RNA-Seq identifies genes whose proteins are upregulated during syncytia development in murine C2C12 myoblasts and human BeWo trophoblasts

The fusion of villous cytotrophoblasts into the multinucleated syncytiotrophoblast is critical for the essential functions of the mammalian placenta. Using RNA-Seq gene expression, quantitative protein expression, and siRNA knockdown we identified genes and their cognate proteins which are similarly upregulated in two cellular models of mammalian syncytia development (human BeWo cytotrophoblast to syncytiotrophoblast and murine C2C12 myoblast to myotube). These include DYSF, PDE4DIP, SPIRE2, NDRG1, PLEC, GPR146, HSPB8, DHCR7, and HDAC5. These findings provide avenues for further understanding of the mechanisms underlying mammalian placental syncytiotrophoblast development

Association of the retail food environment, BMI, dietary patterns, and socioeconomic position in urban areas of Mexico

Copyright: © 2023 Pineda et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.The retail food environment is a key modifiable driver of food choice and the risk of non-communicable diseases (NCDs). This study aimed to assess the relationship between the density of food retailers, body mass index (BMI), dietary patterns, and socioeconomic position in Mexico. Cross-sectional dietary data, BMI and socioeconomic characteristics of adult participants came from the nationally representative 2012 National Health and Nutrition Survey in Mexico. Geographical and food outlet data were obtained from official statistics. Densities of food outlets per census tract area (CTA) were calculated. Dietary patterns were determined using exploratory factor analysis and principal component analysis. The association of food environment variables, socioeconomic position, BMI, and dietary patterns was assessed using two-level multilevel linear regression models. Three dietary patterns were identified-the healthy, the unhealthy and the carbohydrates-and-drinks dietary pattern. Lower availability of fruit and vegetable stores was associated with an unhealthier dietary pattern whilst a higher restaurant density was associated with a carbohydrates-and-drinks pattern. A graded and inverse association was observed for fruit and vegetable store density and socioeconomic position (SEP)-lower-income populations had a reduced availability of fruit and vegetable stores, compared with higher-income populations. A higher density of convenience stores was associated with a higher BMI when adjusting for unhealthy dietary patterns. Upper-income households were more likely to consume healthy dietary patterns and middle-upper-income households were less likely to consume unhealthy dietary patterns when exposed to high densities of fruit and vegetable stores. When exposed to a high concentration of convenience stores, lower and upper-lower-income households were more likely to consume unhealthy dietary patterns. Food environment and sociodemographic conditions within neighbourhoods may affect dietary behaviours. Food environment interventions and policies which improve access to healthy foods and restrict access to unhealthy foods may facilitate healthier diets and contribute to the prevention of NCDs.publishersversionpublishe

Avancées dans une réécriture de l'histoire de la transition du Jurassique au Crétacé dans le Mont Liban

The stratigraphic framework of the Upper Jurassic and Lower Cretaceous strata of Lebanon that dates back to Dubertret's publications required either consolidation or full revision. The preliminary results of our investigations in the Mount Lebanon region are presented here. We provide new micropaleontological and sedimentological information on the Salima Oolitic Limestones, which is probably an unconformity-bounded unit (possibly Early Valanginian in age), and the "Grès du Liban" (Barremian in age). Our revised bio- and holostratigraphic interpretations and the new age assignations lead us to emphasize the importance of the two hiatuses in the sedimentary record below and above the Salima, i.e., at the transition from the Jurassic to the Cretaceous.Le canevas stratigraphique du Jurassique supérieur et du Crétacé inférieur du Liban date des publications anciennes de Dubertret et aurait donc besoin d'être soit toiletté et consolidé, soit révisé de fond en comble. Les résultats préliminaires de nos recherches dans la région du Mont Liban sont exposés ici. Nous fournissons des données micropaléontologiques et sédimentologiques inédites sur les Calcaires oolithiques de Salima, qui constituent vraisemblablement une unité lithostratigraphique particulière, une "UBU", car encadrée par deux discontinuités (probablement d'âge Valanginien inférieur), et sur le Grès du Liban (d'âge barrémien). Nos nouvelles interprétations bio- et holostratigraphiques, ainsi que nos nouvelles attributions chronostratigraphiques, nous permettent de souligner l'importance des deux lacunes sédimentaires encadrant les Calcaires oolithiques de Salima, c'est-à-dire des lacunes significatives situées dans l'intervalle de transition du Jurassique au Crétacé

