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Abstract Background Myotonic dystrophy is an inherited disease characterized by progressive muscle weakness and myotonia. It is a multisystemic disorder that affects different parts of the body, including the eye. Dysfunction of ocular muscles, ptosis and cataract are the most common ophthalmologic manifestations, but it can also present with pigmentary changes in the retina. This report presents and discusses an unusual case of a pigmented pattern dystrophy simulating a fundus flavimaculatus in a patient with myotonic dystrophy. Case presentation We present a case of a woman with a history of myotonic dystrophy and complaints of progressive vision loss who presented bilateral retinal pigmentary changes in posterior pole and midperiphery. The characteristics and distribution of pigmented deposits, as well as ancillary tests, showed a retinal phenotype compatible with a multifocal pattern dystrophy or a fundus flavimaculatus. Conclusions There are a few publications about retinal disorders in patients with myotonic dystrophy. When macular area is affected it tends to adopt a patterned-shape defined as butterfly dystrophy or reticular dystrophy. To our knowledge, this is the first report of a patient with myotonic dystrophy and multifocal pattern dystrophy or fundus flavimaculatus.

While many instructors have reservations against Wikipedia use in academic settings, editing Wikipedia teaches students valuable writing, editing, and critical thinking skills. Wikipedia assignments align with the community of inquiry framework, which focuses on the elements needed for a successful online learning experience. We report on a faculty mentoring network, created by WikiProject Limnology and Oceanography, which helped 14 instructors with little to no prior experience implement a Wikipedia assignment in their classes. We found that Wikipedia assignments increase students’ motivation to produce high quality work and enhance their awareness of reliable scientific sources. Wikipedia assignments can be comparable to other writing assignments in length and complexity, but have a far wider audience than a traditional research paper. Participants in our mentoring network reported challenges with implementing this new type of assignment, and here, we share resources and solutions to those reported barriers.

Drug hypersensitivity reactions (DHRs) to intravenous drugs can be severe and might leave patients and doctors in a difficult position where an essential treatment or intervention has to be suspended. Even if virtually any intravenous medication can potentially trigger a life-threatening DHR, chemotherapeutics, biologics, and antibiotics are amongst the intravenous drugs most frequently involved in these reactions. Admittedly, suspending such treatments may negatively impact the survival outcomes or the quality of life of affected patients.Delabeling pathways and rapid drug desensitization (RDD) can help reactive patients stay on first-choice therapies instead of turning to less efficacious, less cost-effective, or more toxic alternatives. However, these are high-complexity and high-risk techniques, which usually need expert teams and allergy-specific techniques (skin testing, in vitro testing, drug provocation testing) to ensure safety, an accurate diagnosis, and personalized management. Unfortunately, there are significant inequalities within and among countries in access to allergy departments with the necessary expertise and resources to offer these techniques and tackle these DHRs optimally.The main objective of this consensus document is to create a great benefit for patients worldwide by aiding allergists to expand the scope of their practice and support them with evidence, data, and experience from leading groups from around the globe.This statement of the Drug Hypersensitivity Committee of the World Allergy Organization (WAO) aims to be a comprehensive practical guide on the technical aspects of implementing acute-onset intravenous hypersensitivity delabeling and RDD for a wide range of drugs. Thus, the manuscript does not only focus on clinical pathways. Instead, it also provides guidance on topics usually left unaddressed, namely, internal validation, continuous quality improvement, creating a healthy multidisciplinary environment, and redesigning care (including a specific supplemental section on a real-life example of how to design a dedicated space that can combine basic and complex diagnostic and therapeutic techniques in allergy).

