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miRNAs are involved in the development of metabolic associated fatty liver disease (MAFLD) and nonalcoholic steatohepatitis (NASH). We aimed to evaluate modifications by prolonged-release pirfenidone (PR-PFD) on key hepatic miRNAs expression in a MAFLD/NASH model. First, male C57BL/6J mice were randomly assigned into groups and fed with conventional diet (CVD) or high fat and carbohydrate diet (HFD) for 16 weeks. At the end of the eighth week, HFD mice were divided in two and only one half was treated with 300 mg/kg/day of PR-PFD mixed with food. Hepatic expression of miRNAs and target genes that participate in inflammation and lipid metabolism was determined by qRT-PCR and transcriptome by microarrays. Increased hepatic expression of miR-21a-5p, miR-34a-5p, miR-122-5p and miR-103-3p in MAFLD/NASH animals was reduced with PR-PFD. Transcriptome analysis showed that 52 genes involved in lipid and collagen biosynthesis and inflammatory response were downregulated in PR-PFD group. The expression of Il1b , Tnfa , Il6 , Tgfb1 , Col1a1 , and Srebf1 were decreased in PR-PFD treated animals. MAFLD/NASH animals compared to CVD group showed modifications in gene metabolic pathways implicated in lipid metabolic process, inflammatory response and insulin resistance; PR-PFD reversed these modifications.

Approximately 90% of children with cancer live in low-income and middle-income countries (LMICs), where 5-year survival is lower than 20%. Treatment-related mortality in high-income countries is approximately 3–5%; however, in LMICs, treatment-related mortality has been reported in up to 45% of children with cancer. This study aimed to systematically explore the burden of treatment-related mortality in children with cancer in LMICs and to explore the association between country income level and treatment-related mortality. For this systematic review and meta-analysis we identified articles published between Jan 1, 2010, and June 22, 2021, describing treatment-related mortality in paediatric patients (aged 0–21 years) with cancer in LMICs. We searched PubMed, Trip, Web of Science, Embase, and the WHO Global Metric Index databases. The search was limited to full-text articles and excluded case reports (<10 patients) and haematopoietic stem-cell transplantation recipients. Two reviewers independently screened studies for eligibility, extracted data from included publications, and evaluated data quality. Random and mixed-effects models were used to estimate treatment-related mortality burden and trends. The Cochran-Q statistic was used to assess heterogeneity between studies. This study is registered on PROSPERO (CRD42021264849). Of 13 269 identified abstracts, 501 studies representing 68 351 paediatric patients with cancer were included. The treatment-related mortality estimate was 6·82% (95% CI 5·99–7·64), accounting for 30·9% of overall mortality (4437 of 14 358 deaths). Treatment-related mortality was inversely related to country income. Treatment-related mortality was 14·19% (95% CI 9·65–18·73) in low-income countries, 9·21% (7·93–10·49) in lower-middle-income countries, and 4·47% (3·42–5·53) in upper-middle-income countries (Cochran-Q 42·39, p<0·0001). In upper-middle-income countries, the incidence of treatment-related mortality decreased over time (slope –0·002, p=0·0028); however, outcomes remained unchanged in low-income (p=0·21) and lower-middle-income countries (p=0·16). Approximately one in 15 children receiving cancer treatment in LMICs die from treatment-related complications. Although treatment-related mortality has decreased in upper-middle-income countries over time, it remains unchanged in LMICs. There is an urgent need for targeted supportive care interventions to reduce global disparities in childhood cancer survival. American Lebanese Syrian Associated Charities and National Cancer Institute.

