Miracle-dz/UniFAR-FTUs huggingface dataset:
Natural history of unruptured intracranial aneurysms: probability of and risk factors for aneurysm rupture.

OBJECT The authors conducted a study to investigate the long-term natural history of unruptured intracranial aneurysms and the predictive risk factors determining subsequent rupture in a patient population in which surgical selection of cases was not performed. METHODS One hundred forty-two patients with 181 unruptured aneurysms were followed from the 1950s until death or the occurrence of subarachnoid hemorrhage or until the years 1997 to 1998. The annual and cumulative incidence of aneurysm rupture as well as several potential risk factors predictive of rupture were studied using life-table analyses and Cox's proportional hazards regression models including time-dependent covariates. The median follow-up time was 19.7 years (range 0.8-38.9 years). During 2575 person-years of follow up, there were 33 first-time episodes of hemorrhage from previously unruptured aneurysms, for an average annual incidence of 1.3%. In 17 patients, hemorrhage led to death. The cumulative rate of bleeding was 10.5% at 10 years, 23% at 20 years, and 30.3% at 30 years after diagnosis. The diameter of the unruptured aneurysm (relative risk [RR] 1.11 per mm in diameter, 95% confidence interval [CI] 1-1.23, p = 0.05) and patient age at diagnosis inversely (RR 0.97 per year, 95% CI 0.93-1, p = 0.05) were significant independent predictors for a subsequent aneurysm rupture after adjustment for sex, hypertension, and aneurysm group. Active smoking status at the time of diagnosis was a significant risk factor for aneurysm rupture (RR 1.46, 95% CI 1.04-2.06, p = 0.033) after adjustment for size of the aneurysm, patient age, sex, presence of hypertension, and aneurysm group. Active smoking status as a time-dependent covariate was an even more significant risk factor for aneurysm rupture (adjusted RR 3.04, 95% CI 1.21-7.66, p = 0.02). CONCLUSIONS Cigarette smoking, size of the unruptured intracranial aneurysm, and age, inversely, are important factors determining risk for subsequent aneurysm rupture. The authors conclude that such unruptured aneurysms should be surgically treated regardless of their size and of a patient's smoking status, especially in young and middle-aged adults, if this is technically possible and if the patient's concurrent diseases are not contraindications. Cessation of smoking may also be a good alternative to surgery in older patients with small-sized aneurysms.
Veterans affairs primary care clinicians' attitudes toward chronic pain and correlates of opioid prescribing rates.

OBJECTIVES The primary objective of this study was to identify veterans affairs (VA) primary care clinicians' attitudes regarding chronic pain treatment. A secondary objective was to explore relationships between clinician and practice characteristics and an objective measure of opioid prescribing rates. DESIGN Cross-sectional study of clinician survey and pharmacy data. PARTICIPANTS Forty-five VA clinicians from five primary care clinics of one VA medical center. MEASURES Survey of pain-related attitudes and behaviors, satisfaction with treatment resources, and job satisfaction; percentage of patients in clinicians' panels prescribed opioids (PCPO). RESULTS Seventy-one percent of clinicians felt moderately or strongly confident in their ability to treat chronic pain, and 77% moderately or strongly agreed that skilled pain management is a high priority. However, 73% moderately or strongly agreed that patients with chronic pain are a major source of frustration and 38% reported moderate or greater dissatisfaction with their ability to provide optimal pain treatment. Fifty-two percent moderately or strongly agreed that their management is influenced by previous experiences with patients addicted to drugs. The mean PCPO was 16.5% (SD = 6.7). In bivariate comparisons, clinician panel size, job and resource satisfaction, and professional training were associated with opioid prescribing rates. CONCLUSION High clinician confidence and interest in treating chronic pain concurrent with low satisfaction with ability to provide optimal treatment suggests a need for more system support. VA primary care clinicians are frequently influenced by fears of contributing to dependence or addiction. The relationships among panel size, job satisfaction, and opioid prescribing rates merit additional investigation.
The cultural life script as cognitive schema: How the life script shapes memory for fictional life stories

