Miracle-dz/UniFAR-FTUs huggingface dataset:
Next-Generation Sequencing Analysis and Algorithms for PDX and CDX Models

Patient-derived xenograft (PDX) and circulating tumor cell–derived explant (CDX) models are powerful methods for the study of human disease. In cancer research, these methods have been applied to multiple questions, including the study of metastatic progression, genetic evolution, and therapeutic drug responses. As PDX and CDX models can recapitulate the highly heterogeneous characteristics of a patient tumor, as well as their response to chemotherapy, there is considerable interest in combining them with next-generation sequencing to monitor the genomic, transcriptional, and epigenetic changes that accompany oncogenesis. When used for this purpose, their reliability is highly dependent on being able to accurately distinguish between sequencing reads that originate from the host, and those that arise from the xenograft itself. Here, we demonstrate that failure to correctly identify contaminating host reads when analyzing DNA- and RNA-sequencing (DNA-Seq and RNA-Seq) data from PDX and CDX models is a major confounding factor that can lead to incorrect mutation calls and a failure to identify canonical mutation signatures associated with tumorigenicity. In addition, a highly sensitive algorithm and open source software tool for identifying and removing contaminating host sequences is described. Importantly, when applied to PDX and CDX models of melanoma, these data demonstrate its utility as a sensitive and selective tool for the correction of PDX- and CDX-derived whole-exome and RNA-Seq data. Implications: This study describes a sensitive method to identify contaminating host reads in xenograft and explant DNA- and RNA-Seq data and is applicable to other forms of deep sequencing. Mol Cancer Res; 15(8); 1012–6. ©2017 AACR.
Sources and Consequences of Reactive Oxygen Species in Right Ventricular Hypertrophy and Right Ventricular Failure

The present study investigates the role of mitochondrial biogenesis in the development of compensatory right-ventricular (RV) hypertrophy or failure. A rat model in which either stable compensatory RV hypertrophy (HYP) or failure (CHF) is induced by graded pulmonary arterial hypertension following subcutaneous injection of 30 mg/kg or 80mg/kg monocrotaline, respectively, was used to compare a hypertrophic and a failing phenotype in parallel at day 19 and 25. At day 19 neither group shows signs of failure, while at day 25 only the CHF group shows RV failure. We investigated mitochondrial density, expression of mitochondrial membrane proteins adenine nucleotide translocator (ANT), voltage-dependent anion-selective channel (VDAC-1), and expression of transcription factors i.e., nuclear respiratory factor 1 and 2 (NRF-1 and NRF-2), mitochondrial transcription factor A (TFAM) and the co-activator of peroxisome proliferator activated receptor gamma 1α (PGC-1α). Furthermore, intracellular localization of pro-apoptotic Bax, expression of anti-apoptotic caspase inhibitor Apoptosis Repressor with CARD (ARC), and superoxide dismutase 1 and 2 (SOD1 and SOD-2) were investigated. At day 25 and only in HYP did mitochondrial density, VDAC-1 and ANT expression increase. This was accompanied by an increased NRF-1, NRF-2 and TFAM transcription. The HYP group also showed an increased ARC expression and unaltered Bax translocation, whereas the CHF group was characterized by unaltered mitochondrial biogenesis and increased Bax translocation. Conclusion: stable compensatory RV hypertophy due to pressure overload is associated with upregulation of mitochondrial biogenesis, while hypertrophy and decompensation in response to a higher pressure load is associated with the absence of mitochondrial biogenesis and an increase in pro-apoptotic signalling.
Laryngeal exposure during laryngoscopy is better in the 25° back-up position than in the supine position

