Miracle-dz/UniFAR-FTUs huggingface dataset:
Pap smear rates among Australian community-attached lesbian and bisexual women: some good news but disparities persist.

UNLABELLED Background Research in the US and UK shows that lesbian women are less likely than their heterosexual peers to attend for routine Pap smear tests. This study examined Pap smear test rates among community-attached lesbian, bisexual and queer (LBQ) women in New South Wales (NSW), to investigate if rates had changed between 2002 and 2012, compare rates to the general NSW population and identify predictive factors for Pap smear test attendance. METHODS Data was taken from the Sydney Women and Sexual Health (SWASH) survey, a self-completed biennial questionnaire of LBQ women's health and wellbeing. RESULTS Of the 4083 respondents, 83% had ever had a Pap smear test. Recent attendance rates were similar to the general NSW population. Significant predictors for ever having attended for a Pap smear test were older age, post Year 12 education, ever having had a sexually transmissible infection test, being out about sexuality to a regular doctor and ever having had sex with men. CONCLUSIONS Pap smear rates for LBQ women are encouraging when compared with rates from countries such as the US or UK. A significant proportion of LBQ women are never receiving Pap smear tests. Predictive factors suggest a continued perception that women who have not had sex with men are not at risk of human papillomavirus, and highlight the importance of health providers providing a safe and welcoming environment for LBQ women to openly discuss their health.
PIK3CA-associated developmental disorders exhibit distinct classes of mutations with variable expression and tissue distribution

Mosaicism is increasingly recognized as a cause of developmental disorders with the advent of next-generation sequencing (NGS). Mosaic mutations of PIK3CA have been associated with the widest spectrum of phenotypes associated with overgrowth and vascular malformations. We performed targeted NGS using 2 independent deep-coverage methods that utilize molecular inversion probes and amplicon sequencing in a cohort of 241 samples from 181 individuals with brain and/or body overgrowth. We identified PIK3CA mutations in 60 individuals. Several other individuals (n = 12) were identified separately to have mutations in PIK3CA by clinical targeted-panel testing (n = 6), whole-exome sequencing (n = 5), or Sanger sequencing (n = 1). Based on the clinical and molecular features, this cohort segregated into three distinct groups: (a) severe focal overgrowth due to low-level but highly activating (hotspot) mutations, (b) predominantly brain overgrowth and less severe somatic overgrowth due to less-activating mutations, and (c) intermediate phenotypes (capillary malformations with overgrowth) with intermediately activating mutations. Sixteen of 29 PIK3CA mutations were novel. We also identified constitutional PIK3CA mutations in 10 patients. Our molecular data, combined with review of the literature, show that PIK3CA-related overgrowth disorders comprise a discontinuous spectrum of disorders that correlate with the severity and distribution of mutations.
Caregivers’ voices: The experiences of caregivers of children who sustained serious accidental and non-accidental head injury in early childhood

Head injury is a leading cause of mortality and acquired neurological impairment in children. Head-injured children may have neurobehavioural deficits that persist for years following injury. Head injury can result in significant and persistent caregiver burden, including mental health issues, family stress and disorganisation, and unmet social and healthcare service needs. Few studies have examined the healthcare and social service needs of children and their families following head injury sustained at an early age. This qualitative study aims to describe the experiences of caregivers of children who sustained a serious head injury (particularly non-accidental head injury) before the age of 2 years. Caregivers were interviewed up to 15 years following the initial injury. Semi-structured interviews with 21 caregivers of 15 children (aged 3–15 years at the time of interview) were completed. Thematic analysis of interview data generated three key themes: impact, support and information. The study’s findings reveal the broad impact of serious childhood head injury on caregivers, specifically the significant distress and burden brought about through lack of information, challenges in accessing support and inconsistent care. Recommendations for developing a quality ‘model of care’ and improving ease of access to supports for caregivers are provided.
Evaluation of Novel Renal Biomarkers with a Cisplatin Model of Kidney Injury: Gender and Dosage Differences