Societal Impact Statement Maize is one of the most consumed grains worldwide. Its production and international trade are expected to continue increasing because of its use as animal fodder and direct human food. Although maize's history spans millennia, in the last century it underwent significant changes due to genetic engineering, particularly during the Green Revolution. Due to maize's importance for current food security and energy production, it is fundamental to understand this engineering process to assess the implications of current styles of maize production for local and global landscapes, scientific institutions, and transnational networks of agricultural science. Summary This article aims to explain how Mexican agricultural expertise contributed to the development of cytogenetics as a specialized field in the study of the diversity of maize within the framework of the Green Revolution. To this end, the article follows the work of Mexican agronomist Takeo Ángel Kato Yamakake within the activities of the Inter‐American Maize Improvement Program (IMIP), formally established in 1960. By reconstructing the debate on the genetic implications of chromosomal structure and function, this study contributes to the historiography devoted to the role played by local experts in the classification, experimentation, and conservation of maize. The article is based on sources from Mexico and the United States, an interview with Kato, and the consultation of the database “Rockefeller Fellows. Individual Mobility Awards at Rockefeller‐endowed Organizations, 1914‐1970.” Kato's trajectory provides an overview of agronomy in Mexico and shows the relevance of transnational exchange in the establishment of plant cytogenetics. Kato's academic activity features collaborations with key figures such as Edwin Wellhausen, Albert Longley, Barbara McClintock, W. Gallinat, Czeslawa Prywer, and Almiro Blumenschein. A Green Revolution era quest to unravel the origin of maize as a way of perfecting its genetic manipulation fueled the interest in establishing cytogenetics in Mexico. However, the irruption of the molecular approach made the study of the position of chromosomal knobs less of a priority. Despite this, classical cytogenetics, under Kato's leadership, remains a field that contributed to the knowledge of the vegetal genome, even when the IMIP disappeared and the logic of the Green Revolution lost its centrality. Maize is one of the most consumed grains worldwide. Its production and international trade are expected to continue increasing because of its use as animal fodder and direct human food. Although maize's history spans millennia, in the last century it underwent significant changes due to genetic engineering, particularly during the Green Revolution. Due to maize's importance for current food security and energy production, it is fundamental to understand this engineering process to assess the implications of current styles of maize production for local and global landscapes, scientific institutions, and transnational networks of agricultural science.

Oligometastatic disease has been proposed as an intermediate state between localised and systemically metastasised disease. In the absence of randomised phase 3 trials, early clinical studies show improved survival when radical local therapy is added to standard systemic therapy for oligometastatic disease. However, since no biomarker for the identification of patients with true oligometastatic disease is clinically available, the diagnosis of oligometastatic disease is based solely on imaging findings. A small number of metastases on imaging could represent different clinical scenarios, which are associated with different prognoses and might require different treatment strategies. 20 international experts including 19 members of the European Society for Radiotherapy and Oncology and European Organisation for Research and Treatment of Cancer OligoCare project developed a comprehensive system for characterisation and classification of oligometastatic disease. We first did a systematic review of the literature to identify inclusion and exclusion criteria of prospective interventional oligometastatic disease clinical trials. Next, we used a Delphi consensus process to select a total of 17 oligometastatic disease characterisation factors that should be assessed in all patients treated with radical local therapy for oligometastatic disease, both within and outside of clinical trials. Using a second round of the Delphi method, we established a decision tree for oligometastatic disease classification together with a nomenclature. We agreed oligometastatic disease as the overall umbrella term. A history of polymetastatic disease before diagnosis of oligometastatic disease was used as the criterion to differentiate between induced oligometastatic disease (previous history of polymetastatic disease) and genuine oligometastatic disease (no history of polymetastatic disease). We further subclassified genuine oligometastatic disease into repeat oligometastatic disease (previous history of oligometastatic disease) and de-novo oligometastatic disease (first time diagnosis of oligometastatic disease). In de-novo oligometastatic disease, we differentiated between synchronous and metachronous oligometastatic disease. We did a final subclassification into oligorecurrence, oligoprogression, and oligopersistence, considering whether oligometastatic disease is diagnosed during a treatment-free interval or during active systemic therapy and whether or not an oligometastatic lesion is progressing on current imaging. This oligometastatic disease classification and nomenclature needs to be prospectively evaluated by the OligoCare study.

The energy loss in iron can serve as valuable knowledge due to its extended use in technological applications and open topics in fundamental physics. The electronic structure of solid Fe is challenging, given that it is the first of the groups of transition metals with some of the d-electrons promoted to the conduction band while others remain bound. The low energy description, the deviation from velocity proportionality at low impact energies, and the contribution of the loosely bound d-electrons to the energy loss are active featured fields when it comes to the stopping in Fe. Very recent TDDFT calculations have been compared with the first stopping measurements in steel, showing surprisingly good agreement. In the present work, we applied a recent model based on the momentum distribution function of the d-electrons to the case of Fe. A comparison with other models is discussed, as well as with experimental data. We also highlight discrepancies among datasets regarding the stopping maximum and the need for new experimental efforts.

