A reverse-engineering approach to dissect post-translational modulators of transcription factor's activity from transcriptional data.

BACKGROUND: Transcription factors (TFs) act downstream of the major signalling pathways functioning as master regulators of cell fate. Their activity is tightly regulated at the transcriptional, post-transcriptional and post-translational level. Proteins modifying TF activity are not easily identified by experimental high-throughput methods. RESULTS: We developed a computational strategy, called Differential Multi-Information (DMI), to infer post-translational modulators of a transcription factor from a compendium of gene expression profiles (GEPs). DMI is built on the hypothesis that the modulator of a TF (i.e. kinase/phosphatases), when expressed in the cell, will cause the TF target genes to be co-expressed. On the contrary, when the modulator is not expressed, the TF will be inactive resulting in a loss of co-regulation across its target genes. DMI detects the occurrence of changes in target gene co-regulation for each candidate modulator, using a measure called Multi-Information. We validated the DMI approach on a compendium of 5,372 GEPs showing its predictive ability in correctly identifying kinases regulating the activity of 14 different transcription factors. CONCLUSIONS: DMI can be used in combination with experimental approaches as high-throughput screening to efficiently improve both pathway and target discovery. An on-line web-tool enabling the user to use DMI to identify post-transcriptional modulators of a transcription factor of interest che be found at http://dmi.tigem.it

Mejora de la gestión de la productividad de la flota de carguío y acarreo U.M Cuajone, mediante la aplicación de la metodología Six Sigma para disminuir las demoras operativas en el relevo del personal

El presente trabajo de investigación se realizó en la empresa Southern Perú Unidad Minera Cuajone y tuvo como finalidad minimizar los tiempos improductivos en el proceso de relevo del personal que opera equipos de carguío y acarreo en interior mina aplicando la metodología Six Sigma. El procedimiento metodológico aplicado en la mejora de la gestión de la productividad de la flota de carguío y transporte se basó en la aplicación de la metodología Six Sigma desde la recopilación y análisis de datos en gabinete y campo. En la etapa inicial de gabinete se recolectó los datos del sistema de gestión de flota JMineOps y se procedió a revalidar la información en campo y registrar los tiempos improductivos más significantes del cambio de turno, en la fase final de gabinete se analizó la información extraída del anterior y nuevo proceso del relevo de personal , y se realizó una evaluación de los tiempos entre actividades, del tonelaje de arranque en las distintas guardias ,ya que es un parámetro fundamental a incluir para poder evaluar cómo se ve afectada la productividad en la primera hora del turno ,ya que al inicio de guardia se pierde tonelaje a causa de las demoras operativas en el relevo del personal, además, se comparará la disponibilidad física y utilización de la flota de equipos de carguío y transporte. Según el análisis se obtuvo que las demoras más significativas de la operación fueron Espera en Bahía de transporte, Personal Rezagado, Charla de Seguridad y Revisión de Pantallas para asignación de equipos que significaron el 37% ,59%, 77% y 84% respectivamente de las demoras totales. Los resultados fueron favorables, se redujeron las demoras operativas presentes en la primera hora de cada turno. Lo que permitió cuantificar las toneladas que se dejó de mover por la duración de los retrasos sobre la primera hora de turno siendo 1062 toneladas de mineral y 3938 toneladas de desmonte aproximadamente por guardia. Se incrementó la producción de arranque en 2000 toneladas de mineral al día, lo cual equivale a ganancias diarias de 14,348 $y 5,236,985$ al año. Adicionalmente, se optimizó y automatizó el inicio de las operaciones, por ende, se redujeron las demoras operativas en el relevo del personal y con ello se aumentó la disponibilidad física de la flota de Palas y volquetes en 2.5%, en 1.6% la utilización de las palas y en 1.4% la utilización de los volquetes.The present research work was carried out at the Southern Peru Mining Unit Cuajone Company and its purpose was to minimize unproductive times in the process of the Shift Change that operates loading and hauling fleet inside the mine applying the Six Sigma methodology. The methodological procedure applied in the improvement of the productivity management of the loading and hauling fleet was based on the application of the Six Sigma methodology from the collection and analysis of data in the office and in the field. In the initial stage of the office the data from the JMineOps fleet management system was collected and the information was revalidated in the field with the most significant unproductive times of the shift change. In the final phase of the cabinet the information extracted from the previous and new process of the shift change was analyzed. The evaluation of the times between activities and starting tonnage in the different shifts was carried out since it is a fundamental parameter to include to be able to evaluate how productivity is affected in the first hour of the shift. According to the analysis, the most significant delays of the operation were Waiting in the transport bay, Iddle Personnel, Safety Talk and Screen Review for the assignment of equipment that meant 37%, 59%, 77% and 84% respectively of total delays. The results were favorable, the operational delays present in the first hour of each shift were reduced. This allowed to quantify the tons that were not moved due to the duration of the delays in the first hour of the shift, being 1062 tons of ore and 3938 tons of waste approximately per shift. The start-up production was increased by 2000 tons of ore per day, which is equivalent to daily earnings of $14,348 and$5,236,985 per year. In addition, the start-up of operations was optimized and automated, thereby reducing operational delays in personnel replacement and increasing the physical availability of the fleet of shovels and dump trucks by 2.5%, shovel utilization by 1.6% and dump truck utilization by 1.4%.Tesi

