Miracle-dz/UniFAR-FTUs huggingface dataset:
Mature But Not Immature Fas Ligand (CD95L)-Transduced Human Monocyte-Derived Dendritic Cells Are Protected from Fas-Mediated Apoptosis and Can Be Used as Killer APC1

Several in vitro and animal studies have been performed to modulate the interaction of APCs and T cells by Fas (CD95/Apo-1) signaling to delete activated T cells in an Ag-specific manner. However, due to the difficulties in vector generation and low transduction frequencies, similar studies with primary human APC are still lacking. To evaluate whether Fas ligand (FasL/CD95L) expressing killer APC could be generated from primary human APC, monocyte-derived dendritic cells (DC) were transduced using the inducible Cre/Loxp adenovirus vector system. Combined transduction of DC by AdLoxpFasL and AxCANCre, but not single transduction with these vectors, resulted in dose- and time-dependent expression of FasL in >70% of mature DC (mDC), whereas <20% of immature DC (iDC) expressed FasL. In addition, transduction by AdLoxpFasL and AxCANCre induced apoptosis in >80% of iDC, whereas FasL-expressing mDC were protected from FasL/Fas (CD95/Apo-1)-mediated apoptosis despite coexpression of Fas. FasL-expressing mDC eliminated Fas+ Jurkat T cells as well as activated primary T cells by apoptosis, whereas nonactivated primary T cells were not deleted. Induction of apoptosis in Fas+ target cells required expression of FasL in DC and cell-to-cell contact between effector and target cell, and was not dependent on soluble FasL. Induction of apoptosis in Fas+ target cells required expression of FasL in DC, cell-to-cell contact between effector and target cell, and was not dependent on soluble FasL. The present results demonstrate that FasL-expressing killer APC can be generated from human monocyte-derived mDC using adenoviral gene transfer. Our results support the strategy to use killer APCs as immunomodulatory cells for the treatment of autoimmune disease and allograft rejection.
Can Activation of Coagulation and Impairment of Fibrinolysis in Patients With Anxiety and Depression Be Reversed After Improvement of Psychiatric Symptoms?: Results of a Pilot Study

Abstract Anxiety and depression are associated with an activation of coagulation and impairment of fibrinolysis. This study addresses the question whether these findings are reversed after psychotherapy and improvement of psychiatric symptoms. Three factors of coagulation and fibrinolysis as well as level of anxiety and depression were reassessed in 12 patients 1 to 3 years after intensive inpatient psychotherapy. The patients showed a substantial improvement of their severe anxiety disorder and comorbid depressive disorder. Simultaneously, we found a significant decrease in factor VII and plasminogen activator inhibitor. We conclude that reduction of severe anxiety and depression may be associated with a reversal of the procoagulant effect (activation of coagulation and impairment of fibrinolysis) of these psychological states. Because of the small sample size of this pilot study, further research is needed.
Do maritime crew members have sleep disturbances?

Data obtained from surveys of two samples of maritime crew members were studied for differences in self-reported sleep lengths and sleep problems. The data addressed both on- and off-duty variables. Statistical analysis of the data found that on-duty sleep length was shorter than off-duty sleep length for both groups. The two groups' responses to various sleep-problem items were significantly different. Most responses were below the scale mid-point. The differences between on- and off-duty sleep-problem items were not significant. Following a factor analysis, selected sleep-problem items were combined to form a composite Sleep Disturbance Scale. Using this composite measure, the correlation between the composite and sleep length was not significant. Overall, the results indicate that caution should be exercised before labeling shift workers as having "disturbed sleep" or suffering from "sleep disorders. " The results do confirm the previous findings that shiftwork reduces sleep length on workdays.
Body mass index in midlife and late‐life as a risk factor for dementia: a meta‐analysis of prospective studies