Extra-intestinal pathogenic Escherichia coli (ExPEC) belong to a critical priority group of antibiotic resistant pathogens. ExPEC establish gut reservoirs that seed infection of the urinary tract and bloodstream, but the mechanisms of gut colonisation remain to be properly understood. Ucl fimbriae are attachment organelles that facilitate ExPEC adherence. Here, we investigated cellular receptors for Ucl fimbriae and Ucl expression to define molecular mechanisms of Ucl-mediated ExPEC colonisation of the gut. We demonstrate differential expression of Ucl fimbriae in ExPEC sequence types associated with disseminated infection. Genome editing of strains from two common sequence types, F11 (ST127) and UTI89 (ST95), identified a single nucleotide polymorphism in the ucl promoter that changes fimbriae expression via activation by the global stress-response regulator OxyR, leading to altered gut colonisation. Structure-function analysis of the Ucl fimbriae tip-adhesin (UclD) identified high-affinity glycan receptor targets, with highest affinity for sialyllacto-N-fucopentose VI, a structure likely to be expressed on the gut epithelium. Comparison of the UclD adhesin to the homologous UcaD tip-adhesin from Proteus mirabilis revealed that although they possess a similar tertiary structure, apart from lacto-N-fucopentose VI that bound to both adhesins at low-micromolar affinity, they recognize different fucose- and glucose-containing oligosaccharides. Competitive surface plasmon resonance analysis together with co-structural investigation of UcaD in complex with monosaccharides revealed a broad-specificity glycan binding pocket shared between UcaD and UclD that could accommodate these interactions. Overall, our study describes a mechanism of adaptation that augments establishment of an ExPEC gut reservoir to seed disseminated infections, providing a pathway for the development of targeted anti-adhesion therapeutics.

The use of saliva for the diagnosis of SARS-CoV-2 has shown to be a good alternative to nasopharyngeal swabs (NPS), since it permits self-collection, avoids the exposure of healthy persons to infected patients, reduces waiting times, eliminates the need of personal protective equipment and is non-invasive. Yet current saliva testing is still expensive due to the need of specialized tubes containing buffers to stabilize the RNA of SARS-CoV-2 and inactivate the virus. These tubes are expensive and not always accessible in sufficient quantities. We now developed an alternative saliva testing method, using TRIzol for extraction, viral inactivation, and storage of SARS-CoV-2 RNA, combined with RT-qPCR, which was comparable in its performance to NPS. Paired saliva samples and NPS were taken from 15 asymptomatic healthcare workers and one patient with SARS-CoV-2. Further 13 patients with SARS-CoV-2 were only saliva-tested. All the tests were performed according to CDC 2019-Novel Coronavirus (2019-nCoV) Real-Time RT-PCR Diagnostic Panel. Saliva (4 mL) was taken in sterile 50 mL tubes, 1.5 mL TRIzol were added and mixed. Our results show that 5 μL of saliva RNA extracted with TRIzol allow for an adequate detection of the virus in patients positive for SARS-CoV-2 and was equally sensitive to NPS in TRIzol. We conclude that saliva testing using TRIzol is a recommendable method for diagnosis of SARS-CoV-2 since it has several advantages over currently used saliva tests: it can be done with normal sterile tubes, does not need cold-chain handling, is stable at room temperature, is non-invasive and less costly, making it more accessible for low-income countries. Cheaper saliva testing using TRIzol is especially relevant for low-income countries to optimize diagnosis and help define quarantine durations for families, healthcare workers, schools, and other public workplaces, thus decreasing infections and mortality caused by SARS-CoV-2.