Absolute agreement and consistency of the OptoGait system and Freemed platform for measuring walking gait

The gait cycle can be divided into four functional rocker units. Although the widespread use of the OptoGait (OG) system and the Freemed (FM) platform, their accuracy has not been tested. An observational study was completed with eighteen healthy volunteers to determine the accuracy of OG and FM for overground walking gait analysis. The pairwise comparison between data obtained from OG, FM and high-speed video analysis revealed significant differences for most of the measurements (p  0.94) for all measures for OG systems compared to video-analysis. When considering FM vs. video-analysis, ICCs showed good absolute agreement for rocker 1 (ICC = 0.86) and 3 (ICC = 0.82), excellent for rocker 2 (ICC = 0.93) and poor (ICC  0.1) while no heteroscedasticity of error was found when using FM (r2 < 0.1). This study indicates that the OG system and the FM platform can provide consistent foot rockers values when walking at a constant velocity. The differences between the systems assessed and their agreement and consistency values advise against their interchangeable use

TYPE II DIABETES MELLITUS AND MANAGEMENT OF ISOLATED HYPERGLYCEMIA: A REVIEW

Type II Diabetes mellitus (T2DM) is the most common of two types of Diabetes disease. T2DM is a metabolic disease characterized mainly by insulin resistance, reduction of insulin secretion, and hyperglycemia. T2DM is a major public health cause of concern not only by the increase in morbidity and mortality associated with patients with the disease, but also by the significant reduction in quality of life and productivity among the economically active population. Isolated hyperglycemia refers to patients with T2DM with normal fasting plasma glucose and no ketoacidosis. With the rise of T2DM and the presence of hidden symptoms, it is vital to determine a diagnostic sequence, blood-glucose control with sulfonylureas or insulin, and diet and exercise

LUMBAR DISK HERNIATION: EVALUATION OF MEDICAL CARE AND PAIN MANAGEMENT AT THE SPECIALTIES HOSPITAL CREHVITAL AMBATO-ECUADOR: RETROSPECTIVE, CROSS-SECTIONAL STUDY, AND ASSESSMENT OF TWO CLINICAL CASES

Objectives: The objective of the study was to assess medical care and pain management of 237 lumbar disk herniation cases treated from 2011 to 2021 in the Specialties Hospital CREHVITAL, Ambato-Ecuador, and to provide a set of standards for appropriate management. Methods: Retrospective, cross-sectional analysis of archives, and registries of patient’s data provided by the Specialties Hospital CREHVITAL, Ambato-Ecuador. Participants: A total of 237 patients with lumbar disk herniation received medical services from 2011 to 2021; outcome measures were: Pain management, patient characteristics, surgical procedures, and medication after surgery. Results: The 40–50 age range had the highest prevalence of lumbar disk herniation and a higher percentage of the pathology in men (66%) than in women. Of the 237 patients, magnetic resonance imaging (MRI) showed the highest lumbar disk herniation of the L4–L5 (101 men and 20 women), followed by herniation of the L5–S1 (59 men and 51 women). Two types of surgeries were performed: Classical surgery on 157 patients and microsurgery on 80 patients. The average period before receiving treatment was 1.5 years of maintaining back pain, and the early post-operative management consisted of patients receiving diclofenac, ketorolac, and ceftriaxone. Analgesics were used in 73.43% of patients. All cases required strict control, follow-up, and post-operative check-ups. Conclusion: This study provides essential and conclusive evidence and information on treated cases of lumbar disk herniation and its incidence in the medical field

The validity of incremental exercise testing in discriminating of physiological profiles in elite runners

The goal of this study was to determine whether traditional ergoespirometric incremental exercise testing carried out to the point of exhaustion could be useful in distinguishing the physiological profiles of elite runners that compete in races that lasted about 8 minutes versus those that lasted about 2 hours. Ten male marathon runners (performance time: 2:12:04, coefficient of variation (CV) = 2.33%) and 8 male 3000 m steeplechase runners (performance time: 8:37.83, CV = 2.12%) performed an incremental test on the treadmill (starting speed 10 km. h–1; increments, 2 km. h–1; increment duration, 3 min to exhaustion). Heart rate (HR), VO2 , and lactate concentrations were measured at the end of each exercise level. At maximal effort, there were no differences between the groups regarding VO2max and maximal HR; however, the workload time, vVO2max and peak treadmill velocity were significantly higher in the 3000m steeplechase group (p<0.05). At submaximal effort, there were no significant differences between groups for VO2 (ml.kg–1.min–1), HR, or lactate. Our results show that this type of testing was not sufficient for discriminating the physiological profiles of elite runners who competed in middle-distance versus long-distance events (e.g. in the marathon and the 3000 m steeplechase

