PyF2F: a robust and simplified fluorophore-to-fluorophore distance measurement tool for Protein interactions from Imaging Complexes after Translocation experiments.

Structural knowledge of protein assemblies in their physiological environment is paramount to understand cellular functions at the molecular level. Protein interactions from Imaging Complexes after Translocation (PICT) is a live-cell imaging technique for the structural characterization of macromolecular assemblies in living cells. PICT relies on the measurement of the separation between labelled molecules using fluorescence microscopy and cell engineering. Unfortunately, the required computational tools to extract molecular distances involve a variety of sophisticated software programs that challenge reproducibility and limit their implementation to highly specialized researchers. Here we introduce PyF2F, a Python-based software that provides a workflow for measuring molecular distances from PICT data, with minimal user programming expertise. We used a published dataset to validate PyF2F's performance.

Pediatric epileptologist from Latin America.

Experience of how to become a pediatric epileptologist in Colombia.

Textbook Outcome in Bariatric Surgery: Evolution During 15 Years in a Referral Center.

BACKGROUND: Textbook outcome (TO) is a multidimensional measure used to assess the quality of care. It is the "ideal" surgical result, based on a series of established indicators. In the field of bariatric surgery (BS), only one publication on TO is available. OBJECTIVES: To determine TO in our BS unit and identify the factors linked to TO. SETTING: University public hospital in Alicante (Spain). METHODS: Retrospective observational study of all primary BS was performed. TO for BS was defined in relation to the following features: no major postoperative complications (Clavien-Dindo >II), hospital stay <75th percentile, and no mortality or readmissions within 30 days of surgery. Comparative analysis of the characteristics of the TO and non-TO groups was performed, as well as univariate and multivariate logistic regressions, to identify the independent factors associated with obtaining TO. RESULTS: In 970 patients, TO was achieved in 71.5%. The hospital stay was the one that most affected achievement of TO. Analysis according to the type of procedure (sleeve gastrectomy and gastric bypass) did not reveal any differences between both procedures in terms of obtaining TO (71.5 vs 71.26%). Logistic regression identified smoking, heart disease, operative time, and upper gastrointestinal bleeding as independent factors associated with obtaining TO (p<0.05). Analysis of the annual evolution of TO reveals a progressive increase in its achievement (7.7-86.4%). CONCLUSION: In our series, TO was obtained in 71.5% of patients. The standardization of the technique and the experience gained over the years has improved our TO results.

Textbook outcome en cirugía gástrica oncológica, ¿qué implicaciones tiene sobre la supervivencia? / Textbook outcome in gastric surgery, what implications does it have on survival?

Introducción: El textbook outcome (TO), o resultado de libro, es una medida multidimensional para evaluar la calidad de la práctica asistencial. Ésta viene reflejada como el resultado quirúrgico «ideal», atendiendo a una serie de indicadores o puntos de referencia establecidos que se adaptan en función de la patología quirúrgica que queramos analizar. Son pocas las referencias bibliográficas y las series publicadas al respecto, todas ellas muy recientes. Objetivo: Valorar el grado de cumplimiento del TO y su impacto sobre la supervivencia. Método: Estudio observacional retrospectivo de todas las neoplasias gástricas intervenidas en nuestro centro. Periodo: desde enero del 2015 hasta diciembre del 2020. Se determinaron los siguientes criterios TO: márgenes R0, > 15 ganglios linfáticos en el estudio histológico, sin complicaciones mayores (Clavien-Dindo > IIIa), estancia hospitalaria < 21 días, no presentar mortalidad en los 30 días posoperatorios ni readmisión durante esos 30 días. Se realizó un análisis comparativo entre el grupo de TO vs. grupo no TO. Resultados: Se intervinieron 93 pacientes. Alcanzamos el TO en un 34,1% de los pacientes. La variable > 15 ganglios linfáticos fue la que más afectó a conseguir un TO Al realizar el análisis de supervivencia, observamos que el grupo en que se obtuvo el TO presentó mayor supervivencia (p < 0,008). Conclusión: En nuestra serie, la obtención del TO tiene impacto sobre la supervivencia con un grado de cumplimiento del 34,1%. (AU)