The relationship between body mass index (BMI) (in midlife and late‐life) and dementia was investigated in meta‐analyses of 16 articles reporting on 15 prospective studies. Follow‐ups ranged from 3.2 to 36.0 years. Meta‐analyses were conducted on samples including 25 624 participants evaluated for Alzheimer's disease (AD), 15 435 participants evaluated for vascular dementia (VaD) and 30 470 followed for any type of dementia (Any Dementia). Low BMI in midlife was associated with 1.96 [95% confidence interval (CI): 1.32, 2.92] times the risk of developing AD. The pooled relative risks for AD, VaD and Any Dementia for overweight BMI in midlife compared with normal BMI were 1.35 (95% CI:1.19, 1.54), 1.33 (95% CI: 1.02, 1.75) and 1.26 (95% CI: 1.10, 1.44), respectively. The pooled relative risks of AD and Any Dementia for obese BMI in midlife compared to normal BMI were 2.04 (95% CI: 1.59, 2.62) and 1.64 (95% CI: 1.34, 2.00), respectively. Continuous BMI in late‐life was not associated with dementia. Small numbers of studies included in pooled analyses reduce generalizability of findings, and emphasize the need for publication of additional findings. We conclude that underweight, overweight and obesity in midlife increase dementia risk. Further research evaluating late‐life BMI and dementia is required.
Serologic Response of Primates to Influenza Viruses

Summary Nonhuman primate (chimpanzees and baboons) sera were compared with human sera for serological activity to influenza viruses A/Victoria A/3/75 (H3N2) and A/New Jersey 8/76 (Hsw1N1). The results obtained indicate that all three primates reacted similarly to the influenza virus that was present in this area (A/Victoria). The data suggested that the nonhuman primates are not a potential reservoir but react to infection as do humans.
Changes in Nucleic Acid and Protein Content of the Human Brain During Growth

Extract: In order to establish the pattern of cellular growth, nucleic acid and protein content were serially determined in 31 human brains. The eraliest-material was obtained from a fetus with a gestational age of 13 weeks; the latest from a 13-month-old infant. Weight, protein, and RNA content increased linearly during this period. Weight increased from 5 g to 970 g, protein from 193 mg to 53 g, and RNA from 18.5 to 1384 mg. In contrast, increase in DNA content began to level off at about the time of birth and reached a maximum (approximately 900 mg) by five months of age. These data indicate that very little cell division occurs in the human brain after five months of age and that further growth occurs by increase in protein, RNA and, perhaps, lipid content of cells.Speculation: The finding in this study indicate that cell division in the human brain appears to continue until five months of age ceases thereafter. Further growth in by increase in protein. RNA and lipid content per cell. Data obtained from animals indicate that the brain is most sensitive to certain stimuli during the period of active cell division. In the human, cell division occurs during all of prenatal life and the first five months of postnatal life. It is possible that adverse eivironmental factors such as malnutrition and anoxia may be most deleterious during this period.
Impact of esophagogastroduodenoscopy and ileocolonoscopy on diagnosis and therapy in patients with rheumatic diseases—a retrospective cohort study

Abstract Objectives: Many rheumatic diseases as well as their medications may cause gastrointestinal (GI) pathologies; in addition, some primary GI diseases may contribute or lead to rheumatic disease manifestations. The aim of this study is to analyze the clinical relevance of esophagogastroduodenoscopy (EGD) and ileocolonoscopy (IC) in patients suffering from inflammatory rheumatic diseases. Methods: A retrospective chart review was performed for all rheumatological inpatients who underwent EGD and/or IC within 2 years. Results: Within 2 years, 456 patients (261 female, 195 male) underwent 752 endoscopic investigations of the GI tract (419 EGDs and 333 ICs). Of all patients, 152 (33.3%) did not report any GI complaints. However, 28 of these asymptomatic patients (18.4%) suffered from esophagitis, a gastric ulcer could be identified in 20 patients (13%), whereas unspecific colitis was diagnosed in 19 patients (12.5%). In addition, 14 patients (9.2%) suffered from clinically unapparent Crohn's disease and two patients from Whipple's disease. In one patient with polymyalgia rheumatica, colon cancer was diagnosed. Altogether 304 patients reported GI complaints. Of these, 292 (39%) endoscopic investigations had impact on the final diagnosis or therapeutic strategy. The antirheumatic medication or the concomitant medication was changed in 18% of the patients due to the endoscopic findings; in 29 patients (6.5%) the initially clinically presumed diagnosis had to be corrected. In 70 patients (15%) with an undefined rheumatic diagnosis prior to endoscopy, endoscopic findings were decisive to establish the final diagnosis. Conclusion: EGD and IC have a high diagnostic impact on patients with rheumatic diseases presenting with or without concomitant GI symptoms.
Neurodevelopmental abnormalities in neurosphere‐derived neural stem cells from SMN‐depleted mice

