Miracle-dz/UniFAR-FTUs huggingface dataset:
Histological and morphometrical indicators for a biopsy diagnosis of well‐differentiated hepatocellular carcinoma

Among 597 patients with nodular hepatic lesions who underwent ultrasonically guided needle biopsy, 305 were histologically confirmed as having hepatocellular carcinoma, and 37 patients had borderline lesions. Histological reexamination was correlated with morphometrical analysis on selected cases of well‐differentiated, microtrabecular hepatocellular carcinomas (n = 29), borderline lesion (n = 10), typical (mid‐sized and macrotrabecular) hepatocellular carcinomas (n = 15) and cirrhotic liver tissue obtained from extranodular hepatic parenchyma of hepatocellular carcinoma patients (n = 47). Morphometrical analyses revealed that the mean cell size and nucleocytoplasmic ratio were most useful for distinguishing well‐differentiated, microtrabecular hepatocellular carcinoma from cirrhosis. These two parameters were well correlated with nuclear density. The grade of nuclear density, therefore, seemed to be a convenient semiquantitative indicator for diagnosing well‐differentiated hepatocellular carcinoma. A comparison between intranodular and extranodular hepatic tissues was particularly important for its assessment. It is concluded from the results that hepatic nodules presenting a nuclear density larger than two times that of controls could be classified into the overt hepatocellular carcinoma group. From the statistical aspect, the possibility of microtrabecular hepatocellular carcinoma should be considered when a nodule has a nuclear density exceeding 1.3 times that of the extranodular tissue.
Signal-Path-Level Dual-VT Assignment for Leakage Power Reduction

Along with the fast development of dual-threshold voltage (dual-Vt) and multi-threshold technology, it is possible to use them to reduce static power in low-voltage high-performance circuits. In this paper, we propose a new method to realize CMOS digital circuits that are implemented with dual-Vt technology. We first present a new signal-path-level circuit model which effectively deals with the fact that there can be two threshold voltages assigned to a single gate. In order to assign proper threshold voltage to all the signal-paths in the circuit, our new algorithms introduce the concept of subcircuit extraction and include the hierarchy algorithms which are effective and fast. Experimental results show that our algorithms produce a significant reduction for the ISCAS85 benchmark circuits.
Is Kleine-Levin syndrome a variant of bipolar disorder? An hypothesis

Kleine-Levin syndrome (KLS) was first described in 1862 by Brierre de Boismont and gained its eponymous name from the reports of Willi Kleine (1) and Max Levin (2) in the 1920s. It is a rare disorder that occurs worldwide and is characterised by episodes of sleep, behavioural, mood and cognitive disturbance, with usually an onset in adolescence and a variable episodic course. The focus on hypersomnia has resulted in its characterisation as a sleep disorder (3), with hypersomnia and megaphagia being considered to be the core symptoms (4). The disorder has therefore remained in the domains of sleep medicine and neurology, with relatively little attention from psychiatry. A recent comprehensive review of 186 cases published between 1962 and 2004 (5) brought together the features of this syndrome that suggest its complexity and variety. Some similarities with primary mood disorder are obvious, and this paper proposes that there is heuristic value in considering KLS as a variant of bipolar disorder (BD). This paper does not present new data to support this conceptualisation but examines the existing information from a new perspective in order to inform future research.
Leukotriene generation in patients with multiple injuries.

We determined the generation and metabolism of lipoxygenase products in isolated granulocyte fractions of patients with multiple trauma (n = 9) and compared the results with those of healthy volunteers (n = 8). The supernatants of stimulated cells were analyzed by high-performance liquid chromatography. During the first week after injury a significantly reduced capacity to generate LTB4 and an increased metabolism of LTB4 into omega-oxidated products (20-OH-LTB4 and 20-COOH-LTB4) were observed after stimulation of the granulocytes with Ca ionophore. The depressed leukotriene production could be partly abrogated by the addition of arachidonic acid. These findings are comparable with alterations previously described in severely burned patients with postburn sepsis. Additionally, an elevated production of LTC4 by peripheral granulocyte fractions was observed in two patients suffering from adult respiratory distress syndrome (ARDS) as well as an increased number of eosinophils during the time of lung dysfunction. Analysis of bronchoalveolar lavage in patients with multiple trauma (11 patients with ARDS and 11 patients without ARDS) by a specific radio-immunoassay confirmed an elevated production of cysteinyl-leukotrienes. (ABSTRACT TRUNCATED AT 250 WORDS)
P21‐activated kinase 5 is overexpressed during colorectal cancer progression and regulates colorectal carcinoma cell adhesion and migration