A number of novel urinary biomarkers have been identified and partially qualified for use as markers for renal injury in rats. We use two novel multiplex assays to quantify biomarker concentration in multiple urine collections made prior to and following administration of cisplatin, a common nephrotoxicant, to rats. We investigate the correlation of the magnitude of biomarker changes with the severity of histopathological observations and explore the relationship of these to both dose and sex. The novel biomarkers evaluated are urinary albumin, alpha glutathione s-transferase (α-GST), glutathione S-transferase-yb1 (GSTYb1), lipocalin-2, kidney injury molecule-1 (KIM-1), osteopontin, and renal papillary antigen 1 (RPA-1) and plasma cystatin C, alongside the traditional biomarkers of plasma urea, creatinine, and urinary n-acetyl-beta-d-glucosaminidase (NAG), total protein, and glucose. We show for all time points, and for almost all doses, that male rats consistently had either more severely graded or a higher incidence of histologically observed lesions than females; that changes in urinary glucose, total urinary protein, NAG, and the novel urinary biomarkers albumin, osteopontin, and KIM-1 are clearly temporally associated; and that changes are related to the severity of injury. We also found that receiver operating characteristic curve analysis and area under the curve are significantly higher than urea or creatinine for all new biomarkers except aGST, GSTYb1, cystatin c, and total protein in both sexes.
Fludarabine potentiates metabolism of cytarabine in patients with acute myelogenous leukemia during therapy.

PURPOSE A protocol was designed to test the hypothesis that fludarabine infusion before arabinosylcytosine (cytarabine [ara-C]) would increase the accumulation of the active metabolite ara-C triphosphate (ara-CTP) in acute myelogenous leukemia (AML) blasts during therapy. PATIENTS AND METHODS Patients (n = 5) received 1 g/m2 of ara-C infused intravenously (IV) for 2 hours, followed at 20 hours by 30 mg/m2 of fludarabine for 30 minutes. At 24 hours, another identical dose of ara-C was infused. To determine the optimal duration of ara-C infusion following fludarabine, five additional patients were treated on an amended protocol in which the ara-C infusion was extended to 3 g/m2 infused over 6 hours. RESULTS Comparison of ara-CTP pharmacokinetics in circulating AML cells demonstrated that the area under the curve (AUC) of ara-CTP increased significantly (median, 1.8-fold; range, 1.6 to 2.4; P = .004) after fludarabine infusion. Neither the median plasma ara-C concentrations, the levels of its deamination product arabinosyluracil, nor the rate of ara-CTP elimination from circulating blasts was affected by fludarabine infusion. However, the rate of ara-CTP accumulation by AML cells was increased by a median of 2.0-fold (range, 1.8 to 2.2; P = .001) after fludarabine; the peak occurred within 1 hour of the end of the infusion. In vitro incubation of these cells with arabinosyl-2-fluoroadenine (F-ara-A) before ara-C also produced a median 1.7-fold increase in the ara-CTP accumulation rate. Pharmacology studies in patients receiving 6-hour infusions of ara-C demonstrated that the rate of ara-CTP accumulation was potentiated beyond 2 hours, but not for 6 hours. CONCLUSION Infusion of fludarabine before ara-C augments the rate of ara-CTP synthesis in circulating AML blasts during therapy. Evaluation of 6-hour ara-C infusions demonstrated that potentiation of ara-CTP synthesis is maximal up to 4 hours in most patients; this pharmacologically optimized regimen should be considered for combination with other antileukemia drugs.
Bacteriologic and clinical efficacy of oral gatifloxacin for the treatment of recurrent/nonresponsive acute otitis media: an open label, noncomparative, double tympanocentesis study

