Miracle-dz/UniFAR-FTUs huggingface dataset:
Imaging for the diagnosis of hepatocellular carcinoma: A systematic review and meta‐analysis

Multiphasic computed tomography (CT) and magnetic resonance imaging (MRI) are both used for noninvasive diagnosis of hepatocellular carcinoma (HCC) in patients with cirrhosis. To determine if there is a relative diagnostic benefit of one over the other, we synthesized evidence regarding the relative performance of CT, extracellular contrast–enhanced MRI, and gadoxetate‐enhanced MRI for diagnosis of HCC in patients with cirrhosis. We also assessed whether liver biopsy versus follow‐up with the same versus alternative imaging is best for CT‐indeterminate or MRI‐indeterminate liver nodules in patients with cirrhosis. We searched multiple databases from inception to April 27, 2016, for studies comparing CT with extracellular contrast–enhanced MRI or gadoxetate‐enhanced MRI in adults with cirrhosis and suspected HCC. Two reviewers independently selected studies and extracted data. Of 33 included studies, 19 were comprehensive, while 14 reported sensitivity only. For all tumor sizes, the 19 comprehensive comparisons showed significantly higher sensitivity (0.82 versus 0.66) and lower negative likelihood ratio (0.20 versus 0.37) for MRI over CT. The specificities of MRI versus CT (0.91 versus 0.92) and the positive likelihood ratios (8.8 versus 8.1) were not different. All three modalities performed better for HCCs ≥2 cm. Performance was poor for HCCs <1 cm. No studies examined whether adults with cirrhosis and an indeterminate nodule are best evaluated using biopsy, repeated imaging, or alternative imaging. Concerns about publication bias, inconsistent study results, increased risk of bias, and clinical factors precluded support for exclusive use of either gadoxetate‐enhanced or extracellular contrast–enhanced MRI over CT. Conclusion: CT, extracellular contrast–enhanced MRI, or gadoxetate‐enhanced MRI could not be definitively preferred for HCC diagnosis in patients with cirrhosis; in patients with cirrhosis and an indeterminate mass, there were insufficient data comparing biopsy to repeat cross‐sectional imaging or alternative imaging. (Hepatology 2018;67:401‐421).
Effectiveness of Cognitive Behavior Therapy for Severe Mood Disorders in an Acute Psychiatric Naturalistic Setting: A Benchmarking Study

The current study examined the effectiveness of brief cognitive behavior therapy (CBT) for severe mood disorders in an acute naturalistic setting. The sample included 951 individuals with either major depressive disorder (n = 857) or bipolar disorder with depressed mood (n = 94). Participants completed a battery of self-report measures assessing depression, overall well-being, and a range of secondary outcomes both before and after treatment. We found significant reductions in depressive symptoms, worry, self-harm, emotional lability, and substance abuse, as well as significant improvements in well-being and interpersonal relationships, post-treatment. Comparable to outpatient studies, 30% of the sample evidenced recovery from depression. Comparison of findings to benchmark studies indicated that, although the current sample started treatment with severe depressive symptoms and were in treatment for average of only 10 days, the overall magnitude of symptom improvement was similar to that of randomized controlled trials. Limitations of the study include a lack of control group, a limitation of most naturalistic studies. These findings indicate that interventions developed in controlled research settings on the efficacy of CBT can be transported to naturalistic, “real world” settings, and that brief CBT delivered in a partial hospital program is effective for many patients with severe depressive symptoms.
Differential Effects of Anxiety Sensitivity Components in the Relation Between Emotional Non-Acceptance and Post-traumatic Stress Symptoms Among Trauma-Exposed Treatment-Seeking Smokers

