Electrochemical Doping of Two-Dimensional Superatomic Materials.

We report an electrochemical method for doping two-dimensional (2D) superatomic semiconductor Re6Se8Cl2 that significantly improves the material's electrical transport while retaining the in-plane and stacking structures. The electrochemical reduction induces the complete dissociation of chloride anions from the surface of each superatomic nanosheet. After the material is dehalogenated, we observe the electrical conductivity (σ) increases by two orders of magnitude while the 3D electron carrier density (n3D) increases by three orders of magnitude. In addition, the thermal activation energy (Ea) and electron mobility (µe) decrease. We conclude that we have achieved effective electron-doping in 2D superatomic Re6Se8Cl2, which significantly improves the electrical transport properties. Our work sets the foundation for electrochemically doping and tuning the transport properties of other 2D superatomic materials.

The heparin-binding domain of VEGF165 directly binds to integrin αvß3 and VEGFR2/KDR D1: a potential mechanism of negative regulation of VEGF165 signaling by αvß3.

VEGF-A is a key cytokine in tumor angiogenesis and a major therapeutic target for cancer. VEGF165 is the predominant isoform of VEGF-A, and it is the most potent angiogenesis stimulant. VEGFR2/KDR domains 2 and 3 (D2D3) bind to the N-terminal domain (NTD, residues 1-110) of VEGF165. Since removal of the heparin-binding domain (HBD, residues 111-165) markedly reduced the mitogenic activity of the growth factor, it has been proposed that the HBD plays a critical role in the mitogenicity of VEGF165. Here, we report that αvß3 specifically bound to the isolated VEGF165 HBD but not to VEGF165 NTD. Based on docking simulation and mutagenesis, we identified several critical amino acid residues within the VEGF165 HBD required for αvß3 binding, i.e., Arg123, Arg124, Lys125, Lys140, Arg145, and Arg149. We discovered that VEGF165 HBD binds to the KDR domain 1 (D1) and identified that Arg123 and Arg124 are critical for KDR D1 binding by mutagenesis, indicating that the KDR D1-binding and αvß3-binding sites overlap in the HBD. Full-length VEGF165 mutant (R123A/R124A/K125A/K140A/R145A/R149A) defective in αvß3 and KDR D1 binding failed to induce ERK1/2 phosphorylation, integrin ß3 phosphorylation, and KDR phosphorylation and did not support proliferation of endothelial cells, although the mutation did not affect the KDR D2D3 interaction with VEGF165. Since ß3-knockout mice are known to show enhanced VEGF165 signaling, we propose that the binding of KDR D1 to the VEGF165 HBD and KDR D2D3 binding to the VEGF165 NTD are critically involved in the potent mitogenicity of VEGF165. We propose that binding competition between KDR and αvß3 to the VEGF165 HBD endows integrin αvß3 with regulatory properties to act as a negative regulator of VEGF165 signaling.

ATF3 is a neuron-specific biomarker for spinal cord injury and ischaemic stroke.

BACKGROUND: Although many molecules have been investigated as biomarkers for spinal cord injury (SCI) or ischemic stroke, none of them are specifically induced in central nervous system (CNS) neurons following injuries with low baseline expression. However, neuronal injury constitutes a major pathology associated with SCI or stroke and strongly correlates with neurological outcomes. Biomarkers characterized by low baseline expression and specific induction in neurons post-injury are likely to better correlate with injury severity and recovery, demonstrating higher sensitivity and specificity for CNS injuries compared to non-neuronal markers or pan-neuronal markers with constitutive expressions. METHODS: In animal studies, young adult wildtype and global Atf3 knockout mice underwent unilateral cervical 5 (C5) SCI or permanent distal middle cerebral artery occlusion (pMCAO). Gene expression was assessed using RNA-sequencing and qRT-PCR, while protein expression was detected through immunostaining. Serum ATF3 levels in animal models and clinical human samples were measured using commercially available enzyme-linked immune-sorbent assay (ELISA) kits. RESULTS: Activating transcription factor 3 (ATF3), a molecular marker for injured dorsal root ganglion sensory neurons in the peripheral nervous system, was not expressed in spinal cord or cortex of naïve mice but was induced specifically in neurons of the spinal cord or cortex within 1 day after SCI or ischemic stroke, respectively. Additionally, ATF3 protein levels in mouse blood significantly increased 1 day after SCI or ischemic stroke. Importantly, ATF3 protein levels in human serum were elevated in clinical patients within 24 hours after SCI or ischemic stroke. Moreover, Atf3 knockout mice, compared to the wildtype mice, exhibited worse neurological outcomes and larger damage regions after SCI or ischemic stroke, indicating that ATF3 has a neuroprotective function. CONCLUSIONS: ATF3 is an easily measurable, neuron-specific biomarker for clinical SCI and ischemic stroke, with neuroprotective properties. HIGHLIGHTS: ATF3 was induced specifically in neurons of the spinal cord or cortex within 1 day after SCI or ischemic stroke, respectively. Serum ATF3 protein levels are elevated in clinical patients within 24 hours after SCI or ischemic stroke. ATF3 exhibits neuroprotective properties, as evidenced by the worse neurological outcomes and larger damage regions observed in Atf3 knockout mice compared to wildtype mice following SCI or ischemic stroke.

