Search

Aim: Ecological state shifts that alter the structure and function of entire ecosystems are a concerning consequence of human impact. Yet, when, where and why discrete ecological states emerge remains difficult to predict and monitor, especially in high‐diversity systems. We sought to quantify state shifts and their drivers through space and time in the most ecologically complex marine ecosystem: tropical coral reefs. Location: Worldwide. Time Period: 1987–2019. Major Taxa Studied: Coral reef communities. Methods: Using a global dataset of 3375 coral reef surveys, along with 13 time series datasets ranging between 1987 and 2019, we applied a novel double‐dichotomy approach to classify coral reefs into four simplified and discrete states based on the relative contributions of corals versus algae to benthic cover and small‐bodied versus large‐bodied fishes to fish standing stock. We then examined state shifts considering a range of spatial predictors and tested whether states have shifted directionally over time, and the nature of the most common transitions. Results: We show that geographic, environmental and anthropogenic context fundamentally shapes coral reef states at the local scale, which explains disparities among case studies, and stakes out critical baseline expectations for regional management efforts. We also reveal clear multi‐decadal state shifts on coral reefs: over time, systems dominated by reef‐building corals and small‐bodied, planktivorous fishes tend to have been replaced with reefs characterised by algae and larger‐bodied fishes. Main Conclusions: Our results suggest a previously unrecognised transition from systems that harness external subsidies through small‐bodied consumers associated with structurally complex live corals, to herbivore‐dominated systems with stronger bottom‐up dynamics. Overall, the partitioning of complex reef ecosystems into a small suite of discrete ecological states suggests that spatial context‐dependency, shifting baselines and changes in reef functioning are crucial considerations for coral reef management in the 21st century. [ABSTRACT FROM AUTHOR]

Carboxylesterases comprise a major class of α/β‐fold hydrolases responsible for the cleavage and formation of ester bonds. Found ubiquitously in nature, these enzymes are crucial for the metabolism of both endogenous and exogenous carboxyl esters in animals, plants and microorganisms. Beyond their essential physiological roles, carboxylesterases stand out as one of the important classes of biocatalysts for biotechnology. BlEst2, an enzyme previously classified as Bacillus licheniformis esterase, remains largely uncharacterized. In the present study, we elucidate the structural biology, molecular dynamics and biochemical features of BlEst2. Our findings reveal a canonical α/β‐hydrolase fold similar to the ESTHER block L of lipases, further augmented by two additional accessory C‐terminal domains. Notably, the catalytic domain demonstrates two insertions, which occupy conserved locations in α/β‐hydrolase proteins and commonly form the lid domain in lipase structures. Intriguingly, our in vitro cleavage of C‐terminal domains revealed the structure of the active form of BlEst2. Upon activation, BlEst2 showed a markedly elevated hydrolytic activity. This observation implies that the intramolecular C‐terminal domain serves as a regulatory intramolecular inhibitor. Interestingly, despite exhibiting esterase‐like activity, BlEst2 structural characteristics align more closely with lipases. This suggests that BlEst2 could potentially represent a previously unrecognized subgroup within the realm of carboxyl ester hydrolases. [ABSTRACT FROM AUTHOR]

Background: Vaccinating pediatric solid organ transplant candidates against measles and varicella is crucial due to the risk of severe disease in immunosuppressed recipients and general avoidance of live virus vaccines post‐transplantation. The world saw a resurgence of measles starting 2012 prompting the American Society of Transplantation in 2015 to release guidelines on recognition, prevention, and post‐exposure prophylaxis of this disease in solid transplant recipients. This study aims to assess the extent of incomplete immunity to these viruses in candidates and the approach to immunity optimization during a period of heightened awareness. Methods: A cross‐sectional study from 2012 to 2016 at Cleveland Clinic Children's included pediatric solid organ transplant candidates. Data on vaccination history, serology, and demographics were collected. Incomplete immunity was defined by incomplete vaccination or seronegativity. Results: Among 91 candidates, 54.9% had complete varicella vaccination. Serological varicella immunity among patients tested varied by age: < 7 years, 50.0% positive in patients with complete schedules, none in the incomplete; ≥ 7 years, 50.0% positive in patients with complete schedules, 65.5% in the incomplete. For measles, 69.2% had complete vaccination, with immunity varying by age among those tested: < 7 years, 84.6% positive in patients with complete schedules, 42.9% in the incomplete; ≥ 7 years, 81.0% with complete, 62.5% with incomplete. Only 31.1% of those who qualified for a varicella additional dose and 28% who qualified for an additional measles dose received it, respectively. Conclusions: Incomplete immunity to varicella and measles was prevalent in pediatric solid organ transplant candidates at our center during the study period. Despite an increase in global measles activity, our efforts to optimize immunity through additional vaccine doses were only partially successful. Future research should focus on addressing strategies and understanding barriers to ensure timely vaccination for this vulnerable population prior to transplant, especially during periods of increased viral activity. [ABSTRACT FROM AUTHOR]

