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PURPOSE: Partial breast irradiation (PBI) and intraoperative radiation (IORT) represent alternatives to whole breast irradiation (WBI) following breast conserving surgery. However, data is mixed regarding outcomes. We therefore performed a pooled analysis of Kaplan-Meier-derived patient data from randomized trials to evaluate the hypothesis that PBI and IORT have comparable long-term rates of ipsilateral breast tumor recurrence as WBI. METHODS: In February, 2023, PubMed, EMBASE and Cochrane Central were systematically searched for randomized phase 3 trials of early-stage breast cancer patients undergoing breast-conserving surgery with PBI or IORT as compared to WBI. Time-to-event outcomes of interest included ipsilateral breast tumor recurrence (IBTR), overall survival (OS) and distant disease-free survival (DDFS). Statistical analysis was performed with R Statistical Software. RESULTS: Eleven randomized trials comprising 15,460 patients were included; 7,675 (49.6%) patients were treated with standard or moderately hypofractionated WBI, 5,413 (35%) with PBI and 2,372 (15.3%) with IORT. Median follow-up was 9 years. PBI demonstrated comparable IBTR risk compared with WBI (HR 1.20; 95% CI 0.95-1.52; p = 0.12) with no differences in OS (HR 1.02; 95% CI 0.90-1.16; p = 0.70) or DDFS (HR 1.15; 95% CI 0.81-1.64; p = 0.43). In contrast, patients treated with IORT had a higher IBTR risk (HR 1.46; 95% CI 1.23-1.72; p < 0.01) compared with WBI with no difference in OS (HR 0.98; 95% CI 0.84-1.14; p = 0.81) or DDFS (HR 0.91; 95% CI 0.76-1.09; p = 0.31). CONCLUSION: For patients with early-stage breast cancer following breast-conserving surgery, PBI demonstrated no difference in IBTR as compared to WBI while IORT was inferior to WBI with respect to IBTR.

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Hydrogel exhibits attractive mechanical properties that can be regulated to be extremely tough, strong and resilient, adhesive and fatigue-resistant, thus enabling diverse applications ranging from tissue engineering scaffolds, flexible devices, to soft machines. As a liquid-filled porous material composed of polymer networks and water, the hydrogel freezes at subzero temperatures into a new material composed of polymer matrix and ice inclusions: the frozen hydrogel displays dramatically altered mechanical properties, which can significantly affect its safety and reliability in practical applications. In this study, based upon the theory of homogenization, we predicted the effective mechanical properties (e.g., Young's modulus, shear modulus, bulk modulus and Poisson ratio) of a frozen hydrogel with periodically distributed longitudinal ice inclusions. We firstly estimated its longitudinal Young's modulus, longitudinal Poisson ratio and plane strain bulk modulus using the self-consistent method, and then its longitudinal and transverse shear modulus using the generalized self-consistent method; further, the results were employed to calculate its transverse Young's modulus and transverse Poisson ratio. We validated the theoretical predictions against both finite element (FE) simulation and experimental measurement results, with good agreement achieved. We found that the estimated transverse Poisson ratio ranges from 0.3 to 0.53 and, at low volume fraction of ice inclusions, exhibits a value larger than 0.5 that exceeds the Poisson ratios of both the polymer matrix and the ice inclusion (typically 0.33-0.35). Compared with other homogenization methods (e.g., the rule of mixtures, the Halpin-Tsai equations, and the Mori-Tanaka method), the present approach is more accurate in predicting the effective mechanical properties (in particular, the transverse Poisson ratio) of frozen hydrogel. Our study provides theoretical support for the practical applications of frozen liquid-saturated porous materials such as hydrogel.

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Allogeneic hematopoietic stem cell transplantation (alloSCT) is, in many clinical settings, the only curative treatment for acute myeloid leukemia (AML). The clinical benefit of alloSCT greatly relies on the graft-versus-leukemia (GVL) effect. However, AML relapse remains the top cause of posttransplant death; this highlights the urgent need to enhance GVL. Studies of human GVL have been hindered by the lack of optimal clinically relevant models. In this article, we report, the successful establishment of a novel (to our knowledge) humanized GVL model system by transplanting clinically paired donor PBMCs and patient AML into MHC class I/II knockout NSG mice. We observed significantly reduced leukemia growth in humanized mice compared with mice that received AML alone, demonstrating a functional GVL effect. Using this model system, we studied human GVL responses against human AML cells in vivo and discovered that AML induced T cell depletion, likely because of increased T cell apoptosis. In addition, AML caused T cell exhaustion manifested by upregulation of inhibitory receptors, increased expression of exhaustion-related transcription factors, and decreased T cell function. Importantly, combined blockade of human T cell-inhibitory pathways effectively reduced leukemia burden and reinvigorated CD8 T cell function in this model system. These data, generated in a highly clinically relevant humanized GVL model, not only demonstrate AML-induced inhibition of alloreactive T cells but also identify promising therapeutic strategies targeting T cell depletion and exhaustion for overcoming GVL failure and treating AML relapse after alloSCT.

