bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of the IKKβ Binding of Indicaxanthin by Induced-Fit Docking, Binding Pose Metadynamics, and Molecular Dynamics
Authors: Allegra Mario , Tutone Marco , Tesoriere Luisa , Attanzio Alessandro , Culletta Giulia , Almerico Anna Maria 
Published: September 2021

Background: Indicaxanthin, a betaxanthin belonging to the betalain class of compounds, has been recently demonstrated to exert significant antiproliferative effects inducing apoptosis of human melanoma cells through the inhibition of NF-κB as the predominant pathway. Specifically, Indicaxanthin inhibited IκBα degradation in A375 cells. In resting cells, NF-κB is arrested in the cytoplasm by binding to its inhibitor protein IκBα. Upon stimulation, IκBα is phosphorylated by the IKK complex, and degraded by the proteasome, liberating free NF-κB into the nucleus to initiate target gene transcription. Inhibition of the IKK complex leads to the arrest of the NF-κB pathway.Methods: To acquire details at the molecular level of Indicaxanthin’s inhibitory activity against hIKKβ, molecular modeling and simulation techniques including induced-fit docking (IFD), binding pose metadynamics (BPMD), molecular dynamics simulations, and MM-GBSA (molecular mechanics-generalized Born surface area continuum solvation) have been performed.Results: The computational calculations performed on the active and inactive form, and the allosteric binding site of hIKKβ, revealed that Indicaxanthin inhibits prevalently the active form of the hIKKβ. MM-GBSA computations provide further evidence of Indicaxanthin’s stability inside the active binding pocket with a binding free energy of −22.2 ± 4.3 kcal/mol with respect to the inactive binding pocket with a binding free energy of −20.7 ± 4.7 kcal/mol. BPMD and MD simulation revealed that Indicaxanthin is likely not an allosteric inhibitor of hIKKβ.Conclusion: As a whole, these in silico pieces of evidence show that Indicaxanthin can inhibit the active form of the hIKKβ adding novel mechanistic insights on its recently discovered ability to impair NF-κB signaling in melanoma A375 cells. Moreover, our results suggest the phytochemical as a new lead compound for novel, more potent IKKβ inhibitors to be employed in the treatment of cancer and inflammation-related conditions.
Effects of Body Position and Hypovolemia on the Regional Distribution of Pulmonary Perfusion During One-Lung Ventilation in Endotoxemic Pigs
Authors: Wittenstein Jakob , Scharffenberg Martin , Ran Xi , Zhang Yingying , Keller Diana , Tauer Sebastian , Theilen Raphael , Chai Yusen , Ferreira Jorge , Müller Sabine , Bluth Thomas , Kiss Thomas , Schultz Marcus J. , Rocco Patricia R. M. , Pelosi Paolo , Gama de Abreu Marcelo , Huhle Robert 
Published: September 2021

Background: The incidence of hypoxemia during one-lung ventilation (OLV) is as high as 10%. It is also partially determined by the distribution of perfusion. During thoracic surgery, different body positions are used, such as the supine, semilateral, lateral, and prone positions, with such positions potentially influencing the distribution of perfusion. Furthermore, hypovolemia can impair hypoxic vasoconstriction. However, the effects of body position and hypovolemia on the distribution of perfusion remain poorly defined. We hypothesized that, during OLV, the relative perfusion of the ventilated lung is higher in the lateral decubitus position and that hypovolemia impairs the redistribution of pulmonary blood flow.Methods: Sixteen juvenile pigs were anesthetized, mechanically ventilated, submitted to a right-sided thoracotomy, and randomly assigned to one of two groups: (1) intravascular normovolemia or (2) intravascular hypovolemia, as achieved by drawing ~25% of the estimated blood volume (n = 8/group). Furthermore, to mimic thoracic surgery inflammatory conditions, Escherichia coli lipopolysaccharide was continuously infused at 0.5 μg kg−1 h−1. Under left-sided OLV conditions, the animals were further randomized to one of the four sequences of supine, left semilateral, left lateral, and prone positioning. Measurements of pulmonary perfusion distribution with fluorescence-marked microspheres, ventilation distribution by electrical impedance tomography, and gas exchange were then performed during two-lung ventilation in a supine position and after 30 min in each position and intravascular volume status during OLV.Results: During one-lung ventilation, the relative perfusion of the ventilated lung was higher in the lateral than the supine position. The relative perfusion of the non-ventilated lung was lower in the lateral than the supine and prone positions and in semilateral compared with the prone position. During OLV, the highest arterial partial pressure of oxygen/inspiratory fraction of oxygen (PaO2/FIO2) was achieved in the lateral position as compared with all the other positions. The distribution of perfusion, ventilation, and oxygenation did not differ significantly between normovolemia and hypovolemia.Conclusions: During one-lung ventilation in endotoxemic pigs, the relative perfusion of the ventilated lung and oxygenation were higher in the lateral than in the supine position and not impaired by hypovolemia.
Molecular Mechanism and Pathways of Normal Human Parturition in Different Gestational Tissues: A Systematic Review of Transcriptome Studies
Authors: Ding Wenjing , Chim Stephen Siu Chung , Wang Chi Chiu , Lau Caitlyn So Ling , Leung Tak Yeung 
Published: September 2021

