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Abstract The urban heat island effect causes increased heat stress in urban areas. Cool roofs and urban greening have been promoted as mitigation strategies to reduce this effect. However, evaluating their efficacy remains a challenge, as potential temperature reductions depend on local characteristics. Existing methods to characterize their efficacy, such as computational fluid dynamics and urban canopy models, are computationally burdensome and require a high degree of expertise to employ. We propose a data-driven approach to overcome these hurdles, inspired by recent innovations in spatial causal inference. This approach allows for estimates of hypothetical interventions to reduce the urban heat island effect. We demonstrate this approach by modeling evening temperature in Durham, North Carolina, using readily retrieved air temperature, land cover, and satellite data. Hypothetical interventions such as lining streets with trees, cool roofs, and changing parking lots to green space are estimated to decrease evening temperatures by a maximum of 0.7–0.9 $$^{\circ } \hbox {C}$$ ∘ C , with reduced effects on temperature as a function of distance from the intervention. Because of the ease of data access, this approach may be applied to other cities in the U.S. to help them come up with city-specific solutions for reducing urban heat stress.

Abstract Introduction Atopic dermatitis (AD) is a chronic inflammatory skin disorder with limited treatment options for adolescents with moderate-to-severe disease. Lebrikizumab, a monoclonal antibody targeting interleukin (IL)-13, demonstrated clinical benefit in previous Phase 3 trials: ADvocate1 (NCT04146363), ADvocate2 (NCT04178967), and ADhere (NCT04250337). We report 52-week safety and efficacy outcomes from ADore (NCT04250350), a Phase 3, open-label study of lebrikizumab in adolescent patients with moderate-to-severe AD. The primary endpoint was to describe the proportion of patients who discontinued from study treatment because of adverse events (AEs) through the last treatment visit. Methods Adolescent patients (N = 206) (≥ 12 to

Abstract Although a higher prevalence of antiphospholipid autoantibodies (aPL) has been observed in some cohorts of sickle cell disease (SCD) patients, the clinical risk factors for the development of aPL and its associated complications remain unclear. In a retrospective study of 63 SCD patients, a lower hemoglobin concentration and higher white blood cell count were independently associated with an elevated aPL. SCD patients with elevated aPL had increased pregnancy complications (≥3 miscarriages, preterm delivery, pre‐eclampsia) and venous thrombotic events. Our findings suggest that SCD may predispose to the generation of aPL and that aPL itself may contribute to the vasculopathy of SCD. Prospective testing for aPL is warranted in patients with SCD.

Abstract We show that Polycomb Repressive Complex-2 (PRC2) components EED and EZH2 maintain neural identity in cerebellar granule neuron progenitors (CGNPs) and SHH-driven medulloblastoma, a cancer of CGNPs. Proliferating CGNPs and medulloblastoma cells inherit neural fate commitment through epigenetic mechanisms. The PRC2 is an epigenetic regulator that has been proposed as a therapeutic target in medulloblastoma. To define PRC2 function in cerebellar development and medulloblastoma, we conditionally deleted PRC2 components Eed or Ezh2 in CGNPs and analyzed medulloblastomas induced in Eed-deleted and Ezh2-deleted CGNPs by expressing SmoM2, an oncogenic allele of Smo. Eed deletion destabilized the PRC2, depleting EED and EZH2 proteins, while Ezh2 deletion did not deplete EED. Eed-deleted cerebella were hypoplastic, with reduced proliferation, increased apoptosis, and inappropriate muscle-like differentiation. Ezh2-deleted cerebella showed similar, milder phenotypes, with fewer muscle-like cells and without reduced growth. Eed-deleted and Ezh2-deleted medulloblastomas both demonstrated myoid differentiation and progressed more rapidly than PRC2-intact controls. The PRC2 thus maintains neural commitment in CGNPs and medulloblastoma, but is not required for SHH medulloblastoma progression. Our data define a role for the PRC2 in preventing inappropriate, non-neural fates during postnatal neurogenesis, and caution that targeting the PRC2 in SHH medulloblastoma may not produce durable therapeutic effects.