P21‐activated kinase 5 (PAK5) is the recently identified member of the group B p21‐activated kinase (PAK) family which are effectors of the small GTPase Cdc42 and Rac1, known to regulate cell motility and activate cell‐survival signaling pathways. However, overexpression of PAK5 has not been associated with any cancers so far. Interestingly, we found that PAK5 was overexpressed in a variety of colorectal carcinoma (CRC) cell lines in a Western‐blotting examination. Therefore, in this study, we aim to examine the PAK5 expression during CRC progression and to answer if PAK5 is involved in malignant progression of CRC. By immunohistochemistry, our results showed that PAK5 expression was increased with CRC progression through the adenoma to carcinoma sequence, with the most significant increases in invasive and metastatic CRCs (p < 0.0001). Furthermore, increased PAK5 expression was also found with the development of CRC from lower Duke's grades to higher ones (p < 0.01). Moreover, PAK5 was also increased from well to poorly differentiated CRCs (p < 0.01). Using gain and loss of function experiments, we found that PAK5 reduced CRC cell adhesion but promoted their migration on collagen type I. Taken together, our study demonstrated that PAK5 expression increased significantly with malignant progression of CRC and that PAK5 might promote CRC metastasis by regulating CRC cell adhesion and migration. © 2009 UICC
Complex Role of CD 4 + T Cells Initiated Antitumor Responses Require the − Effective Anti-Neu

Purpose: Targeting oncogenic receptors with antibodies has been thought to suppress tumor growth mainly by interrupting oncogenic signals. Recently, the essential role for adaptive immunity, and CD8þ T cells in particular, has been established as a major factor for anti-HER2/neu–mediated tumor regression. However, the role of CD4þ T cells is still being defined. The purpose of this studywas to explorewhether and to what extent CD4þ T cells are involved in mediating the effects of anti-HER2/neu therapy. Experimental Design: The role of CD4þ T cells was examined using a transplant model of the rat HER2/ neu–overexpressing cell line TUBO. Tumor-bearingmice were treated with anti-neu therapy in conjunction with CD4 depletion or CD40L blockade. The effects of CD4 depletion on the antitumor response were examined by tumor growth analysis and enzyme-linked immunospot (ELISPOT). Results: In addition to CD8þ T cells, CD4þ T cells are also essential for anti-neu antibody-mediated tumor regression, but B cells are not required. The role for CD4þ cells is necessary throughout anti-neu therapy and not limited to helping CD8þ T cells. Expression of IFN-g is necessary for anti-neu therapy and IFN-g inducesMHC-II expression in TUBOcells promoting direct recognition byCD4þT cells. Furthermore, intratumoral depletion of CD4þ T cells or blockade of the activating cell-surface protein CD40L inhibits the
Expansion of Schlemm's canal by travoprost in healthy subjects determined by Fourier-domain optical coherence tomography.

PURPOSE To determine the effect of travoprost 0.004% on Schlemm's canal (SC) in healthy human eyes using Fourier-domain optical coherence tomography (FD-OCT). METHODS Twelve healthy volunteers were recruited for a double-blind, placebo-controlled, randomized, and paired comparison study. Right eyes of subjects were randomly assigned to receive either travoprost 0.004% or placebo; the contralateral eye received the other treatment. FD-OCT imaging of SC and measurements of IOP were carried out before and at 1, 2, 4, 6, 8, 12, 24, 36, 48, 60, 72, and 84 hours after eye drop instillation. RESULTS After instillation of travoprost eye drops, IOP gradually reduced, and the SC lumens expanded, while those values remained unchanged in placebo treated eyes. At 8 hours after the travoprost administration, the mean SC area increased 90.30% and 90.20%, respectively, in the nasal and temporal quadrant of the treated eyes as compared with the placebo group. The SC area and IOP showed a similar pattern of changes at most time points examined. In travoprost-treated eyes, a statistically significant correlation between SC area and IOP is observed (r = -0.2817; P = 0.0004). Measurements of the SC area showed sufficient repeatability and reproducibility. CONCLUSIONS SC can be noninvasively imaged and quantitatively assessed in the living healthy human eye by FD-OCT. Travoprost treatment leads to SC lumen expansion accompanied by a drop of IOP in the healthy eye, likely as a result of the enhancement of pressure sensitive trabecular meshwork outflow induced by travoprost.
Letter to the Editor: Comments on ‘Recovery from chronic fatigue syndrome after treatments given in the PACE trial’