Background: Despite the overall safety and efficacy of COVID‐19 vaccinations, rare cases of systemic autoimmune diseases (SAIDs) have been reported post‐vaccination. This study used a global survey to analyze SAIDs in susceptible individuals' post‐vaccination. Methods: A cross‐sectional study was conducted among participants with self‐reported new‐onset SAIDs using the COVID‐19 Vaccination in Autoimmune Diseases (COVAD) 2 study dataset—a validated, patient‐reported e‐survey—to analyze the long‐term safety of COVID‐19 vaccines. Baseline characteristics of patients with new‐onset SAIDs and vaccinated healthy controls (HCs) were compared after propensity score matching based on age and sex in a 1:4 ratio. Results: Of 16 750 individuals, 74 (median age 52 years, 79.9% females, and 76.7% Caucasians) had new‐onset SAID post‐vaccination, mainly idiopathic inflammatory myopathies (IIMs) (n = 23, 31.51%), arthritis (n = 15; 20.53%), and polymyalgia rheumatica (PMR) (n = 12, 16.40%). Higher odds of new‐onset SAIDs were noted among Caucasians (OR = 5.3; 95% CI = 2.9–9.7; p <.001) and Moderna vaccine recipients (OR = 2.7; 95% CI = 1.3–5.3; p =.004). New‐onset SAIDs were associated with AID multimorbidity (OR = 1.4; 95% CI = 1.1–1.7; p <.001), mental health disorders (OR = 1.6; 95% CI = 1.3–1.9; p <.001), and mixed race (OR = 2.2; 95% CI = 1.2–4.2; p =.010), where those aged >60 years (OR = 0.6; 95% CI = 0.4–0.8; p =.007) and from high/medium human development index (HDI) countries (compared to very high HDI) reported fewer events than HCs. Conclusion: This study reports a low occurrence of new‐onset SAIDs following COVID‐19 vaccination, primarily IIMs, PMR, and inflammatory arthritis. Identified risk factors included pre‐existing AID multimorbidity, mental health diseases, and mixed race. Revaccination was well tolerated by most patients; therefore, we recommend continuing COVID‐19 vaccination in the general population. However, long‐term studies are needed to understand the autoimmune phenomena arising post‐vaccination. [ABSTRACT FROM AUTHOR]

Background: Hepatocellular carcinoma (HCC) is a significant cause of oncologic mortality worldwide. Liver transplantation represents a curative option for patients with significant liver dysfunction and absence of metastases. However, this therapeutic option is associated with significant blood loss and frequently requires various transfusions and intraoperative blood salvage for autotransfusion (IBS‐AT) with or without a leukocyte reduction filter. This study aimed to analyze available evidence on long‐term oncologic outcomes of patients undergoing liver transplantation for HCC with and without IBS‐AT. Methods: Per PRISMA guidelines, a systematic review of keywords "Blood Salvage," "Auto‐transfusion," "Hepatocellular carcinoma," and "Liver‐transplant" was conducted in PubMed, EMBASE, and SCOPUS. Studies comparing operative and postoperative outcomes were screened and analyzed for review. Results: Twelve studies totaling 1704 participants were included for analysis. Length of stay, recurrence rates, and overall survival were not different between IBS‐AT group and non IBS‐AT group. Conclusion: IBS‐AT use is not associated with increased risk of recurrence in liver transplant for HCC even without leukocyte filtration. Both operative and postoperative outcomes are similar between groups. Comparison of analyzed studies suggest that IBS‐AT is safe for use during liver transplant for HCC. [ABSTRACT FROM AUTHOR]

The medial prefrontal cortex (mPFC) drives cocaine‐seeking behaviour in rodent models of cocaine use disorder. Parvalbumin (PV)‐containing GABAergic interneurons powerfully control the output of the mPFC, yet few studies have focused on how these neurons modulate cocaine‐seeking behaviour. Most PV neurons are surrounded by perineuronal nets (PNNs), which regulate the firing of PV neurons. We examined staining intensity and number of PV and PNNs after long‐access (6 h/day) cocaine self‐administration in rats followed by either 8–10 days extinction ± cue‐induced reinstatement or short‐term (1–2 days) or long‐term (30–31 days) abstinence ± cue‐induced reinstatement. The intensity of PNNs was increased in the prelimbic and infralimbic PFC after long‐term abstinence in the absence of cue reinstatement and after cue reinstatement following both daily extinction sessions and after a 30‐day abstinence period. PV intensity was increased after 30 days of abstinence in the prelimbic but not infralimbic PFC. Enzymatic removal of PNNs with chondroitinase ABC (ABC) in the prelimbic PFC did not prevent incubation of cue‐induced reinstatement but decreased cocaine‐seeking behaviour at both 2 and 31 days of abstinence, and this decrease at 31 days was accompanied by reduced c‐Fos levels in the prelimbic PFC. Increases in PNN intensity have generally been associated with the loss of plasticity, suggesting that the persistent and chronic nature of cocaine use disorder may in part be attributed to long‐lasting increases in PNN intensity that reduce the ability of stimuli to alter synaptic input to underlying PV neurons. [ABSTRACT FROM AUTHOR]

Chinese hamster ovary (CHO) cells, predominant hosts for recombinant biotherapeutics production, generate lactate as a major glycolysis by‐product. High lactate levels adversely impact cell growth and productivity. The goal of this study was to reduce lactate in CHO cell cultures by adding chemical inhibitors to hexokinase‐2 (HK2), the enzyme catalyzing the conversion of glucose to glucose 6‐phosphate, and examine their impact on lactate accumulation, cell growth, protein titers, and N‐glycosylation. Five inhibitors of HK2 enzyme at different concentrations were evaluated, of which 2‐deoxy‐ d‐glucose (2DG) and 5‐thio‐ d‐glucose (5TG) successfully reduced lactate accumulation with only limited impacts on CHO cell growth. Individual 2DG and 5TG supplementation led to a 35%–45% decrease in peak lactate, while their combined supplementation resulted in a 60% decrease in peak lactate. Inhibitor supplementation led to at least 50% decrease in moles of lactate produced per mol of glucose consumed. Recombinant EPO‐Fc titers peaked earlier relative to the end of culture duration in supplemented cultures leading to at least 11% and as high as 32% increase in final EPO‐Fc titers. Asparagine, pyruvate, and serine consumption rates also increased in the exponential growth phase in 2DG and 5TG treated cultures, thus, rewiring central carbon metabolism due to low glycolytic fluxes. N‐glycan analysis of EPO‐Fc revealed an increase in high mannose glycans from 5% in control cultures to 25% and 37% in 2DG and 5TG‐supplemented cultures, respectively. Inhibitor supplementation also led to a decrease in bi‐, tri‐, and tetra‐antennary structures and up to 50% lower EPO‐Fc sialylation. Interestingly, addition of 2DG led to the incorporation of 2‐deoxy‐hexose (2DH) on EPO‐Fc N‐glycans and addition of 5TG resulted in the first‐ever observed N‐glycan incorporation of 5‐thio‐hexose (5TH). Six percent to 23% of N‐glycans included 5TH moieties, most likely 5‐thio‐mannose and/or 5‐thio‐galactose and/or possibly 5‐thio‐N‐acetylglucosamine, and 14%–33% of N‐glycans included 2DH moieties, most likely 2‐deoxy‐mannose and/or 2‐deoxy‐galactose, for cultures treated with different concentrations of 5TG and 2DG, respectively. Our study is the first to evaluate the impact of these glucose analogs on CHO cell growth, protein production, cell metabolism, N‐glycosylation processing, and formation of alternative glycoforms. [ABSTRACT FROM AUTHOR]

