Miracle-dz/UniFAR-FTUs huggingface dataset:
Prognostic Histologic Indicators of Curatively Resected Hepatocellular Carcinomas: A Multi-institutional Analysis of 425 Patients With Definition of a Histologic Prognostic Index

Despite growing information on the clinical behavior of hepatocellular carcinoma, the histologic features associated with survival are not well characterized. Clinical and pathologic data on 425 patients who underwent complete resection for hepatocellular carcinoma were reviewed. Six microscopic features, namely, microvascular invasion, nuclear pleomorphism, mitosis, tumor architecture, growth interface, and tumor necrosis, were examined. Independent predictors of survival were identified and combined into a simple prognostic index. By univariate analysis, microvascular invasion, seen in 51.3% of patients (p <0.001), nuclear grade 3, present in 42% of the cases (p <0.001), and mitosis (p <0.008) were significant predictors of poor survival. Hepatocellular carcinoma with a compact growth pattern had a better prognosis as compared with macrotrabecular (p = 0.014) and acinar (p = 0.051) patterns. By multiple regression analysis, only microvascular invasion (p <0.001) and nuclear grade 3 (p = 0.008) were independent predictors of poor survival. The predictive values of microvascular invasion and nuclear grade allowed the construction of a hepatocellular prognostic index (HPI) whereby HPI = (microvascular invasion status × 0.459) + (nuclear grade × 0.287), with microvascular invasion either absent (0) or present (1) and nuclear grade scored as 1, 2, or 3. Using a cut-off of 0.746 (corresponding to at least nuclear grade 2 with microvascular invasion), two groups could be segregated: fair prognosis (HPI ≤0.746), with a 50% survival of 5.06 years, and poor prognosis (HPI >0.746) with a 50% survival of 2.71 years (p <0.001). HPI was more discriminating than Edmondson grade, with Edmondson II hepatocellular carcinomas dispersed in both fair and poor prognosis groups. Microvascular invasion and nuclear grade 3 emerge as strong prognostic indicators, and their combination provides adequate prognostic stratification. Practically, hepatocellular carcinoma can be stratified in two groups with regard to prognosis: 1) fair prognosis group (nuclear grade 1 with or without microvascular invasion and nuclear grade 2 without microvascular invasion), and 2) poor prognosis (nuclear grade 2 with microvascular invasion and nuclear grade 3 with or without microvascular invasion). The combination of these histologic parameters provides adequate prognostic stratification.
Language Characteristics of Individuals With Down Syndrome

On average, language and communication characteristics of individuals with Down syndrome (the most common genetic cause of intellectual disability) follow a consistent profile. Despite considerable individual variability, receptive language is typically stronger than expressive language, with particular challenges in phonology and syntax. We review the literature on language and literacy skills of individuals with Down syndrome, with emphasis on the areas of phonology, vocabulary, syntax, and pragmatics. We begin by describing the hearing, oral-motor, cognitive, social, and prelinguistic and early nonverbal communication characteristics of individuals with Down syndrome. We conclude with a discussion of clinical implications and research directions.
Rhythm in Speech and Language

Abstract Like any other aspect of spoken language, rhythm needs to be, and has been, studied from four different perspectives for a comprehensive and insightful account of its nature and functioning in speech communication: symbolic representation, production, perception, communicative function. The paper first gives an overview of the milestones in the analysis of rhythm under the headings of these four approaches over the past 70 years. This survey of the development of scientific ideas in rhythm research prepares the ground for the integration of the four strands in an interrelated framework of linguistic and speech signal analysis. On the basis of a definition of rhythm derived from the theoretical and methodological discussion, a new paradigm is outlined for future research, centred on the listener and on communicative function.
Design flows for resilient energy-efficient systems