BackgroundChildhood overweight and obesity have become major global health problems and are negatively related with the cardiorespiratory fitness (CRF) level in school children and adolescents. Exercise, specifically multicomponent training, is effective for CRF improvement, but the main challenge is to ensure adherence to exercise in children with overweight and obesity. Therefore, new ways of exercising that are more attractive and motivational for this population are needed and playing or training with active video games (AVGs) has been proposed as an effective alternative because they require full-body movement and therefore increase energy expenditure. ObjectiveThe main aim of this study was to investigate the effects of an AVG intervention combined with multicomponent training on CRF at maximal and submaximal intensities in children with overweight or obesity. MethodsWe recruited 28 children (13 girls and 15 boys) aged 9 to 11 years with overweight or obesity from medical centers and divided them into 2 groups, an intervention group (n=20) that participated in a 5-month supervised AVG exercise program combined with multicomponent exercise, and a control group (n=8) that continued daily activities without modification. A maximal stress test to measure CRF using a walking-graded protocol with respiratory gas exchange was performed by the participants. ResultsThe AVG group showed a significant decrease in heart rate and oxygen uptake for the same intensities in the submaximal stages of the maximal treadmill test, as well as a lower oxygen uptake percentage according to the individual maximal oxygen uptake, whereas the control group did not show overall changes. No change in the peak oxygen uptake (VO2peak) was found. ConclusionsA 5-month AVG intervention combined with multicomponent exercise had positive effects on CRF at submaximal intensity, showing a lower heart rate and oxygen uptake at the same intensities and displaying a lower oxygen uptake percentage according to the individual (VO2peak). Greater benefits were found in children with the highest fat percentage. Trial RegistrationClinicalTrials.gov NCT04418713; https://clinicaltrials.gov/show/NCT04418713

Additive manufacturing (AM) alternative technologies, including Fused Filament Fabrication (FFF), offer the possibility to produce both prototypes and low-volume production metallic components. This is the first time that AISI M2 high-speed steel powder is processed by FFF, achieving near full density in a complementary way to Powder Injection moulding (PIM), yet reducing the investment cost and the lead time. A completely optimized FFF process is presented: from the design of a printable highly filled metallic filament that can be fed into conventional 3D printers, to high-quality green parts that are properly debound and sintered. The final specimens (99.6% densified) are thermally treated (one quenching and two tempering) and, then, evaluated in terms of scanning electron microscopy (SEM), X-ray diffraction (XRD) analysis and mechanical characterization (hardness and wear resistance). The effect of the processing technology and the heat treatments are discussed, validating the feasibility of FFF to develop customized high-speed tools with superb performance at a competitive cost.

Abstract Antigen-adjuvant conjugation is known to enhance antigen-specific T-cell production in vaccine models, but scalable methods are required to generate site-specific conjugation for clinical translation of this technique. We report the use of the cell-free protein synthesis (CFPS) platform as a rapid method to produce large quantities (> 100 mg/L) of a model antigen, ovalbumin (OVA), with site-specific incorporation of p-azidomethyl-l-phenylalanine (pAMF) at two solvent-exposed sites away from immunodominant epitopes. Using copper-free click chemistry, we conjugated CpG oligodeoxynucleotide toll-like receptor 9 (TLR9) agonists to the pAMF sites on the mutant OVA protein. The OVA-CpG conjugates demonstrate enhanced antigen presentation in vitro and increased antigen-specific CD8+ T-cell production in vivo. Moreover, OVA-CpG conjugation reduced the dose of CpG needed to invoke antigen-specific T-cell production tenfold. These results highlight how site-specific conjugation and CFPS technology can be implemented to produce large quantities of covalently-linked antigen-adjuvant conjugates for use in clinical vaccines.

Background Skeletal muscle is one of the main components of lean soft tissue mass (LSTM). Low levels in children affect locomotion, posture, and increase the risk of metabolic syndrome. Aim (1) To evaluate the association between muscle cross-sectional area (MCSA) of the lower left leg measured by peripheral quantitative computed tomography (pQCT) and total LSTM; namely, total left leg and left lower leg LSTM assessed by dual-energy X-ray absorptiometry (DXA) in a group of children, (2) to examine if MCSA is a predictor of LSTM, (3) to determine the ability of pQCT to identify children with low LSTM. Subjects and methods Lower left leg MCSA and LSTM were measured using pQCT and DXA, respectively, in 396 children. Results Statistically significant positive correlations were found between the lower leg MCSA – total LSTM (r² = 0.789), total leg LSTM (r² = 0.79), and lower leg LSTM (r² = 0.791) (p

