bluuebunny/crossref_metadata_2025_split huggingface dataset:
A phase I/II study of REGN5093, a MET x MET bispecific antibody, in patients with MET-altered advanced non-small cell lung cancer (NSCLC).
Authors: Rowlands Tracey , Boyapati Anita , Li Siyu , Daly Christopher , Seebach Frank A. , Lowy Israel , Rietschel Petra 
Published: May 2020

TPS9628 Background: Mesenchymal-epithelial transition (MET) factor is a transmembrane tyrosine kinase receptor activated by hepatocyte growth factor (HGF). Aberrant activation of MET via gene amplification or gene mutations, as well as MET protein overexpression, has been reported in NSCLC and other cancer types and can promote tumorigenesis. REGN5093 is a human bispecific antibody that binds to two distinct epitopes of MET, blocking HGF binding and inducing internalization and degradation of MET. REGN5093 prevents MET-mediated signaling and inhibits growth of MET-driven tumor cells without inducing MET-driven biological responses (DaSilva et al, CCR, 2019; PMID: 31848185). Methods: This Phase I/II, first-in-human, multicenter study is investigating the safety, tolerability, pharmacokinetics (PK), and efficacy of REGN5093 in patients with MET-altered advanced NSCLC who have received all available approved therapies (NCT04077099). Key eligibility criteria include age ≥18 years, Eastern Cooperative Oncology Group performance status of ≤1, and documented presence of either MET exon 14 gene mutation and/or MET gene amplification and/or elevated MET protein expression. Patients are required to provide a biopsy during screening for assessment of MET biomarkers. Key exclusion criteria include prior MET-targeted biologic therapy (expansion cohorts only). Prior therapy with tyrosine kinase inhibitors are not exclusionary in any part of the study. For each patient, the study comprises a screening period of up to 28 days, followed by 3-week cycles of REGN5093 monotherapy. Study treatment will continue until confirmed disease progression or other protocol-defined reason for discontinuation. The study has two parts: dose escalation and dose expansion. Dose escalation will proceed via 4+3 design until a maximum-tolerated dose is reached or a recommended Phase II dose selected. The primary objective of the dose escalation part is to assess safety (incidence and severity of adverse events and Grade ≥3 laboratory abnormalities), tolerability (incidence of dose-limiting toxicities), and PK of REGN5093. During the expansion phase, patients will be allocated to cohorts according to the type(s) of documented biomarkers of MET-altered disease. Anti-tumor activity based on objective response rate per Response Evaluation Criteria in Solid Tumors version 1.1, determined by CT or MRI, will be the primary endpoint in the expansion cohorts. The study is currently open for enrollment. Clinical trial information: NCT04077099 .
Phase IIa study of marrow infiltrating lymphocytes (MILs), an adoptive T cell therapy, alone or in combination with nivolumab in non-small cell lung cancer (NSCLC).
Authors: Edelman Martin , Lisberg Aaron Elliott , Koczywas Marianna , Creelan Ben C. , Seiz Amanda , Lutz Eric , Rudraraju Lakshmi , DeOliveria Elizabeth , Shah Monil , Noonan Kim , Johnson Melissa Lynne 
Published: May 2020

TPS9630 Background: Primary or secondary resistance to anti-PD-1 may be due to loss of T cell function. Persistent antigen stimulation can lead to impaired CD8+ T cell function, which often results in acquired resistance to PD-1 inhibition. It is unclear whether reinvigoration of tumor infiltrating cells or recruitment of novel T cells impart the activity of anti-PD-1 therapy. The bone marrow is a reservoir for antigen experienced memory T cells. We have previously shown that MILs can be generated for patients with hematologic malignancies and solid tumors including patients with NSCLC. MILs are the product of the activation and expansion of bone marrow T cells with a polyantigenic memory phenotype that recognize tumor antigens, are cytotoxic to autologous tumor and are able to persist over a long period of time. In a pre-clinical study of NSCLC, MILs were able to be expanded in all patients tested. Furthermore, all of the NSCLC products tested showed specificity to shared NSCLC antigens. The combination of adoptive cell therapy (ACT) with checkpoint inhibitors (CPIs) has distinctive positive effects on CD8 and CD4 T cell subsets, with the possibility for complete tumor control. We hypothesize that patients with NSCLC who have relapsed on anti-PD-1 treatment could benefit from an infusion of non-exhausted, central memory-enhanced, antigen specific T cells i.e. MILs which can delay the induction of tumor-associated anergy and augment the overall effectiveness of immunotherapy. Methods: Patients with advanced NSCLC who have progressed following prior anti-PD-1 therapy, with sufficient bone marrow reserve and an ECOG 0-1 are eligible. In eligible patients, bone marrow (200 mL) will be harvested and processed. Patients will undergo lymphodepletion (fludarabine 300 mg/m2/day and cyclophosphamide 30 mg/m2/day on days -5,-4,-3) followed by infusion of MILs on day 0. In Part 1, up to 6 patients will be administered MILs alone on day 0. In Part 2, approximately 20 subjects will be administered MILs on day 0 followed by NIVO 480 mg Q4W starting on day 1. The objectives of the study are to assess safety of MILs alone and in combination with NIVO, as well as efficacy. The first patient was treated in December 2019. Clinical trial information: NCT04069936 .
Recurrent Amplification of the Osmotic Stress Transcription Factor NFAT5 in Adrenocortical Carcinoma
Authors: Brown Taylor C , Nicolson Norman G , Man Jianliang , Gibson Courtney E , Stenman Adam , Juhlin C Christofer , Korah Reju , Carling Tobias 
Published: May 2020