Spinal muscular atrophy (SMA) is a genetic disorder caused by depletion of survival motor neuron (SMN) protein and characterized by degeneration of α‐motor neurons in the spinal cord. We investigated the morphology and differentiation of neurosphere‐derived neural stem cells (NSCs) generated from the brains of a hypomorphic series of SMA mice. Neurospheres from the Smn−/−;SMN2 mice, which represent a model of very severe SMA, produced NSCs with increased proliferation during growth and differentiation. These cells produced fewer Tuj1‐positive neuronal cells, which displayed morphological alterations and had fewer and shorter neurites. The decrease in the number of Tuj1‐positive cells was not a result of enhanced apoptosis but was accompanied by an increase in the number of nestin‐positive cells. These results provide insight into the most severe model of SMA, in which SMN is nearly completely depleted, and suggest that SMN has a role in neurodevelopment as well as in neuromaintenance. Our work raises the possibility that SMN depletion affects neurodevelopment and neuromaintenance to varying extents, leading to SMA pathogenesis. © 2008 Wiley‐Liss, Inc.
Specific interaction of tissue-type plasminogen activator (t-PA) with annexin II on the membrane of pancreatic cancer cells activates plasminogen and promotes invasion in vitro

Background: Overexpression of tissue plasminogen activator (t-PA) in pancreatic cancer cells promotes invasion and proliferation in vitro and tumour growth and angiogenesis in vivo. Aims: To understand the mechanisms by which t-PA favours cancer progression, we analysed the surface membrane proteins responsible for binding specifically t-PA and studied the contribution of this interaction to the t-PA promoted invasion of pancreatic cancer cells. Methods: The ability of t-PA to activate plasmin and a fluorogenic plasmin substrate was used to analyse the nature of the binding of active t-PA to cell surfaces. Specific binding was determined in two pancreatic cancer cell lines (SK-PC-1 and PANC-1), and complex formation analysed by co-immunoprecipitation experiments and co-immunolocalisation in tumours. The functional role of the interaction was studied in Matrigel invasion assays. Results: t-PA bound to PANC-1 and SK-PC-1 cells in a specific and saturable manner while maintaining its activity. This binding was competitively inhibited by specific peptides interfering with the interaction of t-PA with annexin II. The t-PA/annexin II interaction on pancreatic cancer cells was also supported by co-immunoprecipitation assays using anti-t-PA antibodies and, reciprocally, with antiannexin II antibodies. In addition, confocal microscopy showed t-PA and annexin II colocalisation in tumour tissues. Finally, disruption of the t-PA/annexin II interaction by a specific hexapeptide significantly decreased the invasive capacity of SK-PC-1 cells in vitro. Conclusion: t-PA specifically binds to annexin II on the extracellular membrane of pancreatic cancer cells where it activates local plasmin production and tumour cell invasion. These findings may be clinically relevant for future therapeutic strategies based on specific drugs that counteract the activity of t-PA or its receptor annexin II, or their interaction at the surface level.
Prognostic significance of tumour vascularisation on survival of patients with advanced ovarian carcinoma.

OBJECTIVE The prognostic significance of microvessel density in ovarian cancer is still a matter of debate. Classically, the degree of vascularisation is assessed in areas of high vascular density (hot spots), considered as regions of increased probability of metastasis. Since ovarian tumours have a particular progression and dissemination behaviour, vascularisation outside hot spots may also contribute to their evolution. METHODS In the present study, the degree of tumour vascularisation was estimated both in whole histogical sections and in hot spots, in 235 patients with ovarian carcinoma, using fully automatic image analysis methods. Six parameters were estimated: mean microvessel density (MVD) and mean microvessel surface fraction (MSP) on the whole section, mean and maximum values of MVD and MSP inside hot spots (MVDHS1, MSPHS1 and MVDHS2, MSPHS2). Relationships between vascular parameters and clinicopathologic features were analysed. RESULTS In stage III-IV patients multivariate analysis showed that stage IV disease (hazards ratio (HR)=1.72, p=0.001), post-surgical residual disease 1cm (HR=2.86, p<0.001), upper MVD tercile (HR=1.45, p<0.022) and medial MVDHS1 tercile (HR=1.36, p=0.060) retained an independent prognostic value upon overall survival. CONCLUSION Our results suggest that quantification of blood vessels, both on the whole histological section and in hot spots might be helpful in evaluating prognosis in advanced ovarian carcinomas.
JPEG2000: standard for interactive imaging

