Miracle-dz/UniFAR-FTUs huggingface dataset:
Different angiogenic phenotypes in primary and secondary glioblastomas

Primary and secondary glioblastomas (pGBM, sGBM) are supposed to evolve through different genetic pathways, including EGF receptor and PDGF and its receptor and thus genes that are involved in tumor‐induced angiogenesis. However, whether other angiogenic cytokines are also differentially expressed in these glioblastoma subtypes is not known so far, but this knowledge might be important to optimize an antiangiogenic therapy. Therefore, we studied the expression of several angiogenic cytokines, including VEGF‐A, HGF, bFGF, PDGF‐AB, PDGF‐BB, G‐CSF and GM‐CSF in pGBMs and sGBMs as well as in gliomas WHO III, the precursor lesions of sGBMs. In tumor tissues, expression of all cytokines was observed albeit with marked differences concerning intensity and distribution pattern. Quantification of the cytokines in the supernatant of 30 tissue‐corresponding glioma cultures revealed a predominant expression of VEGF‐A in pGBMs and significantly higher expression levels of PDGF‐AB in sGBMs. HGF and bFGF were determined in nearly all tumor cultures but with no GBM subtype or malignancy‐related differences. Interestingly, GM‐CSF and especially G‐CSF were produced less frequently by tumor cells. However, GM‐CSF secretion occurred together with an increased number of simultaneously secreted cytokines and correlated with a worse patient prognosis and may thus represent a more aggressive angiogenic phenotype. Finally, we confirmed an independent contribution of each tumor‐derived cytokine analyzed to tumor‐induced vascularization. Our data indicate that an optimal antiangiogenic therapy may require targeting of multiple angiogenic pathways that seem to differ markedly in pGBMs and sGBMs. © 2005 Wiley‐Liss, Inc.
Study of Relieving Graft-versus-Host Disease by Blocking CD137-CD137 Ligand Costimulatory Pathway in Vitro

Engagement of the TCR without appropriate costimulation will result in the inability of T-cells to respond to the alloantigen as described earlier. We made a further investigation into the effect of relieving graft-versus-host disease (GVHD) and its mechanism in mice by blocking CD137-CD137L pathway in vitro. Responder cells (spleen cells) from BALB/C donor mice (H-2d) were incubated with stimulator cells (spleen cells) from C57BL/6 recipient mice (H-2b),with or without anti-CD137L monoclonal antibodies (MoAbs). Donor bone marrow cells plus mixed lymphocyte culture (MLC) T-cells were transplanted into lethally irradiated C57BL/6 mice. C57BL/6 mice were divided into 3 groups: group A (allogeneic bone marrow transplantation control group), group B (cyclosporine + methotrexate group), and group C (donor T-cells were treated with anti-CD137L MoAbs). The percentage of CD3+CD4+ and CD3+CD8+ T-cells were detected by flow cytometry, and the levels of cytokines (IFN-γ, interleukin [IL]-2, IL-10, IL-4) by reverse-transcriptase polymerase chain reaction.The incidence of GVHD in group C was 70%, while the incidence of GVHD was 100% in group A and group B. The survival rate of group C was higher than that of group A and B, and the median survival time was longer than that of group A and B(P < .01). Clinical symptoms and histological signs of GVHD in group C were the mildest among all 3 groups. The percentage of CD3+CD8+ T-cells in group C was lower than that in group A and B(P < .01). The levels of IFN-γ in group C were markedly lower than those in group A and B(P < .01), and the levels of IL-10 in group C were significantly higher than those in group A and B(P < .01). The results suggest that treatment of donor T-cells by anti-CD137L MoAbs in vitro may relieve GVHD, thereby improve the survival time and survival rate of recipient mice, which might be related to the increased TH1 cytokine (IFN-γ) and decreased TH2 cytokine (IL-10) as well as the reduced CD3+CD8+ T-cells.
Improved detection of clinically relevant wound bacteria using autofluorescence image‐guided sampling in diabetic foot ulcers