Introduction: The textbook outcome (TO) is a multidimensional measure to assess the quality of healthcare practice. This is reflected as the “ideal” surgical result, attending to a series of indicators or established reference points that are adapted depending on the surgical disease that we want to analyze. There are few references and series published about TO, all of them very recent. Objective: We present a series of gastric surgery from the TO perspective and we analyze its impact on survival. Method: Retrospective observational study of all gastric neoplasms operated on in our center. Period: January 2015 - December 2020. The criteria for TO were: margins R0, > 15 lymph nodes in the histological study, no Clavien-Dindo complications > IIIa, hospital stay < 21 days, no mortality or readmission in the 30 postoperative days. A comparative analysis was performed between the TO group versus the non-TO group. Results: 91 patients were operated on. We reached the TO in 34.1% of the patients. The variable > 15 lymph nodes was the one that most affected to achieve a TO. When performing the survival analysis, we obtained that the group in which the TO was obtained had a greater survival (p < 0.008). Conclusion: In our series, obtaining the TO has an impact on survival which 34,1% of degree of compliance. (AU)

Textbook outcome en cirugía gástrica oncológica, ¿qué implicaciones tiene sobre la supervivencia? / Textbook outcome in gastric surgery, what implications does it have on survival?

Introducción: El textbook outcome (TO), o resultado de libro, es una medida multidimensional para evaluar la calidad de la práctica asistencial. Ésta viene reflejada como el resultado quirúrgico «ideal», atendiendo a una serie de indicadores o puntos de referencia establecidos que se adaptan en función de la patología quirúrgica que queramos analizar. Son pocas las referencias bibliográficas y las series publicadas al respecto, todas ellas muy recientes. Objetivo: Valorar el grado de cumplimiento del TO y su impacto sobre la supervivencia. Método: Estudio observacional retrospectivo de todas las neoplasias gástricas intervenidas en nuestro centro. Periodo: desde enero del 2015 hasta diciembre del 2020. Se determinaron los siguientes criterios TO: márgenes R0, > 15 ganglios linfáticos en el estudio histológico, sin complicaciones mayores (Clavien-Dindo > IIIa), estancia hospitalaria < 21 días, no presentar mortalidad en los 30 días posoperatorios ni readmisión durante esos 30 días. Se realizó un análisis comparativo entre el grupo de TO vs. grupo no TO. Resultados: Se intervinieron 93 pacientes. Alcanzamos el TO en un 34,1% de los pacientes. La variable > 15 ganglios linfáticos fue la que más afectó a conseguir un TO Al realizar el análisis de supervivencia, observamos que el grupo en que se obtuvo el TO presentó mayor supervivencia (p < 0,008). Conclusión: En nuestra serie, la obtención del TO tiene impacto sobre la supervivencia con un grado de cumplimiento del 34,1%. (AU)

Introduction: The textbook outcome (TO) is a multidimensional measure to assess the quality of healthcare practice. This is reflected as the “ideal” surgical result, attending to a series of indicators or established reference points that are adapted depending on the surgical disease that we want to analyze. There are few references and series published about TO, all of them very recent. Objective: We present a series of gastric surgery from the TO perspective and we analyze its impact on survival. Method: Retrospective observational study of all gastric neoplasms operated on in our center. Period: January 2015 - December 2020. The criteria for TO were: margins R0, > 15 lymph nodes in the histological study, no Clavien-Dindo complications > IIIa, hospital stay < 21 days, no mortality or readmission in the 30 postoperative days. A comparative analysis was performed between the TO group versus the non-TO group. Results: 91 patients were operated on. We reached the TO in 34.1% of the patients. The variable > 15 lymph nodes was the one that most affected to achieve a TO. When performing the survival analysis, we obtained that the group in which the TO was obtained had a greater survival (p < 0.008). Conclusion: In our series, obtaining the TO has an impact on survival which 34,1% of degree of compliance. (AU)

Median raphe cysts: A clinico-pathologic and immunohistochemical study of 52 cases.

