Miracle-dz/UniFAR-FTUs huggingface dataset:
Sequential alterations of microrna expression in hepatocellular carcinoma development and venous metastasis

Hepatocellular carcinoma (HCC) is a prevalent cancer with an extremely high mortality rate attributed to HCC metastasis, which is the major cause of tumor recurrence and organ failure. Presence of tumor thrombi in the portal veins (venous metastases) is a clinicopathological feature of metastatic HCCs. In this study, we analyzed the microRNA (miRNA) expression profiles of nontumorous livers, primary HCCs, and venous metastases in the same livers from 20 HCC patients by way of TaqMan low‐density array (TLDA) and identified the precise alterations of miRNA expression from nontumorous livers to primary HCCs and venous metastases globally. By unsupervised clustering analysis, nontumorous livers were distinctly segregated from primary HCCs and venous metastases, whereas no discernible difference in the expression pattern could be found between primary HCCs and venous metastases. However, a marked global reduction of miRNA expression levels was detected in venous metastases, as compared with primary HCCs. These data suggest that miRNA deregulation is an early event in liver carcinogenesis and the later global miRNA down‐regulation aggravates the preexisting miRNA deregulation to further promote HCC metastasis. Conclusion: Our study has enriched the current understanding of the deregulation of miRNAs in HCC progression and highlighted the sequential and distinctive alterations of miRNA expression in primary HCC and venous metastasis formation. (HEPATOLOGY 2012;)
Promoting the Growth, Improvement and Sustainability of School Mental Health Programs Worldwide

This introductory article reviews the development, vision, principles and aims of the International Alliance for Child and Adolescent Mental Health and Schools (Intercamhs), a network of more than 250 people from 26 countries involved in whole-school mental health promotion. Global issues related to child and adolescent mental health promotion and schools are discussed, including those related to language, collaborative practice and partnerships, involvement of young people and families, and research. An overview of the inaugural meeting of Intercamhs held in Portland, Oregon in October, 2003 is presented, along with reviews of seven additional papers and commentary included in this special issue.
The Increasing Frequency of Mania and Bipolar Disorder: Causes and Potential Negative Impacts

Abstract The frequency of mania has not changed during the last century even with the development of new diagnostic criteria sets. More specifically, from the mid-1970s to 2000, the rate of mania (variably labeled major affective disorder–bipolar disorder and bipolar I disorder) was consistently identified in US and international studies as ranging from 0.4% to 1.6%. By the late 1990s to the 2000s, the prevalence reported by some researchers for bipolar disorders (I and II and others) was in the 5% to 7% and higher ranges. The purpose of this paper was to review explanations for this change and the potentially negative impacts on the field.
Evaluation of the Biofidelity of FMVSS No. 218 Injury Criteria

Objective: The biofidelity of the injury criteria used by Federal Motor Vehicle Safety Standards (FMVSS) No. 218 was examined against biomechanically based injury metrics. Methods: An experimental method was developed to measure the helmet contact pressure distribution on a headform during an impact attenuation test. The headform pressure data from eighty impact tests to the front, crown, and side of a helmet were used in finite element model simulations to predict skull fracture. Using headform acceleration data as inputs, the Simulated Injury Monitor software package (SIMon) was used to predict brain injuries for concussion, brain contusion, and subdural hematoma. Results: It was found that FMVSS No. 218 headform peak acceleration is the best correlate with injury metrics. Dwell times over 150 and 200 g both had poor correlation with injury metrics. The failure probability for skull fracture agrees with published results at similar linear accelerations. Concussion results were inconclusive. Conclusions: This research has shown that peak head acceleration can be an acceptable injury metric for the FMVSS No. 218 test method. However, the current 400 g allows for a high probability of head injury. An adjusted linear head acceleration limit of 210 g predicts a 15 percent skull fracture probability. The FMVSS No. 218 test method is adequate for predicting skull fracture based on peak head acceleration limits. However, due to the use of the rigid head/neck assembly that restricts rotation, the test method is likely inadequate for predicting brain injuries.
A model for dropout assessment of candidates with or without hepatocellular carcinoma on a common liver transplant waiting list

