Miracle-dz/UniFAR-FTUs huggingface dataset:
Chronic hepatitis associated with GB virus B persistence in a tamarin after intrahepatic inoculation of synthetic viral RNA

Progress in understanding the pathogenesis of hepatitis C virus (HCV) has been slowed by the absence of tractable small animal models. Whereas GB virus B (GBV-B, an unclassified flavivirus) shares a phylogenetic relationship and several biologic attributes with HCV, including hepatotropism, it is not known to cause persistent infection, a hallmark of HCV. Here, we document persistent GBV-B infection in one of two healthy tamarins (Saguinus oedipus) inoculated intrahepatically with infectious synthetic RNA. High-titer viremia (108 to 109 genome equivalents per ml) and transiently elevated serum alanine transaminase activities were present from weeks 4 to 12 postinoculation in both animals. However, whereas GBV-B was eliminated from one animal by 20 weeks, the second animal remained viremic (103 to 107 genome equivalents per ml) for >2 years, with alanine transaminase levels becoming elevated again before spontaneous resolution of the infection. A liver biopsy taken late in the course of infection demonstrated hepatitis with periportal mononuclear infiltrates, hepatocellular microvesicular changes, cytoplasmic lipid droplets, and disordered mitochondrial ultrastructure, findings remarkably similar to chronic hepatitis C. GBV-B-infected hepatocytes contained numerous small vesicular membranous structures resembling those associated with expression of HCV nonstructural proteins, and sequencing of GBV-B RNA demonstrated a rate of molecular evolution comparable to that of HCV. We conclude that GBV-B is capable of establishing persistent infections in healthy tamarins, a feature that substantially enhances its value as a model for HCV. Mitochondrial structural changes and altered lipid metabolism leading to steatosis are conserved features of the pathogenesis of chronic hepatitis caused by these genetically distinct flaviviruses.
The autonomic control and functional significance of the changes in heart rate associated with air breathing in the jeju, Hoplerythrinus unitaeniatus

SUMMARY The jeju is a teleost fish with bimodal respiration that utilizes a modified swim bladder as an air-breathing organ (ABO). Like all air-breathing fish studied to date, jeju exhibit pronounced changes in heart rate (fH) during air-breathing events, and it is believed that these may facilitate oxygen uptake (MO2) from the ABO. The current study employed power spectral analysis (PSA) of fH patterns, coupled with instantaneous respirometry, to investigate the autonomic control of these phenomena and their functional significance for the efficacy of air breathing. The jeju obtained less than 5% of total MO2 (MtO2) from air breathing in normoxia at 26°C, and PSA of beat-to-beat variability in fH revealed a pattern similar to that of unimodal water-breathing fish. In deep aquatic hypoxia (water PO2=1 kPa) the jeju increased the frequency of air breathing (fAB) tenfold and maintained MtO2 unchanged from normoxia. This was associated with a significant increase in heart rate variability (HRV), each air breath (AB) being preceded by a brief bradycardia and then followed by a brief tachycardia. These fH changes are qualitatively similar to those associated with breathing in unimodal air-breathing vertebrates. Within 20 heartbeats after the AB, however, a beat-to-beat variability in fH typical of water-breathing fish was re-established. Pharmacological blockade revealed that both adrenergic and cholinergic tone increased simultaneously prior to each AB, and then decreased after it. However, modulation of inhibitory cholinergic tone was responsible for the major proportion of HRV, including the precise beat-to-beat modulation of fH around each AB. Pharmacological blockade of all variations in fH associated with air breathing in deep hypoxia did not, however, have a significant effect upon fAB or the regulation of MtO2. Thus, the functional significance of the profound HRV during air breathing remains a mystery.
Influence of Resting Left Ventricular Function on the Left Ventricular Response to Exercise in Patients with Coronary Artery Disease

