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Abstract Introduction Ureteral stricture disease (UTSD) poses significant challenges in reconstructive urology, with recent advances highlighting disparities in healthcare outcomes based on race and ethnicity. This study investigates the impact of race and ethnicity on clinical outcomes following ureteral reconstruction. Methods We conducted a single‐centre prospective analysis of 233 patients who underwent ureteral reconstruction for UTSD from 2014 to 2023. Patient demographics, clinical characteristics, surgical details and outcomes were collected. Patients were stratified by race (White vs. non‐White) and ethnicity (Hispanic vs. non‐Hispanic). Statistical analyses included Kruskal–Wallis, Mann–Whitney U tests, ANOVA, Kaplan–Meier analysis and multivariate logistic regression. Results Our cohort included 233 patients who underwent ureteroplasty with 108 (46.4%) non‐White patients, and 71 (30.5%) were Hispanic. No significant differences were found in recurrence rates, complications, or stricture‐free survival between racial and ethnic groups. Prior reconstructions were more prevalent among non‐White patients (26.9% vs. 16.0%; p = 0.043). Unadjusted and adjusted regressions showed significant associations between non‐White race (unadjusted β = 0.76, p = 0.008; adjusted β = 0.82, p = 0.008) and Hispanic ethnicity (unadjusted β = 0.70, p = 0.025; adjusted β = 0.79, p = 0.020) with increased stricture lengths. Conclusion This study highlights that although recurrence and complication rates do not significantly differ by race or ethnicity, disparities exist in clinical presentations, with non‐White and Hispanic patients presenting with longer stricture lengths and higher body mass index. These findings underscore the need for targeted interventions to address underlying disparities in healthcare delivery and access.

Recirculating aquaculture systems (RAS) accumulate dissolved nitrate in the water, which can harm animals. Denitrification can be used to remove nitrate, although some strategies can be expensive and difficult to operate. The purpose of this project was to help simplify denitrification techniques to facilitate long-term water reuse. Two experiments were conducted: one to testing various substrates in denitrification reactors (Experiment 1), and another to investigate lower carbon: nitrogen ratios on suspended growth denitrification systems (Experiment 2). The results of these experiments were then applied to on-farm demonstrations. Experiment 1 had a control with no media, and three treatments containing either plastic bio-media, expanded clay pellets, or woodchips. Experiment 2 had a control receiving no carbon (0:1) and three treatments with varying C:N ratios (0.2:1, 0.5:1, and 1:1). For experiment 1, nitrate was reduced in all treatments even without media; this fact provided motivation for Experiment 2. In Experiment 2, all of the treatments had significantly lower nitrate-N than the control. The 0.5:1 and 0.2:1 treatments had almost complete removal of N, while the 1:1 had high nitrite-N. The initial nitrate-N was 298.1 mg L−1; the final concentrations in each treatment were: 0.2:1 = 2.3, 0.5:1 = 2.3, and 1:1 = 15.5 mg L−1. Subsequent tests at shrimp farms using the 0.2:1 C:N ratio resulted in almost complete removal of nitrate-N. In one case, nitrate-N was reduced from 493 to 1.4 mg L−1 in 7 days. These results demonstrate that simple, suspended growth denitrification can be highly effective at nitrate removal.

IntroductionThe prostate is densely innervated like many visceral organs and glands. However, studies to date have focused on sympathetic and parasympathetic nerves and little attention has been given to the presence or function of sensory nerves in the prostate. Recent studies have highlighted a role for sensory nerves beyond perception of noxious stimuli, as anterograde release of neuropeptides from sensory nerves can affect vascular tone and local immune responses.MethodsTo identify the degree of sensory innervation in the prostate, we utilized state-of-the-art tissue clearing and microscopy to visualize sensory innervation in the different lobes of the mouse prostate. To determine whether sensory nerves have a role in regulating proliferation within the prostate, we used an intersectional genetic and toxin approach to ablate peptidergic sensory nerves systemically.ResultsWe found that sensory neurons are abundant in the prostate both in nerve bundles along the vasculature and as independent nerve fibers wrapped around prostatic acini in a net-like fashion. In addition to the dense innervation of the prostate, we found that Calca haploinsufficiency, the genotype control for our intersectional ablation model, results in a diminished level of Ki67 staining in the stromal compartment of the dorsal lobe and a diminishing Ki67 trend in other lobes.DiscussionThese findings suggest that sensory neurons might have developmental or homeostatic effects within the prostate. Further studies are warranted to assess the role of sensory neurons and the sensory neuropeptides on prostatic development and on proliferation in the presence of pro-inflammatory stimuli such as bacterial infection or tumor cells.

Abstract One third of epilepsy patients are resistant to treatment with current anti‐seizure medications. The ketogenic diet is used to treat some forms of refractory epilepsy, but the mechanism of its action has not yet been elucidated. In this study, we aimed to investigate whether the hydroxycarboxylic acid receptor 2 (HCA2), a known immunomodulatory receptor, plays a role in mediating the protective effect of this diet. We demonstrate for the first time that selective agonists at this receptor can directly reduce seizures in animal models. Agonists also reduce network activity in rodent and human brain slices. Ketogenic diet is known to increase circulating levels of endogenous HCA2 agonists, and we show that the effect of ketogenic diet in reducing seizures in the 6 Hz seizure model is negated in HCA2‐deficient mice. Our data support the potential of HCA2 as a target for the treatment of epilepsy and potentially for neurodegenerative diseases.

Children museums provide an engaging learning environment for families with exhibits designed to stimulate caregiver-child interactions. Specific types of questions have been shown to support child language learning by scaffolding more elaborative responses. This study analyzed the use of question form types during caregiver-child interactions in a children’s museum, aiming to discern their correlation with child language proficiency. We examined and transcribed two exhibit explorations by 43 caregiver-child dyads (3- to 6-year-old children). Our analysis encompasses various syntactic question types (e.g., yes-no, wh-) and measures of child language proficiency, including lexical diversity, morphosyntactic complexity, and overall language ability. Findings reveal disparities in question form usage among caregivers and children, with caregivers predominantly employing closed questions and children balancing closed and open-ended types. Children of caregivers who predominantly posed closed questions exhibited shorter utterances and lower overall language scores. Details on other question forms are presented (sub-types of polar, wh-, alternative, and echo). These findings contribute to our understanding of how question form influences language development and caregiver–child interactions.

Penile strangulation secondary to utilization of a constrictive ring is a rare urologic emergency that requires urgent decompression to prevent prolonged vascular obstruction resulting in necrosis and gangrene. Current literature is mainly comprised of case presentations that focus on management in the acute setting via removal of the ring. Herein, we describe surgical management of a patient who presents in delayed fashion after self-removal of the constrictive ring. We discuss our penectomy-sparing technique of debridement and split thickness skin graft.

Phyllachora maydis is a fungal plant pathogen that causes tar spot of corn (Zea mays) in North and South America, causing devastating yield losses under favorable conditions. Although the causal agent is relatively easy to diagnose via macroscopic and microscopic observations, other diseases and conditions, such as insect frass, have been mistaken for tar spot of corn. Furthermore, conidia and ascospores in isolation can be difficult to visually distinguish from other fungi, and the development of signs and symptoms of the disease may not be observed until 12 to 20 days after infection. Therefore, we developed a TaqMan quantitative polymerase chain reaction (qPCR) assay for the detection and quantification of this pathogen to be used for diagnostics and airborne spore quantification. The assay was designed for the internal transcribed spacer region of P. maydis. The specificity of the assay was confirmed and tested against various nontarget Phyllachora species, corn pathogens, endophytes, and P. maydis samples from several states in the Midwest and from Mexico. The detection limit of this assay was determined to be 100 fg of genomic P. maydis DNA. To demonstrate the transferability of this technology, the assay was tested in different labs using various qPCR thermal cyclers. This assay can be used in downstream research involving latency period, disease prediction, and diagnostics. [Figure: see text] Copyright © 2024 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.