Abstract Background Obesity in children is one of the most severe public health challenges of the current century and Type 2 Diabetes Mellitus (T2DM) frequency is also escalating. More so, the importance of process evaluation (PE) in complex interventions is increasingly recognized. The present review, aims to identify the effectiveness in terms of body composition parameters in a generation of articles to prevent obesity and T2DM in children. We hypothesise that those studies reporting PE applying the latest implementation guidelines suggested by the researchers would potentially show positive changes in body composition compared to those not reporting it. Additionally, we will evaluate the implementation degree of PE in those articles considering it and describe the PE subcomponents. Lastly, we aim to assess the intervention target used and its results. Methods A literature review was performed in parallel by 2 independent reviewers. A final number of 41 studies were selected for inclusion criteria. Results Meta-analysis of BMI and zBMI found non-significant effects of the proposed interventions. Sub-group analysis revealed only a significant effect in studies which performed PE. Moreover, PE was reported in 42% effective studies and 57% non-effective studies. Fidelity and satisfaction were the most implemented PE subcomponents, although there was a generally low grade of PE use (7/41). The highest proportion of effectiveness (83%) was shown in interventions of physical activity alone while the intervention most used was 3-arm target (diet, PA and BS). Conclusions Overall, obesity and T2DM prevention studies included in this review are not effective in terms of BMI and zBMI. Those studies performing PE reported to be effective in terms of BMI, while studies not reporting PE did not have positive results in terms of BMI and zBMI. In addition, none of the intervention studies included all PE indicators and most studies, which included PE in their interventions, did not provide full report of the PE components, according to the guidelines used for the present review. PROSPERO registration number: CRD42018093667.

Objectives: The World Health Organization pre-qualified single-dose typhoid conjugate vaccine (TCV) and requested data on co-administration with routine vaccines. The co-administration of Typbar TCV (Bharat Biotech International) with routine group A meningococcal conjugate vaccine (MCV-A) and measles–rubella (MR) vaccine was tested. Methods: This was a double-blind, randomized controlled trial performed in Ouagadougou, Burkina Faso. Children were recruited at the 15-month vaccination visit and were assigned randomly (1:1:1) to three groups. Group 1 children received TCV plus control vaccine (inactivated polio vaccine) and MCV-A 28 days later; group 2 children received TCV and MCV-A; group 3 children received MCV-A and control vaccine. Routine MR vaccine was administered to all participants. Safety was assessed at 0, 3, and 7 days after immunization, and unsolicited adverse events and serious adverse events were assessed for 28 days and 6 months after immunization, respectively. Results: A total of 150 children were recruited and vaccinated. Solicited symptoms were infrequent and similar for TCV and control recipients, as were adverse events (group 1, 61.2%; group 2, 64.0%; group 3, 68.6%) and serious adverse events (group 1, 2.0%; group 2, 8.0%; group 3, 5.9%). TCV generated robust immunity without interference with MCV-A vaccine. Conclusions: TCV can be safely co-administered at 15 months with MCV-A without interference. This novel study on the co-administration of TCV with MCV-A provides data to support large-scale uptake in sub-Saharan Africa.

The management of educational policies is a complex issue. There are complexities related to the country’s organizational system (competencies delegated by different areas in some cases), and to the limited resources in the educational system. In addition, there are many variables that need to be managed: ICT resources, special educational needs, human resources available, the socioeconomic characteristics of each district, etc. These types of issues are similar to those dealt with by strategic intelligence management. In this field, commonly included within innovation management, methodological frameworks are established that enable collection and consolidation of data from various sources and their subsequent exploitation to enhance decision-making based on previously identified needs. This article presents the details of a pilot plan aimed at implementing a framework for strategic intelligence management in the educational management system of the Community of Madrid (Spain). These intelligence systems are difficult to deploy in educational organizations that have highly fragmented management as in the case described in our pilot plan, although their implementation leads to more correct and agile decision-makings. This paper describes the steps carried out to define the new management platform requirements, its technical implementation issues, and the validation results that demonstrate its functional validity and acceptance by end-users participating in the described pilot project.

Septoria tritici blotch (STB) is a devastating foliar disease affecting worldwide wheat production. Here, the authors report a cysteine-rich receptor-like kinase that can confer resistance to Zymoseptoria tritici, the pathogen that causes STB, and slow penetration and intercellular growth of the pathogen.

