Miracle-dz/UniFAR-FTUs huggingface dataset:
Inhibition of protein phosphatase 2A with the small molecule LB100 overcomes cell cycle arrest in osteosarcoma after cisplatin treatment

Osteosarcoma is the most common primary malignant bone tumor and affects a significant portion of pediatric oncology patients. Although surgery and adjuvant chemotherapy confer significant survival benefits, many patients go on to develop metastatic disease, particularly to the lungs, secondary to development of drug resistance. Inhibition of protein phosphatase 2A with the small molecule, LB100, has demonstrated potent chemo- and radio-sensitizing properties in numerous pre-clinical tumor models. In this study, we showed that LB100 overcame DNA repair mechanisms in osteosarcoma cells treated with cisplatin, in vitro, and recapitulated these findings in an in vivo xenograft model. Notably, the addition of LB100 to cisplatin prevented development of pulmonary metastases in the majority of treated animals. Our data indicated the mechanism of chemo-sensitization by LB100 involved abrogation of the ATM/ATR-activated DNA damage response, leading to hyperphosphorylation of Chk proteins and persistent cyclin activity. In addition, LB100 exposure suppressed Akt signaling, leading to Mdm2-mediated proteasomal degradation of functional p53. Taken together, LB100 prevented repair of cisplatin-induced DNA damage, resulting in mitotic catastrophe and cell death.
Randomized controlled trial of chlorhexidine dressing and highly adhesive dressing for preventing catheter-related infections in critically ill adults.

RATIONALE Most vascular catheter-related infections (CRIs) occur extraluminally in patients in the intensive care unit (ICU). Chlorhexidine-impregnated and strongly adherent dressings may decrease catheter colonization and CRI rates. OBJECTIVES To determine if chlorhexidine-impregnated and strongly adherent dressings decrease catheter colonization and CRI rates. METHODS In a 2:1:1 assessor-masked randomized trial in patients with vascular catheters inserted for an expected duration of 48 hours or more in 12 French ICUs, we compared chlorhexidine dressings, highly adhesive dressings, and standard dressings from May 2010 to July 2011. Coprimary endpoints were major CRI with or without catheter-related bloodstream infection (CR-BSI) with chlorhexidine versus nonchlorhexidine dressings and catheter colonization rate with highly adhesive nonchlorhexidine versus standard nonchlorhexidine dressings. Catheter-colonization, CR-BSIs, and skin reactions were secondary endpoints. MEASUREMENTS AND MAIN RESULTS A total of 1,879 patients (4,163 catheters and 34,339 catheter-days) were evaluated. With chlorhexidine dressings, the major-CRI rate was 67% lower (0.7 per 1,000 vs. 2.1 per 1,000 catheter-days; hazard ratio [HR], 0.328; 95% confidence interval [CI], 0.174-0.619; P = 0.0006) and the CR-BSI rate 60% lower (0.5 per 1,000 vs. 1.3 per 1,000 catheter-days; HR, 0.402; 95% CI, 0.186-0.868; P = 0.02) than with nonchlorhexidine dressings; decreases were noted in catheter colonization and skin colonization rates at catheter removal. The contact dermatitis rate was 1.1% with and 0.29% without chlorhexidine. Highly adhesive dressings decreased the detachment rate to 64.3% versus 71.9% (P < 0.0001) and the number of dressings per catheter to two (one to four) versus three (one to five) (P < 0.0001) but increased skin colonization (P < 0.0001) and catheter colonization (HR, 1.650; 95% CI, 1.21-2.26; P = 0.0016) without influencing CRI or CR-BSI rates. CONCLUSIONS A large randomized trial demonstrated that chlorhexidine-gel-impregnated dressings decreased the CRI rate in patients in the ICU with intravascular catheters. Highly adhesive dressings decreased dressing detachment but increased skin and catheter colonization. Clinical trial registered with www.clinicaltrials. gov (NCT 01189682).
Murine TOLL-like Receptor 4 Confers Lipopolysaccharide Responsiveness as Determined by Activation of NFκB and Expression of the Inducible Cyclooxygenase*