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ABSTRACT Introduction: Muscle strength is directly related to its cross-sectional area and the volume of its fibers, but there is no absolute linear relationship between hypertrophy and improvement in athletic performance. Under this complex perspective, muscle training strategies have been implemented to promote relevant muscle strength and improve overall athletic ability. Objective: Explore the impacts of muscle strength training on young athletes based on sport kinetic principles. Methods: we adopted the method of intragroup statistical comparison with body indexes of 10 volunteers undergoing muscle training focused on the core and lower limb set. Results: Muscle strength gain was effectively verified via electromyogram, and the test of athletic skills showed an evolution in jumping, balance, and reduction of wrong passes. Conclusion: Evidence-based muscle training can increase muscle strength and promote sports skill gain in young athletes. Level of evidence II; Therapeutic studies - investigation of treatment results.

RESUMO Introdução: A força muscular está ligada diretamente à área de sua seção transversal e ao volume de suas fibras, porém não há relação linear absoluta entre hipertrofia e melhora no desempenho atlético. Sob essa complexa perspectiva, estratégias de treinamento muscular vêm sendo implementadas para promover a força muscular relevante, no intuito de promover a melhora da capacidade atlética geral. Objetivo: Explorar os impactos do treinamento de força muscular nos jovens atletas baseado nos princípios cinéticos do esporte. Métodos: adotou-se o método de comparação estatística intragrupo com índices corporais de 10 voluntários submetidos ao treinamento muscular focado no conjunto do core e membros inferiores. Resultados: O ganho de força muscular foi efetivamente constatado via eletromiograma e o teste das habilidades atléticas demonstrou uma evolução no salto, equilíbrio e redução de passes errados. Conclusão: O treinamento muscular baseado em evidências consegue aumentar a força muscular e promover o ganho de habilidade esportiva nos jovens atletas. Nível de evidência II; Estudos terapêuticos - investigação dos resultados do tratamento.

RESUMEN Introducción: La fuerza muscular está directamente relacionada con su área transversal y con el volumen de sus fibras, pero no existe una relación lineal absoluta entre la hipertrofia y la mejora del rendimiento deportivo. Bajo esta compleja perspectiva, se han implementado estrategias de entrenamiento muscular para promover la fuerza muscular pertinente, con el fin de promover la mejora de la capacidad atlética general. Objetivo: Explorar los impactos del entrenamiento de la fuerza muscular en jóvenes atletas basándose en los principios de la cinética deportiva. Métodos: se adoptó el método de comparación estadística intragrupo con los índices corporales de 10 voluntarios sometidos a un entrenamiento muscular centrado en todo el núcleo y las extremidades inferiores. Resultados: La ganancia de fuerza muscular se verificó eficazmente a través del electromiograma y la prueba de habilidades atléticas mostró una evolución en los saltos, el equilibrio y la reducción de los pases erróneos. Conclusión: El entrenamiento muscular basado en la evidencia puede aumentar la fuerza muscular y promover la ganancia de habilidades deportivas en los atletas jóvenes. Nivel de evidencia II; Estudios terapéuticos - investigación de los resultados del tratamiento.

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INTRODUCTION: Castration-sensitive metastatic prostate cancer is heterogeneous. Our objective is to identify metastatic prostate cancer phenotypes and their prognostic impact on survival. MATERIALS AND METHODS: The National Cancer Database was queried. The Surveillance, Epidemiology, and End Results database was used for validation. Patterns were split into: nonregional lymph node, bone only, and visceral (any brain/liver/lung). Hazard ratios (HR) with 95% confidence intervals (CI) were calculated for the univariate and multivariate Cox proportional hazards regression models, odds ratios were calculated, Kaplan-Meier curves were generated, and a nomogram of the multivariate regression model was created. RESULTS: The training set included 13,818 men; bone only was most common (n = 11,632, 84.2%), then nonregional lymph node (n = 1388, 10.0%), and any visceral (brain/liver/lung; n = 798, 5.8%). Risk of death was increased by metastases to a visceral organ versus nonregional lymph node (HR = 2.26; 95% CI [2.00, 2.56]), bone only metastases versus nonregional lymph node (HR = 1.57; 95% CI [1.43, 1.72]), T-stage 4 versus 1 (HR = 1.27; 95% CI [1.17, 1.36]), Grade Group 5 versus 1 (HR = 1.93; 95% CI [1.61, 2.31]), PSA > 20 ng/mL versus < 10 ng/mL (HR = 1.32; 95% CI [1.23, 1.42]), and age ≥ 80 versus < 50 (HR = 1.96; 95% CI [1.69, 2.29]). On internal validation, the model had C-indices 20.5%, 22.7%, and 14.6% higher than the current staging system for overall survival, 1-year, and 5-year survival, respectively. CONCLUSION: We developed and validated prognostic metastatic prostate cancer phenotypes that can assist risk stratification to potentially personalize therapy. Our nomogram (https://tinyurl.com/prostate-met) may be used to predict survival.

