Miracle-dz/UniFAR-FTUs huggingface dataset:
Certificação digital de exames em telerradiologia: um alerta necessário

A crescente popularizacao das atividades de telemedicina em todo o mundo tem exigido de medicos e demais profissionais da saude novas abordagens em sua pratica profissional. No que se refere a telerradiologia, observamos forte tendencia a transformacao de documentos clinicos - como resultados de exames, que ate hoje existiam na forma de filmes impressos e laudos em papel - em documentos eletronicos, disponibilizados em redes internas de clinicas e hospitais, ou pela internet. Esta tendencia torna necessaria a divulgacao e o esclarecimento de conceitos como a certificacao digital, a criptografia de dados na internet, a confiabilidade de sites, o documento eletronico confiavel e a assinatura digital. Os principios basicos desses conceitos, embora por vezes complexos para os profissionais da saude, podem ser compreendidos de forma efetiva sem que o leitor tenha de mergulhar de cabeca em labirintos como a matematica da criptografia de chaves assimetricas ou os protocolos de comunicacao digital de dados. Neste artigo abordaremos de forma direta e com exemplos praticos os aspectos de seguranca e confiabilidade de documentos clinicos eletronicos baseados na internet, com o objetivo de que os usuarios medicos possam interagir de forma informada, segura e bem fundamentada com servicos de telerradiologia.
Fat‐free muscle mass in magnetic resonance imaging predicts acute‐on‐chronic liver failure and survival in decompensated cirrhosis

Muscle mass seems to be a prognostic marker in patients with liver cirrhosis. However, reported methods to quantify muscle mass are heterogeneous, consented cutoff values are missing, and most studies have used computed tomography. This study evaluated fat‐free muscle area (FFMA) as a marker of sarcopenia using magnetic resonance imaging (MRI) in patients with decompensated cirrhosis with transjugular intrahepatic portosystemic shunt (TIPS). The total erector spinae muscle area and the intramuscular fat tissue area were measured and subtracted to calculate the FFMA in 116 patients with cirrhosis by TIPS and MRI. The training cohort of 71 patients compared computed tomography–measured transversal psoas muscle thickness with FFMA. In 15 patients MRI was performed before and after TIPS, and in 12 patients follistatin serum measurements were carried out. The results on FFMA were confirmed in a validation cohort of 45 patients. FFMA correlated with follistatin and transversal psoas muscle thickness and showed slightly better association with survival than transversal psoas muscle thickness. Gender‐specific cutoff values for FFMA were determined for sarcopenia. Decompensation (ascites, overt hepatic encephalopathy) persisted after TIPS in the sarcopenia group but resolved in the nonsarcopenia group. Sarcopenic patients showed no clinical improvement after TIPS as well as higher mortality, mainly due to development of acute‐on‐chronic liver failure. FFMA was an independent predictor of survival in these patients. Conclusion: This study offers an easy‐to‐apply MRI‐based measurement of fat‐free muscle mass as a marker of sarcopenia in decompensated patients; while TIPS might improve sarcopenia and thereby survival, persistence of sarcopenia after TIPS is associated with a reduced response to TIPS and a higher risk of acute‐on‐chronic liver failure development and mortality. (Hepatology 2018;67:1014–1026)
Should we treat acute hepatitis C? A decision and cost‐effectiveness analysis

It is not standard practice to treat patients with acute hepatitis C virus (HCV) infection. However, as the incidence of HCV in the United States continues to rise, it may be time to re‐evaluate acute HCV management in the era of direct‐acting antiviral (DAA) agents. In this study, a microsimulation model was developed to analyze the trade‐offs between initiating HCV therapy in the acute versus chronic phase of infection. By simulating the lifetime clinical course of patients with acute HCV infection, we were able to project long‐term outcomes such as quality‐adjusted life years (QALYs) and costs. We found that treating acute HCV versus deferring treatment until the chronic phase increased QALYs by 0.02 and increased costs by $483 in patients not at risk of transmitting HCV. The resulting incremental cost‐effectiveness ratio was $19,991 per QALY, demonstrating that treatment of acute HCV was cost‐effective using a willingness‐to‐pay threshold of $100,000 per QALY. In patients at risk of transmitting HCV, treating acute HCV became cost‐saving, increasing QALYs by 0.03 and decreasing costs by $3,655. Conclusion: Immediate treatment of acute HCV with DAAs can improve clinical outcomes and be highly cost‐effective or cost‐saving compared with deferring treatment until the chronic phase of infection. If future studies continue to demonstrate effective HCV cure with shorter 6‐week treatment duration, then it may be time to revisit current HCV guidelines to incorporate recommendations that account for the clinical and economic benefits of treating acute HCV in the era of DAAs. (Hepatology 2018;67:837–846)
A risk score to predict the development of hepatic encephalopathy in a population‐based cohort of patients with cirrhosis