Genetic evidence indicating that TOLL-like receptor 4 (Tlr4) is the lipopolysaccharide (LPS) receptor in mice was reported. However, biochemical evidence that murine Tlr4 confers LPS responsiveness has not been convincingly demonstrated. Inducible cyclooxygenase (COX-2) is selectively expressed in LPS-stimulated macrophages in part mediated through the activation of NFκB. Thus, we determined whether murine Tlr4 confers LPS responsiveness as evaluated by the activation of NFκB and COX-2 expression. Transfection of a murine macrophage-like cell line (RAW264.7) with the constitutively active form (ΔTlr4) of Tlr4 is sufficient to activate NFκB and COX-2 expression. However, the truncated form (ΔTlr4(P712H)) of the missense mutant Tlr4(P712H) found in LPS-hyporesponsive mouse strain (C3H/HeJ) inhibits LPS-induced NFκB activation and COX-2 expression. The inability of ΔTlr4(P712H) to activate NFκB and induce COX-2 expression is rescued by a constitutively active adapter protein myeloid differentiation factor 88 (MyD88), which interacts directly with the cytoplasmic domain of Tlr proteins. Furthermore, MyD88 is co-immunoprecipitated with the wild-type ΔTlr4 but not with the ΔTlr4(P712H) mutant. Together, these results indicate that Tlr4 confers LPS responsiveness in RAW264.7 cells and suggest that hyporesponsiveness of C3H/HeJ mice to LPS is attributed to the disruption of Tlr4-mediated signaling pathways that results from the inability of the mutant Tlr4(P712H) to interact with MyD88.
Job strain and psychiatric morbidity

Background. This study examined the association between job strain and psychiatric morbidity using interview-based assessments of mental health. We assessed the prevalence of neurotic disorder in high job strain (high demand, low control) and low job strain (low demand, high control) school teachers, and compared these rates with data from individuals with similar educational qualifications from the National Psychiatric Morbidity Survey of Great Britain. Methods. One hundred and sixty primary and secondary school teachers were selected from a larger survey on the basis of high or low job strain, and were assessed for psychiatric morbidity using the Revised Clinical Interview Schedule (CIS-R). The prevalence of neurotic symptoms and a total psychiatric morbidity score were calculated. Results. After adjusting for age, gender and occupational grade, the prevalence of psychiatric morbidity was greater in high job strain than low job strain individuals. The prevalence of severe anxiety, worry and fatigue symptoms was significantly greater in the high job strain teachers. In comparison with the British psychiatric morbidity survey, the prevalence of neurotic disorders was greater in the high job strain, but not in low job strain teachers. Individuals in the low job strain group were more likely to report severe anxiety, irritability and fatigue in the week prior to interview, than comparably educated individuals in the national survey. Conclusion. Job strain is associated with psychiatric morbidity. The high levels of neurotic psychopathology among teachers is consistent with previous research that has found teaching to be a highly stressful occupation.
Cutting Edge: Asymmetric Memory T Cell Division in Response to Rechallenge

Clonal selection of a T cell for use in the immune response appears to necessitate proliferative expansion and terminal effector differentiation of some cellular progeny, while reserving other progeny as less-differentiated memory cells. It has been suggested that asymmetric cell division may promote initial cell diversification. Stem cell-like models of adaptive immunity might predict that subsequent encounters with a pathogen would evoke reiterative, self-renewing, asymmetric division by memory T cells. In this study, we show that murine memory CD8+ T cells can divide asymmetrically in response to secondary encounter with pathogen. Critical regulators of signaling and transcription are partitioned to one side of the mitotic spindle in rechallenged memory T cells, and two phenotypically distinct populations of daughter cells are evident from the earliest divisions. Memory T cells may thus use asymmetric cell division to generate cellular heterogeneity when faced with pathogen rechallenge.
Implementation of a novel high frequency ultrasound device for guiding epidural anesthesia-in vivo animal study

Epidural anesthesia has been used widely for anesthesia surgery in many clinical applications. However, the risk of epidural anesthesia may be occurred as the puncture needle was inserted too deeper to cause the dural puncture. In most cases, the anesthetists finish the anesthesia operation according to their clinical experiences. In our previous study, a novel idea of combining the ultrasound needle transducer and epidural catheter has been proposed for guiding the epidural anesthesia insertion. In present study, the implementation of this novel ultrasonic device was performed, and the animal experiments were also carried out for verifying the system performance. The portable device including a high frequency ultrasound pulser/receiver, 40-MHz high frequency needle transducer, high speed analog-to-digital converter, LCD monitor, and a FPGA chip was used to control the pulse signal by adjusting the pulse repetition frequency and pulse frequency. The distance between the tip of the epidural needle, ligamentum flavum, and dura mater can be measured in real-time by monitoring the reflected ultrasound signal in A-mode image display.
Perspectives of three experienced teachers in new positions: a portraiture study