Aggressive energy reduction is a mandatory requirement for many computing systems used in energy-constrained Internet of Things (IoT) platforms. Operating circuits at supply voltages close to the threshold voltage of the transistors, commonly known as near-threshold computing, is a promising approach to achieve such low energy goals. However, maintaining the resiliency at such low supply voltages is very challenging as the impacts of variability sources could be orders of magnitude larger compared the the nominal voltage. This mandates new design automation paradigms to ensure resiliency for aggressively voltage scaled circuits. In this work, we introduce design flows and strategies to improve the resiliency and energy efficiency of circuits at near-thresohold voltage region.
A Prognostic Approach to Defining Chronic Pain Across a Range of Musculoskeletal Pain Sites

Objectives:To test whether the prognostic definition of chronic pain, which has previously been applied in specific anatomic areas, performed well in a cohort of older adults with a range of musculoskeletal pain sites. Methods:Data are taken from the Prognostic Research Study of adults aged 50 years and above consulting their general practitioner with any musculoskeletal pain, who completed postal surveys immediately after consultation and 12 months later. Baseline risk of clinically significant pain persisting at 12 months’ follow-up, defined as a Chronic Pain Grade ≥II, was calculated using the prognostic approach, which includes a range of pain and related factors. The approach was implemented using logistic regression models, and the performance of the approach, including cutoffs in the score to define groups with differing levels of risk, was assessed in terms of calibration and discrimination. Results:Application of the original risk cutoffs created groups with increasing proportions of chronic pain (area under the curve =0.79). However, the probability of chronic pain in each group was higher than expected by the model. New cutoffs were defined for this group of older adults: score ⩽5=probability of chronic pain <20%, ⩽11=probability <50%, ⩽16=probability <80%, which resulted in good calibration of the model. Discussion:The prognostic approach to defining chronic pain is suitable for use in older adults consulting primary care with musculoskeletal pain at a range of sites, but new cutoffs are needed to allow for the higher risk profile in this group. An adapted version of this method may also have the potential for application directly within the clinical consultation.
Differential immunolocalization of VEGF in rat and human adult lung, and in experimental rat lung fibrosis: Light, fluorescence, and electron microscopy

Vascular endothelial growth factor (VEGF) is a cytokine with main angiogenetic functions in embryonic development and tumor‐formation. In the adult lung, reports of the localization of VEGF were controversial. A precise cell typing of VEGF‐positive pulmonary cells is still lacking. Nothing is known about a potential role in pulmonary fibrosis. Immunohistochemistry (IH), double immunofluorescence microscopy (DIF), and immunoelectron microscopy (IEM) were used to study the differential distribution of VEGF in paraffin‐embedded (IH, DIF) and in cryo‐substituted, Lowicryl‐embedded (IEM) specimens of normal rat and human lungs and fibrotic rat lungs. Fibrosis was induced by intratracheal bleomycin treatment. IH and DIF showed that VEGF was present in surfactant protein (SP) D‐positive alveolar type II pneumocytes, bronchiolar Clara cells, smooth muscle (SM) cells, and α‐SM actin‐positive myofibroblasts of normal rat and human lungs. Fibrotic lesions in bleomycin‐treated rat lungs were rich in VEGF‐positive cells presenting with a heterogeneous phenotype (mainly SP‐D‐positive type II pneumocytes, α‐SM actin‐positive myofibroblasts). There were no signs of angiogenesis. Post‐embedding immunogold labeling using protein A‐gold and IgG‐gold technique revealed a specific localization of VEGF to mitochondria, Clara cell secretory granules, and capillary interendothelial cell junctions. The predominant localization of VEGF to bronchiolar and alveolar epithelial and α‐SM actin‐positive cells, and the marked increase of VEGF‐positive type II pneumocytes and myofibroblasts in fibrotic lung lesions, indicate that in adult lungs VEGF is involved in processes other than angiogenesis. Anat Rec 254:61–73, 1999. © 1999 Wiley‐Liss, Inc.
New insights into the prevention and treatment of familial breast cancer