Computer science education efforts are expanding across the globe to equip students with the necessary computing skills for today's digital world. However, preparing students to become literate in computing activities requires the training of tens of thousands of teachers in computer science. The discrepancy between student needs and teacher preparation in computer science has raised questions of quality teachers, particularly for teachers who do not possess adequate content or pedagogical knowledge to teach computer science efficiently. To address this issue, we designed an instrument to measure knowledge needed to teach computer science (i.e., computer science pedagogical content knowledge). Results exhibited that our instrument measured aspects of teachers' computer science pedagogical content knowledge; however, teachers' prior background in teaching did not influence their performance. We discuss implications for future research and practice.

We employ the equal-time formulation of quantum field theory to derive effective kinetic theories, first for a weakly coupled non-relativistic Bose gas, and then for a strongly correlated system of self-interacting $N$-component fields. Our results provide the link between state-of-the-art measurements of equal-time effective actions using quantum simulator platforms, as employed in [Phys. Rev. X 10, 011020 (2020); Nat. Phys. 16, 1012 (2020)], and observables underlying effective kinetic or hydrodynamic descriptions. New non-perturbative approximation schemes can be developed and certified this way, where the a priori time-local formulation of the equal-time effective action has crucial advantages over the conventional closed-time-path approach which is non-local in time.

Los avances sociales y legislativos en pro de la igualdad de las personas LGBTI+ han conducido a una normalización de la convivencia y la reducción de la desigualdad a la que se enfrentan. Sin embargo, las manifestaciones sutiles y explícitas de actitudes negativas persisten en nuestros días, provocando nefastas consecuencias individuales y sociales. Por ello, el presente estudio aporta conocimiento acerca de estas actitudes, así como de los factores que pueden contribuir a su atenuación o amplificación a través de tres objetivos: (i) explorar el conocimiento acerca de las personas trans, por ser un término menos presente en el imaginario colectivo; (ii) determinar el nivel de actitudes negativas hacia las personas trans y personas con diversidad afectivo-sexual y establecer la relación entre ambos constructos; (iii) estudiar diferencias en las actitudes atendiendo a variables ideológicas como la orientación política y la orientación a la dominancia social, el contacto intergrupal, la formación, el género y edad. En el estudio, con un diseño mixto cualitativo-cuantitativo, participaron 97 personas de Andalucía Occidental, Medad = 31.1, Dt = 11. Los resultados mostraron que hay un conocimiento general sobre la transexualidad, y que el nivel de actitudes negativas hacia las personas trans y con diversidad afectivo-sexual no es elevado. Se encuentra, sin embargo, que las actitudes más negativas se producen en participantes con ideología de derecha, mayor orientación a la dominancia social y menor contacto intergrupal. Los hombres, en comparación con las mujeres, mostraron mayor prejuicio en todas las dimensiones evaluadas. Ni la edad, ni haber recibido formación relacionada, produjeron diferencias en el nivel de actitudes negativas. En conjunto, los resultados contribuyen a conocer la percepción acerca de la transexualidad, y los factores que podrían producir un aumento o disminución del prejuicio hacia las personas LGBTI+.

Fusaric acid (FA) is one of the first secondary metabolites isolated from phytopathogenic fungi belonging to the genus Fusarium. This molecule exerts a toxic effect on plants, rhizobacteria, fungi and animals, and it plays a crucial role in both plant and animal pathogenesis. In plants, metal chelation by FA is considered one of the possible mechanisms of action. Here, we evaluated the effect of different nitrogen sources, iron content, extracellular pH and cellular signalling pathways on the production of FA siderophores by the pathogen Fusarium oxysporum (Fol). Our results show that the nitrogen source affects iron chelating activity and FA production. Moreover, alkaline pH and iron limitation boost FA production, while acidic pH and iron sufficiency repress it independent of the nitrogen source. FA production is also positively regulated by the cell wall integrity (CWI) mitogen-activated protein kinase (MAPK) pathway and inhibited by the iron homeostasis transcriptional regulator HapX. Collectively, this study demonstrates that factors promoting virulence (i.e., alkaline pH, low iron availability, poor nitrogen sources and CWI MAPK signalling) are also associated with increased FA production in Fol. The obtained new insights on FA biosynthesis regulation can be used to prevent both Fol infection potential and toxin contamination.

