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One of the factors that threatens the sustainability of rural areas is the hegemonic agroindustrial model with obvious environmental and social impacts which dramatically limits rural life. The study draws attention to the opportunities offered by alternative agri-food systems based on agroecology and food sovereignty as cultural heritage to support sustainable local development. The results of the study demonstrate how the recovery and promotion of traditional ecological knowledge can help increase the capacity of socio-ecological systems to cope with shocks and disruptions and maintain long-term resilience. At the same time, agro-ecological practises allow collective identities to emerge around characteristics of rural space, strengthening local life, focusing on the coevolution of the society-ecosystem of local identity. The case study analyzed in Romania counties shows that rural areas play a critical role in economic and social cohesion, in the resilience of regions and in the contribution of countless services in various local ecosystems, including food production, to their consolidation socio-economic prosperity, the ability to innovate, to achieve a sustainable and inclusive social economy. The types of policies promoted by Romania conceive agro-ecological practices as an intangible collective heritage with a significant potential for transformation towards local sustainability.

Smart tourism innovations are changing tourism. Tourists are increasingly demanding more authentic experiences and non-traditional accommodations (e.g., Airbnb) that offer closer connections to hosts and locals. Airbnb presents lodgings ranging from shared rooms and apartments to treehouses. Peer-to-peer accommodations create value for customers via reasonable prices, flexibility, ease of use, and local-guest interactive communication. Smart tourism has facilitated this new business ecosystem's development within the sharing economy. This study sought to examine guests' experiences in Bucharest Airbnb apartments and the main themes associated with these tourists' subjective well-being. The sample of 750 online reviews were analysed using Leximancer, which revealed five themes-apartment, stay, old, host, and nice (view)-and their positive outcomes-recommend(ation), thank you(s), and value (for money). The results reveal that hosts' friendliness contributes the most to guests' affective well-being, which has theoretical and practical implications for Romania's tourism industry.

The wine tourism developed in a growing manner in the last years contributing to the economic development of the wine regions of the world. The so called wine tourists seek for an authentic experience in the wineries based on the activities they develop during their visit and given by the region attributes. This research aims to emphasize the tourists’ experience in which relates the wine region of Dealu Mare, Prahova county and identifies the main advantages that this tourist area has regarding the agrotourism potential. The data were collected by applying a questionnaire (n=600) and the results were displayed using charts that show the behavior and activities undertaken by tourists during their visit in the wineries. Hence, the tourist’ behavior in which relates wine consumption and winery visitation has been outlined, also their preferences in terms of wine regions of Romania and abroad. The paper presents also some limitations in which relates the study area and the number of the respondents.

Summary: Background: Anti-COVID-19 hyperimmune immunoglobulin (hIG) can provide standardized and controlled antibody content. Data from controlled clinical trials using hIG for the prevention or treatment of COVID-19 outpatients have not been reported. We assessed the safety and efficacy of subcutaneous anti-COVID-19 hyperimmune immunoglobulin 20% (C19-IG20%) compared to placebo in preventing development of symptomatic COVID-19 in asymptomatic individuals with SARS-CoV-2 infection. Methods: We did a multicentre, randomized, double-blind, placebo-controlled trial, in asymptomatic unvaccinated adults (≥18 years of age) with confirmed SARS-CoV-2 infection within 5 days between April 28 and December 27, 2021. Participants were randomly assigned (1:1:1) to receive a blinded subcutaneous infusion of 10 mL with 1 g or 2 g of C19-IG20%, or an equivalent volume of saline as placebo. The primary endpoint was the proportion of participants who remained asymptomatic through day 14 after infusion. Secondary endpoints included the proportion of individuals who required oxygen supplementation, any medically attended visit, hospitalisation, or ICU, and viral load reduction and viral clearance in nasopharyngeal swabs. Safety was assessed as the proportion of patients with adverse events. The trial was terminated early due to a lack of potential benefit in the target population in a planned interim analysis conducted in December 2021. ClinicalTrials.gov registry: NCT04847141. Findings: 461 individuals (mean age 39.6 years [SD 12.8]) were randomized and received the intervention within a mean of 3.1 (SD 1.27) days from a positive SARS-CoV-2 test. In the prespecified modified intention-to-treat analysis that included only participants who received a subcutaneous infusion, the primary outcome occurred in 59.9% (91/152) of participants receiving 1 g C19-IG20%, 64.7% (99/153) receiving 2 g, and 63.5% (99/156) receiving placebo (difference in proportions 1 g C19-IG20% vs. placebo, −3.6%; 95% CI -14.6% to 7.3%, p = 0.53; 2 g C19-IG20% vs placebo, 1.1%; −9.6% to 11.9%, p = 0.85). None of the secondary clinical efficacy endpoints or virological endpoints were significantly different between study groups. Adverse event rate was similar between groups, and no severe or life-threatening adverse events related to investigational product infusion were reported. Interpretation: Our findings suggested that administration of subcutaneous human hyperimmune immunoglobulin C19-IG20% to asymptomatic individuals with SARS-CoV-2 infection was safe but did not prevent development of symptomatic COVID-19. Funding: Grifols.