Evaluation and Management of Malignant Colorectal Polyps.

The detection rate of dysplastic colorectal polyps has significantly increased with improved screening programs. Treatment of dysplastic polyps attempt to limit morbidity of a procedure while also considering the risk of occult lymph node metastasis. Therefore, a variety of methods have been developed to predict the rate of lymph node metastasis to help identify the optimal treatment of patients. These include both the endoscopic and pathologic assessment of the lesion. In order to reduce the morbidity of surgery for patients with low-risk lesions, multiple endoscopic therapies have been developed, including endoscopic mucosal resection, endoscopic submucosal dissection, endoscopic intermuscular dissection, and transanal endoscopic surgery.

Model design choices impact biological insight: Unpacking the broad landscape of spatial-temporal model development decisions.

Computational models enable scientists to understand observed dynamics, uncover rules underlying behaviors, predict experimental outcomes, and generate new hypotheses. There are countless modeling approaches that can be used to characterize biological systems, further multiplied when accounting for the variety of model design choices. Many studies focus on the impact of model parameters on model output and performance; fewer studies investigate the impact of model design choices on biological insight. Here we demonstrate why model design choices should be deliberate and intentional in context of the specific research system and question. In this study, we analyze agnostic and broadly applicable modeling choices at three levels-system, cell, and environment-within the same agent-based modeling framework to interrogate their impact on temporal, spatial, and single-cell emergent dynamics. We identify key considerations when making these modeling choices, including the (i) differences between qualitative vs. quantitative results driven by choices in system representation, (ii) impact of cell-to-cell variability choices on cell-level and temporal trends, and (iii) relationship between emergent outcomes and choices of nutrient dynamics in the environment. This generalizable investigation can help guide the choices made when developing biological models that aim to characterize spatial-temporal dynamics.

Incorporating temporal information during feature engineering bolsters emulation of spatio-temporal emergence.

MOTIVATION: Emergent biological dynamics derive from the evolution of lower-level spatial and temporal processes. A long-standing challenge for scientists and engineers is identifying simple low-level rules that give rise to complex higher-level dynamics. High-resolution biological data acquisition enables this identification and has evolved at a rapid pace for both experimental and computational approaches. Simultaneously harnessing the resolution and managing the expense of emerging technologies-e.g. live cell imaging, scRNAseq, agent-based models-requires a deeper understanding of how spatial and temporal axes impact biological systems. Effective emulation is a promising solution to manage the expense of increasingly complex high-resolution computational models. In this research, we focus on the emulation of a tumor microenvironment agent-based model to examine the relationship between spatial and temporal environment features, and emergent tumor properties. RESULTS: Despite significant feature engineering, we find limited predictive capacity of tumor properties from initial system representations. However, incorporating temporal information derived from intermediate simulation states dramatically improves the predictive performance of machine learning models. We train a deep-learning emulator on intermediate simulation states and observe promising enhancements over emulators trained solely on initial conditions. Our results underscore the importance of incorporating temporal information in the evaluation of spatio-temporal emergent behavior. Nevertheless, the emulators exhibit inconsistent performance, suggesting that the underlying model characterizes unique cell populations dynamics that are not easily replaced. AVAILABILITY AND IMPLEMENTATION: All source codes for the agent-based model, emulation, and analyses are publicly available at the corresponding DOIs: 10.5281/zenodo.10622155, 10.5281/zenodo.10611675, 10.5281/zenodo.10621244, respectively.

Ultrasound for acute pyelonephritis: a systematic review and meta-analysis.