Clinical wound assessment involves microbiological swabbing of wounds to identify and quantify bacterial species, and to determine microbial susceptibility to antibiotics. The Levine swabbing technique may be suboptimal because it samples only the wound bed, missing other diagnostically relevant areas of the wound, which may contain clinically significant bacteria. Thus, there is a clinical need to improve the reliability of microbiological wound sampling. To address this, a handheld portable autofluorescence (AF) imaging device that detects bacteria in real time, without contrast agents, was developed. Here, we report the results of a clinical study evaluating the use of real‐time AF imaging to visualise bacteria in and around the wound bed and to guide swabbing during the clinical assessment of diabetic foot ulcers, compared with the Levine technique. We investigated 33 diabetic foot ulcers (n = 31 patients) and found that AF imaging more accurately identified the presence of moderate and/or heavy bacterial load compared with the Levine technique (accuracy 78% versus 52%, P = 0·048; adjusted diagnostic odds ratio 7·67, P < 0·00022 versus 3·07, P = 0·066) and maximised the effectiveness of bacterial load sampling, with no significant impact on clinical workflow. AF imaging may help clinicians better identify the wound areas with clinically significant bacteria, and maximise sampling of treatment‐relevant pathogens.
Functional analysis of complex hepatitis B virus variants associated with development of liver cirrhosis.

BACKGROUND & AIMS Development of cirrhosis in renal transplant recipients with chronic hepatitis B is associated with the accumulation of complex hepatitis B virus (HBV) variants carrying deletions in the C gene and/or preS region and deletions/insertions in the core promoter. Here, we characterized for the first time the phenotype of these complex HBV variants. METHODS Representative full-length genomes of the HBV variants that were isolated and cloned from serum and liver of an immunosuppressed renal transplant recipient before and during end-stage liver disease were transfected into the human hepatoma cell line HuH7 and functionally analyzed. RESULTS The variant genomes showed considerably reduced levels of precore and surface messenger RNA (mRNA) and of the major spliced pregenomic RNA, an increased level of pregenomic RNA, and a partial or complete defect in hepatitis B e antigen, core, and surface protein expression/secretion. Very low amounts of variant core protein with internal deletion were detectable. Reduced hepatitis B surface antigen secretion of some variants correlated with aberrant localization of surface proteins in endoplasmic reticulum. Despite the defects in viral protein expression, enhanced replication and enrichment in competition to wild-type HBV were observed. Enhanced reverse transcription and possibly increased levels of pregenomic RNA seem to be responsible for this effect. CONCLUSIONS Development of cirrhosis is associated with accumulation of complex variants, which exhibit a drastically altered phenotype combining enhanced replication with defects in protein expression. This phenotype appears to be based on the major mutations in the core promoter and C gene but is considerably influenced by additional mutations throughout the genome.
Information Effects of Bond Rating Changes

This article shows that studies of announcement effects of bond rating changes should take into account the rating prior to the announcement. First, we provide theoretical support for different price effects as a non-linear function of the prior credit rating, using a structural, Merton-type model linking the change in default probability to the change in the stock price. Next, we show that this theoretical prediction is verified in the empirical data. We find much stronger information effects, measured by stock price effects, for rating changes for low-rated firms relative to high-rated firms. Accounting for the role of the rating prior to the announcement explains in large part the puzzling empirical regularity that stock price effects are associated with downgrades but not upgrades. In addition, it eliminates the investment-grade barrier effect reported in previous studies.
Accuracy of Diagnosis and International Classification of Diseases; Tenth Revision Coding for Alcohol Dependence, Alcohol Withdrawal, and Alcohol-withdrawal Delirium Among Inpatients at a University Hospital.