This study examined the perspectives of three experienced new teachers during their first three months in their new schools. Research was conducted using the method of portraiture—a qualitative method that allows the researcher to create first-person narratives that attempt to portray the essence of a study’s participants. The findings of this study revealed that the participants encountered many struggles as experienced new teachers. They expressed concerns about the induction program, the hiring process, learning their new curricula, obtaining materials and teaching supplies, as well as “fitting in. ” In addition, four underlying themes that seemed to determine these three teachers’ levels of satisfaction emerged: the number of previous years spent teaching, the quality of previous teaching experiences, the presence of preconceived ideas about the new school, and the personality of the individual teacher. Implications for further research and for school administrators and colleagues were suggested.
Injection-locked Fabry-Pe/spl acute/rot laser with electronic feedback for clock recovery from high-speed OTDM signals

We demonstrate the use of an injection-locked Fabry-Peacuterot laser diode with electronic feedback for base-rate clock recovery in Ntimes10 Gb/s optical time-division-multiplexing (OTDM) systems. Injection-locking enhances the resonance frequency of the laser and the electrical feedback achieves strong resonance at the base-rate frequency of the injected data streams, enabling ultrastable electrical clock signal generation at the base rate of 10 GHz. Experimental demonstrations for clock recovery at 10 GHz from 40-Gb/s OTDM data streams and 4-1 demultiplexing of the data using the extracted clock after fiber transmission is presented. The timing jitter measured in the recovered electrical clock is less than 0.25 ps
INDUCTION OF SPECIFIC TOLERANCE TO CLASS I‐DISPARATE RENAL ALLOGRAFTS IN MINIATURE SWINE WITH CYCLOSPORINE

Previous studies in miniature swine have suggested that the mechanism underlying the spontaneous development of tolerance in one third of one-haplotype class I disparate renal allografts (i.e., ag→ad) involves a relative T cell help deficit at the time of first exposure to antigen. If this hypothesis were correct, then one might expect the administration of an immunosuppressive agent capable of inhibiting lymphokine production during this period to lead to the induction of tolerance to class I MHC antigens in two-haplotype class I mismatched renal allografts (i.e., gg→dd), which are otherwise uniformly and acutely rejected. This hypothesis was tested in eight two-haplotype class I disparate, class II matched donor-recipient pairs, in which recipients were treated with cyclosporine 10 mg/kg, i.v. q.d. for 12 days. This protocol led to the induction of long-term (>100 days) specific tolerance in 100% of recipients, as compared with control animals that rejected grafts in 13.7 ± 0.9 days (P<0.0001). The specificity of tolerance was assessed both in vivo
Investigational therapies currently in Phase II clinical trials for the treatment of pelvic serous carcinomas

Introduction: Pelvic serous carcinomas (PSCs) are a controversial entity, which mostly comprise fallopian tube carcinoma (FTC), primary peritoneal carcinoma (PPC) and serous ovarian carcinoma (OC). Despite incremental attention towards understanding pelvic serous carcinogenesis, the gold standard treatment and survival rates have not substantially changed in these last decades. Areas covered: This review summarizes and gives a critical overview of the ongoing Phase II trials investigating therapies for PSC. Expert opinion: Several novel molecules have been developed and are currently under investigation for the treatment of PSC, including FTC, PPC and serous OC. The trend of novel targeted agents is one towards individualized, tailored therapy, based on the molecular and biological differences that characterize tumors that seem similar based solely on histological analysis. The task of developing new molecules is particularly difficult for PSC, given the recurrent development of new patterns of drug resistance. However, even if current research is focused towards identifying the best treatments for each woman with a molecularly defined disease, a deeper knowledge of the molecular biology and genetics underlying FTC and its relation as a precursor of PSC is needed.
Collateral Circulation Predicts the Size of the Infarct Core and the Proportion of Salvageable Penumbra in Hyperacute Ischemic Stroke Patients Treated with Intravenous Thrombolysis