In many countries, the allocation of liver grafts is based on the Model of End‐stage Liver Disease (MELD) score and the use of exception points for patients with hepatocellular carcinoma (HCC). With this strategy, HCC patients have easier access to transplantation than non‐HCC ones. In addition, this system does not allow for a dynamic assessment, which would be required to picture the current use of local tumor treatment. This study was based on the Scientific Registry of Transplant Recipients and included 5,498 adult candidates of a liver transplantation for HCC and 43,528 for non‐HCC diagnoses. A proportional hazard competitive risk model was used. The risk of dropout of HCC patients was independently predicted by MELD score, HCC size, HCC number, and alpha‐fetoprotein. When combined in a model with age and diagnosis, these factors allowed for the extrapolation of the risk of dropout. Because this model and MELD did not share compatible scales, a correlation between both models was computed according to the predicted risk of dropout, and drop‐out equivalent MELD (deMELD) points were calculated. Conclusion: The proposed model, with the allocation of deMELD, has the potential to allow for a dynamic and combined comparison of opportunities to receive a graft for HCC and non‐HCC patients on a common waiting list. (HEPATOLOGY 2012;56:149–156)
Concordance Between Road Mortality Indicators in High-Income and Low- and Middle-Income Countries

Objective: Compare concordance between road mortality indicators in high-income (HICs) and low- and middle-income countries (LMICs). Methods: Study design: Ecological study. Population: The most recent (from 2001 to 2006) one-year road traffic data were extracted from the World Road Statistics report, 2008. Analyses: Three road mortality indicators: per 100 000 inhabitants (M1), per 10 000 vehicles registered (M2), per 100 million vehicle kilometers traveled (M3) were computed. Concordances between indicators were assessed using scatterplots and intraclass correlation coefficient (ICC). Results: Out of 192 countries, M1 was available for 125, M2 for 114, and M3 for 60. Despite significant concordances between indicators in HICs (All ICC ≥ 0.42, P ≤ 0.002), M1 rates were widely dispersed against M3, whereas M2 rates were relatively more dispersed at higher M3. Scatter of indicators in LMICs was inconclusive. Conclusion: Indicators in LMICs were not concordant possibly due to methodological differences in measuring traffic exposition and underreporting of fatalities.
Contact Combinations in Epidural Spinal Cord Stimulation

The geometrical characteristics of longitudinal fiber populations in the dorsal columns (DC), recruited by various contact combinations in epidural spinal cord stimulation (SCS), were compared in a theoretical study. A 3-dimensional computer model was used, representing the geometry and electrical conductivity of the low-thoracic spinal cord and surrounding tissues, in combination with a model representing the electrical properties of a myelinated nerve fiber. It was calculated that, among usual dorsomedial contact combinations, the ratio of mediolateral and dorsoventral extent of the recruited area in DC only varied by 2-5%. The model predicts that in bipolar stimulation the relative lateral extent was smallest at a contact separation of 3-3.5 times the dorsal cerebrospinal-fluid width, which seems to fit the highest ratio of discomfort threshold/paresthesia threshold. It is concluded that the optimal combination varies with distance between cathode and DC and that a unique 'best contact combination' does not exist. When both a decrease of primary afferent diameter in DC and collateral branching near their entrance are considered, the model predicts that recruitment of cutaneous afferents will start in lateral DC and proceed medially at increasing stimulus, which fits clinical observations on the spread of paresthesia. The model predicts that large fibers in the posterior spinocerebellar tract will also be recruited in SCS.
Development of a Community-Based Participatory Research Effort to Evaluate Conventional HIV Testing (CHT) and HIV Rapid Testing (HRT)