BACKGROUND: There is little consensus regarding the indications and utility of urinary tract imaging and type of imaging to perform in patients presenting with acute pyelonephritis (APN). AIMS: The aims of this systematic review were to, among patients with APN, (i) identify the proportion of patients investigated with ultrasound (US), (ii) identify the proportion of abnormal US and (iii) identify the proportion of patients with a change in management resulting from abnormal US. METHODS: A comprehensive search covered two electronic databases (Medline and EMBASE), with selection of studies performed independently by two investigators. Inclusion criteria were English language APN diagnosis and quantification of patients assessed with US or abnormal US results. Quality appraisal used the Newcastle-Ottawa instrument. RESULTS: There were 35 studies included. The proportion of patients assessed with US was reported in 16 manuscripts and ranged from 20% to 94%, with significant heterogeneity and publication bias. The proportion of abnormal US was reported in 31 manuscripts and ranged from 7% to 79%. The proportion of abnormal US leading to change in management was reported in five studies and ranged from 7% to 59%. There was marked heterogeneity among studies included in all three subgroups. CONCLUSIONS: Patients with APN are commonly investigated with US, but only a small proportion have abnormalities and appear to be associated with changes in clinical management. The use of routine US for APN is therefore questioned. The identification of clinical variables for appropriate selection of patients to investigate with US requires further research.

Use of Impedance Planimetry in the Diagnosis of Gastric Sleeve Stenosis: The Establishment of New Benchmark Values.

INTRODUCTION: Gastric sleeve stenosis (GSS) is an increasingly common adverse event following sleeve gastrectomy for which objective diagnostic criteria are lacking. Impedance planimetry measurements show promise in characterizing GSS, though normal and abnormal benchmark values have never been established. METHODS: This was a retrospective analysis of upper endoscopies performed with impedance planimetry for suspected GSS. A bariatric endoscopist, blind to impedance planimetry measurements, assessed gastric sleeve anatomy and graded GSS severity. Impedance planimetry of diameter and distensibility index (DI) were obtained using 3 different balloon volumes (30, 40, and 50 mL). RESULTS: A total of 110 upper endoscopies were included. Distribution of GSS was graded as none, mild, moderate, and severe in 19 (17%), 27 (25%), 34 (31%), and 30 (27%) procedures, respectively. In normal gastric sleeve anatomy, mean (±SD) diameter and DI measurements using consecutive balloon volumes ranged from 19.1 (±5.5) to 23.2 (±1.7) and 16.8 (±4.9) to 23.1 (±10.9), respectively. In severe GSS, mean diameter and DI measurements ranged from 10.3 (±3.0) to 16.6 (±2.1) and 7.5 (±2.4) to 7.7 (±2.4), respectively. When stratified by severity, impedance planimetry measurements of diameter and DI were significantly lower with each subsequent increase in GSS grade regardless of balloon fill volumes ( P ≤ 0.001). DISCUSSION: Impedance planimetry measurements provide objective assessment in the diagnosis of GSS and correlate with luminal narrowing. A diameter ≥20 mm and a DI ≥15 mm 2 /mm Hg, as measured by impedance planimetry, are predictive of normal gastric sleeve anatomy. This study provides new benchmark values for the diagnosis and severity of GSS.

The 2022 top 10 list of endoscopy topics in medical publishing: an annual review by the American Society for Gastrointestinal Endoscopy Editorial Board.

Using a systematic literature search of original articles published during 2022 in Gastrointestinal Endoscopy and other high-impact medical and gastroenterology journals, the 10-member Editorial Board of the American Society for Gastrointestinal Endoscopy composed a list of the 10 most significant topic areas in GI endoscopy during the study year. Each Editorial Board member was directed to consider 3 criteria in generating candidate lists-significance, novelty, and global impact on clinical practice-and subject matter consensus was facilitated by the Chair through electronic voting. The 10 identified areas collectively represent advances in the following endoscopic spheres: artificial intelligence, endoscopic submucosal dissection, Barrett's esophagus, interventional EUS, endoscopic resection techniques, pancreaticobiliary endoscopy, management of acute pancreatitis, endoscopic environmental sustainability, the NordICC trial, and spiral enteroscopy. Each board member was assigned a consensus topic area around which to summarize relevant important articles, thereby generating this précis of the "top 10" endoscopic advances of 2022.

The heparin-binding domain of VEGF165 directly binds to integrin αvß3 and plays a critical role in signaling.