Background: We studied the impact of collateral circulation on CT perfusion (CTP) parametric maps and the amount of salvaged brain tissue, the imaging and clinical outcome at 24 h and at 3 months in a retrospective acute (<3 h) stroke cohort (105 patients) with anterior circulation thrombus treated with intravenous thrombolysis. Methods: Baseline clinical and imaging information were collected and groups with different collateral scores (CS) were compared. Binary logistic regression analyses using good CS (CS ≥2) as the dependent variable were calculated. Results: CTP Alberta Stroke Program Early CT Score (ASPECTS) was successfully assessed in 58 cases. Thirty patients displayed good CS. Poor CS were associated with more severe strokes according to National Institutes of Health Stroke Scale (NIHSS) at arrival (15 vs. 7, p = 0.005) and at 24 h (10 vs. 3, p = 0.003) after intravenous thrombolysis. Good CS were associated with a longer mean onset-to-treatment time (141 vs. 121 min, p = 0.009) and time to CTP (102 vs. 87 min, p = 0.047), better cerebral blood volume (CBV) ASPECTS (9 vs. 6, p < 0.001), better mean transit time (MTT) ASPECTS (6 vs. 3, p < 0.001), better noncontrast CT (NCCT) ASPECTS (10 vs. 8, p < 0.001) at arrival and with favorable clinical outcome at 3 months (modified Rankin Scale ≤2, p = 0.002). The fraction of penumbra that was salvageable at arrival and salvaged at 24 h was higher with better CS (p < 0.001 and p = 0.035, respectively). In multivariate analysis, time from the onset of symptoms to imaging (p = 0.037, OR 1.04 per minute, 95% CI 1.00-1.08) and CBV ASPECTS (p = 0.001, OR 2.11 per ASPECTS point, 95% CI 1.33-3.34) predicted good CS. In similar multivariable models, MTT ASPECTS (p = 0.04, OR 1.46 per ASPECTS point, 95% CI 1.02-2.10) and NCCT ASPECTS predicted good CS (p = 0.003, OR 4.38 per CT ASPECTS point, 95% CI 1.66-11.55) along with longer time from the onset of symptoms to imaging (p = 0.045, OR 1.03 per minute, 95% CI 1.00-1.06 and p = 0.02, OR 1.05 per minute, 95% CI 1.00-1.09, respectively). CBV ASPECTS had a larger area under the receiver operating characteristic curve for good CS (0.837) than NCCT ASPECTS (0.802) or MTT ASPECTS (0.752) at arrival. Conclusions: Favorable CBV ASPECTS, NCCT ASPECTS and MTT ASPECTS are associated with good CS along with more salvageable tissue and longer time from the onset of symptoms to imaging in ischemic stroke patients treated with intravenous thrombolysis.
A 4 bit Quantum Voltage Comparator based flash ADC for low noise applications

Analog to Digital Converter (ADC) is an essential part of a mixed signal circuit design, which acts as a bridge between naturally occurring analog signals and digital signals. It has been a continuous effort of the researchers to reduce or keep the noise constant along with the level of advancement made in the field of mixed signal circuit design to increase the speed. This work has been intended towards modification of Quantum Voltage Comparator (QVC) in a 4 bit flash ADC design which results in the reduction of linearity along with noise. The 2×1 multiplexer based decoder in ADC increases the speed of the circuit. QVC is a cascading of two differential comparators as a single comparator with systematically varying sizes of NMOS pair, which eliminates the resistor ladder circuit in a conventional flash ADC. In this work, the modified QVC based flash ADC works on a single input voltage. It has been simulated in GPDK 180 nm CADENCE VIRTUOSO platform with a supply voltage of 1.8 V. This proposed flash ADC design results in a significant drop in noise, yielding an SNR value of 25.4 dB with a sampling rate of 5.12 GS/s with a power consumption of 4.19 mW.
Randomized trial of anaesthetic interventions in external cephalic version for breech presentation.