During the last decades, the tourism market saw the growth of national and regional brands based on characters and places promoted through movies and TV series. One of the most notorious tourism brands based on fictional works is represented by Dracula. With a constantly expanding coverage on entertainment channels, Dracula became widely popular and strongly associated with Romania. However, its capitalization by national tourism actors lacks synergy and integration of spatial features. In this paper, we use an original cartographic approach combining the spatial distribution of Dracula attractions and online data regarding tourist behavior aimed to set up a decision-making toolkit for the enhancement of brand management. The results confirm the existence of a spatial pattern in the distribution and differentiation of Dracula attractions, which affects the overall tourist behavior and satisfaction. The paper provides several recommendations for national actors in order to upgrade the tourism management of Dracula's image.

Aims Vertebral body tethering (VBT) is a non-fusion technique to correct scoliosis. It allows correction of scoliosis through growth modulation (GM) by tethering the convex side to allow concave unrestricted growth similar to the hemiepiphysiodesis concept. The other modality is anterior scoliosis correction (ASC) where the tether is able to perform most of the correction immediately where limited growth is expected. Methods We conducted a retrospective analysis of clinical and radiological data of 20 patients aged between 9 and 17 years old, (with a 19 female: 1 male ratio) between January 2014 to December 2016 with a mean five-year follow-up (4 to 7). Results There were ten patients in each group with a total of 23 curves operated on. VBT-GM mean age was 12.5 years (9 to 14) with a mean Risser classification of 0.63 (0 to 2) and VBT-ASC was 14.9 years (13 to 17) with a mean Risser classification of 3.66 (3 to 5). Mean preoperative VBT-GM Cobb was 47.4° (40° to 58°) with a Fulcrum unbend of 17.4 (1° to 41°), compared to VBT-ASC 56.5° (40° to 79°) with 30.6 (2° to 69°)unbend. Postoperative VBT-GM was 20.3° and VBT-ASC Cobb angle was 11.2°. The early postoperative correction rate was 54.3% versus 81% whereas Fulcrum Bending Correction Index (FBCI) was 93.1% vs 146.6%. The last Cobb angle on radiograph at mean five years’ follow-up was 19.4° (VBT-GM) and 16.5° (VBT-ASC). Patients with open triradiate cartilage (TRC) had three over-corrections. Overall, 5% of patients required fusion. This one patient alone had a over-correction, a second-stage tether release, and final conversion to fusion. Conclusion We show a high success rate (95%) in helping children avoid fusion at five years post-surgery. VBT is a safe technique for correction of scoliosis in the skeletally immature patient. This is the first report at five years that shows two methods of VBT can be employed depending on the skeletal maturity of the patient: GM and ASC. Cite this article: Bone Jt Open 2022;3(2):123–129.

The aim of this study is to determine whether there is a benefit of using stereotactic radiosurgery (SRS) versus surgery or conventional external beam radiotherapy (cEBRT) for spinal oligometastatic disease in terms of tumor control, pain control, toxicity and morbidity. This systematic review was conducted by searching electronic databases such as Pubmed, Medline (Ovid) and Oxford Academic using an adapted version of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses” (PRISMA) checklist. Retrospective and prospective studies were identified and investigated for methods of treatment such as SRS, surgery and radiotherapy of spinal oligometastatic disease. Local Control rates, Overall Survival (OS) rates, Pain Response (PR) and toxicities were extracted to be investigated and compared. A study eligibility criterion was made to ensure that results were valid, statistically significant and relevant to the investigation. One hundred and five articles were relevant to oligometastatic disease with the mention of spinal metastases however 89 of these articles were excluded based on irrelevance to investigation, title, abstract and duplication. Sixteen full text articles were thoroughly screened including 9 of them in the review. For 601 patients the average one year local control rate was 89%, average one year overall survival rate was 88%, evidence of pain relief was present, and some patients suffered low grade toxicities. In conclusion, stereotactic radiosurgery is an excellent modality of treatment of spinal oligometastatic disease as local control rates, overall survival rates, pain response and toxicities indicate improved outcomes in comparison to studies that investigated the same factors with the treatment of surgery or cEBRT. However, there is a lack of data here to make statistically valid claims and require more studies & data to be analyzed and compared.

Increasing evidence suggests that prolonged antibiotic therapy in preterm infants is associated with increased mortality and morbidities, such as necrotizing enterocolitis (NEC), a devastating gastrointestinal pathology characterized by intestinal inflammation and necrosis. While a clinical correlation exists between antibiotic use and the development of NEC, the potential causality of antibiotics in NEC development has not yet been demonstrated. Here, we tested the effects of systemic standard-of-care antibiotic therapy for ten days on intestinal development in neonatal mice. Systemic antibiotic treatment impaired the intestinal development by reducing intestinal cell proliferation, villi height, crypt depth, and goblet and Paneth cell numbers. Oral bacterial challenge in pups who received antibiotics resulted in NEC-like intestinal injury in more than half the pups, likely due to a reduction in mucous-producing cells affecting microbial–epithelial interactions. These data support a novel mechanism that could explain why preterm infants exposed to prolonged antibiotics after birth have a higher incidence of NEC and other gastrointestinal disorders.