Background. Gatifloxacin is an 8-methoxyfluoroquinolone with good activity against respiratory pathogens. Objectives. To document the bacteriologic and clinical efficacy of gatifloxacin in recurrent/nonresponsive acute otitis media (AOM). Methods. One hundred sixty patients 6 to 48 months of age with recurrent/nonresponsive AOM received gatifloxacin suspension (10 mg/kg once daily for 10 days). Recurrent AOM was defined as ≥3 AOM episodes during the previous 6 months or ≥4 AOM episodes during the previous 12 months. Nonresponsive AOM was defined as AOM occurring ≤14 days after completing antibiotic treatment or not improving after ≥48 h of therapy. Middle ear fluid (MEF) obtained by tympanocentesis pretreatment (Day 1) and 3 to 5 days after initiation of treatment (Days 4 to 6) was cultured. Additional MEF cultures were obtained if clinical failure or recurrence of AOM occurred. Bacteriologic failure was defined by culture-positive MEF during treatment. Patients were followed until Days 22 to 28. Susceptibility was determined by broth microdilution. Results. One hundred twenty-eight (80%) patients completed treatment, and 32 discontinued the study prematurely (adverse events, 17; lost to follow-up, 10; consent withdrawal, 3; and laboratory abnormalities, 2). From 89 patients (median age, 1 year; median number of prior AOM episodes, 4; range, 0 to 12), 121 pathogens were recovered:Haemophilus influenzae, 74 (61%); Streptococcus pneumoniae, 36 (30%); Moraxella catarrhalis, 9 (7%); and Streptococcus pyogenes, 2 (2%). The 36 S. pneumoniae isolates were susceptible to gatifloxacin (MIC50 0.25 &mgr;g/ml); 26 of 36 (72%) were penicillin-nonsusceptible (15 fully resistant). All 74 H. influenzae isolates were susceptible to gatifloxacin (MIC ≤ 0.03 mg/ml). Fourteen of 74 (19%) and 9 of 9 (100%) H. influenzae and M. catarrhalis isolates, respectively, produced beta-lactamase. Bacteriologic eradication was achieved for 118 of 121 (98%) pathogens: 74 of 74 H. influenzae; 34 of 36 (94%) S. pneumoniae; 9 of 9 M. catarrhalis; and 1 of 2 S. pyogenes. Clinical improvement/cure at end of treatment was seen in 103 of 114 (90%) clinically evaluable patients. Clinical recurrence of AOM after completion of therapy occurred in 31 patients. Of the 27 recurrent AOM cases in which tympanocentesis was performed, there were 16 (59%) new infections, 4 (15%) culture-negative results and only 7 (26%) true bacteriologic relapses. Adverse events were recorded in 21 of 160 (13%) patients: vomiting, 16; diarrhea, 3; maculopapular rash, 2. No articular adverse events were recorded. Conclusion. Gatifloxacin is efficacious and safe for the treatment of recurrent/nonresponsive AOM.
Fatty Acid Synthase Expression Is Induced by the Epstein-Barr Virus Immediate-Early Protein BRLF1 and Is Required for Lytic Viral Gene Expression

ABSTRACT The Epstein-Barr virus (EBV) immediate-early (IE) protein BRLF1 (R) is a transcription factor that induces the lytic form of EBV infection. R activates certain early viral promoters through a direct binding mechanism but induces transcription of the other EBV IE gene, BZLF1 (Z), indirectly through cellular factors binding to a CRE motif in the Z promoter (Zp). Here we demonstrate that R activates expression of the fatty acid synthase (FAS) cellular gene through a p38 stress mitogen-activated protein kinase-dependent mechanism. B-cell receptor engagement of Akata cells also increases FAS expression. The FAS gene product is required for de novo synthesis of the palmitate fatty acid, and high-level FAS expression is normally limited to liver, brain, lung, and adipose tissue. We show that human epithelial tongue cells lytically infected with EBV (from oral hairy leukoplakia lesions) express much more FAS than uninfected cells. Two specific FAS inhibitors, cerulenin and C75, prevent R activation of IE (Z) and early (BMRF1) lytic EBV proteins in Jijoye cells. In addition, cerulenin and C75 dramatically attenuate IE and early lytic gene expression after B-cell receptor engagement in Akata cells and constitutive lytic viral gene expression in EBV-positive AGS cells. However, FAS inhibitors do not reduce lytic viral gene expression induced by a vector in which the Z gene product is driven by a strong heterologous promoter. In addition, FAS inhibitors do not reduce R activation of a naked DNA reporter gene construct driven by the Z promoter (Zp). These results suggest that cellular FAS activity is important for induction of Z transcription from the intact latent EBV genome, perhaps reflecting the involvement of lipid-derived signaling pathways or palmitoylated proteins. Furthermore, using FAS inhibitors may be a completely novel approach for blocking the lytic form of EBV replication.
Liver Transient Elastography (Fibroscan®): A Place in the Management Algorithms of Chronic Viral Hepatitis

Treatment guidelines are continuously evolving in chronic viral hepatitis, taking into consideration our greater understanding of natural history and therapeutic efficacy and safety. Key in the decision making process is an assessment of liver injury. Traditionally, liver biopsy has provided this information; however, this is an invasive procedure and not completely reliable. Liver transient elastography (Fibroscan®) is exciting new technology that allows estimation of hepatic fibrosis through measurement of liver stiffness. It is acceptably accurate, safe, cheap, quick and widely applicable, and can reduce the need for liver biopsy in chronic hepatitis. In chronic hepatitis C, it can identify those most likely to benefit from treatment, as well as those with cirrhosis who require more specific care. In chronic hepatitis B, it could screen groups previously excluded from treatment (normal alanine aminotransferase and low DNA) to identify the subgroup that would benefit from therapy. It cannot replace biopsy in all settings, but it will narrow the group who do require biopsy, and provide information on liver damage in patients for whom biopsy would probably not have been considered.
Energy from algae using microbial fuel cells