We tested, across three studies, the effect of the cultural life script on memory and its phenomenological properties. We focused in particular on the mnemonic effects of both schema-consistency and frequency in the life script. In addition to testing recognition (in Study 1) and recall (in Studies 2 and 3), we also collected remember/know judgements for remembered events (in Studies 1 and 2) and memory for their emotional valence (in Study 2). Our primary finding was that, across all three studies, higher-frequency events were more memorable than lower-frequency events, as measured through either recognition or recall. We also attained three additional, complementary effects: First, schema-inconsistent events received remember ratings more often than schema-consistent events (in Study 2, with a trend to this effect in Study 1); second, where an event's emotional valence was inconsistent with the life script, memory for its valence was reconstructed to fit the script (in Study 2); and, third, intrusions in recall were disproportionately for life script events (in Study 3), although that was not the case in recognition (in Study 1). We conclude that the life script serves as a cognitive schema in how it shapes memory and its phenomenological properties.
Investigating issues related to pediatric diabetes education: problems and barriers

In this work, we report on findings from a study of pediatric diabetes in everyday life, aimed at better understanding the needs of children and their parents, and the role of interactive technology in supporting them. Through analysis of a series of in-depth interviews with parents, we identified a series of key challenges in developing tools designed to support everyday self-management. In particular, we focus on and discuss educational issues as they clearly emerged as a recurrent concern in our study.
Passenger lymphocyte syndrome in liver transplant recipients: a description of 12 cases.

BACKGROUND Passenger lymphocyte syndrome is an important cause of immune haemolysis after solid organ transplantation. It mainly occurs in minor ABO and Rh mismatched transplants. The haemolysis is usually mild and self-limited. We present our experience in passenger lymphocyte syndrome and liver transplantation and review the literature. MATERIALS AND METHODS We reviewed liver transplants performed in our centre from January 2002 to September 2013, searching for ABO or Rh incompatibility and serological findings of haemolysis. A direct antiglobulin test was systematically performed in each pre-transfusion assessment. RESULTS A total of 1,217 liver transplants were performed and 12 passenger lymphocyte syndromes were detected: of the 56 cases with minor ABO incompatibility, ten patients developed passenger lymphocyte syndrome (17.9%) and of 147 cases with minor Rh incompatibility, two patients developed the syndrome (1.40%). All patients with passenger lymphocyte syndrome had haemolysis, a decrease of haemoglobin (median 6.8 g/dL) and an increase of bilirubin (median 5.15 mg/dL). The treatment of passenger lymphocyte syndrome consisted of increasing the dose of corticosteroids that the patients were receiving as post-transplantation immunosuppressive therapy and, in the majority of cases, transfusion of donor compatible red blood cells. DISCUSSION Passenger lymphocyte syndrome in liver transplantation has significant clinical consequences. It is, therefore, important to make the diagnosis rapidly, performing pre-transfusion direct antiglobulin tests, and manage the problem correctly with donor compatible red blood cell transfusions and/or immunosuppressive treatment.
Multifocal FIGO Stage 1A1 Cervical Squamous Carcinomas have an Extremely Good Prognosis Equivalent to Unifocal Lesions

Early invasive squamous carcinomas of the cervix are sometimes multifocal. There are few guidelines regarding how to measure multifocal carcinomas and options include measuring from the edge of 1 invasive focus to the edge of the furthest invasive focus, adding the maximum horizontal dimension of each invasive focus together or regarding multiple foci as representing distinct small areas of invasion and if clearly separate measure them individually. For tumors with a shallow depth of invasion (<3 mm), this has implications for staging and management because if the maximum horizontal dimension is taken from the edge of 1 invasive focus to the edge of the furthest invasive focus, this could represent a International Federation of Gynaecology and Obstetrics (FIGO) 1B1 carcinoma, whereas alternatively these could be regarded as separate foci of 1A1 disease. It has been our practice to regard such lesions as representing multiple foci of invasion (multifocal FIGO 1A1 carcinomas) if clearly separate, arbitrarily defined by us as a minimum of 2 mm between each separate focus of invasion. In this study, we have obtained follow-up in a series of “multifocal 1A1 cervical squamous carcinomas” treated by local excisional methods (large loop excision of transformation zone or cone biopsy) with margins clear of premalignant and malignant disease. The study included 22 cases, 11 of which (50%) would have been regarded as FIGO stage 1B1 if the horizontal dimension had been measured from the edge of 1 invasive focus to the edge of the furthest invasive focus. In none of the cases was there evidence of recurrence of premalignant or malignant disease during follow-up (9–91 mo; mean and median 48 and 45.5 mo, respectively). Although limited by a relatively small number of cases, our results support the hypothesis that with regard to tumor staging and management, it is best to consider multifocal lesions as representing separate individual foci of invasion, to measure each focus separately, and to determine the FIGO stage on the basis of the highest FIGO stage of an individual focus.
Diffusion-weighted MR imaging in laryngeal and hypopharyngeal carcinoma: association between apparent diffusion coefficient and histologic findings.