Background: Excess body fatness and hyperinsulinemia are both associated with an increased risk of postmenopausal breast cancer. However, whether women with high body fatness but normal insulin levels or those with normal body fatness and high levels of insulin are at elevated risk of breast cancer is not known. We investigated the associations of metabolically defined body size and shape phenotypes with the risk of postmenopausal breast cancer in a nested case–control study within the European Prospective Investigation into Cancer and Nutrition. Methods: Concentrations of C‐peptide—a marker for insulin secretion—were measured at inclusion prior to cancer diagnosis in serum from 610 incident postmenopausal breast cancer cases and 1130 matched controls. C‐peptide concentrations among the control participants were used to define metabolically healthy (MH; in first tertile) and metabolically unhealthy (MU; >1st tertile) status. We created four metabolic health/body size phenotype categories by combining the metabolic health definitions with normal weight (NW; BMI < 25 kg/m2, or WC < 80 cm, or WHR < 0.8) and overweight or obese (OW/OB; BMI ≥ 25 kg/m2, or WC ≥ 80 cm, or WHR ≥ 0.8) status for each of the three anthropometric measures separately: (1) MHNW, (2) MHOW/OB, (3) MUNW, and (4) MUOW/OB. Conditional logistic regression was used to compute odds ratios (ORs) and 95% confidence intervals (CIs). Results: Women classified as MUOW/OB were at higher risk of postmenopausal breast cancer compared to MHNW women considering BMI (OR = 1.58, 95% CI = 1.14–2.19) and WC (OR = 1.51, 95% CI = 1.09–2.08) cut points and there was also a suggestive increased risk for the WHR (OR = 1.29, 95% CI = 0.94–1.77) definition. Conversely, women with the MHOW/OB and MUNW were not at statistically significant elevated risk of postmenopausal breast cancer risk compared to MHNW women. Conclusion: These findings suggest that being overweight or obese and metabolically unhealthy raises risk of postmenopausal breast cancer while overweight or obese women with normal insulin levels are not at higher risk. Additional research should consider the combined utility of anthropometric measures with metabolic parameters in predicting breast cancer risk. [ABSTRACT FROM AUTHOR]

Background: Carotid body tumor (CBT) is a rare neoplasm that has been increasingly studied during the last decades; nevertheless, it continues to be a topic of controversy. This review aims to provide an update on the general features of CBT and particularly review different treatment strategies and primary outcomes. Methods: Data for this literature review were identified by PubMed, Scopus, and Medline. 93 articles from the initial search were included, as well as 28 relevant studies utilizing the snowballing method; totaling 121 articles about CBT. Results: Main features such as anatomy, embryology, genetics, clinical presentation, and diagnosis of CBT are presented, followed by evidence of different treatment strategies such as radiotherapy, preoperative embolization, vascular resection, and vascular reconstruction. Main complications are also discussed. Conclusion: This review summarizes the most critical aspects regarding CBT. Future studies should compare different treatments to attain the best surgical results with lower morbidity rates. [ABSTRACT FROM AUTHOR]

Brain imaging is essential to the clinical care of patients with stroke, a leading cause of disability and death worldwide. Whereas advanced neuroimaging techniques offer opportunities for aiding acute stroke management, several factors, including time delays, inter‐clinician variability, and lack of systemic conglomeration of clinical information, hinder their maximal utility. Recent advances in deep machine learning (DL) offer new strategies for harnessing computational medical image analysis to inform decision making in acute stroke. We examine the current state of the field for DL models in stroke triage. First, we provide a brief, clinical practice‐focused primer on DL. Next, we examine real‐world examples of DL applications in pixel‐wise labeling, volumetric lesion segmentation, stroke detection, and prediction of tissue fate postintervention. We evaluate recent deployments of deep neural networks and their ability to automatically select relevant clinical features for acute decision making, reduce inter‐rater variability, and boost reliability in rapid neuroimaging assessments, and integrate neuroimaging with electronic medical record (EMR) data in order to support clinicians in routine and triage stroke management. Ultimately, we aim to provide a framework for critically evaluating existing automated approaches, thus equipping clinicians with the ability to understand and potentially apply DL approaches in order to address challenges in clinical practice. ANN NEUROL 2022;92:574–587 [ABSTRACT FROM AUTHOR]