White et al. (2013) report various recovery rates from chronic fatigue syndrome (CFS) following the PACE Trial. However, additional information would have been useful. White et al. use a selection of broad criteria to define recovery, none of which allow one to be confident recovery has been achieved. Firstly, Chalder Fatigue Questionnaire (CFQ) and SF-36 Physical functioning (PF) scores within the normal range are in fact possible at baseline. This means it is possible to have fatigue that is classed as ‘severe, disabling and affected physical and mental function’ and yet satisfy this particular recovery criterion. Secondly, not satisfying the Oxford criteria only requires a change on just one measure, and the change may be minimal, across a threshold, e.g. going from an SF-36 PF score of 65 to 70 or a CFQ (bimodal) score of 6 to 5. A sign that this criterion is not that stringent can be seen with the fact that 41% of the specialist medical care (SMC) group, which received no active treatment, no longer met the Oxford criteria at 12 months, much higher than recovery rates seen in previous studies (Cairns & Hotopf, 2005). Finally, a CGI score of 2, which means a participant rated as ‘much better’ but not ‘very much better’ also gives no assurance that somebody had recovered. It seems quite possible that many with CGI scores of 2 have simply improved but not recovered.
Technetium-99m-tetrofosmin uptake in brain tumors by SPECT: comparison with thallium-201 imaging.

UNLABELLED Thallium-201 is clinically used for the assessment of primary and recurrent brain tumors. The biologic properties of 201Tl that allow it to accumulate within the tumor cells render 201Tl useful in evaluating tumor malignancy, but its physical characteristics and nonroutine availability limits its use in some institutions, as compared to 99mTc-labeled compounds. The aim of this study was to assess the feasibility of using 99mTc-tetrofosmin for imaging brain tumors and to compare its uptake with that of 201Tl. METHODS Twenty-six patients with 27 intracranial masses were studied with SPECT. In the first group of seven patients (Group A), the timing for optimal acquisition of the 99mTc-tetrofosmin scan was assessed. In the second group of 19 patients (Group B), two sequential 201Tl (74-148 MBq intravenous) and 99mTc-tetrofosmin (740-925 MBq intravenous) studies were performed 20 min after tracer injection and compared. RESULTS In Group A, no significant difference in the tumor-to-background (T/B) ratio among the 20-, 40- and 120-min postinjection studies was observed. In Group B, the quality of reconstructed images with 99mTc-tetrofosmin, judged visually, was superior to that of 201Tl in 47% of all studies and was comparable in the remaining 53%. A significant relationship between 201Tl and 99mTc-tetrofosmin T/B ratio (r = 0.75, p < 0.01) was found. The T/B ratio of 99mTc-tetrofosmin was significantly higher than that of 201Tl (23.3 +/- 21.5 compared to 6.1 +/- 2.9, p < 0.005). CONCLUSION Technetium-99m-tetrofosmin is a suitable radiotracer for the imaging of intracranial lesions with SPECT. Moreover, a better definition of tumor margins and a higher contrast between neoplastic and normal brain tissue can be achieved.
Depressed Thymidine Kinase Activity in Zinc-Deficient Rat Embryos 1

Summary The activity of thymidine kinase in 12-day fetuses taken from females exposed to a dietary zinc deficiency during pregnancy was significantly lower than in ad libitum (P < .05) and restricted-intake (P < .01) controls. Activity of the enzyme was not restored by in vitro addition of zinc at levels up to 0.075 mM but severe inhibition (approximately 50%) occurred at 0.75 mM. Enzyme activity was also severely reduced (approximately 44%) by 0.017 mM (0.96 μg/ml) of copper which raises the possibility that the reduction in thymidine kinase accompanying zinc deficiency may arise, at least in part, from an absolute or relative change in the intracellular level of copper.
The enigma of CD57+CD28– T cell expansion—anergy or activation?