Millimeter-wave (mm-Wave) phased array systems need to meet the transmitter (Tx) equivalent isotropic radiated power (EIRP) requirement, and that depends mainly on the design of two key sub-components: (1) the antenna array and (2) the Tx power amplifier (PA) in the front-end-modules (FEMs). Simulations using an electromagnetic (EM) solver carried out in Cadence AWR with AXIEM suggest that for two uniform square patch antenna arrays at 24 GHz, the 4 element array has ~6 dB lower antenna gain and twice the half power beam width (HPBW) compared to the 16 element array. We also present measurements and post-layout parasitic-extracted (PEX) EM simulation data taken on two broadband mm-Wave PAs designed in our lab that cover the key portions of the fifth-generation (5G) FR2-band (i.e., 24.25–52.6 GHz) that lies between the super-high-frequency (SHF, i.e., 3–30 GHz) band and the extremely-high-frequency (EHF, i.e., 30–300 GHz) band: one designed in a 22 nm fully depleted silicon on insulator (FD-SOI) CMOS process, and the other in an advanced 40 nm Gallium Nitride (GaN) high-electron-mobility transistor (HEMT) process. The FD-SOI PA achieves saturated output power (POUT,SAT) of ~14 dBm and peak power-added efficiency (PAE) of ~20% with ~14 dB of gain and 3 dB bandwidth (BW) from ~19.1 to 46.5 GHz in measurement, while the GaN PA achieves measured POUT,SAT of ~24 dBm and peak PAE of ~20% with ~20 dB gain and 3 dB BW from ~19.9 to 35.2 GHz. The PAs’ measured data are in good agreement with the PEX EM simulated data, and 3rd Watt-level GaN PA design data are also presented, but with simulated PEX EM data only. Assuming each antenna element will be driven by one FEM and each phased array targets the same 65 dBm EIRP, millimeter wave (mm-Wave) antenna arrays using the Watt-level GaN PAs and FEMs are expected to achieve roughly 2× wider HPBW with 4× reduction in the array size compared with the arrays using Si FEMs, which shall alleviate the thorny mm-Wave line-of-sight (LOS)-blocking problems significantly.

Abstract Developmental and epileptic encephalopathies (DEEs) are a group of rare childhood disorders characterized by severe epilepsy and cognitive deficits. Numerous DEE genes have been discovered thanks to advances in genomic diagnosis, yet putative molecular links between these disorders are unknown. CDKL5 deficiency disorder (CDD, DEE2), one of the most common genetic epilepsies, is caused by loss-of-function mutations in the brain-enriched kinase CDKL5. To elucidate CDKL5 function, we looked for CDKL5 substrates using a SILAC-based phosphoproteomic screen. We identified the voltage-gated Ca2+ channel Cav2.3 (encoded by CACNA1E) as a physiological target of CDKL5 in mice and humans. Recombinant channel electrophysiology and interdisciplinary characterization of Cav2.3 phosphomutant mice revealed that loss of Cav2.3 phosphorylation leads to channel gain-of-function via slower inactivation and enhanced cholinergic stimulation, resulting in increased neuronal excitability. Our results thus show that CDD is partly a channelopathy. The properties of unphosphorylated Cav2.3 closely resemble those described for CACNA1E gain-of-function mutations causing DEE69, a disorder sharing clinical features with CDD. We show that these two single-gene diseases are mechanistically related and could be ameliorated with Cav2.3 inhibitors.

Abstract Phyllachora maydis is a fungal pathogen causing tar spot of corn (Zea mays L.), a new and emerging, yield-limiting disease in the United States. Since being first reported in Illinois and Indiana in 2015, P. maydis can now be found across much of the corn growing regions of the United States. Knowledge of the epidemiology of P. maydis is limited but could be useful in developing tar spot prediction tools. The research presented here aims to elucidate the environmental conditions necessary for the development of tar spot in the field and the creation of predictive models to anticipate future tar spot epidemics. Extended periods (30-day windowpanes) of moderate mean ambient temperature (18–23 °C) were most significant for explaining the development of tar spot. Shorter periods (14- to 21-day windowpanes) of moisture (relative humidity, dew point, number of hours with predicted leaf wetness) were negatively correlated with tar spot development. These weather variables were used to develop multiple logistic regression models, an ensembled model, and two machine learning models for the prediction of tar spot development. This work has improved the understanding of P. maydis epidemiology and provided the foundation for the development of a predictive tool for anticipating future tar spot epidemics.

Abstract Background Genome-wide association studies (GWAS) of Alzheimer’s disease (AD) have identified several risk loci, but many remain unknown. Cerebrospinal fluid (CSF) biomarkers may aid in gene discovery and we previously demonstrated that six CSF biomarkers (β-amyloid, total/phosphorylated tau, NfL, YKL-40, and neurogranin) cluster into five principal components (PC), each representing statistically independent biological processes. Here, we aimed to (1) identify common genetic variants associated with these CSF profiles, (2) assess the role of associated variants in AD pathophysiology, and (3) explore potential sex differences. Methods We performed GWAS for each of the five biomarker PCs in two multi-center studies (EMIF-AD and ADNI). In total, 973 participants (n = 205 controls, n = 546 mild cognitive impairment, n = 222 AD) were analyzed for 7,433,949 common SNPs and 19,511 protein-coding genes. Structural equation models tested whether biomarker PCs mediate genetic risk effects on AD, and stratified and interaction models probed for sex-specific effects. Results Five loci showed genome-wide significant association with CSF profiles, two were novel (rs145791381 [inflammation] and GRIN2D [synaptic functioning]) and three were previously described (APOE, TMEM106B, and CHI3L1). Follow-up analyses of the two novel signals in independent datasets only supported the GRIN2D locus, which contains several functionally interesting candidate genes. Mediation tests indicated that variants in APOE are associated with AD status via processes related to amyloid and tau pathology, while markers in TMEM106B and CHI3L1 are associated with AD only via neuronal injury/inflammation. Additionally, seven loci showed sex-specific associations with AD biomarkers. Conclusions These results suggest that pathway and sex-specific analyses can improve our understanding of AD genetics and may contribute to precision medicine.

Adolescents and adults with Down syndrome are noted to display symptoms consistent with various anxiety disorders. While evidenced-based practices, including psychotherapies and psychopharmacology, exist and effectively treat anxiety in neurotypical populations, less is known about anxiety treatments for persons with Down syndrome. A scoping rapid review was conducted in April 2023 to determine what treatments are being used to target anxiety in adolescents and adults with Down syndrome, the quality of those treatments, and their alignment with current evidence-based practices. A total of eleven articles, primarily single case or case series, published between 1981 and 2022 were identified targeting adolescents and adults with Down syndrome diagnosed with specific phobias, selective mutism, generalized anxiety disorder, agoraphobia with panic, and non-specific anxiety symptoms. Interventions used most often aligned with evidence-based anxiety treatment guidelines and included psychotherapy, complementary and alternative medicine, and psychopharmacology. While most studies reported positive treatment responses showing reductions in anxiety symptoms post-treatment, the quality and generalizability of the studies was primarily poor. More rigorous research evaluating the effects of treatment for anxiety symptoms in the DS population are needed to develop guidelines to address anxiety disorders in this vulnerable population.