First-pass radionuclide angiocardiography was used to assess the left ventricular response to submaximal exercise in 150 patients with coronary artery disease (CAD). To test the hypothesis that resting systolic left ventricular function as determined by left ventricular ejection fraction (LVEF) was a predictor of the hemodynamic response to exercise, the study group included patients with a wide range of resting LVEF (0.12–0.82). The influences of resting LVEF, resting end-diastolic volume, the number of diseased vessels, exercise end point and exercise double product on the change in LVEF (ΔLVEF) during exercise were tested using multiple linear regression analyses. Resting LVEF was a highly significant predictor of the ΔLVEF (p = 0.0001). Exercise duration was not related to either the resting LVEF or the ΔLVEF. For the 112 patients in whom coronary anatomy was known, resting LVEF retained its significance as a predictor of ΔLVEF (p = 0.002) even after adjustment for the significance of the extent of CAD (p = 0.0007) and the exercise end point (p = 0.06). Patients with normal resting LVEF showed the most profound decreases in LVEF, the highest frequency of new regional dysfunction and the largest relative increase in end-diastolic volume during exercise. As rest LVEF decreased, the magnitude of the ΔLVEF and the frequency of new regional dysfunction decreased. Therefore, left ventricular function at rest is an important determinant of the direction and magnitude of change in left ventricular function during exercise.
Violation of the Sphericity Assumption and Its Effect on Type-I Error Rates in Repeated Measures ANOVA and Multi-Level Linear Models (MLM)

We investigated the effects of violations of the sphericity assumption on Type I error rates for different methodical approaches of repeated measures analysis using a simulation approach. In contrast to previous simulation studies on this topic, up to nine measurement occasions were considered. Effects of the level of inter-correlations between measurement occasions on Type I error rates were considered for the first time. Two populations with non-violation of the sphericity assumption, one with uncorrelated measurement occasions and one with moderately correlated measurement occasions, were generated. One population with violation of the sphericity assumption combines uncorrelated with highly correlated measurement occasions. A second population with violation of the sphericity assumption combines moderately correlated and highly correlated measurement occasions. From these four populations without any between-group effect or within-subject effect 5,000 random samples were drawn. Finally, the mean Type I error rates for Multilevel linear models (MLM) with an unstructured covariance matrix (MLM-UN), MLM with compound-symmetry (MLM-CS) and for repeated measures analysis of variance (rANOVA) models (without correction, with Greenhouse-Geisser-correction, and Huynh-Feldt-correction) were computed. To examine the effect of both the sample size and the number of measurement occasions, sample sizes of n = 20, 40, 60, 80, and 100 were considered as well as measurement occasions of m = 3, 6, and 9. With respect to rANOVA, the results plead for a use of rANOVA with Huynh-Feldt-correction, especially when the sphericity assumption is violated, the sample size is rather small and the number of measurement occasions is large. For MLM-UN, the results illustrate a massive progressive bias for small sample sizes (n = 20) and m = 6 or more measurement occasions. This effect could not be found in previous simulation studies with a smaller number of measurement occasions. The proportionality of bias and number of measurement occasions should be considered when MLM-UN is used. The good news is that this proportionality can be compensated by means of large sample sizes. Accordingly, MLM-UN can be recommended even for small sample sizes for about three measurement occasions and for large sample sizes for about nine measurement occasions.
Family history and risk of breast cancer in New Zealand