BACKGROUND: Median raphe cysts (MRC) are epithelial-lined cystic lesions of the genital area that do not communicate with the urethra or the overlying epidermis. Immunohistochemically, MRC show positivity for cytokeratin (CK) 5-6, CK 7, carcinoembryonic antigen, p63 and uroplakin III (URO III). GATA3 and human milk fat globulin 1 (HMFG1) are immunohistochemical markers that have been not previously studied in MRC. METHODS: We conducted a study of 52 patients diagnosed with MRC in the Pathology Departments of eight hospitals between 1990 and 2016. The monoclonal antibodies used were CK5-6, CK7, CK20, URO III, p63, GATA3, and HMFG1. HMFG1 was studied in five cases of apocrine hidrocystomas and compared with five cases of MRC from our series. RESULTS: CK 5-6, CK7, and p63 expression showed strong positivity in the urothelial epithelium of 48 cases. CK20 was focally positive in areas of mucinous differentiation in three cases. GATA3 showed intense nuclear staining in 30 cases. HMFG1 was positive in three cases of MRC and in three cases of apocrine hidrocystoma. CONCLUSION: Positivity of GATA3 and CK7 in MRC supports the urothelial origin of these cysts. We found no differences in HMFG1 expression between MRC and apocrine hidrocystomas.

Textbook outcome in gastric surgery, what implications does it have on survival?

INTRODUCTION: The textbook outcome (TO) is a multidimensional measure to assess the quality of healthcare practice. This is reflected as the "ideal" surgical result, attending to a series of indicators or established reference points that are adapted depending on the surgical disease that we want to analyze. There are few references and series published about TO, all of them very recent. OBJECTIVE: We present a series of gastric surgery from the TO perspective and we analyze its impact on survival. METHOD: Retrospective observational study of all gastric neoplasms operated on in our center. PERIOD: January 2015-December 2020. The criteria for TO were: margins R0, >15 lymph nodes in the histological study, no Clavien-Dindo complications > IIIa, hospital stay < 21 days, no mortality or readmission in the 30 postoperative days. A comparative analysis was performed between the TO group versus the non-TO group. RESULTS: 91 patients were operated on. We reached the TO in 34.1% of the patients. The variable >15 lymph nodes was the one that most affected to achieve a TO. When performing the survival analysis, we obtained that the group in which the TO was obtained had a greater survival (p < 0.008). CONCLUSION: In our series, obtaining the TO has an impact on survival which 34,1% of degree of compliance.

Diagnostic accuracy of uroflowmetry parameters to predict infravesical obstruction / Exactitud diagnóstica de los parámetros de la flujometría para predecir la obstrucción infravesical

Objective: to evaluate the performance statistics of average flow (Qave), voiding time (Vtime), and time to maximum flow (TQmax), in addition to maximum flow (Qmax), for diagnosis of infravesical obstruction. Methods: we reviewed urodynamic studies performed in men > 40 years. Obstruction was considered a grade 3-6 in the Schäfer nomogram. Sensitivity, specificity, positive likelihood ratio (LR+), negative likelihood ratio (LR-), and the receiver operator characteristic (ROC) curve were calculated for the different components of free uroflowmetry. Results: we analyzed 432 studies. Patients with obstruction had lower values of Qmax and Qave, and higher values of Vtime and TQmax. Considering different thresholds, Qmax had sensitivity, specificity, LR + and LR- values of 12-83%, 50-97%, 1.7-4.46 and 0.32-0.9, respectively; Qave had sensitivity, specificity, LR + and LR- values of 65-95%, 21-66%, 1.22-1.94 and 0.19-0.53, respectively; Vtime had sensitivity, specificity, LR + and LR- values of 49-85%, 26-67%, 1.15-1.54, and 0.57-0.74, respectively; TQmax had a sensitivity, specificity, LR + and LR- of 36-81%, 22-72%, 1.04-1.33 and 0.85-0.87, respectively. The areas under the ROC curves for Qmax, Qave, Vtime and TQmax were 0.75 (95% CI = 0.71-0.79, p < 0.001), 0.71 (95% CI = 0.66-0.75, p < 0.001), 0.62 (95% CI = 0.57-0.67, p < 0.001) and 0.55 (95% CI = 0.5-0.6, p = 0.03), respectively. Conclusions: Qave, Vtime, and TQmax showed a statistically significant discriminatory capacity to predict infravesical obstruction, and therefore they have clinical value as a complement to the information provided by Qmax.