Jesús Díez-Manglano,1,2 María Berges Vidal,2 Lucía Martínez Barredo,3 Beatriz Poblador-Plou,2 Antonio Gimeno-Miguel,2 Pilar Martínez Heras,3 Alexandra Prados-Torres2 1Internal Medicine Department, Royo Villanova Hospital, Zaragoza, Spain; 2EpiChron Research Group, Aragon Health Sciences Institute, IIS Aragón, REDISSEC, Zaragoza, Spain; 3Internal Medicine Department, Miguel Servet University Hospital, Zaragoza, SpainCorrespondence: Jesús Díez-Manglano Duquesa Villahermosa nº 163, 8º D, Zaragoza 50009, SpainTel +34976466910Fax +34976466919Email jdiez@aragon.esPurpose: To determine whether chronic obstructive pulmonary disease (COPD) is a risk factor for hip fracture and identify other factors associated with hip fracture.Patients and Methods: Observational nested case–control study was conducted in Aragon, Spain in 2010. We included COPD patients aged > 40 years, in the EpiChron cohort. Each COPD patient was matched for age, sex, and number of comorbidities with a control subject without COPD. Patients with an existing diagnosis of osteoporosis and those with hip fracture before 2011 were excluded. We collected baseline demographic, comorbidity, and pharmacological treatment data. During a 5-year follow-up period, we recorded the incidence of hip fracture. A logistic regression model was constructed to identify factors associated with hip fracture.Results: The study population consisted of 26,517 COPD patients and the same number of controls (median [interquartile range] age, 74 [17] years; women, 24.7%). Smoking and heart failure were more frequent in COPD patients, and obesity, hypertension, diabetes, dyslipidemia, stroke, arthritis, and visual or hearing impairment were less frequent (all p< 0.001). Consumption of benzodiazepines (p=0.037), bronchodilators (p< 0.001), and corticosteroids (p< 0.001) was higher in the COPD group, while that of beta-blockers and thiazides was lower (both p< 0.001). During follow-up, 898 (1.7%) patients experienced hip fracture, with no differences observed between COPD and control patients. Multivariate analysis revealed that independent of COPD status, age, female sex, chronic liver disease, heart failure, and benzodiazepine use were independently associated with a higher risk of hip fracture, and obesity with a lower risk. In COPD patients, use of inhaled anticholinergics was independently associated with hip fracture (OR, 1.390; 95% CI 1.134– 1.702; p=0.001).Conclusion: COPD is not a risk factor for a hip fracture within 5 years. The association between the use of inhaled anticholinergics and risk of hip fracture warrants further study.Keywords: chronic obstructive pulmonary disease, hip fracture, case–control study, incidence

Long-term hemodialysis (HD) patients are considered vulnerable and at high-risk of developing severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection due to their immunocompromised condition. Since COVID-19 associated mortality rates are higher in HD patients, vaccination is critical to protect them. The response towards vaccination against COVID-19 in HD patients is still uncertain and, in particular the cellular immune response is not fully understood. We monitored the humoral and cellular immune responses by analysis of the serological responses and Spike-specific cellular immunity in COVID-19-recovered and naïve HD patients in a longitudinal study shortly after vaccination to determine the protective effects of 1273-mRNA vaccination against SARS-CoV-2 in these high-risk patients. In naïve HD patients, the cellular immune response measured by IL-2 and IFN-ɣ secretion needed a second vaccine dose to significantly increase, with a similar pattern for the humoral response. In contrast, COVID-19 recovered HD patients developed a potent and rapid cellular and humoral immune response after the first vaccine dose. Interestingly, when comparing COVID-19 recovered healthy volunteers (HV), previously vaccinated with BNT162b2 vaccine to HD patients vaccinated with 1273-mRNA, these exhibited a more robust immune response that is maintained longitudinally. Our results indicate that HD patients develop strong cellular and humoral immune responses to 1273-mRNA vaccination and argue in favor of personalized immune monitoring studies in HD patients, especially if COVID-19 pre-exposed, to adapt COVID-19 vaccination protocols for this immunocompromised population.