Abstract Abemaciclib is an orally administered, potent, and selective small molecule inhibitor of cyclin‐dependent kinases 4 and 6, approved for advanced or metastatic breast cancer. This study aimed to use an exposure–response approach to investigate the effect of abemaciclib and its active metabolites (M2 and M20) on QTc interval and delay in cardiac repolarization at clinically relevant exposures. This was a single‐blind, randomized, and placebo‐controlled study of ascending doses of abemaciclib. Thirty‐five healthy participants were administered a single dose of 200–600 mg abemaciclib. Twelve‐lead electrocardiogram tracings and pharmacokinetic samples were collected serially pre‐ and post‐dose. The primary objective was to study the relationship between abemaciclib and its active metabolites (M2 and M20) and QTc interval following ascending oral doses of abemaciclib. The secondary objective included evaluating the safety and tolerability of single ascending doses of abemaciclib in healthy participants. Exposure–response analysis demonstrated that there was no significant relationship between placebo‐corrected change from baseline QTcF (ΔΔQTcF), abemaciclib, and metabolite plasma concentrations. Additionally, the ΔΔQTcF slopes of abemaciclib, its metabolites, and total analyte concentrations were not statistically different from zero. Single doses of abemaciclib, up to 400 mg, were well‐tolerated by healthy participants; however, at the 600 mg dose (three times the highest registered dose), the frequency and severity of treatment‐related gastrointestinal events (primarily diarrhea, nausea, and vomiting) increased. In conclusion, single doses of abemaciclib, up to 400 mg, had no statistically or clinically relevant effects on QTc, and abemaciclib was well tolerated up to a dose of 400 mg in this study.

Abstract Background Tar spot of corn is a significant and spreading disease in the continental U.S. and Canada caused by the obligate biotrophic fungus Phyllachora maydis. As of 2023, tar spot had been reported in 18 U.S. states and one Canadian Province. The symptoms of tar spot include chlorotic flecking followed by the formation of black stromata where conidia and ascospores are produced. Advancements in research and management for tar spot have been limited by a need for a reliable method to inoculate plants to enable the study of the disease. The goal of this study was to develop a reliable method to induce tar spot in controlled conditions. Results We induced infection of corn by P. maydis in 100% of inoculated plants with a new inoculation method. This method includes the use of vacuum-collection tools to extract ascospores from field-infected corn leaves, application of spores to leaves, and induction of the disease in the dark at high humidity and moderate temperatures. Infection and disease development were consistently achieved in four independent experiments on different corn hybrids and under different environmental conditions in a greenhouse and growth chamber. Disease induction was impacted by the source and storage conditions of spores, as tar spot was not induced with ascospores from leaves stored dry at 25 ºC for 5 months but was induced using ascospores from infected leaves stored at -20 ºC for 5 months. The time from inoculation to stromata formation was 10 to 12 days and ascospores were present 19 days after inoculation throughout our experiments. In addition to providing techniques that enable in-vitro experimentation, our research also provides fundamental insights into the conditions that favor tar spot epidemics. Conclusions We developed a method to reliably inoculate corn with P. maydis. The method was validated by multiple independent experiments in which infection was induced in 100% of the plants, demonstrating its consistency in controlled conditions. This new method facilitates research on tar spot and provides opportunities to study the biology of P. maydis, the epidemiology of tar spot, and for identifying host resistance.

This study evaluates the effects of object weight and hand dominance on the end-point kinematics of the hand-to-mouth (withdrawal) movement in a functional reach-to-drink task for typically developing school-aged children. Using 3D motion capture, speed (average velocity and peak velocity), straightness (ratio), and smoothness (number of velocity peaks and log dimensionless jerk) of hand movements were calculated for the withdrawal motion with three different bottle weights (empty, half-filled, and full). Average velocity (550.4 ± 142.0 versus 512.1 ± 145.6 mm/s) and peak velocity (916.3 ± 234 versus 842.7 ± 198.4 mm/s) were significantly higher with the empty versus half-filled bottle and with the non-dominant (average: 543.5 ± 145.2 mm/s; peak: 896.5 ± 207 mm/s) versus dominant (average: 525.2 ± 40.7 mm/s; peak: 864.2 ± 209.2 mm/s) hand. There were no differences in straightness or smoothness. These findings indicate that increasing weight in reach-to-drink task puts greater constraints on the task. The slower movements with the dominant hand might denote better precision control than the non-dominant hand. The quantitative motion capture results show average values for the kinematic variables for a functional reach-to-drink task in a typically developing population of school-aged children with changing weights of the bottles that are relevant to a real-life scenario. These results could inform the design of individualized therapeutic interventions to improve functional upper-extremity use in children with neurodevelopmental motor disorders.

The diagnosis of Clostridioides difficile infection (CDI) in the pediatric population is complicated by the high prevalence of asymptomatic colonization, particularly in infants. Many laboratory diagnostic methods are available, but there continues to be controversy over the optimal laboratory testing approach to diagnose CDI in children. We evaluated commonly used C. difficile diagnostic commercial tests in our pediatric hospital population at Sidra Medicine in Doha, Qatar. Between June and December 2023, 374 consecutive stool samples from pediatric patients aged 0–18 years old were tested using: Techlab C. diff Quik Chek Complete, Cepheid GeneXpert C. difficile, QIAstat-Dx Gastrointestinal Panel, and culture using CHROMagar C. difficile. The results of these tests as standalone methods or in four different testing algorithms were compared to a composite reference method on the basis of turnaround time, ease of use, cost, and performance characteristics including specificity, sensitivity, negative predictive value, and positive predictive value. Our study showed variability in test performance of the different available assays in diagnosing CDI. In our population, a testing algorithm starting with Cepheid GeneXpert C. difficile PCR assay or QIAstat-Dx Gastrointestinal panel as a screening test followed by toxin immunoassay for positive samples using the Techlab C. diff Quik Chek Complete kit showed the best performance (100% specificity and 100% positive predictive value) when combined with clinical review of the patient to assess risk factors for CDI, clinical presentation, and alternative causes of diarrhea.

Abstract Background Initially developed in the intensive care unit (ICU) at St. Joseph’s Healthcare Hamilton (SJHH) the 3 Wishes Project (3WP) provides personalized, compassionate care to dying patients and their families. The objective of this study was to develop and evaluate 3WP expansion strategies for patients cared for on General Internal Medicine (GIM) wards in our hospital. Methods From January 2020-November 2021, we developed a phased, multicomponent approach for program expansion. We enrolled patients on the GIM wards who had a high probability of dying in hospital, then elicited, implemented, and documented wishes for them or their families. Data were analyzed descriptively. Results From March 2020 to November 2020, we implemented staff education and engagement activities, created an Expansion Coordinator position, held strategic consultations, and offered enabling resources. From March 2020 to November 2021, we enrolled 62 patients and elicited 281 wishes (median [1st, 3rd quartiles] 4 [4, 5] wishes/patient). The most common wish categories were personalizing the environment (67 wishes, 24%), rituals and spiritual support (42 wishes, 15%), and facilitating connections (39 wishes, 14%). The median [1st, 3rd] cost/patient was $0 [0, $10.00] (range $0 to $86); 91% of wishes incurred no cost to the program. Conclusions The formal expansion of the 3WP on GIM wards has been successful despite COVID-19 pandemic disruptions. While there is still work ahead, these data suggest that implementing the 3WP on the GIM wards is feasible and affordable. Increased engagement of the clinical team during the pandemic suggests that it is positively received.

Better diagnostic tools are needed to improve the diagnosis of Clostridioides difficile infections (CDI) and reduce the overtreatment of colonized children. In this study, we evaluated two polymerase chain reaction (PCR) assays (Cepheid GeneXpert C. difficile and the Gastroenteritis PCR Panel by QIAstat-Dx) as a standalone method in combination with the PCR cycle threshold (Ct) value in positive samples to predict the presence of free toxins. We also evaluated the clinical impact of reporting toxin production results and provided comments alongside the PCR results in our pediatric population. PCR-positive stool samples from pediatric patients (aged 2 to 18 years old) were included in our study and tested for the presence of toxins A and B using the C. difficile Quik Chek Complete kit. For the clinical intervention, the CDI treatment rates 6 months pre- and post-intervention were compared. The use of PCR Ct value showed excellent sensitivity (100%) at a Ct value cutoff of 26.1 and 27.2 using the Cepheid GeneXpert C. difficile and the Gastroenteritis PCR Panel by QIAstat-Dx, respectively, while the toxin test showed inferior sensitivity of 64% in the PCR-positive samples. In addition, CDI treatment rates were decreased by 23% post-intervention. The results of our study suggest that nucleic acid amplification test (NAAT) assays supplemented by the use of PCR Ct value for positive samples can be used as standalone tests to differentiate CDI from colonization. Furthermore, the reporting of toxin production along with the PCR results can help reduce the unnecessary treatment of colonized children.