VEGF-A is a key cytokine in tumor angiogenesis and a major therapeutic target for cancer. VEGF165 is the predominant isoform and is the most potent angiogenesis stimulant. VEGFR2/KDR domains 2 and 3 (D2D3) bind to the N-terminal domain (NTD, residues 1-110) of VEGF165. Since removal of the heparin-binding domain (HBD, residues 111-165) markedly reduced the mitogenic activity of VEGF165, it has been proposed that the HBD plays a critical role in the mitogenicity of VEGF165. Integrin αvß3 has been shown to bind to VEGF165, but the role of integrin αvß3 in VEGF165 signaling are unclear. Here we describe that αvß3 specifically bound to the isolated HBD, but not to the NTD. We identified several critical amino acid residues in HBD for integrin binding (Arg-123, Arg-124, Lys-125, Lys-140, Arg-145, and Arg-149) by docking simulation and mutagenesis, and generated full-length VEGF165 that is defective in integrin binding by including mutations in the HBD. The full-length VEGF165 mutant defective in integrin binding (R123A/R124A/K125A/K140A/R145A/R149A) was defective in ERK1/2 phosphorylation, integrin ß3 phosphorylation, and KDR phosphorylation, although the mutation did not affect KDR binding to VEGF165. We propose a model in which VEGF165 induces KDR (through NTD)-VEGF165 (through HBD)-integrin αvß3 ternary complex formation on the cell surface and this process is critically involved in potent mitogenicity of VEGF165.

Room-temperature wavelike exciton transport in a van der Waals superatomic semiconductor.

The transport of energy and information in semiconductors is limited by scattering between electronic carriers and lattice phonons, resulting in diffusive and lossy transport that curtails all semiconductor technologies. Using Re6Se8Cl2, a van der Waals (vdW) superatomic semiconductor, we demonstrate the formation of acoustic exciton-polarons, an electronic quasiparticle shielded from phonon scattering. We directly imaged polaron transport in Re6Se8Cl2 at room temperature, revealing quasi-ballistic, wavelike propagation sustained for a nanosecond and several micrometers. Shielded polaron transport leads to electronic energy propagation lengths orders of magnitude greater than in other vdW semiconductors, exceeding even silicon over a nanosecond. We propose that, counterintuitively, quasi-flat electronic bands and strong exciton-acoustic phonon coupling are together responsible for the transport properties of Re6Se8Cl2, establishing a path to ballistic room-temperature semiconductors.

The Effect of a Digital Mental Health Program on Anxiety and Depression Symptoms: Retrospective Analysis of Clinical Severity.

BACKGROUND: Evidence-based digital health programs have shown efficacy in being primary tools to improve emotional and mental health, as well as offering supplementary support to individuals undergoing psychotherapy for anxiety, depression, and other mental health disorders. However, information is lacking about the dose response to digital mental health interventions. OBJECTIVE: The objective of the study was to examine the effect of time in program and program usage on symptom change among individuals enrolled in a real-world comprehensive digital mental health program (myStrength) who are experiencing severe anxiety or depression. METHODS: Eligible participants (N=18,626) were adults aged 18 years and older who were enrolled in myStrength for at least four weeks as part of their employee wellness benefit program, who completed baseline, the 2-week, 2-month, and 6-month surveys querying symptoms of anxiety (Generalized Anxiety Disorder-7 [GAD-7]) and depression (Patient Health Questionnaire-9 [PHQ-9]). Linear growth curve models were used to analyze the effect of average weekly program usage on subsequent GAD-7 and PHQ-9 scores for participants with scores indicating severe anxiety (GAD-7≥15) or depression (PHQ-9≥15). All models were adjusted for baseline score and demographics. RESULTS: Participants in the study (N=1519) were 77.4% female (1176/1519), had a mean age of 45 years (SD 14 years), and had an average enrollment time of 3 months. At baseline, participants reported an average of 9.39 (SD 6.04) on the GAD-7 and 11.0 (SD 6.6) on the PHQ-9. Those who reported 6-month results had an average of 8.18 (SD 6.15) on the GAD-7 and 9.18 (SD 6.79) on the PHQ-9. Participants with severe scores (n=506) experienced a significant improvement of 2.97 (SE 0.35) and 3.97 (SE 0.46) at each time point for anxiety and depression, respectively (t=-8.53 and t=-8.69, respectively; Ps<.001). Those with severe baseline scores also saw a reduction of 0.27 (SE 0.08) and 0.25 (SE 0.09) points in anxiety and depression, respectively, for each additional program activity per week (t=-3.47 and t=-2.66, respectively; Ps<.05). CONCLUSIONS: For participants with severe baseline scores, the study found a clinically significant reduction of approximately 9 points for anxiety and 12 points for depression after 6 months of enrollment, suggesting that interventions targeting mental health must maintain active, ongoing engagement when symptoms are present and be available as a continuous resource to maximize clinical impact, specifically in those experiencing severe anxiety or depression. Moreover, a dosing effect was shown, indicating improvement in outcomes among participants who engaged with the program every other day for both anxiety and depression. This suggests that digital mental health programs that provide both interesting and evidence-based activities could be more successful in further improving mental health outcomes.