TESTICULAR LARGE B-CELL LYMPHOMA IS GENETICALLY SIMILAR TO PRIMARY CENTRAL NERVOUS SYSTEM LYMPHOMA AND DISTINCT FROM NODAL DIFFUSE LARGE B-CELL LYMPHOMA B Introduction: b Testicular large B-cell lymphoma (TLBCL) is an infrequent and aggressive lymphoma presenting in an immune-privileged site, recently recognized as a distinct entity from diffuse large B-cell lymphoma (DLBCL). Compared with nodal DLBCL, localized and disseminated TLBCL have less CNA complexity ( I P i = 0.01 and I P i < 0.04, respectively) but showed a higher number of variants ( I P i = 0.01 and I P i < 0.001, respectively). [Extracted from the article]

Objective: Do veterans of the U.S. armed forces, a population with unique knowledge of and experience with guns, have distinctive views of gun control policies? While veterans are commonly assumed to be conservatives and Republicans, an emerging body of work has begun to explore the complexities of their policy opinions, partisanship, and voting behaviors. Such work provides needed nuance about this symbolically and politically important group. Methods: Using the Guns in American Life Survey (2018, n = 3103), we test whether veterans (with combat and noncombat experiences), family members of veterans, and nonveterans have different perspectives, even after taking into account factors such as gun ownership and partisanship. Results: The findings indicate that veterans (and particularly combat veterans) are more supportive than nonveterans of expanding civilians' gun carrying rights. On the other hand, veterans with and without combat experience are more likely to favor banning AR15 and military‐style rifles and high‐capacity ammunition clips. Veterans are also more likely to favor a 14‐day waiting period for all gun purchases, but they do not have unique positions on mental health screening for gun purchases. Conclusion: Taken together, these findings appear to reflect a veteran population that is positively disposed toward guns in general but also understands the destructive power of military‐style weapons. [ABSTRACT FROM AUTHOR]

Background: Intravenous ketorolac is commonly used for treating migraine headaches in children. However, the prerequisite placement of an intravenous line can be technically challenging, time‐consuming, and associated with pain and distress. Intranasal ketorolac may be an effective alternative that is needle‐free and easier to administer. We aimed to determine whether intranasal ketorolac is non‐inferior to intravenous ketorolac for reducing pain in children with migraine headaches. Methods: We conducted a randomized double‐blind non‐inferiority clinical trial. Children aged 8–17 years with migraine headaches, moderate to severe pain, and requiring parenteral analgesics received intranasal ketorolac (1 mg/kg) or intravenous ketorolac (0.5 mg/kg). Primary outcome was reduction in pain at 60 min after administration measured using the Faces Pain Scale‐Revised (scored 0–10). Non‐inferiority margin was 2/10. Secondary outcomes included time to onset of clinically meaningful decrease in pain; ancillary emergency department outcomes (e.g. receipt of rescue medications, headache relief, headache freedom, percentage improvement); 24‐h follow‐up outcomes; functional disability; and adverse events. Results: Fifty‐nine children were enrolled. We analyzed 27 children who received intranasal ketorolac and 29 who received intravenous ketorolac. The difference in mean pain reduction at 60 min between groups was 0.2 (95% CI −0.9, 1.3), with the upper limit of the 95% CI being less than the non‐inferiority margin. There were no statistical differences between groups for secondary outcomes. Conclusions: Intranasal ketorolac was non‐inferior to intravenous ketorolac for reducing migraine headache pain in the emergency department. [ABSTRACT FROM AUTHOR]

Aims: The aims of the Asthma Academy study were to (1) evaluate the telehealth performance of DNP students, (2) evaluate the perceived learning experience of DNP students and (3) investigate whether an association exists related to student performance and family caregiver outcomes. Design: A descriptive study was conducted with doctor of nursing practice students. Methods: Students conducted telehealth visits to help family caregivers of children with asthma and were rated on their performance by two faculty members using a rubric. Student perception data were gathered via survey. Results: Out of a total possible score of 15 points, the mean telehealth performance score of students was 13.38 points. Students indicated the telehealth experience was valuable and that they were satisfied with their learning. This model of leveraging telehealth to bridge nursing students to the community may be adapted to help family caregivers of children with various disease foci. [ABSTRACT FROM AUTHOR]

The goal of continual learning (CL) is to learn a sequence of tasks without suffering from the phenomenon of catastrophic forgetting. Previous work has shown that leveraging memory in the form of a replay buffer can reduce performance degradation on prior tasks. We hypothesize that forgetting can be further reduced when the model is encouraged to remember the evidence for previously made decisions. As a first step towards exploring this hypothesis, we propose a simple novel training paradigm, called Remembering for the Right Reasons (RRR), that additionally stores visual model explanations for each example in the buffer and ensures the model has "the right reasons" for its predictions by encouraging its explanations to remain consistent with those used to make decisions at training time. Without this constraint, there is a drift in explanations and increase in forgetting as conventional continual learning algorithms learn new tasks. We demonstrate how RRR can be easily added to any memory or regularization-based approach and results in reduced forgetting, and more importantly, improved model explanations. We have evaluated our approach in the standard and fewshot settings and observed a consistent improvement across various CL approaches using different architectures and techniques to generate model explanations and demonstrated our approach showing a promising connection between explainability and continual learning. Our code is available at https://github.com/SaynaEbrahimi/Remembering-for-the-Right-Reasons. [ABSTRACT FROM AUTHOR]

Objective: Although the Centers for Disease Control and Prevention eventually recommended wearing masks in public to slow the spread of the coronavirus, the practice has been unevenly distributed in the United States. Methods: In this article, we model county‐level infrequent mask usage as a function of three pillars of conservatism: (1) Republican political leadership (percentage of votes for Donald Trump in the 2016 presidential election), (2) conservative Protestantism (percentage evangelical Christian), and (3) right‐wing media consumption (Google searches for Fox News). Results: Our analyses indicate that mask usage tends to be lower in counties with greater support for President Trump (in majority Trump counties), counties with more evangelical Christians, and areas with greater interest in Fox News. Conclusion: Given the effectiveness of masks in limiting the transmission of respiratory droplets, conservative ideological resistance to public health and recommended pandemic lifestyles may indirectly support the spread of the coronavirus. [ABSTRACT FROM AUTHOR]

