DifferentialRegulation: a Bayesian hierarchical approach to identify differentially regulated genes.

Although transcriptomics data is typically used to analyze mature spliced mRNA, recent attention has focused on jointly investigating spliced and unspliced (or precursor-) mRNA, which can be used to study gene regulation and changes in gene expression production. Nonetheless, most methods for spliced/unspliced inference (such as RNA velocity tools) focus on individual samples, and rarely allow comparisons between groups of samples (e.g. healthy vs. diseased). Furthermore, this kind of inference is challenging, because spliced and unspliced mRNA abundance is characterized by a high degree of quantification uncertainty, due to the prevalence of multi-mapping reads, ie reads compatible with multiple transcripts (or genes), and/or with both their spliced and unspliced versions. Here, we present DifferentialRegulation, a Bayesian hierarchical method to discover changes between experimental conditions with respect to the relative abundance of unspliced mRNA (over the total mRNA). We model the quantification uncertainty via a latent variable approach, where reads are allocated to their gene/transcript of origin, and to the respective splice version. We designed several benchmarks where our approach shows good performance, in terms of sensitivity and error control, vs. state-of-the-art competitors. Importantly, our tool is flexible, and works with both bulk and single-cell RNA-sequencing data. DifferentialRegulation is distributed as a Bioconductor R package.

DifferentialRegulation: a Bayesian hierarchical approach to identify differentially regulated genes.

Motivation: Although transcriptomics data is typically used to analyse mature spliced mRNA, recent attention has focused on jointly investigating spliced and unspliced (or precursor-) mRNA, which can be used to study gene regulation and changes in gene expression production. Nonetheless, most methods for spliced/unspliced inference (such as RNA velocity tools) focus on individual samples, and rarely allow comparisons between groups of samples (e.g., healthy vs. diseased). Furthermore, this kind of inference is challenging, because spliced and unspliced mRNA abundance is characterized by a high degree of quantification uncertainty, due to the prevalence of multi-mapping reads, i.e., reads compatible with multiple transcripts (or genes), and/or with both their spliced and unspliced versions. Results: Here, we present DifferentialRegulation, a Bayesian hierarchical method to discover changes between experimental conditions with respect to the relative abundance of unspliced mRNA (over the total mRNA). We model the quantification uncertainty via a latent variable approach, where reads are allocated to their gene/transcript of origin, and to the respective splice version. We designed several benchmarks where our approach shows good performance, in terms of sensitivity and error control, versus state-of-the-art competitors. Importantly, our tool is flexible, and works with both bulk and single-cell RNA-sequencing data. Availability and implementation: DifferentialRegulation is distributed as a Bioconductor R package.

Validation of Predictive Analyses for Interim Decisions in Clinical Trials.

PURPOSE: Adaptive clinical trials use algorithms to predict, during the study, patient outcomes and final study results. These predictions trigger interim decisions, such as early discontinuation of the trial, and can change the course of the study. Poor selection of the Prediction Analyses and Interim Decisions (PAID) plan in an adaptive clinical trial can have negative consequences, including the risk of exposing patients to ineffective or toxic treatments. METHODS: We present an approach that leverages data sets from completed trials to evaluate and compare candidate PAIDs using interpretable validation metrics. The goal is to determine whether and how to incorporate predictions into major interim decisions in a clinical trial. Candidate PAIDs can differ in several aspects, such as the prediction models used, timing of interim analyses, and potential use of external data sets. To illustrate our approach, we considered a randomized clinical trial in glioblastoma. The study design includes interim futility analyses on the basis of the predictive probability that the final analysis, at the completion of the study, will provide significant evidence of treatment effects. We examined various PAIDs with different levels of complexity to investigate if the use of biomarkers, external data, or novel algorithms improved interim decisions in the glioblastoma clinical trial. RESULTS: Validation analyses on the basis of completed trials and electronic health records support the selection of algorithms, predictive models, and other aspects of PAIDs for use in adaptive clinical trials. By contrast, PAID evaluations on the basis of arbitrarily defined ad hoc simulation scenarios, which are not tailored to previous clinical data and experience, tend to overvalue complex prediction procedures and produce poor estimates of trial operating characteristics such as power and the number of enrolled patients. CONCLUSION: Validation analyses on the basis of completed trials and real world data support the selection of predictive models, interim analysis rules, and other aspects of PAIDs in future clinical trials.

