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Calculating analytical uncertainties as a part of method validation is a relevant aspect of field and laboratory practices in instrumental analytical chemistry subjects, which usually require complex algorithms. This work describes the development and didactic use of an automatic and straightforward informatics tool, implemented in an Excel macro, for calculating and interpreting the uncertainty of an analytical method against a reference method on field measurements. The software was initially developed for field testing of low-cost air quality monitoring analytical methods against reference methods, and the present work shows its adaptation to a didactic environment. The uncertainty calculation software was implemented through an Excel macro based on Visual Basic as a graphical user interface. It finds a best-fit line that describes the relation between concentrations determined by the candidate and reference methods. The software generates the analytical validation results (slope and intercept with their respective confidence limits, and expanded uncertainty of a concentration determined by the candidate method), hiding the intermediate functions and calculations. The Excel interface eases uncertainty calculations for undergraduate students, although the background mathematics can be quickly unveiled to students for didactic purposes. This tool has been applied to a laboratory exercise focused on validating experimental results obtained in the measurement of ozone levels in ambient air by passive sampling and spectrophotometric detection. The uncertainty calculation software has proved valuable by providing the student a resource to check the analytical quality of the data generated in the laboratory, while assimilating the fundamentals behind the calculations.

US dual language bilingual education (DLBE) programs have a goal to develop students' sociocultural competence, but little is known about how preservice teachers (PSTs) do this. This descriptive study involved quantitative and qualitative analysis of 82 videos of instruction and 76 lesson plans from nine Latinx PSTs placed in Spanish DLBE classrooms across 3 years. PSTs focused more on students' interests or background knowledge than specific family/community and/or cultural practices. Few lessons incorporated culturally relevant/sustaining literature. Findings help teacher educators consider contextual constraints in teacher preparation and ways to better support PSTs in recognizing and developing students' sociocultural competence.

Behavior skills training (BST) with ongoing coaching is an effective form of professional development that creates sustained educator practice change and improves student outcomes. We provide a model for how BST can be used to improve the implementation of evidence-based practices with both teachers and paraprofessionals, the latter of whom often do not receive professional development opportunities or coaching. We propose a model for BST with digital tools that can be used in face-to-face, hybrid, and virtual formats, which is timely given the pandemic. A vignette with a dyad of educators is used to illustrate the model and examples of fidelity and coaching forms are included. A figure of the BST process with visual supports provided to the educators is included.

Many current investigations have analysed adolescents' risky ICT behaviours (such as excessive or addictive use), but few have explored the characteristics of low-risk behaviour in this regard. This study aimed to explore the psychosocial profile of a sample of 593 Spanish adolescents aged 13 to 18 who have been categorized as low-risk ICT users. To this end, the low-risk ICT use group was calculated using the "multitasking while doing homework index" and a set of items on risky ICT behaviour. Chi-squared and t-tests were performed and a forward stepwise binary logistic regression was carried out to determine the explanatory variables for low-risk ICT use. The results showed that some 7.1% were classified as low-risk ICT users, with a higher percentage of girls. These users' profile was characterised by: lower digital self-efficacy with social networking applications; less generalized ICT use and a less dependent attitude; less extroversion and more agreeableness and conscientiousness; higher academic self-concept; having rules for ICT use at home; and less insecure and anxious attachment to parental figures. The variables that predicted the likelihood of low-risk ICT behaviour were: high academic self-concept; low perceived separation anxiety from loved ones; and high agreeableness scores. These results are useful for proposing psycho-socio-educational interventions to promote healthy ICT use.