Over 40% of patients with cirrhosis will develop hepatic encephalopathy (HE). HE is associated with decreased survival, falls, motor vehicle accidents, and frequent hospitalization. Accordingly, we aimed to develop a tool to risk‐stratify patients for HE development. We studied a population‐based cohort of all patients with cirrhosis without baseline HE (n = 1,979) from the Veterans Administration from Michigan, Indiana, and Ohio (January 1, 2005‐December 31, 2010) using demographic, clinical, laboratory, and pharmacy data. The primary outcome was the development of HE. Risk scores were constructed with both baseline and longitudinal data (annually updated parameters) and validated using bootstrapping. The cohort had a mean age of 58.0 ± 8.3 years, 36% had hepatitis C, and 17% had ascites. Opiates, benzodiazepines, statins, and nonselective beta‐blockers were taken at baseline by 24%, 13%, 17%, and 12%, respectively. Overall, 863 (43.7%) developed HE within 5 years. In multivariable models, risk factors (hazard ratio, 95% confidence interval) for HE included higher bilirubin (1.07, 1.05‐1.09) and nonselective beta‐blocker use (1.34, 1.09‐1.64), while higher albumin (0.54, 0.48‐0.59) and statin use (0.80, 0.65‐0.98) were protective. Other clinical factors, including opiate and benzodiazepine use, were not predictive. The areas under the receiver operating characteristics curve for HE using the four significant variables in baseline and longitudinal models were 0.68 (0.66‐0.70) and 0.73 (0.71‐0.75), respectively. Model effects were validated and converted into a risk score. A score ≤0 in our longitudinal model assigns a 6% 1‐year probability of HE, while a score >20 assigns a 38% 1‐year risk. Conclusion: Patients with cirrhosis can be stratified by a simple risk score for HE that accounts for changing clinical data; our data also highlight a role for statins in reducing cirrhosis complications including HE. (Hepatology 2017).
Polyethylene glycol (PEG): a versatile polymer for pharmaceutical applications

ABSTRACT Introduction: Polyethylene glycol (PEG) is a polymer of choice in drug delivery systems. This USFDA-approved polymer is popular due to its tunable properties and well-established safety profile: prime requisites considered during the selection of any excipient in formulation development. Areas covered: The unique properties and applications of PEG have been discussed at length in the existing literature. However, a proper guidance on selection of PEG grade to cater to one’s purpose is lacking. This article provides preliminary guidelines to formulators on selection of appropriate PEG grade, typically based on its physico-chemical properties and role-based functional application in pharmaceuticals. It should be noted that the aim article is not to deep dive in each application area. Expert opinion: Guidance on PEG application and grade of choice is lacking in the available literature. The authors have discussed and provided guidance to formulators on the appropriate PEG grade selection for particular application based on the available in vitro and in vivo literature data. In this review a State-of-the-art use of PEG in therapeutic applications, its clinical status and commercial use is also summarized. Nevertheless, toxicities related to different PEG grades and related impurities are discussed in this review.
Diabetes, metabolic comorbidities, and risk of hepatocellular carcinoma: Results from two prospective cohort studies