Background Chikungunya virus (CHIKV) is a mosquito-borne pathogen, within the Alphavirus genus of the Togaviridae family, that causes ~1.1 million human infections annually. CHIKV uses Aedes albopictus and Aedes aegypti mosquitoes as insect vectors. Human infections can develop arthralgia and myalgia, which results in debilitating pain for weeks, months, and even years after acute infection. No therapeutic treatments or vaccines currently exist for many alphaviruses, including CHIKV. Targeting the phagocytosis of CHIKV by macrophages after mosquito transmission plays an important role in early productive viral infection in humans, and could reduce viral replication and/or symptoms. Methods To better characterize the transcriptional response of macrophages during early infection, we generated RNA-sequencing data from a CHIKV-infected human macrophage cell line at eight or 24 hours post-infection (hpi), together with mock-infected controls. We then calculated differential gene expression, enriched functional annotations, modulated intracellular signaling pathways, and predicted therapeutic drugs from these sequencing data. Results We observed 234 pathways were significantly affected 24 hpi, resulting in six potential pharmaceutical treatments to modulate the affected pathways. A subset of significant pathways at 24 hpi includes AGE-RAGE, Fc epsilon RI, Chronic myeloid leukemia, Fc gamma R-mediated phagocytosis, and Ras signaling. We found that the MAPK1 and MAPK3 proteins are shared among this subset of pathways and that Telmisartan and Dasatinib are strong candidates for repurposed small molecule therapeutics that target human processes. The results of our analysis can be further characterized in the wet lab to contribute to the development of host-based prophylactics and therapeutics.

The increased use of antineoplastic drugs has been associated with a rising number of hypersensitivity reactions to these drugs, which has led to a growth in the demand for assistance from allergy services. The involvement of an allergist is essential to ensure that these patients with hypersensitivity reactions continue to be able to receive appropriate first-line treatment. Chemotherapy and biological agents have specific handling requirements and all the allergy departments involved in the diagnosis and therapeutic management of patients reacting to these drugs should find the means to guarantee safety. There are currently several guidelines on the safe handling of hazardous drugs for healthcare workers. However, specific recommendations are lacking for reducing occupational exposure in staff working in the allergy departments and managing these drugs for the diagnosis and management of hypersensitivity reactions. This review article focuses on the safe handling strategy of the allergy department in the Ramón y Cajal University Hospital and provides details of its implementation and experience over 10 years. This protocol could improve the knowledge of safe handling of antineoplastic drugs in allergy procedures.

Motor competence (MC) as a multidimensional construct is influenced by motor, cognitive, emotional and social variables. It is also determined by schoolchildren interacting with their own context. Thus pre-adolescence is a sensitive stage in development when physical, emotional and cognitive changes are manifested. By taking this context in accountn, the perception of the social referents close to schoolchildren allows for a deeper understanding of the role and influence of all these variables in a broader MC concept. For this purpose, a qualitative study was conducted by discussion groups and semistructured interviews, respectively, for teachers and family members in Primary Education. The content analysis was carried out according to the main study dimensions, associated with the motor, cognitive, affective-emotional and social domains. Both family members and teachers point out that the affective-emotional level has a stronger impact on the development of motor skills than the motor level. For children to develop their MC, it is necessary to create appropriate contexts in which family members and teachers are the main agents of influence. In conclusion, assessing MC in the educational sphere must have a more comprehensive and broad approach. It is necessary to bear in mind a larger number of variables involved in schoolchildren's motor development to make the most objective assessment possible and, likewise, to promote facilitating environments that help their development.