Geospatial Distribution of Age-Adjusted Incidence of the Three Major Types of Pediatric Cancers and Waterborne Agrichemicals in Nebraska

This study was conducted to examine, at the county level, the relationship between pediatric cancer incidence rate and atrazine and nitrate mean concentrations in surface and groundwater. A negative binomial regression analysis was performed to investigate the association between central nervous system (CNS) tumors, leukemia, lymphoma, and atrazine and nitrate mean concentrations in groundwater. The age-adjusted brain and other CNS cancer incidence was higher than the national average in 63% of the Nebraska counties. After controlling for the counties socio-economic status and nitrate concentrations in groundwater, counties with groundwater atrazine concentrations above 0.0002 μg/L had a higher incidence rate for pediatric cancers (brain and other CNS, leukemia, and lymphoma) compared to counties with groundwater atrazine concentrations in the reference group (0.0000–0.0002 μg/L). Additionally, compared to counties with groundwater nitrate concentrations between 0 and 2 mg/L (reference group), counties with groundwater nitrate concentrations between 2.1 and 5 mg/L (group 2) had a higher incidence rate for pediatric brain and other CNS cancers (IRR = 8.39; 95% CI: 8.24–8.54), leukemia (IRR = 7.35; 95% CI: 7.22–7.48), and lymphoma (IRR = 5.59; CI: 5.48–5.69) after adjusting for atrazine groundwater concentration and the county socioeconomic status. While these findings do not indicate a causal relationship, because other contaminants or cancer risk factors have not been accounted for, they suggest that atrazine and nitrate may pose a risk relative to the genesis of pediatric brain and CNS cancers, leukemia, and lymphoma

Advanced EFL learners' beliefs about language learning and teaching: a comparison between grammar, pronunciation, and vocabulary

This paper reports on the results of a study exploring learners’ beliefs on the learning and teaching of English grammar, pronunciation and vocabulary at tertiary level. While the importance of learners’ beliefs on the acquisition process is generally recognized, few studies have focussed on and compared learners’ views on different components of the language system. A questionnaire containing semantic scale and Likert scale items probing learners’ views on grammar, pronunciation and vocabulary was designed and completed by 117 native speakers of Dutch in Flanders, who were studying English at university. The analysis of the responses revealed that (i) vocabulary was considered to be different from grammar and pronunciation, both in the extent to which an incorrect use could lead to communication breakdown and with respect to the learners’ language learning strategies, (ii) learners believed in the feasibility of achieving a native-like proficiency in all three components, and (iii) in-class grammar, pronunciation and vocabulary exercises were considered to be useful, even at tertiary level. The results are discussed in light of pedagogical approaches to language teaching

Developing the Agile Implementation Playbook for Integrating Evidence-Based Health Care Services into Clinical Practice