Type 2 diabetes (T2D) is a risk factor for hepatocellular carcinoma (HCC). However, it is unknown whether T2D duration or additional metabolic comorbidities further contribute to HCC risk. From the Nurses' Health Study (NHS), 120,826 women were enrolled in 1980, and from the Health Professionals Follow‐up Study (HPFS), 50,284 men were enrolled in 1986 and followed through 2012. Physician‐diagnosed T2D was ascertained at baseline and updated biennially. Cox proportional hazards regression models were used to calculate age‐ and multivariable‐adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for incident HCC. Over 32 years of follow‐up (4,488,410 person‐years), we documented 112 cases of HCC (69 women, 43 men). T2D was associated with an increased HCC risk (multivariable HR, 4.59; 95% CI, 2.98‐7.07), as was an increasing T2D duration (Ptrend < 0.001). Compared to nondiabetics, the multivariable HRs for HCC were 2.96 (95% CI, 1.57‐5.60) for 0‐<2 years; 6.08 (95% CI, 2.96‐12.50) for 2‐<10 years; and 7.52 (95% CI, 3.88‐14.58) for ≥10 years. Increasing number of metabolic comorbidities (T2D, obesity, hypertension, and dyslipidemia) was associated with increased HCC risk (Ptrend < 0.001); compared to individuals without metabolic comorbidity, those with four metabolic comorbidities had an 8.1‐fold increased HCC risk (95% CI, 2.48‐26.7). In T2D, neither insulin use nor oral hypoglycemic use was significantly associated with HCC risk (HR, 2.04 [95% CI, 0.69‐6.09] and HR, 1.45 [95% CI, 0.69‐3.07], respectively). Conclusion: T2D is independently associated with increased risk for HCC in two prospective cohorts of U.S. men and women. This risk is enhanced with prolonged diabetes duration and with comorbid metabolic conditions, suggesting the importance of insulin resistance in the pathogenesis of HCC. (Hepatology 2018;67:1797‐1806)
Programs for Calibration‐Based Monte Carlo Simulation of Recharge Areas

One use of groundwater flow models is to simulate contributing recharge areas to wells or springs. Particle tracking can be used to simulate these recharge areas, but in many cases the modeler is not sure how accurate these recharge areas are because parameters such as hydraulic conductivity and recharge have errors associated with them. The scripts described in this article (GEN_LHS and MCDRIVER_LHS) use the Python scripting language to run a Monte Carlo simulation with Latin hypercube sampling where model parameters such as hydraulic conductivity and recharge are randomly varied for a large number of model simulations, and the probability of a particle being in the contributing area of a well is calculated based on the results of multiple simulations. Monte Carlo simulation provides one useful measure of the variability in modeled particles. The Monte Carlo method described here is unique in that it uses parameter sets derived from the optimal parameters, their standard deviations, and their correlation matrix, all of which are calculated during nonlinear regression model calibration. In addition, this method uses a set of acceptance criteria to eliminate unrealistic parameter sets.
The potential of toxin-based drug delivery systems for enhanced nucleic acid therapeutic delivery

ABSTRACT Introduction: The potential of gene replacement therapy has been underscored by the market authorization of alipogene tiparvovec (Glybera) and GSK2696273 (Strimvelis) in the EU and recombinant adenovirus-p53 (Gendicine) in China. Common to these systems is the use of attenuated viruses for ‘drug’ delivery. Whilst viral delivery systems are being developed for siRNA, their application to antisense delivery remains problematic. Non-viral delivery remains experimental, with some notable successes. However, stability and the ‘PEG dilemma’, balancing toxicity and limited (often liver-tropic) pharmacokinetics/oharmacodynamics, with the membrane destabilizing activity, necessary for nucleocytosolic access and transfection remain a problem. Areas covered: Here we review the use of attenuated protein toxins as a delivery vehicle for nucleic acids, their relationship to the PEG dilemma, and their biological properties with specific reference to their intracellular trafficking. Expert opinion: The possibility of using attenuated toxins as antisense and siRNA delivery systems has been demonstrated in vitro. Systems based upon attenuated anthrax toxin have been shown to have high activity (equivalent to nucleofection) and low toxicity whilst not requiring cationic ‘helpers’ or condensing agents, divorcing these systems from the problems associated with the PEG dilemma. It remains to be seen whether these systems can operate safely, efficiently and reproducibly, in vivo or in the clinic.
Stochastic phenotype switching leads to intratumor heterogeneity in human liver cancer