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METHODS: We conducted a retrospective, secondary analysis of an existing, deidentified, prospective data set captured to derive a bruising CDR. Subjects were patients under 3 years with bruising and confirmed acute head trauma. An expert medical panel had previously identified patients with AHT. Measures of the CDR's AHT screening performance (sensitivity, specificity, likelihood ratios) were calculated with 95% confidence intervals (CIs). RESULTS: Expert medical panel members had classified 78 of 117 eligible patients (67%) as AHT, 38 (33%) as non-AHT, and 1 as indeterminate. Excluding the indeterminate case, the PediBIRN-4 demonstrated a sensitivity of 0.96 (95% CI, 0.88-0.99), specificity of 0.29 (95% CI, 0.16-0.46), positive likelihood ratio of 1.35 (95% CI, 1.10-1.67), and negative likelihood ratio of 0.13 (95% CI, 0.04-0.46). Close inspection of the data revealed that 1 of the CDR's predictor variables had lowered specificity without impacting sensitivity. Eliminating this variable would have increased specificity to 0.84 (95% CI, 0.68-0.93). CONCLUSIONS: The PediBIRN 4-variable CDR demonstrated AHT screening sensitivity in the pediatric ED equivalent to pediatric intensive care unit and other inpatient settings, but lower specificity. Further study of a simplified 3-variable PediBIRN AHT screening tool for the ED setting is warranted.

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OBJECTIVE: In this study, we aimed at investigating the role of isoleucyl-tRNA synthetase in the growth, migration, and angiogenesis of human umbilical vein endothelial cells and the underlying molecular mechanism. METHODS: To assess the role of isoleucyl-tRNA synthetase, we silenced isoleucyl-tRNA synthetase in human umbilical vein endothelial cells using lentiviral 2 specific short hairpin RNAs (short hairpin RNAs 1 and 2) and examined silencing efficiency using real time quantitative polymerase chain reaction and western blot analyses. Short hairpin RNAs 1-isoleucyl-tRNA synthetase had greater knockdown efficiency, it was used in the entire downstream analysis. Short hairpin RNAs 1- isoleucyl-tRNA synthetase silencing effects on cell proliferation, cell colony generation, cell migration, as well as angiogenesis were assessed using cell counting kit-8, colony development, cell migration, and angiogenesis tube formation assays, respectively. RESULTS: Compared to the control group, anti-isoleucyl-tRNA synthetase short hairpin RNAs significantly silenced isoleucyl-tRNA synthetase expression in human umbilical vein endothelial cells, and suppressed their proliferation, migration, and angiogenic capacity. To characterize the underlying mechanism, western blot analyses showed that isoleucyl-tRNA synthetase knockdown suppressed phosphorylation of extracellular-regulated kinase ½ and protein-serine- threonine kinase, as well as expression of vascular endothelial growth factor, GSK-3ß, and ß-catenin. CONCLUSIONS: We have shown, for the first time, the critical role of isoleucyl-tRNA synthetase in human umbilical vein endothelial cells. Our data show that isoleucyl-tRNA synthetase knockdown suppresses human umbilical vein endothelial cell proliferation, migration, and angiogenesis. We have also shown that isoleucyl-tRNA synthetase knockdown suppresses phosphorylation of extracellular-regulated kinase ½ and protein-serine- threonine kinase, as well as expression of vascular endothelial growth factor, GSK-3ß, and ß-catenin. Together, these data highlight isoleucyl-tRNA synthetase as a potential antitumor anti-angiogenic target.