Abstract Background A key step in domestication of the grapevine was the transition from separate sexes (dioecy) in wild Vitis vinifera ssp. sylvestris (V. sylvestris) to hermaphroditism in cultivated Vitis vinifera ssp. sativa (V. vinifera). It is known that V. sylvestris has an XY system and V. vinifera a modified Y haplotype (Yh) and that the sex locus is small, but it has not previously been precisely characterized. Results We generate a high-quality de novo reference genome for V. sylvestris, onto which we map whole-genome re-sequencing data of a cross to locate the sex locus. Assembly of the full X, Y, and Yh haplotypes of V. sylvestris and V. vinifera sex locus and examining their gene content and expression profiles during flower development in wild and cultivated accessions show that truncation and deletion of tapetum and pollen development genes on the X haplotype likely causes male sterility, while the upregulation of a Y allele of a cytokinin regulator (APRT3) may cause female sterility. The downregulation of this cytokinin regulator in the Yh haplotype may be sufficient to trigger reversal to hermaphroditism. Molecular dating of X and Y haplotypes is consistent with the sex locus being as old as the Vitis genus, but the mechanism by which recombination was suppressed remains undetermined. Conclusions We describe the genomic and evolutionary characterization of the sex locus of cultivated and wild grapevine, providing a coherent model of sex determination in the latter and for transition from dioecy to hermaphroditism during domestication.

Abstract Background Thymidine kinase 1 (TK1) is a pyrimidine salvage pathway enzyme that is up-regulated in malignant tissues and elevated in the serum of cancer patients. While TK1 has been well established as a tumor biomarker, little has been done to explore its potential as a tumor target. Recently, we reported the membrane expression of TK1 on malignant cells, but not on normal cells. This study explores the possible use of monoclonal antibodies for the targeting of membrane associated TK1 in lung, breast, colon and prostate cancer cells. Methods We generated and evaluated a panel of monoclonal antibodies against six different epitopes exposed in the tetrameric form of TK1. Antibodies were developed with hybridoma technology and validated with Western blot, siRNA TK1 knockdown, enzyme-linked immunosorbent assay (ELISA) and flow cytometry. The therapeutic potential of the antibodies was evaluated in vitro in antibody-dependent cell-mediated-cytotoxicity (ADCC) experiments. Results Binding of the antibodies to TK1 was confirmed by Western blot in purified recombinant protein, cancer serum, and cell lysate. After a TK1 knockdown was performed, a reduction of TK1 expression was observed with five antibodies. Using indirect ELISA, we identified 3B2E11, 9C10, 7H2, 3B4, 8G2 among the most sensitive antibodies (LOD = 10.73–66.9 pg/ml). Surface expression of TK1 on the membrane of various cancer cell lines was analyzed with flow cytometry. Antibodies 8G2, 3B4, 7HD and 5F7G11 detected TK1 on the membrane of various cancer cell lines, including lung, prostate, colon and breast. No significant binding was detected on normal lymphocytes. Increased cytolysis of lung (~ 70%. p = 0.0001), breast (~ 70%, p = 0.0461) and colon (~ 50% p = 0.0216) cancer cells by effector cells was observed when anti-TK1 antibodies were added during ADCC experiments. Conclusions The antibodies developed showed potential to be used to detect and target TK1 on the membrane of various tumor cells. The targeting of TK1 in malignant cells using monoclonal antibodies may be a feasible approach for the elimination of high TK1 expressing tumor cells.

Abstract Background Multicenter studies from Europe and the United States have developed specifically standardized questionnaires for assessing and comparing sedentary behavior, but they cannot be directly applied for South American countries. The aim of this study was to assess the reliability and validity of the South American Youth Cardiovascular and Environmental (SAYCARE) sedentary behavior questionnaire. Methods Children and adolescents from seven South American cities were involved in the test-retest reliability (children: n = 55; adolescents: n = 106) and concurrent validity (children: n = 93; adolescents: n = 94) studies. The SAYCARE sedentary behavior questionnaire was administered twice with two-week interval and the behaviors were parent-reported for children and self-reported for adolescents. Questions included time spent watching television, using a computer, playing console games, passive playing (only in children) and studying (only in adolescents) over the past week. Accelerometer was used for at least 3 days, including at least one weekend day. We compared values of sedentary time, using accelerometers, by quartiles of reported sedentary behavior time and their sum. Results The reliability of sedentary behavior time was moderate for children (rho ≥0.45 and k ≥ 0.40) and adolescents (rho ≥0.30). Comparisons between the questionnaire and accelerometer showed a low overall agreement, with the questionnaire systematically underreporting sedentary time in children (at least, − 332.6 ± 138.5 min/day) and adolescents (at least, − 399.7 ± 105.0 min/day). Conclusion The SAYCARE sedentary behavior questionnaire has acceptable reliability in children and adolescents. However, the findings of current study indicate that SAYCARE questionnaire is not surrogate of total sedentary time.