Intratumor heterogeneity is increasingly recognized as a major factor impacting diagnosis and personalized treatment of cancer. We characterized stochastic phenotype switching as a mechanism contributing to intratumor heterogeneity and malignant potential of liver cancer. Clonal analysis of primary tumor cell cultures of a human sarcomatoid cholangiocarcinoma identified different types of self‐propagating subclones characterized by stable (keratin‐7‐positive or keratin‐7‐negative) phenotypes and an unstable phenotype consisting of mixtures of keratin‐7‐positive and keratin‐7‐negative cells, which lack stem cell features but may reversibly switch their phenotypes. Transcriptome sequencing and immunohistochemical studies with the markers Zeb1 and CD146/MCAM demonstrated that switching between phenotypes is linked to changes in gene expression related but not identical to epithelial–mesenchymal transition. Stochastic phenotype switching occurred during mitosis and did not correlate with changes in DNA methylation. Xenotransplantation assays with different cellular subclones demonstrated increased tumorigenicity of cells showing phenotype switching, resulting in tumors morphologically resembling the invasive component of primary tumor and metastasis. Conclusion. Our data demonstrate that stochastic phenotype switching contributes to intratumor heterogeneity and that cells with a switching phenotype have increased malignant potential. (Hepatology 2017).
Impact of hepatitis C virus polymorphisms on direct‐acting antiviral treatment efficacy: Regulatory analyses and perspectives

Several highly effective, interferon‐free, direct‐acting antiviral (DAA)‐based regimens are available for the treatment of chronic hepatitis C virus (HCV) infection. Despite impressive efficacy overall, a small proportion of patients in registrational trials experienced treatment failure, which in some cases was associated with the detection of HCV resistance‐associated substitutions (RASs) at baseline. In this article, we describe methods and key findings from independent regulatory analyses investigating the impact of baseline nonstructural (NS) 3 Q80K and NS5A RASs on the efficacy of current United States Food and Drug Administration (FDA)‐approved regimens for patients with HCV genotype (GT) 1 or GT3 infection. These analyses focused on clinical trials that included patients who were previously naïve to the DAA class(es) in their investigational regimen and characterized the impact of baseline RASs that were enriched in the viral population as natural or transmitted polymorphisms (i.e., not drug‐selected RASs). We used a consistent approach to optimize comparability of results across different DAA regimens and patient populations, including the use of a 15% sensitivity cutoff for next‐generation sequencing results and standardized lists of NS5A RASs. These analyses confirmed that detection of NS3 Q80K or NS5A baseline RASs was associated with reduced treatment efficacy for multiple DAA regimens, but their impact was often minimized with the use of an intensified treatment regimen, such as a longer treatment duration and/or addition of ribavirin. We discuss the drug resistance‐related considerations that contributed to pretreatment resistance testing and treatment recommendations in drug labeling for FDA‐approved DAA regimens. Conclusion: Independent regulatory analyses confirmed that baseline HCV RASs can reduce the efficacy of certain DAA‐based regimens in selected patient groups. However, highly effective treatment options are available for patients with or without baseline RASs. (Hepatology 2018;67:2430‐2448).
Analysis of Energy Characteristics of Rice and Coffee Husks Blends

Production of first generation biofuels using food crops is under criticism over sustainability issues on food security. Tanzania is showing active interest in developing second generation biofuels to deal with some of such issues, especially from the feedstock point of view. This paper reports work done to determine energy characteristics of rice and coffee husks. The results show that coffee husks have better energy quality than rice husks, while heating values of coffee are 18.34 MJ/kg and 13.24 MJ/kg for rice husk. Thermogravimetric analysis made for coffee husks blended rice husks at a ratio of 75 : 25% vol. show better material degradation characteristics yielding low residual mass of 23.65%, compared to 26.50% of char and ash remaining in pure rice husks. Derivative thermogravimetric analysis shows comparable hemicellulose degradation peak values of −11.5 and −11.2 and cellulose −3.20 and −2.90 in pure coffee and rice husks, respectively. In coffee and rice husks blends, substantial reductions of hemicellulose and cellulose peaks were observed. Use of coffee and rice husks blends applying high temperature gasification would reduce the latter’s flammability, while increasing its flame retention characteristics, hence offering opportunities for production of clean syngas in a sustainable manner.
Patterning of the hepato‐pancreatobiliary boundary by BMP reveals heterogeneity within the murine liver bud