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PURPOSE: Osseointegration at the titanium surface-bone interface is one of the key factors affecting the success rate of dental implants. However, the titanium surface always forms a passive oxide layer and impacts bone marrow-derived mesenchymal stem cell (BMSC) osteogenic differentiation after exposure to the atmosphere, which further leads to poor osseointegration. Given that wet storage helps prevent titanium aging and that weakly alkaline conditions stimulate BMSC osteogenic differentiation, the aim of the present study was to explore whether sodium bicarbonate, a well-known hydrogen ion (pH) buffer, forms an alkaline microenvironment on titanium surfaces to promote BMSC osteogenic differentiation. MATERIAL AND METHODS: In this work, sand-blasted and acid-etched (SLA) titanium discs were soaked in 20 mM, 50 mM, 100 mM, and 200 mM sodium bicarbonate at room temperature for 5 min without rinsing. The influence of this surface modification on BMSC adhesion, proliferation, and osteogenic differentiation was measured. Additionally, cellular osteogenic differentiation-associated signaling pathways were evaluated. RESULTS: We showed that titanium discs treated with sodium bicarbonate created an extracellular environment with a higher pH for BMSCs than the normal physiological value for 5 days, strongly promoting BMSC osteogenic differentiation via the activation of integrin-focal adhesion kinase-alkaline phosphatase (Itg-FAK-ALP). In addition, the proliferation and adhesion of BMSCs were increased after alkaline treatment. These cellular effects were most significant with 100 mM sodium bicarbonate. CONCLUSION: The results indicated that the titanium surface treated with sodium bicarbonate improved BMSC osteogenic differentiation mainly by creating an alkaline microenvironment, which further activated the Itg-FAK-ALP signaling pathway. CLINICAL RELEVANCE: Surfaces modified with 100 mM sodium bicarbonate had the highest initial pH value and thus showed the greatest potential to improve BMSC performance on titanium surfaces, identifying a novel conservation method for dental implants.

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OBJECTIVE: To estimate the impact of the PediBIRN (Pediatric Brain Injury Research Network) 4-variable clinical decision rule (CDR) on abuse evaluations and missed abusive head trauma in pediatric intensive care settings. STUDY DESIGN: This was a cluster randomized trial. Participants included 8 pediatric intensive care units (PICUs) in US academic medical centers; PICU and child abuse physicians; and consecutive patients with acute head injures <3 years (n = 183 and n = 237, intervention vs control). PICUs were stratified by patient volumes, pair-matched, and randomized equally to intervention or control conditions. Randomization was concealed from the biostatistician. Physician-directed, cluster-level interventions included initial and booster training, access to an abusive head trauma probability calculator, and information sessions. Outcomes included "higher risk" patients evaluated thoroughly for abuse (with skeletal survey and retinal examination), potential cases of missed abusive head trauma (patients lacking either evaluation), and estimates of missed abusive head trauma (among potential cases). Group comparisons were performed using generalized linear mixed-effects models. RESULTS: Intervention physicians evaluated a greater proportion of higher risk patients thoroughly (81% vs 73%, P = .11) and had fewer potential cases of missed abusive head trauma (21% vs 32%, P = .05), although estimated cases of missed abusive head trauma did not differ (7% vs 13%, P = .22). From baseline (in previous studies) to trial, the change in higher risk patients evaluated thoroughly (67%→81% vs 78%→73%, P = .01), and potential cases of missed abusive head trauma (40%→21% vs 29%→32%, P = .003), diverged significantly. We did not identify a significant divergence in the number of estimated cases of missed abusive head trauma (15%→7% vs 11%→13%, P = .22). CONCLUSIONS: PediBIRN-4 CDR application facilitated changes in abuse evaluations that reduced potential cases of missed abusive head trauma in PICU settings. TRIAL REGISTRATION: ClinicalTrials.gov: NCT03162354.