Individuals who inherit a deleterious mutation in BRCA1 or BRCA2 are at very high risk for breast cancer but there are several strategies available for successfully managing this risk. Breast cancers that develop in the context of germline BRCA gene mutation present challenges for management but also opportunities. DNA damaging agents, like cisplatin, and the new class of drugs called PARP inhibitors exploit the underlying defect in DNA damage repair to great effect. J. Surg. Oncol. 2011; 103:294–298. © 2011 Wiley‐Liss, Inc.
Neuroprotective sigma ligands interfere with the glutamate‐activated NOS pathway in hippocampal cell culture

We studied neuroprotective properties of 12 structurally different sigma site ligands in primary rat hippocampal cell cultures and analyzed whether they interfere with glutamate‐induced activation of the nitric oxide synthase (NOS) pathway. Neurotoxicity was triggered with 1mM glutamate on day 8 of culture. Cells were treated with various concentrations of the compounds for 7 days before glutamate exposure (prolonged pretreatment), or during glutamate exposure (acute treatment). Protection was seen after prolonged pretreatment (long‐term protection) with sabeluzole, opipramole, haloperidol, ifenprodil, fenpropimorph, carbetapentane, and tiospirone, with pIC50S of 7.30, 7.15, 6.87, 6.68, 6.66, 6.39, and 6.34, respectively. There was no protection with PD 128298, 1,3‐ortho‐di‐tolylguanidine, BMY‐14802, (+)3‐(3‐hydroxyphenyl)‐N‐l(propy1) piperidine, or dextromethorphan. Upon acute treatment, only ifenprodil was protective. Interference of the drugs with glutamate activation of the NOS pathway was determined by measuring glutamate‐activated cGMP formation and citrulline levels. Glutamate‐activated cGMP formation was reduced by all neuroprotective sigma ligands after prolonged pretreatment but not after acute treatment. Sigma ligands added to cell culture iysate did not reduce citrulline formation, evidence that there was no direct effect on the NOS enzyme. We conclude that some but not all sigma ligands exert long‐term protective properties against glutamate‐induced neurotoxicity in primary hippocampal cultures, and that this protection is accompanied by attenuation of cGMP formation in the NOS pathway. However, inhibition of cGMP formation by itself appeared not sufficient for obtaining neuroprotective effects, as inhibition of glutamate‐activated cGMP formation by N‐nitro‐L‐arginine, haemoglobin, or PD128298 did not provide neuroprotection. © 1995 Wiley‐Liss, Inc.
Anthropogenic antibiotic resistance genes mobilization to the polar regions

Anthropogenic influences in the southern polar region have been rare, but lately microorganisms associated with humans have reached Antarctica, possibly from military bases, fishing boats, scientific expeditions, and/or ship-borne tourism. Studies of seawater in areas of human intervention and proximal to fresh penguin feces revealed the presence of Escherichia coli strains least resistant to antibiotics in penguins, whereas E. coli from seawater elsewhere showed resistance to one or more of the following antibiotics: ampicillin, tetracycline, streptomycin, and trim-sulfa. In seawater samples, bacteria were found carrying extended-spectrum β-lactamase (ESBL)-type CTX-M genes in which multilocus sequencing typing (MLST) showed different sequence types (STs), previously reported in humans. In the Arctic, on the contrary, people have been present for a long time, and the presence of antibiotic resistance genes (ARGs) appears to be much more wide-spread than was previously reported. Studies of E coli from Arctic birds (Bering Strait) revealed reduced susceptibility to antibiotics, but one globally spreading clone of E. coli genotype O25b-ST131, carrying genes of ESBL-type CTX-M, was identified. In the few years between sample collections in the same area, differences in resistance pattern were observed, with E. coli from birds showing resistance to a maximum of five different antibiotics. Presence of resistance-type ESBLs (TEM, SHV, and CTX-M) in E. coli and Klebsiella pneumoniae was also confirmed by specified PCR methods. MLST revealed that those bacteria carried STs that connect them to previously described strains in humans. In conclusion, bacteria previously related to humans could be found in relatively pristine environments, and presently human-associated, antibiotic-resistant bacteria have reached a high global level of distribution that they are now found even in the polar regions.
Effect of market competition on hospital performance for heart failure.