PURPOSE To investigate the relationship between the histologic characteristics of head and neck squamous cell carcinoma and apparent diffusion coefficient (ADC) at diffusion-weighted magnetic resonance (MR) imaging. MATERIALS AND METHODS The institutional ethics committee approved this study and waived informed consent. In head and neck squamous cell carcinoma, local failure after chemotherapy and/or radiation therapy correlates with pretreatment ADC. However, the histopathologic basis of this correlation remains unclear. In this study, 16 patients with head and neck squamous cell carcinoma were enrolled (median age, 60 years; range, 49-78 years). Before undergoing total laryngectomy, patients underwent 1.5-T diffusion-weighted MR imaging. After resection, whole-mount hematoxylin-eosin-stained sections were registered to the MR images. Cellular density; nuclear, cytoplasmic, and stromal area; and nuclear-cytoplasmic ratio within the tumor were calculated by using image-based segmentation on four consecutive slices. Mean ADC of the corresponding tumor region was calculated. Spearman correlations between ADC and histologic characteristics were calculated. RESULTS ADC was significantly and inversely correlated with cell density (n = 16, r = -0.57, P = .02), nuclear area (n = 12, r = -0.64, P = .03), and nuclear-cytoplasmic ratio (n = 12, r = -0.77, P ≤ .01). ADC was significantly and positively correlated with percentage area of stroma (n = 12, r = 0.69, P = .01). Additionally, the percentage area of stroma was strongly interdependent with the percentage area of nuclei (n = 12, r = -0.97, P ≤ .01). CONCLUSION ADC was significantly correlated with cellularity, stromal component, and nuclear-cytoplasmic ratio. The positive correlation of ADC and stromal component suggests that the poor prognostic value of high pretreatment ADC might partly be attributed to the tumor-stroma component, a known predictor of local failure.
Differences in Risk Factors for Breast Cancer Molecular Subtypes in a Population-Based Study

Analysis of gene expression data suggests that breast cancers are divisible into molecular subtypes which have distinct clinical features. This study evaluates whether pathologic features and etiologic associations differ among molecular subtypes. We evaluated 804 women with invasive breast cancers and 2,502 controls participating in a Polish Breast Cancer Study. Immunohistochemical stains for estrogen receptor α, progesterone receptor, human epidermal growth factor receptors (HER2 and HER1), and cytokeratin 5 were used to classify cases into five molecular subtypes: luminal A, luminal B, HER2-expresing, basal-like, and unclassified. Relative risks were estimated using adjusted odds ratios and 95% confidence intervals. We observed that compared with the predominant luminal A tumors (69%), other subtypes were associated with unfavorable clinical features at diagnosis, especially HER2-expressing (8%) and basal-like (12%) tumors. Increasing body mass index significantly reduced the risk of luminal A tumors among premenopausal women (odds ratios, 0.71; 95% confidence intervals, 0.57-0.88 per five-unit increase), whereas it did not reduce risk for basal-like tumors (1.18; 0.86-1.64; Pheterogeneity = 0.003). On the other hand, reduced risk associated with increasing age at menarche was stronger for basal-like (0.78; 0.68-0.89 per 2-year increase) than luminal A tumors (0.90; 0.95-1.08; Pheterogeneity = 0.0009). Although family history increased risk for all subtypes (except for unclassified tumors), the magnitude of the relative risk was highest for basal-like tumors. Results from this study have shown that breast cancer risk factors may vary by molecular subtypes identified in expression studies, suggesting etiologic, in addition to clinical, heterogeneity of breast cancer. (Cancer Epidemiol Biomarkers Prev 2007;16(3):439–43)
Gene Expression Profiling of Acute Liver Stress During Living Donor Liver Transplantation