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SUMMARY OBJECTIVE: In this study, we aimed at investigating the role of isoleucyl-tRNA synthetase in the growth, migration, and angiogenesis of human umbilical vein endothelial cells and the underlying molecular mechanism. METHODS: To assess the role of isoleucyl-tRNA synthetase, we silenced isoleucyl-tRNA synthetase in human umbilical vein endothelial cells using lentiviral 2 specific short hairpin RNAs (short hairpin RNAs 1 and 2) and examined silencing efficiency using real time quantitative polymerase chain reaction and western blot analyses. Short hairpin RNAs 1-isoleucyl-tRNA synthetase had greater knockdown efficiency, it was used in the entire downstream analysis. Short hairpin RNAs 1- isoleucyl-tRNA synthetase silencing effects on cell proliferation, cell colony generation, cell migration, as well as angiogenesis were assessed using cell counting kit-8, colony development, cell migration, and angiogenesis tube formation assays, respectively. RESULTS: Compared to the control group, anti-isoleucyl-tRNA synthetase short hairpin RNAs significantly silenced isoleucyl-tRNA synthetase expression in human umbilical vein endothelial cells, and suppressed their proliferation, migration, and angiogenic capacity. To characterize the underlying mechanism, western blot analyses showed that isoleucyl-tRNA synthetase knockdown suppressed phosphorylation of extracellular-regulated kinase ½ and protein-serine- threonine kinase, as well as expression of vascular endothelial growth factor, GSK-3β, and β-catenin. CONCLUSIONS: We have shown, for the first time, the critical role of isoleucyl-tRNA synthetase in human umbilical vein endothelial cells. Our data show that isoleucyl-tRNA synthetase knockdown suppresses human umbilical vein endothelial cell proliferation, migration, and angiogenesis. We have also shown that isoleucyl-tRNA synthetase knockdown suppresses phosphorylation of extracellular-regulated kinase ½ and protein-serine- threonine kinase, as well as expression of vascular endothelial growth factor, GSK-3β, and β-catenin. Together, these data highlight isoleucyl-tRNA synthetase as a potential antitumor anti-angiogenic target.

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OBJECTIVES: To identify and compare serum and lower respiratory tract fluid biomarkers of lung injury using well-characterized mouse models of lung injury. To explore the relationship between these preclinical biomarkers and clinical outcomes in a discovery cohort of pediatric patients with acute respiratory failure from pneumonia. DESIGN: Prospective, observational cohort study. SETTING: A basic science laboratory and the PICU of a tertiary-care children's hospital. PATIENTS: PICU patients intubated for respiratory failure from a suspected respiratory infection. INTERVENTIONS: Prospective enrollment and collection of lower respiratory tract fluid samples. MEASUREMENTS AND MAIN RESULTS: C57BL6/J mice were intranasally inoculated with escalating doses of influenza A virus or toll-like receptor agonists to simulate varying degrees of lung injury. Serum and bronchoalveolar lavage fluid were measured for the presence of cytokines using commercially available multiplex cytokine assays. Elevated levels of C-C motif chemokine ligand 7 at the peak of inflammation in both bronchoalveolar lavage fluid and serum correlated with lethality, with the bronchoalveolar lavage fluid ratio of C-C motif chemokine ligand 7:C-C motif chemokine ligand 22 providing the best prediction in the mouse models. These preclinical biomarkers were examined in the plasma and lower respiratory tract fluid of a discovery cohort of pediatric patients with acute respiratory failure from pneumonia. The primary clinical outcome measure was ventilator-free days, with secondary outcomes of pediatric acute respiratory distress syndrome severity and mortality. Elevation in peak lower respiratory tract fluid C-C motif chemokine ligand 7:C-C motif chemokine ligand 22 ratios demonstrated a significant negative correlation with ventilator-free days (r = -0.805; p < 0.02). CONCLUSIONS: This study provides evidence that lung immune profiling via lower respiratory tract fluid cytokine analysis is feasible and may provide insight into clinical outcomes. Further validation of markers, including the C-C motif chemokine ligand 7:C-C motif chemokine ligand 22 ratio in this limited study, in a larger cohort of patients is necessary.

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Our aim was to determine whether hyponatremia is associated with waiting list or posttransplantation mortality in children having liver transplantation (LT). METHODS: A retrospective analysis of the united network for organ sharing/organ procurement transplantation network database on pediatric LT performed between 1988 and 2016 was conducted. Hyponatremia was defined as a serum sodium of 130 mEq/L or below. Subjects were divided into 2 age groups: I (0-6 y old) and II (7-18 y old). Patient survival before and after LT, as well as graft survival, were compared in patients with and without hyponatremia. Multivariable Cox proportional hazards models were constructed for perioperative mortality. RESULTS: Data from 6606 children were available for analysis of waiting list mortality, and 4478 for postoperative mortality. The prevalence of hyponatremia at the time of registration was 2.8% and 3.7% at the time of LT. Waiting list mortality in patients with hyponatremia was significantly higher in group I (P < 0.001) but not in group II (P = 0.09). In group I, the relative risk of mortality adjusted to pediatric end-stage liver disease score was significantly associated with hyponatremia (P < 0.001). A sodium level below 130 mEq/L (hazard ration [HR] = 1.7), younger age (group I) (HR = 2.01), and need for dialysis (HR = 2.3) were independent predictors for increased waiting list mortality. There was no difference in overall postoperative patient or graft survival related to hyponatremia. CONCLUSIONS: Hyponatremia is associated with increased waiting list mortality for pediatric LT candidates, particularly in younger children. Future studies examining incorporation of age-specific serum sodium levels into organ allocation policies in children seems warranted based on our findings.