Increase in the proportion of CAR T cells expressing PD-1 post-infusion, as we observed in our transient re-expander, warrants further exploration as a biomarker that could predict response to anti-PD1 therapy after CAR T cells. CAR-negative T cells also became activated (73% HLA-DR SP + sp , up from 20% at the day 28 time-point), suggesting non-specific T-cell activation by the Pembro/Elo/Pom/Dex combination. Nonetheless, this proof-of-principle observation that CAR T-cell activity can be modulated in patients with myeloma post-infusion supports further exploration of immune-modulating therapies such as checkpoint inhibitors in combination with CAR T cells. Keywords: myeloma therapy; cellular therapies; immunotherapy; T cells EN myeloma therapy cellular therapies immunotherapy T cells 851 855 5 05/17/21 20210515 NES 210515 Autologous T cells expressing a chimeric antigen receptor (CAR) specific for B-cell maturation antigen (BCMA) have demonstrated high response rates in refractory myeloma,1-3 but relapses remain common. [Extracted from the article]

Substance use disorder is a complex disease created in part by maladaptive learning and memory mechanisms following repeated drug use. Exposure to drug-associated stimuli engages prefrontal cortex circuits, and dysfunction of the medial prefrontal cortex (mPFC) is thought to underlie drug-seeking behaviors. Growing evidence supports a role for parvalbumin containing fast-spiking interneurons (FSI) in modulating prefrontal cortical microcircuit activity by influencing the balance of excitation and inhibition, which can influence learning and memory processes. Most parvalbumin FSIs within layer V of the prelimbic mPFC are surrounded by specialized extracellular matrix structures called perineuronal nets (PNN). Previous work by our group found that cocaine exposure altered PNN-surrounded FSI function, and pharmacological removal of PNNs reduced cocaine-seeking behavior. However, the role of FSIs and associated constituents (parvalbumin and PNNs) in cocaine-related memories was not previously explored and is still unknown. Here, we found that reactivation of a cocaine conditioned place preference memory produced changes in cortical PNN-surrounded parvalbumin FSIs, including decreased parvalbumin intensity, increased parvalbumin cell axis diameter, decreased intrinsic excitability, and increased excitatory synaptic input. Further investigation of intrinsic properties revealed changes in the interspike interval, membrane capacitance, and afterhyperpolarization recovery time. Changes in these specific properties suggest an increase in potassium-mediated currents, which was validated with additional electrophysiological analysis. Collectively, our results indicate that cocaine memory reactivation induces functional adaptations in PNN-surrounded parvalbumin neurons, which likely alters cortical output to promote cocaine-seeking behavior. [ABSTRACT FROM AUTHOR]

Although professional development is widely used to improve the impacts of early childhood education, little is known about the conditions under which such interventions promote child outcomes. This study applies newly developed methods for quantifying intervention impact heterogeneity to understand whether educators' collective workplace stress moderates professional development's impacts on children's language and literacy skills, executive functioning, and learning behaviors. Within a sample of 406 children from the National Center for Research on Early Childhood Education Professional Development Study (Mage  = 4.17; 50% female; 50% Black, 32% Latinx, 11% White), professional development positively impacted child outcomes in centers where educators collectively reported high workplace stress but negatively impacted child outcomes in centers where educators collectively reported low workplace stress. [ABSTRACT FROM AUTHOR]

Polyamines are low molecular weight amines, with versatile and essential functions during the lifespan of prokaryotes and eukaryotes. Modulation of polyamine metabolism under biotic stress has attracted a great deal of interest; however, the precise functions of these amines in plant defence responses to pathogen attack are still poorly understood. Herein we summarise and review important aspects of the regulation of polyamine biosynthesis, catabolism and conjugation under biotic stress that might contribute to improve present‐day knowledge about these compounds in plant immunity. Particular attention is paid to the intracellular localisation of the proteins/enzymes associated to polyamine metabolism, as well as the impact of pathogen effector proteins on the control of plant polyamine metabolism is discussed. [ABSTRACT FROM AUTHOR]

Phosphorus (P), an essential macronutrient for all living organisms, is required in large amounts for the growth and development of plants. Although total soil P level is high, P bioavailability to plants is suboptimal in most soils because of high fixation rates into inorganic and organic insoluble complexes. Hence, plants are highly dependent on mechanisms that allow them to adapt to low‐phosphate stress and/or achieve suitable levels of soluble P on the root surface. In this regard, the rhizospheric microbiota plays a key role in facilitating P nutrition and has long been recognised for their potential use as an environmental‐friendly alternative to chemical P fertilisation. Herein, we outline the advances in the identification of phosphate solubilising bacteria and phosphate mineralising bacteria, collectively known as phosphobacteria, and their role in rendering P accessible to plants. We review and discuss research progress related to the introduction of phosphobacteria and/or P‐mineralising enzymes into soil, as well as plant transformation with bacterial genes that encode such enzymes, as strategies to improve plant growth and P nutrition. We also provide an overview of studies about the impact of variations in soil P levels on the structure of soil and rhizospheric microbial communities and the potential consequences of such perturbations on plant growth. Finally, we discuss possible directions for future research to optimise the efficiency of biofertilisation strategies based on the use of phosphobacteria. [ABSTRACT FROM AUTHOR]