The analyse of land-use change has a meaningful importance in scholars research. Hence, the influence of the urbanisation beneath the conditions that lead to the increase of tourism activity in urban areas it is connected with the extinction of the land-use space. Given the fact that the development of urbanisation leads to tourism development, this paper aims to shape a model of urban growth for the city of Iaşi which emphasises the spatio-temporal growth of the city with impact on tourism growth. The data used was Corine Land Cover (CLC) for 2000 and 2006 years. The type of land use, the areas and the relationship of the driving factors were identified for further analysis. The methodology included Geographic Information System (GIS) spatial analysis and statistic functions of it. In order to obtain the model of urban growth which sustains the hypothesis that the urban increase leads to tourism development, an urban growth simulation was made through Pyhton language programming by cellular automata (CA) method.

Background The physiological function of ADTRP (androgen‐dependent tissue factor pathway inhibitor regulating protein) is unknown. We previously identified ADTRP as coregulating with and supporting the anticoagulant activity of tissue factor pathway inhibitor in endothelial cells in vitro. Here, we studied the role of ADTRP in vivo, specifically related to vascular development, stability, and function. Methods and Results Genetic inhibition of Adtrp produced vascular malformations in the low‐pressure vasculature of zebrafish embryos and newborn mice: dilation/tortuosity, perivascular inflammation, extravascular proteolysis, increased permeability, and microhemorrhages, which produced partially penetrant lethality. Vascular leakiness correlated with decreased endothelial cell junction components VE‐cadherin and claudin‐5. Changes in hemostasis in young adults comprised modest decrease of tissue factor pathway inhibitor antigen and activity and increased tail bleeding time and volume. Cell‐based reporter assays revealed that ADTRP negatively regulates canonical Wnt signaling, affecting membrane events downstream of low‐density lipoprotein receptor‐related protein 6 (LRP6) and upstream of glycogen synthase kinase 3 beta. ADTRP deficiency increased aberrant/ectopic Wnt/β‐catenin signaling in vivo in newborn mice and zebrafish embryos, and upregulated matrix metallopeptidase (MMP)‐9 in endothelial cells and mast cells (MCs). Vascular lesions in newborn Adtrp−/− pups displayed accumulation of MCs, decreased extracellular matrix content, and deficient perivascular cell coverage. Wnt‐pathway inhibition reversed the increased mmp9 in zebrafish embryos, demonstrating that mmp9 expression induced by Adtrp deficiency was downstream of canonical Wnt signaling. Conclusions Our studies demonstrate that ADTRP plays a major role in vascular development and function, most likely through expression in endothelial cells and/or perivascular cells of Wnt‐regulated genes that control vascular stability and integrity.

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In this paper, we review the use of satellite-based remote sensing in combination with in situ data to inform Earth surface modelling. This involves verification and optimization methods that can handle both random and systematic errors and result in effective model improvement for both surface monitoring and prediction applications. The reasons for diverse remote sensing data and products include (i) their complementary areal and temporal coverage, (ii) their diverse and covariant information content, and (iii) their ability to complement in situ observations, which are often sparse and only locally representative. To improve our understanding of the complex behavior of the Earth system at the surface and sub-surface, we need large volumes of data from high-resolution modelling and remote sensing, since the Earth surface exhibits a high degree of heterogeneity and discontinuities in space and time. The spatial and temporal variability of the biosphere, hydrosphere, cryosphere and anthroposphere calls for an increased use of Earth observation (EO) data attaining volumes previously considered prohibitive. We review data availability and discuss recent examples where satellite remote sensing is used to infer observable surface quantities directly or indirectly, with particular emphasis on key parameters necessary for weather and climate prediction. Coordinated high-resolution remote-sensing and modelling/assimilation capabilities for the Earth surface are required to support an international application-focused effort.

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Abstract Background Infections with SARS-CoV-2 have a pronounced impact on the gastrointestinal tract and its resident microbiome. Clear differences between severe cases of infection and healthy individuals have been reported, including the loss of commensal taxa. We aimed to understand if microbiome alterations including functional shifts are unique to severe cases or a common effect of COVID-19. We used high-resolution systematic multi-omic analyses to profile the gut microbiome in asymptomatic-to-moderate COVID-19 individuals compared to a control group. Results We found a striking increase in the overall abundance and expression of both virulence factors and antimicrobial resistance genes in COVID-19. Importantly, these genes are encoded and expressed by commensal taxa from families such as Acidaminococcaceae and Erysipelatoclostridiaceae, which we found to be enriched in COVID-19-positive individuals. We also found an enrichment in the expression of a betaherpesvirus and rotavirus C genes in COVID-19-positive individuals compared to healthy controls. Conclusions Our analyses identified an altered and increased infective competence of the gut microbiome in COVID-19 patients. Video Abstract

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.