Sugar Intake among Preschool-Aged Children in the Guelph Family Health Study: Associations with Sociodemographic Characteristics.

BACKGROUND: It is crucial to develop strategies targeted to promote healthy eating patterns in vulnerable populations, especially young children from diverse sociodemographic groups. Thus, the study objective was to investigate the associations between child age, child sex, child ethnicity, parent number of years living in Canada, annual household income, parent education and parent marital status with total, free and added sugar intakes in young children. METHODS: This cross-sectional study was a secondary analysis of data gathered in the Guelph Family Health Study. The study included 267 children (129M; 138F) from 210 families aged 1.5 to 5 years. Parents completed questionnaires for children on sociodemographic characteristics and an online 24-hour diet recall. The associations between sociodemographic characteristics and sugar intakes were determined using generalized estimating equations applied to linear regression models. RESULTS: The mean age of the children was 3.5 ± 1.2 years (mean ± std dev.). As children's age increased, there was a greater intake of free and added sugar (ß^ = 8.6, p = 0.01, 95% CI = 2.4 to 14.7 and ß^ = 6.5, p = 0.03, 95% CI = 0.8 to 12.2, respectively). Those children who identified as white had a higher total sugar intake than children of other ethnicities (ß^ = 31.0, p = 0.01, 95% CI = 7.2 to 54.7). Additionally, higher annual household income was associated with lower was free sugar intake in children (ß^ = -2.4, p = 0.02, 95% CI = -4.5 to -0.4). CONCLUSIONS: This study underscores the significant influence of multiple sociodemographic characteristics on sugar intake in young children, providing valuable insights for public health policy and nutrition interventions. Moreover, this study highlights the need for early behaviour interventions focusing on reducing sugar intake in young children, while considering sociodemographic factors.

Impact of parental status on US medical student specialty selection.

Medical training occurs during peak childbearing years for most medical students. Many factors influence specialty selection. The aims of this study were (i) to determine whether being a parent is a major deciding factor when picking a specialty and (ii) whether parents are more drawn to family-friendly specialties than non-parents. The authors performed a multicenter web-based survey study of medical students enrolled in Oregon Health and Science University, Dartmouth's Geisel School of Medicine, and University of Michigan Medical School. The 27-item instrument assessed parenthood status, specialty preference, specialty perceptions, and factors influencing specialty choice. A total of 537 out of 2236 (24.0%) students responded. Among respondents, 59 (10.9%) were current or expecting parents. The majority (359, 66.8%) were female and 24-35 years old (430, 80.1%). Of the students who were parents or expecting, 30 (50.9%) were female, and the majority (55, 93.2%) were partnered. Top specialties preferred by both parents and non-parents were family medicine, emergency medicine, obstetrics and gynecology (OB/GYN), internal medicine, psychiatry, and pediatrics. Specialties rated most family-friendly included family medicine, dermatology, pediatrics, psychiatry, radiology, emergency medicine, and pathology. The specialties rated least family-friendly were surgery, neurosurgery, orthopedic surgery, plastic surgery, and OB/GYN. These rankings were the same between groups. Passion for the field, culture of the specialty, and quality of life were the top three factors students considered when choosing a specialty. Being a parent or future parent ranked more highly for parents than non-parents, but was not in the top three factors for either group. US Medical School parents report that being a parent influenced their medical specialty choice "strongly" or "very strongly." However, being a parent was not weighed as heavily as passion for the field, culture of the specialty, and quality of life. These student-parents are entering perceived "non-family friendly" specialties at similar rates as their peers. US Medical school training and simultaneous parenting is daunting, yet student parents are putting their passion first when making a career choice. They must be supported.