This paper presents a broadband millimeter-wave (mm-Wave) low noise amplifier (LNA) designed in a 22 nm fully depleted silicon-on-insulator (FD-SOI) CMOS technology. Electromagnetic (EM) simulations suggest that the LNA has a 3-dB bandwidth (BW) from 17.8 to 42.4 GHz and a fractional bandwidth (FBW) of 81.7%, covering the key frequency bands within the mm-Wave 5G FR2 band, with its noise figure (NF) ranging from 2.9 to 4.9 dB, and its input-referred 1-dB compression point (IP1dB) of −17.9 dBm and input-referred third-order intercept point (IIP3) of −8.5 dBm at 28 GHz with 15.8 mW DC power consumption (PDC). Using the FOM (figure-of-merit) developed for broadband LNAs (FOM = 20 × log((Gain[V/V] × S21-3 dB-BW [GHz])/(PDC [mW] × (F-1)))), this LNA achieves a competitive FOM (FOM = 18.9) among reported state-of-the-art mm-Wave LNAs in the literature.

Abstract To investigate aldo–keto reductase 1C3 (AKR1C3) expression in T and B acute lymphoblastic leukemia/lymphoma (ALL) patients. Three commercial antibodies were evaluated for AKR1C3 immunohistochemistry (IHC) staining performance: Polyclonal Thermofisher scientific (Clone#PA523667), rabbit monoclonal Abcam [EPR16726] (ab209899) and Sigma/Millipore anti-AKR1C3 antibody, mouse monoclonal, clone NP6.G6.A6, purified from hybridoma cell culture. Initial optimization was performed on cell line controls: HCT116 (negative control); genetically modified cell line HCT116 with AKR1C3 overexpression; Nalm and TF1 cell lines. Twenty normal bone marrows from archival B and T-ALL patient samples were subsequently examined. AKR1C3 expression levels in these samples were evaluated by immunohistochemistry, Protein Wes and quantitative RT-PCR. Sigma/Millipore Anti-AKR1C3 antibody (mouse monoclonal, clone NP6.G6.A6) showed higher specificity compared to rabbit polyclonal antibody by immunohistochemistry. H-score was used to quantify percent of nuclear immunoreactivity for AKR1C3 with varying disease involvement. T-ALL samples had a higher H-score (172–190) compared to B-ALL cases (H-score, 30–160). The AKR1C3 expression in peripheral blood by Protein Wes and RT-qPCR showed concordance in relapsed/refractory and/or minimal residual T-ALL cases. Sigma/Millipore Anti-AKR1C3 antibody and mouse monoclonal, clone NP6.G6.A6 can be used to aid in AKR1C expression of T-ALL and in cases of relapsed/refractory and/or minimal residual disease.

Objectives: To assess the outcomes of a conservative management approach to radiation-induced urethral stricture disease (R-USD) in an elderly population with comorbidities. Methods: Patients with R-USD managed with endoscopic procedures and/or clean intermittent catheterization (CIC) between 2007 and 2019 were included. Patients were excluded if they had an obliterative stricture, prior urethral reconstruction/urinary diversion surgery, or < 3 months follow-up. Primary outcome measures were urinary tract infection (UTI), acute urinary retention (AUR), serum creatinine, uroflowmetry/post-void residual, and urinary incontinence (UI). Failure was defined as progression to reconstructive surgery or permanent indwelling catheterization. Results: Ninety-one men were analyzed with a median follow-up of 15.0 months (IQR 8.9 to 37.9). Median age was 75.4 years (IQR 70.0 to 80.0), body mass index was 26.5 kg/m2 (IQR 24.8 to 30.3), and Charlson comorbidity index was 6 (IQR 5 to 8). Median stricture length was 2.0 cm (IQR 2.0 to 3.0). Stricture location was bulbar (12%), bulbomembranous (75%), and prostatic (13%). A total of 90% underwent dilation, and 44% underwent direct visual internal urethrotomy (DVIU). For those that underwent these procedures, median number of dilations and DVIUs per patient was 2 (IQR 1 to 5) and 1 (IQR 1 to 3), respectively. Forty percent used CIC. Thirty-four percent developed a UTI, and 15% had an AUR episode requiring urgent treatment. Creatinine values, uroflowmetry measurements, and UI rates remained stable. Eighty percent avoided reconstructive surgery or indwelling catheterization. Conclusion: Most elderly patients with comorbidities with R-USD appear to be effectively managed in the short-term with conservative strategies. Close observation is warranted because of the risk of UTIs and AUR. The potential long-term consequences of repetitive conservative interventions must be considered

Despite most angiosperms being perennial, once-flowering annuals have evolved multiple times independently, making life history traits among the most labile trait syndromes in flowering plants. Much research has focused on discerning the adaptive forces driving the evolution of annual species, and in pinpointing traits that distinguish them from perennials. By contrast, little is known about how ‘annual traits’ evolve, and whether the same traits and genes have evolved in parallel to affect independent origins of the annual syndrome. Here, we review what is known about the distribution of annuals in both phylogenetic and environmental space and assess the evidence for parallel evolution of annuality through similar physiological, developmental, and/or genetic mechanisms. We then use temperate grasses as a case study for modeling the evolution of annuality and suggest future directions for understanding annual-perennial transitions in other groups of plants. Understanding how convergent life history traits evolve can help predict species responses to climate change and allows transfer of knowledge between model and agriculturally important species.

School-aged youth with behavioral health needs often struggle in the academic environment. When admitted to acute psychiatric hospital settings, the student’s difficulties and needs increase upon discharge and return to the school setting. While the literature describes systemic issues in transitioning from an acute psychiatric hospital to the school setting, limited resources exist for practitioners to plan for and support the successful reintegration of affected students. Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, the purpose of the current systematic review was to collect and synthesize evidence from the literature (N = 20) in the areas of barriers, challenges, and significance of the need for a formal transition planning framework. Four major key factors emerged as important to assist in creating a transition planning framework for acute psychiatric hospitals to school-based settings: (a) Stakeholder Voice (Student, Caregiver, Hospital/Treatment Team, or School Team Voice); (b) Establishing a Point Person for Transition (Medical or School Point Person); (c) Recommendations/Accommodations (Formal or Informal Supports); and (d) Having a Transition Meeting. Other common factors are discussed, and recommendations are provided to aid practitioners in increasing the likelihood that school-age youth succeed in the school environment post-discharge from acute psychiatric settings. Finally, gaps in the literature are identified as areas for further research.

Background Variation in genes involved in ethanol metabolism has been shown to influence risk for alcohol dependence (AD) including protective loss of function alleles in ethanol metabolizing genes. We therefore hypothesized that people with severe AD would exhibit different patterns of rare functional variation in genes with strong prior evidence for influencing ethanol metabolism and response when compared to genes not meeting these criteria. Objective Leverage a novel case only design and Whole Exome Sequencing (WES) of severe AD cases from the island of Ireland to quantify differences in functional variation between genes associated with ethanol metabolism and/or response and their matched control genes. Methods First, three sets of ethanol related genes were identified including those a) involved in alcohol metabolism in humans b) showing altered expression in mouse brain after alcohol exposure, and altering ethanol behavioral responses in invertebrate models. These genes of interest (GOI) sets were matched to control gene sets using multivariate hierarchical clustering of gene-level summary features from gnomAD. Using WES data from 190 individuals with severe AD, GOI were compared to matched control genes using logistic regression to detect aggregate differences in abundance of loss of function, missense, and synonymous variants, respectively. Results Three non-independent sets of 10, 117, and 359 genes were queried against control gene sets of 139, 1522, and 3360 matched genes, respectively. Significant differences were not detected in the number of functional variants in the primary set of ethanol-metabolizing genes. In both the mouse expression and invertebrate sets, we observed an increased number of synonymous variants in GOI over matched control genes. Post-hoc simulations showed the estimated effects sizes observed are unlikely to be under-estimated. Conclusion The proposed method demonstrates a computationally viable and statistically appropriate approach for genetic analysis of case-only data for hypothesized gene sets supported by empirical evidence.