OBJECTIVES To investigate whether market competition is a potential driver of hospital performance on the key evidence-based Joint Commission heart-failure (HF) quality indicators of angiotensin-converting enzyme inhibitor/angiotensin receptor blocker prescribed, left ventricular function assessment, smoking-cessation counseling, and discharge instructions. STUDY DESIGN Retrospective multivariate analysis. METHODS Hospital performance data for HF was obtained from The Joint Commission's ORYX program from 2003 to 2006. The performance data were linked with hospital characteristics from the American Hospital Association Annual Survey and area-level sociodemographic information from the Area Resource File. Healthcare markets were defined as hospital referral regions (HRRs) and market competition intensity was defined by the Herfindahl-Hirschman Index. Hospital-level and HRR-level ordinary least squares fixed effects regression models were used to estimate the relationship between market competition and performance. RESULTS A paired comparison indicated that there was a significant change in the mean hospital-level performance over time on all of the HF quality indicators. From the multivariate analyses, hospitals in the least competitive markets (Quintile 5) performed slightly better (2.9%) than the most competitive markets (Quintile 1) for left ventricular function assessment (P <.01). At the HRR level, however, the least competitive markets (Quintile 5) performed moderately worse (5.1%) on the discharge-instructions quality indicator compared with the most competitive markets (Quintile 1) (P = .05). CONCLUSIONS Market competition intensity was associated with only small differences in hospital performance. The level of market competitiveness may produce only marginal incremental benefits to inpatient HF care.
The role of immunophenotyping in differential diagnosis of chronic lymphocytic leukemia.

INTRODUCTION Accurate diagnosis of chronic lymphocytic leukemia (CLL) acquires immunophenotyping by flow cytometry in order to facilitate differential diagnosis between CLL and other mature B-cell neoplasms (MBCN). OBJECTIVE The aim of this study was to define immunological profile of CLL cells. METHODS Immunophenotyping by flow cytometry was performed on peripheral blood specimens at diagnosis in the group of 211 patients with de novo MBCN. RESULTS Absolute count of B-cells was significantly increased in all MBCN patients comparing to healthy control group (p < 0.05). B-cell monoclonality was detected in 96% of all MBCN patients, by using surface immunoglobulin (sIg) light chain restriction. B-cell antigens, CD19, CD20, CD22, were expressed with very high frequency in CLL and other MBCN. In comparison with other MBCN, in CLL group, the frequency of expression was higher for CD5 and CD23 (p < 0.0001), though lower for FMC7 antigen (p < 0.0001). CLL patients were characterized by lower expression patterns of CD20, CD22, CD79b, and sIg (p < 0.0001) as well as higher expression pattern of CD5 antigen (p < 0.05). Correlation between the final diagnosis of MBCN and values of CLL scoring system showed that the majority of CLL patients (97%) had higher values (5 or 4) whereas the majority of other MBCN patients (96%) had lower score values (0-3). CONCLUSION Our results have shown that characteristic immunophenotype which differentiates CLL from other MBCN is defined by following marker combination--CD19+ CD20(+Iow) CD22(+low) CD5(+high) CD23+ FMC7-CD79b(+Iow) sIg(+Iow). CLL score values of 5 or 4 points are highly suggestive for diagnosis of CLL.
I Scratch and Sense But Can I Program?: An Investigation of Learning with a Block Based Programming Language

This paper reports an investigation into undergraduate student experiences and views of a visual or ‘blocks’ based programming language and its environment. An additional and central aspect of this enquiry is to substantiate the perceived degree of transferability of programming skills learnt within the visual environment to a typical mainstream textual language. Undergraduate students were given programming activities and examples covering four basic programming concepts based on the Sense programming language which is intended to simplify programming. Sense programming statements are represented by blocks which only fit together in ways that produce a meaningful syntactic outcome, which may lower the cognitive barrier to learning. Students were also presented with concepts represented using an equivalent textual construct and asked to consider their understanding of these based on the graphical cases. They were finally asked to complete a short online survey. This paper presents the programming activities, the survey and an analysis of the results.
Playing for the same team? The trio Presidency and agenda-management in European Union sport policy