Objective: Genome-wide transcriptomic studies on gestational tissues in labor provide molecular insights in mechanism of normal parturition. This systematic review aimed to summarize the important genes in various gestational tissues around labor onset, and to dissect the underlying molecular regulations and pathways that trigger the labor in term pregnancies.Data sources: PubMed and Web of Science were searched from inception to January 2021.Study Eligibility Criteria: Untargeted genome-wide transcriptomic studies comparing the gene expression of various gestational tissues in normal term pregnant women with and without labor were included.Methods: Every differentially expressed gene was retrieved. Consistently expressed genes with same direction in different studies were identified, then gene ontology and KEGG analysis were conducted to understand molecular pathways and functions. Gene-gene association analysis was performed to determine the key regulatory gene(s) in labor onset.Results: A total of 15 studies, including 266 subjects, were included. 136, 26, 15, 7, and 3 genes were significantly changed during labor in the myometrium (seven studies, n = 108), uterine cervix (four studies, n = 64), decidua (two studies, n = 42), amnion (two studies, n = 44) and placenta (two studies, n = 41), respectively. These genes were overrepresented in annotation terms related to inflammatory and immune responses. TNF and NOD-like receptor signaling pathways were overrepresented in all mentioned tissues, except the placenta. IL6 was the only gene included in both pathways, the most common reported gene in all included studies, and also the gene in the central hub of molecular regulatory network.Conclusions: This systematic review identified that genes involved in immunological and inflammatory regulations are expressed in specific gestational tissues in labor. We put forward the hypothesis that IL6 might be the key gene triggering specific mechanism in different gestational tissues, eventually leading to labor onset through inducing uterine contraction, wakening fetal membranes and stimulating cervical ripening.Systematic Review Registration: Identifier [CRD42020187975].
RETRACTED: Laparoscopic vs. Open Pancreaticoduodenectomy After Learning Curve: A Systematic Review and Meta-Analysis of Single-Center Studies
Authors: Feng Qingbo , Xin Zechang , Qiu Jie , Xu Mei 
Published: September 2021

Background: Although laparoscopic pancreaticoduodenectomy (LPD) is a safe and feasible treatment compared with open pancreaticoduodenectomy (OPD), surgeons need a relatively long training time to become technically proficient in this complex procedure. In addition, the incidence of complications and mortality of LPD will be significantly higher than that of OPD in the initial stage. This meta-analysis aimed to compare the safety and overall effect of LPD to OPD after learning curve based on eligible large-scale retrospective cohorts and randomized controlled trials (RCTs), especially the difference in the perioperative and short-term oncological outcomes.Methods: PubMed, Web of Science, EMBASE, Cochrane Central Register, and ClinicalTrials.gov databases were searched based on a defined search strategy to identify eligible studies before March 2021. Only clinical studies reporting more than 40 cases for LPD were included. Data on operative times, blood loss, and 90-day mortality, reoperation, length of hospital stay (LOS), overall morbidity, Clavien–Dindo ≥III complications, postoperative pancreatic fistula (POPF), blood transfusion, delayed gastric emptying (DGE), postpancreatectomy hemorrhage (PPH), and oncologic outcomes (R0 resection, lymph node dissection, positive lymph node numbers, and tumor size) were subjected to meta-analysis.Results: Overall, the final analysis included 13 retrospective cohorts and one RCT comprising 2,702 patients (LPD: 1,040, OPD: 1,662). It seems that LPD has longer operative time (weighted mean difference (WMD): 74.07; 95% CI: 39.87–108.26; p &lt; 0.0001). However, compared with OPD, LPD was associated with a higher R0 resection rate (odds ratio (OR): 1.43; 95% CI: 1.10–1.85; p = 0.008), lower rate of wound infection (OR: 0.35; 95% CI: 0.22–0.56; p &lt; 0.0001), less blood loss (WMD: −197.54 ml; 95% CI −251.39 to −143.70; p &lt; 0.00001), lower blood transfusion rate (OR: 0.58; 95% CI 0.43–0.78; p = 0.0004), and shorter LOS (WMD: −2.30 day; 95% CI −3.27 to −1.32; p &lt; 0.00001). No significant differences were found in 90-day mortality, overall morbidity, Clavien–Dindo ≥ III complications, reoperation, POPF, DGE, PPH, lymph node dissection, positive lymph node numbers, and tumor size between LPD and OPD.Conclusion: Comparative studies indicate that after the learning curve, LPD is a safe and feasible alternative to OPD. In addition, LPD provides less blood loss, blood transfusion, wound infection, and shorter hospital stays when compared with OPD.
Identification of a Gene Prognostic Model of Gastric Cancer Based on Analysis of Tumor Mutation Burden
Authors: Ma Weijun , Li Weidong , Xu Lei , Liu Lu , Xia Yu , Yang Liping , Da Mingxu 
Published: September 2021