Anxiety sensitivity (AS), defined as the extent to which individuals believe anxiety and anxiety-related sensations have harmful consequences, may play an important explanatory role in the relation between emotional non-acceptance and the expression of traumatic stress symptoms among trauma-exposed smokers. This investigation examined whether lower-order dimensions of AS (cognitive, physical, and social concerns) differentially explain the relation between emotional non-acceptance and post-traumatic stress (PTS) symptom clusters (re-experiencing, avoidance, hyperarousal) among trauma-exposed daily smokers (N = 169, 46% female; Mage = 41, SD = 12.3). AS and its lower-order facets of cognitive and social concerns were found to mediate the relations between emotional non-acceptance and avoidance and hyperarousal PTS symptoms. Using a multiple mediation model, the mediational effect of AS cognitive concerns for the relation between emotional non-acceptance and post-traumatic avoidance symptoms was found to be uniquely evident relative to social and physical concerns. All observed AS effects were evident above and beyond the variance accounted for by gender, number of traumatic event exposure types, negative affectivity, number of cigarettes smoked per day, and alcohol use problems. The present findings suggest cognitive-based AS concerns may play a mechanistic role in the relation between emotional non-acceptance and certain PTS symptoms among trauma-exposed daily smokers.
Beyond Negative Affectivity: A Hierarchical Model of Global and Transdiagnostic Vulnerabilities for Emotional Disorders

Background: Negative affectivity (NA) has been linked to anxiety and depression (DEP). Identifying the common factors between anxiety and DEP is important when explaining their overlap and comorbidity. However, general factors such as NA tend to have differential relationships with different disorders, suggesting the need to identify mediators in order to explicate these relationships. Methods: The current study tests a theoretically and empirically derived hierarchical model of emotional disorders including both a general factor (NA) and transdiagnostic risk factors [anxiety sensitivity (AS) and intolerance of uncertainty (IoU)] using structural equation modeling. AS was tested as a mid-level factor between NA and panic disorder/agoraphobia, while IoU was tested as a mid-level factor between NA and social phobia, generalized anxiety disorder, obsessive-compulsive disorder, and DEP. Data from 642 clinical outpatients with a heterogeneous presentation of emotional disorders were available for analysis. Results: The hierarchical model fits the data adequately. Moreover, while a simplified model removing AS and IoU fits the data well, it resulted in a significant loss of information for all latent disorder constructs. Limitations: Data were unavailable to estimate post-traumatic stress disorder or specific phobias. Future work will need to extend to other emotional disorders. Conclusions: This study demonstrates the importance of both general factors that link disorders together and semi-specific transdiagnostic factors partially explaining their heterogeneity. Including these mid-level factors in hierarchical models of psychopathology can help account for additional variance and help to clarify the relationship between disorder constructs and NA.
Peripheral γδ T-lymphocytes as an innovative tool in immunotherapy for metastatic renal cell carcinoma

Renal cell carcinoma represents 3% of solid malignancies in adults and nephrectomy remains the main treatment. Failure of conventional approaches for patients presenting with advanced disease has prompted the exploration of new strategies. This review describes the potentialuse of peripheral γδ (Vγ9Vδ2) T-cells in metastatic renal cell carcinoma. This peripheral lymphocyte population from the innate immune system has demonstrated an in vitro antitumor cytotoxicity against primary or established renal cell lines. Moreover, these Vγ9Vδ2 lymphocytes undergo a rapid and extensive expansion in vitro as well as in vivo upon stimulation with a synthetic potent agonist, the bromohydrin pyrophosphate molecule. Preclinical results obtained on specific in vitro amplification of Vγ9Vδ2 T-cells by bromohydrin pyrophosphate in renal cell carcinoma patients are presented in this review, while Phase I clinical trials are currently running. As there is growing evidence for the low efficiency of monotherapy in cancer patients, innovative approaches combining immunomodulatory γδ agonists with classic chemotherapies or administration of antiangiogenic agents are discussed.
Genetic diversity and worldwide distribution of the deltavirus genus: A study of 2,152 clinical strains