Objetivo: evaluar las estadísticas de desempeño del flujo promedio (Qave), el tiempo de evacuación (Vtime) y el tiempo hasta el flujo máximo (TQmax), además del flujo máximo (Qmax), para el diagnóstico de obstrucción infravesical. Métodos: revisamos urodinamias realizadas en hombres > 40 años. La obstrucción se consideró un grado 3-6 en el nomograma de Schäfer. Se calcularon la sensibilidad, la especificidad, la razón de verosimilitud positiva (LR +), la razón de verosimilitud negativa (LR-) y la curva característica operativa del receptor (ROC) para los diferentes componentes de la flujometría libre. Resultados: analizamos 443 estudios. Los pacientes con obstrucción tenían valores más bajos de Qmax y Qave, y valores más altos de Vtime y TQmax. Considerando diferentes umbrales, el Qmax tuvo valores de sensibilidad, especificidad, LR + y LR- de 12-83%, 50-97%, 1.7-4.46 y 0.32-0.9, respectivamente; Qave tuvo valores de sensibilidad, especificidad, LR + y LR- de 65-95%, 21-66%, 1.22-1.94 y 0.19-0.53, respectivamente; Vtime tuvo valores de sensibilidad, especificidad, LR + y LR- de 49-85%, 26-67%, 1.15-1.54 y 0.57-0.74, respectivamente; TQmax tuvo una sensibilidad, especificidad, LR + y LR- de 36-81%, 22-72%, 1.04-1.33 y 0.85-0.87, respectivamente. Las áreas bajo las curvas ROC para Qmax, Qave, Vtime y TQmax fueron 0,75 (95% CI = 0.71-0.79, p < 0,001), 0.71 (95% CI = 0.66-0.75, p < 0,001), 0.62 (95% CI = 0.57-0.67, p < 0,001) y 0.55 (95% CI = 0.5-0.6, p = 0.03), respectivamente. Conclusiones: Qave, Vtime y TQmax mostraron una capacidad discriminatoria estadísticamente significativa para predecir la obstrucción infravesical, por lo que tienen valor clínico como complemento de la información proporcionada por el Qmax.

Improving the Physical Health of Psychiatric Hospital Residents: An Evaluation of an Obesity Education Program for Mental Health Professionals.

BACKGROUND: People living with mental health disorders are at increased risk for developing obesity due to poor diet, physical inactivity, and antipsychotic medications. In the United States, the obesity rate is 36% in the general population and more than 50% for people living with mental health disorders. Although mental health clinicians concentrate on managing psychiatric disorders, they seldom recognize the gradual increase in body mass index of their patients. The result is a disconnection between the clinical management of psychiatric disorders and the medical management of obesity. PURPOSE: This study assessed the effectiveness of an evidence-based education program for improving the obesity management practices of mental health clinicians caring for residents at a state psychiatric hospital. METHODS: This was a quasi-experimental study design with a pretest and posttest evaluation. Convenience sampling was used to recruit mental health professionals, or clinicians, at a large psychiatric hospital in the Southern region of the United States. Data was collected with the Advising and Treating Overweight and Obese Patient questionnaire (17 items). Data analysis included descriptive and inferential statistics. The findings were reported in accordance with the TREND and GREET guidelines. RESULTS: The education program was completed by 50 MHCs. The pretest indicated that 76% of MHCs were not involved in helping obese residents manage their weight, but the posttest indicated 90% were involved. There was a significant increase in MHC knowledge about obesity management and reported actions 90-days after the program. MHCs were unable to arrange follow-up visits for residents, a task not directly within their control. CONCLUSIONS: Mental health clinicians reported increased knowledge and improved clinical practice after an education program. Because the outcomes were reported at 90-days after the program, further research needs to evaluate the longitudinal impact of this type of program, where the reported behaviors are correlated to process and clinical outcome measures for obesity.

Dorsal Vascular Complex Nonligation Method and Preservation of Puboprostatic Ligaments and Endopelvic Fascia During Laparoscopic Radical Prostatectomy: Effect on Continence.