Introduction: Gastric cancer is one of the most common cancers. Although some progress has been made in the treatment of gastric cancer with the improvement of surgical methods and the application of immunotherapy, the prognosis of gastric cancer patients is still unsatisfactory. In recent years, there has been increasing evidence that tumor mutational load (TMB) is strongly associated with survival outcomes and response to immunotherapy. Given the variable response of patients to immunotherapy, it is important to investigate clinical significance of TMB and explore appropriate biomarkers of prognosis in patients with gastric cancer (GC).Material and Methods: All data of patients with gastric cancer were obtained from the database of The Cancer Genome Atlas (TCGA). Samples were divided into two groups based on median TMB. Differently expressed genes (DEGs) between the high- and low-TMB groups were identified and further analyzed. We identified TMB-related genes using Lasso, univariate and multivariate Cox regression analysis and validated the survival result of 11 hub genes using Kaplan-Meier Plotter. In addition, “CIBERSORT” package was utilized to estimate the immune infiltration.Results: Single nucleotide polymorphism (SNP), C &gt; T transition were the most common variant type and single nucleotide variant (SNV), respectively. Patients in the high-TMB group had better survival outcomes than those in the low-TMB group. Besides, eleven TMB-related DEGs were utilized to construct a prognostic model that could be an independent risk factor to predict the prognosis of patients with GC. What’s more, the infiltration levels of CD4+ memory-activated T cells, M0 and M1 macrophages were significantly increased in the high-TMB group compared with the low-TMB group.Conclusions: Herein, we found that patients with high TMB had better survival outcomes in GC. In addition, higher TMB might promote immune infiltration, which could provide new ideas for immunotherapy.
El modelo de aprendizaje TPACK y su impacto en la innovación educativa desde un análisis bibliométrico
Authors: Vásconez Paredes Carlos Darío , Inga Ortega Esteban Mauricio 
Published: September 2021

El TPACK sintetiza los conocimientos que se espera que el docente deba tener a la hora del proceso de enseñanza-aprendizaje. Esta investigación contextualiza el Conocimiento del Contenido Pedagógico Tecnológico (TPACK), a la vez que presenta una revisión y un análisis sistemático de la bibliografía hallada a nivel regional y mundial en las bases de datos Web of Science y Scopus entre los años 2016 y 2020, en el cuál hemos considerado los criterios de mayor número de citas y artículos más relevantes dentro de la búsqueda general con la palabra clave TPACK. De igual forma hemos nutrido este análisis con datos estadísticos provenientes de la Organización para la Cooperación Económica y el Desarrollo (OECD). Los métodos usados para la investigación han sido el método Histórico-Descriptivo y el método Analítico-Sintético. En consecuencia, como fruto de este hemos identificado los problemas o variables más comunes dentro de la aplicación del modelo del TPACK y las (posibles) soluciones o consideraciones planteadas desde las investigaciones con las que se alimenta este estudio lo que constituye un punto de partida para analizar la implementación de TPACK.
Simulation of Light Distribution in Gamma Irradiated UHMWPE Using Monte Carlo Model for Light (MCML) Transport in Turbid Media: Analysis for Industrial Scale Biomaterial Modifications
Authors: Rizwan Ali , Saleem Muhammad , Serbaya Suhail H. , Alsulami Hemaid , Ghazal Aqsa , Mehmood Malik Sajjad 
Published: September 2021