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Antecedentes: el absceso del psoas ilíaco es una entidad poco frecuente y de etiología variable. Su ubicación y cuadro clínico inespecífico la convierte en una entidad de difícil diagnóstico para el cirujano general. La oportunidad de tratar una serie de casos en un período de tiempo relativamente corto para este tipo de patología motivan esta comunicación. Objetivo: a partir de una serie consecutiva de casos, analizar etiología, clínica, y enfoque diagnóstico terapéutico, con especial énfasis en el drenaje percutáneo , como así también una sucinta revisión de la bibliografía reciente. Material y métodos: estudio observacional retrospectivo de una serie consecutiva de casos Resultados: la serie consta de 6 casos, 5 de tipo primario y 1 de tipo secundario. La signos más frecuentes fueron el dolor, la impotencia funcional y la leucocitosis. La Tomografía axial computada de abdomen con y sin contraste fue el método diagnóstico de elección. El drenaje percutáneo fue el tratamiento de elección en 5 casos (83,3%) mientras que en el restante se optó por antibioticoterapia y el drenaje de una colección adyacente. La evolución de todos los casos fue favorable. Conclusión: el absceso de psoas ilíaco es una patología que necesita un alto nivel de sospecha dada su clínica inespecífica. Para su diagnóstico, junto acon la clínica la Tomografía es el método de elección. El drenaje percutáneo de las colecciones bajo control tomográfico es un opción segura y eficaz para el tratamiento de esta entidad.

Background: The of the iliopsoas abscess is a rare entity with a variable etiology. Its location and nonspecific clinical features makes it becomes a diagnostic and therapeutic challenge for the general surgeon. The opportunity to treat a series of cases in a relatively short period of time motivates this communication. Objective: From a consecutive case series, we analyze etiology, clinical features , as well as diagnostic and therapeutic approaches, with special emphasis on percutaneous drainage, as well as a brief review of recent literature. Material and methods: Retrospective analysis of a consecutive series of six patients diagnosed with an ilipsoas abscess in a tertiary care center. Results: The series consists of 6 cases, 5 of primary type and 1 of secondary type. Pain, Limp and leucocitosis were the more prevalent signs; computed tomography of the abdomen was the diagnostic method of choice. Percutaneous drainage was the therapeutic option in 5 cases (83.3%), while in the remaining, antibiotic therapy and the drainage of an adjacent collection were indicated. The evolution of all cases was favorable with no mortality nor morbidity. Conclusion: The iliac psoas abscess is a pathology that needs a high level of suspicion given its nonspecific presentation. For diagnosis, together with the clinic, computed tomography is the method of choice. Percutaneous drainage of collection under tomographic control is a safe and effective option for the treatment of this entity.

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Introduction: Ecuador, a country of 17 million inhabitants with a medium human development index of 0.75, has a small scientific productivity in relation to its size and population. Objective: To analyze Ecuador publications in the Science Citation Index Expanded, focusing on productivity, subjects, institutions, citations, and trends. Methods: We analyzed scientific publications by authors from Ecuador from 1900 to 2017 in the Science Citation Index Expanded and compared it with other tropical countries. Results: We found 16 document types (7 806 articles). The three most productive institutions were Universidad San Francisco de Quito, Pontificia Universidad Católica del Ecuador, and Escuela Politécnica Nacional. USA and Spain were the most frequent collaborating countries. Most articles were in English and ecology, botany, and zoology were common, but no field produced over 8 % of articles. However, ecology represents 11.3 % of the total citations. The most cited papers in the database were from large international biology and physics projects with minimal participation of Ecuadorean scientists. Article citations occurs mostly after the SCI stops counting. Conclusion: Science in Ecuador is growing but needs to greatly increase collaboration among Ecuadorean institutions to reduce its dependence on foreing projects. However, this study did not include articles published by the hundreds of Ecuadorean journals not covered by the SCI Expanded.