Abstract A community-based participatory research (CBPR) project was created to study the effects of changing HIV testing protocols on client risk behaviors in an urban area. Concerns raised by the agency advisory group led to development of research questions that needed to be addressed within the community. The article focuses on development of the research partnership and study enrollment during the first year of the project. Challenges of assimilating rapid advances in health technology while conducting outreach to high-risk clients are discussed. Successes and lessons learned are described, including adaptation of theory-based interventions to research protocol and multi-level community coordination.
Reducing Patient Suffering Through Compassionate Connected Care

Patient experience continues to play an increasingly critical role in quality outcomes and reimbursement. Nurse executives are tasked with helping direct-care nurses connect with patients to improve care experiences. Connecting with patients in compassionate ways to alleviate inherent patient suffering and prevent avoidable suffering is key to improving the patient experience. The Compassionate Connected Care framework identifies strategies for meeting the challenges of connecting with patients and reducing suffering. Methods integrate clinical, operational, cultural, and behavioral aspects of care to target patient needs based on condition. Caregivers learn to better express empathy and compassion to patients, and nurse leaders are better equipped to engage nurses at the bedside.
Comparison of hepatitis C virus treatment between incarcerated and community patients

The prevalence of chronic hepatitis C virus (HCV) infection among incarcerated individuals in the United States is estimated to be between 12% and 31%. HCV treatment during incarceration is an attractive option because of improved access to health care and directly observed therapy. We compared incarcerated and nonincarcerated HCV‐infected patients evaluated for treatment at a single academic center between January 1, 2002 and December 31, 2007. During this period, 521 nonincarcerated and 388 incarcerated patients were evaluated for HCV treatment. Three hundred and nineteen (61.2%) nonincarcerated patients and 234 (60.3%) incarcerated patients underwent treatment with pegylated interferon and ribavirin. Incarcerated patients were more likely to be male, African‐American race, and have a history of alcohol or intravenous drug use. Treated incarcerated patients were less likely to have genotype 1 virus and were less likely to have undergone previous treatment. There was a similar prevalence of coinfection with human immunodeficiency virus (HIV) in both groups. A sustained viral response (SVR) was achieved in 97 (42.9%) incarcerated patients, compared to 115 (38.0%) nonincarcerated patients (P = 0.304). Both groups had a similar proportion of patients that completed a full treatment course. Stepwise logistic regression was conducted, and the final model included full treatment course, non‐genotype 1 virus, younger age at treatment start, and negative HIV status. Incarceration status was not a significant predictor when added to this model (P = 0.075). Conclusion: In a cohort of HCV‐infected patients managed in an academic medical center ambulatory clinic, incarcerated patients were as likely to be treated for HCV and as likely to achieve an SVR as nonincarcerated patients. (HEPATOLOGY 2012)
Subset of Suz12/PRC2 target genes is activated during hepatitis B virus replication and liver carcinogenesis associated with HBV X protein