A national population‐based case‐control study was used to assess the influence on breast cancer risk of a family history of the disease and the possibility of an interaction with reproductive risk factors. A total of 891 women aged 25–54 years with a first diagnosis of breast cancer and 1,864 control subjects randomly selected from the electoral rolls were interviewed. Age‐adjusted relative risks (RR) of breast cancer were similar for mothers (RR = 2.3) and sisters (RR = 2.7) but somewhat higher for first‐degree (RR = 2.6) than for second‐degree (RR = 1.7) relatives. Cases reporting a first‐ or second‐degree relative with breast cancer were no more likely to be diagnosed at an early age than those with no family history. With regard to the age at diagnosis of the relative, the RR was higher if breast cancer had been diagnosed before the age of 45 years than later; this was true for first‐degree as well as for second‐degree relatives. In women with no family history, the falling RRs with increasing age at menarche reflected the usual pattern, but no such trend was apparent in those reporting a mother or sister with breast cancer. For age at first full‐term pregnancy, parity, breast‐feeding, menopausal status, infertility, history of benign breast disease and body mass index, no evidence was seen of effect modification by a family history of breast cancer. Mothers of cases had about twice the cumulative rate of breast cancer as mothers of controls, a similar difference being seen between sisters of cases and sisters of controls. Int. J. Cancer 73:503–507, 1997. © 1997 Wiley‐Liss, Inc.
Pediatric and adult glioblastoma radiosensitization induced by PI3K/mTOR inhibition causes early metabolic alterations detected by nuclear magnetic resonance spectroscopy

Poor outcome for patients with glioblastomas is often associated with radioresistance. PI3K/mTOR pathway deregulation has been correlated with radioresistance; therefore, PI3K/mTOR inhibition could render tumors radiosensitive. In this study, we show that NVP-BEZ235, a dual PI3K/mTOR inhibitor, potentiates the effects of irradiation in both adult and pediatric glioblastoma cell lines, resulting in early metabolic changes detected by nuclear magnetic resonance (NMR) spectroscopy. NVP-BEZ235 radiosensitises cells to X ray exposure, inducing cell death through the inhibition of CDC25A and the activation of p21cip1(CDKN1A). Lactate and phosphocholine levels, increased with radiation, are decreased after NVP-BEZ235 and combination treatment, suggesting that inhibiting the PI3K/mTOR pathway reverses radiation induced metabolic changes. Importantly, NVP-BEZ235 potentiates the effects of irradiation in a xenograft model of adult glioblastoma, where we observed a decrease in lactate and phosphocholine levels after seven days of combination treatment. Although tumor size was not affected due to the short length of the treatment, a significant increase in CASP3 mRNA was observed in the combination group. Taken together, our data suggest that NMR metabolites could be used as biomarkers to detect an early response to combination therapy with PI3K/mTOR inhibitors and radiotherapy in adult and pediatric glioblastoma patients.
Regulation of Progenitor Cell Proliferation and Neuronal Differentiation in Enteric Nervous System Neurospheres

Enteric nervous system (ENS) progenitor cells isolated from mouse and human bowel can be cultured in vitro as neurospheres which are aggregates of the proliferating progenitor cells, together with neurons and glial cells derived from them. To investigate the factors regulating progenitor cell proliferation and differentiation, we first characterised cell proliferation in mouse ENS neurospheres by pulse chase experiments using thymidine analogs. We demonstrate rapid and continuous cell proliferation near the neurosphere periphery, after which postmitotic cells move away from the periphery to become distributed throughout the neurosphere. While many proliferating cells expressed glial markers, expression of the neuronal markers β-tubulin III (Tuj1) and nitric oxide synthase was detected in increasing numbers of post-mitotic cells after a delay of several days. Treatment of both mouse and human neurospheres with the γ-secretase inhibitor N-[N-(3,5-Difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester (DAPT) reduced expression of the transcription factors Hes1 and Hes5, demonstrating inhibition of Notch signaling. DAPT treatment also inhibited progenitor cell proliferation and increased the numbers of differentiating neurons expressing Tuj1 and nitric oxide synthase. To confirm that the cellular effects of DAPT treatment were due to inhibition of Notch signaling, siRNA knockdown of RBPjκ, a key component of the canonical Notch signaling pathway, was demonstrated both to reduce proliferation and to increase neuronal differentiation in neurosphere cells. These observations indicate that Notch signaling promotes progenitor cell proliferation and inhibits neuronal differentiation in ENS neurospheres.
Consequences of temporary inhibition of the medial amygdala on social recognition memory performance in mice