Introducción: Ecuador es un país con 17 millones de habitantes y un indice de desarrollo humano medio de 0.75, pero tiene una baja producción científica en relación con su tamaño y población. Objectivo: Analizar las publicaciones de Ecuador en el Índice de Citación de Ciencia enfocándose en la productividad, categorías, instituciones, citaciones y tendencias. Métodos: En la base de datos Science Citation Index analizamos las publicaciones científicas de autores con dirección ecuatoriana desde 1900 hasta 2017 y comparamos los resultados con otros países tropicales. Resultados: Encontramos 16 tipos de documentos (7 806 artículos). Las tres instituciones más productivas fueron Universidad San Francisco de Quito, Pontificia Universidad Católica del Ecuador, y Escuela Politécnica Nacional. Estados Unidos y España fueron los países con colaboración más frecuente. La mayoría de los artículos fueron escritos en inglés con Ecología, Botánica y Zoología como las categorías más comunes, pero ninguna supera una producción del 8 % del total de las publicaciones. Sin embargo, Ecología representa el 11.3 % del total de citaciones. Los artículos más citados en esa base de datos fueron de grandes equipos internacionales en Biología y en Física, con poca participación de científicos ecuatorianos. La mayoría de las citas se dan después de que el SCI detiene el conteo. Conclusión: La ciencia en Ecuador está creciendo, pero se necesita aumentar la colaboración entre las instituciones ecuatorianas para reducir la dependencia de proyectos extranjeros. Se debe considerar que este estudio no incluyó los artículos publicados por centenares de revistas ecuatorianas que no son cubiertas por el Science Citation Index.

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BACKGROUND: Osteogenic differentiation of bone mesenchymal stem cells (BMSCs) is regulated by numerous signaling pathways. Dopamine (DA), a neurotransmitter, has previously been demonstrated to induce new bone formation by stimulating the receptors on BMSCs, but the essential mediators of DA-induced osteogenic signaling remain unclear. METHODS: In this work, we evaluated the influence of both dopamine D1 and D2 receptor activation on BMSC osteogenic differentiation. Gene and protein expression of osteogenic-related markers were tested. The direct binding of transcriptional factor, Runx2, to those markers was also investigated. Additionally, cellular differentiation-associated signaling pathways were evaluated. RESULTS: We showed that the expression level of the D1 receptor on BMSCs increased during osteogenic differentiation. A D1 receptor agonist, similar to DA, induced the osteogenic differentiation of BMSCs, and this phenomenon was effectively inhibited by a D1 receptor antagonist or by D1 receptor knockdown. Furthermore, the suppression of protein kinase A (PKA), an important kinase downstream of the D1 receptor, successfully inhibited DA-induced BMSC osteogenic differentiation and decreased the phosphorylation of ERK1/2. Compared with P38, MAPK, and JNK, DA mainly induced the phosphorylation of ERK1/2 and led to the upregulation of Runx2 transcriptional activity, thus facilitating BMSC osteogenic differentiation. On the other hand, an ERK1/2 inhibitor could reverse these effects. CONCLUSIONS: Taken together, these results suggest that ERK signaling may play an essential role in coordinating the DA-induced osteogenic differentiation of BMSCs by D1 receptor activation.

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OBJECTIVE: To replicate the previously published finding that the absence of a history of trauma in a child with obvious traumatic head injuries demonstrates high specificity and high positive predictive value (PPV) for abusive head trauma. STUDY DESIGN: This was a secondary analysis of a deidentified, cross-sectional dataset containing prospective data on 346 young children with acute head injury hospitalized for intensive care across 18 sites between 2010 and 2013, to estimate the diagnostic relevance of a caregiver's specific denial of any trauma, changing history of accidental trauma, or history of accidental trauma inconsistent with the child's gross motor skills. Cases were categorized as definite or not definite abusive head trauma based solely on patients' clinical and radiologic findings. For each presumptive historical "red flag," we calculated sensitivity, specificity, predictive values, and likelihood ratio (LR) with 95% CI for definite abusive head trauma in all patients and also in cohorts with normal, abnormal, or persistent abnormal neurologic status. RESULTS: A caregiver's specific denial of any trauma demonstrated a specificity of 0.90 (95% CI, 0.84-0.94), PPV of 0.81 (95% CI, 0.71-0.88), and a positive LR (LR+) of 4.83 (95% CI, 3.07-7.61) for definite abusive head trauma in all patients. Specificity and LR+ were lowest-not highest-in patients with persistent neurologic abnormalities. The 2 other historical red flags showed similar trends. CONCLUSIONS: A caregiver's specific denial of any trauma, changing history of accidental trauma, or history of accidental trauma that is developmentally inconsistent are each highly specific (>0.90) but may provide weaker support than previously reported for a diagnosis of abusive head trauma in patients with persistent neurologic abnormalities.