JPEG2000 is the latest image compression standard to emerge from the Joint Photographic Experts Group (JPEG) working under the auspices of the International Standards Organization. Although the new standard does offer superior compression performance to JPEG, JPEG2000 provides a whole new way of interacting with compressed imagery in a scalable and interoperable fashion. This paper provides a tutorial-style review of the new standard, explaining the technology on which it is based and drawing comparisons with JPEG and other compression standards. The paper also describes new work, exploiting the capabilities of JPEG2000 in client-server systems for efficient interactive browsing of images over the Internet.
Detection of hepatitis B virus DNA in tissues of hepatocellular carcinomas related to hepatitis C virus which are negative for hepatitis B virus surface antigen.

BACKGROUND Uniform conclusions have not yet been drawn as to the frequency and copy number of hepatitis B virus (HBV) DNA in hepatocellular carcinoma (HCC) tissues from patients who are negative for hepatitis B surface antigen (HBsAg). METHODS The existence of HBV DNA was investigated with Southern blot hybridization and polymerase chain reaction (PCR) in HCC tissues from 55 patients who were negative for HBsAg and positive for hepatitis C virus antibody (HCVAb). RESULTS Southern blot hybridization showed that two tissues (4%) contained HBV DNA at a frequency of more than 1 HBV copy per 10 cells. Another 5 tissues were found to be positive for HBV DNA only by PCR analysis but contained less than 3 HBV DNA copies per 10(5) cells. CONCLUSIONS HCC tissues from patients seronegative for HBsAg and seropositive for HCVAb contain HBV DNA less frequently than has generally been claimed.
Relation between elevated ambient temperature and mortality: a review of the epidemiologic evidence.

The effect of elevated temperature on mortality is a public health threat of considerable magnitude. Every year, a large number of hospitalizations and deaths occur in association with exposure to elevated ambient temperatures (1, 2). An average of 400 deaths annually are counted as directly related to heat in the United States, with the highest death rates occurring in persons aged 65 years or more (3). The actual magnitude of heat-related mortality may be notably greater than what has been reported, since we do not have widely accepted criteria for determining heat-related death (4, 5–7), and heat may not be listed on the death certificate as causing or contributing to death. Persons living in urban environments may be at particularly increased risk for mortality from ambient heat exposure, since urban areas typically have higher heat indexes (combinations of temperature and humidity (8)) than surrounding suburban or rural areas, a phenomenon known as the “urban heat island effect” (9). Moreover, urban areas retain heat during the night more efficiently (10). Thus, as the US population becomes more urbanized and the number of elderly people continues to increase (11), the threat of heat-related mortality will probably become more severe. Many of these deaths may be preventable with adequate warning and an appropriate response to heat emergencies, but preventive efforts are complicated by the short time interval that may elapse between high temperature exposure and death. Thus, prevention programs must be based around prospective and rapid identification of high-risk conditions and persons. We carried out this review to assess the current epidemiologic evidence available for this purpose.
Comorbidity measures for use with administrative data.

OBJECTIVES This study attempts to develop a comprehensive set of comorbidity measures for use with large administrative inpatient datasets. METHODS The study involved clinical and empirical review of comorbidity measures, development of a framework that attempts to segregate comorbidities from other aspects of the patient's condition, development of a comorbidity algorithm, and testing on heterogeneous and homogeneous patient groups. Data were drawn from all adult, nonmaternal inpatients from 438 acute care hospitals in California in 1992 (n = 1,779,167). Outcome measures were those commonly available in administrative data: length of stay, hospital charges, and in-hospital death. RESULTS A comprehensive set of 30 comorbidity measures was developed. The comorbidities were associated with substantial increases in length of stay, hospital charges, and mortality both for heterogeneous and homogeneous disease groups. Several comorbidities are described that are important predictors of outcomes, yet commonly are not measured. These include mental disorders, drug and alcohol abuse, obesity, coagulopathy, weight loss, and fluid and electrolyte disorders. CONCLUSIONS The comorbidities had independent effects on outcomes and probably should not be simplified as an index because they affect outcomes differently among different patient groups. The present method addresses some of the limitations of previous measures. It is based on a comprehensive approach to identifying comorbidities and separates them from the primary reason for hospitalization, resulting in an expanded set of comorbidities that easily is applied without further refinement to administrative data for a wide range of diseases.
A population-based study of squamous cell vaginal cancer: HPV and cofactors.