BackgroundMany people attending primary care (PC) have anxiety-depressive symptoms and work-related burnout compounded by a lack of resources to meet their needs. The COVID-19 pandemic has exacerbated this problem, and digital tools have been proposed as a solution. ObjectiveWe aimed to present the development, feasibility, and potential effectiveness of Vickybot, a chatbot aimed at screening, monitoring, and reducing anxiety-depressive symptoms and work-related burnout, and detecting suicide risk in patients from PC and health care workers. MethodsHealthy controls (HCs) tested Vickybot for reliability. For the simulation study, HCs used Vickybot for 2 weeks to simulate different clinical situations. For feasibility and effectiveness study, people consulting PC or health care workers with mental health problems used Vickybot for 1 month. Self-assessments for anxiety (Generalized Anxiety Disorder 7-item) and depression (Patient Health Questionnaire-9) symptoms and work-related burnout (based on the Maslach Burnout Inventory) were administered at baseline and every 2 weeks. Feasibility was determined from both subjective and objective user-engagement indicators (UEIs). Potential effectiveness was measured using paired 2-tailed t tests or Wilcoxon signed-rank test for changes in self-assessment scores. ResultsOverall, 40 HCs tested Vickybot simultaneously, and the data were reliably transmitted and registered. For simulation, 17 HCs (n=13, 76% female; mean age 36.5, SD 9.7 years) received 98.8% of the expected modules. Suicidal alerts were received correctly. For the feasibility and potential effectiveness study, 34 patients (15 from PC and 19 health care workers; 76% [26/34] female; mean age 35.3, SD 10.1 years) completed the first self-assessments, with 100% (34/34) presenting anxiety symptoms, 94% (32/34) depressive symptoms, and 65% (22/34) work-related burnout. In addition, 27% (9/34) of patients completed the second self-assessment after 2 weeks of use. No significant differences were found between the first and second self-assessments for anxiety (t8=1.000; P=.34) or depressive (t8=0.40; P=.70) symptoms. However, work-related burnout scores were moderately reduced (z=−2.07, P=.04, r=0.32). There was a nonsignificant trend toward a greater reduction in anxiety-depressive symptoms and work-related burnout with greater use of the chatbot. Furthermore, 9% (3/34) of patients activated the suicide alert, and the research team promptly intervened with successful outcomes. Vickybot showed high subjective UEI (acceptability, usability, and satisfaction), but low objective UEI (completion, adherence, compliance, and engagement). Vickybot was moderately feasible. ConclusionsThe chatbot was useful in screening for the presence and severity of anxiety and depressive symptoms, and for detecting suicidal risk. Potential effectiveness was shown to reduce work-related burnout but not anxiety or depressive symptoms. Subjective perceptions of use contrasted with low objective-use metrics. Our results are promising but suggest the need to adapt and enhance the smartphone-based solution to improve engagement. A consensus on how to report UEIs and validate digital solutions, particularly for chatbots, is required.

Objetive: To evaluate microleakage of composite resins (CR) placed over different cavitary liners after managing deep caries lesions through selective removal of soft carious tissue to soft dentin (SRCT-S). Material and Methods: Fifty four human teeth were collected for microleakage testing. Each assay comprised ICDAS 5 or ICDAS 6 carious lesions and sound teeth for controls. Sound teeth were prepared with cavities that mirrored the carious teeth cavities, which were prepared with SRCT-S. Sound and carious teeth were further randomly assigned to one of the three experimental groups: Group A: universal adhesive (UA) + CR, Group B: glass ionomer cement liner + UA + CR, and Group C: calcium hydroxide + UA+ CR. Occlusal microleakage (OM) and cervical microleakage (CM) was classified within one of 5 depth categories. ANOVA and Chi-square tests were computed (p0.05). All Group C samples with carious lesions presented some degree of microleakage. However, no statistically significant differences were observed between groups and within each group (p>0.05). Conclusion: Teeth restored with CR after SRCT-S using calcium hydroxide as a liner material seem to exhibit higher microleakage than those restored using glass ionomer or UA alone. Further clinical research is needed to deepen these findings. Clinical significance: The application of calcium hydroxide as a liner under a composite resin may reduce the longevity of a restoration after performing selective or partial removal of carious tissues. Clinicians should rethink the need of using calcium hydroxide for this application, albeit the lack of clinical evidence.