BACKGROUND AND OBJECTIVE: The role of cytoreductive nephrectomy (CN) in the treatment of metastatic renal cell carcinoma (mRCC) has been called into question on the basis of clinical trial data from the tyrosine kinase inhibitor (TKI) era. Comparative analyses of CN for patients treated with immuno-oncology (IO) versus TKI agents are sparse. Our objective was to compare CN timing and outcomes among patients who received TKI versus IO therapy. METHODS: This was a multicenter retrospective analysis of patients who underwent CN using data from the REMARCC (Registry of Metastatic RCC) database. The cohort was divided into TKI versus IO first-line therapy groups. The primary outcome was all-cause mortality (ACM). Secondary outcomes included cancer-specific mortality (CSM). Multivariable analysis was used to identify factors predictive for ACM and CSM. The Kaplan-Meier method was used to analyze 5-yr overall survival (OS) and cancer-specific survival (CSS) with stratification by primary systemic therapy and timing in relation to CN. KEY FINDINGS AND LIMITATIONS: We analyzed data for 189 patients (148 TKI + CN, 41 IO +CN; median follow-up 23.2 mo). Multivariable analysis revealed that a greater number of metastases (hazard ratio [HR] 1.06; p = 0.015), greater primary tumor size (HR 1.10; p = 0.043), TKI receipt (HR 2.36; p = 0.015), and initiation of systemic therapy after CN (HR 1.49; p = 0.039) were associated with worse ACM. A greater number of metastases at diagnosis (HR 1.07; p = 0.011), greater primary tumor size (HR 1.12; p = 0.018), TKI receipt (HR 5.43; p = 0.004), and initiation of systemic therapy after CN (HR 2.04; p

Abstract Rapid global expansion of offshore wind farms, tidal, and wave technologies signifies a new era of renewable energy development. While a promising means to combat the impacts of climate change, such developments necessitate fine-scale monitoring of biological communities to determine impacts associated with construction, operation, and eventual decommission. Here, we evaluate the performance of a gridded, Innovasea Systems, Inc. fine-scale acoustic telemetry positioning system (FSPS, n = 20 acoustic receivers) for tracking behaviors of diverse, temperate fish assemblages in relation to a subsea cable route supporting the Ørsted offshore wind development in coastal New York. We examined array performance through positioning error derived from receiver reference transmitters and tracked animals (n = 260) comprising 17 species of teleost and elasmobranch. We evaluated the effects of environmental variables (temperature, tilt, noise, and depth), transmitter power, individual movement rates, and receiver loss on horizontal positioning error (HPE) and route mean squared error (RMSE). Across a 16-month deployment period, many positions were derived for Atlantic sturgeon (n = 2,612), black sea bass (n = 9,175), clearnose skate (n = 10,306), summer flounder (n = 13,304), and little skate (n = 15,186), suggesting that these species may serve as sentinel candidates for assessing behavioral changes following construction, operation, and decommission. We found that receivers placed at the boundary of the grid exhibited higher HPE and RMSE, however these errors did not significantly change despite large receiver losses (25%). Generalized Linear Models revealed that temperature, noise, tilt, and depth were often significant predictors of HPE and RMSE, however, a substantial amount of variance was not explained by the models (~ 70%). Average movement rates ranged from 1.1 m s−1 (common thresher shark) to 0.03 m s−1 (little skate and summer flounder) but had minimal effects on positioning error. Finally, we observed that higher transmitter powers (158 dB) may lead to higher and more variable HPE values. Overall, these findings provide new insight into the drivers of FSPS array performance and illustrate their broad utility for monitoring fish behavior associated with offshore marine developments.

This case report describes a 23-year-old male who was incidentally diagnosed with Caroli disease while investigating symptoms of recurrent upper quadrant pain and fever. Imagining studies, including magnetic resonance cholangiography revealed the “central dot sign,” which is pathognomonic for this condition, along with cystic dilatations of the intrahepatic bile ducts and the presence of biliary stones. The diagnosis was confirmed and treatment with ursodeoxycholic acid led to a notable reduction in symptoms. This case underscores the need for further research and understanding to develop more effective diagnostic and treatment strategies. Regular follow-up remains essential for managing disease progression and preventing complications.