Bioelectricity production from a phytoplankton, Chlorella vulgaris, and a macrophyte, Ulva lactuca was examined in single chamber microbial fuel cells (MFCs). MFCs were fed with the two algae (as powders), obtaining differences in energy recovery, degradation efficiency, and power densities. C. vulgaris produced more energy generation per substrate mass (2.5 kWh/kg), but U. lactuca was degraded more completely over a batch cycle (73 ± 1% COD). Maximum power densities obtained using either single cycle or multiple cycle methods were 0.98 W/m2 (277 W/m3) using C. vulgaris, and 0.76 W/m2 (215 W/m3) using U. lactuca. Polarization curves obtained using a common method of linear sweep voltammetry (LSV) overestimated maximum power densities at a scan rate of 1 mV/s. At 0.1 mV/s, however, the LSV polarization data was in better agreement with single‐ and multiple‐cycle polarization curves. The fingerprints of microbial communities developed in reactors had only 11% similarity to inocula and clustered according to the type of bioprocess used. These results demonstrate that algae can in principle, be used as a renewable source of electricity production in MFCs. Biotechnol. Bioeng. 2009;103: 1068–1076. © 2009 Wiley Periodicals, Inc.
PENGARUH TEKANAN KETAATAN, SENIORITAS AUDITOR DAN TEKANAN ANGGARAN WAKTU TERHADAP AUDIT JUDGMENT

Auditor is a profession that one of the duties carry out an audit of the financial statements, to carry out the task required an audit judgment. Audit judgment giving effect to the final conclusion. Performance audit the auditor in making the judgment is influenced by various factors. The purpose of this study was to examine the effect of adherence pressure, seniority auditor and time budget pressure on audit judgment. This study uses primary data were collected using a questionnaire as an instrument of data collection techniques that spread to the respondent. Respondents are auditors who worked on KAP in Bali listed on the Indonesian Institute of Certified Public Accountants. The sampling method using saturated sample. Number of questionnaires distributed as much as 87 questionnaires, while that may be used as further analysis of 50 questionnaires. The analysis technique used multiple linear regression analysis. Based on the analysis found that that pressure obedience and time budget pressure on audit judgment, whereas seniority auditor's judgment does not affect the audit.
Use of Healthcare Failure Mode and Effect Analysis (HFMEA) to Quantify Risks of the Human Milk Feeding Process

The complexity of the expressed breast milk feeding process in the neonatal intensive care unit was not fully appreciated until we used a healthcare failure mode and effect analysis. This approach identified latent risks and provided semiquantitative estimates of the effectiveness of recommendations. Findings demonstrated nursing interruptions and multitasking requirements contributed to risk, emphasizing the need for focused and isolated expressed breast milk handling to improve patient safety and outcomes.
Effects of sample size and intraspecific variation in phylogenetic comparative studies: a meta‐analytic review

Comparative analyses aim to explain interspecific variation in phenotype among taxa. In this context, phylogenetic approaches are generally applied to control for similarity due to common descent, because such phylogenetic relationships can produce spurious similarity in phenotypes (known as phylogenetic inertia or bias). On the other hand, these analyses largely ignore potential biases due to within‐species variation. Phylogenetic comparative studies inherently assume that species‐specific means from intraspecific samples of modest sample size are biologically meaningful. However, within‐species variation is often significant, because measurement errors, within‐ and between‐individual variation, seasonal fluctuations, and differences among populations can all reduce the repeatability of a trait. Although simulations revealed that low repeatability can increase the type I error in a phylogenetic study, researchers only exercise great care in accounting for similarity in phenotype due to common phylogenetic descent, while problems posed by intraspecific variation are usually neglected. A meta‐analysis of 194 comparative analyses all adjusting for similarity due to common phylogenetic descent revealed that only a few studies reported intraspecific repeatabilities, and hardly any considered or partially dealt with errors arising from intraspecific variation. This is intriguing, because the meta‐analytic data suggest that the effect of heterogeneous sampling can be as important as phylogenetic bias, and thus they should be equally controlled in comparative studies. We provide recommendations about how to handle such effects of heterogeneous sampling.
Sentinel lymph node biopsy in patients with thick (= 4 mm) melanoma: a single‐centre experience