Different lines of investigation suggest that the medial amygdala is causally involved in the processing of information linked to social behavior in rodents. Here we investigated the consequences of temporary inhibition of the medial amygdala by bilateral injections of lidocaine on long-term social recognition memory as tested in the social discrimination task. Lidocaine or control NaCl solution was infused immediately before learning or before retrieval. Our data show that lidocaine infusion immediately before learning did not affect long-term memory retrieval. However, intra-amygdalar lidocaine infusions immediately before choice interfered with correct memory retrieval. Analysis of the aggressive behavior measured simultaneously during all sessions in the social recognition memory task support the impression that the lidocaine dosage used here was effective as it—at least partially—reduced the aggressive behavior shown by the experimental subjects toward the juveniles. Surprisingly, also infusions of NaCl solution blocked recognition memory at both injection time points. The results are interpreted in the context of the importance of the medial amygdala for the processing of non-volatile odors as a major contributor to the olfactory signature for social recognition memory.
Star Formation History of the Hubble Ultra Deep Field: Comparison with the Hubble Deep Field-North

We use the NICMOS Treasury and ACS HUDF images to measure the extinction-corrected star formation history for 4681 galaxies in the region common to both images using the star formation rate distribution function and other techniques similar to those employed with the NICMOS and WFPC2 images in the HDFN. Unlike the HDFN, the NICMOS region of the HUDF appears to lack highly luminous and high star formation rate galaxies at redshifts beyond 3. The HUDF provides a region that is completely uncorrelated to the HDFN and therefore provides an independent measure of the star formation history of the universe. The combined HUDF and HDFN star formation rates show an average rate of 0.2 M☉ yr-1 Mpc-3. The average SFR of the combined fields at z = 1-3 is 0.29 M☉ yr-1 Mpc-3, while the average at z = 4-6 is 1.2 M☉ yr-1 Mpc-3. The SFRs at all redshifts are within 3 σ of the average over all redshifts.
Diagnostic value of ultrasonography and magnetic resonance imaging in pregnant women at risk for placenta accreta

Abstract Objective: The purpose of this study was to evaluate whether ultrasonography and magnetic resonance imaging can detect placenta accreta reliably in at-risk patients. Patients and methods: Thirty-nine gravid women with abnormal placentation and previous uterine surgery were collected after meeting the inclusion criteria depending on gray scale sonographic findings which suggested placenta accreta. Ultrasonography (US) and resonance imaging (MRI) findings were classified as positive and negative according to presence or absence of imaging criteria of placenta accreta. Results: The surgical findings of our patients confirmed placenta accreta in 8/39 (20.5%) patients. According to gray scale and color Doppler US 11/39 (28.2%) patients were positive and 28/39 (71.8%) were negative for placenta accreta. According to MRI findings, 12/39 (30.7%) patients were positive for placenta accreta and 27/39 (69.3%) were negative. Sensitivity, specificity, positive predictive value, negative predictive value of US and MRI were 82.0%, 89.6%, 72.7%, 92.8% and 88.8%, 86.8%, 66.6%, 96.2%, respectively. Conclusion: US and MRI were useful in the diagnosis of placenta accreta with lacunae and an abnormal color Doppler imaging pattern are the most helpful findings. MRI is most clearly indicated when US findings are ambiguous or there is a posterior placenta.
Artificial neural networks improve the accuracy of cancer survival prediction

The TNM staging system originated as a response to the need for an accurate, consistent, universal cancer outcome prediction system. Since the TNM staging system was introduced in the 1950s, new prognostic factors have been identified and new methods for integrating prognostic factors have been developed. This study compares the prediction accuracy of the TNM staging system with that of artificial neural network statistical models.
TGF-beta, radiation-induced pulmonary injury and lung cancer.