Claves diagnósticas de las cefaleas

La cefalea es un síntoma muy común, afecta a casi todas las personas en algún momento de su vida. Es el quinto motivo de consulta más frecuente en los servicios de urgencias y un número importante de pacientes acude a la consulta ambulatoria por cefalea crónica. La población pediátrica y adolescente también se afecta. Una adecuada historia clínica y un completo examen físico permiten el abordaje diagnóstico y terapéutico. Identificar los factores desencadenantes y antecedentes personales es fundamental. La presencia de cefalea sumada a otros signos y síntomas como alteración del estado de conciencia, focalización neurológica, convulsiones, entre otros, debe alertar al médico. El presente artículo describe las características demográficas y semiológicas de las cefaleas, además aborda los signos de alarma o banderas rojas que obligan a descartar patologías de mayor compromiso

Does Lower-Limb Tendon Structure Influence Walking Gait?

Background: Within the exploration of human gait, key focal points include the examination of functional rockers and the influential role of tendon behavior in the intricate stretch–shortening cycle. To date, the possible relationship between these two fundamental factors in the analysis of human gait has not been studied. Therefore, this study aimed to analyze the relationship between the morphology of the patellar and Achilles tendons and plantar fascia with respect to the duration of the rockers. Methods: Thirty-nine healthy men (age: 28.42 ± 6.97 years; height: 173 ± 7.17 cm; weight: 67.75 ± 9.43 kg) were included. Data of the rockers were recorded using a baropodometric platform while participants walked over a 10 m walkway at a comfortable velocity. Before the trials, the thickness and cross-sectional area were recorded for the patellar tendon, Achilles tendon and plantar fascia using ultrasound examination. The relationship between the morphology of the soft tissue and the duration of the rockers was determined using a pairwise mean comparison (t-test). Results: A significant difference was found for rocker 1 duration, where a longer duration was found in the group of subjects with thicker patellar tendons. Regarding the Achilles tendon and plantar fascia, no significant differences were observed in terms of tendon morphology. However, subjects with thicker Achilles tendons showed a longer duration of rocker 1. Conclusions: The findings underscore a compelling association, revealing that an increased thickness of the patellar tendon significantly contributes to the extension of rocker 1 duration during walking in healthy adults

PD-(L)1 Inhibitors as Monotherapy for the First-Line Treatment of Non-Small-Cell Lung Cancer Patients with High PD-L1 Expression: A Network Meta-Analysis

Programmed cell death-ligand 1 (PD-L1) has emerged as a potential biomarker for selection of patients more likely to respond to immunotherapy and as a prognostic factor in non-small cell lung cancer (NSCLC). In this network meta-analysis, we aimed to evaluate the efficacy of first-line anti-PD-(L)1 monotherapy in advanced NSCLC patients with high PD-L1 expression (≥50%) compared to platinum-based chemotherapy. We also evaluated efficacy outcomes according to tumor mutational burden (TMB). To that end, we conducted a systematic review. Six clinical trials with 2111 patients were included. In head-to-head comparisons, immunotherapy showed a significant improvement in progression-free survival (PFS: HRpooled = 0.69, 95% CI: 0.52–0.90, p = 0.007), overall survival (OS: HRpooled = 0.69, 95% CI: 0.61–0.78; p < 0.001) and overall response rate (ORR) (Risk ratio (RR)pooled = 1.354, 95% CI: 1.04–1.762, p = 0.024). In the assessment of relative efficacy for PFS through indirect comparisons, pembrolizumab (results from KEYNOTE-024) ranked highest followed by cemiplimab and atezolizumab, with statistical significance determined for some of the drugs. In terms of OS, cemiplimab ranked highest followed by atezolizumab and pembrolizumab, although non-significant OS was determined for these drugs. In conclusion, PD-(L)1 inhibitor monotherapy improves efficacy outcomes in the first line setting of advanced NSCLC patients with high PD-L1 expression. Evaluations with longer follow up are still needed to determine the superiority of any specific drug

Estudio de prefactibilidad para el diseño de un sistema de identificación de redes de fibra óptica en la ciudad de Bogotá.

Este trabajo se realiza con el fin de hacer un estudio de mercado para el diseño de un sistema de identificación de redes de fibra óptica en la ciudad de Bogotá, que permita especificar las características de los componentes tecnológicos que debe tener un sistema de identificación de los hilos de la red de fibra óptica, proponiendo la instalación de etiquetas que permitan realizar la marcación física de la líneas