To the Editor: D espite high rates of alcoholrelated problems (World Health Organization, 2015), only a minority of them are recognized and diagnosed by health care professionals (Mitchell et al., 2012; Ratta-apha et al., 2014). Moreover, a substantial number of prevalence studies on alcohol-related disorders in clinical settings use routine clinical data from medical records and chart summaries, which may not accurately reflect the magnitude of problems. Here we aimed to study the accuracy of diagnosis by physicians and the accuracy of International Classification of Diseases; Tenth Revision (ICD-10) coding by medical coders for alcohol dependence, alcohol withdrawal, and alcohol-withdrawal delirium among inpatients at a university hospital. The study was approved by the institutional review board. Among medical records of inpatients who were discharged from a 2117-bed university hospital with 111 wards and 27 departments during 2012
What Do Faculty Observe of Medical Students' Clinical Performance?

Background: An earlier study of our faculty's evaluation of junior medical students indicated that performance ratings were unreliable and reflected 1 underlying dimension. Other researchers have obtained similar results. Purpose: The purpose of this study was to identify which aspects of students' clinical performance faculty actually observe. Methods: We analyzed the responses of 9 faculty members to an open-ended questionnaire concerning which aspects of clinical performance attending faculty observe. We also reviewed and summarized the written comments of 331 faculty evaluations of third-year medical students. Results: Analysis of the questionnaires and evaluations indicated that faculty members gauge medical knowledge, professionalism, and clinical reasoning skills from direct interaction with students. History-taking and physical examination skills are inferred from the quality of verbal presentations. Faculty have little basis for evaluating other important aspects of clinical performance. Conclusions: Faculty primarily observe medical students' cognitive skills and professionalism. Faculty have little basis for evaluating most other features of clinical performance.
Nonlinear laser scanning microscopy of human vocal folds

The purpose of this work was to apply nonlinear laser scanning microscopy (NLSM) for visualizing the morphology of extracellular matrix proteins within human vocal folds. This technique may potentially assist clinicians in making rapid diagnoses of vocal fold tissue disease or damage. Microstructural characterization based on NLSM provides valuable information for better understanding molecular mechanisms and tissue structure.
The Interaction Between Leptin and the Hypothalamic-Pituitary-Thyroid Axis

The description of the adipose tissue hormone leptin has led to important discoveries. Leptin plays a role not only in the regulation of metabolic efficiency, energy expenditure, food intake and adiposity, but also contributes greatly to the adaptation of the organism to starvation. Much of the literature has focused on the physiologic roles of leptin-driven processes as diverse as feeding behavior, body weight, defense to starvation and reproduction. The following discussion summarizes knowledge that has accumulated regarding the interaction between leptin and the hypothalamic-pituitary-thyroid axis.
Reliability of Near-Infrared Angiography and Micro-Doppler Sonography for Evaluating Microvascular Anastomoses

Background: Intraoperative fluorescence angiography has been reported to be a promising method, with rapid and high-quality image production at low cost when used for the detection of microvascular complications. The purpose of this study was to evaluate the reliability of intraoperative near-infrared indocyanine green angiography compared with microvascular Doppler testing in a standardized model in the rat with different vessel patencies. Methods: The carotid, aorta, and femoral vessels of 23 Wistar rats were used. Indocyanine green angiography and microvascular Doppler sonographic testing were performed to assess microanastomosis with a vessel patency randomly narrowed at the anastomosis to an outer patency of 100, 75, 50, 25, and 0 percent. Results: A total of 424 investigations were performed for 68 anastomoses, including both indocyanine green videoangiographic and microvascular Doppler sonographic examinations. The overall sensitivity and specificity of the microvascular Doppler sonographic testing at different degrees of stenoses were 100 and 86.9 percent, respectively. The positive predictive value for all observations was 95.8 percent, and the corresponding negative predictive value was 100 percent. Indocyanine green angiography revealed an overall sensitivity of 95.3 percent and a specificity of 100 percent. The positive predictive value for these observations was 100 percent, and the negative predictive value was 84 percent. Conclusions: Indocyanine green angiography and microvascular Doppler sonography are quick and reliable methods for assessing blood flow in vessels in the laboratory model. The combined use of indocyanine green angiography and microvascular Doppler sonography can increase the accuracy of assessment of microvascular anastomoses intraoperatively. Indocyanine green can be used first, but followed by the microvascular Doppler in cases of a negative result to maximize accuracy.
Current problems of in vivo developmental neurotoxicity tests and a new in vivo approach focusing on each step of the developing central nervous system