OBJECTIVE: To evaluate the impact on continence rate during 1-year follow-up of a preservation technique that included nonligation of the dorsal vascular complex and sparing of the puboprostatic ligaments and the endopelvic fascia during laparoscopic radical prostatectomy. MATERIAL AND METHODS: Information from 30 patients who underwent the preservation technique was prospectively collected and compared with data from 60 patients who underwent the nonpreservation traditional technique. A single surgeon performed all procedures. RESULTS: Demographic and preoperative characteristics were similar. The mean patient age was 59 years in both groups. All patients were stage cT1c or cT2. Operative time was significantly lower in the preservation technique group (229.6 vs. 262.7 minutes, P < .001). There were no significant differences in intraoperative bleeding, discharge hemoglobin level, blood transfusion rate, length of hospitalization, and drop in the hemoglobin level. The probability of continence recovery was significantly higher in the preservation technique group than in the traditional technique group (hazard ratio = 0.50, 95% CI = 0.31-0.81). The continence rate (0 pads/day) for the preservation technique group versus the traditional technique group at 1, 3, 6, and 12 months was, respectively, 53.3% versus 30% (P = .031), 90% versus 45% (P < .001), 90% versus 63.3% (P = .008), and 96.6% versus 78.3% (P = .024). There were no significant differences between the groups regarding potency and oncologic outcomes. CONCLUSION: Nonligation of the dorsal vascular complex and preservation of the puboprostatic ligaments and the endopelvic fascia improved urinary continence compared with the traditional nonpreservation technique, with no impact in terms of bleeding and oncologic outcomes.

Early postoperative complications after gastric bypass revisional surgery in patients with previous sleeve gastrectomy versus primary gastric bypass.

BACKGROUND: Revisional bariatric surgery (RS) is indicated if there is weight regain or insufficient weight loss, no improvement or reappearance of co-morbidities, or previous bariatric surgery complications. It has been associated with higher postoperative morbidity. OBJECTIVE: To evaluate the early postoperative complications (<30 d) of Roux-en-Y gastric bypass RS (RYGB-RS) after primary sleeve gastrectomy (SG-1) compared with primary RYGB (RYGB-1) at a bariatric surgery referral center. SETTING: Department of General and Digestive Surgery of General Universitary Hospital of Alicante, Spain. METHODS: Retrospective cohort study comparing RYGB-RS after SG-1 and RYGB-1 between January 2008 and March 2021. Postoperative complications, hospital stay, mortality, and readmissions were analyzed. RESULTS: Six hundred and twenty-eight RYGB surgeries (48 RYGB-RS, 580 RYGB-1) were studied. The mean age of patients undergoing RYGB-RS was 50 years, compared with 46 years in the RYGB-1 group (P = .017). Mean initial body mass index was 44.2 kg/m2 (RYGB-RS) versus 47.6 kg/m2 (RYGB-1; P = .004). Cardiovascular risk factors were higher in the RYGB-1 group (P < .05). Indications for RS were weight regain or insufficient weight loss (72.9%), weight regain or insufficient weight loss plus gastroesophageal reflux disease (14.6%), and gastroesophageal reflux disease (12.5%). There were no differences in the frequency of complications (RYGB-RS 22.9% vs RYGB-1 20.5%) or in their severity (Clavien-Dindo ≥IIIa; RYGB-RS 10.4% vs RYGB-1 6.4%; P > .05). There were no differences in emergency room visits (RYGB-RS at 12.5% vs RYGB-1 at 14.9%) or in readmissions (RYGB-RS at 12.5% vs RYGB-1 at 9.4%). CONCLUSION: No differences were observed between primary RYGB and revisional RYGB in early morbidity, mortality, emergencies, or readmissions. Revisional bariatric surgery is a safe procedure at referral centers and must be done by expert hands.

Exclusionary discipline practices and their relation to Chilean students' perception of school climate practices.

One of the challenges of school climate policies has been to promote dialogical conflict resolution by reducing punitive practices and encouraging student participation. However, exclusionary punitive practices are still being used, and in Chile, they are considered acceptable forms of conflict resolution. In this study, we analyzed the association between students' reports of punitive and democratic school climate in a sample of 2459 eighth graders (mean age = 13.56, SD = 0.84) from 128 Chilean schools. Multilevel analyses showed that a higher perception of punitive practices and higher academic performance were associated with a higher perception of an inclusive, democratic, and peaceful school climate. The perception of a higher school-level frequency of punishment was associated with a higher perception of an inclusive and democratic school climate. We discuss the implications of these findings for an authoritarian school culture.

Higher Adherence to ERAS Society® Recommendations is Associated with Shorter Hospital Stay Without an Increase in Postoperative Complications or Readmissions in Bariatric Surgery: the Association Between Use of Enhanced Recovery After Surgery Protocols and Postoperative Complications after Bariatric Surgery (POWER 3) Multicenter Observational Study.