The Indian River Lagoon (IRL), a 156-mile-long estuary located on the eastern coast of Florida, experiences phytoplankton bloom events due to increased seasonal temperatures coupled with anthropogenic impacts. This study aimed to gather data on the toxicity to human cells and to identify secondary metabolites found in water samples collected in the IRL. Water samples from 20 sites of the IRL were collected during the wet and dry seasons over a three-year period. A panel of cell lines was used to test cytotoxicity. Hemagglutination, hemolysis, and inhibition of protein phosphatase 2A (PP2A) were also measured. Cytotoxic blooms were seen both in the south (Microcystis) and the north (Pyrodinium) of the IRL. Each toxin induced a consistent pattern of cytotoxicity in the panel of human cell lines assayed. During blooms, cytotoxicity due to a single type of toxin is obvious from this pattern. In the absence of blooms, the cytotoxicity seen reflected either a mixture of toxins or it was caused by an unidentified toxin. These observations suggest that other toxins with the potential to be harmful to human health may be present in the IRL. Moreover, the presence of toxins in the IRL is not always associated with blooms of known toxin-producing organisms.

Endomembrane trafficking is essential for plant growth and often depends on a balance between secretory and endocytic pathways. VPS26C is a component of the retriever complex which has been shown to function in the recycling of integral plasma membrane proteins in human cell culture and is part of a core retriever complex in Arabidopsis that is required for root hair growth. In this work, we report a characterization of the Arabidopsis homologues of CCDC22 and CCDC93, two additional proteins required for retriever function in humans. Phylogenetic analysis indicates that CCDC22 (AT1G55830) and CCDC93 (AT4G32560) are single copy genes in plants that are present across the angiosperms, but like VPS26C, are absent from the grasses. Both CCDC22 and CCDC93 are required for root and root hair growth in Arabidopsis and localize primarily to the cytoplasm in root epidermal cells. Previous work has demonstrated a genetic interaction between VPS26C function and a VTI13-dependent trafficking pathway to the vacuole. To further test this model, we characterized the vti13 ccdc93 double mutant and show that like vps26c, ccdc93 is a suppressor of the vti13 root hair phenotype. Together this work identifies two new proteins essential for root and root hair growth in plants and demonstrate that the endosomal pathway(s) in which CCDC93 functions is genetically linked to a VTI13-dependent trafficking pathway to the vacuole.

OBJECTIVES:. Proliferation of COVID-19 research underscored the need for improved awareness among investigators, research staff and bedside clinicians of the operational details of clinical studies. The objective was to describe the genesis, goals, participation, procedures, and outcomes of two research operations committees in an academic ICU during the COVID-19 pandemic. DESIGN:. Two-phase, single-center multistudy cohort. SETTING:. University-affiliated ICU in Hamilton, ON, Canada. PATIENTS:. Adult patients in the ICU, medical stepdown unit, or COVID-19 ward. INTERVENTIONS:. None. MEASUREMENTS AND MAIN RESULTS:. An interprofessional COVID Collaborative was convened at the pandemic onset within our department, to proactively coordinate studies, help navigate multiple authentic consent encounters by different research staff, and determine which studies would be suitable for coenrollment. From March 2020 to May 2021, five non-COVID trials continued, two were paused then restarted, and five were launched. Over 15 months, 161 patients were involved in 215 trial enrollments, 110 (51.1%) of which were into a COVID treatment trial. The overall informed consent rate (proportion agreed of those eligible and approached including a priori and deferred consent models) was 83% (215/259). The informed consent rate was lower for COVID-19 trials (110/142, 77.5%) than other trials (105/117, 89.7%; p = 0.01). Patients with COVID-19 were significantly more likely to be coenrolled in two or more studies (29/77, 37.7%) compared with other patients (13/84, 15.5%; p = 0.002). Review items for each new study were collated, refined, and evolved into a modifiable checklist template to set up each study for success. The COVID Collaborative expanded to a more formal Department of Critical Care Research Operations Committee in June 2021, supporting sustainable research operations during and beyond the pandemic. CONCLUSIONS:. Structured coordination and increased communication about research operations among diverse research stakeholders cultivated a sense of shared purpose and enhanced the integrity of clinical research operations.

Aromatic L-amino acid decarboxylase deficiency (AADC) is a rare neurodevelopmental disorder. Here the authors describe a clinical trial of MR-guided delivery of AAV2-AADC for the treatment of AADC.

This study employed an explanatory sequential mixed-methods research design to examine the beliefs of Vietnamese EFL students concerning oral corrective feedback (CF) and the role of some individual differences in these beliefs. The data consisted of questionnaires completed by 250 Vietnamese high school students and follow-up interviews with 15 of them. Exploratory factor analysis revealed six latent factors underlying students’ beliefs about CF, namely, (1) output-prompting CF and eliciting recasts, (2) desire for CF, (3) non-verbal cues, (4) important errors, (5) input-providing CF, and (6) less important errors. Descriptive statistics and thematic analysis of the interviews showed that students were positive about CF. They liked both input-providing CF and output-prompting CF for all error types. Metalinguistic feedback was the most strongly preferred, while clarification request was the least preferred. Further statistical analyses revealed some interesting relationships between students’ beliefs about CF and their gender, English learning motivation, and self-rated introversion/extraversion. Females were more positive about CF than males, and extraverted females were more positive about input-providing CF than introverted females. Also, students learning English for exams were more positive about CF than those learning English for communication. Pedagogical implications for effective feedback provision in EFL contexts are discussed.

Abstract Ethanol-induced transcriptional changes underlie important physiological responses to ethanol that are likely to contribute to the addictive properties of the drug. We examined the transcriptional responses of Caenorhabditis elegans across a timecourse of ethanol exposure, between 30 min and 8 h, to determine what genes and genetic pathways are regulated in response to ethanol in this model. We found that short exposures to ethanol (up to 2 h) induced expression of metabolic enzymes involved in metabolizing ethanol and retinol, while longer exposure (8 h) had much more profound effects on the transcriptome. Several genes that are known to be involved in the physiological response to ethanol, including direct ethanol targets, were regulated at 8 h of exposure. This longer exposure to ethanol also resulted in the regulation of genes involved in cilia function, which is consistent with an important role for the effects of ethanol on cilia in the deleterious effects of chronic ethanol consumption in humans. Finally, we found that food deprivation for an 8-h period induced gene expression changes that were somewhat ameliorated by the presence of ethanol, supporting previous observations that worms can use ethanol as a calorie source.