Developmental neurotoxicity (DNT) tests usually focus on postnatal indicators, such as behavior and neuropathology, for the detection of chemically induced neurodevelopmental defects in the central nervous system (CNS). However, low reliability, especially low reproducibility, of behavioral results often causes concern among scientists and the scientific community in general. Guidance of neurohistopathological examination in the DNT guideline also has some shortcomings, especially relating to the methodological aspects. Ongoing international trends in DNT tests have shifted from the use of original in vivo animal (mammalian) studies to in vitro experiments using cell cultures and/or non‐mammalian species, such as fish. In vitro systems might initially be useful to screen test chemicals for their DNT potential. Although in vitro systems are employed as alternative approaches for DNT studies, the use of in vivo studies based on animal models remains an important factor when data are to be extrapolated to the human case. In this review, a new in vivo approach that focuses on histopathological observation of each developmental step of the CNS, such as proliferation of neural stem cells, migration of immature neurons, and formation of neural networks, using fetal and neonatal brains after chemical exposure is introduced, and some queries and arguments for current DNT experimental guidelines are discussed.
A numerical study on the SVD-based retrieval of radiometric data

A numerical study on the singular value decomposition (SVD) approach for enhancing the intrinsic spatial radiometric resolution is presented and discussed for a linear scanning configuration. The SVD approach is novel and attractive in terms of time efficiency due to its structure. The resolution enhancement study is of special relevance for application purposes within the field of environmental monitoring and multisensor data fusion. The results that we present show that, for a SSM/I-like configuration, the novel resolution enhancement procedure is capable of obtaining an 18 km resolution from data of 70 km intrinsic resolution in the presence of 1/spl deg/K root mean square (RMS) additive noise.
Legal expert systems in social administration: From fearing computers to fearing accountants

In the nineteen-eighties, the Tessec expert system was developed and several studies showed that this system could improve administrative decision making under the Netherlands' General Assistance Act. Despite this favourable evaluation, Dutch municipalities did not adopt Tessec and the development of the system was halted. Now, at the beginning of the 21st century, there is a series of new expert systems on the Dutch market, the MR-systems. These MR-systems perform the same tasks as Tessec and are in fact very similar. There is however one important difference: the MR-systems are widely used. In this article, the author tries to find a sound explanation for both the failure of Tessec, and the success of the MR systems. As he argues, this explanation can be found in a shift in attitude towards the role of legislation during the past decade. This shift has facilitated the adoption of legal expert systems.
People's Initiative to Counteract Misinformation and Marketing Practices: The Pembo, Philippines, Breastfeeding Experience, 2006

The Philippines is among 42 countries accounting for 90% of under 5-year-old deaths. Only 16% of 4 to 5 month old Filipinos exclusively breastfeed. In 2006, almost $100 million was spent advertising formula in the Philippines. To counter widespread misinformation and improve breastfeeding a peer counseling intervention was developed to target mothers with infants less than 2 months of age who were not exclusively breastfeeding or had difficulty breastfeeding. Participants received 3 peer counseling visits. At baseline and 3 weeks later, 24-hour food recalls for infants were collected. The number of exclusively formula-fed infants decreased seven-fold (P < .001). Mixed-fed infants decreased 37% (P < .001). Overall, of the 148 nonexclusively breastfeeding infants, 69.5% had changed feeding methods after 3 home visits, 76% of whom to exclusive breastfeeding. Community-based peer counseling was associated with a drastic improvement of exclusive breastfeeding practices. This intervention evolved and became sustainable by engaging political figures, cities, and communities throughout the process. In 2 years, the Department of Health, World Health Organization (WHO) program has scaled up to improve health service delivery for 161 612 persons in depressed urban communities in the Philippines. J Hum Lact. 25(3):341-349.
Methadone use in pregnancy: Evidence of progression in the severity of addiction