Background: Increased interest in hidradenitis suppurativa (HS) research is encouraging. A critical analysis of the state of HS literature may demonstrate the strength of existing knowledge and highlight current gaps. Objectives: To analyse changes in HS literature from 2008 to 2018 with focus on quantity and quality of annual publications. Methods: Review of all indexed publications reporting on HS on PubMed. Publications were categorized based on study design, study topic and treatment type where applicable. Publications were dichotomized into high level of evidence and low level of evidence groups. Linear regression analyses were performed to investigate the change in publication number over time. Annual average growth rate and distribution of high versus low level of evidence publications were calculated. Results: Publication number increased over time overall (R2 = 0.64, P = 0.003) and for all publication types except randomized clinical trials. Case reports and case series represented the majority of HS publications (n = 479, 40.3%). Treatment was the main focus of publications (n = 445, 37.6%) with increasing interest in medical management evident in recent years. Distribution of low level of evidence studies (n = 974) compared with high level of evidence studies over time (n = 209) was significant (x2: 11.45, P = 0.0007). High level of evidence studies had a higher average annual growth rate (49.9%) compared with low level of evidence studies (23.7%). Few randomized clinical trials were performed (n = 16), focusing equally on medical or procedural treatments. Conclusions: Hidradenitis suppurativa research is undergoing a tremendous shift, suggesting rapid maturation of the field. Current HS literature, however, remains primarily based on limited clinical observation data, with a particular lack of randomized clinical trials. Despite this, the increase in high level of evidence studies is encouraging and may herald a shift towards improved disease understanding and treatment paradigms. [ABSTRACT FROM AUTHOR]

Pronghorn (Antilocapra americana) populations in North America were once estimated at nearly 30 million. However, unrestricted harvest of pronghorn was one of the major factors that led to 25,000 individuals by 1924. Through rigorous management, pronghorn populations rebounded to an estimated 1 million individuals by 1984. Within Texas, USA, by the late 1980s, the pronghorn population had recovered to a new estimated historic high of 17,226 individuals through restoration efforts. However, by 2010, the Texas Trans‐Pecos population declined to approximately 4,700 individuals, and declined even further to only 2,751 in 2012. A main contribution to successful recovery has been large‐scale translocations. Since the early 1920s, >30,000 pronghorn have been translocated in 17 states. As one large restoration project in Texas, translocation of pronghorn from the Texas Panhandle to Marfa and Marathon grasslands in the Trans‐Pecos region occurred in January–February 2011, 2013, 2014, 2016, and 2017. However, within the available literature on pronghorn translocations, it was difficult to find a scientific paper that provides sufficient detail to guide the translocation process. Our intent is to summarize the effective methodology behind 5 years of pronghorn translocations, inform others to make evidence‐based recommendations and justifiable‐decisions when selecting translocation methodology, and provide insight regarding design and application of our translocation methodology. Based on our translocation experience, we recommend using halperidol as a sedative given to pronghorn at the site of capture and keeping handling times to ≤4 minutes as well as maintaining pronghorn body temperatures below 40° C during processing. Flunixin meglumine should be used when body temperatures exceed 40° C. In addition, we also recommend utilizing larger, more spacious livestock trailers to transport captured pronghorn versus transport boxes or smaller, more enclosed trailers. We also recommend releasing a minimum of 50–100 individuals/release site to minimize stress from group separation and improve long‐term population sustainability. © 2020 The Wildlife Society. Translocations are done as part of restoration efforts for pronghorn due to population declines. We describe and consolidate evidence from our experience to make translocation guidelines for future management. [ABSTRACT FROM AUTHOR]

We study the dynamic connectedness and predictive causality between oil prices and exchange rates. Our sample includes six important oil‐producing and six net importing countries. Our results show that for the first set of countries, oil prices are net spillover receivers from exchange rate markets. Similarly, there is evidence of bidirectional Granger causality, which is detected for longer time periods from these countries' exchange rates to oil prices. In contrast, for the second set of countries, oil prices are net spillover transmitters, and the causality is stronger from oil prices to exchange rates, mainly in the aftermath of the Global Financial Crisis. However, even for this group of countries, there are long periods of time for which exchange‐rate markets transmit spillovers to oil markets. Overall, oil markets are net receivers of shocks during most of the sample period, thus providing evidence in favor of the oil‐financialization hypothesis. [ABSTRACT FROM AUTHOR]

B Results: b At dasta cutoff (15 June 2022; median follow up: 39.7 m), 14.7% of pts treated with Pola-R-CHP and 15.8% with R-CHOP had died; the main cause of death was disease progression (safety-evaluable population; Table). B Introduction: b In the past decade, disease progression has been reported as the main cause of death in pts with diffuse large B-cell lymphoma (DLBCL) treated with first-line (1L) R-CHOP. [Extracted from the article]

Neurocysticercosis is a parasitic brain disease caused by the larval form (Cysticercus cellulosae) of Taenia solium and is the leading cause of preventable epilepsy worldwide. However, the pathophysiology and relation to the wide range of clinical features remains poorly understood. Axonal swelling is emerging as an important early pathological finding in multiple neurodegenerative diseases and as a cause of brain injury, but has not been well described in neurocysticercosis. Histological analysis was performed on human, rat and porcine NCC brain specimens to identify axonal pathology. Rat infection was successfully carried out via two routes of inoculation: direct intracranial injection and oral feeding. Extensive axonal swellings, in the form of spheroids, were observed in both humans and rats and to a lesser extent in pigs with NCC. Spheroids demonstrated increased immunoreactivity to amyloid precursor protein and neurofilament indicating probable impairment of axonal transport. These novel findings demonstrate that spheroids are present in NCC which is conserved across species. Not only is this an important contribution toward understanding the pathogenesis of NCC, but it also provides a model to analyze the association of spheroids with specific clinical features and to investigate the reversibility of spheroid formation with antihelminthic treatment. [ABSTRACT FROM AUTHOR]