PURPOSE To determine whether changes in TGF-beta plasma levels during radiation therapy may be useful in predicting radiation-induced pulmonary injury and tumour response in non-small-cell lung cancer (NSCLC) patients. MATERIALS AND METHODS Plasma TGF-beta was investigated in 27 patients with stage III NSCLC, who were treated with 60 Gy (2Gy/day) radiotherapy with or without carboplatin. TGF-beta was measured prior to beginning radiotherapy and weekly during treatment; evaluated as a ratio between TGF-beta levels obtained during treatment and the pretreatment TGF-beta level. The endpoints of the study were development of symptomatic radiation pneumonitis and tumour response. RESULTS Nine of the 27 patients developed pneumonitis. The patients who developed pneumonitis had high persistent TGF-beta levels throughout the course of treatment (TGF-beta ratio>1), whereas the TGF-beta levels in patients who did not develop pneumonitis were unchanged or declined towards normal (TGF-beta ratio < 1). Patients who responded to treatment had low or normal TGF-beta levels during treatment compared with patients who failed to respond. Other parameters such as pretreatment TGF-beta values, carboplatin treatment or field size did not appear to have a significant effect, which is probably due to the small number of patients entered in the study. CONCLUSION This pilot study, with a limited number of patients, suggests the hypothesis that elevated TGF-beta levels during radiotherapy may not only indicate patients with a higher risk of developing pulmonary toxicity but also patients with a higher risk of treatment failure. This remains to be tested in a larger clinical study.
Organisation of reperfusion therapy for STEMI in a developing country

Objective Routine evaluation of performance measures for the system of care for patients with ST-elevation myocardial infarction (STEMI) is needed to improve the STEMI network. We sought to evaluate the current status of reperfusion therapy for STEMI in the capital city of a developing country where a STEMI network was introduced in 2010. Methods Data were obtained from a local registry. A total of 28 812 patients admitted to the emergency department of a national cardiovascular hospital in three different periods (2007, 2010 and 2013) were retrospectively analysed; there were 2703 patients with STEMI. Results In 2013 compared with 2007, there was a major increase in the number of primary percutaneous coronary interventions (PCIs) (35% vs 24%, p<0.001), and the proportion of non-reperfused patients fell (62.8% vs 67.7%, p<0.001). An improvement in the overall STEMI mortality rate was also observed (7.5% vs 11.7%, p<0.001). Conclusions Implementation of a regional system of care for STEMI may improve utilisation of primary PCI. Future organisation of reperfusion therapy in a developing country such as Indonesia strongly calls for a strategy that focuses on prehospital care to minimise delay from the first medical contact to reperfusion therapy, and this may reduce the proportion of non-reperfused patients. These strategies are in concordance with guideline recommendations and may reduce or eliminate gaps in healthcare in developing countries, particularly the underutilisation of evidence-based therapies for patients with STEMI. Trial registration number NCT 02319473, Clinicaltrials.gov.
Sexuality: measures of partnerships, practices, attitudes, and problems in the National Social Life, Health, and Aging Study.

OBJECTIVES The National Social Life, Health, and Aging Project (NSHAP) was designed to examine the relationship between sexual behavior, sexual problems, and health among older women and men. We describe measures of sexual partnerships, sexual practices, sexual problems, attitudes toward sex, and nonsexual intimacy in the first wave of NSHAP. METHODS We compare measures of sexuality for those 57-85 years old, by age, separately for men and women. We construct scales of sexual mores, sexual interest, and relationship satisfaction and discuss properties of each scale. RESULTS Sexuality among older adults tends to vary with age and gender. At all ages in this study, men are more likely than women to have a partner, more likely to be sexually active with that partner, and tend to have more positive and permissive attitudes toward sex. The proportions in a sexual partnership, behavior, problems, and attitudes all differ substantially by age. And these age patterns often differ for men and women. DISCUSSION Data obtained in the NSHAP can be used to construct key measures of sexuality among older adults; to examine sexuality itself; and to explore the link between sexuality, health, well-being, and other dimensions of the lives of older adults.