Problem: Despite the more than $32 billion the National Institutes of Health has invested annually, evidence-based health care services are not reliably implemented, sustained, or distributed in health care delivery organizations, resulting in suboptimal care and patient harm. New organizational approaches and frameworks that reflect the complex nature of health care systems are needed to achieve this goal. Approach: To guide the implementation of evidence-based health care services at their institution, the authors used a number of behavioral theories and frameworks to develop the Agile Implementation (AI) Playbook, which was finalized in 2015. The AI Playbook leverages these theories in an integrated approach to selecting an evidence-based health care service to meet a specific opportunity, rapidly implementing the service, evaluating its fidelity and impact, and sustaining and scaling up the service across health care delivery organizations. The AI Playbook includes an interconnected eight-step cycle: (1) identify opportunities; (2) identify evidence-based health care services; (3) develop evaluation and termination plans; (4) assemble a team to develop a minimally viable service; (5) perform implementation sprints; (6) monitor implementation performance; (7) monitor whole system performance; and (8) develop a minimally standardized operating procedure. Outcomes: The AI Playbook has helped to improve care and clinical outcomes for intensive care unit survivors and is being used to train clinicians and scientists in AI to be quality improvement advisors. Next Steps: The authors plan to continue disseminating the details of the AI Playbook and illustrating how health care delivery organizations can successfully leverage it

Predictors of Nodal and Metastatic Failure in Early Stage Non-Small Cell Lung Cancer after Stereotactic Body Radiation Therapy

Introduction/Background Many early-stage non-small cell lung cancer (ES-NSCLC) patients undergoing stereotactic body radiation therapy (SBRT) develop metastases, which is associated with poor outcomes. We sought to identify factors predictive of metastases after lung SBRT and created a risk stratification tool. Materials and Methods We included 363 patients with ES-NSCLC who received SBRT; median follow-up was 5.8 years. The following patient and tumor factors were retrospectively analyzed for their association with metastases (defined as nodal and/or distant failure): sex; age; lobe involved; centrality; previous NSCLC; smoking status; gross tumor volume (GTV); T-stage; histology; dose; minimum, maximum, and mean GTV dose; and parenchymal lung failure. A metastasis risk-score linear-model using beta coefficients from a multivariate Cox model was built. Results A total of 111/406 (27.3%) lesions metastasized. GTV volume and dose were significantly associated with metastases on univariate and multivariate Cox proportional hazards modeling (p<0.001 and HR=1.02 per mL, p<0.05 and HR=0.99 per Gy, respectively). Histology, T-stage, centrality, lung parenchymal failures, and previous NSCLC were not associated with development of metastasis. A metastasis risk-score model using GTV volume and prescription dose was built: [risk score=(0.01611 x GTV)–(0.00525 x dose (BED10))]. Two risk-score cutoffs separating the cohort into low-, medium-, and high-risk subgroups were examined. The risk-score identified significant differences in time to metastases between low-, medium-, and high-risk patients (p<0.001), with 3-year estimates of 81.1%, 63.8%, and 38%, respectively. Conclusion GTV volume and radiation dose are associated with time to metastasis and may be used to identify patients at higher risk of metastasis after lung SBRT

SARS-CoV-2 anti-spike antibody levels following second dose of ChAdOx1 nCov-19 or BNT162b2 in residents of long-term care facilities in England (VIVALDI)

General population studies have shown strong humoral response following SARS-CoV-2 vaccination with subsequent waning of anti-spike antibody levels. Vaccine-induced immune responses are often attenuated in frail and older populations, but published data are scarce. We measured SARS-CoV-2 anti-spike antibody levels in Long-Term Care Facility residents and staff following second vaccination dose with Oxford-AstraZeneca or Pfizer-BioNTech. Vaccination elicited robust antibody responses in older residents, suggesting comparable levels of vaccine-induced immunity to that in the general population. Antibody levels are higher after Pfizer-BioNTech vaccination but fall more rapidly compared to Oxford-AstraZeneca recipients and are enhanced by prior infection in both groups

Functional single-cell analysis of T-cell activation by supported lipid bilayer-tethered ligands on arrays of nanowells