Purpose: In rural settings scare public health resources potentially limits the opportunities for nursing students living in these areas to participate in traditional one to one precepted experiences with public health agencies. To meet the revised Commission on Collegiate Nursing Education Standards related to direct clinical practice, creative strategies are needed for online degree seeking RN-BSN students who live in rural areas. This article explores an alternative learning experience by partnering students with a nonprofit healthcare institute to work on state health initiatives in the geographic region where the students reside. Process: In the absence of adequate opportunities for one to one precepted clinical experiences, student living in rural areas completing an online RN-BS program were partnered with a non-profit health organization. The students participate in an experiential learning experience to fulfill clinical hours in a public health setting as required by the Commission on Collegiate Nursing Education. In this case a cohort of students worked with a nonprofit healthcare institute on New York State’s T-21 campaign to further advance their knowledge on health initiatives driven by state health reform policy and actively participate community-based education. Conclusion: With a growing focus on population-based care and caring for vulnerable populations, particularly in rural areas, seeking clinical activities through partnerships with non-profit healthcare institute to improve health outcomes at the community level offers an alternative approach to engaging online degree seeking RN-BSN students in experiential clinical learning in communities with limited public health agency placements. Keywords: interprofessional learning, nursing accreditation, rural nursing students, service-learning pedagogy DOI: https://doi.org/10.14574/ojrnhc.v21i1.664

Abstract Background Caregiving is a demanding role that can negatively impact a person’s health and well-being. As such, adequate access to health care is important for maintaining the family caregiver’s own personal health. The aims of this study were to identify if family caregivers of older adults had more difficulty accessing health care services than non-caregivers and to identify if family caregivers felt access to additional services would be beneficial for maintaining their own personal health care. Methods National survey of 3026 US adults aged 30 to 89 years old. Participants were grouped based on self-reported caregiving experience. Survey asked about access to care, importance of health care services and whether caregivers had support needed. Descriptive statistics were used to compare caregiver and non-caregiver’s responses. Multivariate logistic regression model assessed correlates of caregivers not having the support they needed. Results Caregivers were older, female, lower educational attainment, lower income, had more multiple chronic health conditions and health condition or disability that impacts their daily life. Caregivers reported difficulty accessing mental health services, dental services, medications, and supportive services at home. Caregivers felt it was important to have care coordinator, long-term relationship with primary care provider and access to house calls, telemedicine, and medications delivered to the home. Age, ethnicity, chronic conditions and confidence in finances were factors influencing whether caregiver had support needed to provide assistance to older care recipient. Conclusion Caregivers provide needed support and care to older adults while also needing support for themselves. Health care services delivered in the home were highly desirable to caregivers and could help them maintain their health and well-being.

Abstract Mucopolysaccharidosis type IIIB (MPS IIIB; Sanfilippo syndrome B) is an autosomal recessive lysosomal storage disorder caused by the deficiency of alpha-N-acetylglucosaminidase activity, leading to increased levels of nondegraded heparan sulfate (HS). A mouse model has been useful to evaluate novel treatments for MPS IIIB, but has limitations. In this study, we evaluated the naturally occurring canine model of MPS IIIB for the onset and progression of biochemical and neuropathological changes during the preclinical stages (onset approximately 24–30 months of age) of canine MPS IIIB disease. Even by 1 month of age, MPS IIIB dogs had elevated HS levels in brain and cerebrospinal fluid. Analysis of histopathology of several disease-relevant regions of the forebrain demonstrated progressive lysosomal storage and microglial activation despite a lack of cerebrocortical atrophy in the oldest animals studied. More pronounced histopathology changes were detected in the cerebellum, where progressive lysosomal storage, astrocytosis and microglial activation were observed. Microglial activation was particularly prominent in cerebellar white matter and within the deep cerebellar nuclei, where neuron loss also occurred. The findings in this study will form the basis of future assessments of therapeutic efficacy in this large animal disease model.

Abstract Background SWI/SNF chromatin remodeling genes are required for normal acute responses to alcohol in C. elegans and are associated with alcohol use disorder in two human populations. In an effort to discover the downstream genes that are mediating this effect, we identified SWI/SNF-regulated genes in C. elegans. Results To identify SWI/SNF-regulated genes in adults, we compared mRNA expression in wild type and swsn-1(os22ts) worms under conditions that produce inactive swsn-1 in mature cells. To identify SWI/SNF-regulated genes in neurons, we compared gene expression in swsn-9(ok1354) null mutant worms that harbor a neuronal rescue or a control construct. RNA sequencing was performed to an average depth of 25 million reads per sample using 50-base, paired-end reads. We found that 6813 transcripts were significantly differentially expressed between swsn-1(os22ts) mutants and wild-type worms and 2412 transcripts were significantly differentially expressed between swsn-9(ok1354) mutants and swsn-9(ok1354) mutants with neuronal rescue. We examined the intersection between these two datasets and identified 603 genes that were differentially expressed in the same direction in both comparisons; we defined these as SWI/SNF-regulated genes in neurons and in adults. Among the differentially expressed genes was cbp-1, a C. elegans homolog of the mammalian CBP/p300 family of histone acetyltransferases. CBP has been implicated in the epigenetic regulation in response to alcohol in animal models and a polymorphism in the human CBP gene, CREBBP, has been associated with alcohol-related phenotypes. We found that cbp-1 is required for the development of acute functional tolerance to alcohol in C. elegans. Conclusions We identified 603 transcripts that were regulated by two different SWI/SNF complex subunits in adults and in neurons. The SWI/SNF-regulated genes were highly enriched for genes involved in membrane rafts, suggesting an important role for this membrane microdomain in the acute alcohol response. Among the differentially expressed genes was cbp-1; CBP-1 homologs have been implicated in alcohol responses across phyla and we found that C. elegans cbp-1 was required for the acute alcohol response in worms.

Inland marine shrimp production is increasing in popularity as recirculating aquaculture systems (RAS) can provide a fresh, high-value product year-round to nearby consumer markets. However, artificial sea salt mixtures are required for inland production, which can be a substantial portion of the production costs. The purpose of this experiment was to compare marine shrimp (L. vannamei) production and water quality dynamics in culture systems with various mixtures of a least cost salt (LCS) formulation and a commercial, complete sea salt (CSS) formulation. Previous research using this same LCS mixture found decreased shrimp production using 100% LCS compared to ratios with 25% CSS inclusion and higher. To further investigate the decreased shrimp performance in 100% LCS, this experiment used six salt different ratios of LCS and CSS between 100% LCS and 75% LCS:25% CSS. The treatments used in this study were 100% LCS, 97.5% LCS, 95% LCS, 90% LCS, 80% LCS, and 75% LCS. The results showed that use of the LCS formulation significantly lowered the cost of salt kg-1 shrimp produced. The LCS formulation cost $8.83 USD to make 1 m3 of water at 15 salinity, compared to $12.89 using the 75%/25% LCS/CSS mixture. Salt mixtures had a significant impact on DO, pH, salinity, and turbidity; however, these differences did not seem to impact shrimp performance, as no significant differences were found in shrimp average weight, biomass, survival, FCR, or growth rate. The results from this study indicate that using the LCS formulation reduces artificial sea salt cost significantly while having no significant impacts on shrimp production.

Understanding whether and how children with typical development adapt their reaches for different functional tasks could inform a more targeted design of rehabilitation interventions to improve upper extremity function in children with motor disabilities. This prospective study compares timing and coordination of a reach-to-drink, reach-to-eat, and a bilateral reaching task in typically developing school-aged children. Average speed, straightness, and smoothness of hand movements were measured in a convenience sample of 71 children, mean age 8.77 ± 0.48 years. Linear mixed models for repeated measures compared the variables by task, phases of the reach, task x phase interactions, and dominant versus non-dominant hands. There were significant main effects for task and phase, significant task x phase interactions (p < 0.05), and a significant difference between the dominant and non-dominant hand for straightness. Hand movements were fastest and smoothest for the reach-to-eat task, and least straight for the bilateral reaching task. Hand movements were also straighter in the object transport phases than the prehension and withdrawal phases. These results indicate that children with typical development change their timing and coordination of reach based on the task they are performing. These results can inform the design of rehabilitation interventions targeting arm and hand function.

Manual ability may be an important consideration when measuring cognition in children with CP because many items on cognitive tests require fine motor skills. This study investigated the association of fine motor dependent (FMD) and fine motor independent (FMI) items within the cognitive domain (COG) of the Bayley Scales of Infant Development—Third Edition (Bayley-III) and Manual Ability Classification System (MACS) in children with cerebral palsy. Children aged 2 to 8 (3.96 ± 1.68) years were included in this study. MACS levels were assigned at baseline. COG was administrated at baseline (n = 61) and nine months post-baseline (n = 28). The 91 items were classified into FMD (52) and FMI (39). Total raw score, FMD, and FMI scores were calculated. The association between MACS and cognitive scores (total, FMD, and FMI) were evaluated using linear regression and Spearman correlation coefficients. We found total, FMD, and FMI scores decrease significantly as the MACS level increases at the baseline. Both FMD and FMI scores decreased as MACS levels increased (worse function). There was a significant difference between the two slopes, with the FMD scores having a steeper slope. Similar patterns were observed nine months post-baseline. Children with lower manual ability scored lower in the cognitive domain at baseline and 9 months post-baseline. The significant difference in the performance of FMD items and FMI items across MACS levels with a steeper slope of changes in FMD items suggests fine motor skills impact cognition.