AbstractTumorigenesis requires mitigation of osmotic stress and the transcription factor nuclear factor of activated T cells 5 (NFAT5) coordinates this response by inducing transcellular transport of ions and osmolytes. NFAT5 modulates in vitro behavior in several cancer types, but a potential role of NFAT5 in adrenocortical carcinoma (ACC) has not been studied. A discovery cohort of 28 ACCs was selected for analysis. Coverage depth analysis of whole-exome sequencing reads assessed NFAT5 copy number alterations in 19 ACCs. Quantitative real-time PCR measured NFAT5 mRNA expression levels in 11 ACCs and 23 adrenocortical adenomas. Immunohistochemistry investigated protein expression in representative adrenal samples. The Cancer Genome Atlas database was analyzed to corroborate NFAT5 findings from the discovery cohort and to test whether NFAT5 expression correlated with ion/osmolyte channel and regulatory protein expression patterns in ACC. NFAT5 was amplified in 10 ACCs (52.6%) and clustered in the top 6% of all amplified genes. mRNA expression levels were 5-fold higher compared with adrenocortical adenomas (P &lt; 0.0001) and NFAT5 overexpression had a sensitivity and specificity of 81.8% and 82.7%, respectively, for malignancy. Increased protein expression and nuclear localization occurred in representative ACCs. The Cancer Genome Atlas analysis demonstrated concomitant NFAT5 amplification and overexpression (P &lt; 0.0001) that correlated with increased expression of sodium/myo-inositol transporter SLC5A3 (r2 = 0.237, P &lt; 0.0001) and 14 other regulatory proteins (P &lt; 0.05) previously shown to interact with NFAT5. Amplification and overexpression of NFAT5 and associated osmotic stress response related genes may play an important role adrenocortical tumorigenesis.
Logical goal-setting frameworks for leprosy projects
Authors: Ogbeiwi Osahon 
Published: May 2020

Background/aims Goal setting is a fundamental practice in the effective management of healthcare services worldwide. This study investigated the extent to which leprosy goal formulation in Nigeria is logical and SMART. Methods Document review of baseline problems, goal statements and goal attainments for 2016 in six leprosy projects using a customised logical framework matrix. Results A total of 15 main problems, 6 aims, 19 objectives and 42 indicators were found. The goals were problem-based and logically linked, with a pattern of a single aim per project, multiple objectives per aim, and multiple indicators per objective. Goal statements specified only impact in 5 out of 6 aims, and only outcome and terminal timeframe in 17 out of 19 (89.5%) objectives. Only one objective stated all four SMART components of outcome, indicator, target and timeframe. While three (7.1%) indicators and two (10.5%) objectives were measurable, no target was attainable. Conclusions Goal-setting frameworks for leprosy projects should be problem based and logical according to best practice. That most leprosy objectives were not completely SMART is similar to the reported structure of objectives published by other health organisations globally.
IT-Governance, Risiko- und Compliance-Management (IT‑GRC) – Ein Kompetenz-orientierter Ansatz für KMU
Authors: Johannsen A. , Kant D. 
Published: May 2020