Supported lipid bilayers are an important biomolecular tool for characterizing immunological synapses. Immobilized bilayers presenting tethered ligands on planar substrates have yielded both spatio-temporal and structural insights into how T cell receptors (TCRs) reorganize during the initial formation of synapses upon recognition of peptide antigens bound to major histocompatibility complex (MHC) molecules. The prototypical configuration of these assays, however, limits the extent to which the kinetics and structure of the supramolecular activation clusters of the synapse (that occur in seconds or minutes) can be related to subsequent complex cellular responses, such as cytokine secretion and proliferation, occurring over hours to days. Here we describe a new method that allows correlative measures of both attributes with single-cell resolution by using immobilized lipid bilayers and tethered ligands on the surface of dense arrays of subnanoliter wells. This modification allows each nanowell to function as an artificial antigen-presenting cell (APC), and the synapses formed upon contact can be imaged by fluorescence microscopy. We show that the lipid bilayers remain stable and mobile on the surface of the PDMS, and that modifying the ligands tethered to the bilayer alters the structure of the resulting synapses in expected ways. Finally, we demonstrate that this approach allows the subsequent characterization of secreted cytokines from the activated human T cell clones by microengraving in both antigen- and pan-specific manners. This new technique should allow detailed investigations on how biophysical and structural aspects of the synapse influence the activation of individual T cells and their complex functional responses.National Institute of Allergy and Infectious Diseases (U.S.) (5P01AI045757)National Cancer Institute (U.S.) (Cancer Center Support (Core) Grant P30-CA14051

Amber and the Cretaceous Resinous Interval

Amber is fossilized resin that preserves biological remains in exceptional detail, study of which has revolutionized understanding of past terrestrial organisms and habitats from the Early Cretaceous to the present day. Cretaceous amber outcrops are more abundant in the Northern Hemisphere and during an interval of about 54 million years, from the Barremian to the Campanian. The extensive resin production that generated this remarkable amber record may be attributed to the biology of coniferous resin producers, the growth of resiniferous forests in proximity to transitional sedimentary environments, and the dynamics of climate during the Cretaceous. Here we discuss the set of interrelated abiotic and biotic factors potentially involved in resin production during that time. We name this period of mass resin production by conifers during the late Mesozoic, fundamental as an archive of terrestrial life, the `Cretaceous Resinous Interval (CREI).This work was supported by the Spanish Ministerio de Ciencia, Innovación y Universidades [research agreement CRE CGL2017-84419 AEI/FEDER, UE] and by the Consejería de Industria, Turismo, Innovación, Transporte y Comercio of the Gobierno de Cantabria through the public enterprise EL SOPLAO S.L. [research agreement #20963 with University of Barcelona and research contract Ref. VAPC 20225428 to CN-IGME CSIC, both 2022–2025]; the Conselho Nacional de Pesquisa (Brazil) [research grand PQ 304529/19–2]; National Geographic Global Exploration Fund Northern Europa [research agreement GEFNE 127-14]; Deutsche Forschungsgemeinschaft (DFG) [research agreement SO 894/6-1]; VolkswagenStiftung [research agreement 90946]; the Secretary of Universities and Research (Government of Catalonia) and by the Horizon 2020 program of research and innovation of the European Union under the Marie-Curie [research contract no. 801370, Beatriu de Pinós]; the Secretary of Universities and Research (Government of Catalonia) and the European Social Fund [research contract 2021FI_B2 00003]; this work is a contribution to the grant RYC2021-032907-I, funded by the MCIN/AEI/10.13039/501100011033 and by the European Union «NextGenerationEU»/PRTR; and the National Agency for Research and Development (ANID) Scholarship Program [BECAS CHILE 2020-Folio 72210321].Abstract Keywords 1. Introduction 2. Definition of the Cretaceous Resinous Interval 3. Conditional factors on resin production and preservation 3.1. Abiotic factors 3.1.1. Atmospheric gas composition, temperature, and wildfires 3.1.2. Volcanism and changes in sea level 3.1.3. Oceanic physicochemical properties and hurricanes 3.1.4. Climatic overview throughout the CREI 3.2. Biotic factors 4. Present limitations and future directions 5. Conclusions Funding Author contributions Declaration of Competing Interest Acknowledgements Appendix A. Supplementary data Data availability Reference