Data sources and applied methods for paclitaxel safety signal discernment.

Background: Following the identification of a late mortality signal, the Food and Drug Administration (FDA) convened an advisory panel that concluded that additional clinical study data are needed to comprehensively evaluate the late mortality signal observed with the use of drug-coated balloons (DCB) and drug-eluting stent (DES). The objective of this review is to (1) identify and summarize the existing clinical and cohort studies assessing paclitaxel-coated DCBs and DESs, (2) describe and determine the quality of the available data sources for the evaluation of these devices, and (3) present methodologies that can be leveraged for proper signal discernment within available data sources. Methods: Studies and data sources were identified through comprehensive searches. original research studies, clinical trials, comparative studies, multicenter studies, and observational cohort studies written in the English language and published from January 2007 to November 2021, with a follow-up longer than 36 months, were included in the review. Data quality of available data sources identified was assessed in three groupings. Moreover, accepted data-driven methodologies that may help circumvent the limitations of the extracted studies and data sources were extracted and described. Results: There were 39 studies and data sources identified. This included 19 randomized clinical trials, nine single-arm studies, eight registries, three administrative claims, and electronic health records. Methodologies focusing on the use of existing premarket clinical data, the incorporation of all contributed patient time, the use of aggregated data, approaches for individual-level data, machine learning and artificial intelligence approaches, Bayesian approaches, and the combination of various datasets were summarized. Conclusion: Despite the multitude of available studies over the course of eleven years following the first clinical trial, the FDA-convened advisory panel found them insufficient for comprehensively assessing the late-mortality signal. High-quality data sources with the capabilities of employing advanced statistical methodologies are needed to detect potential safety signals in a timely manner and allow regulatory bodies to act quickly when a safety signal is detected.

Satisfacción laboral y condiciones laborales en odontólogos de Cartagena de Indias-Colombia / Labor satisfaction and labor conditions in dentists of Cartagena de Indias-Colombia

Objetivo: relacionar satisfacción laboral con la condición laboral de odontólogos de Cartagena, Colombia. Materiales y métodos: estudio descriptivo transversal en una muestra no probabilística de 107 odontólogos generales que laboraban de manera independiente en centros odontológicos en el año 2016. Se diseña y aplica cuestionario para indagar satisfacción laboral, variables sociodemográficas y condiciones laborales. Resultados: 55,1 % de los odontólogos se sentían satisfechos laboralmente; de estos 62,6 % refirieren sentirse insatisfechos con la remuneración obtenida y así mismo 75,7 % insatisfechos con las condiciones del mercado laboral. Se hallan relaciones con significancia estadística entre satisfacción laboral y tener menos de 44 años (p =0,003), sexo masculino (p= 0,007) y estar casado (p= 0,038); igualmente entre condiciones laborales y duración de jornada laboral (p= 0,016), remuneración recibida (p=0,000), competencia laboral (p=0,001) y haber estado alguna vez desempleado (p=0,034). Conclusión: la satisfacción de los odontólogos, las condiciones laborales y el cumplimiento de expectativas se relaciona con factores que generan resultados de percepción negativa indicando que la situación de la odontología no es la mejor en la actualidad. Estudios más a fondo se recomiendan para determinar las raíces del problema y tomar decisiones gubernamentales respecto al futuro..Au