ZusammenfassungKleine und mittlere Unternehmen aller Branchen versuchen sich nach wie vor angemessen mit den Herausforderungen der Globalisierung und der digitalen Transformation auseinanderzusetzen. Sie bilden in diesem Zusammenhang wachsende Kompetenz in der Produktionsautomatisierung (Industrie 4.0) und in digitalen Geschäfts- und Verwaltungsprozessen aus. In Bezug auf IT-GRC bleiben KMU demgegenüber faktisch oft noch unreif. Bestehende Ansätze des IT-Governance‑, Risiko- und Compliance-Managements sind noch zu wenig für KMU ausgestaltet. Der Artikel stellt vor diesem Hintergrund einen zunächst aus der Literatur abgeleiteten, und dann zusammen mit Feedback von 14 IT-GRC Experten aufgestellten, Kompetenz-orientierten Ansatz zur Wahrnehmung, Messung und Steuerung des IT-Governance, Risiko- und Compliance-Managements in KMU vor. Der Ansatz enthält sechs relevante Kompetenzkategorien. Der Beitrag stellt dann zwei abgeleitete, webbasierte Tools zur Messung und Erfassung der Handlungsbedarfe und zur Unterstützung von Management-Maßnahmen vor. Der Ansatz sowie die prototypisch realisierten Tools unterstützen das IT-GRC Management von KMU gemäß ihrem Reifegrad und bedarfsorientiert. Bei der Unterstützung wird der Fokus darauf gelegt, KMU bei der Umsetzung der ständig wachsenden IT-GRC-Anforderungen schlanke und konkrete Methoden, Werkzeuge und Hilfsmittel an die Hand zu geben und die verschiedenen Stakeholder einzubinden.
„Wenn ich es nicht schaffe, liegt es an meiner Person und nicht an meiner Leistung“ – Die Individualisierung struktureller Probleme im Coaching weiblicher Führungskräfte. Genderlinguistische und gendertheoretische Erkenntnisse für die Praxis.
Authors: Graf Eva-Maria , Fleischhacker Melanie 
Published: May 2020

ZusammenfassungDiese Fallstudie fokussiert die Individualisierung struktureller, d. h. organisationaler und sozialer, Probleme im Rahmen einer Coaching-Erstsitzung zwischen einer weiblichen Führungskraft und einer weiblichen Coach. Die Gesprächsdaten werden mit Hilfe der Kritischen Diskursiven Psychologie und ihren Konzepten interpretative repertoires, ideological dilemmas und subject positions analysiert. Die Analyse nimmt dabei explizite und implizite Genderrepräsentationen in den Blick und zeigt auf wie die Beteiligten stereotype Annahmen über Gender im Kontext des Anliegens reproduzieren und (unhinterfragt) übernehmen; dabei wird es versäumt, vom Individuum der Klientin auf die zugrundeliegenden strukturellen Bedingungen des Systems zu verweisen und so Entlastung herbeizuführen. Das Ziel der angewandt-genderlinguistischen Studie ist es, ein Bewusstsein bei Coaches für die Omnipräsenz und Omnirelevanz von oftmals naturalisierten und normalisierten Genderdiskursen im Coaching von weiblichen Führungskräften zu schaffen.
Adsorción de Cadmio, Cobre y Plomo en Bentonita, Caolín y Zeolita Naturales y Modificadas: Una Revisión de los Parámetros de Operación, Isotermas y Cinética
Authors: Carbonel Dalia 
Published: May 2020

Contexto: La adsorción es un proceso efectivo para el tratamiento de aguas residuales contaminadas con metales pesados. El uso de adsorbentes de bajo costo incrementa la ventaja y competitividad de este proceso. Arcillas y zeolitas, naturales y modificadas, han sido usadas ampliamente para la remoción de metales pesados de aguas residuales.
Método: Se revisaron, analizaron y compararon los estudios, realizados durante la última década, referentes a la adsorción de cadmio, cobre y plomo por bentonita, caolín y zeolita, naturales y modificadas.
Resultados: Se analizan diferentes parámetros de operación, condiciones de equilibrio y cinética. Los parámetros de operación estudiados son la concentración inicial de metales, pH de la solución, dosis de adsorbente y temperatura del sistema. Se presenta una recopilación de la eficiencia de los sistemas respecto a la capacidad máxima de adsorción. Se discuten los modelos de isotermas usados para analizar el equilibrio de adsorción así como los modelos cinéticos y de difusión en los estudios revisados.
Conclusiones: El uso de bentonita, caolín y zeolita es efectivo para la remoción de cadmio, cobre y plomo de soluciones acuosas. La influencia de diversos parámetros de operación se ve reflejado en la variabilidad de las capacidades de adsorción de cadmio, cobre y plomo. En relación al equilibrio de adsorción en la mayoría de estudios revisados la isoterma de Langmuir es la que mejor se ajusta a los datos. En cuanto a la cinética el modelo de pseudo-segundo orden es el que mejor se ajusta a los datos.
Métrica de Hausdorff en el ambiente difuso
Authors: Ochoa Castillo Carlos Orlando , Forero Vega Laura Victoria 
Published: May 2020