PURPOSE: The effectiveness of enhanced recovery after surgery (ERAS) pathways in patients undergoing bariatric surgery remains unclear. Our objective was to determine the effect of the ERAS elements on patient outcomes following elective bariatric surgery. MATERIALS AND METHODS: Prospective cohort study in adult patients undergoing elective bariatric surgery. Each participating center selected a single 3-month data collection period between October 2019 and September 2020. We assessed the 24 individual components of the ERAS pathways in all patients. We used a multivariable and multilevel logistic regression model to adjust for baseline risk factors, ERAS elements, and center differences RESULTS: We included 1419 patients. One hundred and fourteen patients (8%) developed postoperative complications. There were no differences in the incidence of overall postoperative complications between the self-designated ERAS and non-ERAS groups (54 (8.7%) vs. 60 (7.6%); OR, 1.14; 95% CI, 0.73-1.79; P = .56), neither for moderate-to-severe complications, readmissions, re-interventions, mortality, or hospital stay (2 [IQR 2-3] vs. 3 [IQR 2-4] days, 0.85; 95% CI, 0.62-1.17; P = .33) Adherence to the ERAS elements in the highest adherence quartile (Q1) was greater than 72.2%, while in the lowest adherence quartile (Q4) it was less than 55%. Patients with the highest adherence rates had shorter hospital stay (2 [IQR 2-3] vs. 3 [IQR 2-4] days, 1.54; 95% CI, 1.09-2.17; P = .015), while there were no differences in the other outcomes CONCLUSIONS: Higher adherence to ERAS Society® recommendations was associated with a shorter hospital stay without an increase in postoperative complications or readmissions. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03864861.

Integrative Genomic and Transcriptomic Profiling Reveals a Differential Molecular Signature in Uterine Leiomyoma versus Leiomyosarcoma.

The absence of standardized molecular profiling to differentiate uterine leiomyosarcomas versus leiomyomas represents a current diagnostic challenge. In this study, we aimed to search for a differential molecular signature for these myometrial tumors based on artificial intelligence. For this purpose, differential exome and transcriptome-wide research was performed on histologically confirmed leiomyomas (n = 52) and leiomyosarcomas (n = 44) to elucidate differences between and within these two entities. We identified a significantly higher tumor mutation burden in leiomyosarcomas vs. leiomyomas in terms of somatic single-nucleotide variants (171,863 vs. 81,152), indels (9491 vs. 4098), and copy number variants (8390 vs. 5376). Further, we discovered alterations in specific copy number variant regions that affect the expression of some tumor suppressor genes. A transcriptomic analysis revealed 489 differentially expressed genes between these two conditions, as well as structural rearrangements targeting ATRX and RAD51B. These results allowed us to develop a machine learning approach based on 19 differentially expressed genes that differentiate both tumor types with high sensitivity and specificity. Our findings provide a novel molecular signature for the diagnosis of leiomyoma and leiomyosarcoma, which could be helpful to complement the current morphological and immunohistochemical diagnosis and may lay the foundation for the future evaluation of malignancy risk.

Frequentist and Bayesian Hypothesis Testing: An Intuitive Guide for Urologists and Clinicians / Pruebas de hipótesis frecuentista y bayesiana: Una Guía intuitiva para urólogos y clínicos

Given the limitations of frequentist method for null hypothesis significance testing, different authors recommend alternatives such as Bayesian inference. A poor understanding of both statistical frameworks is common among clinicians. The present is a gentle narrative review of the frequentist and Bayesian methods intended for physicians not familiar with mathematics. The frequentist p-value is the probability of finding a value equal to or higher than that observed in a study, assuming that the null hypothesis (H0) is true. The H0 is rejected or not based on a p threshold of 0.05, and this dichotomous approach does not express the probability that the alternative hypothesis (H1) is true. The Bayesian method calculates the probability of H1 and H0 considering prior odds and the Bayes factor (Bf). Prior odds are the researcher's belief about the probability of H1, and the Bf quantifies how consistent the data is concerning H1 and H0. The Bayesian prediction is not dichotomous but is expressed in continuous scales of the Bf and of the posterior odds. The JASP software enables the performance of both frequentist and Bayesian analyses in a friendly and intuitive way, and its application is displayed at the end of the paper. In conclusion, the frequentist method expresses how consistent the data is with H0 in terms of p-values, with no consideration of the probability of H1. The Bayesian model is a more comprehensive prediction because it quantifies in continuous scales the evidence for H1 versus H0 in terms of the Bf and the