BACKGROUND Successful external cephalic version (ECV) for breech presenting fetus reduces the need for Caesarean section (CS). We aimed to compare the success rate of ECV with either spinal anaesthesia (SA) or i.v. analgesia using remifentanil. METHODS In a double-phased, stratified randomized blinded controlled study we compared the success rates of ECV, performed under spinal anaesthesia (SA), i.v. analgesia (IVA) using remifentanil or no anaesthetic interventions. In phase I, 189 patients were stratified by parity before randomization to ECV, performed by blinded operators, under SA using either hyperbaric bupivacaine 9 mg with fentanyl 15 µg, i.v. remifentanil infusion 0.1 µg kg min(-1), or Control (no anaesthetic intervention). Operators performing ECV were blinded to the treatment allocation. In phase 2, patients in the Control group in whom the initial ECV failed were further randomized to receive either SA (n=9) or IVA (n=9) for a re-attempt. The primary outcome was the incidence of successful ECV. RESULTS The success rate in Phase 1 was greatest using SA [52/63 (83%)], compared with IVA [40/63 (64%)] and Control [40/63 (64%)], (P=0.027). Median [IQR] pain scores on a visual analogue scale (range 0-100), were 0 [0-0] with SA, 35 [0-60] with IVA and 50 [30-75] in the Control group (P<0.001). Median [IQR] VAS sedation scores were highest with IVA [75 (50-80)], followed by SA, [0 (0-50)] and Control [0 (0-0)]. In phase 2, 7/9 (78%) of ECV re-attempts were successful with SA, whereas all re-attempts using IVA failed (P=0.0007). The incidence of fetal bradycardia necessitating emergency CS within 30 min, was similar among groups; 1.6% (1/63) in the SA and IVA groups and 3.2% (2/63) in the Control group. CONCLUSIONS SA increased the success rate and reduced pain for both primary and re-attempts of ECV, whereas IVA using remifentanil infusion only reduced the pain. There was no significant increase in the incidence of fetal bradycardia or emergency CS, with ECV performed under anaesthetic interventions. Relaxation of the abdominal muscles from SA appears to underlie the improved outcomes for ECV.
Translated mutation in the Nurr1 gene as a cause for Parkinson's disease

Multiple genes have been now identified as causing Parkinson's disease (PD). In 2003, two mutations were identified in exon 1 of the Nurr1 gene in 10 of 107 individuals with familial PD. To date, investigators have only focused on screening for these known mutations of the Nurr1 gene. All individuals were recruited from two Parkinson's disease clinics in Canada. Following PCR amplification of each exon of the Nurr1 gene, samples underwent denaturing high‐performance liquid chromatography (DHPLC) analysis. Ten individuals also underwent direct sequencing as well as any samples where variants were identified. The Nurr1 gene was evaluated for 202 PD individuals, 37% of whom had at least one relative with PD and 100 control non‐PD individuals. Using DHPLC and direct sequencing, we did not detect any sequence variants in exon 1. Variants in amplicon 6 were seen and direct sequencing confirmed a known NI6P polymorphism in intron 6. Novel polymorphisms were also identified in exon 3 and intron 5. A novel mutation was identified in exon 3 in one nonfamilial PD individual. This heterozygous C‐to‐G transversion resulted in a serine‐to‐cysteine substitution and was not identified in any of the other 602 chromosomes screened. Mutations in the Nurr1 gene in our large cohort of familial and sporadic PD individuals are rare. The novel mutation in exon 3 is predicted to affect phosphorylation and functional studies to assess this are underway. This is the first coding mutation identified in the Nurr1 gene for Parkinson's disease. © 2006 Movement Disorder Society
Audit committee effectiveness and financial reporting timeliness: The case of Tunisian listed companies

Purpose The purpose of this paper is to investigate whether there is any relationship between the effectiveness of an audit committee and the financial reporting timeliness of Tunisian listed companies as proxied by external audit delay (AD). Analysis focuses on five audit committee characteristics: authority, financial expertise, independence, size and diligence. Design/methodology/approach Empirical tests address 162 firm-year observations drawn from Tunisian listed companies during 2011-2013. Findings Multivariate analyses indicate that audit committees with members who have financial expertise are significantly associated with shorter AD. Thus, the results suggest that audit committee financial expertise contributes to the improvement of financial statements’ timeliness. Research limitations/implications The audit committee attributes examined in this study were based on DeZoort et al. (2002) framework. There could be other aspects of audit committee effectiveness such as audit committee tenure and audit committee chair characteristics, which were not addressed in the present study. Thus, future research may consider and examine these other components of audit committee effectiveness. Practical implications Findings have managerial implications. Companies can re-look into how to further improve audit committee composition in order to enhance the timeliness of financial reporting. The issues of audit committee effectiveness and timely reporting also affect regulators and policy makers since they need to play a role in the establishment of effective audit committees and the improvement of financial reporting timeliness. Originality/value This study is one of few that have examined the impact of audit committee effectiveness on ADs in an emerging market country. Findings lend credence to the belief that audit committee members’ financial expertise enhances the quality of financial reporting by firms in a North African market criticized for the lack of maturity of its corporate governance system (Klibi, 2015; Fitch Ratings, 2009).