Background Good visualization of the glottis is important for tracheal intubation. This study evaluated whether the 25° back-up position improves the quality of the laryngeal view during laryngoscopy. Methods Laryngoscopy with a curved blade was performed on 40 anaesthetized patients. The patients were randomly assigned to two groups. Laryngeal views were captured with a rigid 0° endoscope. Views were recorded for each patient in Group A (n = 20) during laryngoscopies performed with the patient lying first in the supine position and then in the 25° back-up position. Laryngeal views for patients in Group B (n = 20) were first captured while the patient was in the 25° back-up position and then while the patient was in the flat supine position. An anaesthetist blinded to the position graded the quality of the images using the percentage of glottic opening (POGO) score. Results Comparing the two positions, mean ( sd ) POGO scores increased significantly from 42.2 (27.4)% in supine position to 66.8 (27.6)% in 25° back-up position (P Conclusions During laryngoscopy, the laryngeal view, as assessed by POGO scores, improves significantly in the 25° back-up position when compared with the flat supine position.
The effect of caffeine mouth rinse on self-paced cycling performance

The aim of the study was to determine whether caffeine mouth rinse would improve 30 min self-paced cycling trial. Twelve healthy active males (age 20.5±0.7 years, mass 87.4±18.3 kg) volunteered for the study. They attended the laboratory on 3 separate occasions performing a 30 min self-paced cycling trial. On one occasion water was given as a mouth rinse for 5 s (PLA), on another occasion a 6.4% maltodextrin (CHO) solution was given for 5 s and finally a caffeine solution (containing 32 mg of caffeine dissolved in 125 ml water; CAF) was given for 5 s. Distance cycled, heart rate, ratings of perceived exertion, cadence, speed and power output were recorded throughout all trials. Distance cycled during the CAF mouth rinse trial (16.2±2.8 km) was significantly greater compared to PLA trial (14.9±2.6 km). There was no difference between CHO and CAF trials (P=0.89). Cadence, power and velocity were significantly greater during the CAF trial compared to both PLA and CHO (P<0.05). There were no differences betwe.
Prediction of Mortality and Morbidity With a 6-Minute Walk Test in Patients With Left Ventricular Dysfunction

Objective. —To study the potential usefulness of the 6-minute walk test, a self-paced submaximal exercise test, as a prognostic indicator in patients with left ventricular dysfunction. Design. —Data were collected during a prospective cohort study, the Studies of Left Ventricular Dysfunction (SOLVD) Registry Substudy. Setting. —Twenty tertiary care hospitals in the United States, Canada, and Belgium. Participants. —A stratified random sample of 898 patients from the SOLVD Registry who had either radiological evidence of congestive heart failure and/or an ejection fraction of 0.45 or less were enrolled in the substudy and underwent a detailed clinical evaluation including a 6-minute walk test. Patients were followed up for a mean of 242 days. Outcome Measures. —Mortality and hospitalization. Results. —During follow-up, 52 walk-test participants (6.2%) died and 252 (30.3%) were hospitalized. Hospitalization for congestive heart failure occurred in 78 participants (9.4%), and the combined endpoint of death or hospitalization for congestive heart failure occurred in 114 walk-test participants (13.7%). Compared with the highest performance level, patients in the lowest performance level had a significantly greater chance of dying (10.23% vs 2.99%;P=.01), of being hospitalized (40.91% vs 19.90%;P=.002), and of being hospitalized for heart failure (22.16% vs 1.99%;P Conclusion. —The 6-minute walk test is a safe and simple clinical tool that strongly and independently predicts morbidity and mortality in patients with left ventricular dysfunction. (JAMA. 1993;270:1702-1707)
Complicações das vias aéreas relacionadas à intubação endotraqueal

escrevemos as principais complicacoes das vias aere-as relacionadas a intubacao endotraqueal, por meio de revi-sao da literatura e apresentacao dos resultados de pesquisasclinicas e experimentais realizadas pelo nosso grupo de es-tudo. Procuramos alertar os profissionais de saude quanto aalta incidencia de complicacoes secundarias a intubacao, asquais podem ser reduzidas com a adocao de medidasprofilaticas simples e de cunho pratico, estabelecidas aposa compreensao da fisiopatologia das lesoes.
Effect of short term administration of konjac glucomannan hydrolysates on adult blood lipid parameters and glucose concentrations