Hepatitis delta virus (HDV) is responsible for the most severe form of acute and chronic viral hepatitis. We previously proposed that the Deltavirus genus is composed of eight major clades. However, few sequences were available to confirm this classification. Moreover, little is known about the structural and functional consequences of HDV variability. One practical consequence is the failure of most quantification assays to properly detect or quantify plasmatic HDV RNA. Between 2001 and 2014, 2,152 HDV strains were prospectively collected and genotyped in our reference laboratory by means of nucleotide sequencing and extensive phylogenetic analyses of a 400‐nucleotide region of the genome (R0) from nucleotides 889 to 1289 encompassing the 3′ end of the delta protein–coding gene. In addition, the full‐length genome sequence was generated for 116 strains selected from the different clusters, allowing for in‐depth characterization of the HDV genotypes and subgenotypes. This study confirms that the HDV genus is composed of eight genotypes (HDV‐1 to HDV‐8) defined by an intergenotype similarity >85% or >80%, according to the partial or full‐length genome sequence, respectively. Furthermore, genotypes can be segregated into two to four subgenotypes, characterized by an intersubgenotype similarity >90% (>84% for HDV‐1) over the whole genome sequence. Systematic analysis of genome and protein sequences revealed highly conserved functional nucleotide and amino acid motifs and positions across all (sub)genotypes, indicating strong conservatory constraints on the structure and function of the genome and the protein. Conclusion: This study provides insight into the genetic diversity of HDV and a clear view of its geographical localization and allows speculation as to the worldwide spread of the virus, very likely from an initial African origin. (Hepatology 2017;66:1826–1841)
Pembrolizumab for metastatic hepatocellular carcinoma following live donor liver transplantation: The silver bullet?

Treatment options for hepatocellular carcinoma (HCC) recurrence following liver transplantation (LT) are extremely limited. HCCs are a heterogenous group of tumors driven by inflammation and hence the rationale to evaluate immunotherapy in these patients. The immune checkpoint protein, programmed death receptor 1 (PD-1), is an inhibitory molecule expressed on the surface of multiple tissue types and keeps T cells from attacking tumor cells. We report on a case of metastatic HCC following LT that responded dramatically to pembrolizumab, a PD-1 inhibitor, after failure of therapy with sorafenib.
Adding care to cure for patients with liver disease: A cultural shift

Innes et al. must be commended for showing robust evidence that “at least half (in other term, more than half) the excess mortality risk for individuals with chronic hepatitis C in the US may be due to health risk behaviours rather than chronic hepatitis C. ” This deserves comment, as I fear Innes et al. may be blowing in the wind. Indeed, this study confirms previous findings. For example, among health risk behaviors, smoking ranks first as an independent and dose-related cause of hepatocellular carcinoma. In a large European cohort, the population-attributable percentage for tobacco use for hepatocellular carcinoma (48%) was more than twice that of the second-most attributed risk factor, hepatitis C (21%). This is also a concern elsewhere; for example, 50% of Chinese males are smokers, and smoking prevalence increases in developing countries. Sadly, raising concerns about health risk behaviors seems futile. First, there is enduring denial within the scientific community. Some editors, fearing scientific debate, reject comments challenging the relevance of studies of hepatocellular carcinoma that ignore smoking and conclude that screening improves survival despite raw data analysis. However, this notion is demonstrated by two recent reports by Cucchetti and Singal, in which the age of those screened was 60.3 years with a 14.6month survival versus 61.6 years and 6.0 months for patients who were not screened. Accordingly, screened patients died at a younger age than those who were not screened, despite previous warnings. Second is the rise of “sciensationalism” (i.e., sensationalism in science). The list of sciensationalist publications is too long to list here, even in journals that are not tabloids, but two recent examples are “The 8-Week Cure for Hepatitis C” and “The Discovery of Sofosbuvir: A Revolution for Therapy of Chronic Hepatitis C. ” A search of all PubMed data since 2015 obtained 19 hits for “revolution” and “hepatitis” in the same article title.
Hepatitis B virus sensitivity to interferon‐α in hepatocytes is more associated with cellular interferon response than with viral genotype