Associations Between Social Cognitive Determinants and Movement-Related Behaviors in Studies Using Ecological Momentary Assessment Methods: Systematic Review.

BACKGROUND: The social cognitive framework is a long-standing framework within physical activity promotion literature to explain and predict movement-related behaviors. However, applications of the social cognitive framework to explain and predict movement-related behaviors have typically examined the relationships between determinants and behavior across macrotimescales (eg, weeks and months). There is more recent evidence suggesting that movement-related behaviors and their social cognitive determinants (eg, self-efficacy and intentions) change across microtimescales (eg, hours and days). Therefore, efforts have been devoted to examining the relationship between social cognitive determinants and movement-related behaviors across microtimescales. Ecological momentary assessment (EMA) is a growing methodology that can capture movement-related behaviors and social cognitive determinants as they change across microtimescales. OBJECTIVE: The objective of this systematic review was to summarize evidence from EMA studies examining associations between social cognitive determinants and movement-related behaviors (ie, physical activity and sedentary behavior). METHODS: Studies were included if they quantitatively tested such an association at the momentary or day level and excluded if they were an active intervention. Using keyword searches, articles were identified across the PubMed, SPORTDiscus, and PsycINFO databases. Articles were first assessed through abstract and title screening followed by full-text review. Each article was screened independently by 2 reviewers. For eligible articles, data regarding study design, associations between social cognitive determinants and movement-related behaviors, and study quality (ie, Methodological Quality Questionnaire and Checklist for Reporting Ecological Momentary Assessment Studies) were extracted. At least 4 articles were required to draw a conclusion regarding the overall associations between a social cognitive determinant and movement-related behavior. For the social cognitive determinants in which a conclusion regarding an overall association could be drawn, 60% of the articles needed to document a similar association (ie, positive, negative, or null) to conclude that the association existed in a particular direction. RESULTS: A total of 24 articles including 1891 participants were eligible for the review. At the day level, intentions and self-efficacy were positively associated with physical activity. No other associations could be determined because of conflicting findings or the small number of studies investigating associations. CONCLUSIONS: Future research would benefit from validating EMA assessments of social cognitive determinants and systematically investigating associations across different operationalizations of key constructs. Despite the only recent emergence of EMA to understand social cognitive determinants of movement-related behaviors, the findings indicate that daily intentions and self-efficacy play an important role in regulating physical activity in everyday life. TRIAL REGISTRATION: PROSPERO CRD42022328500; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=328500.

Endoscopic severity of gastric sleeve stenosis can be quantified using impedance planimetry.

BACKGROUND: Gastric sleeve stenosis (GSS) is an adverse event following sleeve gastrectomy for which objective tools are needed for diagnosis and treatment. Endoscopic treatment with serial pneumatic balloon dilation may relieve symptoms and prevent the need for conversion to Roux-en-Y gastric bypass. Endoluminal functional impedance planimetry (EndoFLIP) is an endoscopic tool that measures luminal diameter and distensibility indices (DI) and could be used to characterize severity of GSS. METHODS: This was a retrospective analysis of a prospective database of patients referred for symptoms suggestive of GSS. Severity was determined at each endoscopy by a bariatric endoscopist blinded to EndoFLIP measurements. Successive pneumatic balloon dilations were performed until symptoms resolved; failure was defined as referral for conversion. EndoFLIP measurements of stenosis diameter and DI were obtained pre- and post-dilation. Primary outcomes were pre- and post-dilation luminal diameter and DI of GSS. Secondary outcomes were endoscopic severity of GSS, patient characteristics, and need for surgical revision. RESULTS: 26 patients were included; 23 (85%) were female. Mean age was 45.3 (± 9.9) years. Mean number of dilations was 2.4 (± 1.3) and 10 (38%) patients were referred for conversion. Mild, moderate, and severe GSS was found in 10 (38%), 6 (23%), and 10 (38%) patients, respectively. Moderate and severe GSS underwent more dilations (2.5 ± 1.0 and 3.2 ± 1.6) than mild GSS (1.8 ± 0.8) and were more likely to be referred for conversion. Both pre- and post-dilation diameters were significantly larger in mild versus moderate or severe GSS. Additionally, pre- and post-dilation DI at 30 ml were significantly higher for mild compared to moderate and severe GSS. DISCUSSION: EndoFLIP measurements correlate well with endoscopic assessment of GSS. While more data are needed to determine ideal balloon size and threshold measurements, our results suggest EndoFLIP may help expedite diagnosis and treatment of GSS.