Purpose – This paper aims to evaluate the effect of depolymerised glucomannan in regulating blood lipid and glucose concentrations. Design/methodology/approach – Twenty adult volunteers were recruited. Blood samples were taken at Day 0. The volunteers consumed drinks containing 3.0 g active glucomannan hydrolysates (AMH) for 14 days, after which time blood samples were retaken (Day 15). Blood samples were analysed to determine the blood lipid and glucose concentrations. Findings – The average fasting blood glucose at the start of the trial was 2.54 mmol/L but reduced slightly to 2.49 mmol/L after consumption of the glucomannan. The total average cholesterol at the start of the trial was higher (6.69 mmol/L) than desirable ( < 5.0 mmol/L). This was reduced after consuming the glucomannan to 6.44 mmol/L (3.74 per cent). The triglyceride content was also higher initially than recommended (2.88 mmol/L) but was reduced by 11.5 per cent. The high-density lipoprotein (HDL) was within the desirable range before a.
An investigation of type 2 diabetes self-management in Taiwan.

In Taiwan, as in other countries, type 2 diabetes is a major public health problem. Taiwanese nurses are being called upon to play an increasingly large role in diabetes care, but little is known about the factors that contribute to good or poor diabetes self-management in the Taiwanese context. This study is an exploratory investigation of Taiwanese women’s experiences of living with type 2 diabetes. Adopting an open-ended qualitative approach, the research aimed to discern personal characteristics, strategies, socio-cultural and health system factors that affected women’s ability to manage their condition effectively. Thirty-eight women were interviewed. These included twenty women who were nominated by health professionals as being effective at diabetes self-management and eithteen who were considered to have difficulties, in controlling their HbA1c. Five senior diabetes nurses were also interviewed. Data was analysed thematically. The study found that for many women, their diabetes diagnosis was marked by profound shock and change in their sense of self. Learning to live with diabetes was an ongoing ‘journey’ in which women engaged in a range of strategies to acquire information and support, to gain a sense of control over their condition and to find a health care provider they could trust. The findings challenge the prevailing medical model that defines ‘successful’ self-management on the basis of clinical outcomes alone. Rather, self-management was found to be highly contingent upon individual life circumstances. From women’s own perspectives, successful self-management involved coping with a context of severe social stigma and juggling their own self-care alongside maintenance of multiple social gender roles and financial responsibilities, often in the face of social or economic difficulties. The research points to a need for health professionals to adopt a non-judgemental, individualised and empowering philosophy in their approach to diabetes care whereby education and treatment is tailored to the specific and complex needs of individual patients.
Estrategias de afrontamiento ante el estrés y fuentes de recompensa profesional en médicos especialistas de la Comunidad Valenciana: Un estudio con entrevistas semiestructuradas

Fundamento. Los profesionales de la medicina estan particularmente expuestos a factores de riesgo psicosocial que pueden afectar su calidad de vida. La identificacion de estrategias de afrontamiento frente al estres y las fuentes de recompensa profesional permitiria instaurar medidas preventivas tendentes a moderar el efecto negativo de estos factores de riesgo. Los objetivos del presente trabajo son identificar las estrategias de afrontamiento ante el estres que utilizan los medicos especialistas de seis hospitales publicos de la provincia de Valencia, y describir sus fuentes de recompensa y satisfaccion profesional. Metodos. Estudio cualitativo realizado por entrevistas semiestructuradas individuales a 47 medicos especialistas de seis hospitales publicos de la provincia de Valencia. Las entrevistas han sido grabadas en audio y transcritas posteriormente. Se ha realizado un analisis del contenido del discurso. Resultados. Las estrategias de afrontamiento referidas con mas frecuencia por los facultativos entrevistados, analizadas de manera general, son las centradas en las emociones y en concreto la desconexion conductual y la busqueda de apoyo social emocional. Sin embargo, ante factores estresantes puntuales concretos de la practica diaria, las estrategias mas frecuentes son las centradas en el problema. Una parte importante de los medicos entrevistados manifiesta no tener ninguna recompensa laboral. Entre los que si expresan elementos de recompensa, refieren en primer lugar el salario, seguido de la satisfaccion personal por la dedicacion a la medicina. Conclusiones. La inclusion de formacion sobre estrategias de afrontamiento activo frente al estres en el curriculo profesional de los medicos, podria aumentar sus recursos personales para hacer frente al mismo. Ademas se deberian instaurar cambios organizacionales que aumenten las recompensas laborales.
Cancer as a life-changing process: Women's experiences fi ve years after treatment for gynaecological cancer