BACKGROUND Little is known about the etiology of in situ or invasive squamous cell cancer of the vagina. It is thought that some vaginal cancers may have the same etiology as cervical cancer. It is also not known whether in situ and invasive vaginal cancer share the same etiologic factors. We conducted a study to evaluate risk factors for in situ and invasive vaginal cancer and their potential relationship to prior exposure to human papillomaviruses (HPV). METHODS A population-based case-control study included 156 women with squamous cell in situ or invasive vaginal cancer diagnosed between January 1981 and June 1998 and 2041 control women identified through random-digit dialing in western Washington state. Cases and controls were interviewed in person and provided blood samples; archival tumor tissue was retrieved for cases. Blood samples were tested for antibodies to HPV, and tumor tissue was tested for HPV DNA. RESULTS Women with vaginal cancer were more likely to have five or more lifetime sexual partners (OR = 3.1, 95% CI 1.9 to 4.9), to have an early age at first intercourse (<17 years OR = 2.0, 95% CI 1.2 to 3.5), and to be current smokers at diagnosis (OR = 2.1, 95% CI 1.4 to 3.1) than control women. Approximately 30% of all cases had been treated for a prior anogenital tumor, most often of the cervix. Prior hysterectomy was a risk factor only among women who had no history of prior anogenital cancer (OR = 3.9 95% CI 2.5 to 6.1). Antibodies to HPV16 L1 were strongly related to risk of vaginal cancer (OR = 4.3, 95% CI 3.0 to 6.2). We detected HPV DNA in tumor blocks from over 80% of the patients with in situ and 60% of the patients with invasive cancers. CONCLUSIONS In situ and invasive vaginal neoplasia have many of the same risk factors as cervical cancer, including a strong relationship to HPV infection. Women who have been treated for a prior anogenital cancer, particularly of the cervix, have a high relative risk, although low absolute risk, of being diagnosed with vaginal cancer.
Generation of Mature Murine Monocytes from Heterogeneous Bone Marrow and Description of Their Properties

Monocytes are involved in a wide range of physiological and pathological processes, many of which are studied in mouse models. Current protocols to isolate murine monocytes are few and result in unsatisfactory cell yield and purity. Here, we describe a novel approach to efficiently differentiate large numbers of mature inflammatory monocytes from heterogeneous bone marrow cell suspensions. Bone marrow cell suspensions were isolated by flushing femurs and tibias from Balb/c and C57Bl/6 mice, supplemented with macrophage colony–stimulating factor (M-CSF), and were cultured on ultra-low attachment surfaces to inhibit adherence-mediated maturation. Cells were harvested at indicated time points, underwent time-line analysis of the differentiation processes, and were subsequently extensively phenotyped to verify their monocytotic properties. In order to confirm downstream compatibility, we tested for typical monocyte behavior. Our protocol yielded 24 ± 6 × 106 differentiated cells per donor mouse, 10-fold higher than yields obtained using previously described peripheral blood isolation methods. Differentiated cells consisted of approximately 47% ± 12% monocytes, the rest being mature macrophages. We increased monocyte purity to 86% ± 6% by depleting adherent macrophages. Our findings indicate that bone marrow–derived monocytes (BMDMs) are an attractive tool to study, for example, the innate and adaptive immune system, atherosclerosis, and cellular migration during infection. Moreover, BMDM transplantation could be used to test novel, therapeutic in vivo approaches in mice disease models.
Distributed Sensing at Centimeter-Scale Spatial Resolution by BOFDA: Measurements and Signal Processing

In this paper, we demonstrate high spatial (≈3 cm) and spectral (≈30 MHz) resolution Brillouin sensing by use of Brillouin optical frequency-domain analysis (BOFDA) and signal processing. An iterative method is employed to correct the acquired data from spurious effects associated to acoustic wave modulation and relevant in the high spatial resolution regime. Experimental tests demonstrate that the proposed algorithm allows to reconstruct the Brillouin shift profile with the full spatial resolution allowed by the system bandwidth.