Alzheimer’s disease (AD) is the most frequent neurodegenerative disease with an increasing prevalence in industrialized, aging populations. AD susceptibility has an established genetic basis which has been the focus of a large number of genome-wide association studies (GWAS) published over the last decade. Most of these GWAS used dichotomized clinical diagnostic status, i.e., case vs. control classification, as outcome phenotypes, without the use of biomarkers. An alternative and potentially more powerful study design is afforded by using quantitative AD-related phenotypes as GWAS outcome traits, an analysis paradigm that we followed in this work. Specifically, we utilized genotype and phenotype data from n = 931 individuals collected under the auspices of the European Medical Information Framework for Alzheimer’s Disease Multimodal Biomarker Discovery (EMIF-AD MBD) study to perform a total of 19 separate GWAS analyses. As outcomes we used five magnetic resonance imaging (MRI) traits and seven cognitive performance traits. For the latter, longitudinal data from at least two timepoints were available in addition to cross-sectional assessments at baseline. Our GWAS analyses revealed several genome-wide significant associations for the neuropsychological performance measures, in particular those assayed longitudinally. Among the most noteworthy signals were associations in or near EHBP1 (EH domain binding protein 1; on chromosome 2p15) and CEP112 (centrosomal protein 112; 17q24.1) with delayed recall as well as SMOC2 (SPARC related modular calcium binding 2; 6p27) with immediate recall in a memory performance test. On the X chromosome, which is often excluded in other GWAS, we identified a genome-wide significant signal near IL1RAPL1 (interleukin 1 receptor accessory protein like 1; Xp21.3). While polygenic score (PGS) analyses showed the expected strong associations with SNPs highlighted in relevant previous GWAS on hippocampal volume and cognitive function, they did not show noteworthy associations with recent AD risk GWAS findings. In summary, our study highlights the power of using quantitative endophenotypes as outcome traits in AD-related GWAS analyses and nominates several new loci not previously implicated in cognitive decline.

This study evaluates the ability of a random forest classifier to identify tropical cyclone (TC) intensification or weakening prior to landfall over the western region of the Southwest Pacific Ocean (SWPO) basin. For both Australia mainland and SWPO island cases, when a TC first crosses land after spending ≥24 h over the ocean, the closest hour prior to the intersection is considered as the landfall hour. If the maximum wind speed (Vmax) at the landfall hour increased or remained the same from the 24-h mark prior to landfall, the TC is labeled as intensifying and if the Vmax at the landfall hour decreases, the TC is labeled as weakening. Geophysical and aerosol variables closest to the 24 h before landfall hour were collected for each sample. The random forest model with leave-one-out cross validation and the random oversampling example technique was identified as the best-performing classifier for both mainland and island cases. The model identified longitude, initial intensity, and sea skin temperature as the most important variables for the mainland and island landfall classification decisions. Incorrectly classified cases from the test data were analyzed by sorting the cases by their initial intensity hour, landfall hour, monthly distribution, and 24-h intensity changes. TC intensity changes near land strongly impact coastal preparations such as wind damage and flood damage mitigations; hence, this study will contribute to improve identifying and prioritizing prediction of important variables contributing to TC intensity change before landfall.

The COVID-19 outbreak has caused panic around the world as it is highly infectious and has caused about 5 million deaths globally. A robust wireless non-contact vital signs (NCVS) sensor system that can continuously monitor the respiration rate (RR) and heart rate (HR) of patients clinically and remotely with high accuracy can be very attractive to healthcare workers (HCWs), as such a system can not only avoid HCWs’ close contact with people with COVID-19 to reduce the infection rate, but also be used on patients quarantined at home for telemedicine and wireless acute-care. Therefore, we developed a custom Doppler-based NCVS radar sensor system operating at 2.4 GHz using a software-defined radio (SDR) technology, and the novel biosensor system has achieved impressive real-time RR/HR monitoring accuracies within approximately 0.5/3 breath/beat per minute (BPM) on student volunteers tested in our engineering labs. To further test the sensor system’s feasibility for clinical use, we applied and obtained an Internal Review Board (IRB) approval from Texas Tech University Health Sciences Center (TTUHSC) and have used this NCVS monitoring system in a doctor’s clinic at TTUHSC; following testing on 20 actual patients for a small-scale clinical trial, we have found that the system was still able to achieve good NCVS monitoring accuracies within ~0.5/10 BPM across 20 patients of various weight, height and age. These results suggest our custom-designed NCVS monitoring system may be feasible for future clinical use to help combatting COVID-19 and other infectious diseases.

The circadian clock affects immune responses, but its role in influenza infection is not well understood. Here, Sengupta et al. show that time of infection and the circadian clock have no effect on lung virus titers, but affect inflammation, morbidity and mortality.

Abstract Background Clinical trials management can be studied using project management theory. The CYCLE pilot randomized controlled trial (RCT) was conducted to determine the feasibility of a future rehabilitation trial of early in-bed cycling in the intensive care unit (ICU). In-bed cycling is a novel intervention, not typically available in ICUs. Implementation of this intervention requires personnel with specialized clinical expertise caring for critically ill patients and use of the in-bed cycle. Our objective was to describe the implementation and conduct of our pilot RCT using a project management approach. Methods We retrospectively reviewed activities, timelines, and personnel involved in the trial. We organized activities into four project management phases: initiation, planning, execution, and monitoring and controlling. Data sources included Methods Centre documents used for trial coordination and conduct, and the trial data set. We report descriptive statistics as counts and proportions and also medians and quartiles, and we summarize the lessons learned. Results Seven ICUs in Canada participated in the trial. Time from research ethics board and contracts submission to first enrolment was a median (first quartile, third quartile) of 185 (146, 209) and 162 (114, 181) days, respectively. We trained 128 personnel on the CYCLE pilot RCT protocol, and 80 (63%) completed trial-related activities. Four sites required additional training after start-up due to staff turnover and leaves of absence. Over 15 months, we screened 864 patients: 256 were eligible and 66 were enrolled. Despite an 85% consent rate, 74% (190/256) of eligible patients were not randomized, largely (80% [152/190]) due to physiotherapist availability. Thirteen percent of recruitment weeks were lost due to physiotherapist staffing shortages. We highlight five key lessons learned: (1) prepare and anticipate site needs; (2) communicate regularly; (3) proactively analyse and act on process measure data; (4) develop contingency plans; (5) express appreciation to participating sites. Conclusions Our analysis highlights the scope of relevant activities, rigorous training and monitoring, number and types of required personnel, and time required to conduct a multicentre ICU rehabilitation intervention trial. Our lessons learned can help others interested in implementing complex intervention trials, such as rehabilitation. Trial registration ClinicalTrials.gov, NCT02377830. Registered prospectively on 4 March 2015.