This article presents and discusses the essential structure appearing in a phenomenological study focusing on women's experiences of living as long-term survivors after gynaecological cancer, namely Cancer as a life-changing process. The aim of the study was to gain a deeper understanding of living beyond gynaecological cancer. The study is founded on a phenomenological lifeworld perspective, and based on 32 in-depth interviews with 16 women aged 39 to 66, all free of illness. The interviews were made fi ve and six years after treatment for cancer, respectively. Surviving cancer entails living with profound life-changes, demanding as well as enriching, even though the women have been declared cured. The essential structure consists of two interrelated constituents; “living between life courage and life anxiety” and “living between existential loneliness and relational caring”. The constituents are illuminated by the perspective of Danish life-philosophy, represented by Ludvig Feilberg and Knud Ejler Logstrup—and Mogens Pahuus' interpretation of their thinking. The empirics clearly show that life phenomena are still “ploughed up” fi ve to six years after treatment when the women have been declared long-term survivors. The study points out that experiencing cancer can move the women deeply in their lives. This may challenge health care personnel in their encounters with women surviving gynaecological cancer. Key words: Gynaecological cancer, long-term survival, life phenomena, vulnerability, cancer care.
The complete mitogenome of Jankowskia athleta (Lepidoptera: Geometridae)

Abstract We have sequenced the entire mitochondrial genome of Jankowskia athleta, that is 15 534 bp in length with a 79.53% A + T content (GenBank accession no. KR822683). The mt genome of J. athleta encodes 37 genes that are typically found in metazoan mt genomes, consists of 13 protein-coding genes, 2 ribosomal RNA genes, and 22 transfer RNA genes. Within the mt genome of J. athleta, there are six gene reading frame overlaps. The gene order is consistent with other yet sequenced mt genome in Geometridae. The mt genome of J. athleta has a 475 bp A + T-rich region with an A + T content of 93.47%. The result of phylogenetic analysis infers that J. athleta is more closely related to species of Geometridae than other moths.
Treatment Facility Neighborhood Environment and Outpatient Treatment Completion

The current study focuses on three dimensions of treatment neighborhood environments that may influence treatment retention: neighborhood disadvantage, stability, and concentrated immigration. We examined treatment outcomes for a total of 9,319 individuals who were admitted for initial treatment in 56 outpatient clinics in Cook County, Illinois. Census-tract-level data were used to measure facility neighborhood environment. We found that neighborhood disadvantage was unrelated to individual treatment completion. Immigrant concentration was found to increase the likelihood of substance abuse treatment completion, although it was attenuated after controlling for patient problem severity and referral sources. Neighborhood stability was found to be positively related to treatment completion. These results suggest that knowledge of neighborhood context should be an important consideration when making placement decisions of new treatment facilities. Knowledge of neighborhood impact on treatment attrition should also be considered essential information to be used for client placement, treatment program design, and discharge protocols.
Percutaneous edge-to-edge mitral valve repair escorted by left atrial intracardiac echocardiography (ICE).

Percutaneous mitral valve repair (PMVR) using the MitraClip system is an innovative method allowing treatment of mitral regurgitation (MR) for a patient that is not accessible by conventional operation.1 Consequently, novel pitfalls and obstacles become apparent. PMVR is generally performed under transesophageal echocardiographic guidance. However, in some patients, visualization of structures by transesophageal echocardiography (TOE) is not sufficient. Furthermore, as a consequence of continuous TOE during PMVR, general anesthesia and or tracheal intubation are required and represent a major weaknesses of the procedure, bringing about drops in blood pressure, potential aspiration, or neurological disorders to these frail patients. Intracardiac echocardiography (ICE) from the right atrium has been shown to be a safe imaging method during procedures such as atrial septal defect or complex PFO closure.2 Here, we report visualization of a PMVR procedure via left atrial ICE. A 76-year-old man with a grade-IV functional mitral valve regurgitation (Figure, A) and severely impaired left ventricular (LV) function (LV ejection fraction, 30%) resulting from dilated cardiomyopathy was admitted to our intensive care unit with recurrent left ventricular decompensation. He had recently had multiple implantable cardioverter defibrillator shocks as a …
Single-Variant and Multi-Variant Trend Tests for Genetic Association with Next-Generation Sequencing That Are Robust to Sequencing Error