Contexto: De manera intuitiva, se ha establecido el concepto de conjunto como una colección distinta de elementos, esto es, un conjunto se determina vía la relación de pertenencia de un elemento de un universo al conjunto. La situación, por supuesto, es si pertenece o no pertenece; en un subconjunto difuso a cada elemento del universo se le asocia con un grado de pertenencia, que es un número entre 0 y 1. Los subconjuntos difusos se establecen como una correspondencia entre cada elemento del universo y un grado de pertenencia.Método: El estudio fue basado en trabajos anteriores como artículos o libros, en donde autores exponen ideas sobre la importancia de los subconjuntos difusos y la necesidad de crear con ellos nuevas teorías y espacios.Resultados: Al combinar dos teorías, se genera un nuevo ambiente de estudio que permite afirmar que la distancia de Hausdorff corresponde, extiende y ajusta la nocion de distancia entre subconjuntos no vacíos compactos en el ambiente de los espacios métricos, mas exactamente en (R n , du).Conclusiones: La construcción realizada permite obtener un espacio métrico con varias cualidades, en donde se puede afirmar que son consequencia del objeto de estudio inicial
Modelación Integrada de Sistemas Socio-ecológicos Complejos: Caso de Estudio la Ecorregión de la Mojana
Authors: Villegas Gonzalez Paula Andrea , Florez Florez Maria Juliana , Triviño León Nathaly , Escobar Jorge Alberto , Obregón Neira Nelson , González Méndez Alex Mauricio , González Salazar Ramon Eduardo 
Published: May 2020

Contexto: Se ha observado que la modelación de sistemas socio-ecológicos complejos a partir de simulaciones basadas en agentes, tienen la ventaja de integrar diferentes procesos, escalas, variables y la posibilidad de generar escenarios con actores en el marco de procesos de modelación participativa.Método: Se diseña una herramienta computacional para la planificación y apoyo a los procesos de toma de decisión relacionados con la gestión de los recursos hídricos, específicamente para el caso de las inundaciones en la ecorregión de la Mojana (Colombia). Son desarrollados talleres de participación social relacionados con creencias, valores, redes sociales y resiliencia.Resultados: El modelo tiene dos componentes: el primero representa la hidrodinámica de las inundaciones por medio de la plataforma numérica ISIS 2D; el segundo, en relación con los aspectos sociales de la región, se maneja a través de modelado de sistemas de agentes. Ambos sistemas están integrados en la plataforma NetLogo.Conclusiones: La modelación integrada de sistemas socio-ecológicos complejos permite visualizar el comportamiento de la población y los recursos naturales en un territorio, contribuyendo al diseño de políticas y los procesos educativos con la participación de diferentes disciplinas y actores. Trabajos futuros, pueden enfocarse en la modelación regional y el análisis del impacto producido por el uso de estas herramientas.
Liquid biopsy for cancer management: a revolutionary but still limited new tool for precision medicine
Authors: Arechederra María , Ávila Matías A. , Berasain Carmen 
Published: May 2020

Abstract
The term liquid biopsy is used in contraposition to the traditional “solid” tissue biopsy. In the oncology field it has opened a new plethora of clinical opportunities as tumor-derived material is shedded into the different biofluids from where it can be isolated and analyzed. Common biofluids include blood, urine, saliva, cerebrospinal fluid (CSF), pleural effusion or bile. Starting from these biological specimens several analytes can be isolated, among which we will review the most widely used: circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), circulating tumor RNA (ctRNA), proteins, metabolites, and exosomes. Regarding the nature of the biomarkers it will depend on the analyte, the type of tumor and the clinical application of the liquid biopsy and it includes, somatic point mutations, deletions, amplifications, gene-fusions, DNA-methylated marks, tumor-specific miRNAs, proteins or metabolites. Here we review the characteristics of the analytes and the methodologies used for their isolation. We also describe the applications of the liquid biopsy in the management of patients with cancer, from the early detection of cancers to treatment guidance in patients with advanced tumors. Finally, we also discuss some current limitations and still open questions.
Variante en gen HARS detectada en exoma clínico: etiología de neuropatía periférica tras más de 20 años sin diagnóstico
Authors: Lahoz Alonso Raquel , Sienes Bailo Paula , Capablo Liesa Jose Luis , Álvarez de Andrés Sara , Bancalero Flores Jose Luis , Izquierdo Álvarez Silvia 
Published: May 2020

Resumen

Objetivos
Describimos un caso con enfermedad de Charcot Marie Tooth axonal tipo 2W, trastorno neurólogico caracterizado por una neuropatía periférica, que afecta principalmente a las extremidades inferiores y provoca dificultades en la marcha y deterioro sensitivo-motor distal.