Abstract Background The two Caenorhabditis elegans somatic gonadal precursors (SGPs) are multipotent progenitors that generate all somatic tissues of the adult reproductive system. The sister cells of the SGPs are two head mesodermal cells (hmcs); one hmc dies by programmed cell death and the other terminally differentiates. Thus, a single cell division gives rise to one multipotent progenitor and one differentiated cell with identical lineage histories. We compared the transcriptomes of SGPs and hmcs in order to learn the determinants of multipotency and differentiation in this lineage. Results We generated a strain that expressed fluorescent markers specifically in SGPs (ehn-3A::tdTomato) and hmcs (bgal-1::GFP). We dissociated cells from animals after the SGP/hmc cell division, but before the SGPs had further divided, and subjected the dissociated cells to fluorescence-activated cell sorting to collect isolated SGPs and hmcs. We analyzed the transcriptomes of these cells and found that 5912 transcripts were significantly differentially expressed, with at least two-fold change in expression, between the two cell types. The hmc-biased genes were enriched with those that are characteristic of neurons. The SGP-biased genes were enriched with those indicative of cell proliferation and development. We assessed the validity of our differentially expressed genes by examining existing reporters for five of the 10 genes with the most significantly biased expression in SGPs and found that two showed expression in SGPs. For one reporter that did not show expression in SGPs, we generated a GFP knock-in using CRISPR/Cas9. This reporter, in the native genomic context, was expressed in SGPs. Conclusions We found that the transcriptional profiles of SGPs and hmcs are strikingly different. The hmc-biased genes are enriched with those that encode synaptic transmission machinery, which strongly suggests that it has neuron-like signaling properties. In contrast, the SGP-biased genes are enriched with genes that encode factors involved in transcription and translation, as would be expected from a cell preparing to undergo proliferative divisions. Mediators of multipotency are likely to be among the genes differentially expressed in SGPs.

Abstract Background Understanding the evolution of novel features requires homology assessments at different levels of biological organization. In flowering plants, floral coronas that play various roles in plant–pollinator interactions have evolved multiple times independently, but are highly variable in their final position and overall morphology. Coronas of the Solanaceae species Jaltomata calliantha are found between the corolla and stamens, adjacent to the gynoecium, and form cups that house copious amounts of their characteristic blood red nectar. To test the hypothesis that J. calliantha coronas evolved as an outgrowth of stamens and therefore have staminal identity, we assessed their development, floral organ identity gene expression, and cellular morphology. Results Jaltomata calliantha coronas emerge after the initiation of all conventional floral organs on the abaxial side of the proximally modified stamens and then expand medially and laterally to form nectar cups. Overlapping expression of the B-class organ identity genes JcAPETALA3 and both JcPISTILLATA/GLOBOSA orthologs (JcGLO1 and JcGLO2), and the C-class-like gene JcAGAMOUS1-like, unites the stamens and corona. Epidermal cell shape also connects the adaxial surface of coronas and petals, and the stamen base, with remaining floral organs showing divergent cell types. Conclusions Our data, based on multiple lines of evidence, support a largely staminal origin for J. calliantha coronas. However, since slightly enlarged stamen bases are found in Jaltomata species that lack coronas, and J. calliantha stamen bases share cell types with petals, we hypothesize that stamen bases recruited part of the petal identity program prior to fully expanding into a corona.

Background Cardiac rehabilitation (CR) is a structured exercise program prevalent in the United States for people with cardiovascular disease that has been shown to increase cardiovascular endurance and improve quality of life. Despite similar cardiovascular risk factors, stroke is not among the covered diagnoses for CR. The purpose of this study was to examine the participant impact of integrating survivors of stroke into the exercise portion of an existing hospital‐based CR program through measures of physical function and other health impacts and through qualitative evaluation of participant perception. Methods and Results Subacute and chronic survivors of stroke were integrated into a standard 12‐week, 3 sessions per week, exercise‐based CR program. A total of 29 began the program, 24 completed the program, and 18 were available for 6‐month follow‐up. Quantitative measures were compared preprogram with postprogram with t‐test or equivalent, and preprogram with postprogram to 6‐month follow‐up with ANOVA or equivalent. Semistructured interviews were completed with 11 participants postprogram. Exercise‐based CR had significant impacts on cardiovascular endurance preprogram to postprogram, with maintenance at 6‐month follow‐up. The participants improved on the 6‐minute walk test on average by 61.92 m(95% CI, 33.99–89.84 m), and maximum metabolic equivalents improved by a median of 3.6 (interquartile range, 2.35). Five times sit to stand (functional strength) improved preprogram to postprogram by a median of 2.85 s (interquartile range, 4.03 s). Qualitative findings highlight additional health improvements. Most participants (83% [15/18]) reported continued exercise at follow‐up. Conclusions Exercise‐based CR has the potential to improve cardiovascular endurance, health status, and quality of life for survivors of stroke. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT03706105.

Background. Structural integrity of the ipsilesional corticospinal tract (CST) is important for upper limb motor recovery after stroke. However, additional neuromechanisms associated with motor function poststroke are less well understood, especially regarding the lower limb. Objective. To investigate the neural basis of upper/lower limb motor deficits poststroke by correlating measures of motor function with diffusion tensor imaging-derived indices of white matter integrity (fractional anisotropy (FA), mean diffusivity (MD)) in primary and secondary motor tracts/structures. Methods. Forty-three individuals with chronic stroke (time poststroke, 64.4±58.8 months) underwent a comprehensive motor assessment and MRI scanning. Correlation and multiple regression analyses were performed to examine relationships between FA/MD in a priori motor tracts/structures and motor function. Results. FA in the ipsilesional CST and red nucleus (RN) was positively correlated with motor function of both the affected upper and lower limb (r=0.36‐0.55, p≤0.01), while only ipsilesional RN FA was associated with gait speed (r=0.50). Ipsilesional CST FA explained 37.3% of the variance in grip strength (p

The use of telescopic intramedullary rods for the treatment of lower extremity deformity in children with osteogenesis imperfecta has been well described. The reinforcement of these weakened weightbearing bones with intramedullary devices leads to improvements in mobility that progress into adulthood. Although the current telescopic intramedullary rod systems are an upgrade from earlier systems, they are still associated with high rates of reoperation and complication. We describe a unique complication encountered during a revision which involved the male retriever system for the Fassier–Duval rod (FDR) (Pega Medical, Quebec, CA) experienced intraoperatively. To our knowledge, this mechanism of failure has not been previously described in the literature.

Dynamic Functional Connectivity (dFC) in the resting state (rs) is considered as a correlate of cognitive processing. Describing dFC as a flow across morphing connectivity configurations, our notion of dFC speed quantifies the rate at which FC networks evolve in time. Here we probe the hypothesis that variations of rs dFC speed and cognitive performance are selectively interrelated within specific functional subnetworks.In particular, we focus on Sleep Deprivation (SD) as a reversible model of cognitive dysfunction. We found that whole-brain level (global) dFC speed significantly slows down after 24h of SD. However, the reduction in global dFC speed does not correlate with variations of cognitive performance in individual tasks, which are subtle and highly heterogeneous. On the contrary, we found strong correlations between performance variations in individual tasks –including Rapid Visual Processing (RVP, assessing sustained visual attention)– and dFC speed quantified at the level of functional sub-networks of interest. Providing a compromise between classic static FC (no time) and global dFC (no space), modular dFC speed analyses allow quantifying a different speed of dFC reconfiguration independently for sub-networks overseeing different tasks. Importantly, we found that RVP performance robustly correlates with the modular dFC speed of a characteristic frontoparietal module.

Background: The amygdala and the hippocampus are two limbic structures that play a critical role in cognition and behavior, however their manual segmentation and that of their smaller nuclei/subfields in multicenter datasets is time consuming and difficult due to the low contrast of standard MRI. Here, we assessed the reliability of the automated segmentation of amygdalar nuclei and hippocampal subfields across sites and vendors using FreeSurfer in two independent cohorts of older and younger healthy adults. Methods: Sixty-five healthy older (cohort 1) and 68 younger subjects (cohort 2), from the PharmaCog and CoRR consortia, underwent repeated 3D-T1 MRI (interval 1–90 days). Segmentation was performed using FreeSurfer v6.0. Reliability was assessed using volume reproducibility error (ε) and spatial overlapping coefficient (DICE) between test and retest session. Results: Significant MRI site and vendor effects (p ​0.43, p ​ ​0.80). Conclusion: Our results support the use of volumetric measures of larger amygdalar nuclei and hippocampal subfields in multisite MRI studies. These measures could be useful for disease tracking and assessment of efficacy in drug trials.