Dadas las limitaciones del método de significancia frecuentista basado en la hipótesis nula, diferentes autores recomiendan alternativas como la inferencia bayesiana. Es común entre los médicos una comprensión deficiente de ambos marcos estadísticos. Esta es una revisión narrativa amigable de los métodos frecuentista y bayesiano dirigida quienes no están familiarizados con las matemáticas. El valor de p frecuentista es la probabilidad de encontrar un valor igual o superior al observado en un estudio, asumiendo que la hipótesis nula (H0) es cierta. La H0 se rechaza o no con base en un umbral p de 0.05, y este enfoque dicotómico no expresa la probabilidad de que la hipótesis alternativa (H1) sea verdadera. El método bayesiano calcula la probabilidad de H1 y H0 considerando las probabilidades a priori y el factor de Bayes (fB). Las probabilidades a priori son la creencia del investigador sobre la probabilidad de H1, y el fB cuantifica cuán consistentes son los datos con respecto a H1 y H0. La predicción bayesiana no es dicotómica, sino que se expresa en escalas continuas del fB y de las probabilidades a posteriori. El programa JASP permite realizar análisis frecuentista y bayesiano de una forma simple e intuitiva, y su aplicación se muestra al final del documento. En conclusión, el método frecuentista expresa cuán consistentes son los datos con H0 en términos de valores p, sin considerar la probabilidad de H1. El modelo bayesiano es una predicción más completa porque cuantifica en escalas continuas la evidencia de H1 versus H0 en términos del fB y de las probabilidades a posteriori.

Probing tissue transglutaminase mediated vascular smooth muscle cell aging using a novel transamidation-deficient Tgm2-C277S mouse model.

Tissue transglutaminase (TG2), a multifunctional protein of the transglutaminase family, has putative transamidation-independent functions in aging-associated vascular stiffening and dysfunction. Developing preclinical models will be critical to fully understand the physiologic relevance of TG2's transamidation-independent activity and to identify the specific function of TG2 for therapeutic targeting. Therefore, in this study, we harnessed CRISPR-Cas9 gene editing technology to introduce a mutation at cysteine 277 in the active site of the mouse Tgm2 gene. Heterozygous and homozygous Tgm2-C277S mice were phenotypically normal and were born at the expected Mendelian frequency. TG2 protein was ubiquitously expressed in the Tgm2-C277S mice at levels similar to those of wild-type (WT) mice. In the Tgm2-C277S mice, TG2 transglutaminase function was successfully obliterated, but the transamidation-independent functions ascribed to GTP, fibronectin, and integrin binding were preserved. In vitro, a remodeling stimulus led to the significant loss of vascular compliance in WT mice, but not in the Tgm2-C277S or TG2-/- mice. Vascular stiffness increased with age in WT mice, as measured by pulse-wave velocity and tensile testing. Tgm2-C277S mice were protected from age-associated vascular stiffening, and TG2 knockout yielded further protection. Together, these studies show that TG2 contributes significantly to overall vascular modulus and vasoreactivity independent of its transamidation function, but that transamidation activity is a significant cause of vascular matrix stiffening during aging. Finally, the Tgm2-C277S mice can be used for in vivo studies to explore the transamidation-independent roles of TG2 in physiology and pathophysiology.

A Bayesian approach to extracting free-energy profiles from cryo-electron microscopy experiments.

Cryo-electron microscopy (cryo-EM) extracts single-particle density projections of individual biomolecules. Although cryo-EM is widely used for 3D reconstruction, due to its single-particle nature it has the potential to provide information about a biomolecule's conformational variability and underlying free-energy landscape. However, treating cryo-EM as a single-molecule technique is challenging because of the low signal-to-noise ratio (SNR) in individual particles. In this work, we propose the cryo-BIFE method (cryo-EM Bayesian Inference of Free-Energy profiles), which uses a path collective variable to extract free-energy profiles and their uncertainties from cryo-EM images. We test the framework on several synthetic systems where the imaging parameters and conditions were controlled. We found that for realistic cryo-EM environments and relevant biomolecular systems, it is possible to recover the underlying free energy, with the pose accuracy and SNR as crucial determinants. We then use the method to study the conformational transitions of a calcium-activated channel with real cryo-EM particles. Interestingly, we recover not only the most probable conformation (used to generate a high-resolution reconstruction of the calcium-bound state) but also a metastable state that corresponds to the calcium-unbound conformation. As expected for turnover transitions within the same sample, the activation barriers are on the order of [Formula: see text]. We expect our tool for extracting free-energy profiles from cryo-EM images to enable more complete characterization of the thermodynamic ensemble of biomolecules.