Expansion of a CD57+CD8+ T lymphocyte subset has been reported in HIV and human cytomegalovirus (HCMV) infection. Almost all of these T cells lack CD28 expression. While CD28– cells are often associated with anergy, some authors believe their expansion in HIV infection precipitates immunodeficiency. We studied 15 randomly chosen patients with immune activation and observed that CD57+CD28– T cell expansion may occur in various conditions and to the same degree as in HIV infection without resulting in immunodeficiency. Triple colour flow cytometry also revealed that the CD57 and CD28 antigens are coexpressed in only 3% of CD8+ T cells, irrespective of the underlying condition, so that almost all CD57+CD8+ cells are always CD28–. Analysis of Fas (CD95) expression with respect to CD28 expression on CD4+ and CD8+ T cells from 10 additional patients indicated no increased commitment to apoptosis in CD28– T cells. Semiquantitative polymerase chain reaction (PCR) comparing CD28+ and CD28–CD8+ T cells with respect to cytokine gene expression (tumour necrosis factor‐alpha (TNF‐α), interferon‐gamma (IFN‐γ), IL‐1β) in five renal transplant patients with expansion of the CD57+ subset detected no cytokine gene expression deficit in CD28– T cells. A direct association of increased proportions of CD57+CD28–CD8+ T cells with immunodeficiency/anergy is disputed.
Distinguishing cardiac and noncardiac dyspnea in 48 dogs using plasma atrial natriuretic factor, B-type natriuretic factor, endothelin, and cardiac troponin-I.

BACKGROUND It is challenging to differentiate congestive heart failure (CHF) from noncardiac cause of dyspnea. HYPOTHESIS Circulating concentrations of atrial natriuretic peptide (NT-proANP), B-type natriuretic peptide (BNP), endothelin-I (ET-1), and cardiac troponin-I (cTnI) can be used to help distinguish between cardiac and noncardiac causes of dyspnea in dogs. ANIMALS Forty-eight client-owned dogs admitted to a veterinary teaching hospital for respiratory distress. METHODS Blood samples from patients were prospectively obtained. The etiology of dyspnea was determined by using physical examination, thoracic radiographs, and echocardiography. RESULTS CHF was diagnosed in 22 dogs, and dyspnea of noncardiac origin (noHD group) was diagnosed in 26 dogs. Analyses revealed significant difference between groups for NT-proANP (geometric mean, 95% confidence [CI]; no HD: 0.26 nmol/mL, 95% CI 0.17-1.09; CHF: 1.38 nmol/mL, 95% CI 1.09-1.74 nmol/mL; P < .0001), BNP (noHD: 12.18 pg/mL, 95% CI 10.91-16.17 pg/mL; CHF: 34.97 pg/mL, 95% CI 23.51-52.02 pg/mL; P < .0001), and ET-1 (noHD: 0.32 fmol/mL, 95% CI 0.23-0.46 fmol/mL; CHF: 1.26 fmol/mL, 95% CI 0.83-1.91 fmol/mL; P < .0001). Plasma cTnI concentrations were not significantly different between groups (noHD: 0.29 ng/mL, 95% CI 0.12-0.72 ng/mL; CHF: 0.42 ng/mL, 95% CI 0.18-0.97, P = .53). Receiver operating curves indicated areas under the curve for NT-proANP, BNP, and ET-1 of 0.946, 0.886, and 0.849, respectively. CONCLUSIONS AND CLINICAL IMPORTANCE Plasma NT-proANP, BNP, and ET-1, but not cTnI, appear useful for distinguishing between dogs with cardiac and noncardiac causes of dyspnea, with plasma NT-proANP having the highest sensitivity (95.5%) and specificity (84.6%).
Runaway breakdown and electrical discharges in thunderstorms 2

4 [1] This review considers the precise role played by runaway breakdown (RB) in 5 the initiation and development of lightning discharges. RB remains a fundamental research 6 topic under intense investigation. The question of how lightning is initiated and 7 subsequently evolves in the thunderstorm environment rests in part on a fundamental 8 understanding of RB and cosmic rays and the potential coupling to thermal runaway 9 (as a seed to RB) and conventional breakdown (as a source of thermal runaways). In 10 this paper, we describe the basic mechanism of RB and the conditions required to initiate 11 an observable avalanche. Feedback processes that fundamentally enhance RB are 12 discussed, as are both conventional breakdown and thermal runaway. Observations 13 that provide clear evidence for the presence of energetic particles in thunderstorms/ 14 lightning include g‐ray and X‐ray flux intensifications over thunderstorms, g‐ray and 15 X‐ray bursts in conjunction with stepped leaders, terrestrial g‐ray flashes, and neutron 16 production by lightning. Intense radio impulses termed narrow bipolar pulses 17 (or NBPs) provide indirect evidence for RB particularly when measured in association 18 with cosmic ray showers. Our present understanding of these phenomena and their 19 enduring enigmatic character are touched upon briefly.
Ultrasound biomicroscopic assessment of zonular appearance in exfoliation syndrome.