Chronic hepatitis B virus (HBV) infection is a major risk factor for developing liver cancer, and the HBV X protein (pX) has been implicated as a cofactor in hepatocyte transformation. We have shown that HBV replication as well as in vitro transformation by pX are associated with induction of the mitotic polo‐like kinase 1 (Plk1) and down‐regulation of the chromatin remodeling components Suz12 and Znf198. Herein, we demonstrate the same inverse relationship between Plk1 and Suz12/Znf198 in liver tumors from X/c‐myc bitransgenic mice and woodchuck hepatitis virus (WHV)‐infected woodchucks. Employing these animal models and the HBV replicating HepAD38 cells we examined the effect of Suz12/Znf198 down‐regulation on gene expression. Genes analyzed include hepatic cancer stem cell markers BAMBI, DKK1,2, DLK1, EpCAM, MYC, and proliferation genes CCNA1, CCND2, IGFII, MCM4‐6, PLK1, RPA2, and TYMS. Suz12 occupancy at the promoters of BAMBI, CCND2, DKK2, DLK1, EpCAM, and IGFII was demonstrated by chromatin immunoprecipitation in untransformed hepatocytes, but was markedly reduced in pX‐transformed and Suz12 knockdown cells. Accordingly, we refer to these genes as “Suz12 repressed” genes in untransformed hepatocytes. The Suz12 repressed genes and proliferation genes were induced in HBV‐replicating HepAD38 cells and, interestingly, they exhibited distinct expression profiles during hepatocellular carcinoma (HCC) progression in X/c‐myc bitransgenics. Specifically, CCND2, EpCAM, and IGFII expression was elevated at the proliferative and preneoplastic stages in X/c‐myc bitransgenic livers, whereas BAMBI and PLK1 were overexpressed in hepatic tumors from X/c‐myc bitransgenics and WHV‐infected woodchucks. Importantly, most of these genes were selectively up‐regulated in HBV‐induced HCCs. Conclusion: The distinct expression profile of the identified Suz12 repressed genes in combination with the proliferation genes hold promise as biomarkers for progression of chronic HBV infection to HCC. (HEPATOLOGY 2012)
Characterization of Vertebral Angle and Torso Depth by Gender and Age Groups With a Focus on Occupant Safety

Objective: The human body changes as it becomes older. The automotive safety community has been interested in understanding the effect of age on restraint performance. Focus has been placed on characterizing the body's structural changes associated with age and gender. In this study, spine alignment and torso depth were assessed, because both variables have been shown to affect injury risk. Methods: The data was obtained from computed tomography (CT) scans of more than 24,000 patients aged 16 and older. The data consisted of thoracic and lumbar vertebral angles relative to a fixed plane, as well as vertebra-to-front skin and spine-to-back skin distances. Angle measurements were taken in the sagittal plane at each vertebra level from T1 to L5; distance measurements were taken from T6 to L5. The data were analyzed as a function of gender and age with the young group defined as 16 to 29 years old and the older group as 75 and up. Results: Vertebral angles were different depending on location. They varied from −24.5 ± 8.9° at T2 to 12.2 ± 5.6° at L1. The vertebral angles also varied with age. Angles in the older male group were 1.74 times larger at T1 and 2.03 times larger at T7 than in the young male group. Similar findings were observed for females. The effect of age and gender was modeled with forward/backward selection using a regression model. The vertebra-to-front skin distance also differed depending on vertebral level. It was highest at T10 at 162.5 ± 30.9 mm and lowest at L4 at 125.3 ± 37.3 mm for the entire study population. On average, males had larger distances than females. The spine-to-back distances were greatest in the lumbar area. The spine-to-back distance increased with lower vertebral level, regardless of age. The vertebral angle and distance data were analyzed for a male subgroup approximating the height and weight of a 50th percentile male dummy. The results showed that the vertebra-to-front skin distance increased with age. There was not a clear trend for the spine-to–back skin distance and L1 vertebral angle. Conclusions: The changes in the vertebral angles, as well as the anterior and posterior spine-to-skin distances along the sagittal plane, were determined as a function of age and gender. The effect was greatest in the mid-thoracic area. Spine alignment and body shape differences need to be considered in human mathematical models used to develop safety countermeasures for the older population, because they may affect the loading path and lead to different seating postures or belt positioning. Supplemental materials are available for this article. Go to the publisher's online edition of Traffic Injury Prevention to view the supplemental file.
Out-of-Position Rear Impact Tissue-Level Investigation Using Detailed Finite Element Neck Model