Abstract Background Radiopharmaceuticals have been considered a special group of medicines in Europe since 1989. The use of radiopharmaceuticals that have marketing authorization should always be the first option in clinical use, however due to their special properties the availability of approved radiopharmaceuticals is limited. For this reason, they can be produced on a small scale outside the marketing authorization process. Main body The in-house radiopharmaceutical preparations represent an important source of these special medicines for routine nuclear medicine practice. However, a lack of harmonization in Member States’ regulations leads to extreme differences in the use and availability of radiopharmaceuticals across Europe. The aim of this work is to provide an overview of the different national regulatory frameworks in which Directive 2001/83/UE is adopted on the preparation of radiopharmaceuticals outside the marketing authorization track in Europe. Nine different national regulations have been studied to describe how unlicensed radiopharmaceuticals are prepared. Special attention is paid to reflect the minimum standards that these preparations should meet as well as the educational requirements to be a radiopharmacist in charge of them. Conclusion The rapid development of new radiopharmaceuticals used in radiometabolic therapy requires a common regulation that allows balance between the use and preparation of licensed and unlicensed radiopharmaceuticals. The absence of a harmonized regulation for the radiopharmaceutical small-scale preparation and the implementation of Good Manufacture Practices, leads to extreme differences in the use, quality assurance and availability of radiopharmaceuticals in Europe.

Abstract Background Health disparities have been highlighted among patient with prostate adenocarcinoma (PRAD) due to ethnicity. Mexican men present a more aggressive disease than other patients resulting in less favorable treatment outcome. We aimed to identify the mutational landscape which could help to reduce the health disparities among minority groups and generate the first genomics exploratory study of PRAD in Mexican patients. Methods Paraffin-embedded formalin-fixed tumoral tissue from 20 Mexican patients with early-stage PRAD treated at The Instituto Nacional de Cancerología, Mexico City from 2017 to 2019 were analyzed. Tumoral DNA was prepared for whole exome sequencing, the resulting files were mapped against h19 using BWA-MEM. Strelka2 and Lancet packages were used to identify single nucleotide variants (SNV) and insertions or deletions. FACETS was used to determine somatic copy number alterations (SCNA). Cancer Genome Interpreter web interface was used to determine the clinical relevance of variants. Results Patients were in an early clinical stage and had a mean age of 59.55 years (standard deviation [SD]: 7.1 years) with 90% of them having a Gleason Score of 7. Follow-up time was 48.50 months (SD: 32.77) with recurrences and progression in 30% and 15% of the patients, respectively. NUP98 (20%), CSMD3 (15%) and FAT1 (15%) were the genes most frequently affected by SNV; ARAF (75%) and ZNF419 (70%) were the most frequently affected by losses and gains SNCA’s. One quarter of the patients had mutations useful as biomarkers for the use of PARP inhibitors, they comprise mutations in BRCA, RAD54L and ATM. SBS05, DBS03 and ID08 were the most common mutational signatures present in this cohort. No associations with recurrence or progression were identified. Conclusions This pilot study reveals the mutational landscape of early-stage prostate adenocarcinoma in Mexican men, providing a first approach to understand the mutational patterns and actionable mutations in early prostate cancer can inform personalized treatment approaches and reduce the underrepresentation in genomic cancer studies.

Abstract Recessive dystrophic epidermolysis bullosa (RDEB) is a rare genetic disease caused by loss of function mutations in the gene coding for collagen VII (C7) due to deficient or absent C7 expression. This disrupts structural and functional skin architecture, leading to blistering, chronic wounds, inflammation, important systemic symptoms affecting the mouth, gastrointestinal tract, cornea, and kidney function, and an increased skin cancer risk. RDEB patients have an extremely poor quality of life and often die at an early age. A frequent class of mutations in RDEB is premature termination codons (PTC), which appear in homozygosity or compound heterozygosity with other mutations. RDEB has no cure and current therapies are mostly palliative. Using patient-derived keratinocytes and a library of 8273 small molecules and 20,160 microbial extracts evaluated in a phenotypic screening interrogating C7 levels, we identified three active chemical series. Two of these series had PTC readthrough activity, and one upregulated C7 mRNA, showing synergistic activity when combined with the reference readthrough molecule gentamicin. These compounds represent novel potential small molecule-based systemic strategies that could complement topical-based treatments for RDEB.