Background. Newborn hyperbilirubinemia is considered a worldwide health problem that demands medical evaluation. Noninvasive transcutaneous bilirubin (TcB) has been used as a screening method with different devices but there has not been any evaluation of reproducibility of the same brand devices. The BiliCare™ system is evaluated to demonstrate consistency between measurements with four different devices. Methods. 336 TcB measurements were obtained with four BiliCare™ devices in 21 Mexican icteric newborns with a mean postnatal age of 44.1 hours of life and 38 weeks of gestation (33–41). Two measurements were taken in the same ear alternatively at the scaphoid fossa with each device. TcB values were compared between devices. Validity was compared with total serum bilirubin (TB). Results. intraclass correlation coefficient demonstrates a minimum limit in the study of 0.945 and maximum of 0.988 with the same device. Correlations with serum and between devices gave results above 0.932. Conclusions. BiliCare™ transcutaneous bilirubin measurement instrument has very good intra- and interdevice reproducibility; also correlation of TcS with serum bilirubin gave statistically the same results. [ABSTRACT FROM AUTHOR]

Summary: Objective: To evaluate the efficacy and safety associated with use of a 589‐nm solid‐state laser for treatment of facial erythema. Methods: A prospective, IRB‐approved study was conducted. Participants who were interested in treatment for facial erythema were recruited. They received four monthly treatments with the 589‐nm laser. Erythema of the right and left face was graded on a scale of 0‐4, 4 being most severe, by both investigators and participants prior to each treatment and at follow‐up. Safety was assessed by any reported side effects. Results: Twenty‐four participants enrolled in the study, 16 women (67%) and 8 men (33%), with an average age of 51.1 years. Investigator grades showed a statistically significant improvement in erythema of 31% for both the right and left face. Participant grades showed a statistically significant improvement in erythema of 23.2% for the right face and 22.8% for the left face. Side effects were limited to transient erythema posttreatment. Conclusion: A 589‐nm solid‐state laser achieved a modest improvement in facial erythema when evaluating results 1 month after four monthly treatments. No major safety issues were reported. [ABSTRACT FROM AUTHOR]

Abstract: Background: Dipeptidyl peptidase‐4 (DPP‐4) inhibitors have increasingly been identified as causative agents of bullous pemphigoid. The clinical and immunological characteristics of this pemphigoid variant are still unclear. The objective of our study was to analyze the clinical and immunological features of patients with pemphigoid induced by DPP‐4 inhibitors. Methods: All patients diagnosed with DPP‐4 inhibitor‐associated bullous pemphigoid at dermatology departments in three Spanish centers during the period 2013 to 2015 were included. ELISA assays for the NC16A domain of BP180 and BP230 were performed. Immunoblot studies using epidermal/dermal extracts and the C‐terminal, NC16A and LAD‐1 regions of BP180 were also carried out. Results: A total of eight patients were identified (5 treated with vildagliptin, 2 with linagliptin, and one with sitagliptin). Of these, four presented the classical inflammatory phenotype of bullous pemphigoid and four a noninflammatory phenotype. The ELISA for BP180 (NC16A domain) was positive in six patients at diagnosis. Most patients reacted to more than one BP180 antigenic site (LAD‐1 and/or C‐terminal domain) on the immunoblot. Two patients showed no reaction against the NC16A domain of BP180 on either the ELISA or immunoblot but recognized either LAD‐1 or both LAD‐1 and the C‐terminal domain. Only one of the NC16A‐negative patients had a noninflammatory subtype of bullous pemphigoid. Conclusions: Patients with DPP‐4 inhibitor‐induced BP may present either an inflammatory or a noninflammatory phenotype of BP. IgG response against other BP180 regions different from the NC16A domain, such as LAD‐1 and the C‐terminal domain, could be pathogenically relevant to the onset of DPP‐4 inhibitor‐induced BP. [ABSTRACT FROM AUTHOR]

Abstract: We study the determinants of housing price bubbles' duration for a set of OECD countries between 1970 and 2015. Our topic of study is of major importance, as duration is a proxy for other dimensions, such as the magnitude of bubbles, the extent of macroeconomic imbalances, and the chance that a rational bubble turns into an irrational one. We answer two related questions: (i) Does prolonged domestic monetary‐policy easing increase the duration of housing price bubbles? (ii) Does prolonged monetary‐policy easing in the United States influence the housing bubbles' duration in other OECD countries? We show that the answer to the first question is a clear yes but that the answer to the second question is not as clear. Our main result is that monetary‐policy tightening can accelerate the termination of a housing bubble. In this sense, our findings provide support for ‘leaning against the wind’ policies. [ABSTRACT FROM AUTHOR]

Abstract: FV is primarily produced in the liver, and congenital FV deficiency is a disorder with an incidence of one in 1 million. Standard care is to treat severe bleeding phenotypes with FFP as there is no recombinant or plasma‐derived FV concentrate. We present a case of a neonate with known severe FV deficiency diagnosed after prolonged bleeding after circumcision who represented at age 2 months with a large left intraparenchymal hemorrhage. His bleed was treated with FFP, platelet transfusion, recombinant VIIa, and emergent evacuation. He was maintained on plasma infusions but was unable to space his infusions beyond 48 hours. Liver transplantation was considered as a definitive treatment for this condition. While awaiting a suitable liver, his FV trough levels occasionally dropped below 5%, and he suffered from a second acute intracranial bleed. He received an orthotopic liver transplant at age 5 months, resulting in correction of his FV levels. He has not required any plasma infusions post‐transplantation and has had no further bleeding episodes. Liver transplantation should be considered as definitive treatment early in the course for patients with severe FV deficiency and first time life‐threatening bleed. [ABSTRACT FROM AUTHOR]