As with any new technology, next-generation sequencing (NGS) has potential advantages and potential challenges. One advantage is the identification of multiple causal variants for disease that might otherwise be missed by SNP-chip technology. One potential challenge is misclassification error (as with any emerging technology) and the issue of power loss due to multiple testing. Here, we develop an extension of the linear trend test for association that incorporates differential misclassification error and may be applied to any number of SNPs. We call the statistic the linear trend test allowing for error, applied to NGS, or LTTae,NGS. This statistic allows for differential misclassification. The observed data are phenotypes for unrelated cases and controls, coverage, and the number of putative causal variants for every individual at all SNPs. We simulate data considering multiple factors (disease mode of inheritance, genotype relative risk, causal variant frequency, sequence error rate in cases, sequence error rate in controls, number of loci, and others) and evaluate type I error rate and power for each vector of factor settings. We compare our results with two recently published NGS statistics. Also, we create a fictitious disease model based on downloaded 1000 Genomes data for 5 SNPs and 388 individuals, and apply our statistic to those data. We find that the LTTae,NGS maintains the correct type I error rate in all simulations (differential and non-differential error), while the other statistics show large inflation in type I error for lower coverage. Power for all three methods is approximately the same for all three statistics in the presence of non-differential error. Application of our statistic to the 1000 Genomes data suggests that, for the data downloaded, there is a 1.5% sequence misclassification rate over all SNPs. Finally, application of the multi-variant form of LTTae,NGS shows high power for a number of simulation settings, although it can have lower power than the corresponding single-variant simulation results, most probably due to our specification of multi-variant SNP correlation values. In conclusion, our LTTae,NGS addresses two key challenges with NGS disease studies; first, it allows for differential misclassification when computing the statistic; and second, it addresses the multiple-testing issue in that there is a multi-variant form of the statistic that has only one degree of freedom, and provides a single p value, no matter how many loci.
Classical transient receptor potential channel 1 in hypoxia-induced pulmonary hypertension.

RATIONALE Pulmonary hypertension (PH) is a life-threatening disease, characterized by pulmonary vascular remodeling. Abnormal smooth muscle cell proliferation is a primary hallmark of chronic hypoxia-induced PH. Essential for cell growth are alterations in the intracellular Ca(2+) homeostasis. Classical transient receptor potential (TRPC) proteins have been suggested to contribute to PH development, as TRPC1 and TRPC6 are predominantly expressed in precapillary pulmonary arterial smooth muscle cells (PASMC). Studies in a TRPC6-deficient mouse model revealed an essential function of TRPC6 in acute but not in chronic hypoxia. OBJECTIVES We aimed to identify the importance of TRPC1 in the pathogenesis of chronic hypoxia-induced PH in mice. METHODS TRPC1 expression analysis was performed using real-time polymerase chain reaction. TRPC1 function was assessed by in vivo experiments in TRPC1(-/-) animals as well as in isolated precapillary murine PASMC after TRPC1 knockdown by TRPC1-specific small interfering RNAs. MEASUREMENTS AND MAIN RESULTS Only TRPC1 mRNA was up-regulated under hypoxia in isolated murine PASMC (1% O2 for 72 h). Hypoxia-induced proliferation of murine PASMC was attenuated in cells treated with small interfering RNA against TRPC1 and in cells isolated from TRPC1(-/-) animals compared with untreated and wild-type cells. TRPC1(-/-) mice did not develop PH in response to chronic hypoxia (FI(O2) 0.10 for 21 d) and had less vascular muscularization but a similar degree of right ventricular hypertrophy compared with wild-type mice. CONCLUSIONS Our results indicate an important role of TRPC1 in pulmonary vascular remodeling underlying the development of hypoxia-induced PH.