Background and objective Lymphatic mapping/sentinel lymph node biopsy (LM/SLNB) have become routine techniques for staging the regional lymph nodes in early stage melanoma, yet their role in the management of thick (= 4 mm) melanoma is debated. The aim of the present study is to review our experience with LM/SLNB in a series of patients with thick primary melanoma, to evaluate its utility in this melanoma subset.
A Dual Stable Isotope Tracer Method for the Measurement of Surfactant Disaturated-Phosphatidylcholine Net Synthesis in Infants with Congenital Diaphragmatic Hernia

The aim of the study was to measure for the first time in humans surfactant disaturated-phosphatidylcholine (DSPC) net synthesis and kinetics by using a novel, dual stable isotope tracer approach. Ten infants with congenital diaphragmatic hernia [CDH; birth weight, 3.4 ± 0.2; gestational age, 39.8 ± 0.4 wk] and 6 age-matched control subjects with no lung disease (birth weight, 3.2 ± 0.3 kg; gestational age, 39.1 ± 1.1 wk), all of whom were admitted to the neonatal intensive care unit (Padua, Italy), were studied. A ll infants received simultaneously an intratracheal (carbon-13 di-palmitoyl-phosphatidylcholine) and an i.v. (deuterated palmitic acid) stable isotope tracer. Isotopic enrichment curves of DSPC from sequential tracheal aspirates were analyzed by mass spectrometry. DSPC kinetic data were expressed as mean ± SEM and compared by the Mann-Whitney test. DSPC net synthesis from plasma palmitate was nearly identical in infants with CDH and control subjects (8.6 ± 2.2 and 8.1 ± 1.5 mg·kg−1·d−1; P = 0.7). DSPC apparent pool size was 36.7 ± 7.5 and 58.5 ± 9.1 mg/kg (P = 0.07) and half-life was 26.7 ± 4.5 and 50.3 ± 9.7 h (P = 0.03) in infants with CDH and control subjects, respectively. Both DSPC turnover and percentage of catabolism/recycling significantly correlated with duration of mechanical ventilation. In conclusion, the measurements of net DSPC synthesis and catabolism/recycling were reported for the first time in humans. Mean net DSPC synthesis was ∼8 mg·kg−1·d−1. No significant differences were found between control subjects and infants with CDH. DSPC turnover was faster in infants with CDH, presumably reflecting an increased DSPC catabolism/recycling. Whether this may ultimately lead to a secondary surfactant deficiency in infants with CDH is still to be ascertained.
Methotrexate associated to lipid core nanoparticles improves cardiac allograft vasculopathy and the inflammatory profile in a rabbit heart graft model

Coronary allograft vasculopathy is an inflammatory-proliferative process that compromises the long-term success of heart transplantation and has no effective treatment. A lipid nanoemulsion (LDE) can carry chemotherapeutic agents in the circulation and concentrates them in the heart graft. The aim of the study was to investigate the effects of methotrexate (MTX) associated to LDE. Rabbits fed a 0.5% cholesterol diet and submitted to heterotopic heart transplantation were treated with cyclosporine A (10 mg·kg–1·day–1 orally) and allocated to treatment with intravenous LDE-MTX (4 mg/kg, weekly, n=10) or with weekly intravenous saline solution (control group, n=10), beginning on the day of surgery. Animals were euthanized 6 weeks later. Compared to controls, grafts of LDE-MTX treated rabbits showed 20% reduction of coronary stenosis, with a four-fold increase in vessel lumen and 80% reduction of macrophage staining in grafts. Necrosis was attenuated by LDE-MTX. Native hearts of both LDE-MTX and Control groups were apparently normal. Gene expression of lipoprotein receptors was significantly greater in grafts compared to native hearts. In LDE-MTX group, gene expression of the pro-inflammatory factors tumor necrosis factor-α, monocyte chemoattractant protein-1, interleukin-18, vascular cell adhesion molecule-1, and matrix metalloproteinase-12 was strongly diminished whereas expression of anti-inflammatory interleukin-10 increased. LDE-MTX promoted improvement of the cardiac allograft vasculopathy and diminished inflammation in heart grafts.