Objective: Whiplash injuries can occur in automotive crashes and may cause long-term health issues such as neck pain, headache, and visual and auditory disturbance. Evidence suggests that nonneutral head posture can significantly increase the potential for injury in a given impact scenario, but epidemiological and experimental data are limited and do not provide a quantitative assessment of the increased potential for injury. Although there have been some attempts to evaluate this important issue using finite element models, none to date have successfully addressed this complex problem. Methods: An existing detailed finite element neck model was evaluated in nonneutral positions and limitations were identified, including musculature implementation and attachment, upper cervical spine kinematics in axial rotation, prediction of ligament failure, and the need for repositioning the model while incorporating initial tissue strains. The model was enhanced to address these issues and an iterative procedure was used to determine the upper cervical spine ligament laxities. The neck model was revalidated using neutral position impacts and compared to an out-of-position cadaver experiment in the literature. The effects of nonneutral position (axial head rotation) coupled with muscle activation were studied at varying impact levels. Results: The laxities for the ligaments of the upper cervical spine were determined using 4 load cases and resulted in improved response and predicted failure loads relative to experimental data. The predicted head response from the model was similar to an experimental head-turned bench-top rear impact experiment. The parametric study identified specific ligaments with increased distractions due to an initial head-turned posture and the effect of active musculature leading to reduced ligament distractions. Conclusions: The incorporation of ligament laxity in the upper cervical spine was essential to predict range of motion and traumatic response, particularly for repositioning of the neck model prior to impact. The results of this study identify a higher potential for injury in out-of-position rear collisions and identified at-risk locations based on ligament distractions. The model predicted higher potential for injury by as much as 50% based on ligament distraction for the out-of-position posture and reduced potential for injury with muscle activation. Importantly, this study demonstrated that the location of injury or pain depends on the initial occupant posture, so that both the location of injury and kinematic threshold may vary when considering common head positions while driving.
Capturing Change: Creating a Template to Examine the Educational Experiences and Outcomes of the AONE Foundation Nurse Manager Fellowship

OBJECTIVE The aim of the study is to create a mixed-methods evaluation template to examine the educational experiences and outcomes of participants in the Nurse Manager Fellowship (NMF) sponsored by the American Organization of Nurse Executives (AONE) Foundation. The focus was to capture change as reported by the nurse manager (NM) fellows and the senior leaders who sponsored them and to gain access to the participants’ lived experiences as leadership learners. BACKGROUND The AONE Foundation’s NMF conducts a yearlong professional development program with a cohort of 30 fellows who meet 4 times a year in face-to-face sessions and complete a capstone project. METHODS Four data collection methods were used. Participants completed 2 quantitative leadership program outcome surveys, as well as 1 qualitative measure to focus on self-perceived change outcomes. Their sponsors completed a qualitative perception of change measure. RESULTS The participants’ reflections, self-reports, and the sponsor observations capture impactful changes in the NM fellows’ increases in knowledge and application in the spheres of self, organization, and community. The enhancement of the participants’ self-identification as leaders was also demonstrated. CONCLUSIONS The variety of data collection methods suggests both distinct choices in creating future evaluation templates for the fellowship and approaches that might be adapted by other organizations.
A model of dirigent proteins derived from structural and functional similarities with allene oxide cyclase and lipocalins

Dirigent proteins impart stereoselectivity on the phenoxy radical‐coupling reaction, yielding optically active lignans from two molecules of coniferyl alcohol. By an unknown mechanism, they direct the coupling of two phenoxy radicals toward the formation of optically active (+)‐ or (−)‐pinoresinol. We show here that the dirigent protein AtDIR6 from Arabidopsis thaliana is a homodimeric all‐beta protein in the superfamily of calycins. Based on its homology with calycins, the structure of AtDIR6 was modeled using allene oxide cyclase as template. The structural model of AtDIR6 was supported experimentally by confirmation of a predicted disulfide bridge and by the characterization of two N‐linked glycans at the solvent‐exposed protein surface. The model shows AtDIR6 as an eight‐stranded antiparallel β‐barrel with a central hydrophobic cavity for substrate binding, suggesting that dirigent proteins evolved from hydrophobic ligand‐binding proteins. The data are fully consistent with the current view of the dirigent protein mode of action, according to which each subunit of the homodimer captures one of the substrate radicals and orients them in a way that precludes undesired reaction channels, thus favoring the formation of the optically pure coupling product.