Resumen La Sociedad Argentina de Periodoncia ha formulado un Comentario, analizando los condicionantes del contexto nacional, para determinar si las recomendaciones generadas en la Guía de Práctica Clínica de nivel S3 de la Federación Europea de Periodoncia para el tratamiento de la periodontitis en estadios I-III, podrían ser aplicadas para dar respuesta a la demanda de la población, en lo referido a la salud periodontal// Abstract The Argentine Society of Periodontics has formulated a Commentary, analyzing the determining factors of the national context, to determine if the recommendations generated in the Level S3 Clinical Practice Guideline of the European Federation of Periodontics for the treatment of periodontitis in stages I-III could be applied to respond to the demand of the population, regarding periodontal health.

In the last few years, several studies have questioned the value of the second-to-fourth digit ratio (2D:4D) as a measure of exposure to sex hormones before birth. Controversy has also extended to the 2D:4D association with individual features previously related to this exposure such as handedness and sexual orientation. Given that it has been argued that sex differences in 2D:4D could be a consequence of body-size differences, we have tested in a large sample the allometric relationship between finger lengths and body size. Our results show that the association is either allometric or isometric, depending on the analyses performed. In any case, the deviation from isometry is not large enough to explain the typically observed sex difference in this trait. We have also tested the association between sexual orientation and 2D:4D, finding a relationship between 2D:4D and sexual orientation in men but not in women. We attribute this discordance with previously published meta-analysis to differences in genetic background, a variable that has gained relevance in recent years in studies involving 2D:4D. Finally, we did not find any relationship between 2D:4D and handedness, evaluated through self-reported preference and hand performance. Our main conclusion is that 2D:4D shows differences between sexes beyond their disparity in body size. In our opinion, 2D:4D can be used cautiously as an indicator of intrauterine exposure to sex hormones taking into account some considerations, such as analysing a very large sample and taking careful measurements of the ethnicity of the sample.

The Dominican Republic (DR) has the second-highest prevalence of HIV infection in the Caribbean, but viral suppression and treatment adherence are not well understood. We conducted a cross-sectional study among people living with HIV/AIDS(PLWHA) to fill in the knowledge gap. Questionnaire was used to collect demographic data, antiretroviral therapy (ART) adherence, and barriers and facilitators to HIV care. Viral load and other clinical information were extracted through chart reviews. Descriptive analyzes and logistic regression were conducted to explore factors associated with non-viral suppression and imperfect ART adherence. Of 193 PLWHA 83.9% were virally suppressed. Those that were non-virally suppressed were more likely of being male (odds ratio [OR]: 2.55, 95% confidence interval [CI]: 1.17-5.58) and less likely of being unemployed (OR: 0.28, 95% CI: 0.08-0.96). However, being male (OR: 0.78, 95% CI:0.40-1.53) and unemployed (OR: 0.28, 95% CI:0. 08-1.21) were less likely to report imperfect adherence. Tailored interventions are needed to improve adherence and viral suppression in DR.

Urolithiasis is a worldwide problem and a risk factor for kidney injury. Oxidative stress-associated renal endothelial dysfunction secondary to urolithiasis could be a key pathogenic factor, similar to obesity and diabetes-related nephropathy. The aim of the present study was to characterize urolithiasis-related endothelial dysfunction in a hyperoxaluria rat model of renal lithiasis. Experimental approach: Endothelial dysfunction was assessed in preglomerular arteries isolated from control rats and in which 0.75% ethylene glycol was administered in drinking water. Renal interlobar arteries were mounted in microvascular myographs for functional studies; superoxide generation was measured by chemiluminescence and mRNA and protein expression by RT-PCR and immunofluorescence, respectively. Selective inhibitors were used to study the influence of the different ROS sources, xanthine oxidase, COX-2, Nox1, Nox2 and Nox4. Inflammatory vascular response was also studied by measuring the RNAm expression of NF-κB, MCP-1 and TNFα by RT-PCR. Results: Endothelium-dependent vasodilator responses were impaired in the preglomerular arteries of the hyperoxaluric group along with higher superoxide generation in the renal cortex and vascular inflammation developed by MCP-1 and promoted by NF-κB. The xanthine oxidase inhibitor allopurinol restored the endothelial relaxations and returned superoxide generation to basal values. Nox1 and Nox2 mRNA were up-regulated in arteries from the hyperoxaluric group, and Nox1 and Nox2 selective inhibitors also restored the impaired vasodilator responses and normalized NADPH oxidase-dependent higher superoxide values of renal cortex from the hyperoxaluric group. Conclusions: The current data support that hyperoxaluria induces oxidative stress-mediated endothelial dysfunction and inflammatory response in renal preglomerular arteries which is promoted by the xanthine oxidase, Nox1 and Nox2 pathways.