During development, the endoderm initiates organ‐restricted gene expression patterns in a spatiotemporally controlled manner. This process, termed induction, requires signals from adjacent mesodermal derivatives. Fibroblast growth factor (FGF) and bone morphogenetic protein (BMP) emanating from the cardiac mesoderm and the septum transversum mesenchyme (STM), respectively, are believed to be simultaneously and uniformly required to directly induce hepatic gene expression from the murine endoderm. Using small molecule inhibitors of BMP signals during liver bud induction in the developing mouse embryo, we found that BMP signaling was not uniformly required to induce hepatic gene expression. Although BMP inhibition caused an overall reduction in the number of induced hepatoblasts, the STM‐bounded posterior liver bud demonstrated the most severe loss of the essential hepatic transcription factor, hepatocyte nuclear factor 4‐α (HNF4α), whereas the sinus venosus–lined anterior liver bud was less affected. We found that the posterior liver bud progenitors were anteriorly displaced and aberrantly activated pancreatobiliary markers, including sex‐determining region Y‐box 9 (SOX9). Additionally, we found that ectopically expressed SOX9 inhibited HNF4α and that BMP was indirectly required for hepatoblast induction. Finally, because previous studies have demonstrated that FGF signals are essential for anterior but not posterior liver bud induction, we examined synchronous BMP and FGF inhibition and found this led to a nearly complete loss of hepatoblasts. Conclusion: BMP signaling is required to maintain the hepato‐pancreatobiliary boundary, at least in part, by indirectly repressing SOX9 in the hepatic endoderm. BMP and FGF signals are each required for the induction of spatially complementary subsets of hepatoblasts. These results underscore the importance of studying early inductive processes in the whole embryo. (Hepatology 2018;68:274‐288).
Molecular karyotyping in routine diagnostics – a view back and forth1)

Abstract Since its introduction in the routine diagnostics of patients with mental retardation/developmental delay, array-comparative genomic hybridization (aCGH) has become an indispensable tool for the detection of clinically relevant copy number variants (CNVs). Despite the current tendency for higher resolution arrays, the growing number of public internet databases as well as better calling algorithms allow save reporting and a better classification of CNVs. The application of combined aCGH plus single nucleotide polymorphism (SNP) arrays will increase detection rates by revealing copy number neutral changes, such as uniparental disomy. In the future, next generation sequencing techniques will lead to a further increase in resolution with the simultaneous detection of unbalanced and even balanced chromosomal aberrations.
Ocular Dominance Stability and Reading Skill: A Controversial Relationship

Purpose. Evidence is mixed concerning the relationship between stability of ocular dominance and reading deficits. Contrasting results may be due to the use of different tests of dominance, different samples of readers, and different scoring methods. The aim of this study was to investigate the relationship among ocular dominance, general visual abilities, and reading performance, and to evaluate the consistency and reliability of different tests of ocular dominance and the effects of different types of eye dominance scoring. Methods. In a group of young adults, we measured: (a) main optometric parameters; (b) reading time and accuracy; and (c) ocular dominance in two sighting and four motor tests. Dominance was determined using different scoring methods (relative, absolute, and binary scores). Results. All dominance tests showed good levels of internal reliability. Sighting tests were consistent regardless of the scoring method, and all participants had stable dominance. Three of four motor tests were moderately consistent when dominance was measured with relative scores but not when it was measured with absolute or binary scores. No relationship was found between stability of dominance and reading performance, regardless of the type of test or scoring method. No systematic pattern of correlation was found between binocular vision variables and dominance measures. Conclusions. Choosing the type of motor test to measure ocular dominance is crucial, because the level of consistency among tests is low to moderate. Furthermore, motor tests were not correlated with reading performances. Present results suggest caution when trying to link reading difficulties with specific profiles of ocular dominance.
Attitudes and actions of West Indian dog owners towards neutering their animals: A gender issue?

Abstract A study of the attitudes and actions of 281 dog owners towards neutering their animals is reported from New Providence, The Bahamas. Owner attitudes towards neutering are associated with different sterilization rates of dogs. While owners' gender is associated with differences in attitudes, these differences are not necessarily associated with owner behavior with respect to neutering their animals. Men, more than women, want to have animals for long-term breeding. No evidence is found to support the belief that men are less likely to neuter their dogs than women, but younger owners are less likely than older owners to neuter their dogs. A comparison with a study from Australia suggests that Bahamians are more likely to project human traits on to their animals and so appear more reluctant to have their dogs neutered.