Objective: to relate job satisfaction with the working condition of dentists in Cartagena-Colombia. Materials and methods: cross-sectional descriptive study in a non-probabilistic sample of 107 general dentists who work in dental centers in 2016. A questionnaire was designed and applied to investigate job satisfaction, sociodemographic variables and working conditions. A descriptive statistic and a test with 95% confidence were performed for the significance of the relationships. Results: 55.1% of dentists felt satisfied at work; Of these, 62.6% reported dissatisfaction with remuneration and 75.7% dissatisfied with labor market conditions. The relationships with statistical significance between job satisfaction and having less than 44 years (p = 0.003), male sex (p = 0.007) and being married (p = 0.038); just like relate working conditions with the duration of the working day (p = 0.016), remuneration received (p = 0.000), labor competence (p = 0.001) and having been unemployed at some time (p = 0.034). Conclusion: the satisfaction of dentists, working conditions and the fulfillment of expectations are related to factors, which generate negative perception results indicating that the dentistry situation is not the best at present. Further studies are recommended to determine the roots of the problem and make government decisions regarding the future..Au

Considerations for the Selection and Use of Disinfectants Against SARS-CoV-2 in a Health Care Setting.

Proper disinfection using adequate disinfecting agents will be necessary for infection control strategies against coronavirus disease 2019 (COVID-19). However, limited guidance exists on effective surface disinfectants or best practices for their use against severe acute respiratory coronavirus 2. We outlined a process of fully characterizing over 350 products on the Environmental Protection Agency List N, including pH, method of delivery, indication for equipment sterilization, and purchase availability. We then developed a streamlined set of guidelines to help rapidly evaluate and select suitable disinfectants from List N, including practicality, efficacy, safety, and cost/availability. This resource guides the evaluation of ideal disinfectants amidst practical considerations posed by the COVID-19 pandemic.

Quadhelix: una herramienta en el manejo del paciente con secuela de fisuralabio-alveolo-palatina. Reporte de tres casos / Quadhelix: a tool for cleft lip and palate patients management. Report of three cases

Las fisura labio-alveolo-palatina son las anomalías congénitas más frecuentes, por lo que el ortodoncista debe conocer el manejo transversal en estos pacientes, su omisión puede hacer que se agrave la fisura, porque los efectos biomecánicos en estos pacientes merecen especial cuidado debido a su estructura maxilar. La serie de casos incluye tres pacientes, uno con secuela de fisura labio-alveolo-palatina unilateral derecho, el otro bilateral y el último unilateral izquierdo. La constricción transversal maxilar y la discrepancia en relación con el ancho mandibular, llevó a la elección del uso del quadhelix para resolver este problema. En los tres casos se lograron los objetivos transversales del tratamiento. Se concluyó que, el quadhelix representa una alternativa razonable teniendo como ventajas ser un dispositivo de expansión lenta que produce menos resistencia tisular alrededor de las estructuras circunmaxilares y, mejora la formación de hueso en la sutura intermaxilar; de igual manera al tener mayores efectos dentoalveolares, no produce pérdida ósea a nivel vestibular; adicionalmente presenta una mejor adaptación muscular y bajas probabilida-des de recidiva.

As cleft lip and palate is one of the most frequent congenital anomalies, orthodontists should know about transverse management in these patients, to ignore it might aggravate the fissure, as the biomechanical effects in these patients require special care due to their maxillary structure. This case series include three patients, one with a sequel of right unilateral cleft lip and palate, one bilateral and the last one with left unilateral cleft lip and palate. The maxillary transverse constriction and the discrepancy with the mandib-ular width, led to choice quadhelix appliance to solve this problem. In all three cases the transversal treatment objectives were achieved. In conclusion the quadhelix appliance is a reliable alternative which has advantages such as a slow expansion producing less tissue resistance around the circummaxillary structures and improves bone formation in the intermaxillary suture; similarly, it has greater dentoalveolar effects that does not cause buccal cortical bone loss; additionally, it shows better muscular adaptation and low chance of relapse

[EFFECT OF A BEVERAGE MADE FROM CACTUS PEAR (NOPALEA COCHENILLIFERA (L) SALM-DYCK) IN A RURAL POPULATION OF HIDALGO, MEXICO; A PILOT CLINICAL TRIAL]. / EFECTO DE UNA BEBIDA A BASE DE NOPAL (NOPALEA COCHENILLIFERA (L) SALM-DYCK) EN PACIENTES DE UNA POBLACIÓN RURAL DE HIDALGO, MÉXICO; ENSAYO CLÍNICO PILOTO.