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Portal vein thrombosis (PVT) is associated with inferior pretransplantation and posttransplantation outcomes. We aimed to create a predictive model to risk stratify transplant candidates for PVT. Data on adult transplants in the United States during the Model for End-Stage Liver Disease (MELD) era through September 2016 were reviewed. We constructed and validated a scoring system composed of routine, readily available clinical information to predict the development of incident PVT at 12 months from transplantation listing. A total of 66,568 liver transplant candidates were dichotomized into 2 groups to construct (n = 34,751) and validate (n = 31,817) a scoring system. In general, the derivation and validation cohorts were clinically similar. Although nonalcoholic steatohepatitis was a significant predictor of incident PVT (hazard ratio, 1.29; 95% confidence interval, 1.08-1.54; P < 0.001), age, MELD score, and moderate-to-severe ascites were also associated with increased risk. African American race was associated with decreased risk. A scoring system (PVT risk index [RI]) of these 5 variables had an area under the curve of 0.71 and 0.70 in both derivation and validation cohorts, respectively. By applying the low cutoff score of 2.6, incident PVT could be accurately excluded (negative predictive value 94%). Using the high cutoff score of 4.6 (positive predictive value 85%), PVT could be diagnosed with high accuracy. The PVT-RI predicts which candidates awaiting lifesaving liver transplantation will and will not develop future PVT. Although this scoring system will require prospective validation, it provides a powerful new tool for the clinician when risk stratifying cirrhosis patients prior to liver transplantation for future PVT development.

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Post-stroke depression (PSD) is a very common complication that leads to increased physical disability, poor functional outcome, and higher mortality. Therefore, early detection and treatment are very important. Since there are currently no specific guidelines for this disorder in China, the purpose of this study was to develop PSD guidelines and provide suggestions for clinicians and related workers.

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OBJECTIVES: To determine the relationship between theophylline trough levels and urine output in critically ill children administered aminophylline as adjunctive diuretic therapy. DESIGN: Retrospective cohort study. SETTING: The PICU of a tertiary care children's hospital. PATIENTS: A mixed population of medical/surgical including postoperative cardiothoracic surgery patients less than 18 years old. INTERVENTIONS: Electronic medical records of all PICU patients admitted from July 2010 to June 2015 were reviewed, and patients who received aminophylline as diuretic therapy were identified. MEASUREMENTS AND MAIN RESULTS: Patient cohort data including demographics, daily aminophylline, furosemide and chlorothiazide dosing, theophylline trough levels, fluid intake, urine output and total fluid balance, blood urea nitrogen, and creatinine levels were abstracted. Multivariate analysis based on a generalized estimating equations approach demonstrated that aminophylline administration, when analyzed as a categorical variable, was associated with an increase in urine output and decreased fluid balance. However, aminophylline dosing, when analyzed as a continuous variable, was associated with neither an increase in urine output nor decreased fluid balance. Theophylline trough levels were not correlated with urine output at 24 hours (p = 0.78) and were negatively correlated with urine output at 48 hours (r = 0.078; p < 0.005). CONCLUSIONS: Aminophylline administration provided a measure of increased diuresis, regardless of dosage, and theophylline trough levels. Therefore, achieving a prescribed therapeutic trough level may not be necessary for full diuretic effect. Because, as opposed to the diuretic effect, the side effect profile of aminophylline is dose-dependent, low maintenance dosing may optimize the balance between providing adjunctive diuretic effect while minimizing the risk of toxicity.

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OBJECTIVE: To characterize racial and ethnic disparities in the evaluation and reporting of suspected abusive head trauma (AHT) across the 18 participating sites of the Pediatric Brain Injury Research Network (PediBIRN). We hypothesized that such disparities would be confirmed at multiple sites and occur more frequently in patients with a lower risk for AHT. STUDY DESIGN: Aggregate and site-specific analysis of the cross-sectional PediBIRN dataset, comparing AHT evaluation and reporting frequencies in subpopulations of white/non-Hispanic and minority race/ethnicity patients with lower vs higher risk for AHT. RESULTS: In the PediBIRN study sample of 500 young, acutely head-injured patients hospitalized for intensive care, minority race/ethnicity patients (n = 229) were more frequently evaluated (P < .001; aOR, 2.2) and reported (P = .001; aOR, 1.9) for suspected AHT than white/non-Hispanic patients (n = 271). These disparities occurred almost exclusively in lower risk patients, including those ultimately categorized as non-AHT (P = .001 [aOR, 2.4] and P = .003 [aOR, 2.1]) or with an estimated AHT probability of ≤25% (P <.001 [aOR, 4.1] and P <.001 [aOR, 2.8]). Similar site-specific analyses revealed that these results reflected more extreme disparities at only 2 of 18 sites, and were not explained by local confounders. CONCLUSION: Significant race/ethnicity-based disparities in AHT evaluation and reporting were observed at only 2 of 18 sites and occurred almost exclusively in lower risk patients. In the absence of local confounders, these disparities likely represent the impact of local physicians' implicit bias.

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