During liver transplantation, the donor graft is subjected to a number of acute stresses whose molecular basis is not well‐understood. The effects of surgical stress, preservation and reperfusion injury were studied in 24 consecutive living donor liver transplant (LDLT) operations. Liver biopsies were taken early in the donor operation (OPENING), after transection of the donor liver (PRECLAMP) and following implantation of the graft (post hepatic artery, [PHA]); these were evaluated for histology, tissue glutathione content and gene expression using a 19K‐human cDNA microarray. LDLT was associated with an ischemia/reperfusion injury, with accumulation of small numbers of neutrophils and decreased glutathione in the PHA biopsies. Following reperfusion, the expression of 129 genes increased and 106 genes decreased when compared to OPENING levels (> or <2‐fold, p < 0.01). By real‐time PCR a subset of 25 genes was verified (15 increased, 10 decreased). These genes were similarly altered in another condition of acute liver stress (the response to braindeath), but not in three chronic liver disease states (HCV, HBV and PBC). This study has identified a set of genes whose expression is altered in acute, but not chronic, liver stress, likely to play a central role in the pathogenesis of acute liver injury of liver transplantation.
Phosphorylation‐dependent localization of the response regulator FrzZ signals cell reversals in Myxococcus xanthus

The life cycle of Myxococcus xanthus includes co‐ordinated group movement and fruiting body formation, and requires directed motility and controlled cell reversals. Reversals are achieved by inverting cell polarity and re‐organizing many motility proteins. The Frz chemosensory pathway regulates the frequency of cell reversals. While it has been established that phosphotransfer from the kinase FrzE to the response regulator FrzZ is required, it is unknown how phosphorylated FrzZ, the putative output of the pathway, targets the cell polarity axis. In this study, we used Phos‐tag SDS‐PAGE to determine the cellular level of phospho‐FrzZ under different growth conditions and in Frz signalling mutants. We detected consistent FrzZ phosphorylation, albeit with a short half‐life, in cells grown on plates, but not from liquid culture. The available pool of phospho‐FrzZ correlated with reversal frequencies, with higher levels found in hyper‐reversing mutants. Phosphorylation was not detected in hypo‐reversing mutants. Fluorescence microscopy revealed that FrzZ is recruited to the leading cell pole upon phosphorylation and switches to the opposite pole during reversals. These results are consistent with the hypothesis that the Frz pathway modulates reversal frequency through a localized response regulator that targets cell polarity regulators at the leading cell pole.
Spectral optimization of chest CT angiography with reduced iodine load: experience in 80 patients evaluated with dual-source, dual-energy CT.

PURPOSE To determine the energy levels that provide optimal imaging of thoracic circulation at dual-energy computed tomographic (CT) angiography with reduced iodine load in comparison with a standard technique. MATERIALS AND METHODS The institutional review board approved the study with waiver of patient consent. Eighty patients underwent a dual-source, dual-energy CT examination after administration of low-concentration contrast material (170 mg of iodine per milliliter), and eight series of images were reconstructed, including the original polychromatic images at 80 and 140 kV and six series of virtual monochromatic spectral images at 50, 60, 70, 80, 90, and 100 keV. For each vascular compartment, the energy level that provided optimal evaluation on virtual monochromatic spectral images was determined, and these series were compared with the polychromatic dual-energy images and with standard chest CT images that were used as controls. Comparisons between groups were performed by using the paired Student t test for continuous variables and the McNemar test for categorical variables. Comparisons between dual-energy and standard CT images were performed by using the unpaired Student t test for continuous variables and the χ(2) test for categorical variables. RESULTS For the aorta, pulmonary arteries, and veins, the reconstruction at 60 keV provided adequate attenuation without marked beam-hardening artifacts in 90% of patients, with the highest contrast-to-noise and signal-to-noise ratios, the lowest level of subjective noise, and no significant differences with images at 80 kV (mean energy, 54 keV). For the superior vena cava and brachiocephalic veins, the reconstructions at 100 keV enabled artifact-free analysis of the perivascular anatomic zone without a significant difference with images at 140 kV (mean energy, 92 keV). Compared with standard CT images acquired after administration of a 35% iodinated contrast agent, there was a statistically significant reduction in the frequency of artifacts around systemic veins at 100 keV (P < .001) and similar overall image quality for central vessels at 60 keV (P > .05). CONCLUSION An optimal analysis of thoracic circulation can be achieved on virtual monochromatic spectral images at 60 keV and 100 keV and on the original polychromatic images at 80 kV and 140 kV. SUPPLEMENTAL MATERIAL http://radiology.rsna. org/lookup/suppl/doi:10.1148/radiol.12120195/-/DC1.
Melatonin induces apoptosis through biomolecular changes, in SK‐LU‐1 human lung adenocarcinoma cells