PURPOSE To assess zonular appearance using biomicroscopy (UBM) in exfoliation syndrome (XFS). METHODS Normal eyes and eyes with XFS were enrolled in this prospective, consecutive, comparative cohort study. Following pupillary dilation, XFS patients were classified into three clinical stages (early, moderate or severe) by a single examiner (R.R.). Cross-sectional zonular UBM images were obtained circumferentially at eight evenly spaced locations. Five experienced observers evaluated the images using a standardized scoring system based on the zonular appearance (0, none; 1, early; 2, moderate; 3, severe). The extent of zonular involvement on UBM based on UBM score of all observers was correlated with the clinical stage of XFS using a five-stage classification. RESULTS We enrolled 44 eyes (44 patients), 11 normal and 33 with XFS (10 early, 10 moderate and 13 severe) [mean age 69.4 +/- 9.9 (SD) years; range 50-87 years]. UBM scores of all observers were significantly different between the normal/early and moderate/severe groups (P < 0.001, t-test). With discriminant analysis, the predicted XFS stage showed good agreement with the clinical staging [all kappa > 0.61, area under receiver operating characteristic (ROC) curve > 0.86]. CONCLUSION UBM can detect zonular involvement in XFS and may be useful in preoperative planning. This may be important in eyes with posterior synechiae in which a diagnosis and the severity of XFS cannot be determined on slit-lamp examination.
[Two-year follow-up of infants born at 24 weeks gestation; first outcomes following implementation of the new 'Guideline for perinatal policy in cases of extreme prematurity'].

OBJECTIVE Since 2010 the guideline 'Guideline for perinatal policy in cases of extreme prematurity' has advised an active policy in infants born at 24 weeks gestation. We investigated how infants born at 24 and 25 weeks gestation in the first year following the implementation of the guideline had developed by the age of 2 years. DESIGN Retrospective national cohort study. METHOD The study population consisted of all surviving infants born in the Netherlands at 24 or 25 weeks gestation in the period from 1 October 2010 to 1 October 2011. At a corrected age of 2 years the children underwent a general physical and neurological examination, and their cognitive scores were determined on the 'Bayley scales of infant and toddler development' (Bayley III). Examinations took place in the 10 neonatal intensive care units (NICU's) in the Netherlands. RESULTS Of 185 extremely premature infants, 166 were admitted to a NICU. A total of 95 survived to a corrected age of 2 years; 78 (82%) children were examined. Their average cognitive score on the Bayley III scale was 88 (SD: 16). Among the children born at 24 weeks gestation, 20% had mild disabilities and 20% had moderate to severe disabilities. Among the children born at 25 weeks gestation, 17% had mild disabilities and 12% had moderate to severe disabilities. CONCLUSION Of the children born at 24 weeks gestation in the first year after the introduction of active policy in the Netherlands and surviving to 2 years of age (46%), more than half had developed without disabilities. This was comparable to children born at 25 weeks gestation. Of all children born at 24 weeks gestation, 25% survived to 2 years of age without disabilities.
Evaluation of serum lipoprotein(a) levels in Greek schoolchildren

This study aimed to provide associations of age and gender with serum lipoprotein(a) [Lp(a)] levels and percentile distribution data for Greek children. In total, 3298 children (1590M, 1708F, aged 6–14 y) participated in the study. Lp(a) levels were evaluated with an immunosorbent assay. Mean Lp(a) levels were 153–157 mg l‐1 for boys and 146–151 mg l‐1 for girls, and median levels 133–139 mg l1 for boys and 100–108 mg l‐1 for girls.
Background acoustic noise reduction in mobile telephony

This paper discusses the problem of background acoustic noise in mobile telephony. The background acoustic noise inside the cabin of a car is analysed, and some experimental results are presented. The analysis includes a characterization of the various sources of background noise. Different methods for reducing the background acoustic noise at the transmitter are presented. The methods are based on adaptive filtering techniques. Finally, some design considerations are discussed; such as the filter configuration and the adaptation algorithm along with some preliminary results.