Presentación del caso
Es un caso en el que la aplicación de las nuevas técnicas de secuenciación masiva (NGS) a través del exoma clínico en los laboratorios de genética permitió detectar la presencia de variantes candidatas de la clínica del paciente.

Conclusiones
La variante detectada en el gen HARS podría apoyar la causalidad en el contexto clínico del paciente tras 20 años sin diagnóstico y con empeoramiento de la clínica.
Critical appraisal and meta-analysis of biological variation studies on glycosylated albumin, glucose and HbA1c
Authors: Ricós Carmen , Fernández-Calle Pilar , Gonzalez-Lao Elisabet , Simón Margarida , Díaz-Garzón Jorge , Boned Beatriz , Marqués-García Fernando , Minchinela Joana , Perich Maria Carmen , Tejedor-Ganduxé Xavier , Corte Zoraida , Aarsand Aasne K. , Aslan Berna , Carobene Anna , Coskun Abdurrahman , Sandberg Sverre 
Published: May 2020

Abstract

Objectives
Numerous biological variation (BV) studies have been performed over the years, but the quality of these studies vary. The objectives of this study were to perform a systematic review and critical appraisal of BV studies on glycosylated albumin and to deliver updated BV estimates for glucose and HbA1c, including recently published high-quality studies such as the European Biological Variation study (EuBIVAS).

Methods
Systematic literature searches were performed to identify BV studies. Nine publications not included in a previous review were identified; four for glycosylated albumin, three for glucose, and three for HbA1c. Relevant studies were appraised by the Biological Variation Data Critical Appraisal Checklist (BIVAC). Global BV estimates were derived by meta-analysis of BIVAC-compliant studies in healthy subjects with similar study design.

Results
One study received BIVAC grade A, 2B, and 6C. In most cases, the C-grade was associated with deficiencies in statistical analysis. BV estimates for glycosylated albumin were: CVI=1.4% (1.2–2.1) and CVG=5.7% (4.7–10.6), whereas estimates for HbA1c, CVI=1.2% (0.3–2.5), CVG=5.4% (3.3–7.3), and glucose, CVI=5.0% (4.1–12.0), CVG=8.1% (2.7–10.8) did not differ from previously published global estimates.

Conclusions
The critical appraisal and rating of BV studies according to their methodological quality, followed by a meta-analysis, generate robust, and reliable BV estimates. This study delivers updated and evidence-based BV estimates for glycosylated albumin, glucose and HbA1c.
A nonlinear dynamical approach to analysis of emotions using EEG signals based on the Poincaré map function and recurrence plots
Authors: Khodabakhshi Mohammad Bagher , Saba Valiallah 
Published: May 2020

AbstractDynamic variations of electroencephalogram (EEG) contain significant information in the study of human emotional states. Transient time methods are well suited to evaluate short-term dynamic changes in brain activity. Human affective states, however, can be more appropriately analyzed using chaotic dynamical techniques, in which temporal variations are considered over longer durations. In this study, we have applied two different recurrence-based chaotic schemes, namely the Poincaré map function and recurrence plots (RPs), to analyze the long-term dynamics of EEG signals associated with state space (SS) trajectory of the time series. Both approaches determine the system dynamics based on the Poincaré recurrence theorem as well as the trajectory divergence producing two-dimensional (2D) characteristic plots. The performance of the methods is compared with regard to their ability to distinguish between levels of valence, arousal, dominance and liking using EEG data from the “dataset for emotion analysis using physiological” database. The differences between the levels of emotional feelings were investigated based on the analysis of variance (ANOVA) test and Spearman’s statistics. The results obtained from the RP features distinguish between the emotional ratings with a higher level of statistical significance as compared with those produced by the Poincaré map function. The scheme based on RPs was particularly advantageous in identifying the levels of dominance. Out of the 32 EEG electrodes examined, the RP-based approach distinguished the dominance levels in 23 electrodes, while the approach based on the Poincaré map function was only able to discriminate dominance levels in five electrodes. Furthermore, based on nonlinear analysis, significant correlations were observed over a wider area of the cortex for all affective states as compared with that reported based on the analysis of EEG power bands.