(1) Background: This study investigated the miscibility of carbon-based fillers within industrial scale polymers for the preparation of superior quality polymer composites. It focuses on finding the light distribution in gamma irradiated ultra-high molecular weight polyethylene (UHMWPE). (2) Methods: The Kubleka–Munk model (KMM) was used to extract the optical properties, i.e., absorption coefficients (μa) and scattering coefficients (μs). Samples amounting to 30 kGy and 100 kGy of irradiated (in the open air) UHMWPE from 630 nm to 800 nm were used for this purpose. Moreover, theoretical validation of experimental results was performed while using extracted optical properties as inputs for the Monte Carlo model of light transport (MCML) code. (3) Conclusions: The investigations revealed that there was a significant decrease in absorption and scattering coefficient (μa & μs) values with irradiation, and 30 kGy irradiated samples suffered more compared to 100 kGy irradiated samples. Furthermore, the simulation of light transport for 800 nm showed an increase in penetration depth for UHMWPE after gamma irradiation. The decrease in dimensionless transport albedo μs(μa+μs) from 0.95 to 0.93 was considered responsible for this increase in photon absorption per unit area with irradiation. The report results are of particular importance when considering the light radiation (from 600 nm to 899 nm) for polyethylene modification and/or stabilization via enhancing the polyethylene chain mobility.
Obesity, Anion Accumulation, and Anion Gap Metabolic Acidosis: A Cohort Study
Authors: Lambert Douglas C. , Abramowitz Matthew K. 
Published: September 2021

Key Points

Obesity is characterized by the accumulation of high serum levels of abnormal, negatively charged solutes and acid.Findings were present among patients with normal kidney function, suggesting acid overproduction rather than acid retention.

Background
Obesity is associated with low serum bicarbonate, an indicator of metabolic acidosis and a CKD risk factor. To further characterize acid-base disturbance and subclinical metabolic acidosis in this population, we examined prospective associations of body mass index (BMI) with elevated anion gap and whether anion gap values in obesity associate with low bicarbonate.

Methods
Data from adult outpatients (n=94,448) in the Bronx, New York were collected from 2010 to 2018. Mixed effects models and Cox proportional hazards models were used to examine associations of BMI with elevated anion gap and anion gap metabolic acidosis and of baseline anion gap with incident low bicarbonate and anion gap metabolic acidosis. Anion gap was defined using traditional and albumin-corrected calculations.

Results
Greater BMI was associated with higher anion gap over time and with progressively greater risk of developing an elevated anion gap (hazard ratio [HR] for body mass index [BMI]≥40 kg/m2 versus 18 to <25 kg/m2, 1.32; 95% confidence interval [95% CI], 1.23 to 1.42 for traditional and HR for BMI≥40 kg/m2 versus 18 to <25 kg/m2, 1.74; 95% CI, 1.63 to 1.85 for corrected). Higher BMI was also associated with increased risk of developing anion gap metabolic acidosis (HR for BMI≥40 kg/m2, 1.53; 95% CI, 1.39 to 1.69). Among patients with obesity, higher anion gap was associated with increased risk of incident low bicarbonate (HR for fourth versus first quartile, 1.29; 95% CI, 1.23 to 1.44 for traditional and HR for fourth versus first quartile, 1.36; 95% CI, 1.26 to 1.48 for corrected) and higher risk of anion gap metabolic acidosis (HR for fourth versus first quartile, 1.78; 95% CI, 1.59 to 1.99).

Conclusions
Obesity is characterized by unmeasured anion accumulation and acid retention or overproduction. Modest elevations in anion gap among patients with obesity are associated with previously unrecognized anion gap metabolic acidosis.
Tobacco Farming and Illness Induced Poverty in Pakistan
Authors: Shahzad Muhammad , Shah Anwar , Chaloupka Frank Joseph 
Published: September 2021