Online courses, particularly in the massive open online course (MOOC) format, have been lauded for their potential to democratize access to educational opportunities but criticized for their markedly low completion rates. Yet educators continue to enroll in online courses, including MOOCs, in high numbers. For teachers at under-resourced schools, free online courses may be the only professional development option. It thus remains important to understand whether online courses, in their various formats, can serve as vehicles to support teacher learning and whether this can happen on a large-scale. Extending prior research that explores the relationship between contextual factors, engagement, and learning in online settings, this mixed-method study examines outcomes in a MOOC designed for teachers of English learners (ELs). In particular, the study identifies and examines structural and social supports that were available to some course participants (release time, stipends, participating with colleagues, and having a facilitator who convened face-to-face meetings) and investigates whether these local conditions were significantly related to completion and learning. Findings indicate that participants who received more supports were significantly more likely to complete the course. While participants, on average, showed evidence of learning, participants receiving supports did not show evidence of learning more than other participants. This is potentially due to omitted variable bias because participants who completed the course without supports may differ from participants who completed the course with supports in important, unaccounted for ways. This study extends prior research about how learning environments impact online learning experiences and suggests that structural and social supports may be useful in facilitating MOOC completion.

The cell wall is a ubiquitous structure in the fungal kingdom, with some features varying depending on the species. Additional external structures can be present, such as the capsule of Cryptococcus neoformans (Cn), its major virulence factor, mainly composed of glucuronoxylomannan (GXM), with anti-phagocytic and anti-inflammatory properties. The literature shows that other cryptococcal species and even more evolutionarily distant species, such as the Trichosporon asahii, T. mucoides, and Paracoccidioides brasiliensis can produce GXM-like polysaccharides displaying serological reactivity to GXM-specific monoclonal antibodies (mAbs), and these complex polysaccharides have similar composition and anti-phagocytic properties to cryptococcal GXM. Previously, we demonstrated that the fungus Histoplasma capsulatum (Hc) incorporates, surface/secreted GXM of Cn and the surface accumulation of the polysaccharide enhances Hc virulence in vitro and in vivo. In this work, we characterized the ability of Hc to produce cellular-attached (C-gly-Hc) and secreted (E-gly) glycans with reactivity to GXM mAbs. These C-gly-Hc are readily incorporated on the surface of acapsular Cn cap59; however, in contrast to Cn GXM, C-gly-Hc had no xylose and glucuronic acid in its composition. Mapping of recognized Cn GXM synthesis/export proteins confirmed the presence of orthologs in the Hc database. Evaluation of C-gly and E-gly of Hc from strains of distinct monophyletic clades showed serological reactivity to GXM mAbs, despite slight differences in their molecular dimensions. These C-gly-Hc and E-gly-Hc also reacted with sera of cryptococcosis patients. In turn, sera from histoplasmosis patients recognized Cn glycans, suggesting immunogenicity and the presence of cross-reacting antibodies. Additionally, C-gly-Hc and E-gly-Hc coated Cn cap59 were more resistant to phagocytosis and macrophage killing. C-gly-Hc and E-gly-Hc coated Cn cap59 were also able to kill larvae of Galleria mellonella. These GXM-like Hc glycans, as well as those produced by other pathogenic fungi, may also be important during host-pathogen interactions, and factors associated with their regulation are potentially important targets for the management of histoplasmosis.