Interferon‐α (IFN‐α) is used to treat chronic hepatitis B virus (HBV) infection, but only 20%‐40% of patients respond well. Clinical observations have suggested that HBV genotype is associated with the response to IFN therapy; however, its role in viral responsiveness to IFN in HBV‐infected hepatocytes remains unclear. Here, we produced infectious virions of HBV genotypes A to D to infect three well‐recognized cell–culture–based HBV infection systems, including primary human hepatocytes (PHH), differentiated HepaRG (dHepaRG), and HepG2‐NTCP cells to quantitatively compare the antiviral effect of IFN‐α on HBV across genotypes and cell models. The efficacy of IFN‐α against HBV in hepatocytes was generally similar across genotypes A2, B5, C2, and D3; however, it was significantly different among the infection models given that the half maximal inhibitory concentration value of IFN‐α for inhibition of viral DNA replication in PHH (<20 U/mL) and dHepaRG cells were much lower than that in HepG2‐NTCP cells (>500 U/mL). Notably, even in PHH, IFN‐α did not reduce HBV covalently closed circular DNA at the concentrations for which viral antigens and DNA replication intermediates were strongly reduced. The three cell‐culture models exhibited differential cellular response to IFN‐α. The genes reported to be associated with responsiveness to IFN‐α in patients were robustly induced in PHH while weakly induced in HepG2‐NTCP cells upon IFN‐α treatment. Reduction or promotion of IFN response in PHH or HepG2‐NTCP cells significantly attenuated or improved the inhibitory capacity of IFN‐α on HBV replication, respectively. Conclusion: In the cell–culture–based HBV infection models, the sensitivity of HBV to IFN‐α in hepatocytes is determined more by the cell‐intrinsic IFN response than by viral genotype, and improvement of the IFN response in HepG2‐NTCP cells promotes the efficacy of IFN‐α against HBV. (Hepatology 2018;67:1237‐1252).
Imaging Protein Deposits on Contact Lens Materials

Purpose. The majority of studies investigating protein deposition on contact lens materials require that the deposit of interest be removed, potentially resulting in erroneous results if some proteins are not removed adequately. The purpose of this study was to investigate the use of in situ imaging methods to examine protein deposition on conventional poly(2-hydroxyethyl methacrylate) (polyHEMA)-based and silicone hydrogel contact lens materials. Methods. Six silicone hydrogel and five polyHEMA-based hydrogel contact lens materials were examined by Atomic Force Microscopy (AFM) and/or Scanning Electron Microscopy (SEM) techniques, after being deposited with proteins in an in vitro model. AFM studies examined lenses deposited solely with lysozyme at approximate physiological concentrations and SEM studies were conducted on lenses exposed to a dilute mixture of lysozyme and albumin-conjugated gold spheres. Results. AFM studies demonstrated that the lens materials had markedly differing surface topographies. SEM results showed that galyfilcon A and balafilcon A lenses deposited both lysozyme and albumin in relatively large aggregates, as compared with lotrafilcon A and B, in which the proteins were deposited in a more evenly spread, monolayer formation. Polymacon lenses deposited more protein than any of the silicone hydrogel materials and much of the protein was aggregated together. AFM data indicated that balafilcon A, lotrafilcon A and polymacon deposited lysozyme in a similar manner, with very little lysozyme being deposited in discrete areas. Galyfilcon A behaved very differently, with the lysozyme exhibiting both aggregates as well as string-like formations over the lens surface. Conclusions. Imaging techniques that allow proteins to be examined in situ show much promise for determining the extent and physical characterization of protein on contact lens materials. These techniques indicate that the pattern of deposition of proteins onto silicone hydrogel contact lens materials differs between materials, depending upon their bulk and surface composition.
MicroRNA‐21 and Dicer are dispensable for hepatic stellate cell activation and the development of liver fibrosis