Abstract Background Imprinting disorders are rare diseases resulting from altered expression of imprinted genes, which exhibit parent-of-origin-specific expression patterns regulated through differential DNA methylation. A subgroup of patients with imprinting disorders have DNA methylation changes at multiple imprinted loci, a condition referred to as multi-locus imprinting disturbance (MLID). MLID is recognised in most but not all imprinting disorders and is also found in individuals with atypical clinical features; the presence of MLID often alters the management or prognosis of the affected person. Some cases of MLID are caused by trans-acting genetic variants, frequently not in the patients but their mothers, which have counselling implications. There is currently no consensus on the definition of MLID, clinical indications prompting testing, molecular procedures and methods for epigenetic and genetic diagnosis, recommendations for laboratory reporting, considerations for counselling, and implications for prognosis and management. The purpose of this study is thus to cover this unmet need. Methods A comprehensive literature search was conducted resulting in identification of more than 100 articles which formed the basis of discussions by two working groups focusing on clinical diagnosis (n = 12 members) and molecular testing (n = 19 members). Following eight months of preparations and regular online discussions, the experts from 11 countries compiled the preliminary documentation and determined the questions to be addressed during a face-to-face meeting which was held with the attendance of the experts together with four representatives of patient advocacy organisations. Results In light of available evidence and expert consensus, we formulated 16 propositions and 8 recommendations as interim guidance for the clinical and molecular diagnosis of MLID. Conclusions MLID is a molecular designation, and for patients with MLID and atypical phenotypes, we propose the alternative term multi-locus imprinting syndrome. Due to the intrinsic variability of MLID, the guidelines underscore the importance of involving experts from various fields to ensure a confident approach to diagnosis, counselling, and care. The authors advocate for global, collaborative efforts in both basic and translational research to tackle numerous crucial questions that currently lack answers, and suggest reconvening within the next 3–5 years to evaluate the research advancements and update this guidance as needed.

Background The benefit of patent foramen ovale closure (PFOC) ≤9 months after a cryptogenic stroke has been demonstrated in several randomised clinical trials. There is, however, insufficient data to support PFOC in non-recent cryptogenic strokes.Aims The objective of the study was to evaluate the effectiveness of PFOC in relation to the time since the patient’s most recent cryptogenic cerebrovascular event (CVE) or systemic embolism (SE).Methods We conducted a multicentre, retrospective cohort study with international participation, to assess the results of an early closure (EC,

Tunicate maize (Zea mays var. tunicata A. St. Hil) is a landrace that constitutes a fundamental aspect of the socio-cultural identity of Ixtenco, Tlaxcala (Mexico) and represents an exotic phenotype whose kernels are enclosed in leaflike glumes. Despite multiple studies conducted worldwide on plant growth-promoting-rhizobacteria (PGPR) in commercial maize varieties grown under monoculture systems, very little is known about bacteria inhabiting native maize landraces in agroecosystems, but for tunicate maize such knowledge is non-existent. This research described and profiled functional groups of culturable rhizobacteria from tunicate maize at two phenological stages (tasseling and maturity/senescence) in a polyculture system, highlighting potential PGPR for biotechnological purposes. Ninety-five rhizobacteria were isolated and molecularly identified, and their physiological activities such as plant growth promotion, production of exogenous lytic enzymes, and antagonism against fungal pathogens were determined. The culturable rhizobacterial community associated to tunicate maize comprised 42 genera, dominated by Bacillaceae, Comamonadaceae, Microbacteriaceae, Micrococcaceae, Oxalobacteraceae, Pseudomonadaceae, and Rhizobaceae families. At tasseling stage, the identified bacteria corresponded to Arthrobacter, Priestia, Herbaspirillum, Pseudomonas, and Rhizobium, and exhibited redundant capabilities for stimulating plant growth and nutrition, and inhibiting fungal phytopathogens. At maturity/senescence stage, the main genera Arthrobacter and Microbacterium displayed lytic capabilities to support mineralization process. We recorded potential novel rhizosphere functional bacteria such as Rhizobium, Sphingobium, and Arthrobacter which are not previously described associated to maize landraces, as well as their bioprospection as PGPR detected at plant phenological stages poorly explored (like maturity/senescence). This taxonomic and functional diversity was attributed to the application of agricultural practices as well as the rhizosphere effect during specific phenological stages. Results described the diversity and functionality of culturable rhizosphere bacteria from tunicate maize in polyculture systems that allowed us the detection of potential rhizobacteria for further developing of biofertilizers and biocontrollers directed as biotechnology for sustainable agriculture, and for generating strategies for conservation of native plants and their microbial genetic resources.