Free sugar intake from snacks and beverages in Canadian preschool- and toddler-aged children: a cross-sectional study.

BACKGROUND: Excess consumption of free sugar (FS) increases the risk of dental caries and unhealthy weight gain. However, the contribution of snacks and beverages to young children's FS intake is not well understood. The purpose of this study was to determine FS intake from snacks and beverages among preschool-aged Canadian children. METHODS: This cross-sectional study examined baseline data from 267 children 1.5 to 5 y enrolled in the Guelph Family Health Study. Dietary assessment was completed over a 24-h period using ASA24-Canada-2016 to, 1) estimate the proportion of children whose FS intake from snacks and beverages consumed exceeded 5% total energy intake (TE) and 10% TE, and 2) identify the top snack and beverage sources of FS. RESULTS: FS contributed 10.6 ± 6.9% TE (mean ± SD). 30 and 8% of children consumed ≥ 5% TE and ≥ 10% TE from snack FS, respectively. Furthermore, 17 and 7% of children consumed ≥ 5% TE and ≥ 10% TE from beverages FS, respectively. Snacks and beverages accounted for 49 ± 30.9% of FS energy. Top snack sources of FS (% children, children's %TE from FS) were bakery products (55%, 2.4%), candy and sweet condiments (21%, 3.0%), and sugar-containing beverages (20%, 4.1%). Top sugar-containing beverage sources of FS (48%, 5.3%) were 100% fruit juice (22%, 4.6%) and flavored milk (11%, 3.1%). CONCLUSIONS: Snacks and beverages contributed nearly half of FS intake among a sample of young children in Canada. Thus, long-term monitoring of snacking behavior and consumption of FS is warranted. These findings may help inform nutritional strategies and public policies to improve diet quality and FS intake in preschool-aged children. TRIAL REGISTRATION: The Clinical Trial Registry number is NCT02939261 from clinicaltrials.gov. Date of Registration: October 20, 2016.

Associations between sleep-related symptoms, obesity, cardiometabolic conditions, brain structural alterations and cognition in the UK biobank.

OBJECTIVES: Sleep disturbances are increasingly recognized as adversely affecting brain health in aging. Our aim was to investigate interrelations between subjective sleep-related symptoms, obesity, cardiometabolic disorders, brain structure and cognitive decline in a population-based aging sample. METHODS: Data were extracted from the UK Biobank for anthropometric and demographic information, self-reported sleep behaviours, cardiometabolic measures, structural brain magnetic resonance imaging and cognitive test scores. "Sleep-related symptoms" (SRS) were measured using four questionnaire items: loud snoring, daytime sleepiness, likelihood to nap and difficulty getting up in the morning. Associations were tested using a structural equation model (SEM), adjusted for confounders. Further, multiple regression analysis was used to test for direct relationships between SRS and specific cognitive domains. RESULTS: Among 36,468 participants with an average age of 63.6 (SD 7.5) years and 46.7% male, we found that SRS were associated with obesity and several pre-existing cardiometabolic disturbances. In turn, cardiometabolic disorders were associated with increased white matter hyperintensities and cortical thinning, which were related to cognitive dysfunction. SRS were also directly related to several structural brain changes and to cognitive dysfunction. Regression analyses showed that SRS were directly associated with slower reaction times, and lower scores in fluid intelligence, working memory and executive function. CONCLUSIONS: Self-reported sleep-related symptoms were associated with cognitive dysfunction directly and through pre-existing cardiometabolic disorders and brain structural alterations. These findings provide evidence that symptoms of sleep disturbances, here defined primarily by hypersomnolence and snoring, are important risk factors or markers for cognitive dysfunction in an aging population.

The in silico lab: Improving academic code using lessons from biology.

"Good code" is often regarded as a nebulous, impractical ideal. Common best practices toward improving code quality can be inaccessible to those without a rigorous computer science or software engineering background, contributing to a gap between advancing scientific research and FAIR practices. We seek to equip researchers with the necessary background and context to tackle the challenge of improving code quality in computational biology research using analogies from biology to synthesize why certain best practices are critical for advancing computational research. Improving code quality requires active stewardship; we encourage researchers to deliberately adopt and share practices that ensure reusability, repeatability, and reproducibility.