Background Communication between providers and patients' families is an integral part of clinical care. Family concern is a validated component of Pediatric Early Warning Systems (PEWS); however, little is known about the impact of PEWS on provider‐family communication. Methods Semi‐structured interviews were conducted with 83 ward and Pediatric Intensive Care Unit (PICU) providers involved in the care of patients with deterioration at two pediatric oncology hospitals of different resource levels: St. Jude Children's Research Hospital (n = 42) in the United States and Unidad Nacional de Oncología Pediátrica (UNOP, n = 41) in Guatemala. Interviews were conducted in the participants' native language (English or Spanish), transcribed, and translated into English. Transcripts were coded by two researchers and analyzed for thematic content surrounding family communication and concern. Results All participants recognized patients' families as a valuable part of the care team, particularly during events requiring escalation of care. Perceived barriers to communication included limited time spent at the bedside, and, at UNOP, language and literacy challenges which occasionally limited providers' ability to assess family concern and involve families in patient care. Despite these barriers, providers perceived PEWS improved communication by facilitating more interaction with families, allowing for relationship‐building, anticipatory guidance, and destigmatization of the PICU. PEWS assessments also allowed families to contribute to identification of deterioration. Conclusions PEWS improve the quality of communication between providers and families by providing more opportunities for interaction, building relationships, and trust. These findings further support the use of PEWS in the care of children with cancer in hospitals of all resource‐levels. In this qualitative analysis of provider interviews, we identify PEWS as facilitators of communication between providers and patient families in resource‐limited and high‐resource pediatric oncology hospitals. Our findings demonstrate that providers perceive the family concern component of PEWS allows greater inclusion of patient families as a part of the healthcare team.

Background and aims. Metabolic Associated Fatty Liver Disease (MAFLD) encompasses a spectrum of diseases from simple steatosis to nonalcoholic steatohepatitis (NASH). Here, we investigated the hepatoprotective role of Moringa oleifera aqueous extract on hepatic miRNAs, genes and protein expression, as well as histological and biochemical parameters in an experimental model of NASH. Methods. Male C57BL/6J mice were fed with a high fat diet (HFD, 60% lipids, 42 gr/L sugar in water) for 16 weeks. Moringa extract was administered via gavage during the final 8 weeks. Insulin Tolerance Test (ITT) and HOMA-IR were calculated. Serum levels of insulin, resistin, leptin and PAI-1 and hepatic expression of miR-21a-5p, miR-103-3p, miR-122-5p, miR-34a-5p and SIRT1, AMPKα and SREBP1c protein were evaluated. Alpha-SMA immunohistochemistry and hematoxylin-eosin, Masson’s trichrome and sirius red staining were made. Hepatic transcriptome was analyzed using microarrays. Results. Animals treated with Moringa extract improved ITT and decreased SREBP1c hepatic protein, while SIRT1 increased. Hepatic expression of miR-21a-5p, miR-103-3p and miR-122-5p, miR34a-5p was downregulated. Hepatic histologic analysis showed in Moringa group (HF + MO) a significant decrease in inflammatory nodules, macro steatosis, fibrosis, collagen and αSMA reactivity. Analysis of hepatic transcriptome showed down expression of mRNAs implicated in DNA response to damage, endoplasmic reticulum stress, lipid biosynthesis and insulin resistance. Moringa reduced insulin resistance, de novo lipogenesis, hepatic inflammation and ER stress. Conclusions. Moringa prevented progression of liver damage in a model of NASH and improved biochemical, histological and hepatic expression of genes and miRNAs implicated in MAFLD/NASH development.

Objective Largely, watchful waiting is the initial policy for patients with small-sized or medium-sized vestibular schwannoma, because of slow growth and relatively minor complaints, that do not improve by an intervention. If intervention (microsurgery, radiosurgery or fractionated radiotherapy) becomes necessary, the choice of intervention appears to be driven by the patient's or clinician's preference rather than by evidence based. This study addresses the existing evidence based on controlled studies of these interventions. Design A systematic Boolean search was performed focused on controlled intervention studies. The quality of the retrieved studies was assessed based on the Sign-50 criteria on cohort studies. Data sources Pubmed/Medline, Embase, Cochrane Central Register of Controlled Trials and reference lists. Study selection Six eligibility criteria included a controlled intervention study on a newly diagnosed solitary, vestibular schwannoma reporting on clinical outcomes. Two prospective and four retrospective observational, controlled studies published before November 2011 were selected. Data analysis Two reviewers independently assessed the methodological quality of the studies and extracted the outcome data using predefined formats. Results Neither randomised studies, nor controlled studies on fractionated radiotherapy were retrieved. Six studies compared radiosurgery and microsurgery in a controlled way. All but one were confined to solitary tumours less than 30 mm in diameter and had no earlier interventions. Four studies qualified for trustworthy conclusions. Among all four, radiosurgery showed the best outcomes: there were no direct mortality, no surgical or anaesthesiological complications, but better facial nerve outcome, better preservation of useful hearing and better quality of life. Conclusions The available evidence indicates radiosurgery to be the best practice for solitary vestibular schwannomas up to 30 mm in cisternal diameter.