Wastewater from the yeast production industry (WWY) is potentially harmful to surface water due to its high nitrogen and organic matter content; it can be used to produce compounds of higher commercial value, such as polyhydroxyalkanoates (PHA). PHA are polyester-type biopolymers synthesized by bacteria as energy reservoirs that can potentially substitute petrochemical-derived plastics. In this exploratory work, effluent from WWY was used to produce PHA, using a three-step setup of mixed microbial cultures involving one anaerobic and two aerobic reactors. First, volatile fatty acids (VFA; 2.5 g/L) were produced on an anaerobic batch reactor (reactor A) fed with WWY, using a heat pretreated sludge inoculum to eliminate methanogenic activity. Concurrently, PHA-producing bacteria were enriched using synthetic VFA in a sequencing batch reactor (SBR, reactor C) operated for 78 days. Finally, a polyhydroxybutyrate (PHB)-producing reactor (reactor B) was assembled using the inoculum enriched with PHA-producing bacteria and the raw and distilled effluent from the anaerobic reactor as a substrate. A maximum accumulation of 17% of PHB based on cell dry weight was achieved with a yield of 1.2 g PHB/L when feeding with the distilled effluent. Roche 454 16S rRNA gene amplicon pyrosequencing of the PHA-producing reactor showed that the microbial community was dominated by the PHA-producing bacterial species Paracoccus alcalophilus (32%) and Azoarcus sp. (44%). Our results show promising PHB accumulation rates that outperform previously reported results obtained with real substrates and mixed cultures, demonstrating a sustainable approach for the production of PHA less prone to contamination than a pure culture.

In this paper, we argue that, like a three-legged stool, participatory programs require three elements for stability: a supply of participatory institutions, a demand from citizens to participate, and citizens with capabilities for participation. We illustrate the importance of these three elements using case studies from forest management in central India and southern Mexico, and use the evidence from these cases to suggest hypotheses for future investigation. We argue that when participatory programs are implemented in places where demand for citizen engagement is weak and citizens lack the capability to engage, participation is unlikely. On the other hand, where people demand to participate and have the capability to do so, they are sometimes able to overcome obstacles to utilizing participatory institutions. Individuals’ agency for citizen engagement is developed in interaction with the structures of participation; this means that there may be a long-term synergy between the supply of participatory institutions and the development of skills and demand for citizen engagement. Our work implies that designers of participatory programs should pay equal attention to cultivating participatory capabilities, providing incentives that enhance demand for participation, and building institutions to open spaces for participation in governance. Building participatory environmental governance may thus require long-term, sustained attention to both citizenship and institution-building.

Anelice Ribetto es psicóloga formada en la Facultad de Psicología de la Universidad Nacional de Córdoba (Argentina), Master y Doctora en Educación por la Universidade Federal Fluminense (Brasil). Es profesora de la Universidade do Estado do Rio de Janeiro y desempeña tareas de enseñanza, extensión e investigación en el Departamento de Educación y el Programa de Pós- Graduação em Educação- Processos Formativos e Desigualdades Sociais de la Faculdade de Formação de Professores da UERJ. También integra el colectivo Diferenças e Alteridade na Educação. En esta entrevista, la autora nos propone preguntarnos sobre la escritura, pero no cualquier escritura sino aquella que discurre en el campo educativo, aquella que hace habitar lo otro y a los otros (en especial esos sujetos que dislocan toda normalidad). El ejercicio, interesante, es repensarla como parte constitutiva de la experiencia en los espacios disciplinares y en la formación docente. Del mismo modo, problematiza aspectos como lo (inter)subjetivo y lo político; establece relaciones posibles entre escritura e investigación, a la vez que reconoce lo constitutivo del trabajo escritural colectivo para la producción y circulación del conocimiento.