Anti‐cancer effects of melatonin (N‐acetyl‐5‐methoxytryptamine, an indole‐amine), have been widely reported, however, little has been known, regarding its mechanism(s) of action in lung cancer. Thus, we investigated its induction of apoptosis through biomolecular changes (lipid, protein and nucleic acid/DNA) in the SK‐LU‐1 human lung cancer cell line.
Spontaneous activation and signaling by overexpressed epidermal growth factor receptors in glioblastoma cells

Overexpressed epidermal growth receptor factor receptors (EGFRs) are thought to contribute to the malignant phenotype of human glioblastomas (GBMs), but the mechanism is not well understood. We found that SKMG‐3 cells, a rare GBM cell line that maintains EGFR gene amplification in vitro, produced high levels of EGFR protein. The cells also expressed the related receptors HER2/neu and HER4, but not HER3. Immunoblots and tryptic phosphopeptide maps showed that the SKMG‐3 EGFRs were intact and functional and that a subset of these receptors were spontaneously autophosphorylated. EGF treatment stimulated phosphorylation of the EGFRs as well as the downstream effectors Erk, AKT1, stat3 and c‐Cbl. Under minimal growth conditions, the unstimulated SKMG‐3 cells contained constitutively phosphorylated Erk and AKTI but no detectable stat3 DNA‐binding complexes. The EGFR kinase inhibitor PD158780 reduced the constitutive phosphorylation of the receptor and Erk but not that of AKT1. In contrast, inhibition of phosphatidylinositol‐3‐kinase (PI3K) blocked the constitutive phosphorylation of Erk and AKT‐1 but not the EGFR. We conclude that the SKMG‐3 cells represent the subset of GBMs with amplified EGFR genes that overexpress intact receptors. The results also suggest that in some GBMs, signals from overexpressed EGFRs contribute to the constitutive phosphorylation of Erk, but these signals may not required for the constitutive activation of PI3K or AKT1. © 2002 Wiley‐Liss, Inc.
Genome‐Wide Scan for Loci Influencing Quantitative Immune Response Traits in the Belém Family Study: Comparison of Methods and Summary of Results

Here we report the results from a genome‐wide linkage scan to identify genes and chromosomal regions that influence quantitative immune response traits, using multi‐case leprosy and tuberculosis families from north‐eastern Brazil. Total plasma IgE, antigen‐specific IgG to Mycobacterium leprae soluble antigen (MLSA), M. tuberculosis soluble antigen (MTSA) and M. tuberculosis purified protein derivative (PPD), and antigen‐specific lymphocyte proliferation (stimulation index or SI) and interferon‐γ (IFN‐γ) release to MLSA and PPD, were measured in 16 tuberculosis (184 individuals) and 21 leprosy (177 individuals) families. The individuals were genotyped at 382 autosomal microsatellite markers across the genome. The adjusted immune‐response phenotypes were analysed using a variety of variance components and regression‐based methods. These analyses highlighted a number of practical issues and problems with regard to implementation of the methods and, interestingly, differences were observed between several standard statistical and genetic analysis packages used. From this we determined that, for this set of traits in these pedigrees, significant p values for linkage using variance components analysis, supported by significance using the Visscher‐Hopper modification of the Haseman‐Elston method, provided the most compelling evidence for linkage. Using these criteria, linkage (5.8 × 10−5 < p < 0.008) was seen for: total plasma IgE on chromosome 2; IgG to MLSA on chromosomes 8, 17 and 21; IgG to PPD on chromosome 12; SI to PPD on chromosome 1; IFN‐γ to MLSA on chromosomes 6, 7, 10, 12 and 14; and IFN‐γ to PPD on chromosomes 1, 16 and 19.