INTRODUCTION: cactus pear has been used in Mexican traditional medicine. However, clinical studies are limited to demonstrate the effectiveness as anti-diabetic. OBJECTIVE: to evaluate the effect of a fresh beverage made from Nopalea cochenillifera (l.) Salm-dyck on glucose levels, glycosylated hemoglobin, weight, waist circumference and blood pressure. METHODS: the beverage (50 g/250 mL) was daily administered in twenty patients for 30 days. RESULTS AND DISCUSSION: differences statistically significant were found in some time of the supplementation for all measured variables excepting for glucose levels, this suggests that values might be significant to a longer administration or bigger doses. CONCLUSIONS: although preliminary data, the results demonstrated that cactus pear used in this study may be an alternative for the management of patients with diabetes type 2. Nevertheless, further trials must be conducted with a bigger sample size and more control groups so that the effectiveness can be fully evaluated.

Introducción: el nopal ha sido usado en la medicina tradicional mexicana. Sin embargo, los estudios clínicos para demostrar la eficacia como antidiabético son limitados. Objetivo: evaluar el efecto de una bebida fresca a base de nopal (Nopalea cochenillifera (l.) Salm-dyck), sobre los niveles de glucosa, hemoglobina glicosilada, peso corporal, circunferencia de cintura y presión sanguínea. Métodos: la bebida (50 g/250 mL) se administró diariamente a 20 pacientes durante 30 días. Resultados y discusión: se encontraron diferencias estadísticamente significativas en algún momento de la suplementación, excepto para la glucosa, sugiriendo que los valores podrían ser significativos en un tiempo mayor de administración a dosis mayores. Conclusiones: aunque preliminares, los resultados demostraron que el nopal usado en este estudio podría ser útil en el manejo de pacientes con diabetes tipo 2. No obstante, deben efectuarse futuros ensayos con un tamaño de muestra más grande y más grupos control, para que la efectividad pueda ser totalmente evaluada.

Efecto de una bebida a base de nopal (Nopalea cochenillifera (l) Salm-dyck) en pacientes de una población rural de Hidalgo, México; ensayo clínico piloto / Effect of a beverage made from cactus pear (nopalea cochenillifera (l) salm-dyck) in a rural population of hidalgo, Mexico; a pilot clinical trial

Introducción: el nopal ha sido usado en la medicina tradicional mexicana. Sin embargo, los estudios clínicos para demostrar la eficacia como antidiabético son limitados. Objetivo: evaluar el efecto de una bebida fresca a base de nopal (Nopalea cochenillifera (l.) Salm-dyck), sobre los niveles de glucosa, hemoglobina glicosilada, peso corporal, circunferencia de cintura y presión sanguínea. Métodos: la bebida (50 g/250 mL) se administró diariamente a 20 pacientes durante 30 días. Resultados y discusión: se encontraron diferencias estadísticamente significativas en algún momento de la suplementación, excepto para la glucosa, sugiriendo que los valores podrían ser significativos en un tiempo mayor de administración a dosis mayores. Conclusiones: aunque preliminares, los resultados demostraron que el nopal usado en este estudio podría ser útil en el manejo de pacientes con diabetes tipo 2. No obstante, deben efectuarse futuros ensayos con un tamaño de muestra más grande y más grupos control, para que la efectividad pueda ser totalmente evaluada (AU)

Introduction: cactus pear has been used in Mexican traditional medicine. However, clinical studies are limited to demonstrate the effectiveness as anti-diabetic. Objective: to evaluate the effect of a fresh beverage made from Nopalea cochenillifera (l.) Salm-dyck on glucose levels, glycosylated hemoglobin, weight, waist circumference and blood pressure. Methods: the beverage (50 g/250 mL) was daily administered in twenty patients for 30 days. Results and discussion: differences statistically significant were found in some time of the supplementation for all measured variables excepting for glucose levels, this suggests that values might be significant to a longer administration or bigger doses. Conclusions: although preliminary data, the results demonstrated that cactus pear used in this study may be an alternative for the management of patients with diabetes type 2. Nevertheless, further trials must be conducted with a bigger sample size and more control groups so that the effectiveness can be fully evaluated (AU)