The innate immune kinase TBK1 initiates inflammatory responses to combat infectious pathogens by driving production of type I interferons. TBK1 also controls metabolic processes and promotes oncogene-induced cell proliferation and survival. Here, we demonstrate that TBK1 activates mTOR complex 1 ( mTORC1) directly. In cultured cells, TBK1 associates with and activates mTORC1 through site-specific mTOR phosphorylation (on S2159) in response to certain growth factor receptors (i.e., EGF-receptor but not insulin receptor) and pathogen recognition receptors ( PRRs) (i.e., TLR3; TLR4), revealing a stimulus-selective role for TBK1 in mTORC1 regulation. By studying cultured macrophages and those isolated from genome edited mTOR S2159A knock-in mice, we show that mTOR S2159 phosphorylation promotes mTORC1 signaling, IRF3 nuclear translocation, and IFN-β production. These data demonstrate a direct mechanistic link between TBK1 and mTORC1 function as well as physiologic significance of the TBK1- mTORC1 axis in control of innate immune function. These data unveil TBK1 as a direct mTORC1 activator and suggest unanticipated roles for mTORC1 downstream of TBK1 in control of innate immunity, tumorigenesis, and disorders linked to chronic inflammation. [ABSTRACT FROM AUTHOR]

Copyright of Tropical Medicine & International Health is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

This article bridges research to practice by summarizing an interactive content-enriched shared book reading approach that Spanish-speaking parents of preschool-age children can easily use in the home to accelerate content vocabulary knowledge in Spanish. The approach was implemented in preschool classrooms using a transitional bilingual education model in Central Texas and in a Saturday Spanish heritage language school in the Midwestern United States. Spanish-speaking emergent bilingual children from both lower and higher socioeconomic status backgrounds learned content-related vocabulary via parent-child discussions of Spanish storybooks and informational texts organized by compelling science and social studies themes and topics. The authors provide recommendations for how teachers can support Spanish-speaking parents' ability to develop informal knowledge-building experiences through home-based interactive book discussions in Spanish. [ABSTRACT FROM AUTHOR]

Triethylsiloxymethylamine, Et3SiOCH2NMe2, readily synthesized in high yield by the hydrosilylation reaction between Et3SiH and DMF, is an excellent (N,N-dimethylamino) methyl transfer agent to a representative range of aliphatic alcohols, thiols, and Ph2PH (E-H) materials. The reactions are almost instantaneous at room temperature in inert solvents and require no activating agents to produce E-CH2NMe2 prod-ucts in high yields and illustrate the title compound as an excellent addition to the family of organic reagents. For aromatic alcohols, electrophilic substitution of the aromatic ring occurs in high yield. Crystal structures of new materials such as the cholestero-CH2NMe2 derivative, 2-4-[bis(N,N-dimethylamino)- methyl]-1-naphthol, and the phosphine oxide derived from Ph2PCH2NMe2 are reported. [ABSTRACT FROM AUTHOR]

We describe the first reported pediatric patient to our knowledge with a spindle cell pseudotumor caused by Mycobacterium genavense in a hematopoietic stem cell transplant recipient, and review the literature of such an entity in the transplant population. [ABSTRACT FROM AUTHOR]

The present investigation examined 460 school psychology trainers' attitudes and beliefs about the conditions for the education and training of evidence-based practices (i.e., assessments and interventions) in training programs in the United States and Canada using an online survey. Trainer attitudes and beliefs about education and training in evidence-based practices were measured using a 24-item five-point Likert scale. Overall, trainers had positive views of evidence-based practices, as well as program and organizational support for such training. However, trainers rated the education and training of evidence-based assessments more favorably than evidence-based interventions. In general, trainer characteristics nor program accreditation status, model, or type of degree offered were found to influence trainers' perceptions about evidence-based practices. However, trainers with prior experience teaching evidence-based intervention courses were found to have more supportive views of evidence-based assessments and interventions than those without such experience. Implications for future training and school practice are discussed. [ABSTRACT FROM AUTHOR]

Econometric tests are performed for the detection and migration of asset-price bubbles in the housing, currency and stock markets of seven countries. This set of countries includes both developed and emerging economies that have good historical data on housing prices. Our empirical results suggest that this type of exuberant behaviour in prices occurs more frequently in the housing market than in the currency and stock markets. Additionally, we find significant evidence of bubble migration across markets within some of the studied countries. [ABSTRACT FROM AUTHOR]

Background: Latinas have the highest rates of cervical cancer in the United States and the second highest rate of cervical cancer mortality. One factor in the disparity is the relatively low rate of screening for cervical cancer in this population.Methods: Eligible women who were out of adherence with cervical cancer screening (>3 years since their last Papanicolaou [Pap] test) were identified via medical record review by a federally qualified local health center. The effects of a low-intensity intervention (video delivered to participants' homes; n = 150) and a high-intensity intervention (video plus a home-based educational session; n = 146) on cervical cancer screening uptake in comparison with a control arm (usual care; n = 147) were investigated. A cost-effectiveness analysis of the interventions was conducted: all intervention costs were calculated, and the incremental cost-effectiveness ratio was computed. Finally, women with positive Pap tests were provided navigation by a community health educator to ensure that they received follow-up care.Results: A total of 443 Latinas participated. Seven months after randomization, significantly more women in the high-intensity arm received a Pap test (53.4%) in comparison with the low-intensity arm (38.7%; P < .001) and the usual-care arm (34.0%; P < .01). The incremental cost-effectiveness ratio for high-intensity women versus the control group amounted to $4.24. Twelve women had positive Pap tests, which encompassed diagnoses ranging from atypical squamous cells of unknown significance to invasive cancer; these women received navigation for follow-up care.Conclusions: A culturally appropriate, in-home, promotora-led educational intervention was successful in increasing cervical cancer screening among Latinas. Cancer 2017;123:666-674. © 2016 American Cancer Society. [ABSTRACT FROM AUTHOR]