HIF2A gain-of-function mutation modulates the stiffness of smooth muscle cells and compromises vascular mechanics.

Heterozygous gain-of-function (GOF) mutations of hypoxia-inducible factor 2α (HIF2A), a key hypoxia-sensing regulator, are associated with erythrocytosis, thrombosis, and vascular complications that account for morbidity and mortality of patients. We demonstrated that the vascular pathology of HIF2A GOF mutations is independent of erythrocytosis. We generated HIF2A GOF-induced pluripotent stem cells (iPSCs) and differentiated them into endothelial cells (ECs) and smooth muscle cells (SMCs). Unexpectedly, HIF2A-SMCs, but not HIF2A-ECs, were phenotypically aberrant, more contractile, stiffer, and overexpressed endothelin 1 (EDN1), myosin heavy chain, elastin, and fibrillin. EDN1 inhibition and knockdown of EDN1-receptors both reduced HIF2-SMC stiffness. Hif2A GOF heterozygous mice displayed pulmonary hypertension, had SMCs with more disorganized stress fibers and higher stiffness in their pulmonary arterial smooth muscle cells, and had more deformable pulmonary arteries compared with wild-type mice. Our findings suggest that targeting these vascular aberrations could benefit patients with HIF2A GOF and conditions of augmented hypoxia signaling.

Competitive Adsorption of Xylenes at Chemical Equilibrium in Zeolites.

The separation of xylenes is one of the most important processes in the petrochemical industry. In this article, the competitive adsorption from a fluid-phase mixture of xylenes in zeolites is studied. Adsorption from both vapor and liquid phases is considered. Computations of adsorption of pure xylenes and a mixture of xylenes at chemical equilibrium in several zeolite types at 250 °C are performed by Monte Carlo simulations. It is observed that shape and size selectivity entropic effects are predominant for small one-dimensional systems. Entropic effects due to the efficient arrangement of xylenes become relevant for large one-dimensional systems. For zeolites with two intersecting channels, the selectivity is determined by a competition between enthalpic and entropic effects. Such effects are related to the orientation of the methyl groups of the xylenes. m-Xylene is preferentially adsorbed if xylenes fit tightly in the intersection of the channels. If the intersection is much larger than the adsorbed molecules, p-xylene is preferentially adsorbed. This study provides insight into how the zeolite topology can influence the competitive adsorption and selectivity of xylenes at reaction conditions. Different selectivities are observed when a vapor phase is adsorbed compared to the adsorption from a liquid phase. These insight have a direct impact on the design criteria for future applications of zeolites in the industry. MRE-type and AFI-type zeolites exclusively adsorb p-xylene and o-xylene from the mixture of xylenes in the liquid phase, respectively. These zeolite types show potential to be used as high-performing molecular sieves for xylene separation and catalysis.

Contributions of Individual, Family, and School Characteristics to Chilean Students' Social Well-Being at School.

Schools are an essential part of students' lives and can promote and facilitate their well-being. Although research on well-being among school-aged children and adolescents has distinguished subjective well-being from social well-being, very few studies examined student's social well-being at school (SWS). SWS is understood as students' valuation of the circumstances and functioning of their school. This framework posits that the context of the schools can shape students' perception of feeling integrated and making significant contributions to their schools. However, not much is known regarding the joint contribution of individual, family, and school characteristics to students' SWS. This study analyzed these joint contributions in a nationally representative sample of 6,389 children and adolescents enrolled in 5th-11th grades. Findings show that being female and younger were individual predictors of SWS. Students' satisfaction with their family and fewer changes of schools were also significant contributors. When students' perceptions of their schools were incorporated, the individual and family characteristics decreased or lost significance. In the full model, the highest contribution to SWS was explained by the school-level aggregated perception of school climate. These findings call for integrated policies and practices to foster students' sense of belonging, feeling integrated, and contribution to their schools, with a focus on school-level interventions to improve SWS through positive and engaging school climates that foster students' sense of agency.