Tobacco has been projected for its economic prosperity in Pakistan and many other developing countries while the opportunity cost of domestic labor, health issues and associated health cost related with tobacco farming are often overlooked. Various health conditions associated with tobacco farming result in catastrophic health expenditures which not only increase the chances of poverty head counts but also deepens it further. Taking into account the opportunity cost of domestic labor and health cost associated with tobacco induced illnesses obscure the tobacco prosperity rhetoric. This study examined effect of incremental health cost associated with tobacco farming on poverty head counts and severity. Using survey data from the tobacco producing districts in Khyber Pakhtunkhwa, Pakistan, this study found that tobacco farmers experienced higher proportion of sever health hazards and illnesses like CVD and respiratory issues. The severe nature of ailments caused them higher share of out of pocket expenditures as compared to non-tobacco farmers and general population. Increase in health expenditures not only increased their poverty head counts by four and half percent but also severity of poverty worsened further by 8 percentage points using the Cost of Basic Needs (CBN) approach for measuring poverty. This study concludes that it is not only tobacco consumption associated with various health conditions but also tobacco farming. It is recommended that health cost associated with tobacco farming be considered both in setting up of minimum indicative prices for tobacco and consideration of health cost can be used as a tool against prosperity rhetoric which is used to block tobacco control policy.
Escuela tecnificada y sociedad del conocimiento
Authors: Martínez-Otero Pérez Valentín 
Published: September 2021

El recorrido por estas páginas permite comprobar que la sociedad del conocimiento muestra luces y sombras. El imparable progreso técnico y la descomunal disponibilidad de información, desigualmente repartidos, por cierto, no se acompañan de genuino acrecentamiento humano. Iberoamérica, por ejemplo, se ve afectada en gran medida por una bochornosa “destecnologización” que frena el desarrollo de centenares de millones de personas.
El esfuerzo inversor en tecnología y la distribución más justa y estratégica de la misma han de ser dos requisitos generales de la política educativa. En aras de una pedagogía tecnológica consistente, capaz de mejorar sustancialmente la realidad escolar y social de Iberoamérica, es igualmente necesaria la mayor y mejor coordinación internacional.
Actitud y contexto ante los quehaceres escolares: el estudio de un caso en primaria en España
Authors: Gil Madrona Pedro , Roblizo Colmenero Manuel Jacinto , Gómez Barreto Isabel 
Published: September 2021

A lo largo de los últimos cursos académicos, el profesorado del centro escolar en el que hemos enfocado nuestro estudio ha ido detectando en el alumnado una significativa falta de motivación con respecto a la escuela y las tareas escolares, observable tanto en aquellos estudiantes que tienen "éxito escolar" como en los que tienen ciertas dificultades y precisan apoyos o refuerzos educativos.
Partiendo de esta realidad, y desde una vocación aplicada que trata de mitigar esta carencia para atenuar asimismo sus efectos, el propósito de nuestro trabajo ha sido conocer cuál es la percepción que los distintos colectivos implicados en el proceso educativo tienen acerca de la motivación de los alumnos del centro y cuáles son las condiciones contextuales y los usos o rutinas de los estudiantes que pueden incidir en su actitud frente a las tareas escolares.
Usar la lengua en la escuela
Authors: Tolchinsky Liliana 
Published: September 2021

La meta del proceso de aprendizaje de la lectura y la escritura en un sentido amplio es la participación activa de los nuevos miembros en las prácticas letradas de su comunidad. Dado que lo que se busca es pericia en determinadas prácticas, el mejor camino para alcanzarla es por medio de la inmersión en versiones auténticas de esas prácticas, en las cuales el uso de la lengua y de los textos responde a propósitos que van más allá de la enseñanza de la lectura y la escritura. Una vez discutidas las evidencias empíricas que apoyan esta propuesta, se presentará un enfoque transversal de la lectura y la escritura. Según este enfoque, la formación de miembros activos de la cultura escrita ha de realizarse no solamente desde la clase de lengua sino desde otras disciplinas curriculares no lingüísticas. A diferencia de lo que sucede en el área de lengua, en la cual hay que tratar de que se cree la necesidad para que tenga sentido introducir diversos tipos de texto, en las otras áreas curriculares se trata de crear los textos para responder a necesidades que ya existen. En las áreas no lingüísticas es donde hay más posibilidades de utilizar con sentido textos auténticos con diversas finalidades.
La propuesta de transversalidad ha encontrado escollos importantes para atender los requerimientos de diversidad y autenticidad de los textos, la interacción entre lengua oral y escrita y el intercambio entre pares, entre ellos, el uso exclusivo de libros de texto, la dificultad de encarar en las aulas un trabajo diversificado y la fragmentación de responsabilidades. Estos escollos reflejan los cambios cruciales que esta propuesta implica y algunos aspectos de nuestra cultura escolar que convendría superar si se quiere formar lectores comprensivos y críticos, ciudadanos hábiles en el manejo de la información escrita.