigan, metropolitan area. Our main objectives were to improve healthcare accessibility, quality and equity in our community during the novel coronavirus pandemic. While initially focused on SARS-CoV-2 testing, our program quickly evolved to include preventive health services. The MHU program began as a location-based SARS-CoV-2 testing strategy coordinated with local and state public health agencies. Community needs motivated further program expansion to include additional preventive healthcare and social services. MHU deployment was targeted to disease "hotspots" based on publicly available SARS-CoV-2 testing data and community-level information about social vulnerability. This formative evaluation explores whether our MHU deployment strategy enabled us to reach patients from communities with heightened social vulnerability as intended. From 3/20/20-3/24/21, the Detroit MHU program reached a total of 32,523 people. The proportion of patients who resided in communities with top quartile Centers for Disease Control and Prevention Social Vulnerability Index rankings increased from 25% during location-based "drive-through" SARS-CoV-2 testing (3/20/20-4/13/20) to 27% after pivoting to a mobile platform (4/13/20-to-8/31/20; p = 0.01). The adoption of a data-driven deployment strategy resulted in further improvement; 41% of the patients who sought MHU services from 9/1/20-to-3/24/21 lived in vulnerable communities (Cochrane Armitage test for trend, p

Nitrogen (N) fertilizer is largely responsible for barley grain yield potential and quality, yet excessive application leads to environmental pollution and high production costs. Therefore, efficient use of N is fundamental for sustainable agriculture. In the present study, we investigated the performance of 282 barley accessions through hydroponic screening using optimal and low NH4NO3 treatments. Low-N treatment led to an average shoot dry weight reduction of 50%, but there were significant genotypic differences among the accessions. Approximately 20% of the genotypes showed high (>75%) relative shoot dry weight under low-N treatment and were classified as low-N tolerant, whereas 20% were low-N sensitive (≤55%). Low-N tolerant accessions exhibited well-developed root systems with an average increase of 60% in relative root dry weight to facilitate more N absorption. A genome-wide association study (GWAS) identified 66 significant marker trait associations (MTAs) conferring high nitrogen use efficiency, four of which were stable across experiments. These four MTAs were located on chromosomes 1H(1), 3H(1), and 7H(2) and were associated with relative shoot length, relative shoot and root dry weight. Genes corresponding to the significant MTAs were retrieved as candidate genes, including members of the asparagine synthetase gene family, several transcription factor families, protein kinases, and nitrate transporters. Most importantly, the high-affinity nitrate transporter 2.7 (HvNRT2.7) was identified as a promising candidate on 7H for root and shoot dry weight. The identified candidate genes provide new insights into our understanding of the molecular mechanisms driving nitrogen use efficiency in barley and represent potential targets for genetic improvement.