In 2007 the rotating Presidency of the Council of the European Union (EU) was reformed by the introduction of the so-called trio Presidency . The trio mechanism encourages policy continuity by grouping incumbent Presidencies in teams of three and inviting them to coordinate. This thesis seeks to contribute original knowledge on EU policy-making by mapping how trio practices are established, exploring which factors explain how Member States coordinate, and by assessing how the trio arrangement affects the EU agenda. Empirically, the trio function is examined through its implementation in the policy area of sport, focusing on the three trios to assume office after the coming into force of the Lisbon Treaty in 2009. The analysis is structured around a number of carefully selected dossiers adopted between 2010 and 2013. Guided by a conceptual framework based on agenda-setting and new institutionalism, these decisions are submitted to in depth process-tracing. The analysis draws on qualitative research, primarily official documents and 37 semi-structured interviews. The findings reveal that actors approach the trio with differing preferences and expectations, leading to much variation in how the arrangement is performed. The thesis identifies a number of factors that explain variation. Thus, a fixed agenda supports trios in coordinating priorities and activities ex ante. Moreover, coordination is conditioned by trio composition, as federal and new Member States are more inclined to cooperate. Further, trio practices are shaped by factors such as multiannual planning and focusing events, with the intenseness of trio coordination reflecting whether the agenda includes issues that demand sustained attention. The thesis concludes that the introduction of the trio mechanism has preserved the ability of Member States to use the Council Presidency to prioritise national priorities whilst also encouraging and facilitating EU policy continuity. By extending agenda-management beyond a six month spell, the trio can strengthen the agenda-setting powers of incumbent Member States, particularly on issues that concern establishing urgent responses or developing Council procedures. Moreover, evidence suggests that the arrangement can produce a specific spirit of collegiality, trio solidarity, which sees trio Member States support each other during negotiations, thus affecting EU policy-making beyond agenda-management.
Space-time analysis of the Air Quality Model Evaluation International Initiative (AQMEII) Phase 1 air quality simulations

This study presents an evaluation of summertime ozone concentrations over North America (NA) and Europe (EU) using the database generated from Phase 1 of the Air Quality Model Evaluation International Initiative (AQMEII). The analysis focuses on identifying temporal and spatial features that can be used to stratify operational model evaluation metrics and to test the extent to which the various modeling systems can replicate the features seen in the observations. Using a synoptic map typing approach, it is demonstrated that model performance varies with meteorological conditions associated with specific synoptic-scale flow patterns over both eastern NA and EU. For example, the root mean square error of simulated daily maximum 8-hr ozone was twice as high when cloud fractions were high compared with when cloud fractions were low over eastern NA. Furthermore, results show that over both NA and EU the regional models participating in AQMEII were able to better reproduce the observed variance in ambient ozone levels than the global model used to specify chemical boundary conditions, although the variance simulated by almost all regional models is still less that the observed variance on all spatiotemporal scales. In addition, all modeling systems showed poor correlations with observed fluctuations on the intraday time scale over both NA and EU. Furthermore, a methodology is introduced to distinguish between locally influenced and regionally representative sites for the purpose of model evaluation. Results reveal that all models have worse model performance at locally influenced sites. Overall, the analyses presented in this paper show how observed temporal and spatial information can be used to stratify operational model performance statistics and to test the modeling systems’ ability to replicate observed temporal and spatial features, especially at scales the modeling systems are designed to capture. Implications: The analyses presented in this paper demonstrate how observed temporal and spatial information can be used to stratify operational model performance and to test the modeling systems’ ability to replicate observed temporal and spatial features. Decisions for the improvement of regional air quality models should be based on the information derived from only regionally representative sites.