Fibrosis and cancer represent two major complications of chronic liver disease. MicroRNAs have been implicated in the development of fibrosis and cancer, thus constituting potential therapeutic targets. Here, we investigated the role of microRNA‐21 (miR‐21), a microRNA that has been implicated in the development of fibrosis in multiple organs and has also been suggested to act as an “oncomir. ” Accordingly, miR‐21 was the microRNA that showed the strongest up‐regulation in activated hepatic stellate cells (HSCs) in multiple models of fibrogenesis, with an 8‐fold to 24‐fold induction compared to quiescent HSCs. However, miR‐21 antisense inhibition did not suppress the activation of murine or human HSCs in culture or in liver slices. Moreover, genetic deletion of miR‐21 in two independently generated knockout mice or miR‐21 antisense inhibition did not alter HSC activation or liver fibrosis in models of toxic and biliary liver injury. Despite a strong up‐regulation of miR‐21 in injury‐associated hepatocellular carcinoma and in cholangiocarcinoma, miR‐21 deletion or antisense inhibition did not reduce the development of liver tumors. As inhibition of the most up‐regulated microRNA did not affect HSC activation, liver fibrosis, or fibrosis‐associated liver cancer, we additionally tested the role of microRNAs in HSCs by HSC‐specific Dicer deletion. Although Dicer deletion decreased microRNA expression in HSCs and altered the expression of select genes, it only exerted negligible effects on HSC activation and liver fibrosis. Conclusion: Genetic and pharmacologic manipulation of miR‐21 does not inhibit the development of liver fibrosis and liver cancer. Moreover, suppression of microRNA synthesis does not significantly affect HSC phenotype and activation. (Hepatology 2018;67:2414‐2429).
Accommodation, Acuity, and Their Relationship to Emmetropization in Infants

Purpose. To evaluate the relationship between accommodation, visual acuity, and emmetropization in human infancy. Methods. Defocus at distance and near (57 cm) was assessed using Mohindra and dynamic retinoscopy, respectively, in 262 normal birthweight infants at 3, 9, and 18 months of age. Preferential looking provided acuity data at the same ages. The spherical equivalent refractive error was measured by cycloplegic retinoscopy (cyclopentolate 1%). Results. Univariate linear regression analyses showed no associations between the change in refractive error and defocus at distance or near. Change in refractive error was linearly related to the accommodative response at distance (R2 = 0.17, p < 0.0001) and near (R2 = 0.13, p < 0.0001). The ten subjects with the poorest emmetropization relative to the change predicted by the linear effects of their refractive error had higher average levels of hyperopic defocus at distance and near (p < 0.043). Logistic regression showed a decrease in the odds of reaching +2.00 diopter or less hyperopia by 18 months with increasing levels of hyperopia at 3 months, or if Mohindra retinoscopy was myopic combined with acuity better than the median level of 1.25 logMAR [area under the receiver operating characteristic curve = 0.78 (95% CI = 0.68 to 0.88)]. Conclusions. The level of cycloplegic refractive error was the best single factor for predicting emmetropization by 18 months of age, with smaller contributions from visual acuity and Mohindra retinoscopy. The lack of correlation between defocus and change in refractive error does not support a simple model of emmetropization in response to the level of hyperopic defocus. Infants were capable of maintaining accurate average levels of accommodation across a range of moderate hyperopic refractive errors at 3 months of age. The association between the change in refractive error and accommodative response suggests that accommodation is a plausible visual signal for emmetropization.
Field Study of Subsurface Heterogeneity with Steady‐State Hydraulic Tomography

Remediation of subsurface contamination requires an understanding of the contaminant (history, source location, plume extent and concentration, etc.), and, knowledge of the spatial distribution of hydraulic conductivity (K) that governs groundwater flow and solute transport. Many methods exist for characterizing K heterogeneity, but most if not all methods require the collection of a large number of small‐scale data and its interpolation. In this study, we conduct a hydraulic tomography survey at a highly heterogeneous glaciofluvial deposit at the North Campus Research Site (NCRS) located at the University of Waterloo, Waterloo, Ontario, Canada to sequentially interpret four pumping tests using the steady‐state form of the Sequential Successive Linear Estimator (SSLE) ( Yeh and Liu 2000 ). The resulting three‐dimensional (3D) K distribution (or K‐tomogram) is compared against: ( 1 ) K distributions obtained through the inverse modeling of individual pumping tests using SSLE, and ( 2 ) effective hydraulic conductivity (Keff) estimates obtained by automatically calibrating a groundwater flow model while treating the medium to be homogeneous. Such a Keff is often used for designing remediation operations, and thus is used as the basis for comparison with the K‐tomogram. Our results clearly show that hydraulic tomography is superior to the inversions of single pumping tests or Keff estimates. This is particularly significant for contaminated sites where an accurate representation of the flow field is critical for simulating contaminant transport and injection of chemical and biological agents used for active remediation of contaminant source zones and plumes.