The increasing use of chemical fertilizers causes the loss of natural biological nitrogen fixation in soils, water eutrophication and emits more than 300 Mton CO2 per year. It also limits the success of external bacterial inoculation in the soil. Nitrogen fixing bacteria can be inhibited by the presence of ammonia as its presence can inhibit biological nitrogen fixation. Two aerobic sludges from wastewater treatment plants (WWTP) were exposed to high ammonium salts concentrations (>450 mg L−1 and >2 dS m−1). Microbial analysis after treatment through 16S pyrosequencing showed the presence of Fluviicola sp. (17.70%), a genus of the Clostridiaceae family (11.17%), and Azospirillum sp. (10.42%), which were present at the beginning with lower abundance. Denaturing gradient gel electrophoresis (DGGE) analysis based on nifH genes did not show changes in the nitrogen-fixing population. Nitrogen-Fixing Bacteria (NFB) were identified and associated with other microorganisms involved in the nitrogen cycle, presumably for survival at extreme conditions. The potential use of aerobic sludges enriched with NFB is proposed as an alternative to chemical fertilizer as this bacteria could supplement nitrogen to the plant showing competitive results with chemical fertilization.

The Australian sexually deceptive orchid, Chiloglottis trapeziformis, employs a unique UV-B-dependent floral volatile, chiloglottone 1, for specific male wasp pollinator attraction. Chiloglottone 1 and related variants (2,5-dialkylcyclohexane-1,3-diones), represent a unique class of specialized metabolites presumed to be the product of cyclization between two fatty acid (FA) precursors. However, the genes involved in the biosynthesis of precursors, intermediates, and transcriptional regulation remains to be discovered. Chiloglottone 1 production occurs in the aggregation of calli (callus) on the labellum under continuous UV-B light. Therefore, deep sequencing, transcriptome assembly, and differential expression (DE) analysis were performed across different tissue types and UV-B treatments. Transcripts expressed in the callus and labellum (∼23,000 transcripts) were highly specialized and enriched for a diversity of known and novel metabolic pathways. DE analysis between chiloglottone-emitting callus versus the remainder of the labellum showed strong coordinated induction of entire FA biosynthesis and β-oxidation pathways including genes encoding Ketoacyl-ACP Synthase, Acyl-CoA Oxidase, and Multifunctional Protein. Phylogenetic analysis revealed potential gene duplicates with tissue-specific differential regulation including two Acyl-ACP Thioesterase B and a Ketoacyl-ACP Synthase genes. UV-B treatment induced the activation of UVR8-mediated signaling and large-scale transcriptome changes in both tissues, however, neither FA biosynthesis/β-oxidation nor other lipid metabolic pathways showed clear indications of concerted DE. Gene co-expression network analysis identified three callus-specific modules enriched with various lipid metabolism categories. These networks also highlight promising candidates involved in the cyclization of chiloglottone 1 intermediates (e.g., Bet v I and dimeric α,β barrel proteins) and orchestrating regulation of precursor pathways (e.g., AP2/ERF) given a strong co-regulation with FA biosynthesis/β-oxidation genes. Possible alternative biosynthetic routes for precursors (e.g., aldehyde dehydrogenases) were also indicated. Our comprehensive study constitutes the first step toward understanding the biosynthetic pathways involved in chiloglottone 1 production in Chiloglottis trapeziformis – supporting the roles of FA metabolism in planta, gene duplication as a potential source of new genes, and co-regulation of novel pathway genes in a tissue-specific manner. This study also provides a new and valuable resource for future discovery and comparative studies in plant specialized metabolism of other orchids and non-model plants.

The use of alternative medicines, including herbs, is common among HIV-positive patients, even in those on antiretroviral treatment. Equisetum arvense , known as “horsetail,” is mainly used for its diuretic properties. There are limited data about the pharmacological properties of this compound and the potential drug–herb interactions. The authors report 2 cases in which a possible drug–herb interaction may have led to virological breakthrough in patients who were maintained on the same regimen for many years, including lamivudine (3TC)/zidovudine (ZDV)/efavirenz (EFV) and emtricitabine (FTC)/tenofovir (TDF)/EFV, respectively. Therefore, a drug–herb interaction may be expected when these agents are taken concurrently. Until additional data are available, the authors advise clinicians to avoid this combination when possible.