The number of opiate users is well documented; however, the severity of opiate use has received little attention. This retrospective study in a North of England hospital updates the progression in the severity of addiction in pregnancy. Patients treated were reviewed and the doses of prescribed methadone documented. Historical data were also used for comparison. The severity in addiction in pregnancy was assessed by the woman's drug usage expressed as the daily dose of prescribed methadone at the end of pregnancy. From 2001 to 2008 there was an increase in the mean dose of methadone prescribed at delivery from 28.2 ml/day in 2001 to 57.9 ml/day in 2008. Historically, the use was 27.3 ml/day in 1992–1996 and 32.4 ml/day in 1997–2003. No trend was noted in the number of pregnant users. In conclusion, we observed no recent increase in the number of methadone users presenting, but the severity of drug usage in pregnancy has increased.
Elicitor-Induced l-Tyrosine Decarboxylase from Plant Cell Suspension Cultures : II. Partial Characterization.

Properties of purified l-tyrosine decarboxylase (EC 4.1.1.25) from elicitor-induced cell suspension cultures of Eschscholtzia californica Cham. and Thalictrum rugosum Ait. are described. l-Tyrosine decarboxylase is a dimeric enzyme with a molecular weight of 112,600 +/- 600 daltons. The isoelectric point was estimated to be at pH 5.2 and pH 5.4 for the enzyme from E. californica and T. rugosum, respectively. The purified enzymes were stabilized in the presence of pyridoxal-5-phosphate. Optimum pH for the enzyme from both plants was found to be 8.4. Enzyme activity was dependent on exogeneously supplied pyridoxal-5-phosphate. The enzyme decarboxylated l-tyrosine and l-beta-3,4-dihydroxyphenylalanine but was inactive toward l-phenylalanine and l-tryptophan. Apparent K(m) values of Eschscholtzia- and Thalictrum-decarboxylase for l-tyrosine were 0.25 +/- 0.03 and 0.27 +/- 0.04 millimolar, respectively. Similar affinities were found for l-3,4-dihydroxyphenylalanine. Eschscholtzial-tyrosine decarboxylase was strongly inhibited by the phenylalanine analogue l-alpha-aminooxy-beta-phenylpropionate and largely unaffected by d,l-alpha-monofluoromethyl-3,4-dihydroxyphenylalanine and alpha-difluoromethyltyrosine.
Sensitivity and specificity of sonohysterography for the evaluation of the uterine cavity in perimenopausal patients.

Sonohysterography is a technique for evaluating the uterine cavity by the instillation of sterile saline solution through an 8 Fr Foley catheter, before performing an ultrasonographic evaluation. The sensitivity and specificity of the procedure were evaluated in comparison to hysteroscopy. In a prospective double‐blind study, 47 postmenopausal patients were evaluated first by sonohysterography, and within 1 week by hysteroscopy. After comparing the hysteroscopic and sonohysterographic results, sonohysterography showed a sensitivity of 86% and specificity of 100%. Sonohysterography is an accurate mode of diagnosis for pathologic intrauterine processes in perimenopausal patients.
Rivastigmine for refractory REM behavior disorder in mild cognitive impairment.

BACKGROUND Mild Cognitive Impairment (MCI) and REM Behavior Disorder (RBD) are both associated with a degeneration of ponto-medullary cholinergic pathways. METHODS We conducted a placebo-controlled, cross-over pilot trial of Rivastigmine (RVT) in 25 consecutive patients with MCI, who presented RBD refractory to conventional first-line treatments (melatonin up to 5 mg/day and clonazepam up to 2 mg/day). RESULTS RVT treatment was followed by a significant reduction of RBD episodes when compared with placebo. CONCLUSIONS Our data suggest that, in MCI patients with RBD resistant to conventional therapies (muscle relaxants benzodiazepines or melatonin,) treatment with RVT may induce a reduction in the frequency of RBD episodes compared to placebo.