Abstract The genus Passiflora comprises a large group of plants popularly known as passionfruit, much appreciated for their exotic flowers and edible fruits. The species (∼500) are morphologically variable (e.g., growth habit, size, and color of flowers) and are adapted to distinct tropical ecosystems. In this study, we generated the genome of the wild diploid species Passiflora organensis Gardner by adopting a hybrid assembly approach. Passiflora organensis has a small genome of 259 Mbp and a heterozygosity rate of 81%, consistent with its reproductive system. Most of the genome sequences could be integrated into its chromosomes with cytogenomic markers (satellite DNA) as references. The repeated sequences accounted for 58.55% of the total DNA analyzed, and the Tekay lineage was the prevalent retrotransposon. In total, 25,327 coding genes were predicted. Passiflora organensis retains 5,609 singletons and 15,671 gene families. We focused on the genes potentially involved in the locus determining self‐incompatibility and the MADS‐box gene family, allowing us to infer expansions and contractions within specific subfamilies. Finally, we recovered the organellar DNA. Structural rearrangements and two mitoviruses, besides relics of other mobile elements, were found in the chloroplast and mt‐DNA molecules, respectively. This study presents the first draft genome assembly of a wild Passiflora species, providing a valuable sequence resource for genomic and evolutionary studies on the genus, and support for breeding cropped passionfruit species.

Sustainable intensification (SI) of agriculture is a promising strategy for boosting the capacity of the agricultural sector to meet the growing demands for food and non-food products and services in a sustainable manner. Assessing and quantifying the options for SI remains a challenge due to its multiple dimensions and potential associated trade-offs. We contribute to overcoming this challenge by proposing an approach for the ex-ante evaluation of SI options and trade-offs to facilitate decision making in relation to SI. This approach is based on the utilization of a newly developed SI metrics framework (SIMeF) combined with agricultural systems modelling. We present SIMeF and its operationalization approach with modelling and evaluate the approach’s feasibility by assessing to what extent the SIMeF metrics can be quantified by representative agricultural systems models. SIMeF is based on the integration of academic and policy indicator frameworks, expert opinions, as well as the Sustainable Development Goals. Structured along seven SI domains and consisting of 37 themes, 142 sub-themes and 1128 metrics, it offers a holistic, generic, and policy-relevant dashboard for selecting the SI metrics to be quantified for the assessment of SI options in diverse contexts. The use of SIMeF with agricultural systems modelling allows the ex-ante assessment of SI options with respect to their productivity, resource use efficiency, environmental sustainability and, to a large extent, economic sustainability. However, we identify limitations to the use of modelling to represent several SI aspects related to social sustainability, certain ecological functions, the multi-functionality of agriculture, the management of losses and waste, and security and resilience. We suggest advancements in agricultural systems models and greater interdisciplinary and transdisciplinary integration to improve the ability to quantify SI metrics and to assess trade-offs across the various dimensions of SI.

Childhood obesity is one of the main public health concerns in Europe. The aim was to identify possible risk factors associated with overweight/obesity in Spanish preschool and school-age children. The sample (1075 (50.7% girls) children aged 3 to 12) is part of the project ‘Alimentando el Cambio’ whose objective is to promote healthy lifestyles in schools. Child height and weight were measured, and parents filled out questionnaires related to the children’s lifestyle. There was a positive and significant association between sweetened beverage consumption and body mass index (BMI) z-score in both sexes and age groups. There was a negative and significant association between BMI z-score and dairy products in girls of both age groups. There was also a protective effect of regular nut consumption on overweight/obesity in girls 6–12 y. Night-time sleep during weekdays showed a negative association with BMI z-score for older boys and girls. A positive and significant association was found between total screen time and BMI z-score during weekdays. Regarding emotional well-being and self-esteem, having girls 6–12 y laughing and feeling happy and good about themselves in the last week was a protective factor against overweight/obesity. Childhood obesity prevention efforts may benefit from targeting these key risk factors.